Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

Macular Degeneration Research: 2002-2006
        
Ophthalmology. 2006 Aug 24; [Epub ahead of print]
Proton Beam Irradiation for Neovascular Age-Related Macular Degeneration.
Zambarakji HJ, Lane AM, Ezra E, Gauthier D, Goitein M, Adams JA, Munzenrider JE, Miller JW, Gragoudas ES.
Retina Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

OBJECTIVE: To evaluate safety and visual outcomes after proton therapy for subfoveal neovascular age-related macular degeneration (AMD). DESIGN: Randomized dose-ranging clinical trial. PARTICIPANTS: One hundred sixty-six patients with angiographic evidence of classic choroidal neovascularization resulting from AMD and best-corrected visual acuity of 20/320 or better. METHODS: Patients were assigned randomly (1:1) to receive 16-cobalt gray equivalent (CGE) or 24-CGE proton radiation in 2 equal fractions. Visual acuity was measured using standardized protocol refraction. Complete ophthalmological examinations, color fundus photography, and fluorescein angiography were performed before and 3, 6, 12, 18, and 24 months after treatment. MAIN OUTCOME MEASURE: Proportion of eyes losing 3 or more lines of vision from baseline. Kaplan-Meier statistics were used to compare cumulative rates of vision loss between the 2 treatment groups. RESULTS: At 12 months after treatment, 36 eyes (42%) and 27 eyes (35%) lost 3 or more lines of vision in the 16-CGE and 24-CGE groups, respectively. Rates increased to 62% in the 16-CGE group and 53% in the 24-CGE group by 24 months after treatment (P = 0.40). Radiation complications developed in 15.7% of patients receiving 16 CGE and 14.8% of patients receiving 24 CGE. CONCLUSIONS: No significant differences in rates of visual loss were found between the 2 dose groups. Proton radiation may be useful as an adjuvant therapy or as an alternative for patients who decline or are not appropriate for approved therapies.

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Surgeon. 2006 Aug;4(4):231-6.
Review of photodynamic therapy.
Awan MA, Tarin SA.
Wolverhampton Eye Infirmary, Wolverhampton, UK. dramer_awan@yahoo.co.uk

INTRODUCTION: Photodynamic Therapy (PDT) is an emerging treatment for a variety of conditions including ocular and extra ocular diseases. The porphyrins have been used extensively, as dyes, which are laser-activated to achieve desired clinical effects. Commonly used agents are verteporfin and porfimer sodium. METHODS: We performed a literature search of the PubMed database using the medical search headings: photodynamic therapy, photosensitizer verteporfin, visudyne, porfimer sodium and photofrin. We also performed a manual search using references from these articles, review articles and manufacturers' product monographs. RESULTS: Verteporfin and porfimer sodium are commonly used photosensitizing agents with their wide applications in different fields of medicine. Both have well established safety profiles. They are most commonly used in wet age-related macular degeneration, gastrointestinal diseases and bronchial cancers. CONCLUSION: PDT is a well established treatment entity in ophthalmology and other medical fields. In ophthalmology, it has rekindled interest and hopes in the common yet sight-threatening problem of age-related macular degeneration (AMD). This problem is still considered to be a serious issue as far as management is concerned. However in selective cases of AMD, it has shown success in restoring sight, especially in the 'classic' form of the disease. PDT is also being used to treat a range of solid cancers and non malignant conditions

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Br J Ophthalmol. 2006 Aug 2; [Epub ahead of print]
Intravitreal Triamcinolone and Laser Photocoagulation for Retinal angiomatous proliferation.
Krieglstein TR, Kampik A, Ulbig M.
Ophthamlology Department LMU Munich, Germany.

BACKGROUND: Recently the entity of retinal angiomatous proliferation (RAP) as a subtype of exsudative age-related macular degeneration (ARMD) has been described, but no treatment options are established as yet. The only two therapeutic modalities being discussed are surgical lysis of the feeding arteriole and draining venule, and the use of PDT combined with intravitreal Triamcinolone injection. In this study focal laser treatment of early extrafoveal intraretinal neovascularisation of RAP was examined. METHODS: Prospective Case series. We included 13 consecutive patients with an extrafoveal RAP stage 1 lesion. All patients underwent a complete ophthalmic examination including fluoresceine angiography and optical coherence tomography (OCT III) before treatment and at 2 weeks, 1 month, 2 months, and 4 months afterwards. In cases with marked macular edema (>350microm retinal thickening in OCT III, 12 patients) we performed intravitreal injection of 4mg Triamcinolone prior to focal laser treatment in order to reduce the edema. RESULTS: This case series indicates anatomical improvement or stabilization in patients with an extrafoveal RAP lesion after treatment. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen chart. Calculating logharrythmic values we found that VA improved by 2 to 5 log lines in 5 cases, deteriorated in 4 cases ( -2 to 5 log lines), and stabilized in 4 cases (-1 to +1 log line change). Exsudation on fluoresceine angiography was stopped in 11 cases. CONCLUSIONS: This preliminary case series suggests laser photocoagulation combined with prior intravitreal Triamcinolone injection as a viable treatment option for extrafoveal RAP stage 1. In cases with marked macular edema intravitreal triamcinolone injection improved visual acuity. For long-term stabilization additional laser treatment is mandatory. These preliminary results warrant a more detailed prospective clinical trial.

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Ophthalmic Surg Lasers Imaging. 2006 Jul-Aug;37(4):272-7.
Transpupillary thermotherapy with indocyanine green dye enhancement for the treatment of occult subfoveal choroidal neovascularization in age-related macular degeneration.
Kim JE, Shah KB, Han DP, Connor TB Jr.
The Eye Institute, Medical College of Wisconsin, Milwaukee 53226, USA.

BACKGROUND AND OBJECTIVES: Transpupillary thermotherapy (TTT) with indocyanine green (ICG) dye enhancement (TTT+) and TTT alone were compared for safety and effectiveness as a treatment of occult subfoveal choroidal neovascularization in age-related macular degeneration. PATIENTS AND METHODS: Twenty-one patients were randomized to receive TTT (12 eyes) or TTT+ (9 eyes) and observed for at least 6 months. ETDRS visual acuity and fluorescein and ICG angiography were obtained every 3 months. RESULTS: The median initial visual acuity was 20/80 in the TTT group and 20/100 in the TTT+ group. At 6 months, loss of less than 3 lines of visual acuity was present in 7 of 12 eyes (58%) in the TTT group and 5 of 9 eyes (56%) in the TTT+ group. At the final examination, there was no active choroidal neovascularization exudation in 6 of 12 eyes (50%) in the TTT group and 5 of 9 eyes (56%) in the TTT+ group. The median final visual acuity was 20/125 in the TTT group and 20/160 in the TTT+ group. Ocular or systemic complications were not encountered in either group. CONCLUSION: TTT with ICG dye enhancement was as safe and effective as TTT alone in this study. However, modifications of treatment protocol would be needed to see whether there is any advantage to using ICG dye enhancement.

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Ann Pharmacother. 2006 Jul-Aug;40(7-8):1322-6. Epub 2006 Jul 18.
Pegaptanib: a novel approach to ocular neovascularization.
Chapman JA, Beckey C.
Veterans Affairs Medical Center, West Palm Beach, FL 33410, USA. Julie.chapman3@med.va.gov

OBJECTIVE: To review pegaptanib, a novel aptamer for the treatment of age-related macular degeneration (AMD). DATA SOURCES: A literature search using MEDLINE (1980-January 2006) and the Cochrane Database of Systematic Reviews (1978-January 2006) for peer-reviewed, English-language publications was conducted. Abstracts from recent meetings, including the Association for Research in Vision and Ophthalmology and American Society of Retinal Specialists, were reviewed for relevant abstracts and poster presentations. STUDY SELECTION AND DATA EXTRACTION: Pharmacokinetic and pharmacology data were extracted from animal and human studies, and double-blind, randomized, controlled trials were included to describe the efficacy and adverse effects of pegaptanib. DATA SYNTHESIS: The efficacy of pegaptanib has been evaluated in 2 concurrent, prospective, randomized, double-blind trials. Patients with AMD were randomly assigned to receive placebo or pegaptanib intravitreous injection into 1 eye every 6 weeks for 48 weeks. The effectiveness of pegaptanib was realized as early as week 6 and continued through week 54. At week 54, 38% of patients receiving pegaptanib 0.3 mg were classified as legally blind versus 56% of those receiving the sham injection. CONCLUSIONS: Pegaptanib, a new inhibitor of ocular neovascularization, provides patients with an alternative to photodynamic therapy with verteporfin and offers a novel approach to future drug developments for AMD. Pegaptanib offers the advantage of not requiring photodynamic therapy in conjunction with drug delivery and may be a viable option for institutions where this service is not easily accessible. Results of clinical trials have shown that pegaptanib is effective in delaying progression of AMD.

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Retina. 2006 Jul-Aug;26(6):602-12.
Photodynamic therapy and high-dose intravitreal triamcinolone to treat exudative age-related macular degeneration: 1-year outcome.
Ruiz-Moreno JM, Montero JA, Barile S, Zarbin MA.
Department of Ophthalmology, Miguel Hernandez University School of Medicine, Alicante, Spain. jm.ruiz@umh.es

PURPOSE: To evaluate the efficacy of photodynamic therapy with verteporfin (PDT) and high-dose intravitreous triamcinolone acetonide to treat choroidal new vessels (CNVs) associated with age-related macular degeneration (AMD). METHODS: In this prospective, consecutive, comparative, nonrandomized, interventional case series, 30 consecutive eyes of 30 patients with subfoveal CNVs associated with AMD were treated with PDT followed by the intravitreal injection of 19.4 +/- 2.1 mg /0.1 mL triamcinolone 5 days later. Fifteen eyes had received no previous treatment (group 1), and 15 had been treated previously with PDT alone (group 2). A group of 15 eyes of 15 patients treated with PDT alone, matched for age and CNV composition and size, served as controls. Changes in best-corrected visual acuity (BCVA; logMAR), the number of Snellen lines improved or lost, and the number of PDT sessions were considered as primary outcome indicators. RESULTS: Group 1 improved an average of 0.7 +/- 3.7 Snellen lines (range, -5 to 10) (P = 0.62), group 2 lost an average of -0.7 +/- 1.5 Snellen lines (range, -5 to 1) (P = 0.08), and the control group lost an average of -2.2 +/- 0.4 Snellen lines (range, -9 to 4) (P = 0.06; Wilcoxon signed rank test). The average number of PDT treatments during the 12-month follow-up was 1.6, 1.2, and 2.8 for group 1, group 2, and the control group, respectively. Intraocular pressure rose in 8 (57%) of 14 eyes in group 1 and in 7 (50%) of 14 eyes in group 2. Cataracts developed in 4 eyes (31%) in group 1 and in 4 eyes (33%) in group 2. CONCLUSION: Combined PDT/intravitreal triamcinolone acetonide as treatment for AMD-associated CNVs was associated with improved final BCVA and reduced the need for retreatment compared with historical controls.

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J Am Geriatr Soc. 2006 Jul;54(7):1130-5.
Age-related macular degeneration: a practical approach to a challenging disease.
Bourla DH, Young TA.
Jules Stein Eye Institute, Retina Division, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.

Age-related macular degeneration (AMD) is the leading cause of blindness in older North Americans. The clinical spectrum, risk factors, pathophysiology, and potential therapeutic options for AMD warrant a careful review. Despite the growth in treatment options for this disease, there is no current curative therapy. Of critical importance is attention to modifiable risk factors--improvements in cardiovascular status, including smoking cessation, and routine ophthalmic monitoring for opportunities to provide early intervention. In addition, a low-vision assessment to investigate the potential use of visual assistive devices may be beneficial to any patient who has experienced a decrease in vision. Finally, education regarding the clinical course of age-related macular degeneration and accurate information with respect to the known benefits of available treatments will impart a better understanding of this disease to patients.

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Ophthalmology. 2006 Jul 5; [Epub ahead of print]
Year 2 Efficacy Results of 2 Randomized Controlled Clinical Trials of Pegaptanib for Neovascular Age-Related Macular Degeneration.
VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group.

OBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of >/=15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining >/=0, >/=1, >/=2, and >/=3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a second year were less likely to lose >/=15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in patients who were randomized to receive therapy with pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.

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Ophthalmology. 2006 Jul;113(7):1165-72; quiz 1172-3, 1178.
Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a systematic review.
Hodge WG, Schachter HM, Barnes D, Pan Y, Lowcock EC, Zhang L, Sampson M, Morrison A, Tran K, Miguelez M, Lewin G.
Department of Ophthalmology, University of Ottawa Eye Institute, Ottawa, Canada. whodge@ottawahospital.on.ca

TOPIC: What is the evidence for efficacy of dietary and/or supplemental omega-3 fatty acids in preventing age-related macular degeneration (AMD)? CLINICAL RELEVANCE: Age-related macular degeneraion is the leading cause of blindness and vision impairment in persons older than 50 years living in North America. There is no cure for AMD, and treatment does not usually restore vision but only prevents disease progression to a modest degree. omega-3 fatty acids are considered potentially important antioxidants and are being considered as an arm of the Age-Related Eye Disease Study II clinical trial. METHODS/LITERATURE REVIEWED: Keywords were searched in Medline, Pre-Medline, Embase, and the Cochrane Library on Ovid. There was no restriction on the year or language of publication. RESULTS: There were 6 observational studies found, but the specific outcomes, exposures, and covariates studied all varied greatly. CONCLUSION: There is some clinical evidence for protection of AMD from omega-3 fatty acids. However, the results are not consistent. Hence, our conclusion is that this issue is neither clearly supported nor refuted by the present world literature. This is an intriguing and extremely important question but needs further study first with prospective cohort designs and, if positive, randomized clinical trials.

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Rev Prat. 2006 Jun 15;56(11):1194-201.
[Age-related macular degeneration]
[Article in French]
Benyelles N, Soubrane G.
Centre ophtalmologique universitaire de Creteil, centre hospitalier intercommunal. nabil.benyelles@chicreteil.fr

Age-related macular degeneration (AMD) is the commonest overall cause of irreversible blindness in patients aged 50 or over in the western world. It is a spectrum of related diseases that have in common the progressive decline of vision as a consequence of dysfunction of the central retina and its underlying supporting elements, principally the retinal pigment epithelium and choroid in older adults. The disease has been traditionally classified into early and late stages with its dry and wet forms. Patients with age-related maculopathy should consider taking a dietary supplement such as that used in AREDS. There is no effective treatment for geographic atrophy. The exudative AMD is approached depending on the type and localisation of choroidal new vessels. Laser photocoagulation has only been shown to be beneficial for extra and juxtafoveal well defined lesions. PDT with verteporfin is effective in the management of patients with subfoveal predominantly classic lesions. A variety of molecules such as bevacizumab, pegaptanib sodium and ranibizumab, specifically targeted to different pathologic pathways in AMD, have been identified to their therapeutic potential. Research is actively being pursued in preclinical models both in academic laboratories and in the pharmaceutical industry, including multiple early stage clinical trials. There is no strong evidence to support benefits of submacular surgery in the management of neovascular AMD.

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Insight. 2006 Jan-Mar;31(1):11-4.
Macugen treatment for wet age-related macular degeneration.
Tobin KA.
Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, USA. Kathleen_Tobin@MEEI.Harvard.edu

Macugen (pegaptanib sodium), manufactured by Eyetech Pharmaceuticals, Inc., and Pfizer, Inc., is the first treatment approved by the U.S. Food and Drug Administration for all forms of wet macular degeneration. Although the cause of wet macular degeneration is not known, it is believed that vascular endothelial growth factor (VEGF) induces angiogenesis, resulting in a neovascular process, the hallmark of wet macular degeneration. Macugen is a VEGF antagonist. In two controlled, double-blinded identical studies, Macugen 0.3 mg was shown to slow the progression of wet macular degeneration. Using strict aseptic technique, Macugen 0.3 mg is administered via intravitreal injection every six weeks for one to two years. Serious adverse reactions include endophthalmitis, retinal detachment, and iatrogenic traumatic cataract. Macugen is administered after a topical anesthetic, a subconjuctival block, or a combination of both is used to numb the injection site on the temporal sclera. Post-procedure patients may initially complain of transient vision loss, burning, pressure, eye pain, or "floaters". At time of discharge, patients should be informed of the signs and symptoms of infection and instructed in the administration of antibiotic drops and in proper follow-up care. Most patients are seen for follow up one week after injection and again in five weeks for additional treatment.

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Graefes Arch Clin Exp Ophthalmol. 2006 Mar 15; [Epub ahead of print]
Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with an open-label extension TAP Report No. 8.
Kaiser PK; Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group.
Cole Eye Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk i3, Cleveland, OH, 44195, USA, pkkaiser@aol.com.

PURPOSE: To report vision and safety outcomes up to 5 years from an extension of the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Investigation evaluating verteporfin therapy in patients with subfoveal choroidal neovascularization (CNV) in age-related macular degeneration. METHODS: Patients who completed the 2-year randomized, placebo-controlled portion of the TAP Investigation could participate in the open-label extension study for an additional 3 years. Patients in the study extension received open-label verteporfin therapy in the study eye, fellow eye or both eyes, irrespective of original treatment assignment to placebo or verteporfin, if leakage from CNV was evident on fluorescein angiography. Follow-up visits occurred at 3-month intervals through to month 48, with a final follow-up visit at month 60. RESULTS: Of the 402 verteporfin-treated patients in the randomized trials, 320 (80%) enrolled in the extension study; 193 (60%) of these completed the extension study up to 5 years. Patients received an average of approximately two treatments during the 3 years of the extension study. Seventy-seven (62%) of the 124 verteporfin-treated patients with predominantly classic lesions at baseline who enrolled in the extension completed the month 60 examination. Twenty-six (34%) of these 77 patients had lost 3 or more lines of visual acuity by month 24 and 27 (35%) had lost this amount of vision by month 60; the mean change in visual acuity from baseline was also similar at the month 24 and month 60 examinations (-1.5 and -1.6 lines, respectively). When visual acuity results were examined for all extension patients who received verteporfin at baseline, regardless of baseline lesion composition and extension study completion status, a similar pattern of visual acuity stabilization was evident. Few additional instances of infusion-related back pain or photosensitivity reactions were reported from month 24 to month 60. No additional safety issues were noted after bilateral treatment. CONCLUSIONS: Vision outcomes remained relatively stable from month 24 to month 60 even though the treatment rate was low during this period. The TAP Study Group identified no new safety concerns to preclude repeating verteporfin therapy as described in this study through 5 years.

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Am J Ophthalmol. 2006 Mar 7; [Epub ahead of print]
Long-Term Effect of Laser Treatment for Dry Age-Related Macular Degeneration on Choroidal Hemodynamics.
Figueroa M, Schocket LS, Dupont J, Metelitsina TI, Grunwald JE.
Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (M.F., T.I.M., J.E.G., J.D.).

PURPOSE: To determine whether laser treatment applied according to the complications of age-related macular degeneration prevention trial (CAPT) has an effect on the choroidal circulation. DESIGN: Randomized controlled trial. METHODS: This study included 30 CAPT patients with bilateral drusen. Laser Doppler flowmetry was used to measure relative choroidal blood flow (Ch(flow)) in the fovea. Measurements were obtained through dilated pupils in both eyes of each patient before photocoagulation was applied in one eye. Measurements were repeated at 3 months (30 patients) and 28 months (23 patients). RESULTS: Average Ch(flow) at baseline, 3 months, and 28 months was 7.2 +/- 2.1 (+/-1 SD), 7.3 +/- 2.5, and 6.8 +/- 2.7 arbitrary units (AU) in the control eyes and 6.6 +/- 1.6, 7.0 +/- 2.3, and 7.8 +/- 3.0 AU in the treated eyes. In comparison to control eyes, there was no significant change in Ch(flow) in the treated eyes at 3 months after treatment. At 28 months, however, there was a 5.6% drop in Ch(flow) in control eyes and an 18.2% increase in Ch(flow) in treated eyes from baseline. The average difference of 23.8% between the percentage changes in Ch(flow) observed in the control and treated eyes was statistically significant (paired two-tailed Student t test; P = .05). CONCLUSIONS: Our results suggest an increase in choroidal blood flow 28 months after laser treatment according to the CAPT protocol. This increase may play a role in the mechanism leading to the disappearance of drusen after photocoagulation. Whether removal of drusen after photocoagulation is beneficial to the patients is not known at this time.

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Graefes Arch Clin Exp Ophthalmol. 2006 Mar 9; [Epub ahead of print]
Photodynamic therapy with verteporfin for retinal angiomatous proliferation.
Boscia F, Parodi MB, Furino C, Reibaldi M, Sborgia C.
Dipartimento di Oftalmologia ed Otorinolaringoiatria, Universita di Bari, Piazza Giulio Cesare 11, Bari, Italy, francescoboscia@hotmail.com.

PURPOSE: The aim of this study was to evaluate the results of photodynamic therapy (PDT), using verteporfin, for subfoveal neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) with pigment epithelial detachment (PED) and/or choroidal neovascularization (CNV). METHODS: In this non-comparative, consecutive, interventional, case series, the data on 21 eyes (19 with stage 2 and two with stage 3 RAP) of 20 patients were reviewed. Serous PED occupied more than 50% of the lesion in 19 eyes. PDT was performed as per TAP protocol. Biomicroscopy and fluorescein and indocyanine-green angiography were performed to evaluate anatomical results and need for retreatment. Changes from baseline in best-corrected visual acuity (BCVA), and complications, were assessed. RESULTS: A mean of 3.5+/-0.9 treatments was performed. After 13.7+/-2.2 months, mean BCVA decreased from 20/80 to 20/174 (P=0.0063). In six eyes (28.6%) BCVA remained stable, whereas in 15 eyes (71.5%) it decreased. Occlusion of RAP and flattening of PED was observed in three (14.2%) eyes, conversion to disciform lesion in one (4.7%), and persistence of PED in 11 eyes (52.3%). One eye (4.7%) evolved to haemorrhagic PED, and one (4.7%) toward stage 3 RAP. A tear in the retinal pigment epithelium (RPE) was observed in four eyes (19%). Eleven (52.3%) showed progression of leakage, six moderate leakage (28.6%), and three (14.2%) absence of leakage. CONCLUSIONS: Timely PDT with verteporfin in the early stages in eyes with smaller lesions has the potential for a beneficial effect on vision, whereas it might worsen the natural course of larger lesions, with most eyes undergoing enlargement, disciform transformation or RPE tear.

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Ophthalmic Physiol Opt. 2006 Mar;26(2):169-79.
Effects of task lighting on visual function in age-related macular degeneration.
Haymes SA, Lee J.
Department of Optometry and Vision Sciences, The University of Melbourne, Victoria, Australia. haymesdomain@eastlink.ca

The purpose was to investigate the effects of the spectral power distribution (SPD) and illuminance of task lighting on visual function in age-related macular degeneration (ARMD) compared to normal healthy eyes. Twenty-eight subjects with ARMD and 18 age-matched normal subjects were studied. The effects on visual function were determined for four common task light sources: standard pearl coat incandescent (SP), daylight blue incandescent (DL), warm white fluorescent (WW) and cool white fluorescent (CW). Apart from a small, statistically significant improvement in contrast sensitivity with DL compared to SP lighting (0.5 dB, p = 0.01), there were no significant effects of SPD on other visual functions and no differences in the effects for subjects with ARMD and those with normal vision. Thus, for task lighting typically used in low vision rehabilitation, the SPD would seem to be of minimal clinical importance to visual function. However, increasing the task illuminance had a greater effect on visual function, in particular for subjects with ARMD (p < 0.01). For an increase in illuminance from 300 to 3000 lux, the mean increase in contrast sensitivity and near visual acuity was 1.5 dB and 0.13 log MAR, respectively. Although this effect is not large, we suggest that it is clinically relevant and supports the provision of additional task illuminance as an important part of low vision rehabilitation for patients with ARMD.

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Ophthalmology. 2006 Mar;113(3):363-372.e5. Epub 2006 Feb 3.
Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.
Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ.
California Retina Consultants, Santa Barbara, California 93103, USA.

PURPOSE: To report the short-term safety, biologic effect, and a possible mechanism of action of intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD). DESIGN: Interventional, consecutive, retrospective case series. PARTICIPANTS: Eighty-one eyes of 79 patients with subfoveal neovascular AMD. METHODS: Patients received intravitreal bevacizumab (1.25 mg) on a monthly basis until macular edema, subretinal fluid (SRF), and/or pigment epithelial detachment (PED) resolved. Ophthalmic evaluations included nonstandardized Snellen visual acuity (VA), complete ophthalmic examination, fluorescein angiography, and optical coherence tomography (OCT). MAIN OUTCOME MEASURES: Assessments of safety, changes in Snellen VA, OCT retinal thickness, and angiographic lesion characteristics were performed. RESULTS: No significant ocular or systemic side effects were observed. Most patients (55%) had a reduction of >10% of baseline retinal thickness at 1 week after the injection. At 4 weeks after injection, 30 of 81 eyes demonstrated complete resolution of retinal edema, SRF, and PEDs. Of the 51 eyes with 8 weeks' follow-up, 25 had complete resolution of retinal thickening, SRF, and PEDs. At 1, 4, 8,and 12 weeks, the mean retinal thickness of the central 1 mm was decreased by 61, 92, 89, and 67 mum, respectively (P<0.0001 for 1, 4, and 8 weeks and P<0.01 for 12 weeks). At 4 and 8 weeks, mean VA improved from 20/200 to 20/125 (P<0.0001). Median vision improved from 20/200 to 20/80(-) at 4 weeks and from 20/200 to 20/80 at 8 weeks. CONCLUSIONS: Short-term results suggest that intravitreal bevacizumab (1.25 mg) is well tolerated and associated with improvement in VA, decreased retinal thickness by OCT, and reduction in angiographic leakage in most patients, the majority of whom had previous treatment with photodynamic therapy and/or pegaptanib. Further evaluation of intravitreal bevacizumab for the treatment of choroidal neovascularization is warranted.

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Drug Saf. 2006;29(3):189-99.
A preliminary benefit-risk assessment of verteporfin in age-related macular degeneration.
Wickens J, Blinder KJ.
Barnes Retina Institute, Department of Ophthalmology, Washington University School of Medicine, St Louis, Missouri, USA.

The prevalence of neovascular age-related macular degeneration (AMD) is expected to increase significantly during the next 20 years. New treatment alternatives to laser photocoagulation are on the horizon - the first of these, photodynamic therapy (PDT) with verteporfin, was approved by the US FDA in 2000. In this article we present a preliminary risk-benefit assessment of verteporfin in AMD, focusing on the landmark randomised, double-blind, placebo-controlled studies. The TAP (Treatment of Age-related macular degeneration with Photodynamic therapy) trial established the efficacy of PDT for classic subfoveal neovascularisation in AMD at 2 years follow-up. The VIP (Verteporfin in Photodynamic therapy) study concentrated on subfoveal occult-only lesions not included in the TAP study. After 2 years, treated eyes were less likely to experience visual loss. Exploratory analyses of TAP and VIP suggest that lesion size is a more significant predictor of the treatment benefit than either lesion composition or visual activity. The VIM (Visudyne((R)) in Minimally classic) trial altered the standard PDT light fluence rate in the treatment of subfoveal minimally classic lesions. This trial again demonstrated a beneficial effect for those receiving treatment with PDT. The VIO (Visudyne((R)) in Occult) trial, evaluating PDT in occult-only lesions as a confirmatory study of the VIP trial, did not achieve its primary end-point at 2 years. Further analyses are pending.PDT with verteporfin has an excellent safety profile that has been established with >1 million treatment applications. Cost-effectiveness data are limited but suggest that PDT may be a cost-effective treatment modality. Other FDA-approved treatments (pegaptanib, ranibizumab and bevacizumab) for neovascular AMD are discussed, as well as investigational substances such as anecortave acetate.

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Ophthalmology. 2006 Feb 13; [Epub ahead of print]
Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration A Phase I/II Multicenter, Controlled, Multidose Study.
Heier JS, Antoszyk AN, Pavan PR, Leff SR, Rosenfeld PJ, Ciulla TA, Dreyer RF, Gentile RC, Sy JP, Hantsbarger G, Shams N.
Ophthalmic Consultants of Boston, Boston, Massachusetts.

OBJECTIVE: To assess safety of repeated intravitreal injections of ranibizumab in treating neovascular age-related macular degeneration (AMD), and to assess changes in visual acuity (VA) and AMD lesion characteristics. DESIGN: Multicenter, controlled, open-label, clinical trial. PARTICIPANTS: Sixty-four patients with subfoveal predominantly or minimally classic AMD-related choroidal neovascularization. METHODS: In part 1, subjects were randomized to monthly intravitreal ranibizumab for 3 months (4 injections of 0.3 mg or 1 injection of 0.3 mg followed by 3 injections of 0.5 mg; n = 53) or usual care (UC; n = 11). In part 2, subjects could continue their regimen for 3 additional months or cross over to the alternative treatment. MAIN OUTCOME MEASURES: Adverse events (AEs), intraocular pressure (IOP), VA, and lesion characteristics assessed by fluorescein angiography and fundus photography. RESULTS: Of the 64 randomized subjects, 62 completed the 6-month study. Twenty of 25 subjects (80%) randomized to 0.3 mg, and 22 of 28 subjects (79%) randomized to 0.5-mg ranibizumab in part 1 continued on that treatment in part 2; 9 of 11 (82%) subjects randomized to UC in part 1 crossed over to ranibizumab treatment in part 2. The most common AEs with ranibizumab were reversible inflammation and minor injection-site hemorrhages. Serious AEs were iridocyclitis, endophthalmitis, and central retinal vein occlusion (1 subject each). Postinjection, IOP increased transiently in 22.6% of ranibizumab-treated eyes in parts 1 and 2. After 4 ranibizumab injections (day 98), mean (+/- standard deviation) VA had increased 9.4+/-13.3 and 9.1+/-17.2 letters in the 0.3- and 0.5-mg groups, respectively, but had decreased 5.1+/-9.6 letters with UC. In part 2 (day 210), VA increased from baseline 12.8+/-14.7 and 15.0+/-14.2 letters in subjects continuing on 0.3 and 0.5 mg, respectively. Visual acuity improved from baseline >/=15 letters in 26% (day 98) and 45% (day 210) of subjects initially randomized to and continuing on ranibizumab, respectively, and areas of leakage and subretinal fluid decreased. No UC subject had a >/=15-letter improvement at day 98. CONCLUSIONS: Repeated intravitreal injections of ranibizumab had a good safety profile and were associated with improved VA and decreased leakage from choroidal neovascularization in subjects with neovascular AMD.

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Arch Ophthalmol. 2006 Feb;124(2):183-8.
Iris pigment epithelial translocation in the treatment of exudative macular degeneration: a 3-year follow-up.
Aisenbrey S, Lafaut BA, Szurman P, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU, Thumann G.
Center of Ophthalmology, Department of Vitreoretinal Surgery, Eberhard-Karls University Tuebingen, Tuebingen, Germany.

OBJECTIVE: To report the functional and anatomical outcome of 20 patients who underwent surgical removal of choroidal neovascularization combined with transplantation of autologous iris pigment epithelial cells to the subretinal space 3 years after treatment. METHODS: Freshly isolated autologous iris pigment epithelial cells were translocated to the subretinal space in 20 patients after membrane extraction. Patients were followed up by funduscopy, angiography, microperimetry, and visual acuity testing. RESULTS: After a follow-up of 3 years, 1 patient showed improved visual acuity, 13 patients retained stable visual acuity, and 3 patients had reduced visual acuity. No macular edema or recurrent choroidal neovascularization was apparent at any time during the follow-up. CONCLUSIONS: Transplanted autologous iris pigment epithelial cells were well tolerated for 3 years and stabilization of visual acuity was achieved in most patients. These results suggest that iris pigment epithelial cells may serve as a substitute for retinal pigment epithelial cells after choroidal neovascularization removal in patients with exudative macular degeneration; however, whether these cells will be of any value for the restoration of vision and possible protection against choroidal neovascularization recurrence awaits further clinical observation and additional research.

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Am J Ophthalmol. 2006 Feb;141(2):276-81. Comment in: Am J Ophthalmol. 2006 Feb;141(2):354-5.
Prophylactic laser treatment hastens choroidal neovascularization in unilateral age-related maculopathy: final results of the drusen laser study.
Owens SL, Bunce C, Brannon AJ, Xing W, Chisholm IH, Gross M, Guymer RH, Holz FG, Bird AC; Drusen Laser Study Group.
Moorfields Eye Hospital, London, United Kingdom, and the Universitatsklinikum Benjamin Franklin, Berlin, Germany. Sarah.Owens@moorfields.nhs.uk

PURPOSE: The Drusen Laser Study evaluated macular laser to prevent choroidal neovascularization (CNV) and vision loss in high-risk age-related maculopathy (ARM). DESIGN: Prospective, interventional, randomized, controlled clinical trial in five hospital centers. METHODS: Patients in the unilateral group had neovascular ARM and drusen in the study eye. Study eyes were randomized to laser-treated or no-laser groups. For patients in the bilateral drusen group, eyes were randomized to right eye, laser or no laser; and left eye, alternative. Laser treatment comprised 12 argon spots. Outcome was best-corrected visual acuity and CNV signs, which were monitored for 3 years. RESULTS: In the unilateral group, vision loss occurred in 21 (28.8%) of 73 patients in laser vs 13 (19.7%) of 66 no-laser patients (P=.214). Incidence of CNV was 27 (29.7%) of 91 in laser vs 15 (17.65%) of 85 no-laser patients (P=.061). CNV onset was approximately 6 months earlier in laser-treated compared with no-laser patients (P=.05). In the bilateral group, vision loss occurred in six (8.3%) of 72 laser-treated vs 10 (13.9%) of 72 fellow eyes (P=.3877). CNV incidence was 12 (11.6%) of 103 in laser-treated vs seven (6.8%) of 103 fellow eyes (P=.225). There was no difference in onset of CNV. CONCLUSIONS: Results do not support prophylactic laser of the fellow eye of patients with neovascular ARM. Its role in patients with bilateral drusen remains unclear.

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Clin Ther. 2006 Jan;28(1):36-44.
Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: a review.
Kourlas H, Schiller DS.
Division of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201-5497, USA. helen.kourlas@liu.edu

OBJECTIVE: This article reviews available information on the new selective vascular endothelial growth factor aptamer pegaptanib in the treatment of neovascular age-related macular degeneration (ARMD). The pharmacology, pharmacokinetics, pharmacodynamics, contraindications, and drug-interaction potential of pegaptanib are discussed, and the results of clinical trials evaluating its efficacy and tolerability are summarized. METHODS: Relevant articles were identified through searches of MEDLINE (1966-June 2005) and International Pharmaceutical Abstracts (1970-June 2005). The search terms included pegaptanib sodium, Macugen, age-related macular degeneration, and choroidal neovascularization. The reference lists of identified articles were reviewed for additional publications, and further information was obtained from the manufacturer of pegaptanib. Included studies were review articles and Phase II, III, and IV clinical trials, with preference given to available Phase III studies. RESULTS: Only 1 research group has evaluated the tolerability and efficacy of pegaptanib in patients with neovascular ARMD. The VEGF Inhibition Study in Ocular Neovascularization involved 2 concurrent randomized trials of intravitreous injections of pegaptanib 0.3 mg (n = 294), 1 mg (n = 300), and 3 mg (n = 296) compared with sham injections (n = 296) every 6 weeks for 54 weeks in patients with neovascular ARMD. Assessments were conducted at 6, 12, 18, 24, 30, 42, 48, and 54 weeks. The primary end point was the proportion of patients losing <15 letters on the study eye chart at 54 weeks. This end point was achieved in 70%, 71%, and 65% of patients who received pegaptanib 0.3 (P < 0.001), 1 (P < 0.001), and 3 mg (P = 0.03), respectively, compared with 55% of those receiving the sham injections. Significant improvements in visual acuity with pegaptanib compared with the sham-injection group were seen at all time points (0.3 and 1 mg: P < 0.002; 3 mg: P < 0.05). The sham-injection group was twice as likely to have severe vision loss (loss of > or =30 letters or 6 lines on the eye chart) compared with those receiving pegaptanib 0.3 or 1 mg (P < 0.001). Adverse events reported significantly more often in the pegaptanib group compared with the sham-injection group included vitreous floaters (33% vs 28%, respectively; P < 0.001), vitreous opacities (18% vs 10%; P < 0.001), and anterior-chamber inflammation (14% vs 6%; P = 0.001). Injection-related adverse events during the first year of pegaptanib treatment included endophthalmitis in 12 (1.3%) patients, retinal detachment in 6 (0.7%) patients, and traumatic injury to the lens in 5 (0.6%) patients. CONCLUSIONS: There are few published clinical data on pegaptanib. In 2 clinical comparisons with sham injections, pegaptanib was well tolerated and effective in slowing the decline in visual acuity in patients with neovascular ARMD. This agent may be considered an option for the treatment of neovascular ARMD.

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Ophthalmology. 2006 Jan;113(1):3-13. Epub 2005 Dec 20.
Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration.
Slakter JS, Bochow TW, D'Amico DJ, Marks B, Jerdan J, Sullivan EK, Robertson SM, Slakter JS, Sullins G, Zilliox P; Anecortave Acetate Clinical Study Group.
Vitreous-Retina-Macula Consultants of New York, New York, New York, USA.

PURPOSE: To compare 1-year safety and efficacy of anecortave acetate 15 mg with photodynamic therapy (PDT) with verteporfin in patients eligible for initial PDT treatment. DESIGN: Prospective, masked, randomized, multicenter, parallel group, active control, noninferiority clinical trial. PARTICIPANTS: Five hundred thirty patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration were randomized to treatment with either anecortave acetate 15 mg or PDT. METHODS: In the anecortave acetate group, the drug was administered under the Tenon's capsule as a periocular posterior juxtascleral depot (PJD) at the beginning of the study and at month 6. Before the first administration of anecortave acetate, patients in this treatment group received a sham PDT treatment, and sham PDT treatments were repeated every 3 months if there was evidence of leakage on fluorescein angiography (FA). Patients assigned to PDT received up to 4 PDT treatments at 3-month intervals, as needed based upon FA, and a sham PJD procedure at the beginning of the study and at month 6. Best-corrected visual acuity was determined at baseline and all follow-up visits. Safety data were regularly reviewed by an independent safety committee. MAIN OUTCOME MEASURE: Percent responders (patients losing <3 lines of vision) at month 12. RESULTS: Percent responders in the anecortave acetate and PDT groups were 45% and 49%, respectively (not statistically different, P = 0.43). The confidence interval (CI) for the difference ranged from -13.2% favoring PDT to +5.6% favoring anecortave acetate. The month 12 clinical outcome for anecortave acetate was improved in patients for whom reflux was controlled and who were treated within the 6-month treatment window (57% vs. 49%; 95% CI, -4.3% favoring PDT to +21.7% favoring anecortave acetate). No serious adverse events related to the study drug were reported in either treatment group. CONCLUSIONS: The safety and efficacy outcomes in this study demonstrate that the benefits of anecortave acetate for the treatment of choroidal neovascularization outweigh the risks associated with either the drug or the PJD administration procedure.

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Ophthalmology. 2006 Jan;113(1):14-22. Epub 2005 Dec 19.
Verteporfin therapy combined with intravitreal triamcinolone in all types of choroidal neovascularization due to age-related macular degeneration.
Augustin AJ, Schmidt-Erfurth U.
Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany. 106020.560@compuserve.com

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy with verteporfin combined with intravitreal triamcinolone in choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: One hundred eighty-four patients undergoing treatment for neovascular AMD at one retinal referral center. METHODS: One hundred eighty-four eyes of 184 consecutive patients (63.6% female, 36.4% male) with a mean age of 76.5 years and a follow-up of a median of 38.8 weeks (range, 12-103) were included in a case series. One hundred forty-eight (80.4%) patients had subfoveal choroidal neovascularization, 19 patients (10.3%) had juxtafoveal choroidal neovascularization, and 17 patients (9.2%) had extrafoveal choroidal neovascularization. Verteporfin photodynamic therapy was performed using the recommended standard procedure. A solution containing 25 mg of triamcinolone was injected intravitreally 16 hours after photodynamic therapy in 184 patients. The combined therapy procedure was repeated at the 3-month follow-up visits whenever persistent choroidal neovascularization leakage was documented angiographically. MAIN OUTCOME MEASURES: Mean change in best-refracted visual acuity (VA) between baseline and the last visit, and number of treatments necessary to achieve absence of leakage. RESULTS: Visual acuity improved in the majority of patients (baseline VA, mean 20/125) by a mean increase of 1.22 Snellen lines and 1.43 lines using laser interferometry (P<0.01). The mean number of required treatments was 1.21. Twenty-three eyes (12.5%) required 2 treatments, 6 eyes (3.26%) required 3 treatments, and 1 eye (0.5%) required 4 treatments. The combination treatment including laser and intravitreal steroid administration was well tolerated. Forty-six patients (25%) required glaucoma therapy due to a transient steroid-induced intraocular pressure (IOP) increase. Twelve patients (6.5%) were on topical medication for preexisting glaucoma. Two patients (1%) whose IOP increase could not be controlled with topical therapy required surgery. CONCLUSIONS: Verteporfin photodynamic therapy combined with intravitreal triamcinolone may improve the outcome of standard verteporfin photodynamic therapy in the treatment of choroidal neovascularization secondary to AMD. A significant improvement in VA was observed in a majority of treated patients and was maintained during the maximum follow-up. In addition, retreatment rates were lower than anticipated.

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Retina. 2006 Jan;26(1):58-64.
Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal Triamcinolone and photodynamic therapy with Verteporfin. 
Nicolo M, Ghiglione D, Lai S, Nasciuti F, Cicinelli S, Calabria G.
>From *Dipartimento di Neuroscienze, Oftalmologia e Genetica, Sezione di Clinica Oculistica, Universita di Genova, Italy; and daggerIstituto Biosanitas, Genoa, Italy.

PURPOSE:: To examine combined treatment with intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS:: In this prospective, interventional case series, 11 eyes of 10 consecutive patients with occult with no classic CNV underwent a single injection (25 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) protocol refraction. RESULTS:: Median best-corrected visual acuity was 20/160, 20/80, 20/80, 20/50, and 20/80 at baseline and 1, 3, 6, and 12 months, respectively. Best-corrected visual acuity at baseline was statistically different (P < 0.05) than best-corrected visual acuity at 1, 3, and 6 months. Of 11 eyes, 5 (45.5%), 7 (63.6%), 7 (63.6%), and 4 (36.3%) had improved best-corrected visual acuity of at least 3 ETDRS lines at 1, 3, 6, and 12 months, respectively, while 6 (54.5%), 9 (81.8%), 10 (91%), and 8 (73%) had improved best-corrected visual acuity of at least 2 ETDRS lines at 1, 3, 6, and 12 months, respectively. Two eyes (18%) lost >3 lines at 12 months. One eye had intraocular hypertension at 3 months and was treated with a combination of topical antiglaucomatous drugs. One eye developed a dense cataract at the last follow-up visit. No endophthalmitis, retinal detachment, or vitreous hemorrhage developed. Fluorescein leakage and retinal thickness reduced significantly after treatment. CONCLUSIONS:: Improvement of best-corrected visual acuity and lack of fluorescein leakage suggest combination treatment with IVT and PDT for occult with no classic CNV merits further investigation.

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Acta Ophthalmol Scand. 2005 Dec;83(6):645-63.
Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and neovascular diseases.
Jonas JB.
Department of Ophthalmology, Faculty of Clinical Medicine Mannheim, Ruprecht-Karls-University of Heidelberg, Germany.

Intravitreal triamcinolone acetonide (IVTA) has increasingly been applied as treatment for various intraocular neovascular and oedematous diseases. Comparing the various diseases with respect to effect and side-effects of the treatment, the best response in terms of gain in visual acuity (VA) has been achieved for intraretinal oedematous diseases such as diffuse diabetic macular oedema, branch retinal vein occlusion, central retinal vein occlusion and pseudophakic cystoid macular oedema. In eyes with various types of non-infectious uveitis, including acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease, VA increased and the degree of intraocular inflammation decreased. Some studies have suggested that intravitreal triamcinolone may be useful as angiostatic therapy in eyes with iris neovascularization and proliferative ischaemic retinopathies. Intravitreal triamcinolone may possibly be helpful as adjunct therapy for exudative age-related macular degeneration (AMD), particularly in combination with photodynamic therapy. In eyes with chronic, therapy-resistant ocular hypotony, intravitreal triamcinolone can induce an increase in intraocular pressure (IOP) and may stabilize the eye. The complications of intravitreal triamcinolone therapy include: secondary ocular hypertension in about 40% of the eyes injected; medically uncontrollable high IOP leading to antiglaucomatous surgery in about 1-2% of the eyes; posterior subcapsular cataract and nuclear cataract leading to cataract surgery in about 15-20% of elderly patients within 1 year of injection; postoperative infectious endophthalmitis occurring at a rate of about one per 1000; non-infectious endophthalmitis, perhaps due to a reaction to the solvent agent, and pseudo-endophthalmitis with triamcinolone acetonide crystals appearing in the anterior chamber. Intravitreal triamcinolone injection can be combined with other intraocular surgeries, including cataract surgery, particularly in eyes with iris neovascularization. Cataract surgery performed some months after the injection does not show a markedly elevated complication rate. The injection may be repeated if the resultant benefits decrease after the initial IVTA injection. In non-vitrectomized eyes, the duration of the effect and side-effects of a single intravitreal injection of triamcinolone is about 6-9 months for a dosage of about 20 mg, and about 2-4 months for a dosage of 4 mg. So far, it has remained unclear whether the solvent agent should be removed, and if so, how.

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JAMA. 2005 Dec 28;294(24):3101-7.
Dietary intake of antioxidants and risk of age-related macular degeneration.
van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, de Jong PT.
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands;

CONTEXT: Age-related macular degeneration (AMD) is the most prevalent cause of irreversible blindness in developed countries. Recently, high-dose supplementation with beta carotene, vitamins C and E, and zinc was shown to slow the progression of AMD. OBJECTIVE: To investigate whether regular dietary intake of antioxidants is associated with a lower risk of incident AMD. DESIGN: Dietary intake was assessed at baseline in the Rotterdam Study (1990-1993) using a semiquantitative food frequency questionnaire. Incident AMD until final follow-up in 2004 was determined by grading fundus color transparencies in a masked way according to the International Classification and Grading System. SETTING: Population-based cohort of all inhabitants aged 55 years or older in a middle-class suburb of Rotterdam, the Netherlands. PARTICIPANTS: Of 5836 persons at risk of AMD at baseline, 4765 had reliable dietary data and 4170 participated in the follow-up. MAIN OUTCOME MEASURE: Incident AMD, defined as soft distinct drusen with pigment alterations, indistinct or reticular drusen, geographic atrophy, or choroidal neovascularization. RESULTS: Incident AMD occurred in 560 participants after a mean follow-up of 8.0 years (range, 0.3-13.9 years). Dietary intake of both vitamin E and zinc was inversely associated with incident AMD. The hazard ratio (HR) per standard deviation increase of intake for vitamin E was 0.92 (95% confidence interval [CI], 0.84-1.00) and for zinc was 0.91 (95% CI, 0.83-0.98). An above-median intake of all 4 nutrients, beta carotene, vitamin C, vitamin E, and zinc, was associated with a 35% reduced risk (HR, 0.65; 95% CI, 0.46-0.92) of AMD. Exclusion of supplement users did not affect the results. CONCLUSION: In this study, a high dietary intake of beta carotene, vitamins C and E, and zinc was associated with a substantially reduced risk of AMD in elderly persons.

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Arch Ophthalmol. 2005 Dec;123(12):1644-50.
Treatment of retinal angiomatous proliferation in age-related macular degeneration: a series of 104 cases of retinal angiomatous proliferation.
Bottoni F, Massacesi A, Cigada M, Viola F, Musicco I, Staurenghi G.
Department of Ophthalmology, San Giuseppe Hospital, Milan, Italy. ferdinando.bottoni@fastwebnet.it

OBJECTIVE: To report the management of retinal angiomatous proliferation (RAP), a recently described intraretinal neovascular lesion occurring in age-related macular degeneration. METHODS: This was a retrospective review of consecutive patients with age-related macular degeneration who underwent treatment of RAP from January 1, 2000, through January 31, 2003. Inclusion criteria were age 55 years or older, signs of age-related macular degeneration, and diagnosis of RAP based on dynamic indocyanine green angiography. Baseline angiograms were reviewed and RAP was classified into the following 3 stages: stage 1, intraretinal neovascularization, early stage; stage 2, subretinal neovascularization, middle stage; and stage 3, choroidal neovascularization, late stage. Treatment and concomitant treatment results were assessed separately for each RAP stage. The clinical data were statistically analyzed (chi2 test and analysis of variance) for 2 main outcome measures--complete obliteration of the lesion and final visual acuity. RESULTS: Eighty-one patients (99 eyes) with 104 RAPs were identified. Forty-two lesions were at stage 1, 42 at stage 2, and 20 at stage 3. The following 5 treatments were performed: direct laser photocoagulation of the vascular lesion, laser photocoagulation of the feeder retinal arteriole, scatter "gridlike" laser photocoagulation, photodynamic therapy, and transpupillary thermotherapy. Complete obliteration of RAP was achieved in about 24 (57.1%) of the stage 1 lesions (direct laser photocoagulation of the vascular lesion, 73% success rate; photodynamic therapy, 45%), 11 (26.2%) of the stage 2 lesions (scatter gridlike laser photocoagulation, 38% success rate; direct laser photocoagulation of the vascular lesion, 17%), and only 3 (15.0%) of stage 3 lesions (P = .001). Predictive factors with a significant effect on final visual acuity were initial visual acuity (P = .003) and early lesion stage (P = .04). Best final visual acuity was 0.41 (mean, direct laser photocoagulation of the vascular lesion in stage 1) and 0.39 (mean, photodynamic therapy in stage 1), with a mean decrease of 2.5 and 3 lines from baseline, respectively. CONCLUSIONS: Treatment of RAP remains difficult. Early detection of the lesion and subsequent direct conventional laser photocoagulation seems to be associated with better anatomical and functional outcome. Once the vascular complex is well established, anatomical closure is rarely achieved. Further study is warranted to assess the long-term efficacy and the need for re-treatment.

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Internist (Berl). 2005 Dec 9; [Epub ahead of print]
[Modern pharmacotherapy of age-related macular degeneration.]
[Article in German]
Holz FG, Helb HM, Bindewald-Wittich A, Scholl HP.
Universitats-Augenklinik, Bonn.

Age-related macular degeneration (AMD) is now the most common cause for blind registration in all developed countries. Epidemiologic data indicate that there are 4.5 mio affected in Germany with constant increase in incidence and prevalence with subsequent considerable health economic implications. Late manifestations of the disease result in the inability to read and to perform daily tasks. Therefore, there is an urgent need for efficacious prophylactic and therapeutic measures to prevent irreversible loss of central vision. Based on a better understanding of the underlying molecular mechanisms new therapeutic approaches have been brought forward and expand previous approaches such as thermal laser surgery or photodynamic therapy. Repeated intravitreal injection of anti-VEGF (vascular endothelial growth factor) agents as well as cosrticosteroids have a beneficial effect on growth and permeability of neovascular membranes. The risk for progression from early to late stages of AMD can be reduced with certain antioxidative preparations (AREDS medication) in presence of defined funduscopic signs. Early diagnosis is key for all currently availabe interventions since a beneficial effect can only be achieved in early stages of the disease process.

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Retina. 2005 Dec;25(8):1065-84.
Neovascular age-related macular degeneration: natural history and treatment outcomes.
Pauleikhoff D.
>From the Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany.

BACKGROUND:: This review summarizes the data reported in peer-reviewed literature and presents current knowledge on differentiation, natural history, and therapeutic outcomes of neovascular age-related macular degeneration (AMD). METHODS:: The MEDLINE database was searched to review natural history of neovascular AMD and therapeutic effects of available treatments. RESULTS:: The search produced >7,000 articles. Research suggests that fluorescein angiographic characterization of location, composition, and size of neovascular lesions may be important in prognosis and should be considered for evaluation of treatment benefits in conjunction with evidence of recent disease progression for lesions not composed of predominantly classic choroidal neovascularization (CNV). Laser photocoagulation, photodynamic therapy with verteporfin, and administration of pegaptanib sodium reduce the risk of vision loss in selected cases of neovascular AMD, while submacular surgery can reduce the risk of severe visual acuity loss in selected cases of predominantly hemorrhagic CNV; further approaches are under investigation. CONCLUSION:: Visual prognosis of neovascular AMD is variable according to lesion location, composition, and size. Often, lesions have a poor prognosis, resulting in rapid and progressive loss of visual acuity and contrast sensitivity. Such losses have a profound effect on patients' quality of life and ability to perform everyday tasks. Reducing the risk of further loss of visual acuity and contrast sensitivity might enable patients with neovascular AMD to maintain better functional abilities.

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Graefes Arch Clin Exp Ophthalmol. 2005 Dec 6;:1-5 [Epub ahead of print]
A new treatment regimen in combined intravitreal injection of triamcinolone acetonide and photodynamic therapy.
Krebs I, Binder S, Stolba U.
Department of Ophthalmology, Rudolf Foundation Clinic, Juchgasse 25, 1030, Vienna, Austria.

BACKGROUND: Combined photodynamic therapy (PDT) and intravitreal injection of triamcinolone acetonide is a new option in the treatment of the neovascular form of age-related macular degeneration. With the aim of increasing safety and efficacy we examined whether it is possible to administer the intravitreal injection prior to PDT. METHODS: Patients with retinal angiomatous proliferation, who have an unfavourable prognosis when treated with PDT alone, were recruited to this study. Intravitreal injection of triamcinolone acetonide was applied 1 day before PDT. Distance acuity testing, retinal thickness measurement and fluorescein angiography were performed before treatment and 6 weeks and 3 months thereafter. RESULTS: Twenty-five patients were included: 18 were female, 7 male. Their mean age was 79 years. The distance acuity was 68 letters before treatment and at the follow-up examinations. The retinal thickness decreased significantly from mean 470.8 mum to 335.4 mum at week 6 and 360.8 mum at month 3. At month 3, 48% showed signs of activity in the fluorescein angiography needing retreatment. Visualisation of the fundus was not reduced by the triamcinolone crystals. DISCUSSION: PDT was possible without difficulty after intravitreal injection of triamcinolone acetonide. Stabilisation of the visual acuity was possible, although only eyes with retinal angiomatous proliferation were included.

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Can J Ophthalmol. 2005 Oct;40(5):573-84.
The use of subretinal triamcinolone acetonide in the management of neovascular age-related macular degeneration: a pilot study.
Kertes PJ, Coupland SG.
University of Ottawa Eye Institute, Ottawa, Ont. peter.kertes@sw.ca

BACKGROUND: We conducted this study to investigate the toxicity and efficacy of pars plana vitrectomy combined with a single dose of sub-retinally administered triamcinolone acetonide (4 mg) in patients with subfoveal choroidal neovascular membranes secondary to age-related macular degeneration (AMD). METHODS: The important eligibility criteria included eyes with recent and progressive onset of decreased vision (<or= 20/400) secondary to active subfoveal choroidal neovascularization secondary to AMD demonstrable on fluorescein angiography, in which subretinal hemorrhage accounted for < 25% of the area of the choroidal neovascular complex. Eligible patients were offered vitrectomy surgery combined with subretinal injection of 0.1 mL of triamcinolone acetonide (40 mg/mL) followed by air-fluid exchange. Two eyes of 2 patients were enrolled and followed for 28 and 35 months with regular and serial complete ophthalmologic examinations, fluorescein and indocyanine green videoangiography, and multifocal electro-retinography. The primary outcome measures were best-corrected visual acuity, changes in the fluorescein angiographic area and in the greatest linear dimension of leakage of the choroidal neovascular complex, and changes in amplitude and latency of the multifocal electroretinogram (ERG). RESULTS: Patient 1 sustained a limited subretinal hemorrhage intraoperatively that cleared spontaneously over approximately 3 months, as well as a rise in intraocular pressure that required the use of 2 topical medications to control. Patient 2 demonstrated progression of his nuclear sclerosis and posterior subcapsular lens changes over the 35 months of follow-up. Best-corrected visual acuity improved from 20/400 to 20/200 in patient 1 and improved from counting fingers to 20/320 in patient 2. For patient 1, the area of the neovascular complex increased from 4.5 mm2 at baseline to 7.2 mm2 at the 6-month follow-up; for patient 2, this increase was from 6.2 mm2 to 8.4 mm2. Over the same interval, the greatest linear dimension increased from 3.8 mm to 4.8 mm for patient 1 and from 4.1 mm to 4.8 mm for patient 2. With respect to the multifocal ERG, the response density increased in the first 4 months for patient 1 and declined marginally thereafter. For patient 2, the electro-retinal response density function was stabilized for a 5-month period but declined and stabilized thereafter. INTERPRETATION: Our results from this pilot study suggest that vitrectomy combined with subretinal injections of 0.1 mL of triamcinolone acetonide (40 mg/mL) and air-fluid exchange is easily accomplished. Although some complications were encountered, these did not appear to be prohibitive. A salutary effect was clearly demonstrated, not unlike the course seen with photodynamic therapy. Further study, perhaps in combination with other antiangiogenic agents, is warranted.

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J Chin Med Assoc. 2005 Sep;68(9):419-24.
Photodynamic therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration.
Shyong MP, Lee FL, Chen SJ, Tung TH, Tsai DC, Hsu WM.
Su-Ao Veterans Hospital, I-Lan, Taiwan.

BACKGROUND: To evaluate the safety and efficacy of verteporfin photodynamic therapy (PDT) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: We retrospectively reviewed the chart records and fluorescein angiography of patients with subfoveal CNV who were treated with verteporfin PDT between September 2001 and March 2003 and who completed at least 1 year of follow-up. The primary efficacy outcomes were the proportions of patients whose Snellen visual acuities had more than 1 line increase, no change or more than 1 line decrease 1 year after study entry compared with their baseline examinations. The secondary efficacy outcome was the changes in the logarithm of the minimum angle of resolution visual acuities at 1-year follow-up. Complications were monitored and tabulated. RESULTS: Forty-eight eyes of 48 patients with subfoveal CNV secondary to AMD were enrolled in this study. The mean follow-up was 12.56 +/- 1.37 months. At their last visit, 10.4% of eyes had more than 1 line improvement in Snellen visual acuity, 72.9% of eyes had no change, and 16.7% experienced more than 1 line of visual acuity loss (7 eyes lost < 3 lines of Snellen visual acuity, 1 eye lost between 3 and 6 lines). None experienced more than 6 lines of visual loss. There was no statistically significant difference between baseline and final visual acuity for eyes with predominantly classic CNV, minimally classic CNV and occult without classic CNV (Wilcoxon Signed Rank test, p = 0.59 ). There was a positive correlation between baseline visual acuity and final visual outcome (Kruskal-Wallis test, p = 0.002). No severe systemic and ocular adverse events were encountered. CONCLUSION: Of our patients with subfoveal CNV secondary to AMD, 83.3% could maintain or improve their visual acuity 1 year after verteporfin PDT. The risk of deterioration in visual acuity due to subfoveal CNV could be reduced by verteporfin PDT. Baseline visual acuity is significantly correlated with the final proportion of visual outcome.

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Retina. 2005 Sep;25(6):719-26.
Indocyanine green-mediated photothrombosis with and without intravitreal triamcinolone acetonide for subfoveal choroidal neovascularization in age-related macular degeneration: a pilot study.
Arevalo JF, Mendoza AJ, Fernandez CF.
Retina and Vitreous Service, Clinica Oftalmologica Centro Caracas, Venezuela. areval1@telcel.net.ve

PURPOSE: To determine the feasibility, safety, and clinical effect of treating patients with subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) with indocyanine green (ICG)-mediated photothrombosis (IMP) with and without intravitreal triamcinolone acetonide (TA). METHODS: Fifteen patients (19 eyes) participated in the study. Nine eyes of seven patients were treated with IMP immediately followed by an intravitreal injection of 4 mg of TA (Group A), and 10 eyes of 8 patients were treated with IMP only (Group B). Patients had a mean follow-up of 6.9 months (range: 3 to 12 months). Patients underwent single or two sessions of IMP. RESULTS: In Group A, visual acuity (VA) showed stability in 6 eyes (66.7%), improvement of VA in 2 eyes (22.2%), and worsening of VA in 1 eye (11.1%). Group B presented VA stability in 9 eyes (90%), and improvement in 1 eye (10%). In total, of the 15 patients (19 eyes) with IMP with or without intravitreal TA, 3 eyes (15.8%) showed improvement, 15 eyes (78.9%) stability, and 1 eye (5.3%) showed worsening of VA. A significant regression of the CNV and diminishing of subretinal fluid was demonstrated with fluorescein angiography and optical coherence tomography in both groups. No patient in Group A required retreatment. Four of 10 eyes (40%) in Group B required one retreatment during the study period. CONCLUSIONS: ICG-mediated photothrombosis with and without intravitreal TA may provide stability or improvement in visual acuity and fundus findings in subfoveal CNV in AMD. Further evaluation in a multicenter, randomized, placebo-controlled clinical trial with longer follow-up is needed to accurately assess the safety and efficacy of this new treatment modality.

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Br J Radiol. 2005 Sep;78(933):827-31.
A phase I trial of stereotactic external beam radiation for subfoveal choroidal neovascular membranes in age-related macular degeneration.
Barak A, Hauser D, Yipp P, Morse L, Leigh B, Kubo D, Goldberg Z, Earle J, Handa JT.
Department of Ophthalmology, UC Davis, Sacramento, CA, USA.

Effective treatment for neovascular age-related macular degeneration (AMD) is currently limited. Radiation therapy, a therapeutic approach with known antiangiogenic properties, has been investigated as a modality to prevent severe visual loss in AMD. Most of the studies using external beam radiation employed <25 Gy to the whole eye, which is below the dose of radiation that is toxic to the retina and optic nerve ( approximately 50 Gy and approximately 59 Gy, respectively). Stereotactic fractionated external beam radiation (St-EBR) is a method that allows radiation to be delivered to a small, defined area. We investigated the effects of St-EBR in incremental doses up to 40 Gy on neovascular AMD. Patients with clinical signs and fluorescein angiography demonstrating neovascular AMD, visual acuity (VA) better than 20/400 and ineligible for laser treatment (MPS criteria) or who refused to have laser photocoagulation were enrolled in the study. Each patient was treated with radiation at incremental dosages from 20 Gy to 40 Gy. After completion of the radiation course, all patients were followed-up at 3 and 7 weeks and 3, 6, and 12 months. Best-corrected VA (ETDRS), slit-lamp and fluorescein angiographic evaluations were performed at each visit. 94 eyes of 89 patients were treated from October 1997 to April 2000. The VA was 0.82+/-0.35 before treatment, 0.83+/-0.36 at 6 months, and 0.89+/-0.33 at 12 months. No patients suffered any significant acute side effects. No significant benefits in either VA or in membrane size were derived from increasing the doses of radiation. Our results are consistent with trends of a palliative benefit of radiotherapy in neovascular AMD and support further investigation of radiotherapy. Since there is no evidence that therapeutic effectiveness is dose dependent, our data provide no justification for potentially dangerous escalations in radiation dosage for treating neovascular AMD.

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Ugeskr Laeger. 2005 Aug 29;167(35):3301-5.
[Treatment of neovascular age-related macular degeneration with intravitreal vascular endothelial growth factor inhibitor--secondary publication]
[Article in Danish]
Larsen M, Sander B, Villumsen JE, Haamann PH, la Cour M, Lund-Andersen H; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group.
Amtssygehuset i Herlev, Ojenafdelingen, og Kobenhavns Universitet, Klinisk Institut for Oto-Rhino-Laryngologi, Oftalmologi og Dermato-Venerologi. mla@dadlnet.dk

Subfoveal neovascularization is the most frequent cause of severe visual loss in patients with age-related macular degeneration (AMD). Pharmacologic inhibition of vascular endothelial growth factor (VEGF) is a new principle of treatment of this condition. The effects of intravitreal pegaptanib administered every sixth week for 48 weeks in three different dosages were examined in a prospective, double-masked, randomised trial against subconjunctival sham injection with change in visual acuity as the outcome parameter in 1,186 patients with subfoveal neovacularization in AMD. 70% of the patients treated with pegaptanib avoided moderate visual loss, compared to only 55% of the control group (p < 0.001 for 0.3 mg pegaptanib versus the control group, p < 0.001 for 1.0 mg and p = 0,03 for 3.0 mg). The improved visual prognosis was detectable beginning six weeks after the first injection (p < 0.002). Adverse events included endophthalmitis (1.3% of patients), traumatic lens damage (0.7%), retinal detachment (0.6%) and severe visual loss in one patient (0.1%). Intravitreal pegaptanib improves the visual prognosis in neovascular AMD. The long-term effect and safety of the treatment are not known.

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Arch Ophthalmol. 2005 Aug;123(8):1042-50.
A randomized controlled trial to determine the effectiveness of prism spectacles for patients with age-related macular degeneration.
Smith HJ, Dickinson CM, Cacho I, Reeves BC, Harper RA.
Department of Optometry and Neuroscience, University of Manchester Institute of Science and Technology, Manchester, England. heatherj.smith@rjah.nhs.uk

OBJECTIVE: To determine the effectiveness of prism spectacles in people with age-related macular degeneration by relocating the retinal image. METHODS: We implemented a randomized, placebo-controlled, double-masked trial. Participants with age-related macular degeneration received a standard low-vision assessment and the prescription of conventional low-vision aids 6 weeks before the study intervention. Participants were randomized to receive 1 of the following, including the optimal refractive correction: (1) custom, incorporating bilateral prisms to match participants' preferred power and base direction; (2) standard, incorporating standard bilateral prisms (6 prism diopters [Delta] base up for logMAR [logarithm of the minimum angle of resolution] visual acuity (VA) of 0.48-1.00 and 10Delta base up for logMAR VA of 1.02-1.68); or (3) placebo, consisting of spectacles matched in weight and thickness to prism spectacles but without prism. MAIN OUTCOME MEASURES: Outcomes measured binocularly at baseline and 3-month follow-up included distance logMAR VA, reading speed, critical print size, visual functioning questionnaires, and observed visual task performance. Scores on the 25-item National Eye Institute Visual Functioning Questionnaire and the Melbourne Low-Vision ADL (Activities of Daily Living) Index were converted to linear estimates using Rasch analysis. The Manchester Low Vision Questionnaire was used to collect descriptive data. RESULTS: A total of 225 participants completed the trial (median age, 81 years). We found no significant effect of treatment group on any of the outcome measures, including VA, the primary outcome (adjusted for baseline) (P = .63). Participants' responses to the Manchester Low Vision Questionnaire suggested that the prism spectacles added to their problems. CONCLUSIONS: Prism spectacles are no more effective than conventional spectacles for people with age-related macular degeneration.

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Eye. 2005 Aug 5; [Epub ahead of print]
Low power vs standard power transpupillary thermotherapy in patients with age-related macular degeneration and subfoveal choroidal neovascularization ineligible for photodynamic therapy.
Hogan AC, Kilmartin DJ.
1Research Foundation, Royal Victoria Eye & Ear Hospital, Dublin, Ireland.

AimTo assess the effect of standard power vs low power transpupillary thermotherapy (TTT) in patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration ineligible for photodynamic therapy (PDT) by original treatment of age-related macular degeneration with photodynamic therapy (TAP) study group recommendations.MethodsRetrospective review of 79 patients with active predominantly occult subfoveal choroidal neovascularization or predominantly classic subfoveal choroidal neovascularization but Snellen visual acuity <20/200. All patients were treated with TTT administered via a Mainster wide field fundus contact lens with a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27) and 181 mW/mm in the low power group (n=52). The primary outcome was stabilization (<1 Snellen line change) or improvement (two or more Snellen lines) in visual acuity. Clinical and fluorescein angiographic resolution of overlying exudation was documented.ResultsAt 24 month follow-up, 17 patients (63%) in the standard power and 36 patients (69%) in the low power group achieved stable or improved vision. Improved vision (mean three lines) was observed in 22% of the standard power and 23% of the low power group. Overlying exudation was reduced clinically with minimal or no leakage on fluorescein angiogram in 85% of standard power and 90% of low power group. Subgroup analysis in the low power group demonstrated a visual benefit in patients with subfoveal lesions, which had any classic component.ConclusionsLow power TTT is as effective as standard power in stabilizing or improving vision and reducing overlying exudation in patients with active subfoveal choroidal neovascularization ineligible for PDT.Eye advance online publication, 5 August 2005; doi:10.1038/sj.eye.6702028.

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Drugs. 2005;65(11):1571-7; discussion 1578-9.
Pegaptanib: in exudative age-related macular degeneration.
Siddiqui MA, Keating GM.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Pegaptanib, an aptamer, is an antagonist of vascular endothelial growth factor that has shown efficacy in the treatment of patients with exudative age-related macular degeneration (AMD). In two randomised, double-masked trials in patients with exudative AMD (n=1208), the proportion of responders (those losing <15 letters of visual acuity) at 54 weeks was significantly higher in intravitreous pegaptanib 0.3 mg recipients than in those receiving sham injections (70% vs 55%; p<0.001). These trials were conducted concurrently and analysed as a single study; the treatments were given every 6 weeks for 48 weeks. The improvement in visual acuity with pegaptanib was maintained in a 1-year extension of these trials. Similar favourable results with pegaptanib 0.3 mg were seen in terms of the secondary efficacy endpoints (e.g. proportion of patients experiencing severe loss of visual acuity or legal blindness in the study eye). These vision-improving effects of pegaptanib were associated with beneficial angiographic effects. Intravitreous pegaptanib 0.3-3 mg was well tolerated with most ocular adverse events being mild-to-moderate and transient. Serious injection-related adverse events occurred in <or=1.3% of patients treated with pegaptanib. There were no systemic adverse events that could be definitely attributed to pegaptanib.

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Am J Ophthalmol. 2005 Jul 15; [Epub ahead of print]
New Intraocular Lens Technology.
Olson RJ, Werner L, Mamalis N, Cionni R.
Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah (R.J.O., L.W., N.M.).

PURPOSE: To review the current status of phakic intraocular lenses (IOL), intraocular treatment of presbyopia, and IOLs that filter some blue light. DESIGN: Review of current information on the subject from numerous sources. METHODS: Medline search and Internet search engines on the topics of phakic IOL, presbyopia or multifocal IOLS, and blue light and macular degeneration. RESULTS: An iris fixated phakic IOL is now approved in the United States (US). There are concerns for corneal endothelial stability and late dislocation. Other approaches include anterior chamber fixation with concerns of corneal endothelial stability and pupil elongation, and posterior chamber fixation with concerns of cataract formation, IOL dislocation, and pigment dispersion. Intraocular treatment of presbyopia includes monovision, multifocal, and accommodative IOLs. Which approach is superior today is still not clear. There are IOLs designed to block some blue light to potentially lessen the risk of age-related macular degeneration (ARMD). While there is presumptive evidence of this, no definitive study shows such a correlation. Color perception issues are unlikely to be a problem. While decreased scotopic vision has been proposed, there is no study that proves this is an issue of clinical significance. CONCLUSIONS: The IOL field is dynamic with many new choices. Phakic IOLs and treatment of presbyopia will be an increasingly important part of ophthalmology; however, there are important unresolved issues. With better evidence that blue light is an important variable in ARMD, such an approach could rapidly become the standard.

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Expert Opin Pharmacother. 2005 Jul;6(8):1421-3.
Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration.
Doggrell SA.
Auckland University of Technology-Akoranga Campus, School of Nursing Northcote, Auckland, New Zealand. s_doggrell@yahoo.com

Age-related macular degeneration is the leading cause of irreversible visual loss in the industrialised world. Angiogenesis underlies the neovascularisation, and vascular endothelial growth factor (VEGF) is an angiogenesis growth factor. In the VEGF Inhibition Study in Ocular Neovascularisation-1 (VISION-1) trial, pegaptanib (an aptamer inhibitor of VEGF) was tested in neovascular age-related macular degeneration. The 1186 patients received a sham injection or intravitreous injection of pegaptanib (0.3, 1.0 or 3.0 mg) every 6 weeks over a period of 48 weeks. The primary end point was the proportion of patients who lost < 15 letters of visual acuity between baseline and 54 weeks, and this occurred in 164/296 patients (55%) who received the sham injection. A higher percentage of patients maintained this visual acuity if they were treated with pegaptanib 0.3 mg (54/206 patients, 70%). There was no evidence that pegaptanib 1 or 3 mg was more effective than 0.3 mg. There was no excess of systemic adverse effects with pegaptanib, but ocular adverse effects occurred more commonly with pegaptanib than with sham injection; vitreous floaters (33 versus 8%), vitreous opacities (18 versus 10%) and anterior chamber inflammation (14 versus 6%). Although these results represent a new, beneficial and relatively safe approach to age-related macular degeneration, the progression was not halted or reversed, and further improvement to treatment for this condition should be sought.

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Graefes Arch Clin Exp Ophthalmol. 2005 Jul 12;:1-6 [Epub ahead of print]
Verteporfin photodynamic therapy for extrafoveal choroidal neovascularisation secondary to age-related macular degeneration.
Voelker M, Gelisken F, Ziemssen F, Wachtlin J, Grisanti S.
Department of Ophthalmology I, University of Tubingen, Schleichstrasse 12, 72076, Tubingen, Germany, Faik.Gelisken@med.uni-tuebingen.de.

PURPOSE: To report the results of verteporfin photodynamic therapy (PDT) of extrafoveal predominantly classic choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). METHODS: In this retrospective study 20 consecutive patients (20 eyes) undergoing verteporfin PDT for extrafoveal predominantly classic CNV in AMD were examined. Colour photography of the fundus, fluorescein angiography and complete ophthalmic examination, including visual acuity assessment with ETDRS charts, were performed before treatment and at 3-month intervals thereafter. The primary outcome criterion was the change in visual acuity. The secondary outcome criterion was the extension of the CNV beneath the centre of the fovea during the follow-up period. RESULTS: Mean follow-up time of the patients was 24.2 months (range 12 to 58 months). Visual acuity at baseline varied from 20/200 to 20/20 (mean 20/50+/-2.3 lines). Final visual acuity ranged from 20/1000 to 20/20 (mean 20/200+/-5.1 lines) (P<0.001). In 85% (17/20) of the eyes visual acuity worsened. Visual acuity improved in 15% (3/20) of the eyes. During the course of the follow-up period, subfoveal extension of the CNV was detected in 80% (16/20) of the eyes. CONCLUSION: In 85% of the eyes with extrafoveal predominantly classic CNV secondary to AMD, visual acuity worsened after verteporfin PDT in an average follow-up time of 24 months. Subfoveal CNV was found in 80% of the eyes during follow-up. Even though verteporfin PDT can preserve visual acuity in selected cases, deterioration was seen in the majority of the patients.

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Can J Ophthalmol. 2005 Jun;40(3):378-83.
Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration.
Maberley DA, Chew H, Ma P, Chang A, Hollands H, Maberley A.

Background: The purpose of this study was to compare photodynamic therapy (PDT) against subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Methods: Patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If they declined PDT, then TTT was offered. Results: We evaluated and followed 115 consecutive patients for an average of 1 year. The primary outcome measure was visual acuity, but the interventions were also compared on the basis of lesion size and angiographically determined lesion activity. Baseline comparisons between the 2 treatment groups showed significant differences in pretreatment visual acuity, lesion size, and lesion composition. Univariate analysis of outcomes demonstrated equivalence between the treatment groups in final lesion size, angiographic activity, and visual acuity. Multivariate analysis also demonstrated equivalence between the treatment groups in final visual acuity while controlling for age, pretreatment visual acuity, and lesion category. Predominantly classic lesions were associated with poorer visual outcomes. Interpretation: The PDT and TTT groups were equivalent in terms of all outcome parameters evaluated.

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Can J Ophthalmol. 2005 Jun;40(3):332-40.
Rheopheresis for age-related macular degeneration: clinical results and putative mechanism of action.
Pulido JS, Sanders D, Klingel R.

Background: Rheopheresis is being evaluated in a clinical trial. The rationale and available results are presented.Methods: We reviewed the literature about the pathophysiology of age-related macular degeneration (AMD) that might support the use of rheopheresis. In addition, we reviewed the previously published results of the use of rheopheresis for AMD.Results: There appears to be a diffusion barrier caused by accumulation of cross-linked proteins known as advanced macular oxidation products (AMOPS) in AMD. Rheopheresis allows removal of uncross-linked proteins and facilitates antioxidant entry into Bruch's membrane, preventing further accumulation of AMOPS. The Multicenter Investigation of Rheopheresis for AMD (MIRA-1), an ongoing double-masked randomized trial, should determine the efficacy of rheopheresis in preventing the progression of AMD. The interim results, from an analysis of visual acuity data for 43 patients, are encouraging, confirming the potential of rheopheresis as a therapeutic option for dry AMD. The benefit was evident immediately after treatment and remained essentially stable throughout the 12-month period of evaluation. Eyes with late-stage, high-risk, dry AMD appeared to be at significant risk for substantial vision loss over the 12 months if not treated. Subgroup analysis demonstrated that the timing of rheopheresis in the course of a patient's disease may have a pronounced effect on outcome.Interpretation: There appears to be a rationale for the use of rheopheresis in AMD. Further results of the clinical trial are awaited.

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Can J Ophthalmol. 2005 Jun;40(3):320-31.
Laser prophylaxis for age-related macular degeneration.
Hsu J, Maguire MG, Fine SL.

Background: Age-related macular degeneration (AMD) is the most common cause of severe and irreversible vision loss among people 50 years of age or older in many Western countries. Most of the available treatments for AMD are intended for the late stage, specifically for choroidal neovascularization (CNV). Effective preventive treatments could have an even greater impact on the vision of the millions of people at risk for vision loss from AMD. Drusen are typically the earliest lesions seen in patients with AMD and precede the development of CNV. In 1973, Gass noted the disappearance of drusen in eyes that received laser photocoagulation, which led to the hypothesis that laser-induced drusen reduction could alter the natural course of AMD.Methods: We reviewed relevant articles found through a search of MEDLINE through February 2005 by means of the following key words, alone or in combination: drusen, laser, photocoagulation, age-related macular degeneration, macula and choroidal neovascularization.Results: Reports ranging from individual cases and case series to randomized controlled pilot studies have described various laser treatment protocols and their effects on eyes with high-risk drusen but no neovascular changes. These reports provide evidence that laser photocoagulation can induce drusen reduction. Although some investigators have reported a corresponding improvement in visual function, others have found no change or even worsening. The results in several of the larger randomized controlled studies suggest that CNV may occur at an increased rate in laser-treated eyes with high-risk drusen in patients who have neovascular AMD in the other eye. The long-term effects of laser treatment in patients with high-risk drusen in both eyes and no neovascular changes have yet to be determined.Interpretation: The outcome of clinical trials such as the Prophylactic Treatment of Age-Related Macular Degeneration and the Complications of Age-Related Macular Degeneration Prevention Trial will help to determine the role of laser prophylaxis in patients with AMD.

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Prog Retin Eye Res. 2005 Jun 11; [Epub ahead of print]
Gene therapy in the cornea.
Mohan RR, Sharma A, Netto MV, Sinha S, Wilson SE.
The Cole Eye Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Mail Code i-31, Cleveland, OH 44195, USA.

Technological advances in the field of gene therapy has prompted more than three hundred phase I and phase II gene-based clinical trials for the treatment of cancer, AIDS, macular degeneration, cardiovascular, and other monogenic diseases. Besides treating diseases, gene transfer technology has been utilized for the development of preventive and therapeutic vaccines for malaria, tuberculosis, hepatitis A, B and C viruses, AIDS, and influenza. The potential therapeutic applications of gene transfer technology are enormous. The cornea is an excellent candidate for gene therapy because of its accessibility and immune-privileged nature. In the last two decades, various viral vectors, such as adeno, adeno-associated, retro, lenti, and herpes simplex, as well as non-viral methods, were examined for introducing DNA into corneal cells in vitro, in vivo and ex vivo. Most of these studies used fluorescent or non-fluorescent marker genes to track the level and duration of transgene expression in corneal cells. However, limited studies were directed to evaluate prospects of gene-based interventions for corneal diseases or disorders such as allograft rejection, laser-induced post-operative haze, herpes simplex keratitis, and wound healing in animal models. We will review the successes and obstacles impeding gene therapy approaches used for delivering genes into the cornea.

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Ophthalmologica. 2005 May-Jun;219(3):154-66.
Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.
Feher J, Kovacs B, Kovacs I, Schveoller M, Papale A, Balacco Gabrieli C.
Ophthalmic Neuroscience Program, Department of Ophthalmology, University of Rome 'La Sapienza', Rome, Italy. j.feher@libero.it

The aim of this randomized, double-blind, placebo-controlled clinical trial was to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus alterations in early age-related macular degeneration (AMD). One hundred and six patients with a clinical diagnosis of early AMD were randomized to the treated or control groups. The primary efficacy variable was the change in the visual field mean defect (VFMD) from baseline to 12 months of treatment, with secondary efficacy parameters: visual acuity (Snellen chart and ETDRS chart), foveal sensitivity as measured by perimetry, and fundus alterations as evaluated according to the criteria of the International Classification and Grading System for AMD. The mean change in all four parameters of visual functions showed significant improvement in the treated group by the end of the study period. In addition, in the treated group only 1 out of 48 cases (2%) while in the placebo group 9 out of 53 (17%) showed clinically significant (>2.0 dB) worsening in VFMD (p = 0.006, odds ratio: 10.93). Decrease in drusen-covered area of treated eyes was also statistically significant as compared to placebo when either the most affected eyes (p = 0.045) or the less affected eyes (p = 0.017) were considered. These findings strongly suggested that an appropriate combination of compounds which affect mitochondrial lipid metabolism, may improve and subsequently stabilize visual functions, and it may also improve fundus alterations in patients affected by early AMD.

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Expert Opin Investig Drugs. 2005 May;14(5):671-82.
Pegaptanib sodium for the treatment of neovascular age-related macular degeneration.
Moshfeghi AA, Puliafito CA.
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA.

This article reviews pegaptanib sodium, a compound developed by Eyetech Pharmaceuticals Inc. and Pfizer Inc., for the treatment of neovascular age-related macular degeneration (AMD). Traditional treatment approaches to neovascular AMD have included destructive therapies such as thermal laser photocoagulation and photodynamic therapy; the use of pegaptanib sodium heralds a new treatment approach that is a non-destructive therapy based on the inhibition of vascular endothelial growth factor activity in the eye. This diminishes the neovascular drive in the pathologically hyperpermeable state of the diseased eye. Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers. The chemistry, mechanism of action, pharmacokinetics and rationale for the clinical use of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.

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Curr Med Res Opin. 2005 May;21(5):705-14.
Verteporfin therapy in combination with triamcinolone: published studies investigating a potential synergistic effect.
Kaiser PK.
Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.

Evidence from randomized, placebo-controlled, double-masked studies has demonstrated that verteporfin (Visudyne) therapy is effective in reducing the risk of visual acuity loss in selected groups of patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). Pilot studies of intravitreal triamcinolone acetonide monotherapy revealed promising results in patients with CNV due to AMD, but the visual acuity outcomes in a randomized, controlled study were lower than anticipated. Recently, however, there has been growing interest in the adjunctive use of triamcinolone to improve visual acuity and reduce regrowth of CNV in patients receiving verteporfin therapy. This review article surveys the currently available evidence, based on a Medline search covering the years 1980-2005 and abstracts from recent scientific meetings. A number of small-scale, uncontrolled pilot studies have indicated that the combination of triamcinolone acetonide with verteporfin therapy may be beneficial. Evidence is now needed from randomized, controlled studies to determine whether the potential benefits of combination therapy outweigh the possible risks of increased intraocular pressure, endophthalmitis, and progression of cataract that have been observed in trials of triamcinolone monotherapy.

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MMW Fortschr Med. 2005 May 26;147(21):35-8.
[Age-related macular degeneration]
[Article in German]
Gandorfer A, Haritoglou C, Priglinger S.
Operative und konservative Retinologie, Intraokulare Chirurgie, Augenklinik der LMU, Munchen. arnd.gandorfer@med.uni-muenchen.de

In the western world, macular degeneration is the most common cause of severe loss of vision and blindness in persons older than 50. The underlying cause of the condition is a disturbance in the interaction between the retina and choroid of the macula. Apart from age itself, genetic disposition and smoking are confirmed risk factors. In the initial stages, the patient experiences merely a mild blurring of vision. The wet form, which is usually progressive, is experienced as an acute loss of vision or distortion of the objects viewed. Underlying this wet macular degeneration is of new vessel growth from the choroid, known as choroidal neovascularization, which as a result of exudation of fluid and bleeding into the macula, destroys central vision. Apart from the administration of vitamins to slow down progression, laser coagulation, photodynamic treatment or vitreoretinal surgery may be helpful in some cases. A specific causal therapy is, however, not available.

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Klin Monatsbl Augenheilkd. 2005 May;222(5):409-12.
[Cataract surgery in cases of age-related macular degeneration]
[Article in German]
Eter N, Holz FG.
Universitats-Augenklinik Bonn. eter@uni-bonn.de

It has been noted for some time that cataract surgery in the presence of retinal comorbidity such as diabetic macular edema may generate a progression of macular changes and result in a poor visual outcome. Recent findings show that adverse events may also occur in the presence of age-related macular degeneration (AMD). Therefore, when indicating cataract surgery the surgeon needs to consider the risks both for progression of early into late stages of AMD or further deterioration of late manifestations of AMD. Furthermore, in the presence of advanced atrophic or neovascular AMD the question arises whether or not the patient may benefit from cataract surgery in spite of an already existing central visual loss. Here we critically review results from recent studies.

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Am J Ophthalmol. 2005 Mar;139(3):405-20.
Age-related macular degeneration 1969-2004: A 35-year personal perspective.
Fine SL.
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.

PURPOSE: To provide a personal perspective concerning diagnosis, treatment, and evaluation of treatment for early and late stages of age-related macular degeneration (AMD) over a 35 year period, 1969-2004. DESIGN: Literature review, personal recollections, and conversations with investigators who participated in trials to evaluate treatments for AMD. METHODS: The author reviewed the literature pertaining to evaluation and treatment of patients with AMD and conversed with investigators who, over the past 35 years, designed, conducted and participated in trials to assess new and existing treatments for AMD. RESULTS: In 1969, patients with AMD constituted a small part of a typical ophthalmic practice. From 1969 to 2004, the prevalence of AMD has increased, and the methods of evaluation and treatment have changed dramatically. The emergence of fluorescein angiography and the development of laser photocoagulation and photodynamic therapy have substantially altered clinical practice. Several promising pharmacologic interventions are now being assessed in clinical trials. Nevertheless, AMD remains the leading cause of severe and irreversible vision loss in the United States because there are no highly effective treatments available for most patients. CONCLUSIONS: Because of an aging population and the lack of highly effective treatments, late AMD remains a major unsolved problem. However, there is extensive research being conducted with support from the National Eye Institute and from industry. There is also great interest in prevention trials. Accordingly, the author is optimistic that over the next 35 years there will be significant improvements in our ability to prevent severe vision loss from late AMD.

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Ophthalmology. 2005 Mar;112(3):488-94.
The use of cholesterol-lowering medications and age-related macular degeneration.
McGwin G Jr, Xie A, Owsley C.
Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama 35294-0009, USA. mcgwin@uab.edu

PURPOSE: To evaluate the association between cholesterol-lowering medications and age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: The Atherosclerosis Risk in Communities study is a prospective, population-based, cohort study conducted in 4 communities across the United States. A total of 15792 individuals aged 45 to 65 years were enrolled between 1987 and 1989; fundus photographs were added to the study protocol at the 6-year follow-up (1993-1995). Cases were subjects who were identified as having AMD after applying a standard definition to their fundus photographs; controls did not have AMD. METHODS: The use of cholesterol-lowering medications at any time during the study was determined and compared between cases and controls, adjusting for the potentially confounding effect of demographic, behavioral, and medical characteristics. MAIN OUTCOME MEASURES: Presence of AMD and the use of cholesterol-lowering medications. RESULTS: A total of 871 AMD cases and 11,717 controls were identified. Of the AMD cases, 11% made use of cholesterol-lowering medications, as compared with 12.3% of controls (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.71-1.11). Adjusting for the confounding influence of age, gender, and race revealed a statistically significant relationship between AMD and use of cholesterol-lowering medications (OR, 0.79; 95% CI, 0.63-0.99). CONCLUSIONS: The results of this study add to the growing body of evidence that cholesterol-lowering medications may reduce the risk of developing AMD. Additional research is needed to document the mechanism responsible for this association. A clinical trial of the impact of statins on AMD deserves consideration.

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Ophthalmology. 2005 Feb;112(2):301-4.
Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization.
Spaide RF, Sorenson J, Maranan L.
LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York, USA. rickspaide@yahoo.com

PURPOSE: To examine the 12-month results of a group of patients treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Noncomparative case series. PARTICIPANTS: Twenty-six eyes of 26 patients with CNV secondary to AMD. Thirteen with CNV, without restriction to type, were not treated with prior PDT (newly treated group). Thirteen patients with prior PDT therapy who experienced visual loss while being treated with PDT alone comprised the remainder (prior PDT group). METHODS: Patients with CNV were treated with PDT, immediately followed by an intravitreal injection of 4 mg of triamcinolone acetonide. Visual acuity was measured by Early Treatment Diabetic Retinopathy Study protocol refraction. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. MAIN OUTCOME MEASURES: Visual acuity and retreatment rate. RESULTS: In the newly treated group, the mean acuity change was an improvement of 2.5 lines (last observation carried forward [LOCF], +2.4 lines; P = 0.011, Wilcoxon signed ranks test, as compared with baseline acuity) for patients completing the 12-month follow-up. In the prior PDT group, the mean change was an improvement of +0.44 lines (LOCF, +0.31 lines; P = 0.53). Retreatment rates were 1.24 for the newly treated group and 1.2 for the prior PDT group over the first year. Ten patients (38.5%) developed an intraocular pressure (IOP) of >24 mmHg during follow-up, a threshold used to institute pressure reduction therapy. No patient developed endophthalmitis. CONCLUSION: Although the number of patients in this pilot study was limited, the improvement of acuity and the reduced treatment frequency in these patients suggest that combination therapy with PDT and intravitreal triamcinolone acetonide, particularly when used as first-line therapy, merits further investigation. Elevated IOP seems to be the most frequent early side effect of the treatment.

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Expert Opin Emerg Drugs. 2005 Feb;10(1):119-35.
Future pharmacological treatment options for nonexudative and exudative age-related macular degeneration.
Comer GM, Ciulla TA, Heier JS, Criswell MH.
Indiana University School of Medicine, Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the industrialised world. Within the past decade, researchers have introduced many promising prevention and treatment options in an attempt to minimise the central vision loss imparted from AMD. Based on large-scale, randomised, prospective, placebo-controlled trials, a specially formulated combination of the antioxidants vitamin C, vitamin E, beta-carotene, copper and zinc is the only proven means of AMD prophylaxis. Thermal laser photocoagulation and photodynamic therapy with verteporfin are the only standard treatment options. However, efficacy is limited and treatment is only applicable to a minority of AMD patients. Thus, alternative pharmacological interventions are in all phases of clinical development. Researchers are guardedly optimistic that these advances may change the entire approach to AMD management in the near future. This review article will detail the currently accepted treatment options, as well as describe several of the more promising investigational pharmacological approaches to AMD.

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Eur J Ophthalmol. 2005 Jan-Feb;15(1):74-80.
Clinical outcome and subjective quality of life after photodynamic therapy in patients with age-related macular degeneration.
Krummenauer F, Braun M, Dick HB.
Department of Medical Biometry, Epidemiology and Informatics, Universitat of Mainz, Mainz, Germany. Frank.Krummenauer@uniklinikum-dresden.de

PURPOSE: Whereas the efficacy of photodynamic therapy (PDT) in preventing the progression of age-related macular degeneration (ARMD) is established, its effect on quality of life is under discussion. METHODS: All patients who underwent PDT during 2000 and 2001 at the University Eye Hospital of Mainz were interviewed using a standardized 82-item questionnaire on quality of life and patient satisfaction in ophthalmologic patients. Information was assessed in terms of 82 questions; global scores ranging from 1.0 (optimum self-estimated quality of life) to 4.0 (worst) were derived. Cataract patients' scores were used to characterize the ARMD patients' subjective outcome; the latter were then related to clinical outcome parameters via logistic regressions. RESULTS: A total of 84 patients (50% female, median age 77 years) were interviewed, who underwent a median of three PDT interventions. During the period of PDT treatment, their median decrease in visual acuity was 3 lines from 0.125 to 0.063. Patients who reported a subjective increase in visual function during this period showed a median private flexibility score of 1.86; patients with the subjective impression of visual function decrease, a median score of 2.71; the median scores for mobility were 2.00 versus 3.00, for flexibility in reading 1.91 versus 3.64, for psychological stress 1.56 versus 2.25, and for communicational flexibility 1.72 versus 2.25. The difference in reading flexibility was statistically significant (p=0.001) after correction for clinical cofactors. CONCLUSIONS: The established clinical benefit of PDT treatment concerning its efficacy in ARMD progression prevention coincides with an at least slight subjective benefit in quality of life and patient satisfaction. However, the latter is associated with the patients' subjective impression of visual acuity progression rather than with clinically validated outcome after PDT treatment.

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Oftalmologia. 2004;48(4):5-12.
[The place of photodynamic therapy in the treatment of age-related macular degeneration]
[Article in Romanian]
Munteanu G.

Age-related macular degeneration (ARMD) is a multifactorial disease, with unknown etiology, which represents one of the main causes of legal cecity. At this moment, the only treatment for ARMD is symptomatic and concerns the distinction of the choroidal neovascularisation (CNV). There are many therapeutical procedures, and their classification is difficult. The dynamic phototherapy (PDT) with intravenous injection of verteporfirin (Visudyne), a recent therapeutic concept based on a photochemical reaction, represents the only standard procedure for destroying the macular CNVs. The paper presents new therapeutical procedures, discussing them in relation with PDT. Beside the PDT and its supporting methods, other competing techniques (transpupillary thermotherapy, surgical removal, antiangiogenesis and antioxidants) are presented.

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Curr Eye Res. 2004 Dec;29(6):387-401.
AMD and micronutrient antioxidants.
Hogg R, Chakravarthy U.
Ophthalmology & Vision Science, Institute of Clinical Science, The Royal Victoria Hospital, Belfast, Northern Ireland.

Age-related maculopathy (ARM) is a common clinical entity. The late-stage manifestations of ARM, which are known as age-related macular degeneration (AMD), have devastating consequences for vision. Various risk factors have been identified in the development of the condition, which are consistent with the premise that oxidative stress plays an important role in its pathogenesis. Thus, the possibility that antioxidant balance can be manipulated through diet or supplementation has created much interest. Associations between diet and nutrition and the clinical features of ARM have been described. Scrutiny of the literature shows consistency in the report of notable reductions in serum micronutrients in wet AMD, however, the evidence for causation is still circumstantial. In this comprehensive review of the clinical literature, we have assessed the evidence for a link between diet and nutrition as risk factors for the development of ARM and AMD. All published case control, population-based, and interventional studies on ARM were examined. Although initial support appeared to be moderate and somewhat contradictory, the evidence that lifetime oxidative stress plays an important role in the development of ARM is now compelling. The positive outcomes in the Age-Related Eye Diseases Study, a major controlled clinical trial, have given hope that modulation of the antioxidant balance through supplementation can help prevent progression of ARM to AMD.

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Med J Malaysia. 2004 Oct;59(4):562-8, quiz 569.
Age related visual impairment in the elderly.
Loh KY, Ogle J.
Department of Family Medicine, International Medical University Malaysia, Seremban, Negeri Sembilan, Malaysia.

Visual impairment among the elderly is a major health problem. With advancing age, the normal function of eye tissues decreases and there is an increased incidence of ocular pathology. Demographic studies have shown that age is the best predictor of blindness and visual impairment. The most common causes of age related visual impairment in the elderly are presbyopia, cataracts, age related macular degeneration, primary open angle glaucoma and diabetic retinopathy. Untreated visual impairment leads to physical handicap, increased incidence of fall, depression, social isolation and dependency. Active screening for visual loss in the elderly should be part of the health examination. The elderly should be encouraged to come for formal 1-2 yearly eye assessment for early detection of visual impairment and to treat all associated problems in order to prevent permanent visual loss.

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Nippon Yakurigaku Zasshi. 2004 Dec;124(6):435-44.
Preclinical and clinical profile of verteporfin, a potent photodynamic therapy drug for CNV secondary to AMD.
Arita J, Okuyama T.
Development Division, Novartis Pharma K.K.

Age-related macular degeneration (AMD) is the leading cause of blindness among people aged over 50 years in the western world. Verteporfin (Visudyne((R))) is the first light-activated drug indicated for the treatment of patients with AMD caused by subfoveal choroidal neovascularization (CNV). This form of AMD is characterized by the development of abnormal blood vessels on the back of the retina that leak and cause scarring, resulting in central vision loss. Following intravenous administration, verteporfin selectively accumulates within proliferating tissue, including neovasculature, probably via low density lipoprotein receptors. The verteporfin is then activated by shining a specific wavelength of light with a nonthermal laser on the affected area in the eye. This process, called photodynamic therapy (PDT), generates reactive free radicals and highly reactive singlet oxygen in the target cells in the eye, causing damage and occlusion of the CNV and resulting in closure of the abnormal vessels and cessation of leakage. In experimentally induced CNV in animal models and in randomized, controlled clinical trials of patients with CNV due to AMD, verteporfin PDT has been shown to selectively occlude abnormal vessels without significantly altering overlying photoreceptors. Verteporfin therapy for CNV in Japanese patients had a similar or better angiographic and vision effect as that observed in Caucasian patients, with the same safety profile.

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Br J Ophthalmol. 2004 Dec;88(12):1568-72.
Effect of niacin on the choroidal circulation of patients with age related macular degeneration.
Metelitsina TI, Grunwald JE, Dupont JC, Ying GS.
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA. juangrun@mail.med.upenn.edu.

AIM: To investigate the effects of niacin on choroidal blood flow in age related macular degeneration (AMD). METHODS: 12 AMD patients with bilateral drusen and visual acuity of 20/40 or better in the study eye received a single oral dose of niacin (six subjects received 500 mg and six received 250 mg) or matching placebo on two separate occasions. Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChB(Vel)), volume (ChB(Vol)), and flow (ChB(Flow)) in the foveola of the study eye at baseline, 30, and 90 minutes after dosing. RESULTS: In comparison with placebo, a statistically significant 24% increase in ChB(Vol) was observed 30 minutes after niacin administration (ANOVA, p = 0.01). In comparison with placebo, a significant decrease in ChB(Vel) of 23% was observed in the 500 mg group (p = 0.04) and no significant change in ChB(Vel) was seen in the 250 mg group at 30 minutes. No significant changes in ChB(Flow) were detected at 30 or 90 minutes. Also, there were no statistically significant changes in ChB(Vol) or ChB(Vel) at 90 minutes. CONCLUSION: In comparison with placebo, a significant 24% increase in ChB(Vol) was observed 30 minutes after niacin administration. Owing to simultaneous decrease in ChB(Vel), however, no significant change in ChB(Flow) was detected.

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Br J Ophthalmol. 2004 Dec;88(12):1557-62.
Factors influencing visual acuity after intravitreal triamcinolone acetonide as treatment of exudative age related macular degeneration.
Jonas JB, Kreissig I, Degenring RF.
Universitats-Augenklinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Jost.Jonas@ma.augen.uni-heidelberg.de.

AIM: To evaluate factors influencing change in visual acuity (VA) after intravitreal injection of triamcinolone acetonide as treatment of exudative age related macular degeneration (AMD). METHODS: This prospective, interventional, comparative non-randomised clinical case series study included 94 patients (99 eyes) showing progressive exudative AMD with occult (n = 61 eyes), minimally classic (n = 18), predominantly classic (n = 1), or totally classic (n = 8) subfoveal neovascularisation. Mean follow up was 8.5 (SD 4.7) months (median, 7.3 months; range 3.1-24.5 months). All patients received an intravitreal injection of 20-25 mg of triamcinolone acetonide. RESULTS: An increase in best VA of at least one line on the Snellen charts was found in 63 (63.1%) eyes. Correspondingly, mean VA increased significantly (p<0.001) from 0.17 (SD 0.13) to 0.22 (SD 0.17) after the injection. Postoperative increase in VA was significantly (p<0.001) and negatively correlated with preoperative VA (correlation coefficient, -0.49). Gain in visual acuity was significantly (p = 0.009) higher if preoperative visual acuity was less than 0.08 (gain: 3.2 (SD 2.9) Snellen lines) than if preoperative VA ranged between 0.08 and 0.20 (gain: 1.2 (SD 2.2) Snellen lines). Change in VA was significantly (p = 0.016) less if preoperative VA was higher than 0.20 (change: -0.8 (SD 3.4) Snellen lines). Maximal gain in VA was significantly (p = 0.035) larger in eyes with retinal pigment epithelium detachment than in eyes with minimally classic subfoveal neovascularisation. This was statistically independent of age (p = 0.99), refractive error (p = 0.88), sex (p = 0.92), and duration of follow up (p = 0.46). CONCLUSIONS: Gain in VA after intravitreal injection of 20-25 mg of triamcinolone acetonide is significantly and negatively correlated with preoperative VA. It is significantly larger in eyes with retinal pigment epithelium detachment than in eyes with minimally classic subfoveal neovascularisation.

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Am J Ophthalmol. 2004 Nov;138(5):818-28.
The age-related macular degeneration radiotherapy trial (AMDRT): one year results from a pilot study.
Marcus DM, Peskin E, Maguire M, Weissgold D, Alexander J, Fine S, Followill D; AMDRT Research Group.
University of Pennsylvania, Department of Ophthalmology, Philadelphia, Pennsylvania, USA.

PURPOSE: To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 x 4 Gy fractions among patients having age-related macular degeneration (AMD). DESIGN: A multicenter prospective randomized controlled pilot study. METHODS: Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N = 41]) or no radiotherapy (sham radiotherapy [N = 22] or observation [N = 25]). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or >/=50% of the lesion [N = 13]). The primary outcome measure was loss of >/=3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects. RESULTS: At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost >/=3 lines of visual acuity (P = .04; stratified chi(2) test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost >/=3 visual acuity lines (P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy. CONCLUSIONS: External beam radiation at 5 x 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.

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Clin Rehabil. 2004 Nov;18(7):828-32.
Prismatic correction in patients affected by age-related macular degeneration.
Parodi MB, Toto L, Mastropasqua L, Depollo M, Ravalico G.
Eye Clinic, University of Trieste, Italy. maubp@yahoo.it

OBJECTIVE: To evaluate by means of a controlled clinical trial the effectiveness and the tolerance of prismatic correction in improving visual function in patients affected by advanced bilateral age-related macular degeneration. SETTING: Department of Ophthalmology, Eye Clinic, University of Trieste. SUBJECTS AND INTERVENTIONS: Each patient underwent an ophthalmologic examination, complete with distance visual acuity measurement using the Standard Early Treatment Diabetic Retinopathy Study chart. Patients were then randomly assigned to the treatment or control group. The treatment group received spectacles lenses with a prismatic correction of low power (5-7 prismatic dioptres) in the better eye. MAIN MEASURES: Visual acuity was measured at baseline and 1, 90, 180 and 360 days after prescription in both groups. RESULTS: The treatment group consisted of 14 patients, while the control group was of 14 patients. The prismatic correction was well tolerated in 85.7% of cases. Visual acuity in the treatment group improved mostly at three-month follow-up, with a slight further improvement at the six- and 12-month follow-ups, showing a statistically significant difference in comparison with the control group. No visual acuity improvement was registered in the control group. CONCLUSION: Monolateral prismatic correction may be considered a viable means to improve visual function in patients affected by bilateral age-related macular degeneration at an advanced stage.

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Ophthalmology. 2004 Nov;111(11):1993-2006.
Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13.
Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, MacCumber MW, Marsh MJ, Redford M, Sternberg P Jr, Thomas MA, Williams GA; Submacular Surgery Trials (SST) Research Group.
SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. nmboffice@jhmi.edu

PURPOSE: To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. DESIGN: Randomized clinical trial (SST Group B Trial). PARTICIPANTS: Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. INTERVENTION: Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. MAIN OUTCOME MEASURE: A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. RESULTS: Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). CONCLUSIONS: Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the primary outcome of interest) and was associated with a high risk of rhegmatogenous RD, but did reduce the risk of severe VA loss in comparison with observation. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

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Ophthalmology. 2004 Nov;111(11):1967-80.
Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings: SST report no. 11.
Hawkins BS, Bressler NM, Miskala PH, Bressler SB, Holekamp NM, Marsh MJ, Redford M, Schwartz SD, Sternberg P Jr, Thomas MA, Wilson DJ; Submacular Surgery Trials (SST) Research Group.
SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. bhawkins@jhmi.edu

PURPOSE: To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). DESIGN: Randomized clinical trial. PARTICIPANTS: Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm2]). METHODS: Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. MAIN OUTCOME MEASURE: A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. RESULTS: Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. CONCLUSIONS: Submacular surgery, as performed in this clinical trial, did not improve or preserve VA for 24 months in more eyes than observation and is not recommended for patients with similar lesions. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

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Invest Ophthalmol Vis Sci. 2004 Nov;45(11):4151-60.
Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial.
Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A, Kellner L, Stanzel BV, Jahn C, Feichtinger H.
Department of Ophthalmology, Rudolf Foundation Clinic, Vienna, Austria. susanne.binder@wienkav.at

PURPOSE: To present the outcome of a consecutive series of patients who had foveal choroidal neovascularization (fCNV) in age-related macular degeneration (AMD) and were treated with subretinal surgery combined with simultaneous transplantation of autologous retinal pigment epithelial (RPE) cells. METHODS: Patients with fCNV who were not eligible for laser or photodynamic therapy were included in the study. They underwent subretinal membrane excision with simultaneous transplantation of autologous RPE cells. Eyes with membrane excision alone served as the control. Tests included best corrected visual acuity for far and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger charts, multifocal (mf)ERG, central visual field analysis, optical coherence tomography (OCT), and angiography, before surgery, and 1 month and 3 months after treatment, and at 3-month intervals thereafter. RESULTS: The results of final examinations of 53 eyes are presented. In 39 eyes, RPE transplantation was performed (group 1); 14 eyes had membrane excision alone (group 2). In group 1, visual acuity improved significantly, two or more lines in 21 (53.8%) patients; remained stable in 12 patients (30.8%); and decreased two or more lines in 6 patients (15.4%; P=0.0062). In group 2, the corresponding values were 21.1%, 57.8%, and 21.1% (P=0.5377 NS). Statistical analysis of results in the two groups showed a trend in favor of group 1 (P=0.9714). The difference in reading acuity was significant between the two groups (mean change in group 1: 1.85 +/- 0.42 vs. 0.43 +/- 0.47 in group 2; P=0.0001). mfERG response density changes were significantly different between groups 1 and 2 (P=0.0094). No significant decreases in central visual field defects were detected. OCT showed the postoperative median retinal thickness in the lesion area in group 1 to be higher (242.31 +/- 12.30 microm) than in group 2 (202.07 +/- 10.68 microm), showing a trend (P=0.0682). CONCLUSIONS: Patients undergoing fCNV removal with autologous transplantation of RPE reached significantly better reading acuity and higher mfERG-response density than control subjects. The results provide evidence that autologous transplantation of RPE is a beneficial supplement to membrane excision alone in patients with fCNV in AMD and may be regarded as a reasonable treatment option.

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Cochrane Database Syst Rev. 2004 Oct 18;4:CD004004.
Radiotherapy for neovascular age-related macular degeneration.
Sivagnanavel V, Evans J, Ockrim Z, Chong V.

BACKGROUND: Radiotherapy has been proposed as a treatment to prevent new vessel growth in people with neovascular age-related macular degeneration (AMD). OBJECTIVES: The aim of this review was to examine the effects of radiotherapy on neovascular AMD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library Issue 2, 2004, MEDLINE (1966 to May 2004), EMBASE (1980 to June 2004) and LILACS (Latin American and Caribbean Health Sciences Literature Database) (May 2004). We also wrote to investigators of trials included in the review to ask if they were aware of any other studies. SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with subfoveal choroidal neovascularisation secondary to AMD. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data. Relative risks were combined using a random effects model. The percentage of the variability in effect estimates that was due to heterogeneity, rather than sampling error, was estimated using I(2). MAIN RESULTS: Eleven trials randomising a total of 1078 people were included in this review. All trials used a similar method of delivering the radiotherapy treatment (external beam). Dosage ranged from 7.5 to 24 Gy. Most trials found effects (not always significant) that favoured treatment. However, there was considerable inconsistency in the results between trials (I(2 )> 50%). As only 11 trials were included in the review and only some of these trials provided data for each outcome our ability to determine the causes of the heterogeneity between trials was limited. Subgroup analyses did not reveal any statistically significant interactions although with small numbers of trials in each subgroup (range two to four) this was not surprising. There was some indication that trials with no sham irradiation reported a greater effect of treatment as did trials with a greater percentage of participants with classic choroidal neovascularisation. REVIEWERS' CONCLUSIONS: This review currently does not provide evidence that external beam radiotherapy is an effective treatment for neovascular AMD. If further trials are to be considered to evaluate radiotherapy in AMD then adequate masking of the control group must be considered. Given the recent evidence that most lesions are amenable to treatment with photodynamic therapy if identified at a small lesion size, trials evaluating radiotherapy against photodynamic therapy are warranted.

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Br J Ophthalmol. 2004 Oct;88(10):1270-3.
A prospective study of visual function and quality of life following PDT in patients with wet age related macular degeneration.
Armbrecht AM, Aspinall PA, Dhillon B.
Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh EH3 9HA, UK. amarmbrecht@yahoo.com

AIMS: (1) A prospective study to assess visual function measures and quality of life (QoL) in patients with wet age related macular degeneration (AMD) treated with photodynamic therapy (PDT). (2) To assess if PDT prevents severe visual loss (loss of six or more lines of distance visual acuity) in the treated eye. METHODS: 48 of 51 recruited patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary AMD who were treated with PDT were followed up for 1 year. Assessment included distance and near visual acuity, contrast sensitivity, vision related quality of life and fluorescein angiography. Photodynamic therapy using Visudyne was carried out according to standard protocol. Patients were followed up every 3 months and treatment repeated if there was significant leakage from CNV. RESULTS: At the 12 month follow up, 71% (n = 34) of the patients lost less than three lines of best corrected distance visual acuity. Although there were significant decreases in some of the QoL items tested, patients were significantly less anxious and more independent outdoors at the 12 month follow up. CONCLUSION: This study is in keeping with published literature with PDT preventing severe visual loss in two thirds of treated patients with predominantly classic CNV.

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Ophthalmologe. 2004 Aug 6 [Epub ahead of print]
[Transplantation of iris pigment epithelium]
[Article in German]
Thumann G, Kirchhof B.
Universitatsklinikum, Koln.

Transplantation of iris pigment epithelial (IPE) cells to the subretinal space has been attempted as a therapeutic modality for the treatment of age-related macular degeneration (AMD). IPE cells are used because autologous cells are readily available and because IPE and RPE cells share a common embryonic origin, possess the capacity of transdifferentiation into other ocular cells, and share common morphological and functional characteristics. Once the technique of IPE cell transplantation was established in an animal mode, several clinical studies analyzed the behavior of IPE cell suspensions transplanted to the subretinal space of patients with AMD following surgical membrane extraction. In our experience, as well as that of other investigators, transplantation of IPE cells to the subretinal space of AMD patients prevents the recurrence of the subretinal neovascularization and stabilizes but does not improve visual acuity. Since IPE cells transplanted as a cell suspension do not appear to form a cell monolayer in the subretinal space, the transplantation of preformed IPE or RPE cell monolayers is being investigated as the development of an functional cell monolayer is mandatory if functional success, i.e., recovery of vision in AMD patients, is the ultimate goal of IPE cell transplantation.

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Retina. 2004 Aug;24(4):512-20.
Verteporfin therapy in age-related macular degeneration (VAM): an open-label multicenter photodynamic therapy study of 4,435 patients.
Bessler NM; Vam Study Writing Committee.
Baltimore, MD 21205, USA. nmboffice@jhmi.edu

PURPOSE: To provide broad clinical experience and to gather safety data on photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel, Switzerland), also termed verteporfin therapy, in patients with predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The Verteporfin in Age-related Macular Degeneration (VAM) Study was designed to provide expanded access to verteporfin therapy after beneficial results for these cases were reported but before regulatory approval in North America. METHODS: This open-label multicenter study from September 1999 through June 2000 enrolled among 222 centers patients 50 years or older in the United States, or 40 years or older in Canada, with age-related macular degeneration and subfoveal CNV with a lesion composition that was predominantly classic CNV on fluorescein angiography. Corrected visual acuity with habitual eyewear in the office setting was 20/40 to 20/200, inclusive. All patients received verteporfin therapy and returned for follow-up every 3 months. At those follow-up examinations, additional courses of treatment were recommended if any fluorescein leakage from CNV was identified. Safety information was collected from patient self-reporting, questioning (in person and by telephone), and physician evaluation. Safety was assessed by evaluating the effect of treatment on corrected distance visual acuity and by evaluating adverse events. RESULTS: A total of 4,435 patients were enrolled of whom 4,051 (91%) completed the study after receiving 6,701 treatments. Most patients received only one treatment in VAM before regulatory approval of verteporfin in the United States and Canada. Three hundred patients (6.8%) experienced an adverse event considered by the treating ophthalmologist to be associated with treatment, including 115 (2.6%) with abnormal or decreased vision, of whom 25 (0.6%) experienced acute severe visual acuity decrease, and 14 (0.3%) with transient infusion-related back pain. Patients were advised to avoid exposure to direct sunlight for 24 hours; however, after verteporfin administration only 2 (0.05%) reported a photosensitivity reaction. An additional course of verteporfin therapy was administered to 1,739 of 2,314 patients (75.2%) who had a month 3 examination that was not their close-out visit and 177 of 266 (66.5%) who had a month 6 examination that was not their close-out visit. CONCLUSIONS: Verteporfin therapy exhibited no additional or new safety concerns. The therapy associated with a low incidence of adverse events when expanded access was provided in a large, open-label, multicenter study, including a low incidence (0.05%) of reported photosensitivity reactions despite a short photosensitivity protection period (24 hours) following verteporfin administration.

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J Fr Ophtalmol. 2004 Jun;27(6 Pt 1):589-96.
[Prismatic treatment in low-vision rehabilitation of patients with age-related macular degeneration]
[Article in French]
Vettard S, Dubois E, Quaranta M, Mauget-Faysse M.
Centre Ophtalmologique d'Imagerie et de Laser, 12-14, rue Rabelais, 69003 Lyon. centrerabelais@wanadoo.fr

PURPOSE: To evaluate visual improvement in an age-related macular degeneration (ARMD) population with bilateral central scotomas, after a 3- to 6-month prismatic treatment. PATIENTS AND METHODS: Prisms prescribed for both eyes were oriented according to eccentric fixation. Criteria were visual acuity (VA), reading ability, contrast sensitivity subjective visual comfort, prism wearing frequency and autonomy level. RESULTS: Thirty-one patients (23 women, 8 men) 65-95 years old (mean, 78 years) were selected. Mean long distance VA remained stable (0.249 at inclusion and 0.261 after prismatic treatment); long distance VA was unchanged for 51.6% of patients, improved by at least one line for 35.5% and decreased for 12.9%. Reading ability was slightly improved (average of 1 line), as was short distance VA (P14 at inclusion, P12 after prismatic treatment); reading ability was unchanged for 45.2% of patients, improved by at least one line for 38.7%, and decreased for 16.1%. Contrast sensitivity was improved for all levels: to 98% of contrasts (mean at inclusion 0.248 and 0.280 after prismatic treatment), to 50% of contrasts (0.214 at inclusion and 0.238 after prismatic treatment) and to 25% of contrasts (0.157 at inclusion and 0.185 after prismatic treatment). Visual comfort improved immediately after prismatic treatment for 90.3% of patients; 80.6% of patients wore their prismatic correction regularly. DISCUSSION AND CONCLUSION: Prismatic treatment in this population mainly improves contrast sensitivity and visual comfort. It provides patients with better initiation and stabilization of their eccentric viewing. Most of the time, prismatic treatment must be associated with low-vision rehabilitation.

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Eye. 2004 Jun 25 [Epub ahead of print]
Exudative age-related macular degeneration treated by intravitreal triamcinolone acetonide. A prospective comparative nonrandomized study.
Jonas JB, Degenring RF, Kreissig I, Friedemann T, Akkoyun I.
1Department of Ophthalmology, Faculty of Clinical Medicine, Mannheim of the University, Heidelberg, Germany.

PURPOSE: To report on visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide as treatment of progressive exudative age-related macular degeneration. METHODS: The prospective comparative nonrandomized clinical interventional study included 187 consecutive patients with progressive exudative age-related macular degeneration, divided into a study group of 115 patients receiving an intravitreal injection of 25 mg triamcinolone acetonide, and a control group of 72 patients without treatment. The mean follow-up was 6.0+/-4.2 months. RESULTS: Visual acuity increased significantly (P=0.03) in the study group, and decreased significantly (P=0.01) in the control group, at 1 month and 3 months after start of the study. Between the study group and control group, the differences in change of visual acuity were significant (P=0.001). In the study group, the number of patients with an increase in visual acuity of 2 or more Snellen lines was significantly (P=0.001) larger than in the control group. Correspondingly, the number of patients with a decrease of 2 or more Snellen lines was significantly (P=0.007) smaller in the study group. In all, 43 (37.4%) patients of the study group experienced an increase in best visual acuity by 2 or more Snellen lines. CONCLUSIONS: Visual acuity increased in patients with exudative age-related macular degeneration at 1 month and 3 months after an intravitreal injection of 25 mg triamcinolone acetonide.Eye advance online publication, 25 June 2004; doi:10.1038/sj.eye.6701438

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Arch Ophthalmol. 2004 Mar;122(3):336-40.
Safety of an intravitreal injection of triamcinolone: results from a randomized clinical trial.
Gillies MC, Simpson JM, Billson FA, Luo W, Penfold P, Chua W, Mitchell P, Zhu M, Hunyor AB.
Save Sight and Eye Health Institute, Department of Clinical Ophthalmology, School of Public Health, and Sydney Eye Hospital, University of Sydney, Sydney, New South Wales, Australia.

OBJECTIVE: To determine the safety of a single intravitreal injection of triamcinolone acetonide (4 mg) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration. METHODS: A double-masked, placebo-controlled, randomized clinical trial was conducted at a public tertiary referral eye hospital. Patients participating had age-related macular degeneration with evidence of choroidal neovascularization, any part of which was classic; age older than 59 years; and best-corrected visual acuity of 20/200 or better. Eyes were assigned to active study treatment or to placebo. Intraocular pressure and cataract grading were performed every 6 months for 3 years. Adverse events, from mild to vision-threatening or life-threatening, were recorded as procedure-related or corticosteroid-related. RESULTS: Seventy-five eyes were assigned to study treatment and 76 eyes to placebo. There were no moderate or severe adverse events related to the surgical procedure in either group. Triamcinolone-treated eyes had a significantly increased risk of developing mild or moderate elevation of the intraocular pressure. Topical glaucoma medication reduced intraocular pressure to acceptable levels in all patients. There was significant progression of cataract in the triamcinolone-treated eyes. CONCLUSION: Despite a significant adverse event profile, intravitreal triamcinolone is generally well tolerated by the human eye as long as patients are carefully followed up by their surgeon and treated appropriately, when necessary.

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Drugs Aging. 2004;21(3):203-9.
Spotlight on verteporfin in subfoveal choroidal neovascularisation.
Keam SJ, Scott LJ, Curran MP.
Adis International Limited, Auckland, New Zealand.

Verteporfin (Visudyne((R))) therapy (photodynamic therapy with intravenous liposomal verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS).In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS.Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. Conclusion: Photodynamic therapy with verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.

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Clin Experiment Ophthalmol 2003 Apr;31(2):103-9
Limited macular translocation for subfoveal choroidal neovascularization in age-related
macular degeneration.
Chang AA, Tan W, Beaumont PE, Zeldovich A.
Sydney Retina, and Vitreoretinal Unit, Sydney Eye Hospital, Sydney, New South Wales, Australia.

Purpose: To examine the safety and efficacy of limited macular translocation followed by laser photocoagulation in the management of subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Methods: A prospective study was conducted on eight consecutive patients undergoing limited macular translocation followed by laser photocoagulation for the treatment of subfoveal classic CNV form of AMD. Patients were followed up for a minimum of 12 months. The magnitude of foveal translocation, visual outcomes and complications were assessed. Results: In all cases the fovea was successfully translocated inferiorly, with a median displacement of 1.1 mm. Thermal laser photocoagulation was subsequently performed in all cases. Visual acuity improved in five eyes, remained unchanged in two eyes and worsened in one eye. The mean improvement in visual acuity was by 0.19 logMAR. At 12 months, six of the eight patients (75%) achieved Snellen visual acuity of at least 6/15, with four patients (50%) achieving Snellen visual acuity of 6/9. Conclusion: In this small case series, limited macular translocation was found to be an effective and reproducible means of treating small well-defined subfoveal CNV.

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Retina 2003 Feb;23(1):14-23
Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD): interim (month 6) analysis of clinical safety and efficacy.
D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger S, Luna S, Robertson SM, Russell S, Singerman L, Slakter JS, Sullivan EK, Yannuzzi L, Zilliox P; The Anecortave Acetate Clinical Study Group.

PURPOSE: To evaluate clinical safety and efficacy of the angiostatic agent anecortave acetate for treatment of subfoveal choroidal neovascularization secondary to AMD. METHODS: 128 patients were randomized to placebo treatment or one of three anecortave acetate doses. Study medication was administered as a posterior juxtascleral injection onto the posterior scleral surface. Best-corrected logMAR vision was obtained at baseline and follow-up visits. Fluorescein angiograms were evaluated for eligibility before enrollment and posttreatment. RESULTS: Six months after a single treatment, visual acuity (mean change from baseline logMAR values) was significantly better (P = 0.003) after anecortave acetate 15 mg than placebo. More patients treated with anecortave acetate 15 mg than placebo maintained vision (88% versus 70%, P = 0.080), especially those with predominantly classic lesions (92% versus 65%, P = 0.021). Anecortave acetate 15 mg inhibited lesion growth significantly better than placebo (P = 0.001). Trends favoring the other doses over placebo were observed for vision preservation and lesion inhibition, but statistical significance was not achieved. The Independent Safety Committee overseeing this study identified no clinically relevant treatment-related changes. CONCLUSION: Anecortave acetate 15 mg is safe and effective for preserving or improving vision and for inhibiting lesion growth in patients with subfoveal AMD.

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Br J Ophthalmol 2003 Apr;87(4):462-8
Intravitreal triamcinolone acetonide for exudative age related macular degeneration.
Jonas JB, Kreissig I, Hugger P, Sauder G, Panda-Jonas S, Degenring R.
Department of Ophthalmology and Eye Hospital, Faculty for Clinical Medicine Mannheim, Ruprecht-Karls-University Heidelberg, Germany.

Aim: To evaluate the effect of intravitreal triamcinolone acetonide on the visual acuity of patients with exudative age related macular degeneration, to assess the duration of a possible effect, and to evaluate clinical side effects of the treatment. METHODS: The study included 67 patients (71 eyes) who presented with exudative age related macular degeneration of predominantly or total occult type (n = 68) or classic type (n = 3), and who received once, or repeatedly, an intravitreal injection of 25 mg of crystalline triamcinolone acetonide. Mean follow up time was 7.46 (SD 3.54) months (range 3.1-19.57 months). RESULTS: Visual acuity increased significantly (p <0.001) from 0.16 (0.11) to a mean maximum of 0.23 (0.17). Postoperative visual acuity was highest 1-3 months after the injection. 47 (66.2%) eyes gained in maximal visual acuity and 11 (15.5%) eyes lost in visual acuity. Intraocular pressure increased significantly (p <0.001) from 15.1 (3.1) mm Hg at baseline to a maximal value of 23.0 (8.25) mm Hg. At the end of follow up, intraocular pressure again decreased significantly (p<0.001) to 16.8 (4.9) mm Hg. No cases of postoperative infectious endophthalmitis, rhegmatogenous retinal detachment, or proliferative vitreoretinopathy occurred. Owing to a decrease in visual acuity after an initial increase, six patients received a second intravitreal triamcinolone acetonide injection after which visual acuity increased again in three eyes. CONCLUSIONS: Intravitreal injection of 25 mg of crystalline triamcinolone acetonide merits further study for the treatment of exudative age related macular degeneration.

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Eye 2003 Mar;17(2):207-15
Beta irradiation: new uses for an old treatment: a review.
Kirwan JF, Constable PH, Murdoch IE, Khaw PT.

Beta radiation has a long history as a treatment modality in ophthalmology. It is a convenient and practical method of applying radiation and has the advantage of minimal tissue penetration. There has been a recent resurgence in the use of beta radiation in other areas in medicine, such as the prevention of restenosis after coronary artery stenting. Beta radiation has been shown in vitro and in vivo to inhibit proliferation of human Tenon's fibroblasts, which enter a period of growth arrest but do not die. Effects on the cell cycle controller p53 have been shown to be important in this process.In ophthalmology, beta radiation has been used widely for the treatment of pterygium and is under evaluation for treatment of age-related macular degeneration and for controlling wound healing after glaucoma drainage surgery. In this latter role, beta radiation may be particularly appropriate for use in developing countries to improve the results of trabeculectomy while potentially avoiding some of the side effects of other antimetabolites.

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Invest Ophthalmol Vis Sci 2003 Apr;44(4):1740-6
Estrogens Reduce the Expression of YKL-40 in the Retina: Implications for Eye and Joint Diseases.
Rakic JM, Lambert V, Deprez M, Foidart JM, Noel A, Munaut C.
Department of Ophthalmology, University Hospital, Sart-Tilman, Liege, Belgium. Tumor and Development Biology and. Neuropathology, University of Liege, Liege, Belgium.

PURPOSE. To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially expressed genes that could be relevant to the natural history of human age-related macular degeneration (AMD). METHODS. Chorioretinal tissues from two groups of 25 treated and untreated OVX mice were analyzed by using cDNA array technology. The expression level of selected genes was confirmed in triplicate by RT-PCR and related to the estrogenic status of the animals. Expression of the YKL-40 gene was further investigated in intact or diseased human retinas and in a murine model of experimental choroidal neovascularization (CNV), using laser pressure catapulting. RESULTS. Of the approximately 10,000 genes screened, only YKL-40 expression was significantly downregulated by 17-beta-estradiol. YKL-40 was expressed in intact human neural retina and in the RPE. The expression of YKL-40 was upregulated in experimental CNV and in neovascular membranes extracted from patients affected by the exudative form of AMD. CONCLUSIONS. These observations indicate that YKL-40 expression in the retina is modulated by serum levels of estradiol. This protein could be relevant to the development of AMD and is also a new mediator to take into account when evaluating the broad consequences of hormonal replacement therapy.

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Presse Med 2002 Aug 24;31(27):1282-7
[Age-related macular degeneration]
[Article in French]
Soubrane G, Haddad WM, Coscas G.
Clinique ophtalmologique universitaire de Creteil, Universite Paris XII, Creteil. gisele.soubrane@chicreteil.fr

EPIDEMIOLOGICAL AND PATHOGENIC DATA: Age-related macular degeneration (ARMD) is the first cause of blindness in industrialized countries in patients over the age of 55. Its prevalence increases with age, affecting up to 25% of the population aged over 75. The pathogenesis of this disease is not well known. Not only aging, but also other varying degrees of genetic and environmental factors are implied. CLINICAL ASPECTS: Precursors (first clinical signs of ARMD) can be observed on examination of the fundus: drusen (localized deposits of lipids and lipoproteins) and alterations in retinal pigment epithelium (RPE) (hypo- or hyperpigmentation). Two forms of complications are observed: atrophic (or "dry") and exudative (or "wet"). The atrophic form is defined by the presence of degeneration in the central RPE, choriocapillaris and photoreceptors, resulting from the enlargement and/or coalescence of small areas of peri-foveolar atrophy (or "geographic" atrophy). The exudative form, responsible for the majority of cases of blindness due to ARMD, is characterized by the appearance of choroidal new vessels, identifiable on fluorescein angiography and responsible for serous retinal detachment, edema and hemorrhage, leading to the destruction of the macular photoreceptors. FROM A THERAPEUTIC POINT OF VIEW: Treatment of the atrophic form is currently only palliative (visual aids and re-habilitation of low vision). Treatments of the exudative form having demonstrated their efficacy are laser photocoagulation and dynamic phototherapy with verteporfine, providing relative stabilization of visual acuity in around 2/3 of the eyes. Other treatments are under evaluation: anti-angiogenic treatments, surgical techniques (ablation of the new vessels, foveal translocation), new laser treatments (transpupillary thermotherapy, selective photocoagulation of the feeder vessels). Photoreceptor and pigment epithelium transplantations or implantation of microphotodiodes represent other long-term alternatives.

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Lakartidningen 2002 Aug 8;99(32-33):3194-7
[Age-related macular degeneration—new possibilities for prophylactic measures]
[Article in Swedish]
Frennesson C, Nilsson SE.
Ogonkliniken, Universitetssjukhuset, Linkoping. Christina.Frennesson@lio.se

Age-related macular degeneration (AMD) is the most common cause of severely reduced vision in the Western World. The only treatment method previously available, thermal laser photocoagulation of choroidal neovascularization (CNV), has considerable limitations. More recently, new methods for prophylactic measures and therapy have been developed. A randomised pilot study has shown that prophylactic laser treatment of soft drusen maculopathy reduced the risk of exudative AMD significantly. Larger studies are in progress. A randomised and placebo controlled study of 3.600 patients for six years showed recently that a combination of antioxidants and zinc reduced the risk of severe AMD in patients with soft drusen maculopathy by 25%. Large, randomised and placebo controlled studies showed that photodynamic treatment of certain forms of CNV significantly reduced the risk of severe vision loss. Other methods, such as transpupillary thermotherapy, surgical treatment and pharmacological treatment are being further developed. Visual rehabilitation, using eccentric viewing, has been found successful.

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Trans Am Ophthalmol Soc 2002;100:85-106; discussion 106-7
Multicenter prospective, randomized, double-masked, placebo-controlled study of Rheopheresis to treat nonexudative age-related macular degeneration: interim analysis.
Pulido JS; Multicenter Investigation of Rheopheresis for AMD (MIRA-1) Study Group.
Department of Ophthalmology and Visual Sciences, UIC Eye Center, University of Illinois at Chicago, USA.

OBJECTIVE: To evaluate the safety and efficacy of Rheopheresis blood filtration to treat intermediate- to late-stage preangiogenic age-related macular degeneration (AMD) with soft drusen. DESIGN: Multicenter, prospective, randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: First 43 randomized patients (28 Rheopheresis and 15 placebo-control patients) with available baseline and 3-month postbaseline best corrected visual acuity (BCVA) measurements and intermediate- to late-stage preangiogenic AMD with multiple large soft drusen and elevated serum levels of targeted macromolecules. INTERVENTION: Patients were randomly assigned to receive eight Rheopheresis or eight placebo procedures over 10 weeks. MAIN OUTCOME MEASURES: ETDRS BCVA measurements at baseline, 3, 6, 9, and 12 months postbaseline. RESULTS: In primary eyes, the mean LogMAR line difference between Rheopheresis and placebo-control eyes was 1.6 lines at 12 months postbaseline; the difference was significant throughout the first posttreatment year (P = .0011, repeated measures analysis). Thirteen percent of Rheopheresis compared with 0% of placebo-control eyes had a > or = 3-line improvement in BCVA at 12 months postbaseline. Four percent of Rheopheresis compared with 18% of placebo-control eyes had a > or = 3-line loss in BCVA. The subgroup of patients whose primary eyes had baseline BCVA worse than 20/40 demonstrated a mean LogMAR difference between Rheopheresis and placebo-control eyes equaling 3.0 lines at 12 months postbaseline; the difference was significant throughout the first posttreatment year (P = .0014, repeated measures analysis). Sixteen percent of Rheopheresis compared with 0% of the placebo-control eyes had a > or = 3-line improvement in BCVA at 12 months postbaseline. Five percent of Rheopheresis compared with 29% of placebo-control eyes had a > or = 3-line loss in BCVA. Fifty-eight percent of Rheopheresis eyes improved to 20/40 or better, compared with 14% of placebo-control eyes. No serious treatment-related adverse events were observed. CONCLUSIONS: Rheopheresis demonstrated statistically significant and clinically relevant effects on BCVA when compared with placebo controls for the 12-month study interval. Untreated patients with BCVA worse than 20/40 with intermediate- to late-stage preangiogenic AMD, soft drusen, and elevated blood factors were at risk for substantial visual loss. A sample size larger than 43 patients is important to provide a basis for widespread adoption of novel therapeutic options for AMD such as Rheopheresis. Therefore, enrollment to 150 patients is continuing.

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Can J Ophthalmol 2002 Dec;37(7):399-404
[Photodynamic therapy for age related macular degeneration with and without antioxidants]
[Article in French]
Scorolli L, Scalinci SZ, Limoli PG, Morara M, Vismara S, Scorolli L, Corazza D, Meduri R.
Du Departement d'optique physiopathologique de la Clinique d'ophtalmologie, hopital universitaire Sant'Orsola, Bologne, Italie. luciascorolli@yahoo.it

BACKGROUND: Antioxidants may affect the lipid components of membrane receptors. The purpose of this study was to determine whether treatment with antioxidants after photodynamic therapy for age-related macular degeneration (AMD) improves visual acuity recovery time after a flicker test METHODS: The study was conducted in a university-affiliated ophthalmology clinic in Bologna, Italy, from April 2000 to April 2001. Thirty-five patients (21 men and 14 women aged 55 to 86 years [mean 72 (standard deviation [SD] 8.4) years]) with bilateral AMD and neovascular membranes were enrolled in the study. Patients were randomly assigned to either receive (20 patients) or not receive (15 patients) vitamin E (200 mg/d given orally) and polyunsaturated fatty acids (1,000 mg/d given orally) after photodynamic therapy. The outcome measures were visual acuity (logMAR) after 20, 40 and 60 days, and retinal metabolic function, as evidenced by visual acuity recovery after the Magder flicker test. RESULTS: There was no significant difference in visual acuity between the two groups at 20, 40 or 60 days. At 20 days, the visual acuity recovery time was significantly shorter in the group that received antioxidants than in the group that received photodynamic therapy only (phase II .94 [SD 0.39] minutes vs. 2.56 [SD 0.57] minutes, phase II 2.13 [SD 0.68] minutes vs. 2.83 [SD 0.60] minutes, and phase III 2.19 [SD 0.70] minutes vs. 2.92 [SD 0.65] minutes) (p < 0.001). There was no significant difference between the two groups at 40 or 60 days. INTERPRETATION: Treatment with antioxidants after photodynamic therapy for AMD improves retinal metabolic function in the short term but not in the medium term.

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Ophthalmol Clin North Am 2002 Dec;15(4):437-44, v
Use of radiation in the treatment of age-related macular degeneration.
Flaxel CJ.
Doheny Retina Institute of the Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. flaxel@hsc.usc.edu

In this century, macular degeneration is likely to reach epidemic proportions. New treatment modalities are being evaluated for wet or neovascular age-related macular degeneration (AMD) and include radiation treatment. Radiation is known to potentially destroy vascular tissue, and low-dose radiation has been shown to inhibit new blood vessel growth. Potential advantages to radiation therapy in treating AMD include the absence of iatrogenic mechanical or laser damage, the absence of systemic side effects, and the absence of local side effects caused by periocular and intraocular injection. An additional advantage is that eyes with primarily large, occult choroidal neovascularization are potentially eligible for treatment, and only one treatment would be necessary. The major potential side effect is radiation retinopathy, which is dose dependent.

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Oftalmologia 2002;53(2):97-102
[Age related macular degeneration surgery]
[Article in Romanian]
Carstocea B, Gafencu O, Armegioiu M, Musat O, Ionita N, Postaliu D, Stanca H, Asandi R.

Age related macular degeneration (ARMD) is a disease in which the retinal pigment epithelium (RPE) is damaged in the central retinal area. In the exudative form, the vision loss is due to choroidal neovascularization, while in the nonexudative or atrophic form, there is a vision loss because of the retinal pigment epithelium atrophy. Treatment which proved to be efficient in lowering the risk of severe vision loss in the exudative form includes laser photocoagulation, photodynamic therapy, transpupilary thermotherapy and as surgical treatment, the controversial subretinal membrane extraction. In all these situations the RPE is damaged by the disease itself and by the therapeutic procedure too. Retinal translocation is a surgical procedure that intends to remove the neurosensory retina from an area with damaged RPE to an healthy RPE area, through a 360 degrees retinotomy or through a limited one. This paper present some ARMD cases treated by subretinal membrane extraction and one by limited retinal translocation. The question which is still remaining is which are the risks and benefits for the following treatment procedures: laser photocoagulation, photodynamic therapy, transpupilary thermotherapy and surgical approach?

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Am J Ophthalmol 2002 Dec;134(6):905-6
Proton therapy for exudative age-related macular degeneration: a randomized,
sham-controlled clinical trial.
Ciulla TA, Danis RP, Klein SB, Malinovsky VE, Soni PS, Pratt LM, Pugh NO, Morphis JG, Bloch C, Cameron J.
Retina Service, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. thomasciulla@yahoo.com

PURPOSE: To examine the effect of proton beam irradiation on subfoveal choroidal neovascular membranes (CNVM) associated with age-related macular degeneration (AMD).Randomized, prospective, sham-controlled, double-masked treatment trial. METHODS: Thirty-seven subjects with subfoveal CNVM due to AMD were randomly assigned to 16-Gy proton irradiation delivered in two fractions 24 hours apart or to sham control treatment. Recruitment was halted at 37 subjects for ethical reasons regarding randomization to sham treatment when Food and Drug Administration approval of Visudyne was anticipated. RESULTS: Proton irradiation was associated with a trend toward stabilization of visual acuity, but this association did not reach statistical significance. No correlations were found within the fluorescein angiography data, including greatest linear dimension of CNVM total size, area of active leakage, area of associated subretinal hemorrhage, and intensity. CONCLUSIONS: With the acceptance of photodynamic therapy, future studies will require more complex design and larger sample size to determine whether radiation can play either a primary or adjunctive role in treating these lesions.

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Br J Ophthalmol 2002 Dec;86(12):1330-5
Cataract surgery and quality of life in patients with age related macular degeneration.
Lundstrom M, Brege KG, Floren I, Lundh B, Stenevi U, Thorburn W.
Department of Ophthalmology, Blekinge Hospital, SE-371 85 Karlskrona, Sweden. mats.lundstrom@ltblekinge.se

BACKGROUND: The coexistence of cataract and age related macular degeneration (AMD) is not unusual, especially in the very elderly. The outcome of cataract surgery in these cases depends on the effect of AMD on vision. In this study the authors have compared the outcome of cataract patients with AMD to that of cataract patients with no vision threatening ocular comorbidity, and analysed possible predictors of good or poor outcome. METHODS: An observational prospective study on consecutive cases operated for cataract during 1 month at six surgical departments affiliated to the Swedish National Cataract Register (NCR). Data were collected according to the protocol of NCR and subjects completed the Catquest questionnaire before and 6 months after surgery. 90 subjects with AMD were compared to 335 subjects with no sight threatening ocular comorbidity. RESULTS: Difficulties in performing various daily life activities improved significantly for AMD subjects after surgery (p<0.001, Wilcoxon signed rank test). Satisfaction with vision also improved significantly after surgery (p<0.001, Wilcoxon signed rank test). Activity level and independence were unchanged. Subjects with no ocular comorbidity had a still better outcome. The most important variable related to a good self assessed functional outcome was postoperative visual acuity irrespective of the presence of AMD. AMD subjects scheduled for second eye surgery and AMD subjects dissatisfied with their vision before surgery had a poorer outcome. CONCLUSION: Subjects with various stages of dry AMD and cataract improved their self assessed visual function and satisfaction with vision significantly after cataract extraction.

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Retina 2002 Oct;22(5):536-44
Effects of verteporfin therapy on contrast sensitivity: Results From the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation-TAP report No 4.
Rubin GS, Bressler NM; The Treatment of Age-Related Macular Degeneration with Photodynamic therapy (TAP) study group.
Institute of Ophthalmology, University College London, United Kingdom. g.rubin@ucl.ac.uk

BACKGROUND: In the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation, verteporfin therapy reduced the risk of at least moderate vision loss (defined as a loss of at least 15 letters of visual acuity) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). This report presents detailed analyses of 24-month contrast sensitivity outcomes in these patients. METHODS: The patients included in the TAP investigation had subfoveal CNV secondary to ARMD and received verteporfin therapy (n = 402) or placebo (n = 207) at the first visit, with retreatment at each 3-month follow-up visit if angiography revealed fluorescein leakage from CNV. Contrast sensitivity was determined at each visit using a Pelli-Robson chart. RESULTS: At the month 24 examination, verteporfin-treated patients were less likely to lose at least 6 or 15 letters of contrast sensitivity than placebo-treated patients (86 [21%] versus 94 [45%], and 27 [7%] versus 24 [12%], respectively; P < 0.05 for both comparisons). The superiority of verteporfin therapy over placebo was greater in patients with predominantly classic CNV at baseline, although verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes. CONCLUSIONS: Consistent with visual acuity outcomes, verteporfin therapy reduced the risk of a clinically relevant loss of contrast sensitivity in the total study population, with the greatest effect in patients with predominantly classic subfoveal CNV secondary to ARMD. Verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes than patients who received placebo. Given the association between contrast sensitivity and visual disability, the beneficial effects of verteporfin therapy on contrast sensitivity outcomes are expected to have a favorable impact on patients' daily activities.

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Arch Ophthalmol 2002 Nov;120(11):1443-54
Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition's impact on vision outcomes-TAP report No. 3.
Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group.
Wilmer Photograph Reading Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2002, USA. nmboffice@jhmi.edu

OBJECTIVE: To explore how baseline lesion composition influenced vision outcomes in patients with age-related macular degeneration (AMD) undergoing photodynamic therapy with verteporfin (Visudyne) for subfoveal choroidal neovascularization (CNV) in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Investigation. METHODS: Patients with subfoveal lesions secondary to AMD with evidence of classic CNV were categorized into 2 subgroups based on baseline color photographs and fluorescein angiograms assessed by graders at the Wilmer Photograph Reading Center (The Johns Hopkins University School of Medicine) before any outcome analyses as follows: (1) predominantly classic CNV (area of classic CNV >/=50% of the area of the entire lesion) or (2) minimally classic CNV (area of classic CNV <50% but >0% of the area of the entire lesion). Additional exploratory analyses were performed in the predominantly classic subgroup to investigate the effects of visual acuity, lesion size, prior laser photocoagulation, phakic status, micronutrient use, and presence of occult CNV on vision outcomes. MAIN OUTCOME MEASURES: Subgroup analyses of vision and fluorescein angiographic outcomes at 1 and 2 years after study enrollment were examined in an intent-to-treat analysis from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials. RESULTS: Compared with patients who had minimally classic CNV, patients with predominantly classic CNV had a worse initial mean visual acuity and smaller lesions and were more likely to have lesions that included blood or blocked fluorescence. When evaluated by treatment assignment and lesion composition, 84% to 88% completed the month 24 examination. In the subgroup with predominantly classic lesions, visual acuity outcomes were consistently better in verteporfin-treated patients. Outcomes for patients with predominantly classic lesions without occult CNV tended to be better than outcomes for patients with predominantly classic lesions with occult CNV, although the former tended to have smaller lesions and lower levels of visual acuity at baseline. Contrast sensitivity and fluorescein angiographic outcomes (total lesion size, progression of classic CNV, and absence of classic CNV) were better in verteporfin-treated patients than in placebo-treated patients in the predominantly classic and the minimally classic CNV subgroups. In patients with predominantly classic CNV, no interaction of the treatment benefit by phakic status, micronutrient use, or prior laser photocoagulation therapy was noted. CONCLUSIONS: Verteporfin therapy can safely reduce the risk of moderate and severe vision loss in patients with subfoveal lesions that are predominantly classic CNV secondary to AMD. While this benefit seemed to be even greater in the absence of occult CNV, the effect may be related to the smaller lesions and worse visual acuity associated with predominantly classic lesions without occult CNV and not solely to the lesion composition itself. These analyses support initial reports that verteporfin therapy should be used to treat patients with AMD who have predominantly classic CNV, with or without occult CNV, but suggest that further investigations should be performed to determine if lesions with a minimally classic composition might benefit when they are smaller and have lower levels of visual acuity.

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Arch Soc Esp Oftalmol 2002 Nov;77(11):617-22
[Transpupillary thermotherapy in occult subretinal neovascularization in age-related macular degeneration. Preliminary results]
[Article in Spanish]
Salinas Alaman A, Garcia Layana A, Juberias Sanchez JR, Sanchez Tocino H, Sadaba Echarri LM, Moreno Montanes J.
Departamento de Oftalmologia, Clinica Universitaria de Navarra, Universidad de Navarra, Pamplona, Espana. asalinas@unav.es

PURPOSE: To determine the efficacy of transpupillary thermotherapy (TTT) to treat choroidal neovascularization (CNV) in patients with age-related macular degeneration (ARMD). PATIENTS AND METHODS: Eight patients (ten eyes) with occult CNV were treated by TTT. A 810 nm diode laser was used to perform TTT. The diode laser was delivered through a panfunduscopic contact lens. RESULTS: Three eyes showed a visual acuity improvement and a decrease in exudation on fluorescein angiography. Four eyes remained stable. Nevertheless, lesions worsened after treatment in three cases. One of these cases suffered an overtreatment. CONCLUSIONS: TTT may be a useful therapy in some cases of CNV in patients with age-related macular degeneration. Randomized and multicentric studies are necessary to establish precise indications of this therapy.

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J Fr Ophtalmol 2002 Sep;25(7):753-5
[Photodynamic therapy]
[Article in French]
Soubrane G, Kuhn D, Oubraham H, Coscas G.
Clinique Ophtalmologique Universitaire de Creteil, Universite Paris-XII, 40 avenue de Verdun, 94010 Creteil.

Photodynamic therapy with Verteporfine (Visudyne Novartis Ophthalmics) achieves a photo occlusion of subfoveal choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) in phase 1 and 2 studies. Thereafter, two international randomized clinical trials evaluated the product's efficacy in term of visual acuity. Eyes with neovascular lesions due to AMD of less than 5,400 micro, in size involving the fovea and presenting well-defined CNV on fluorescein angiography could be included when visual acuity was between 5 and 1/10. Six hundred and nine patients were subsequently randomized either to Verteporfine or to placebo (proportion 2:1). A follow-up of 3 months made it possible to consider retreatment when a fluorescein leakage was observed. Functional and angiographic results demonstrated the efficacy of PDT with Verteporfine in comparison with placebo at each examination during follow-up. A visual acuity decrease of less than 15 letters on ETDRS (or 3 lines or approximately 1.5/10) occured less frequently in the treated group with PDT (61% out of 402 treated eyes compared with 46% of 207 placebo eyes). Subgroup analysis of predominantly well-defined CNV (involving 50% or more of the total of the exsudative lesion) showed even more favourable effects (67% of treated eyes versus 39% of placebo eyes). Conversely, when well-defined CNV extended to a smaller area, the results were not significant. The most frequent side effect was Verteporfine extravasation at the injection site. As dynamic phototherapy with Verteporfine limits the decrease in visual acuity always occurring in the natural history of CNV caused by AMD, it is desirable that patients presenting subfoveal predominantly well-defined lesions benefit from this new treatment approach.

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J Fr Ophtalmol 2002 Sep;25(7):747-52
[Age related macular degeneration: a review of anti-angiogenic treatments]
[Article in French]
Razavi S, Coscas G, Soubrane G.
Service Universitaire d'Ophtalmologie de Creteil, Centre Hospitalier Intercommunal de Creteil, 40 avenue de Verdun, 94010 Creteil, France.

In Western countries, age-related macular degeneration is the leading cause of visual loss in people aged 65 and over. Laser photocoagulation has been shown to be beneficial in patients with extra- or juxta-foveal classic choroidal neovascularization (CNV), but the majority of patients with exudative maculopathy have occult or subfoveal CNV. Laser photocoagulation is plagued by recurrences, which occur in more than 50% of cases. Because of the limited efficacy of laser photocoagulation and the small number of patients who are eligible for treatment, investigators are attempting to develop new modalities to treat CNV. These modalities can be classified into three major categories: surgery, photodynamic and pharmacological treatments.The general mechanism, the regulation of ocular angiogenesis, and current anti-angiogenic treatments are the subject of this review of the recent literature.

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J Fr Ophtalmol 2002 Sep;25(7):740-6
[Current treatment of choroidal neovascularization in age-related macular degeneration]
[Article in French]
Donati G.
Clinique d'Ophtalmologie, Departement de Neurosciences Cliniques, HCUG, 22 Rue A. Jentzer, 1211 Geneve 14.

Age-related macular degeneration (AMD) is currently the leading cause of severe visual acuity loss in people over the age of 50 in the Western world. Most of the visual loss is due to choroidal neovascularization (CNV). Laser photocoagulation is the only proven treatment for selected cases of AMD; however, it can only be used with less than 20% of patients at the time of diagnosis. Among experimental therapies currently being tested, photodynamic therapy has recently proven its efficacy in randomized multicenter studies for predominantly classic subfoveal pure occult type CNVs.

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J Fr Ophtalmol 2002 Sep;25(7):694-700
[Progression of choroidal neovascularization after macular translocation in age-related macular degeneration and degenerative myopia]
[Article in French]
Simon P, Glacet-Bernard A, Coscas G, Soubrane G.
Clinique ophtalmologique universitaire de Creteil, Hopital Intercommunal et Hopital Henri Mondor (Assistance Publique des Hopitaux de Paris), Universite Paris XII, 40 avenue de Verdun, 94000 Creteil, France.

PURPOSE: To study the progression of choroidal neovascularization (CNV) after macular translocation in age-related macular degeneration (AMD) and degenerative myopia. PATIENTS AND METHODS: The data from 42 consecutive eyes (28 AMD, and 14 degenerative myopia) operated on by limited macular translocation (DeJuan technique), with a follow-up of 6 months or more, were prospectively analyzed. In the AMD group, neovascularization was classic in 54% of eyes and classic and occult in 46% of eyes. Previous laser treatment was applied on extra- or juxtafoveal CNV in 3 eyes. The major outcome measures were visual acuity, fluorescein and indocyanine green angiographies. RESULTS: After translocation, foveal displacement was greater in AMD than in myopic eyes (mean: 1 260 and 812 micro m, respectively). Laser photocoagulation was applied postoperatively onto extra-or juxtafoveal CNV in 26 (93%) AMD eyes and 12 myopic eyes (86%). Mean follow-up was 10 months (range, 6-18 months). Recurrence of CNV occurred in 14 AMD eyes (50%) and 2 myopic eyes (14%) an average of 5.6 months after surgery (range, 1-18 months). Recurrence was more frequent in AMD eyes with preoperative occult CNV (66%) than without (36%). Recurrence reached the new fovea in 69% of cases. Supplementary laser treatment was possible and successful on extra- or juxtafoveal recurrence in 3 eyes. Recurrence was significantly correlated with a poor visual prognosis: eyes without recurrence or with extra- or juxtafoveal recurrence had a final gain in visual acuity of 2.4 lines, eyes with subfoveal recurrence had a loss of 1.3 lines, and eyes with diffuse recurrence had a loss of 4.2 lines. CNV appeared in a new area at a BSS injection site in one eye. Occult CNV seemed to fade relatively within the first postoperative weeks, but were unchanged at the end of follow-up. In one eye, a small polypoidal lesion near the disc noted preoperatively disappeared after surgery. CONCLUSION: Our results suggest that the surgical procedure does not affect the course of classic or occult CNV. The rate of recurrence of CNV after macular translocation seemed similar to that observed after conventional laser treatment for extrafoveal CNV in AMD. Neovascular recurrence is the most frequent postoperative complication and was frequently directed at the new fovea. Despite these complications, macular translocation moves CNV outside of the subfoveolar zone so the eyes can be treated with conventional laser, leading to a favorable outcome at the last follow-up in 57% of cases. Further studies are required to confirm these findings and to define the best criteria for treatment.

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Am J Ophthalmol 2002 Oct;134(4):560-5
Macular translocation with 360 degree retinotomy for management of age-related macular degeneration with subfoveal choroidal neovascularization.
Pertile G, Claes C.
Department of Ophthalmology, Zivojnovic Foundation, Middelheim Hospital, Antwerp, Belgium. grazia.pertile@belgacom.net

PURPOSE: The aim of this study is to evaluate the functional outcome in a group of patients treated with full macular translocation (FMT) with 360-degree retinotomy for treatment of age-related macular degeneration (ARMD) with subfoveal choroidal neovascularization.DESIGN: Consecutive interventional case series.METHODS: Fifty consecutive eyes (50 patients) with ARMD and subfoveal neovascularization who underwent a FMT in our department from January 1999 to July 2000 are included in this study. Compensatory muscle surgery, as described by Eckardt and associates, was performed on all the eyes. The median follow-up is 21 months (range, 12 to 36; SD, 5.4).RESULTS: The best-corrected postoperative visual acuity (BCVA) was improved by 2 or more Snellen lines in 33 eyes (66%) and remained stable (+/-1 line) in 14 eyes (28%). Only 3 eyes (6%) experienced a deterioration of the BCVA of 2 or more lines. The final BCVA was 20/50 or better in 32% of the cases; only 8 eyes (16%) had a final BCVA < 20/200. Thirty-four (68%) patients are able to read newspaper print (3.3/10) with normal (+3 diopters to +4 diopters) or increased (+5 diopters to +8 diopters) reading ads. Other patients are able to read with magnifying systems. Complications included proliferative vitreoretinopathy (PVR) in 9 eyes (18%), recurrent choroidal neovascularization in 5 eyes (10%), diplopia in 3 eyes (6%), choroidal hemorrhage in 2 eyes (4%), macular hole in 1 eye, and temporary hypotony in 1 eye.CONCLUSIONS: As 68% of the patients in the study group regained reading vision with reading glasses, FMT can be considered an effective approach in cases of subfoveal choroidal neovascularization. Further investigations are necessary to determine which patients will have the most benefit from this complex therapeutic method.

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Ophthalmologe 2002 Oct;99(10):780-4
[Rheophoresis. A systematic approach to therapy of age-related macular degeneration (AMD)?]
[Article in German]
Fell AJ, Engelmann K, Richard G, Fassbender C, Wahls W, Klingel R.
Klinik und Poliklinik fur Augenheilkunde, Universitatsklinikum Hamburg-Eppendorf, Germany. fell@uke.uni-hamburg.de

BACKGROUND: Choroidal microcirculation is impaired in age-related macular degeneration (AMD), and leads to deposition of lipids and proteins in Bruch's membrane. Rheophoresis can improve choroidal microcirculation by eliminating high molecular weight, rheologically relevant plasma proteins. The objective of this post-certification study was to analyse the effect of rheophoresis in 10 AMD patients. PATIENTS AND METHODS: A total of 6 patients with early AMD and 4 with late AMD in one eye (initial visual acuity equivalent 0.2-0.8) received rheophoresis treatment 10 times over an 18-week period. Visual acuity and color vision were determined initially and after 3, 5 and 12 months and fluorescein angiography was performed. RESULTS: Patients with early AMD showed improvement of visual acuity (2 lines on ETDRS charts) in 2 out of 6 cases and a stable visual acuity in 4 out of 6 cases 1 year after rheophoresis, whereas patients with late AMD showed improvement of visual acuity (2 lines on ETDRS charts) in 1 out of 4 cases and a stable visual acuity in 3 out of 4 cases. In red-free fundus photography, a reduction in drusen size and number could be observed in 4 out of 10 cases. CONCLUSION: The results of this investigation seem to be in accordance with data from previously published controlled clinical trials. Recommendations for the indication of rheopheresis for AMD should be further defined and evaluated within the framework base of a multicentric cooperative study.

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Wien Med Wochenschr 2002;152(15-16):423-6
[Ginkgo extract in impaired vision--treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration]
[Article in German]
Fies P, Dienel A.

The therapeutic efficacy of Ginkgo special extract Egb 761 was investigated in a controlled, double-blind trial involving 99 patients with impaired vision due to senile, dry macular degeneration. The primary objective target variable was the change in the corrected visual acuity of the more severely impaired eye at baseline, during a six months treatment period with either 240 mg/die (group I = 50 patients) or 60 mg/die (group II = 49 patients) Egb 761. Marked improvement of the study participants' vision was observed in both treatment groups already after four weeks, with more pronounced improvements in group I (acuity increases by 0.13 in group I vs. 0.10 in group II after 24 weeks). The fraction of patients with improvement of visual acuity > or = 0.2 was nearly twice as large in the group treated with 240 mg/die Egb 761 as in patients receiving the lower dosage (p = 0.08). Subjective health impairments, if present, could be improved during treatment as well. The investigator rated a favorable tolerability for both dosages of Egb 761. In conclusion, the results demonstrate the therapeutic efficacy of Egb 761 in patients with senile, dry macular degeneration, with obvious benefits in every-day life.

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Proc Natl Acad Sci U S A 2002 Oct 1;99(20):13090-5
Autologous transplantation of genetically modified iris pigment epithelial cells: a promising concept for the treatment of age-related macular degeneration and other disorders of the eye.
Semkova I, Kreppel F, Welsandt G, Luther T, Kozlowski J, Janicki H, Kochanek S, Schraermeyer U.
Center for Molecular Medicine Cologne (ZMMK), Center of Ophthalmology, Department of Retinal Surgery, Institute for Anatomy, University of Cologne, Kerpener Strasse 34, D-50931 Cologne, Germany.

Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.

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Klin Monatsbl Augenheilkd 2002 Jul;219(7):512-8
[Intravitreal injection of rt-PA and gas in the management of minor submacular haemorrhages secondary to age-related macular degeneration]
[Article in German]
Hattenbach LO, Brieden M, Koch F, Gumbel H.
Klinik fur Augenheilkunde, Klinikum der Johann Wolfgang Goethe-Universitat, Frankfurt am Main, Germany.

BACKGROUND: Subfoveal haemorrhage is a serious complication of choroidal neovascularization in age-related macular degeneration (ARMD). Recent studies have demonstrated that intravitreal injections of the fibrinolytic agent recombinant tissue plasminogen activator (rt-PA) and expansile gas may be effective in displacing submacular blood and facilitating visual improvement. However, in most of these studies, this technique has been used for the management of major haemorrhages. The purpose of our study was to investigate the efficacy of treating minor subfoveal haemorrhages with intravitreal rt-PA and pneumatic displacement. PATIENTS AND METHODS: In a prospective study, 25 consecutive eyes of 25 patients with recent (</= 28 days) subfoveal haemorrhage secondary to ARMD and severe visual loss were treated with intravitreous injections of rt-PA (50 micro g) and sulfur hexafluoride (0,5 ml). The extent of the haemorrhage ranged from R to 2 disc areas. Patient follow-up ranged between 4 and 18 months. RESULTS: Best postoperative visual acuity compared with preoperative visual acuity was improved by two or more Snellen lines in 11 of 25 eyes (44 %). Seven eyes (28 %) maintained this level at the final visit. Duration of haemorrhage was associated with a better gain of lines of vision. In a subgroup of 9 eyes with duration of haemorrhage </= 14 days, 7 (78 %) improved by two or more Snellen visual acuity lines, whereas only 4 of 16 eyes (25 %) with duration of haemorrhage > 14 days showed a comparable outcome (p = 0.017). There were no side effects or complications. CONCLUSIONS: Our findings suggest that intravitreous injections of rt-PA and sulfur hexafluoride are of value for an improved and accelerated visual recovery in ARMD patients with minor subfoveal haemorrhages. Duration of haemorrhage </= 14 is associated with a better gain of lines of vision. Final visual outcome, however, is limited by the underlying ARMD. In addition, a rapid displacement of subfoveal haemorrhages may reveal discrete choroidal neovascular membranes amenable to further treatment. The complication rate of this therapeutic approach appears to be low.

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Acta Ophthalmol Scand 2002 Aug;80(4):368-71
Neovascular age-related macular degeneration and its relationship to antioxidant intake.
Snellen EL, Verbeek AL, Van Den Hoogen GW, Cruysberg JR, Hoyng CB.
Department of Epidemiology and Biostatistics, University Medical Centre, Nijmegen, Netherlands.

PURPOSE: Experimental and epidemiological studies suggest that low antioxidant intake may be associated with the occurrence of neovascular age-related macular degeneration (AMD). METHODS: We investigated this hypothesis further with a case-control study involving 72 case and 66 control patients attending the Ophthalmology Department of the University Hospital in Nijmegen. Data were collected by interview on antioxidant intake (i.e. in fruit and vegetables), cigarette smoking, sunlight exposure and familial predisposition. Antioxidant intake was calculated according to the method described in the Framingham Eye Study. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The prevalence rate of AMD in patients with low antioxidant intake and low lutein intake (dichotomized at the median value) was about twice as high as that in patients with high intake: OR = 1.7, 95% CI (0.8-3.7), and OR = 2.4, 95% CI (1.1-5.1). Further specification of intake data into quartiles of antioxidant intake and lutein/zeaxanthine intake showed a clear dose-response relationship. CONCLUSION: The effect of dietary antioxidants upon macular health warrants preventive studies.

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Cesk Slov Oftalmol 2002 Jul;58(4):215-23
[Transpupillary thermotherapy in age-related macular degeneration. Preliminary results]
[Article in Czech]
Karel I, Zahlava J, Boguszakova J, Dubska Z, Lestak J.
Katedra oftalmologie IPVZ, Praha.

OBJECTIVE: To evaluate anatomical and functional results of transpupillary thermotherapy (TTT) in age-related macular degeneration (ARMD) with a chorioid neovascular membrane (CNVM). MATERIAL AND METHODS: TTT was performed by means of a diode laser (Iris Medical Oculight Six) in 38 eyes of 35 patients aged 46-93 years, mean 70.6 years. Ocult CNVM was treated in 34 eyes, classical CNVM in 4 eyes. In TTT we applied 1 to 5 points (on average 1.9 spot) and used a laser beam with a diameter of 0.5-3 mm (mean width 1.61 mm). In 10 eyes with occult CNVM (29%) TTT was repeated after 1-6 months. The patients were followed up after TTT for 6-18 months on average for 9.5 months. RESULTS: The final visual acuity (VA) improved after TTT in two eyes (5.3%), remained unchanged in 22 eyes (57.9%) and deteriorated in 14 eyes (36.8%). The mean VA after TTT declined from 0.23 to 0.17. Biomicroscopic manifestations of exudation disappeared or receded in 29 eyes with occult CNVM (85.3%) and in 3 eyes with classical CNVM (75%). Fluoroangiographic examination revealed a reduced or absent extravasation of the dye in 24 eyes with occult CNVM (70.5%) and in 3 eyes with classical CNVM (75%). Optic coherent tomography confirmed regression of exudative changes and the development of a chorioretinal scar in 23 eyes with occult CNVM (67.6%) and 3 eyes with classical CNVM (75%). CONCLUSION: TTT is a new potential therapy of ACMD with CNVM. It is indicated in particular in occult CNVM. It can be however used also in classical CNVM. TTT is not economically pretentious and can be used also in other than large clinical departments. It is important to test the possibilities and limitations of TTT on a large number of patients and assess its position among other therapeutic procedures.

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Ther Apher 2002 Aug;6(4):271-81
Rheopheresis for age-related macular degeneration: a novel indication for therapeutic
apheresis in ophthalmology.
Klingel R, Fassbender C, Fischer I, Hattenbach L, Gumbel H, Pulido J, Koch F.
Apheresis Research Institute, Cologne, Germany. afi@apheresis-research.de

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly. Successful therapy is not yet available for the majority of patients, especially not for patients with dry AMD. AMD at cellular and molecular levels is at least in part a microcirculatory disorder of the retina. Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders and represents a novel treatment option for patients with dry AMD. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, cholesterol, von Willebrand factor, and alpha 2-macroglobulin results in the reduction of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma viscosity performed as a series of Rheopheresis treatments lead to rapid changes of blood flow, subsequently inducing sustained improvement of microcirculation and recovery of retinal function. Two controlled randomized clinical trials demonstrated the safety and efficacy of Rheopheresis for the treatment of AMD patients, especially for those with the dry form. Recently the interim analysis of the sham-controlled, double blind, randomized multicenter Multicenter Investigation of Rheopheresis for AMD (MIRA-I) trial confirmed these results. The framework of completed and still ongoing controlled clinical trials in combination with postcertification studies including the RheoNet registry represents a comprehensive quality management approach for this novel interdisciplinary therapy for AMD. The development and continuous update of guidelines for the precise indication of Rheopheresis for AMD follows the requirements of evidence-based medicine.

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Ophthalmic Physiol Opt 2002 Jul;22(4):300-11
Benefit of coloured lenses for age-related macular degeneration.
Wolffsohn JS, Dinardo C, Vingrys AJ.
Neurosciences Research Institute, School of Life and Health Sciences, Aston University, Birmingham, UK. j.s.w.wolffsohn@aston.ac.uk

PURPOSE: To evaluate and compare the functional and perceived benefits of wearing coloured lenses by patients with age-related macular degeneration (ARMD). METHOD: Ten subjects with early ARMD and five elderly controls wore a selection of NoIR wrap-around coloured lenses (yellow 29.7% light transmission, orange 22.9%, red 16.8% and grey 10.3%), each for a duration of 7 days. Contrast sensitivity, colour vision, visual acuity, the effect of glare and peripheral sensitivity were measured for each lens and compared with a control (no lens) condition. Subjective ratings of visual performance were also scored. RESULTS: Compared with the no filter condition, red and grey lenses reduced contrast sensitivity whereas yellow and orange lenses increased contrast sensitivity. These objective changes were supported by subjective ratings in subjects with ARMD. Grey lenses reduced the loss of contrast sensitivity usually suffered in the presence of glare, whereas visual acuity and peripheral sensitivity decreased with red lenses. Colour vision became distorted with red lenses in control subjects, but was relatively unaffected by the use of coloured lenses in subjects with ARMD. CONCLUSIONS: The subjective benefit of coloured lenses appears to be due to a minor enhancement of contrast sensitivity.

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Arch Ophthalmol 2002 Aug;120(8):1029-38
Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration.
Hart PM, Chakravarthy U, Mackenzie G, Chisholm IH, Bird AC, Stevenson MR, Owens SL, Hall V, Houston RF, McCulloch DW, Plowman N.
Department of Ophthalmology, The Royal Victoria Hospital, Queen's University of Belfast, Northern Ireland.

OBJECTIVE: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. DESIGN: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. SETTING: Three United Kingdom-based hospital units. PARTICIPANTS: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. METHODS: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. RESULTS: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P =.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P =.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. CONCLUSION: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

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Arch Soc Esp Oftalmol 2002 Jul;77(7):353-9
[Dynamic angiography in age related macular degeneration]
[Article in Spanish]
Torron Fernandez-Blanco C, Perez Olivan S, Melcon Sanchez-Friera B, Ferrer Novella E, Ruiz-Moreno O, Honrubia Lopez FM.
Servicio de Oftalmologia, Hospital Miguel Servet, Zaragoza, Espana.

PURPOSE: To evaluate the utility of dynamic angiography with fluorescein and indocyanine green with scanning laser ophthalmoscope (SLO) in exudative age-related macular degeneration. METHOD: We retrospectively studied 95 patients with exudative age-related macular degeneration (ARMD) between April 98 and April 01. RESULTS: We studied 102 eyes of 95 patients with ARMD. Mean age was 75.3 years with a mean follow-up time of 16.8 months. We found an occult or mixed angiographic membrane pattern with fluorescein angiography in 85 eyes (83.3%). Angiography with indocyanine green showed choroidal neovascular membranes in 94 of 102 eyes (92.1%). The most frequent location found was sub-foveal (53.2%). Laser photocoagulation was used in 55 eyes and photodynamic therapy in 5 eyes. In 17 eyes laser treatment failed to close the membrane. CONCLUSION: Dynamic angiography with fluorescein or indocyanine green allowed neovascular membrane identification in more than 90% of the cases of ARMD. Successful treatment was achieved in 42% of cases.

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BMJ 2002 Jul 6;325(7354):11
Comment in: BMJ. 2002 Jul 6;325(7354):1-2.
Vitamin E supplementation and macular degeneration: randomised controlled trial.
Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ.
Centre for Eye Research Australia, University of Melbourne, Locked Bag 8, East Melbourne, Victoria, Australia, 8002. h.taylor@unimelb.edu.au

OBJECTIVE: To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD). DESIGN: Prospective randomised placebo controlled clinical trial. SETTING: An urban study centre in a residential area supervised by university research staff. PARTICIPANTS: 1193 healthy volunteers aged between 55 and 80 years; 73% completed the trial on full protocol. INTERVENTIONS: Vitamin E 500 IU or placebo daily for four years. MAIN OUTCOME MEASURES: Primary outcome: development of early age related macular degeneration in retinal photographs. Other measures included alternative definitions of age related macular degeneration, progression, changes in component features, visual acuity, and visual function RESULTS: The incidence of early age related macular degeneration (early AMD 3) was 8.6% in those receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95% confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus 0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in secondary outcomes. CONCLUSION: Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration.

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Expert Opin Pharmacother 2002 Jul;3(7):931-8
An update on photodynamic therapy in age-related macular degeneration.
Rechtman E, Ciulla TA, Criswell MH, Pollack A, Harris A.
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, 46202, USA.

Age-related macular degeneration (AMD) is the leading cause of irreversible loss of central vision in people aged > 50 years in the western world. Until recently, the only proven treatment to reduce the risk of vision loss from its more severe neovascular form was laser photocoagulation, but this treatment was suitable for only 15% of cases. Photodynamic therapy (PDT) with verteporfin was recently proposed to be effective in reducing the risk of visual loss for an estimated 20 - 30% of neovascular AMD patients. This review covers AMD epidemiology, the mechanism of PDT, the 2-year results of the two major clinical studies of PDT with verteporfin, the cost-effectiveness of PDT and the current research status of other drugs for PDT in AMD.

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Cochrane Database Syst Rev 2002;(2):CD000254
Update of: Cochrane Database Syst Rev. 2002;(1):CD000254.
Antioxidant vitamin and mineral supplements for age-related macular degeneration.
Evans JR.
Research and Development Department, Institute of Ophthalmology (UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD. jennifer.evans@ucl.ac.uk

BACKGROUND: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals produced in the process of light absorption. OBJECTIVES: The objective of this review is to assess the effects of antioxidant vitamin and/or mineral supplementation on the progression of age-related macular degeneration. SEARCH STRATEGY: The Cochrane Controlled Trials Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group specialised register (Cochrane Library Issue 3 2001), MEDLINE (1966 to August 2001), EMBASE (1980 to September 2001), the Science Citation Index, and the reference lists of relevant articles were searched. Investigators of included studies were contacted for further information. SELECTION CRITERIA: Randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control in people with age-related macular degeneration are included in this review. DATA COLLECTION AND ANALYSIS: The reviewer extracted data and assessed trial quality. Due to the variable methods of collecting and presenting outcome data, no statistical summary measure was calculated. MAIN RESULTS: Seven trials, which randomised 4119 people with signs of age-related macular degeneration, are included in this review. One unpublished trial of zinc supplementation (170 participants) is awaiting assessment. The majority of people (88%) were randomised in one trial that found a modest beneficial effect of antioxidant and zinc supplementation on progression to advanced age-related macular degeneration (odds ratio 0.72, 99% confidence interval 0.52 to 0.98). People supplemented with antioxidants and zinc were less likely to lose 15 or more letters of visual acuity (equivalent to a doubling of the visual angle) (odds ratio 0.79, 99% confidence interval 0.60 to 1.04). This effect was seen more strongly in people with moderate to severe disease. There were few events in people with early signs of the disease. The trial evaluated many safety outcomes, of which hospitalisation for genitourinary problems was more common in people taking zinc and yellowing of skin was more common in people taking antioxidant micronutrients. The other six trials in this review were small and the results were inconsistent. REVIEWER'S CONCLUSIONS: The evidence as to the effectiveness of antioxidant vitamin and mineral supplementation in halting the progression of age-related macular degeneration is dominated by one large trial that showed modest benefit in people with moderate to severe signs of the disease. There is no evidence at present that people with early signs of the disease should take supplementation, however, current studies are underpowered to answer that question. Long term harm from supplementation cannot be ruled out, particularly in smokers. The generalisability of these findings to other populations with different nutritional statuses is not known. Further large well-conducted randomised controlled trials in other populations are required.

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Ann Acad Med Singapore 2002 May;31(3):399-404
Age-related macular degeneration: what's new.
Koh AH, Ang CL.
Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751. adrian_koh@snec.com.sg

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed western world, accounting for approximately 50% of all cases of registered blindness. The rising prevalence of this disease in Asia seems to parallel the same trend in the developed world. Because of the socio-economic impact of this disorder, much attention has been paid to elucidating the underlying pathogenic mechanisms, as well as seeking alternative forms of treatment. This review discusses the latest advances in AMD diagnosis, treatment and prophylaxis. METHODS: Medline search with emphasis on randomised controlled clinical trials and large case-control series. Only articles cited on the Index Medicus were included in this review. RESULTS: Recent advances in the diagnosis and treatment of AMD include conventional argon laser photocoagulation, photodynamic therapy (PDT), radiation therapy, surgical options and gene therapy. CONCLUSIONS: There have been numerous advances in the management of AMD and exciting new research applications have emerged. The introduction of exciting new modalities, such as PDT, has revolutionised the approach to treating CNVM and their effects on central vision. However, there has been no breakthrough in achieving satisfactory outcomes with the available techniques for treating occult neovascular lesions. As results of large prospective randomised clinical trials evaluating new treatment alternatives become available, a treatment algorithm for neovascular AMD will emerge that best minimises visual loss and may even result in visual improvement.

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Curr Opin Ophthalmol 2002 Jun;13(3):171-5
Risk factors for age-related macular degeneration: an update.
Hyman L, Neborsky R.
Stony Brook University, Department of Preventive Medicine, Stony Brook, New York 11794-8036, USA. lhyman@notes.cc.sunysb.edu

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States and other western nations. Limited treatment is available, and there are no established means of prevention. The detection of modifiable risk factors is important to suggest preventive behaviors that can reduce disease occurrence or prevent the progression to the late stages of AMD. Results of recent studies suggest that the etiology and pathogenesis of AMD are a complex interaction of genetic and external factors. Although a number of factors seem promising, only age and cigarette smoking are confirmed as increasing AMD risk. Other factors that most likely play a significant role in AMD are nutritional factors, e.g., antioxidants, and hypertension or other underlying atherosclerotic disease processes. The results of the Age-Related Eye Disease Study suggest a moderate beneficial effect of antioxidant, vitamin, and zinc supplementation in reducing progression to severe AMD.

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J Am Board Fam Pract 2002 Mar-Apr;15(2):142-52
Early detection and treatment of neovascular age-related macular degeneration.
Bressler NM.
The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore 21205-2005, USA.

BACKGROUND: The neovascular form of age-related macular degeneration (AMD) can rapidly lead to severe loss of central vision and adversely affect the patient's quality of life. During the 1990s the only proven treatment for neovascular AMD was laser photocoagulation. Only a minority of patients are eligible to receive this treatment, however, and the treatment itself can cause acute retinal damage with immediate vision loss. Verteporfin therapy is a new treatment option involving photodynamic therapy that was recently shown to be relatively safe and effective in reducing the risk of vision loss in selected cases. METHODS: Recent literature was reviewed on management of choroidal neovascularization caused by AMD that proved beneficial in large-scale randomized clinical trials. These studies were selected through a MEDLINE search of files from 1982 to the present using the keywords "randomized clinical trials," "choroidal neovascularization," and "age-related macular degeneration," as well as through personal knowledge of recently completed trials. RESULTS AND CONCLUSIONS: Primary care physicians can effect good treatment outcomes by detecting early signs of AMD and educating patients about the necessity of prompt referral to an ophthalmologist. Immediate referral is increasingly important because, compared with laser photocoagulation, current photodynamic therapy with verteporfin is applicable to more patients. Greater patient awareness of neovascular AMD and the importance of self-testing of vision can also be communicated to patients in primary care.

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Graefes Arch Clin Exp Ophthalmol 2002 May;240(5):337-41
Side effects after radiotherapy of age-related macular degeneration with the Nijmegen technique.
Hoyng CB, Tromp AI, Meulendijks CF, Leys A, van der Maazen RW, Deutman AF, Vingerling JR.
Department of Ophthalmology, University Medical Centre Nijmegen, P.O. Box 9101, The Netherlands. c.hoyng@ohk.azn.nl

BACKGROUND: In a randomized trial concerning radiotherapy for age-related macular degeneration, fluorescein angiograms were taken of controls and patients. In this study the frequency of side effects in eyes receiving radiotherapy with the Nijmegen technique is compared with the findings in the eyes of controls. METHODS: Patients receiving treatment were irradiated by two isocentric photon beams in four fractions of 6 Gy that were directed to the macular area at 30 degrees and -30 degrees with regard to the optical axis. The most recent fluorescein angiograms of the randomized eyes (32 treated and 31 control eyes) were scored by two independent researchers, using a scoring form with nine features of radiation retinopathy: nonperfusion, macular edema, microaneurysms, retinal hemorrhages, cotton-wool spots, perifoveal telangiectasis, vascular sheathing, retinal neovascularization, and radiation-associated choroidal neovasculopathy. The results were graded as: no retinopathy (grade 0), mild retinopathy (grade 1), moderate retinopathy (grade 2), and severe retinopathy (grade 3). RESULTS: In the treated group 6 patients (18.8%) were grade 1, 10 patients (31.2%) were grade 2 and 7 patients (21.9%) were grade 3. In the control group 9 patients (29.0%) were grade 1, 11 patients (35.5%)were grade 2 and 2 patients (6.5%) were grade 3. There were no patients with retinal neovascularization. CONCLUSION: With the Nijmegen technique a relatively high dose of radiation can be applied to a small retinal area. In only a minority of cases does some evidence of radiation retinopathy occur.

   

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