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.
   

On Downloading (Please Read Carefully)   
To download or print the Macular Degeneration File, point your mouse to "File" in the top bar of your Explorer or Netscape window, and click once. Now click once on either "Save As" (download), or "Print" (print), and follow the appropriate prompts.
  
Previous Macular Degeneration Research: 2002-2006   
The Macular Degeneration File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Macular Degeneration, click HERE.
 

Latest Research on
Macular Degeneration
   
Ophthalmology. 2008 Aug;115(8):e39-46.
Time course of morphologic effects on different retinal compartments after ranibizumab therapy in age-related macular degeneration.
Ahlers C, Golbaz I, Stock G, Fous A, Kolar S, Pruente C, Schmidt-Erfurth U.
Medical University of Vienna, Vienna, Austria.

PURPOSE: To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual function. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration. METHODS: Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS). MAIN OUTCOME MEASURES: Morphology and time course of different retinal and subretinal compartments. RESULTS: High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation. CONCLUSION: Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.

------

Am J Health Syst Pharm. 2008 Jul 1;65(13):1232-8.
Lutein and zeaxanthin for macular degeneration.
Zhao L, Sweet BV.
University of Michigan College of Pharmacy (UMCP), Ann Arbor, Michigan, USA.

PURPOSE: The effects of increasing lutein and zeaxanthin dosages in people with age-related macular degeneration (AMD) are discussed. SUMMARY: AMD is a disorder of the macula, the area associated with the sharpest visual acuity. AMD is classified as dry (nonneovascular) or wet (neovascular) and is associated with several risk factors, the biggest being age. The pathogenesis of AMD is unknown. Like many chronic illnesses, prevention is a key factor for managing AMD. Lutein and zeaxanthin, natural xanthophylls not synthesized by the human body, have been investigated for their use in promoting visual health. Lutein and zeaxanthin are dietary carotenoids that are components of a normal diet. The mechanism of protection that they confer is unknown, but two mechanisms have been hypothesized. Several studies have been conducted to assess the relationship between plasma levels of lutein and zeaxanthin and the risk of developing AMD and have yielded conflicting results. Increased dietary intake of or supplementation with lutein and zeaxanthin was found to result in increased plasma levels, which were positively and significantly associated with macular pigment optical density. Limited data have suggested that supplementation may also improve visual function. The optimal dose of lutein and zeaxanthin for the prevention or treatment of AMD has not yet been defined. CONCLUSION: A definite association between lutein and zeaxanthin supplementation and clinical benefit has yet to be shown; however, it may still be an appropriate cautionary measure for patients at high risk for developing AMD.

------

Surv Ophthalmol. 2008 Jul-Aug;53(4):359-67.
Cataract surgery and the development or progression of age-related macular degeneration: a systematic review.
Bockelbrink A, Roll S, Ruether K, Rasch A, Greiner W, Willich SN.
Institute for Social Medicine, Epidemiology, and Health Economics, Charité-University Medical Center, Berlin, Germany. angelina.bockelbrink@charite.de

Age-related macular degeneration and cataract are the most frequent eye disorders of elderly people worldwide. The aim of this systematic review was to evaluate the effect of cataract surgery on the development and progression of age-related macular degeneration. Data were collected by means of a systematic literature search in 28 databases and an additional update in Pubmed. Search results were evaluated using pre-defined inclusion and exclusion criteria. All relevant publications were rated in terms of scientific quality and analyzed regarding their results. The literature search generated a total of 2,827 hits. Seven publications on five observational studies and two non-randomized clinical trials were eligible for analysis. The observational studies provided some evidence for an increased incidence of late age-related macular degeneration, respectively, for a promoting influence of cataract surgery on the progression of early types of age-related macular degeneration. The clinical trials did yield inconsistent results. In conclusion, only a small number of published studies investigated the development or progression of age-related macular degeneration following cataract surgery. The scientific level of evidence of these articles was not high and results were inconsistent, nevertheless a promoting influence of cataract surgery on the progression of early age-related macular degeneration can be assumed.

------

BMC Med Genet. 2008 Jun 9;9:51.
The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration.
Zhang H, Morrison MA, Dewan A, Adams S, Andreoli M, Huynh N, Regan M, Brown A, Miller JW, Kim IK, Hoh J, Deangelis MM.
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. hong.zhang@yale.edu

BACKGROUND: To examine if the significantly associated SNPs derived from the genome wide allelic association study on the AREDS cohort at the NEI (dbGAP) specifically confer risk for neovascular age-related macular degeneration (AMD). We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS classification 1 or less and was past the age at which the affected sibling was diagnosed (268 subjects). Genotyping was performed by both direct sequencing and Sequenom iPLEX system technology. Single SNP analyses were conducted with McNemar's Test (both 2 x 2 and 3 x 3 tests) and likelihood ratio tests (LRT). Conditional logistic regression was used to determine significant gene-gene interactions. LRT was used to determine the best fit for each genotypic model tested (additive, dominant or recessive). RESULTS: Before release of individual data, p-value information was obtained directly from the AREDS dbGAP website. Of the 35 variants with P < 10-6 examined, 23 significantly modified risk of neovascular AMD. Many variants located in tandem on 1q32-q22 including those in CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was the most significantly associated with AMD risk (P < 10-6). Haplotype analysis supported our findings of single SNP association, demonstrating that the most significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated with the greatest risk of developing neovascular AMD (P < 10-6). Other than variants on 1q32-q22, only two SNPs, rs9288410 (MAP2) on 2q34-q35 and rs2014307 (PLEKHA1/HTRA1) on 10q26 were significantly associated with AMD status (P = .03 and P < 10-6 respectively). After controlling for smoking history, gender and age, the most significant gene-gene interaction appears to be between rs10801575 (CFH) and rs2014307 (PLEKHA1/HTRA1) (P < 10-11). The best genotypic fit for rs10801575 and rs2014307 was an additive model based on LRT. After applying a Bonferonni correction, no other significant interactions were identified between any other SNPs. CONCLUSION: This is the first replication study on the NEI dbGAP SNPs, demonstrating that alleles on 1q, 2q and 10q may predispose an individual to AMD.

------

Am J Clin Nutr. 2008 Jun;87(6):1837-43.
Prospective study of lutein/zeaxanthin intake and risk of age-related macular degeneration.
Cho E, Hankinson SE, Rosner B, Willett WC, Colditz GA.
Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. eunyoung.cho@channing.harvard.edu

BACKGROUND: The association between lutein/zeaxanthin intake and age-related macular degeneration (AMD) risk may differ by smoking status, vitamin C and E intakes, and body fatness. OBJECTIVE: The objective was to evaluate the association between lutein/zeaxanthin intake and AMD risk by smoking status, intake of antioxidant vitamins, and body fatness. DESIGN: We conducted a prospective follow-up study of 71 494 women and 41 564 men aged >or=50 y and had no diagnosis of AMD or cancer. Diet was assessed with a validated semiquantitative food-frequency questionnaire. RESULTS: During up to 18 y of follow-up, we documented 673 incident cases of early AMD and 442 incident cases of neovascular AMD with a visual loss of 20/30 or worse due primarily to AMD. Lutein/zeaxanthin intake was not associated with the risk of self-reported early AMD. There was a statistically nonsignificant and nonlinear inverse association between lutein/zeaxanthin intake and neovascular AMD risk; the pooled multivariate relative risks for increasing quintiles of intake were 1.00 (referent), 0.80, 0.84, 0.97, and 0.72 (95% CI: 0.53, 0.99) (P for trend = 0.14). For early AMD, the association with lutein/zeaxanthin intake did not vary by smoking status, intakes of vitamins C and E, or body mass index. For neovascular AMD, a nonlinear inverse association was found among never smokers. CONCLUSIONS: These data do not support a protective role of lutein/zeaxanthin intake on risk of self-reported early AMD. The suggestion of inverse associations related to the risk of neovascular AMD needs to be examined further.

------

Am J Geriatr Psychiatry. 2008 Jun;16(6):454-9.
Preventing late-life depression in age-related macular degeneration.
Rovner BW, Casten RJ.
Department of Psychiatry and Neurology, Jefferson Medical College, Jefferson Medical College, Philadelphia, PA 19107, USA. barry.rovner@jefferson.edu

OBJECTIVE: To determine whether problem-solving treatment (PST) can prevent depressive disorders in patients with age-related macular degeneration (AMD). DESIGN: Two hundred six patients with AMD were randomly assigned to PST (n = 105) or usual care (n = 101). PST therapists delivered six PST sessions over 8 weeks in subjects' homes. MEASUREMENTS: Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Diagnoses of Depressive Disorders, Hamilton Depression Rating Scale scores, and rates of relinquishing valued activities were assessed at 2 months for short-term effects and 6 months for maintenance effects. RESULTS: The 2-month incidence rate of depressive disorders in PST-treated subjects was significantly lower than controls (11.6% versus 23.2%, respectively; OR = 0.43; 95% CI [0.20, 0.95]). PST also reduced the odds of relinquishing a valued activity (OR = 0.48; 95% CI [0.25, 0.96]); this effect mediated the relationship between treatment group and depression. By 6 months most earlier observed benefits had diminished. Secondary analyses showed that a minimal level of depressive symptoms were disabling and predicted incident depressive disorders. CONCLUSION: PST prevented depressive disorders and loss of valued activities as a short-term treatment but these benefits were not maintained over time. To sustain PST's effect, an intervention that uses a problem-solving framework to enhance rehabilitative skills may be necessary.

------

Arch Ophthalmol. 2008 Jun;126(6):834-9.
Alcohol consumption and risk of aging macula disorder in a general population: the Rotterdam Study.
Boekhoorn SS, Vingerling JR, Hofman A, de Jong PT.
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands.

OBJECTIVE: To investigate the possible relationship between overall or specific alcohol consumption and risk of aging macula disorder (AMD), a synonym for age-related macular degeneration, in a general population. METHODS: Alcohol consumption and risk of early or late incident AMD (iAMD) were examined among all participants in the prospective population-based Rotterdam Study, with complete data on alcohol consumption among 4229 subjects at risk of AMD. Aging macula disorder was graded according to the International Classification and Grading System for AMD by 2 trained professionals who were masked for all other determinants. We used Cox proportional hazards regression models to estimate hazard ratios and corresponding 95% confidence intervals. RESULTS: During a mean follow-up period of 8.0 years, 600 cases of iAMD were identified, of which 519 were early iAMD and 81 were late iAMD. After correction for age, sex, smoking, complement factor H genotype status, and other potential confounders, we did not find an association between overall or specific alcohol consumption and development of early iAMD or dry or wet late iAMD. CONCLUSION: Our findings suggest that overall or specific alcohol consumption is not a risk factor for AMD.

------

Arch Ophthalmol. 2008 Jun;126(6):826-33.
Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis.
Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH.
Centre for Eye Research Australia, University of Melbourne, Victoria, Australia.

OBJECTIVE: To systematically review the evidence on dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration (AMD). METHODS: Seven databases were systematically searched with no limits on publication year or language using standardized criteria. Randomized controlled trials and prospective cohort, case-control, and cross-sectional studies were included. Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and 3 cross-sectional studies met the criteria. Measures of associations were pooled quantitatively using meta-analytic methods. RESULTS: Nine studies provided data on a total sample of 88 974 people, including 3203 AMD cases. A high dietary intake of omega-3 fatty acids was associated with a 38% reduction in the risk of late AMD (pooled odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.82). Fish intake at least twice a week was associated with a reduced risk of both early AMD (pooled OR, 0.76; 95% CI, 0.64-0.90) and late AMD (pooled OR, 0.67; 95% CI, 0.53-0.85). CONCLUSIONS: Although this meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, there is insufficient evidence from the current literature, with few prospective studies and no randomized clinical trials, to support their routine consumption for AMD prevention.

------

Retina. 2008 Jun;28(6):789-93.
Combination treatment with reduced-fluence photodynamic therapy and intravitreal injection of triamcinolone for subfoveal choroidal neovascularization in macular degeneration.
Singh CN, Saperstein DA.
Department of Ophthalmology, University of Washington, Seattle, WA, USA.

PURPOSE: To evaluate combination treatment with reduced-fluence photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVT) injection for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). METHODS: This is a retrospective consecutive case series of 23 previously untreated eyes of 22 patients with subfoveal CNV secondary to AMD. Six eyes were treated with 50 J/cm; 8, with 40 J/cm; and 9, with 25 J/cm. PDT was immediately followed by a 4-mg IVT injection. Patients were observed for 6 months at 6-week intervals. RESULTS:: The 50 J/cm subset lost a mean of 2.2 lines of Snellen visual acuity at the 6-month follow-up compared with a 1-line lost in the 40 J/cm subset and a 0.9-line gain in the 25 J/cm subset. In the 50 J/cm subset, 60% lost < or =3 lines of Snellen visual acuity, 33% gained > or =0 line, and 33% gained > or =3 lines. In the 40 J/cm subset, 75% lost < or =3 lines of Snellen visual acuity, 50% gained > or =0 line, and 25% gained > or =3 lines. In the 25 J/cm subset, 89% lost < or =3 lines of Snellen visual acuity, 56% gained > or =0 line, and 33% gained > or =3 lines. Fifty percent of the 50 J/cm subset, 50% of the 40 J/cm subset, and 33% of the 25 J/cm subset required retreatment by 6 months. CONCLUSION: Although the sample in this study was small, there was a dose-response trend toward better visual outcomes and fewer treatments in the group treated with IVT injection and reduced-fluence PDT. This study along with other previously reported work suggests that studies using PDT in combination treatment for CNV should consider adding a reduced-fluence PDT arm.

------

Ophthalmic Epidemiol. 2008 May-Jun;15(3):148-54.
LOC387715, smoking and their prognostic impact on visual functional status in age-related macular degeneration-The Muenster Aging and Retina Study (MARS) cohort.
Neuner B, Wellmann J, Dasch B, Dietzel M, Farwick A, Stoll M, Pauleikhoff D, Hense HW.
Institute of Epidemiology and Social Medicine, Clinical Epidemiology Section, University of Muenster, Muenster, Germany. neuner@uni-muenster.de

PURPOSE: To prospectively evaluate the impact of homozygosity in the A69S-SNP of the LOC387715-gene, smoking history, and their interaction on visual functional status (v-FS) in age-related macular degeneration (AMD). METHODS: The Muenster Aging and Retina Study (MARS) cohort (n = 656; 58.8% women, mean age 70.2 years) was followed over a mean of 2.5 years. AMD-status, genotype and smoking history were assessed at baseline. V-FS [from 0 (low) to 100 (unimpaired) points in general-, near- and far-vision], were AMD-status assessed at baseline and at follow-up. Linear models with stepwise adjustments for covariates were used to analyze decline of v-FS over time. RESULTS: In initial models, homozygosity for the A69S-variant was negatively associated with all three dimensions of the v-FS. After including smoking history, ever smoking was negatively associated with declines in near and far vision (-4.82 and -5.12 points, respectively; each p < 0.05). In smokers homozygous for the A69S-variant the number of cigarettes smoked per day (smoking intensity) was negatively associated with all three dimensions of the v-FS (interaction term each p < 0.05). Time since smoking cessation in former smokers protected against declines in near and far vision. These effects were independent of the AMD-status at baseline. CONCLUSIONS: The interaction of homozygosity for the A69S-variant and smoking intensity had a negative impact on general-, near-, and far visual functional status independent of AMD-status. Quitting smoking seemed to have a time-dependent protective effect on near and far vision.

------

Ann Ophthalmol (Skokie). 2008 Spring;40(1):28-30.
Anecortave acetate for fibrotic lesions with presence of residual peripheral activity in age-related macular degeneration.
Aggermann T, Haas P, Binder S.
Ludwig Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery, Vienna, Austria. tina@aggermann.at

We retrospectively examined the efficacy of a single juxtascleral anecortave acetate depot injection for the treatment of fibrotic choroidal neovascular lesions with presence of residual peripheral activity in age related macular degeneration in 20 consecutive patients who rejected intravitreal treatment. As a second line-therapy of classic and occult fibrotic lesions with active peripheral zones, anecortave seems to be a vision conserving therapeutic option.

------

Rev Med Interne. 2008 Mar;29(3):215-223. Epub 2007 Oct 31.
[Age-related macular degeneration.]
[Article in French]
Parier V, Soubrane G.
Département universitaire d’ophtalmologie, centre hospitalier intercommunal de Créteil-universitaire Paris-12, 94010 Créteil, France.

PURPOSE: Age-related macular degeneration is the commonest overall cause of irreversible blindness in patients aged 50 or over in the Western world. CURRENT KNOWLEDGE AND KEY POINTS: Because of the interaction of genetic and environmental origin, the pathogenesis of this affection remains imperfectly elucidated. The disease has been traditionally classified into early and late stages with its dry and wet forms. In association with fluorescein angiography, essential for diagnosis, green indocyanin angiography and optical coherence tomography made it possible to better know the clinical forms of the disease. Patients with age-related maculopathy should consider taking a dietary supplement such as that used in the age-related eye disease study. Exudative age-related macular degeneration is approached depending on the type and localisation of the choroidal new vessels. Laser photocoagulation has only been shown to be beneficial for extra and juxtafoveal classic lesions. Photodynamic therapy with verteporfin is effective in the management of eyes with subfoveal predominantly classic lesions. The encouraging results of new therapeutic with antiangiogenic aiming against vascular endothelial growth factor are a hope to preserve the sight of our patients. FUTURE PROSPECTS AND PROJECTS: In the future, many therapeutics inhibiting neo-vessels will widen our therapeutic options in the treatment of exsudative age-related macular degeneration.

-----

Br Med Bull. 2008;85:127-49.
Age-related macular degeneration: diagnosis and management.
Cook HL, Patel PJ, Tufail A.
Correspondence to Mr A. Tufail Moorfields Eye Hospital City Road London EC1V 2PD adnan.tufail@moorfields.nhs.uk.

Background Age-related macular degeneration (AMD) is a leading cause of blind registration in Western Europe and the third leading cause of blindness worldwide. Methods The management of AMD is discussed with a review of current and new treatments. Results Although there is no treatment for advanced dry AMD (geographic atrophy), there have been considerable advances in the management of neovascular AMD (nAMD). Established therapies for nAMD include laser photocoagulation and photodynamic therapy (PDT), but these have largely been superseded by agents which block the action of vascular endothelial growth factor (anti-VEGF agents). Current preventative strategies involve cessation of smoking and use of specific nutritional supplements to reduce the risk of developing nAMD. Conclusions There have been exciting advances in the treatment of nAMD and increased understanding of the genetics and pathogenic mechanisms involved will hopefully lead to the development of new therapies in
the future.

-----

Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1079-83.
Phacoemulsification does not induce neovascular age-related macular degeneration.
Baatz H, Darawsha R, Ackermann H, Scharioth GB, de Ortueta D, Pavlidis M, Hattenbach LO.
Recklinghausen Eye Centre, Recklinghausen, Germany; the.

PURPOSE: To investigate whether cataract surgery by phacoemulsification induces progression of early age-related macular degeneration (AMD) to neovascular AMD. METHODS: Retrospective case-control study. Included were consecutive patients who had undergone phacoemulsification from January 2000 to February 2006 at the Recklinghausen Eye Centre, who had a preexisting diagnosis of early AMD and who were followed up for at least 1 year after surgery (n = 1152 eyes of 696 patients). The control group comprised phakic patients diagnosed with early AMD from January 2000 to February 2006, who did not undergo eye surgery and were followed up for at least 1 year (n = 334 eyes of 202 patients). RESULTS: At baseline, control eyes had significantly better visual acuity than those of patients who were going to have cataract surgery (0.30/0.35 +/- 0.34 vs. 0.40/0.49 +/- 0.34, respectively; median/mean +/- SD; P < 0.001, Mann-Whitney rank sum test). After 1 year, visual acuity in the control group was worse than in surgical eyes (0.30/0.39 +/- 0.38 vs. 0.20/0.26 +/- 0.30, respectively; median/mean +/- SD; P < 0.001, Mann-Whitney rank sum test). In the cataract surgery group, neovascular AMD developed in 28 (2.43%) of 1152 eyes in the first postoperative year. In the control group, it developed in 6 (1.74%) of 344 eyes within 1 year. There was no significant difference between the groups in the incidence of neovascular AMD (P = 0.57, odds ratio 1.30, 95% CI 0.52-3.24, logistic regression analysis, adjusted for age and baseline visual acuity). CONCLUSIONS: The results indicate that cataract surgery in eyes with early AMD is not a causative factor in neovascular AMD.

-----

Am J Ophthalmol. 2008 Mar 3 [Epub ahead of print]
Ranibizumab Combined With Verteporfin Photodynamic Therapy in Neovascular Age-related Macular Degeneration (FOCUS): Year 2 Results.
Antoszyk AN, Tuomi L, Chung CY, Singh A; on behalf of the FOCUS STUDY GROUP.
Charlotte Eye, Ear, Nose and Throat Associates, Charlotte, North Carolina.

PURPOSE: To assess the efficacy and adverse-events profile of combined treatment with ranibizumab and verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration. DESIGN: Two-year, multicenter, randomized, single-masked, controlled study. METHODS: Patients received monthly intravitreal injections of ranibizumab 0.5 mg (n = 106) or sham injections (n = 56). All patients received PDT on day zero, then quarterly as needed. Efficacy assessment included changes in visual acuity (VA) and lesion characteristics and PDT frequency. Adverse events were summarized by incidence and severity. RESULTS: At month 24, 88% of ranibizumab + PDT patients had lost <15 letters from baseline VA (vs 75% for PDT alone), 25% had gained >/=15 letters (vs 7% for PDT alone), and the two treatment arms differed by 12.4 letters in mean VA change (P < .05 for all between-group differences). The VA
benefit of adding ranibizumab to PDT in year one persisted through year two. On average, ranibizumab + PDT patients exhibited less lesion growth and greater reduction of CNV leakage and subretinal fluid accumulation, and required fewer PDT retreatments, than PDT-alone patients (mean = 0.4 vs 3.0 PDT retreatments). Endophthalmitis and serious intraocular inflammation occurred, respectively, in 2.9% and 12.4% of ranibizumab + PDT patients and 0% of PDT-alone patients. Incidences of serious nonocular adverse events were similar in the two treatment groups. CONCLUSIONS: Through two years, ranibizumab + PDT was more effective than PDT alone and had a low rate of associated adverse events.

-----

Retina. 2008 Feb;29(2):289-297.
12-month retrospective study and review of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration
Incorvaia C, Campa C, Parmeggiani F, Menzione M, D'Angelo S, Corte MD, Rinaldi M, Romano M, Dell'omo R, Costagliola C.
From *Department of Ophthalmology, University of Ferrara, Ferrara, Italy; †Eye Clinic, Federico II University, Naples, Italy; and ‡Department of Health Sciences, University of Molise, Campobasso, Italy.

PURPOSE:: To evaluate the 12-month visual outcome of photodynamic therapy with verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration and to verify the predictive role of visual and angiographic factors. METHODS:: This retrospective, interventional, consecutive case series study included subjects with different forms of subfoveal CNV. All patients received PDT-V according to Treatment of Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in Photodynamic Therapy guidelines. A review of medical and angiographic records was performed. RESULTS:: Two hundred sixteen patients were divided into 4 study groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was moderately decreased, without reaching a statistically noticeable level during the entire follow-up; lesion size reduction only reached significance in group I. Groups III and IV showed evident worsening of BCVA (P < 0.05), despite concomitant reduction in CNV size (statistically remarkable only for occult CNV). All study groups exhibited a significant correlation between higher baseline BCVA and better final visual outcome. In groups II and IV, smaller baseline CNV sizes also favorably influenced final BCVA. CONCLUSIONS:: Standardized PDT-V minimizes deterioration of central vision only in patients with classic and predominantly classic CNV. Irrespective of the CNV type, better BCVA at presentation represents a good predictive sign. In predominantly classic and occult lesions, minor initial CNV dimension is also a positive prognostic element.

-----

Ophthalmologe. 2008 Feb 27 [Epub ahead of print]
[Intravitreal anti-VEGF therapy with bevacizumab for neovascular AMD.]
[Article in German]
Schaal KB, Engler C, Schütt F, Scheuerle A, Dithmar S.
Schwerpunkt Retinologie, Universitäts-Augenklinik, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland.

PURPOSE: To report on the efficacy of intravitreal bevacizumab as off-label therapy in different angiographic subtypes in neovascular age-related macular degeneration (AMD). METHODS: Seventy-five patients with neovascular AMD and recent disease progression were classified into different angiographic subtypes and were treated with intravitreal bevacizumab (1.25 mg/0.05 ml) at 6-week intervals. Patients with subfoveal classic choroidal neovascularization (CNV) also received photodynamic therapy. ETDRS visual acuity, ophthalmic exams, and optic coherence tomography (OCT) were performed before treatment, 1 week after treatment, and then on a 6-week basis. Fluorescein angiographies and medical check-ups were also done. RESULTS: Bevacizumab led to stabilization of visual acuity (loss of less than 15 letters) in all angiographic subtypes during a follow-up of 37+/-13 weeks. Patients with occult extrafoveal CNV (n=6) profited the most and gained 2+/-2 lines. Treatment with intravitreal bevacizumab was very well tolerated in all patients, with neither systemic nor intraocular side effects, with the exception of one retinal pigment epithelium tear. CONCLUSION: Intravitreal bevacizumab treatment is efficacious in all angiographic CNV subtypes and leads to reduction of macular edema and stabilization or improvement in visual acuity.

-----

Ophthalmologe. 2008 Feb 27 [Epub ahead of print]
[Intravitreal administration of triamcinolone and bevacizumab for pigment epithelial detachment in conjunction with AMD.]
[Article in German]
Frimpong-Boateng A, Varde MA, Rüfer F, Bunse A, Roider J.
Augenklinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Hegewischstr. 2, 24105, Kiel, Deutschland, afrimpong@ophthalmol.uni-kiel.de.

BACKGROUND: The effect of the vascular endothelial growth factor (VEGF) inhibitors triamcinolone and bevacizumab (Avastin) on serous pigment epithelial detachment (PED) related to age-dependent macular degeneration (AMD) was analysed retrospectively. PATIENTS AND METHODS: Data of 45 patients (45 eyes) were evaluated: 11 patients received an intravitreal injection with triamcinolone and 16 with bevacizumab. The remaining 18 patients received no therapy. Visual acuity (VA), height of the PED, retinal thickness and the cystoid component of the PED were compared after 6 months follow-up. RESULTS: Over 90% showed a stabilisation or improvement in VA after bevacizumab therapy; 63% of those who received triamcinolone showed VA stabilisation. Patients who received no therapy had a significant decrease in VA. CONCLUSIONS: Our data seem to implicate that VA outcome is much better after bevacizumab treatment. VA outcome seems to correlate with the cystoid component of the foveal oedema rather than with the height of PED. A greater number of patients with a longer period of follow-up are necessary to confirm these results.

-----

Ophthalmic Surg Lasers Imaging. 2008 Jan-Feb;39(1):12-6.
The temporal sequence of combined intravitreal triamcinolone acetonide and photodynamic therapy for exudative age-related macular degeneration.
Roth DB, Kulkarni KM, Feuer WJ.
Retina Vitreous Center, Department of Ophthalmology, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick 08901-1977, USA.

BACKGROUND AND OBJECTIVE: To compare visual acuity results in patients with exudative age-related macular degeneration treated with two different temporal sequences of combination intravitreal triamcinolone acetonide and photodynamic therapy with verteporfin. PATIENTS AND METHODS: A retrospective, comparative, interventional case series was used. Thirty-one eyes received intravitreal triamcinolone acetonide 1 week prior to photodynamic therapy, and 30 eyes received intravitreal triamcinolone acetonide followed by photodynamic therapy the same day. RESULTS: There was no significant difference in visual acuity between the groups at baseline (P = .084), 6 to 12 weeks of follow-up (P = .085), or 1 year of follow-up (P= .093). When visual acuity outcomes were adjusted for baseline visual acuity, spot size, lesion type, age, and gender, there was no significant difference in visual acuity at 6 to 12 weeks (P = .44) or 1 year (P= .28). CONCLUSIONS: There appears to be no significant
difference in visual outcomes in eyes with exudative age-related macular degeneration treated with intravitreal triamcinolone acetonide 1 week prior to photodynamic therapy or those treated with intravitreal triamcinolone acetonide on the same day as photodynamic therapy.

-----

Clin Exp Optom. 2008 Jan;91(1):78-84.
A review of the potential to restore vision with stem cells.
Mooney I, Lamotte J.
Southern California College of Optometry, Fullerton, California, USA.

Vision research involving stem cells is a rapidly evolving field. Animal experiments have shown that in response to environmental cues, stem cells can repopulate damaged retinas, regrow neuronal axons, repair higher cortical pathways, and restore pupil reflexes, light responses and basic pattern recognition. Viable corneas have been grown from stem cells and transplanted into humans. Similarly, human trials to repair damaged retinas in retinitis pigmentosa and age-related macular degeneration patients have produced preliminary successes. This review attempts to place the collective contributions toward stem cell/vision research into a broader clinical model of how stem cells might ultimately be used to restore the entire visual pathway.

-----

Ophthalmologe. 2007 Dec 14 [Epub ahead of print]
[Lutein and antioxidants in the prevention of age-related macular degeneration.]
[Article in German]
Rehak M, Fric E, Wiedemann P.
Klinik und Poliklinik für Augenheilkunde, Universität Leipzig, Liebigstraße 10–14, 04103, Leipzig, Deutschland, augen@medizin.uni-leipzig.de.

Demographic developments in Europe and North America are causing an increase of age-related diseases. Age-related macular degeneration (AMD) is one of the leading causes of severe central visual acuity loss in elderly people and seems to be an economic problem, too. There is evidence that oxidative damage is an important factor for exacerbation of AMD. Macular pigment with its antioxidative effect may serve as"natural sunglasses" filtering the blue light acting as a possible source of photooxidative damage to the neurosensory retina. The macular pigment consists mostly of lutein and zeaxanthin. These micronutrients from the group of carotenoids, as is the case for vitamins (vitamins C, E, and beta-carotene), cannot be synthesized in mammals and that is the reason why the role of micronutrition or its supplementation and its correlation to AMD progression has been discussed for years.The results of currently published studies are often contradictory. At present there are no results from randomized controlled studies confirming that supplementation of lutein and zeaxanthin can reduce the risk for AMD. Several epidemiological studies investigating the impact of antioxidants and omega-3 fatty acids on the incidence of AMD provided conflicting results.Up to now, AREDS is the largest randomized controlled study investigating the effect of supplementation of antioxidants, zinc, and copper on the progression of AMD. AREDS showed a significant effect of this supplementation in some particular groups of patients with AMD. The supplementation of lutein and omega-3 fatty acids is not toxic but a positive effect has not been proven by randomized studies.

-----

Aust Fam Physician. 2007 Dec;36(12):1026-8.
Age related macular degeneration--should your patients be taking additional supplements?
Jones AA.
City Eye Centre, Brisbane, Queensland. draajones@hotmail.com

BACKGROUND: The use of over-the-counter complementary medicines and supplements is growing. Patients with age related macular degeneration (AMD) are likely to have heard of, or are possibly already taking, additional supplements that may increase their chances of retaining useful eyesight. OBJECTIVE: This article looks specifically at evidence regarding the effects of over-the-counter oral supplements such as antioxidants and omega-3 fatty acids on AMD. DISCUSSION: Diet manipulation and supplementation has a role to play in modifying the risk of disease progression in AMD patients. A combination of vitamins C and E, beta carotene, zinc oxide and cupric oxide has been shown to reduce the rate of visual loss in dry AMD. However, commercially available preparations do not always recommend the correct intake that would match levels found in clinical trials. Other carotenoids such as lutein and zeaxanthin may also be beneficial, intake of these can be increased by altering diet alone. Other useful dietary changes include reducing both animal and vegetable fats and increasing the consumption of fish and nuts.

-----

Graefes Arch Clin Exp Ophthalmol. 2007 Dec 11 [Epub ahead of print]
Time-dependent effects on contrast sensitivity, near and distance acuity: difference in functional parameters? (Prospective, randomized pilot trial of photodynamic therapy versus full macular translocation).
Ziemssen F, Lüke M, Bartz-Schmidt KU, Gelisken F.
Department for Ophthalmology, University Eye Hospital, Eberhard-Karls University, Schleichstr. 12-16, 72076, Tuebingen, Germany, focke.ziemssen@med.uni-tuebingen.de.

PURPOSE: To report the change of contrast sensitivity (CS) after photodynamic therapy (PDT) vs full macular translocation (FMT) for neovascular age-related macular degeneration (AMD), and to relate this to other measures of visual function (distance and near acuity). METHODS: Fifty patients (50 eyes) with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. CS was measured with Pelli-Robson charts. Acuity scores of near visual function (NVS) were calculated after testing with visual acuity cards of the Swiss National Association of and for the Blind (SNAB). Best corrected distance visual acuity (DVA) was determined according to a standardized protocol with EDTRS charts. Primary end point was the change of CS at 12-month examination from baseline. The interaction of the CS with NVS and DVA was analysed. RESULTS: Mean CS showed a decrease in both treatment groups (FMT: -2 letters, PDT: -3 letters, p = 0.969) at 12-month examination from baseline. While mean NVS improved by seven letters in the FMT group, a decrease of more than ten letters was seen in the PDT group (p < 0.05). We found no agreement between CS and high-contrast acuity (NVS, DVA). In FMT patients, the parameters at baseline (CS, NVS, DVA) correlated poorly with the corresponding 12-month results, therefore providing no informative basis to predict the later functional development. In contrast, PDT patients showed strong baseline-to-outcome coherence with baseline measures also associated with better final values. CONCLUSIONS: Although FMT can initiate recovery of near and distance acuity over the period of 1 year in selected patients with classic CNV, CS did not differ between FMT and PDT. We found no close connection of CS with DVA or NVS, especially after FMT. Knowledge about the unequal variation of visual parameters can provide more comprehensive information when advising patients on different therapeutic options. That also applies in particular to vascular endothelial growth factor inhibitors, which seem to promise an even higher extent of gain in CS and to reach the peak of recovery at an earlier time.

-----

Ophthalmology. 2007 Dec;114(12):2183-9.
Triamcinolone acetonide as adjunctive treatment to verteporfin in neovascular age-related macular degeneration: a prospective randomized trial.
Chaudhary V, Mao A, Hooper PL, Sheidow TG.
Ivey Eye Institute, University of Western Ontario, London, Canada. vchaudha@uwo.ca

PURPOSE: To examine the use of intravitreal triamcinolone acetonide (IVTA) as adjunctive therapy to photodynamic therapy (PDT) in the treatment of occult and minimally classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Single-center prospective randomized pilot clinical trial. PARTICIPANTS: Thirty eyes of 30 patients with occult or minimally classic CNV secondary to AMD. METHODS: Patients were randomized prospectively to receive either PDT alone or combined PDT plus IVTA treatment for CNV secondary to AMD. Standard verteporfin PDT was performed in all patients. In the PDT plus IVTA group, a 12-mg intravitreal injection of triamcinolone acetonide was given 30 minutes after PDT. Active lesions were retreated every 3 months for 1 year. MAIN OUTCOME MEASURES: Change in visual acuity and retreatment rate. RESULTS: Mean visual acuity remained stable in the PDT plus IVTA group (-1.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; P = 0.58), but declined significantly in the PDT alone group (-13.3 ETDRS letters; P = 0.02). The treatment rate was 1.13 in the PDT plus IVTA group and 3.6 in the PDT alone group (P<0.0001). Mean contrast sensitivity increased by 3.6 letters (P = 0.09) in the PDT plus IVTA group and decreased by -1.84 letters (P = 0.07) in the PDT alone group. Cataract progression was noted in 4 of 7 phakic eyes in the PDT plus IVTA group. Six patients (40%) in the combined PDT plus IVTA group required topical glaucoma therapy for control of elevated intraocular pressure. CONCLUSIONS: This pilot study demonstrated effective stabilization of visual acuity and reduced treatment frequency at 12 months with combination PDT plus IVTA therapy versus PDT alone. Larger randomized trials are ongoing to determine the efficacy and risks of PDT with IVTA.

-----

Am J Ophthalmol. 2007 Dec;144(6):970-972.
Verteporfin Therapy of Subfoveal Occult Choroidal Neovascularization in AMD Using Delayed Light Application: One-year Results of the VALIO Study.
Rosenfeld PJ, Boyer DS, Bressler NM, Fish G, Grizzard WS, Hao Y, Hnik P, Hudson HL, Singerman L, Slakter JS; VALIO Study Group.
Bascom Palmer Eye Institute, Miami, Florida.

PURPOSE: To compare photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) using either standard or delayed light application. DESIGN: Phase II, multicenter, masked, randomized clinical trial. METHODS: Sixty patients with occult with no classic choroidal neovascularization (CNV) resulting from age-related macular degeneration were assigned randomly (1:1) to verteporfin infusion followed by light application either at 15 minutes (standard light) or 30 minutes (delayed light) after the start of the infusion. The assigned treatment was repeated every three months if fluorescein leakage was detected. RESULTS: At month 12, patients lost a mean of 15.7 letters and 11.4 letters from baseline in the standard and delayed light groups, respectively (P = .38). Twelve (52%) of 23 patients in the standard light group and 11 (42%) of 26 in the delayed light group lost at least 15 letters of visual acuity (P = .57). CONCLUSIONS: There were no statistically significant differences between verteporfin therapy using the delayed light regimen of 30 minutes or the standard light regimen of 15 minutes in eyes with occult with no classic CNV.

-----

Drugs Aging. 2007;24(7):581-602.
Sustained-release ophthalmic drug delivery systems for treatment of macular disorders: present and future applications.
Booth BA, Vidal Denham L, Bouhanik S, Jacob JT, Hill JM.
Department of Ophthalmology, LSU Health Sciences Center, New Orleans, Louisiana, USA.

Macular disease currently poses the greatest threat to vision in aging populations. Historically, most of this pathology could only be dealt with surgically, and then only after much damage to the macula had already occurred. Current pathophysiological insights into macular diseases have allowed the development of effective new pharmacotherapies. The field of drug delivery systems has advanced over the last several years with emphasis placed on controlled release of drug to specific areas of the eye. Its unique location and tendency toward chronic disease make the macula an important and attractive target for drug delivery systems, especially sustained-release systems. This review evaluates the current literature on the research and development of sustained-release posterior segment drug delivery systems that are primarily intended for macular disease with an emphasis on age-related macular degeneration.Current effective therapies include corticosteroids and anti-vascular endothelial growth factor compounds. Recent successes have been reported using anti-angiogenic drugs for therapy of age-related macular degeneration. This review also includes information on implantable devices (biodegradable and non-biodegradable), the use of injected particles (microspheres and liposomes) and future enhanced drug delivery systems, such as ultrasound drug delivery. The devices reviewed show significant drug release over a period of days or weeks. However, macular disorders are chronic diseases requiring years of treatment. Currently, there is no 'gold standard' for therapy and/or drug delivery. Future studies will focus on improving the efficiency and effectiveness of drug delivery to the posterior chamber. If successful, therapeutic modalities will significantly delay loss of vision and improve the quality of life for patients with chronic macular disorders.

-----

Acta Ophthalmol Scand. 2007 Aug;85(5):486-94.
Guidance for the treatment of neovascular age-related macular degeneration.
Schmidt-Erfurth UM, Richard G, Augustin A, Aylward WG, Bandello F, Corcòstegui B, Cunha-Vaz J, Gaudric A, Leys A, Schlingemann RO; on behalf of the European Society for Retina Specialists' Guidelines Committee (EURETINA).
Department of Ophthalmology, Medical University of Vienna, Austria.

Neovascular age-related macular degeneration is becoming an increasing socio-medical problem as the proportion of the aged population is continuously increasing. However, new insights in the pathogenesis of the disease offer the opportunity to develop targeted therapies that attack the disease process more successfully than ever. This review article will focus on summarizing the actual options in the management of neovascular age-related macular degeneration and provide a short overview about recent therapeutic options in clinical and preclinical evaluation. The recent development of anti-VEGF substances for use in clinical routine has markedly improved the prognosis of patients with neovascular AMD. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF), for the first time in the history of AMD treatments, results in a significant increase in visual acuity in patients with neovascular AMD. Overall, antiangiogenic approaches provide vision maintenance in over 90% and substantial improvement in 25-40% of patients. The combination with occlusive therapies like photodynamic therapy (PDT) potentially offers a reduction of re-treatment frequency and long-term maintenance of the treatment benefit. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. Nevertheless, the growing number of novel therapeutic options will have to provide proof of concept in randomized controlled clinical trials, a major challenge in view of the rapidly evolving field. For those therapies, which are already in clinical use, reasonable diagnostic tools for follow-up need to be developed, as the burden of continuous clinical monitoring of all patients and all indications is significant for patients and doctors. Ultimately, economic issues will be the limiting factor for the clinical availability of different treatment options.

-----

Retina. 2007 Jul-Aug;27(6):693-700.
Effect of adjunctive diclofenac with verteporfin therapy to treat choroidal neovascularization due to age-related macular degeneration: phase II study.
Adjunctive Diclofenac with Verteporfin (ADD-V) Study Group, Boyer DS, Beer PM, Joffe L, Koester JM, Marx JL, Weisberger A, Yoser SL.

BACKGROUND: To determine short-term effects of topical diclofenac administered in conjunction with verteporfin therapy for predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: Randomized, multicenter (14), prospective, placebo-controlled, double-masked clinical trial. Patients (n=61) were randomly assigned to treatment with diclofenac sodium ophthalmic solution 0.1% or placebo and followed for 12 weeks. Patients instilled diclofenac or placebo two drops four times daily, 2-4 days before verteporfin treatment until 2 weeks after treatment, then two drops twice daily for 10 weeks. This exploratory study was not powered to detect differences between treatment groups. Statistical analyses were conducted solely to aid interpretation of results. RESULTS: In diclofenac-treated eyes, mean changes in visual acuity letter score from baseline in the diclofenac and placebo groups were +1.8 letters and -1.0 at week 1 (P=0.505 between groups). Mean visual acuity letter scores decreased in both groups at all subsequent visits, with a mean change at 12 weeks of -7.4 with diclofenac and -2.6 with placebo (P=0.213). Percentages of eyes with stable or improved vision (change <or=4 or increase >or=5 letters) were similar in the diclofenac and placebo groups at all study visits. No significant between-group differences in changes from baseline in lesion area, greatest linear dimension (GLD), fluorescein leakage, or retinal thickness were detected. CONCLUSION: In patients with predominantly classic subfoveal CNV due to AMD, administration of topical diclofenac with verteporfin therapy was associated with similar vision outcomes to placebo plus verteporfin therapy.

-----

Acta Ophthalmol Scand. 2007 Jul 25; [Epub ahead of print]
Reading performance with low-vision aids and vision-related quality of life after macular translocation surgery in patients with age-related macular degeneration.
Nguyen NX, Besch D, Bartz-Schmidt K, Gelisken F, Trauzettel-Klosinski S.
Department of Ophthalmology II, University Eye Hospital, Tübingen, Germany.

Purpose: The aim of the present study was to evaluate the power of magnification required, reading performance with low-vision aids and vision-related quality of life with reference to reading ability and ability to carry out day-to-day activities in patients after macular translocation. Methods: This study included 15 patients who had undergone macular translocation with 360-degree peripheral retinectomy. The mean length of follow-up was 19.2 +/- 10.8 months (median 11 months). At the final examination, the impact of visual impairment on reading ability and quality of life was assessed according to a modified 9-item questionnaire in conjunction with a comprehensive clinical examination, which included assessment of best corrected visual acuity (BCVA), the magnification power required for reading, use of low-vision aids and reading speed. Patients rated the extent to which low vision restricted their ability to read and participate in other activities that affect quality of life. Responses were scored on a scale of 1.0 (optimum self-evaluation) to 5.0 (very poor). Results: In the operated eye, overall mean postoperative BCVA (distance) was not significantly better than mean preoperative BCVA (0.11 +/- 0.06 and 0.15 +/- 0.08, respectively; p = 0.53). However, 53% of patients reported a subjective increase in visual function after treatment. At the final visit, the mean magnification required was x 7.7 +/- 6.7. A total of 60% of patients needed optical magnifiers for reading and in 40% of patients closed-circuit TV systems were necessary. All patients were able to read newspaper print using adapted low-vision aids at a mean reading speed of 71 +/- 40 words per minute. Mean self-reported scores were 3.2 +/- 1.1 for reading, 2.5 +/- 0.7 for day-to-day activities and 2.7 +/- 3.0 for outdoor walking and using steps or stairs. Patients' levels of dependency were significantly correlated with scores for reading (p = 0.01), day-to-day activities (p < 0.001) and outdoor walking and using steps (p = 0.001). Conclusions: The evaluation of self-reported visual function and vision-related quality of life in patients after macular translocation is necessary to obtain detailed information on treatment effects. Our results indicated improvement in patients' subjective evaluations of visual function, without significant improvement in visual acuity. The postoperative clinical benefits of treatment coincide with subjective benefits in terms of reading ability, quality of life and patient satisfaction. Our study confirms the importance and efficiency of visual rehabilitation with aids for low vision after surgery.

-----

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004763.
Laser photocoagulation for neovascular age-related macular degeneration.
Virgili G, Bini A.

BACKGROUND: Laser photocoagulation was the first treatment introduced to try to halt the progression of neovascular age-related macular degeneration (AMD), in which newly formed vessels or choroidal neovascularisation (CNV) grow under the macula leading to the occurrence of a scotoma or blind spot in the central visual field. OBJECTIVES: The aim of this review was to examine the effects of laser photocoagulation for neovascular AMD. SEARCH STRATEGY: We searched the CENTRAL, MEDLINE, EMBASE, LILACS, NRR and ZETOC in March 2007. SELECTION CRITERIA: We included randomised trials of laser photocoagulation in people with CNV due to AMD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. The risk ratio (RR) of severe visual loss (loss of six or more lines of visual acuity) was estimated at three months and two years after treatment. MAIN RESULTS: Fifteen trials were included in the review (2064 participants). Three types of photocoagulation were used in the trials: direct photocoagulation of the entire CNV (11 trials), perifoveal photocoagulation (one trial) and grid photocoagulation (three trials). In 12 trials the control group was observation only. One trial compared photocoagulation to submacular surgery and two trials compared different lasers. Data on the progression of visual loss could be extracted from five of the eight trials of direct photocoagulation of the CNV versus observation. The treatment effect was in the direction of harm in all studies at three months follow up (RR 1.41, 95% confidence intervals (CI) 1.08 to 1.82). After two years the treatment effect was in the direction of benefit (RR 0.67, 95% CI 0.53 to 0.83). These studies were clinically heterogenous with participants having CNV lesions in different locations and different baseline visual acuities. There was little evidence of statistical heterogeneity at three months but substantial statistical heterogeneity at two years. However, all treatment effects in the individual trials were in the direction of benefit. One study comparing perifoveal photocoagulation or observation of subfoveal CNV found benefits that were statistically significant only at two years (RR 0.36, 95% CI 0.18 to 0.72). Other comparisons did not demonstrate differences. AUTHORS' CONCLUSIONS: In the medium to long term laser photocoagulation of CNV slows the progression of visual loss in people with neovascular AMD. However, it is associated with an increased risk of visual loss immediately after treatment and this period may be longer in people with subfoveal AMD. With the advent of modern pharmacological therapies, and concern for the impact of iatrogenic scotoma in subfoveal CNV, laser photocoagulation of subfoveal CNV is not recommended. No studies have compared photocoagulation with modern pharmacological agents for AMD for non-subfoveal CNV.

-----

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD002030.
Photodynamic therapy for neovascular age-related macular degeneration.
Wormald R, Evans J, Smeeth L, Henshaw K.

BACKGROUND: In neovascular age-related macular degeneration (AMD) new vessels grow under the retina distorting vision and leading to scarring. This is exacerbated if the blood vessels leak. Photodynamic therapy (PDT) has been investigated as a way to treat the neovascular membranes without affecting the retina. OBJECTIVES: The aim of this review was to examine the effects of PDT in the treatment of neovascular AMD. SEARCH STRATEGY: We searched CENTRAL (Issue 1, 2007), MEDLINE (1966 to March 2007), EMBASE (1980 to March 2007). We contacted experts in the field and searched the reference lists of relevant studies. SELECTION CRITERIA: We included randomised trials of PDT in people with choroidal neovascularisation due to AMD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. Risk ratios were combined using a fixed-effect model after testing for heterogeneity. MAIN RESULTS: Three published trials were identified that randomised 1022 participants to verteporfin therapy compared to 5% dextrose in water. The TAP and VIP trials were performed by the same investigators using largely the same clinical centres and funded by manufacturers of verteporfin. Outcome data were available at 12 and 24 months after the first treatment. Participants received on average five treatments over two years. The risk ratio of losing three or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.77 (95% confidence interval 0.69 to 0.87). The risk ratio of losing six or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.62 (95% confidence interval 0.50 to 0.76). The results at 12 months were similar to those at 24 months. The most serious adverse outcome, acute (within seven days of treatment) severe visual acuity decrease, occurs in about one in 50 patients. Some outcomes from the more recent VIM trial could be included in the meta-analysis but have not greatly altered the findings. AUTHORS' CONCLUSIONS: Photodynamic therapy in people with choroidal neovascularisation due to AMD is probably effective in preventing visual loss though there is doubt about the size of the effect. Outcomes and potential adverse effects of this treatment should be monitored closely. Further independent trials of verteporfin are required to establish that the effects seen in this study are consistent and to examine important issues not yet addressed, particularly relating to quality of life and cost. However, the advent of new interventions for AMD make this unlikely.

-----

Optom Vis Sci. 2007 Jul;84(7):559-72.
Current treatment of age-related macular degeneration.
Zarbin M, Szirth B.
Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark, New Jersey 07103, USA. zarbin@umdnj.edu

PURPOSE: To review proved and experimental treatments for exudative and nonexudative complications of age-related macular degeneration (AMD), to consider the impact of current therapy on the structure of future clinical trials, and to consider the role of improved diagnostic imaging techniques on the effectiveness of current therapy as well as the structure of future clinical trials in AMD patients. RESULTS: Defining the cell biology of choroidal new vessel (CNV) formation and geographic atrophy will lead to identification of different biochemical pathways that are the target of AMD treatment. Many treatments and treatment combinations are under study for AMD, but all work through a finite number of pathways. Currently, the most effective proved therapy for AMD-associated CNVs is administered by repeated intravitreal injection of agents that inhibit vascular endothelial growth factor, e.g., ranibizumab. Improved drug delivery will enhance patient satisfaction and possibly will enhance the effectiveness and reduce the risk of current pharmacotherapy for AMD-associated CNVs. Combination therapy (e.g., verteporfin-photodynamic therapy + ranibizumab) appears to reduce the risk and enhance the effectiveness of CNV treatment compared with monotherapy with currently available agents. Improved noninvasive diagnostic imaging may lead to better visual outcomes with existing therapeutic modalities. Improved imaging also may alter favorably the design of future clinical trials for AMD-associated CNVs and thus reduce cost and increase the diversity of sight-saving treatments. CONCLUSIONS: Delineation of the biochemical basis for CNV formation has led to development of pathway-based pharmacotherapy for AMD patients. Areas of investigation that will advance the field further include combination therapy, improved drug delivery, and improved noninvasive, high-resolution diagnostic imaging. The logistics of future clinical trials will be complicated by the need for an active treatment control group, more stringent definition of successful treatment, and the increased numbers of patients required for combination therapy studies.

-----

BioDrugs. 2007;21(4):245-57.
Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.
Emerson MV, Lauer AK.
Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA.

Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein kinase C activity, has shown positive results in the prevention of diabetic retinopathy progression, and the resolution of DME. Combination therapy has been investigated, and may prove to be quite effective in the management of both DME and AMD-associated CNV, although ongoing and future studies will be crucial to treatment optimization for each condition.

-----

Retina. 2007 April/May;27(4):458-461.
Photodynamic therapy and high-dose intravitreal Triamcinolone to treat exudative age-related macular degeneration: 2-year outcome.
Ruiz-Moreno JM, Montero JA, Zarbin MA.
>From the Department of Ophthalmology, Miguel Hernandez University School of Medicine, Alicante, Spain; the Alicante Institute of Ophthalmology, VISSUM, Vitreo-Retinal Unit, Alicante, Spain; and the Institute of Ophthalmology and Visual Science, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.

PURPOSE:: To evaluate the efficacy of photodynamic therapy (PDT) and high-dose intravitreal triamcinolone acetonide (TA) injection to treat choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) at the 2-year follow-up. METHODS:: In this prospective, consecutive, comparative, nonrandomized, interventional case series, 30 eyes of 30 consecutive patients with subfoveal CNV associated with AMD were treated by PDT followed by intravitreal injection of 19.4 +/- 2.1 mg TA. Fifteen eyes were naive to treatment (group 1), and 15 had been treated previously by PDT alone (group 2). A group of 15 eyes of 15 patients treated by PDT alone served as controls. The number of Snellen lines gained or lost and PDT sessions were evaluated. RESULTS:: Best-corrected visual acuity (BCVA) did not change significantly in group 1 from baseline (0.0 +/- 3.4 Snellen line; range, -5 to 9 Snellen lines; P = 0.81); group 2 lost an average -0.6 +/- 2.5 line (range, -7 to 3 Snellen lines) (P = 0.41), and the control group lost an average of -2.2 +/- 3.4 lines (range, -8 to 2 Snellen lines) (P = 0.03, Wilcoxon signed rank test). The average number of PDT sessions during the 24-month follow-up was 1.9, 1.2, and 3.9 for group 1, group 2, and the control group, respectively. CONCLUSION:: Two years after combined PDT/high-dose intravitreal TA to treat AMD-associated CNV, final BCVA was stable, and the need for retreatment was reduced compared with historical controls.

-----

Retina. 2007 Apr-May;27(4):445-50.
Intravitreal bevacizumab for refractory pigment epithelial detachment with occult choroidal neovascularization in age-related macular degeneration.
Chen E, Kaiser RS, Vander JF.
>From the Retina Service, Wills Eye Hospital, Philadelphia, Pennsylvania.

PURPOSE:: New medications targeting vascular endothelial growth factor show promise in the treatment of wet macular degeneration. This study describes the clinical response and optical coherence tomography (OCT) findings for patients with refractory pigment epithelial detachment (PED) and occult choroidal neovascular membranes (CNVMs) who were treated with intravitreal bevacizumab. METHODS:: A retrospective analysis of data for 10 patients with fibrovascular PEDs, initially treated with intravitreal pegaptanib, thermal laser, or photodynamic therapy with or without triamcinolone acetonide administration, was performed. All patients were refractory to previous treatment. They received monthly injections of bevacizumab and were followed by clinical examination, angiography, and OCT. RESULTS:: Nine of 10 patients had stable or improved vision. Angiogram findings showed resolution of leakage from CNVMs. OCT demonstrated resolution of the subretinal or intraretinal fluid but persistence of the PED itself. Vision improvement was correlated with OCT changes. CONCLUSION:: Intravitreal bevacizumab may be a viable option in treating patients with fibrovascular PEDs. OCT findings suggest that visual improvement is secondary to resolution of subretinal and intraretinal edema without resolution of the PED.

-----

Retina. 2007 Apr-May;27(4):439-44.
Intravitreal bevacizumab (avastin) treatment of neovascular age-related macular degeneration.
Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, Emerson GG, Schlesinger TK, Nolte SK, Klein ML.
>From the Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.

PURPOSE:: To report the change in visual acuity and central retinal thickness by optical coherence tomography (OCT) after intravitreal injections of bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). METHODS:: A retrospective case series in a university-based practice evaluated patients with subfoveal choroidal neovascularization (CNV) due to AMD. Patients received intravitreal injections (1.25 mg) of bevacizumab and were monitored monthly with determination of best-corrected ETDRS visual acuity and OCT for persistence of retinal thickening. Eyes were retreated on an "as needed" basis, defined by presence of intraretinal or subretinal fluid. Patients were monitored every 2 months to 3 months for persistence of angiographic leakage. RESULTS:: Seventy-nine eyes of 74 consecutive patients received the initial injection of bevacizumab between August 1, 2005, and January 30, 2006. Sixty-eight eyes (86%) of 64 patients had at least 3 months of follow-up. Mean central retinal thickness +/- SD decreased from 304 +/- 83 mum at baseline to 237 +/- 105 mum at 3 months (P = 0.00002). Mean ETDRS visual acuity gained 4 letters from 20/100 at baseline to 20/80-1 at 3 months (P = 0.040). Twenty eyes (25%) appeared to have a sustained response to a single injection and did not require further injections through 3 months. Two patients had a potentially drug-related adverse event (ischemic stroke and myocardial infarction). No serious injection-related adverse events occurred. CONCLUSIONS:: Intravitreal bevacizumab injection affects a rapid decrease in retinal thickness to normal or near-normal levels and improvement in visual acuity in eyes with CNV due to AMD. The sustainability of changes in retinal thickness and visual acuity in response to bevacizumab treatment warrant further investigation and long-term follow-up.

-----

Retina. 2007 April/May;27(4):432-438.
INTRAVITREAL BEVACIZUMAB FOR PREVIOUSLY TREATED CHOROIDAL NEOVASCULARIZATION FROM AGE-RELATED MACULAR DEGENERATION.
Goff MJ, Johnson RN, McDonald HR, Ai E, Jumper JM, Fu A.
>From the Pacific Vision Foundation, California Pacific Medical Center, and Retina Research Fund of St. Mary's Medical Center, San Francisco, California.

PURPOSE:: To report the optical coherence tomography (OCT) findings and visual results in a series of patients treated with intravitreal bevacizumab for choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), and to determine if a difference in treatment effect exists between previously treated and treatment naive patients. METHODS:: A retrospective review of all patients treated with intravitreal bevacizumab for CNV from AMD with visual acuity greater than or equal to 20/320 between September 2005 and February 2006 was performed. OCT data recorded included central macular thickness and the presence or absence of cystic intraretinal fluid, subretinal fluid, or pigment epithelial detachment at the time of the initial injection, at 1-week, 1-month, and 3-month intervals, as well as at the end of follow-up. Visual acuity measurements were recorded using Early Treatment Diabetic Retinopathy Study charts. Any ocular or systemic adverse events were recorded. Statistical analysis was performed to determine if OCT and visual acuity results were significant and to determine if a difference in outcomes existed between previously treated patients and treatment naive patients. RESULTS:: Fifty-four eyes of 51 patients treated with intravitreal bevacizumab for CNV from AMD were identified. A total of 178 injections were performed. Mean number of days of follow-up was 138 with 91% of patients having at least 90 days of follow-up. Seventy percent of patients had undergone previous treatment for CNV. The mean number of intravitreal bevacizumab injections per eye was 3.3. Combined treatment with photodynamic therapy was provided in 20% of cases at the initial intravitreal injection. OCT data for all patients revealed an initial mean thickness of 362 mum, which was decreased at 1 week to 278 mum (P = 0.001), 235 mum at 1 month (P < 0.0001), 238 mum at 3 months (P = 0.0004), and 244 mum for the end of follow-up (P < 0.0001). Cystic retinal edema, subretinal fluid, and pigment epithelial detachment resolved in the majority of cases, but pigment epithelial detachment frequently took longer to resolve. Initial mean visual acuity was 20/125 (logMAR 0.8), and final mean visual acuity was 20/100 (logMAR 0.7) (P = 0.03). There was no difference in OCT or visual acuity outcomes (P = 0.62 and P = 0.28, respectively) between previously treated and treatment naive patients. There was no difference in OCT or visual acuity outcomes (P = 0.67 and P = 0.21, respectively) between patients who received combination therapy and those who received monotherapy with intravitreal bevacizumab. No systemic or ocular adverse events were recorded. CONCLUSION:: Intravitreal bevacizumab for CNV from AMD results in a rapid decrease in OCT-measured retinal thickness in a majority of cases. Visual acuity also improved in this series, suggesting a potential corresponding visual benefit. This series suggests that previously treated and treatment naive patients have similar outcomes.

-----

Cardiovasc Hematol Agents Med Chem. 2007 Apr;5(2):147-154.
Current and Emerging Concepts in the Management of Neovascular Age-Related Macular Degeneration.
Maloney SC, Godeiro KD, Odashiro AN, Burnier MN Jr.
The Henry C. Witelson Ocular Pathology Laboratory and Registry. McGill University, Montreal Quebec. 3775 University Street, Lyman Duff Building, Room 216, Montreal Quebec, H3A 2B4, Canada. shawn.maloney@mail.mcgill.ca.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. The more severe form of the disease, known as neovascular AMD, is characterized by aberrant growth of blood vessels from the choroid into the subretinal space. This pathologic choroidal neovascularization can have drastic consequences, often seriously impairing vision in affected individuals. Current treatment approaches focus on combination therapies that include photodynamic therapy in conjunction with numerous forms of antiangiogenic or anti-inflammatory drug intervention. To date, however, no adequate treatment is available for the majority of affected individuals. The threat of a rapidly aging population provides the impetus for aggressive efforts to control the prevalence and progression of this disease. This review will outline the currently available pharmacotherapies, discussing the justification for their use as well as their shortcomings. Furthermore, drugs that are currently under investigation as monotherapies and adjuncts will be highlighted. The potential for alternate targets will also be examined, with a focus on the most promising candidates.

-----

Am J Ophthalmol. 2007 Apr;143(4):566-83.
An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration.
Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW Jr, Esquiabro M.
Pacific Eye Associates, California Pacific Medical Center, San Francisco, California, USA.

PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study. METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab. RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary. CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.

-----

Eur J Ophthalmol. 2007 Mar-Apr;17(2):230-7.
Intravitreal bevacizumab therapy for choroidal neovascularization secondary to age-related macular degeneration: 6-month results of an open-label uncontrolled clinical study.
Giansanti F, Virgili G, Bini A, Rapizzi E, Giacomelli G, Donati MC, Verdina T, Menchini U.
Department of Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic, University of Firenze, Firenze - Italy.

PURPOSE. To investigate the 6-month safety and clinical outcomes of intravitreal injections of bevacizumab administered to treat choroidal neovascularization secondary to age-related macular degeneration. METHODS. Twenty-seven patients underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar intravitreal injection was administered to all eyes at 1 and 2 month follow-up visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients underwent best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Laboratory testing, visual field analyses, and endothelial cell counts were performed at baseline and third and sixth months. RESULTS. At 3 months, the mean BCVA remained substantially stable at 20/100. Mean central retinal thickness (CRT) decreased from 373 to 279 microm (p<0.01). Mean lesion greatest linear dimension (GLD) decreased from 4087 to 3782 microns (p<0.01). At 6 months, mean BCVA slightly decreased from 20/100-1 to 20/125-3 (not significant, p=0.40). Mean CRT was still inferior to baseline (305 microm, p<0.01). Mean lesion GLD was 4186 microm, not different from baseline values (p=0.59), but superior to 3-month mean GLD (p<0.01). Significant visual field defects or endothelial cell losses were not detected at 3 and 6 months. Laboratory testing did not reveal any clinically significant deviations compared to baseline values. CONCLUSIONS. Intravitreal therapy using bevacizumab over 6 months showed stabilization of visual acuity and choroidal neovascularization activity; the safety data were convincing.

-----

J Fr Ophtalmol. 2007 Mar;30(3):233-8.
[Quality of life in patients with wet age-related macular degeneration treated with photodynamic therapy]
[Article in French]
Laouar K, Dupeyron G, Audemard D, Arnaud B, Arndt C.
Service d'Ophtalmologie, Hopital Gui de Chauliac, CHU de Montpellier, Montpellier.

PURPOSE: To analyze the benefit of photodynamic therapy in terms of quality of life in patients with wet age-related macular degeneration. METHODS: A retrospective study was conducted on 33 patients with subretinal neovascularization receiving visual rehabilitation in a low vision clinic (ARAMAV, Nimes) in southern France. Twenty had been treated with photodynamic therapy (PDT group) and 13 had not (non-PDT group). In the non-PDT group, the patients had been treated with thermal photocoagulation, transpupillary thermotherapy, or external radiotherapy, or had not received any treatment. Visual acuity, reading speed, reading endurance, and quality of life were compared. Two quality-of-life scales were employed: the VF-14 and NEI-VFQ-25. RESULTS: A significant difference between the two groups in terms of quality of life was observed. The VF-14 score (p<0.01) and two parameters (near activities and distant activities) of the NEI VFQ-25 were significantly higher (both p<0.01) in the PDT group. Visual acuity, reading speed, and reading endurance were similar in both groups. CONCLUSION: Although no difference in terms of functional parameters was observed, photodynamic therapy could preserve the central retina and thus enable a better use of the residual visual function, which could explain the better quality of life perceived by the patients in the PDT group.

-----

Curr Med Res Opin. 2007 Mar;23(3):477-87.
Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for combination therapy in exudative age-related macular degeneration.
Kaiser PK.
Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. pkkaiser@aol.com

OBJECTIVE: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches. SCOPE: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. FINDINGS: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation. CONCLUSIONS: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials.

-----

Graefes Arch Clin Exp Ophthalmol. 2006 Dec 21; [Epub ahead of print]
Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration.
Aisenbrey S, Ziemssen F, Volker M, Gelisken F, Szurman P, Jaissle G, Grisanti S, Bartz-Schmidt KU.
Center of Ophthalmology, University of Tuebingen, Schleichstrasse 12, 72076, Tuebingen, Germany, sabine.aisenbrey@med.uni-tuebingen.de.

BACKGROUND: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. METHODS: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. RESULTS: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). CONCLUSIONS: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

-----

Eur J Ophthalmol. 2006 Nov-Dec;16(6):824-34.
Verteporfin therapy and triamcinolone acetonide: convergent modes of action for treatment of neovascular age-related macular degeneration.
Augustin AJ, Schmidt-Erfurth U.
Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe - Germany.

PURPOSE. Choroidal neovascularization associated with age-related macular degeneration is the primary cause of blindness in the elderly in developed countries, due to a number of pathogenic effects, including angiogenesis, cell-mediated inflammation, leukocyte adhesion and extravasation, and matrix remodeling. METHODS. By producing photochemical effects at the site of target tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood flow stasis, leading to occlusion of vascularization and lesion leakage. RESULTS. PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective in reducing the risk of vision loss in patients with classic containing subfoveal CNV and occult with no classic CNV. However, in predominantly occult CNV, the treatment may be most effective in smaller lesions, and less in larger lesions. Most important, visual acuity rarely is improved. CONCLUSIONS. Pilot studies and large case series suggest that a combination of PDT and intravitreal triamcinolone acetonide has the potential to improve visual outcomes and reduce the need for additional treatments. Randomized, prospective clinical trials are underway to confirm the efficacy and safety of this novel treatment modalita.

-----

Ophthalmic Surg Lasers Imaging. 2006 Nov-Dec;37(6):446-54.
Safety and efficacy of intravitreal bevacizumab followed by pegaptanib maintenance as a treatment regimen for age-related macular degeneration.
Hughes MS, Sang DN.
Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF)-A, both necessary and sufficient in promoting ocular neovascularization, is an attractive therapeutic target. Combining nonselective and selective VEGF blockade may provide clinical benefit with minimal risks in the treatment of neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty patients with all subtypes of neovascular AMD and a broad range of baseline vision were treated with intravitreal bevacizumab followed by pegaptanib sodium for 54 weeks. Visual acuity measurements, biomicroscopy, funduscopy, fluorescein angiography, optical coherence tomography, and adverse event assessments were performed. RESULTS: Mean visual acuity improved from approximately 20/200 at baseline to 20/80. All patients experienced an improvement in retinal thickness, ranging from -47 to -297 microns. Adverse events were limited to transient irritation or redness. No significant elevation in intraocular pressure occurred following either bevacizumab or pegaptanib injections. CONCLUSIONS: Nonselective VEGF blockade with bevacizumab induction and selective VEGF165 blockade with pegaptanib as maintenance therapies may offer clinically meaningful outcomes with acceptable safety profiles in patients with AMD.

-----

Retina. 2006 Nov-Dec;26(9):994-8.
Visual improvement following intravitreal bevacizumab (Avastin) in exudative age-related macular degeneration.
Yoganathan P, Deramo VA, Lai JC, Tibrewala RK, Fastenberg DM.
Department of Ophthalmology, North Shore-Long Island Jewish Health System, Great Neck, NY, USA.

PURPOSE: To study the visual and anatomic outcome of intravitreal bevacizumab injection in the treatment of exudative age-related macular degeneration (AMD). METHODS: Retrospective review of patients who received one or more intravitreal bevacizumab injections for exudative AMD. Outcome measures include standardized visual acuity, optical coherence tomography (OCT), macular thickness and volume, intraocular pressure, and blood pressure at 24 or more weeks follow-up. RESULTS: Fifty eyes of 48 patients were identified. Patients were observed for a median length of follow-up of 34 weeks (range, 24-50 weeks). Thirty-six eyes (72%) had prior treatment with pegaptanib (Macugen) and/or photodynamic therapy (PDT) and 14 eyes (28%) were treatment-naive. Mean visual acuity increased by 6.5 letters (P < 0.01) at 4 weeks and 5.3 letters (P < 0.01) at 24 weeks after initial bevacizumab injection. At 24 weeks, naive eyes had a mean increase of 14.2 letters (P < 0.001) and previously treated eyes had a mean increase of 2.8 letters (P = 0.06). Overall, mean OCT macular thickness and volume decreased by 73 micro m (P < 0.001) and 1.0 mm3 (P < 0.001) respectively at last follow-up. At last follow-up, all eyes received an average of 3.5 injections and experienced an average of 1.08 recurrences. There was no incidence of severe vision loss or adverse effect. CONCLUSION: Intravitreal bevacizumab has the potential for improvement in vision in both naive and previously treated eyes for at least 6 months. The benefit is more pronounced in eyes without prior pegaptanib and/or PDT.

-----

Retina. 2006 Nov-Dec;26(9):988-93.
Combined photodynamic therapy with verteporfin and intravitreal bevacizumab for choroidal neovascularization in age-related macular degeneration.
Dhalla MS, Shah GK, Blinder KJ, Ryan EH Jr, Mittra RA, Tewari A.
Barnes Retina Institute, St Louis, MO, USA.

PURPOSE: To examine the 7-month results for patients treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: This is a retrospective series of 24 eyes with juxtafoveal or subfoveal CNV secondary to AMD. Patients were treated with PDT with verteporfin and 1.25 mg of intravitreal bevacizumab. All patients were naive to treatment and had either treatment within a 14-day interval. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and retreatment rate. RESULTS: At the 7-month follow-up, 20 (83%) of 24 patients had stabilization of visual acuity. Sixteen eyes (67%) had improvement in visual acuity. Mean improvement in visual acuity (n = 24) was 2.04 Snellen lines. Fifteen eyes (63%) required only a single combined treatment for CNV resolution. There were no complications, including endophthalmitis, uveitis, and ocular hypertension. CONCLUSION: The results of this study suggest that combined treatment of PDT with verteporfin and intravitreal bevacizumab may be useful in treating neovascular AMD by reducing retreatment rates and improving visual acuity. Further investigation with large, controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.
  
Previous Macular Degeneration Research: 2002-2006   
The Macular Degeneration File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Macular Degeneration, click HERE.

   

The Macular Degeneration FileSM Compiled and Maintained by    The Center for Current Research, Inc. 708 Aubrey Avenue • Ardmore PA USA 19003 Phone: 610-649-3165 Email: customerservice@lifestages.com Website: www.lifestages.com

©Copyright 1992-date by The Center for Current Research. The Macular Degeneration File is a proprietary compilation of the Center for Current Research. The information in the File is solely for your use, and the use of your family, friends, and doctors. The information is the property of the individual researchers and institutions that produced it. It is an infringement of copyright law to attempt to "resell" the information as it is presented here.