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Uveitis Research: 2002-2006
Curr Opin Ophthalmol. 2006 Dec;17(6):567-73.
Interferon therapy for ocular disease.
Mackensen F, Max R, Becker MD.
aDepartment of Ophthalmology, Germany bDepartment of Internal Medicine,
Interdisciplinary Uveitis Center, University of Heidelberg, Germany.
PURPOSE OF REVIEW: Interferons were first known for their antiviral action.
Immunomodulatory therapy with interferons has been studied in various diseases.
This paper summarizes the role and presumed mechanisms of action of type 1
interferons in the treatment of ocular disease. RECENT FINDINGS: Preliminary
data show beneficial effects of interferons in ocular disease such as Behcet
disease and multiple sclerosis-associated uveitis in terms of visual acuity,
intraocular inflammation activity, and chronic macular edema. Another mode of
application is topical as an adjuvant treatment in viral keratitis or ocular
surface malignancies. SUMMARY: Interferons are gaining a place in the treatment
of ocular disease. Evidence is growing of their potential in ocular Behcet
disease and multiple sclerosis-associated uveitis. Randomized, controlled
clinical trials are needed to confirm this observation. Further insights into
the complex mechanisms of action of interferons in health and disease will
increase understanding of their mechanisms of action as a therapeutic substance.
-----
Acta Ophthalmol Scand. 2006 Dec;84(6):795-8.
The relationship between stress and acute anterior uveitis.
Carrim ZI, Ahmed TY, Taguri AH.
Department of Ophthalmology, Southern General Hospital, Glasgow, UK.
Purpose: To examine the relationship between stress and anterior uveitis using
the General Health Questionnaire (GHQ) and the Social Readjustment Rating
Questionnaire (SRRQ). Methods: Patients attending eye casualty with acute
anterior uveitis (AAU) and suitable controls were asked to complete the GHQ and
the SRRQ. A follow-up postal survey, using the same questionnaires, was repeated
at least 3 months later amongst AAU patients only. Scores for the GHQ and SRRQ
at initial presentation and at follow-up were compared for different groups.
Results: Over 12 months, 42 patients and 25 controls participated in the first
stage of this study. Patients with AAU had higher GHQ scores than controls (mean
6.8 versus 3.2, p = 0.01). A total of 25 patients responded to the follow-up
postal survey. At follow-up, 13 had experienced resolution and 12 had
recurrence. In the group with resolution, there was a significant fall in GHQ
scores (mean 6.1 versus 1.5, p = 0.0044). Patients with recurrence had higher
GHQ scores than those with resolution (mean 6.8 versus 1.5, p = 0.02).
Conclusions: Using the GHQ reveals a clear relationship between stress and the
recurrence of AAU in susceptible individuals.
-----
Ann Rheum Dis. 2006 Oct 26; [Epub ahead of print]
Infliximab and etanercept in the treatment of chronic uveitis
associated with refractory juvenile idiopathic arthritis.
Tynjala P, Lindahl P, Honkanen V, Lahdenne P, Kotaniemi K.
Helsinki University Central Hospital, the Hospital for Children and Adolescents,
Finland.
OBJECTIVE: Evaluation of the anti-tumor necrosis factor (TNF) therapy on
juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: Twenty-four
patients with uveitis were on etanercept and twenty-one on infliximab. The end-
point ophthalmologic evaluation was at 24 months or at the termination of the
first biological agent. The ocular inflammatory activity was graded based on the
number of anterior chamber cells. RESULTS: Of the 45 patients, uveitis improved
in 14 (31%), no change was observed in 14 (31%), and in 17 (38%) the activity of
uveitis increased. Inflammatory activity improved more frequently (p=0.047) in
the patients on infliximab than on etanercept. The number of uveitis flares/year
was higher (p=0.015) in the patients on etanercept (mean 1.4, range 0-3.2)
compared to infliximab (mean 0.7, range 0-2.0). Uveitis developed for the first
time while on anti-TNF therapy in five patients - four on etanercept (2.2 /100
patient-years) and one on infliximab (1.1 /100 patient-years). CONCLUSIONS:
During anti-TNF therapy, the ophthalmologic condition improved in one-third of
the patients with uveitis. In chronic anterior uveitis, associated with
refractory JIA, infliximab may be more effective than etanercept.
-----
Br J Ophthalmol. 2006 Oct 18; [Epub ahead of print]
Efficacy of interferon alpha in the treatment of refractory and
sight-threatening uveitis : a retrospective monocentric study of 45 patients.
Bodaghi B, Gendron G, Wechsler B, Terrada C, Cassoux N, Le Thi Huong D, Lemaitre
C, Fardeau C, Lehoang P, Piette JC.
Dept of Ophthalmology, University of Paris VI, France.
PURPOSE: Severe uveitis is potentially associated with visual impairment or
blindness in young patients. Therapeutic strategies remain controversial.
Efficacy of interferon alpha-2a (IFN-alpha2a) in severe uveitis, refractory to
steroids and conventional immunosuppressive agents has been evaluated. Patients
and METHODS: Patients were included after a major relapse of uveitis occurring
under corticosteroids and immunosuppressants. IFN-alpha2a (3 millions units
three times a week) was administered subcutaneously. Efficacy was assessed by
the improvement of visual acuity, decrease of vitreous haze, resolution of
retinal vasculitis and macular edema, assessed by fundus examination and
fluoresecin angiography and decrease of oral prednisone threshold. RESULTS:
Forty-five patients were included. Median age was 32.3 years (range 8-58 years)
and sex ratio (F/M) was 0.66. Uveitis was associated with Behcet's disease (BD)
in 23 cases (51.1%) and with other entities in 22 cases (48.9%). Median duration
of uveitis before interferon therapy was 34.9 months (range 3.4- 168.7 months)
and an average of 3.26 relapses under corticosteroids and immunosuppressants was
noted. Uveitis was controlled in 82.6% of patients with BD and 59% of patients
with other types of uveitis (p=0.07). During a mean follow-up of 29.6 months
(range 14-55 months), median oral prednisone threshold decreased significantly
from 23.6 mg/d (range 16-45 mg/d) to 10 mg/d (range 4-14 mg/d) (p<0.001).
Interferon was discontinued in 10 patients (22.2%) with BD and 4 patients
without BD. Relapses occurred in 4 and 1 cases, respectively. CONCLUSIONS:
Interferon-therapy seems an efficient strategy in severe and relapsing forms of
BD but also other uveitic entities. However, it seems more suspensive than
curative. Therefore, IFN- 2a may be proposed as a second line strategy after the
failure of conventional immunosuppressants.
-----
Ophthalmic Res. 2006;38(6):318-23. Epub 2006 Oct 13.
Intraocular lens implantation in patients with juvenile
idiopathic arthritis-associated uveitis.
Kotaniemi K, Penttila H.
Rheumatism Foundation Hospital, Heinola, Finland.
Objective: To evaluate the development of cataract and the results of cataract
surgery with intraocular lens (IOL) implantation in patients with chronic
uveitis associated with juvenile idiopathic arthritis (JIA). Patients and
Methods: A hospital-based retrospective case series consisted of 25 patients
with JIA-associated uveitis. The mean age of the patients was 5.8 years at the
onset of arthritis and 6.8 years at the onset of uveitis. During the 15-year
study period cataract surgery with implantation of an IOL was performed in 36
eyes. In 17 eyes phacoemulsification and initial posterior capsulectomy with
anterior core vitrectomy were performed. The treatment of JIA and uveitis was
carefully adjusted with systemic immunosuppressive drugs and topical
corticosteroids perioperatively. The mean postoperative follow-up period was 3.3
years. Results: The first signs of cataract were observed 2.3 years (mean) after
the diagnosis of uveitis and the cataract operation of the first eye was
performed 4.5 years (mean) after the diagnosis of uveitis. After IOL surgery the
visual result was good (>/=0.5) in 64%, moderate (0.3 to <0.5) in 11% and
impaired (<0.3) in 25% of eyes. Secondary cataract developed in 16 eyes but in
none of the eyes with initial posterior capsulectomy and core vitrectomy.
Secondary glaucoma developed in 18 eyes, retinal detachment in 2, cystoid
macular edema in 16 and band keratopathy in 12 eyes. Conclusion: Cataract is an
early complication of JIA-associated uveitis. Under strict control of uveitis,
IOL implantation is an important alternative in visual rehabilitation for this
type of patient. Copyright (c) 2006 S. Karger AG, Basel.
-----
Br J Ophthalmol. 2006 Oct 11; [Epub ahead of print]
Adalimumab in the Therapy of Uveitis in Childhood.
Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D,
Zierhut M.
University of Tuebingen, Germany.
PURPOSE: Chronic anterior uveitis in children often takes a serious course.
Despite various immunosuppressive drugs some children do not sufficiently
respond with a high risk of becoming seriously disabled. Anti-TNF alpha therapy
has been shown by our group and others to be mostly ineffective (Etanercept) or
partly effective (Infliximab) with the risk of anaphylactic reactions. Here we
report on 18 young patients treated with Adalimumab (Humira(R)), a complete
humanized anti-TNF alpha antibody. METHODS: We retrospectively analysed 18
patients, who were treated with Adalimumab (20-40 mg, every 2 weeks, when
ineffective every week); 17 had juvenile idiopathic arthritis, 1 was without
detectable underlying disease. The age at onset of arthritis varied from 0.5-15
years and for uveitis from 2-19 years. Patients were included when the previous
anti- inflammatory therapy had been ineffective. It consisted of systemic
steroids (n=18), Cyclosporin A (n=18), Methotrexate (n=18), Azathioprine (n=12),
Mycophenolate mofetil (n=4), Cyclophosphamide (n=2), Leflunomide (n=3),
Etanercept (n=8) and Infliximab (n=5). The grading for uveitis was: effective:
no relapse or more than 2 relapses less than before treatment, mild: one relapse
less than before treatment, no response: no change in relapse rate, worsening:
more relapses under treatment than before. The grading for arthritis (depending
on the clinical findings, using 3 out of 6 parameters of the ACR PED Criteria)
was: effective, mild, no response, worsening. RESULTS: For arthritis (n=16) the
response to Adalimumab was effective in 10 of 16 patients, mild in 3 patients, 3
did not respond. For uveitis (n=18) Adalimumab was effective in 16, mild in 1
child, and 1 patient did not show any effect. After a very good response
initially a shorter application time had to be used to maintain the good
anti-inflammatory effect in 1 child. Additional immunosuppressive treatment was
used in 7 of the effectively treated children. Due to elevation of liver enzymes
in 1 patient, who also took MTX, Adalimumab had to be discontinued. No
anaphylactic reactions or increased frequency of infections since start of
Adalimumab treatment was reported. CONCLUSIONS: For our group of children with
long lasting disease our results show that Adalimumab was effective or mildly
effective against the arthritis in 81%, but in uveitis in 88%. While these
results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept),
Adalimumab seems to be much more effective against uveitis than Etanercept.
Anaphylactic reactions, found in a previous study from our group after
Infliximab treatment, are not seen with Adalimumab. The necessary dosage and the
treatment period, which probably have to be defined individually for each
patient, remain unclear.
-----
Ophthalmology. 2006 Sep 21; [Epub ahead of print]
Differential Effectiveness of Etanercept and Infliximab in the
Treatment of Ocular Inflammation.
Galor A, Perez VL, Hammel JP, Lowder CY.
Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio.
PURPOSE: Anti-tumor necrosis factor alpha (anti-TNF-alpha) agents are being used
increasingly in refractory inflammatory eye diseases. We reviewed our patients
on etanercept and infliximab to determine whether these medications are equally
efficacious in controlling ocular inflammation. DESIGN: Exploratory
retrospective analysis. PARTICIPANTS: Patients with ocular inflammatory disease
on an anti-TNF-alpha agent (etanercept, infliximab). METHODS: Case records of 22
patients treated with anti-TNF-alpha therapy were reviewed for demographic
information, ocular and systemic diagnosis, duration and dose of anti-TNF-alpha
treatment, concomitant ocular and systemic immunosuppressive medications, and
treatment response. MAIN OUTCOME MEASURES: Uveitis recurrence rate, initial
treatment response, treatment response, and medication use at 6 months, 1 year,
and last visit. RESULTS: Patients treated with infliximab had a significant
decrease in uveitis recurrences after starting therapy compared with those
treated with etanercept (59% vs. 0%, P = 0.004). One year after treatment
initiation and at final visit, more infliximab-treated patients had an
improvement in their ocular inflammation (100% vs. 33%, P = 0.002, and 94% vs.
0%, P<0.001, respectively) and a decreased requirement for topical prednisolone
acetate 1% (94% vs. 33%, P = 0.009, and 89% vs. 29%, P = 0.007, respectively)
compared with those treated with etanercept. No significant differences in the
use of oral corticosteroids and immunosuppressive agents were noted between the
2 groups at 6 months, 1 year, and final visit. CONCLUSIONS: Infliximab was more
effective than etanercept in the treatment of recalcitrant uveitis and decreased
the use of topical steroids.
-----
Ann Rheum Dis. 2006 Aug 10; [Epub ahead of print]
Efficacy of Tumor Necrosis Factor blockers in reducing uveitis
flares in spondylarthropathy patients : a retrospective study.
Guignard S, Gossec L, Salliot C, Ruyssen-Witrand A, Luc M, Duclos M, Dougados M.
Cochin Hospital, France.
OBJECTIVE: The objective of this study was to evaluate the efficacy of
anti-Tumor Necrosis Factor (TNF) therapies (given for rheumatologic
manifestations) in reducing uveitis flares in spondylarthropathy patients in
daily practice. METHODS: Retrospective observational study of all
spondylarthropathy patients with at least one uveitis flare treated with anti-TNF
in one center (December 1997- December 2004). The rate of uveitis flares per 100
patient-years was compared before and during anti-TNF treatment, each patient
was his/her own control. A relative risk ratio (RR) and a number needed to treat
(NNT) were calculated. RESULTS: Forty six patients with spondylarthropathy
treated with anti-TNF suffered from at least one uveitis flare (33 treated with
anti-TNF anti-bodies, infliximab or adalimumab, 13 with soluble TNF receptor,
etanercept). Mean age at first symptoms was 26 years, 71% were men. Patients
were followed up for 15.2 years (mean) before anti-TNF versus 1.2 years with
anti-TNF treatment. The number of uveitis flares per 100 patient-years before
and during anti-TNF were respectively: - For all anti-TNF: 51.8 versus 21.4
(p=0.03), RR=2.4, NNT=3 (95% confidence interval (CI): 2; 5). - For soluble TNF
receptor: 54.6 versus 58.5 (p=0.92), RR=0.9. - For anti-TNF antibodies: 50.6
versus 6.8 (p=0.0008), RR=7.4, NNT=2 (95% CI:2 ; 5). CONCLUSION: Anti-TNF were
efficacious in decreasing the number of uveitis flares in spondylarthropathy
patients. However anti-TNF anti- bodies decreased the rate of uveitis flares
whereas soluble TNF receptor did not seem to decrease this rate. These results
could have consequences for the choice of anti-TNF in certain patients.
-----
Drugs Aging. 2006;23(7):535-58.
Chronic non-infectious uveitis in the elderly : epidemiology,
pathophysiology and management.
Gupta R, Murray PI.
Academic Unit of Ophthalmology, Division of Immunity and Infection, University
of Birmingham, Birmingham, UK.
Intraocular inflammatory diseases are collectively known as uveitis. The
aetiology of this condition can be diverse, as inflammation may result from
direct involvement of the uveal tract or indirect inflammation of adjacent
tissues. Uveitis can present challenges to diagnosis and treatment, and is
potentially a severe sight-threatening disease. In the elderly, uveitis can
present de novo after the age of 60 years or may represent a process earlier in
life continuing after the age of 60 years, although many cases will have become
quiescent by that time. More recent studies suggest that uveitis presenting
after 60 years of age is more common than previously believed. Most cases of
uveitis are of unknown aetiology and are classed as idiopathic, although
sarcoidosis, ocular ischaemia and birdshot chorioretinopathy are recognised
non-infectious causes of uveitis in the elderly. Systemic immunosuppression,
with its well known complications, may be required to preserve vision. In this
age group, one should always have high suspicion of a masquerade syndrome,
particularly a primary CNS non-Hodgkin's lymphoma. With the demographics of the
elderly population changing and mean life expectancy increasing, it is important
that clinicians are familiar with uveitis as a potential cause of visual
impairment in this age group.
-----
Graefes Arch Clin Exp Ophthalmol. 2006 Aug 2; [Epub ahead of print]
Prospective optical coherence tomographic evaluation of the
efficacy of oral and posterior subtenon corticosteroids in patients with
intermediate uveitis.
Venkatesh P, Abhas Z, Garg S, Vohra R.
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of
Medical Sciences, New Delhi, India.
PURPOSE: To prospectively evaluate the efficacy of oral corticosteroids and
posterior subtenon injection in the treatment of macular edema in patients with
intermediate uveitis using optical coherence tomography (OCT). METHODS:
Twenty-two patients with intermediate uveitis were treated with posterior
subtenon injection when the disease was unilateral (group A, n=11) or with oral
steroids when the disease was bilateral (group B, n=11). Changes in macular
thickness from baseline was determined using OCT in both groups at day 0, day 3,
day 14, 6 weeks and 12 weeks. RESULTS: Statistically significant improvement in
Snellen visual acuity in group A was seen at 6 weeks and in group B at 2 weeks.
In patients receiving oral corticosteroids, foveal thickness decreased by 63% by
day 3. In those treated with posterior subtenon injection, even at day 14 only a
55% reduction of foveal thickness was evident. Spearman's correlation
coefficient for visual acuity and foveal thickness was found to be significant.
CONCLUSION: OCT confirms a significantly more rapid decrease in macular edema in
patients treated with oral corticosteroids. A short course of oral steroids may
be useful in enabling earlier visual recovery in patients treated with posterior
subtenon injection for unilateral uveitic macular edema.
-----
Curr Rheumatol Rep. 2006 Aug;8(4):260-6.
Uveitis: advances in understanding of pathogenesis and treatment.
Read RW.
Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL
35233, USA. rwr@uab.edu
Uveitis is a leading cause of blindness affecting individuals of all ages,
genders, and races. Uveitis may be due to autoimmune, infectious, toxic,
malignant, or traumatic processes. Some evidence supports an association between
conditions previously presumed to be autoimmune and viral infectious agents. For
autoimmune uveitis, therapy is nonspecific, typically beginning with
corticosteroids. For nonresponsive disease or for corticosteroid sparing, recent
reports on mycophenolate mofetil, infliximab, and interferon therapy show
success for various forms of uveitis. Treatment of the complications of uveitis,
especially cystoid macular edema, is difficult. Vitamin E appears to offer
little benefit, whereas octreotide may be effective. Recent collaborative
efforts at standardization in the field should enhance studies on these
conditions.
-----
Ophthalmology. 2006 Jul 31; [Epub ahead of print]
Visual Outcomes in Children with Juvenile Idiopathic
Arthritis-Associated Uveitis.
Kump LI, Castaneda RA, Androudi SN, Reed GF, Foster CS.
Massachusetts Eye Research and Surgery Institute, Cambridge, Massachusetts;
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
PURPOSE: To analyze visual outcomes in children affected by juvenile idiopathic
arthritis (JIA)-associated uveitis. DESIGN: Retrospective interventional case
series. PARTICIPANTS: Eighty-nine children with JIA-associated uveitis. METHODS:
Charts of children with JIA-associated uveitis were reviewed. MAIN OUTCOME
MEASURE: Change in patients' visual acuities (VAs). RESULTS: Of 269 children
with uveitic syndromes referred, 89 (33%) had JIA-associated uveitis. The
process was bilateral in 76 children. Seventy-three patients were female, and
84% of patients were Caucasian. Mean age of onset of uveitis was 5.7 years. Mean
follow-up was 2.96 years. Antinuclear antibody positivity was detected in 56
patients, 44 of them female. Patients with JIA-associated uveitis developed
numerous complications in the course of their disease: of 165 affected eyes, 105
(64%) developed cataracts, 33 (20%) developed increased intraocular pressure,
and 76 (46%) developed band keratopathy; posterior synechiae were present in 96
(58%). Of 89 children, 73% were treated with immunomodulators, 40% were treated
with nonsteroidal antiinflammatory agents alone or in combination with
immunomodulators, and 21% were treated with topical and/or systemic steroids. Of
65 children who required immunomodulation, only one chemotherapeutic agent was
used in 30, two agents in 21, and >/=3 in 14. Visual acuities of 65 children
(122 eyes) were documented and compared at standard intervals. By mixed-models
linear regression, improvement in VA of 0.03 logarithm of the minimum angle of
resolution units per year was not found to be statistically significant
(standard error, 0.02, P = 0.089). CONCLUSIONS: Juvenile idiopathic
arthritis-associated uveitis is a sight-threatening disease. However, much of
the children's vision can be preserved if patients are treated appropriately.
-----
Br J Ophthalmol. 2006 Jul 6; [Epub ahead of print]
Mycophenolate mofetile in the treatment of uveitis in children.
Doycheva DG, Deuter CM, Stuebiger N, Biester S, Zierhut M.
University Eye Hospital-Tuebingen, Germany.
BACKGROUND: Mycophenolate Mofetil (MMF) is a new immunosuppressive agent which
inhibits selectively the proliferation of T- and B-lymphocytes. It has been
shown to be a useful immunosuppressant in the control of intraocular
inflammation with minimal side effects. There is no study investigating the role
of MMF in the treatment of uveitis in pediatric patients. PURPOSE: To assess the
efficacy of MMF in uveitis of childhood and to analyse the possible side
effects. Materials and methods: A retrospective analysis was performed on 17
children (32 eyes) with intraocular inflammation treated with MMF and followed
up at the University Eye Hospital Tuebingen between 2000 and 2005. All children
had chronic noninfectious uveitis (idiopathic intermediate uveitis, JIA-associated
uveitis, sarcoidosis and TINU-syndrome) and received MMF for 6 months at least.
Treatment with steroids and/or other immunosuppressive agents was carried out in
all patients prior to MMF initiation. The rational for using MMF was the high
frequency of sight-threatening recurrences of uveitis and intolerance to high
dose steroids or other immunosuppressive drugs with severe adverse reactions.
RESULTS: 17 children (10 males and 7 females) with a mean age of eight at the
onset of the uveitis (range: 2 to 13 years) were evaluated. The average duration
of follow-up after initiation of MMF was 3 years (range from 2 to 5 years). A
steroid-sparing effect was achieved in 88% of the patients. The oral
prednisolone was successfully discontinued in 41% and reduced to a daily dose of
5mg or less in 47% of the children. Relapse-free during the therapy remained 24%
of the patients, but a reduction of the relapse rate was observed in all other
patients except one. Visual acuity was increased or maintained in 13 children
(76%). Mild side effects (headache, skin rash, gastrointestinal discomfort)
occurred in 7 patients (41%) and were the cause of discontinuation of MMF
therapy in one child. CONCLUSION: The results of our study are encouraging and
suggest that MMF is an effective agent also in the treatment for uveitis in
children with significant steroid-sparing potential and an acceptable side
effect profile.
-----
Best Pract Res Clin Rheumatol. 2006 Jun;20(3):487-505.
Uveitis.
Munoz-Fernandez S, Martin-Mola E.
Servicio de Reumatologia, Hospital Universitario La Pas, Madrid, Spain.
smunoz.hulp@salud.madrid.org
Uveitis is a prevalent disease that mainly affects young people. It leads to a
significant number of visual losses. Acute anterior uveitis is the most
prevalent form, and it is often associated with spondyloarthritides in which
uveitis can be the first manifestation of disease. Precise patterns of uveitis
are frequently associated with systemic diseases. Thus, the close collaboration
between ophthalmologists and rheumatologists avoids unnecessary diagnostic tests
and is essential for the correct assessment and treatment of these patients.
Acute anterior uveitis usually has a good prognosis compared with other forms of
uveitis. However, it is a cause of disability when flares are frequent. Small
prospective studies conducted with sulphasalazine have demonstrated a reduction
in the number of flares. Other patterns of uveitis have a worse prognosis, and
systemic corticosteroids and/or immunosuppressive drugs are usually required.
Infliximab is a promising therapeutic option in selected patients.
-----
J Fr Ophtalmol. 2006 Apr;29(4):392-7.
[Interferon and retinal vasculitis.]
[Article in French]
Fardeau C.
Service d'Ophtalmologie, Hopital de la Pitie-Salpetriere, 47-83, boulevard de
l'Hopital, 75651 Paris cedex 13.
The treatment of noninfectious posterior uveitis can lead to severe vision loss,
and the first-line conventional treatment includes systemic steroids. When the
prednisone doses necessary to control intraocular inflammation are above
0.3mg/day, a therapeutic association is proposed in order to lower the daily
prednisone dose. The combined drugs are immunosuppressive or immunomodulative.
The side effects of immunosuppressive drugs are oncogenic, infectious, and
hematological, and can involve reproductive troubles, associated with specific
toxic effects depending on the drug used. Recently adding polyclonal or
monoclonal antibodies and the interferons to immunomodulative drugs has been
suggested. Interferon alpha has been shown to be effective in Behcet's disease.
The efficacy of interferon needs to be evaluated in other etiologies of retinal
vasculitis through randomized studies.
-----
Cytokine. 2006 Mar 13; [Epub ahead of print]
Anti-TNF therapies in the management of acute and chronic uveitis.
Hale S, Lightman S.
Department of Clinical Ophthalmology, Institute of Ophthalmology and Moorfields
Eye Hospital, City Road, London, EC1V 2PD, UK.
Patients with anterior uveitis may be treated with topical therapy alone but
patients with posterior uveitis and those with sight threatening complications
of anterior uveitis usually require systemic treatment especially if the disease
is bilateral. The mainstay of treatment is corticosteroids and additional
immunosuppressive agents such as cyclosporin and mycophenolate are used when
necessary. There remains a significant cohort of patients in whom this therapy
is either not tolerated or is ineffective. The use of the anti-tumour necrosis
factor (TNF) antibodies has been very successful in controlling other
immune-mediated disorders such as rheumatoid arthritis and has subsequently been
extended to use in other arthritidies and other disorders such as psoriasis and
Crohn's disease. TNF is known to play a key role in ocular inflammation as shown
by animal studies and its detection in the ocular fluids of inflamed eyes in
man. In some disorders all types of anti-TNF antibodies have similar efficacy
but that does not appear to be the case with uveitis where infliximab is at
present looking to be more effective than etanercept. The data on the use of
anti-TNF drugs in uveitis is presented together with new data on its role as a
steroid sparing agent.
-----
Am J Ophthalmol. 2006 Mar;141(3):571-3.
Topical ibopamine in the treatment of chronic ocular hypotony
attributable to vitreoretinal surgery, uveitis, or penetrating trauma.
Ugahary LC, Ganteris E, Veckeneer M, Cohen AC, Jansen J, Mulder PG, van Meurs JC.
The Rotterdam Eye Hospital, PO Box 70030, 3000 LM Rotterdam, The Netherlands.
Ugahary@oogziekenhuis.nl
PURPOSE: To study whether topical ibopamine effectively increases the
intraocular pressure in patients with ocular hypotony after vitreoretinal
surgery, uveitis, or penetrating trauma. DESIGN: A prospective randomized,
double-blind, placebo controlled, crossover study. METHODS: In ten patients with
ocular hypotony, an ibopamine 2% solution or placebo eyedrop was administered at
8 am and frequent applanation tonometry was performed during 10 hours on 2 days,
2 weeks apart. RESULTS: The mean IOP integral after administration of ibopamine
was 2.4 mm Hg higher (95% CI for median difference in AUC over 480 minutes [P =
.010]) compared with placebo. CONCLUSIONS: The results of the study show that an
ibopamine 2% eyedrop twice a day may increase the IOP for a period of over 8
hours in patients with hypotony.
-----
Rheumatology (Oxford). 2006 Feb 3; [Epub ahead of print]
Tumour necrosis factor {alpha} inhibitors in the treatment of
childhood uveitis.
Saurenmann RK, Levin AV, Rose JB, Parker S, Rabinovitch T, Tyrrell PN, Feldman
BM, Laxer RM, Schneider R, Silverman ED.
Division of Rheumatology, Hospital for Sick Children, Toronto, Canada.
Objective. To describe the efficacy of anti-TNF-alpha agents in the treatment of
childhood uveitis. Methods. We performed a retrospective chart review of all
children with uveitis treated with TNF-alpha blockers at The Hospital for Sick
Children, Toronto. Results. Twenty-one children with uveitis were treated with
the anti-TNF-alpha agents etanercept (11 patients) and infliximab (13 patients),
resulting in 24 treatment courses. All patients had persistently active uveitis
despite treatment with at least one standard immunosuppressive drug before the
start of anti-TNF-alpha therapy. Six of 21 patients (29%) had idiopathic uveitis.
In the other 15 patients, the underlying disease was juvenile idiopathic
arthritis in 12 (57%), Behcet disease in two (9%) and sarcoidosis in one (5%).
Response to etanercept treatment was good in 27%, moderate in 27% and poor in
45% of patients. Response to infliximab treatment was good in 38%, moderate in
54% and poor in 8% of patients. The difference in the percentage of patients
with a moderate or good response was statistically significant (P=0.0481). We
also observed a lower rate of complications, such as new-onset or worsening
glaucoma or cataract in the infliximab-treated group. Conclusion. Anti-TNF-alpha
treatment was beneficial in a high percentage of patients with childhood uveitis
refractory to standard immunosuppressive treatment. Infliximab resulted in
better clinical responses with less ocular complications than etanercept.
-----
Ophthalmology. 2006 Feb;113(2):308-14. Epub 2006 Jan 10.
Retrospective case review of pediatric patients with uveitis
treated with infliximab.
Rajaraman RT, Kimura Y, Li S, Haines K, Chu DS.
Joseph M. Sanzari's Children Hospital, Hackensack University Medical Center,
Hackensack, New Jersey, USA.
PURPOSE: To assess the response and adverse events associated with infliximab
treatment for refractory, noninfectious pediatric uveitis. DESIGN: Retrospective
noncomparative case series of pediatric patients with refractory uveitis treated
with infliximab. PARTICIPANTS: Six patients were identified. Diagnoses of the
participants included idiopathic uveitis (n = 1), juvenile rheumatoid arthritis
with uveitis (n = 3), idiopathic retinal vasculitis with uveitis (n = 1), and
bilateral pars planitis, with vitreitis and papillitis of the left eye (n = 1).
Uveitis developed in the patients (5 female, 1 male) at a mean age of 9.0 years
(+/-5.0 years; range, 0.9-14.8 years). All patients had bilateral eye
involvement. These patients were refractory to or dependent on topical steroids
(n = 4), oral prednisone (n = 3), or both, and were also refractory to the
following therapies: methotrexate (n = 6), cyclosporine (n = 3), mycophenolate
mofetil (n = 3), etanercept (n = 3), and daclizumab (n = 1). INTERVENTION: All
patients initially received infliximab at doses between 5 and 10 mg/kg at 2- to
4-week intervals, and then were maintained at 4- to 8-week intervals at doses of
5 to 18 mg/kg. Mean follow-up time on treatment has been 48.1 weeks (+/-14.9
weeks; range, 32-74 weeks). MAIN OUTCOME MEASURES: Primary outcome measures
included the quantitative measurement of the amount of ocular inflammation in
different locations within the eye. Patients were monitored for infusion
reactions as well as other potential side effects. The children's clinical
status, complete blood counts, and liver function panels were monitored by
pediatric rheumatologists every 6 weeks. RESULTS: All 6 patients showed
reduction in their intraocular inflammation after infliximab therapy was
initiated. Furthermore, control of ocular inflammation was achieved while
receiving infliximab therapy. Topical and systemic corticosteroids were able to
be discontinued in all patients except for 1 patient, who is currently weaning
off prednisone. The only adverse reactions seen were the development of vitreous
hemorrhage in 1 patient and a case of transient upper respiratory infusion
reaction. No patient has had to discontinue treatment. CONCLUSIONS: Infliximab
seems to be an effective agent for the treatment of refractory pediatric uveitis
without apparent serious toxicity in this series of patients.
-----
Am J Ophthalmol. 2006 Jan;141(1):193-4.
Vitamin E in the treatment of uveitis-associated macular edema.
Nussenblatt RB, Kim J, Thompson DJ, Davis MD, Chew E, Ferris FL, Buggage R.
Laboratory of Immunology, National Eye Institute, National Institutes of Health,
Building 10, Rm. 10S219, 10 Center Drive, Bethesda, MD 20892, USA. drbob@nei.nih.gov
PURPOSE: To investigate whether high-dose alpha-tocopherol (vitamin E) could
reduce vision loss and retinal thickening associated with uveitis-associated
cystoid macular edema. DESIGN: A double-masked, randomized study. METHODS:
Uveitis patients with macular edema seen at the NIH were randomized and received
either 1600 IU/day of vitamin E or placebo for 4 months. Visual acuity and
retinal thickening were collected for the efficacy and the safety of the high
dose of vitamin E. RESULTS: Changes in visual acuity and retinal thickening.
CONCLUSIONS: Four-month oral supplementation with 1600 IU/d of vitamin E had no
apparent effect on uveitis-associated macular edema or visual acuity in this
small study.
-----
Acta Ophthalmol Scand. 2005 Dec;83(6):645-63.
Intravitreal triamcinolone acetonide for treatment of intraocular
oedematous and neovascular diseases.
Jonas JB.
Department of Ophthalmology, Faculty of Clinical Medicine Mannheim,
Ruprecht-Karls-University of Heidelberg, Germany. Jost.Jonas@augen.ma.uni-heidelberg.de
Intravitreal triamcinolone acetonide (IVTA) has increasingly been applied as
treatment for various intraocular neovascular and oedematous diseases. Comparing
the various diseases with respect to effect and side-effects of the treatment,
the best response in terms of gain in visual acuity (VA) has been achieved for
intraretinal oedematous diseases such as diffuse diabetic macular oedema, branch
retinal vein occlusion, central retinal vein occlusion and pseudophakic cystoid
macular oedema. In eyes with various types of non-infectious uveitis, including
acute or chronic sympathetic ophthalmia and Adamantiadis-Behcet's disease, VA
increased and the degree of intraocular inflammation decreased. Some studies
have suggested that intravitreal triamcinolone may be useful as angiostatic
therapy in eyes with iris neovascularization and proliferative ischaemic
retinopathies. Intravitreal triamcinolone may possibly be helpful as adjunct
therapy for exudative age-related macular degeneration (AMD), particularly in
combination with photodynamic therapy. In eyes with chronic, therapy-resistant
ocular hypotony, intravitreal triamcinolone can induce an increase in
intraocular pressure (IOP) and may stabilize the eye. The complications of
intravitreal triamcinolone therapy include: secondary ocular hypertension in
about 40% of the eyes injected; medically uncontrollable high IOP leading to
antiglaucomatous surgery in about 1-2% of the eyes; posterior subcapsular
cataract and nuclear cataract leading to cataract surgery in about 15-20% of
elderly patients within 1 year of injection; postoperative infectious
endophthalmitis occurring at a rate of about one per 1000; non-infectious
endophthalmitis, perhaps due to a reaction to the solvent agent, and pseudo-endophthalmitis
with triamcinolone acetonide crystals appearing in the anterior chamber.
Intravitreal triamcinolone injection can be combined with other intraocular
surgeries, including cataract surgery, particularly in eyes with iris
neovascularization. Cataract surgery performed some months after the injection
does not show a markedly elevated complication rate. The injection may be
repeated if the resultant benefits decrease after the initial IVTA injection. In
non-vitrectomized eyes, the duration of the effect and side-effects of a single
intravitreal injection of triamcinolone is about 6-9 months for a dosage of
about 20 mg, and about 2-4 months for a dosage of 4 mg. So far, it has remained
unclear whether the solvent agent should be removed, and if so, how.
-----
Am J Ophthalmol. 2005 Dec;140(6):1096-105.
Vitrectomy in the treatment of uveitis.
Becker M, Davis J.
Bascom Palmer Eye Institute, University of Miami School of Medicine, 900 NW 17th
Street, Miami, FL 33136, USA.
PURPOSE: To assess the evidence that pars plana vitrectomy (PPV) is useful in
improving vision, reducing disease activity, or ameliorating cystoid macular
edema (CME) in patients with uveitis. DESIGN: Review of the literature. METHODS:
A Medline search was conducted for relevant articles published in English,
German, or French. Articles were analyzed for content and evidence level.
RESULTS: A total of 44 interventional case series published between 1981 and
2005 were identified that included 1575 patients (1762 eyes). Evidence level was
grade CII-3 indicating possibly improved clinical outcomes with fair or poor
evidence. The average age of patients was 36 years with a median duration of
uveitis before surgery of 48 months and a median follow-up of 1.9 years.
Intermediate uveitis was present in 841 eyes. Cystoid macular edema and cataract
were common co-morbidities, and there were large numbers of additional surgical
procedures. Visual outcomes in 39 articles were stated as improved in 708 eyes
(68%), unchanged in 202 eyes (20%), and worsened in 124 eyes (12%). Reduction in
systemic medication following PPV was reported in 25 studies. The median
reported percentage of patients per study with CME was 36% preoperatively and
18% postoperatively. CONCLUSIONS: Based on the evidence in the literature, PPV
is possibly relevant to the outcomes of improving vision and reducing
inflammation and CME. Randomized, controlled, collaborative trials or
hypothesis-based case series with precise outcome measures that incorporate
control groups would improve the quality of evidence supporting PPV as an
adjunct to the medical treatment of uveitis.
-----
Adv Drug Deliv Rev. 2005 Dec 13;57(14):2063-2079. Epub 2005 Nov 28.
Recent progress in ocular drug delivery for posterior segment
disease: Emphasis on transscleral iontophoresis.
Myles ME, Neumann DM, Hill JM.
Department of Ophthalmology, LSU Health Sciences Center, New Orleans, LA, USA.
Age-related macular degeneration, diabetic retinopathy, posterior uveitis, and
retinitis due to glaucoma are leading causes of vision loss in the United States
and other developed countries. Because these diseases are located in the
posterior segment of the eye, topical application of ophthalmic medicines is of
limited benefit, since topically applied drugs rarely reach therapeutic levels
in the affected posterior tissues such as the choroid and retina. Intravitreal
injections can deliver drugs to the posterior segment without the side effects
associated with systemic administration. However, the repeated and long-term
injections often needed may cause complications, such as vitreous hemorrhage,
retinal detachment, or endophthalmitis. Recent advances in ocular drug delivery
methods and the development of novel biopharmaceutical agents could lead to new
regimens for the treatment of disease of the posterior retina, choroids, and
macula. This review will summarize recent literature concerning ocular drug
delivery of bioactive compounds to the posterior segment of the eye with
emphasis on transscleral iontophoresis.
-----
Curr Opin Ophthalmol. 2005 Dec;16(6):356-63.
Update on Fuchs' uveitis syndrome.
Mohamed Q, Zamir E.
Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
PURPOSE OF REVIEW: This update aims to summarize the current knowledge on Fuchs'
uveitis syndrome and review publications in the last 10 years. Theories on the
pathogenesis and etiology of Fuchs' uveitis syndrome are revisited and the
management of cataract and glaucoma is updated to reflect recent surgical
change. RECENT FINDINGS: Retrospective reviews have highlighted that patients
with Fuchs' uveitis syndrome are often initially misdiagnosed. Studies comparing
local inflammatory mediators and cell types have found differences in Fuchs'
uveitis syndrome, but the differences in steroid response and degree of
inflammation remain poorly understood. Local production of antibodies to rubella
has been recently reported in the aqueous of all patients with Fuchs' uveitis
syndrome and no controls. Excellent visual outcomes from phacoemulsification
have been reported with reduced complications compared with extracapsular
cataract extraction. SUMMARY: Although a single etiological agent and a
sensitive laboratory test for the diagnosis of Fuchs' uveitis syndrome is
alluring, the diagnosis of Fuchs' uveitis syndrome remains clinical, at least
for now. Phacoemulsification has increased the safety of cataract extraction,
and the use of intraocular lens is generally safe. The ideal lens material and
design are not yet known, but silicone lenses may be best avoided. Glaucoma is
often resistant to treatment and should actively be screened for in patients
with Fuchs' uveitis syndrome. Medical and surgical treatment for reducing
intraocular pressure should be especially aggressive in these patients.
Vitrectomy appears to be safe in patients with visually significant vitreous
opacification.
-----
Adv Drug Deliv Rev. 2005 Dec 13;57(14):2033-2046. Epub 2005 Nov 2.
Intraocular sustained drug delivery using implantable polymeric
devices.
Yasukawa T, Ogura Y, Sakurai E, Tabata Y, Kimura H.
Kurashiki Central Hospital, Kurashiki 710-8602, Japan; Department of
Ophthalmology, Nagoya City University Medical School, Aichi 467-8601, Japan.
Vitreoretinal diseases involving age-related macular degeneration (AMD) are
refractory to most topical or systemic drugs. The retina and the vitreous cavity
have a unique position regarding pharmacokinetics in that the inner and outer
blood retinal barriers separate the retina and vitreous from the systemic
circulation. Eye drops achieve minimal therapeutic concentrations in the
vitreoretinal tissue. Drug delivery systems are a strategy to address this.
Intraocular sustained drug release using implantable devices has been
investigated to treat vitreoretinal diseases. Possible targeted diseases include
those in which repeated intraocular injections are effective (cytomegalovirus
retinitis, uveitis), diseases requiring surgery (proliferative vitreoretinopathy),
and chronic diseases (AMD, macular edema, retinitis pigmentosa). Hydrophobic or
hydrophilic polymers shaped into a sheet, disc, rod, plug, or a larger device
can be implanted into the subretinal space, intrascleral space, vitreous space,
peribulbar space, or at the pars plana. Many researchers suggest the feasibility
of these implants to treat AMD.
-----
Ophthalmology. 2005 Nov;112(11):1916. Epub 2005 Sep 19.
Outcome of intravitreal triamcinolone in uveitis.
Kok H, Lau C, Maycock N, McCluskey P, Lightman S.
Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye
Hospital, London, United Kingdom.
PURPOSE: To report the short-term outcome of intravitreal triamcinolone acetate
(TA) in the treatment of uveitic cystoid macular edema (CME). DESIGN:
Retrospective noncomparative (nonrandomized, uncontrolled) interventional case
series. PARTICIPANTS: Sixty-five eyes of 54 patients with uveitis-related CME
inadequately responsive to treatment combinations of oral corticosteroid,
periocular orbital floor corticosteroid injections, and second-line
immunosuppressive agents. INTERVENTION: Intravitreal injection of 4 mg/0.1 ml of
TA. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP),
levels of inflammation, and immunosuppressive therapy were assessed. Other
potential complications, including cataract progression, vitreous hemorrhage,
endophthalmitis, and retinal detachment (RD), were looked for. RESULTS: The mean
follow-up was 8.0 months (range, 3-51), and the mean improvement of VA after
intravitreal TA was 0.26 (from 0.65 to 0.39 logarithm of the minimum angle of
resolution; Snellen, 6/24-6/12, approximately). This occurred at a mean of 4
weeks (range, 1-30). The improvement in VA was more significant if the duration
of CME before intravitreal TA was < or =12 months (P = 0.006) and if patients
were < or =60 years old (P = 0.005). Patients with the worst vision before
treatment also improved the least. The most important side effect was raised IOP
(mean rise, 10.3 mmHg), with 28 eyes (43.1%) experiencing an IOP rise of >10
mmHg. Patients younger than 40 years were more likely to experience this IOP
rise than those older than 40. Thirty-three eyes (51%) were treated with
antiglaucoma medications, with a mean duration of treatment of 17.4+/-13.3
weeks, and no patient required trabeculectomy or lost vision. The dosage of oral
corticosteroids and/or second-line immunosuppressive medication was reduced or
stopped altogether in 18 of 33 eyes (54.5%) during the study period. There were
no cases of injection-related vitreous hemorrhage, endophthalmitis, or RD.
CONCLUSIONS: In patients with uveitic CME, intravitreal TA can effectively
reduce CME and improve VA and, in some eyes, allows the cessation and/or
reduction of immunosuppressive therapy. The period of effectivity varies in
different patients and, in some eyes, is limited. Treatment was associated in
43.1% with a rise in IOP, which was transient and treatable medically.
-----
Acta Ophthalmol Scand. 2005 Oct;83(5):595-9.
Intravitreal triamcinalone acetonide for refractory uveitic
cystoid macular oedema: longterm management and outcome.
Angunawela RI, Heatley CJ, Williamson TH, Spalton DJ, Graham EM, Antcliffe RJ,
Stanford MR.
GKT Department of Ophthalmology, Rayne Institute, St Thomas' Hospital, London,
UK.
PURPOSE: To establish the role of intravitreal triamcinalone acetonide (TA) in
the long term management of refractory uveitic cystoid macular oedema (CMO) and
to determine the long term visual outcome in these patients. METHOD: This is a
retrospective observational case series. All patients had resistant CMO and
active inflammation. The primary outcome measure was complete resolution of CMO
on ocular coherence tomography. Visual acuity and intraocular pressure were also
monitored. Twelve eyes of twelve patients received 2 (n = 10) to 4 (n = 2) mg of
intravitreal TA. All had previously been unresponsive to orbital floor steroids.
Fluorescein angiography was performed where indicated. RESULTS: There was
complete resolution of CMO in all patients. Nine patients had improvement in
acuity at there final follow up (mean follow up 40.5 months). Seven had improved
by 2 lines (58%). In 3 patients there was no visual improvement. These 3 failed
to respond to re-treatment. Five other patients were re-treated because of
recurring CMO and deteriorating VA (median time to re-treatment 4 mths). The
mean number of re-treatments for this group with orbital floor TA was three.
41.6% of patients developed ocular hypertension (33.8 mhg mean). One required a
trabeculectomy. CONCLUSIONS: 2 mg of intravitreal TA is effective even in cases
of resistant uveitic CMO. Although re-treatment is often required, the initial
response to treatment can be maintained by subsequent orbital floor steroid
injections.
-----
Clin Experiment Ophthalmol. 2005 Oct;33(5):461-8.
Infliximab for juvenile idiopathic arthritis-associated uveitis.
Richards JC, Tay-Kearney ML, Murray K, Manners P.
Department of Ophthalmology, Royal Perth Hospital, Perth, Australia.
BACKGROUND: Infliximab is a murine-human recombinant antitumour necrosis factor
monoclonal antibody recently introduced for the treatment of autoimmune diseases
in which tumour necrosis factor is thought to be a key mediator. Its role in the
treatment of juvenile idiopathic arthritis-associated uveitis is as yet
undefined. METHODS: Six children with juvenile idiopathic arthritis-associated
uveitis, inadequately controlled on currently available therapy, were treated
with infliximab between September 2002 and November 2004. All children were
required to remain on low-dose immunomodulatory treatment in conjunction with
the infliximab. A retrospective review of two electronic databases containing
details of ophthalmology and rheumatology visits was conducted. RESULTS: In all
six children, institution of infliximab therapy was associated with increased
ease of management. Ocular inflammation and intraocular pressure control
improved in all. It was also possible to reduce the dose or withdraw some
glaucoma, steroid and other immunomodulatory drugs. Two children underwent
intraocular surgery without noticeable flare of intraocular inflammation. No
patient developed any serious systemic complications attributable to infliximab.
CONCLUSION: Infliximab may be a useful adjunct to the management of refractory
juvenile idiopathic arthritis-associated uveitis. In our series it was
associated with improved uveitis control and simplification of drug use as well
as possibly improving safety of surgical intervention. This study suggests that
its role is likely to be in conjunction with maintenance immunomodulatory
treatment to provide more optimal disease control. Controlled studies are
required to confirm its efficacy and safety, and the potential breadth of its
use in uveitis and related disorders.
-----
Curr Opin Ophthalmol. 2005 Oct;16(5):281-8.
Management of chronic pediatric uveitis.
Levy-Clarke GA, Nussenblatt RB, Smith JA.
aLaboratory of Immunology and bDivision of Clinical Research and Epidemiology,
National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
PURPOSE OF REVIEW: The diagnosis and management of chronic pediatric uveitis can
be particularly challenging, with an estimated 25-33% of childhood uveitis cases
resulting in severe, life-long visual disability. This paper reviews the recent
literature on the management of chronic pediatric uveitis. RECENT FINDINGS: This
review highlights recent advances in the diagnosis and medical and surgical
management of pediatric uveitis. Several systemic diseases associated with
chronic uveitis in children are highlighted, including juvenile idiopathic
arthritis, sarcoidosis and Behcet's disease. The treatment of primary ocular
diseases associated with chronic pediatric uveitis such as intermediate uveitis
and Fuchs' heterochromic iridocyclitis is discussed. The management of
infectious causes of pediatric uveitis is not covered in this review. SUMMARY:
Knowledge of the ocular complications of chronic pediatric uveitis can help to
customize efficacious therapeutic regimens for each patient, maximize the visual
potential and minimize complications of these diseases. In addition a close
relation should be fostered between pediatricians, pediatric rheumatologists and
ophthalmologists to effectively monitor these patients who have multiple
medical, surgical and refractive needs. Finally, surgical intervention must be
appropriately timed with expert perioperative management of immunosuppressive
medications with pediatric concerns in mind.
-----
Br J Ophthalmol. 2005 Oct;89(10):1254-7.
Interferon as a treatment for uveitis associated with multiple
sclerosis.
Becker MD, Heiligenhaus A, Hudde T, Storch-Hagenlocher B, Wildemann B,
Barisani-Asenbauer T, Thimm C, Stubiger N, Trieschmann M, Fiehn C.
MD, PhD, FEBO, Interdisciplinary Uveitis Center, University of Heidelberg, Im
Neuenheimer Feld 350, 69120 Heidelberg, Germany. matthias.becker@uveitiscenter.de.
AIM: In addition to optic neuritis (ON), multiple sclerosis (MS) may also
involve the eye with a typically bilateral intermediate uveitis. The aim of this
pilot study was to evaluate the efficacy of type I interferons (IFN) for the
treatment of MS associated uveitis. METHODS: In this non-randomised,
retrospective observational case series 13 patients (eight female, five male)
with proved MS and associated uveitis from five uveitis centres who were treated
with interferon beta1a were included. Visual acuity (VA), cell count in the
aqueous humour and vitreous, as well as the presence of cystoid macula oedema (CMO)
were observed. RESULTS: All except one patient had a bilateral form of
intermediate uveitis (total of 24 eyes). Seven patients had documented CMO
before IFN treatment (n = 13 eyes). Median duration of treatment was 24.6 months
(range 7.9-78.7). VA improved in 17 eyes (comparing VA before therapy and at
last follow up); while 10 eyes (36%) improved >/=3 Snellen lines. Aqueous cell
count improved by 1.2 (SD 1.1) grades in all eyes. Vitreous cell count improved
by 1.7 (1.4) in all eyes. Only two patients still had minimal CMO on last follow
up angiographically. CMO resolved after or during IFN treatment in nine eyes.
CONCLUSIONS: IFN has been shown to have beneficial effects in patients with MS
and/or ON. As shown in the models of experimental allergic encephalomyelitis (EAE)
and uveitis, the neurological and ophthalmological manifestations seem to share
similar pathogenic mechanisms. Treatment of MS associated uveitis with IFN
appears to have beneficial effects on VA, intraocular inflammation activity, and
the presence of CMO.
-----
Ophthalmology. 2005 Sep 17; [Epub ahead of print]
Outcome of Intravitreal Triamcinolone in Uveitis.
Kok H, Lau C, Maycock N, McCluskey P, Lightman S.
Department of Clinical Ophthalmology, Institute of Ophthalmology, Moorfields Eye
Hospital, London, United Kingdom.
PURPOSE: To report the short-term outcome of intravitreal triamcinolone acetate
(TA) in the treatment of uveitic cystoid macular edema (CME). DESIGN:
Retrospective noncomparative (nonrandomized, uncontrolled) interventional case
series. PARTICIPANTS: Sixty-five eyes of 54 patients with uveitis-related CME
inadequately responsive to treatment combinations of oral corticosteroid,
periocular orbital floor corticosteroid injections, and second-line
immunosuppressive agents. INTERVENTION: Intravitreal injection of 4 mg/0.1 ml of
TA. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP),
levels of inflammation, and immunosuppressive therapy were assessed. Other
potential complications, including cataract progression, vitreous hemorrhage,
endophthalmitis, and retinal detachment (RD), were looked for. RESULTS: The mean
follow-up was 8.0 months (range, 3-51), and the mean improvement of VA after
intravitreal TA was 0.26 (from 0.65 to 0.39 logarithm of the minimum angle of
resolution; Snellen, 6/24-6/12, approximately). This occurred at a mean of 4
weeks (range, 1-30). The improvement in VA was more significant if the duration
of CME before intravitreal TA was </=12 months (P = 0.006) and if patients were
</=60 years old (P = 0.005). Patients with the worst vision before treatment
also improved the least. The most important side effect was raised IOP (mean
rise, 10.3 mmHg), with 28 eyes (43.1%) experiencing an IOP rise of >10 mmHg.
Patients younger than 40 years were more likely to experience this IOP rise than
those older than 40. Thirty-three eyes (51%) were treated with antiglaucoma
medications, with a mean duration of treatment of 17.4+/-13.3 weeks, and no
patient required trabeculectomy or lost vision. The dosage of oral
corticosteroids and/or second-line immunosuppressive medication was reduced or
stopped altogether in 18 of 33 eyes (54.5%) during the study period. There were
no cases of injection-related vitreous hemorrhage, endophthalmitis, or RD.
CONCLUSIONS: In patients with uveitic CME, intravitreal TA can effectively
reduce CME and improve VA and, in some eyes, allows the cessation and/or
reduction of immunosuppressive therapy. The period of effectivity varies in
different patients and, in some eyes, is limited. Treatment was associated in
43.1% with a rise in IOP, which was transient and treatable medically.
-----
Retina. 2005 Sep;25(6):751-8.
Subconjunctival antibiotics in the treatment of endophthalmitis
managed without vitrectomy.
Smiddy WE, Smiddy RJ, Ba'Arath B, Flynn HW Jr, Murray TG, Feuer WJ, Miller D.
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami
School of Medicine, Miami, Florida, USA.
PURPOSE: To determine if the treatment outcomes for endophthalmitis are
influenced by subconjunctival antibiotics. METHODS: A retrospective,
nonrandomized consecutive series of patients with clinically diagnosed bacterial
endophthalmitis confirmed with positive cultures who presented between December
1, 1995, and February 28, 2002, was studied. Patients with cataract surgery,
glaucoma filtering blebs, or trauma who presented with visual acuity of hand
motions or better were included. All patients received intravitreal and topical
antibiotics. Management by pars plana vitrectomy or vitreous tap and use or
nonuse of subconjunctival antibiotics were at the discretion of the treating
physician. RESULTS: There were 59 patients identified; 54 met the follow-up
criteria. These patients were divided into two groups based on whether
subconjunctival antibiotics were used (group ABX; n = 21) or not used (group
noABX; n = 33). The median pretreatment visual acuity was hand motions in both
groups. The median age in both groups was 74 years. Etiology, duration of
symptoms, vitreous culture organisms, percentage of cases with wound
complications such as leaks or vitreous incarceration, and intraocular lens type
were similar in the two study groups. Intravitreal and topical antibiotics and
corticosteroids used were not significantly different in the two groups, except
that topical ceftazidime was used less frequently in group ABX than in group
noABX (43% vs. 82%, respectively; P = 0.007). The median follow-up was 13 months
in both groups (range: 3-87 months for group ABX and 3-63 months for group noABX).
Final visual acuity in groups ABX and noABX was at least 20/50 (33% vs. 39%,
respectively), 20/60 to 5/200 (29% vs. 39%, respectively), 4/200 to better than
hand motions (0 vs. 3%, respectively), or hand motions or worse (38% vs. 18%,
respectively). These differences were not significant (P = 0.37). Reinjection
rates (14% vs. 15%, respectively) were also similar in groups ABX and noABX. The
additional procedures rate was significantly higher in group ABX than in group
noABX (P = 0.024), with cumulative rates of 33% and 3%, respectively, at the
12-month follow-up. CONCLUSIONS: These data suggest that subconjunctival
antibiotics may not be necessary to treat infectious endophthalmitis managed
with otherwise standard tap and injection techniques and topical antibiotics.
-----
Optometry. 2005 Aug;76(8):450-60.
Complications of intravitreal steroid injections.
Reichle ML.
VA Connecticut Healthcare System, Newington Campus, Newington, Connecticut, USA.
mlreichle@yahoo.com
BACKGROUND: Intravitreal corticosteroid injections are a new therapeutic
procedure used to treat various retinal edematous and neovascular conditions.
They have been used in the treatment of diabetic macular edema, exudative
macular degeneration, pseudophakic cystoid macular edema, macular edema
associated with retinal vein occlusion, and chronic uveitis as well as other
conditions. Because the use of this therapeutic technique is becoming
increasingly more common, adverse effects are now being seen. The most common
adverse effects associated with intravitreal steroid injection are elevation of
intraocular pressure and progression of cataract. Endophthalmitis,
pseudoendophthalmitis, and retinal detachment have also been reported. CASE
REPORTS: This report describes 2 patients who were followed up at the VA
Connecticut Healthcare System Newington Campus Optometry Clinic for
steroid-induced elevation of intraocular pressure after intravitreal
corticosteroid injection. One patient exhibited elevation of intraocular
pressure after his first intravitreal steroid injection for treatment of
clinically significant macular edema secondary to diabetes. The second patient
did not exhibit a steroid response to the first intravitreal steroid injection
utilized as treatment for choroidal neovascularization from age-related macular
degeneration. However, he did show a rise in intraocular pressure after a second
intravitreal corticosteroid injection. Intraocular pressures, treatment, and
frequency of follow-up in both patients pre- and postinjection are discussed.
CONCLUSION: Elevation of intraocular pressure after intravitreal steroid
injection can commonly be controlled with topical glaucoma medications. Cataract
progression is common in patients after intravitreal injection of
corticosteroid; however, findings show these patients are at no additional risk
for cataract surgery complications. Therefore, these do not appear to be major
contraindications. However, because 30% to 50% of patients experience
intraocular pressure rise up to a few months postinjection, and patients are at
higher risk for complications such as endophthalmitis, optometrists should be
aware of appropriate management after this increasingly utilized therapeutic
procedure.
-----
Ophthalmology. 2005 Aug;112(8):1472-7.
Mycophenolate mofetil therapy for inflammatory eye disease.
Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP.
Department of Ophthalmology, Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA. jthorne@jhmi.edu
PURPOSE: To evaluate treatment outcomes with mycophenolate mofetil in patients
with inflammatory eye disease. DESIGN: Retrospective case series. PARTICIPANTS:
Eighty-four consecutive patients with inflammatory eye disease treated with
mycophenolate mofetil at an academic referral center. METHODS: Medical records
were reviewed for treatment with mycophenolate mofetil. Dose of mycophenolate
mofetil, response to therapy, dose of prednisone, use of other immunosuppressive
drugs, and side effects associated with the use of mycophenolate mofetil were
recorded. MAIN OUTCOME MEASURES: Ability to control ocular inflammation with
mycophenolate mofetil and to taper prednisone to < or =10 mg daily, and
incidence of treatment-related side effects. RESULTS: Of the 84 patients treated
with mycophenolate mofetil, 61% had uveitis, 17% had scleritis, 11% had mucous
membrane pemphigoid, and 11% had orbital or other inflammatory disease.
Forty-three percent of patients treated with mycophenolate mofetil had been
treated with at least one other immunosuppressive drug previously. The median
dose of prednisone at the start of mycophenolate mofetil therapy was 40 mg, and
82% of the patients were considered a treatment success, as judged by the
ability to control the inflammation and taper prednisone to < or =10 mg daily.
Median time to treatment success was 3.5 months. Mycophenolate mofetil therapy
was discontinued due to insufficient efficacy at a rate of 0.10 per person-year
(PY) and due to side effects at a rate of 0.08/PY. The most frequent side effect
was gastrointestinal upset, with a rate of 0.19/PY. CONCLUSIONS: These data
suggest that mycophenolate mofetil may be an effective corticosteroid-sparing
agent in the treatment of inflammatory eye disease with a manageable side effect
profile.
-----
Ocul Immunol Inflamm. 2005 Jul-Aug;13(4):289-93.
Long-term follow-up of patients with birdshot retinochoroidopathy
treated with systemic immunosuppression.
Becker MD, Wertheim MS, Smith JR, Rosenbaum JT.
Casey Eye Institute, Oregon Health Sciences University, Portland, OR, USA.
Matthias.Becker@urz.uni-heidelberg.de
PURPOSE: Birdshot retinochoroidopathy (BRC) is a rare uveitis syndrome of
presumed autoimmune etiology. Therapy with systemic and periocular
corticosteroids is of inconsistent efficacy, attendant with numerous potential
long-term side effects. Corticosteroid-sparing strategies with agents such as
cyclosporine A or azathioprine have been suggested for this disease. METHODS: We
retrospectively reviewed the medical charts of patients with BRC who were
evaluated consecutively at a tertiary-care, referral-based North American
uveitis clinic over a 15-year period. RESULTS: Eleven Caucasian patients (22
eyes) were diagnosed with BRC, representing approximately 1% of all cases seen
at the uveitis clinic. HLA-A29 was positive in all 11 patients. We elected to
treat five patients with azathioprine, methotrexate, cyclosporine A,
mycophenolate mofetil, and/or IvIg, as well as systemic or periocular
corticosteroid injections. The median period of follow-up for the five treated
patients was six years (range: 8 months-13 years). Inflammation was reduced or
stabilized in five of five patients. CONCLUSION: Although the definitive
strategy for the management of BRC is unknown, control of intraocular
inflammation and preservation of vision is possible with corticosteroid-sparing
immunosuppressive agents.
-----
Br J Ophthalmol. 2005 Jul;89(7):806-8.
The use of low dose methotrexate in children with chronic
anterior and intermediate uveitis.
Malik AR, Pavesio C.
MD, FRCOphth, Moorfields Eye Hospital, London EC1V 2PD, UK. carlos.pavesio@moorfields.nhs.uk.
AIM: To assess the efficacy of low dose methotrexate (MTX) therapy for children
with chronic anterior and intermediate uveitis. METHODS: A retrospective case
review of 10 children who received MTX for chronic uveitis at a tertiary
referral centre was performed. The following data were recorded for each
patient: age, sex, race, duration of uveitis, primary diagnosis, anatomical
localisation of uveitis, corticosteroid therapy, dose range of MTX, duration of
MTX therapy, and side effects of MTX therapy. Several clinical parameters were
evaluated to study the effect of MTX. These included visual acuity, anterior
chamber inflammation, and topical and oral corticosteroid requirement. RESULTS:
After MTX VA of 6/6 or better was present in 100% right eyes and 80% left eyes
(p = 0.055 and p = 0.016, respectively). Anterior chamber inflammation decreased
in 60% of children after MTX (p = 0.0168). The requirement of topical steroid
decreased from a mean of 5.6 times a day before MTX to 1.5 times a day after MTX
(p = 0.005). The dose of oral steroid decreased from a mean of 18 mg per day to
2.85 mg per day (p = 0.012). The most common adverse effect was nausea (20%). No
patient required discontinuation of MTX because of side effects. CONCLUSION: MTX
is effective and safe for chronic anterior and intermediate uveitis in children.
An increase awareness of its efficacy is required among paediatricians and
ophthalmologists to prevent sight threatening complication of chronic uveitis
and its treatment with long term use of steroids.
-----
Ophthalmology. 2005 Jul;112(7):1192-8.
Long-term follow-up results of a pilot trial of a fluocinolone
acetonide implant to treat posterior uveitis.
Jaffe GJ, McCallum RM, Branchaud B, Skalak C, Butuner Z, Ashton P.
Department of Ophthalmology, Duke University Medical Center, Durham, North
Carolina, USA. Jaffe001@mc.duke.edu
PURPOSE: To investigate the safety and efficacy of a fluocinolone acetonide
intravitreal implant in the treatment of noninfectious posterior uveitis.
DESIGN: Noncomparative interventional case series, dose randomized, dose masked,
prospective. PARTICIPANTS: Thirty-six eyes of 32 patients with a history of
recurrent noninfectious posterior uveitis. METHODS: Patients were randomized to
receive either a 0.59-mg or a 2.1-mg fluocinolone acetonide intravitreal
implant. Patients were observed every 4 to 6 weeks for the first 3 months and
then every 3 months thereafter. MAIN OUTCOME MEASURES: Preoperative and
postoperative ocular inflammation, visual acuity (VA), antiinflammatory
medication use, and safety. RESULTS: Mean follow-up duration was 683+/-461 days
(range, 204-1817). Mean baseline visual acuity for the device-implanted eyes was
+1.1 logarithm of the minimum angle of resolution (logMAR) units (20/250), which
improved significantly to +0.81 logMAR units (20/125) at 30 months (P<0.05).
Inflammation was effectively controlled over the follow-up period. The average
number of recurrences in the 12 months before implantation was 2.5 episodes per
eye. None of these eyes experienced a recurrence for the first 2 years after
implantation. There was a reduction in systemic and local therapy use in the
device-implanted eyes; of the patients who remained on systemic medication after
implantation, dosage was reduced in 68%. The posterior sub-Tenon's capsule
injection rate significantly decreased from a mean of 2.2 injections per eye per
year to 0.07 injections per eye per year (P<0.0001) The most common adverse
event was intraocular pressure (IOP) rise. At baseline, 11.0% of eyes used
pressure-lowering agents, versus 56.1% over the follow-up period (P = 0.005).
Filtering procedures were performed in 7 (19.4%) eyes. Four of the 8 phakic
eyes, each of which had some level of cataract at device implantation,
subsequently underwent cataract extraction. There were no device explantations
or patients lost to follow-up during the investigation. CONCLUSION: The
fluocinolone acetonide intravitreal implant effectively controlled intraocular
inflammation in the studied population. Elevated IOP and cataracts that occurred
in fluocinolone device-implanted eyes were managed by standard means. The
fluocinolone acetonide sustained drug delivery implant seems to be promising in
patients with posterior uveitis who do not respond to or are intolerant to
conventional treatment.
-----
Br J Ophthalmol. 2005 Jun;89(6):666-9.
The efficacy of sirolimus in the treatment of patients with
refractory uveitis.
Shanmuganathan VA, Casely EM, Raj D, Powell RJ, Joseph A, Amoaku WM, Dua HS.
Division of Ophthalmology and Visual Science, B Floor, Eye and ENT Centre,
Queens Medical Centre, Nottingham NG7 2UH, UK.
AIMS: To determine the efficacy of sirolimus in the treatment of patients with
severe non-infectious uveitis. METHODS: Eight patients with severe
non-infectious uveitis were recruited to an open study. Inclusion criteria were
limited to patients whose disease was not controlled with at least two or more
separate steroid sparing immunosuppressants (either because of unacceptable side
effects or ineffectiveness of the drug) or who required regular doses of
corticosteroids either as high dose systemic or orbital floor injections in
order to control their disease. Intraocular inflammation, visual acuity,
symptoms, corticosteroid burden, drug toxicity, and side effects were monitored.
RESULTS: Sirolimus therapy was effective in five of the eight patients, all of
whom had their dose of corticosteroids reduced or discontinued. Treatment in
three patients was considered a failure as it caused intolerable side effects
and/or failed to control the uveitis. Side effects were common and were
typically gastrointestinal or cutaneous in nature. The severity of symptoms was
dose dependent in most cases and occurred at trough blood levels above 25 ng/ml.
CONCLUSION: Sirolimus is an effective and potent immunosuppressive treatment in
the majority of patients with non-infectious uveitis and can reduce the need for
long term supplementary corticosteroid therapy. Further studies are required to
establish the long term efficacy and safety of sirolimus alone or in combination
with other steroid sparing immunosuppressants.
-----
J Fr Ophtalmol. 2005 May;28(5):556-61.
[News on therapies for uveitis]
[Article in French]
de Smet MD.
Centre Medical Academique, Universite d'Amsterdam, Pays-Bas.
The immunosuppression required for the treatment of uveitis can be achieved
through conventional agents or through the use of specific modulators of
inflammation. Whatever the choice, it is important to limit side effects: by
restricting access to certain drugs in patients presenting a high risk of
complications (tuberculosis screening before using Remicade), reducing side
effects through preventive measures (use of alendronates during oral
corticotherapy), or choosing a local delivery route (intraocular triamcinolone).
Intraocular triamcinolone has certain beneficial characteristics such as high
local dosage without systemic effect. However, it can cause a pressure rise in
10% to 20% of patients. It requires certain precautions when given to prevent
development of a pseudo-endophthalmitis. Remicade is a novel synthetic
immunosuppressant directed against TNF-alpha. This chimeric antibody can be
useful in the treatment of severe uveitis that is unresponsive to conventional
therapy. It is currently being tested in clinical trials in uveitis both in
Europe and the USA.
-----
Clin Tech Small Anim Pract. 2005 May;20(2):117-20.
Feline uveitis: diagnosis and treatment.
Colitz CM.
Dept. of Veterinary Clinical Sciences, The Ohio State University College of
Veterinary Medicine, 601 Vernon Tharp St., 335 VMAB, Columbus, OH 43210, USA.
colitz.1@osu.edu
Uveitis is the inflammation of any or all parts of the vascular tunic of the
eye; the vascular tunic includes the iris, the ciliary body, and choroid. A good
knowledge base, up-to-date reference materials, and good instruments will
improve the diagnosis of uveitis. Feline uveitis can be caused by numerous
infectious agents in addition to neoplasia and less likely trauma. The
infectious causes most commonly associated with feline uveitis include feline
leukemia virus, feline immunodeficiency virus, feline infectious peritonitis,
systemic fungal infections, toxoplasmosis, and bartonellosis. Neoplastic causes
of uveitis can be primary or secondary. Iris melanoma is the most common primary
uveal neoplasia and trauma-associated sarcoma is the second most common primary
uveal neoplasia. Treatment for the clinical signs of anterior uveitis include
topical steroidal or non-steroidal anti-inflammatory agents, parasympatholytic
agents for ciliary spasm, to keep the pupil dilated, and to prevent posterior
synechia. Posterior uveitis should be treated with systemic medications that
will address the underlying cause. Enucleation of blind, painful eyes not
responsive to medications is a means to alleviate the animal's discomfort and to
further diagnose the underlying cause.
-----
Arch Ophthalmol. 2005 May;123(5):634-41.
Cyclosporine vs tacrolimus therapy for posterior and intermediate
uveitis.
Murphy CC, Greiner K, Plskova J, Duncan L, Frost NA, Forrester JV, Dick AD.
Division of Ophthalmology, University of Bristol, Bristol Eye Hospital, Lower
Maudlin Street, Bristol BS1 2LX, England.
OBJECTIVES: To compare the efficacy and tolerability of tacrolimus and
cyclosporine therapy for noninfectious posterior segment intraocular
inflammation and to evaluate their effect on peripheral blood CD4(+) T-cell
phenotype and activation status. METHODS: Thirty-seven patients who required
second-line immunosuppression for posterior segment intraocular inflammation
were enrolled in this prospective randomized trial of tacrolimus vs cyclosporine
therapy. The main outcome measures were visual acuity, binocular indirect
ophthalmoscopy score, adverse effects, and quality of life. In addition,
peripheral blood CD4(+) T-cell phenotype and activation status were evaluated by
flow cytometry before treatment and at 2, 4, and 12 weeks using CD69, chemokine
receptor (CCR4, CCR5, and CXCR3), and intracellular cytokine (tumor necrosis
factor alpha, interferon-gamma, and interleukin 10) expression. RESULTS:
Thirteen patients (68%) taking tacrolimus and 12 patients (67%) taking
cyclosporine responded to treatment. Cyclosporine therapy was associated with a
higher incidence of reported adverse effects. Mean arterial pressure and serum
cholesterol level were significantly higher at 3 months in the cyclosporine
group than the tacrolimus group. No significant difference was detected with
regard to effect on quality of life or CD4(+) T-cell phenotype. CONCLUSIONS:
Tacrolimus and cyclosporine were similar with regard to efficacy for posterior
segment intraocular inflammation, but the results suggested a more favorable
safety profile for tacrolimus therapy.
-----
Ophthalmology. 2005 May;112(5):764-70.
Initial evaluation of subcutaneous daclizumab treatments for
noninfectious uveitis: a multicenter noncomparative
interventional case series.
Nussenblatt RB, Peterson JS, Foster CS, Rao NA, See RF, Letko E, Buggage RR.
Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 20892, USA.
PURPOSE: To assess the feasibility of a study design that may determine whether
subcutaneous administration of the interleukin-2 receptor antibody daclizumab
can safely reduce the dependence on standard systemic corticosteroids or other
immunosuppressive regimens in patients with sight-threatening, noninfectious
intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Prospective,
multicenter, nonrandomized, noncomparative, open-label interventional trial.
PARTICIPANTS: Fifteen patients, 5 each at 3 clinical centers, with noninfectious
intermediate, posterior, or panuveitis, who require a currently stable
immunosuppression regimen of systemic corticosteroids and/or other systemic
treatments to control noninfectious intraocular inflammation. METHODS: After
enrollment and baseline ophthalmic evaluations, 2 induction treatments were
given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous
daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg
for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks
in a staggered fashion beginning with the first induction treatment. Safety
evaluations were performed at each treatment visit, with a primary efficacy
evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks. MAIN
OUTCOME MEASURES: Best-corrected visual acuity (Early Treatment of Diabetic
Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant
systemic immunosuppression medication load (tabulated by use of a weighted
scoring system) was assessed; target for success was defined as a 50% or greater
reduction in concomitant immunosuppression load by 12 weeks while maintaining
visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was
assessed at each visit with standardized grading scales. RESULTS: Ten of 15
patients (67%) receiving SC daclizumab treatments every other week successfully
achieved the primary efficacy end point of reducing their concomitant
immunosuppression load by at least 50% while maintaining their baseline visual
acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well
tolerated with no serious adverse events observed during the 6 months of
treatments, although 3 patients experienced possibly related, nonserious adverse
events. CONCLUSIONS: Subcutaneous daclizumab induction treatments at 2 mg/kg
followed by 1 mg/kg maintenance treatments every other week seems safe and, in
most cases, may reduce the concomitant immunosuppressive load required to treat
noninfectious uveitis for 12 to 26 weeks.
-----
Int Ophthalmol. 2004 May;25(3):147-53.
Efficacy and safety of 1% rimexolone versus 1% prednisolone
acetate in the treatment of anterior uveitis—a randomized
triple masked study.
Biswas J, Ganeshbabu TM, Raghavendran SR, Raizada S, Mondkar SV, Madhavan HN.
Medical and Vision Research Foundations, Sankara Nethralaya, 18, College Road,
Chennai 600 006, India. mrf@sankaranethralaya.org
PURPOSE: To evaluate the efficacy and safety of 1% rimexolone versus 1%
prednisolone acetate ophthalmic suspension in the treatment of anterior uveitis.
METHODS: A randomised triple masked, parallel comparison of rimexolone and
prednisolone acetate ophthalmic suspensions was carried out on 78 patients with
acute, chronic and recurrent anterior uveitis. Treatment regimen included
instillation of one or two drops of drug one hourly through the waking hours
during the first week, two hourly in the second week, four times a day in the
third week, two times a day for the first 4 days and once a day for the 3 days
in the last week. The patient was clinically evaluated on the 3-4th, 7-10th,
14th, 21st and 28th days. The patient was also reviewed on the 30th day.
Anterior chamber cells and flare reactions were compared for evaluating the
efficacy of the drugs. RESULT: Rimexolone is as effective as prednisolone
acetate ophthalmic suspension in the treatment of anterior uveitis. The largest
difference found was 0.1 in the flare reaction (statistically insignificant; p =
0.3) and 0.2 score units (statistically significant; p = 0.01) in the cells.
Overall, comparison of the drugs shows no clinical significance in the treatment
of anterior uveitis by either drug. Difference in intraocular pressure (IOP) was
also statistically insignificant (p > 0.05). However, three patients in the
prednisolone acetate group and 1 patient from the rimexolone group showed a rise
in IOP. CONCLUSION: Rimexolone 1% ophthalmic suspension is as effective as and
safer than prednisolone acetate 1% ophthalmic suspension in the treatment of
anterior uveitis.
-----
Br J Ophthalmol. 2005 Apr;89(4):444-8.
Uveitis in children and adolescents.
Benezra D, Cohen E, Maftzir G.
Department of Ophthalmology, Hadassah University Hospital, PO Box 12000,
Jerusalem 91120, Israel. benezra@md.huji.ac.il.
AIMS: To study the relative occurrence of uveitis (intraocular inflammation) and
its causes in children and adolescents. METHODS: Patients with uveitis examined
and followed during a period of 10 years were categorised by age and sex. All
underwent ocular examination and an individually tailored battery of laboratory
tests. The intraocular manifestations were classified according to the
anatomical location of the inflammation and their most probable cause. The final
diagnosis was based on typical clinical ocular and extraocular symptoms and
signs and on the results of specific laboratory investigations. RESULTS: Out of
821 patients, 276 (33.1%) were 18 years of age or younger with a male to female
ratio of 1 to 1. In these 276 children and adolescents, 70.3% had bilateral
ocular involvement. Intermediate uveitis was the most frequent anatomical
diagnosis. In many cases, symptoms were mild despite the prominent signs and
marked decrease of vision. The underlying cause for the uveitis was evaluated as
non-infectious in 184 cases (66.7%) and infectious in 92 cases (33.3%). A
potential aetiology and/or a definite clinical diagnosis were established in
74.6% of the cases and only 25.4% of the 276 patients were classified as
idiopathic. Juvenile idiopathic arthritis (JIA) was the most common systemic
disease association diagnosed in 14.9% of these children. Parasite infestation
was the most common infectious association. CONCLUSIONS: Uveitis in children and
adolescents is not as low as previously reported. Parasite infestation on the
one hand and JIA on the other hand are the most common aetiologies associated
with the uveitis in these young patients.
-----
Surv Ophthalmol. 2005 Mar-Apr;50(2):167-82.
Applications of liposomes in ophthalmology.
Ebrahim S, Peyman GA, Lee PJ.
Department of Ophthalmology, Tulane University Health Sciences Center, New
Orleans, LA, USA.
This review outlines the applications of liposomal formulations in
ophthalmology. In ophthalmology, liposomes have been used to treat disorders of
both the anterior and posterior segments. These include dry eyes, keratitis,
corneal transplant rejection, uveitis, endophthalmitis, and proliferative
vitreoretinopathy. Liposomes also have shown promise as vectors for genetic
transfection and monoclonal antibody-directed vehicles. Furthermore,
heat-activated liposomes have spurred research in focal laser and heat-induced
release of liposomal drugs and dyes for selective drug delivery. These
techniques have been useful in selective tumor and neovascular vessel occlusion,
angiography, and retinal and choroidal blood-flow studies. Although verteporfin
is the only liposomal drug currently approved for use in the eye, the benefits
of liposomes will likely be applied widely in all treatment, diagnostic, and
research aspects of ophthalmology in the future.
-----
Eye. 2005 Mar 11; [Epub ahead of print]
Ahmed valve implantation in glaucoma secondary to chronic uveitis.
Ozdal PC, Vianna RN, Deschenes J.
1Department of Ophthalmology, Uveitis Service, McGill University, Montreal,
Canada.
PURPOSE: To evaluate the efficacy of Ahmed valve (AV) implantation in patients
with uveitic glaucoma. METHODS: In total, 18 patients (19 eyes) with glaucoma
secondary to chronic uveitis, who underwent AV implantation were retrospectively
reviewed. Visual acuity, intraocular pressure (IOP), and glaucoma medications at
the most recent examination prior to surgery, were compared with those of last
postoperative examination. The surgical success was defined as IOP less than 21
mmHg and greater than 4 mmHg without loss of light perception and visually
devastating complications at the last postoperative examination. Decrease in the
number of glaucoma medications was also a criterion for surgical success.
RESULTS: The mean follow-up period was 26+/-9.7 months. The mean preoperative
and postoperative IOPs were 33.3+/-9.7 (range, 20-57) mmHg and 17.3+/-10.8
(range, 6-40) mmHg respectively (P<0.0001). The mean number of antiglaucoma
medications was 3.5+/-0.8 (range, 2-5) preoperatively and 1.4+/-1.3 (range, 0-4)
postoperatively (P<0.0001). Valve occlusion (five eyes, 26.3%) was the most
commonly observed complication. Surgical success was achieved in 13 eyes
(68.4%). The cumulative probability of success was 94.4% at 1 year and 60% at 2
years. Five eyes (26.3%) with IOP greater than 21 mmHg and one (5.3%) with
corneal decompensation requiring penetrating keratoplasty were considered as
failures. CONCLUSIONS: The implantation of AV is an effective surgical procedure
for the management of uveitic glaucoma. The inflammatory background might
contribute to the occurrence of valve occlusion, which is the most common
complication. Prevention of this complication is an essential factor for
improving the surgical outcome.Eye advance online publication, 11 March 2005;
doi:10.1038/sj.eye.6701841.
-----
Retina. 2005 Feb-Mar;25(2):182-8.
Long-term effect of acetazolamide treatment of patients with
uveitic chronic cystoid macular edema is limited by persisting inflammation.
Schilling H, Heiligenhaus A, Laube T, Bornfeld N, Jurklies B.
University Eye Hospital Essen, Essen, Germany. harald.schilling@uni-essen.de
PURPOSE: To assess the long-term effect of acetazolamide treatment on patients
with cystoid macular edema (CME) in the course of intermediate or posterior
chronic uveitis and to define those patients who may particularly benefit from
the drug. METHODS: Fifty-two eyes (45 patients) with chronic uveitic CME were
treated with acetazolamide at an initial dosage of 500 mg/d. The effect of
treatment was assessed by fluorescein angiography, ophthalmoscopy, visual
acuity, and Amsler testing. Therapy was withdrawn when CME did not improve at 3
weeks. In cases with CME improvement, the dosage was gradually tapered. RESULTS:
The mean follow-up was 3.1 years (minimum, 1.5 years). Two subgroups were
identified: group 1, quiescence of uveitis with acetazolamide as the single
therapeutic agent (33 eyes); and group 2, chronically active uveitis requiring
additional systemic antiinflammatory drugs (19 eyes). In both groups, visual
acuity improvement was statistically significant (group 1, P = 0.012; group 2, P
= 0.025). In 12 patients with a stable visual acuity gain, the medication dose
could be tapered off completely without any recurrent edema shown by fluorescein
angiography after a minimum follow-up of 1 year. Sixteen patients required a
maintenance dosage, ranging from 125 to 500 mg daily. No major adverse effects
of the medication were observed. CONCLUSIONS: During long-term follow-up,
low-dose acetazolamide can be a useful therapeutic option for chronic CME in
uveitis. The effect was better in patients with quiescence of uveitis than in
those with chronically active uveitis. Permanent therapy is not imperative in
every case.
-----
South Med J. 2005 Feb;98(2):192-204.
Role of biological agents in immune-mediated inflammatory
diseases.
Efthimiou P, Markenson JA.
Hospital for Special Surgery, Weill Medical College of Cornell University, New
York, New York 10021, USA. pee2001@med.cornell.edu
A new era in the treatment of immune-mediated inflammatory disorders has begun
with the clinical availability of anticytokine therapy. Biological agents that
are currently available include 3 agents that decrease the activity of tumor
necrosis factor-alpha (infliximab, adalimumab, etanercept) and an interleukin-1
receptor antagonist (anakinra), with many more in development. Those
extraordinarily effective medications are an important addition to our
therapeutic armamentarium, and, although originally developed for rheumatoid
arthritis and Crohn disease, have been found to be efficacious in the treatment
of seronegative spondyloarthropathies (psoriatic arthritis, ankylosing
spondylitis) and juvenile rheumatoid arthritis. Their role is currently being
defined in other autoimmune disorders such as uveitis, sarcoidosis, interstitial
lung disease, vasculitis, inflammatory myopathies, graft-versus-host disease,
and Sjogren syndrome.
-----
Drugs. 2005;65(4):497-519.
Management of sight-threatening uveitis : new therapeutic
options.
Becker MD, Smith JR, Max R, Fiehn C.
Interdisciplinary Uveitis Center, University of Heidelberg, Heidelberg,
GermanyDepartment of Ophthalmology, University of Heidelberg, Heidelberg,
Germany.
Over the past 2 decades therapy for the treatment of intraocular inflammation (uveitis)
has developed into a highly differentiated approach with an increasing number of
drug options. This paper primarily summarises literature from the past 5 years
(2000 to May 2004), gives an update on systemic immunosuppressive therapy for
non-infectious uveitis and speculates about new developments that could become
relevant in the near future for the treatment of uveitis patients. The spectrum
of immunosuppressive drugs has been notably expanded by tumor necrosis factor
inhibitors, but with some limitations to uveitis. Behcet's disease is an example
of uveitis where a multisystem disorder can affect the eye very severely. This
clinical example has been used to investigate the utility of many different
types of immunosuppressive therapies and the clinical approach is extensively
discussed in this review. An accompanying table summarises the proposed mode of
action, standard dosage, common adverse effects, as well as estimated cost of
current treatment options.
-----
Isr Med Assoc J. 2005 Feb;7(2):86-90.
The effect of the Dead Sea environment on uveitis.
Yagev R, Tsumi E, Avigur J, Polyakov P, Levy J, Lifshitz T.
Department of Ophthalmology, Soroka University Medical Center and Faculty of
Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. yagev@bgumail.bgu.ac.il
BACKGROUND: Uveitis is an acute or chronic inflammatory process of the uvea
caused by a number of etiologies. In many patients the etiology is unknown.
OBJECTIVE: To investigate the effect of the Dead Sea environment (climatotherapy)
on the signs, symptoms and clinical course of chronic uveitis. METHODS:
Fifty-five patients with chronic uveitis were examined at the beginning and end
of a 3-4 week stay at the Dead Sea region and on repeat visits to the region.
Study data included demographic information, medical history, etiology,
diagnosis, medication, and a complete ophthalmic examination. RESULTS:
Statistically significant improvements were seen between the two examinations
within each visit in four parameters (negative values indicate improvement): a)
visual acuity for near and far: Jaeger (-0.98 +/- 0.18, P < or = 0.001) and best
corrected visual acuity (-0.22 +/- 0.04, P < or = 0.0001); b) anterior chamber
flare (-0.18 +/- 0.06, P < or = 0.01); c) anterior chamber cells (-0.12 +/-
0.03, P < or = 0.0001); and d) vitreous cells (-0.17 +/- 0.05, P < or = 0.001).
There was a significant mean improvement during visits to the Dead Sea area and
a slight dissipation of the effect during the intervals between visits.
Sixty-four percent of the patients reported that they required less medication
and had fewer and milder attacks of uveitis following the visits. CONCLUSIONS:
The results of this study provide evidence of short- and possibly long-term
improvement in the signs and symptoms of uveitis following exposure to the Dead
Sea environment.
-----
J Rheumatol. 2005 Feb;32(2):362-5.
Methotrexate is an effective treatment for chronic uveitis
associated with juvenile idiopathic arthritis.
Foeldvari I, Wierk A.
Pediatric Rheumatologic Clinic, Allgemeines Krankenhaus Eilbek, Hamburg,
Germany. Sprechstunde@kinderrheumatologie.de
OBJECTIVE: To assess the effectiveness of methotrexate (MTX) in the treatment of
juvenile idiopathic arthritis (JIA) associated uveitis, which is still one of
the most common causes of visual impairment. METHODS: A retrospective chart
review of patients with the diagnosis of uveitis associated with JIA between
July 1, 2002, and December 31, 2002. RESULTS: Four hundred sixty-seven patients
with JIA were followed. Thirty-eight had uveitis: 31 associated with
oligoarticular JIA and 7 with psoriatic JIA. Twenty-five of the 38 patients
received MTX; in 23 patients uveitis was the indication for MTX therapy. In the
MTX treated group 46/50 eyes had uveitis, the mean (range) age at onset of
uveitis was 7.82 years (1.8-15.8), and the mean age at onset of arthritis was
7.25 years (1.25-15.7). MTX treatment was started an average of 11.4 months
(0-72) after the onset of uveitis. The mean MTX dose was 15.6 mg/m2. Remission
occurred after 4.25 months (1-12). Mean duration of remission was 10.3 months
(3-27). The total duration of MTX therapy was 661 months and patients were in
remission for 417/661 months. In 6 patients MTX was discontinued after 12 months
of remission. Four patients were still in remission after 7.5 months (1-14).
CONCLUSION: MTX seems to be an effective therapy for JIA associated uveitis.
-----
Clin Experiment Ophthalmol. 2004 Dec;32(6):563-8.
Clinical trial to compare efficacy and side-effects of injection
of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in
the management of posterior uveitis.
Ferrante P, Ramsey A, Bunce C, Lightman S.
Moorfields Eye Hospital, London, UK.
Abstract Aim: To compare the efficacy and side-effects of posterior sub-Tenon
injection of triamcinolone acetonide (Kenalog) with orbital floor injection of
methylpredisolone acetate (Depomedrone) in the management of posterior uveitis.
Methods: Non-randomized comparative prospective clinical study. Sixty-four eyes
from 60 consecutive patients with non-infectious posterior uveitis requiring
treatment were allocated on an alternate 1:1 basis to receive either orbital
floor methylprednisolone or sub-Tenon triamcinolone using standard procedures
and assessed at 6 and 12 weeks. Results: After five eyes of five patients who
had received the same treatment bilaterally were excluded from the statistical
analysis, 14 out of 29 eyes treated with orbital floor methylprednisolone and 10
out of the 30 eyes given sub-Tenon triamcinolone improved at 6 weeks. There was
no statistically significant difference in the improvement rate between the two
groups. However, two patients given triamcinolone had prolonged upper lid ptosis,
which required surgery, and another two developed markedly raised intraocular
pressure, neither of which occurred in the methylprednisolone-treated group.
Conclusions: Although the two drugs and routes compared were of similar
efficacy, lid ptosis occurred in the triamcinolone-treated but not the
methylprednisolone group. This should be borne in mind when choosing the
preferred route of delivery of periocular corticosteroid in the treatment of
posterior uveitis.
-----
J Glaucoma. 2004 Dec;13(6):445-9.
Goniosurgery for glaucoma secondary to chronic anterior uveitis:
prognostic factors and surgical technique.
Ho CL, Walton DS.
Singapore National Eye Centre, Singapore, Republic of Singapore.
PURPOSE: To describe the preoperative prognostic factors that correlate with the
surgical success of goniosurgery for glaucoma complicating chronic anterior
uveitis and to describe the surgical technique. METHODS: The medical records of
31 patients with 31 eyes with glaucoma secondary to chronic anterior uveitis for
which 38 goniotomy procedures were performed were reviewed. Uveitis etiology,
gender, age of onset of iritis, duration of iritis before recognition of
glaucoma, duration of iritis and duration of glaucoma until initial goniosurgery,
preoperative gonioscopic findings, lens status, surgical outcome, age at initial
goniosurgery, duration of postoperative observation, lens status, preoperative
and postoperative intraocular pressures, topical steroid, and glaucoma
medication use were reviewed. Complete success was defined by an intraocular
pressure (IOP) < or = 21 mm Hg, and qualified success as IOP < or = 21 mm Hg
with use of glaucoma medications. The surgical technique used to perform the
goniosurgery was reviewed. RESULTS: Overall surgical success was achieved in 22
(71%) of 31 eyes. The mean age at surgery was 10.2 +/- 4.2 years (range, 4-21
years). All but 8 patients were female. Mean follow-up interval was 10.3 +/- 6.4
years (range, 1.5-22 years). Significant correlation was found between outcome
and age at initial surgery, lens status, duration of glaucoma before
goniosurgery, duration of iritis before glaucoma surgery, and hours of
peripheral anterior synechia (PAS). The mean number of clock hours of
preoperative (PAS) was 0.5 hours in eyes with success versus 2.5 hours in eyes
with failure. Age of onset of iritis, duration of iritis before recognition of
glaucoma, trabecular meshwork pigmentation (TM), TM opacification, and
circumferential ciliary body band narrowing did not correlate with surgical
outcome. CONCLUSION: Goniosurgery is an effective treatment of glaucoma
secondary to chronic anterior uveitis. The outcome of surgery was unfavorably
influenced by older age, longer duration of glaucoma, and evidence of more
advanced preoperative filtration angle abnormalities secondary to uveitis.
Goniosurgery for this secondary glaucoma can be successfully performed utilizing
the standard goniotomy technique.
-----
Curr Opin Ophthalmol. 2004 Dec;15(6):531-6.
Herpes zoster virus infection.
Liesegang TJ.
Mayo Clinic Medical School, Jacksonville, Florida, USA.
PURPOSE OF REVIEW: The virology, pathophysiology, and treatment of the varicella
zoster virus (VZV) have been investigated for many years now. Infection with VZV
has different ramifications for people of different ages and immune status. The
various aspects of VZV disease make it difficult to treat. Selected aspects of
VZV disease that pertain to ocular disease are presented. RECENT FINDINGS: The
risk factors for VZV disease in the different age spectrums and with concomitant
immunodeficiencies have been further clarified. Studies suggest that the VZV may
persist for prolonged periods on the cornea after herpes zoster ophthalmicus (HZO).
Herpes Simplex Virus (HSV) or VZV may cause many cases of idiopathic uveitis
with sectoral iris atrophy. The different patterns of retinal disease caused by
VZV may relate to the immune status. Systemic antiviral medications for herpes
zoster should be instituted within 72 hours of the rash but could be used later.
Systemic antivirals combined with systemic corticosteroids improve the early
quality of life in HZ patients. Postherpetic neuralgia is not prevented by early
systemic antivirals or corticosteroids. Present systemic antivirals are all
effective, but Famvir offers the best dosing schedule. The VZV vaccine is
effective but there are some issues that suggest the need for a different
vaccination regimen. SUMMARY: Further research must be performed on the clinical
and therapeutic aspects of the VZV disease. Although both the vaccine and
systemic antivirals have brought tremendous improvements, the disease persists.
Therapy lessens but does not eliminate many of the complications. The disease
may manifest in unpredictable patterns in this era of vaccination.
-----
Eye. 2004 Sep 24; [Epub ahead of print]
Long-term treatment of refractory posterior uveitis with anti-TNFalpha
(infliximab).
Benitez-Del-Castillo JM, Martinez-De-La-Casa JM, Pato-Cour E, Mendez-Fernandez
R, Lopez-Abad C, Matilla M, Garcia-Sanchez J.
1Department of Ophthalmology, Instituto de Investigaciones Oftalmologicas Ramon
Castroviejo, Hospital Clinico San Carlos, Universidad Complutense de Madrid,
Spain.
PURPOSE: To evaluate the long-term efficacy and safety of infliximab as
treatment for noninfectious posterior uveitis. METHODS: An open-label clinical
trial including seven patients (12 eyes) with posterior uveitis refractory to
conventional treatment regimens with corticosteroids and at least one
immunosuppressive agent. Three intravenous doses of 5 mg/kg of infliximab were
administered at weeks 0, 2, and 6. Infliximab infusion was repeated in patients
undergoing a relapse of uveitis after initial remission. Improvement was defined
as amelioration of visual acuity or disappearance of retinal exudates and/or
haemorrhages, decreased macular oedema and/or vitreous opacities. All patients
were followed up for at least 36 months. RESULTS: Six of the seven patients
(five diagnosed with Behcet's disease and one diagnosed with sarcoidosis) showed
a significant improvement after the first infliximab dose. Only in one patient
diagnosed with chronic idiopathic multifocal choroiditis did the drug have no
effect, and this patient was withdrawn from the study. At the end of follow-up,
one eye had lost one line of vision and three eyes showed improved vision. All
eyes had improved in terms of signs of inflammation. No adverse effects of
treatment were observed. CONCLUSION: Infliximab is efficient and safe for the
long-term management of refractory posterior uveitis, especially in patients
with predominant retinal vasculitis and vitritis.Eye advance online publication,
24 September 2004; doi:10.1038/sj.eye.6701689
-----
Reumatismo. 2004 Jul-Sep;56(3):185-9.
[The treatment of recurrent uveitis with TNFalpha inhibitors]
[Article in Italian]
Falappone PC, Iannone F, Scioscia C, Grattagliano V, Covelli M, Lapadula G.
DIMIMP--Sezione di Reumatologia, Universita degli studi di Bari, Bari.
OBJECTIVE: Uveitis is a severe manifestation of rheumatic diseases since it can
lead to visual impairment and even blindness. Ocular involvement is frequently a
clinical challenge because its occurrence often requires changes of the
therapeutic strategy. There are growing evidence that tumor necrosis factor
alpha (TNFalpha) inhibitors may be an effective treatment of refractory uveitis.
Purpose of this study was to evaluate the efficacy and safety of TNFalpha
blocking agents in patients with seronegative spondylo-arthropathies (SNSA) and
Behcet disease (BD) associated relapsing uveitis. METHODS: Five consecutive
patients with chronic or relapsing uveitis were prospectively studied. Two
patients with SNSA had recurrent anterior uveitis and three patients had BD
associated uveitis (one anterior, two posterior uveitis). All of the patients
were taking systemic and topical corticosteroids and three of them were also
treated with DMARDs (methotrexate, cyclosporine, sulphasalazine) without
clinical benefit. Four patients received infliximab, an anti-TNFalpha monoclonal
antibody, at a dosage of 5 mg/kg body weight and one patient was treated with
etanercept, a TNFalpha receptor p75-Fc fusion protein, at a dosage of 25 mg
twice weekly. RESULTS. Both infliximab and etanercept induced a marked
improvement in uveitis and none relapse was observed throughout all the study.
Systemic corticosteroids were progressively tapered and stopped in all patients.
Also methotrexate and sulphasalazine were discontinued, while cyclosporine dose
has been reduced by 30%. No side effects were observed. CONCLUSIONS. Therapy
with TNFalpha blockers, infliximab and etanercept, was effective and safe in the
treatment of rheumatic disease associated uveitis. A complete remission was
achieved even in patients with severe steroid resistant uveitis. Further
controlled studies on larger number of patients are needed to better define the
different forms of ocular involvement that can benefit from the therapy with
TNFalpha inhibitors.
-----
Br J Ophthalmol. 2004 Sep;88(9):1122-4.
Steroid prophylaxis in eyes with uveitis undergoing
phacoemulsification.
Meacock WR, Spalton DJ, Bender L, Antcliff R, Heatley C, Stanford MR, Graham EM.
Tremona Road, Eye Unit, Southampton General Hospital, Southampton, Hants, UK.
wmeacock@hotmail.com
AIM: To compare the efficacy of two preoperative steroid regimens for cataract
surgery in patients with uveitis. METHODS: 40 uveitis patients with cataract
underwent phacoemulsification and intraocular lens (IOL) implantation.
Preoperatively they were randomised into two groups: group 1 (20 patients)
received a single dose of intravenous methylprednisolone (15 mg/kg) half an hour
before surgery, and group 2 (20 patients) received a 2 week course of oral
prednisolone (0.5 mg/kg) which was tapered postoperatively. Preoperatively
patients had aqueous flare and cells measured with the Kowa laser flare meter.
On days 1, 7, 28, and 90 aqueous flare and cells were measured, and on days 7
and 90 fluorescein angiography was performed to determine the incidence of
cystoid macular oedema (CMO). RESULTS: At all postoperative visits the mean
increase in flare was greater for group 1 (intravenous steroid). Patients with
posterior synechiae had greater blood-aqueous barrier damage (BAB)
postoperatively. There were no statistically significant differences in logMAR
visual acuity and incidences of CMO between the two groups at 7 and 90 days.
CONCLUSION: A 2 week course of oral prednisolone, tapered postoperatively,
produced a better recovery of the BAB than a single dose of intravenous
methylprednisolone and is thus the recommended preoperative regimen.
-----
Curr Opin Ophthalmol. 2004 Aug;15(4):293-8.
Review of immunosuppressive drug therapy in uveitis.
Dunn JP.
Department of Ophthalmology, Division of Ocular Immunology, The Wilmer Eye
Institute, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
jpdunn@jhmi.edu
PURPOSE OF REVIEW: Uveitis is an important cause of functional visual loss and
blindness in the developed world. Immunosuppressive drugs may be required to
treat severe noninfectious uveitis successfully, but the efficacy and safety of
such treatments are often limited by the small numbers of patients enrolled in
clinical trials or studied retrospectively, the absence of control participants,
and the variable natural course of some types of uveitis. This review was
undertaken to highlight recent clinical advances in the treatment of severe
noninfectious uveitis. RECENT FINDINGS: A literature search emphasizing the
research published since 2001 was undertaken. The role of previously available
immunosuppressives such as antimetabolites, calcineurin inhibitors, and
alkylating agents continues to develop. In recent years, more specific drugs,
collectively known as biologics, have been used in the treatment of uveitis. A
persistent limitation of the published literature remains the general lack of
randomized, controlled clinical trials. The long-term risks of most
immunosuppressive drugs and the risk of relapse after discontinuation of therapy
are also not well established. Tumor necrosis factor-alpha antagonists are
promising but extremely expensive, and they may be more effective for
rheumatologic and nonocular autoimmune disorders than for uveitis. SUMMARY: The
number of options available for the treatment of severe noninfectious uveitis
has expanded in the past few years. While promising, the new drugs are
expensive, and their long-term efficacy and safety are not known; consequently,
older immunosuppressive drugs still play an important role in the treatment of
uveitis.
-----
Eye. 2004 Aug 20 [Epub ahead of print]
The surgical management of chronic hypotony due to uveitis.
De Smet MD, Gunning F, Feenstra R.
1Department of Ophthalmology, Academic Medical Center, University of Amsterdam,
Amsterdam, The Netherlands.
PURPOSE: Evaluate surgery in chronic hypotony secondary to uveitis. METHOD:
Retrospective analysis of six patients operated for chronic hypotony (</=5 mmHg)
of at least 1 month's duration. Surgery involved removal of all traction and
membranes on the ciliary processes. Use of oil was limited to patients with
atrophic ciliary processes. RESULTS: The average postoperative follow-up was 24
months (12-43). The average pressure increase was 7 mmHg at 6 months. Four of
six uveitis patients had significantly increased vision. CONCLUSION: Improved
vision, and a sustained pressure rise are possible in hypotonous uveitis. The
presence of ciliary processes is necessary. However, they do not need to be
intact.Eye advance online publication 20 August 2004; doi:10.1038/sj.eye.6701425
-----
Ophthalmologica. 2004 Jul-Aug;218(4):223-36.
Uveitis: a potentially blinding disease.
Durrani OM, Meads CA, Murray PI.
Academic Unit of Ophthalmology, The University of Birmingham, Birmingham, UK.
Uveitis (intraocular inflammation) is a potentially blinding group of, probably
autoimmune, conditions predominantly occurring in the working age group.
Although the aetiology is unknown in most cases, many patients have an
associated underlying systemic disease. Central vision loss, in the form of
cystoid macular oedema, is the commonest type of visual impairment. Although
historical incidence and prevalence data exists, little is known about the
degree of vision loss experienced, and the social and financial consequences of
having temporary or permanent visual impairment in this age group. The
literature is also full of uncontrolled studies and case reports of different
modalities of drug therapy for uveitis. This article attempts to raise the
awareness of uveitis as an important sight-threatening group of conditions by
highlighting the paucity of evidence-based data on epidemiological, quality of
life, socioeconomic, and therapeutic aspects. Copyright 2004 S. Karger AG, Basel
-----
Eye. 2004 Jul 2 [Epub ahead of print]
Long-term results of cataract extraction with intraocular lens
implantation in patients with uveitis.
Rahman I, Jones NP.
1The Royal Eye Hospital, Manchester, UK.
OBJECTIVE: To investigate the long-term visual results after cataract extraction
in patients with uveitis, and to demonstrate the long-term viability of
intraocular lenses. DESIGN: In all, 61 patients (72 eyes), with update clinical
examination, were retrospectively evaluated. Comparison of preoperative,
postoperative, and latest visual function including best-corrected Snellen
visual acuity, progression of uveitis and its complications, need for
postoperative medical or surgical interventions. RESULTS: After a minimum
follow-up of 5 years (mean 7 years 7 months), 82% of eyes maintained a visual
improvement of two Snellen lines, 74% maintained 6/9 or better, and 14% had 6/18
or worse. The mode acuity was better than 6/6. The prevalence of macular oedema
or scarring was 24%, of posterior capsule opacification 96%, and of glaucoma
drainage, 15%. CONCLUSIONS: We report the long-term follow-up of cataract
extraction and intraocular lens (IOL) implantation performed by a single surgeon
on patients with uveitis attending a regional tertiary referral uveitis clinic.
Using stringent perioperative and postoperative control of inflammation,
patients with uveitis usually maintain high visual acuity over long-term
follow-up. The incidence of sight-threatening postoperative complications is low
and no ongoing complication has been attributed to IOL implantation.Eye advance
online publication, 2 July 2004; doi:10.1038/sj.eye.6701450
-----
Arch Ophthalmol. 2004 Jun;122(6):845-51.
Neutralizing tumor necrosis factor activity leads to remission in
patients with refractory noninfectious posterior uveitis.
Murphy CC, Greiner K, Plskova J, Duncan L, Frost A, Isaacs JD, Rebello P,
Waldmann H, Hale G, Forrester JV, Dick AD.
Division of Ophthalmology, University of Bristol, Bristol, England.
OBJECTIVE: To evaluate the efficacy and safety of tumor necrosis factor (TNF)
inhibition with the p55 TNF receptor fusion protein (TNFr-Ig) for severe
sight-threatening noninfectious posterior segment intraocular inflammation.
METHODS: Seventeen patients with refractory noninfectious posterior segment
intraocular inflammation received TNFr-Ig by intravenous infusion in this
nonrandomized, open-label, pilot study. The primary outcome measure was logMAR
visual acuity. Secondary outcome measures were binocular indirect ophthalmoscopy
score, cystoid macular edema, adverse effects, and vision-related (visual core
module 1) and health-related (36-Item Short-Form Health Survey) quality of life.
RESULTS: Within 1 month of TNFr-Ig therapy, 9 patients (53%) achieved at least a
2-line improvement in visual acuity, 8 (57%) of 14 patients with vitreous haze
before treatment achieved an improvement in binocular indirect ophthalmoscopy
score to 0, and macular edema resolved in 5 (56%) of 9 affected patients. Twelve
(71%) of the patients achieved complete cessation of intraocular inflammation
following TNFr-Ig therapy. A reduction in concomitant immunosuppression was
possible for 11 patients (65%) following TNFr-Ig therapy. However, all but 1
patient required continuing adjuvant therapy during the response to TNFr-Ig,
which had a median duration of 3 months. Adverse effects included mild infusion
reactions in 3 patients and transient lymphocytopenia in 2 patients. CONCLUSION:
Therapy with TNFr-Ig was safe and effective for treating patients with
sight-threatening noninfectious posterior segment intraocular inflammation
resistant to conventional immunotherapy, but adjuvant immunosuppression and
repeat infusions would be required to maintain long-term remission.
-----
Retina. 2004 Jun;24(3):376-82.
Long-term results of treatment of macular complications in eyes
with immune recovery uveitis using a graded treatment approach.
El-Bradey MH, Cheng L, Song MK, Torriani FJ, Freeman WR.
Shiley Eye Center, San Diego, CA 92093-0946, USA.
PURPOSE: To evaluate the results of a graded treatment approach in a cohort of
eyes with macular complications of immune recovery uveitis. METHODS: A cohort of
18 eyes of 13 patients representing all eyes with these complications at the
University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes
were classified into three groups and treated according to a graded protocol.
RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better)
were observed. These six eyes maintained good vision with only one dropping to
20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of
9 patients), repository sub-Tenon steroid injections were used repeatedly. There
were no complications of steroid use but visual improvement occurred in only 40%
of eyes. Macular edema persisted. In eyes with structural macular changes, such
as epiretinal membrane, vitrectomy resulted in vision improvement in three of
four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild
cases of immune recovery uveitis and macular edema may be observed. In eyes with
reduction of vision due to cystoid macular edema, there was only a modest
treatment effect using repository corticosteroids. Eyes with immune recovery
uveitis that develop epiretinal membrane undergo some visual improvement after
removal of the membrane. The macular edema of immune recovery uveitis is
resistant to corticosteroid treatment.
-----
J Fr Ophtalmol. 2004 May;27(5):528-37.
[Viral uveitis]
[Article in French]
Bodaghi B.
Service d'Ophtalmologie, Hopital Pitie-Salpetriere, 47-83, boulevard de
l'Hopital, 75013 Paris. bahram.bodaghi@psl.ap-hop-paris.fr
Viral eye diseases are common and associated with different well-known forms of
uveitis. However, experimental models and clinical observations have led to an
infectious, in particular a viral etiology in different autoimmune conditions.
The use of molecular techniques is particularly informative, not only to
characterize the previously well-known subgroup of presumed viral uveitis, but
also to define the role of these agents or emerging viruses in atypical forms of
autoimmune uveitis resistant to conventional therapy. PCR detection of viral DNA
in patients with uveitis is a rapid, sensitive and accurate procedure.
Therefore, aqueous humor could be analyzed when uveitis is unresponsive to
anti-inflammatory molecules, in order to exclude a viral condition and
dramatically modify the therapeutic management. Several new viral entities have
recently been identified such as cytomegalovirus-associated chronic anterior
uveitis and non-necrotizing herpetic retinopathies in immunocompetent hosts.
Systemic antiviral drugs should be proposed rapidly in order to control viral
replication before the use of corticosteroids. Maintenance therapy based on
low-dose antivirals can reduce the rate of recurrence and should be considered.
-----
Klin Monatsbl Augenheilkd. 2004 May;221(5):339-42.
Deep sclerectomy for the management of uncontrolled uveitic
glaucoma: preliminary data.
Auer C, Mermoud A, Herbort CP.
Inflammatory Eye Diseases, Centre Ophtalmologique de la Source, Lausanne,
Switzerland.
BACKGROUND: If medical treatment fails in uveitic glaucoma a surgical approach
should be considered. Classical trabeculectomy is known to have a less
favourable outcome in uveitis. Our intention is to report the first series of
uveitis patients with glaucoma resistant to medical therapy who were treated
with deep sclerectomy (DS). PATIENTS AND METHODS: Fourteen eyes of 13 patients
(mean age 39.0 +/- 18.5 years; range 8 to 76 years) with chronic uveitis
underwent non-penetrating filtering surgery from 1995 to 2003. All patients had
their uveitis controlled before and after surgery by immunomodulatory therapy.
Non-penetrating filtering surgery consisted of DS with collagen implant (Staar(R))
in 4 eyes, DS with draining device (T-Flux Ioltech(R)) in 2 patients, DS without
implant in 7 patients and with viscocanalostomy in 1 patient. Nine eyes (65 %)
received mitomycin C peri-operatively. RESULTS: Intra-ocular pressure (IOP) was
reduced from a mean pre-operative value of 42.8 +/- 13.6 mmHg to a 1-year mean
post-operative value of 12.1 +/- 4.0 (71.7 % reduction). Eleven of the 14 eyes
completed 12 months of follow-up, resulting in complete success in 5 (45.4 %)
and in qualified success in 5 (45 %) and in failure in one patient (9.2 %),
later controlled by a second operation. Anti-glaucomatous medication was reduced
from a mean of 3.7 +/- 0.5 medications preoperatively to 1.2 +/- 0.8 medications
(71.4 % reduction) at the 12 month follow-up. Nine of the 14 patients achieved a
24 month follow-up with a mean IOP of 14.1 +/- 3.8 mmHg and mean of
anti-glaucomatous medications of 1.6. Four patients have been examined 4 years
after the DS: mean IOP was 13.2 +/- 2.2 mmHg and mean medication 1.7 +/- 1.0.
Post-operative complications included one case of lens opacity and 2 cases of
hypotony lasting for five months and four weeks after the intervention
respectively. CONCLUSION: Non-penetrating filtering surgery controlled the
intra-ocular pressure in 90 % of eyes with uveitic glaucoma resistant to medical
therapy at 12 months. Surgical complications were low which may explain the high
success rate of the procedure, compared to classical penetrating surgery.
-----
Klin Monatsbl Augenheilkd. 2004 May;221(5):324-7.
Phacoemulsification with intraocular lens implantation in
patients with uveitis.
Moschos MM, Bui MA, Guex-Crosier Y.
Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland.
BACKGROUND: Cataract remains a challenge for ophthalmologists in uveitic eyes.
The aim of this study is to report the clinical course of phacoemulsification
with intraocular lens implantation in eyes suffering from uveitis. PATIENTS AND
METHODS: Patients presenting a uveitis were prospectively followed from June
2001 to June 2003. Ocular surgery was performed according to a standard
protocol, autoimmune follow-up visits were focused on the early detection of
complications of uveitis: increased ocular inflammation, synechiae, retraction
of the rhexis, opacification of the posterior capsule or onset of cystoid
macular edema. RESULTS: Thirty-two eyes of 24 patients suffering from uveitis
were operated with cataract surgery between June 2001 and June 2003. The mean
age at surgery was 56 years (range 24 - 86 years). Mean preoperative visual
acuity in uveitis patients presenting cataract was 0.3 +/- 0.3, and final visual
acuity was 0.8 +/- 0.3. Three patients presented minor postoperative
complications. One patient had a cystoid macular edema that appeared 5 months
after surgery and one patient had a relapse of herpetic dendritic keratopathy
despite topical antiviral therapy combined with steroid drops. The latter
presented a slight increase of intraocular pressure (24 mm Hg). CONCLUSIONS: In
patients with uveitis requiring cataract surgery, intraocular lens implantation
is safe. Visual prognosis is better when pre- and postoperative inflammation is
minimized. Macular scars or other retinal lesions are poor prognostic
indicators.
-----
Ophthalmology. 2004 May;111(5):960-5.
Pulse IV cyclophosphamide in ocular inflammatory
disease; Efficacy and short-term safety.
Durrani K, Papaliodis GN, Foster CS.
Immunology & Uveitis Service, Department of Ophthalmology,
Massachusetts Eye & Ear Infirmary, Boston, Massachusetts,
USA.
PURPOSE: To assess the efficacy and short-term safety of appropriately
monitored pulse IV cyclophosphamide therapy in the treatment of
patients with severe or treatment-resistant autoimmune ocular
inflammatory disease. DESIGN: Retrospective noncomparative interventional
case series. PARTICIPANTS: Thirty-eight patients with severe or
recalcitrant ocular inflammation of diverse etiologies. METHODS:
Charts of patients seen on the Ocular Immunology & Uveitis
Service at the Massachusetts Eye & Ear Infirmary were reviewed.
Thirty-eight consecutive patients treated with pulse IV cyclophosphamide
between January 1995 and March 2002 were analyzed. MAIN OUTCOME
MEASURES: The control of inflammation, steroid-sparing effect,
visual acuity, and adverse reactions. RESULTS: A positive response
to treatment occurred in 68% of patients during the study period,
with 55% achieving complete quiescence. A steroid-sparing effect
was achieved in all patients previously on systemic steroid, allowing
successful discontinuation of the drug in 41%. Visual acuity was
maintained in 66% and improved in 21% of involved eyes. The most
common side effects observed were fatigue (63%), nausea (32%),
and headache (22%). None required a permanent discontinuation
of therapy. CONCLUSIONS: Pulse IV cyclophosphamide is an effective
therapeutic modality in patients with severe or treatment-resistant
ocular inflammatory disease.
-----
Transplant Proc. 2004 Mar;36(2 Suppl):372S-377S.
Experience with cyclosporine in endogenous uveitis
posterior.
Hesselink DA, Baarsma GS, Kuijpers RW, van Hagen PM.
Department of Internal Medicine, Renal Transplant Unit, Erasmus
Medical Center, Rotterdam, The Netherlands. d.a.hesselink@erasmusmc.nl
Treatment with cyclosporine (CsA) has considerably improved
the visual prognosis of patients suffering from endogenous posterior
uveitis (EPU). However, the therapeutic benefits of CsA are partially
outweighed by its many side effects, most notably nephrotoxicity
and hypertension. Low-dose CsA regimens have reduced toxicity
but have not been able to completely eliminate this problem. New
therapeutic approaches, such as anti-tumor necrosis factor alpha
treatment or immunosuppression with drugs including tacrolimus,
sirolimus, and interleukin-2 receptor antibodies, are currently
under evaluation. Hopefully such strategies will further reduce
the morbidity of EPU and minimize the adverse effects associated
with conventional therapies.
-----
Clin Infect Dis. 2004 Feb 15;38(4):542-6. Epub 2004 Jan 26.
Postoperative endophthalmitis.
Hanscom TA.
Jules Stein Eye Institute, University of California-Los Angeles
School of Medicine, and Saint John's Hospital, Santa Monica, California,
USA. retinalsurg@earthlink.net
Postoperative endophthalmitis remains a serious clinical problem
in ophthalmology, with an incidence of approximately 0.5%. Prognosis
is largely determined by the virulence of the offending organism.
The Endophthalmitis Vitrectomy Study (EVS) was a prospective,
randomized trial comparing various diagnostic and treatment modalities
in cases of endophthalmitis that followed cataract surgery. The
EVS found that vitrectomy was only beneficial for patients presenting
with very poor visual acuity and that intravenous antibiotic treatments
had no additional benefit, compared with intravitreal antibiotic
therapy alone. However, weaknesses of the EVS leave these conclusions
open to modification in the future. Preoperative application of
povidone-iodine preparation to the skin and conjunctiva is the
only proven endophthalmitis prophylaxis. Endophthalmitis may be
chronic and may follow glaucoma surgery and intravitreal injection
of gas and drugs. The EVS did not study these issues, although
they are associated with specific features that may require alterations
in patient management.
-----
Am J Ophthalmol. 2004 Jan;137(1):38-42.
Endophthalmitis isolates and antibiotic sensitivities:
a 6-year review of culture-proven cases.
Benz MS, Scott IU, Flynn HW Jr, Unonius N, Miller D.
Bascom Palmer Eye Institute, University of Miami School of Medicine,
Miami, Florida, USA. mbenz@bcm.tmc.edu
PURPOSE: To investigate the spectrum of organisms causing culture-proven
endophthalmitis and their sensitivities to commonly used antimicrobial
agents. DESIGN: Retrospective, noncomparative, consecutive case
series. METHODS: Medical records were reviewed of all patients
with culture-proven endophthalmitis at a single institution between
January 1, 1996, and December 31, 2001. Endophthalmitis categories
included postoperative, posttraumatic, endogenous, and miscellaneous
(for example, keratitis). The outcome measures included intravitreal
isolates identified, antibiotic sensitivities, and category of
endophthalmitis. RESULTS: In all, 313 organisms were isolated
from 278 patients during the study interval. The most common organisms
identified were Staphylococcus epidermidis in 27.8% (87/313),
Streptococcus viridans group in 12.8% (40/313), other coagulase-negative
staphylococci in 9.3% (29/313), Staphylococcus aureus in 7.7%
(24/313), and Propionibacterium acnes in 7.0% (22/313). Overall,
246 of 313 (78.5%) isolates were gram-positive organisms, 37 (11.8%)
were gram-negative organisms, and 27 (8.6%) were fungi. For gram-positive
organisms, sensitivities were the following: vancomycin 100%,
gentamicin 78.4%, ciprofloxacin 68.3%, ceftazidime 63.6%, and
cefazolin 66.8%. For gram-negative organisms, sensitivities were
the following: ciprofloxacin 94.2%, amikacin 80.9%, ceftazidime
80.0%, and gentamicin 75.0%. Fungal isolates were Candida species
(9/313), Aspergillus species (9/313), and other molds (9/313).
Among the endophthalmitis categories, the most frequent organisms
were the following: (1) acute-onset postoperative: S epidermidis,
46.9%; (2) delayed-onset postoperative: S epidermidis, 22.7%;
(3) delayed-onset bleb-associated: fastidious gram-negative rods,
20.4%; (4) posttraumatic: S epidermidis, 20.8%; (5) endogenous:
Aspergillus species, 20.8%; and (6) miscellaneous: molds (other),
36.4%. CONCLUSIONS: In considering antibiotic treatment of endophthalmitis,
it is important to recognize that no single antibiotic provided
coverage for all of the microbes isolated from eyes with endophthalmitis.
Combination therapy is recommended as the initial empiric treatment
of suspected bacterial endophthalmitis. Appropriate history and
characteristic clinical features may justify the use of initial
antifungal agents. Knowledge of the most frequent causative organisms
in various categories will help direct appropriate initial therapy.
-----
Am J Ophthalmol. 2004 Jan; 137(1): 38-42.
Endophthalmitis isolates and antibiotic sensitivities:
a 6-year review of culture-proven cases.
Benz MS, Scott IU, Flynn HW Jr, Unonius N, Miller D.
Bascom Palmer Eye Institute, University of Miami School of Medicine,
Miami, Florida, USA. mbenz@bcm.tmc.edu
PURPOSE: To investigate the spectrum of organisms causing culture-proven
endophthalmitis and their sensitivities to commonly used antimicrobial
agents. DESIGN: Retrospective, noncomparative, consecutive case
series. METHODS: Medical records were reviewed of all patients
with culture-proven endophthalmitis at a single institution between
January 1, 1996, and December 31, 2001. Endophthalmitis categories
included postoperative, posttraumatic, endogenous, and miscellaneous
(for example, keratitis). The outcome measures included intravitreal
isolates identified, antibiotic sensitivities, and category of
endophthalmitis. RESULTS: In all, 313 organisms were isolated
from 278 patients during the study interval. The most common organisms
identified were Staphylococcus epidermidis in 27.8% (87/313),
Streptococcus viridans group in 12.8% (40/313), other coagulase-negative
staphylococci in 9.3% (29/313), Staphylococcus aureus in 7.7%
(24/313), and Propionibacterium acnes in 7.0% (22/313). Overall,
246 of 313 (78.5%) isolates were gram-positive organisms, 37 (11.8%)
were gram-negative organisms, and 27 (8.6%) were fungi. For gram-positive
organisms, sensitivities were the following: vancomycin 100%,
gentamicin 78.4%, ciprofloxacin 68.3%, ceftazidime 63.6%, and
cefazolin 66.8%. For gram-negative organisms, sensitivities were
the following: ciprofloxacin 94.2%, amikacin 80.9%, ceftazidime
80.0%, and gentamicin 75.0%. Fungal isolates were Candida species
(9/313), Aspergillus species (9/313), and other molds (9/313).
Among the endophthalmitis categories, the most frequent organisms
were the following: (1) acute-onset postoperative: S epidermidis,
46.9%; (2) delayed-onset postoperative: S epidermidis, 22.7%;
(3) delayed-onset bleb-associated: fastidious gram-negative rods,
20.4%; (4) posttraumatic: S epidermidis, 20.8%; (5) endogenous:
Aspergillus species, 20.8%; and (6) miscellaneous: molds (other),
36.4%. CONCLUSIONS: In considering antibiotic treatment of endophthalmitis,
it is important to recognize that no single antibiotic provided
coverage for all of the microbes isolated from eyes with endophthalmitis.
Combination therapy is recommended as the initial empiric treatment
of suspected bacterial endophthalmitis. Appropriate history and
characteristic clinical features may justify the use of initial
antifungal agents. Knowledge of the most frequent causative organisms
in various categories will help direct appropriate initial therapy.
-----
Curr Opin Ophthalmol. 2003 Dec;14(6):399-412.
Use of immunosuppressive agents in uveitis.
Lustig MJ, Cunningham Jr ET.
SUMMARY: PURPOSE OF REVIEW This review summarizes current patterns
in the use of immunosuppressive agents in patients with uveitis.RECENT
FINDINGS A number of immunosuppressive agents are currently available
for the treatment of uveitis. Reports of safety and efficacy,
although numerous, have been largely nonrandomized and performed
without controls, limiting, to some extent, the strength and generalizability
of their conclusions. Nonetheless, the volume of case reports
and case series provides compelling evidence that immunosuppressive
agents are effective at providing long-term control in patients
with moderate to severe chronic or recurrent uveitis. The choice
of immunosuppressive agent is complex, and depends on the cause
and severity of the patient's underlying inflammation, the presence
or absence of associated systemic inflammation, and the patient's
prior response to immunosuppressive treatments.SUMMARY Although
corticosteroids remain the primary initial treatment for patients
with uveitis, use of noncorticosteroid immunosuppressive agents
in selected patients with uveitis allows for improved control
and decreased risk of corticosteroid-induced side effects.
-----
Ocul Immunol Inflamm. 2003 Dec; 11(4): 299-303.
Effect of a drug combination treatment on ocular
perfusion in recurrent idiopathic intermediate uveitis.
Cimino L, Finzi G, Mora P, Zavota L, Gandolfi SA, Orsoni
JG.
Ocular Immunology and Immunopathology Center, Glaucoma Research
and Care Center of University Eye Clinic, Community Hospital,
Parma, Italy.
PURPOSE: To test the effect of a drug combination therapy on
ocular perfusion in human eyes affected by idiopathic intermediate
uveitis. METHODS: Seven patients (12 eyes) showing active signs
of intermediate uveitis, with at least two more similar episodes
reported within the previous 12 months, were enrolled in a prospective
case series. Two fellow healthy eyes of two of the enrolled patients
were studied as internal controls. Color Doppler imaging of the
central retinal artery (CRA), the ophthalmic artery (OA), and
the posterior ciliary arteries (PCAs) was performed at the time
of enrollment, and at 6 and 12 months after starting treatment
with oral fluorocortolone, cyclosporine, and parenteral methotrexate.
The best-corrected visual acuity was concurrently measured as
a second parameter. RESULTS: In the 12 affected eyes, the mean
visual acuity (+/-SD) improved from 0.15(+/-0.12) to 0.04(+/-0.18)
LogMAR (paired samples Student's t-test: p = 0.015). The resistivity
index (RI +/- SD) of the CRA decreased from 0.81(+/-0.13) to 0.71(+/-0.13)(p
= 0.0091). Further, the variation of the RI in the PCAs reached
a borderline significance (p = 0.062), decreasing from 0.71(+/-0.12)
to 0.61(+/-0.12). No significant changes were observed in the
OA. Moreover, eyes showing a visual improvement of > or =0.1
(LogMAR) were more likely to show a > or =10% improvement of
the RI for the CRA (Fisher's exact test: p = 0.018; power = 90%;
alpha probability = 5%; odds ratio = 2,4). CONCLUSIONS: In eyes
affected by idiopathic intermediate uveitis, treated with a systemic
drug combination therapy, the improvement of the visual acuity
seems to correlate with a proportional improvement of the retrobulbar
circulation.
-----
Am J Ophthalmol. 2003 Dec; 136(6): 1114-9.
Childhood-onset uveitis in Behcet disease:a descriptive
study of 36 cases.
Tugal-Tutkun I, Urgancioglu M.
Department of Ophthalmology, Istanbul University, Istanbul Faculty
of Medicine, Istanbul, Turkey. tutkun@turk.net
PURPOSE: To describe the demographic and clinical features,
complications, treatment, and visual results in patients with
childhood-onset Behcet uveitis. DESIGN: Observational case series.
METHODS: A retrospective study was made of 36 consecutive patients
with Behcet disease seen at the Uveitis Service, Department of
Ophthalmology, Istanbul Faculty of Medicine, Istanbul University,
between January 1975 and January 2002. Inclusion criteria were
fulfillment of the classification criteria of the International
Study Group for Behcet Disease and onset of uveitis at 16 years
of age or younger. The medical records of 36 patients with childhood-onset
Behcet uveitis were reviewed. The main outcome measures were sex,
age at onset of uveitis, the initial symptom of Behcet disease,
clinical ocular features, ocular complications, systemic treatment,
complications of treatment, and final visual acuity. RESULTS:
Twenty-five patients were male, 11 were female. Mean age at onset
of uveitis was 13.6 years. The initial symptom was oral ulcer
in 63.8% of the patients. The majority of patients (83.3%) had
bilateral involvement. Panuveitis was the most common form (86.2%).
Retinal vasculitis and retinitis were the most common ocular findings
seen in 83.3% and 68.2% of the involved eyes, respectively. Cataract,
maculopathy, and optic atrophy were the most common complications
seen in 46.9%, 45.4%, and 39.4% of the involved eyes, respectively.
Immunosuppressive therapy was administered to 75% of the patients.
Response to treatment was variable. The most common complications
of systemic treatment were associated with corticosteroid therapy.
Final visual acuity was worse than 0.1 in 22.7% of the involved
eyes. CONCLUSIONS: Childhood-onset Behcet uveitis was more common
among males. Bilateral panuveitis with retinal vasculitis and
retinitis was the most common form of ocular involvement, similar
to the adult patient. The treatment is challenging, as the use
oral corticosteroids is associated with significant complications
and the response to conventional immunosuppressive therapy is
variable.
-----
Rev Med Interne. 2003 Dec;24(12):794-802.
[Chronic severe uveitis: classification, search
for etiology and therapeutic approach]
[Article in French]
Bodaghi B, Wechsler B, Du-Boutin LT, Cassoux N, LeHoang P, Piette
JC.
Service d'ophtalmologie, CHU Pitie-Salpetriere, 43, boulevard
de l'Hopital, 75013 Paris, France. bahram.bodaghi@psl.ap-hop-paris.fr
PURPOSE: Severe chronic and refractory uveitis is a major diagnostic
and therapeutic challenge for ophthalmologists and internists.
Molecular tools, such as PCR but also new imaging techniques,
have significantly changed the diagnostic approach during the
last 10 years. Presumed and empirical diagnosis should be excluded
in the face of atypical clinical presentations. CURRENT KNOWLEDGE
AND KEY POINTS: A retrospective study based on 927 consecutive
patients presenting with severe uveitis between 1991-1996, has
recently defined the epidemiological characteristics and the visual
outcome of this group of patients. An associated condition was
determined in 67.5% of cases, divided in 4 different subgroups:
infectious uveitis; uveitis associated with a systemic disease;
eye-limited, presumed immune-mediated disorder and idiopathic
eye-limited disorder. The management of patients with sight-threatening
forms of uveitis is efficiently performed in collaboration with
internists and depends on a complete diagnostic procedure and
a well-adapted treatment. FUTURE PROSPECTS AND PROJECTS: Extensive
work-up is mandatory when the therapeutic response seems atypical
with resistance to corticosteroids and classical immunosuppressive
drugs. Infectious uveitis should be excluded in severe and intractable
forms of uveitis. Thereafter, new therapeutic strategies based
on type I interferon and anti-TNF molecules can be proposed in
order to decrease the potential risk of blindness in this young
group of patients.
-----
J Pediatr Ophthalmol Strabismus. 2003 Nov-Dec;40(6):335-40.
Uveitis in childhood.
Kadayifcilar S, Eldem B, Tumer B.
Department of Ophthalmology, Hacettepe University School of Medicine,
Ankara, Turkey.
PURPOSE: To review the etiologic factors and complications
of uveitis in patients younger than 16 years. PATIENTS AND METHODS:
Between January 1989 and December 1999 in the Department of Ophthalmology
of Hacettepe University School of Medicine, 219 patients were
diagnosed or observed as having pediatric uveitis. After complete
ocular and physical examinations, routine and specific laboratory
and radiologic investigations were performed. Medical or surgical
treatment was employed when necessary. RESULTS: Of the 219 patients,
112 were girls, with a mean age of 7.4 +/- 4.2 years, and 107
were boys, with a mean age of 8.3 +/- 3.4 years. In 24.2% of the
cases, no etiologic factor could be ascertained; these cases comprised
the idiopathic group. Among the remaining cases, the most common
etiologies were toxoplasmosis, juvenile rheumatoid arthritis (JRA),
pars planitis, Behcet's disease, and Fuchs' heterochromic iridocyclitis.
Anatomically, anterior uveitis was the most common form. The mean
follow-up time was 37 +/- 6.2 months. Complications for which
surgical treatment was employed were identified in 71 eyes (20.9%),
most of which were due to JRA, pars planitis, or Behcet's disease.
CONCLUSION: Uveitis in childhood may be idiopathic or most commonly
due to toxoplasmosis, JRA, and pars planitis. Due to inflammation
itself or to prolonged therapy especially with corticosteroids,
pediatric uveitis entities (mostly JRA, pars planitis, or Behcet's
disease) may result in complications necessitating a surgical
approach.
-----
Ophthalmologe. 2003 Nov; 100(11): 991-1006; quiz 1007-8.
[Glaucoma and uveitis. Causes of and treatment
options for increased intraocular pressure in cases of inflammatory
ophthalmology]
[Article in German]
Dietlein TS.
Universitats-Augenklinik Cologne. Thomas-Dietlein@uni-koeln.de
Uveitic secondary glaucoma poses one of the most difficult
problems for differential diagnostics and therapeutics in the
field of clinical glaucomatology. The prevalence of glaucoma among
uveitis patients ranges between 5 and 20% with great fluctuations
depending on the underlying disease, duration of the disease,
and the patient's age. Based on slit-lamp examination, uveitis
can be classified as granulomatous and non-granulomatous. The
effects of uveitic glaucoma on the quality of life and central
visual acuity are particularly serious during childhood. Surgical
reduction of eye pressure in cases of uveitic secondary glaucoma
should only be performed if medical treatment of the underlying
disease or ocular inflammation does not lower the eye pressure
level and if in the presence of glaucomatous damage to the optic
nerve the level of intraocular pressure is so high that a drastic
decrease in pressure that cannot be achieved by medication becomes
necessary.
-----
J Ocul Pharmacol Ther. 2003 Aug;19(4):325-43.
Systemic management of posterior uveitis.
Song J.
Duke University Medical Center, Durham, NC 27710, USA. Song0012@notes.duke.edu
In the treatment of uveitis, corticosteroids are usually included
in first-line therapy due to its rapid onset of action and excellent
safety profile. Systemic immunosuppressive agents also play an
important role in the management of posterior uveitis. The purpose
of this study was to review systemic agents for treating uveitis:
prednisone, methotrexate, cyclosporine, and azathioprine. This
study was a review of the literature using Medline. Thirty-eight
references were incorporated. Immunosuppressants take several
weeks for their full effect and are considered when long-term
therapy is anticipated. When long-term therapy is anticipated,
immunosuppressant agents may be added, which allows for the reduction
and eventual discontinuation of prednisone. Combination therapy
of various immunosuppressants also allows for long-term therapy,
which reduces the relapse rate. However, immunosuppressives can
be associated with serious side-effects. The use of immunosuppressants
requires careful monitoring.
-----
Br J Ophthalmol. 2003 Aug;87(8):1010-4.
Pars plana vitrectomy assisted by triamcinolone
acetonide for refractory uveitis: a case series study.
Sonoda KH, Enaida H, Ueno A, Nakamura T, Kawano YI, Kubota
T, Sakamoto T, Ishibashi T.
Department of Ophthalmology, Kyushu University Graduate School
of Medicine, Fukuoka, Japan. sonodak@med.kyushu-u.ac.jp
AIM: To examine the outcome of a triamcinolone acetonide (TA)
assisted pars plana vitrectomy (PPV) for refractory uveitis. METHODS:
Six patients suffering from proliferative vitreoretinopathy (PVR)
with refractory uveitis underwent a TA assisted PPV. The patients
consisted of one with Vogt-Koyanagi-Harada disease, one with acute
retinal necrosis, one with Behcet's disease, and three with sarcoidosis.
TA was inoculated into the vitreous cavity to visualise the vitreous.
In four of six patients, 4 mg of TA were intentionally left in
the vitreous cavity to reduce the degree of postoperative inflammation.
RESULTS: The vitreous body was clearly seen using TA during surgery,
which greatly helped us to perform a posterior hyaloid resection
safely and thoroughly. As we previously observed in other disease,
TA allowed us to visualise the transparent vitreous and thus was
helpful in removing the vitreous cortex from the retina completely
in uveitis. One patient (Behcet's disease, in whom TA was intentionally
left) showed an elevated intraocular pressure (IOP) transiently
after surgery which was controllable by topical eye drops. The
remaining TA diminished day by day and had almost completely disappeared
within a month from operation. CONCLUSION: TA improved the visibility
of the hyaloid and the safety of the surgical procedures and no
serious complications were observed after TA assisted PPV in uveitis.
Although the long term effects are still unknown, this method
appears to be potentially useful as an improved treatment for
PVR associated with refractory uveitis
-----
Br J Ophthalmol. 2003 Aug;87(8):968-71.
Trans-Tenon's retrobulbar triamcinolone infusion
for the treatment of uveitis.
Okada AA, Wakabayashi T, Morimura Y, Kawahara S, Kojima
E, Asano Y, Hida T.
Kyorin Eye Center, Kyorin University School of Medicine, Tokyo,
Japan. aokada@po.iijnet.or.jp
AIM: To assess efficacy and complications of trans-Tenon's
retrobulbar infusion of triamcinolone acetonide for posterior
uveitic inflammation. METHODS: Non-randomised, uncontrolled, retrospective
study of 51 eyes of 37 patients who underwent triamcinolone infusion
for vitritis, cystoid macular oedema (CMO), or posterior retinal
vasculitis using a long blunt cannula via an incision made through
conjunctiva and Tenon's capsule. RESULTS: Overall clinical efficacy
was 86%; 96% for vitritis, 82% for CMO, and 33% for posterior
retinal vasculitis. Mean visual acuity improved within 1 month
after triamcinolone infusion (p <0.05). Cataract progression
and intraocular pressure elevation were observed in 31% and 27%
of eyes, respectively. CONCLUSION: Trans-Tenon's retrobulbar triamcinolone
infusion may be a safe and effective treatment for posterior uveitic
inflammation.
-----
Ophthalmology. 2003 Jul;110(7):1449-53.
Infliximab in the treatment of refractory posterior
uveitis.
Joseph A, Raj D, Dua HS, Powell PT, Lanyon PC, Powell RJ.
Department of Ophthalmology and Visual Sciences, B Floor, Eye
and ENT Block, Queen's Medical Centre, Nottingham NG7 2UH, United
Kingdom.
PURPOSE: To determine the efficacy and safety of infliximab
in the treatment of refractory posterior uveitis. DESIGN: Noncomparative
interventional case series. PARTICIPANTS: Five patients with posterior
uveitis were treated: 3 had Behcet's syndrome, and 2 had idiopathic
posterior uveitis. INTERVENTIONS: Patients with sight-threatening
uveitis refractory to other immunosuppressive agents were treated
with infliximab. MAIN OUTCOME MEASURES: Intraocular inflammation,
by using binocular indirect ophthalmoscopy score, retinal vasculitis,
and visual acuity. Adverse effects of infliximab were documented.
RESULTS: Within 2 weeks of the first infusion of infliximab, 4
of 5 patients showed marked improvement in vitreous haze and visual
acuity. By the 6-month follow-up, the same four patients had achieved
remission of posterior uveitis and had successfully withdrawn
all other immunosuppressive therapy. Further infusions of infliximab
were required in 3 patients. One patient developed ocular and
systemic tuberculosis, which responded to antituberculous treatment.
CONCLUSIONS: Infliximab is effective in the treatment of sight-threatening
refractory posterior uveitis. However, patients should be thoroughly
screened for tuberculosis before treatment and followed up closely
during and after therapy with infliximab.
-----
Ocul Immunol Inflamm. 2003 Jun; 11(2): 131-9.
Methotrexate as a first-line corticosteroid-sparing
therapy in a cohort of uveitis and scleritis.
Kaplan-Messas A, Barkana Y, Avni I, Neumann R.
Aviv Center, Eye Institute, Maccabi Health Care Services, Ramat
Aviv, Israel.
PURPOSE: To evaluate the clinical experience with methotrexate
as a first-line corticosteroid-sparing drug in patients with resistant
ocular inflammation. METHODS: We retrospectively studied 39 consecutive
patients with uveitis (n = 36) or scleritis (n = 3) who were treated
with methotrexate following inadequate control with corticosteroids
lasting five years. Criteria for initiating treatment with methotrexate
and defining outcome were strictly defined. RESULTS: The cohort
included 21 females and 18 males, all Caucasians, with a mean
age of 26.6 years (range: 3-73 years). Patients were followed
up for 21.5 +/- 12.6 months. Treatment was discontinued due to
side effects in 10 patients (26%). Of the remaining 29 patients,
full or partial control of inflammation was achieved in 23 (79%).
Response to treatment was observed after a mean of 2.4 +/- 0.8
months. Ten patients were fully controlled and discontinued methotrexate
therapy after a mean of 20.9 +/- 9.2 months, with no recurrence
of inflammation. Use of topical and systemic corticosteroids was
markedly reduced in responsive patients. CONCLUSIONS: Methotrexate
is recommended as a first-line adjunct to or replacement of systemic
corticosteroids in the treatment of ocular inflammation.
-----
Ocul Immunol Inflamm. 2003 Jun; 11(2): 83-90.
Chemokines--their role in immunotherapy for intraocular
inflammation.
Kawashima H.
Department of Ophthalmology, University of Tokyo, Hongoln, Japan.
hidemeali.thy@umin.ac.jp
Chemotactic cytokines are responsible for leukocyte migration
and the immunopathogenesis of various inflammatory lesions. Together
with other types of cytokines, chemokines play a major role in
inducing/regulating inflammation and various immune responses.
By targeting chemokines, immunotherapies could become another
option for treating patients with uveitis. Indeed, a variety of
chemokine-based therapies have been tested for their possible
application for various pathological diseases, including intraocular
inflammation. An example of chemokine-based therapy is anti-tumor
necrosis factor (TNF)-alpha therapy, a very successful treatment.
Chemokine- and cytokine-based therapies, therefore, appear to
be a promising choice for the treatment of intraocular inflammation.
-----
J Fr Ophtalmol. 2003 Jun;26(6):609-13.
[Uveitis in children: about 20 cases]
[Article in French]
Laghmari M, Karim A, Guedira K, Ibrahimy W, Dahreddine M, Essakalli
NH, Mohcine Z.
Service d'Ophtalmologie A, Hopital des Specialites, Rabat, Maroc.
INTRODUCTION: Uveitis in children is rare: 3%-8% of all cases.
It requires the same diagnostic and etiological processes as uveitis
in adults, with additional difficulties at examination and a sometimes
insidious progression. MATERIAL AND METHODS: Retrospective study
of 20 cases of childhood uveitis from 1995 to 2000. All patients
received an ophthalmologic examination and an etiological search,
with specific and/or symptomatic treatment and follow-up lasting
from 6 months to 5 years. RESULTS: The 20 children presenting
uveitis were 4-16 years old, with etiologies as follows: 8 cases
of Behcet's disease, 2 cases of Vogt-Koyanagi-Harada's disease,
1 case of sarcoidosis, 1 case of uveitis associated with coeliac
disease, 1 case of toxoplasmosis, 1 case of sympathetic ophthalmia,
1 case of uveitis with streptococcal infection, 3 cases of ocular
toxocarosis, and 2 cases with unknown etiology. Treatment based
on the etiological findings was started in the cases of toxoplasmosis
and uveitis from streptococcal infection. The others were treated
with high- and then digressive-doses of corticosteroids. ANALYSIS:
We have noted the high incidence of Behcet's disease in our series.
Progression was marked by frequent recurrence for one case of
Vogt-Koyanagi-Harada's syndrome and one case of toxoplasmosis.
This study also revealed a few cases of complicated cataract.
DISCUSSION: Clinical characteristics, diagnosis, and treatment
of uveitis in children are discussed.
-----
Bull Soc Belge Ophtalmol. 2003;(288):9-14.
Vitrectomy and silicone oil in the treatment of
acute endophthalmitis. Preliminary results.
Bali E, Huyghe P, Caspers L, Libert J.
Dept. of Ophthalmology, C.H.U. St Pierre-Brugmann U.L.B. Brussels,
Belgium.
PURPOSE: To evaluate the role of pars plana vitrectomy (PPV)
and silicone oil injection in the treatment strategy of severe
endophthalmitis. PATIENTS AND METHODS: This study analyses a retrospective
case series of 34 patients with signs and symptoms of severe endophthalmitis
with visual acuity limited to light perception. All underwent
PPV with intraocular injection of antibiotics (IOAB), together
with topical and oral antibiotics. In 10 patients (group 1), this
treatment alone was sufficient to control infection. In 10 other
patients (group 2) with the same initial treatment, a new vitrectomy
was needed: 8 because of retinal detachment, 2 because of persistent
infection. In 2 patients (group 3), initially treated with PPV
and IOAB, a second vitrectomy with IOAB and silicone oil tamponade
was needed to stop infection. In 12 patients (group 4), with the
worse prognosis related to the severity of infection and/or to
associated retinal necrosis, PPV, IOAB and silicone oil tamponade
were conducted at first surgery. Final anatomic status and visual
acuity were assessed to compare the effectiveness of these different
treatments. RESULTS: In 22 patients (group 1, 2 and 3) treated
initially without silicone oil, 12 patients (55%) needed further
surgery, either for persistent infection or retinal detachment.
Twelve patients (group 4) treated at first with silicone oil had
a rapid control of the infectious process and better anatomical
results with this procedure only. Final visual acuity was also
better in the silicone oil groups (group 3 and 4) than in the
non silicone groups (group 1 and 2). CONCLUSION: These results
suggest that silicone oil tamponade might be beneficial in the
treatment strategy of severe endophthalmitis.
-----
Ophthalmology. 2003 Apr;110(4):786-9.
Treatment of ocular inflammatory disorders with
daclizumab.
Papaliodis GN, Chu D, Foster CS.
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston,
Massachusetts 02114, USA.
PURPOSE: To evaluate the efficacy and safety of daclizumab
therapy for patients with various ophthalmologic inflammatory
disorders (all having previously failed standard treatment methods).
DESIGN: Retrospective, nonrandomized case series. PARTICIPANTS:
Fourteen patients. METHODS: Fourteen patients were treated with
daclizumab after previously failing standard treatment methods.
MAIN OUTCOME MEASURES: Inflammation and visual acuity. RESULTS:
Twelve of 27 (44%) eyes and 5 of 14 (36%) patients had improvement
in visual acuity; 9 of 27 (33%) eyes and 5 of 14 (36%) patients
had no change in visual acuity; and 6 of 27 (22%) eyes and 4 of
14 (27%) patients had continued visual loss. Based on degree of
inflammation, 16 of 27 eyes (59%) had improvement, 3 of 27 (11%)
eyes had no change, and 8 of 27 (30%) eyes worsened. CONCLUSIONS:
Daclizumab is safe and, at least in some patients, appears to
be an effective medication in the treatment of ocular inflammatory
disorders.
-----
Eye 2003 Mar;17(2):221-227
Vitreous surgery in the management of chronic
endogenous posterior uveitis.
Scott RA, Haynes RJ, Orr GM, Cooling RJ, Pavesio CE, Charteris
DG.
Objectives There is evidence that pars plana vitrectomy (PPV)
has a beneficial effect on the clinical course of chronic endogenous
posterior uveitis (EPU) possibly by physically removing any resident
inflammatory cells with the vitreous. We assessed the anatomical
and therapeutic effects of PPV performed on patients with chronic
EPU for any indication.Patients and methods Retrospective review
of 41 eyes of 38 consecutive patients with EPU who underwent a
PPV for any reason, over a 5-year period. The mean age of the
patients was 36.2 years, 46% of the eyes had intermediate uveitis,
32% panuveitis, and 22% posterior uveitis. The visual acuity,
disease activity, and the requirement for medications to control
it were recorded for 12 months pre- and postoperatively.Results
Overall, 61% of the eyes gained more than 2 Snellen lines (P&<0.001)
and the incidence of cystoid macular oedema (CMO) significantly
reduced from 44 to 20% (P&<0.05). Postoperatively, there
was a significant decrease in the recurrence rate of intermediate
uveitis, posterior uveitis, and panuveitis (P&<0.001).
The use of systemic and local depot immunosuppressive agents did
not change over the study period, although the use of topical
agents increased (P&<0.05).Conclusion PPV appears to have
a beneficial effect on the clinical course of EPU in selected
cases. This may be mediated by the physical clearance of inflammatory
debris, the anti-inflammatory effect of replacing vitreous by
aqueous humour, by a reduction of CMO and/or the anatomical correction
of sight-threatening retinal pathology.
-----
Ophthalmologe 2003 Jan;100(1):33-43
[Pars plana vitrectomy in cystoid macular edema
of different forms of chronic uveitis]
[Article in German]
Wiechens B, Reichelt JA, Urbat C, Nolle B.
Augenklinik, Klinikum Hannover.
BACKGROUND. Cystoid macular edema (CME) is a common complication
in different forms of chronic uveitis. In spite of immunosuppressive
and anti-inflammatory therapy, chronic or relapsing courses can
occur which may have a negative impact on visual prognosis. Pars
plana vitrectomy (PPV) is known to positively influence chronic
uveitis.This retrospective study was performed to investigate
the role of PPV in the therapy refractive uveitic CME. PATIENTS
AND METHODS. PPV for CME was performed in eyes with CME in intermediate
uveitis (IMU, n=42), chronic iridocyclitis in juvenile rheumatoid
arthritis (CIC, n=14) and multifocal chorioretinitis (MFC, n=12).In
none of the eyes had immunosuppressive and/or anti-inflammatory
therapy or antiedema treatment (e.g.acetazolamide) led to regression
of the CME.After a postoperative follow-up period of 7 and 106
months all patients were re-examined. RESULTS. Postoperative complete
or partial regression of CME was observed as follows: IMU: 25/42
(59.5%), CIC: 8/14 (57.1%),MFC: 5/12 (41.7%). A significant increase
in visual acuity of 2 lines and more was observed in 50%,71.4%
and 41.7% of eyes, respectively. In the long-term follow-up best
functional results were achieved in eyes with IMU. CONCLUSIONS.
Response to PPV was variable according to the type of underlying
form of uveitis.The lowest success rate could be observed in eyes
with MFC. Although the postoperative regression rate of CME was
satisfactory in eyes with CIC, long-term visual acuity results
were disappointing due to secondary complications of CIC in this
young age group.Best results were achieved in patients with IMU
(statistically not significant). A multicenter study in a larger
series of patients is needed to investigate the exact role of
PPV in different forms of chronic uveitis.
-----
Br J Ophthalmol 2003 Apr;87(4):423-431
Human recombinant interferon alfa-2a for the treatment
of Behcet's disease with sight threatening posterior or panuveitis.
Kotter I, Zierhut M, Eckstein AK, Vonthein R, Ness T, Gunaydin
I, Grimbacher B, Blaschke S, Meyer-Riemann W, Peter HH, Stubiger
N.
University Hospital, Departments of Internal Medicine II (Hematology,
Oncology, Immunology and Rheumatology) and Ophthalmology, Tubingen,
Germany University Hospital, Department of Ophthalmology I, Tubingen,
Germany University Hospital, Department of Ophthalmology, Essen,
Germany Department of Medical Biometry, University of Tubingen,
Germany University Hospital, Department of Ophthalmology, Freiburg,
Germany University Hospital, Division of Rheumatology and Clinical
Immunology, Freiburg, Germany University Hospital, Department
of Nephrology and Rheumatology, Gottingen, Germany University
Hospital, Department of Ophthalmology, Gottingen, Germany University
Hospital, Division of Rheumatology and Clinical Immunology, Freiburg,
Germany.
BACKGROUND: Behcet's disease is a multisystem vasculitis of
unknown origin. Standard treatment mainly comprises systemic immunosuppressive
agents. Ocular involvement, mostly posterior uveitis with retinal
vasculitis, leads to blindness in 20-50% of the involved eyes
within 5 years. The efficacy of interferon alfa-2a was studied
in patients with sight threatening posterior uveitis or retinal
vasculitis. METHODS: 50 patients were included in this open, non-randomised,
uncontrolled prospective study. Recombinant human interferon alfa-2a
(rhIFNalpha-2a) was applied at a dose of 6 million units subcutaneously
daily. Dose reduction was performed according to a decision tree
until discontinuation. Disease activity was evaluated every 2
weeks by the Behcet's disease activity scoring system and the
uveitis scoring system. RESULTS: Response rate of the ocular manifestations
was 92% (three non-responder, one incomplete response). Mean visual
acuity rose significantly from 0.56 to 0.84 at week 24 (p<0.0001).
Posterior uveitis score of the affected eyes fell by 46% every
week (p<0.001). Remission of retinal inflammation was achieved
by week 24. Mean Behcet's disease activity score fell from 5.8
to 3.3 at week 24 and further to 2.8 at week 52. After a mean
observation period of 36.4 months (range 12-72), 20 patients (40%)
are off treatment and disease free for 7-58 months (mean 29.5).
In the other patients maintenance IFN dosage is three million
units three times weekly. CONCLUSIONS: rhIFNalpha-2a is effective
in ocular Behcet's disease, leading to significant improvement
of vision and complete remission of ocular vasculitis in the majority
of the patients.
-----
Am J Med Sci 2003 Feb;325(2):75-92
New indications for treatment of chronic inflammation
by TNF-alpha blockade.
Reimold AM.
Rheumatic Diseases Division, University of Texas Southwestern
Medical Center, Dallas 75390, USA. andreas.reimold@utsouthwestern.edu
The impressive anti-inflammatory effects of the tumor necrosis
factor (TNF)alpha blockers etanercept and infliximab have led
to their use in multiple inflammatory diseases besides their original
indication, rheumatoid arthritis (RA). The well-studied clinical
effects of both agents in RA are the reduction of signs and symptoms
of joint inflammation as well as the arrest of bone destruction.
Infliximab has also been Food and Drug Administration-approved
in the treatment of Crohn disease; etanercept is now FDA-approved
for juvenile chronic arthritis and psoriatic arthritis. Favorable
initial clinical trials have been reported in other rheumatic
diseases, including ankylosing spondylitis and adult Still disease.
In addition, TNF alpha blockade is being studied in the treatment
of uveitis, myelodysplastic syndromes, and graft-versus-host disease.
Studies in sepsis and septic shock have identified small subsets
of patients that may benefit from TNF alpha blockade, but broader
use in septic patients has not improved survival. The TNF alpha
blockers have had relatively infrequent serious side effects,
especially compared with the immunosuppressive and cytotoxic agents
otherwise employed to treat these diseases. Further studies of
optimal dosing, combination with other therapies, and long-term
benefits and side effects will emerge from future trials.
-----
Prog Retin Eye Res 2002 Nov;21(6):577-89
Oral tolerance for treating uveitis—new hope
for an old immunological mechanism.
Thurau SR, Wildner G.
Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstr.
8, 80336, Munchen, Germany.
Oral tolerance induction has evolved as an attractive approach
for the treatment of autoimmune uveitis. This approach is effective
and generally void of the side effects associated with conventional
immunosuppression. Following uptake of soluble antigen via the
gut mucosa a specific systemic tolerance is generated. Experimental
autoimmune diseases such as uveitis can efficiently be treated
when autoantigens are fed to animals. The immunological mechanisms
of oral tolerance are not well understood but are thought to involve
the recognition of tolerogenic epitopes, generation of suppressor
T cells and altered regulation of selected cytokines. The dose,
purity of the antigen (tissue extract vs. single peptide) and
concomitant treatment with cytokines were evaluated with the aim
to enhance oral tolerance. Immunomodulatory drugs can abrogate
oral tolerance. This requires careful evaluation with respect
to therapeutic approaches in patients. The first clinical trials
for treatment of uveitis with oral retinal autoantigen or an HLA-peptide
crossreactive with S-Antigen show a promising therapeutic effect
and confirmed the safety of this approach.
-----
Int Rev Immunol 2002 Mar-Jun;21(2-3):273-89
Bench to bedside: new approaches to the immunotherapy
of uveitic disease.
Nussenblatt RB.
Laboratory of Immunology, National Institute of Health, Bethesda,
Maryland, USA. drbob@intra.nei.nih.gov
Intraocular inflammatory disease, or uveitis, appears to be
due in large part to non-infectious, cell-mediated mechanisms.
Experimental autoimmune uveitis (EAU) has been a valuable tool
to better understand underlying mechanisms of this disorder, and
it provides the possibility to evaluate new approaches to immunotherapy
as well. Two approaches described here are oral tolerance and
anti-IL2 receptor therapy. Both therapies were evaluated in the
animal model and showed positive therapeutic effects. Based on
these observations, both approaches were used in the treatment
of patients with uveitis. Oral tolerance showed initial promising
results. Anti-IL2 receptor therapy has been used for over 4 years
in uveitis patients with an additional study evaluating this therapy
in Behcet's disease. Future plans are to expand this approach
to a larger number of patients. The use of animal models has been
very useful in better understanding mechanisms of ocular disease
and bringing new therapeutic approaches to the clinic.
-----
Ophthalmology 2002 Dec;109(12):2256-60
Outcome of Baerveldt glaucoma drainage implants
for the treatment of uveitic glaucoma.
Ceballos EM, Parrish RK 2nd, Schiffman JC.
Department of Ophthalmology, University of Miami School of Medicine,
Bascom Palmer Eye Institute, Miami, Florida, USA.
OBJECTIVE: To evaluate the efficacy and safety of Baerveldt
glaucoma drainage devices in the management of uveitic glaucoma.
DESIGN: Retrospective, noncomparative case series. PARTICIPANTS:
Twenty-four eyes of 24 patients who underwent implantation of
Baerveldt glaucoma drainage devices between 1996 and 2000 for
the treatment of uveitic glaucoma refractory to medical therapy.
INTERVENTION: Implantation of Baerveldt glaucoma drainage device.
MAIN OUTCOME MEASURES: Control of intraocular pressure (IOP),
number of glaucoma medications needed for adequate IOP control,
visual acuity, complications associated with the surgery, and
the effect of subsequent surgery on the ability of the device
to control IOP. Success was defined as IOP >/=5 and </=21
mmHg with or without antiglaucoma medications and without need
for further glaucoma surgery, loss of light perception, or phthisis.
RESULTS: Cumulative life-table success rates were 95.8% at 3 months
and 91.7% at 6 months, 12 months, and 24 months. The mean postoperative
follow-up was 20.8 months. The IOP was reduced from a preoperative
mean of 30.5 +/- 8.96 mmHg with 3.1 +/- 0.99 antiglaucoma medications
to a postoperative mean at 6 months or 1 year of 13.0 +/- 4.6
mmHg (P < 0.001) with 0.8 +/- 0.8 antiglaucoma medications
(P < 0.001). At last follow-up 14 of 24 eyes (58.3%) required
no antiglaucoma medications. Best-corrected visual acuity improved
or remained within 2 lines of preoperative visual acuity in 19
(79.2%) eyes. The most common complications were choroidal effusions
in four (16.7%), hypotony in three (12.5%) eyes, cystoid macular
edema in three (12.5%) eyes, and failure of corneal grafts in
two (8.3%). Seven of 22 eyes (31.8%) in which successful control
of IOP with the Baerveldt implant was achieved underwent subsequent
nonglaucoma-related incisional surgery. None of these eyes (0%)
lost IOP control after the subsequent procedure. CONCLUSIONS:
The Baerveldt glaucoma drainage device offers reasonable safety
and effectiveness for the control of IOP in eyes with uveitis
and refractory glaucoma.
-----
Isr Med Assoc J 2002 Nov;4(11 Suppl):928-30
Interferon alfa combined with azathioprine for
the uveitis of Behcet's disease: an open study.
Hamuryudan V, Ozyazgan Y, Fresko Y, Mat C, Yurdakul S, Yazici
H.
Behcet's Syndrome Research Center, Cerrahpaa Medical Faculty,
University of Istanbul, Istanbul, Turkey. vedath@isbank.net.tr
BACKGROUND: Eye involvement is the main cause of morbidity
in Behcet's syndrome. The efficacy of the combined use of azathioprine
and interferon alfa in treating this condition has not been studied.
METHODS: Ten male BD patients with retinal involvement but no
irreversible structural changes were treated with azathioprine
2.5 mg/kg/day and IFN alpha 2b three times weekly for 24 weeks
in an open trial. At week 24, IFN alpha was stopped and the patients
continued to use azathioprine or received other immunosuppressives
as indicated. Clinical response was assessed by visual acuity
changes of either eye under the combination treatment and during
the follow-up after stopping interferon. RESULTS: As compared
to the study entry, the mean visual acuities of either eye increased
significantly at the end of the combination treatment (right eye
5.8 +/- 1.26 vs. 8.3 1.14; P = 0.043; left eye 6.3 1.15 SEM vs.
9.1 +/- 0.9 SEM; P = 0.027). The improvement in visual acuity
persisted in the nine patients who were followed for 7.2 +/- 1.6
SEM months after stopping interferon. Reversible hematologic toxicity,
mostly in the form of leukopenia, was detected in six patients
during the combination treatment. CONCLUSIONS: The combination
of IFN alpha and azathioprine appears to be effective for eye
involvement of BD. However, the frequent occurrence of myelosuppression
mandates close monitoring.
-----
Vestn Oftalmol 2002 Jul-Aug;118(4):34-6
[Study of the effectiveness of ultraviolet irradiation
of blood in the treatment of traumatic uveitis]
[Article in Russian]
Aznabaev MT, Karabanova IV, Babushkin AE.
Sixty-five patients (65 eyes) with traumatic uveitis were treated.
Ultraviolet irradiation of autoblood was included in therapeutic
complexes of 28 patients. 37 patients received traditional therapy
(corticosteroids, nonsteroid inflammatory agents, etc.). Addition
of UV exposure of autoblood to combined therapy for traumatic
uveitis more effectively (92.9 vs. 75.7%) and sooner liquidated
posttraumatic inflammatory reaction (8.10 +/- 1.5 vs. 12.7 +/-
1.7 days), decreased the hospital stay (11.0 +/- 2.0 vs. 15.8
+/- 1.3 days), and eventually more often improved the visual acuity
(in 42.9 vs. 24.3% patients). Hence, UV exposure of autoblood
is an effective, safe, and virtually atraumatic method of treatment.
-----
Ophthalmologe 2002 Sep;99(9):691-4
[Efficiency of mycophenolate mofetil in the treatment
of intermediate and posterior uveitis]
[Article in German]
Greiner K, Varikkara M, Santiago C, Forrester JV.
Department of Ophthalmology, Grampian University Hospitals, Aberdeen,
Scotland, U.K. k.greiner@abdn.ac.uk
BACKGROUND: The severity of disease and the side-effects of
long-term corticosteroid treatment support the rationale for other
immunosuppressive drugs in the management of uveitis. Mycophenolate
mofetil (MMF) is a selective inhibitor of ionosine monophosphate
dehydrogenase and exerts its major effects by modulation of the
function of T and B lymphocytes. This study was undertaken to
evaluate the clinical effect of MMF in the control of intermediate
and posterior uveitis. METHODS: A retrospective study of 18 consecutive
patients with intermediate or posterior uveitis treated with MMF
was performed. Activity of intraocular inflammation was graded
according to the guidelines of the international uveitis study
group before and during treatment with MMF. Furthermore, the ability
of MMF treatment to reduce the steroid dosage and/or substitute
other immunosuppressive agents with unacceptable side-effects
(cyclosporin A, tacrolimus, azathioprine) was evaluated. RESULTS:
The indication for treatment with MMF in all 18 patients (age
range: 11-73 years) was either poor control of ocular inflammation
by the previous immunosuppressive therapy or unacceptable side-effects
of this therapy. The daily MMF dose was 2 g and therapy was combined
with cyclosporin A and/or prednisolone. One patient received MMF
monotherapy. Corticosteroids were discontinued in 4 patients and
the steroid dose could be reduced in 14 patients following MMF
therapy. Marked resolution of ocular inflammatory activity occurred
in 13 patients. The most frequently observed side-effects of MMF
were myalgia, fatigue, headache and gastrointestinal problems.
CONCLUSION: MMF was effective in disease control in the majority
of patients with intermediate and posterior uveitis and proved
to be a useful second line immunosuppressant for refractory intraocular
inflammatory disease with an acceptable profile of side-effects.
--
Acta Clin Belg 2002 Jun-Jul;57(3):142-7
Uveitis management: a multidisciplinary approach
to assess systemic involvement and side
effects of treatments.
Peretz A, Guillaume MP, Casper-Velu L.
Internal Medicine Department, Centre Hospitalier Universitaire
Brugmann, Universite Libre de Bruxelles, Belgique. aperetz@ulb.ac.be
OBJECTIVE: Non-infectious uveitis is often associated with
systemic diseases severe enough to require corticosteroids (CS)
and immunosuppressive drugs, which have potential serious side
effects. METHODS: 28 patients with non-infectious uveitis were
referred by the ophthalmologist. RESULTS: A systemic disease was
found in 17/28 patients (60%): sarcoidosis in 11, spondylarthropathy
in 3, Behcet's disease in 2, Crohn's disease in 1 patient. Eighteen
patients received CS, 21 patients received immunosuppressive drugs.
Most side effects were due to CS treatment: Cushing's syndrome
in 12, cataract in 11, glucose intolerance in 3, gastric ulcus
in 1, hypertension in 1, osteoporosis in 17, avascular bone necrosis
in 3 patients. Prophylaxis or treatment of corticosteroids induced
osteoporosis consists in calcium, 500 mg/day and vitamin D 400
IU in most of them with in addition hormone replacement therapy
(n = 8) or bisphosphonates (n = 13). CONCLUSION: Sixty percent
of patients with severe uveitis had a systemic disease. CS were
the most deleterious drugs in spite of bi- or tri-therapy with
CS sparing immunosuppressive drugs.
-----
Nippon Rinsho 2002 Mar;60(3):556-62
[Monoclonal antibody therapy for uveitis]
[Article in Japanese]
Kawashima H.
Department of Ophthalmology, Faculty of Medicine, University of
Tokyo.
Uveitis, or intraocular inflammation, is caused by various
reasons. Since many of the cases are of unknown origin, non-specific
anti-inflammatory therapy is often the only choice for the treatment
of uveitis. Furthermore, some of the patients are indeed refractory
to every available modality and are suffering from severe visual
disturbances. Stronger medicine is needed. Monoclonal antibodies
against tumor necrosis factor-alpha, TNF-alpha, are one of the
candidates in giving us more opportunities to treat such patients
more effectively. We are especially hopeful of its application
to refractory Behcet's disease. Its unique adverse side effects,
though, should be carefully monitored. On balance, this monoclonal
antibody therapy may become the last anchor for treating sight-threatening
uveitis in the near future.
-----
Ophthalmol Clin North Am 2002 Sep;15(3):389-94
Corticosteroids in uveitis.
Rothova A.
Uveitis Center, FC Donders Institute of Ophthalmology, University
Medical Center Utrecht, E.03-136, Heidelberglaan 100, 3584 CX
Utrecht, The Netherlands. A.Rothova@azu.nl
No strong evidence exists with which to answer questions about
the effectiveness of CS in treating visual loss from intraocular
inflammation. Steroids are valuable and quickly working anti-inflammatory
medications, which may prevent visual loss in many patients with
noninfectious uveitis. The value of prolonged treatment in uveitis
is not yet established. The literature on efficacy of CS in diverse
uveitic entities contains no results from randomized clinical
trials; all of the information originated from case series. In
addition, a quality of life assessment was not studied. These
are serious limitations; the information about the effect of medication
should be obtained by comparing a treated group with an untreated
control group similar in all the important respects. Necessary
documentation would include details about the patient selection
criteria. Use of standardized follow-up intervals and outcomes
assessment would further improve the quality of information, as
would comparisons with the natural history of the untreated patient
population. Because case series have no control group and do not
use randomization, there is no way to estimate how CS might have
changed a final outcome. Because of the severe adverse effects
associated with chronic use of CS and unknown efficacy on final
visual prognosis, it is recommended for those of need of long-term
anti-inflammatory medication to start CS in the acute stage of
the disease and taper off subsequently with use of CS-sparing
medications. Randomized clinical trials are needed to determine
the short- and long-term effectiveness of CS in uveitis.
-----
Ophthalmol Clin North Am 2002 Sep;15(3):309-17
Intermediate uveitis.
Lai WW, Pulido JS.
Vitreoretinal Service, University of Illinois Eye and Ear Infirmary,
Department of Ophthalmology and Visual Sciences, University of
Illinois, Chicago Eye Center, 1905 West Taylor Street, Chicago,
IL 60612, USA. wicolai@yahoo.com
The cause of intermediate uveitis remains unknown. It is important
to rule out other causes of the condition before initiating therapy.
Many patients presenting with a mild form of the disease and who
have good visual acuity may not require treatment. Those with
decreased vision because of inflammation or cystoid macular edema
may require periocular injections or systemic administration of
corticosteroids (Fig. 2). Those who develop recalcitrant disease
and those who experience severe side effects from the steroid
therapy may require other immunosuppressive agents. Close monitoring
of systemic side effects is required. Laser photocoagulation or
cryotherapy of the peripheral retina is useful in patients who
develop neovascularization of the vitreous base, in those who
are not responsive to periocular injections, and in those who
develop severe side effects from corticosteroids. This should
be considered before starting systemic immunosuppressive agents.
Pars plana vitrectomy with or without cryotherapy or laser photocoagulation
is indicated in patients with marked vitreous debris, cystoid
macular edema, and in those who develop.
-----
Ophthalmol Clin North Am 2002 Sep;15(3):297-307
HLA-B27—associated uveitis.
Smith JR.
Casey Eye Institute, Oregon Health and Science University, 3375
SW Terwilliger Boulevard, Portland, OR 97201-4197, USA. smithjus@ohsu.edu
HLA-B27--associated acute anterior uveitis, a relatively common
form of uveal inflammation, has a sufficiently characteristic
presentation that the diagnosis is often suggested by clinical
assessment, although testing for HLA-B27 status provides strong
support for the diagnosis. This condition usually responds readily
to topical corticosteroid therapy, and the prognosis is generally
good. Atypical cases may be chronic, complicated by visually disabling
complications or posterior eye involvement. Chronic or progressive
forms of the disorder may require systemic immunosuppression.
A diagnosis of HLA-B27--associated uveitis may bring an associated
systemic condition to medical attention for the first time. Ongoing
research promises to elucidate the intriguing relationship between
the HLA-B27 molecule, gram-negative bacterial infection, and inflammatory
disease.
-----
Vestn Oftalmol 2002 Nov-Dec;118(6):29-31
[Preference for transscleral cryocoagulation of
peripheral exudate in intermediate uveitis before traditional
methods of treatment]
[Article in Russian]
Ermakova NA.
The term intermediate uveitis (IU) describes an anatomic distribution
of ocular inflammation rather than a distinct clinicopathologic
condition and includes pars planitis, chronic posterior cyclitis
and peripheral uveitis. In the treatment of IU corticosteroids
and cytostatic agents are of value but since the disease tends
to have a long course they produce perminant side effects. Especially
this therapy is undesirable in children. In some patients immunosuppressive
therapy is not effective, particularly with peripheral neovascularization.
Cryotherapy performed in 11 patients (16 eyes, 5 men, 6 women,
mean age 22.9 +/- 8.1 years) with IU controlled inflammation during
13-37 months and prevented vitreous hemorrhage.
-----
Ophthalmol Clin North Am 2002 Sep;15(3):319-26, vi
Sarcoidosis and uveitis.
Jones NP.
Uveitis Clinic, Royal Eye Hospital, Manchester M13 9WH, UK. njones@central.cmht.nwest.nhs.uk
Sarcoidosis is a disease initiated by one or more unknown antigens
in predisposed hosts, and causes noncaseating granulomatous inflammation.
Uveitis is common and may affect any part of the eye. Protean
systemic manifestations occur but pulmonary and cutaneous involvement
is most common. Diagnosis is important; any suspicious uveitis
should be investigated by relevant hematologic, radiologic, and
invasive tests. A high proportion of patients require systemic
corticosteroid or immunosuppressive treatment for uveitis. A significant
minority become visually disabled because of macular scarring,
glaucoma, or chorioretinal ischemia.
-----
Int Rev Immunol 2002 Mar-Jun;21(2-3):231-53
Cytokines in immunotherapy of experimental uveitis.
de Kozak Y, Verwaerde C.
INSERM U450, Paris, France. ydekozak@ccr.jussieu.fr
A better understanding of the basic mechanisms of uveitis and
of the role of cytokines in experimental ocular inflammation autoimmune
diseases should allow us to define new approaches for therapy.
Modulation of the cytokine network by either blocking cytokine
activity or administration of regulatory Th2 cytokines has shown
its efficacy in several experimental autoimmune diseases including
uveitis. However, cytokines present pleiotropic activities and
thus may exert different effects depending on the autoimmune diseases,
making interventions on their production complex. Anti-cytokine
therapy or a combination of anti-cytokine drugs, antibodies, and
cytokine gene therapy to synergize the therapeutical effects of
other treatments appear to be of interest. Improvements in drug
delivery and in biotechnology will also allow us to elaborate
new and safe immunomodulatory strategies.
-----
Eye 2002 Sep;16(5):587-93
Corticosteroid-induced osteoporosis in patients
with uveitis.
Jones NP, Anderton LC, Cheong FM, Whallett A, Stanford MR, Murray
PI, Lesnik-Oberstein S, Pavesio C.
The Royal Eye Hospital, Manchester, UK. njones@central.cmht.nwest.nhs.uk
AIMS: To estimate the prevalence of low bone density and osteoporosis
in a population of patients with uveitis taking systemic steroid
treatment; to clarify the risks of steroid-induced fracture and
to suggest a protocol for the prevention and management of bone
loss in patients with ophthalmic inflammatory disease. METHODS:
Bone densitometry was performed on 129 adult patients with prednisolone-treated
uveitis from four centres. Information on uveitis diagnosis, associated
risk factors, steroid dosage and treatment duration, prophylaxis
and management, was collected. Juveniles, patients with scleritis
and those who had used deflazacort, were excluded. RESULTS: Steroid
treatment time varied from 13 weeks to 31 years, and the total
dosage from 1.29 g to 166.5 g. Twenty-six percent of patients
also used one or more immunosuppressives. Forty-eight percent
had additional risk factors for bone loss. Bone density was abnormally
low in 44.2%, and 15.5% had osteoporosis. Osteoporosis was substantially
more common in males (20.6%, all under 60 yrs) than in females
(9.8%). Seven symptomatic fractures occurred in patients on treatment.
Bone loss correlated with total steroid dose, mean dose, duration
of treatment and the presence of pre-existing risk factors. CONCLUSIONS:
The prevalence of steroid-induced osteoporosis and fracture is
low for patients with uveitis but young males are at risk. Patients
at high risk should be identified, and prophylaxis and treatment
should be used as required. The guideline of the National Osteoporosis
Society is recommended as a management protocol.
-----
Curr Eye Res 2002 Feb;24(2):92-8
Characterization of T lymphocyte subtypes in endotoxin-induced
uveitis and effect of
pentoxifylline treatment.
Avunduk AM, Avunduk MC, Oztekin E, Baltaci AK.
Department of Ophthalmology, School of Medicine, Louisiana State
University, New Orleans, LA, USA. a_avunduk@hotmail.com
PURPOSE: The aims of the study were twofold: 1) to investigate
the role of T lymphocyte subtypes in the pathogenesis of endotoxin-induced
uveitis (EIU) and 2) to study the possible beneficial effect of
pentoxifylline, an inhibitor of neutrophil motility, and Tumor
Necrosis Factor-alpha on this disease. METHODS: Forty-two inbred
male Lewis rats were divided into seven equal groups. 200 microg
of Escherichia coli 055: B55 lipopolysaccharide (LPS) was injected
in one hind footpad of the Group 2, 3, 4, 5, 6, and 7 rats. Group
5, 6, and 7 rats also received concomitant intraperitoneal pentoxifylline
(PTX) during food pad injection of LPS. Group 1 rats were used
as controls with intra-peritoneal normal saline injection. Eight,
24, and 48 hours after treatment, the rats were euthanized. Neutrophil
leukocyte, mononuclear cells, and CD4+, CD8+, and CD45RA+ cell
infiltration in the anterior uveal tissue were determined either
by hematoxylin-eosin or monoclonal antibody staining. Tumor Necrosis
Factor-alpha (TNF-alpha) levels were also measured in the aqueous
and blood samples. We compared the numbers of infiltrating cells
in the different groups. RESULTS: We found that peak infiltration
of lymphocyte, neutrophils, and CD4+ cells occurred at 24 hours.
However, CD8+ and CD45RA+ cell number reached their highest levels
at 48 hours. There was no inflammatory cell infiltration in the
control rats. Concomitant pentoxifylline treatment did not affect
any of these parameters, although it effectively reduced TNF-alpha
concentrations in the anterior chamber and the serum. CONCLUSION:
We conclude that, 1) T lymphocytes might be involved in the pathogenesis
of endotoxin-induced uveitis. 2) The potential role of pentoxifylline
in the treatment of human uveitis is questionable. However, these
are initial findings and need confirmation by additional studies.
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Laryngoscope 2002 Apr;112(4):658-60
Adenotonsillectomy as a treatment option for poststreptococcal
uveitis.
Ovchinsky A, Schulman S, Rosenfeld RM.
Department of Otolaryngology, State University of New York Health
Science Center at Brooklyn, USA. ovchinsa@hotmail.com
OBJECTIVES: To report recurrent uveitis as a manifestation
of poststreptococcal syndrome and discuss a role of adenotonsillectomy
as a treatment option. STUDY DESIGN: Case study. METHODS: A case
report of a 6-year-old, otherwise healthy girl with group A streptococcal
uveitis managed successfully with adenotonsillectomy. RESULTS:
In the year after surgery there were only two episodes of uveitis,
contrasted with a preoperative 3-year history of 8 to 10 annual
episodes despite corticosteroid therapy. Moreover, as a result
of the postoperative improvement the child was able to avoid impending
methotrexate therapy. CONCLUSIONS: Although the role of tonsillectomy
in managing poststreptococcal uveitis is unknown, our results
suggest a positive impact independent of the baseline tonsillitis
frequency. Otolaryngologists should be aware of these uncommon
sequelae of streptococcal infection and the potential role of
tonsillectomy in treatment.
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J Glaucoma 2002 Jun;11(3):189-96
Trabeculectomy with antiproliferative agents in
uveitic glaucoma.
Ceballos EM, Beck AD, Lynn MJ.
Department of Ophthalmology, Emory University School of Medicine
and Department of Biostatistics, Rollins School of Public Health
of Emory University, Atlanta, Georgia 30322, USA.
PURPOSE: To evaluate the outcome of trabeculectomy with antiproliferative
agents in patients with uveitic glaucoma METHODS: A retrospective
chart review of 44 eyes of 44 patients with uveitic glaucoma who
underwent trabeculectomy with mitomycin C or 5-fluorouracil. The
authors defined complete success as an intraocular pressure of
21 mm Hg or lower without pressure-lowering medications, qualified
success as an intraocular pressure of 21 mm Hg or lower with medications,
and failure as an intraocular pressure of more than 21 mm Hg with
medications, loss of light perception, or the need for reoperation.
RESULTS: The cumulative probability of complete or qualified success
was 78% at 1 year and 62% at 2 years. At 2 years, success rates
were 39% in males and 71% in females (P = 0.02), 74% in white
patients and 55% in black patients (P = 0.58), and 45% in patients
with idiopathic uveitis and 74% in patients with sarcoid uveitis
(P = 0.17). Sixteen of 31 (51.6%) phakic patients developed new
cataracts or had progression of existing cataracts and required
cataract extraction. Four of 16 eyes (25%) lost intraocular pressure
control and needed repeat trabeculectomy after undergoing cataract
surgery. CONCLUSIONS: Patients with uveitic glaucoma can have
good outcomes after trabeculectomy with antiproliferative agents.
Male gender was the only statistically significant risk factor
for trabeculectomy failure. Cataract management in the presence
of a filtering bleb poses a treatment dilemma between improvement
of visual acuity and loss of intraocular pressure control.
-----
Chung Hua Yen Ko Tsa Chih 2002 Apr;38(4):204-6
[Therapeutic vitrectomy for severe uveitis and
its complications]
[Article in Chinese]
Li J, Tang S, Lu L, Zhang S, Li M.
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou
510060, China. leejiaching@163.net
OBJECTIVE: To investigate the therapeutic value of vitrectomy
for uveitis and its complications. METHODS: Vitrectomy was performed
on 14 patients (14 eyes) with uveitis. In these 14 eyes, there
were 6 eyes with severe opacity of vitreous, 5 eyes with cataract,
5 eyes with retinal detachment, and 3 eyes with poor response
to medication. Pars plana lenectomy, scleral cryopexy, buckling
procedure, endolaser photocoagulation, gas-fluid exchange or silicone
oil intraocular tamponade were added according to the different
needs. The follow-up varied from 18 to 45 months. RESULTS: Twelve
of the 14 eyes obtained better visual acuity, and in the other
two light perception remained; less drugs were used after operation
in all cases, and the uveitis was controlled. CONCLUSION: Vitrectomy
is an effective method for severe uveitis and its complications
both in the improvement or stabilization of visual acuity and
in the reduction or cessation of systemic treatment.
-----
Curr Opin Rheumatol 2002 Jul;14(4):337-41
Anterior uveitis: current concepts of pathogenesis
and interactions with the spondyloarthropathies.
Martin TM, Smith JR, Rosenbaum JT.
Oregon Health & Science University, Casey Eye Institute, Portland,
Oregon 97201, USA. martint@ohsu.edu
Anterior uveitis describes inflammation that involves the iris
or ciliary body. Anterior uveitis may be part of a systemic illness
such as a spondyloarthropathy. It may also arise from an infection
such as herpes simplex; be part of an ocular syndrome, such as
Fuchs' heterochromic iridocyclitis; be part of trauma, as in cataract
surgery; or result from an idiopathic eye disease with a presumed
immune pathogenesis. During 2001, progress has been made understanding
uveitis in general, as well as specifically, in association with
spondyloarthropathy. Here, we review recent insights into anterior
uveitis with regard to clinical presentation, immune mechanisms,
genetics, and anti-tumor necrosis factor therapy.
-----
Ophthalmology 2002 May;109(5):879-82
Cytomegalovirus as a cause of anterior uveitis
with sectoral iris atrophy.
Markomichelakis NN, Canakis C, Zafirakis P, Marakis T, Mallias
I, Theodossiadis G.
Ocular Inflammation and Immunology Service, Department of Ophthalmology,
General Hospital of Athens, Athens, Greece.
OBJECTIVE: To report two cases of recurrent anterior uveitis
with sectoral iris atrophy and ocular hypertension during attacks
caused by cytomegalovirus (CMV). DESIGN: Two observational case
reports. PARTICIPANTS: Two immunocompetent patients with a history
of recurrent unilateral hypertensive anterior uveitis with sectoral
iris atrophy were referred to us with the presumptive diagnosis
of herpetic uveitis. MAIN OUTCOME MEASURES: Comprehensive ophthalmic
examination, aqueous humor polymerase chain reaction (PCR), and
peripheral blood serologic studies were performed on both patients.
RESULTS: Examination of aqueous humor by PCR was positive for
CMV and negative for herpesvirus. Serum IgG/IgM titers disclosed
past CMV infection. Both patients responded well to antiviral
therapy with ganciclovir. The final visual acuity level was 20/20
in both eyes of both patients. CONCLUSIONS: CMV infection can
produce recurrent attacks of anterior uveitis with clinical characteristics
indistinguishable from those previously considered highly suggestive
or even pathognomonic for herpetic infection. This observation
has implications for the therapeutic management of such patients.
-----
Br J Ophthalmol 2002 May;86(5):521-3
High dose intravenous steroid therapy for severe
posterior segment uveitis in Behcet's disease.
Toker E, Kazokoglu H, Acar N.
Department of Ophthalmology, Marmara University Medical School.
AIM: To evaluate the safety and effectiveness of high dose
intravenous steroid therapy (HDIST) in Behcet's disease patients
with severe posterior segment uveitis attacks. METHODS: Five patients
with ocular Behcet's disease were treated with HDIST for severe
posterior segment attacks. Two patients had vasculitis, one patient
had papillitis, and the other two had retinitis; four patients
also had accompanying severe vitritis. The visual acuities and
improvement in ocular signs after HDIST were evaluated. RESULTS:
During HDIST, patients had no systemic complications caused by
treatment. All patients responded to HDIST with evidence of a
decrease in intraocular inflammatory activity and improved visual
acuities within a mean time of 7 (1-15) days of commencing treatment.
During follow up three out of five patients had new posterior
segment attacks. CONCLUSION: HDIST is effective in controlling
severe, vision threatening acute posterior segment Behcet's uveitis
attacks and in improving visual function in a short period of
time.
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Paediatr Drugs 2002;4(3):183-9
Management of uveitis in pediatric patients: special
considerations.
Smith JR.
Casey Eye Institute, Oregon Health Sciences University, Portland,
Oregon 97201-4197, USA. smithjus@ohsu.edu
Uveitis refers to inflammation involving the uvea or middle
coat of the eye. This condition occurs uncommonly, particularly
in persons aged <or=16 years. However, pediatric uveitis deserves
special consideration for reasons that include the relatively
poor prognosis, unique systemic associations, and various age-related
treatment considerations. Accurate diagnosis requires history
from both patient and parents, a complete ophthalmic examination
that may require general anesthesia, and carefully selected investigations.
Infections and masquerade syndromes, such as leukemia and retinoblastoma,
must be excluded before treatment is commenced with immunosuppressive
agents. Noninfectious anterior uveitis generally responds to topical
corticosteroid and mydriatic therapy. Although used frequently
in adults with posterior uveitis, periocular corticosteroid injections
may require a general anesthetic, and systemic corticosteroids
may cause serious adverse effects, including growth retardation,
in pediatric patients. Consequently, in children, one or more
corticosteroid-sparing immunosuppressive drugs are usually employed
for vision-threatening noninfectious posterior eye inflammation.
Methotrexate is the most commonly used systemic immunosuppressive
agent for pediatric uveitis. It is effective in small retrospective
clinical series, generally well tolerated, easy to administer,
and inexpensive. Cyclosporin has also been used successfully in
children with uveitis, being associated with a low risk of renal
toxicity when used at standard doses. Although prescribed for
severe ocular inflammation in adults, alkylating agents are generally
contraindicated in children owing to risks including secondary
malignancy, sterility and bone marrow suppression. Drugs that
inhibit tumor necrosis factor-alpha have recently been used successfully
to treat children with uveitis; however, in some patients there
may be a risk of potentiating the ocular inflammation. Randomized
clinical trials would provide valuable information about the relative
efficacy of the various available treatment options.
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