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Purpose: To evaluate relationships between retinal vessel caliber and tests of visual function among people with AIDS., Design: Longitudinal, observational cohort study., Methods: We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Visual function was evaluated with best-corrected visual acuity, Goldmann perimetry, automated perimetry (Humphrey Field Analyzer), and contrast sensitivity (CS) testing. Semi-automated grading of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, sought independent relationships between indices and visual function variables., Results: Included were 1250 participants. Smaller AVR was associated with reduced visual field by Goldmann perimetry (P = .003) and worse mean deviation (P = .02) on automated perimetry and possibly with worse pattern standard deviation (PSD) on automated perimetry (P = .06). There was a weak association between smaller AVR and worse CS (P = .07). Relationships were independent of antiretroviral therapy and level of immunodeficiency (CD4+ T lymphocyte count, human immunodeficiency virus [HIV] RNA blood level). On longitudinal analysis, retinal vascular indices at baseline did not predict changes in visual function., Conclusions: Variation in retinal vascular indices is associated with abnormal visual function in people with AIDS, manifested by visual field loss and possibly by reduced CS. Relationships are consistent with the hypothesis that HIV-related retinal vasculopathy is a contributing factor to vision dysfunction among HIV-infected individuals. Longitudinal studies are needed to determine whether changes in indices predict change in visual function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate relationships between retinal vessel caliber, AIDS-related factors, and mortality., Design: Longitudinal, observational cohort study., Methods: We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Semi-automated evaluation of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, identified independent relationships between indices and various host- and disease-related variables., Results: Included were 1250 participants. Mean follow-up for determination of mortality was 6.1 years. Smaller CRAE was related to increased age (P < .001) and hypertension (P < .001); larger CRAE was related to lower hematocrit (P = .002). Larger CRAE and CRVE were associated with black race (P < .001). Larger CRVE was related to smoking (P = .004); smaller CRVE was related to age (P < .001) and higher mean corpuscular volume (P = .001). We observed the following relationships with AIDS-associated factors: smaller CRAE and larger CRVE with history of highly active antiretroviral therapy (HAART; P < .001); and larger CRAE with lower CD4+ T lymphocyte count (P = .04). We did not identify independent relationships with human immunodeficiency virus RNA blood levels. There was a 12% (95% CI, 2%-21%) increase in mortality risk per quartile of decreasing AVR (P = .02)., Conclusions: Variations in retinal vascular caliber are associated with AIDS-specific factors and are markers for increased mortality risk. Relationships are consistent with the hypothesis that the vasculature is altered by known atherogenic effects of chronic HAART or the prolonged inflammatory state associated with AIDS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Studies have used central retinal arteriolar (CRAE) and central retinal venular (CRVE) calibers, measured from images produced with computerized image analysis, to detect risk factors for systemic diseases. The authors explored suboptimal image focus as a possible contributing factor to artificially larger vascular caliber measurements., Methods: From the reading center image collections, 30 digital retinal images were selected for optimum quality. Image analysis software was used to derive nine progressively blurred versions of the originals. IVAN measurement software was used to measure CRAE and CRVE in the original and the blurred series derived from them. To check the adequacy of the simulation, progressively defocused series of images were taken of several volunteers., Results: For CRAE, each level of simulated blurring produced a statically significant increase in apparent vessel caliber from the original (P<0.01, Wilcoxon signed rank test). For an average CRAE of 160 μm, mean broadening with minimal/moderate/severe blurring was 3 μm/12 μm/33 μm. For CRVE, every blurring level beyond the first was found to be significant (P<0.01). From an average CRVE of 200 μm, mean broadening ranged from 0 to 11 μm with minimal to severe blurring. Analysis of the progressively defocused series taken of volunteers yielded similar results overall., Conclusions: Suboptimal focus can result in erroneously larger vessel caliber measurements. Slight blurring has a minimal effect, but more severe blurring has a progressively greater effect.

Purpose: To compare grading of diabetic retinopathy (DR) and diabetic macular edema (DME) from stereoscopic film versus stereoscopic digital photographs obtained from a subset of Diabetic Retinopathy Clinical Research Network (DRCR.net) participants., Methods: In this photographic media comparison study, digital and film images were obtained at a single study visit from some of the subjects enrolled in active DRCR.net clinical study protocols. Digital camera systems and digital and film photographers were certified to obtain images according to standard procedures. Images were graded for DR severity and DME in a masked fashion by Fundus Photograph Reading Center (Madison, WI) graders. Agreement between gradings was assessed by calculating the percentage of agreement and κ statistics., Results: Images obtained with both film and digital media were submitted for 155 eyes of 96 study participants. On a nine-step Early Treatment Diabetic Retinopathy study DR severity scale, grading agreed exactly in 74%, and was within one step of agreement in 93%, with a weighted κ statistic of 0.82 (95% confidence interval [CI], 0.71-0.92). On a nine-step DME severity scale and three-step clinically significant macular edema (CSME) scale, grading agreed exactly in 39% and 88%, respectively, and within one step in 70% and 92% (weighted κ statistic, 0.44 [95% Cl, 0.34-0.54] and 0.72 [95% Cl, 0.55-0.90], respectively)., Conclusions: Among clinical sites participating in the DRCR.net, agreement between film and digital images was substantial to almost perfect for DR severity level and moderate to substantial for DME and CSME severity levels, respectively. Replacement of film fundus images with digital images for DR severity level should not adversely affect clinical trial quality. (ClinicalTrials.gov numbers, NCT00367133, NCT00369486, NCT00444600, NCT00445003, NCT00709319.)

Objective: Safety and efficacy of daclizumab during an 11-year period., Design: Structured, retrospective chart review., Participants: Thirty-nine patients., Methods: Patients with chronic, noninfectious intermediate and/or posterior uveitis., Results: Thirty-nine patients (78 eyes) were treated for a mean of 40.3 months. Visual acuity improved by ≥2 lines in the better eye in 7 patients (18.4%) and worsened by 2 lines in 6 patients (15.8%) with a mean of 2.8 Snellen lines of vision lost per eye. Six eyes with vitreous cell less than grade 2 lost 2 lines of vision and 7 eyes with less than grade 2 vitreous cell improved 2 lines. Mean number of immunosuppressive medications per patient decreased from 1.89 medications/patient to 1.17 medications/patient. The average number of periocular injections per patient was 1.46 (range, 0-9). The mean number of flares was 2.05/patient (range, 0-12), with the rate being 0.62 flares per patient-year. Four patients developed cancer during the course of this study. Mean time to onset of malignancy was 26 months and the mean age in this group was 49 years., Conclusions: Daclizumab demonstrated efficacy in the reduction of concomitant immunosuppressive medication, stabilization of visual acuity, and the prevention of uveitic flares in most cases. Dermatologic complications were the most frequently observed adverse event in our series. Four patients developed solid tumor malignancies during this 11-year period., (Published by Elsevier Inc.)

Purpose: To describe the 5-year outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the era of highly active antiretroviral therapy (HAART)., Design: Prospective, multicenter, observational study., Participants: A total of 503 patients with AIDS and CMV retinitis., Methods: Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and retinal photographs. Participants were classified as having previously diagnosed CMV retinitis and immune recovery (CD4+ T cells ≥ 100 cells/μl), previously diagnosed retinitis and immune compromise, and newly diagnosed CMV retinitis (diagnosis <45 days before enrollment)., Main Outcome Measures: Mortality, retinitis progression (movement of the border of a CMV lesion ≥ ½ disc diameter or occurrence of a new lesion), retinal detachment, immune recovery uveitis (IRU), and visual loss (< 20/40 and ≥ 20/200)., Results: Overall mortality was 9.8 deaths/100 person-years (PY). Rates varied by group at enrollment from 3.0/100 PY for those with previously diagnosed retinitis and immune recovery to 26.1/100 PY for those with newly diagnosed retinitis. The rate of retinitis progression was 7.0/100 PY and varied from 1.4/100 PY for those with previously diagnosed retinitis and immune recovery to 28.0/100 PY for those with newly diagnosed retinitis. The rate of retinal detachment was 2.3/100 eye-years (EY) and varied from 1.2/100 EY for those with previously diagnosed retinitis and immune recovery to 4.9/100 EY for those with newly diagnosed retinitis. The rate of IRU was 1.7/100 PY and varied from 1.3/100 PY for those with previously diagnosed retinitis and immune recovery at enrollment to 3.6/100 PY for those with newly diagnosed retinitis who subsequently experienced immune recovery. The rates of visual loss to < 20/40 and to ≤ 20/200 were 7.9/100 EY and 3.4/100 EY, respectively; they varied from 6.1/100 EY and 2.7/100 EY for those with previously diagnosed retinitis and immune recovery to 11.8/100 EY and 5.1/100 EY for those with newly diagnosed retinitis. Although the event rates tended to decline with time, in general, at no time did they reach zero., Conclusions: Despite the availability of HAART, patients with AIDS and CMV retinitis remain at increased risk for mortality, retinitis progression, complications of the retinitis, and visual loss over a 5-year period., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: To evaluate and compare the intra-session repeatability of retinal thickness measurements from the Topcon 3D OCT 1000 (Topcon Medical Systems; Paramus, NJ), a spectral-domain optical coherence tomography (SD-OCT) system, with the Stratus (Carl Zeiss Meditec, Inc., Dublin, CA), a time-domain OCT (TD-OCT) system, in eyes with retinal diseases., Patients and Methods: Repeated scans with both SD-OCT and TD-OCT were taken. Thickness measurements from high-quality scans were used to assess repeatability and compare measurements between the two instruments., Results: Paired scans from 127 eyes were evaluated, of which 63 pairs were of high quality. Coefficients of repeatability and variation for the central subfield were 20.1 μm (2.6%) with SD-OCT and 27.4 μm (4%) with TD-OCT (P = .38). The mean difference in central subfield thickness between the two instruments was 24.5 μm (standard deviation = 20.9)., Conclusion: Repeatability of retinal thickness measurements with the Topcon 3D OCT 1000 is comparable to the Stratus. The measurements of the two machines differ significantly and cannot be used interchangeably., (Copyright 2010, SLACK Incorporated.)

Background: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy., Methods: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy., Results: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29)., Conclusions: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.), (2010 Massachusetts Medical Society)

Purpose: To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation., Design: Retrospective cohort study., Participants: A total of 373 patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007 inclusive., Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers., Main Outcome Measures: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity., Results: Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of inflammation over at least 2 visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone < or = 10 mg/day) was achieved by 22.1% by 6 months and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year by 10.7% of the population. Patients aged more than 55 years were more than 3-fold more likely to discontinue therapy because of toxicity than patients aged 18 to 39 years. Doses of 151 to 250 mg/day tended to be more successful than lower doses and were not associated with a higher discontinuation for toxicity rate; higher doses did not seem to offer a therapeutic advantage., Conclusions: Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was tolerated by the majority of patients, toxicity was more frequent with increasing age; alternative agents may be preferred for patients aged more than 55 years., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the risk of and risk factors for hypopyon among patients with uveitis and to evaluate the risk of visual changes and complications after hypopyon., Design: Retrospective cohort study., Participants: Patients with uveitis at 4 academic ocular inflammation subspecialty practices., Methods: Data were ascertained by standardized chart review., Main Outcome Measures: Prevalence and incidence of hypopyon, risk factors for hypopyon, and incidence of visual acuity changes and ocular complications after hypopyon., Results: Among 4911 patients with uveitis, 41 (8.3/1000) cases of hypopyon were identified at the time of cohort entry. Of these, 2885 initially free of hypopyon were followed over 9451 person-years, during which 81 patients (2.8%) developed hypopyon (8.57/1000 person-years). Risk factors for incident hypopyon included Behçet's disease (adjusted relative risk [RR]=5.30; 95% confidence interval [CI], 2.76-10.2), spondyloarthropathy (adjusted RR=2.86; 95% CI, 1.48-5.52), and human leukocyte antigen (HLA)-B27 positivity (adjusted RR=2.04; 95% CI, 1.17-3.56). Patients with both a spondyloarthropathy and HLA-B27 had a higher risk than either factor alone (crude RR=4.39; 95% CI, 2.26-8.51). Diagnosis of intermediate uveitis (+/- anterior uveitis) was associated with a lower risk of hypopyon (with respect to anterior uveitis only, adjusted RR=0.35; 95% CI, 0.15-0.85). Hypopyon incidence tended to be lower among patients with sarcoidosis (crude RR=0.22; 95% CI, 0.06-0.90; adjusted RR=-0.28; 95% CI, 0.07-1.15). Post-hypopyon eyes and eyes not developing hypopyon had a similar incidence of band keratopathy, posterior synechiae, ocular hypertension, hypotony, macular edema, epiretinal membrane, cataract surgery, or glaucoma surgery. Post-hypopyon eyes were more likely than eyes not developing hypopyon to gain 3 lines of vision (crude RR=1.54; 95% CI, 1.05-2.24) and were less likely to develop 20/200 or worse visual acuity (crude RR=0.41; 95% CI, 0.17-0.99); otherwise, visual outcomes were similar in these groups., Conclusions: Hypopyon is an uncommon occurrence in patients with uveitis. Risk factors included Behçet's disease, HLA-B27 positivity, and spondyloarthropathy. Intermediate uveitis cases (+/- anterior uveitis) had a lower risk of hypopyon. On average, post-hypopyon eyes were no more likely than other eyes with uveitis to develop structural ocular complications or lose visual acuity., (Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the outcomes of cyclophosphamide therapy for noninfectious ocular inflammation., Design: Retrospective cohort study., Participants: Two hundred fifteen patients with noninfectious ocular inflammation observed from initiation of cyclophosphamide., Methods: Patients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at 4 centers. Dose of cyclophosphamide, response to therapy, corticosteroid-sparing effects, frequency of discontinuation, and reasons for discontinuation were obtained by medical record review of every visit., Main Outcome Measures: Control of inflammation, corticosteroid-sparing effects, and discontinuation of therapy., Results: The 215 patients (381 involved eyes) meeting eligibility criteria carried diagnoses of uveitis (20.4%), scleritis (22.3%), ocular mucous membrane pemphigoid (45.6%), or other forms of ocular inflammation (11.6%). Overall, approximately 49.2% (95% confidence interval [CI], 41.7%-57.2%) gained sustained control of inflammation (for at least 28 days) within 6 months, and 76% (95% CI, 68.3%-83.7%) gained sustained control of inflammation within 12 months. Corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less among those not meeting success criteria initially) was gained by 30.0% and 61.2% by 6 and 12 months, respectively. Disease remission leading to discontinuation of cyclophosphamide occurred at the rate of 0.32/person-year (95% CI, 0.24-0.41), and the estimated proportion with remission at or before 2 years was 63.1% (95% CI, 51.5%-74.8%). Cyclophosphamide was discontinued by 33.5% of patients within 1 year because of side effects, usually of a reversible nature., Conclusions: The data suggest that cyclophosphamide is effective for most patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg prednisone or less, although 1 year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in most patients who were able to tolerate therapy. To titrate therapy properly and to minimize the risk of serious potential side effects, a systematic program of laboratory monitoring is required. Judicious use of cyclophosphamide seems to be beneficial for severe ocular inflammation cases where the potentially vision-saving benefits outweigh the substantial potential side effects of therapy, or when indicated for associated systemic inflammatory diseases., (Copyright (c) 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation., Design: Retrospective cohort study., Participants: Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive., Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers., Main Outcome Measures: Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy., Results: Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone

Context: Whether immunosuppressive treatment adversely affects survival is unclear., Objective: To assess whether immunosuppressive drugs increase mortality., Design: Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis., Setting: Five tertiary ocular inflammation clinics. Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up. Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors., Main Outcome Measures: Overall mortality, cancer mortality., Results: Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01)., Conclusions: Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

Purpose: To report an unusual case of granulomatous sclerochoroiditis., Design: Interventional case report., Methods: A patient with ANCA-associated granulomatous vasculitis presented with nodular necrotizing scleritis, which was recalcitrant to multiple systemic immunosuppressive therapies and progressed to a blind painful eye, which was enucleated., Results: Histopathology revealed extensive occlusive vasculitis, diffuse T- and B- cellular infiltration, and lymphoid granulomatous formation. Enhanced MHC class II antigens, adhesion molecules, and Fas (CD95) and FasL (CD95L) were detected in the lesion., Conclusion: Granulomatous sclerochoroiditis with aggressive immune reaction can be a complication of ANCA-associated granulomatous vasculitis.

Purpose: To estimate the risk of structural ocular complications and loss of visual acuity (VA) in cases of Behçet disease (BD) and to evaluate potential risk and protective factors for these events., Design: Retrospective cohort study., Methods: A total of 168 consecutive patients with BD-associated ocular inflammation treated at five academic center ocular inflammation subspecialty practices were included. Clinical data for these patients were ascertained by standardized chart review. Main outcome measures included VA, structural ocular complications of inflammation, and intraocular pressure (IOP)., Results: Over a median follow-up of 1.05 years, the incidence of specific structural complications and IOP disturbances were common: the incidence rate of any ocular complication was 0.45 per eye-year (EY). Rates of loss of VA to 20/50 or worse and to 20/200 or worse were 0.12 per EY and 0.09 per EY, respectively. Risk factors for loss of VA during follow-up were persistent inflammatory activity, presence of posterior synechiae, presence of hypotony, and presence of elevated IOP. In a time-dependent analysis, current activity of ocular inflammation was associated with an increased risk of loss of VA to 20/50 or worse (relative risk [RR], 2.45; 95% confidence interval [CI], 1.1 to 5.5; P = .03) and to 20/200 or worse (RR, 2.67; 95% CI, 1.2 to 5.8; P = .01)., Conclusions: Loss of VA and occurrence of ocular complications were common in patients with ocular inflammation associated with BD, even with aggressive therapy. Ongoing inflammation during follow-up, presence or occurrence of posterior synechiae, hypotony, and elevated IOP were associated with an increased risk of loss of VA.

Purpose: To critically assess potentially carcinogenic effects of immunosuppressive therapy in the ocular inflammation setting., Design: Focused evidence assessment., Methods: Relevant publications were identified by MEDLINE and EMBASE queries and reference list searches., Results: Extrapolation from transplant, rheumatology, skin disease, and inflammatory bowel disease cohorts to the ocular inflammation setting suggest that: 1) alkylating agents increase hematologic malignancy risk and cyclophosphamide increases bladder cancer risk, but less so with < or =18 months' duration of therapy and hydration, respectively; 2) calcineurin inhibitors and azathioprine probably do not increase total cancer risk to a detectable degree, except perhaps some other risk factors (uncommon in ocular inflammation patients) might interact with the former to raise risk; 3) tumor necrosis factor (TNF) inhibitors may accelerate diagnosis of cancer in the first six to 12 months, but probably do not increase long-term cancer risk; and 4) changes in risk with methotrexate, mycophenolate mofetil, and daclizumab appear negligible, although nontransplant data are limited for the latter agents. Immunosuppression in general may increase skin cancer risk in a sun exposure-dependent manner., Conclusion: Use of alkylating agents for a limited duration seems justifiable for severe, vision-threatening disease, but otherwise cancer risk may be a relevant constraint on use of this approach. Antimetabolites, daclizumab, TNF inhibitors, and calcineurin inhibitors probably do not increase cancer risk to a degree that outweighs the expected benefits of therapy. Monitoring for skin cancer may be useful for highly sun-exposed patients. Data from ocular inflammation patients are needed to confirm the conclusions made in this analysis by extrapolation.

Purpose: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study., Methods: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented., Results: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immunosuppressives is ascertained from medical records of approximately 9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over approximately 100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents., Conclusions: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases.

Purpose: To describe the occurrence of nodular scleritis in a patient developing tubulointerstitial nephritis and uveitis (TINU) syndrome., Design: Observational case report., Method: The case notes of a 57-year-old female presenting with recurrent nodular scleritis, who later developed interstitial nephritis with bilateral uveitis, were reviewed., Results: Common and established causes of scleritis were not present in an adult who developed the TINU syndrome a decade later., Conclusions: Although scleritis has not been reported as a tubulointerstitial nephritis-associated ocular inflammation, it may be part of the possible spectrum of ocular inflammation occurring as part of the TINU syndrome.