Search

Purpose: Evaluation of longer-term effectiveness of three intravitreal therapies (methotrexate, ranibizumab, or dexamethasone implant) for participants enrolled in the randomized comparative effectiveness trial the Macular Edema Ranibizumab versus Intravitreal anti-inflammatory Therapy (MERIT) Trial followed for24 weeks., Design: Multicenter randomized controlled clinical trial with masked evaluation of retinal thickness and visual acuity., Participants: Patients with persistent or recurrent uveitic macular edema., Methods: Participants from 33 centers were randomized 1:1:1 (stratified by presence or absence of concomitant systemic immunosuppression for uveitis) to receive a sequence of intravitreal treatments with dexamethasone implant, methotrexate or ranibizumab. Participants with bilateral macular edema received the same treatment bilaterally. During 24 weeks' follow-up, non-assigned treatments were permitted beginning from12 weeks for those meeting retreatment criteria., Main Outcome Measures: Central subfield thickness change (CST) from baseline optical coherence tomography (OCT) measurement was the main outcome. Secondary outcomes included change in mean standard letters from baseline best-corrected visual acuity (BCVA). Analyses were conducted according to two principles: 1) "As-Assigned" in which outcomes were analyzed according to their original randomized treatment; and 2) a supplementary "Censored" analysis in which data were excluded after an eye received non-assigned treatment., Results: Among 194 enrolled participants (225 eligible eyes), 177 (207 eyes) completed 24 weeks' follow-up. Eyes assigned to methotrexate (55%) and ranibizumab (37%) more frequently received non-assigned treatments (88% dexamethasone implant or intravitreal corticosteroid injection) compared to dexamethasone (7%). In the As-Assigned analysis, dexamethasone had superior improvement in macular edema compared to ranibizumab (CST: 34% vs 19%, p=0.01) but not compared to methotrexate (CST: 31%, p=0.59) after being superior to both other regimens at 12 weeks. However, in the Censored analysis, only dexamethasone was associated with improvements in macular edema [CST: 34% vs 8% (p<0.001) and 5% (p<0.001)] and BCVA improvement >5 letters compared to methotrexate and ranibizumab, respectively. Dexamethasone more often was associated with IOP elevations ≥ 24 mmHg (32%) and ≥30 mmHg (10%)., Conclusions: Dexamethasone was more effective that methotrexate and ranibizumab for the treatment of persistent or recurrent uveitic macular edema through 24 weeks, with manageable side effects., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess noninfectious uveitis (NIU) risk after coronavirus disease 2019 (COVID-19) vaccination in patients without a history of uveitis., Design: A retrospective matched cohort study and self-controlled case series (SCCS) analysis using a longitudinal data asset with claims data from the OptumLabs Data Warehouse from December 11, 2020, through November 30, 2021., Participants: The matched cohort analysis included patients continuously enrolled for 730 days before December 11, 2020, who received a COVID-19 vaccination during the study period. This COVID-19-vaccinated group was matched to a COVID-19-unvaccinated historical cohort enrolled in 2018 and 2019. The SCCS design included individuals from the vaccinated cohort who experienced an NIU event during the study period. Enrollees with a history of uveitis were excluded., Methods: Hazard ratios (HRs) were calculated using Cox proportional hazards models in the matched cohort design. Incidence rate ratios (IRRs) comparing NIU incidence in exposed risk periods after vaccination and unexposed control periods within individuals were calculated using conditional Poisson regression models in the SCCS design. Models were adjusted for age, recent receipt of non-COVID-19 vaccinations, corticosteroid or immunosuppressive use, and smoking history. Subgroup analyses were conducted by vaccination type and age group., Main Outcome Measures: Rates of NIU identified with International Classification of Diseases, Tenth Revision, codes., Results: The matched cohort analysis included 4 611 378 patients, with 2 305 689 per cohort. The adjusted HR comparing NIU incidence in the COVID-19-vaccinated and unvaccinated cohort was 0.91 (95% confidence interval [CI], 0.75-1.10; P = 0.33). The SCCS analysis included 686 patients. The IRR comparing NIU risk after vaccination with risk during control intervals was 1.05 (95% CI, 0.89-1.23; P = 0.57). An increased risk was found in the subgroup aged 5 to 44 years (IRR, 1.40; 95% CI, 1.04-1.87; P = 0.024)., Conclusions: The matched cohort and SCCS analyses did not detect increased NIU risk after COVID-19 vaccination overall in individuals without history of uveitis, providing reassurance about the vaccine's safety. The finding of increased risk in the youngest subgroup suggests heightened immune responses in younger individuals, warranting further investigation., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression., Design: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression., Participants: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer., Methods: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study., Main Outcome Measures: Overall mortality and CM., Results: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration., Conclusions: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

Purpose: To evaluate the effectiveness of 3 different intravitreal treatments for persistent or recurrent uveitic macular edema (ME): dexamethasone implant, methotrexate, and ranibizumab., Design: Single-masked, randomized controlled clinical trial., Participants: Patients with minimally active or inactive uveitis and persistent or recurrent uveitic ME in one or both eyes., Methods: Patients at 33 centers were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME received the same treatment in both eyes., Main Outcome Measures: The primary outcome, measured at 12 weeks, was reduction in central subfield thickness (CST) expressed as a proportion of baseline (CST per CST at baseline) assessed with spectral-domain OCT by readers masked to treatment assignment. Secondary outcomes included improvement and resolution of ME, change in best-corrected visual acuity (BCVA), and elevations in intraocular pressure (IOP)., Results: One hundred ninety-four participants (225 eligible eyes) were randomized to dexamethasone (n = 65 participants and 77 eyes), methotrexate (n = 65 participants and 79 eyes), or ranibizumab (n = 64 participants and 69 eyes). All received at least 1 injection of the assigned treatment. At the 12-week primary outcome point, each group showed significant reductions in CST relative to baseline: 35%, 11%, and 22% for dexamethasone, methotrexate, and ranibizumab, respectively. Reduction of ME was significantly greater in the dexamethasone group than for either methotrexate (P < 0.01) or ranibizumab (P = 0.018). Only the dexamethasone group showed a statistically significant improvement in BCVA during follow-up (4.86 letters; P < 0.001). Elevations of IOP by 10 mmHg, to 24 mmHg or more, or both were more common in the dexamethasone group; IOP spikes to 30 mmHg or more were uncommon overall and were not significantly different among groups. Reductions in BCVA of 15 letters or more were more common in the methotrexate group and typically were attributable to persistent ME., Conclusions: At 12 weeks, in eyes with minimally active or inactive uveitis, dexamethasone was significantly better at treating persistent or recurrent ME than methotrexate or ranibizumab. Risk of IOP elevation was greater with dexamethasone, but elevations to levels of 30 mmHg or more were infrequent., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the dose-dependent risk of systemic corticosteroids (SCs) and the risk of other immunosuppressive therapies on coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in patients with noninfectious uveitis (NIU)., Design: A retrospective cohort study from January 20, 2020, to December 31, 2020 (an era before widespread COVID-19 vaccination), using the Optum Labs Data Warehouse, a US national de-identified claims database., Participants: Patients who had at least 1 NIU diagnosis from January 1, 2017., Methods: Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of SC exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models as a continuous variable, in addition to the dichotomous variable., Main Outcome Measures: Incidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death., Results: This study included 52 286 NIU patients of whom 12 000 (23.0%) were exposed to immunosuppressive medications during the risk period. In adjusted models, exposure to SCs was associated with increased risk of COVID-19 infection (HR, 2.66; 95% confidence interval [CI], 2.19-3.24; P < 0.001), hospitalization (HR, 3.26; 95% CI, 2.46-4.33; P < 0.001), and in-hospital death (HR, 1.99; 95% CI, 0.93-4.27; P = 0.08). Furthermore, incremental increases in the dosage of SCs were associated with a greater risk for these outcomes. Although tumor necrosis factor-α (TNF-α) inhibitors were associated with an increased risk of infection (HR, 1.48; 95% CI, 1.08-2.04; P = 0.02), other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization, or death., Conclusions: This study from an era before widespread COVID-19 vaccination demonstrates that outpatient SC exposure is associated with greater risk of COVID-19 infection and severe outcomes in patients with NIU. Future studies should evaluate the impact of immunosuppression in vaccinated NIU patients. Limiting exposure to SCs and use of alternative therapies may be warranted., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil., Design: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial., Participants: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017., Methods: Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group., Main Outcome Measures: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity., Results: Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 μm and 342 μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 μm (interquartile range [IQR], -132.3 to 4.0) and 54 μm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, -32.3 to -0.5) and 50 μm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92)., Conclusions: Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify if noninfectious uveitis (NIU) is associated with a greater risk of Coronavirus Disease 2019 (COVID-19) infection, hospitalization, and death., Design: A retrospective cohort study from January 20, 2020 to December 31, 2020, using a national claims-based database., Participants: Enrollees who had continuous enrollment with both medical and pharmacy coverage for 3 years before January 20, 2020. Patients with an NIU diagnosis within 3 years of the start of the study were included in the NIU cohort. Those with infectious uveitis codes or new NIU diagnoses during the risk period were excluded., Methods: Cox proportional hazard models were used to identify unadjusted hazard ratios (HRs) and adjusted HRs for all covariates for each outcome measure. Adjusted models accounted for patient demographics, health status, and immunosuppressive medication use during the risk period., Main Outcome Measures: Rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death identified with International Classification of Disease 10 th revision codes., Results: This study included 5 806 227 patients, of whom 29 869 (0.5%) had a diagnosis of NIU. On unadjusted analysis, patients with NIU had a higher rate of COVID-19 infection (5.7% vs. 4.5%, P < 0.001), COVID-19-related hospitalization (1.2% vs. 0.6%, P < 0.001), and COVID-19-related death (0.3% vs. 0.1%, P < 0.001). However, in adjusted models, NIU was not associated with a greater risk of COVID-19 infection (HR, 1.05; 95% confidence interval [CI], 1.00-1.10; P = 0.04), hospitalization (HR, 0.98; 95% CI, 0.88-1.09; P = 0.67), or death (HR, 0.90, 95% CI, 0.72-1.13, P = 0.37). Use of systemic corticosteroids was significantly associated with a higher risk of COVID-19 infection, hospitalization, and death., Conclusions: Patients with NIU were significantly more likely to be infected with COVID-19 and experience severe disease outcomes. However, this association was due to the demographics, comorbidities, and medications of patients with NIU, rather than NIU alone. Patients using systemic corticosteroids were significantly more likely to be infected with COVID-19 and were at greater risk of hospitalization and in-hospital death. Additional investigation is necessary to identify the impact of corticosteroid exposure on COVID-19-related outcomes., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population., Design: Retrospective, observational cohort study., Participants: Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios., Main Outcome Measures: Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed., Results: From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval [CI], 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%)., Conclusions: The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites., Design: Secondary analysis of a randomized controlled trial., Participants: Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico., Methods: From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests., Main Outcome Measures: Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months)., Results: Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively)., Conclusions: Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the incidence rate (IR) of herpes zoster ophthalmicus (HZO) and differences by age, gender, race, and region from 1994 through 2018., Design: Retrospective, observational cohort study., Participants: Patients with a new International Classification of Diseases, Ninth or Tenth Edition, codes for herpes zoster (HZ) and HZO from January 1, 1994, through December 31, 2018, in the OptumLabs Data Warehouse (OptumLabs, Cambridge, MA)., Methods: OptumLabs Data Warehouse, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data, was used to identify enrollees with continuous enrollment in the database for 365 days or more. Patients with no history of HZ or HZO and a new code for HZ and HZO were counted as incident cases. The IR of HZO was calculated by year, 10-year age groups, gender, race, and region., Main Outcome Measures: Differences in IR from 1994 through 2018 by 10-year age groups and gender., Results: From 1994 through 2018, 633 474 cases of HZ were reported, with 49 745 (7.9%) having HZO. The incidence of HZO increased from 1994 through 2018 by an estimated 1.1 cases per 100 000 person-years annually (95% confidence interval [CI], 1.0-1.3; P < 0.001). The estimated relative increase was 3.6% annually (95% CI, 3.0%-4.1%). HZO IR increased in all ages over 10 years until 2007, then began declining in individuals younger than 21 and older than 60, stabilizing in individuals 21 to 30 years old, and increasing more slowly among individuals 31 to 60 years old. Men showed an HZO incidence rate ratio (IRR) of 0.74 compared with women. Compared with white patients, the IRRs were 0.70, 0.75, and 0.64 for Asians, black patients, and Hispanics, respectively., Conclusions: The incidence of HZO has increased 3.6% per year from 1994 to 2018 in the United States. Since 2008, HZO incidence declined in individuals younger than 21 years and older than 60 years while increasing at a lower rate in middle-aged adults. Given the continued increase, greater efforts should be made to vaccinate eligible adults 50 years of age and older. More research on earlier vaccination is warranted., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI)., Design: Multicenter, randomized clinical trial., Participants: Patients with uveitic ME., Methods: Patients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes., Main Outcome Measures: The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks., Results: All treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56-0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups., Conclusions: Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine which clinical features distinguish ocular sarcoidosis from other forms of uveitis in an international population and to estimate the sensitivity and specificity of the International Workshop on Ocular Sarcoidosis (IWOS) clinical signs and laboratory tests., Design: Multicenter, retrospective medical record review., Participants: Eight hundred eighty-four patients with uveitis from 19 centers in 12 countries., Methods: Data collected included suspected cause of uveitis, clinical findings, and laboratory investigations within 6 months of presentation. The IWOS criteria were used to classify patients as having definite (biopsy-proven), presumed (evidence of bilateral hilar lymphadenopathy [BHL] on chest radiograph or CT scan), probable, or possible ocular sarcoidosis. Patients with biopsy positive results or BHL on chest radiograph or CT scan were considered sarcoidosis cases., Main Outcome Measures: Sensitivity and specificity of clinical signs and laboratory investigations for diagnosing ocular sarcoidosis., Results: Of the 884 uveitis patients, 264 (30%) were suspected to have ocular sarcoidosis. One hundred eighty patients (20%) met the IWOS criteria; 98 were definite (biopsy-proven) disease, 69 presumed disease (BHL), 10 probable disease, and 3 possible disease. Among sarcoidosis cases, the most common clinical signs were bilaterality (86%); snowballs or string of pearls (50%); mutton-fat keratic precipitates, iris nodules, or both (46%); and multiple chorioretinal peripheral lesions (45%). Sixty-two percent of sarcoidosis cases had elevated angiotensin converting enzyme or lysozyme and 5% demonstrated abnormal liver enzyme test results. Of the patients suspected of having sarcoidosis, 97 (37%) did not meet the IWOS criteria., Conclusions: With the exception of BHL, IWOS clinical findings and investigational tests had low sensitivities for diagnosing ocular sarcoidosis. In particular, liver function tests seem to have little usefulness in diagnosing ocular sarcoidosis. Many patients suspected of having sarcoidosis did not fit into the classification system, indicating that the guidelines may need to be reconsidered. Adding novel laboratory tests and using more advanced statistical methods may lead to the development of a more generalizable classification system., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess whether cigarette smoking is associated with the development of uveitis in a population-based setting., Design: Retrospective, population-based, case-control study., Participants: Patients aged ≥ 18 years who were seen at a Kaiser Permanente Hawaii clinic between January 1, 2006, and December 31, 2007. Analysis included 100 confirmed incident uveitis cases, 522 randomly selected controls from the general Kaiser Hawaii population, and 528 randomly selected controls from the Kaiser Hawaii ophthalmology clinic., Methods: International Classification of Diseases, 9th revision (ICD-9), diagnosis codes were used to identify possible uveitis cases. A uveitis fellowship-trained ophthalmologist then conducted individual chart review to confirm case status. Multivariate logistic regression models were used to evaluate the association between smoking and uveitis, adjusting for age, sex, race, and socioeconomic status., Main Outcome Measures: Development of uveitis., Results: Current smokers had a 1.63 (95% confidence interval [CI], 0.88-3.00; P = 0.12) and 2.33 (95% CI, 1.22-4.45; P = 0.01) times greater odds of developing uveitis compared with those who never smoked using the general and ophthalmology control groups, respectively. The association was even stronger with noninfectious uveitis, which yielded odds ratios of 2.10 (95% CI, 1.10-3.99; P = 0.02) and 2.96 (95% CI, 1.52-5.77; P = 0.001) using the general and ophthalmology control groups, respectively., Conclusions: Cigarette smoking is significantly associated with new-onset uveitis within a population-based setting. The association was stronger for noninfectious uveitis. Given the well-established risks of smoking with regard to other inflammatory disorders, these results reaffirm the importance of encouraging patients to avoid or cease smoking., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis., Design: Multicenter, block-randomized, observer-masked clinical trial., Participants: Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India., Intervention: Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered., Main Outcome Measures: Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence., Results: Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31)., Conclusions: There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial., Design: Experimental study using data from a randomized comparative trial., Participants: Of the 323 patients enrolled in the trial, we were able to obtain MIC values from 221 patients with monocular fungal keratitis., Methods: The Mycotic Ulcer Treatment Trial I was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines. The relationship between MIC and clinical outcome was assessed., Main Outcome Measures: The primary outcome was 3-month best spectacle-corrected visual acuity. Secondary outcomes included 3-month infiltrate or scar size; corneal perforation and/or therapeutic penetrating keratoplasty; and time to re-epithelialization., Results: A 2-fold increase in MIC was associated with a larger 3-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI], 0.10-0.31; P < 0.001) and increased odds of perforation (odds ratio, 1.32; 95% CI, 1.04-1.69; P = 0.02). No correlation was found between MIC and 3-month visual acuity. For natamycin-treated cases, an association was found between higher natamycin MIC with larger 3-month infiltrate or scar size (0.29 mm; 95% CI, 0.15-0.43; P < 0.001) and increased perforations (odds ratio, 2.41; 95% CI, 1.46-3.97; P < 0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study., Conclusions: Decreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate agreement between fluorescein angiography (FA) and optical coherence tomography (OCT) results for diagnosis of macular edema in patients with uveitis., Design: Multicenter cross-sectional study., Participants: Four hundred seventy-nine eyes with uveitis from 255 patients., Methods: The macular status of dilated eyes with intermediate uveitis, posterior uveitis, or panuveitis was assessed via Stratus-3 OCT and FA. To evaluate agreement between the diagnostic approaches, κ statistics were used., Main Outcome Measures: Macular thickening (MT; center point thickness, ≥ 240 μm per reading center grading of OCT images) and macular leakage (ML; central subfield fluorescein leakage, ≥ 0.44 disc areas per reading center grading of FA images), and agreement between these outcomes in diagnosing macular edema., Results: Optical coherence tomography (90.4%) more frequently returned usable information regarding macular edema than FA (77%) or biomicroscopy (76%). Agreement in diagnosis of MT and ML (κ = 0.44) was moderate. Macular leakage was present in 40% of cases free of MT, whereas MT was present in 34% of cases without ML. Biomicroscopic evaluation for macular edema failed to detect 40% and 45% of cases of MT and ML, respectively, and diagnosed 17% and 17% of cases with macular edema that did not have MT or ML, respectively; these results may underestimate biomicroscopic errors (ophthalmologists were not explicitly masked to OCT and FA results). Among eyes free of ML, phakic eyes without cataract rarely (4%) had MT. No factors were found that effectively ruled out ML when MT was absent., Conclusions: Optical coherence tomography and FA offered only moderate agreement regarding macular edema status in uveitis cases, probably because what they measure (MT and ML) are related but nonidentical macular pathologic characteristics. Given its lower cost, greater safety, and greater likelihood of obtaining usable information, OCT may be the best initial test for evaluation of suspected macular edema. However, given that ML cannot be ruled out if MT is absent and vice versa, obtaining the second test after negative results on the first seems justified when detection of ML or MT would alter management. Given that biomicroscopic evaluation for macular edema erred frequently, ancillary testing for macular edema seems indicated when knowledge of ML or MT status would affect management., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To provide a population-based estimate of the incidence of herpes zoster ophthalmicus (HZO) with comparisons across racial, sex, and age groups, as well as to estimate the frequency of postherpetic neuralgia (PHN)., Design: Retrospective, population-based cohort study., Participants: All patients enrolled in the Kaiser Permanente Hawaii health plan during the study period (N = 217 061)., Methods: All patient encounters between January 1, 2006, and December 31, 2007, in the electronic medical record of Kaiser Permanente Hawaii were queried for International Classification of Diseases, 9th edition (ICD-9) codes corresponding to HZO. Charts were reviewed to confirm a diagnosis of HZO and to collect information about specific ocular manifestations. Demographic data and information on PHN were collected electronically. Incidence rates were calculated per 100 000 person-years for the entire population and for age-, sex-, and race-specific subgroups., Main Outcome Measures: Clinical diagnosis of HZO during the study period., Results: A total of 134 cases of HZO were identified in this population of 217 061 people. The overall incidence was 30.9 per 100 000 person-years (95% confidence interval [CI], 25.9-36.6). The incidence rate for the population aged ≥65 years was 104.6 per 100 000 person-years (95% CI, 79.0-135.9), approximately 5 times the remainder of the population (P < 0.001). The most common manifestation of HZO was dermatitis, followed by keratitis and conjunctivitis. The incidence of HZO for Pacific Islanders was 19.0 per 100 000 person-years (95% CI, 12.4-28.3), which was significantly lower than the rate for non-Pacific Islanders (P = 0.007). Twenty-one percent of patients with HZO developed PHN. Older age and HZO with keratitis, conjunctivitis, or uveitis were found to be risk factors for PHN., Conclusions: This study provides a population-based estimate of HZO and highlights differences across various age and racial groups. It also suggests that demographic characteristics may be useful in determining the risk of developing HZO., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the association between tobacco smoking history and uveitis., Design: Retrospective, case-control study., Participants: A total of 564 patients with ocular inflammation seen in the Proctor Foundation uveitis clinic between 2002 and 2009, and 564 randomly selected patients seen in the comprehensive eye clinic within the same time period., Methods: A retrospective medical record review of all cases and controls., Main Outcome Measures: A logistic regression analysis was conducted with ocular inflammation as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, race, and median income., Results: The odds of a smoker having ocular inflammation were 2.2-fold that of a patient who had never smoked (95% confidence interval [CI], 1.7-3.0; P<0.001). All anatomic subtypes of uveitis were associated with a positive smoking history, with odds ratios (ORs) of 1.7 (95% CI, 1.2-2.4; P = 0.002) for anterior uveitis, 2.7 (95% CI, 1.4-5.6; P = 0.005) for intermediate uveitis, 3.2 (95% CI, 1.3-7.9; P = 0.014) for posterior uveitis, and 3.9 (95% CI, 2.4-6.1; P<0.001) for panuveitis. In patients with panuveitis and cystoid macular edema (CME), the OR was 8.0 (95% CI, 3.3-19.5; P<0.001) compared with 3.1 (95% CI, 1.8-5.2; P<0.001) for patients without CME. Patients with intermediate uveitis and CME also had a higher OR (OR 8.4; 95% CI, 2.5-28.8; P = 0.001) compared with patients without CME (OR 1.5; 95% CI, 0.6-3.8; P = 0.342). Patients with a smoking history were at greater odds of having infectious uveitis (OR 4.5; 95% CI, 2.3-9.0; P<0.001) than noninfectious uveitis (OR 2.1; 95% CI, 1.6-2.8; P<0.001), although both were associated with smoking., Conclusions: A history of smoking is significantly associated with all anatomic subtypes of uveitis and infectious uveitis. The association was greater in patients with intermediate uveitis and panuveitis with CME compared with those without CME. In view of the known risks of smoking, these findings, if replicated, would give an additional reason to recommend smoking cessation in patients with uveitis., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess pharmacodynamic responses to ranibizumab, an inhibitor of vascular endothelial growth factor A (VEGF-A), in a study of the treatment of minimally classic or occult with no classic choroidal neovascularization secondary to age-related macular degeneration (AMD) (designated MARINA [Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD]) and to compare these responses with those in a sham-injection control group., Design: Retrospective (prespecified and ad hoc) analyses of 24-month data., Participants: Seven hundred sixteen patients, randomized to 0.3-mg ranibizumab (n = 238), 0.5-mg ranibizumab (n = 240), or a sham injection (n = 238)., Methods: Stereoscopic fundus photography and fluorescein angiography (FA) were done at baseline and months 3, 6, 12, and 24. Optical coherence tomography (OCT) was performed at a subset of investigative sites (46 patients) at baseline, day 7, and months 1 and 12., Main Outcome Measures: Prespecified secondary end points were mean change from baseline in total area of choroidal neovascularization and total area of leakage from choroidal neovascularization at months 12 and 24. Prespecified exploratory FA end points included mean change from baseline in the areas of the choroidal neovascularization lesion and serous sensory retinal detachment (SSRD) at months 12 and 24. Post hoc exploratory FA outcome measures included the proportion of patients with no leakage from choroidal neovascularization and mean change from baseline over time in the area of subretinal fibrous tissue/disciform scar. The prespecified exploratory end point for OCT was mean change from baseline over time in center point thickness., Results: At 12 and 24 months, statistically significant benefits of ranibizumab over sham treatment were observed for mean change from baseline in the areas of choroidal neovascularization lesion, total choroidal neovascularization, leakage from choroidal neovascularization, SSRD, and disciform scar/subretinal fibrosis. At 12 months (final OCT), the mean change in foveal center point thickness on OCT was a significant decrease in the ranibizumab group compared with the sham group., Conclusions: Patients with minimally classic or occult with no classic neovascular AMD treated with ranibizumab demonstrated improvement that was consistent for visual acuity, FA, and OCT outcomes and superior to that in sham-treated patients.

Objective: An examination of clinically relevant subgroups of patients in the MARINA study of ranibizumab in treatment of minimally classic or occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) was done. Objectives were to determine the effectiveness of ranibizumab across subgroups, compare the effectiveness of ranibizumab with that of sham injection within subgroups, and evaluate the relationship between selected baseline characteristics and visual acuity (VA) outcomes., Design: Retrospective subgroup analyses of 24-month data from the MARINA study., Participants and Controls: Seven hundred sixteen patients were randomly assigned to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment (n = 238)., Methods: Efficacy outcomes were compared across subgroups based on patients' gender, age, baseline VA score, baseline CNV lesion size, CNV lesion type, and duration of neovascular AMD using univariate analyses. Multivariate analyses were performed on the change from baseline to 24 months in VA score to assess further the correlation between baseline characteristics and VA outcome., Main Outcome Measures: Proportion of patients losing <15 letters from baseline, proportion gaining > or =15 letters from baseline, and mean VA score change from baseline., Results: For each of the 3 VA end points, all subgroups of ranibizumab-treated patients did better on average than the sham-treated patients. Increasing age, larger CNV lesion size at baseline, and a higher baseline VA score were all associated with greater loss of letters in the sham group or less gain of letters in the ranibizumab groups. However, the net benefit of ranibizumab versus sham treatment was greater in patients who scored higher than in those who scored lower in baseline VA., Conclusions: This subgroup analysis of 24-month data from the MARINA study indicates that ranibizumab treatment was associated with an average increase from baseline VA in all subgroups evaluated, and that ranibizumab treatment was superior to sham treatment across all subgroups. The most important predictors of VA outcomes were, in decreasing order of importance, baseline VA score, CNV lesion size, and age.

The present study was carried out in 33 cases of cyanotic congenital heart disease (CCHD) to determine the prevalence of iron deficiency anemia (IDA) and its correlation to hyperviscosity symptoms in terms of hematocrit levels. Furthermore, the study was aimed at assessing the response to low dose iron therapy (60 mg of elemental iron once daily) in relieving symptoms of hyperviscosity. All these cases were evaluated for presence of symptoms of hyperviscosity and later subjected to various hematological & biochemical parameters of iron deficiency anemia including hemoglobin (Hb), pack cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), serum iron, total iron binding capacity respectively. Results showed presence of IDA in 6/33 cases (18.2%) and hyperviscosity symptoms in 10/33 cases (30.3%). Amongst the group with symptoms of hyperviscosity, in the subset having IDA these symptoms were observed at PCV levels of 0.52 L/L to 0.58 L/L in contrast to the subset not deficient in iron where the symptoms occurred at a PCV 0.68 L/L. Relief of symptoms of hyperviscosity was evident with a minimal rise of mean hemoglobin by 2.1 gm/dl. It was concluded that IDA was not an uncommon finding in CCHD cases and that it leads to symptoms of hyperviscosity at a level of PCV much lower than those known to produce these symptoms. Finally low dose iron therapy was found effective in relieving the symptoms of hyperviscosity.