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Purpose: The choroidal thickening and serous retinal detachments that characterize Vogt-Koyanagi-Harada (VKH) disease can be imaged in detail using spectral domain optical coherence tomography (SD-OCT). Whether specific qualitative and quantitative SD-OCT features at presentation were associated with visual outcomes in a randomized controlled trial comparing methotrexate to mycophenolate for steroid-sparing control of uveitis were evaluated., Methods: An exploratory subanalysis of data from the FAST trial in which SD-OCT images from VKH participants were analyzed for presence/absence of bacillary detachments, retinal pigment epithelium (RPE) folds, and internal limiting membrane (ILM) fluctuations was performed. A modified RPE undulation index was calculated to provide a quantifiable surrogate marker for choroidal folds., Results: SD-OCT images were available from 158 eyes with VKH. At baseline, bacillary detachments were present in 23.5% of eyes, RPE folds in 22.8% of eyes, and ILM fluctuations in 35.2% of eyes. For each 0.1 unit increase in modified RPE undulation index, there was an associated 0.13 increase in mean logMAR BSCVA at baseline. None of the SD-OCT features were associated with BSCVA at the 6-month primary endpoint. Indeed, mean final BSCVA was similar in those with and without the SD-OCT features of interest at baseline, and was between 0.1 and 0.2 logMAR (Snellen visual acuity 20/25 to 20/30)., Conclusions: While eyes with VKH may present with a variety of SD-OCT imaging pathology prior to starting immunosuppression with methotrexate or mycophenolate mofetil, final visual outcome in our study was excellent. With appropriate immunosuppression, good visual outcomes are possible in VKH.ClinicalTrials.gov Identifier NCT01829295Date of Registration: April 11, 2013.

Purpose: Some patients taking methotrexate (MTX) or mycophenolate mofetil (MMF) experience intolerable side effects at full doses. We evaluated whether dose reduction affected treatment outcomes in uveitis patients., Methods: Subanalysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. Patients were randomized to receive MTX (25 mg weekly) or MMF (3 g daily). A pre-specified dose reduction protocol could be employed for intolerable side effects. Primary analysis was performed at 6 months., Results: 43/194 patients (22%) required dose reduction. 88/151 patients (58%) on maximum doses and 32/43 patients (74%) on reduced doses were deemed treatment successes at 6 months. The odds ratio point estimate (1.60, 95% CI 0.72-3.74) favored dose-reduction but this was not significant. Following reduction, adverse events improved at the subsequent study visit (79 events reduced to 63 events)., Conclusion: Dose reduction of antimetabolites was not associated with worse outcomes in this subanalysis of a uveitis trial.

Purpose: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease., Methods: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX vs MMF) and disease stage (acute vs chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25 mg weekly oral MTX or 1.5 g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD)., Results: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P = .12) or in BSCVA improvement (P = .78). MTX was superior to MMF in reducing CST (P = .003) and resolving SRD (P = .02). There was no significant difference in treatment success by disease stage (P = .25), but patients with acute VKH had greater improvement in BSCVA (P < .001) and reduction of CST (P = .02) than chronic VKH patients., Conclusions: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. NOTE: Publication of this article is sponsored by the American Ophthalmological Society TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites., Methods: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint., Results: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure., Conclusion: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment. Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference.

Importance: The recombinant zoster vaccine (RZV) is currently recommended for immunocompetent adults aged 50 years or older and immunocompromised adults aged 19 years or older and is effective in preventing herpes zoster ophthalmicus (HZO). However, questions about the safety of RZV in patients with a history of HZO remain., Objective: To evaluate whether there is an increased risk of HZO recurrence after RZV in patients with a history of HZO., Design, Setting, and Participants: This retrospective cohort study used medical and outpatient pharmacy claims data for commercial and Medicare Advantage enrollees from the Optum Labs Data Warehouse. Patients with incident HZO from January 1, 2010, to December 31, 2021, were identified; the study period ended on March 31, 2022. The vaccinated group consisted of patients with at least 1 dose of RZV more than 90 days following the initial HZO diagnosis. The unvaccinated group consisted of patients without any record of RZV in the study period. Vaccinated and unvaccinated patients were matched using exact k:1 matching without replacement., Exposure: Recombinant zoster vaccination., Main Outcomes and Measures: The main outcome was the number of HZO recurrences with and without RZV exposure., Results: A total of 16 408 patients were included in the matched analysis, of whom 12 762 were unvaccinated (7806 [61.2%] female; mean [SD] age at diagnosis, 68.8 [10.3] years) and 3646 were vaccinated (2268 [62.2%] female; mean [SD] age at diagnosis, 67.4 [9.8] years). Within the primary risk period of 56 days after the index date (ie, the start of follow-up for the outcome), the incidence of HZO recurrence after any RZV exposure was 37.7 per 1000 person-years compared with 26.2 per 1000 person-years in the unexposed group. After controlling for race and ethnicity, inpatient stays, emergency department visits, concomitant vaccines, and eye care practitioner visits, the association between vaccination status and HZO exacerbation in the primary risk period had an adjusted hazard ratio for any RZV exposure of 1.64 (95% CI, 1.01-2.67; P = .04)., Conclusions and Relevance: In this study, RZV exposure was associated with a higher likelihood of HZO recurrence in patients with a history of HZO compared with no RZV exposure. These findings support consideration that patients with a history of HZO may benefit from monitoring after receiving RZV in case of HZO recurrence.

Purpose: The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers., Methods: C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on culture-exclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model., Results: Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P < 0.001] and increased ulcer area (OR = 1.03, P < 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P < 0.001), ulcer area (OR = 1.02, P < 0.001), and fungal etiology (OR = 9.8, P < 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study., Conclusions: The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management., Competing Interests: V.L. Perez has financial relationships with Alcon, Dompe, EyeGate, Kala, Trefoil, Novartis, and Oculis. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Herpes zoster ophthalmicus (HZO) after COVID-19 vaccination has been reported in numerous case studies. However, no large-scale epidemiologic studies have been conducted to date. The purpose of this study was to determine whether COVID-19 vaccination is associated with an increased risk of HZO., Design: Retrospective before-and-after risk interval analysis., Methods: RESULTS: In total, 1,959,157 patients received a dose of a COVID-19 vaccine during the study period and met eligibility criteria. A total of 80 individuals without a prior history of HZO were included in the analysis because they developed HZO in the risk or control period. Patients had a mean age of 54.0 years (SD = 12.3 years). There were 45 cases of HZO in the risk interval after COVID-19 vaccination. There was not an increased risk of HZO after vaccination with BNT162b2 (IRR = 0.90, 95% CI: 0.49-1.69, P = .74), mRNA-1273 (IRR = 0.74, 95% CI: 0.36-1.54, P = .42), or Ad26.COV2.S (IRR = 0.50, 95% CI: 0.07-2.56, P = .42)., Conclusions: This study found no evidence of increased risk of HZO after COVID-19 vaccination, providing reassurance for patients and providers who may be concerned about the safety profile of the COVID-19 vaccines., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The aims of this study were to examine the trends in the initial management of herpes zoster ophthalmicus (HZO) in the United States from 2010 to 2018 and compare them with the treatment preferences of corneal specialists., Methods: A retrospective, observational deidentified cohort study was conducted on individuals enrolled in the OptumLabs Data Warehouse who had a new diagnosis of HZO from 1/1/2010 to 12/31/2018. An online survey ascertaining HZO management perspectives was distributed to The Cornea Society listserv. The main outcome assessed was proportion of cases with systemic antiviral prescriptions, eye care provider involvement, and follow-up visits after the initial HZO diagnosis., Results: Approximately 50% of patients received systemic antivirals the day of initial HZO diagnosis or within 7 days (45.6% and 53.7%, respectively). Most initial diagnoses were made by ophthalmologists (45.0%), followed by optometrists (19.2%). Referral rate to ophthalmology within a year of initial diagnosis was 38.6%. 48.7% cases had at least 1 follow-up visit with any type of provider within 30 days. Our survey of corneal specialists found 97% would prescribe systemic antivirals to those with ocular involvement, but 66% would prescribe antivirals to those without ocular or eyelid involvement. Seventy percent supported all patients having follow-up with an eye care provider within a month., Conclusions: HZO antiviral therapies seem to be underprescribed in the United States, referral rates to ophthalmology are low, and follow-up is suboptimal, which are not aligned with recommendations from corneal specialists. More research is needed to establish standardized guidelines for treatment, referral, and follow-up with ophthalmology for HZO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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 determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies., Design: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database., Participants: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW., Methods: Incidence rates (IRs) were calculated for each COVID-19 outcome. 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 systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models., Main Outcome Measures: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death., Results: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P  < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P  < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P  = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P  = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P  = 0.04)., Conclusions: Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

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.)

Introduction: Vogt-Koyanagi-Harada (VKH) syndrome is an inflammatory condition characterized by bilateral, granulomatous panuveitis with or without systemic manifestations, and accounts for up to 18% of referrals for panuveitis at tertiary centers in the United States of America. Despite ongoing research, there is limited evidence and no clear consensus on how to diagnose and treat patients with VKH, leading to variations in practice patterns among uveitis specialists., Methods: An anonymous, online survey was distributed to uveitis specialists in the American Uveitis Society (AUS). The survey included 21 questions that asked for non-identifiable demographics and covered topics such as preferred imaging modalities, treatment for the first episode of VKH, and perceived efficacy of immunomodulatory therapy (IMT)., Results: A total of 104 surveys were included for analysis, representing a 38.4% response rate from the AUS listserv. A majority of respondents were uveitis fellowship trained and practiced in North America in an academic setting. Fluorescein angiography and enhanced depth imaging with optical coherence tomography were rated as the most consistently useful methods for the diagnosis of VKH. For treatment of acute initial-onset VKH, responses were divided between a preference for high-dose systemic corticosteroids with IMT (61.5%) and without IMT (37.5%). Methotrexate and mycophenolate mofetil were the most common IMTs to be used as first-line therapies, but adalimumab and infliximab were perceived to be the most effective for the treatment for VKH., Discussion: While there are some common trends in the practice patterns for the diagnosis and treatment of patients with VKH, there was no clear consensus on the topic of IMT. There was a slight preference among uveitis specialists to use both IMT and systemic corticosteroids for the first episode of acute VKH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choo, Acharya and Shantha.)

The relationship between Epstein-Barr virus (EBV) infection and uveitis is unclear. We conducted an observational cross-sectional study to determine the prevalence of EBV in uveitis and to describe the clinical features of EBV-positive uveitis cases. This study was carried out at the F.I. Proctor Foundation at the University of California, San Francisco. All patients with suspected infectious uveitis who underwent unbiased metagenomic deep sequencing (MDS) were included. Demographics, testing information, and clinical features were documented. Eleven out of 288 patients with suspected infectious uveitis had EBV detected by RNA-seq in intraocular fluid. The prevalence of EBV in uveitis in our study sample is 4%. Three out of 11 EBV-positive eyes (27%) were found to have biopsy-proven vitreoretinal lymphoma. Future studies are needed to determine if EBV may drive the development of vitreoretinal lymphoma and if its presence should heighten the suspicion of vitreoretinal lymphoma.

Background: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis., Main Body: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF., Conclusion: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics., (© 2023. The Author(s).)

Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk., Objective: To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection., Design, Setting, and Participants: This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19-vaccinated cohort who had herpes zoster during either a risk or control interval., Exposures: Any dose of a COVID-19 vaccine., Main Outcomes and Measures: Incident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis., Results: Among 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P < .001]; second dose of COVID-19 vaccine: HR, 0.79 [95% CI, 0.71-0.88; P < .001]) or the early pandemic period (first dose of COVID-19 vaccine: HR, 0.89 [95% CI, 0.80-1.00; P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09])., Conclusions and Relevance: In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.

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 identify peripheral blood transcriptome differences in uveitis patients with sarcoidosis compared to those with Vogt-Koyanagi-Harada (VKH) syndrome and controls., Methods: Ten patients with uveitis compatible with sarcoidosis (eight with pulmonary sarcoidosis, one with central nervous system sarcoidosis, and one with conjunctival sarcoidosis), nine patients with VKH, and nine healthy controls were prospectively enrolled., Results: Ten genes exhibited a four-fold difference in expression in sarcoidosis patients compared to controls, many being involved in regulating inflammatory processes or cellular responses to microbes., Conclusions: This research suggests that the transcriptome in sarcoidosis is robust enough to be detected in the peripheral blood and that sarcoidosis can be distinguished from healthy controls. Differentially expressed genes may serve as candidates warranting further investigation with respect to disease pathophysiology and may provide additional information, such as ability to stratify patients based on associated disease severity and anatomical location of inflammation within the eye.

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.)

Importance: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce., Objective: To evaluate changes in antifungal resistance over time., Design, Setting, and Participants: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021., Interventions: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute., Main Outcomes and Measures: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole., Results: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001)., Conclusions and Relevance: This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world., Trial Registration: ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.

Purpose: Sub-analysis of the FAST Trial comparing change in CD4 (∆CD4) from baseline through 12 months in uveitis patients treated with mycophenolate mofetil (MMF) and methotrexate (MTX)., Methods: Patients were randomly allocated to 1.5 g twice daily MMF or 25 mg weekly MTX. Individuals with CD4 counts at baseline, 6 months (or treatment failure prior), and 12 months (or treatment failure between 6 and 12 months) were included. The association between treatment and ∆CD4 (cells/μL) was analyzed using multivariable linear regression., Results: There was no significant difference in ∆CD4 between MMF and MTX at 6 months (-31.7 cells/μL for MMF compared to MTX; 95% CI: -358.2 to 294.8, P = .85) and 12 months (-78.3 cells/μL for MMF compared to MTX; 95% CI: -468.0 to 311.3; P = .69)., Conclusion: There was no significant difference in ∆CD4 between MMF and MTX from baseline to 12 months, suggesting that MMF does not confer additional risk of CD4 lymphopenia in uveitic patients.ClinicalTrials.gov Identifier: NCT01829295.

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.)

Background: The incidence of herpes zoster (HZ) has been increasing in recent decades. Although 2 vaccines for HZ are available, there have been few studies on the incidence rates of HZ and postherpetic neuralgia (PHN) since their introduction. This study examined the incidence rates of HZ and PHN from 1994 to 2018 in the United States to determine if they have continued to increase since introduction of the HZ vaccines., Methods: A de-identified longitudinal administrative claims database, the OptumLabs Data Warehouse, was used to assess incidence rates among individuals continuously enrolled in the database for ≥365 days with no prior history of HZ or PHN. Unstandardized and standardized incidence rates were calculated by year, 10-year age groups, sex, and race/ethnicity., Results: There were 610 766 individuals with HZ (median age, 56.3; interquartile range, 43.0-68.7 years; 59.8% women; 70.6% white). From 1994 to 2018, the incidence of HZ increased from 286.0 (95% confidence interval [CI], 259.1-312.8) to 579.6 (95% CI, 554.2-605.0) cases per 100 000 person-years, an annual increase of 3.1% (95% CI, 2.5-3.6%). Since 2007, annual HZ incidence rates have decreased in individuals ≤20 and >60 years old. The overall incidence rate of PHN was 57.5 (95% CI, 56.0-59.0) cases per 100 000 person-years. The proportion of individuals with HZ who developed PHN was higher from 2007 to 2018 than from 1994 to 2006., Conclusions: HZ incidence rates have continued to increase in age groups for which HZ vaccines are not currently recommended, warranting a review of current vaccine recommendations., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Aims: To establish expert recommendations for the management of ocular sarcoidosis (OS)., Methods: A question-based survey on the management of OS was circulated to international uveitis experts (members of the International Uveitis Study Group and the International Ocular Inflammation Society) electronically. Subsequently, a consensus workshop was conducted at the 7th International Workshop on Ocular Sarcoidosis (IWOS) in June 2019 in Sapporo, Japan as part of the Global Ocular Inflammation Workshops. Statements on the management of OS that were supported by a two-thirds majority of 10 international panel members of the workshop, after discussion and voting, were taken as consensus agreement., Results: A total of 98 participants from 29 countries responded to the questionnaire survey. The subsequent consensus workshop established recommendations for the management of OS in five sections. The first section concerned evaluation and monitoring of inflammation. The second, third and fourth sections described ocular manifestations that were indications for treatment, and the management of anterior uveitis, intermediate uveitis and posterior uveitis. In the fifth section, the use of systemic corticosteroids and systemic immunosuppressive drugs were detailed., Conclusions: Recommendations for management of OS were formulated through an IWOS consensus workshop., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The recombinant zoster vaccine had over 90% efficacy in preventing herpes zoster in clinical trials. However, its effectiveness outside of a clinical trial setting has not been investigated. This study aimed to assess the effectiveness of the recombinant zoster vaccine in general practice., Methods: A de-identified administrative claims database, the OptumLabs Data Warehouse, was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against herpes zoster in nonimmunocompromised, vaccine age-eligible individuals enrolled in the database for ≥365 days., Results: A total of 4 769 819 adults were included in this study, with 173 745 (3.6%) adults receiving 2 valid doses of the recombinant zoster vaccine. The incidence rate of herpes zoster was 258.8 (95% confidence interval [CI], 230.0-289.4) cases per 100 000 person-years in vaccinated persons compared with 893.1 (95% CI, 886.2-900.0) in unvaccinated persons. Recombinant zoster vaccine effectiveness was 85.5% (95% CI, 83.5-87.3%) overall, with an effectiveness of 86.8% (95% CI, 84.6-88.7%) in individuals 50 to 79 years old compared with 80.3% (95% CI, 75.1-84.3%) in individuals aged 80 and older. In patients with a history of live zoster vaccine within 5 years of study inclusion, vaccine effectiveness was 84.8% (95% CI, 75.3-90.7%)., Conclusions: Recombinant zoster vaccine effectiveness against herpes zoster was high in a real-world setting. Given the low vaccine coverage and high effectiveness, a major public health effort is needed to identify and address barriers to vaccination and increase immunization rates., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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.)

Background: The incidence of herpes zoster (HZ) has been on the rise for decades in the United States. Clinical trials for the recombinant zoster vaccine (RZV) demonstrated vaccine efficacy of over 90% in preventing herpes zoster. However, there is limited information on its effectiveness outside of a clinical trial setting, as well as its effectiveness against herpes zoster ophthalmicus (HZO)., Methods: A de-identified electronic health records database from Kaiser Permanente Hawaii (KPH) was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against HZ and HZO in immunocompetent, vaccine age-eligible individuals without a prior history of HZ, who were continuously enrolled in KPH for ≥365 days prior to becoming age-eligible for RZV between January 1, 2018, through December 31, 2019., Results: A total of 78 356 adults were included in this study, with 11 864 (15.1%) adults receiving two valid doses of the recombinant zoster vaccine. The incidence rate of HZ was 325.6 (95% CI: 217.7 to 464.4) cases per 100 000 person-years in vaccinated persons compared to 1063.3 cases per 100 000 person-years (95% CI: 1006.0 to 1122.8) in the unvaccinated group. The incidence rate of HZO was 11.9 (95% CI: 0.7 to 52.3) cases per 100 000 person-years in the vaccinated group compared to 72.1 (95% CI: 58.0 to 88.3) in the unvaccinated group. RZV was 83.5% (95% CI: 74.9% to 89.2%) effective against HZ and 93.3% (95% CI: 48.7% to 99.1%) effective against HZO., Conclusions: RZV has demonstrated high effectiveness against both HZ and HZO outside of a clinical trial setting in the United States. Vaccine coverage is low, emphasizing the need for public health efforts to increase vaccination to reduce morbidity from HZ and HZO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Macular edema (ME) is the most frequent cause of irreversible visual impairment in patients with uveitis. To date, little data exists about the clinical course of ME in pediatric patients. A retrospective, observational study was performed to examine the visual and macular thickness outcomes of ME associated with chronic, noninfectious uveitis in pediatric patients., Methods: Pediatric patients with noninfectious uveitis complicated by ME seen in the University of California San Francisco Health System from 2012 to 2018 were identified using ICD-9 and ICD-10 codes. Data were collected from medical records including demographics, diagnoses, ocular history, OCT imaging findings, complications, and treatments at first encounter and at 3, 6, 9, and 12-month follow-up visits. Cox proportional hazards regression was used to investigate the association between different classes of treatment (steroid drops, steroid injections, oral steroids and other immunosuppressive therapies) and resolution of macular edema., Results: The cohort comprised of 21 children (26 eyes) with a mean age of 10.5 years (SD 3.3). Undifferentiated uveitis was the most common diagnosis, affecting 19 eyes (73.1%). The majority of observed macular edema was unilateral (16 patients, 76.2%) and 5 patients had bilateral macular edema. The mean duration of follow-up at UCSF was 35.3 months (SD 25.7). By 12 months, 18 eyes (69.2%) had achieved resolution of ME. The median time to resolution was 3 months (IQR 3-6 months). Median best-corrected visual acuity (BCVA) at baseline was 0.54 logMAR (Snellen 20/69, IQR 20/40 to 20/200). Median BCVA at 12 months was 0.1 logMAR (Snellen 20/25, IQR 20/20 to 20/50) Corticosteroid injections were associated with a 4.0-fold higher rate of macular edema resolution (95% CI 1.3-12.2, P = 0.01)., Conclusions: Although only 15% of the pediatric patients with uveitis in the study cohort had ME, it is clinically important to conduct OCTs to detect ME in this population. Treatment resulted in 69% of eyes achieving resolution of ME by 12 months, accompanied with improvement in visual acuity. Corticosteroid injections were significantly associated with resolution of macular edema.

Background: Molecular diagnostics such as pathogen-directed PCRs have transformed testing for ocular infections since the late 1990s. Although these assays remain important diagnostic tools for samples with low biomass, the lack of diagnostic range motivates alternative molecular approaches for ocular infections. The aim of this study was to determine the performance of a high-throughput RNA sequencing approach, RNA-seq, to detect infectious agents in ocular samples from patients with presumed ocular infections., Methods: We compared the performance of RNA-seq to pathogen-directed PCRs using remnant nucleic acids from 41 aqueous or vitreous samples of patients with presumed ocular infections. Pathogen-directed PCRs were performed at the CLIA-certified Stanford Clinical Virology Laboratory. RNA-seq was performed in a masked manner at the Proctor Foundation at the University of California San Francisco. Percent positive and negative agreement between the two testing approaches were calculated. Discordant results were subjected to orthogonal testing., Results: The positive percent agreement between RNA-seq and pathogen-directed PCRs was 100% (95% confidence interval (CI): 78.5%-100%). The negative percent agreement was 92.6% (95% CI: 76.6%-97.9%). RNA-seq identified pathogens not on the differential diagnosis for 9.7% (4/41) of the samples. Two pathogens solely identified with RNA-seq were confirmed with orthogonal testing., Conclusions: RNA-seq can accurately identify common and rare pathogens in aqueous and vitreous samples of patients with presumed ocular infections. Such an unbiased approach to testing has the potential to improve diagnostics although practical clinical utility warrants additional studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose : To describe high-resolution DNA typing of HLA-A29 in patients with familial birdshot chorioretinopathy (BSCR). Methods : A retrospective clinical chart review was performed of all patients at the Francis I. Proctor Foundation with BSCR with a documented family history of HLA-A29 positive BSCR. High-resolution HLA-A29 typing was performed for these patients. Results : Two families with familial BSCR were identified. Family 1 consisted of a mother, daughter and maternal aunt with BSCR. All were positive for the HLA-A29*02 allele. Family 2 consisted of two sisters with BSCR who were both positive for the HLA-A29*02 allele. Conclusions : Familial BSCR is rare and we report the high-resolution DNA typing of HLA-A29 in two families with familial BSCR and their associated clinical outcomes, including the first documented case of multigenerational BSCR.

Background: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab., Methods: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg)., Discussion: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab., Trial Registration: ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 2019.

Background: Herpes zoster (HZ) and herpes zoster ophthalmicus (HZO) are common and debilitating diseases. There is no consensus in the literature whether HZ and HZO exhibit seasonal patterns., Objectives: To determine whether HZ and HZO are seasonal., Study Design: All patients in the OptumLabs® Data Warehouse (OLDW), a longitudinal, insurance claims database with de-identified lives between January 1, 2006 and December 31, 2017 with 365 days or more of continuous enrollment were considered in the study. The database was queried for patients reporting a new ICD-9/ICD-10 code for HZ or HZO and monthly counts of each administrative code were modeled using Morelet wavelets and analyzed for annual periodicity using Fisher's g test., Results: There were a total of 513,911 new cases of HZ during this time period; 40,166 cases (7.8 %) were reported as HZO. Administrative coding for new cases of HZ exhibited annual periodicity (P < .001) with a peak in the summer. No periodicity was evident for HZO., Conclusions: These results contribute to a growing body of evidence suggesting that HZ may be seasonal and help characterize the epidemiology of this common, painful disease., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. 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.)

Importance: Corneal opacity is a leading cause of visual impairment worldwide; however, the specific features of corneal scars, which decrease visual acuity, have not been well characterized., Objective: To investigate which features of a postfungal keratitis corneal scar contribute to decreased visual acuity after an episode of infectious keratitis and evaluate whether any corneal features may be used as outcomes for clinical trials., Design, Setting, and Participants: In this ancillary, prospective cross-sectional study, a subset of study participants treated for fungal keratitis (n = 71) as part of the Mycotic Ulcer Treatment Trial I (MUTT I) underwent best spectacle-corrected visual acuity (BSCVA) and best contact lens-corrected visual acuity examination, Scheimpflug imaging, and anterior segment optical coherence tomography at a referral hospital in India approximately 2 years after enrollment. Data were collected from December 3, 2012, to December 19, 2012, and analyses were performed from December 2, 2013, to October 2, 2019., Main Outcomes and Measures: Linear regression models were used to evaluate the importance of various corneal features for BSCVA and to assess whether these features could be used to differentiate the 2 treatment arms of the MUTT I trial., Results: Seventy-one patients (42 men [59.1%]; median age, 48 [range, 39-60] years) were examined at a median (IQR) time of 1.8 (1.4-2.2) years after enrollment. The mean (SD) logMAR BSCVA was 0.17 (0.19) (Snellen equivalent, 20/32). In multivariable linear regression models, BSCVA was most associated with irregular astigmatism (1.0 line of worse BSCVA per 1-line difference between BSCVA and contact lens visual acuity; 95% CI, 0.6-1.4) and corneal scar density (1.5 lines of worse vision per 10-unit increase in the mean central corneal density; 95% CI, 0.8-2.3). The thinnest point of the cornea was the metric that best discriminated between the natamycin- and voriconazole-treated ulcers in MUTT I, with 29.3 μm (95% CI, 7.1-51.6 μm) less thinning in natamycin-treated eyes., Conclusions and Relevance: Both irregular astigmatism and corneal scar density may be important risk factors for BSCVA in a population with relatively mild, healed fungal corneal ulcers. The thinnest point of the corneal scar may be a cornea-specific outcome that could be used to evaluate treatments for corneal ulcers.