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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 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.

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.

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: 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 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.

Purpose : To assess treatment outcomes in juvenile idiopathic arthritis (JIA)-associated uveitis and relapse rates upon discontinuation of immunomodulatory therapy (IMT). Methods : Medical records of patients with JIA-associated uveitis seen at the University of Illinois at Chicago and the F.I. Proctor Foundation uveitis clinics from September 14, 1988 to January 5, 2011 were reviewed. The main outcome was time to relapse after attempting to discontinue IMT. Results : Of 66 patients with JIA-associated uveitis, 51 (77%) received IMT as either sole or combination therapy. Of a total of 51, 41 (80%) patients achieved corticosteroid-sparing control. Attempts were made to discontinue treatment in 19/51 (37%) patients. Of a total of 19 patients, 13 (68%) attempting to discontinue IMT relapsed, with a median time to relapse of 288 days from the time of attempted taper/discontinuation (IQR: 108-338). Conclusions : Corticosteroid-sparing control of inflammation was achieved in the majority of patients; however, attempts to stop IMT were often unsuccessful. Close follow-up of patients after discontinuation of therapy is warranted.

Purpose: To evaluate the recurrence of uveitis after discontinuation of infliximab once control of inflammation is achieved., Methods: A retrospective cohort study was conducted of patients seen at the Proctor Foundation between 1998 and 2010 who discontinued infliximab after achieving corticosteroid-sparing control by Standardization of Uveitis Nomenclature criteria. The main outcome was the proportion of patients who had a relapse of uveitis., Results: Eighteen patients attempted to discontinue infliximab after achieving control of inflammation, and 11 patients had a relapse. Median time to relapse was 603 days (95% CI: 85-1461 days). Patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 4) relapsed faster (median time to relapse: 76 days, p = 0.002) compared with patients who did not have JIA-associated uveitis (median = 1169 days)., Conclusions: The majority of patients who achieved control of inflammation on infliximab had a recurrence after discontinuing therapy. Patients with JIA experienced recurrence faster compared to other patients.

Purpose: To describe the corticosteroid-sparing success in controlling chronic uveitis in patients treated with TNFα inhibitors., Methods: Retrospective longitudinal case series of patients started on infliximab (n = 31) or adalimumab (n = 12) for chronic noninfectious uveitis at a tertiary referral center. The main outcome was corticosteroid-sparing success. Secondary outcomes were sustained control of inflammation regardless of corticosteroid-sparing effect, tapering of concurrent nonbiologic therapy, and discontinuation., Results: Sustained control of inflammation with corticosteroid-sparing success on infliximab and adalimumab, respectively, was achieved in 33.3 and 37.5% at 3 months, 60.7 and 62.5% at 6 months, and 60.9 and 57.1% at 12 months. Median time to this outcome was 98 days for infliximab and 169 days for adalimumab. Six infliximab patients had adverse reactions., Conclusions: Infliximab and adalimumab improve control of ocular inflammation and are successful corticosteroid-sparing agents. However, time to corticosteroid-sparing control of inflammation may take a few months with either agent, and adverse reactions may limit treatment.

Purpose: To report treatment results with infliximab in 2 pediatric Vogt-Koyanagi-Harada syndrome (VKH) patients., Design: Interventional case series., Methods: Medical records of 2 patients were reviewed., Results: In 1 case with bilateral complete serous detachments, there was improvement but persistent fluid after 2 months of high-dose prednisone, methotrexate, and infliximab therapy. Infliximab was discontinued, and cyclophosphamide monthly intravenous injections were initiated with resolution of all subretinal fluid within 3 weeks. The second patient had mild subretinal fluid around the right optic nerve head tracking into the macula. Treatment with prednisone, methotrexate, and infliximab was initiated, with resolution of the subretinal fluid. Prednisone was tapered off within 4 months, and the inflammation remains controlled., Conclusions: Infliximab as adjunctive therapy in pediatric VKH showed a benefit in reducing systemic corticosteroid exposure in 1 patient, but incomplete timely resolution of inflammation in another patient.

Purpose: To describe the use of fluocinolone acetonide implants (Retisert) in Vogt-Koyanagi-Harada disease (VKH)., Design: Interventional case series., Methods: Retrospective review of medical records., Results: Two patients with VKH requiring high-dose systemic corticosteroid therapy to control their inflammation and bilateral serous retinal detachments received bilateral fluocinolone acetonide implants. Upon tapering of systemic corticosteroids, one patient had recurrent serous retinal detachments and the other patient's anterior chamber and vitreous inflammation returned., Conclusions: The authors' experience with fluocinolone acetonide implants in VKH has been mixed with an inability to fully taper off of systemic corticosteroids.