Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.

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.

Reduced Dose Methotrexate and Mycophenolate Mofetil in Noninfectious Uveitis: A Sub-Analysis from the First-Line Antimetabolites as Steroid Sparing Therapy (FAST) Trial.

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.

Peripheral ulcerative keratitis due to systemic diseases.

PURPOSE OF REVIEW: To discuss peripheral ulcerative keratitis, with a focus on the evaluation and management of associated systemic diseases. RECENT FINDINGS: Peripheral ulcerative keratitis (PUK) is a sight-threatening condition that is often defined by the presence of a crescent-shaped area of peripheral corneal thinning, an epithelial defect, and an inflammatory corneal infiltrate. It is highly associated with rheumatoid arthritis, systemic necrotizing vasculitides like granulomatosis with polyangiitis, and collagen vascular diseases like systemic lupus erythematosus. Undertreated PUK carries a risk of vision loss and premature death. SUMMARY: Multidisciplinary collaboration between the ophthalmologist, rheumatologist, and other consultants is required. Early and aggressive steroid-sparing therapy should be considered in cases due to noninfectious systemic disease.

Occult cause of uveitis-glaucoma-hyphema syndrome diagnosed during treatment with endocyclophotocoagulation (ECP).

Purpose: To describe uveitis-glaucoma-hyphema (UGH) syndrome secondary to a posterior chamber intraocular lens (PCIOL) within the capsular bag in which pathogenic changes to the ciliary body were observed and treated with endocyclophotocoagulation (ECP). Observations: An 85-year-old woman who had cataract surgery in her right eye four years ago presented with recurrent, unilateral, open-angle, hypertensive uveitis in her right eye. Her presentations were characterized by decreased vision, elevated intraocular pressure, corneal edema, a mixed anterior chamber reaction, and pigmented anterior vitreous cells. She had a frank vitreous hemorrhage during two episodes. Ultrasound biomicroscopy revealed a dense Soemmerring ring in her right eye without evidence of PCIOL-iris or PCIOL-ciliary body chafe. Subsequent ECP revealed whitened and atrophic ciliary processes adjacent to a tilted haptic within the capsular bag, consistent with chronic PCIOL-ciliary body chafe. ECP was applied to the affected ciliary processes, which successfully eliminated recurrences. Conclusions and importance: UGH can rarely occur due to an PCIOL within the capsular bag. In cases where ultrasound biomicroscopy (UBM) does not show abnormalities and clinical suspicion remains high, ECP can be a useful adjunct to observe and treat abnormalities of the ciliary body.

Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration.

Purpose: Basal laminar deposit (BLamD) is a consistent finding in age-related macular degeneration (AMD). We quantified BLamD thickness, appearance, and topography in eyes of aged donors with and without AMD and evaluated its relationship to other components of the retinal pigment epithelium-basal lamina/Bruch's membrane (RPE-BL-BrM) complex. Methods: Donor eyes (n = 132) were classified as normal (n = 54), early to intermediate AMD (n = 24), geographic atrophy (GA; n = 13), and neovascular AMD (NV; n = 41). In high-resolution histology, we assessed RPE, BLamD, and BrM thicknesses and phenotypes at 3309 predefined locations in the central (foveal and perifovea) and superior (perifoveal) sections. Pre-mortem optical coherence tomography (OCT) imaging of a 90-year-old woman was compared to postmortem histopathology. Results: In non-atrophic areas of AMD eyes, the RPE-BLamD is thick (normal = 13.7 µm, early-intermediate = 16.8 µm, GA = 17.4 µm, NV = 18.7 µm), because the BLamD is thick (normal = 0.3 µm, early-intermediate = 5.5 µm, GA = 4.1 µm, NV = 5.3 µm). RPE layer thickness is similar across these stages. Disease-associated variants of BLamD (thick, late, basal mounds) cluster subfoveally. A thick BLamD is visible on OCT as a hyporeflective split in the RPE-BL-BrM complex. BrM is thin (3.5 µm) in NV (normal = 4.2 µm, early to intermediate = 4.4 µm, and GA = 4.2 µm). Conclusions: The RPE-BL-BrM complex is thick in AMD, driven by the accumulation and expansion of BLamD rather than expansion of either three-layer BrM, RPE-BL, or RPE. BLamD is clinically appreciable by OCT in some patients as a non-neovascular "split RPE-BL-BrM complex" or "double-layer sign." BLamD may contribute toward the formation and progression of high-risk drusen yet also exhibit protective properties.