Optic Disc Edema Is an Under-Recognized Feature of Birdshot Chorioretinitis.

BACKGROUND: Optic disc edema is a feature of many ophthalmic and neurologic conditions. It remains an underappreciated feature of birdshot chorioretinitis (BSCR), leading to delay in diagnosis and treatment. The purpose of our study was to identify clinical features that are concomitant with optic disc edema and suggest a diagnosis of BSCR. METHODS: Retrospective multicenter case series of 29 patients who were referred to a neuro-ophthalmologist or uveitis specialist for evaluation of disc edema and were ultimately diagnosed with BSCR. RESULTS: Fifty-four eyes of 30 patients, from the practices of 15 uveitis specialists, met the eligibility criteria. In addition to disc edema, concomitant features in all patients included vitritis, chorioretinal lesions, and retinal vasculitis. Visual recovery to 20/40 or better occurred in 26 of 29 patients. Visual acuity remained 20/100 or worse in 2 patients previously diagnosed with idiopathic intracranial hypertension, 1 patient previously diagnosed with optic neuritis, and 1 patient for whom treatment was delayed for years, leading to optic disc atrophy. CONCLUSIONS: Optic disc edema is a presenting feature in some cases of BSCR. A diagnosis of BSCR should be considered when disc edema occurs with vitritis, chorioretinal inflammation, and retinal vasculitis. Patients should be referred to a uveitis specialist for treatment.

Shifts in ophthalmic care utilization during the COVID-19 pandemic in the US.

BACKGROUND: Healthcare restrictions during the COVID-19 pandemic, particularly in ophthalmology, led to a differential underutilization of care. An analytic approach is needed to characterize pandemic health services usage across many conditions. METHODS: A common analytical framework identified pandemic care utilization patterns across 261 ophthalmic diagnoses. Using a United States eye care registry, predictions of utilization expected without the pandemic were established for each diagnosis via models trained on pre-pandemic data. Pandemic effects on utilization were estimated by calculating deviations between observed and expected patient volumes from January 2020 to December 2021, with two sub-periods of focus: the hiatus (March-May 2020) and post-hiatus (June 2020-December 2021). Deviation patterns were analyzed using cluster analyses, data visualizations, and hypothesis testing. RESULTS: Records from 44.62 million patients and 2455 practices show lasting reductions in ophthalmic care utilization, including visits for leading causes of visual impairment (age-related macular degeneration, diabetic retinopathy, cataract, glaucoma). Mean deviations among all diagnoses are 67% below expectation during the hiatus peak, and 13% post-hiatus. Less severe conditions experience greater utilization reductions, with heterogeneities across diagnosis categories and pandemic phases. Intense post-hiatus reductions occur among non-vision-threatening conditions or asymptomatic precursors of vision-threatening diseases. Many conditions with above-average post-hiatus utilization pose a risk for irreversible morbidity, such as emergent pediatric, retinal, or uveitic diseases. CONCLUSIONS: We derive high-resolution insights on pandemic care utilization in the US from high-dimensional data using an analytical framework that can be applied to study healthcare disruptions in other settings and inform efforts to pinpoint unmet clinical needs.

The COVID-19 pandemic disrupted healthcare services globally, including eye care in the United States. Using a US eye disease database, we measured how the pandemic impacted patient visits for 261 eye diagnoses by comparing actual visit volumes for each diagnosis with what would have been expected without the pandemic. We identified groups of conditions with similar changes in visit levels and examined whether these shifts were related to characteristics of the diagnoses studied. We found extended decreases in patient presentations for most eye conditions, with greater reductions for less severe diagnoses, and with anomalies and differences in this trend across diagnosis categories and pandemic sub-periods. This highlights areas of potentially unmet need in vision care arising from the pandemic.

Rhegmatogenous Retinal Detachment in Syphilitic Uveitis: A Case Series and Comprehensive Review of the Literature.

PURPOSE: Uveitis is the most common ocular manifestation of syphilis. However, an association between syphilitic uveitis and rhegmatogenous retinal detachment (RRD) is not widely recognized. We report a consecutive series of six new cases of syphilitic uveitis complicated by RRD and describe the typical characteristics, clinical course, and surgical management of such cases. METHODS: Consecutive case series and comprehensive review of the literature. RESULTS: We identified a total of 19 cases (23 eyes) with syphilitic uveitis subsequently complicated by RRD, including six new cases (seven eyes) reported here and 13 cases (16 eyes) previously reported in the literature. Fifteen patients (79%) were positive for human immunodeficiency virus (HIV) and not on combination antiretroviral therapy. Most retinal detachments developed within two months of uveitis presentation; retinal breaks were often found in areas of previous retinitis. Sixteen eyes (70%) were complicated by early proliferative vitreoretinopathy. Twenty-one eyes underwent surgical repair, of which six (26%) suffered re-detachment. Surgical management commonly involved pars-plana vitrectomy and silicone oil tamponade, with or without scleral buckling. Visual outcomes were generally poor: only six eyes (26%) attained visual acuity of 20/40 or better and 11 eyes (48%) remained 20/200 or worse. CONCLUSIONS: Patients with syphilitic uveitis, as with viral retinitis, should be monitored closely for the development of retinal tears and RRD. A combination of pars plana vitrectomy with silicone oil tamponade and/or scleral buckle placement is a prudent surgical approach to most cases of syphilitic RRD, although visual prognosis remains guarded.

Efficacy of Biosimilar Infliximab-Dyyb in Non-Infectious Uveitis.

PURPOSE: To describe the frequency of uveitis recurrences in patients with non-infectious uveitis treated with the biosimilar infliximab-dyyb. DESIGN: Retrospective case series. METHODS: Records of uveitis patients treated with the biosimilar infliximab-dyyb between 2016 and 2022 at two institutions were reviewed. Data extracted included patient demographics, diagnosis, previous originator infliximab use, additional immunosuppression medications, infliximab-dyyb use, reason for switch, disease activity, and follow-up time. RESULTS: A total of 14 patients were identified. Seven patients were switched from originator infliximab to a biosimilar for nonmedical/non-ocular reasons (insurance prompted the switch). One patient was started directly on infliximab-dyyb due to active joint disease despite well-controlled uveitis. None of these eight patients developed inflammation after the switch. Six patients were started directly on infliximab-dyyb due to poorly controlled uveitis. Of these, five patients achieved disease quiescence during follow-up. The mean dose of originator was 1.79 mg/kg/week, with a median dosing schedule of 4 weeks prior to therapy with infliximab-dyyb. The mean final infliximab-dyyb dosage was 1.81 mg/kg/week, with a median dosing schedule of 4 weeks. CONCLUSION: Infliximab-dyyb appears to be efficacious in achieving and maintaining uveitis control.

UNILATERAL OPTIC NEURITIS AND CENTRAL RETINAL VASCULITIS DUE TO OCULAR SYPHILIS.

PURPOSE: Report a case of concurrent unilateral optic neuritis and central retinal artery occlusion as the presenting signs of syphilis. METHODS: A case report of a 22-year-old man with progressive unilateral vision loss. RESULTS: With no known previous history of syphilis, genital lesions, or other extraocular manifestations, the patient presented with pain with eye movements and decreased color vision. His vision dramatically worsened after a course of oral steroids. Examination was remarkable for severe right optic disk edema with a macular cherry-red spot and mild posterior uveitis. Magnetic resonance imaging of the orbits with contrast revealed enhancement and enlargement of the distal right optic nerve. Fluorescein angiography demonstrated delayed filling of the right central retinal artery, suggestive of impending central retinal artery occlusion. Syphilis serologies were positive from the serum, and cerebrospinal fluid Venereal Disease Research Laboratory test was reactive, consistent with neurosyphilis. Oral steroids were discontinued and vision improved with 2 weeks of intravenous penicillin. CONCLUSION: This unusual case highlights one of the possible initial presentations of syphilis: unilateral optic neuritis and central retinal artery vasculitis with mild posterior uveitis. The worsening of vision after administration of oral steroids also highlights a potential complication of oral steroid use in the absence of a known etiology of vision loss. A thorough history and examination may be helpful in identifying risk factors for infectious causes, including syphilis, and should prompt additional evaluation.

A Proposal of Conducting Bioequivalence Trials with Gastric pH Modulators for Two Oral Formulations Demonstrating Different Dissolution Profiles at Elevated pH.

In this paper, a special case for bioequivalence evaluation of oral formulations is discussed. Drug formulations with different forms of active moieties (e.g., free base and salt) may yield different dissolution characteristics and, thus, differ in absorption at elevated gastric pH. However, routine bioequivalence trials using subjects with normal gastric pH (i.e., ~ 1) may fail to identify these differences because dissolution/absorption profiles of the two formulations at normal gastric pH are similar. In the case of palbociclib, it is confirmedthat the free base and salt formulations showed different absorption in patients with different gastric pH. Significant reduction in drug absorption was observed only in patients with elevated gastric pH using free base formulation. The discovery that the free base had significantly reduced absorption hinged on the inclusion of enough patients with elevated gastric pH to detect a difference in a bioequivalence trial. This raises a concern, as demonstrated through simulation, that dissolution/absorption differences in other formulations could be missed in routine bioequivalence trials. Aside from differences in active pharmaceutical ingredients (APIs), other factors, such as changes in excipients or manufacturing methods, may also lead to exposure differences between formulations at elevated gastric pH. For formulations containing different forms of the same active moiety or the same API and showing different dissolution profiles at elevated pH (i.e., pH ~ 4-6.8), evaluation of bioequivalence with gastric pH modulators (e.g., a H2 blocker) in addition to routine bioequivalence assessments may help to ensure therapeutic equivalence in patients with elevated gastric pH.

Case Report: Ocular Toxocariasis: A Report of Three Cases from the Mississippi Delta.

Ocular toxocariasis can be vision threatening, and is commonly reported from tropical or subtropical regions. Knowledge of clinical manifestations from the United States, particularly in underserved areas such as the American South, is lacking. We report three cases of ocular toxocariasis in individuals from the Mississippi Delta, a rural community with prevalent poverty. Visual acuity was severely affected in two of the three cases. Increased awareness of ocular toxocariasis, which may have under-recognized frequency, will contribute to prompt diagnosis and treatment, which will ultimately improve patient health in the region.

Drug-induced uveitis.

PURPOSE OF REVIEW: Nearly one-half of all uveitis cases seen at tertiary referral centers have no identifiable cause. Many systemic, paraocular, intraocular, topical medications, and even vaccines can induce intraocular inflammation, scleritis, and rarely orbititis and are often overlooked as causes of uveitis. This review was undertaken to elucidate the strength of association of these medications with uveitis and to make clinicians aware of these associations, especially among newer medications. RECENT FINDINGS: Medication-induced uveitis has become particularly important and more frequently seen because of the advent of biologic therapies such as immune checkpoint inhibitors (ICPIs), BRAF, and MEK inhibitors, antivascular endothelial growth factor agents, and antitumor necrosis factor agents, as well as newer systemic bisphosphonates are strongly associated with uveitis. SUMMARY: The ever-broadening scope of pharmaceuticals now available to treat previously untreatable conditions, such as advanced metastatic cutaneous melanoma, have resulted in unintended ocular inflammatory diseases. Ophthalmologists must recognize that drugs such as ICPIs, BRAF, and MEK inhibitors, anti-vascular endothelial growth factor agents, tumor necrosis factor-α inhibitors, cidofovir, bisphosphonates, topical prostaglandin analogues, topical brimonidine, BCG vaccination can cause of uveitis. Utilizing a thorough review of systems, physicians may readily identify medications that may cause uveitis and avoid expensive and unnecessary laboratory testing.

Impact of the US FDA "Biopharmaceutics Classification System" (BCS) Guidance on Global Drug Development.

The FDA guidance on application of the biopharmaceutics classification system (BCS) for waiver of in vivo bioequivalence (BE) studies was issued in August 2000. Since then, this guidance has created worldwide interest among biopharmaceutical scientists in regulatory agencies, academia, and industry toward its implementation and further expansion. This article describes how the review implementation of this guidance was undertaken at the FDA and results of these efforts over last dozen years or so across the new, and the generic, drug domains are provided. Results show that greater than 160 applications were approved, or tentatively approved, based on the BCS approach across multiple therapeutic areas; an additional significant finding was that at least 50% of these approvals were in the central nervous system (CNS) area. These findings indicate a robust utilization of the BCS approach toward reducing unnecessary in vivo BE studies and speeding up availability of high quality pharmaceutical products. The article concludes with a look at the adoption of this framework by regulatory and health policy organizations across the globe, and FDA's current thinking on areas of improvement of this guidance.