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.

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.

Paraproteinemic maculopathy.

PURPOSE: Paraproteinemia relates to monoclonal gammopathy-producing pathologic antibodies with serous macular detachment being an uncommon ocular manifestation. We ascertained the clinical course of maculopathy in paraproteinemia and investigated the effect of various therapeutic methods on the resolution of subretinal deposits. DESIGN: Multicenter, retrospective, observational case series. PARTICIPANTS: The records of patients with paraproteinemia with optical coherence tomography (OCT) documentation of serous macular detachment were reviewed. METHODS: Data collection included coexisting morbidity, rheology data (immunoglobulin level, hematocrit, and blood viscosity), clinical examination results, and OCT findings. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), height and basal area of the serous macular detachment, and systemic versus local therapies. RESULTS: A total of 33 cases were collected: 10 new and 23 previously reported in the literature. Diabetes was present in 7 patients, systemic hypertension in 9 patients, and anemia in 18. Mean initial immunoglobulin level was 6497 mg/dl, and mean serum viscosity was 5.5 centipoise (cP). Mean logarithm of the minimum angle of resolution initial vs. final BCVA was 0.55 (Snellen equivalent, 20/71) vs. 0.45 (20/56) in the right eye and 0.38 (20/48) vs. 0.50 (20/63) in the left eye. After mean follow-up of 7 months (range, 0-51 months). Systemic therapies included plasmapheresis (18), chemotherapy (30), blood transfusions (2), transplantation of progenitor hematopoietic cells (2), and oral rituximab (10). Immunoglobulin levels normalized in 8 patients and were unchanged in 1 after plasmapheresis, chemotherapy, or both. Ocular therapy in 8 patients included vitrectomy (1), laser photocoagulation (4), intravitreal bevacizumab (5), intravitreal triamcinolone (2), intravitreal dexamethasone implant (1), intravitreal rituximab (1), and sub-Tenon corticosteroid (1). The maculopathy resolved partially or completely in 17 patients and worsened or remained unchanged in 14 patients over median follow-up of 7 months. Maculopathy was unilateral in 9 cases and occurred at a lower initial immunoglobulin level in diabetics. There was a positive correlation between area of the detachment and serum viscosity. CONCLUSIONS: Paraproteinemic maculopathy can be unilateral. Decreasing the blood immunoglobulin level is the primary goal of therapy for paraproteinemic maculopathy, and this can be achieved by a systemic route. Coexisting diabetes facilitates leakage of immunoglobulins at lower levels than in nondiabetics.

Common Practice Patterns in the Diagnosis and Management of Acute Retinal Necrosis: A Survey Study of Uveitis Specialists.

PURPOSE: Due to lack of large randomized clinical trials to determine best practices in treating acute retinal necrosis (ARN), there is not a clear consensus amongst ophthalmologists on how to best manage this potentially blinding condition. The aim of this study is to survey common practice patterns and analyze the factors that affect ophthalmologists' management of ARN. METHODS: An anonymous survey was distributed to uveitis and retina specialists who are members of the American Uveitis Society (AUS) via email to query practice patterns regarding ARN. The survey included 22 questions with an additional 10 questions based on response. Survey question topics included demographic information, diagnostic testing, antiviral therapy, corticosteroids, and surgical procedures. RESULTS: 67 surveys were included for analysis. Most respondents (87%) always or frequently obtain intraocular aqueous fluid for diagnostic PCR testing. The majority of respondents would administer intravitreal antiviral injections to a unilateral immunocompetent ARN patient (67%), but would be even more likely to do so for a bilateral immunosuppressed ARN patient (87%). Respondents tend to treat ARN with systemic rather than local corticosteroids, with the majority (63%) of respondents initiating corticosteroid treatment 48 hours after treatment. Most respondents (79%) never perform a vitrectomy to manage ARN unless the patient has a retinal detachment or tear. The majority (63%) rarely or never perform prophylactic laser barricade, but may consider laser treatment if there is extensive retinal involvement. CONCLUSION: Current practice patterns for diagnosis and management of ARN among AUS members generally align with the suggested practices outlined by the American Academy of Ophthalmology.

Use of VESsel GENeration with Optical Coherence Tomography Angiography and Fluorescein Angiography for Detection and Quantification of Vascular Changes in Mild and Moderate Diabetic Retinopathy.

(1) Background: Previously, VESsel GENeration (VESGEN) software was used to map and quantify vascular changes observed on fluorescein angiography (FA) in subjects (n = 15 eyes) with retinal pathology ranging from mild non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). In the current study, we used VESGEN for the assessment of individuals with early-stage NPDR imaged by FA (Cohort 1) and by optical coherence tomography angiography (OCTA; Cohort 2). (2) Methods: Cohort 1 included type 2 diabetics (T2D), represented 21 eyes (ranging from no DR to moderate DR), and also included nondiabetic controls (NDC; n = 15 eyes). Cohort 2 consisted of 23 eyes from T2D subjects (including no DR subjects and moderate DR subjects) and NDC (n = 18 eyes). (3) Results: In the FA-VESGEN study, total tortuosity (Tv) of microvessels (G ≥ 6) increased in T2D with mild DR compared to the controls. In contrast, the VESGEN analysis of OCTA images showed that vessel length (characterized as density) was lower in T2D subjects before the diagnosis of DR and following the diagnosis of DR when compared to the controls. Additionally, T2D showed a significant decrease in vessel area (density). (4) Conclusions: FA elucidated the vessel morphology of small-generation microvessels to a greater degree than OCTA; however, OCTA identified changes in vessel density better than FA. VESGEN analysis can be used with both standard FA and OCTA to facilitate our understanding of early events in DR, including before the clinical diagnosis of DR.

Drug-induced uveitis.

PURPOSE OF REVIEW: Although more than 50% of all uveitis cases have no identifiable cause, certain medications can cause ocular inflammation and are often overlooked. Drug-induced ocular inflammation has increased in frequency with the advent of new bisphosphonates, antitumor necrosis factor biologic agents, and intravitreal triamcinolone and antivascular endothelial growth factor medications. Identification of these inciting drugs will simplify work-up and management of patients with uveitis and improve visual outcomes. RECENT FINDINGS: This review briefly focuses on the drugs that have long been known to be strongly associated with uveitis and emphasize new observations about these associations. It will also highlight the newest medications associated with uveitis and scleritis. The strength of the association between each drug and uveitis will be quantified and categorized into definite, probable, possible, and unlikely causes of uveitis utilizing Naranjo's classification criteria. SUMMARY: Drug-induced uveitis has become increasingly recognized in association with a number of commonly used systemic, intraocular, and topical medications. A detailed history is often all that is needed to identify these important, often overlooked, and readily curable causes of uveitis. Most cases of drug-induced uveitis respond promptly to discontinuation of the suspected agent in conjunction with topical corticosteroid and cycloplegic therapy.

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.

The spectrum of COVID-19-associated chorioretinal vasculopathy.

Purpose: Although conjunctivitis represents the most common ocular manifestation of COVID-19 infection, sight-threatening retinal involvement has been reported. Herein, we report and characterize with multimodal retinal imaging 5 cases of acute vision loss secondary to presumed chorioretinal vasculopathy temporally associated with COVID-19 infection with varying severity, visual morbidity, and treatment response, and review the available literature on the association between COVID-19 infection and retinal microvascular changes. Design: Observational case series and literature review. Methods: Multicenter case series of 5 patients who presented to academic centers and private offices with acute vision loss temporally associated with COVID-19 infection. A review of the literature was conducted using online databases. Results: 10 eyes of 5 patients, 3 men and 2 women, with a mean age of 30.8 years (median 33, range 16-44) were described. All patients had a recently preceding episode of COVID-19, with symptomatology ranging from mild infection to life-threatening encephalopathy. Treatment for their retinal disease included topical, oral, intravitreal, and intravenous steroids, steroid-sparing immunosuppression, retinal photocoagulation, antivirals, and antiplatelet and anticoagulant agents. Treatment response and visual recovery ranged from complete recovery of baseline acuity to permanent vision loss and need for chronic immunosuppression. Conclusions and Importance: Clinicians should be mindful of the potential for vision-threatening retinal involvement after COVID-19 infection. If found, treatment with both anti-inflammatory therapy and anticoagulation should be considered, in addition to close monitoring, as some patients with this spectrum of disease may require chronic immune suppression and/or anti-VEGF therapy.

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.

Ocular toxocariasis: epidemiologic, anatomic, and therapeutic variations based on a survey of ophthalmic subspecialists.

PURPOSE: To assess the current burden of ocular toxocariasis (OT) and to gain knowledge regarding the diagnostic and treatment practices used in the ophthalmologic community in the United States. DESIGN: Web-based, cross-sectional survey. PARTICIPANTS: Subspecialty ophthalmologists who are currently practicing in the United States. METHODS: An electronic survey was sent to 3020 ophthalmologic subspecialists belonging to the American Uveitis Society (AUS), the American Society of Retina Specialists (ASRS), or the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) to capture demographic, clinical, diagnostic, and treatment data on patients with OT seen in their practices between September 2009 and September 2010. MAIN OUTCOME MEASURES: The demographic, epidemiologic, and clinical characteristics of each reported patient with OT. RESULTS: A total of 159 patients with OT were reported by 559 respondents (19%). The median patient age was 11.5 years (range, 1-66 years). Seventy-two patients (45%) with OT lived in the Southern region of the United States. Thirty-one (69%) of 45 patients with OT owned a dog or cat. Vision loss was reported in 46 (85%) of 54 patients with OT; 32 (71%) of 45 patients had permanent vision loss, 13 patients (29%) had temporary vision loss, and duration of vision loss was unreported for 1 patient. Of the 32 patients with OT with permanent vision loss, 30 (94%) had a subretinal granulomatous mass/scar, peripheral granuloma with traction bands, or posterior pole granuloma noted on ophthalmologic examination. Subretinal granulomatous mass/scar, vitritis, and scotoma were the most common ophthalmologic signs found on examination of patients with OT. CONCLUSIONS: Ocular toxocariasis continues to occur in the United States, where it affects mainly children and causes permanent vision loss in many patients. Healthcare professionals should counsel patients and their family members about prevention strategies in an effort to decrease infection rates and morbidity due to Toxocara. Further improvement of diagnostic and treatment tools is needed to assist ophthalmologists in treating patients with OT. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of Dupilumab with Intraocular Inflammation.

PURPOSE: To report four cases of uveitis after treatment with dupilumab for atopic dermatitis. METHODS: Retrospective case series. RESULTS: Data was collected from four patients with inflammation that developed after treatment with dupilumab. The first patient was thought to have developed posterior scleritis or Harada's-type disease related to her treatment with dupilumab, with recurrence of intraocular inflammation upon restarting treatment. The second patient developed anterior and intermediate uveitis as well as cystoid macular edema in her right eye about two years after starting dupilumab treatment. The third patient developed a distinct relentless placoid chorioretinitis while on therapy with dupilumab. The fourth patient developed bilateral cystoid macular edema while on treatment with dupilumab. CONCLUSION: We report a case series of patients treated with dupilumab who developed intraocular manifestations of inflammatory disease.

Long-term, multicenter evaluation of subconjunctival injection of triamcinolone for non-necrotizing, noninfectious anterior scleritis.

PURPOSE: We sought to characterize the long-term outcomes and complications of subconjunctival triamcinolone acetonide injection (STI) for non-necrotizing, noninfectious anterior scleritis. DESIGN: Retrospective, interventional, noncomparative, multicenter study. PARTICIPANTS: Sixty-eight eyes of 53 patients from 9 participating hospitals in the United States, Singapore, and Australia. Only eyes with 6 or more months of follow-up were included. INTERVENTION: Subconjunctival injection of 2 to 8 mg of triamcinolone acetonide was administered to eyes with non-necrotizing, noninfectious anterior scleritis. MAIN OUTCOME MEASURES: Resolution of signs and symptoms, time to recurrence of scleritis, and side effect profile. RESULTS: Median follow-up was 2.3 years (range, 6 months to 8.3 years). Sixty-six eyes (97.0%) experienced improvement of signs and symptoms after 1 injection. Twenty-four months after a single injection, 67.6% of eyes remained recurrence-free, whereas at 48 months, 50.2% were recurrence-free. Some 55.0% of patients who had adverse effects from systemic medications were off all systemic medications at last follow-up; 55.0% of patients who were taking systemic medications at the time of first triamcinolone acetonide injection were not taking prednisone and immunosuppressants at this time; 76.2% of patients still requiring systemic agents had associated systemic disease. Fourteen eyes (20.6%) had ocular hypertension not requiring intraocular pressure (IOP)-lowering therapy. Two eyes (2.9%) were treated with topical IOP-lowering agents alone, and 2 eyes required surgical intervention for glaucoma. None developed scleral necrosis or melt. CONCLUSIONS: This retrospective, international study carried out at 9 hospitals suggests that STI can treat non-necrotizing, noninfectious anterior scleritis with side effects limited to elevated IOP in a few patients. Although no cases of scleral melt or necrosis were observed, we cannot definitively conclude that this may not occur after STI. Intraocular pressure should be closely monitored after STI. Subconjunctival triamcinolone acetonide injection may be useful as adjuvant therapy or to decrease systemic medication burden. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Acute pulmonary histoplasmosis in a patient with uveitis after infliximab therapy.

The purpose of this study is to report a case of disseminated histoplasmosis in a patient with uveitis, after treatment with infliximab. The method employed in this study is single case report. Infliximab can be useful in controlling idiopathic uveitis, but can give rise to disseminated histoplamosis, especially in patients living in geographic areas where histoplasmosis is endemic. Clinicians should be aware of the possibility of rapid onset histoplasmosis in patients receiving anti-tumor necrosis factor agents. In such cases, these agents should be immediately stopped, investigations performed, and appropriate treatment started.

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.

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.