Long-Term Clinical Outcomes of the 0.18 Mg Fluocinolone Acetonide Intravitreal Implant Following Local Corticosteroid Burst in Noninfectious Uveitis.

PURPOSE: The 0.18 mg fluocinolone acetonide implant (FAi) is marketed for up to 36 months for treatment of noninfectious uveitis. An additional short-term corticosteroid burst prior to the 0.18 mg FAi, followed by attempt at long-term inflammation control with the 0.18 mg FAi may be beneficial given the low dose of the implant. We retrospectively reviewed all patients undergoing this treatment approach at our institution to determine its efficacy. METHODS: Patients who received a corticosteroid burst followed by the 0.18 mg FAi with at least 6-month follow-up post 0.18 mg FAi were included. The primary outcome, treatment escalation (defined as worsening inflammation requiring escalation of therapy), was modeled using Kaplan-Meier analysis. Secondary outcomes included cystoid macular edema (CME), central macular thickness, retinal vasculitis, visual acuity, anterior chamber and vitreous cell, use of systemic therapy, use of corticosteroid drops, IOP, number of IOP lowering medications, need for glaucoma surgery, need for cataract surgery, and additional local corticosteroids. RESULTS: 32 eyes were included (mean follow-up: 19.8 months). Prior to corticosteroid burst, 37.5% were on systemic therapy, 53% had CME, and 25% had retinal vasculitis. At FAi visit, CME had decreased to 18.8%. Mean time to treatment escalation after FAi was 20.3 months (95% CI 14.8-25.7 months). No patient discontinued systemic therapy and on average 15.0% of eyes required additional local corticosteroids at each follow-up interval. CONCLUSIONS: This treatment approach demonstrates that the 0.18 mg FAi is a useful adjuvant for the treatment of noninfectious uveitis but may not be adequate as solo therapy.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Regulatory and Informational Gaps in the Over-the-Counter Eye Care Product Industry-Over the Counter, Under the Radar.

This Viewpoint describes the limitations of regulatory oversight for over-the-counter eye care products and challenges in providing clinical recommendations.

Tubulointerstitial Nephritis and Uveitis Syndrome in Pediatric Patients.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a disorder that was originally described in 1975. The syndrome, although diagnosed in all age ranges, is more frequently reported in pediatric patients. Diagnosis can be difficult, and its clinical spectrum is still being defined. In this article, we review the epidemiology, diagnosis, pathogenesis, clinical findings, prognosis, and treatment of both the ocular and renal disease. We comment on the current difficulties in diagnosis and study of the disease, its expanding clinical spectrum, and treatment strategies in pediatric patients.

Cranial Nerve Palsies in the Setting of Arachnoid Cysts: A Case Series and Literature Review.

BACKGROUND: Arachnoid cysts (ACs) are benign lesions typically believed to not cause neurologic defects in the adult population and are most often found incidentally on imaging. We describe 2 patients with ACs potentially leading to isolated cranial nerve (CN) dysfunction. METHODS: We describe 2 patients, 1 with a fourth nerve palsy and the other with a sixth nerve palsy found to have ACs on MRI brain imaging in locations that potentially caused a compressive CN palsy. We review previous literature of ACs presenting with CN III, IV, or VI palsy. RESULTS: Patient 1 was a 62-year-old man who presented with a 22-year history of diplopia with strabismus examination consistent with a congenital CN IV palsy. Despite multiple surgeries, his CN IV palsy insidiously worsened. An AC in the posterior fossa with mass effect on the quadrigeminal plate and asymmetric atrophy of the right superior oblique was identified on imaging. Patient 2 was an 80-year-old man who presented with an 18-year history of diplopia and was found to have a left esotropia and abduction deficit consistent with complete CN VI palsy. An AC in the left cavernous sinus was identified on imaging. He underwent strabismus surgery with satisfactory resolution of diplopia. We identified a total of 18 previously published cases: 8 reports of CN III palsy, 4 reports of CN IV palsy, and 6 reports of CN VI palsy. Patient ages ranged from 1 to 67 with a median of 34.5. In 16/18 (89%) cases, the diagnosis of ACs was made within 1 year of symptom onset. Surgical removal of the AC was successful in resolving diplopia in 7/12 (58%) cases. In no case was strabismus surgery performed as primary treatment. CONCLUSIONS: Although ACs are typically congenital asymptomatic lesions, we present a case series of 2 patients with ACs in anatomic locations that potentially caused chronic, progressive, isolated CN palsies leading to strabismus. Our literature review revealed that most published cases detailing this clinical scenario resulted in neurosurgical fenestration of ACs with mixed results. Our cases represent 2 patients with AC-associated CN palsy treated with strabismus surgery.

Clinical outcomes in neovascular age-related macular degeneration: a cohort study of patients with care delay due to the COVID-19 pandemic.

The COVID-19 pandemic has led to both intentional and unintentional care delay among age-related neovascular macular degeneration (nvAMD) patients. Prior studies have demonstrated that patients who discontinue nvAMD treatment for prolonged intervals are at high risk for vision loss, but less is known regarding shorter-term delay, such as during the height of the pandemic. Previous studies have looked at COVID-19 related delay in care and have shown a loss of visual acuity (VA) among these patients, but studies are limited by short follow-up or insufficient comparisons. This was an observational cohort study of nvAMD patients from March 1, 2019, through July 1, 2021, who experienced care delay. VA was modeled using a linear longitudinal mixed-effects model comparing historic data pre-lockdown to data post-lockdown. Covariates included baseline anatomic variables, demographic variables, and time intervals (treatment interval, delay interval). Secondary anatomic and treatment outcomes were modeled using a multilevel binary logistic regression model. 163 eyes among 116 patients were included. Initial longitudinal mixed-effects models found that although overall VA decreased at a yearly rate, when comparing pre-lockdown and post-lockdown time periods, VA slopes were not statistically different. Single-covariate longitudinal models showed that age, sex, and delay interval significantly affected VA slope. The multivariate longitudinal model found that a longer delay interval significantly decreased rate of VA loss. Multilevel binary logistic regression models showed a significant increase in odds of anti-VEGF treatment, presence of subretinal fluid, and macular hemorrhages in the post-lockdown period. Overall, when compared to historic data, rate of VA loss among our cohort did not vary significantly in pre-versus post-lockdown time periods, although treatment and anatomic variables did worsen post-lockdown suggesting that patients may be appropriately delayed but this comes at the risk of increased need for treatment.

Multimodal imaging of an acute presentation of ocular histoplasmosis syndrome in an immunocompetent patient.

Purpose: Presumed ocular histoplasmosis syndrome (POHS) is a posterior segment disorder that is usually subclinical unless choroidal neovascular membrane (CNVM) develops. It is thought to be the sequela of a prior systemic infection with Histoplasma capsulatum, and evidence supporting this association is based on epidemiologic, animal, and few enucleation studies. Acute presentation of chorioretinal involvement during an initial histoplasmosis systemic infection in immunocompetent patients is rarely reported, presumably due to the usual lack of or minimal symptoms of both the systemic and ocular disease. We report on an immunocompetent male with choroidal lesions detected during disseminated histoplasmosis infection and characterize the lesions using multimodal imaging. Observations: A 17-year-old male presented when routine optometry screening detected two deep, yellowish-white lesions in the left fundus. Optical coherence tomography (OCT) imaging confirmed a choroidal mass with extension through Bruch's membrane into the subretinal space and a small amount of subretinal fluid. Fluorescein angiography was suggestive of CNVM. There were no clinical findings of intraocular inflammation, and the patient was initially lost to follow-up. Eight weeks after last follow-up, the patient presented to the emergency department with fatigue, mild respiratory symptoms, and abdominal pain for the last month. Imaging revealed a mediastinal mass with hilar extension and innumerable nodules throughout the lung and spleen. Serum Histoplasma IgM/IgG were positive, and biopsy of the mediastinal mass revealed Histoplasma organisms. The patient was treated with antifungals and discharged. The patient underwent an extensive immunologic evaluation while admitted, which did not reveal an underlying immunodeficiency. On last follow-up, the choroidal lesions were smaller and more consolidated, and the subretinal fluid had resolved. Conclusions and Importance: We present a patient with choroidal lesions in the setting of disseminated systemic histoplasmosis infection and characterize a lesion using multimodal imaging. The presentation of acute chorioretinal lesions in the setting of biopsy proven systemic Histoplasma infection supports H. capsulatum as the etiology of POHS.

The Microbiome and Uveitis: A Narrative Review.

The human intestinal microbiome is composed of hundreds of species and has recently been recognized as an important source of immune homeostasis. While dysbiosis, an altered microbiome from the normal core microbiome, has been associated with both intestinal and extraintestinal autoimmune disorders, including uveitis, causality has been difficult to establish. There are four proposed mechanisms of how the gut microbiome may influence the development of uveitis: molecular mimicry, imbalance of regulatory and effector T cells, increased intestinal permeability, and loss of intestinal metabolites. This review summarizes current literature on both animal and human studies that establish the link between dysbiosis and the development of uveitis, as well as provides evidence for the above mechanisms. Current studies provide valuable mechanistic insights as well as identify potential therapeutic targets. However, study limitations and the wide variability in the intestinal microbiome among populations and diseases make a specific targeted therapy difficult to establish. Further longitudinal clinical studies are required to identify any potential therapeutic that targets the intestinal microbiome.

Comparison of Uveitis Incidence by Medication in Juvenile Idiopathic Arthritis and Implications for Screening.

PURPOSE: To determine uveitis incidence in juvenile idiopathic arthritis (JIA) patients treated with disease-modifying antirheumatic drugs (DMARD) medications, and to evaluate uveitis risk-stratification protocols. DESIGN: Retrospective clinical cohort study. METHODS: Medical records of patients with JIA seen by ophthalmology at a single institution from April 2014 to April 2022 and ≥18 months' follow-up were reviewed. Exclusion criteria included uveitis history prior to study period, Still disease, or <18 months' follow-up. Patient characteristics, medications, and uveitis status were recorded. Factors associated with uveitis development were analyzed and statistically significant metrics used to determine empiric risk-stratification criteria. These criteria and American College of Rheumatology (ACR) risk-stratification guidelines were applied retroactively to determine predictive power. RESULTS: One hundred eighty-four patients met inclusion criteria and were included. Twenty-one new cases of uveitis developed during the study period. There were no statistically significant differences between no DMARD treatment, methotrexate (MTX), and etanercept (ETA) groups in uveitis incidence, whereas the adalimumab (ADA) and other biologics groups had no uveitis cases. Under the empirically determined criteria, the ratio of uveitis incidence between high- and low-risk groups was 8.21 (2.68-33.55; P < .0001), whereas it was 1.90 (0.72-4.93; P = .15) under the ACR criteria. CONCLUSION: Patients on MTX, ETA, and no DMARD treatment were comparable in JIA-associated uveitis incidence, whereas there were no new cases with ADA or other biologics. Further, we found increased predictive power in the empiric criteria in comparison to current ACR risk stratification.

Low absolute CD4+ T cell counts in peripheral blood: an independent predictor of inferior survival in natural killer/T-cell lymphoma-a retrospective cohort study.

Background: Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4+ T cell count (ACD4C), which has previously been identified as an independent prognostic factor in other hematologic malignancies. However, there is limited data available regarding the prognostic value of peripheral blood T lymphocyte subsets in ENKTL patients. The purpose of this study was to investigate the prognostic value of lymphocyte subsets, especially the ACD4C in ENKTL as a clinical biomarker. Methods: We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University from 2000 to 2018, including baseline clinical factors and ACD4C detected by flow cytometry, and examined the correlation between the results and clinical parameters and long-term outcomes. Results: The complete response rate of the high ACD4C group was 57.6%, which was significantly higher than that of the low ACD4C group (15.1%, P<0.001). The univariate analysis results showed that at a median follow-up time of 58.2 months, patients with a high ACD4C had significantly superior progression-free survival (PFS) and overall survival (OS) (P=0.034 and P=0.001, respectively). The multivariate analysis results revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and the ACD4C were independent prognostic factors for OS [RR (95% CI): 2.288 (1.209-4.328), P=0.011 and RR (95% CI): 2.058 (1.070-3.968), P=0.031, respectively]. ECOG PS was also an independent prognostic factor for PFS [RR (95% CI): 1.858 (1.064-3.244), P=0.029], while ACD4C tended to be independently correlated with PFS (P=0.085). Conclusions: In this large cohort study, we found that the ACD4C was associated with survival outcomes in ENKTL patients. It is a potential biomarker, which may potentially be applied to clinical.

Neuro-ophthalmic manifestations of cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmic manifestations of cancer are vast and early recognition of a serious ocular condition due to either cancer or its therapy is important for both vision preservation as well as providing valuable treatment and prognostic information regarding the underlying malignancy. This review focuses on direct and indirect effects of cancer on the eye and its adnexa, hematologic malignancy, complications of traditional and novel oncologic therapies, and paraneoplastic syndromes as they relate to the eye as these disorders can lead to potentially devastating or irreversible vision loss. METHODS: PubMed was searched primarily for the following topics: optic nerve infiltration, primary vitreoretinal lymphoma (PVRL), ocular paraneoplastic disorders, and ophthalmic complications of cancer therapeutics. Literature was selected based on historical significance and landmark studies (e.g., Cross et al. series of paraneoplastic optic neuritis patients; Chan's textbook on primary intraocular lymphoma) as well as publications published after 2000. References from select studies were additionally included. Given the sparsity of literature on many subjects, most publications were included during this time frame in our review. KEY CONTENT AND FINDINGS: There are several ophthalmic entities that the oncologist should be aware of including leukemic optic nerve infiltration, PVRL, paraneoplastic syndromes as they related to the eye, and adverse effects of therapeutics. Unfortunately, given the rarity of some of these entities [e.g., paraneoplastic optic neuropathy (PON), cancer-associated retinopathy (CAR)], diagnosis can be difficult and treatment options are often limited. CONCLUSIONS: Oncologists can develop a set of basic ophthalmology examination skills that will help to triage and manage patient eye complaints. In certain instances, oncologists have the potential to avert devastating vision loss with early recognition of neuro-ophthalmic complications.

Pharmacologic Mydriasis Secondary to Topical Glycopyrronium Tosylate Cloths: Clinical Characterization From a Multicenter Analysis.

BACKGROUND: Topical glycopyrronium tosylate (GT) is an anticholinergic medication for treatment of axillary hyperhidrosis. Pharmacologic mydriasis and anisocoria from topical GT has been reported and may be underrecognized. This study aims to clinically characterize patients presenting with pharmacologic mydriasis from exposure to this medication. METHODS: This study is a retrospective observational case series. A multicenter chart review of 16 patients diagnosed with pharmacologic mydriasis secondary to topical GT was performed. RESULTS: Eight patients (50.0%) were age 18 years and younger, and 14 patients (87.5%) were female. Unilateral mydriasis (anisocoria) occurred in 14 patients (87.5%). Fourteen patients (87.5%) did not initially volunteer topical GT as a "medication," and the history of topical GT exposure needed to be elicited with further questioning. Hand hygiene details were known for 12 patients, and all reported that they did not wash their hands after GT application. Six patients (37.5%) were soft contact lens users. One patient had possible exposure through a family member's use of the medication. Ocular symptoms were common (blurry vision [11 patients, 68.8%] and eye dryness [7 patients, 43.8%]), but systemic anticholinergic symptoms were uncommon (such as constipation [1 patient, 6.3%] and urinary symptoms [3 patients, 18.8%]). CONCLUSIONS: Mydriasis associated with topical GT seems to be a consequence of local exposure rather than systemic toxicity. Because patients may not volunteer topical GT as a medication, eliciting a history of exposure often requires further specific questioning. Soft contact lens wear and poor postapplication hand hygiene seem to be associated with mydriasis in GT use.

The use of multimodal imaging in the evaluation of a patient with central retinal artery occlusion in the setting of asteroid hyalosis: a case report.

BACKGROUND: A central retinal artery occlusion (CRAO) is an ophthalmic emergency due to its strong association with cerebrovascular and cardiovascular morbidity and mortality. A timely diagnosis is necessary but difficult in the setting of dense asteroid hyalosis, as typical fundoscopic findings can be obscured. We present a case where multimodal imaging in an eye with an obscured fundus could lead to timely diagnosis and management of CRAO in a patient with acute vision loss. CASE PRESENTATION: A 94-year-old Caucasian woman with a history of exudative macular degeneration presented to the retina clinic with acute vision loss in one eye over the course of an afternoon. The patient had dense asteroid hyalosis, and a direct retinal exam was not possible. Multimodal imaging suggested a CRAO diagnosis. The patient received digital ocular massage directly prior to undergoing fluorescein angiography (FANG), which confirmed the diagnosis. The patient was transported from clinic to the emergency room for an emergency stroke workup, which revealed a spontaneous echo in the left atrial appendage, and the patient was started on antiplatelet therapy. When she presented for follow-up within a week, the patient noted that her vision had improved at the time of digital ocular massage and continued to improve thereafter. Her FANG showed marked reperfusion of the retina, and she subsequently has completely regained her baseline visual acuity. CONCLUSIONS: Multimodal imaging is useful in evaluating visual loss in patients with acute vision loss. In addition, ocular massage is a simple, low-risk intervention that may have benefit in the treatment of acute CRAO. Patients who present to ophthalmologists with an acute CRAO need an emergency referral for evaluation of cerebrovascular and cardiovascular comorbidities.

Retinal Detachment and Laser Retinopexy Rates During the COVID-19 Pandemic.

Purpose: At the start of March 2020, the COVID-19 pandemic placed an unprecedented burden on the healthcare system. Throughout much of the United States, shelter-in-place orders were imposed to reduce transmission. A consequence of this crisis, risk mitigation orders, and patient fear of exposure may have led to underutilization of emergency services. We aimed to quantify 2 emergent interventions in ophthalmology, specifically acute laser retinopexy procedures and retinal detachment repair, to determine whether these procedures decreased during the start of the pandemic. Methods: All retinal detachment surgeries and laser retinopexy procedures were identified using Current Procedural Terminology codes. Rate data during the study period (March 1 through May 31, 2020) was compared to historical data from the year prior (March 2019 through May 2019; epoch 1) as well as the immediate 3 months prior to the study period (December 2019 through February 2020; epoch 2). Results: Combined procedures fell by 38.5% (P = .01) and 36.0% (P = .02) when compared to epoch 1 and epoch 2, respectively. The rate of laser retinopexy procedures fell by 45.5% (P = .02) and 33.0% (P = .14) when compared to epoch 1 and epoch 2, respectively. The rate of retinal detachment repair fell by 29.4% (P = .24) and 38.0% (P = .07) when compared to epoch 1 and epoch 2, respectively. Conclusions: Procedures fell during the study period, suggesting underutilization of emergent ophthalmology care. It is necessary for ophthalmologists to emphasize the need to seek care for concerning symptoms.

Ophthalmic Drug Discovery in the United States over the past Two Decades.

PURPOSE: Pharmaceutical development has slowed since the turn of the century and there has been recent legislation passed that aims to accelerate drug approval. Ophthalmic drug discovery has unique challenges that may benefit from these legislative changes. We report original pharmaceutical approvals for ophthalmic indications in order to determine whether ophthalmic drug approvals are similarly decreasing. METHODS: This observational study extracted all original drug approvals for ocular use from the publicly available Drugs@FDA database from January 1st, 2000 through December 31st, 2019. Drug approvals included new molecular entities, biologic license applications, as well as reformulations, combinations and new indication approvals. Data mined from each approval included: approval date, active ingredient, manufacturer, new drug application classification type, priority or standard review, and orphan drug status. Data were analyzed in four 5-year time periods. RESULTS: A total of 99 ophthalmic agents were approved for ocular use during the study period. On average, drug approvals rose by 2.2 approvals per 5-year quartile. Out of these, new molecular entities and biologics constituted 22% of all drug approvals and fell at an average rate of 0.4 approvals per quartile. CONCLUSION: The majority of ophthalmic drug approvals represented reformulations of prior pharmaceuticals. In line with the overall industry, new molecular entities and novel biologics fell on average during the study period. Legislation that aims to ease challenges to drug approval may be beneficial to increase novel therapeutic development but should be weighed against the risks of decreased patient safety or drug efficacy.

Ocular Cosmetics: Public Safety Problem or Harmless Products?

PURPOSE: This perspective explores the safety profile of ocular cosmetics and explores the role ophthalmologists can play in mitigating potential ocular harm from unsafe products. METHODS: N/A. RESULTS: Cosmetics and personal care products represent a large industry that is currently unregulated in any meaningful way. Products intended for use around the eyes carry a risk of serious side effects including contact dermatitis and bacterial infection. Currently, legislation has been proposed to change regulation to provide more meaningful oversight of cosmetics. CONCLUSIONS: Ophthalmologists are often the first to recognize patterns in harmful products intended for use around the eye and can help mitigate potential future ocular harm by reporting adverse events to the Food and Drug Administration and by advocating for cosmetic regulation change.