Bilateral Occlusive Retinal Vasculitis in a Patient with Dermatomyositis.

A 48-year-old woman with a history of dermatomyositis (DMS) presented with 2 weeks of worsening myalgias, weakness, and diffuse edema following cessation of her systemic immunosuppression and subsequently developed severe bilateral vision loss consistent with bilateral frosted branch angiitis. Multimodal imaging was performed, and the patient was successfully treated with pulse-dose steroids and intravenous immunoglobulin, as well as intravitreal aflibercept. Ophthalmic involvement of DMS is typically limited to episcleritis, conjunctivitis, and uveitis. We present an uncommon case of bilateral occlusive retinal vasculitis with frosted branch angiitis in a patient with DMS. The significant improvement anatomically and in visual acuity in our patient suggests a role of combined anti-vascular endothelial growth factor and systemic immunosuppression in the management of DMS -related frosted branch angiitis. We suggest that retinal vasculitis should be considered in patients with known DMS and acute vision loss, with prompt referral for ophthalmologic evaluation.

Socioeconomic and Demographic Factors Contributing to COVID-19-Related Delays and Reductions in Primary Retinal Detachment Repair in a US Hot Spot.

Purpose: This work evaluates demographic and socioeconomic predictors of delayed care for rhegmatogenous retinal detachments (RRDs) during the spring 2020 COVID-19 shutdown in a US hot spot. Methods: This multicenter, retrospective, case-control study took place in 3 academic vitreoretinal practices in metropolitan Boston. Consecutive patients treated for RRD during the COVID-19 state of emergency were compared with patients treated during the same period in 2018 and 2019. The primary outcome was macula status for RRD. Secondary outcomes included visual acuity, symptom duration, proportion with proliferative vitreoretinopathy, time to procedure, method of repair, and patient demographics. Results: The total number of acute RRD decreased by 13.7% from 2018 to 2020 and 17.2% from 2019 to 2020. Symptom duration was significantly longer in 2020 than 2018 and 2019 (median, 7 vs 4 days) with a higher proportion of macula-off detachments (80 of 125 [64%] in 2020 vs 75 of 145 [51.7%] in 2018 and 78 of 151 [51.6%] in 2019). The 2020 cohort included significantly fewer patients in the racial and/or ethnic minority group than in 2019 (P = .02), and use of low-income, government-sponsored health insurance was a predictor of macula-off status during the pandemic (P = .04). Conclusions: RRDs during the spring 2020 COVID-19 lockdown were more likely to be macula-off at presentation. Because sociodemographic factors including race, ethnicity, and income level were associated with deferral of care, ophthalmologists should consider measures targeting vulnerable populations to avoid preventable vision loss as the pandemic continues or in future health care emergencies.

Chorioretinal paracoccidioidomycosis treated with intravitreal voriconazole and therapeutic vitrectomy.

PURPOSE: To report a case of aggressive chorioretinal paracoccidioidomycosis requiring treatment with systemic antifungal agents, frequent intravitreal voriconazole injections, and surgical excision. OBSERVATIONS: A Brazilian man in his mid-30s with a history of chronic, biopsy-proven cutaneous paracoccidioidomycosis, chronic sinusitis, and perichondritis secondary to paracoccidioidomycosis presented with profound vision loss. He was found to have significant vitreous inflammation and a large chorioretinal lesion in the posterior pole concerning for ocular involvement. He was treated initially with combined topical and systemic steroids as well as systemic antifungals and antibiotics, then with serial intravitreal voriconazole injections resulting in a significant reduction of intraocular inflammation and subretinal fluid. The residual tractional retinal detachment from the chorioretinal lesion was addressed surgically by pars plana vitrectomy. CONCLUSION AND IMPORTANCE: Intravitreal voriconazole can be an effective adjuvant treatment for the vitreous inflammation and subretinal fluid associated with chorioretinal paracoccidioidomycosis. Surgical intervention may be indicated in cases complicated by tractional retinal detachment.

Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy.

In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of novel cytokines involved in the pathogenesis of PDR provides candidate therapeutic targets that may stand alone or work synergistically with current therapies in the management of diabetic retinopathy. Undiluted vitreous humor specimens were collected from 74 patients undergoing vitrectomy for various vitreoretinal disorders. Quantitative immunoassay was performed for a panel of 36 neuroinflammatory cytokines in each specimen and assessed to identify differences between PDR (n = 35) and non-PDR (n = 39) patients. Levels of interleukin-8 (IL-8), IL-15, IL-16, vascular endothelial growth factor (VEGF), VEGF-D, c-reactive protein (CRP), serum amyloid-A (SAA), and intracellular adhesion molecule-1 (ICAM1) were significantly increased in the vitreous of PDR patients compared to non-PDR patients (p < 0.05). We report novel increases in IL-15 and IL-16, in addition to the expected VEGF, in the human vitreous humor of patients with PDR. Additionally, we confirm the elevation of ICAM-1, VCAM-1, SAA, IL-8 and CRP in the vitreous of patients with PDR, which has previously been described.

Risk factors for fellow eye treatment in protocol T.

PURPOSE: To identify risk factors for fellow eye treatment of diabetic retinopathy with Vascular Endothelial Growth Factor (VEGF) injections during the Diabetic Retinopathy Clinical Research Network (DRCR.Net) Protocol T trial METHODS: In this post-hoc analysis of randomized clinical trial data, Cox regression analysis was performed at 52 and 104 weeks to determine risk factors for treatment in 360 fellow eyes. Survival analysis was performed to determine mean time to treatment based upon medication used. RESULTS: Of 360 fellow eyes, 142 (39.4%) required treatment between weeks 4 and 104. Risk factors predicting a lower likelihood of year 1 treatment included older subject age (Hazard Ratio [HR]=0.98, 95% CI 0.96-0.99; p = 0.02) and higher baseline study eye ETDRS score (HR=0.98, 95% CI 0.97-0.99, p = 0.04). Center-involving DME at baseline in the fellow eye was predictive of a higher treatment need at both 52 (HR=1.89, 95% CI 1.42-2.51, p < 0.0001) and 104 weeks (HR=2.68, 95% CI 1.75-4.11, p < 0.0001). Subjects treated in the study eye with aflibercept (HR=0.574, 95% CI 0.371-0.887, p = 0.013) and ranibizumab (HR=0.58, 95%CI 0.36-0.94, p = 0.03) were less likely to require first year fellow eye injection than subjects treated with bevacizumab although this difference was no longer significant at week 104 (aflibercept HR=0.77, 95% CI 0.52-1.16, p = 0.21; ranibizumab HR=0.66, 95% CI 0.43-1.00, p = 0.05). Mean time to treatment was significantly shorter in the bevacizumab group (bevacizumab 25.83 weeks, aflibercept 38.75 weeks, ranibizumab 34.70 weeks (p=0.012)). CONCLUSION: Bilateral treatment with intravitreal anti-VEGF injections was common during the DRCR.net Protocol T. Medication choice may impact the risk of fellow eye treatment.

Discontinuation and nonpublication of interventional clinical trials conducted in ophthalmology.

OBJECTIVE: Discontinuation of interventional clinical trials and nonpublication of completed trials represent a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in ophthalmology patients. METHODS: A retrospective, cross-sectional study of ophthalmology-based interventional clinical trials in ClinicalTrials.gov dating back to 1972 was conducted. χ2 tests were used to determine any potential associations between trial characteristics and trial completion. The Mann-Whitney U test was used to compare median time to publication between academic and industry-sponsored trials. RESULTS: Of 2926 included trials, 413 (14%) were discontinued early with only 19 of these studies being published. A total of 2027 (81%) of the 2513 completed trials were not published. A total of 277 419 participants were enrolled in unpublished, completed trials, whereas an estimated 20 843 participants were enrolled in trials that were never completed and never to led to publication. The odds of study discontinuation among industry-sponsored trials were 27% greater than government/academia-sponsored (National Institutes of Health, National Eye Institute, National Institutes of Health Clinical Center, U.S. and foreign university-based teaching hospitals) trials (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.03-1.57, p = 0.03). Furthermore, the odds of nonpublication among industry-sponsored trials were 55% more than those funded by government/academia (OR = 1.55, 95% CI 1.27-1.89, p < 0.0001). CONCLUSIONS: The nonpublication of many completed trials and of preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Greater transparency through the publication of the entire spectrum of clinical trials' results as well as those that are terminated early could minimize publication bias and thus lead to a more robust medical literature.

Intraocular foreign bodies: A review.

Intraocular foreign body injuries may result in a wide range of intraocular pathology and visual outcomes based on the mechanism of injury, type of foreign body, and subsequent complications. We have reviewed the literature to describe the epidemiology and mechanisms of such injuries; types of foreign bodies; imaging tools for diagnosis; current trends in management, presurgical, and surgical interventions; as well as visual prognosis and potential complications. The purpose of this review is to familiarize clinicians with the recent advances in diagnosis and management of such injuries.

Mechanisms of mouse neural precursor expansion after neonatal hypoxia-ischemia.

Neonatal hypoxia-ischemia (H-I) is the leading cause of brain damage resulting from birth complications. Studies in neonatal rats have shown that H-I acutely expands the numbers of neural precursors (NPs) within the subventricular zone (SVZ). The aim of these studies was to establish which NPs expand after H-I and to determine how leukemia inhibitory factor (LIF) insufficiency affects their response. During recovery from H-I, the number of Ki67(+) cells in the medial SVZ of the injured hemisphere increased. Similarly, the number and size of primary neurospheres produced from the injured SVZ increased approximately twofold versus controls, and, upon differentiation, more than twice as many neurospheres from the damaged brain were tripotential, suggesting an increase in neural stem cells (NSCs). However, multimarker flow cytometry for CD133/LeX/NG2/CD140a combined with EdU incorporation revealed that NSC frequency diminished after H-I, whereas that of two multipotential progenitors and three unique glial-restricted precursors expanded, attributable to changes in their proliferation. By quantitative PCR, interleukin-6, LIF, and CNTF mRNA increased but with significantly different time courses, with LIF expression correlating best with NP expansion. Therefore, we evaluated the NP response to H-I in LIF-haplodeficient mice. Flow cytometry revealed that one subset of multipotential and bipotential intermediate progenitors did not increase after H-I, whereas another subset was amplified. Altogether, our studies demonstrate that neonatal H-I alters the composition of the SVZ and that LIF is a key regulator for a subset of intermediate progenitors that expand during acute recovery from neonatal H-I.

Opposite effect of inflammation on subventricular zone versus hippocampal precursors in brain injury.

OBJECTIVE: Inflammation promotes epidermal wound healing but is considered detrimental to recovery from central nervous system injury. Sick infants have increased levels of cytokines in their cerebrospinal fluid that correlate with poor neurological outcome. In this study, we investigated the role of neuroinflammation and more specifically interleukin 6 (IL-6) in the amplification of subventricular zone (SVZ) and subgranular zone (SGZ) neural precursors after neonatal brain injury. METHODS: Neonatal hypoxia/ischemia (H/I) was induced in P6 rat pups, and IL-6 was quantified with or without indomethacin administration. Neural precursor responses were evaluated by neurosphere assays as well as by stereological analyses. Studies were performed to determine how IL-6 and leukemia-inhibiting factor (LIF) affect SVZ cell expansion, proliferation, and self-renewal. RESULTS: Consistent with earlier studies, medially situated SVZ cells expanded after H/I. Contrary to our expectations, indomethacin significantly decreased both the initial reactive increase in these precursors and their ability to self-renew. By contrast, indomethacin increased proliferation in the SGZ and lateral SVZ. Indomethacin diminished the accumulation of microglia/macrophages and IL-6 production after H/I. In vitro IL-6 enhanced neurosphere growth, self-renewal, and tripotentiality and was more effective than LIF in promoting self-renewal. Enhanced precursor self-renewal also was obtained using prostaglandin E2, which is downstream of cyclooxygenase 2 and a target of indomethacin. INTERPRETATION: These data implicate neuroinflammation and in particular IL-6 as a positive effector of primitive neural precursor expansion after neonatal brain injury. These findings have important clinical implications, as indomethacin and other anti-inflammatory agents are administered to premature infants for a variety of reasons.