First Report: Rare RNF213 Variant Associated with Familial Moyamoya Disease in an African American Family.

OBJECTIVE: To investigate potential genetic susceptibility for moyamoya disease (MMD) in an African American family. MATERIALS AND METHODS: Neurovascular imaging and analyses of MMD susceptibility genes RNF213 and/or ACTA2 in a young proband with MMD and two first-degree relatives. RESULTS: The proband presented with pseudobulbar affect and chorea, then had a right hemispheric ischaemic stroke and rapidly fatal course. One relative had a mild haemorrhagic thalamic stroke and clinically silent ischaemic infarct. Despite evidence of slowly progressive disease, he remained clinically stable. Another relative was neurologically intact with normal cerebrovascular imaging to date. All three have the rare R4131C (p.Arg4131Cys or p.R4131C, c.12391C>T) variant of the RNF213 gene. They are the first Black people and only the 5th family worldwide known to harbour this variant. MMD was confirmed in both of the patients with neurological events. CONCLUSIONS: Our report provides compelling evidence that MMD is a clinically complex, heritable genetic disease. It supports the probable pathogenicity of R4131C. Furthermore, it illustrates the wide phenotypic spectrum of R4131C, from asymptomatic carrier to late presenting, mild disease to catastrophic, rapidly fatal childhood disease. To our knowledge, this is also the first report of heritable MMD in a Black family. Finally, this study highlights the importance of racially and ethnically diverse participants in biomedical research.

Prevalence of asteroid hyalosis and systemic risk factors in United States adults.

BACKGROUND/OBJECTIVE: Asteroid hyalosis (AH) is an uncommon clinical entity of unknown aetiology that is associated with older age. Previous epidemiologic studies have reported various systemic and demographic risk factors for AH but remain limited due to regional constraints of their study populations. Additionally, Hispanic and Non-Hispanic black populations remain under sampled. The aim of this study is to examine the prevalence of asteroid hyalosis in the United States and identify associated factors at a national level. SUBJECTS/METHODS: This is a population-based, cross-sectional study of 5578 subjects aged 40 and older from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES). The primary outcome measured was asteroid hyalosis on retinal imaging in any eye. Evaluated risk factors included patient demographics, medical history, body measures, serum markers, and fundus photography findings. RESULTS: Prevalence of asteroid hyalosis was 0.86% overall, 0.86% in Caucasians, 0.79% in African-Americans, and 0.88% in Hispanics. Asteroid hyalosis was associated with older age (p < 0.0001, 95% confidence interval [CI], 0.06-0.12; odds ratio [OR], 1.09) but not ethnicity or sex. After adjusting for age, greater bodyweight (p = 0.049; 95% CI, 0.001-0.04; OR, 1.02), and history of myocardial infarction (p = 0.022; 95% CI, 0.07-1.55; OR, 2.36) were also found to be significant risk factors. CONCLUSION: Asteroid hyalosis is a rare entity in the US associated with older age, greater body weight, and prior history of MI. A potential relationship between AH and cardiovascular disease remains plausible.

Clinical Outcomes of 27-Gauge Pars Plana Vitrectomy for Diabetic Tractional Retinal Detachment Repair.

Purpose: To analyze the clinical outcomes of 27-gauge pars plana vitrectomy (PPV) repair of diabetic tractional retinal detachment (TRD) of various severities. Methods: This retrospective case series examined the outcomes of 27-gauge PPV to repair diabetic TRD from 2016 to 2020. The effect of medical and ophthalmologic history parameters and baseline detachment characteristics on visual acuity (VA) and retinal reattachment was analyzed. A grading system was established to stage the severity of the baseline vitreoretinal traction or detachment and compare the visual and anatomic outcomes between stages. Results: The study comprised 79 eyes (79 patients). The overall redetachment rate was 10.1% (8/79). The proportion of eyes with severe visual impairment (worse than 20/200) decreased from 81.0% (64/79) preoperatively to 56.9% (37/65) 6 months postoperatively (P < .001). Worse preoperative logMAR VA was associated with greater odds of redetachment (P = .017) and worse postoperative VA (P < .001). Insulin dependence was associated with better VA at 6 months (P = .017). A shorter known duration of diabetes (P = .026) and evidence of neovascularization of the iris (NVI) or angle (P = .004) were associated with worse visual outcomes. Eyes with detachment involving the posterior pole extending beyond the equator had worse VA at 6 months (P = .048). Conclusions: The primary reattachment rate after 27-gauge PPV was 89.9%. There was significant VA improvement, with a roughly 40% reduction in the number of eyes with severe visual impairment by the final follow-up. Insulin dependence, duration of diabetes, presence of NVI before surgery, and baseline posterior pole detachment extending beyond the equator were predictors of visual outcomes.

Clinical Applications of Machine Learning in the Management of Intraocular Cancers: A Narrative Review.

Purpose: There is great promise in use of machine learning (ML) for the diagnosis, prognosis, and treatment of various medical conditions in ophthalmology and beyond. Applications of ML for ocular neoplasms are in early development and this review synthesizes the current state of ML in ocular oncology. Methods: We queried PubMed and Web of Science and evaluated 804 publications, excluding nonhuman studies. Metrics on ML algorithm performance were collected and the Prediction model study Risk Of Bias ASsessment Tool was used to evaluate bias. We report the results of 63 unique studies. Results: Research regarding ML applications to intraocular cancers has leveraged multiple algorithms and data sources. Convolutional neural networks (CNNs) were one of the most commonly used ML algorithms and most work has focused on uveal melanoma and retinoblastoma. The majority of ML models discussed here were developed for diagnosis and prognosis. Algorithms for diagnosis primarily leveraged imaging (e.g., optical coherence tomography) as inputs, whereas those for prognosis leveraged combinations of gene expression, tumor characteristics, and patient demographics. Conclusions: ML has the potential to improve the management of intraocular cancers. Published ML models perform well, but were occasionally limited by small sample sizes owing to the low prevalence of intraocular cancers. This could be overcome with synthetic data enhancement and low-shot ML techniques. CNNs can be integrated into existing diagnostic workflows, while non-neural networks perform well in determining prognosis.

Perioperative systemic blood pressure parameters and clinical outcomes following 27g vitrectomy for diabetic tractional detachment repair.

BACKGROUND: Extremes in perioperative blood pressures are known risk factors for adverse outcomes after surgical interventions. There is scarce literature studying these parameters as predictors of outcomes after ocular surgery. METHODS: This was a retrospective single-centre interventional cohort analysis to evaluate the relationship between perioperative (preoperative and intraoperative) blood pressure value and variability and postoperative visual and anatomic outcomes. Included were patients who underwent primary 27-gauge (27g) vitrectomy for repair of diabetic tractional retinal detachment (DM-TRD) with at least 6 months of follow-up. Univariate analyses were conducted via independent two-sided t-tests and Pearson's χ2 tests. Multivariate analyses were conducted via generalised estimating equations. RESULTS: 71 eyes of 57 patients were included in the study. Higher preprocedure mean arterial pressure (MAP) was associated with fewer Snellen lines of improvement at postoperative month 6 (POM6) (p<0.01). Higher mean intraoperative systolic blood pressure (SBP), diastolic blood pressure and MAP were associated with visual acuity 20/200 or worse at POM6 (p<0.05). Patients with sustained intraoperative hypertension had 1.77 times the risk of visual acuity 20/200 or worse at POM6 compared with those without sustained intraoperative hypertension (p=0.006). Higher SBP variability was associated with worse visual outcomes at POM6 (p<0.05). Blood pressure was not associated with macular detachment at POM6 (p>0.10). CONCLUSIONS: Higher average perioperative blood pressure and blood pressure variability are associated with worse visual outcomes in patients undergoing 27g vitrectomy for DM-TRD repair. Patients with sustained intraoperative hypertension were approximately twice as likely to have visual acuity 20/200 or worse at POM6 compared to those without sustained intraoperative hypertension.

Tissue glue for management of large iris cyst.

Purpose: To present a novel technique utilizing fibrin glue-assisted adhesion as adjuvant to fine needle aspiration for management of post-surgical peripheral iris stromal cyst. Observations: A 61 year-old male presented with a 4.20 × 7.56 × 8.22 mm well-circumscribed, fluid-filled peripheral cystic lesion involving the central visual axis with local posterior displacement of the intraocular lens. Surgical drainage was performed with the adjuvant use of fibrin glue to enhance the annealing of cyst walls. The patient tolerated the procedure without significant complications. At final post-operative visit, vision improved to 20/30 and there was no recurrence of the cyst. Conclusions and importance: To our knowledge, this is the first report describing the use of fibrin glue to successfully treat a post-surgical peripheral iris stromal cyst. Fibrin glue may serve as an effective alternative to ethanol and sclerosing agents in the management of iris cysts.

Multiple evanescent white dot syndrome-like reaction associated with ipilimumab and nivolumab immune checkpoint inhibitor therapy for metastasis of choroidal melanoma.

PURPOSE: To present a rare case of multiple evanescent white dot syndrome (MEWDS)-like presentation associated with immune checkpoint inhibitor therapy for metastatic choroidal melanoma. OBSERVATIONS: A 67-year-old non-myopic Caucasian female presented with bilateral worsening vision, flashes, and floaters after receiving two doses of ipilimumab and nivolumab for metastatic class 2 peripheral choroidal melanoma. Fundus imaging of the right eye revealed hypopigmented, extra-foveal scattered chorioretinal lesions with foveal granularity. Fluorescein angiogram and autofluorescence of the right eye demonstrated corresponding hyperfluorescent and hyperautofluorescent lesions in a wreath-like configuration. Optical coherence tomography of the right eye revealed subretinal fluid. Due to concurrent systemic side effects, checkpoint inhibitor therapy was paused and the patient was started on oral prednisone. At her one month follow up visit, her vision in her right eye returned to baseline and subretinal fluid resolved. CONCLUSIONS: This is the first reported case of a MEWDS-like chorioretinopathy after two cycles of ipilimumab/nivolumab therapy for metastatic choroidal melanoma. As immune checkpoint inhibitor therapy is still an evolving field, more research is needed to characterize ocular side effect profiles of these agents.