High Reliability of Cone Cell Measurements With Adaptive Optics Scanning Laser Ophthalmoscopy in a Simulated Real-Life Clinical Setting.

BACKGROUND AND OBJECTIVE: The authors evaluated adaptive optics scanning laser ophthalmoscopy (AO-SLO) in a simulated real-life clinical setting to identify factors that impact its reliability in this setting. PATIENTS AND METHODS: For this prospective study, macular cones were imaged in five healthy eyes using an AO-SLO prototype machine. Multilevel mixed-effect regression was used to compare the cone densities across different analysis parameters. Intergrader, intragrader, interphotographer, and intersession reliabilities were determined with intraclass correlation coefficients (ICCs). RESULTS: Cone densities in the largest measurement window size, 150 µm × 150 µm, were most consistent. Image quality strongly impacted cone analysis. Intragrader and intergrader ICCs were 0.99 and 0.98, respectively. Intersession and interphotographer reliability both had an ICC of 0.72. CONCLUSIONS: Larger measurement window sizes and higher image quality improve the reliability of cone density measurement. Although there were excellent intergrader and intragrader reliabilities, intersession and interphotographer reliabilities were not as robust. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:228-235.].

Phage Immunoprecipitation Sequencing of Autoantigens in Autoimmune Retinopathy.

PURPOSE: To identify autoantigens in autoimmune retinopathy patients by phage immunoprecipitation sequencing (PhIP-Seq), a new technique for autoantigen discovery. METHODS: PhIP-Seq was used to sequence putative autoantibodies in plasma from 11 patients with autoimmune retinopathy and eight controls. We compared the autoantibodies' molecular weights with those of proteins detected by Western blot. RESULTS: Several autoantigens were found in cases and not detected in the controls. Autoantigens RTN3, PRPF6, TRPC6, and B3GNT8, four proteins expressed in the retina, were detected in plasma as autoantibodies from one patient each and no controls. Only one patient had an autoantibody, B3GNT8 (43.4 kDa), within a similar weight range as that detected by antiretinal antibody Western blot (42 kDa). Autoantibody POLR3A, which has a well-characterized role in scleroderma, was detected in two cases and no controls. CONCLUSION: PhIP-Seq detected autoantigens that are expressed in the retina as well as scleroderma-related autoantigens in autoimmune retinopathy patients.

Outcomes in Autoimmune Retinopathy Patients Treated With Rituximab.

PURPOSE: To evaluate clinical and ancillary testing, including adaptive optics, outcomes in autoimmune retinopathy (AIR) patients treated with rituximab. DESIGN: Retrospective, interventional case series. METHODS: patients: Sixteen AIR patients treated with rituximab. OBSERVATION PROCEDURES: All patients were treated with a loading and maintenance dose schedule of intravenous rituximab. Visual acuity (VA), electroretinography (ERG), and spectral-domain optical coherence tomography (SDOCT) and visual field (VF) results were recorded. A subset of patients was also imaged using adaptive optics scanning laser ophthalmoscopy (AO-SLO). MAIN OUTCOME MEASURES: Rates of VA change before vs after rituximab initiation were compared with mixed-model linear regression. RESULTS: The rate of visual decline was significantly less after rituximab initiation compared with the rate of visual decline prior to rituximab initiation (P = .005). Seventy-seven percent of eyes had stable or improved VA 6 months after rituximab initiation. Amplitudes and implicit times on ERG, mean deviation on VF, central subfield mean thickness, and total macular volume did not decrease to a significant degree over the rituximab treatment period. Six eyes had serial AO-SLO imaging. Cone densities did not change significantly over the treatment period. CONCLUSION: VA was stable or improved in a majority of AIR patients while they were being treated with rituximab. OCT and ERG parameters, as well as AO-SLO cone densities, were stable during treatment. Studies with additional patients and longer follow-up periods are needed to further explore the utility of rituximab in the management of AIR.

African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans.

PURPOSE: To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS: Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS: In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS: In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.