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Inherited retinal dystrophies cause progressive vision loss and are major contributors to blindness worldwide. Advances in gene therapy have brought molecular approaches into the realm of clinical trial for these incurable illnesses. Select phase I, II and III trials are complete and provide some promise in terms of functional outcomes and safety; although questions do remain over the durability of their effects and the prevalence of inflammatory reactions. This article reviews gene therapy as it can be applied to inherited retinal dystrophies, provides an update of results from recent clinical trials, and discusses the future prospects of gene therapy and genome surgery. I. Introduction: The retina transmits visual information to the brain, and is thus delicate neural tissue without plasticity [1]. An unfortunate consequence is that cells of the retina affected by inherited dystrophies do not regenerate in humans. For this reason, treatment of retinal degeneration is extremely difficult as photoreceptor death results in irreversible blindness [1, 2]. For approximately 1 in 2000 individuals worldwide, inherited retinal dystrophies (IRDs) cause progressive photoreceptor loss and eventual blindness [3]. The pathophysiology of various §

Aim: To perform an independent validation of deep learning (DL) algorithms for automated scleral spur detection and measurement of scleral spur-based biometric parameters in anterior segment optical coherence tomography (AS-OCT) images. Methods: Patients receiving routine eye care underwent AS-OCT imaging using the ANTERION OCT system (Heidelberg Engineering, Heidelberg, Germany). Scleral spur locations were marked by three human graders (Reference, Expert, and Novice) and predicted using DL algorithms developed by Heidelberg Engineering that prioritize a false positive rate <4% (FPR4) or true positive rate >95% (TPR95). Performance of human graders and DL algorithms were evaluated based on agreement of scleral spur locations and biometric measurements with the Reference Grader. Results: 1,308 AS-OCT images were obtained from 117 participants. Median differences in scleral spur locations from reference locations were significantly smaller (p<0.001) for the FPR4 (52.6±48.6μm) and TPR95 (55.5±50.6μm) algorithms compared to the Expert (61.1±65.7μm) and Novice (79.4±74.9μm) Graders. Inter-grader reproducibility of biometric measurements was excellent overall for all four (intraclass correlation coefficient [ICC] range 0.918-0.997). Inter-grader reproducibility of the Expert Grader [0.567-0.965] and DL algorithms [0.746-0.979] exceeded that of the Novice Grader [0.146-0.929] for images with narrow angles, defined as angle opening distance 500μm from the scleral spur (AOD500) <150μm. Conclusions: DL algorithms on the ANTERION approximate expert-level measurement of scleral spur-based biometric parameters in an independent patient population. These algorithms could enhance clinical utility of AS-OCT imaging, especially for evaluating patients with angle closure and performing intraocular lens (IOL) calculations.

Purpose To assess the potential efficacy of broad internal limiting membrane peeling with adjunctive plasma–thrombin instillation to treat large macular holes and to make qualitative comparisons to internal limiting membrane peeling without adjunctive treatment and internal limiting membrane peeling with inverted and free internal limiting membrane flaps. Methods A systematic literature review and a retrospective case series. Participants in the case series (N = 39) had idiopathic macular holes larger than 400 µm as measured on spectral-domain optical coherence tomography and underwent pars plana vitrectomy, internal limiting membrane peeling, placement of autologous plasma and bovine thrombin over the hole, and gas tamponade. Repeat imaging and clinical data were collected from 1, 2, 3, 6, and 12 months postoperatively. Results Macular hole closure rate was 97%; 82% had U-type closures. At 12 months, 11% had defects in the external limiting membrane and 22% in the ellipsoid zone. This closure rate is similar to prior studies of internal limiting membrane flaps, while the U-type closure rate and retinal layer restoration compare favorably to those reported for internal limiting membrane peeling alone and internal limiting membrane flaps; 75% experienced a three-line improvement in visual acuity by 6 months, which exceeds results by either method. Conclusion Plasma–thrombin instillation over macular holes may be a less-complicated alternative adjunct to internal limiting membrane flaps that can achieve similar outcomes when combined with internal limiting membrane peeling.