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Thirty-eight patients from 37 families with retinitis pigmentosa (RP) underwent macular 6 × 6-mm swept-source optical coherence tomography angiography (SS-OCTA) and 30° near-infrared fundus autofluorescence (NIR-FAF) acquisitions in one eye. Superficial vascular complex (SVC), deep capillary complex (DCC) and choriocapillaris (CC) angiograms were registered with NIR-FAF acquisitions to comparatively assess subjects with and without central area of preserved NIR-FAF (APA). On the subset of patients showing an APA, the vessel densities for SVC and DCC and flow deficits for CC were assessed in three directions (superior, inferior and temporal) from the fovea and compared to healthy 1:1 age-matched controls. Nine patients with no APA had evidence of severe central OCTA alterations at all levels, especially in the DCC. In the other 29 subjects presenting APA, all OCTA parameters were similar to healthy eyes within the APA, where the retina preserves its structural integrity. Outside the APA, both the DCC and CC were significantly reduced in all directions. These alterations are probably related to the outer retinal atrophy outside the APA. Comparing OCTA to other imaging modalities is helpful to determine the potential interest of OCTA findings as an outcome measure for disease status and progression.

Purpose: To describe outer retinal structure in patients with Best vitelliform macular dystrophy (BVMD) using spectral-domain optical coherence tomography (OCT) and correlate these results with best-corrected visual acuity (BCVA) and patient age., Design: Retrospective cross-sectional study., Methods: Patients with molecularly confirmed BVMD were compared with normal control subjects (NCs). A complete clinical evaluation was performed, including BCVA, fundus photography, spectral-domain OCT, and fundus autofluorescence. Spectral-domain OCT images were analyzed to determine the stage of the lesion, the central macular thickness (CMT), the foveal outer nuclear layer (ONL) thickness, and tomographic structural changes., Results: Forty-two patients with BVMD (42 eyes) with a molecular diagnosis and 42 NCs (42 eyes) were included. Clinical stages (Gass clinical classification) were distributed as follows: 4.8% for stage 1, 23.8% for stage 2, 16.6% for stage 3, 45.2% for stage 4, and 9.5% for stage 5. The presence of subretinal fluid and vitelliform material was noted in 76% and 79% of the BVMD eyes examined, respectively, and was not associated with BCVA modification (P = .758 and P = .968, respectively). The median ONL thickness was significantly lower compared with the NCs (P < .001). BCVA was significantly correlated with stage (R = 0.710; P < .01), age (R = 0.448; P < .01), CMT (R = -0.411; P < .01), and ONL thickness (R = -0.620; P < .01). The disruption of the external limiting membrane and the ellipsoid zone was associated with a decreased BCVA (P < .001 for both). Among the 32 eyes with subretinal detachment, photoreceptor outer segment length was significantly correlated with BCVA (R = -0.467; P < .01) and ONL thickness (R = 0.444; P = < .01)., Conclusion: This study shows the correlation between BCVA, age, and spectral-domain OCT features in patients with BVMD. ONL thickness as well as photoreceptor outer segment length are relevant functional correlates and outcome measures to follow photoreceptor impairments and disease progression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

MER tyrosine kinase (MERTK) encodes a surface receptor localized at the apical membrane of the retinal pigment epithelium. It plays a critical role in photoreceptor outer segment internalization prior to phagocytosis. Mutations in MERTK have been associated with severe autosomal recessive retinal dystrophies in the RCS rat and in humans. We present here a comprehensive review of all reported MERTK disease causing variants with the associated phenotype. In addition, we provide further data and insights of a large cohort of 1,195 inherited retinal dystrophies (IRD) index cases applying state-of-the-art genotyping techniques and summarize current knowledge. A total of 79 variants have now been identified underlying rod-cone dystrophy and cone-rod dystrophy including 11 novel variants reported here. The mutation spectrum in MERTK includes 33 missense, 12 nonsense, 12 splice defects, 12 small deletions, two small insertion-deletions, three small duplications, and two exonic and three gross deletions. Altogether, mutations in MERTK account for ∼2% of IRD cases with a severe retinal phenotype. These data are important for current and future therapeutic trials including gene replacement therapy or cell-based therapy., (© 2018 Wiley Periodicals, Inc.)

Purpose: To investigate the elementary temporal properties of electrically evoked percepts in blind patients chronically implanted with an epiretinal prosthesis., Methods: Nine subjects were presented with isolated stimuli of variable duration and pulse rate. Stimulation amplitude was set to the upper comfortable level and a group of 2 × 2 adjacent electrodes was simultaneously activated. First, subjects were asked to verbally describe their visual perception paying particular attention to the time-course of brightness. Then, in subsequent trials, they described the brightness time dependence using a joystick while auditory feedback of joystick position was provided., Results: All subjects described a bright, well-localized percept at stimulus onset. Only one subject reported such a bright, well-localized visual sensation during an entire 10-second stimulation trial. For the remaining eight subjects, it faded more or less rapidly (in four cases <0.5 second) and was often followed by a percept described as less bright, poorly localized, and having different color. Only initial percepts at stimulation onset seemed bright and localized enough to reconstruct a patterned image. Changing stimulation pulse rate influenced the time course of perception only in some cases but the effect was not systematic., Conclusions: Percepts differed considerably across subjects, probably because of the considerable variations in the progression and remodeling processes associated with the disease. Appropriate coding of a patterned image under such conditions appears challenging. Further research of the underlying mechanisms of visual perception upon electrical stimulation of the retina is required to optimize stimulation paradigms and to better establish patient selection criteria.

The Argus II 60 channel epiretinal prosthesis has been developed in order to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date the device has been implanted in 21 subjects as part of a feasibility study. In 6 month post-implantation door finding and line tracking orientation and mobility testing, subjects have shown improvements of 86% and 73%, respectively, for system on vs. system off. In high-contrast Square Localization tests using a touch screen monitor 87% of tested subjects performed significantly better with the system on compared with off. These preliminary results show that the Argus II system provides some functional vision to blind subjects.

This mini-review summarizes our current knowledge concerning the age-related changes that affect the retina. Over the last 10 years, our understanding of the genetics of hereditary retinal diseases has improved considerably. However, the modifications that occur in the retina as a result of aging are still under investigation. In this review, we place particular emphasis on the normal retinal alterations that occur with aging (gene modulation; psychophysical, structural and cellular alterations). We describe the events that occur during the pathological aging process, such as in age-related macular degeneration. Understanding these different modifications is essential if we are to find key players on which to base therapeutic interventions that may help to prevent the passage of normal aging process to the pathological aging process.

Purpose: To define the nature and estimate the molecular weight range of soluble endogenous retinal trophic activities on cone photoreceptor survival in two models of cone degeneration., Methods: Diffusible factors from dissociated retinal cell cultures of 8-day normal-sighted (C57BL/6J) mice were tested for cone-survival-promoting activity by two approaches and by using two independent photoreceptor degeneration models. In the first approach, mouse retinal cells were cultured on semi-permeable membranes apposed to dissociated cultures of chick embryo retina. In the second approach, conditioned medium was collected from normal mouse retinal cultures and added to embryonic chicken retina cultures or to retinal explants obtained from 5-week retinal degeneration (rd1) mice. In some experiments, conditioned medium was heated or sequentially fractionated in dialysis tubing with molecular weight cutoffs of 8, 15, and 25 kDa. The number of chicken cones and viability were determined by using morphologic criteria, colorimetric assays, and labeling with antibodies raised against visinin. Mouse cones were counted by differential double immunolabeling with antibodies against rhodopsin (rods) and arrestin (rods and cones)., Results: . Coculturing with normal mouse retinal cells delayed cone loss in dispersed embryonic chicken retina, by a maximum of 50% relative to the control. Conditioned medium derived from normal mouse retinas also significantly delayed cone loss in chicken cone cultures by a maximum of 1300%, compared with the control, and 40% in rd1 mouse retinal explant cultures. The survival activity in conditioned medium was destroyed by heat denaturation, and was partially retained by dialysis with a molecular weight cutoff of 25 kDa in both models., Conclusions: These strategies have identified cone-survival-stimulating activities in normal mouse retina, capable of acting across species and enhancing both structural protection and viability. Such molecules may represent candidates for clinical treatment of inherited retinal degeneration.

Tumor necrosis factor (TNF) is an important factor in various acute and chronic neurodegenerative disorders. In retinal ischemia, we show early, transient upregulation of TNF, TNF receptor 1 (TNF-R1), and TNF-R2 6 hr after reperfusion preceding neuronal cell loss. To assess the specific role of TNF and its receptors, we compared ischemia-reperfusion-induced retinal damage in mice deficient for TNF-R1, TNF-R2, or TNF by quantifying neuronal cell loss 8 d after the insult. Surprisingly, TNF deficiency did not affect overall cell loss, yet absence of TNF-R1 led to a strong reduction of neurodegeneration and lack of TNF-R2 led to an enhancement of neurodegeneration, indicative of TNF-independent and TNF-dependent processes in the retina, with TNF-R1 augmenting neuronal death and TNF-R2 promoting neuroprotection. Western blot analyses of retinas revealed that reduction of neuronal cell loss in TNF-R1/ animals correlated with the presence of activated Akt/protein kinase B (PKB). Inhibition of the phosphatidylinositol 3-kinase signaling pathway reverted neuroprotection in TNF-R1-deficient mice, indicating an instrumental role of Akt/PKB in neuroprotection and TNF-R2 dependence of this pathway. Selective inhibition of TNF-R1 function may represent a new approach to reduce ischemia-induced neuronal damage, being potentially superior to strategies aimed at suppression of TNF activity in general.

Background: To evaluate novel grading system used to quantify optical coherence tomography (OCT) scans for cystic macular lesions (CML) in Usher syndrome (USH) patients, focusing on CML associated alterations in MOY7A and USH2A mutations.Methods: Two readers evaluated 76 patients' (mean age 42 ± 14 years) data prospectively uploaded on Eurush database. OCT was used to obtain high quality cross-sectional images through the fovea. The CML was graded as none, mild, moderate or severe, depending on the following features set: subretinal fluid without clearly detectable CML boundaries; central macular thickness; largest diameter of CML; calculated mean of all detectable CML; total number of detectable CML; retinal layers affected by CML. Intra-and inter-grader reproducibility was evaluated.Results: CML were observed in 37 % of USH eyes, while 45 % were observed in MYO7A and 29 % in USH2A cases. Of those with CML: 52 % had mild, 22 % had moderate and 26 % had severe changes, respectively. CML were found in following retinal layers: 50 % inner nuclear layer, 44 % outer nuclear layer, 6 % retinal ganglion cell layer. For the inter-grader repeatability analysis, agreements rates for CML were 97 % and kappa statistics was 0.91 (95 % CI 0.83-0.99). For the intra-grader analysis, agreement rates for CML were 98 %, while kappa statistics was 0.96 (95 % CI 0.92-0.99).Conclusions: The novel grading system is a reproducible tool for grading OCT images in USH complicated by CML, and potentially could be used for objective tracking of macular pathology in clinical therapy trials. [ABSTRACT FROM AUTHOR]

Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome.This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2–4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients. [ABSTRACT FROM AUTHOR]