UNASSIGNED: To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the centrosomal protein 290 (CEP290) gene.
UNASSIGNED: Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial.
UNASSIGNED: A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15-41 years) selected for detailed analyses. Medical histories of 4 participants were consistent with congenital binocular blindness, whereas 1 participant showed evidence of spatial vision in early life that was later lost.
UNASSIGNED: Participants received a single intravitreal injection of sepofarsen (160 or 320 μg) into the study eye.
UNASSIGNED: Full-field stimulus testing (FST), visual acuity (VA), and transient pupillary light reflex (TPLR) were measured at baseline and for 3 months after the injection.
UNASSIGNED: All 5 participants with LP vision demonstrated severely abnormal FST and TPLR findings. At baseline, FST threshold estimates were 0.81 and 1.0 log cd/m2 for control and study eyes, respectively. At 3 months, study eyes showed a large mean improvement of -1.75 log versus baseline (P < 0.001), whereas untreated control eyes were comparable with baseline. Blue minus red FST values were not different than 0 (P = 0.59), compatible with cone mediation of remnant vision. At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline. Specialized tests performed in 1 participant confirmed and extended the standardized results from all 5 participants.
UNASSIGNED: By subjective and objective evidence, intravitreal sepofarsen provides improvement of light sensitivity for individuals with LP vision. However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity.

OBJECTIVE: Choriocapillaris insufficiency may play a role in centripetal retinitis pigmentosa (RP) progression involving the fovea. However, the relationship between choriocapillaris integrity and foveal damage in RP is unclear. We examined the relationship between choriocapillaris flow and the presence of foveal photoreceptor involvement in RP.
METHODS: We categorized the severity of central involvement in RP by the occurrence of foveal ellipsoid zone (EZ) disruption: present (severe RP) or absent (mild RP). Using optical coherence tomography angiography (OCTA, AngioVue, Optovue) in cases and unaffected age-matched controls, we compared vessel density (VD) between the groups using the generalized linear mixed model, controlling for age, gender, and scan quality.
RESULTS: Fifty-seven eyes (20 severe RP, 18 mild RP, and 19 controls) were included. Foveal and parafoveal mean outer retinal thickness (µm) were lower in severe RP (fovea: 101.3 ± 14.5; parafovea: 68.4 ± 11.7) than controls (fovea: 161.2 ± 8.9; parafovea: 142.1 ± 11.8; p ≤ 0.001) and mild RP (fovea: 162.0 ± 14.7; parafovea: 116.8 ± 29.4; p ≤ 0.0001). Foveal choriocapillaris VD (%) was lower in severe RP (56.7 ± 6.8) than controls (69.9 ± 4.6; p = 0.008) and mild RP (65.3 ± 5.3; p = 0.01). The parafoveal choriocapillaris VD was lower in severe RP than controls (64.4 ± 5.9 vs. 68.3 ± 4.1; p = 0.04) but no different than in mild RP (p = 0.4).
CONCLUSIONS: Choriocapillaris flow loss was associated with fovea-involving photoreceptor damage in RP. Further research is warranted to validate this putative association and clarify causation. Choriocapillaris imaging using OCTA may provide information to supplement structural OCT findings when evaluating subjects with RP in neuroprotective or regenerative clinical trials.

OBJECTIVE: To document with spectral-domain optical coherence tomography the structural stabilization of the fovea and the sealing of outer macular defects by Müller cells.
METHODS: A retrospective case series of 45 eyes of 34 patients is described.
RESULTS: In cases of a cystic disruption of the foveola as in macular telangiectasia type 2 and vitreomacular traction, the Müller cell cone provides the structural stability of the fovea. In cases of a detachment or disruption of the Müller cell cone, e.g., in foveal pseudocysts, outer lamellar holes, and degenerative and tractional lamellar holes, Müller cells of the foveal walls may provide the structural stability of the fovea by the formation of a hyperreflective external limiting membrane (ELM) which bridges the holes in the central outer nuclear layer (ONL). Müller cells of the foveal walls and parafovea mediate the regeneration of the foveal architecture in cases of outer lamellar and full-thickness macular holes. The regeneration proceeds by a centripetal displacement of photoreceptor cell somata which closes the holes in the central ONL. The closure may be supported by the formation of a glial tissue band at the ELM which seals the hole.
CONCLUSIONS: The Müller cell cone provides the foveal stability in cases of a cystic disruption of the foveola. The structural stability of the outer foveal layers is mainly provided by the Müller cells of the foveal walls and parafovea; these cells also mediate the regeneration of the outer fovea in cases of a defect of the central ONL.

Diabetic retinopathy (DR) is the leading cause of blindness in type 1 Diabetes Mellitus (DM) patients, as a consequence of impaired blood flow in the retina. Optical coherence tomography angiography (OCTA) is a newly developed, non-invasive, retinal imaging technique that permits adequate delineation of the perifoveal vascular network. It allows the detection of paramacular areas of capillary non perfusion and/or enlargement of the foveal avascular zone (FAZ), representing an excellent tool for assessment of DR. The relationship of these microvascular changes with systemic factors such as metabolic control or duration of the disease still needs to be elucidated.
Prospective, consecutive, large-scale OCTA study. A complete ocular examination including a comprehensive series of OCTA images of different scan sizes captured with 2 OCT devices (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA, USA, and Triton Deep Range Imaging OCT, Topcon Corp, Topcon, Japan) will be obtained as part of the yearly routine follow up visits in type 1 DM patients seen in the Diabetes Unit of the Endocrinology department which give written informed consent to participate in the project. The aim of this study is to investigate the relationship between OCTA-derived parameters and systemic factors, as metabolic control (Hb1Ac, lipid profile, cholesterol, etc), and other relevant clinical factors as demographics or duration of the disease.
This study is directed to investigate the relationship between the status of the perifoveal vascular network and systemic markers of the disease, and in particular to study whether these changes reflect those occurring elsewhere in the body affected by diabetic microvascular disease, as the kidneys or the brain. If these relationships were demonstrated, early detection of these microvascular changes by OCTA could lead to modifications in the pharmacological management of type 1 diabetic patients, as a way to reduce the risk of future complications in both the eye and other organs.
ClinicalTrials.gov, trial number NCT03422965.

Previous studies on the ultrastructure of the primate foveola suggested the presence of an inverted cone-like structure which is formed by 25-35 specialized Müller cells overlying the area of high photoreceptor density. We investigated the ultrastructure of the Müller cells in the foveola of a human and macaque retina. Sections through the posterior poles of an eye of a 40 years-old human donor and an eye of an adult cynomolgus monkey (Macaca fascicularis) were investigated with transmission electron microscopy. The foveola consisted of an inner layer (thickness, 5.5-12 μm) which mainly contained somata (including nuclei) and inner processes of Müller cells; this layer overlaid the central Henle fibers and outer nuclear layer. The inner layer contained numerous watery cysts and thin lamelliform and tubular Müller cell processes which spread along the inner limiting membrane (ILM). The cytoplasm of the outer Müller cell processes became increasingly dispersed and electron-lucent in the course towards the outer limiting membrane. The ILM of the foveola was formed by a very thin basal lamina (thickness, <40 nm) while the basal lamina of the parafovea was thick (0.9-1 μm). The data show that there are various conspicuous features of foveolar Müller cells. The numerous thin Müller cell processes below the ILM may smooth the inner surface of the foveola (to minimize image distortion resulting from varying light refraction angles at an uneven retinal surface), create additional barriers to the vitreous cavity (compensating the thinness of the ILM), and provide mechanical stability to the tissue. The decreasing density of the outer process cytoplasm may support the optical function of the foveola.

Following a period of quiescence at the end of last century, the study of microsaccades has now regained strong impetus and broad attention within the vision research community. This wave of interest, partly fueled by the advent of user-friendly high-resolution eyetrackers, has attracted researchers and led to novel ideas. Old hypothesis have been revisited and new ones formulated. This article is designed to serve as a practical guide for researchers in the field. Because of the history of the field and the difficulty of measuring very small eye movements, the study of microsaccades presents peculiar challenges. Here, we summarize some of the main challenges and describe methods for assessing and improving the quality of the recordings. Furthermore, we examine how these experimental challenges have influenced analysis of the visual functions of microsaccades and critically review current evidence on three long-debated proposals: the maintenance of fixation, the prevention of visual fading, and the exploration of fine spatial detail.