Assessing Photoreceptor Status in Retinal Dystrophies: From High-Resolution Imaging to Functional Vision

Abstract

To describe the value of integrating phenotype/genotype data, disease staging, and evaluation of functional vision in patient-centered management of retinal dystrophies. • METHODS: (1) Cross-sectional structure-function and retrospective longitudinal studies to assess the correlations between standard fundus autofluorescence (FAF), optical coherence tomography, visual acuity (VA), and perimetry (visual field [VF]) examinations to evaluate photoreceptor functional loss in a cohort of patients with rod-cone dystrophy (RCD); (2) flood-illumination adaptive optics (FIAO) imaging focusing on photoreceptor misalignment and orientation of outer segments; and (3) evaluation of the impact of visual impairment in daily life activities, based on functional (visual and mobility) vision assessment in a naturalistic environment in visually impaired subjects with RCD and subjects treated with Luxturna R for RPE65 -related Leber congenital amaurosis before and after therapy. • RESULTS: The results of the cross-sectional transversal study showed that (1) VA and macular sensitivity were weakly correlated with the structural variables; and (2) functional impairment (VF) was correlated with reduction of anatomical markers of photoreceptor structure and increased width of autofluorescent ring. The dimensions of the ring of increased FAF evolved faster. Other criteria that differed among groups were the lengths of the ellipsoid zone, the external limiting membrane, and

Dysfunction of the glutamatergic photoreceptor synapse in the P301S mouse model of tauopathy

“…The retina is a relatively easily accessible part of the central nervous system for both imaging and cell recording. Various tools are available for assessing structural alterations to the retina [ 55 ] and the physiology of visual information processing by the retina (ERG, VEP recordings) in both animal models and in humans. Amyloid burden and tau aggregation share similar effects on the visual system in animal models and humans [ 29 , 32 , 38 , 39 ].…”

Development and validation of a novel mobility test for IRDs, from reality to virtual reality

“…Participants were included in a prospective, interventional, non-invasive, longitudinal study designed to compare the performance of RP patients and control participants in behavioral tasks. Inclusion and screening were conducted at the XV-XX National Ophthalmology Hospital in Paris, France, whereas all behavioral assessments were conducted at Streetlab (6), Paris, France. The study was approved by the Ouest V Ethics Committee (CPP 19.01446.190402-MS03; IDRCB: 2019-A00483-54; ClinicalTrials.gov ID: NCT04448860) in accordance with the Declaration of Helsinki.…”

“…Translational researchers have worked to build performance-based outcomes for a variety of activities of daily living, such as orientation and mobility(6, 12–14), corresponding to a major difficulty for IRD patients, especially under low light conditions(15). The approval of VN therapy was based on such metrics, and a multi-luminance mobility test (MLMT) performance was even used as the primary outcome of the phase III VN trial(3).…”

“…The approval of Voretigene Neparvovec (VN) for the treatment of IRDs caused by mutations in RPE65(3) gene, marked an important milestone, leading to numerous trials in gene and cell therapy, while prosthetic vision technologies were in development (4). A crucial factor in determining the efficacy of the therapy is the selection of appropriate outcome measures (5)(6)(7). In addition to evaluating retinal structure or visual function outcomes, such as visual acuity, contrast sensitivity and visual field, it is key to quantify functional vision, as defined by the patient's ability to perform visiondependent tasks that are essential to maintain autonomy (8,9).…”

Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials

“…It is illuminated evenly by a set of luminaires that can provide constant light levels ranging from 0 to 2,000 lux and which can be varied in correlated color temperature (2,700 to 6,500K). 114 A 3D sound system is also included, as is the facility for objective measurement via integrated image capturing techniques. These include an eye-tracker, a motion capture system, and inertial sensors which can record complex behavior patterns that, at present, have been analyzed by predetermined metrics (e.g.…”