Functional evaluation in inherited retinal disease

Abstract

Functional assessments are a fundamental part of the clinical evaluation of patients with inherited retinal diseases (IRDs). Their importance and impact have become increasingly notable, given the significant breadth and number of clinical trials and studies investigating multiple avenues of intervention across a wide range of IRDs, including gene, pharmacological and cellular therapies. Moreover, the fact that many clinical trials are reporting improvements in vision, rather than the previously anticipated structural stability/slowing of degeneration, makes functional evaluation of primary relevance. In this review, we will describe a range of methods employed to characterise retinal function and functional vision, beginning with tests variably included in the clinic, such as visual acuity, electrophysiological assessment and colour discrimination, and then discussing assessments often reserved for clinical trials/research studies such as photoaversion testing, full-field static perimetry and microperimetry, and vision-guided mobility testing; addressing perimetry in greatest detail, given it is commonly a primary outcome metric. We will focus on how these tests can help diagnose and monitor particular genotypes, also noting their limitations/challenges and exploring analytical methodologies for better exploiting functional measurements, as well as how they facilitate patient inclusion and stratification in clinical trials and serve as outcome measures.

Prognostication in Stargardt Disease Using Fundus Autofluorescence: Improving Patient Care

“…This, in direct contrast, illustrates that functional changes may manifest before structural changes are visible, which would be the most common observation in inherited retinal disease. 30 …”

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

“…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).…”

“…C: Correlations between the average physical (RL) and virtual (VR) performance score in binocular condition. D: Performance score as a function of light level (from low[1] to high[5] light levels). RL and VR conditions are depicted in green and brown, respectively, as control group is transparent and RP group opaque.…”

PHYH c.678+5G>T Leads to In-Frame Exon Skipping and Is Associated With Attenuated Refsum Disease

“…Inherited retinal diseases (IRDs) are a heterogeneous group of genetic disorders that lead to subnormal vision, primarily due to abnormalities in photoreceptors and retinal pigment epithelium cells. 1 IRDs may develop as an isolated ocular condition or as part of a syndrome, accompanied by a range of extraocular manifestations. 2 Visual symptoms of syndromic IRDs may arise before systemic manifestations (e.g., CLN3 –Batten disease), 3 at the same time (e.g., SCA7 –spinocerebellar ataxia), 4 or after (e.g., Usher syndrome type 1).…”