Ranked Importance of Visual Function Outcome Measures in Choroideremia Clinical Trials.

Purpose: Clinical trials of novel therapies for choroideremia require robust and clinically meaningful visual function outcome measures. Best-corrected visual acuity (BCVA) is mostly insensitive to changes in disease state, until late stages, and hence also to potential therapeutic gains after gene therapies. While the insensitivity of BCVA as an effective outcome measure is common wisdom, its low importance has not been rigorously demonstrated in the literature.

Exploring Scotopic Microperimetry as an Outcome Measure in Choroideremia.

Purpose: Choroideremia is an X-linked outer retinal degeneration. Early symptoms include nyctalopia and progressive visual field loss, but visual acuity is preserved until late disease stages. Dark-adapted two-color fundus-controlled perimetry (also known as scotopic microperimetry) has been developed to enable spatial assessment of rod and cone photoreceptor function.

Establishing Clinical Trial Endpoints in Selecting Patients for RPGR Retinal Gene Therapy.

Purpose: Clinical trials for X-linked retinitis pigmentosa (RP) often assess retinal structure using optical coherence tomography (OCT) and function using microperimetry to evaluate initial eligibility and endpoints. Therefore, we seek to determine which parameters might be most sensitive in screening new patients for enrollment.

Methods: Thirty-one patients (62 eyes) with confirmed retinitis pigmentosa GTPase regulator (RPGR) mutations attending Oxford Eye Hospital were included in this retrospective analysis.

Investigating the impact of asymmetric macular sensitivity on visual acuity chart reading in choroideremia.

Introduction: Degeneration in choroideremia, unlike typical centripetal photoreceptor degenerations, is centred temporal to the fovea. Once the fovea is affected, the nasal visual field (temporal retina) is relatively spared, and the preferred retinal locus shifts temporally. Therefore, when reading left to right, only the right eye reads into a scotoma.

Correlation Between Fundus Autofluorescence Pattern and Retinal Function on Microperimetry in Choroideremia.

Purpose: In patients with choroideremia, it is not known how smooth and mottled patterns on short-wavelength fundus autofluorescence (AF) imaging relate to retinal function.

Methods: A retrospective case-note review was undertaken on 190 patients with choroideremia at two specialist centers for retinal genetics. Twenty patients with both smooth and mottled zones on short-wavelength AF imaging and concurrent mesopic microperimetry assessments were included.

Choroideremia: The Endpoint Endgame.

Choroideremia is an X-linked retinal degeneration resulting from the progressive, centripetal loss of photoreceptors and choriocapillaris, secondary to the degeneration of the retinal pigment epithelium. Affected individuals present in late childhood or early teenage years with nyctalopia and progressive peripheral visual loss. Typically, by the fourth decade, the macula and fovea also degenerate, resulting in advanced sight loss.

Microperimetry as an Outcome Measure in RPGR-associated Retinitis Pigmentosa Clinical Trials.

Purpose: To explore which microperimetry sensitivity index (pointwise sensitivity, mean sensitivity, and volume sensitivity) is suitable as a microperimetry outcome measure in patients with X-linked RPGR-associated retinitis pigmentosa (RP).

Methods: Microperimetry data from patients with RPGR-associated RP were collected and analyzed retrospectively. Fourteen participants completed triplicate microperimetry testing, across 2 consecutive days for the repeatability analyses.

A cross-sectional study to assess the clinical utility of modern visual function assessments in patients with inherited retinal disease: a mixed methods observational study protocol.

Background: Treatment options for patients with inherited retinal disease are limited, although research into novel therapies is underway. To ensure the success of future clinical trials, appropriate visual function outcome measures that can assess changes resulting from therapeutic interventions are urgently required. Rod-cone degenerations are the most common type of inherited retinal disease.

Microperimetry Reliability Assessed From Fixation Performance.

Purpose: Microperimetry provides an accurate assessment of central retinal sensitivity due to its fundus-tracking capability, but it has limited reliability indicators. One method currently employed, fixation loss, samples the optic nerve blind spot for positive responses; however, it is unclear if these responses arise from unintentional button presses or from tracking failure leading to stimuli misplacement. We investigated the relationship between blind spot scotoma positive responses (termed scotoma responses) and fixation.

A Network Meta-Analysis of Retreatment Rates following Bevacizumab, Ranibizumab, Aflibercept, and Laser for Retinopathy of Prematurity.

Topic: To compare bevacizumab, ranibizumab, aflibercept, and laser treatment as primary therapies for retinopathy of prematurity (ROP) in terms of retreatment rate.

Clinical Relevance: Anti-VEGF agents are increasingly used as primary treatment for ROP and may provide superior outcomes compared with laser in posterior disease. Head-to-head comparisons between different anti-VEGFs are lacking.

Characterizing Visual Fields in RPGR Related Retinitis Pigmentosa Using Octopus Static-Automated Perimetry.

Purpose: Peripheral visual fields have not been as well defined by static automated perimetry as kinetic perimetry in RPGR-related retinitis pigmentosa. This study explores the pattern and sensitivities of peripheral visual fields, which may provide an important end point when assessing interventional clinical trials.

Methods: A retrospective observational cross-sectional study of 10 genetically confirmed RPGR subjects was performed.

Scotopic microperimetry: evolution, applications and future directions.

For many inherited and acquired retinal diseases, reduced night vision is a primary symptom. Despite this, the clinical testing options for spatially resolved scotopic vision have until recently been limited. Scotopic microperimetry is a relatively new visual function test that combines two-colour perimetry with fundus-controlled perimetry performed in scotopic luminance conditions.

Structural and Functional Characteristics of Color Vision Changes in Choroideremia.

Color vision is considered a marker of cone function and its assessment in patients with retinal pathology is complementary to the assessments of spatial vision [best-corrected visual acuity (BCVA)] and contrast detection (perimetry). Rod-cone and chorioretinal dystrophies-such as choroideremia-typically cause alterations to color vision, making its assessment a potential outcome measure in clinical trials. However, clinical evaluation of color vision may be compromised by pathological changes to spatial vision and the visual field.

Microperimetry Hill of Vision and Volumetric Measures of Retinal Sensitivity.

Purpose: Mean retinal sensitivity is the main output measure used in microperimetry. It is, however, of limited use in patients with poor vision because averaging is weighted toward zero in those with significant scotomas creating an artificial floor effect. In contrast, volumetric measures avoid these issues and are displayed graphically as a hill of vision.

Low Luminance Visual Acuity and Low Luminance Deficit in Choroideremia and RPGR-Associated Retinitis Pigmentosa.

Introduction: Choroideremia and RPGR-associated retinitis pigmentosa (RP) are two distinct inherited rod-cone degenerations, where good visual acuity (VA) is maintained until late disease stages, limiting its usefulness as a disease marker. Low luminance VA and low luminance deficit (standard VA minus low luminance VA) may be more sensitive visual function measures.

Methods: Standard VA was obtained using Early Treatment Diabetic Retinopathy Study letter charts (Precision Vision, Bloomington, IL, USA).

Clinical applications of microperimetry in RPGR-related retinitis pigmentosa: a review.

Microperimetry, or fundus-tracked perimetry, is a precise static-automated perimetric technique to assess central retinal function. As visual acuity only deteriorates at a late disease stage in RPGR-related retinitis pigmentosa (RP), alternative markers for disease progression are of great utility. Microperimetry assessment has been of critical value as an outcome measure in a recently reported phase I/II gene therapy trial for RPGR-related RP, both in terms of detecting safety and efficacy signals.

Low luminance visual acuity as a clinical measure and clinical trial outcome measure: a scoping review.

Purpose: The measurement of standard visual acuity (VA) is the most well-known part of any ophthalmic examination to indicate visual function. Despite this, it is insensitive in detecting early disease changes. Therefore, other visual function tests have been developed including low luminance VA (LLVA) and low luminance deficit (LLD).