Patient-Reported Outcomes in RLBP1 Retinal Dystrophy: Longitudinal Assessment in a Prospective Natural History Study.

Purpose: To evaluate the performance of two non-disease-specific patient-reported outcome (PRO) instruments, the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and the Low Luminance Questionnaire (LLQ), in patients with retinaldehyde-binding protein 1 retinal dystrophy (RLBP1 RD).

Methods: PROs were assessed using the VFQ-25 and LLQ. Rasch analysis was conducted to estimate person and item measures of the VFQ-25 and LLQ questionnaires to determine the association between the two PROs.

Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial.

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation.

Retinal Dystrophy Associated With RLBP1 Retinitis Pigmentosa: A Five-Year Prospective Natural History Study.

Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation.

Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments.

ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update).

The multifocal electroretinogram (mfERG) is an electrophysiological test that allows the function of multiple discrete areas of the retina to be tested simultaneously. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV standard for clinical mfERG and defines minimum protocols for basic clinical mfERG recording and reporting so that responses can be recognized and compared from different laboratories worldwide. The major changes compared with the previous mfERG standard relate to the minimum length of m-sequences used for recording, reporting of results and a change in document format, to be more consistent with other ISCEV standards.

Qualitative Interviews to Better Understand the Patient Experience and Evaluate Patient-Reported Outcomes (PRO) in RLBP1 Retinitis Pigmentosa (RLBP1 RP).

Introduction: RLBP1 RP is an autosomal recessive form of retinitis pigmentosa (RP), characterized by night blindness, prolonged dark adaptation, constricted visual fields and impaired macular function. This study aimed to better understand the patient experience of RLBP1 RP and evaluate the content validity of existing patient reported outcome (PRO) instruments in this condition.

Methods: Semi-structured concept elicitation and cognitive debriefing interviews were conducted with RLBP1 RP patients in Canada and Sweden.

Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa.

Purpose: To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa.

Methods: Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry.

Method for deriving visual field boundaries from OCT scans of patients with retinitis pigmentosa.

The location of the loss of the inner segment (IS)/outer segment (OS) border, as seen with frequency domain optical coherence tomography (fdOCT), was determined on fdOCT scans from patients with retinitis pigmentosa. A comparison to visual field loss supported the hypothesis, based upon previous work, that the point at which the IS/OS border disappears provides a structural marker for the edge of the visual field. Repeat fdOCT measures showed good within day reproducibility, while data obtained on average 22.

A primer on common statistical errors in clinical ophthalmology.

Although biomedical statistics is part of any scientific curriculum, a review of the current scientific literature indicates that statistical data analysis is an area that frequently needs improvement. To address this, we here cover some of the most common problems in statistical analysis, with an emphasis on an intuitive, tutorial approach rather than a rigorous, proof-based one. The topics covered in this manuscript are whether to enter eyes or patients into the analysis, issues related to multiple testing, pitfalls surrounding the correlation coefficient (causation, insensitivity to patterns, range confounding, unsuitability for method comparisons), and when to use standard deviation (SD) versus standard error of the mean (SEM) "antennas" on graphs.

Scotopic sensitivity and color vision with a blue-light-absorbing intraocular lens.

Purpose: To investigate possible adverse effects of a yellow-tinted intraocular lens (IOL) on scotopic sensitivity and hue discrimination.

Setting: Departments of Ophthalmology, Columbia University and New York University School of Medicine, New York, New York, USA.

Methods: Nine patients with a yellow-tinted IOL in 1 eye and a colorless ultraviolet IOL in the fellow eye and 9 young phakic subjects with and without a yellow-tinted clip-on lens were tested.

Test-retest reliability of the multifocal electroretinogram and humphrey visual fields in patients with retinitis pigmentosa.

We examined the reliability of Humphrey visual field thresholds and multifocal electroretinogram (mfERG) amplitudes and timing in a group of patients with Retinitis Pigmentosa (RP). Eight patients with RP and seven control subjects were tested five times: at baseline (visit #0), at three weekly follow-up visits (visits #1 - #3), and at three months (visit #4). For the Humphrey thresholds, differences between dB values on repeat visits were obtained.

The multifocal visual evoked potential: an objective measure of visual fields?

We examined the effects of inter-modal attention and mental arithmetic on Humphrey visual field sensitivity and multifocal visual evoked potential (mfVEP) amplitude. Four normally sighted subjects (ages ranging from 24 to 58 years) participated in this study. Monocular visual field sensitivity was measured under two conditions: (1) standard testing condition and (2) while the subject performed a Paced Auditory Serial Addition Task (PASAT).

Multidimensional visual field maps: relationships among local psychophysical and local electrophysiological measures.

Multidimensional psychophysical and electrophysical maps of the central retina are essential for assessing the functioning of the diseased retina. In this study, grating acuity, contrast sensitivity, duration for letter identification, multifocal electroretinograms, and Humphrey visual field thresholds were measured at equivalent positions throughout the central 20 degrees. We found that the rates of sensitivity loss were not equivalent for all psychophysical measures.

Rod and cone photoreceptor function in patients with cone dystrophy.

Purpose: To determine the extent of rod and cone photoreceptor dysfunction in patients with cone dystrophy using psychophysical and electrophysiological tests.

Methods: Ten patients with cone dystrophy participated. Rod and cone system psychophysical thresholds were measured as a function of retinal eccentricity.

Electrophysiology.

Numerous electrophysiologic tests are available for use in the clinic. When properly recorded and analyzed, these tests provide important diagnostic and prognostic information about the site and nature of the disease process. If the results from these tests are combined with psychophysical findings (color vision, acuity, visual fields), their usefulness in defining disease can be further extended.

The effect of variably tinted spectacle lenses on visual performance in cataract subjects.

Purpose: A body of clinical and laboratory evidence suggests that tinted spectacle lenses may have an effect on visual performance. The aim of this study was to quantify the effects of spectacle lens tint on the visual performance of 25 subjects with cataracts.

Methods: Cataracts were scored based on best-corrected acuity and by comparison with the Lens Opacity Classification System (LOCS III) plates.

Multifocal electroretinography as a function of age: the importance of normative values for older adults.

Purpose: To determine the influence of age on local electroretinographic responses in humans.

Methods: Multifocal electroretinograms (mfERGs) were obtained from 62 normally sighted subjects ranging in age from 21 to 81 years. A stimulus array of 103 scaled hexagons was used to measure electrical signals within a retinal area approximately 46 degrees in diameter.

Local cone and rod system function in progressive cone dystrophy.

Purpose: To compare the patterns of local cone and rod system impairment in patients with progressive cone dystrophy (CD) using psychophysical and electrophysiological techniques.

Methods: Local cone system function was assessed by measuring cone system thresholds (visual fields) and cone-mediated multifocal electroretinograms (mfERGs). Rod system function was assessed by measuring rod system thresholds (visual fields) and rod-mediated mfERGs.

The spatial distribution of selective attention assessed using the multifocal visual evoked potential.

To determine the manner in which attention is distributed among numerous locations in the visual space, we used a multifocal recording technique that allowed simultaneous recordings of evoked cortical activity from 12 visual field areas out to 23.6 degrees. We found that multifocal visual evoked potential (mfVEP) amplitude was larger when a region of visual space was attended than when it was not attended.

Effect of variable tinted spectacle lenses on visual performance in control subjects.

Purpose: To evaluate quantitatively the effects of tinted spectacle lenses on visual performance in individuals without visual pathology.

Methods: Twenty-five subjects were assessed by measuring contrast sensitivity with and without glare. Gray, brown, yellow, green, purple, and blue lens tints were evaluated.

A method for comparing psychophysical and multifocal electroretinographic increment thresholds.

The multifocal electroretinogram (mfERG) has been commonly used as a method for obtaining objective visual fields. Although qualitative comparisons have been good, quantitative comparisons between the results from mfERG and the results from Humphrey Visual Field Analyser (HVFA) have found variable degrees of agreement depending upon the mfERG response parameter examined and/or the disease studied. Lack of agreement may be due to differences in methodology, differences in the sites of response generation, and/or differences derived from comparing suprathreshold versus threshold responses.