Development and Validation of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.

PURPOSE: To develop and validate a novel patient-reported outcome (PRO) measure to assess vision-related functioning in individuals with severe peripheral field loss (PFL). DESIGN: Prospective outcome measure development/validation study. METHODS: A 127-item questionnaire was developed based on a prior qualitative interview study. A total of 116 participants with severe PFL due to retinitis pigmentosa (RP) or glaucoma were recruited at the Kellogg Eye Center and completed the Likert-scaled telephone-administered questionnaire. Included participants had a horizontal extent of their visual field <20 degrees (RP) or a mixed or generalized stage 4 to 5 defect using the Enhanced Glaucoma Staging System (glaucoma) in the better seeing eye (or in 1 eye if the fellow eye visual acuity was <20/200). Response data were analyzed using exploratory factor analysis and Rasch modeling. Poorly functioning items were eliminated, confirmatory factor analysis was used to ensure scale unidimensionality, and the model was refit to produce the final instrument. RESULTS: The final Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire contains 53 items across 6 domains: mobility, object localization, object recognition, reading, social functioning, and technology. There were 74 items removed because of high missingness, poor factor loadings, low internal consistency, high local dependency, low item information, item redundancy, or differential item functioning. Using Rasch item calibrations, person ability scores could be calculated for each of the 6 unidimensional LV-SCOPE domains with good test-retest stability. CONCLUSIONS: The LV-SCOPE Questionnaire provides a valid and reliable measure of vision-related functioning across 6 key domains relevant to individuals with severe PFL. Findings support the clinical utility of this psychometrically valid instrument.

Local progression kinetics of macular atrophy in recessive Stargardt disease.

BACKGROUND: To determine the effect of lesion topography on progression in Stargardt disease (STGD1). METHODS: Fundus autofluoresence (excitation 488 nm) images of 193 eyes in patients with proven ABCA4 mutation were semi-automatically segmented for autofluoresence changes: (DDAF) and questionably decreased autofluoresence (QDAF), which are proxies for retinal pigment epithelial (RPE) atrophy. We calculated topographic incidence of DDAF and DDAF + QDAF, as well as velocity of progression of the border of lesions using Euclidean distance mapping. RESULTS: Incidence of atrophy was highest near the fovea, then decreased in incidence with increased foveal eccentricity. However, the rate of atrophy progression followed the opposite pattern; rate of atrophy increased with distance from foveal center. The mean growth rate 500 microns from the foveal center for DDAF + QDAF was 39 microns per year (95% CI = 28-49), whereas the mean growth rate 3000 microns from the foveal center was 342 microns per year (95% CI = 194-522). No difference in growth rate was noted by axis around the fovea. CONCLUSIONS: Incidence and progression of atrophy by fundus autofluorescence follow opposite patterns in STGD1. Further, atrophy progression increases significantly with distance from foveal center, which should be taken into consideration in clinical trials.

Positive feedback loop between vision-related anxiety and self-reported visual difficulty.

BACKGROUND: Patients with Inherited Retinal Diseases typically experience progressive, irreversible vision loss resulting in low vision and blindness. As a result, these patients are at high risk for vision-related disability and psychological distress, including depression and anxiety. Historically, the relationship between self-reported visual difficulty (encompassing metrics of vision-related disability and quality of life, among others) and vision-related anxiety has been regarded as an association and not a causal relationship. As a result, there are limited interventions available that address vision-related anxiety and the psychological and behavioral components of self-reported visual difficulty. MATERIALS AND METHODS: We applied the Bradford Hill criteria to evaluate the case for a bidirectional causal relationship between vision-related anxiety and self-reported visual difficulty. RESULTS: There is sufficient evidence to satisfy all nine of the Bradford Hill criteria of causality (strength of association, consistency, biological gradient, temporality, experimental evidence, analogy, specificity, plausibility, and coherence) for the relationship between vision-related anxiety and self-reported visual difficulty. CONCLUSIONS: The evidence suggests that there is a direct positive feedback loop-a bidirectional causal relationship-between vision-related anxiety and self-reported visual difficulty. More longitudinal research on the relationship between objectively-measured vision impairment, self-reported visual difficulty, and vision-related psychological distress is needed. Additionally, more investigation of potential interventions for vision-related anxiety and visual difficulty is needed.

The validation of inherited retinal disease-specific patient-reported outcome measures in adolescent patients.

PURPOSE: To determine the validity of the validate the adult patient-reported outcome measure tools, the Michigan Retinal Degeneration Questionnaire (MRDQ) and Michigan Vision-Related Anxiety Questionnaire (MVAQ), in adolescent patients with inherited retinal diseases (IRDs). METHODS: Ninety-one adolescent patients diagnosed with IRDs were recruited at the Hospital for Sick Children (University of Toronto) and the Kellogg Eye Center (University of Michigan). The patients were administered the MRDQ, MVAQ, and Patient Health Questionnaire-4 (PHQ-4). Test-retest variability was assessed in eighteen patients within 14 days of the initial administration. Adolescent responses were analyzed for validity and reliability. As a further validation step, comparisons were made to adult data from the original MRDQ and MVAQ studies to ensure consistency in response ranges. RESULTS: The existing MRDQ and MVAQ content and format could accurately detect the impact of IRD on activities of daily living in adolescents with IRDs. No floor/ceiling effects were identified, test-retest reliability was established (r = 0.73-0.86), and no items were excluded after differential item functioning analysis. Domain and trait associations with visual acuity and IRD phenotypes were similar between adolescents and adults. CONCLUSIONS: The MRDQ and MVAQ are psychometrically validated questionnaires for which we have shown validity for use in adolescent patients with IRDs.

Self-reported visual function and psychosocial impact of visual loss in EYS-associated retinal degeneration in a Portuguese population.

PURPOSE: To evaluate self-reported visual function and the psychosocial impact of visual loss EYS-associated retinal degeneration (EYS-RD) using two patient-reported outcome (PRO) measures: Michigan Retinal Degeneration Questionnaire (MRDQ) and Michigan Vision-related Anxiety Questionnaire (MVAQ). METHODS: Cross-sectional, single-center study conducted at a tertiary care hospital in Portugal. Patients with biallelic EYS variants were invited to participate. Clinical data including demographics, ETDRS best-corrected visual acuity (BCVA) in the better-seeing eye and genetic testing results were collected. Interviews were carried out during clinic visits or by phone between November 2021 and February 2022. A blind grader used horizontal and vertical spectral domain optical coherence tomography (SD-OCT) scans to manually measure ellipsoid zone (EZ) width in the nasal, temporal, superior and inferior macular quadrants to calculate the EZ area. RESULTS: Forty-nine patients (53.1% males; mean age 53 ± 14 years) were included. A positive correlation (p < .05) was found between age and most MRDQ domain scores (central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision and mesopic peripheral vision). A negative correlation was found between both BCVA and EZ area across all MRDQ domains. In MVAQ, SD-OCT EZ area negatively correlated with both rod function and cone function-related anxiety. Neither age, BCVA or gender correlated with MVAQ domains. CONCLUSIONS: This study provides strong evidence supporting a correlation between PRO measures and both functional and structural clinician-reported outcomes. The use of MRDQ and MVAQ adds a new dimension to our understanding of EYS-RD and establishes both PRO measures as important disease outcome measures.

USH2A Gene Mutations in Rabbits Lead to Progressive Retinal Degeneration and Hearing Loss.

Purpose: Mutations in USH2A gene are responsible for the greatest proportion of the Usher Syndrome (USH) population, among which more than 30% are frameshift mutations on exon 13. A clinically relevant animal model has been absent for USH2A-related vision loss. Here we sought to establish a rabbit model carrying USH2A frameshift mutation on exon 12 (human exon 13 equivalent). Methods: CRISPR/Cas9 reagents targeting the rabbit USH2A exon 12 were delivered into rabbit embryos to produce an USH2A mutant rabbit line. The USH2A knockout animals were subjected to a series of functional and morphological analyses, including acoustic auditory brainstem responses, electroretinography, optical coherence tomography, fundus photography, fundus autofluorescence, histology, and immunohistochemistry. Results: The USH2A mutant rabbits exhibit hyper-autofluorescent signals on fundus autofluorescence and hyper-reflective signals on optical coherence tomography images as early as 4 months of age, which indicate retinal pigment epithelium damage. Auditory brainstem response measurement in these rabbits showed moderate to severe hearing loss. Electroretinography signals of both rod and cone function were decreased in the USH2A mutant rabbits starting from 7 months of age and further decreased at 15 to 22 months of age, indicating progressive photoreceptor degeneration, which is confirmed by histopathological examination. Conclusions: Disruption of USH2A gene in rabbits is sufficient to induce hearing loss and progressive photoreceptor degeneration, mimicking the USH2A clinical disease. Translational Relevance: To our knowledge, this study presents the first mammalian model of USH2 showing the phenotype of retinitis pigmentosa. This study supports the use of rabbits as a clinically relevant large animal model to understand the pathogenesis and to develop novel therapeutics for Usher syndrome.

Construct Validity of Inherited Retinal Disease-Specific Patient-Reported Outcome Measures.

PURPOSE: To evaluate aspects of construct validity of the Michigan Retinal Degeneration Questionnaire (MRDQ) and the Michigan Vision-related Anxiety Questionnaire (MVAQ). METHODS: Subjects with a clinical diagnosis of an inherited retinal disease (IRD) were recruited prospectively and 3 tests were used to assess construct validity: the ability to distinguish different IRD phenotypes; test a priori hypothesis of an association between vision-related anxiety and vision-related disabilities; and correlate MRDQ and MVAQ with the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and the Impact of Vision Impairment (IVI). One-way analysis of variance (ANOVA) was used to compare different phenotypes for mean domain scores for MRDQ/MVAQ. Pearson correlations were performed between; Cone-Function Anxiety and Central Vision controlling for better eye visual acuity, Rod-Function Anxiety and Scotopic Function controlling for visual field area (III4e and IV4e), and scores of MRDQ/MVAQ, NEI VFQ-25, and IVI. RESULTS: The study sample consisted of 146 patients evenly divided between males and females, and mean age was 50 years. The 1-way ANOVA test was significant for distinguishing IRD phenotypes in 6 domains of MRDQ/MVAQ. Cone-Function Anxiety correlated with Central Vision controlling for visual acuity, Rod-Function Anxiety correlated with Scotopic Function controlling for visual field area, and all domains in MRDQ/MVAQ had significant correlations with NEI VFQ-25 and IVI composite scores. CONCLUSION: MRDQ and MVAQ domenstrate aspects of construct-validity set forth by the US Food and Drug Administration. The study futher supports the use of both patient-reported outcome measures in IRD clinical trials and natural history studies.NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Effects of duration and number of symptoms on vision-related anxiety in patients with Inherited Retinal Diseases.

BACKGROUND: Patients with Inherited Retinal Diseases (IRDs) are at increased risk for vision-related anxiety due to progressive and irreversible vision loss, yet little is known about risk factors for anxiety in these patients. MATERIALS AND METHODS: This was a single-center, retrospective cross-sectional study at a large academic center. 128 adults with an IRD and without other significant eye conditions were recruited between December 2016 and March 2020. Participants were asked about the duration and number of symptoms they had in the following vision domains: reading, contrast vision, color vision, glare/light sensitivity, night vision, and peripheral vision. The outcomes of interest were the two domains of the Michigan Vision-Related Anxiety Questionnaire (MVAQ), rod- and cone-function related anxiety. We conducted an adjusted analysis to isolate the independent effect of duration and number of symptoms on vision-related anxiety. RESULTS: Of 126 participants had complete data, 62 (49%) were female and 64 (51%) were male, with an average age of 49 years (range: 18-87). Patients with duration of symptoms for greater than 25 years had an adjusted anxiety theta that was one-half standard deviations lower than patients with symptoms for less time. Patients with higher number of symptoms had higher anxiety theta after adjusting for confounding variables (p < 0.0001). CONCLUSIONS: The number of symptoms but not the duration of symptoms, is an independent risk factor for vision-related anxiety. Patients with more symptoms are at higher risk for vision-related anxiety. Having symptoms for longer than 25 years may reduce this anxiety.

Question: How does the duration and number of symptoms that patients with Inherited Retinal Diseases have affect their vision-related anxiety?Findings: In this cross-sectional study of 126 patients with Inherited Retinal Diseases, the number of symptoms, but not the duration of symptoms, was associated with higher vision-related anxiety. Patients with symptoms for longer than 25 years had less vision-related anxiety.Meaning: Patients with more vision-related symptoms may experience more vision-related anxiety.

Automated Segmentation of Autofluorescence Lesions in Stargardt Disease.

OBJECTIVE: To train a deep learning (DL) algorithm to perform fully automated semantic segmentation of multiple autofluorescence lesion types in Stargardt disease. DESIGN: Cross-sectional study with retrospective imaging data. SUBJECTS: The study included 193 images from 193 eyes of 97 patients with Stargardt disease. METHODS: Fundus autofluorescence images obtained from patient visits between 2013 and 2020 were annotated with ground-truth labels. Model training and evaluation were performed using fivefold cross-validation. MAIN OUTCOMES MEASURES: Dice similarity coefficients, intraclass correlation coefficients, and Bland-Altman analyses comparing algorithm-predicted and grader-labeled segmentations. RESULTS: The overall Dice similarity coefficient across all lesion classes was 0.78 (95% confidence interval [CI], 0.69-0.86). Dice coefficients were 0.90 (95% CI, 0.85-0.94) for areas of definitely decreased autofluorescence (DDAF), 0.55 (95% CI, 0.35-0.76) for areas of questionably decreased autofluorescence (QDAF), and 0.88 (95% CI, 0.73-1.00) for areas of abnormal background autofluorescence (ABAF). Intraclass correlation coefficients comparing the ground-truth and automated methods were 0.997 (95% CI, 0.996-0.998) for DDAF, 0.863 (95% CI, 0.823-0.895) for QDAF, and 0.974 (95% CI, 0.966-0.980) for ABAF. CONCLUSIONS: A DL algorithm performed accurate segmentation of autofluorescence lesions in Stargardt disease, demonstrating the feasibility of fully automated segmentation as an alternative to manual or semiautomated labeling methods.

Challenges of Cost-Effectiveness Analyses of Novel Therapeutics for Inherited Retinal Diseases.

PURPOSE: To investigate the challenges and potential improvement strategies of cost-effectiveness analyses performed for therapeutics targeting inherited retinal diseases (IRDs). DESIGN: Perspective. METHODS: A literature review was conducted with discussion of current limitations and improvement recommendations. RESULTS: Cost-effectiveness analysis (CEA) performed for IRD therapeutics has multiple limitations. First, the available methods used to measure health-related quality of life and health utilities can be inaccurate when used in IRDs. Second, the financial burden to patients and society from vision impairment associated with IRDs has been inadequately studied and includes a variety of expenditures ranging from direct costs of IRD specialty health care to indirect expenses associated with daily living activities. Third, our collective understanding is limited in the areas of IRD natural history and health benefits gained from new IRD treatments (eg, gene therapies). In addition, the therapeutic effect from a patient perspective and its duration of action are not fully understood. Due to the scarcity of data, CEA for newly approved therapies has relied on assumptions and creations of predictive models for both costs and health benefits for these new therapeutics in order to calculate the incremental cost-effectiveness ratio. CONCLUSIONS: CEA studies performed for IRD therapeutics have been limited by the established health utilities in ophthalmology and the lack of disease-specific information. The assumptions and extrapolations in these studies create substantial uncertainty in incremental cost-effectiveness ratio results. An improved framework is required for CEA of IRD therapeutics in order to determine the cost-effectiveness of each therapy brought from clinical trials to clinical practice.

A Novel Think Tank Program to Promote Innovation and Strategic Planning in Ophthalmic Surgery.

BACKGROUND: Continuous quality improvement is a pillar of all surgical groups. Innovation is a critical aspect to continuously improve, but traditional staff retreats have several disadvantages which limit their utility in identifying needs and developing innovative solutions. To address these challenges, we designed the novel Think Tank Program to spur innovation and strategic planning for an academic ophthalmology department including the Kellogg Eye Center 6 operating rooms. METHODS: The Think Tank program is a structured seven-phase program for faculty in small teams to identify, innovate, and implement meaningful change. Participants brainstormed problems and possible solutions to those problems, formed teams, acquired data, and implemented meaningful change in clinical care, research, education, and administration. RESULTS: The program generated 19 novel proposals and significant faculty engagement and discussion in improving the department. A case example of improving the operating room (OR) utilization resulted in improved OR utilization from 63.8% to 74.6% over a 3 month period before and after implementation. It also resulted in a reduction of cancelled or rescheduled surgeries within 2 weeks or surgery from 29.8% to 15.2%. This resulted in an estimated positive financial margin of over $141,000 to the institution in addition to improvement in patient, surgeon, and staff satisfaction with the quality of care. CONCLUSIONS: Engaged faculty, critical data analysis, and value proposition analysis with data-driven metrics and accountability can result in a significant increase in OR utilization and reduction in surgical cancellations. Think Tank serves as a model transformative program to assist practices and institutions to best fulfill their mission while actively engaging and retaining their members.

Calculation of test-retest variability in phase I/IIa clinical trials for Inherited Retinal Degenerations.

Background: Several novel treatments of inherited retinal degenerations have undergone phase I/IIa clinical trials with limited sample size, yet investigators must still determine if toxicity or an efficacy signal occurred or if the change was due to test-retest variability (TRV) of the measurement tool.Materials and Methods: Synthetic datasets were used to compare three types of TRV estimators under different sample sizes, mean drift, skewness, and number of baseline measurements.Results: Mixed effects models underestimated the standard deviation of measurement error (SDEM); the unbiased change score estimator method (UBS) was more accurate. The fixed effect model had less bias and smaller standard deviation than UBS if >2 baseline measurements. The change score estimator had no bias; other estimators introduced bias for lower variability. With sample size <10, all estimators had high variance. With sample size ≥10, the differences between methods were often minimal. The pooled estimator model did not capture drift, whereas a fixed effect regression or mixed effects models accounted for drift while maintaining an accurate measure of variance. With small sample sizes, the bootstrap estimates of SDEM were severe underestimates, while the jackknife estimates were mildly low but much better. The jackknife was more accurate for the unbiased change score method than for the pooled estimator.Conclusions: The ideal phase I/IIa study has ≥20 subjects and uses UBS or its fixed effect model generalization if >2 baseline measurements. With non-ideal study parameters, investigators should at least quantify the error estimate present in their data analysis.

Association of No-Cost Genetic Testing Program Implementation and Patient Characteristics With Access to Genetic Testing for Inherited Retinal Degenerations.

IMPORTANCE: The benefits of no-cost genetic testing initiatives have not been characterized. The no-cost My Retina Tracker Genetic Testing Study (MRT-GTS) research registry for inherited retinal degenerations (IRDs) was launched in 2017 in the US. OBJECTIVE: To investigate the associations of MRT-GTS implementation and patient characteristics with access to genetic testing for IRDs. DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional design, analysis of new patients evaluated 12 months before (July 1, 2016, to June 13, 2017) and 12 months after (June 14, 2017, to June 30, 2018) MRT-GTS implementation at a single academic referral eye center was conducted. Participants included 369 patients with IRD. Data analysis was conducted from February to June 2020. MAIN OUTCOMES AND MEASURES: Change in rates of successfully obtaining genetic testing, odds ratios (ORs) of association between patient characteristics and obtaining testing, and days elapsed from clinic visit to reporting of results. RESULTS: Among 369 patients (mean [SD] age, 39.5 [20.8] years; 193 [52.3%] women), 144 were evaluated in the pre-MRT-GTS period and 225 in the post-MRT-GTS period. The baseline rate of successfully obtaining testing was 51.4% (95% CI, 42.6%-60.2%). The initiation of MRT-GTS was associated with a 28.9-percentage point increase in testing rate (95% CI, 16.7%-41.1%; P < .001). Patient characteristics that increased the odds of obtaining testing were eligibility for MRT-GTS (OR, 14.15; 95% CI, 7.36-27.24; P < .001) and worse visual acuity (logMAR +1.0; Snellen equivalent decrease from 20/20 to 20/200) in the better-seeing eye (OR, 1.92; 95% CI, 1.27-2.91; P < .01). Patients had decreased odds when identifying as Black or African American (OR, 0.10; 95% CI, 0.04-0.24; P < .001) or other race (OR, 0.37; 95% CI, 0.15-0.91; P = .03) compared with White race, and when the primary language was not English (OR, 0.13; 95% CI, 0.03-0.55; P < .01). The proportion of test results reported within 90 days was 81.5% (95% CI, 74.8%-86.4%) when eligible for MRT-GTS compared with 48.1% (95% CI, 35.6%-58.1%) when not eligible (P < .001). CONCLUSIONS AND RELEVANCE: In this study, the implementation of MRT-GTS was associated with an increase in the proportion of patients who successfully obtained testing, suggesting the potential clinical value of this approach. Patient-level demographic and clinical factors appear to be associated with decisions to pursue testing.

Vision-related quality of life in adults with severe peripheral vision loss: a qualitative interview study.

BACKGROUND: Existing patient-reported outcome (PRO) measures may not be relevant to the full range of functional and vision-related quality of life (VR-QOL) concerns of individuals with vision impairment due to severe peripheral field loss (PFL). Measurement of VR-QOL in severe PFL is important in order to determine the effectiveness of vision rehabilitation interventions for this population. The purpose of this study was to characterize the impact of severe PFL due to retinitis pigmentosa (RP) and glaucoma on VR-QOL as the initial phase in the development of a novel PRO measure. METHODS: Individuals with severe PFL due to RP or glaucoma were recruited from the Kellogg Eye Center and the Association for the Blind and Visually Impaired. Participants completed semi-structured qualitative interviews, the Impact of Vision Impairment (IVI) questionnaire and the RAND 36-Item Health Survey. Interviews were analyzed by two coders using thematic analysis. A matrix analysis was conducted to compare VR-QOL by cause of severe PFL. Sample size was determined by thematic saturation. RESULTS: The study included 37 participants (19 RP, 18 glaucoma). Median best-corrected visual acuity for those with RP and glaucoma was 20/40 and 20/27.5, while Pelli-Robson contrast sensitivity was 1.2 log contrast sensitivity (logCS) and 1.1 logCS, respectively. Median domain scores on the IVI (reading, mobility, well-being) ranged from a low of - 0.2 to a high of 0.7 logits in those with RP and from 0.5 to 1.2 logits in those with glaucoma. Qualitative interviews identified six VR-QOL themes relevant across participants with both RP and glaucoma, including activity limitations, driving, emotional well-being, reading, mobility, and social function. VR-QOL concerns were largely consistent among those with severe PFL due to RP and glaucoma. These overarching themes contained content relevant to specific challenges related to severe PFL. CONCLUSIONS: There are commonly occurring VR-QOL concerns among individuals with severe PFL due to RP and glaucoma. The outlined themes will serve as the basis for development of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.

The Michigan Retinal Degeneration Questionnaire: A Patient-Reported Outcome Instrument for Inherited Retinal Degenerations.

PURPOSE: To create a psychometrically validated patient-reported outcome measure for inherited retinal degenerations. DESIGN: Qualitative and quantitative patient-reported outcome (PROs) questionnaire development using item response theory validation. METHODS: One hundred twenty-eight patients with a diagnosis of an inherited retinal degeneration at the Kellogg Eye Center (University of Michigan) were recruited and administered a 166-item questionnaire comprising 7 expert-defined domains. The questionnaire was re-administered 4-16 days later to a subset of 25 participants to assess test-retest variability. Graded response models were fit by Cai's Metropolis-Hastings Robbins-Monro algorithm using the R (version 3.6.3) package mirt. Model data were fit to assess questionnaire dimensionality, to estimate item information, and to score participants. Poorly functioning items were removed, and the model was refit to create the final questionnaire. RESULTS: The psychometrically validated PROs measure was reduced to a 59-item questionnaire measuring 7 unidimesnional domains: central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity. A total of 39 items were removed because of poor factor loading, low item information, poor person-ability differentiation, or high item-level interdependence. This novel questionnaire produces a reliable domain score for person ability that does not show significant test-retest variability across repeated administration. CONCLUSIONS: The final PRO questionnaire, known as the Michigan Retinal Degeneration Questionnaire, is psychometrically validated and available for use in the evaluation of patients with inherited retinal degenerations.

Coats-like Exudative Vitreoretinopathy in Retinitis Pigmentosa: Ocular Manifestations and Treatment Outcomes.

PURPOSE: To provide a comprehensive review of the ocular manifestations, outcomes, and genetic findings in patients with Coats-like retinitis pigmentosa (RP). DESIGN: Multicenter, retrospective, nonconsecutive case series. PARTICIPANTS: Patients with a diagnosis of RP demonstrating Coats-like exudative vitreoretinopathy between January 1, 2008, and October 1, 2019. METHODS: Evaluation of ocular findings at RP diagnosis and at time of presentation of Coats-like exudative vitreoretinopathy, pedigree analysis, genetic testing, retinal imaging, and anatomic outcomes after treatment. MAIN OUTCOME MEASURES: Visual acuity, ophthalmoscopy results, OCT results, fluorescein angiography results, and identification of genetic mutations. RESULTS: Nine patients diagnosed with RP and demonstrating Coats-like exudative vitreoretinopathy were included. Median age at time of RP diagnosis was 8 years (range, 1-22 years), and median age at presentation of Coats-like exudative vitreoretinopathy was 18 years (range, 1-41 years). Seven patients were female, and 2 were male. The genetic cause of disease was identified in 6 patients. Three patients demonstrated Coats-like fundus findings at the time of RP diagnosis. Exudative retinal detachment (ERD) localized to the infratemporal periphery was present in all patients, with bilateral disease observed in 7 patients. In all treated patients, focal laser photocoagulation was used to treat leaking telangiectasias and to limit further ERD expansion. Cystoid macular edema refractory to carbonic anhydrase inhibitor therapy and ultimately amenable to treatment with intravitreal anti-vascular endothelial growth factor injection was observed in 4 patients. CONCLUSIONS: Coats-like vitreoretinopathy is present in up to 5% of all RP patients. The term Coats-like RP is used colloquially to describe this disease state, which can present at the time of RP diagnosis or, more commonly, develops late during the clinical course of patients with longstanding RP. Coats-like RP is distinct from Coats disease in that exudative pathologic features occur exclusively in the setting of a coexisting RP diagnosis, is restricted to the infratemporal retina, can affect both eyes, and does not demonstrate a male gender bias. Given the risk of added vision loss posed by exudative vitreoretinopathy in patients with RP, a heightened awareness of this condition is critical in facilitating timely intervention.

The Michigan Vision-Related Anxiety Questionnaire: A Psychosocial Outcomes Measure for Inherited Retinal Degenerations.

OBJECTIVE: We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations. DESIGN: Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback. METHODS: Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of "worry" and "anxiety." The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis-Hastings Robbins-Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test-retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later. RESULTS: The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test-retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety). CONCLUSIONS: The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.