Poster Session: Development and validation of a virtual reality based toolkit to assess functional vision in Ultra Low Vision.

Ultra-Low Vision (ULV) refers to a level of vision that is ≦ 20/1600. There are a growing number of vision restoration treatments that recruit people with ULV or restore vision to the ULV level. At present, limited standardized outcome measures are available to assess visual potential before and after such vision restoration treatments. The ULV toolkit was developed as a standardized outcome measure for people with ULV. Three virtual reality (VR) based modules were developed to assess visual information gathering, hand-eye coordination and wayfinding in people with ULV. Each module consisted of a range of visually guided tasks related to activities of daily life (e.g., direction of motion of cars, flipping a light switch, boarding a train). Each correct/incorrect response was scored as '1'/ '0'. These raw scores were then analyzed to estimate item difficulty (item measure) and person ability (person measure). Item measures showed a wide range of difficulty levels that can be used to evaluate visual performance in people with ULV. Person measures were correlated with estimated logMAR visual acuity as well as completion rates, number of collisions and reaction times. This study bridges a big gap in the field of ULV where little is known about visual potential and usefulness in activities of daily life. VR provides portability and consistency for testing across participants with ULV thereby allowing for standardization of measurements across vision restoration studies.

CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA: A Long-Term Follow-Up Study.

PURPOSE: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). METHODS: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP. RESULTS: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20°) and blindness (central visual field <10°), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 ≤ BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's ρ = 0.733; P < 0.001). CONCLUSION: Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies.

CLINICAL AND GENETIC CHARACTERISTICS OF MALE PATIENTS WITH RPGR-ASSOCIATED RETINAL DYSTROPHIES: A Long-Term Follow-up Study.

PURPOSE: To describe the phenotype and clinical course of patients with RPGR-associated retinal dystrophies, and to identify genotype-phenotype correlations. METHODS: A multicenter medical records review of 74 male patients with RPGR-associated retinal dystrophies. RESULTS: Patients had retinitis pigmentosa (RP; n = 52; 70%), cone dystrophy (COD; n = 5; 7%), or cone-rod dystrophy (CORD; n = 17; 23%). The median follow-up time was 11.6 years (range 0-57.1). The median age at symptom onset was 5.0 years (range 0-14 years) for patients with RP and 23.0 years (range 0-60 years) for patients with COD/CORD. The probability of being blind (best-corrected visual acuity <0.05) at the age of 40 was 20% and 55% in patients with RP and COD/CORD, respectively. RPGR-ORF15 mutations were associated with high myopia (P = 0.01), which led to a faster best-corrected visual acuity decline in patients with RP (P < 0.001) and COD/CORD (P = 0.03). Patients with RP with RPGR-ORF15 mutations had a faster visual field decline (P = 0.01) and thinner central retina (P = 0.03) than patients with mutations in exon 1 to 14. CONCLUSION: Based on best-corrected visual acuity survival probabilities, the intervention window for gene therapy for RPGR-associated retinal dystrophies is relatively broad in patients with RP. RPGR-ORF15 mutations were associated with COD/CORD and with a more severe phenotype in RP. High myopia is a risk factor for faster best-corrected visual acuity decline.

The Effect of a Head-mounted Low Vision Device on Visual Function.

SIGNIFICANCE: Head-mounted low vision devices have received considerable attention in recent years owing to rapidly developing technology, facilitating ease of use and functionality. Systematic clinical evaluations of such devices remain rare but are needed to steer future device development. PURPOSE: The purpose of this study was to investigate, in a multicenter prospective trial, the short- and medium-term effects of a head-worn vision enhancement device (eSight Eyewear). METHODS: Participants aged 13 to 75 years with stable vision (distance acuity, 20/60 to 20/400; visual field diameter >20°) were recruited across six sites. Data were collected at baseline (no device), at fitting (with device), and after 3 months of everyday use. Outcome measures were visual ability measured by the Veterans Affairs Low Vision Visual Functioning Questionnaire 48, distance acuity (Early Treatment Diabetic Retinopathy Study), reading performance (MNREAD chart), contrast sensitivity (MARS chart), face recognition, and a modified version of the Melbourne Low Vision Activities of Daily Living (ADL) Index. RESULTS: Among the 51 participants, eSight introduction immediately improved distance acuity (0.74 ± 0.28 logMAR), contrast sensitivity (0.57 ± 0.53 log units), and critical print size (0.52 ± 0.43 logMAR), all P < .001, without any further change after 3 months; reading acuity improved at fitting (0.56 ± 0.35 logMAR) and by one additional line after 3 months, whereas reading speed only slightly increased across all three time points. The Melbourne ADL score and face recognition improved at fitting (P < .01) with trends toward further improvement at 3 months. After 3 months of use, Veterans Affairs Low Vision Visual Functioning Questionnaire 48 person measures (in logits) improved: overall, 0.84, P < .001; reading, 2.75, P < .001; mobility, 0.04, not statistically significant; visual information, 1.08, P < .001; and visual motor, 0.48, P = .02. CONCLUSIONS: eSight introduction yields immediate improvements in visual ability, with face recognition and ADLs showing a tentative benefit of further use. Overall, visual ability, reading, and visual information showed greatest benefit with device use. Further studies need to examine benefits of practice and training and possible differential effects of underlying pathology or baseline vision.

Genetic analysis of 10 pedigrees with inherited retinal degeneration by exome sequencing and phenotype-genotype association.

Our purpose was to identify causative mutations and characterize the phenotype associated with the genotype in 10 unrelated families with autosomal recessive retinal degeneration. Ophthalmic evaluation and DNA isolation were carried out in 10 pedigrees with inherited retinal degenerations (IRD). Exomes of probands from eight pedigrees were captured using Nimblegen V2/V3 or Agilent V5+UTR kits, and sequencing was performed on Illumina HiSeq. The DHDDS gene was screened for mutations in the remaining two pedigrees with Ashkenazi Jewish ancestry. Exome variants were filtered to detect candidate causal variants using exomeSuite software. Segregation and ethnicity-matched control sample analysis were performed by dideoxy sequencing. Retinal histology of a patient with DHDDS mutation was studied by microscopy. Genetic analysis identified six known mutations in ABCA4 (p.Gly1961Glu, p.Ala1773Val, c.5461-10T>C), RPE65 (p.Tyr249Cys, p.Gly484Asp), PDE6B (p.Lys706Ter) and DHDDS (p.Lys42Glu) and ten novel potentially pathogenic variants in CERKL (p.Met323Val fsX20), RPE65 (p.Phe252Ser, Thr454Leu fsX31), ARL6 (p.Arg121His), USH2A (p.Gly3142Ter, p.Cys3294Trp), PDE6B (p.Gln652Ter), and DHDDS (p.Thr206Ala) genes. Among these, variants/mutations in two separate genes were observed to segregate with IRD in two pedigrees. Retinal histopathology of a patient with a DHDDS mutation showed severe degeneration of retinal layers with relative preservation of the retinal pigment epithelium. Analysis of exome variants in ten pedigrees revealed nine novel potential disease-causing variants and nine previously reported homozygous or compound heterozygous mutations in the CERKL, ABCA4, RPE65, ARL6, USH2A, PDE6B, and DHDDS genes. Mutations that could be sufficient to cause pathology were observed in more than one gene in one pedigree.

Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study.

PURPOSE: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies. DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families. METHODS: A medical record review of 55 patients for age at onset, medical history, initial symptoms, best-corrected visual acuity, ophthalmoscopy, fundus photography, full-field electroretinography (ffERG), Goldmann visual fields (VFs), and spectral-domain optical coherence tomography. MAIN OUTCOME MEASURES: Age at onset, visual acuity survival time, visual acuity decline rate, and electroretinography and imaging findings. RESULTS: A retinitis pigmentosa (RP) phenotype was present in 50 patients, 34 of whom were from a Dutch genetic isolate (GI), and 5 patients had a Leber congenital amaurosis phenotype. The mean follow-up time was 15.4 years (range, 0-55.5 years). For the RP patients, the median age at symptom onset was 4.0 years. In the RP group, median ages for reaching low vision, severe visual impairment, and blindness were 18, 32, and 44 years, respectively, with a visual acuity decline rate of 0.03 logarithm of the minimum angle of resolution per year. The presence of a truncating mutation did not alter the annual decline rate significantly (P = 0.75). Asymmetry in visual acuity was found in 31% of patients. The annual VF decline rate was 5% in patients from the genetic isolate, which was significantly faster than in non-GI patients (P < 0.05). Full-field electroretinography responses were extinguished in 50% of patients, were pathologically attenuated without a documented rod or cone predominance in 30% of patients, and showed a rod-cone dysfunction pattern in 20% of RP patients. Cystoid fluid collections in the macula were found in 50% of RP patients. CONCLUSIONS: Mutations in the CRB1 gene are associated with a spectrum of progressive retinal degeneration. Visual acuity survival analyses indicate that the optimal intervention window for subretinal gene therapy is within the first 2 to 3 decades of life.

Performance of real-world functional vision tasks by blind subjects improves after implantation with the Argus® II retinal prosthesis system.

BACKGROUND: The main objective of this study was to test Argus II subjects on three real-world functional vision tasks. DESIGN: The study was designed to be randomized and prospective. Testing was conducted in a hospital/research laboratory setting at the various participating centres. PARTICIPANTS: Twenty eight Argus II subjects, all profoundly blind, participated in this study. METHODS: Subjects were tested on the three real-world functional vision tasks: Sock Sorting, Sidewalk Tracking and Walking Direction Discrimination task MAIN OUTCOME MEASURES: For the Sock Sorting task, percentage correct was computed based on how accurately subjects sorted the piles on a cloth-covered table and on a bare table. In the Sidewalk Tracking task, an 'out of bounds' count was recorded, signifying how often the subject veered away from the test course. During the Walking Direction Discrimination task, subjects were tested on the number of times they correctly identified the direction of testers walking across their field of view. RESULTS: The mean percentage correct OFF versus ON for the Sock Sorting task was found to be significantly different for both testing conditions (t-test, P < 0.01). On the Sidewalk Tracking task, subjects performed significantly better with the system ON than they did with the system OFF (t-test, P < 0.05). Eighteen (18) of 27 subjects (67%) performed above chance with the system ON, and 6 (22%) did so with system OFF on the Walking Direction Discrimination task. CONCLUSIONS: Argus II subjects performed better on all three tasks with their systems ON than they did with their systems OFF.

The Bionic Eye: A Quarter Century of Retinal Prosthesis Research and Development.

This article describes the history of visual prostheses, with emphasis on the development of the Argus II retinal prosthesis system (Second Sight Medical Products, Inc., Sylmar, CA). A brief overview of cortical electrical stimulation in the blind is provided, followed by an account of the design and development of retinal stimulation equipment at the Duke Eye Center in the late 1980s; the first human intraoperative tests there and the subsequent 8 years of tests at the Wilmer Eye Institute; the transfer of the project to the Doheny Eye Institute at the University of Southern California and the founding of Second Sight Medical Products; and the development and clinical trials of the Argus I and Argus II systems. In a series of vignettes, we pay tribute to the many colleagues and patient volunteers without whose help the work would not have been possible.

Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa.

PURPOSE: USH2A mutations are an important cause of retinitis pigmentosa (RP) with or without congenital sensorineural hearing impairment. We studied genotype-phenotype correlations and compared visual prognosis in Usher syndrome type IIa and nonsyndromic RP. DESIGN: Clinic-based, longitudinal, multicenter study. PARTICIPANTS: Consecutive patients with Usher syndrome type IIa (n = 152) and nonsyndromic RP (n = 73) resulting from USH2A mutations from ophthalmogenetic clinics in the Netherlands and Belgium. METHODS: Data on clinical characteristics, visual acuity, visual field measurements, retinal imaging, and electrophysiologic features were extracted from medical charts over a mean follow-up of 9 years. Cumulative lifetime risks of low vision and blindness were estimated using Kaplan-Meier survival analysis. MAIN OUTCOME MEASURES: Low vision and blindness. RESULTS: Participant groups had similar distributions of gender (48% vs. 45% males in Usher syndrome type IIa vs. nonsydromic RP; P = 0.8), ethnicity (97% vs. 99% European; P = 0.3), and median follow-up time (6.5 years vs. 3 years; P = 0.3). Usher syndrome type IIa patients demonstrated symptoms at a younger age (median age, 15 years vs. 25 years; P < 0.001), were diagnosed earlier (median age, 26 years vs. 36.5 years; P < 0.001), and became visually impaired 13 years earlier (median age, 41 years vs. 54 years; P < 0.001) based on VF and 18 years earlier based on VA (median age, 54 years vs. 72 years; P < 0.001) than nonsyndromic RP patients. The presence of 2 truncating mutations in USH2A was associated mostly with the syndromic phenotype, whereas other combinations were present in both groups. We found novel variants in Usher syndrome type IIa (25%) and nonsyndromic RP (19%): 29 missense mutations, 10 indels, 14 nonsense mutations, 9 frameshift mutations, and 5 splice-site mutations. CONCLUSIONS: Most patients with USH2A-associated RP have severe visual impairment by age 50. However, those with Usher syndrome type IIa have an earlier decline of visual function and a higher cumulative risk of visual impairment than those without nonsyndromic RP. Complete loss of function of the USH2A protein predisposes to Usher syndrome type IIa, but remnant protein function can lead to RP with or without hearing loss.

Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

PURPOSE: The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. DESIGN: Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. PARTICIPANTS: Thirty participants in 10 centers in the United States and Europe. METHODS: The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. RESULTS: Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. CONCLUSIONS: The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.

Electrically evoked electroretinograms and pupil responses in Argus II retinal implant wearers.

PURPOSE: We have recorded the electrically evoked electroretinogram (eERG) and flash ERG in Argus II retinal prosthesis wearers with end-stage retinitis pigmentosa to estimate response properties of the degenerated inner retina to local electrical stimulation. In addition, we have recorded pupil diameters during electrical stimulation. METHODS: Raw corneal eERGs were recorded at multiple stimulus levels in three subjects. eERG signals were heavily contaminated with various artifacts, including switching artifacts generated by the implant electronics, stimulus, blink, and eye-movement artifacts. Pupil responses were recorded in one subject using a pupil tracker. RESULTS: eERGs were decontaminated by a variety of techniques, including wavelet transformation and response averaging. The dominant component was a negative wave peaking at approximately 200 ms. eERG amplitudes correlated significantly with stimulus level, but peak latencies did not correlate with stimulus level. Pupil constriction correlated significantly with stimulus level and pupil responses could be accurately used to estimate subjective threshold. CONCLUSION: eERG recordings hold the potential to be developed further for use as a diagnostic tool for retinal implants. A straightforward approach to increase eERG amplitudes would be the development of intraocular recording methods based on reverse telemetry. The robust pupil response to electrical stimulation in one subject indicates that pupillography can be exploited to assess implant functionality, but reliable pupil recordings could not be obtained in all subjects.

Worldwide Argus II implantation: recommendations to optimize patient outcomes.

BACKGROUND: A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. METHODS: Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. RESULTS: Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon's capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. CONCLUSIONS: Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.

Variability and Errors of Manually Digitized Goldmann Visual Fields.

PURPOSE: Goldmann visual fields (GVFs) are useful for tracking changes in areas of functional retina, including the periphery, in inherited retinal degeneration patients. Quantitative GVF analysis requires digitization of the chart coordinates for the main axes and isopter points marked by the GVF operator during testing. This study investigated inter- and intra-digitizer variability among users of a manual GVF digitization program. METHODS: Ten digitizers were trained for 1 hour, then digitized 23 different GVFs from inherited retinal degeneration patients in each of three testing blocks. Digitizers labeled each isopter as seeing or non-seeing, and its target size. Isopters with the same test target within each GVF were grouped to create isopter groups. RESULTS: The standard deviation of isopter group area showed an approximate square-root relationship with total isopter group area. Accordingly, the coefficient of variation for isopter group area decreased from 68% to 0.2% with increasing isopter group area. A bootstrap version of ANOVA did not reveal a significant effect of digitizers on isopter group area. Simulations involving random sampling of digitizers showed that five to seven digitizers would be required to catch 95% to 99% of labeling errors and isopter misses, on the basis of data discrepancies, with 99% probability. CONCLUSIONS: These data suggest that any minimally trained digitizer would be capable of reliably determining any isopter area, regardless of size. Studies using this software could either use five to seven minimally trained digitizers for each GVF, three digitizers who demonstrate low frequencies of errors on a practice set of GVFs, or two digitizers with an expert reader to adjudicate discrepancies and catch errors.

Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial.

BACKGROUND: Leber congenital amaurosis, caused by mutations in RPE65 and LRAT, is a severe form of inherited retinal degeneration leading to blindness. We aimed to assess replacement of the missing chromophore 11-cis retinal with oral QLT091001 (synthetic 9-cis-retinyl acetate) in these patients. METHODS: In our open-label, prospective, phase 1b trial, we enrolled patients (aged ≥6 years) with Leber congenital amaurosis and RPE65 or LRAT mutations at McGill University's Montreal Children's Hospital. Patients received 7 days of oral QLT091001 (10-40 mg/m(2) per day). We assessed patients at baseline and days 7, 9, 14, and 30, and then 2 months and every 2 months thereafter for up to 2·2 years for safety outcomes and visual function endpoints including Goldmann visual fields (GVF), visual acuity, and functional MRI assessment. We regarded patients as having an improvement in vision if we noted at least a 20% improvement in retinal area on GVF compared with baseline or a visual acuity improvement of five or more letters compared with baseline in two consecutive study visits (or any improvement from no vision at baseline). This study is registered with ClinicalTrials.gov, number NCT01014052. FINDINGS: Between December, 2009, and June, 2011, we enrolled and treated 14 patients aged 6-38 years who were followed up until March, 2012. Ten (71%) of 14 patients had an improvement in GVF areas (mean increase in retinal area of 28-683%). Six (43%) patients had an improvement in visual acuity (mean increase of 2-30 letters). Self-reported or parent-reported improvements in activities of daily living supported these findings. After 2 years, 11 (79%) patients had returned to their baseline GVF retinal area and ten (71%) had returned to baseline visual acuity letter values. Thus, three (21%) patients had a sustained GVF response and four (30%) had a sustained visual acuity response. Four patients had functional MRI scans, which correlated with visual response or absence of response to treatment. No serious adverse events occurred, although we noted transient headaches (11 patients), photophobia (11 patients), reduction in serum HDL concentrations (four patients), and increases in serum triglycerides (eight patients) and aspartate aminotransferase concentrations (two patients). INTERPRETATION: Non-invasive oral QLT091001 therapy is well tolerated, and can rapidly improve visual function in some patients with Leber congenital amaurosis and RPE65 and LRAT mutations. FUNDING: QLT, Foundation Fighting Blindness Canada, CIHR, FRSQ, Reseau Vision.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind.

PURPOSE: Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN: The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS: There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS: The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES: The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS: A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS: The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Benefits of thermal and distance-filtered imaging for wayfinding with prosthetic vision.

Visual prostheses such as the Argus II provide partial vision for individuals with limited or no light perception. However, their effectiveness in daily life situations is limited by scene complexity and variability. We investigated whether additional image processing techniques could improve mobility performance in everyday indoor environments. A mobile system connected to the Argus II provided thermal or distance-filtered video stimulation. Four participants used the thermal camera to locate a person and the distance filter to navigate a hallway with obstacles. The thermal camera allowed for finding a target person in 99% of trials, while unfiltered video led to confusion with other objects and a success rate of only 55% ([Formula: see text]). Similarly, the distance filter enabled participants to detect and avoid 88% of obstacles by removing background clutter, whereas unfiltered video resulted in a detection rate of only 10% ([Formula: see text]). For any given elapsed time, the success rate with filtered video was higher than with unfiltered video. After 90 s, participants' success rate reached above 50% with filtered video and 24% and 3% with normal camera in the first and second tasks, respectively. Despite individual variations, all participants showed significant improvement when using the thermal and distance filters compared to unfiltered video. Adding a thermal and distance filter to a visual prosthesis system can enhance the performance of mobility activities by removing clutter in the background, showing people and warm objects with the thermal camera, or nearby obstacles with the distance filter.

Functional Vision in Patients With Biallelic USH2A Variants.

PURPOSE: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (VTOT) at baseline in patients with biallelic USH2A variants. DESIGN: Multicenter, international, cross-sectional study. METHODS: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations. The VALVVFQ-48 was administered verbally to participants ≥18 years old. VA was measured in both eyes; VTOT was determined from static perimetry in the study eye (better VA). FV scores were calculated using Rasch analysis. RESULTS: Median age of 121 participants (76 with USH2, 45 with ARRP) was 41 years (range: 19-80); 54% were female. FV scores varied from -2.0 to 7.6 logits (median [interquartile range (IQR)]: 2.8 [1.5-3.8]). ARRP and USH2 participants had similar FV scores, both before [mean (95% CI): 2.8 (2.3-3.4) and 2.7 (2.3-3.2), respectively], and after [mean (95% CI): 2.5 (2.1-3.0) and 2.9 (2.6-3.3), respectively; P = .24] adjusting for age, VA, disease duration, and VTOT. VA and VTOT accounted for 29% and 26% of the variance in FV scores, respectively (P < .001 for each). Together, they accounted for 36% of variance observed. CONCLUSIONS: Biallelic USH2A variants were associated with a large range of FV, yet similar in ARRP and USH2, despite hearing loss in USH2. The modified VALVVFQ-48 we evaluated is not ideal for detecting the impact of USH2A-associated retinal degenerations on activities of daily living.

Self-Reported Functional Vision in USH2A-Associated Retinal Degeneration as Measured by the Michigan Retinal Degeneration Questionnaire.

Purpose: The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements. Design: An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene. Methods: The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments. Results: Of the study sample, 58% were female participants and the median disease duration was 13 years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA). Conclusions: Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes.

Self-Reported Visual Ability Versus Task Performance in Individuals With Ultra-Low Vision.

Purpose: Visual functioning questionnaires are commonly used as patient-reported outcome measures to estimate visual ability. Performance measures, on the other hand, provide a direct measure of visual ability. For individuals with ultra-low vision (ULV; visual acuity (VA) <20/1600), the ultra-low vision visual functioning questionnaire (ULV-VFQ) and the Wilmer VRI-a virtual reality-based performance test-estimate self-reported and actual visual ability, respectively, for activities of daily living. But how well do self-reports from ULV-VFQ predict actual task performance in the Wilmer VRI? Methods: We administered a subset of 10 matching items from the ULV-VFQ and Wilmer VRI to 27 individuals with ULV. We estimated item measures (task difficulty) and person measures (visual ability) using Rasch analysis for ULV-VFQ and using latent variable signal detection theory for the Wilmer VRI. We then used regression analysis to compare person and item measure estimates from self-reports and task performance. Results: Item and person measures were modestly correlated between the two instruments, with r2 = 0.47 (P = 0.02) and r2 = 0.36 (P = 0.001), demonstrating that self-reports are an imperfect predictor of task difficulty and performance. Conclusions: While self-reports impose a lower demand for equipment and personnel, actual task performance should be measured to assess visual ability in ULV. Translational Relevance: Visual performance measures should be the preferred outcome measure in clinical trials recruiting individuals with ULV. Virtual reality can be used to standardize tasks.

Measuring visual information gathering in individuals with ultra low vision using virtual reality.

People with ULV (visual acuity ≤ 20/1600 or 1.9 logMAR) lack form vision but have rudimentary levels of vision that can be used for a range of activities in daily life. However, current clinical tests are designed to assess form vision and do not provide information about the range of visually guided activities that can be performed in daily life using ULV. This is important to know given the growing number of clinical trials that recruit individuals with ULV (e.g., gene therapy, stem cell therapy) or restore vision to the ULV range in the blind (visual prosthesis). In this study, we develop a set of 19 activities (items) in virtual reality involving spatial localization/detection, motion detection, and direction of motion that can be used to assess visual performance in people with ULV. We estimated measures of item difficulty and person ability on a relative d prime (d') axis using a signal detection theory based analysis for latent variables. The items represented a range of difficulty levels (- 1.09 to 0.39 in relative d') in a heterogeneous group of individuals with ULV (- 0.74 to 2.2 in relative d') showing the instrument's utility as an outcome measure in clinical trials.