Assessing the role of visual dysfunctions in the association between visual symptomatology and the use of digital devices / Evaluación del papel de las disfunciones visuales en la asociación entre la sintomatología visual y el uso de dispositivos digitales

Purpose: To evaluate the association between visual symptoms and use of digital devices considering the presence of visual dysfunctions. Methods: An optometric examination was conducted in a clinical sample of 346 patients to diagnose any type of visual anomaly. Visual symptoms were collected using the validated SQVD questionnaire. A threshold of 6 hours per day was used to quantify the effects of digital device usage and patients were divided into two groups: under and above of 35 years old. A multivariate logistic regression was employed to investigate the association between digital device use and symptoms, with visual dysfunctions considered as a confounding variable. Crude and the adjusted odds ratio (OR) were calculated for each variable. Results: 57.02 % of the subjects reported visual symptoms, and 65.02% exhibited some form of visual dysfunction. For patients under 35 years old, an association was found between having visual symptoms and digital device use (OR = 2.10, p = 0.01). However, after adjusting for visual dysfunctions, this association disappeared (OR = 1.44, p = 0.27) and the association was instead between symptoms and refractive dysfunction (OR = 6.52, p < 0.001), accommodative (OR = 10.47, p < 0.001), binocular (OR = 6.68, p < 0.001) and accommodative plus binocular dysfunctions (OR = 46.84, p < 0.001). Among patients over 35 years old, no association was found between symptoms and the use of digital devices (OR = 1.27, p = 0.49) but there was an association between symptoms and refractive dysfunction (OR = 3.54, p = 0.001). Conclusions: Visual symptoms are not dependent on the duration of digital device use but rather on the presence of any type of visual dysfunction: refractive, accommodative and/or binocular one, which should be diagnosed.(AU)

Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

TORONTO: A trial-oriented multidimensional psychometric testing algorithm.

Bayesian adaptive methods for sensory threshold determination were conceived originally to track a single threshold. When applied to the testing of vision, they do not exploit the spatial patterns that underlie thresholds at different locations in the visual field. Exploiting these patterns has been recognized as key to further improving visual field test efficiency. We present a new approach (TORONTO) that outperforms other existing methods in terms of speed and accuracy. TORONTO generalizes the QUEST/ZEST algorithm to estimate simultaneously multiple thresholds. After each trial, without waiting for a fully determined threshold, the trial-oriented approach updates not only the location currently tested but also all other locations based on patterns in a reference data set. Since the availability of reference data can be limited, techniques are developed to overcome this limitation. TORONTO was evaluated using computer-simulated visual field tests: In the reliable condition (false positive [FP] = false negative [FN] = 3%), the median termination and root mean square error (RMSE) of TORONTO was 153 trials and 2.0 dB, twice as fast with equal accuracy as ZEST. In the FP = FN = 15% condition, TORONTO terminated in 151 trials and was 2.2 times faster than ZEST with better RMSE (2.6 vs. 3.7 dB). In the FP = FN = 30% condition, TORONTO achieved 4.2 dB RMSE in 148 trials, while all other techniques had > 6.5 dB RMSE and terminated much slower. In conclusion, TORONTO is a fast and accurate algorithm for determining multiple thresholds under a wide range of reliability and subject conditions.

Vision-related quality of life after unilateral occipital stroke.

BACKGROUND/OBJECTIVES: Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision-related quality of life (VR-QoL) is impacted by time since stroke. SUBJECTS/METHODS: We conducted a retrospective meta-analysis of 95 occipital stroke patients (female/male = 26/69, 27-78 years old, 0.5-373.5 months poststroke) in whom VR-QoL was estimated using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ) and its 10-item neuro-ophthalmic supplement (Neuro10). Visual deficit severity was represented by the perimetric mean deviation (PMD) calculated from 24-2 Humphrey visual fields. Data were compared with published cohorts of visually intact controls. The relationship between VR-QoL and time poststroke was assessed across participants, adjusting for deficit severity and age with a multiple linear regression analysis. RESULTS: Occipital stroke patients had significantly lower NEI-VFQ and Neuro10 composite scores than controls. All subscale scores describing specific aspects of visual ability and functioning were impaired except for ocular pain and general health, which did not differ significantly from controls. Surprisingly, visual deficit severity was not correlated with either composite score, both of which increased with time poststroke, even when adjusting for PMD and age. CONCLUSIONS: VR-QoL appears to improve with time postoccipital stroke, irrespective of visual deficit size or patient age at insult. This may reflect the natural development of compensatory strategies and lifestyle adjustments. Thus, future studies examining the impact of rehabilitation on daily living in this patient population should consider the possibility that their VR-QoL may change gradually over time, even without therapeutic intervention.

Portable multi-focal visual evoked potential diagnostics for multiple sclerosis/optic neuritis patients.

PURPOSE: Multiple sclerosis (MS) is a neuro-inflammatory disease affecting the central nervous system (CNS), where the immune system targets and damages the protective myelin sheath surrounding nerve fibers, inhibiting axonal signal transmission. Demyelinating optic neuritis (ON), a common MS symptom, involves optic nerve damage. We've developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from the scalp using custom electroencephalography electrodes. METHODS: Subject vision is evaluated using a short 2.5-min full-field visual evoked potentials (ffVEP) test, followed by a 12.5-min multifocal VEP (mfVEP) test. The ffVEP evaluates the integrity of the visual pathway by analyzing the P100 component from each eye, while the mfVEP evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEPs. Key metrics from patients' ffVEP results were statistically evaluated against data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification. RESULTS: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging and Optical Coherence Tomography findings. CONCLUSION: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

Wide-Field Optical Coherence Tomography Imaging Improves Rate of Change Detection in Progressing Glaucomatous Eyes Compared With Standard-Field Imaging.

Purpose: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images. Methods: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included. Results: Thirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27). Conclusions: In this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

Differences in Systemic Pulse Waveform Between Individuals With Glaucoma, Glaucoma Suspects, and Healthy Controls.

Purpose: It has been hypothesized that compromised ocular circulation in glaucoma may be concomitant of systemic changes. The purpose of this study is to test whether systemic blood flow pulse waveform patterns differ between individuals with glaucoma (GL), glaucoma suspects (GLS), and normal healthy controls (HC). Methods: The study included 35 bilateral GL, 67 bilateral GLS, 29 individuals with unilateral GL who were considered GLS in the other eye, and 44 healthy controls. Systemic pulsatile blood pressure waveforms were recorded using a finger cuff. A continuous 200 Hz plethysmography recording is made to obtain a pulse waveform. Waveform parameters were extracted using custom software from an average of eight pulse cycles. These were compared between GL, GLS, and HC groups on a per-eye basis, using generalized estimating equation models to account for intereye correlations; and plotted against disease severity by visual field linearized mean deviation (MDlin) and retinal nerve fiber layer thickness (RNFLT). Results: Averaged blood pressure was significantly lower in the HC group (mean ± standard deviation 91.7 ±11.7 mm Hg) than the GLS (102.4 ± 13.9) or GL (102.8 ± 13.7) groups, with P < 0.0001 (generalized estimating equation regression). Waveform parameters representing vascular resistance were higher in both GLS and GL groups than the HC group; and were correlated with RNFLT and MDlin (P ≤ 0.05). Conclusions: The shape of the systemic pulsatile waveform differs in individuals with GL/GLS suspects, compared to HC eyes. Blood pressure changes more rapidly in individuals with GL, which suggests higher arterial stiffness.

Retinal Ganglion Cell Content Underlying Standard Automated Perimetry Size I to V Visual Sensitivities in the Non-Human Primate Experimental Glaucoma Model.

Purpose: To determine the relationship between visual sensitivities from white-on-white Goldmann size I to V stimuli and the underlying retinal ganglion cell (RGC) content in the non-human primate (NHP) experimental glaucoma model. Methods: Normative data were collected from 13 NHPs. Unilateral experimental glaucoma was induced in seven animals with the least variable fields who were monitored using optical coherence tomography and 30-2 full-threshold standard automated perimetry (SAP). At varying endpoints, animals were euthanized followed by perfusion fixation, and 1-mm retinal punches were obtained from 34 corresponding SAP locations. RGCs were immunolabeled with an antibody against an RNA-binding protein (RBPMS) marker and imaged using confocal microscopy. RGC counts from each location were then related to visual sensitivities for each stimulus size, after accounting for ocular magnification. Results: At the endpoint, the circumpapillary retinal nerve fiber layer thickness for experimental glaucoma eyes ranged from 47 to 113 µm. RGC density in control eyes was greatest for the 4.24° sample (18,024 ± 6869 cells/mm2) and decreased with eccentricity. Visual sensitivity at each tested location followed that predicted by spatial summation, with the critical area increasing with eccentricity (slope = 0.0036, R2 = 0.44). The relationship between RGC counts and visual sensitivity was described using a two-line fit, where the intercept of the first segment and hinge points were dependent on eccentricity. Conclusions: In NHPs, SAP visual thresholds are related to the underlying RGCs. The resulting spatial summation based structure-function model can be used to estimate RGC content from any standard white-on-white stimulus size.

Assessment of local sensitivity in incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) lesions in intermediate age-related macular degeneration (iAMD).

Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings.

Contributions of Brain Microstructures and Metabolism to Visual Field Loss Patterns in Glaucoma Using Archetypal and Information Gain Analyses.

Purpose: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures. Methods: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with 16 archetypal VF loss patterns. We also ranked neuroimaging, ophthalmic, and demographic attributes in terms of their information gain to determine their importance to glaucoma. Results: In dMRI, decreasing fractional anisotropy, radial kurtosis, and tortuosity and increasing radial diffusivity correlated with greater overall VF loss bilaterally. Regionally, decreasing intra-axonal space and extra-axonal space diffusivities correlated with greater VF loss in the superior-altitudinal area of the right eye and the inferior-altitudinal area of the left eye. In MRS, both early and advanced glaucoma patients had lower gamma-aminobutyric acid (GABA), glutamate, and choline levels than healthy controls. GABA appeared to associate more with superonasal VF loss, and glutamate and choline more with inferior VF loss. Choline ranked third for importance to early glaucoma, whereas radial kurtosis and GABA ranked fourth and fifth for advanced glaucoma. Conclusions: Our findings highlight the importance of non-invasive neuroimaging biomarkers and analytical modeling for unveiling glaucomatous neurodegeneration and how they reflect complementary VF loss patterns.

Does using a bioptic telescope improve visual recognition of the on-road environment?

SIGNIFICANCE: Individuals with reduced visual acuity (VA) may drive with bioptic telescopes in some jurisdictions. The effect of bioptic telescope use on on-road recognition distances is important for driving safety, as increased recognition distances increase the time available to react to road signs or driving events. PURPOSE: This study aimed to investigate the impact of bioptic telescope use on visual recognition of road signs, traffic lights, and hazards in an on-road driving environment in individuals with reduced VA. METHODS: Ten individuals (mean ± standard deviation age, 39.1 ± 19.1 years) with reduced VA (trained to use bioptic telescopes) participated in a repeated-measures on-road experiment for two viewing conditions, with and without a bioptic telescope (randomized order). Participants underwent a clinical low vision assessment, including high-contrast VA with and without the bioptic telescope aligned, visual fields, and contrast sensitivity testing. For the driving component, participants seated in the front passenger seat of a moving car reported all road signs, traffic lights, and hazards (unpredictable road events that represent a risk to driving safety including other vehicles, cyclists, pedestrians) seen along a route that included suburban roads and highways. Video cameras captured participants' viewing behavior, verbal commentary, and the distance at which three pre-selected road signs were reported. RESULTS: In the eye with the bioptic telescope, high-contrast VA improved from 0.75 ± 0.17 (without) to 0.25 ± 0.1 logMAR with the bioptic telescope. Bioptic telescope use did not affect the percentage of road signs, traffic lights, or hazards correctly recognized but did result in 2.6 times longer recognition distances (49 ± 23 vs. 19 ± 11 m, t9 = 5.02, p<0.001). CONCLUSIONS: Road signs were recognized at significantly longer distances when using a bioptic telescope, confirming their positive impact on timely visual recognition of objects within the driving scene. Future work should explore whether this effect generalizes to individuals using bioptic telescopes when driving a vehicle.

The impact of vision loss on attitudes toward autonomous vehicles: A vision-centric analysis.

SIGNIFICANCE: Autonomous vehicles (AVs) have the promise to be an alternative transportation solution for those with vision loss. However, the impact of vision loss on the perceptions and concerns of AVs is unknown. This study therefore examined whether AVs are perceived differently by blind, visually impaired (VI), and normally sighted people. PURPOSE: This study compared the perceptions of AVs among the blind, VI, and normally sighted. METHODS: Participants' opinions on four perception measures (general opinion, trust, impact on quality of life, and intention to use AVs) and nine concerns regarding AVs were measured. The survey was administered to 51 normally sighted, 68 VI, and 65 blind participants. Analyses of covariance assessed whether the four perception measures and nine concerns varied by vision status (normal vision, VI, blind) and driving status (driver, nondriver). Univariate correlations and multiple regression analyses identified associations and predictors of AV perceptions and concerns from demographic, mood, cognition, travel behavior, and vision measures, which included visual acuity, contrast sensitivity, and visual field. RESULTS: The blind (p<0.001), VI (p<0.001), and nondrivers (p<0.001) showed a greater intention to use AVs compared with those with normal vision and drivers. Similar findings were found for the other perception measures. As visual acuity, contrast sensitivity, and visual field extent declined, positivity toward AVs increased (p<0.001). Visual field extent best predicted general opinion and trust in AVs, whereas driving measures were the best predictors of impact on quality of life and intention to use AVs. Concerns about AVs showed no differences based on vision (p=0.94) or driving (p=0.63) status. CONCLUSIONS: Individuals with vision loss expressed more acceptance of AVs despite their concerns. How positive someone is toward AVs appears to be dependent on their visual field extent and driving status.

Pilot study of a pedestrian collision detection test for a multisite trial of field expansion devices for hemianopia.

SIGNIFICANCE: Performance-based outcome measures are crucial for clinical trials of field expansion devices. We implemented a test simulating a real-world mobility situation, focusing on detection of a colliding pedestrian among multiple noncolliding pedestrians, suitable for measuring the effects of homonymous hemianopia and assistive devices in clinical trials. PURPOSE: In preparation for deploying the test in a multisite clinical trial, we conducted a pilot study to gather preliminary data on blind-side collision detection performance with multiperiscopic peripheral prisms compared with Fresnel peripheral prisms. We tested the hypothesis that detection rates for colliding pedestrians approaching on a 40° bearing angle (close to the highest collision risk when walking) would be higher with 100Δ oblique multiperiscopic (≈42° expansion) than 65Δ oblique Fresnel peripheral prisms (≈32° expansion). METHODS: Six participants with homonymous hemianopia completed the test with and without each type of prism glasses, after using them in daily mobility for a minimum of 4 weeks. The test, presented as a video on a large screen, simulated walking through a busy shopping mall. Colliding pedestrians approached from the left or the right on a bearing angle of 20 or 40°. RESULTS: Overall, blind-side detection was only 23% without prisms but improved to 73% with prisms. For multiperiscopic prisms, blind-side detection was significantly higher with than without prisms at 40° (88 vs. 0%) and 20° (75 vs. 0%). For Fresnel peripheral prisms, blind-side detection rates were not significantly higher with than without prisms at 40° (38 vs. 0%) but were significantly higher with prisms at 20° (94 vs. 56%). At 40°, detection rates were significantly higher with multiperiscopic than Fresnel prisms (88 vs. 38%). CONCLUSIONS: The collision detection test is suitable for evaluating the effects of hemianopia and prism glasses on collision detection, confirming its readiness to serve as the primary outcome measure in the upcoming clinical trial.

The effects of simulated monocular and binocular vision impairment on football penalty kick performance.

Sports performance is relatively robust under high levels of binocular blur. However, the limited research studies investigating monocular impairments has shown it has a larger impact on sport performance. This research study is relevant for classification in sports for athletes with vision impairment (VI), where visual acuity (VA) from the better eye is used during classification. Across two experiments, we aimed to establish the point at which binocular and monocular impairments affected performance in a football penalty kick (PK) through simulating varying severities of degraded VA and contrast sensitivity (CS) in active football players. In experiment one, 25 footballers performed PKs as VA and CS were systematically decreased in both eyes, and in one condition, visual field (VF) was reduced. The most severe VA/CS condition and reduced VF significantly impacted outcome, ball velocity and placement (ball kicked closer to the centre of the goal) (p < 0.05). In experiment two, 29 different footballers performed PKs as VA and CS of only the dominant eye were systematically decreased and in one condition the dominant eye was occluded, and participants viewed their environment through the non-dominant eye (monocular viewing). No differences were observed when assessing monocular impairments influence on outcome, velocity and ball placement. PKs have a high resilience to VI, but binocular impairment has a more immediate effect, suggesting binocular measures should be used in classification processes in football.

Rates of retinal nerve fiber layer loss in early-stage pseudoexfoliation and primary open-angle glaucoma patients using optical coherence tomography.

PURPOSE: To characterize glaucoma progression in early-stage patients with retinal nerve fiber layer (RNFL) using the change analysis software (CAS), which was utilized to track RNFL thinning. METHODS: We retrospectively analyzed 92 eyes of 92 patients with early-stage glaucoma. Patients were divided into two subgroups based on their diagnosis of pseudoexfoliation glaucoma (PEG) and primary open-angle glaucoma (POAG). A complete ophthalmologic examination was performed on all patients. Additionally, automated perimetry was conducted on each patient. Furthermore, Fourier-domain optical coherence tomography (OCT) was employed to measure RNFL and central corneal thickness. Using the OCT device's CAS, we computed the annual rate of total and glaucomatous RNFL thinning for each patient. RESULTS: A total of 44 PEG and 48 POAG patients were included in the study. The right eye measurements of these patients were analyzed and compared. The two groups were not significantly different in age, gender, and the number of visits per year (p > 0.05, for each). However, the difference between the mean RNFL thickness at baseline (91.39 ± 10.71 and 96.9 ± 8.6 µm) and at the last visit (85.2 ± 15.76 µm and 91.56 ± 9.58 µm) was statistically significant between the two groups (p = 0.043, p = 0.039, respectively). Additionally, the difference in annual RNFL thinning rates (1.43 ± 0.81 µm and 1.07 ± 0.32 µm) between the two groups was statistically significant (p = 0.009). CONCLUSION: The annual rate of glaucomatous RNFL loss in early-stage PEG patients (1.23 µm) was higher than in POAG patients (0.87 µm). However, despite these loss rates, scotoma was not detected in the visual field tests of these patients. Therefore, using CAS in the follow-up of early-stage glaucoma patients is a useful alternative for monitoring glaucomatous progression. Furthermore, this method can be utilized in future research for the diagnosis and follow-up of glaucoma in special populations (e.g., those with pathological myopia or high hyperopia) that are not included in normative databases.

Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector.

Purpose: To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector. Design: Single-center, retrospective chart review. Methods: In this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated. Results: Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector. Conclusions: We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes. Translational Relevance: Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

Purpose: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Methods: Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. Results: At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Conclusions: Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.

Visual Field Prognosis From Macula and Circumpapillary Spectral Domain Optical Coherence Tomography.

Purpose: To explore the structural-functional loss relationship from optic-nerve-head- and macula-centred spectral-domain (SD) Optical Coherence Tomography (OCT) images in the full spectrum of glaucoma patients using deep-learning methods. Methods: A cohort comprising 5238 unique eyes classified as suspects or diagnosed with glaucoma was considered. All patients underwent ophthalmologic examination consisting of standard automated perimetry (SAP), macular OCT, and peri-papillary OCT on the same day. Deep learning models were trained to estimate G-pattern visual field (VF) mean deviation (MD) and cluster MD using retinal thickness maps from seven layers: retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL + IPL), inner nuclear layer and outer plexiform layer (INL + OPL), outer nuclear layer (ONL), photoreceptors and retinal pigmented epithelium (PR + RPE), choriocapillaris and choroidal stroma (CC + CS), total retinal thickness (RT). Results: The best performance on MD prediction is achieved by RNFL, GCL + IPL and RT layers, with R2 scores of 0.37, 0.33, and 0.31, respectively. Combining macular and peri-papillary scans outperforms single modality prediction, achieving an R2 value of 0.48. Cluster MD predictions show promising results, notably in central clusters, reaching an R2 of 0.56. Conclusions: The combination of multiple modalities, such as optic-nerve-head circular B-scans and retinal thickness maps from macular SD-OCT images, improves the performance of MD and cluster MD prediction. Our proposed model demonstrates the highest level of accuracy in predicting MD in the early-to-mid stages of glaucoma. Translational Relevance: Objective measures recorded with SD-OCT can optimize the number of visual field tests and improve individualized glaucoma care by adjusting VF testing frequency based on deep-learning estimates of functional damage.