Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele.

BACKGROUND: Disease-causing variants in the KCNV2 gene are associated with "cone dystrophy with supernormal rod responses," a rare autosomal recessive retinal dystrophy. There is no previous report of hypomorphic variants in the disease. MATERIAL AND METHODS: Medical history, genetic testing, ocular examination, high-resolution retinal imaging including adaptive optics scanning light ophthalmoscopy (AOSLO), and functional assessments. RESULTS: A 16-year-old male with mild cone-rod dystrophy presented with reduced central vision and photophobia. Genetic testing showed two variants in KCNV2, c.614_617dupAGCG (p.207AlafsTer166) and c.854T>G (p.Met285Arg), the latter which was previously considered benign. Electrophysiological assessment revealed the pathognomic electroretinogram waveforms associated with KCNV2-retinopathy. Optical coherence tomography showed discrete focal ellipsoid zone disruption, while fundus autofluorescence was normal. Non-waveguiding cones corresponding to areas of loss of photoreceptor integrity were visible on adaptive optics scanning light ophthalmoscopy. Retinal sensitivity and fixation were relatively preserved, with a demonstrable deterioration after 14 months of follow-up. CONCLUSIONS: We provide functional and structural evidence that the variant M285R is disease-causing if associated with a loss-of-function variant. To the best of our knowledge, this is the first hypomorphic allele reported in KCNV2.

Use of electronic devices by people attending vision rehabilitation services in Italy: A study based on the device and aids registry (D.A.Re).

PURPOSE: To investigate the characteristics of electronic device users, specifically smartphones and tablets, in the Device & Aids Register (D.A.Re), from several low-vision rehabilitation services in Italy. METHODS: We collected general and clinical information about ocular and systemic diseases, visual function, reading speed and Instrumental Activities of Daily Living (IADL) questionnaire score. Technological details of each optical and electronic device, (including screen size, touch-screen and OCR functions, text-to-speech function) were also collected. RESULTS: 1218 patients (752 females and 466 males) were included in our analysis, mean age 71.5 (±18.8) years. Users of electronic aids (n.237) were slightly younger (67 vs 72 years, p < 0.001) than non-users (n.981), had a worse reading speed (38 vs 65 words/minute), critical print size (43 vs 28 print size, p < 0.001), poorer visual acuity (VA)(1.0 logMAR or less: 30% non-users vs 73% users, p < 0.001) and more commonly visual field restriction within 10° (23% vs 14%, p = 0.001). A similar proportion of users and non-users were retired (about 70%) and about 16-17% were employed. The use of portable electronic devices (5″or less, p < 0.001; 6″ to 18″ screen size, p = 0.017) was associated with better IADL scores, and the use of stand devices with worse IADL score (p < 0.001); Furthermore, using smartphones and tablets (193 subjects) was strongly associated with better IADL scores. CONCLUSION: We found that using electronic devices, and especially smartphone and tablets, were associated with better vision-related quality of life in low-vision people attending rehabilitation services. While this association does not mean causality, these findings seemed robust to confounder adjustment.

Low-vision rehabilitation in Italy: Cross-sectional data from the Device and Aids Registry (D.A.Re).

OBJECTIVES: We are reporting on the characteristics of low-vision adults attending large rehabilitation services which provide data to D.A.Re (Devices & Aids REgister) in Italy. D.A.Re aims to gather information about low-vision aids owned by Italian patients with visual impairment. METHODS: We included consecutive patients attending low-vision rehabilitation centres providing data to D.A.Re from 2019 to July 2021. Demographic features, self-reported use of technology and aids, vision performance, and the Instrumental Activity of Daily Living (IADL) score were collected. RESULTS: 720 patients were included in the D.A.Re. About half of the patients were affected by Age-related Macular Degeneration (389, 54.9%). Patients reported a long interval between onset of vision disability and access to low-vision rehabilitation, which was over two years in almost 30% of cases. Blindness registration status was almost complete when reported, but almost 40% were unable to report on this. IADL scores were higher for younger people and those with better visual acuity and critical print size (CPS), and lower for visual field restriction (p < 0.01 for all predictors). Of interest, better IADL scores were recorded for those with computer knowledge who used optical aids and software in univariate analyses and multivariate analyses, adjusting for level of visual disability and employment status (p < 0.01 for all predictors). CONCLUSIONS: We report on the profile of low-vision patients using rehabilitation services in Italy. Longitudinal data during and after vision rehabilitation were collected. Our results support the validity of the D.A.Re to monitor the use of low-vision devices in Italy.

The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 (VA LV VFQ-48): Performance of the Italian version.

PURPOSE: The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 is among the most validated tools to collect patient-reported outcomes in a low-vision population. We have aimed to conduct a pilot validation of the Italian version of the Veterans Affairs Low-Vision Visual Functioning Questionnaire-48. METHODS: The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 was translated using a standardized procedure and then administered to consecutive low-vision patients attending rehabilitation services in three centers. Patients were interviewed by a trained psychologist regarding the individual items of the tool. RESULTS: We included 131 patients with a mean visual acuity of 0.91 logMAR (standard deviation: 0.42 logMAR), mostly affected by age-related macular degeneration. The Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 showed high internal consistency (Cronbach's alpha: 0.98) and good item-test and item-rest correlation (median: 0.73 and 0.71, respectively). Both the overall score and the subscale (reading, visual motor, mobility and visual information) scores significantly correlated with visual acuity, reading acuity and speed. Reading speed achieved the best absolute correlation with the Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 scores (Spearman r: 0.39-0.49). CONCLUSION: The Italian version of the Veterans Affairs Low-Vision Visual Functioning Questionnaire-48 is a valid tool to assess patients attending low-vision services. Revising a few items may further improve the tool.

Perceptual learning leads to long lasting visual improvement in patients with central vision loss.

BACKGROUND: Macular Degeneration (MD), a visual disease that produces central vision loss, is one of the main causes of visual disability in western countries. Patients with MD are forced to use a peripheral retinal locus (PRL) as a substitute of the fovea. However, the poor sensitivity of this region renders basic everyday tasks very hard for MD patients. OBJECTIVE: We investigated whether perceptual learning (PL) with lateral masking in the PRL of MD patients, improved their residual visual functions. METHOD: Observers were trained with two distinct contrast detection tasks: (i) a Yes/No task with no feedback (MD: N = 3; controls: N = 3), and (ii) a temporal two-alternative forced choice task with feedback on incorrect trials (i.e., temporal-2AFC; MD: N = 4; controls: N = 3). Observers had to detect a Gabor patch (target) flanked above and below by two high contrast patches (i.e., lateral masking). Stimulus presentation was monocular with durations varying between 133 and 250 ms. Participants underwent 24- 27 training sessions in total. RESULTS: Both PL procedures produced significant improvements in the trained task and learning transferred to visual acuity. Besides, the amount of transfer was greater for the temporal-2AFC task that induced a significant improvement of the contrast sensitivity for untrained spatial frequencies. Most importantly, follow-up tests on MD patients trained with the temporal-2AFC task showed that PL effects were retained between four and six months, suggesting long-term neural plasticity changes in the visual cortex. CONCLUSION: The results show for the first time that PL with a lateral masking configuration has strong, non-invasive and long lasting rehabilitative potential to improve residual vision in the PRL of patients with central vision loss.

Clinical and microperimetric predictors of reading speed in low vision patients: a structural equation modeling approach.

PURPOSE: To investigate the simultaneous association of several psychophysical measures with reading ability in patients with mild and moderate low vision attending rehabilitation services. METHODS: Standard measurements of reading ability (Minnesota Reading [MNREAD] charts), visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] charts), contrast sensitivity (Pelli-Robson charts), reading contrast threshold (Reading Explorer [REX] charts), retinal sensitivity, and fixation stability and localization (Micro Perimeter 1 [MP1] fundus perimetry) were obtained in 160 low vision patients with better eye visual acuity ranging from 0.3 to 1.0 logarithm of the minimum angle of resolution and affected by either age-related macular degeneration or diabetic retinopathy. RESULTS: All variables were moderately associated with reading performance measures (MNREAD reading speed and reading acuity and REX reading contrast threshold), as well as among each other. In a structural equation model, REX reading contrast threshold was highly associated with MNREAD reading speed (standardized coefficient, 0.63) and moderately associated with reading acuity (standardized coefficient, -0.30). REX test also mediated the effects of Pelli-Robson contrast sensitivity (standardized coefficient, 0.44), MP1 fixation eccentricity (standardized coefficient, -0.19), and the mean retinal sensitivity (standardized coefficient, 0.23) on reading performance. The MP1 fixation stability was associated with both MNREAD reading acuity (standardized coefficient, -0.24) and MNREAD reading speed (standardized coefficient, 0.23), while ETDRS visual acuity only affected reading acuity (standardized coefficient, 0.44). CONCLUSIONS: Fixation instability and contrast sensitivity loss are key factors limiting reading performance of patients with mild or moderate low vision. REX charts directly assess the impact of text contrast on letter recognition and text navigation and may be a useful aid in reading rehabilitation.

Clinical and Rehabilitative Management of Retinitis Pigmentosa: Up-to-Date.

The term retinitis pigmentosa (RP) indicates a heterogeneous group of genetic rare ocular diseases in which either rods or cones are prevalently damaged. RP represents the most common hereditary cause of blindness in people from 20 to 60 years old. In general, the different RP forms consist of progressive photo-receptorial neuro-degenerations, which are characterized by variable visual disabilities and considerable socio-sanitary burden. Sometimes, RP patients do not become visually impaired or legally blind until their 40-50 years of age and/or maintain a quite acceptable sight for all their life. Other individuals with RP become completely blind very early or in middle childhood. Although there is no treatment that can effectively cure RP, in some case-series the disease's progression seems to be reducible by specific preventive approaches. In the most part of RP patients, the quality of vision can be considerably increased by means of nanometer-controlled filters. In the present review, the main aspects of the routine clinical and rehabilitative managements for RP patients are described, particularly focusing on the importance of specific referral Centers to practice a real multidisciplinary governance of these dramatic diseases.

Reducing crowding by weakening inhibitory lateral interactions in the periphery with perceptual learning.

We investigated whether lateral masking in the near-periphery, due to inhibitory lateral interactions at an early level of central visual processing, could be weakened by perceptual learning and whether learning transferred to an untrained, higher-level lateral masking known as crowding. The trained task was contrast detection of a Gabor target presented in the near periphery (4°) in the presence of co-oriented and co-aligned high contrast Gabor flankers, which featured different target-to-flankers separations along the vertical axis that varied from 2λ to 8λ. We found both suppressive and facilitatory lateral interactions at target-to-flankers distances (2λ - 4λ and 8λ, respectively) that were larger than those found in the fovea. Training reduces suppression but does not increase facilitation. Most importantly, we found that learning reduces crowding and improves contrast sensitivity, but has no effect on visual acuity (VA). These results suggest a different pattern of connectivity in the periphery with respect to the fovea as well as a different modulation of this connectivity via perceptual learning that not only reduces low-level lateral masking but also reduces crowding. These results have important implications for the rehabilitation of low-vision patients who must use peripheral vision to perform tasks, such as reading and refined figure-ground segmentation, which normal sighted subjects perform in the fovea.

Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor.

OBJECTIVE: To analyze the association between age-related macular degeneration (AMD) and polymorphisms in vascular endothelial growth factor (VEGF) and VEGF receptor KDR gene polymorphisms. A complex, multifactorial disease in which genetic and environmental factors interact, AMD is the leading cause of blindness in the elderly. Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is considered an important factor for the pathogenetic processes of AMD. Previous studies investigated the possible association between VEGF-A gene polymorphisms and AMD, with contrasting data. No study examined the possible role of VEGF receptor KDR gene polymorphisms. DESIGN: Case-control study. PARTICIPANTS AND CONTROLS: We enrolled 226 AMD cases and 248 controls from an ophthalmology hospital center. METHODS: Genotypying for 16 polymorphic markers (single nucleotide polymorphisms [SNPs]) in VEGF-A and KDR genes. MAIN OUTCOME MEASURES: Distribution of genotypes in AMD cases and controls. RESULTS: Two polymorphisms (rs833069 in intron 2 of the VEGF-A gene, rs2071559 in the promoter of the KDR gene) were significantly associated with risk of AMD. In particular, for VEGF-A rs833069 the AMD risk was increased >5-fold for G homozygotes compared with homozygous carriage of the A allele. For KDR rs2071559 the AMD risk was increased >3-fold for T homozygotes compared with homozygous carriage of the C allele. Carriers of risk alleles for both markers have a >6-fold increased risk of AMD with respect to carriers of non-risk alleles. CONCLUSIONS: We expand previous data on the association of AMD with VEGF-A gene variations and identify for the first time an association with variations in the KDR gene. Because the SNP-604T-bearing KDR promoter has higher transcription activity, our findings further support the role of the VEGF pathway in the pathophysiology of AMD. It is possible that applications of haplotype/genotype analysis in these genes will play a role in risk assessment and pharmacogenomic approaches to AMD diagnosis and management.