To investigate the applicability of liquid crystal displays (LCD) as suitable replacement for cathode ray tube monitors (CRT) as stimulator for the sweep VEP for estimating visual acuity.

Best-corrected visual acuity (BCVA) is assessed at a single standardized luminance with maximum optotype contrast, not reflecting the constantly changing daily-life viewing conditions. For a more realistic estimation of visual performance at varying object contrasts (Cs) and ambient luminances (ALs), we developed a new VA test, VA-CAL.

To call attention to the danger of extinction of the panda bear, the Lithuanian artist Ilja Klemencov created the artwork "They can disappear". The illustration is composed of black-and-white zigzagged lines, which form the famous panda logo of the World Wild Fund For Nature (WWF) when seen from a distance. If one is too close to the artwork, it is difficult to spot the bear, however, if one steps back or takes off one's glasses the panda suddenly appears. This led us to ask if the ability to see the panda is related to the visual acuity of the observer and if therefore, the panda illusion can be used to assess the spatial resolution of the eye. Here we present the results of the comparison between visual acuity determined using the Landolt C and that predicted from the panda illusion in 23 healthy volunteers with artificially reduced visual acuity. Furthermore, we demonstrate that the panda illusion is based on a 2D pulse-width modulation, explain its technical history, and provide the equations required to create the illusion. Finally, we explain why the illusion indeed can be used to predict visual acuity and discuss the neural causes of its perception with best-corrected visual acuity.

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.

Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy). Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks). Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs) were transient and mostly of mild to moderate intensity. Conclusions: Psychophysical and subjective data show that RETINA IMPLANT Alpha AMS is reliable, well tolerated and can restore limited visual functions in blind patients with degenerations of the outer retina. Compared with the previous implant Alpha IMS, longevity of the new implant Alpha AMS has been considerably improved. Alpha AMS has meanwhile been certified as a commercially available medical device, reimbursed in Germany by the public health system.

In contrast to USH2A, variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in terms of nyctalopia onset, best corrected visual acuity (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) features. There was no statistical difference in the median age at onset (30 and 18 years; Mann-Whitney U test, p = 0.13); the mean age when 50% of the patients reached legal blindness (≥1.0 log MAR) based on visual acuity (64 years for both groups; log-rank, p = 0.3); the risk of developing advanced retinal degeneration (patch or atrophy) with age (multiple logistic regression, p = 0.8); or the frequency of cystoid macular edema (31% vs. 26%, Fisher's exact test, p = 0.4). ADGRV1 and USH2A retinopathy were indistinguishable in all major functional and structural characteristics, suggesting that the loss of function of the corresponding proteins produces similar effects in the retina. The results are important for counseling ADGRV1 patients, who represent the minor patient subgroup.

Cone dystrophies are a rare subgroup of inherited retinal dystrophies and hallmarked by color vision defects, low or decreasing visual acuity and central vision loss, nystagmus and photophobia. Applying genome-wide linkage analysis and array comparative genome hybridization, we identified a locus for autosomal dominant cone dystrophy on chromosome 16q12 in four independent multigeneration families. The locus is defined by duplications of variable size with a smallest region of overlap of 608 kb affecting the IRXB gene cluster and encompasses the genes IRX5 and IRX6. IRX5 and IRX6 belong to the Iroquois (Iro) protein family of homeodomain-containing transcription factors involved in patterning and regionalization of embryonic tissue in vertebrates, including the eye and the retina. All patients presented with a unique progressive cone dystrophy phenotype hallmarked by early tritanopic color vision defects. We propose that the disease underlies a misregulation of the IRXB gene cluster on chromosome 16q12 and demonstrate that overexpression of Irx5a and Irx6a, the two orthologous genes in zebrafish, results in visual impairment in 5-day-old zebrafish larvae.

Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a ≥20% increase and 4 of 18 (22%) showed a ≥40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a ≥5 and ≥10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 ± 4.8 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity.

Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors, while cones remain initially unaffected. Extensive rod loss in advanced stages of the disease triggers cone death by a mechanism that is still largely unknown. Here, we show that secondary cone cell death in animal models for RP is associated with increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at late stages of the disease, when the majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival in two mouse models for RP, affected by mutations in the phosphodiesterase 6b gene. Moreover, the surviving cones remained light-sensitive, leading to an improvement in visual function. RNA-seq analysis of protected cones demonstrated that HDAC inhibition initiated multi-level protection via regulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique opportunity for targeted pharmacological protection of secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients even in advanced disease stages.