Photopic Response Research Articles

THE GENETIC BASIS OF CLINICALLY SUSPECTED ACHROMATOPSIA IN THE UNITED ARAB EMIRATES.

Achromatopsia (ACHM) is a genetically heterogenous relatively stationary congenital autosomal recessive cone disorder characterized typically by photophobia, low vision, nystagmus, hyperopia, grossly normal retinal appearance, and absent photopic responses by full-field electroretinography. Incomplete forms occur as well. This study investigates the genetic basis of clinically suspected ACHM in the United Arab Emirates. Retrospective case series (January 2016-December 2023) of patients with (1) clinically suspected ACHM or (2) mutations in ACHM-associated genes ( CNGA3 , CNGB3 , GNAT2 , PDE6C , PDE6H , AT6 ). Twenty-two clinically suspected patients (19 probands) were identified. Biallelic disease genes and the number of probands were CNGA3 (9), CNGB3 (6), PDE6C (1), GNAT2 (1), RGS9BP (1), and CNNM4 (1). Some mutant alleles were recurrent across different families. Two probands had their diagnoses revised after genetic testing and phenotypic reassessment to RGS9BP -related bradyopsia and CNNM4 -related Jalili syndrome. Three additional cases (making 22 total probands) were identified from ACHM gene mutation review-one each related to PDE6C , to AT6 , and to CNGB3 in concert with CNGA3 (triallelic disease). All three presented with macular discoloration, an atypical finding for classic ACHM. CNGA3 was the single most frequent implicated gene. Bradyopsia and Jalili syndrome can resemble incomplete ACHM. Recurrent mutant alleles may represent founder effects. Macular discoloration on presentation can occur in PDE6C -related disease, AT6 -related disease, and triallelic CNGB3 / CNGA3 -related disease. The possibility for triallelic disease exists and requires genetic counseling beyond that of simple autosomal recessive inheritance.

The Effect of High-Dose Erythropoietin Perinatally on Retinal Function in School-Aged Children Born Extremely or Very Preterm

To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm. Randomized, double-blind clinical trial follow-up plus cohort study. Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period. participation in an ongoing neuropediatric study (EpoKids), written informed consent. previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited. term birth, informed consent. any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses. The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group. Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only). No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups. Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.

Shine Amidst Darkness—A Case of Oguchi Disease

Abstract An 11-year-old boy presented with complaints of defective night vision. Visual acuity was 6/6 in both eyes. The fundus showed a golden-to-grey discoloration in light and on dark adaptation, the fundus reverted to its normal appearance demonstrating the classical Mizuo-Nakamura phenomenon. The electroretinogram showed abnormal rod responses and normal photopic responses. An electroretinogram done after overnight dark adaptation showed partial recovery with subsequent attenuation. Screening of family members showed abnormal electroretinogram findings in his father and brother. This case is portrayed on account of its rarity.

Changes in Retinal Structure and Function in Mice Exposed to Flickering Blue Light: Electroretinographic and Optical Coherence Tomographic Analyses.

The harmful effects of blue light on the retina and health issues attributed to flickering light have been researched extensively. However, reports on the effects of flickering blue light at a frequency in the visible range on the retina are limited. This study aimed to non-invasively investigate the structural and functional changes in mice retinas following exposure to flickering blue light. BALB/c mice were subjected to non-flickering and flickering blue light, and changes in the retinal function and structure were assessed using electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT), respectively. Retinal damage progression was monitored on days 3, 7, 14, and 42 following light exposure. Significant reductions in scotopic and photopic ERG responses were observed on day 3 (p<0.05). On day 7, the non-flickering and flickering groups demonstrated different functional changes: the flickering group showed further ERG response reduction, while the non-flickering group showed no reduction or slight improvement that was statistically insignificant (p>0.05). A similar trend lasted by day 14. On day 42, however, the difference between the non-flickering and flickering groups was significant, which was corroborated by the normalized amplitudes at 0, 0.5, and 1 log cd s/m2 (p<0.05). Quantitative and qualitative SD-OCT assays revealed more severe and progressive retinal damage in the flickering group throughout the study. Flickering blue light causes more persistent and severe retinal damage than non-flickering blue light and may be a risk factor for retinal degeneration even at frequencies as low as 20 Hz.

ERG Responses in Albinism, Idiopathic Infantile Nystagmus, and Controls.

Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses. Dilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings. For the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P < 0.0001), with responses in both groups decreasing with age. In contrast, photopic a-wave amplitudes increased with age in albinism (P = 0.0035). For the secondary aim, more intense nystagmus significantly reduced the success rate of measurable responses. Within-subject changes in nystagmus intensity generated small, borderline significant differences in photopic b-wave peak times and a-and b-wave amplitudes under scotopic conditions with standard flash. Age-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region.

Hyperglycemia and circadian disruption lead to retinal dysfunction in a stabilized colony of the fat sand rat Psammomys obesus

PurposeThe Fat Sand Rat (Psammomys obesus) recapitulates several features of human pre-proliferative diabetic retinopathy, but data are restricted to wild animals, incompatible with stringent biomedical research criteria. To overcome this barrier, we characterized retinal changes in a colony of P. obsesus maintained under strictly controlled housing conditions. MethodsAnimals were maintained on low or high caloric energy diets, and raised under either standard (12 h light/12 h dark) or shortened (5 h light/5 h dark) photoperiods. Visual responses were tested by electroretinography, while structural/molecular changes were assayed by immunochemistry and molecular biology (RNAseq and qPCR). ResultsWhereas high calorie diet alone did not induce hyperglycemia, coupled with short photoperiod >80 % animals developed severe hyper-insulinemia by 15 weeks, and 16 % animals further developed hyperglycemia. In these groups, electroretinography showed significant declines in visual responses in both hyper-insulinemic and hyperglycemic animals, especially in photopic (cone) responses. Transcriptomics analysis of hyperglycemic compared to low caloric controls revealed major upregulation in pathways involved in glial activation, extracellular matrix remodeling, inflammation, cytokine production, partial ischemic responses and angiogenesis. Western blotting against rhodopsin and cone opsin also showed decreased levels in both groups, overall decreases being greater for cones than rods in hyperglycemic animals. ConclusionsP. obesus maintained in rigorously monitored captive conditions, albeit showing attenuated responses to dietary overload compared to wild counterparts, nevertheless do develop some retinal features of diabetic retinopathy-like degeneration. Such a colony with known sanitary status opens their broader use for biomedical research.

Semitransparent Near‐Infrared Organic Photodetectors: Flexible, Large‐Area, and Physical‐Vapor‐Deposited for Versatile Advanced Optical Applications

AbstractOrganic photodetectors (OPDs) have experienced remarkable performance improvements over the past decade thanks to significant advancements in organic material synthesis and device architecture engineering. In this study, high‐performance near‐infrared (NIR) OPDs with versatile advanced properties, including large detection areas, mechanical flexibility, and high transparency are realized. By incorporating a thin photo‐absorbing layer, functional blocking layers with a large energy gap, and semitransparent electrodes, the OPDs achieve an average visible transmittance (AVT) of up to 53.4% and color rendering index (CRI) of up to 95 within the human vision photopic response window of 380–780 nm. Both the small (6.44 mm2) and large (256 mm2) detection‐area semitransparent OPDs demonstrate an impressive external quantum efficiency (EQE) of 34% and 36%, and specific detectivity (D*) of 1.4 × 1013 and 1.1 × 1012 Jones, respectively, comparable to silicon‐based inorganic photodetectors. As application demonstrations, OPDs with rigid and flexible substrates are employed for NIR imaging and biosensing, respectively. Notably, the flexible semitransparent OPDs are utilized as signal receivers in conjunction with semitransparent NIR organic light‐emitting diodes (OLEDs) operating as signal producers, demonstrating the feasibility of invisible optical communication. These OPDs represent the best‐performing see‐through devices with flexibility, making them promising candidates for integratable, bio‐compatible, and invisible optical‐sensing applications.

The role of electrophysiology tests and multimodal imaging in evaluation of nystagmus

Purpose This work aimed to highlight the role of electrophysiology testing and multimodal imaging in evaluation of nystagmus. Patients and methods This is a retrospective multi-centered analytic study that recruited patients with nystagmus from the outpatient clinics referred to the electrophysiology units of the hospitals of the University of Minia, Ain Shams, Banha, and Cairo, Egypt. The study included 60 (120 eyes) patients. The performed investigations included full-field electroretinography (ffERG), pattern electroretinography, flash visual evoked potential (FVEP), pattern visual evoked potential, optical coherence tomography (OCT), OCT-angiography (OCT-A), and fundus autofluorescence (FAF), whenever possible. Results There were no or minimal detectable fundus changes in 78 (65%) eyes, of which 40 (33.3%) eyes showed severe loss of photopic responses on ffERG, with Bull’s eye pattern observed on FAF and loss of foveal photoreceptors in OCT, while 18 (12.5%) eyes showed reduced photopic and scotopic responses in ffERG with loss of foveal photoreceptors and thinned parafovea in OCT, 14 (11.7%) eyes showed average photopic and scotopic responses with different stages of foveal hypoplasia in OCT and OCT-A, and six (5%) eyes showed normal results in tests assessing the function and structure of the macula and optic nerve, including ERG, FVEP, and OCT. On the other hand, macular or optic nerve abnormalities were observed in 42 (35%) eyes, of which 20 (16.7%) eyes showed significant loss of photopic responses in ffERG and abnormal fovea in OCT and FAF tests, 10 (8.3%) eyes showed loss of photopic and scotopic responses in ffERG and abnormal results in the OCT and FAF, four (3.3%) eyes had normal results in ERG and FVEP, but showed fovea hypoplasia in OCT, and eight (6.7%) eyes had normal photopic and scotopic responses by ffERG, but with abnormal visual evoked potential responses and thinning of the nerve fiber layer in the OCT. Conclusion Electrophysiological tests and multimodal imaging are crucial to diagnosing the underlying causes of nystagmus, especially in patients with normal fundus.

Changes in visual function in long‐term type 1 diabetic patients without diabetic retinopathy using full‐field electroretinogram

Aims/Purpose: To evaluate changes in retinal function in type 1 diabetic patients (DM1) without diabetic retinopathy (DR) using full‐field electroretinogram (ffERG).Methods: Forty‐six eyes of long term DM1 patients without DR were compared to 46 eyes of healthy subjects. None of them had any ophthalmic pathology that could alter the findings. All the subjects were evaluated following the standardized international ISCEV guidelines. The amplitude and implicit time (IT) of each component of scotopic and photopic responses were evaluated, along with interocular differences.Results: There were no age differences between groups. A significant increase in the rod response IT of the DM1 patients was observed compared to the control group (p = 0.0012). The b wave amplitude in the mixed response was statistically reduced in the DM1 group compared to the control group (p = 0.03). There was an increase in the IT of both a and b‐wave in the mixed response at the higher stimulus intensity in the DM1 compared to control (p = 0.023 and p = 0.004 respectively). b/a rate was similar in both groups. The oscillatory potentials (OPs) showed an increase in their IT (p = 0.008) and a decrease in OP2 amplitude in the DM1 group. Cone mediated b‐wave was diminished in DM1.Conclusions: Full‐field electroretinogram enables the detection of subclinical findings in long term DM1 patients suggesting the existence of neurodegeneration prior the appearance of DR, particularly in the rod system and OPs.

Cone dystrophy with supernormal rod response – A rare case report

Cone dystrophy with supernormal rod response (CDSRR), also known as potassium channel subfamily V, member 2 (KCNV2) retinopathy, is a rare autosomal recessive cone rod dystrophy, which derives its name from its characteristic full-field electroretinography (ERG) features and the causative gene mutation (KCNV2 gene). It is one of the rare eye retinal dystrophies where ERG is pathognomonic and directly carries the genetic imprint of the condition. Here, we discuss the case of a 9-year-old Indian child with history of diminution of vision in both eyes. Full-field ERG showed a characteristic response of supranormal scotopic b-wave amplitude at high luminance intensities along with broadened trough of the a-wave with late negative component with reduced and delayed photopic response suggestive of CDSRR.

Silicone oil insulation effects on flash electroretinogram and visual evoked potential in patients with retinal detachment

BackgroundSilicone oil is used as endotamponade following vitreoretinal surgery to maintain the retina reattached when indicated. This study investigates the hypothesis that silicone oil causes insulation effects on the retina by affecting its response to light. MethodsElectrophysiological responses to a flash stimulus were recorded using full-field electroretinography (ERG) and visual evoked potentials (VEP). Recordings were performed in 9 patients who underwent surgery for retinal detachment, before (1–2 days) and after (2–3 weeks) silicone oil removal (SOR) in both the study and the control eye. Flash ERG and VEP recordings were performed according to the ISCEV standard protocol. ResultsStatistically significant differences were found in the study eye in the amplitudes of the ERG responses and their corresponding ratios, i.e. the amplitude after SOR over the amplitude before SOR, in all conditions tested. No differences were observed in the control eye. The mean ratio of photopic ERG response was 3.4 ± 2.4 for the study and 1.0 ± 0.3 for the control eye (p<0.001). The mean ratio of ERG flicker response was 3.1 ± 2.4 and 1.0 ± 0.3, respectively (p = 0.003). Scotopic flash ERG ratio was 5.0 ± 4.4 for the study and 1.3 ± 0.6 for the control eye (p = 0.012). No differences were observed for the amplitude and latency of flash VEP response after SOR. ConclusionsSilicone oil causes a reduction in flash ERG responses; no effect was found on flash VEP responses. ERGs in eyes filled with silicone oil should not be considered representative of retinal functionality, in contrast to VEPs, which are not affected by silicone oil presence.

The Involvement of Unfolded Protein Response in the Mechanism of Nitrogen Mustard-Induced Ocular Toxicity.

Nitrogen mustard (NM) is a known surrogate of sulfur mustard, a chemical-warfare agent that causes a wide range of ocular symptoms, from a permanent reduction in visual acuity to blindness upon exposure. Although it has been proposed that the two blistering agents have a similar mechanism of toxicity, the mode of NM-induced cell death in ocular tissue has not been fully explored. Therefore, we hypothesized that direct ocular exposure to NM in mice leads to retinal tissue injury through chronic activation of the unfolded protein response (UPR) PERK arm in corneal cells and VEGF secretion, eventually causing cell death. We topically applied NM directly to mice to analyze ocular and retinal tissues at 2 weeks postexposure. A dramatic decline in retinal function, measured by scotopic and photopic electroretinogram responses, was detected in the mice. This decline was associated with enhanced TUNEL staining in both corneal and retinal tissues. In addition, exposure of corneal cells to NM revealed 228 differentially and exclusively expressed proteins primarily associated with the UPR, ferroptosis, and necroptosis. Moreover, these cells exhibited activation of the UPR PERK arm and an increase in VEGF secretion. Enhancement of VEGF staining was later observed in the corneas of the exposed mice. Therefore, our data indicated that the mechanism of NM-induced ocular toxicity should be carefully examined and that future research should identify a signaling molecule transmitted via a prodeath pathway from the cornea to the retina. SIGNIFICANCE STATEMENT: This study demonstrated that NM topical exposure in mice results in dramatic decline in retinal function associated with enhanced TUNEL staining in both corneal and retinal tissues. We also found that the NM treatment of corneal cells resulted in 228 differentially and exclusively expressed proteins primarily associated with ferroptosis. Moreover, these cells manifest the UPR PERK activation and an increase in VEGF secretion. The latter was also found in the corneas of the cexposed mice.

Pathogenicity and functional analysis of CFAP410 mutations causing cone-rod dystrophy with macular staphyloma.

Cone-rod dystrophy (CORD) caused by pathogenic variants in CFAP410 is a very rare disease. The mechanisms by which the variants caused the disease remained largely unknown. CFAP410 pathogenic variants were identified in a cone-rod dystrophy with macular staphyloma patient. We explored the pathogenicity and performed functional analysis of two compound heterozygous mutations. A 6-year-old boy complained decreased vision for 1 year, underwent ocular examinations together with systemic X-ray check. Blood sample was taken for targeted next generation sequencing (Tg-NGS). Pathogenicity of identified variants was determined by ACMG guideline. Mutated plasmids were constructed and transferred to HEK293T cells. Cell cycle, protein stability, and protein ubiquitination level was measured. The best-corrected visual acuity of proband was 0.20 bilaterally. Fundus showed macular staphyloma and uneven granular pigment disorder in the periphery of the retina. SS-OCT showed thinning and atrophy of the outer retina, residual ellipsoid zone (EZ) in the fovea. Scotopic and photopic ERG responses severe reduced. Two heterozygous missense pathogenic variants, c.319 T > C (p.Tyr107His) and c.347 C > T (p.Pro116Leu) in exon 4 of the CFAP410, were found and were pathogenic by the ACMG guideline. In vitro, pathogenic variants affect cell cycle. Immunofluorescence and western blotting showed that the mutant proteins decreased expression levels protein stability. Meanwhile, co-IP data suggested that ubiquitination level was altered in cells transferred with the mutated plasmids. Compound heterozygous pathogenic variants c.319 T > C and c.347 C > T in CFAP410 caused CORD with macular staphyloma. The pathogenic mechanisms may be associated with alternations of protein stability and degradation through the ubiquitin-proteasome pathway.

Microcephaly and Chorioretinopathy Relevance as a Differential Diagnosis.

Microcephaly and chorioretinopathy are genetic disorders that are inherited in an autosomal recessive manner. The most frequent ocular manifestation is the presence of lacunar atrophy in the retina and choroid. The diagnosis of this condition can be challenging as several potential causes and related syndromes need to be ruled out. We present two cases of microcephaly and chorioretinopathy in Mexican patients, their clinical characterization, and discuss the differential diagnoses that should be considered. An 8-year-old girl was examined due to a history of decreased vision in both eyes. Fundus examination showed excavated, well-defined, sectorial, bilateral, and symmetrical areas of chorioretinal atrophy. An 18-year-old male had a history of poor vision since childhood. Previous ophthalmological examinations reported bilateral symmetric chorioretinal atrophy with pigment accumulation. Both patients had a prior diagnosis of microcephaly and language delay. Blood tests and a comprehensive systemic evaluation ruled out intrauterine infections. The electroretinogram showed decreased amplitude and increased implicit time in the photopic and scotopic responses. Genetic tests revealed mutations in the TUBGCP4 gene, leading to a diagnosis of microcephaly and chorioretinopathy. As observed in these cases, there was variability in retinal lesions. The presence of chorioretinal lacunae and genetic testing can help to correctly diagnose this disorder.

Sex-related differences in retinal function in Wistar rats: implications for toxicity and safety studies.

Introduction: Wistar Han rats are a preferred strain of rodents for general toxicology and safety pharmacology studies in drug development. In some of these studies, visual functional tests that assess for retinal toxicity are included as an additional endpoint. Although the influence of gender on human retinal function has been documented for more than 6decades, preclinically it is still uncertain if there are differences in retinal function between naïve male and female Wistar Han rats. Methods: In this study, sex-related differences in the retinal function were quantified by analyzing electroretinography (ERG) in 7-9-week-old (n = 52 males and 51 females) and 21-23-week-old Wistar Han rats (n = 48 males and 51 females). Optokinetic tracking response, brainstem auditory evoked potential, ultrasonic vocalization and histology were tested and evaluated in a subset of animals to investigate the potential compensation mechanisms of spontaneous blindness. Results/Discussion: Absence of scotopic and photopic ERG responses was found in 13% of 7-9-week-old (7/52) and 19% of 21-23-week-old males (9/48), but none of female rats (0/51). The averaged amplitudes of rod- and cone-mediated ERG b-wave responses obtained from males were significantly smaller than the amplitudes of the same responses from age-matched females (-43% and -26%, respectively) at 7-9weeks of age. There was no difference in the retinal and brain morphology, brainstem auditory responses, or ultrasonic vocalizations between the animals with normal and abnormal ERGs at 21-23weeks of age. In summary, male Wistar Han rats had altered retinal responses, including a complete lack of responses to test flash stimuli (i.e., blindness), when compared with female rats at 7-9 and 21-23weeks of age. Therefore, sex differences should be considered when using Wistar Han rats in toxicity and safety pharmacology studies with regards to data interpretation of retinal functional assessments.

Multimodal Phenomap of Stargardt Disease Integrating Structural, Psychophysical, and Electrophysiologic Measures of Retinal Degeneration

To cluster the diverse phenotypic features of Stargardt disease (STGD) using unsupervised clustering of multimodal retinal structure and function data. Retrospective cross-sectional study. Eyes of subjects with STGD and fundus autofluorescence (FAF), OCT, electroretinography (ERG), and microperimetry (MP) data available within 1year of the baseline evaluation. A total of 46 variables from FAF, OCT, ERG, and MP results were recorded for subjects with STGD as defined per published criteria. Factor analysis of mixed data identified the most informative variables. Unsupervised hierarchical clustering and silhouette analysis identified the optimal number of clusters to classify multimodal phenotypes. Phenotypic clusters of STGD subjects and the corresponding cluster features. We included 52 subjects and 102 eyes with a mean visual acuity (VA) at the time of multimodal testing of 0.69±0.494 logarithm of minimum angle of resolution (20/63 Snellen). We identified 4 clusters of eyes. Compared to the other clusters, cluster 1 (n=16) included younger subjects, VA greater than that of clusters 2 and 3, normal or moderately low total macular volume (TMV), greater preservation of scotopic and photopic ERG responses and fixation stability, less atrophy, and fewer flecks. Cluster 2 (n=49) differed from cluster 1 mainly with less atrophy and relatively stable fixation. Cluster 3 (n=10) included older subjects than clusters 1 and 2 and showed the lowest VA, TMV, ERG responses, and fixation stability, with extensive atrophy. Cluster 4 (n=27) showed better VA, TMV similar to clusters 1 and 2, moderate ERG activity, stable fixation, and moderate-high atrophy and flecks. Reflecting the phenotypic complexity of STGD, an unsupervised clustering approach incorporating phenotypic measures can be used to categorize STGD eyes into distinct clusters. The clusters exhibit differences in structural and functional measures including quantity of flecks, extent of retinal atrophy, visual fixation accuracy, and ERG responses, among other features. If novel pharmacologic, gene, or cell therapy modalities become available in the future, the multimodal phenomap approach may be useful to individualize treatment decisions, and its utility in aiding prognostication requires further evaluation. Proprietary or commercial disclosure may be found after the references.

2‐in‐1 Optimization for High Performance Semitransparent Perovskite Solar Cells

AbstractOrganic lead halide perovskites are regarded as qualified candidates for the photoactive layers of semitransparent solar cells. The critical aspect of boosting the performance of semitransparent perovskite solar cells (PSCs) to a higher level lies in preparing perovskite films with both excellent photoelectric properties and high transmittance. Herein, it is realized that, through theoretical analysis, perovskite materials with bandgap of 2.00–2.30 eV are suitable for the preparation of semitransparent PSCs that can simultaneously achieve low thermal‐energy loss, allow transmission of light for high photopic response, and provide acceptable transmittance for photovoltaic greenhouses. Then the study aims at improving the crystallinity and morphology of wide‐bandgap perovskite films by using additive engineering. As such, PSCs with absorber bandgaps of 2.02, 2.16, and 2.32 eV deliver maximum power‐conversion efficiencies of 12.08%, 9.17%, and 8.42%, respectively. Then the corresponding semitransparent PSCs are crafted with average transmittance of light detectable by the human eye of 9.41%, 23.26%, and 43.47%, respectively. Furthermore, the crop growth factors are predicted to be 21.25%, 29.48%, and 37.07%, respectively. This work gives full play to bandgap modulation in the fabrication of semitransparent PSCs, which will broaden the application of semitransparent solar cells in the field of building integrated photovoltaics.

Familial exudative vitreoretinopathy with retinitis pigmentosa

Familial exudative vitreoretinopathy (FEVR) is a rare inherited slowly progressive disorder characterized by failure of vascularization of the peripheral retina and poor vascular differentiation. Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous inherited retinal disorders characterized by diffuse progressive dysfunction of predominantly rod photoreceptors with subsequent involvement of cone photoreceptors. A 13-year-old boy presented with nyctalopia and low vision for 10 years. Fundus evaluation showed retinal pigmentary changes in the mid-periphery. The fundus fluorescein angiogram showed straightening of retinal vessels, vascular leakage, and avascularity of the peripheral retina, suggestive of FEVR. Full-field electroretinogram (FFERG) showed grossly reduced scotopic and photopic responses in both eyes, pointing toward retinitis pigmentosa (RP). To the best of our knowledge, this case is the second one internationally, and the first in India to show the coexistence of FEVR and RP in the same patient.

Sigma 1 receptor activation improves retinal structure and function in the RhoP23H/+ mouse model of autosomal dominant retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of devastating inherited retinal diseases that leads to visual impairment and oftentimes complete blindness. Currently no cure exists for RP thus research into prolonging vision is imperative. Sigma 1 receptor (Sig1R) is a promising small molecule target that has neuroprotective benefits in retinas of rapidly-degenerating mouse models. It is not clear whether Sig1R activation can provide similar neuroprotective benefits in more slowly-progressing RP models. Here, we examined Sig1R-mediated effects in the slowly-progressing RhoP23H/+ mouse, a model of autosomal dominant RP. We characterized the retinal degeneration of the RhoP23H/+ mouse over a 10 month period using three in vivo methods: Optomotor Response (OMR), Electroretinogram (ERG), and Spectral Domain-Optical Coherence Tomography (SD-OCT). A slow retinal degeneration was observed in both male and female RhoP23H/+ mice when compared to wild type. The OMR, which reflects visual acuity, showed a gradual decline through 10 months. Interestingly, female mice had more reduction in visual acuity than males. ERG assessment showed a gradual decline in scotopic and photopic responses in RhoP23H/+ mice. To investigate the neuroprotective benefits of Sig1R activation in the RhoP23H/+ mouse model, mutant mice were treated with a high-specificity Sig1R ligand (+)-pentazocine ((+)-PTZ) 3x/week at 0.5 mg/kg and examined using OMR, ERG, SD-OCT. A significant retention of visual function was observed in males and females at 10 months of age, with treated females retaining ∼50% greater visual acuity than non-treated mutant females. ERG revealed significant retention of scotopic and photopic b-wave amplitudes at 6 months in male and female RhoP23H/+ mice treated with (+)-PTZ. Further, in vivo analysis by SD-OCT revealed a significant retention of outer nuclear layer (ONL) thickness in male and female treated RhoP23H/+ mice. Histological studies showed significant retention of IS/OS length (∼50%), ONL thickness, and number of rows of photoreceptor cell nuclei at 6 months in (+)-PTZ-treated mutant mice. Interestingly, electron microscopy revealed preservation of OS discs in (+)-PTZ treated mutant mice compared to non-treated. Taken collectively, the in vivo and in vitro data provide the first evidence that targeting Sig1R can rescue visual function and structure in the RhoP23H/+ mouse. These results are promising and provide a framework for future studies to investigate Sig1R as a potential therapeutic target in retinal degenerative disease.

Long-term blue light rearing does not affect in vivo retinal function in young rhesus monkeys.

Exposure to blue light is thought to be harmful to the retina. The purpose of this study was to determine the effects of long-term exposure to narrowband blue light on retinal function in rhesus monkeys. Young rhesus monkeys were reared under short-wavelength "blue" light (n = 7; 465nm, 183 ± 28lx) on a 12-h light/dark cycle starting at 26 ± 2days of age. Age-matched control monkeys were reared under broadband "white" light (n = 8; 504 ± 168lx). Light- and dark-adapted full-field flash electroretinograms (ERGs) were recorded at 330 ± 9days of age. Photopic stimuli were brief red flashes (0.044-5.68cd.s/m2) on a rod-saturating blue background and the International Society for Clinical Electrophysiology of Vision (ISCEV) standard 3.0 white flash on a 30cd/m2 white background. Monkeys were dark adapted for 20min and scotopic stimuli were ISCEV standard white flashes of 0.01, 3.0, and 10cd.s/m2. A-wave, b-wave, and photopic negative response (PhNR) amplitudes were measured. Light-adapted ERGs in young monkeys were compared to ERGs in adult monkeys reared in white light (n = 10; 4.91 ± 0.88years of age). For red flashes on a blue background, there were no significant differences in a-wave (P = 0.46), b-wave (P = 0.75), and PhNR amplitudes (P = 0.94) between white light and blue light reared monkeys for all stimulus energies. ISCEV standard light- and dark-adapted a- and b-wave amplitudes were not significantly different between groups (P > 0.05 for all). There were no significant differences in a- and b-wave implicit times between groups for all ISCEV standard stimuli (P > 0.05 for all). PhNR amplitudes of young monkeys were significantly smaller compared to adult monkeys for all stimulus energies (P < 0.05 for all). There were no significant differences in a-wave (P = 0.19) and b-wave (P = 0.17) amplitudes between young and adult white light reared monkeys. Long-term exposure to narrowband blue light did not affect photopic or scotopic ERG responses in young monkeys. Findings suggest that exposure to 12h of daily blue light for approximately 10months does not result in altered retinal function.