Electroretinographic Findings Research Articles

Retinal Function in Advanced Multiple Sclerosis.

People with multiple sclerosis (pwMS) experience autoimmunity-mediated inflammation and neurodegeneration throughout the central nervous system. There remains a need for clinically accessible, reliable functional markers of neurodegeneration in MS. Previous research has described changes to electroretinography (ERG)-derived measures of retinal bipolar cell function in pwMS early in the disease course. We, therefore, investigated ERG as a potential outcome measure in individuals with more advanced disease. This cross-sectional observational study included pwMS with Expanded Disability Status Scale (EDSS) scores of ≥3.0 and healthy control (HC) participants who underwent ERG, optical coherence tomography, high- and low-contrast visual acuity measurement, and an ophthalmological examination. ERG findings in MS eyes with and without previous optic neuritis (MS +ON; MS -ON) were compared with those in HC eyes. Effects of EDSS, disease duration, ON, and treatment status on selected ERG outcomes were measured. Additional exploratory analyses assessed potential influences of MS phenotype and disease status (clinically active, radiologically active, and disease progression). Delays to two ERG peak times (dark-adapted 3.0 b-wave; light-adapted flicker) were recorded in MS +ON and MS -ON eyes. No influences of EDSS score, disease duration, previous ON, or treatment status were observed. Exploratory analyses were consistent with no effects of MS phenotype or disease status. ERG findings are abnormal in individuals with moderate-severe disability caused by MS; however, these findings are not distinct from those observed earlier in the disease course. Although bipolar dysfunction appears to be common in pwMS throughout the disease course, ERG is likely not useful in monitoring or prognostication of MS.

Synthesis, Properties, and Biocompatibility of 4-Carboxyphenyboronic Acid-Modified Gelatin-Methacryloyl: A Hydrogel for Retinal Surgeries.

The current surgical adjunctive for vitreoretinal surgeries fails to provide an adequate 3D structure for cellular regeneration. A one-pot synthesis of gelatin-methacryloyl (GelMA) followed by modification with 4-carboxyphenylboronic acid (4-CPBA) was performed to fabricate 4-CPBA-modified GelMA (4CPBA@GelMA), a gelatin-based hydrogel. 4CPBA@GelMA was photo-cross-linked by 405 nm violet light and examined using nuclear magnetic resonance (NMR), Fourier-transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), and rheometry. In vitro biocompatibility was examined by Müller cell proliferation assays exposed to 4CPBA@GelMA and violet light. In vivo retinal biocompatibility was evaluated by electroretinography of rat eyes that were exposed to intravitreally injected and photo-cross-linked 4CPBA@GelMA at days 3, 7, 14, and 28 post-injection. Following electroretinography, histology and immunohistochemistry were performed on the retinas. The NMR results indicated amidation of GelMA by 4-CPBA, and FTIR confirmed the presence of the CPBA ring in 4CPBA@GelMA samples. SEM revealed that 4CPBA@GelMA had significantly larger pores than GelMA (56.9 ± 9.5 vs 35.1 ± 2.8 μm; P < 0.001). Rheological findings showed that, unlike GelMA and gelatin, 4CPBA@GelMA has Newtonian fluid properties at room temperature. Exposure to 4CPBA@GelMA did not significantly affect Müller cell viability in a proliferation assay; moreover, electroretinography findings indicated normal waveforms and implicit times, and histology and immunohistochemistry examinations revealed no significant changes. In this study, we established the high retinal compatibility of 4CPBA@GelMA. The low viscosity of 4CPBA@GelMA is ideal for injection via small-gauge needles, and the larger pore size and three-dimensional network both potentiate cellular migration and growth. These features made 4CPBA@GelMA a candidate for vitreoretinal surgical adjunctive that might promote retinal regeneration.

A - 102 Neuropsychological Insights into Kearns-Sayre Syndrome: a Case Study

Abstract Objective Kearns-Sayre Syndrome (KSS) is a genetic mitochondrial and neuromuscular condition with multisystemic effects, including the eyes, heart, muscles, and cognition. Very little is known regarding the cognitive profile of patients with KSS, and existing studies have presented mixed findings. Results in one study revealed impairments in visuospatial abilities and attention, while another study found impairments in global cognition and word-finding. Interestingly, both studies revealed impairments in executive functions. Method This abstract presents the case of a 46-year-old right-handed, African American female diagnosed with KSS in 2021. Symptoms of KSS first appeared in 2010 with progressive vision loss and bilateral ptosis. Genetic testing revealed MT-T1 mutation consistent with KSS. Electroretinography findings revealed mild cone atrophy and mild-to-moderate concentric visual field defects. Attentional difficulties were noted in 2016 and resulted in a diagnosis of ADHD. Memory problems were first noticed in 2016 and have persisted since then. Magnetic resonance imaging results from May 2023 revealed no structural abnormalities in the brain. Results A comprehensive neuropsychological evaluation completed in March 2024 revealed mostly intact neurocognitive functioning. Notably, performance on memory and visuospatial measures were within normal limits. However, poor performance was revealed on one measure of executive functioning. Conclusions It remains unclear whether the poor performance seen on a measure of executive functioning reflects a true cognitive deficit or just chance variation. Even so, with little information regarding the cognitive profile of KSS, baseline neuropsychological testing should be considered to monitor related cognitive changes over time.

Assessment of retinal atrophy in mixed breed dogs using spectral domain optical coherence tomography (SD-OCT) and electroretinography.

The aim of the study was to characterize retinal atrophy (RA) with progressive retinal atrophy symptoms in mixed breed dogs using ophthalmoscopy, spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG).The study was performed on 13 mixed breed dogs affected by retinal atrophy (11 males and 2 females that were 1.5-14 years old). Depending on the advancement of RA, SD-OCT examinations identified retinal abnormalities ranging from layer disorganisation to advanced atrophy. The most advanced RA occurred ventral to the optic disc. Total retinal thickness in both eyes (mean ± SD) was lower in dogs with RA compared to controls dorsally (77.7 ± 39.5 μm vs 173.5 ± 13.3 μm), ventrally (33.4 ± 29.9 μm vs 139.5 ± 10.8 μm), nasally (65.0 ± 34.5 μm vs 163.9 ± 11.0 μm) and temporally (61.8 ± 41.7 μm vs 171.9 ± 11.1 μm) to the optic disc. In dogs with locally normal architecture of inner retina, loss of definition of outer retinal layers occurred in many regions. Dark and light-adapted ERGs were reduced in 2 dogs with RA and were unrecordable in 11 dogs. Lesions evident in SD-OCT scans of mixed breed dogs affected with retinal atrophy initially appear ventrally to the optic disc and ventro-dorsally in advanced RA. In all mixed breed dogs with retinal atrophy, clinical signs and SD-OCT results correlate with ERG findings.

Co-occurring Usher syndrome Type 1 and Renal Failure.

To describe a patient with a rare co-occurrence of Usher syndrome type 1C (USH1C) and renal disease, suspected to be secondary to Alport syndrome. Case report and literature review of cases with Usher syndrome and renal failure. Clinical examination, color fundus photography, visual field tests, electroretinography and whole exome sequencing were used to diagnose and document the patient's clinical presentation. An 18-year-old female with known history of congenital hearing loss and chronic renal failure, presents with progressive night and peripheral visual impairment suspicious for an inherited retinal disease. Visual field testing, fundus exam and electroretinography findings supported the diagnosis of Usher syndrome. Whole exome sequencing (WES) identified a novel homozygous frameshift variant (c.238del) in USH1C. WES also identified a homozygous COL4A3 variant of unknown significance, which may be responsible for concomitant Alport syndrome. By presenting this rare case of co-occurring Usher syndrome Type 1 and renal failure, we highlight the importance of conducting further investigations that could reveal an additional underlying etiology when these entities are present.

Electroretinography Findings in Patients Treated with Hydroxychloroquine

Electroretinography Findings in Patients Treated with Hydroxychloroquine

RETINAL AGING IN COMPANION DOGS

Abstract Companion dogs cohabit with humans in approximately 45% of US households. They experience similar environmental exposures and lifestyles to their human companions, and have shown sensory, cognitive, and neurological decline with aging. The relationship between age and retinal neurologic function in dogs has not been described. The aim of this study was to determine associations between age and retinal full-field electroretinographic measures in companion dogs, an important translational model species for human neurologic aging. Healthy adult companion dogs with no ophthalmic abnormalities were included (n=54, 18 male, 36 female, median weight 25.7kg, median age 89 months). Unilateral full-field light-adapted and dark-adapted electroretinography (ERG) was performed using a handheld device, with mydriasis and topical anesthesia. Standard least squares effect leverage models were used with log transformed data to determine the cross-sectional effect of age, sex, and bodyweight on ERG amplitudes and peak times. Age and sex were significantly associated with ERG outcome variables, more consistently with ERG amplitude than peak time; age had the largest and most significant effect leverage on outcomes (significantly affecting 3/9 peak time and 8/10 amplitude outcome variables). Younger and female dogs had higher ERG amplitudes. Body weight had no significant effect on any outcome. Our finding that aged companion dogs have reduced ERG amplitudes and prolonged peak times mirror ERG findings in aging humans. Because dogs have a shorter lifespan compared with humans, they may act as a sentinel species to monitor for emerging risk factors for age-related neurologic decline.

Optical coherence tomography findings of the peripheral retina in patients with congenital X-linked retinoschisis.

Congenital X-linked retinoschisis (XLRS) presents as macular retinoschisis/degeneration in almost all patients and as peripheral retinoschisis in half the patients. Although the optical coherence tomography (OCT) findings of macular retinoschisis have been well investigated, those of peripheral retinoschisis have rarely been reported. This study aimed to report the ultra-widefield OCT findings of the peripheral retina in patients with XLRS. Medical records of 10 Japanese patients (19 eyes) with clinically and/or genetically diagnosed XLRS were retrospectively reviewed. Funduscopic, electroretinographic, and OCT findings were reviewed and evaluated. Some were also genetically evaluated for the RS1 gene. OCT of the macula revealed schises and/or cystoid changes in the inner nuclear layer (INL) and outer nuclear layer. In contrast, OCT of the peripheral retina revealed schises and/or cystoid changes in the INL in eight eyes (44%), and/or splitting in the ganglion cell layer (GCL) in 10 (56%) of the 18 eyes with clear OCT images. No schisis or cystoid changes were found in the peripheral OCT images of eight eyes (44%). A 16-year-old boy presented with retinal splitting of the GCL and INL of the inferior retina, although he had no ophthalmoscopic peripheral retinoschisis. Genetic examinations were performed on three patients, all of whom had reported missense mutations in the RS1 gene. In XLRS, peripheral bullous retinoschisis results from GCL splitting in the retina. One of the 10 patients with XLRS showed intraretinal retinoschisis in the GCL in the inferior periphery, which was unremarkable on ophthalmoscopy (occult retinoschisis). Although both peripheral bullous retinoschisis and occult retinoschisis showed splitting/cystic changes in the GCL, further studies are needed to determine whether occult retinoschisis progresses to bullous retinoschisis.

KCNV2-associated retinopathy: genotype–phenotype correlations – KCNV2 study group report 3

Background/aimsTo investigate genotype–phenotype associations in patients with KCNV2 retinopathy.MethodsReview of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination...

The Value of Electroretinography in Identifying Candidate Genes for Inherited Retinal Dystrophies: A Diagnostic Guide.

Inherited retinal dystrophies (IRDs) are a group of heterogeneous diseases caused by genetic mutations that specifically affect the function of the rod, cone, or bipolar cells in the retina. Electroretinography (ERG) is a diagnostic tool that measures the electrical activity of the retina in response to light stimuli, and it can help to determine the function of these cells. A normal ERG response consists of two waves, the a-wave and the b-wave, which reflect the activity of the photoreceptor cells and the bipolar and Muller cells, respectively. Despite the growing availability of next-generation sequencing (NGS) technology, identifying the precise genetic mutation causing an IRD can be challenging and costly. However, certain types of IRDs present with unique ERG features that can help guide genetic testing. By combining these ERG findings with other clinical information, such as on family history and retinal imaging, physicians can effectively narrow down the list of candidate genes to be sequenced, thereby reducing the cost of genetic testing. This review article focuses on certain types of IRDs with unique ERG features. We will discuss the pathophysiology and clinical presentation of, and ERG findings on, these disorders, emphasizing the unique role ERG plays in their diagnosis and genetic testing.

Characteristics of Vitamin A Deficiency Retinopathy at a Tertiary Referral Center in the United States

To explore the risk factors and fundus imaging features of vitamin A deficiency retinopathy (VADR) in an academic tertiary referral center in Atlanta, GA, United States, and to propose guidance regarding diagnostic workup and management of affected patients. Single-center retrospective case series. Nine patients seen between 2015 and 2021 at the Emory Eye Center diagnosed with VADR. Retrospective chart review. Baseline serum retinol level, Snellen visual acuity, multimodal fundus imaging findings, and electroretinography findings. Nine patients, 4 (44.4%) female, with a median (range) age of 68 (50-75) years were identified. The most common underlying etiologies for vitamin A deficiency included history of gastrointestinal surgery (55.6%), liver disease (44.4%), and nutritional depletion due to low-quality diet (44.4%). Only 1 (11.1%) patient had a history of bariatric surgery. Four (44.4%) patients were on some form of vitamin A supplementation before the diagnosis of VADR. Median (range) serum retinol level was 0.06 (< 0.06-0.19) mg/L. All patients had macular subretinal hyperreflective deposits resembling subretinal drusenoid deposits, although in some cases, these were scant and sparsely distributed. Six eyes of 3 patients with longstanding deficiency had defects in the external limiting membrane (ELM). Three of these eyes additionally had macular areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA). Full-field electroretinography demonstrated severe rod dysfunction and mild to moderate cone system dysfunction. Many findings of VADR were reversible with vitamin A repletion. However, all eyes with ELM defects or cRORA had persistence or continued growth of these lesions. Vitamin A deficiency retinopathy is uncommon in the developed world. However, given that early intervention can lead to dramatic visual improvement and avoid potentially permanent retinal damage, retina specialists should be familiar with its clinical presentation. The presence of nyctalopia and subretinal hyperreflective deposits in a patient with a history of gastrointestinal surgery, liver disease, and/or poor diet can be suggestive of this diagnosis, even in the presence of ongoing vitamin A supplementation. Vitamin A supplementation can vary in route and dosage and can be tailored to the individual with serial testing of serum retinol. The authors have no proprietary or commercial interest in any materials discussed in this article.

Zellweger Spectrum Disorder: Ophthalmic Findings from a New Natural History Study Cohort and Scoping Literature Review

Individuals with Zellweger spectrum disorder (ZSD) manifest a spectrum of clinical phenotypes but almost all have retinal degeneration leading to blindness. The onset, extent, and progression of retinal findings have not been well described. It is crucial to understand the natural history of vision loss in ZSD to define reliable endpoints for future interventional trials. Herein, we describe ophthalmic findings in the largest number of ZSD patients to date. Retrospective review of longitudinal data from medical charts and review of cross-sectional data from the literature. Sixty-six patients with ZSD in the retrospective cohort and 119 patients reported in the literature, divided into 4 disease phenotypes based on genotype or clinical severity. We reviewed ophthalmology records collected from the retrospective cohort (Clinicaltrials.gov NCT01668186) and performed a scoping review of the literature for ophthalmic findings in patients with ZSD. We extracted available ophthalmic data and analyzed by age and disease severity. Visual acuity (VA), posterior and anterior segment descriptions, nystagmus, refraction, electroretinography findings, visual evoked potentials, and OCT results and images. Visual acuity was worse at younger ages in those with severe disease compared with older patients with intermediate to mild disease for all 78 participants analyzed, with a median VA of 0.93 logarithm of the minimum angle of resolution (Snellen 20/320). Longitudinal VA data revealed slow loss over time and legal blindness onset at an average age of 7.8 years. Funduscopy showed retinal pigmentation, macular abnormalities, small or pale optic discs, and attenuated vessels with higher prevalence in milder severity groups and did not change with age. Electroretinography waveforms were diminished in 91% of patients, 46% of which were extinguished and did not change with age. OCT in milder patients revealed schitic changes in 18 of 23 individuals (age range 1.8 to 30 years), with evolution or stable macular edema. In ZSD, VA slowly deteriorates and is associated with disease severity, serial electroretinography is not useful for documenting vision loss progression, and intraretinal schitic changes may be common. Multiple systematic measures are required to assess retinal dystrophy accurately in ZSD, including functional vision measures. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Fundus autofluorescence, optical coherence tomography and electroretinography abnormalities in a patient with digoxin retinopathy that resemble those in KCNV2-associated retinopathy.

Digoxin related retinal toxicity causes blurred vision, photophobia, central scotoma, color vision abnormality, and electroretinography (ERG) abnormalities. Here, we report a case with transient abnormalities in vison, in which fundus autofluorescence (FAF), optical coherence tomography (OCT), and ERG findings resembled those in KCNV2 (potassium voltage-gated channel modifier subfamily V member 2)-associated retinopathy. An 89-year-old woman presented with complaints of acute blurred vision, nyctalopia, photophobia, and color vision abnormality. She received digoxin for tachycardia induced by atrial fibrillation for a month. The fundi showed a faint white ring at the fovea, which showed hyperfluorescence in FAF. OCT showed a thickened EZ in the macula. A dark-adapted (DA)-30 ERG showed a reduced and "squaring (trough-flattened)" a-wave, and a delayed, supernormal b-wave, resulting in a high b/a-wave amplitude ratio. The digoxin dose was reduced following an elevation in serum levels. Five weeks later, her visual acuities improved, and abnormal hyperfluorescence on FAF disappeared. After 6months, no visual symptoms were reported. The ellipsoid-zone thickening in OCT improved; however, the b/a-wave amplitude ratio on DA-30 ERG remained high. The b-wave in LA-long-flash ERG was initially reduced, which improved after correction of serum level of digoxin. The patient's clinical findings resembled those of patients with KCNV2-associated retinopathy or temporal hyperkalemia. These disorders appear to have a common pathogenesis, which may be related to abnormal extracellular potassium levels in the retina. The on-bipolar cells seemed to be more affected than the off-bipolar cells in digoxin related retinal toxicity.

Electroretinographic and Optical Coherence Tomographic Evaluations of Eyes with Vitreoretinal Lymphoma.

Vitreoretinal lymphomas (VRLs) present with different clinical characteristics. However, only a few case reports have been published that evaluated the retinal function and the retinal morphology. The relationship between retinal morphology and function of eyes with a vitreoretinal lymphoma (VRL) was investigated via optical coherence tomography (OCT) and electroretinography (ERG). The ERG and OCT findings in 11 eyes of 11 patients (69.4 ± 11.5 years old) who were diagnosed with VRL at the Saitama Medical University Hospital between December 2016 to May 2022 were studied. The decimal best-corrected visual acuity ranged from hand movements to 1.2 (median 0.2). Histopathological studies of the vitreous specimens showed class II VRL in one eye, class III VRL in seven eyes, class IV VRL in two eyes, and class V VRL in one eye. The IgH gene rearrangement was positive in three of the six eyes tested. The OCT images showed morphological abnormalities in 10 of the 11 (90.9%) eyes. Severe attenuation was found for the amplitudes of the b-wave of the DA 0.01 ERG in 6 of 11 eyes (54.5%), the DA 3.0 a-wave in 5 of 11 eyes (45.5%), the DA 3.0 b-wave in 36.4%, the LA 3.0 a-wave in 36.4%, the LA 3.0 b-wave in 18.2%, and flicker responses in 36.4% of the eyes. None of the DA 3.0 ERGs had a negative shape (b/a < 1.0). In the five eyes in which the a-wave was severely attenuated, hyperreflective dots were observed subretinally. The ERG analysis in eyes with a VRL indicates a relatively severe dysfunction of the outer retinal layer and was helpful in determining the site of the morphological changes in eyes with VRL.

Multifocal electroretinographic findings in angiographic macular leakage in the setting of intermediate, posterior, or panuveitis

ObjectifÉvaluer les retombées fonctionnelles de l'exsudat maculaire visible à l'angiographie en l'absence de liquide intrarétinien lors de la tomographie par cohérence optique (OCT) dans des yeux présentant une uvéite intermédiaire, une uvéite postérieure ou encore une panuvéite. MéthodesIl s'agit d'une étude rétrospective portant sur des patients qui ont reçu un diagnostic d'uvéite intermédiaire, d'uvéite postérieure ou encore de panuvéite. Ont été inclus les patients qui ont fait l'objet d'une angiographie à la fluorescéine, d'une OCT et d'une électrorétinographie multifocale (ERGmf) selon un échéancier déterminé. Les données démographiques et cliniques comprenaient le type d'inflammation oculaire, la meilleure acuité visuelle corrigée (MAVC) et les résultats de l'OCT, de l'angiographie à la fluorescéine et de l'ERGmf. Les patients ont été répartis en 2 groupes en fonction de la présence d'un exsudat maculaire visible à l'angiographie et d'un œdème maculaire: groupe 1 (aucun œdème maculaire ni exsudat maculaire) et groupe 2 (présence d'un exsudat maculaire sans œdème maculaire). RésultatsAu total, 29 patients (43 yeux) ont été inclus dans l’étude : 13 patients (17 yeux) dans le groupe 1 et 16 patients (26 yeux) dans le groupe 2. On n'a pas noté de différence statistiquement significative entre les 2 groupes au chapitre des paramètres suivants : âge, sexe, cellules de la chambre antérieure, état du cristallin, cellules du vitré, flou vitréen, MAVC ou épaisseur sous-fovéale centrale moyenne. Aucune des mesures obtenues à l'ERGmf, notamment l'amplitude et les temps de culmination des ondes N1 et P1 dans les anneaux 1–5, n'a différé de manière statistiquement significative entre les 2 groupes. Enfin, aucune corrélation n'a pu être établie entre la MAVC ou l’épaisseur sous-fovéale centrale moyenne et l'une ou l'autre des mesures obtenues à l'ERGmf pour les anneaux 1–3. ConclusionsDans des yeux atteints d'uvéite exempts d’œdème maculaire, l'atteinte de la fonction maculaire n'est pas nécessairement pire en présence d'un exsudat maculaire visible à l'angiographie.

Ophthalmic Manifestations of ROSAH (Retinal Dystrophy, Optic Nerve Edema, Splenomegaly, Anhidrosis, and Headache) Syndrome, an Inherited NF κB–Mediated Autoinflammatory Disease with Retinal Dystrophy

We aimed to characterize the ocular phenotype of patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome and their response to therapy. Single-center observational case study. Eleven patients with a diagnosis of ROSAH syndrome and mutation in ALPK1 were included. Patients with molecularly confirmed ROSAH syndrome underwent ophthalmic evaluation, including visual acuity testing, slit-lamp and dilated examinations, color fundus and autofluorescence imaging, fluorescein angiography, OCT, and electrophysiologic testing. Visual acuity, electrophysiology, fluorescein angiography, and OCT findings. Eleven individuals (6 female and 5 male patients) from 7 families ranging in age from 7.3 to 60.2 years at the time of the initial evaluation were included in this study. Seven patients were followed up for a mean of 2.6 years (range, 0.33-5.0 years). Best-corrected visual acuity at baseline ranged from 20/16 to no light perception. Variable signs or sequelae of intraocular inflammation were observed in 9 patients, including keratic precipitates, band keratopathy, trace to 2+ anterior chamber cells, cystoid macular edema, and retinal vasculitis on fluorescein angiography. Ten patients were observed to show optic disc elevation and demonstrated peripapillary thickening on OCT. Seven patients showed retinal degeneration consistent with a cone-rod dystrophy, with atrophy tending to involve the posterior pole and extending peripherally. One patient with normal electroretinography findings and visual evoked potential was found to have decreased Arden ratio on electro-oculography. Leveraging insights from the largest single-center ROSAH cohort described to date, this study identified 3 main factors as contributing to changes in visual function of patients with ROSAH syndrome: optic nerve involvement; intraocular inflammation, including cystoid macular edema; and retinal degeneration. More work is needed to determine how to arrest the progressive vision loss associated with ROSAH syndrome. Proprietary or commercial disclosure may be found after the references.

Stargardt Disease

Stargardt disease is a slowly progressing macular dystrophy with an onset of disease most commonly in children and young adults. Numerous genes have been found to be associated with this disease, with variants in the retina specific ATP- binding cassette transporter (ABCA4) gene being most common. Each variant may have distinct clinical features, however, patients generally experience bilateral central vision loss and poor visual acuity ranging from 20/70 to 20/200. Diagnosis is often made through clinical presentation and may be assisted by fluorescein angiography (FA), spectral domain optical coherence tomography (OCT), fundus autofluorescence (FAF) or electrophysiological assessment. Currently, there are multiple classification systems of Stargardt disease that include Fishman STGD classification system, groupings due to electroretinography (ERG) findings, and types based on FAF imaging. Though there are currently no clinically proven treatments for Stargardt disease, physicians often recommend patients avoid direct sunlight, smoking cigarettes, and excessive intake of vitamin A. Potential treatments currently under investigation include strategies using gene replacement therapy, stem cell therapy, and pharmacologic agents. The purpose of this paper is to review the current knowledge of the genetics, classifications, and treatments of Stargardt disease, while underscoring the need for further research in potential treatment routes.

Delineating the Clinical Phenotype of Patients With the c.629C>G, p.Pro210Arg Mutation in Peripherin-2.

PurposeMore than 200 different mutations in peripherin-2 (PRPH2) are associated with multiple subtypes of inherited retinal diseases (IRDs), including retinitis pigmentosa and cone or macular diseases. Our goal was to understand how the poorly characterized PRPH2 mutation p.Pro210Arg (P210R) affects visual function and retinal structure as well as gain insight into the mechanism driving the clinical pathology.MethodsEleven patients had clinical assessments including best-corrected visual acuity (BCVA), full field and multifocal electroretinography (ERG), static (spot size V) and kinetic perimetry (Octopus 900), and dark-adapted chromatic (DAC; Medmont; spot size V) perimetry. Images were acquired with the Optos ultra-wide field camera and spectral-domain optical coherence tomography (SD-OCT). Molecular characteristics of the P210R mutant protein were evaluated in vitro.ResultsPatients with the P210R mutation had BCVA (Snellen) ranging from 20/15 to 20/80. Perimetry showed a reduction in sensitivity, while ERG findings suggested that cone function was more impaired than rod function. Scotomas were identified corresponding to atrophic retinal lesions. Imaging revealed heterogeneous outer retinal changes such as hyperfluorescent flecks, hypo-autofluorescence (AF) regions of atrophy, and thinning of the photoreceptor layer on SD-OCT. In vitro findings suggested that P210R-Prph2 retains the ability to interact with binding partner Rom1 but abnormally accumulates in the endoplasmic reticulum (ER), suggesting the protein does not fold properly.ConclusionsRod and cone sensitivities were decreased in subjects with the P210R mutation in PRPH2. There was scotomatous vision loss that occurred within the macula, likely due to atrophy that occurs after drusen have formed and have begun to resolve. This suggests that although rod and cone photoreceptors are dependent on PRPH2, preventing blindness in this specific subgroup of patients could involve therapeutics that impede the formation or lifecycle of drusen.

Vitamin A deficiency and the retinal "double carrot" sign with optical coherence tomography.

Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT, this study aimed to characterize and follow a novel retinal abnormality in patients with VAD and intramuscular supplementation. Patients with VAD were retrospectively reviewed, including SD-OCT and electroretinography. Three patients had VAD following bariatric or colon surgery and varying supplementation. All had nyctalopia, extinguished scotopic rod-specific function with ERG, and decreased serum vitamin A. None demonstrated surface abnormalities. All received intramuscular vitamin A with subjective resolution of symptoms. On SD-OCT, four of six eyes exhibited homogenous foveal hyperreflectivity anterior to retinal pigment epithelium-Bruch complex, reminiscent of a "double carrot", which improved following supplementation. ERG findings demonstrated improved scotopic rod-specific function in all cases; however, photopic function remained diminished in two cases. Structural improvement of the proposed "double carrot" sign occurs soon after vitamin A supplementation. While scotopic function improves rapidly following supplementation, cone function recovers more slowly. Therefore, foveal changes such as the "double carrot" sign suggest that structural recovery of cones precedes functional recovery.

Clinical and genetic findings in TRPM1-related congenital stationary night blindness.

Congenital stationary night blindness (CSNB) is a heterogeneous group of Mendelian retinal disorders that present in childhood. Biallelic variants altering the protein-coding region of the TRPM1 gene are one of the commonest causes of CSNB. Here, we report the clinical and genetic findings in 10 unrelated individuals with TRPM1-retinopathy. Study subjects were recruited through a tertiary clinical ophthalmic genetic service at Manchester, UK. All participants underwent visual electrodiagnostic testing and panel-based genetic analysis. Study subjects had a median age of 8 years (range: 3-20 years). All probands were myopic and had electroretinographic findings in keeping with complete CSNB. Notably, three probands reported no night vision problems. Fourteen different disease-associated TRPM1 variants were detected. One individual was homozygous for the NM_001252024.2 (TRPM1):c.965 + 29G>A variant and a mini-gene assay highlighted that this change results in mis-splicing and premature protein termination. Additionally, two unrelated probands who had CSNB and mild neurodevelopmental abnormalities were found to carry a 15q13.3 microdeletion. This copy number variant encompasses seven genes, including TRPM1, and was encountered in the heterozygous state and in trans with a missense TRPM1 variant in each case. Our findings highlight the importance of comprehensive genomic analysis, beyond the exons and protein-coding regions of genes, for individuals with CSNB. When this characteristic retinal phenotype is accompanied by extraocular findings (including learning and/or behavioural difficulties), a 15q13.3 microdeletion should be suspected. Focused analysis (e.g. microarray testing) is recommended to look for large-scale deletions encompassing TRPM1 in patients with CSNB and neurodevelopmental abnormalities.