Electroretinographic Abnormalities Research Articles

Retinopathy in Mucopolysaccharidoses.

PurposeTo determine the pattern(s) of onset, variation, and progression of retinopathy in patients with Mucopolysaccharidosis (MPS). DesignProspective, longitudinal, observational study. ParticipantsBetween November 2015 and March 2023, individuals with MPS were recruited from Ophthalmology clinics at the Manchester Royal Eye Hospital, United Kingdom. MethodsParticipants underwent assessment of visual acuity, corneal clouding, intraocular pressure, along with fundoscopy, ultra-widefield (UWF) colour fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), and electroretinography (ERG), where feasible. Main Outcome MeasuresEvaluation of findings from clinical examination, retinal imaging, and electroretinogram studies, to ascertain the presence and patterns of retinopathy. ResultsData was collected for 75 patients, including 45 MPS I, 9 MPS II, 13 MPS IVA, and 8 MPS VI, aged 3-58 years. Fundus photography was conducted in 65 patients, FAF in 61, OCT in 58, and electrodiagnostic studies in 36 participants. Retinopathy was defined as signs of retinal disease evident through retinal examination or fundus photography such as depigmentation, bone-spicule pigmentation, vascular tortuosity, retinal pigment epithelium (RPE) mottling/other changes, macular atrophy/puckering/epiretinal membranes, FAF findings such as a central hyperautofluorescent dot, hyperautofluorescent parafoveal ring, hypoautofluorescent lesions around fovea (double bull’s eye), areas of hyper/hypoautofluorescence, and extrafoveal changes, OCT imaging features such as central external limiting membrane (ELM) thickening, RPE disturbance, photoreceptor layer loss, parafoveal retinal atrophy, and outer retinal/intrachoroidal cavities, or electroretinogram studies revealing rod-mediated retinopathy or rod-cone dystrophy. Retinopathy was confirmed in 32 patients, including 25 MPS I, 4 MPS II, 1 MPS IVA, and 2 MPS VI. Five participants were first diagnosed with retinopathy with clinical examination, while 31 participants were identified on UWF colour fundus photography supported by FAF and OCT. 21 patients exhibited ERG abnormalities consistent with retinopathy. Fifteen of the total 32 participants described symptoms of nyctalopia. The onset of retinopathy varied substantially, with initial detection between 2 and 53 years of age. ConclusionsMPS patients as young as 2 may develop retinopathy, diagnosed through fundus examination, ophthalmic imaging, or ERG. Emerging treatments, including gene therapy, may prevent or stabilise retinopathy. Phenotypic data and natural history of MPS-related retinopathy are thus of paramount importance.

The retina in Alzheimer’s disease: Anatomy and Pathology

AbstractGrowing evidence suggests that Alzheimer’s disease (AD) pathology is not confined to the brain but also appears in the neurosensory retina. Perceived as an extension of the brain, the retina is visible directly and noninvasively at the vascular, cellular and molecular resolution. Aβ accumulation, vascular amyloidosis, hyperphosphorylated (p)tau, microgliosis, astrogliosis, Müller glia changes, abnormal electroretinography patterns, and neuronal degeneration have all been described in the postmortem retina of AD patients, including in early‐stage cases. Although a few studies were unable to consistently repeat these findings, increased proportion of positive studies from subsequent histological, biochemical, and imaging studies validated the original findings. Several studies further provided data suggesting that the brain and retina follow a similar trajectory during AD progression, potentially due to their common embryonic origin and anatomical proximity. A host of retinal vascular abnormalities including reduced blood flow, foveal avascular zone and arteriole‐to‐venule ratio were observed by in vivo fundus imaging, optical coherence tomography (OCT) or OCT‐angiopathy in preclinical, prodromal and clinical AD patients. Further, retinal vascular platelet‐derived growth factor receptor‐β (PDGFRβ) expression and pericyte loss have been associated with retinal vascular amyloidosis and cerebral amyloid angiopathy in mild cognitively impaired (MCI) and AD patients. A recent proteomics profiling study revealed common molecular signatures in the AD retina and brain, with enriched pathways related to inflammation, vascular and photoreceptor vulnerability. Novel imaging techniques, such as curcumin fluorescence, have correlated increases in retinal amyloid burden with brain amyloid PET load and hippocampal atrophy in patients, and together with vascular changes predicted cognitive deficits. This perspective provides an overview on the evidence of AD pathology in the retina and current gaps in knowledge. Future studies exploring retinal pathology in AD and other neurodegenerative diseases may fundamentally contribute to the development of validated retinal biomarkers for improved noninvasive disease diagnosis and monitoring.

Neurodegeneration with Brain Iron Accumulation Disorders and Retinal Neurovascular Structure.

The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. To investigate NBIA's neurological and ophthalmological manifestations. This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations. Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome. Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society.

Neurodegenrative changes in retina of rats with streptozotocin-induced diabetes under conditions of treatment with niacin-oxy-ethylidene-diphosphonate germanate (MIGU-4)

Background: Diabetes is accompanied by neurodegenerative changes in the retina. The determination of retinal function parameters under conditions of experimental diabetes may allow for the development of new approaches to pharmacological vision correction. Purpose: To assess changes in the metabolic (lipid peroxidation and antioxidant defence) and functional characteristics (electroretinography (ERG)) of the retina in the rat with streptozotocin (STZ)-induced diabetes, treated with niacin-oxy-ethylidene-diphosphonate germanate (MIGU-4) and a reference drug, diazepam. Material and Methods: Diabetes was induced intraperitoneally (i.p.) in Wistar male rats by streptozotocin (STZ 65 mg/kg). Four weeks thereafter, the rats received a two-week course of a daily dose of MIGU-4 (5.0 mg/kg or 25.0 mg/kg) or diazepam (0.5 mg/kg or 1.5 mg/kg). The electroretinogram (ERG) was obtained, the animals were euthanized and retinal malondialdehyde (MDA) levels and superoxide dismutase (SOD) and catalase (CAT) activity were determined. Results: In rats with untreated STZ-induced diabetes, the retinal MDA level was 3.71 times increased and CAT activity was 35% lower, compared to controls, whereas the SOD activity was half of the activity found in controls (р less 0.05). In diabetic animals treated with MIGU-4 i.p. at a 25.0-mg/kg daily dose, the retinal MDA level was 63.2% lower, whereas the CAT activity and SOD activity were 41.9% and 27.6%, respectively, higher, than in untreated diabetic rats (р less 0.05). In diabetic animals treated with diazepam i.p. at a 1.5-mg/kg daily dose, the retinal MDA level was 59.2% lower, whereas the CAT activity and SOD activity were 44.4% and 32.1%, respectively, higher, than in untreated diabetic rats (р less 0.05). In untreated diabetic rats, the ERG b-wave amplitude was 39.2% lower, ERG a-wave and b-wave latencies, 23.4% and 14.0%, respectively, higher, and the a-wave amplitude recovery rate, 38.8% lower than in controls (р less 0.05). The use of a 25.0-mg/kg daily dose of MIGU-4 resulted in a 29.7% and 33.9%, respectively, increase in the ERG b-wave amplitude and the a-wave amplitude recovery rate compared to untreated diabetic rats (р less 0.05). The use of a 1.5-mg/kg daily dose of diazepam resulted in a 25.0% and 30.0%, respectively, increase in the above ERG parameters compared to untreated diabetic rats (р less 0.05). In untreated diabetic rats, the number of squares crossed (SK) was 29.4% lower (р less 0.05); the number of central squares crossed (CSC), 52.1% lower (р less 0.05); the number of upright postures (UP), 34.2% lower; and the defecation bolus number, 32.4% higher than in controls (р less 0.05). After MIGU-4 (25-mg/kg) withdrawal, there were no more differences in SK, CSC, UP and defecation bolus numbers between treated diabetic rats and controls. In addition, the number of CSC was 4.27 times lower than in controls, and half of that in untreated diabetic animals (р less 0.05). In diabetic rats treated with diazepam, the number of UP was 2.56 times lower than in controls (р less 0.05), and 40.7% lower than in untreated diabetic rats (р less 0.05), whereas the defecation bolus number was 40.5% higher than in controls (р less 0.05). Conclusion: STZ-induced diabetes is accompanied by an impairment of the oxidant/ antioxidant balance in the retina with an increase in retinal MDA, decrease in retinal SOD and CAT activity, and ERG abnormalities such as reduced ERG amplitude and increased ERG latency. A course treatment with niacin-oxy-ethylidene-diphosphonate germanate (MIGU-4) i.p. at a daily dose of 25.0 mg/kg provides for a decrease in retinal MDA and an increase in retinal SOD and CAT activity and ERG wave amplitude The withdrawal of a two-week treatment with MIGU-4 i.p. at a daily dose of 25.0 mg/kg decreased open-field anxiety-like behaviors, whereas the withdrawal of a two-week treatment with diazepam i.p. at a daily dose of 1.5 mg/kg increased open-field anxiety-like behaviors. The corrective effect of treatment with MIGU-4 corresponds to the corrective effect of treatment with diazepam.

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.

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.

Impact of keratoprosthesis implantation on retinal and visual pathway function assessed by electrophysiological testing.

To investigate the impact of Boston Type I Keratoprosthesis (BI-Kpro) implantation on retinal and visual pathway function, respectively, assessed by full-field electroretinography (ERG) and visually evoked potentials (VEPs). This is a prospective interventional longitudinal study, and patients with BI-Kpro implantation were assessed preoperatively and at 3 and 12months after surgery. ERG, flash, and pattern-reversal VEPs (15' and 60' checks) along with visual acuity (VA) were performed. A total of 13 patients (24 to 88years of age) were included. Mean baseline VA (logMAR) improved from 2.30 to 1.04 at 3months and to 1.00 at 12months. Flash VEPs were normal in 6 (46%) patients and in 10 (77%) patients at the 12-month follow-up. PVEP was non-detectable in all patients preoperatively for both check sizes. For 15' check size, 6 (46%) patients showed responses after 3 and 12months except for 1 patient with normal responses at 12months with the remaining non-detectable. For 60' checks, 11 (85%) patients had responses 3months after surgery with only 9 (70%) showing responses at 12months. Abnormal full-field ERGs were found in all patients preoperatively. Amplitude improvement was found in 10 (77%) patients from baseline to 3months and in 8 (62%) patients from the 3- to the 12-month follow-up. In this small cohort of patients with BI-Kpro implantation, a remarkable improvement on visual function quantitatively assessed by electrophysiological testing was found in the majority of cases. Visual electrophysiological testing can contribute to objectively assess functional outcomes in this population.

Whole genome sequencing identifies a homozygous nonsense mutation in the JPH2 gene in Shih Tzu dogs with progressive retinal atrophy.

Progressive retinal atrophy (PRA), common autosomal recessive disorder affecting several dog breeds including Shih Tzu, is characterized by degeneration of photoreceptors leading to blindness. To identify PRA genetic variants, three affected and 15 unaffected Shih Tzu and 20 non-Shih Tzu were recruited. Dogs underwent ophthalmologic examination and electroretinography, revealing hallmark retina pathological changes and an abnormal electroretinography in all affected dogs but not in unaffected dogs. WGS was performed. Non-synonymous homozygous variants were searched in coding regions of genes involved in retinal diseases/development; the criterion was that variants should only be present in affected dogs and should be absent in both unaffected and 46 genomes of dogs (from an available evolutionary database). Only one out of the 109 identified variants is predicted to harbor a high-impact consequence, a nonsense c.452A>C (p.L151X) in the JPH2 gene. The genotype of JPH2 variant in all 38 dogs was determined with Sanger sequencing. All three affected dogs, but none of the 35 unaffected, were homozygous for the nonsense variant. JPH2 has been previously found to be expressed in several excitable cells/tissues including retina photoreceptors. Hence, JPH2 is a candidate gene for PRA in Shih Tzu.

Transient electroretinographic abnormalities that mimic those of KCNV2 retinopathy: a case report

PurposeThe purpose of this report was to describe the case of a 68-year-old male patient with stage IV colon cancer who exhibited electroretinographic abnormalities that are similar to those of KCNV2 retinopathy.MethodsThe patient presenting with photophobia, reduced visual acuity, and poor general conditions, the onset of which occurred ten days before presentation, was examined using fundoscopy, full-field electroretinography, blood tests, and abdominal computed tomography.ResultsThe patient’s decimal best-corrected visual acuity (BCVA) was 0.4 in each eye. Fundoscopy showed bull's eye-like maculopathy in both eyes. Electroretinographic findings were similar to the characteristic findings of KCNV2 retinopathy: Rod electroretinogram showed delayed and preserved b-wave amplitudes; bright-flash electroretinogram showed double troughs of a-waves; b/a ratios shown by bright-flash electroretinogram were higher than those shown by standard-flash electroretinogram; and both cone and 30-Hz flicker electroretinograms showed extinguished responses. His serum potassium level increased to 6.2 mmol/L (normal range 3.6–4.8 mmol/L) owing to hydronephrosis resulting from disseminated carcinoma. After performing an emergency surgery to treat this condition, the serum potassium level immediately decreased to a normal range. Eleven days after presentation, rod and standard/bright-flash electroretinography showed improvement in the implicit time of the rod b-waves and the a-waves. Unexpectedly, the responses recorded by cone and 30-Hz flicker electroretinography became normal. The symptoms and maculopathy disappeared, and his BCVA improved to 1.2.ConclusionsThe abnormal electroretinographic findings might be associated with the transient increase in serum potassium level.

Re: Commentary on ten-year incidence of cataract surgery in urban south China: the Liwan Eye Study

Marfan's syndrome (MS) is an inherited disease of connective tissue. The most characteristic ocular change is dislocation of lens, but myopia and retinal detachment also can occur. We examined 11 MS patients using electroretinography (ERG). 6 cases showed normal ERG. 5 cases had abnormal ERG. One had retinal detachment. 3 had myopia and 1 case suffered from secondary glaucoma. The defects of visual function were shown by electrophysiological test in those MS patients.

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis.

PurposeMesopic flash electroretinography (fERG) as a tool to identify N-methyl-d-aspartate receptor (NMDAR) hypofunction in subjects with schizophrenia shows great potential. We report the first fERG study in a genetic mouse model of schizophrenia characterized by NMDAR hypofunction from gene silencing of serine racemase (SR) expression (SR–/–), an established risk gene for schizophrenia. We analyzed fERG parameters under various background light adaptations to determine the most significant variables to allow for early identification of people at risk for schizophrenia, prior to onset of psychosis. SR is a risk gene for schizophrenia, and negative and cognitive symptoms antedate the onset of psychosis that is required for diagnosis.MethodsThe scotopic, photopic, and mesopic fERGs were analyzed in male and female mice in both SR–/– and wild-type (WT) mice and also analyzed for sex differences. Amplitude and implicit time of the a- and b-wave components, b-/a-wave ratio, and Fourier transform analysis were analyzed.ResultsMesopic a- and b-wave implicit times were significantly delayed, and b-wave amplitudes, b/a ratios, and Fourier transform were significantly decreased in the male SR–/– mice compared to WT, but not in female SR–/– mice. No significant differences were observed in photopic or scotopic fERGs between genotype.ConclusionsThe fERG prognostic capability may be improved by examination of background light adaptation, a larger array of light intensities, considering sex as a variable, and performing Fourier transform analyses of all waveforms. This should improve the ability to differentiate between controls and subjects with schizophrenia characterized by NMDAR hypofunction.

Different rate of retinal degenerations in mice with two distinct mutations in the Mitf gene

AbstractPurposeThe microphthalmia‐associated transcription factor (Mitf) gene is crucial for development of the retinal pigment epithelium (RPE) and photoreceptors. Loss of function mutations in this gene can cause ocular hypopigmentation, microphthalmia and blindness. Mice heterozygous for the Mitfmi‐wh/+ mutation have been used as a model for Waardenburg and Tietz syndromes in humans. The compound heterozygote Mitfmi‐wh/Mitfmi has two different mutant alleles in the Mitf gene each of which have quite severe effects on the phenotype. The purpose of this study was to examine changes over time in retinal function and structure in these mice, between 1 and 5 months of age, to elucidate the rate of progression of the retinal degenerations.MethodsB6‐Mitfmi‐wh/+ and B6‐Mitfmi‐wh/Mitfmi mice were examined and compared to C5BL/6J mice as control. Mice were anesthetized by an intraperitoneal injection of 40 mg/kg‐1 Ketamine and 4 mg/kg‐1 Xylazine. Fundus and optical coherence tomography (OCT) images were obtained with a Micron IV. Flash electroretinography (ERG) from mice with a corneal electrode was used to determine retinal function.ResultsFundus images from all mutant mice show hypopigmentation at 1 month, with large non‐pigmented areas forming at later stages. Mitfmi‐wh/+ mice are either blind or not at 1 month, with the ERG normal in amplitude in some animals and absent in others. The Mitfmi‐wh/+ mice with ERG responses at 1 month show slow retinal degeneration, with reduced responses at 5 months. Mitfmi‐wh/Mitfmi mice show either abnormal ERG responses at 1 month, or a flat ERG. The ERG responses in some of the Mitfmi‐wh/Mitfmi mice decrease with time, and at 4 months is flat. OCT images reveal that retinal layers in animals with flat ERG are thinner than in mice showing reduced ERG, but abnormally thin in both.ConclusionsWe conclude that Mitfmi‐wh/Mitfmi mutant mice show evidence of fast retinal degeneration. The Mitfmi‐wh/+ mutant mice are either blind at 1 month or show evidence of slow degeneration. Mice with these Mitf mutations may serve as models of retinal degenerations progressing at different rates, due to mutations in a gene expressed in the RPE.

Prolonged Cone b-Wave on Electroretinography Is Associated with Severity of Inflammation in Noninfectious Uveitis

This study sought to investigate retinal function in patients with noninfectious uveitis by using full-field electroretinography (ERG) and correlate the ERG to disease duration and severity of inflammation. Prospective cohort study. Patients (n= 200) with noninfectious uveitis and a disease duration of <1 year (group A [n= 80]) and those with a disease duration of >5 years (group B [n= 120]) were included. ERGs of the total 355 uveitis eyes were measured according to an extended International Society for Clinical Electrophysiology of Vision protocol. ERG abnormalities were related to demographics and uveitis characteristics, including anatomical classification, duration of uveitis, severity of inflammation, best corrected visual acuity (BCVA), cystoid macular edema (CME), and the highest fluorescein angiography (FA) score during the course of the disease. ERGs showed abnormalities in 235 eyes (66.2%). The most frequent and pronounced ERG abnormality was a prolonged implicit time of the cone b-wave (151 eyes [42.5%]), which was associated with vitritis (P= .005); cells in the anterior chamber (P=.007); the highest fluorescein angiography score (P= .011); age (P < 0.001); and pupil diameter (P < 0.001). BCVA was relatively good (0.05 logMAR [interquartile range {IQR}, 0.011, 0.22]) and not associated with this ERG abnormality. There were no differences between the ERG abnormalities in group A and those in group B and no significant associations between ERG abnormalities and anatomical classification or specific diagnoses. ERG results are frequently affected in cases of noninfectious uveitis of all anatomic subtypes, including anterior uveitis without apparent inflammation of the posterior segment. ERG abnormalities appear tobeassociated with the severity of inflammation fromboth the present and the past and therefore may be seen even when signs of retinal inflammation have disappeared.

The Effect of Citicoline on Electroretinography Abnormalities in Patients with Non-proliferative Diabetic Retinopathy

Introduction : to determine the effect of citicoline 1000 mg oral supplementation given for 4 weeks on electroretinography abnormalities in patients with NPDR (non-proliferative diabetic retinopathy).&#x0D; Methods : prospective, double blind, randomized clinical trial. Thirty-eight patients who matched the inclusion and exclusion criteria were randomized into two groups: the placebo (P-NPDR) and citicoline (C-NPDR). In the end, there were 18 eyes in citicoline group and 16 eyes in placebo group. The primary outcome was P50 and N95 amplitude in PERG within group and intergroup which were taken at the baseline and 4 weeks after treatment.&#x0D; Results : at the end of treatment, the N95 amplitude in C-NPDR showed improvement, 4.85 (1.9-10.3) µV, before treatment to 5.7 (1.9-17.1) µV, after treatment with P = 0.04. Median P50 amplitude improved in both groups, with C-NPDR: 3.1 µV to 3.8 µV (p = 0.89), and P-NPDR: 3.5 µV, to 4.5 µV (p = 0.10). Delta ∆N95 amplitude is higher in C-NPDR, while delta ∆P50 amplitude is higher in P-NPDR, with P values 0.35 and 0.45.&#x0D; Conclusion : Oral citicoline may induce a significant improvement in mean N95 amplitude before and after the treatment. P-NPDR showed positive trend in P50 amplitude while in C-NPDR showed positive trend in N95 amplitude, but these values were not statistically significant (P = 0.45; P= 0.35).

Unilateral pigmentary retinopathy: a retrospective case series.

To review the clinical characteristics and address the aetiology in a group of patients presenting with unilateral retinal pigmentary changes, best described as unilateral pigmentary retinopathy (UPR). The cohort of 42 patients was identified retrospectively from the Moorfields Eye Hospital electrophysiology database. All had undergone full-field [electroretinography (ERG)] and pattern electroretinography (PERG), with 13 additionally having multifocal ERG (mfERG). The clinical findings, fundus photographs and fundus autofluorescence (AF) images were reviewed. All index eyes showed ERG evidence of generalized photoreceptor dysfunction with most showing a similar degree of rod and cone involvement. However, although the fellow eyes all had a normal fundus examination, there were bilateral but asymmetrical ERG abnormalities in eight patients and a further four patients had PERG evidence of macular dysfunction in the fellow eye. A relevant medical history or the diagnosis of an ophthalmologic entity that might be related to the unilateral fundus changes was ascertained in 15 cases (~36%) including acute zonal occult outer retinopathy, trauma, systemic malignancy or autoimmune disease, retinal vasculitis, presumed pregnancy-related choroidal ischaemia and meningitis. Two patients had a family history of retinitis pigmentosa (RP; 4.8%). The underlying aetiology in most cases of UPR cannot accurately be identified, but an heritable cause is unlikely. Aspects of the history clearly suggest an acquired disorder in some patients. Twenty-five patients (60%) with nongenetic UPR did not adhere to the pattern of rod greater than cone dysfunction that occurs in RP (rod-cone dystrophy), and the pattern of rod>cone dysfunction seen in true RP is thus not a feature of most patients with UPR.

Biallelic mutations in USP45, encoding a deubiquitinating enzyme, are associated with Leber congenital amaurosis

BackgroundLeber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophies. In approximately 56% of Chinese probands, genetic defects can be detected in known LCA-causing genes....

Compound Danshen Dripping Pill Inhibits Retina Cell Apoptosis in Diabetic Rats.

Scope: Diabetic retinopathy (DR) is a severe microvascular complication of diabetes. Previous clinical trials have shown that Compound Danshen Dripping Pill (CDDP) improves DR symptoms. However, the mechanism involved remains unclear.Procedures: Rats fed a high-fat diet and injected with streptozotocin (STZ) were used as an experimental type 2 diabetes rodent model. CDDP was administered to two groups of diabetic rats at 0.2 and 0.4 g/kg/day via gastric gavage for 12 weeks. After the 12 weeks of treatment, retinal function was evaluated by electroretinography (ERG). Histological staining and TdT-mediated dUTP nick-end labeling (TUNEL) assays were also performed. Retinal genome expression was determined by gene array.Results: We found that CDDP moderated ERG and histological abnormalities in diabetic rats, independent of blood glucose level. A gene array showed that CDDP changed 262 genes significantly in the diabetic retina. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that differentially expressed genes in the CDDP-treated groups were involved mainly in the apoptosis pathway. Moreover, CDDP reduced the number of TUNEL-positive cells in the diabetic retinas. CDDP prevented the reduction in Bcl-2 expression and the increase in BCL-2 associated X (Bax) and caspase-3 (Casp3) expression in diabetic rats.Conclusion: Our results suggest that CDDP exerts its neuroprotective functions by inhibiting cell apoptosis in diabetic rats.

Electroretinogram abnormalities in nonanterior childhood uveitis.

PurposeA major point of concern in uveitis is the development of irreversible retinal changes after inflammation. In this study, we assess how nonanterior childhood uveitis affects retinal function using full‐field electroretinography (ERG).MethodsCross‐sectional study. ERGs of 63 uveitis eyes (33 children) were measured according to extended International Society for Clinical Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were investigated in relation to the following clinical parameters: demographics, uveitis characteristics, including severity of inflammation, treatment, best corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence tomography and fluorescein angiography score.ResultsThe ERG showed abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were prolonged implicit times of the cone b‐wave (37%; n = 23/63) and an abnormal 30‐Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00–0.15 LogMAR).ConclusionThe ERG is frequently affected in childhood uveitis indicating a global retinal dysfunction. ERG abnormalities seem to be associated with a more severe posterior segment inflammation and a younger age. If an association between ERG abnormalities and long‐term visual outcome can be made in the future, these early ERG findings during the course of childhood uveitis have significance for treatment strategies.

Abnormal Electroretinography in Patients with Long-Duration Diabetes but No Retinopathy

Retinopathy increases with duration of diabetes but the presence of this microvascular complication in individual patients remains unpredictable. Retinal neurophysiological changes have been postulated to be important in modulating susceptibility. We performed electroretinography (ERG) on patients with long duration of diabetes (&amp;gt;15 years) but no retinopathy to determine whether this setting of “normal retinal morphology” is also characterised by normal electrophysiology of the eyes. ERG was performed with a handheld RETeval-DR™ device. Flickering lights at 30Hz was used to stimulate retinal electrical activity recorded by skin electrodes placed below the lower eye lids. Implicit time (electrical conduction time, msec), amplitude (uV) and pupil diameter (mm) were recorded. A composite score &amp;lt; 20 of these three parameters indicates a &amp;lt;1% risk of vision threatening retinopathy. Altogether 26 type 2 and 9 type 1 patients with no retinopathy and diabetes duration 22.5±4.5 and 32.8±9.4 years respectively were studied. Nondiabetic individuals (fasting BGL&amp;lt;6.0mM or HbA1c&amp;lt;6.0% n=25) acted as controls. Results in Table 1 showed the implicit time of individuals with diabetes but no retinopathy was only minimally increased but the amplitude was significantly reduced by ∼30% (p&amp;lt;0.01). We conclude that the eyes of these patients protected from diabetic retinopathy nevertheless showed retinal neural dysfunction. Disclosure B. Brooks: None. D. Yue: None. E. Landy: None. Y. Shi: None.

Multimodal Imaging in Autosomal Dominant Cone-Rod Dystrophy Caused by Novel CRX Variant

Aim: To characterize by multimodal approach the phenotype of patients from a 3 generations pedigree, affected by autosomal dominant cone-rod dystrophy (CRD), found to carry a novel pathogenic variant in the cone-rod homeobox-containing (CRX) gene. Methods: Examination of the adult patients included the following tests: visual acuity, multicolour imaging, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and OCT angiography (OCT-A) recordings. In a 2.5-year-old child, cycloplegic refraction, fundoscopy, ocular motility evaluation and electrophysiological exams were performed. Next Generation Sequencing of patients’ DNA has been carried out. Results: A novel CRX pathogenic variant has been identified in our patients. The 2.5-year-old child in the third generation was found to have inherited the variant, with no clinical signs of the condition, but electroretinographic abnormalities in the scotopic component. In the adult patients, diffuse atrophy of the retinal pigment epithelium/photoreceptor complex in the macular region was evident at the OCT and FAF, while OCT-A showed choriocapillaris density reduction. Conclusions: Multimodal study allowed the characterization of a peculiar form of CRD. The novel pathogenic variant seems to have a different effect on the phenotype if compared with a previously described similar one, giving an insight into the pathogenic mechanism of CRX-related retinal dystrophies and offering valuable information that could lead to the development of possible future therapies.