Electrophysiological effects of hyperbaric oxygen treatment on the healthy retina.

PURPOSE: The study aimed to investigate the electrophysiological effects of hyperbaric oxygen treatment (HBOT) on the retina after ten sessions in healthy eyes. METHODS: This prospective, interventional study evaluated forty eyes of twenty patients who were treated with HBOT of ten sessions with the diagnosis of an extraocular health problem. All patients underwent a complete ophthalmologic examination, including assessments of best-corrected visual acuity (BCVA), slit-lamp and pupil-dilated fundus examinations, full-field electroretinography (ffERG) measurements before and after HBOT within 24 h of the 10th session. The ffERG was recorded according to the International Society for Clinical Electrophysiology of Vision protocol using the RETI-port system. RESULTS: The mean age of patients was 40.5 years ranging from 20 to 59 years. Thirteen patients were administered HBOT for avascular necrosis, six patients for sudden hearing loss, and one patient for chronic osteomyelitis of the vertebra. BCVA acuity was 20/20 in all eyes. The mean spherical refractive was 0.56 dioptre (D), and the mean cylindrical refractive error was 0.75 D. Dark-adapted b-wave amplitude in 3.0 ERG was the only variable for the b-wave that showed a statistically significant decrease (p = 0.017). The amplitude of the a-waves in dark-adapted 10.0 ERG and light-adapted 3.0 ERG reduced significantly (p = 0.024, p = 0.025). The amplitude of N 1-P 1 in light-adapted 30 Hz Flicker ERG also demonstrated a statistically significant decrease (p = 0.011). Implicit times did not differ significantly in any of the ffERG data (p > 0.05). CONCLUSIONS: HBOT caused the deterioration of a-wave and b-wave amplitudes in ffERG after ten treatment sessions. The results showed that photoreceptors were adversely affected in the short term after HBOT treatment.

CDHR1-Related Cone-Rod Dystrophy: Clinical Characteristics, Imaging Findings, and Genetic Test Results-A Case Report.

Background: Cone-rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. Case presentation: A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months. The best-corrected visual acuity (BCVA) at presentation was 0.4 in the right eye (RE) and 1.0 in the left eye (LE). Fundus fluorescein angiography (FFA) revealed granular hyperfluorescence in the macula and concomitant areas of capillary atrophy. Flash full-field electroretinography (ffERG) showed lowering of a and b waves as well as prolonged peak time in light-adapted conditions. However, outcomes of dark-adapted ERGs were within normal limits. Based on the constellation of clinical, angiographic, and electrophysiological tests findings, a diagnosis of IRD was suspected. Genetic testing showed a homozygous, pathogenic c.783G>A mutation in the cadherin-related family member 1 (CDHR1) gene, which confirmed CRD type 15 (CRD15). Conclusions: We demonstrate the clinical characteristics, retinal imaging outcomes, and genetic test results of a patient with CRD15. Our case contributes to expanding our knowledge of the clinical involvement of the pathogenic mutation c.783G>A in CDHR1 variants.

Retinal dysfunction parallels morphologic alterations and precede clinically detectable vascular alterations in Meriones shawi, a model of type 2 diabetes.

Diabetic retinopathy is a major cause of reduced visual acuity and acquired blindness. The aim of this work was to analyze functional and vascular changes in diabetic Meriones shawi (M.sh) an animal model of metabolic syndrome and type 2 diabetes. The animals were divided into four groups. Two groups were fed a high fat diet (HFD) for 3 and 7 months, two other groups served as age-matched controls. Retinal function was assessed using full field electroretinogram (Ff-ERG). Retinal thickness and vasculature were examined by optical coherence tomography, eye fundus and fluorescein angiography. Immunohistochemistry was used to examine key proteins of glutamate metabolism and synaptic transmission. Diabetic animals exhibited significantly delayed scotopic and photopic ERG responses and decreases in scotopic and photopic a- and b-wave amplitudes at both time points. Furthermore, a decrease of the amplitude of the flicker response and variable changes in the scotopic and photopic oscillatory potentials was reported. A significant decrease in retinal thickness was observed. No evident change in the visual streak area and no sign of vascular abnormality was present; however, some exudates in the periphery were visible in 7 months diabetic animals. Imunohistochemistry detected a decrease in the expression of glutamate synthetase, vesicular glutamate transporter 1 and synaptophysin proteins. Results indicate that a significant retinal dysfunction was present in the HFD induced diabetes involving both rod and cone pathways and this dysfunction correlate well with the morphological abnormalities reported previously. Furthermore, neurodegeneration and abnormalities in retinal function occur before vascular alterations would be detectable in diabetic M.sh.

A GUCY2D variant associated cone-rod dystrophy with electronegative ERG: A case report and review.

Purpose: Cone-rod dystrophies (CORD) are inherited retinal dystrophies characterized by primary cone degeneration with secondary rod involvement. We report two patients from the same family with a dominant variant in the guanylate cyclase 2D (GUCY2D) gene with different phenotypes in the electroretinogram (ERG). Observations: A 21-year-old lady (Patient 1) was referred due to experiencing blurry vision and color vision impairment. Visual field testing revealed a central scotoma. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) documented macula dysfunction. Reduced amplitude was observed in the photopic responses of ERG. Her 54-year-old father (Patient 2) had similar issues with blurry vision. A dilated fundus examination displayed bilateral macular atrophy. Loss of the ellipsoid zone line and collapse of the outer nuclear segment were noted on the SD-OCT. Photopic ERG responses were extinguished, and an electronegative ERG was observed in the dark-adapted 3.0 ERG. The gene report revealed a c.2512C > T (p.Arg838Cys) variant in GUCY2D for both patients. They were respectively diagnosed as cone dystrophy (COD) and cone-rod dystrophy (CORD). Conclusions: We report two different clinical phenotypes in GUCY2D-associated COD despite sharing the same variant. A dysfunction in the synaptic junction between the photoreceptor and the secondary neuron was proposed to explain the electronegative ERG. This explanation might extend to other gene-related cases of CORD with electronegative ERG.

Unilateral Retinitis Pigmentosa Associated with Possible Ciliopathy and a Novel Mutation.

Unilateral retinitis pigmentosa (URP) is a rare retinal dystrophy. We describe the clinical course of two patients with (URP) unilateral retinitis pigmentosa confirmed by genetic testing, indicating ciliary dysfunction. Methods: The methods used in this study included a detailed ophthalmic examination, multimodal retinal imaging, Goldmann visual fields, full-field electroretinography (ffERG) and targeted next-generation sequencing. Results: A 32-year-old female (patient 1) and 65-year-old male (patient 2) were found to have URP. ffERG showed a non-recordable response in the affected eye and a response within normal limits in the fellow eye of patient 1, while patient 2 showed non-recordable responses in the apparently unaffected eye and a profound reduction in the photopic and scotopic responses in the affected eye. Next-generation sequencing revealed novel compound heterozygous c.373 C>T (p.Arg125Trp) and c.730-22_730-19dup variants in AGBL5 in patient 1, and a novel hemizygous c.1286 C>T (p.Pro429Leu) in patient 2; both gene mutations were 0%. Segregation analysis was not possible for either of the mutations. Conclusion: This report expands the clinical and molecular genetic spectrum of URP.

Ocular phenotype and electroretinogram abnormalities in Lafora disease and correlation with disease stage.

BACKGROUND: Lafora disease (LD) is a neurodegenerative disorder featuring action and stimulus-sensitive myoclonus, epilepsy, and cognitive deterioration. Mutations in the EPM2A/EPM2B genes classically prove causative for the disease in most cases. Since full-field electroretinogram (ffERG) may reveal early-stage changes in a wide spectrum of diseases, we aimed to evaluate retinal cones and rods dysfunction in a cohort of Italian LD patients. METHODS: Patients with genetically confirmed LD were recruited and subjected to ffERG analysis following the International Society for Clinical Electrophysiology of Vision (ISCEV) protocol. RESULTS: Six patients aged between 13 and 26 years (mean 19.5 years) were included. The mean age at disease onset was 12.5 years with a mean disease duration of 7 years. The ffERG analysis revealed a global mild to severe generalized cones dysfunction in all patients. Linear correlation was identified between disease stage and the degree of cones and rods dysfunction, as well as between the type of mutation and the cones and rods dysfunction. CONCLUSIONS: This study brings further evidence of early retinal alterations in LD patients. The cones and rods dysfunction grade is related to disease duration. The ffERG is an important tool to determine the disease stage, allowing to evaluate either natural or treatment-related disease progression in a minimally invasive way.

A novel KCNV2 mutation in a patient taking hydroxychloroquine associated with cone dystrophy with supernormal rod response.

BACKGROUND: Cone dystrophy with supernormal rod response (CDSRR) is a rare inherited retinal degeneration. A patient superimposed with medical conditions requiring use of hydroxychloroquine (HCQ) may obscure accurate diagnosis of CDSRR. Herein, we report a referral case for HCQ retinopathy screening. Comprehensive ophthalmic examinations, however, guided the diagnosis of CDSRR from a novel mutation in potassium voltage-gated channel modifier subfamily V member 2 (KCNV2) gene. MATERIALS AND METHODS: Comprehensive ophthalmic examinations were evaluated for two patients whose parents are first cousins. Direct sanger sequencing of KCNV2 was applied to confirm the mutation. RESULTS: A 38-year-old male proband was referred for HCQ retinopathy screening after taking HCQ for systemic lupus erythematosus (SLE). Fundus examination showed bull's eye pattern, and photoreceptor loss in the foveal region of both eyes was noted on spectral domain-optical coherence tomography (SD-OCT). The full-field electroretinography (ffERG) revealed a disproportionate increase in scotopic maximal response with implicit time delay, as well as universal cone dysfunction. Proband's 24-year-old sister had similar ffERG pattern in both eyes. Direct sanger sequencing of KCNV2 gene revealed a novel homozygous mutation c.280_281 insG (p.Ala94GlyfsTer278), confirming a diagnosis of CDSRR. CONCLUSIONS: We report a novel KCNV2 mutation in a consanguineous family. The unique ffERG features of CDSRR are pathognomonic and thus crucial in guiding clinicians toward genetic testing of the KCNV2 gene. Altogether, multimodal imaging, ffERG, and detailed history taking are important diagnostic tools for differentiating between acquired and inherited retinal disorders.