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IntroductionMethodsResultsDiscussionGalloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder classically characterized by central nervous system and renal abnormalities. Optic atrophy has been reported as a common ophthalmic feature, and other characteristics, including nystagmus, strabismus, oculomotor apraxia, and retinopathy have been reported; however, data on retinal involvement and dysfunction is limited. In this case report, we aim to describe retinal findings in a female adolescent diagnosed with GAMOS due to a homozygous variant in the WDR73 gene.A comprehensive ophthalmologic examination, including dilated fundus examination, fundus photography, electroretinogram (ERG), and optical coherence tomography (OCT), was performed. Systemic findings were obtained from medical records.The patient’s visual testing was significant for oculomotor apraxia, large angle esotropia, and cross fixation. On fundus examination, bilateral optic nerve pallor and retinal vessel attenuation were noted. OCT revealed bilateral retinal thinning. ERG demonstrated non-recordable rod and cone responses.This case report describes multimodal imaging findings in a patient diagnosed with GAMOS due to biallelic homozygous variants in the WDR73 gene with comparison of retinal findings and ERG results to previously reported cases. Furthermore, we present OCT and fundus images for the first time in the literature. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a prevalent complication of type 2 diabetes mellitus, characterized by progressive damage to the retinal structure and function. Photobiomodulation therapy, using red or near-infrared light, has been proposed as a non-invasive intervention to mitigate retinal damage, but has been tested generally with short-term stimuli. This study aimed to evaluate the effects of prolonged photobiomodulation with deep red light on retinal structure and function in a type 2 diabetes mouse model. Transgenic LepRdb/J (db/db) mice were exposed to photobiomodulation therapy via LED devices emitting 654 nm light for 12 h daily over ten weeks and compared to untreated mice. Retinal function was evaluated by flash electroretinography, while structural changes were assessed through histology and immunohistochemistry to detect astro- and microgliosis. At 33 weeks of age, db/db mice were obese and severely diabetic, but exhibited only incipient indicators of retinal deterioration. Electroretinogram b-wave peak latencies were prolonged at intermediate flash intensities, while the outer plexiform layer displayed significantly elevated IBA1 expression. Photobiomodulation therapy prevented these two markers of early retinal deterioration but had no effect on other morphological and functional parameters. Photobiomodulation is well-tolerated and maintains potential as a complementary treatment option for diabetic retinopathy but requires further optimization of therapeutic settings and combinatory treatment approaches. [ABSTRACT FROM AUTHOR]

Background: Electroretinographic dysfunction is observed in psychosis, with a-wave and b-wave amplitudes potentially serving as biomarkers. Insulin resistance (IR) and childhood trauma (CT) have also been associated with psychosis-spectrum disorders, particularly schizophrenia. Electroretinographic dysfunction in early-course psychosis (EP) lacks exploration. This case-control exploratory study aimed to understand electroretinographic dysfunction in EP and its relationship with IR and CT. Methods: The study involved healthy controls (n=13) and EP individuals (n=14) and included photopic and scotopic flash-electroretinography (fERG), blood collection for IR assessment, and the Childhood Trauma Questionnaire (CTQ). Data were analyzed using SPSS v.29.0. Case-control differences across fERG conditions were explored using repeated-measures ANCOVA (3 flash conditions X 2 groups) adjusted for gender and age. Sub-analyses included Fisher’s, Mann-Whitney, partial correlations, and logistic and linear regressions. Results: Compared to controls, EP participants showed (1) lower photopic a-wave and b-wave amplitudes, specifically in the left eye and under the P1 condition, (2) greater odds for IR, and (3) higher CTQ scores. IR was associated with a higher CTQ score and a lower P2b amplitude. A higher CTQ score was associated with lower P2b amplitude in the left eye when adjusting for its interacting effect with IR. Conclusion: These findings suggest lower photopic a-wave and b-wave amplitudes, IR, and CT are explanatory markers in EP. CT may dysregulate the hypothalamic-pituitary-adrenal axis, increasing the risk of experiencing later-life psychosis. IR might be a biomarker in psychosis, contributing to electroretinographic dysfunction and neurodegeneration of cone post-synaptic cells. Further investigations are needed.

Worldwide, around 40,000 people progressively lose their eyesight as a consequence of retinitis pigmentosa (RP) caused by pathogenic variants in the ADGRV1 gene, for which currently no treatment options exist. A model organism that mimics the human phenotype is essential to unravel the exact pathophysiological mechanism underlying ADGRV1-associated RP, and to evaluate future therapeutic strategies. The introduction of CRISPR/Cas-based genome editing technologies significantly improved the possibilities of generating mutant models in a time- and cost-effective manner. Zebrafish have been recognized as a suitable model to study Usher syndrome-associated retinal dysfunction. Using CRISPR/Cas9 technology we introduced a 4bp deletion in adgrv1 exon 9 (adgrv1rmc22). Immunohistochemical analysis showed that Adgrv1 was absent from the region of the photoreceptor connecting cilium in the adgrv1rmc22 zebrafish retina. Here, the absence of Adgrv1 also resulted in reduced levels of the USH2 complex members usherin and Whrnb, suggesting that Adgrv1 interacts with usherin and Whrnb in zebrafish photoreceptors. When comparing adgrv1rmc22 zebrafish with wild-type controls, we furthermore observed increased levels of aberrantly localized rhodopsin in the photoreceptor cell body, and decreased electroretinogram (ERG) B-wave amplitudes which indicate that the absence of Adgrv1 results in impaired retinal function. Based on these findings we present the adgrv1rmc22 zebrafish as the first ADGRV1 mutant model that displays an early retinal dysfunction. Moreover, the observed phenotypic changes can be used as quantifiable outcome measures when evaluating the efficacy of future novel therapeutic strategies for ADGRV1-associated RP. [ABSTRACT FROM AUTHOR]

Worldwide, around 40,000 people progressively lose their eyesight as a consequence of retinitis pigmentosa (RP) caused by pathogenic variants in the ADGRV1 gene, for which currently no treatment options exist. A model organism that mimics the human phenotype is essential to unravel the exact pathophysiological mechanism underlying ADGRV1-associated RP, and to evaluate future therapeutic strategies. The introduction of CRISPR/Cas-based genome editing technologies significantly improved the possibilities of generating mutant models in a time- and cost-effective manner. Zebrafish have been recognized as a suitable model to study Usher syndrome-associated retinal dysfunction. Using CRISPR/Cas9 technology we introduced a 4bp deletion in adgrv1 exon 9 (adgrv1rmc22). Immunohistochemical analysis showed that Adgrv1 was absent from the region of the photoreceptor connecting cilium in the adgrv1rmc22 zebrafish retina. Here, the absence of Adgrv1 also resulted in reduced levels of the USH2 complex members usherin and Whrnb, suggesting that Adgrv1 interacts with usherin and Whrnb in zebrafish photoreceptors. When comparing adgrv1rmc22 zebrafish with wild-type controls, we furthermore observed increased levels of aberrantly localized rhodopsin in the photoreceptor cell body, and decreased electroretinogram (ERG) B-wave amplitudes which indicate that the absence of Adgrv1 results in impaired retinal function. Based on these findings we present the adgrv1rmc22 zebrafish as the first ADGRV1 mutant model that displays an early retinal dysfunction. Moreover, the observed phenotypic changes can be used as quantifiable outcome measures when evaluating the efficacy of future novel therapeutic strategies for ADGRV1-associated RP.

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs. • Fluorescent proteins have been widely used to trace biological events in animal models. • TdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. • Retinal dysfunction was seen as the reduced photopic responses and lower contrast sensitivity. • It caused by mitochondrial damages characterized with cellular redistribution, morphological modifications. [ABSTRACT FROM AUTHOR]

Ivabradine, a hyperpolarization-activated cyclic nucleotide–gated (HCN) channel inhibitor, has been reported to induce photosensitivity-related visual disturbances such as phosphene in humans. Ivabradine-induced visual disturbances are caused by inhibition of HCN channels in the retina, and the mechanisms have been verified using HCN channel knockout mice and electroretinography (ERG). However, in rats, classical ERG using single flash light stimulus with standard analyses of waveform amplitude and latency has not revealed abnormal retinal function after administration of ivabradine. To verify whether retinal dysfunction after ivabradine administration was detectable in rats, we performed ERG using multistep flash light stimulation at the time when plasma concentration of ivabradine was high. Furthermore, the mechanism of the change in the waveform that appeared after the b-wave was investigated. Ivabradine and cilobradine, a selective HCN channel inhibitor, were administered subcutaneously to rats at 4–40 mg/kg as a single dose, and flash or long-duration ERG recordings at each light stimulus luminance were conducted 1.5 h after administration. Plasma and retinal concentrations of both compounds were measured immediately after the ERG recordings. In the flash ERG, prolongation of a- and/or b-wave latencies were detected at each light stimulus, and dose-dependent waveform changes after the b-wave were recorded at the specific light stimulus luminance for both compounds. These ERG changes increased in response to increasing plasma and retinal concentrations for both ivabradine and cilobradine. In the long-duration light stimulus ERG, a change in the waveform of the b-wave trough and attenuation of the c-wave were recorded, suggesting that the feedback control in the photoreceptor cells may be inhibited. This study revealed that the retinal dysfunction by HCN channel inhibitors in rats can be detected by multistep light stimulus ERG. Additionally, we identified that the inhibition of feedback current and the sustained responses in the photoreceptor cells cause the retinal dysfunction of HCN channel inhibitors in rats. • Retinal dysfunction by HCN inhibitor is detectable by ERG in in vivo study. • HCN inhibitors induce specific waveform changes after b-wave. • HCN inhibitors decrease K+ concentration in subretinal space and alter c-wave in ERG. • Inhibition of retinal feedback control may be induced by HCN inhibitor. • Visual disturbance by HCN inhibitor depends on plasma and retinal concentrations. [ABSTRACT FROM AUTHOR]

The impact of chronic hyperlipidemia on the retinal defense against oxidative stress, the integrity of the blood-retinal barrier, and leukocyte adhesion to retinal vasculature that have a bearing on retinal function have not been addressed. In this study, we assessed the risk factors of retinal dysfunction, and modulatory potentials of oxidation stable oleic acid and highly unsaturated oxidation susceptible EPA + DHA in hyperlipidemic rat model. The results showed that, hyperlipidemia significantly (p

Abstract Background Galloway-Mowat syndrome (GMS) is a rare autosomal recessive condition first described in 1968 and characterized by microcephaly and infantile onset of central nervous system (CNS) abnormalities resulting in severely delayed psychomotor development, cerebellar atrophy, epilepsy, and ataxia, as well as renal abnormalities such as nephrotic syndrome, proteinuria, end-stage renal disease (ESRD), and hiatal hernia. Case presentation We describe a GMS case diagnosed with homozygous missense mutation in the WDR73 gene, with absence of renal abnormalities. We expanded the clinical phenotype of GMS with WDR73 gene defect to include retinal dysfunction with missense mutation and developmental dysplasia of the hip. We compared eye findings of our case to previously reported cases, and we present an electroretinogram (ERG) picture for the first time in the literature. Conclusion We recommend that clinicians screen patients with GM syndrome for retinal dysfunction and that a skeletal survey should be done to detect developmental dysplasia of the hip (DDH) so as to provide for early intervention.

Loss of retinal function due to manifestation of chronic inflammation and oxidative stress in hyperglycemia is well addressed. However, the effect of hyperlipidemia on retinal inflammation and microvascular integrity, and the modulatory effects of oxidation-stable oleic acid and long-chain n-3 fatty acids have never been addressed. The objective of this investigation was to assess the retinoprotective effect of oxidation stable oleic acid and oxidation-susceptible EPA + DHA on retinal inflammation and microvascular integrity, under hyperlipidemic conditions. Male Wistar rats were fed with control (7.0% lard), high-fat (35.0% lard), high-fat with fish oil (17.5% fish oil + 17.5% lard), high-fat with olive oil (17.5% olive oil + 17.5% lard), and high-fat with fish oil and olive oil (11.66% fish oil + 11.66% of olive oil + 11.66% of lard) diet for 90 days. Systemic and retinal inflammation, as measured by eicosanoids and cytokines, retinal expression of NF-kB, capillary degeneration, and pericyte loss, were assessed. Hyperlipidemia significantly (p < 0.05) increased the markers of inflammation (PGE2, LTB4, LTC4, IL-1β, MCP-1, and TNF-α) in serum and retina. Besides, the retinal NF-kB-p65 expression, capillary degeneration, and pericyte loss were significantly (p < 0.05) increased under hyperlipidemic conditions. Dietary incorporation of oleic acid and EPA + DHA significantly (p < 0.05) suppressed hyperlipidemia-induced effects in the retina. In conclusion, hyperlipidemia causes retinal aberrations by compromising the balance in the inflammatory response and microvascular integrity. Dietary incorporation of oleic acid and long-chain n-3 fatty acids prevents hyperlipidemia-induced aberrations in the retina. [ABSTRACT FROM AUTHOR]

Lisa Ford,1 Jeffrey L Goldberg,2 Fred Selan,1 Howard E Greenberg,1 Yingqi Shi1 1Janssen Research & Development, LLC, Titusville, NJ, 2Byers Eye Institute, Stanford University, Palo Alto, CA, USA Objective: The objective of this study was to analyze clinical patterns of visual field defects (VFDs) reported with topiramate treatment and assess possible mechanism of action (MOA) for antiepileptic drug (AED) associated VFDs.Methods: A comprehensive topiramate database review included preclinical data, sponsor’s clinical trials database, postmarketing spontaneous reports, and medical literature. All treatment-emergent adverse events (TEAEs) suggestive of retinal dysfunction/damage were summarized. Relative risk (RR) was computed from topiramate double-blind, placebo-controlled trials (DBPCTs) data.Results: Preclinical studies and medical literature review suggested that despite sharing gamma-aminobutyric acid (GABA)-ergic MOA with other AEDs, topiramate treatment was not associated with VFDs. TEAEs suggestive of retinal dysfunction/damage were observed in 0.3%–0.7% of adults and pediatric patients with topiramate (N=4,679) versus ≤0.1% with placebo (N=1,834) in DBPCTs for approved indications (epilepsy and migraine prophylaxis); open-label trials (OLTs) and DBPCTs for investigational indications had similar incidence. Overall, 88% TEAEs were mild or moderate in severity. Serious TEAEs were very rare (DBPCTs: 0%; OLTs: ≤0.1%), and most were not treatment limiting, and resolved. The most common visual TEAEs (approved indications) were VFD, scotoma, and optic atrophy. The incidence of TEAEs in DBPCTs (approved and investigational indications) was higher in topiramate-treated (N=9,169) versus placebo-treated patients (N=5,023; 0.36% vs 0.24%), but the RR versus placebo-treated patients was not significant (RR: 1.51 [95% confidence interval: 0.78, 2.91]).Conclusion: VFDs do not appear to be a class effect for AEDs with GABA-ergic MOA. The RR for VFDs is not significantly different between topiramate and placebo treatment. Keywords: gamma-aminobutyric acid, retinal dysfunction, scotoma, topiramate, visual field defects

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model. [ABSTRACT FROM AUTHOR]

Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A -associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene ( ush2a rmc1 : c.2337_2342delinsAC; p.Cys780GlnfsTer32 and ush2a b1245 : c.15520_15523delinsTG; p.Ala5174fsTer). Homozygous mutants were viable and displayed no obvious morphological or developmental defects. Immunohistochemical analyses with antibodies recognizing the N- or C-terminal region of the ush2a -encoded protein, usherin, demonstrated complete absence of usherin in photoreceptors of ush2a rmc1 , but presence of the ectodomain of usherin at the periciliary membrane of ush2a b1245 -derived photoreceptors. Furthermore, defects of usherin led to a reduction in localization of USH2 complex members, whirlin and Adgrv1, at the photoreceptor periciliary membrane of both mutants. Significantly elevated levels of apoptotic photoreceptors could be observed in both mutants when kept under constant bright illumination for three days. Electroretinogram (ERG) recordings revealed a significant and similar decrease in both a- and b-wave amplitudes in ush2a rmc1 as well as ush2a b1245 larvae as compared to strain- and age-matched wild-type larvae. In conclusion, this study shows that mutant ush2a zebrafish models present with early-onset retinal dysfunction that is exacerbated by light exposure. These models provide a better understanding of the pathophysiology underlying USH2A -associated RP and a unique opportunity to evaluate future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal dysfunctions with cognitive impairment. AD can affect visual pathways and visual cortex and result in various visual changes and problems. However, how early the visual dysfunctions occur in AD is still a matter of discussion. Here, we used electrophysiological techniques to show the presence of early anomalies in AD visual system. To this aim, we used a familial AD (FAD) model, the 5xFAD transgenic mouse, characterized by severe progressive amyloid pathology and cognitive deficits. We investigated the retina and primary visual cortex responsivity together with behavioral assessment of the visual acuity. Visual tests and recordings were conducted at different ages in 5xFAD mice, corresponding to different phases of neurodegeneration and beta amyloid accumulation. We showed that the visual system is impaired in 5xFAD mice. In particular, we found that the inner retina impairment precedes neuronal disorders in other brain areas and cognitive deficits. Thus, noninvasive retinal electrophysiology can provide a support for assessing early visual dysfunctions in AD. [ABSTRACT FROM AUTHOR]

Purpose: Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Studies have shown retinal abnormalities in patients and mouse models with HD; however, to our knowledge, no prior research papers evaluated retinal structure and function in a presymptomatic patient with HD. The aim of this report is to present a case of retinal dysfunction in a presymptomatic patient with HD.Methods: We investigated retinal structure and function in a 25-year-old male who tested positive for the gene that causes HD, but did not have any symptoms normally associated with HD. Vision and ocular testing included a comprehensive dilated ophthalmic examination, 24-2 full-threshold Humphrey visual field, spectral-domain optical coherence tomography (SD-OCT), fundus photography, full-field electroretinogram (ERG), and multifocal electroretinogram (mfERG).Results: Visual electrophysiology testing showed rod and cone functional anomalies in both eyes. Full-field ERG amplitudes were subnormal in both eyes for the dark-adapted (DA) 0.01 ERG, DA 3 ERG, DA 3 oscillatory potentials (OPs), DA 10 ERG, light-adapted (LA) 3 ERG, and LA 30 Hz flicker, but peak times for the six standard ERG responses were not significantly different from normals. mfERGs revealed functional anomalies of the central retina with attenuated P1 amplitudes for five of the six concentric rings in the right eye and all six rings in the left eye. mfERG P1 peak times were normal at all eccentricities. Dilated fundus examination, SD-OCT, and fundus photography were unremarkable in both eyes. The visual field was normal in the right eye, but there was a mild paracentral field defect in the left eye.Conclusions: Our results illustrate that the ERG and mfERG detected early retinal dysfunction in a presymptomatic patient with HD consistent with electroretinogram findings in animal models of HD. However, our report was limited to one patient and additional studies are needed to verify whether the ERG and/or mfERG can uncover neural dysfunction before motor, behavioral, and cognitive abnormalities are discernible in patients with HD. [ABSTRACT FROM AUTHOR]

This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Müller cells. The electroretinogram was used to evaluate retinal functions. Müller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT-PCR, ELISA and western-blotting. Glutamate uptake was measured as H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Müller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate whether Institute for Cancer Research (ICR) derived retinal dysfunction (IRD) 1 and IRD2 mice, spontaneous mouse models of rod-cone and rod dysfunction, respectively, develop age-related retinal degeneration. Materials and Methods: Morphological and morphometric examinations were performed in the retinas of both mutants from 1 to 18 months of age. The rate of apoptotic cell death was determined by TUNEL techniques. Electroretinography was performed on the IRD2 mice at various ages. Age-matched ICR mice were used as controls. Results: IRD1 and IRD2 mice showed a decrease in the thickness of the outer nuclear layer and a higher frequency of TUNEL-positive photoreceptor cells at 6 months of age compared with controls, and showed almost complete absence of the outer nuclear layer at 18 months of age. Light deprivation had no effect on the severity of the retinal degeneration. There were no differences in the number of cone nuclei among ICR, IRD1, and IRD2 mice at 12 months of age and the cones of the IRD2 mice were still functional at this age. Conclusions: IRD1 and IRD2 mice showed late-onset and progressive retinal degeneration. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the multifocal electroretinography (mfERG) changes in patients on ethambutol therapy.MethodsA cross-sectional observational study of 17 visually asymptomatic patients receiving antituberculosis therapy with ethambutol. Patients underwent complete ophthalmic examination and mfERG recordings. The first-order mfERG N1 and P1 response amplitudes and implicit times of six concentric rings were analysed and compared with 17 normal age-similar controls. Correlation analyses were performed between the patients’ mfERG parameters with parameters of ethambutol usage (daily dose of ethambutol per body weight, duration of ethambutol therapy, cumulative dose of ethambutol, and cumulative dose of ethambutol per body weight).ResultsThe mean duration of ethambutol therapy was 3.6 months (range: 2–9 months) and the mean daily dose per body weight was 13.2 mg/kg/day. Analysis of response amplitude measures showed no significant difference in the mfERG N1 and P1 response amplitudes between the ethambutol and control groups at all ring eccentricities (P>0.05). For implicit times, there were significant delays in the mfERG P1 implicit times of rings 4–6 in the ethambutol group compared with controls (P=0.012 to P=0.041). Correlation analyses showed no significant correlation between the mfERG and ethambutol parameters (P>0.05).ConclusionsThe mfERG findings suggested that visually asymptomatic patients receiving ethambutol therapy might have localized mild electrophysiological changes involving the peripheral macula. These changes might be related to localized alteration of metabolism or physiological changes associated with ethambutol therapy.Eye (2009) 23, 1707–1713; doi:10.1038/eye.2008.361; published online 5 December 2008 [ABSTRACT FROM AUTHOR]

Purpose : We developed two strains of mouse with retinal dysfunction, named the ICR-derived retinal dysfunction (IRD)1 and IRD2, from one male ICR mouse with a retinal dysfunction but a normal fundus. The purpose of this study was to describe the features of retinal dysfunction in both mutant mice. Methods : Scotopic and photopic electroretinograms (ERGs) were recorded from IRD1 and IRD2 mice at 1 month of age to evaluate retinal function, and then the structures of the retinas in both mutant mice were observed by light microscopy at 1 and 3 months of age. In a mating study, the inheritance pattern and the genetic relation of IRD1 and IRD2 mice were defined. Results : At 1 month of age, IRD1 mice showed affected scotopic and photopic ERGs, and IRD2 mice exhibited normal photopic but affected scotopic ERGs. The retinal structures of both mutant mice remained normal even at 3 months of age. The IRD1, and IRD2 phenotypes showed an autosomal recessive pattern of inheritance and in the IRD1 backcross offspring some mice that had only cone dysfunction were seen in addition to normal, IRD1, and IRD2 phenotypes. All F 1 (IRD1 × IRD2) offspring exhibited IRD2 phenotype, rod dysfunction. Conclusions : IRD1 and IRD2 mice had affected rod systems caused by a homozygous mutation in the same rod function–related gene, and additionally IDR1 mice had affected cone systems caused by a homozygous mutation in the cone function–related gene, without apparent anatomical abnormalities in the retinas of either mutant mice even at 3 months of age. We believe that these mice could be new spontaneous animal models for the study of human inherited retinal disorders. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to give a brief overview on the application of multifocal stimulation techniques in ophthalmology. The use of m-sequences as a stimulus sequence alloys a high-resolution topographic mapping of sensory function. Outer retinal dysfunction can readily be detected with the multifocal ERG (mfERG). When the inner retinal contribution to the mfERG response is enhanced through adapting the stimulation sequence, the sensitivity of the mfERG to detect retinal dysfunction in glaucoma can be increased. Testing of the entire visual pathway with multifocal cortical evoked visual potentials is also possible and recent studies have focused on reducing interindividual variability. The use of m-sequence stimulation in magnetic encephalography offers new ways to study visual processing without the need to apply electrodes. [ABSTRACT FROM AUTHOR]

ABSTRACT. Purpose: To describe the clinical and electrophysiological findings in a young boy with decreased vision possibly due to retinal damage by rifabutin. Methods: An 8-year-old boy with osteomyelitis was referred due to visual disturbance. During a period of 4 years, the boy was examined six times with electroretinography. Ophthalmological examination included testing of visual acuity, slit-lamp inspection, fundus inspection, fundus photography and kinetic perimetry. Two electrophysiological methods were performed for objective evaluation of retinal function, namely full-field electroretinography and multifocal electroretinography. Results: We found a slightly reduced visual acuity, a slowly increasing amount of yellow-white deposits on the posterior surface of the cornea and on the anterior part of the lens, a normal fundus appearance, and normal visual fields. However, the electroretinogram was abnormal on several occasions during therapy with rifabutin, but returned to normal 3 months after withdrawal of the medication. The multifocal electroretinogram returned to normal after the full-field electroretinogram had done so. The anterior chamber deposits still remain. Conclusion: Long-term treatment with rifabutin may have a reversible and previously undescribed side-effect on retinal function. The drug may also accumulate irreversibly on the posterior surface of the cornea and on the anterior surface of the lens. We suggest that objective evaluation of retinal function with electrophysiological methods should be performed in patients with visual disturbance during treatment with rifabutin. [ABSTRACT FROM AUTHOR]

Background-Recent reports have established that eye changes occur in patients treated with vigabatrin. Aim-To identify the eye changes associated with vigabatrin, based on a prospective study of children treated for seizures. Methods-Twenty nine children on vigabatrin (mainly as add on therapy) were followed up for 6.5 years. Ophthalmic examination was performed before starting treatment and then six monthly in the outpatient clinic. Results-Twenty one children fulfilled the inclusion criteria. Most had epileptic syndromes with infantile spasms-namely West syndrome, Lennox-Gastaut syndrome, and partial seizures. Vigabatrin dose was 25-114 mg/kg/day (mean 55.8); duration of therapy was 6-85 months (mean 35.7). Four children (19%) developed eye changes (retinal pigmentation, hypopigmented retinal spots, vascular sheathing, and optic atrophy). Visual evoked potentials were abnormal in 16 children. Electroretinography and electro-oculography, which could have picked up eye changes in early stages, were not performed, as this facility was not available. Conclusions-Vigabatrin causes eye damage. Most children with epileptic syndromes on vigabatrin cannot complain of their eye problems, hence 3-6 monthly ophthalmic follow up is strongly advised, along with regular electroretinography, electrooculography, and visual evoked potentials if possible. [ABSTRACT FROM AUTHOR]

Purpose: To examine the retinal function with different electrophysiological methods in twelve Swedish patients on long-term treatment (2–10 years) with the anti-epileptic drug vigabatrin. Methods: Ophthalmological examination of twelve consecutive patients included testing of visual acuity, fundus inspection and fundus photography, kinetic perimetry, full-field ERG and multifocal ERG. Results: All patients had a visual acuity of 0.7 or better. Fundus inspection revealed no pathology except in one patient who had a pallor of the optic disc. All patients had a normal appearance of the macula. The result of kinetic perimetry was normal in five patients while seven patients had a concentric defect of the visual field. The 30 Hz flicker cone b-wave amplitude in the full-field ERG was abnormal in all of the seven patients with a visual field defect. None of the patients with normal visual fields had a reduction of the 30 Hz flicker cone b-wave amplitude. Six of the twelve patients had a reduced multifocal ERG response but without any correlation with visual field defect. Conclusion: Long-term treatment with vigabatrin seems to selectively reduce retinal cone function. The visual field defects in patients taking vigabatrin correlate with pathology in the full-field ERG (reduction of the cone b-wave amplitude). The results from this study indicate that electroretinography can be used for monitoring patients taking vigabatrin in a more objective manner than with visual field testing. [ABSTRACT FROM AUTHOR]