Rod-sparing in a bardet-biedl syndrome patient with mutations in the ARL6 gene.

PURPOSE: Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder characterized by pleiotropism that affects multiple organ systems. The primary features of BBS include rod-cone dystrophy, renal anomalies, post axial polydactyly, and neurologic deficits. The clinical picture of BBS is extensively heterogenous, with inter and intra familial patients varying in levels of syndromic manifestations and severity of symptoms. METHODS: In this study we examined a monocular BBS patient who was compound heterozygous for mutations in the ARL6 (BBS3) gene. RESULTS: The patient reported visual complaints consistent with a clinical picture of cone or cone-rod dystrophy. Fundus imaging showed retinal mottling on color photos and a parafoveal hyperfluorescent ring on short wave autofluorescence (SW-AF). Full field electroretinogram (ffERG) revealed normal scotopic step tracings and diminished amplitudes in the photopic steps. CONCLUSION: This rod-sparing result was consistent with cone-dystrophy and is the first known case of a rod-sparing ffERG phenotype in a BBS patient with mutations in the ARL6 gene. This contributes to the existing phenotype and may potentially contribute to furthering our understanding of BBS pathophysiology.

Retinal functional and structural changes in patients with Parkinson's disease.

BACKGROUND: Visual dysfunction have been well reported as one of the non-motor symptoms in Parkinson's disease (PD). The aim of this study was to evaluate the functional and structural changes in the retina in patients with PD, and to correlate these changes with disease duration and motor dysfunction. METHODS: For this case-control study, we recruited patients fulfilling the diagnostic criteria for idiopathic PD according to British Brain Bank criteria, aged between 50 and 80 years. Age- and sex-matched healthy controls aged between 50 and 80 years were also recruited. Motor function for PD patients was assessed using Modified Hoehn and Yahr staging scale (H & Y staging) and Unified Parkinson's Disease Rating Scale (UPDRS). Optical Coherence Tomography (OCT) and full field electroretinogram (ff-ERG) were done to all participants. RESULTS: Data from 50 patients and 50 healthy controls were included in the analysis. Patients with idiopathic Parkinson's had significantly reduced peripapillary retinal nerve fiber layer (RNFL) thickness and macular ganglion cell complex (GCC) thickness compared to healthy controls (P-value < 0.05 in all parameters). They also had significantly delayed latency and reduced amplitude in both dark-adapted rods and the light-adapted cone for both a & b waves compared to healthy controls (P-value < 0.001 in all parameters). There were statistically significant negative correlations between disease duration, and left superior, right inferior and right & left average RNFL thickness [(r) coef. = -0.327, -0.301, -0.275, and -0.285 respectively]. UPDRS total score was negatively correlated with the amplitude of light-adapted of both RT and LT a & b wave and with dark-adapted RT b-wave latency [(r) coef. = -0.311, -0.395, -0.362, -0.419, and -0.342]. CONCLUSION: The retinal structure and function were significantly affected in patients with PD in comparison to healthy controls. There was a significant impact of disease duration on retinal thickness, and there was a significant negative correlation between the degree of motor dysfunction in patients with PD and retinal function.

Dark-adapted threshold and electroretinogram for diagnosis of Usher syndrome.

PURPOSE: To determine the utility of ophthalmology evaluation, dark-adapted threshold, and full-field electroretinogram for early detection of Usher syndrome in young patients with bilateral sensorineural hearing loss. METHODS: We identified 39 patients with secure genetic diagnoses of Usher Syndrome. Visual acuity, spherical equivalent, fundus appearance, dark-adapted threshold, and full-field electroretinogram results were summarized and compared to those in a group of healthy controls with normal hearing. In those Usher patients with repeated measures, regression analysis was done to evaluate for change in visual acuity and dark-adapted threshold with age. Spherical equivalent and full-field electroretinogram responses from dark- and light-adapted eyes were evaluated as a function of age. RESULTS: The majority of initial visual acuity and spherical equivalent results were within normal limits for age. Visual acuity and dark-adapted threshold worsened significantly with age in Usher type 1 but not in Usher type 2. At initial test, full-field electroretinogram responses from dark- and light-adapted eyes were abnormal in 53% of patients. Remarkably, nearly half of our patients (17% of Usher type 1 and 30% of Usher type 2) would have been missed by tests of retinal function alone if evaluated before age 10. CONCLUSIONS: Although there is an association of abnormal dark-adapted threshold and full-field electroretinogram at young ages in Usher patients, it appears that a small but important proportion of patients would not be detected by tests of retinal function alone. Thus, genetic testing is needed to secure a diagnosis of Usher syndrome.

7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection.

To analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) (n = 24) and the other (n = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group (n = 6). Treated rats were analyzed 7 (n = 14), 14 (n = 14) or 21 d (n = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a+), α-like (OPN+), α-OFF like (OPN+Brn3a+) or M4-like/α-ON sustained RGCs (OPN+Tbr+). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs decreased to less than one half and OPN+Brn3a+RGCs decreased to approximately 0.5%, and Brn3a+RGCs showed a progressive loss with time, while OPN+RGCs and OPN+Tbr2+RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPN+RGCs and OPN+Tbr2+RGCs for up to 14 d and of Brn3a+RGCs for up to 21 days. DHF affords significant rescue of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs, but not OPN+Brn3a+RGCs, and preserves functional ERG responses after IONT.

Comparison between broadband and monochromatic photopic negative response in full-field electroretinogram in controls and subjects with primary open-angle glaucoma.

PURPOSE: A prospective, cross-sectional, case-control study was conducted to investigate the role of broadband and monochromatic photopic negative response (PhNR) of the full-field flash electroretinogram (ERG) in the evaluation of ganglion cell damage in primary open-angle glaucoma (POAG) subjects. METHODS: Subjects with POAG and age-matched normal subjects were recruited from the outpatient department of a tertiary eye care center in South India. A total of 25 patients with POAG and 50 age-matched normal subjects were recruited. ERG was recorded using broadband (3.5 cd.s/m2 white stimulus on 10 cd/m2 white background) and monochromatic (3.5 cd.s/m2 red stimulus on 10 cd/m2 blue background and 1 cd.s/m2 blue stimulus on 10 cd/m2 yellow background) stimuli. RESULTS: The reduction in PhNR amplitude in POAG compared to normal individuals was higher in red-on-blue PhNR [26.37 µV; p < 0.001, confidence interval (CI) 19.34 to 33.4] as compared to broadband stimuli (16.41 µV; p < 0.001, CI 8.68 to 24.13), and blue on yellow (21.96 µV; p < 0.001, CI 10.12 to 33.8). Red-on-blue PhNR amplitudes correlated better with mean deviation (MD; r = - 0.66, p < 0.05), pattern standard deviation (PSD; r = - 0.4, p = 0.04), visual field index (VFI; r = - 0.58, p < 0.05), and retinal nerve fiber layer thickness (r = - 0.67, p < 0.05) in comparison with broadband and monochromatic blue-on-yellow PhNR. Receiver operating characteristic curve revealed largest area under the curve (0.89) in red-on-blue PhNR compared to broadband (0.76) and blue on yellow (0.74). The sensitivity and specificity was also higher in red-on-blue PhNR (72% and 80%, respectively) as compared to the other stimuli (sensitivity and specificity of broadband 0.68 and 0.7, blue on yellow 0.64 and 0.7, respectively). CONCLUSION: Correlation of PhNR with Humphrey visual field parameters and retinal nerve fiber layer thickness showed that red-on-blue PhNR can be a useful additional tool for clinical assessment of retinal ganglion cell dysfunction in glaucoma patients. Red-on-blue PhNR was more sensitive as compared to white-on-white and blue-on-yellow PhNR in identifying ganglion cell dysfunction and correlates well with other structural and functional tests for glaucoma such as MD, PSD, VFI, and RNFL thickness.

A Chronic Ocular-Hypertensive Rat Model induced by Injection of the Sclerosant Agent Polidocanol in the Aqueous Humor Outflow Pathway.

BACKGROUND: To induce a moderate chronic ocular hypertension (OHT) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway. METHODS: Intraocular pressure (IOP) was monitored for up to 6 months. Pattern and full-field electroretinogram (PERG and ERG) were recorded and retinal ganglion cells (RGC) and retinal nerve fiber layer (RNFL) thickness were assessed in vivo with optical coherence tomography (OCT) and ex vivo using Brn3a immunohistochemistry. RESULTS: In the first 3 weeks post-injection, a significant IOP elevation was observed in the treated eyes (18.47 ± 3.36 mmHg) when compared with the control fellow eyes (12.52 ± 2.84 mmHg) (p < 0.05). At 8 weeks, 65% (11/17) of intervention eyes had developed an IOP increase >25% over the baseline. PERG responses were seen to be significantly reduced in the hypertensive eyes (2.25 ± 0.24 µV) compared to control eyes (1.44 ± 0.19 µV) (p < 0.01) at week 3, whereas the ERG components (photoreceptor a-wave and bipolar cell b-wave) remained unaltered. By week 24, RNFL thinning and cell loss in the ganglion cell layer was first detected (2/13, 15.3%) as assessed by OCT and light microscopy. CONCLUSIONS: This novel OHT rat model, with moderate levels of chronically elevated IOP, and abnormal PERG shows selective functional impairment of RGC.

7-Hexagon Multifocal Electroretinography for an Objective Functional Assessment of the Macula in 14 Seconds.

PURPOSE: We present the multifocal electroretinogram (mfERG) with a 7-hexagon array as an objective test of macular function that can be recorded in 14 s. We provide normal values and investigate its reproducibility and validity. METHODS: Healthy participants underwent mfERG testing according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards using the Espion Profile/D310 multifocal ERG system (Diagnosys, LLC, Lowell, MA, USA). One standard recording of a 61-hexagon array and 2 repeated recordings of a custom 7-hexagon array were obtained. RESULTS: A total of 13 subjects (mean age 46.9 years) were included. The median response densities were 12.5 nV/deg2 in the center and 5.2 nV/deg2 in the periphery. Intereye correlations were strong in both the center (ρCenter = 0.821; p < 0.0001) and the periphery (ρPeriphery = 0.862; p < 0.0001). Intraeye correlations were even stronger: ρCenter = 0.904 with p < 0.0001 and ρPeriphery = 0.955 with p < 0.0001. Bland-Altman plots demonstrated an acceptable retest mean difference in both the center and periphery, and narrow limits of agreement. We found strong correlations of the center (ρCenter = 0.826; p < 0.0001) and periphery (ρPeriphery = 0.848; p < 0.0001), with recordings obtained by the 61-hexagon method. CONCLUSIONS: The 7-hexagon mfERG provides reproducible results in agreement with results obtained according to the ISCEV standard.

Two-color pupillometry in enhanced S-cone syndrome caused by NR2E3 mutations.

PURPOSE: The purpose of this study was to evaluate pupillary light reflexes (PLRs) mediated by rod, cone, and intrinsically photosensitive retinal ganglion cell pathways as indices of outer- and inner-retinal function in patients who have enhanced S-cone syndrome (ESCS) due to NR2E3 mutations. METHODS: Four patients with ESCS (ages 16-23 years) participated in the study. Subjects were tested with long- and short-wavelength single-flash full-field ERG stimuli under light-adapted conditions. They were also tested with an established pupillometry protocol involving 1-s duration, long- and short-wavelength stimuli under dark- and light-adapted conditions. The PLR was measured as a function of stimulus luminance. Transient PLRs were measured under all conditions, and sustained PLRs were measured under the highest luminance dark-adapted condition. RESULTS: Two-color light-adapted full-field ERGs demonstrated larger amplitude responses for short-wavelength stimuli relative to long-wavelength stimuli of the same photopic luminance, with three of four ESCS patients having super-normal a-wave amplitudes to the short-wavelength stimulus. b/a wave ratios were reduced in all four cases. Transient PLRs elicited by low-luminance stimuli under dark-adapted conditions (rod-mediated) were unrecordable, whereas the sustained PLRs elicited by high-luminance stimuli (melanopsin-mediated) were normal. Cone-mediated PLRs were recordable for all four patients, but generally lower than normal in amplitude. However, the cone-mediated PLR was larger for the short-wavelength stimulus compared to the photopically matched long-wavelength stimulus at high luminances, a pattern that was not observed for control subjects. None of the PLR conditions demonstrated "super-normal" responses. CONCLUSION: ESCS patients appear to have generally well-preserved cone- and melanopsin-mediated PLRs, indicating intact inner-retinal function. Two-color pupillometry demonstrates greater sensitivity to short-wavelength light under higher-luminance conditions and could complement the ERG as a tool for evaluating retinal function in ESCS.

Spectral-domain optical coherence tomography combined with electroretinography in the assessment of conbercept for neovascular age-related macular degeneration: a preliminary study.

Objective: To observe the effect of three consecutive intravitreal injections of conbercept in the treatment of neovascular age-related macular degeneration (nAMD), to investigate the correlation between retinal anatomy and retinal function by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), to evaluate the short-term clinical efficacy of conbercept in the treatment of nAMD, and to explore the value of ERG as a predictor of treatment efficacy. Method: A retrospective investigation was conducted on 36 patients (36 eyes) treated with intravitreal injections of conbercept at 0.5 mg a month for three consecutive courses. Data collected included the best corrected visual acuity (BCVA), central retinal thickness (CRT), retinal pigment epithelium (RPE) elevation volume in 1 mm-diameter (1RV), 3 mm-diameter (3RV), and 6 mm-diameter circles around the fovea (6RV), amplitude density and latency of the P1 wave in the multifocal electroretinography (mf-ERG) R1 ring and amplitude and latency in full-field electroretinography (ff-ERG) at baseline and monthly. The paired t test was used to compare the difference between pre- and posttreatment. Pearson correlation analysis was used to analyze the correlation between macular retinal structure and function. The difference was significant when p < 0.05. Results: At 12 weeks, the BCVA, CRT, 1RV, 3RV, 6RV, the P1 wave amplitude density of the mf-ERG R1 ring and the ff-ERG amplitude parameters were all significantly improved (p < 0.001). The BCVA in logMAR was positively correlated with CRT; 1RV, 3RV, and 6RV were negatively correlated with the amplitude density and latency of the mf-ERG R1 ring P1 wave. There were no severe ocular or systemic complications during the follow-up period. Conclusion: Conbercept is useful for the short-term treatment of nAMD. It can safely improve the visual acuity of affected eyes and restore the structure and function of the retina. ERG could serve as an objective indicator of function for evaluating the efficacy of and determining the need for retreatment during nAMD treatment.

An atypical form of retinitis pigmentosa: A case report.

Key Clinical Message: This case contributes to the new knowledge of unilateral pericentral RP. Multimodal imaging provides valuable information to better understand the disease. The development is significantly slow and defines a better clinical course than typical RP. Pericentral RP presents with unremarkable night blindness, which can be easily misdiagnosed by ophthalmologists. Abstract: Unilateral pericentral retinitis pigmentosa (RP) is a rare, atypical, mild form of RP that affects the pericentral retina close to the vascular arcades and tends to spare the far-peripheral retina in one eye, while the fellow eye remains completely unaffected. A 71-year-old Chinese woman presented with blurred vision in her right eye for several decades, however, her left eye was unaffected. Fundus photography revealed bone-spicule pigmentation located at the pericentral retina of her right eye. Spectral-domain optical coherence tomography revealed significant atrophy of the outer retina and retinal pigment epithelium, and an evident absence of the ellipsoid zone in the right eye. The visual field showed a wide-range paracentral scotoma in the right eye. The full-field electroretinogram demonstrated subnormal amplitudes of dark and light adaption in the right eye. No significant changes were observed during a further 5-year follow-up. Multimodal imaging provides valuable information to better understand unilateral pericentral RP. The development of unilateral pericentral RP is significantly slow and defines a better clinical course than the typical RP. Pericentral RP presents with slight visual reduction and unremarkable night blindness, which can be easily misdiagnosis by ophthalmologists. Reasonable prevention measures, screening methods, and timely diagnosis are beneficial for RP patients.

Application of Electrophysiology in Non-Macular Inherited Retinal Dystrophies.

Inherited retinal dystrophies encompass a diverse group of disorders affecting the structure and function of the retina, leading to progressive visual impairment and, in severe cases, blindness. Electrophysiology testing has emerged as a valuable tool in assessing and diagnosing those conditions, offering insights into the function of different parts of the visual pathway from retina to visual cortex and aiding in disease classification. This review provides an overview of the application of electrophysiology testing in the non-macular inherited retinal dystrophies focusing on both common and rare variants, including retinitis pigmentosa, progressive cone and cone-rod dystrophy, bradyopsia, Bietti crystalline dystrophy, late-onset retinal degeneration, and fundus albipunctatus. The different applications and limitations of electrophysiology techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP), in the diagnosis and management of these distinctive phenotypes are discussed. The potential for electrophysiology testing to allow for further understanding of these diseases and the possibility of using these tests for early detection, prognosis prediction, and therapeutic monitoring in the future is reviewed.

Inverse pattern of photoreceptor abnormalities in retinitis pigmentosa and cone-rod dystrophy.

PURPOSE: To determine the characteristics of the photoreceptor abnormalities in retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). METHODS: We evaluated the photoreceptor abnormalities using spectral-domain optical coherence tomography (SD-OCT) in 28 patients with RP and 17 patients with CRD. The OCT images and full-field electroretinograms were obtained from 21 eyes in normal subjects who were age-matched to patients with RP and CRD and served as controls. RESULTS: Eyes with RP and CRD had markedly decreased rod responses (6.5 and 57.5 % of normal value), maximal responses (9.6 and 51.6 %), cone (16.5 and 25.8 %), and 30-Hz flicker responses (17.8 and 30.1 % of normal value), and their P values were smaller than 0.0003. On comparison of ERG data between RP and CRD, they had statistically significant differences in rod responses (P < 0.0003) and maximal responses (P < 0.0003). However, there were no statistical differences in cone response and a weak difference in 30-Hz flicker responses (P < 0.017). The best-corrected visual acuity was -0.03 ± 0.09 (logMAR, mean ± standard deviation [SD]) in eyes with RP, but 0.57 ± 0.54 in eyes with CRD. SD-OCT showed that eyes with RP had an intact reflective line at the junction between the photoreceptor inner and outer segment (IS/OS) at the fovea, while eyes with CRD had no IS/OS. The extent of the central visual field was correlated with the IS/OS length at the macula in eyes with RP. CONCLUSION: The distribution patterns of the IS/OS line help to differentiate between RP and CRD.

Infliximab recovers central cone dysfunction with normal fundus in a patient with ulcerative colitis.

PURPOSE: To report the efficacy of anti-tumor necrosis factor α (anti-TNFα) on autoimmune-mediated macular cone dysfunction in a Japanese woman with ulcerative colitis (UC). OBSERVATIONS: A 41-year-old woman presented with bilateral visual acuity loss and photophobia. She suffered from UC, and had been treated with prednisolone and 5-aminosalicylate since age 37. Although fundus photographs and optic coherence tomography images were unremarkable, electroretinograms (ERGs) were abnormal. A full-field electroretinogram (full-field ERG) revealed mildly decreased cone responses and oscillatory potential responses bilaterally. Importantly, focal-macular ERG (fmERG) and a multifocal electroretinogram (mfERG) revealed severe macular cone dysfunction in both eyes. Infliximab, a chimeric monoclonal anti-TNFα antibody, was administrated to treat recurrent abdominal symptoms and continued at 8-week intervals. Almost 6 months after infliximab therapy, the mfERG response (especially in the central retina), the fmERG response, and visual acuity recovered bilaterally. Abdominal symptoms also improved after infliximab therapy. CONCLUSIONS AND IMPORTANCE: Bilateral cone dysfunction with normal fundus were observed in a UC patient, resulting in loss of visual acuity and photophobia. This retinopathy may have been caused by an autoimmune mechanism, such as an autoimmune retinopathy or acute zonal occult outer retinopathy, which is most identifiable by ERG changes. This is the first report demonstrating the efficacy of infliximab in autoimmune retinal dysfunction.

Electrophysiological Monitoring of Focal and Entire Retinal Function during Treatment with Intravitreal Methotrexate for Intraocular Lymphoma.

We describe the electroretinographic findings of a case of primary intraocular lymphoma (PIOL) wherein the patient received intravitreal injections of methotrexate (ivMTX). A 62-year-old man developed blurred vision and complained of decreased visual acuity (VA) in his right eye. Fundus examination showed vitreous opacity and multiple subretinal yellowish lesions. Optical coherence tomography (OCT) revealed subretinal and intraretinal infiltrations. The full-field electroretinogram (ffERG) showed subnormal combined rod-cone response and multifocal electroretinogram (mfERG) recorded using skin electrodes showed severe attenuation of the response compared with the other eye. Pars prana vitrectomy, phacoemulsification, and lens implantation were performed to remove the opacity, and vitreous biopsy revealed a high ratio of interleukin 10-6 (76.0). There was no systemic malignant lesion, and the patient was diagnosed with PIOL. Treatment with ivMTX (400 µg/0.1 mL) was started. One month later, the intraretinal infiltration had disappeared, and mfERG revealed recovery of the response density from the central area. Two months later, OCT showed recovery of the foveal ellipsoid and interdigitation zones, and VA recovered to 20/17; mfERG showed maintenance of macular function. However, the amplitude of a- and b-waves in the ffERG gradually decreased. Macular function recovered, but there was also a decrease in total retinal function. mfERG and ffERG recorded using skin electrodes were useful in monitoring macular and entire retinal function with repeated examinations and showed recovery and maintenance of macular function in a case of PIOL treated with ivMTX.

Multimodal Imaging in Ocular Siderosis.

Purpose: This report aims to characterize ocular changes in a case of ocular siderosis with iron toxicity using multimodal imaging and electroretinography. Methods: A 34-year-old woman presented with ocular siderosis of the left eye following penetrating injury with an iron-containing foreign body. The patient's uncorrected visual acuities were 20/60 and 20/150 in the right and left eye, respectively, with abnormal pupillary function and presence of a cataract in the left eye. She underwent successful intraocular foreign body removal and cataract surgery with no postoperative complications. Cone contrast threshold (CCT), full-field electroretinogram, spectral-domain optical coherence tomography (OCT), and OCT angiography (OCTA) were used to characterize ocular alterations preoperatively and postoperatively. Results: CCT color vision testing showed abnormal color vision, and OCTA revealed increased vascular flow density associated with the foreign body. Conclusions: CCT color vision testing, OCTA, OCT, and full-field electroretinogram can characterize retinal changes in cases of ocular siderosis.

A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma.

There is indication that nutritional supplements protect retinal cells from degeneration. In a previous study, we demonstrated that dietary supplementation with an association of forskolin, homotaurine, spearmint extract and B vitamins efficiently counteracts retinal dysfunction associated with retinal ganglion cell (RGC) death caused by optic nerve crush. We extended our investigation on the efficacy of dietary supplementation with the use of a mouse model in which RGC degeneration depends as closely as possible on intraocular pressure (IOP) elevation. In this model, injecting the anterior chamber of the eye with methylcellulose (MCE) causes IOP elevation leading to RGC dysfunction. The MCE model was characterized in terms of IOP elevation, retinal dysfunction as determined by electrophysiological recordings, RGC loss as determined by brain-specific homeobox/POU domain protein 3A immunoreactivity and dysregulated levels of inflammatory and apoptotic markers. Except for IOP elevation, dysfunctional retinal parameters were all recovered by dietary supplementation indicating the involvement of non-IOP-related neuroprotective mechanisms of action. Our hypothesis is that the diet supplement may be used to counteract the inflammatory processes triggered by glial cell activation, thus leading to spared RGC loss and the preservation of visual dysfunction. In this respect, the present compound may be viewed as a potential remedy to be added to the currently approved drug therapies for improving RGC protection.

Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female.

Peroxisomal biogenesis disorders (PBD) are rare autosomal recessive disorders with various degrees of severity caused by hypomorphic mutations in 13 different peroxin (PEX) genes. In this study, we report the clinical and molecular characterization of a 9-years-old female presenting an apparently isolated pre-lingual sensorineural hearing loss (SNHL) and early onset Retinitis Pigmentosa (RP) that may clinically overlap with Usher syndrome. Genetic testing by clinical exome sequencing identified two variants in PEX1: the missense variant c.274G > C; p.(Val92Leu) that was already reported in a PBD patient, and the variant c.2140_2145dup; p.(Ser714_Gln715dup) which is a novel, non-frameshift variant, absent in control databases. On the basis of the molecular analysis, a thorough clinical examination revealed nail and dental abnormalities, a mild cognitive impairment, learning disabilities and poor feeding, apart from the retinal and audiological features initially identified. The clinical and molecular findings led us to the diagnosis of a mild form of PBD. This study further emphasizes that mild forms of PBD can be a differential diagnosis of Usher syndrome and suggests that patients with mild cognitive impairment associated to visual and hearing loss should perform a comprehensive mutation screening that includes PEX genes.

Effect of axial length on full-field and multifocal electroretinograms.

PURPOSE: The aim was to investigate the effect of axial length on full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG) in young Indian subjects. METHODS: One hundred subjects (44 male) with refractive errors from +0.50 to -18.00 DS and no myopic retinopathy underwent axial length measurement. ffERG was measured, which included scotopic and photopic responses according to International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines. The mfERG was recorded after correcting for refractive error according to ISCEV standards. The dark-adapted and light-adapted parameters of ffERG and N1, P1 parameters of six rings in mfERG were analysed with axial length, controlled for refractive error. The subjects were divided into seven groups based on axial length. The b/a ratio of dark-adapted and light-adapted 3.0 ffERG and P1/N1 ratio of mfERG amplitudes were analysed for seven groups of axial length. RESULTS: The axial length ranged from 21.79 to 30.55 mm. Significant negative correlations were noted for ffERG and mfERG amplitudes, whereas implicit times showed minimal delay with increase in axial length. In ffERG, the scotopic responses were more decreased compared to photopic responses. In mfERG, P1 and N1 amplitudes were significantly decreased in all the rings in all groups and more reduction was noted in the central ring compared to peripheral rings. The P1 amplitudes were more affected as compared to N1 amplitudes. The light-adapted and dark-adapted 3.0 ERG b/a ratio and P1/N1 ratio for seven axial length groups did not show statistically significant difference. The ERG parameters were not significant with refractive error. CONCLUSION: This study quantifies the relationship of axial length with ffERG and mfERG parameters in a young Indian population. Although the amplitudes were reduced significantly, the implicit times were not significantly affected. The ERG parameters were more related to axial length than refractive error. Hence, interpretation of ffERG and mfERG parameters needs careful consideration in subjects with increasing axial length.

Padronização do eletrorretinograma de campo total em cães / Full field electrorretinogram standartization in dogs

Eletrorretinograma (ERG) é o meio diagnóstico objetivo e não-invasivo para avaliar a função retiniana e detectar precocemente, em várias espécies, lesões nas suas camadas mais externas. As indicações mais comuns para ERG em cães são: avaliação pré-cirúrgica de pacientes com catarata, caracterização de distúrbios que causam cegueira, além de servir como importante modelo para o estudo da distrofia retiniana que acomete o homem. Vários são os fatores que podem alterar o ERG tais como: eletrorretinógrafo, fonte de estimulação luminosa, tipo do eletrodo, tempo de adaptação ao escuro, tamanho pupilar, opacidade de meios e protocolo de sedação ou anestesia; além da espécie, raça e idade. Objetivou-se com este estudo padronizar o ERG para cães submetidos à sedação, seguindo o protocolo da International Society for Clinical Electrophysiology of Vision (ISCEV), utilizando Ganzfeld e eletrodos Burian Allen. Foram realizados 233 eletrorretinogramas em cães, 147 fêmeas e 86 machos, com idades entre um e 14 anos. Dos 233 cães examinados, 100 apresentavam catarata em diferentes estágios de maturação, 72 eram diabéticos e apresentavam catarata madura ou hipermadura, 26 apresentaram eletrorretinograma compatível com degeneração retiniana progressiva, três apresentaram eletrorretinograma compatível com síndrome da degeneração retiniana adquirida subitamente e 32 não apresentaram lesão retiniana capaz de atenuar as respostas do ERG, sendo considerados normais quanto à função retiniana. A sedação foi capaz de produzir boa imobilização do paciente sem rotacionar o bulbo ocular, permitindo adequada estimulação retiniana bilateralmente, com auxílio do Ganzfeld. O sistema eletrodiagnóstico Veris registrou com sucesso e simultaneamente de ambos os olhos, as cinco respostas preconizadas pela ISCEV. Como o ERG de campo total tornou-se exame fundamental na rotina oftalmológica, sua padronização é indispensável quando se objetiva comparar resultados de laboratórios distintos...

Electroretinogram (ERG) is an objective non invasive diagnostic method to evaluate retinal function which permits the early detection of lesions at retinal external layers, even before the appearance of clinical signs. In dogs, ERG is mostly utilized for preoperative evaluation in patients presenting cataracts; characterization of disturbances causing blindness, among the utilization of dogs as animal models in scientific research. Several factors interfere in ERG responses, such as the ERG machine, light stimulation, electrode, time spent on dark adaptation, pupil size, means opacity, sedation or anesthetization, species, breed and age. The purpose of this study was to standardize the full field ERG in sedated dogs, according to the International Society for Clinical Electrophysiology of Vision (ISCEV) protocol, using Ganzfeld and bipolar electrodes. Two hundred thirty threes ERGs were performed in 147 female and 86 male with ages from 1 to 14 years old. Among those 233 dogs, 100 presented cataracts in different stages of maturation, 72 were diabetic and presented mature or hypermature cataracts, 26 presented ERG compatible to progressive retinal degeneration, 3 presented ERG compatible to sudden acquired retinal degeneration syndrome; for 32 dogs no abnormal ERG was registered and they were considered as having normal retinal function. Sedation was capable to induce a good immobilization with no bulb rotation, resulting uniform retinal stimulation, using Ganzfeld. Veris system successfully registered all 5 ISCEV responses, simultaneously from both eyes, at the same time. Full field ERG became a fundamental ophthalmic exam, then, its standardization is mandatory to allow comparison between ERGs from different laboratories. The reliability and reproducibility of this protocol has shown very good responses, using ISCEV protocol, Veris system, Ganzfeld and Burian Allen electrodes in sedated dogs.

Importância do eletrorretinograma de campo total (Full field ERG) em cães da raça Cocker Spaniel Inglês portadores de catarata / Full field electroretinogram in English Cocker Spaniels presenting cataracts

Com o aumento do número de intervenções cirúrgicas para a remoção da catarata em cães, observa-se a necessidade de exames específicos que devem ser realizados antes da indicação cirúrgica. A catarata é uma das principais causas de cegueira em cães. Nos estágios mais avançados, impossibilita o exame fundoscópico e inviabiliza a observação de alterações retinianas como a atrofia progressiva da retina (APR), degeneração retiniana hereditária de acometimento bilateral que, quando diagnosticada, contra-indica a cirurgia. Com o intuito de reestabelecer a visão, o eletrorretinograma de campo total (Full field ERG) torna-se indispensável na avaliação pré-cirúrgica da remoção da catarata. Como os cães da raça Cocker Spaniel Inglês são predispostos à catarata e a degenerações retinianas, objetivamos neste estudo avaliar as respostas dos ERGs realizados nestes animais. Foram avaliados 136 eletrorretinogramas de cães da raça Cocker Spaniel Inglês (62 machos e 74 fêmeas, com idades entre 3 e 15 anos) no período de Setembro de 2004 a Maio de 2009. Todos os animais apresentavam baixa de visão e catarata durante o exame. O diagnóstico de degeneração retiniana foi baseado nos valores de amplitude pico a pico e tempo de culminação da onda-b nas 3 respostas (resposta escotópica de bastonetes, máxima resposta e resposta fotópica de cones), idade do paciente e estágio de maturação da catarata. Nos cães sem degeneração retiniana, a média da amplitude e do tempo de culminação nas três respostas obtidas foram, respectivamente: 71,55mV/65,15ms; 149,17mV/33,03ms; 31,06mV/27,90ms. Nos cães com degeneração retiniana, 38 animais apresentaram ERG extinto. Dentre os restantes que apresentavam baixas respostas, a média da amplitude e do tempo de culminação nas três respostas obtidas foram, respectivamente: 12,88mV/65,04ms; 24,16mV/36,25ms; 8,36mV/31,38ms. Foi observado que em 122 animais (89,7 por cento) os exames eram compatíveis com diagnóstico de atrofia progressiva ...

Cataracts are one of the most frequent ocular disorders that affects dogs and leads to blindness. In the late stages, lens opacity unables fundoscopy and consequently the diagnosis of retinal degeneration such as progressive retinal atrophy (PRA), which contraindicates surgery. Aiming the return of vision, full field electroretinogram (full field ERG) becomes indispensable before surgery. As English Cocker Spaniels are predisposed to cataracts and retinal degeneration, the objective of this study is the evaluation of the full field ERG records performed in dogs. One hundred thirty-six full field ERGs were recorded from English Cocker Spaniels (62 males and 74 females, with ages ranging from 3 to 15 years old), between September, 2004 and May, 2009. Each examined dog presented cataracts and vision loss before the exam. Diagnosis of retinal degeneration was made based on ERG parameters which were measured from peak to peak amplitude and b-wave implicit time in the 3 different responses (rod response, maximal response and cone response). Amplitude measured in rod, maximal and cone response, as well as the implicit time recorded from dogs that did not present retinal degeneration were respectively: 71.55mV/65.15ms; 149.17mV/33.03ms; and 31.06mV/27.90ms. No response was recorded in 38 dogs. Low responses were recorded from the remaining dogs: 12.88mV/65.04ms, 24.16mV/36.25ms, and 8.36mV/31.38ms. Results showed that 122 animals (89.7 percent) presented progressive retinal atrophy. Therefore, we conclude that full field ERG must be performed in English Cocker Spaniels presenting cataracts before its removal due to high incidence of retinal degeneration in this breed.