Photopic ERG Research Articles

A pedigree of dominant drusen with high hypermetropia

Objectives To observe the clinical features of a pedigree of dominant drusen with high supermetropia.Methods Three patients in a family with dominant drusen were retrospectively reviewed.The refractive conditions were confirmed by computer and manual refraction examination with pupils dilated by tropicamide.Color fundus photography and fluorecein angiography were carried out with a FF450 Plus Zeiss camera.The fundus fluorescein angiography (FFA) photos were analyzed.Standard electroretinogram responses (ERGs) were also recorded.The characteristics of refractive condition,color fundus photos,FFA and ERG of the patients were analyzed.Results Various degrees of drusen were observed in the retinae of the three patients.The disease in the younger brother of the proband was mild and in the mother is severe.A large number of drusen existed in the peripheral retina as well as macula in the mother of the proband.FFA revealed window defects corresponding to the drusen. The dilated refractive results showed high supermetropic refractive error in the three patients.All of the eyes except the left eye of the mother of the proband showed refractive amblyopia.The amplitude of the photopic ERGs were decreased but the scotopic ERGs were normal in the younger brother of the proband.The scotopic and photopic ERGs of the proband and her mother were normal. Conclusion Patients with dominant drusen in combinnation with high hypermetropic refractive error and amblyopia may occur. Key words: Retinal drusen/congenital; Hyperopia; Genes,dominant; Pedigree

Endogenous Erythropoietin Protects Neuroretinal Function in Ischemic Retinopathy

Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy.

Localization of Melatonin Receptor 1 in Mouse Retina and Its Role in the Circadian Regulation of the Electroretinogram and Dopamine Levels

Melatonin modulates many important functions within the eye by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylate cyclase. In the mouse, Melatonin Receptors type 1 (MT1) mRNAs have been localized to photoreceptors, inner retinal neurons, and ganglion cells, thus suggesting that MT1 receptors may play an important role in retinal physiology. Indeed, we have recently reported that absence of the MT1 receptors has a dramatic effect on the regulation of the daily rhythm in visual processing, and on retinal cell viability during aging. We have also shown that removal of MT1 receptors leads to a small (3–4 mmHg) increase in the level of the intraocular pressure during the night and to a significant loss (25–30%) in the number of cells within the retinal ganglion cell layer during aging. In the present study we investigated the cellular distribution in the C3H/f+/+ mouse retina of MT1 receptors using a newly developed MT1 receptor antibody, and then we determined the role that MT1 signaling plays in the circadian regulation of the mouse electroretinogram, and in the retinal dopaminergic system. Our data indicate that MT1 receptor immunoreactivity is present in many retinal cell types, and in particular, on rod and cone photoreceptors and on intrinsically photosensitive ganglion cells (ipRGCs). MT1 signaling is necessary for the circadian rhythm in the photopic ERG, but not for the circadian rhythm in the retinal dopaminergic system. Finally our data suggest that the circadian regulation of dopamine turnover does not drive the photopic ERG rhythm.

Electrophysiological assessment of fundus albipunctatus

AbstractPurpose Fundus Albipunctatus is a congenital, stationary retinal disease with rod system degeneration. The disorder is caused by mutation in the RDH5 gene. It is characterized by impaired night vision and numerous small white‐yellow retinal lesions. Flash ERG reveals severe rod function impairment after usual period of dark‐adaptation, which normalize after prolonged dark adaptation.Methods A case of a 12‐year‐old female presented with symptoms of poor night vision. The patient underwent the visual acuity, colour vision tests (D15), fundus photography, fluorescein angiography, automated static perimetry. The standard dark adapted electroretinogram (30min) and a prolonged dark adaptated ERG (120 min), photopic ERG and multifocal electroretinogram (mfERG) were performed.Results Visual acuity of both eyes was not decreased. In the peripheral visual field a concentric restriction was found. Scotopic ERG rod responses (0.009 and 0.017 cd x s /m2) were significantly reduced and a standard ERG response was borderline. Photopic ERG was normal. In the mfERG P1 densities were slightly reduced in the eccentric rings (R4‐R5).Conclusion The comparison of standard adapted scotopic ERG (30 min) and prolonged dark adapted Scotopic ERG (120 min) is the most useful clinical test in diagnosis and differentation of Fundus Albipunctatus. The mfERG can be helpful in detecting patients suffering from Fundus Albipunctatus with progressive cone dystrophy.

Quantifying end‐stage electrophysiological function in progressive retinal degenerative disorders (PRDD)

AbstractPurpose PRDD, such as Retinitis Pigmentosa, are accompanied with a gradual reduction of ERG signal to non‐measurable amplitudes. We compared alternative means of quantifying normal and pathological ERGs.Methods Photopic ERGs (DTL electrode, background 30 cd.m‐2; flash stimuli: ‐2.62 to 0.64 log cd.sec.m‐2 in 17 steps of ~ ‐0.2 log‐unit) were recorded from 85 normal subjects and 55 patients with PRDD. In a subset of 6 normal subjects, focal ERGs (fERGs) were obtained with the use of a eye patch to restrict the stimulus centrally and at 20o or 40o nasally. ERG descriptors, obtained with Direct Wavelet Transform D(WT) of the ERGs, were compared to the traditional amplitude measurements.Results In normal, the ERG amplitude gradually decreased from 131.42±31.27µV (Vmax) to 0.71±0.12 µV (dimmest flash used) in two distinct pseudo‐asymptotical steps of ‐15.2±2.0µV.s (step 1) and ‐0.42±0.1µV.s per decrement respectively (9 steps each). Pathological ERGs as well as normal focal ERGs could always be fitted to this model. Furthermore, while the traditional measurements frequently failed to quantify residual ERGs, including the normal fERGs, the DWT was always able to extract quantifiable and comparable information from the residual response, thus permitting a more favourable prognosis.Conclusion Analysis of the ERG response in the time and frequency domain (such as DWT) allows for a more precise quantification of the ERG signal especially when it reaches residual amplitudes such as that observed in end‐stage PRDD. Our results suggest that modeling ERG attenuation with the DWT improves the staging and prognosis of patients affected with severe PRDD. Supported by FFB (USA).

Transplantation of Photoreceptor and Total Neural Retina Preserves Cone Function in P23H Rhodopsin Transgenic Rat

BackgroundTransplantation as a therapeutic strategy for inherited retinal degeneration has been historically viewed to restore vision as a method by replacing the lost retinal cells and attempting to reconstruct the neural circuitry with stem cells, progenitor cells and mature neural retinal cells.Methods and FindingsWe present evidence for an alternative strategy aimed at preventing the secondary loss of cones, the most crucial photoreceptors for vision, by transplanting normal photoreceptors cells into the eye of the P23H rat, a model of dominant retinitis pigmentosa. We carried out transplantation of photoreceptors or total neural retina in 3-month-old P23H rats and evaluated the function and cell counts 6 months after surgery. In both groups, cone loss was significantly reduced (10%) in the transplanted eyes where the cone outer segments were found to be considerably longer. This morphological effect correlated with maintenance of the visual function of cones as scored by photopic ERG recording, but more precisely with an increase in the photopic b-wave amplitudes by 100% and 78% for photoreceptor transplantation and whole retinal transplantation respectively.ConclusionsWe demonstrate here that the transplanted tissue prevents the loss of cone function, which is further translated into cone survival.

Ocular safety profile and intraocular pharmacokinetics of an antagonist of EphB4/EphrinB2 signalling

AimsTo characterise the ocular safety profile of sEphB4 and its pharmacokinetics in rabbit eyes.Methods15 rabbits with single intravitreal injection of sEphB4 in the right eye (1000 μg, 465 μg, 160...

Exploring new strategies to record and analyse clinical electroretinograms

Abstract Purpose Investigate if the combination of time‐frequency domain analysis and ERG dipole rotation reveals hidden features of the normal ERG that could be instrumental in the interpretation of nearly extinguished ERG responses. Methods Analyses were conducted on photopic ERGs (Photopic Hills: PH) obtained from normal subjects (n=75) and patients (n=65) affected with various retinopathies. A Discrete Wavelet Transform (DWT) was done on each ERGs and key descriptors (Holder exponent and wavelet coefficient maxima) were calculated. Dipole rotation was obtained by combining 11 gaze positions (0, 8, 16, 24, 32 and 40 degrees nasal or temporal to center) with 4 electrode locations [corneal (CE), lower lid (LL), external (EC) and internal canthi (IC)]. Results The Holder exponent follows a parabola, while some of the local wavelet maxima seem to follow a PH‐like like distribution (b‐wave and OPs) or a logistic growth function (a‐wave). In still recordable pathological ERGs, the wavelet maxima matched that found in normal ERGs evoked at low stimulus intensities while in nearly extinguished ERGs (<10% of normal) the wavelet coefficients were significantly lower. Irrespective of the direction of gaze, there was little variation in DTL ERGs. EC ERGs were the only ones to reverse in polarity (seen 5 degrees nasal to fixation in nasal to temporal shift). Conclusion The parameters obtained with the DWT offers useful and reproducible tools to help identify subtle features of residual ERGs and therefore should allow for a more accurate quantification of low‐voltage ERGs responses. Finally, our results suggest that varying the gaze and electrode positions would represent a valuable addition to the recording of clinical ERGs. Funded by NSERC.

Specific deficits in visual electrophysiology without retinal cellular apoptosis in a mouse model of dominant optic atrophy

Abstract Purpose Autosomal dominant optic atrophy (ADOA) due to mutations in OPA1 is a slowly progressive optic neuropathy. OPA1 is ubiquitously expressed and plays a key role in mitochondrial fusion. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with previously reported visual defects and optic nerve changes, were assessed for retinal sequelae. Methods ERGs and VEPs were recorded in 12 month old B6;C3‐Opa1Q285STOP mice (n=4) and age/sex matched wildtype littermate controls. Full scotopic and photopic intensity series were recorded in response to brief (4 ms) single flash stimuli delivered in a ganzfeld dome. End‐organ evidence for apoptosis was explored on TUNEL stained retinal sections. Results Quantification of the major ERG components (a‐wave and b‐wave) confirmed no detectable difference in the amplitude or implicit time of scotopic ERGs across the full intensity range tested. This was also true for the VEP components. Quantification of the photopic ERG responses revealed a significant reduction in the PhNR amplitude in Opa1+/‐ animals relative to wildtypes at the brightest intensity tested. The photopic VEP was also abnormal in mutant mice. There was no increased apoptosis in retinal sections from mutant animals. Conclusion Opa1+/‐ mice display a functional deficit on electrophysiology that is indicative of specific ganglion cell dysfunction. Despite a 50% reduction in Opa1 protein there does not appear to be a significant increase in apoptosis in the retina. This suggests that the protein truncating mutation in this model may lead to RGC dysfunction without triggering RGC death.

Sodium Iodate Selectively Injuries the Posterior Pole of the Retina in a Dose-Dependent Manner: Morphological and Electrophysiological Study

Sequential morphological and functional features of retinal damage in mice exposed to different doses (40 vs. 20 mg/kg) of sodium iodate (NaIO3) were analyzed. Retinal morphology, apoptosis (TUNEL assay), and function (electroretinography; ERG) were examined at several time points after NaIO3 administration. The higher dose of NaIO3 caused progressive degeneration of the whole retinal area and total suppression of scotopic and photopic ERG. In contrast, the lower dose induced much less severe degeneration in peripheral part of retina along with a moderate decline of b- and a-wave amplitudes in ERG, corroborating the presence of regions within retina that retain their function. The peak of photoreceptor apoptosis was found on the 3rd day, but the lower dose induced more intense reaction within the central retina than in its peripheral region. In conclusion, these results indicate that peripheral area of the retina reveals better resistance to NaIO3 injury than its central part.

Asymmetrical growth of the photopic hill during the light adaptation effect

In response to progressively stronger flashes delivered against a rod saturating background light, the amplitude of the photopic ERG b-wave first increases, reaches a maximal value (V (max)) and then decreases gradually to a plateau where the amplitude of the b-wave equals that of the a-wave, a phenomenon known as the photopic hill (PH). The purpose of this study was to investigate how the PH grew during the course of the light adaptation (LA) process that follows a period of dark adaptation (DA): the so-called light adaptation effect (LAE). Photopic ERG (time-integrated) luminance-response (LR) functions were obtained prior to (control-fully light adapted) and at 0, 5 and 10min of LA following a 30-min period of DA. A mathematical model combining a Gaussian and a logistic growth function, suggested to reflect the OFF and ON retinal contribution to the PH respectively, was fitted to the LR functions thus obtained. Our results indicate that the magnitude of the cone ERG LAE is modulated by the stimulus luminance, with b-wave enhancements being maximal for luminance levels that result in the descent of the PH. The Gaussian function grew significantly with LA while the logistic growth function remained basically unchanged. Our findings would therefore suggest that the LAE reflects primarily an increase in the retinal OFF response during LA.

Novel functions of photoreceptor guanylate cyclases revealed by targeted deletion

Targeted deletion of membrane guanylate cyclases (GCs) has yielded new information concerning their function. Here, we summarize briefly recent results of laboratory generated non-photoreceptor GC knockouts characterized by complex phenotypes affecting the vasculature, heart, brain, kidney, and other tissues. The main emphasis of the review, however, addresses the two GCs expressed in retinal photoreceptors, termed GC-E and GC-F. Naturally occurring GC-E (GUCY2D) null alleles in human and chicken are associated with an early onset blinding disorder, termed "Leber congenital amaurosis type 1" (LCA-1), characterized by extinguished scotopic and photopic ERGs, and retina degeneration. In mouse, a GC-E null genotype produces a recessive cone dystrophy, while rods remain functional. Rod function is supported by the presence of GC-F (Gucy2f), a close relative of GC-E. Deletion of Gucy2f has very little effect on rod and cone physiology and survival. However, a GC-E/GC-F double knockout (GCdko) phenotypically resembles human LCA-1 with extinguished ERGs and rod/cone degeneration. In GCdko rods, PDE6 and GCAPs are absent in outer segments. In contrast, GC-E(-/-) cones lack proteins of the entire phototransduction cascade. These results suggest that GC-E may participate in transport of peripheral membrane proteins from the endoplasmic reticulum (ER) to the outer segments.

Novel mutations and electrophysiological findings in RGS9 and R9AP associated retinal dysfunction (Bradyopsia)

Abstract Purpose To describe the phenotypic characteristics of patients with mutation in RGS9 or R9AP, which give rise to the disorder "bradyopsia" Methods Patients were ascertained according to history, examination and electrophysiological recordings. ERGs were performed in excess of the ISCEV standard better to characterise retinal function, and included S‐cone ERGs, ON‐OFF ERGs, and dark adapted ERGs to a bright flash with extended inter‐stimulus intervals. Blood samples were taken for DNA extraction from affected subjects and where possible unaffected relatives. Mutation screening of RGS9 and R9AP was performed. Results Four subjects were found to harbour mutations in RGS9 or R9AP, with three being novel. Three subjects, two Pakistani sisters and an Afghani female, had mutations in R9AP. The remaining patient, a British male, had a compound heterozygous mutation in RGS9. All mutation positive subjects had characteristic electrophysiological findings with, in particular, severely abnormal photopic cone ERGs (with relative S‐cone sparing) but normal dark adapted cone ERGs, and the need to use a prolonged inter‐stimulus interval to allow recovery from a dark‐adapted bright flash. Clinically, the patients had a stationary cone dysfunction syndrome, including mild photophobia; normal colour vision; normal fundi; and no nystagmus. Conclusion Novel electrophysiological features are described in association with RGS9 and R9AP mutations. The distinctive electrophysiological features associated with RGS9 and R9AP mutations enable directed genetic screening, and allow the distinction from patients with Oligocone Trichromacy, who present with a similar clinical phenotype.

Extensive macular atrophy with pseudodrusen‐like appearance (EMAP), a new clinical entity

Abstract Purpose To describe a previously unreported clinical entity of progressive extensive macular atrophy and pseudo‐drusen appearance in middle age patients. Methods The database of the outpatient clinic for genetic sensory diseases was screened for patients over 40 years with uncharacterized macular dystrophy. Patients with extensive macular atrophy and pseudodrusen‐like appearance were included. Clinical investigations included visual acuity, eye examination, color fundus imaging, OCT scan, autofluorescence, Farnsworth 15‐HUE color testing, Goldman perimetry and ISCEV full‐field ERG. Results Eighteen patients of 45 screened records matched the inclusion criteria. Bilateral polycyclic well‐delineated chorioretinal atrophy extending to the temporal vascular arcades, with a larger vertical axis and without sparing of the fovea featured the macular lesion. The pseudodrusen‐like appearance was widespread thoughout the posterior pole and the peripheral retina. In the extreme periphery, paving stone lesions were mostly located in the inferior quadrants. In contrast to age‐related macular degeneration, a rapid progression of the atrophy was observed with an early involvement of the foveal zone, thus leading to a severe visual loss. All the patients except two were legally blind at the end of the follow‐up. In all patients, the scotopic and photopic ERG responses were reduced. Conclusion The cause of Extensive Macular Atrophy with Pseudodrusen (EMAP) remains unknown. Extensive Macular Atrophy with pseudodrusen (EMAP) should be considered as a possible pattern of severe macular dystrophy occurring in the middle‐aged adult.

Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU). A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 +/- 0.4 muV; control, 6.2 +/- 0.3 muV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa. Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss.

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental-isoflurane (TI), medetomidine-ketamine (MK), and xylazine-ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m(2)), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m(2)), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.

AAV-Mediated Gene Therapy for Retinal Degeneration in therd10Mouse Containing a Recessive PDEβ Mutation

To test AAV-mediated gene therapy in the rd10 mouse, a natural model of recessive RP caused by mutation of the beta-subunit of rod photoreceptor cGMP phosphodiesterase. One eye of a cohort of rd10 mice kept in a dark environment was subretinally injected at postnatal day (P) 14 with 1 microL AAV5-smCBA-PDEbeta. The contralateral eye was not injected. The animals were then maintained for 2 weeks in the dark before they were moved to a normal 12-hour light/12-hour dark cycling light environment for visually guided behavioral training. Three weeks after injection, treated rd10 mice were examined by scotopic and photopic electroretinography and then killed for biochemical and morphologic examination. Substantial scotopic ERG signals were maintained in treated rd10 eyes, whereas untreated eyes in the same animals showed minimal signals. Treated eyes showed photopic ERG b-wave amplitudes similar to those of the normal eyes; in untreated partner eyes, only half the normal amplitudes remained. Strong PDEbeta expression was observed in photoreceptor outer segments only in treated eyes. Light microscopy showed a substantial preservation of the outer nuclear layer in most parts of the treated retina only. Electron microscopy showed good outer segment preservation only in treated eyes. A visually guided water maze behavioral test under dim light showed significantly improved performance in one eye-treated rd10 mice compared with untreated mice. These data demonstrate that P14 administration of AAV5-smCBA-PDEbeta can prevent retinal degeneration in rd10 mice, as reflected by significant structural, biochemical, electrophysiological, and behavioral preservation/restoration. These results serve as a baseline for studying long-term retinal rescue in rd10 mice.

Electrophysiological evaluation of retinal photoreceptor function after repeated bevacizumab injections

Bevacizumab (Avastin, Genentech) was one of the first anti-VEGF substances used to treat macular edema or choroidal neovascularization in patients with vascular ocular pathologies. However, only few studies evaluate the safety of intravitreal bevacizumab injections in regard to retinal photoreceptor function. We evaluated retinal function after repeated (2-3) monthly injections of bevacizumab in a prospective case series of 10 patients with various retinal diseases. Study endpoints were visual acuity (VA) using ETDRS charts and 3 full-field electroretinography sessions with a flash intensity range of 0.0005-2 cds/m(2). V-log-I b-wave amplitudes were fitted by a Naka-Rushton model. No significant changes in scotopic or photopic ERG measures were observed between baseline ERG and last follow-up ERG. Individual patients showed transient alterations of ERG measures on the first follow-up visit. Mean visual acuity was stable over the time course of the study (logMAR = 0.42 at baseline and logMAR = 0.48 at last follow-up). In conclusion, three monthly repeated injections of bevacizumab do not affect mid-term electrophysiological retinal function. Transient alterations in ERG readings of individual patients 1 week after intravitreal bevacizumab injection may be attributed to short-term disruption of the retinal equilibrium through the trauma of injection. Evaluation of patients receiving more than three injections of anti-VEGF substances should be the focus of future studies.

Retinal Dysfunction in Combined Methylmalonic Aciduria and Homocystinuria (Cblc) Disease: A Spectrum of Disorders

Cobalamin C methylmalonic aciduria with homocystinuria (cblC disease) is a rare hereditary inborn error of cobalamin metabolism, characterised by neurological, haematological and ophthalmological abnormalities. Three consecutive patients with Cblc disease were examined. Investigations included slit lamp and fundus examination and full-field ERG. A maculopathy associated with both photopic and scotopic abnormal ERG was present in two cases and a salt and pepper retinopathy with abnormal photopic ERG was detected in the third patient. Despite early treatment and regular metabolic controls, all our patients exhibited both retinal and ERG abnormalities. There was no correlation between funduscopic appearance and the type of photoreceptor dysfunction. A literature review disclosed a retinopathy in 29 / 70 cases with cblC disease, with an abnormal ERG in 8 of the 12 tested cases, most with retinopathy. Retinal dysfunction in cblC disease may be more frequent than previously thought, and can involve cones only or both rods and cones. We recommend a formal ocular examination with full-field ERG in patients with Cblc disease.

Photopic ON- and OFF- Responses in Korean Normal Subjects

Purpose: To explore the effects of stimulus duration, stimulus intensity, and background luminance on the amplitude and waveform of the ON- and OFF- responses of photopic ERG and to provide standard parameters of ON- and OFF- responses for normal Korean populations. Methods: Twenty normal subjects (20 eyes) were enrolled to record photopic ON-and OFF-responses using a contact lens electrode with built-in LEDs and an LED-driver. The influence of stimulus duration on wave amplitudes was studied at flash durations that varied from 5 to 200 ms. The influence of stimulus intensity was studied with 0.4, 0.7, 1.1, 1.4, 1.7, 1.9, 2.0, and 2.1 log cd/m2. In addition, the influence of background luminance was studied with 20, 30, 40, and 50 cd/m2. Result: Among 20 normal subjects, the d-waves in 16 subjects were isolated from b-waves with more than 50 ms of stimulus duration. The d-wave was observed for a 30-ms stimulus duration in 3 subjects and for a 100-ms duration in 1 subject. The amplitudes of the b-and d-waves increased as stimulus intensity was increased. The amplitudes of b-and d-waves decreased as background luminance was increased. Conclusions: Our results suggest that the clinical use of ON-and OFF-response recording can be obtained with stimulus parameters from 100 to 150 ms in duration and a 1.7-2.1 log cd/m2 intensity under 30-40 cd/m2 background luminance.