Rod-mediated Responses Research Articles

Products of the visual cycle are detected in mice lacking retinol binding protein 4, the only known vitamin A carrier in plasma

Efficient delivery of vitamin A to the retinal pigment epithelium is vital to the production of the light-sensitive visual chromophore 11-cis-retinal. Nevertheless, retinol binding protein 4 (RBP4) is the only known carrier of vitamin A in plasma. Here, we present new findings that further characterize the visual cycle in the presence of Rbp4 deficiency. In the face of impaired delivery of retinol in Rbp4-/- mice, we determined that 11-cis-retinaldehyde reached levels that were ∼60% of WT at 4months of age and all-trans-retinyl ester was 18% of normal yet photoreceptor cell loss was apparent by 8months of age. The lack of Rbp4 appeared to have a greater impact on scotopic rod-mediated responses than on cone function at early ages. Also, despite severely impaired delivery of retinol, bisretinoid lipofuscin that forms as a byproduct of the visual cycle was measurable by HPLC and by quantitative fundus autofluorescence. In mice carrying an Rpe65 amino acid variant that slows visual cycle kinetics, Rbp4 deficiency had a less pronounced effect on 11-cis-retinal levels. Finally, we found that ocular retinoids were not altered in mice expressing elevated adipose-derived total Rbp4 protein (hRBP4+/+AdiCre+/-). In conclusion, our findings are consistent with a model in which vitamin A can be delivered to the retina by Rbp4-independent pathways.

Correlations of Full-Field Stimulus Threshold With Functional and Anatomical Outcome Measurements in Advanced Retinitis Pigmentosa

To compare full-field stimulus (FST) threshold values to conventional functional and anatomical measures commonly used in clinical practice. Cross-sectional study. Patients with retinitis pigmentosa with nondetectable electroretinogram rod-mediated responses and light-adapted 3.0 cd·s·m2 30-Hz flicker (LA 3.0 flicker) amplitudes of 15 mV or less were included in this study. The threshold values for blue, white, and red stimuli on FST were correlated with best-corrected visual acuity, LA 3.0 flicker amplitude and implicit times, length of the ellipsoid zone (EZ) band and thickness of outer nuclear layer measurements on optical coherence tomography, and the vertical and horizontal diameters of the autofluorescent ring on autofluorescence imaging. Forty-two eyes of 21 patients were included in the study. The mean FST thresholds were -22.5 ± 15.5 dB, -17.6 ± 11.5 dB, and -12.7 ± 6.0 dB for the blue, white, and red stimuli, respectively. The threshold values for the 3 FST stimuli were significantly correlated with selected functional and anatomical outcome measures. Specifically, they were strongly correlated with LA 3.0 flicker amplitude and EZ band length measured on optical coherence tomography. Using linear regression, blue and white stimulus values on FST were found to be predictive of EZ band length (R2=0.579 and 0.491, respectively), and the vertical (R2=0.694 and 0.532, respectively) and horizontal (R2=0.626 and 0.400, respectively) diameters of the hyperautofluorescent ring. The significant correlations between FST and other clinical outcome measures highlight its potential as an adjunct outcome measure.

NPHP1 Full Deletion Causes Nephronophthisis and a Cone-Rod Dystrophy.

To describe in detail the structural and functional phenotype of a patient with cone-rod dystrophy associated with a full deletion of the NPHP1 gene. A 30-year-old male with history of end-stage renal disease (ESRD) presented with progressive vision loss in early adulthood prompting evaluation for retinal disease. Ophthalmic evaluation was performed including, kinetic fields, electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), fundus auto-fluorescence (FAF), wide-angle fluorescein angiography and near infrared imaging (NIR). Visual acuity was 20/60 in each eye. Fundus examination revealed a subtle bull's-eye maculopathy confirmed with fundus autofluorescence. SD-OCT demonstrated perifoveal loss of the outer retinal layers with structural preservation further peripherally. Testing of retinal function confirmed loss of cone greater than rod sensitivities in a manner that co-localized to structural findings. ERG revealed decreased photopic and scotopic responses. Genetic testing confirmed a homozygous whole gene deletion of the NPHP1 gene. NPHP1-associated retinal degeneration may present as a cone-rod dystrophy in addition to the previously reported rod-predominant phenotypes and can notably be associated with systemic abnormalities, including renal disease. Our work further expands upon the growing literature describing retinal disease associated with systemic ciliopathies.

Gene Supplementation Rescues Rod Function and Preserves Photoreceptor and Retinal Morphology in Dogs, Leading the Way Toward Treating Human PDE6A-Retinitis Pigmentosa.

Mutations in the phosphodiesterase 6A gene (PDE6A) result in retinitis pigmentosa (RP) type 43 (RP43) and are responsible for about 4% of autosomal recessive RP. There is currently no treatment for this blinding condition. The aim of this project was to use a large-animal model to test a gene supplementation viral vector designed to be translated for use in a clinical trial for the treatment of RP43. Seven Pde6a-/- puppies were given sub-retinal injections of an adeno-associated viral vector (AAV) serotype 2/8 delivering human PDE6A cDNA under control of a short rhodopsin promoter (AAV8-PDE6A). Three puppies received ∼1 × 1011 vg in one eye and four puppies ∼5 × 1011 vg/per eye, with both eyes being injected in two animals. In vivo outcome measures included vision testing and electroretinography (ERG), as well as fundus and spectral domain-optical coherence tomography imaging. Some puppies were euthanized and their eyes processed for immunohistochemistry. All puppies had improved rod-mediated vision in the treated eye. ERGs showed improved rod-mediated responses in the higher-dose group but in only one of the lower-dose group animals. Receptor+ thickness was preserved and photoreceptor morphology improved in the treated retinal regions in all puppies. Treatment resulted in PDE6A transgene expression, accompanied by much increased levels of Pde6b, in rod outer segments in the injected retinal regions. There were several indications of improved retinal health in the PDE6A-expressing regions, including lack of abnormal cyclic guanosine monophosphate accumulation, appropriate rod opsin localization to the outer segments with a large reduction in mislocalization to other regions of the rod cell, and reduced Müller cell activation. Additionally, cone photoreceptors showed morphological improvement in the treated region, with normal-appearing inner and outer segments. AAV8-PDE6A gene supplementation therapy restored rod vision in Pde6a-/- puppies and preserved retinal morphology. These positive outcomes are an important step toward a human clinical trial to treat PDE6A-RP.

The aging rat retina: from function to anatomy

In healthy beings, age is the ultimate reason of cellular malfunction and death. In the rat retina, age causes a functional decline and loss of specific neuronal populations. In this regard, controversial conclusions have been reported for the innermost retina. Here, we have studied the albino and pigmented retina for the duration of the rat life-span. Independent of age (21 days–22 months), the electroretinographic recordings and the volume of the retina and its layers are smaller in albinos. Functionally, aging causes in both strains a loss of cone- and rod-mediated responses. Anatomically, cell density decreases with age because the retina grows linearly with time; no cell loss is observed in the ganglion cell layer; and only in the pigmented rat, there is a decrease in cone photoreceptors. In old animals of both strains, there is gliosis in the superior colliculi and a diminution of the area innervated by retinal ganglion cells. In conclusion, this work provides the basis for further studies linking senescence to neurodegenerative retinal diseases.

Pupillary responses in non-proliferative diabetic retinopathy

The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities.

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses

Rod photoreceptors contribute to vision over an ∼ 6-log-unit range of light intensities. The wide dynamic range of rod vision is thought to depend upon light intensity-dependent switching between two parallel pathways linking rods to ganglion cells: a rod → rod bipolar (RB) cell pathway that operates at dim backgrounds and a rod → cone → cone bipolar cell pathway that operates at brighter backgrounds. We evaluated this conventional model of rod vision by recording rod-mediated light responses from ganglion and AII amacrine cells and by recording RB-mediated synaptic currents from AII amacrine cells in mouse retina. Contrary to the conventional model, we found that the RB pathway functioned at backgrounds sufficient to activate the rod → cone pathway. As background light intensity increased, the RB's role changed from encoding the absorption of single photons to encoding contrast modulations around mean luminance. This transition is explained by the intrinsic dynamics of transmission from RB synapses.

Intravitreal Injection of Triamcinolone Acetonide into Healthy Rabbit Eyes Alters Retinal Function and Morphology

Aim: To study the effects of intravitreally injected triamcinolone acetonide (TA) and/or its preservative benzyl alcohol (BA) in healthy rabbit retina.Methods: Forty-eight rabbits (aged 4 months, body weight ≈3 kg) were randomized into four groups (n = 12). They were examined with electroretinography (ERG) prior to drug exposure, and then injected intravitreally with a combination of TA and BA, TA without BA, BA alone or a balanced saline solution (BSS). The electroretinograms were assessed 1 week and 7 weeks post-injection. The rabbits were euthanized and the sectioned retinas were studied. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells.Results: Rabbits injected with BA showed a significantly lower rod-mediated b-wave amplitude than the controls 1 week after injection. TA-injected rabbits demonstrated significantly higher a- and b-wave amplitudes in the total retinal response than the controls 1 week post-injection. The rabbits injected with TA + BA demonstrated a significantly higher b-wave amplitude in the total retinal response than the controls 1 week after injection. The significantly higher a-wave amplitude in the total retinal response remained in the TA-injected rabbits 7 weeks after injection. Immunohistochemistry revealed that protein kinase C alpha (PKC α) was down-regulated in both the perikarya and the axons of bipolar cells in histological sections from rabbit retina injected with TA + BA, BA and TA.Conclusions: Intravitreal injection of the preservative BA reduces the isolated rod-mediated retinal response in the rabbit, transiently and selectively. Intravitreal injection of TA increases the total retinal response in the rabbit up to seven weeks after injection. The effects observed are not only limited to retinal function, but also include changes in the expression of PKC α in rod bipolar cells, indicating drug-related interference with normal retinal physiology in the healthy rabbit eye.

Retinal Function and Morphology in Rabbit After Intravitreal Injection of VEGF Inhibitors

Purpose/Aim: To explore changes in morphology and function in the rabbit retina after intravitreal high-dose injection of three commonly used VEGF inhibitors.Materials and methods: Forty-eight rabbits of mixed strain (6 months of age, body weight ≈ 3 kg) were randomized into four groups (n = 12). They were examined with full-field electroretinography (ERG) and with multifocal electroretinography (mf ERG) prior to drug exposure. The rabbits were then injected intravitreally with bevacizumab, ranibizumab, pegaptanib, or with a balanced saline solution. The dose of VEGF inhibitor was chosen to achieve a vitreous concentration approximately three times higher than the one clinically used in the adult human eye. ERG was then performed 8 weeks postinjection, and mf ERG 9 weeks postinjection. After 9 weeks, the rabbits were sacrificed and the sectioned retina was studied. Immunohistochemical analysis was performed of rods, cones, rod bipolar cells, horizontal cells, and amacrine cells.Results: Rabbits injected with VEGF inhibitors all showed significantly lower amplitude of the dark-adapted b-wave rod-mediated response to dim light, compared to the rabbits injected with BSS. The a wave (reflecting photoreceptor function) in the response to single flash white light was however not affected. Immunohistochemistry revealed a significant reduction in PKC labeling of rod bipolar cells in pegaptanib and ranibizumab injected eyes whereas bevacizumab injected eyes displayed normal PKC labeling. No apparent morphological change was seen with markers for remaining retinal cells.Conclusions: Our results indicate that the use of high-dose intravitreal VEGF inhibitors in the rabbit eye affects rod-mediated retinal function and PKC expression in rod bipolars cells for at least 9 weeks after drug administration. The three VEGF inhibitors influence the retina slightly differently. These results are important for the understanding of drug action and when devising therapeutical strategies in new areas such as retinopathy of prematurity where vitreous volume is significantly lower compared to the adult eye.

Spectral and Temporal Sensitivity of Cone-Mediated Responses in Mouse Retinal Ganglion Cells

The retina uses two photoreceptor types to encode the wide range of light intensities in the natural environment. Rods mediate vision in dim light, whereas cones mediate vision in bright light. Mouse photoreceptors include only 3% cones, and the majority of these coexpress two opsins (short- and middle-wavelength sensitive, S and M), with peak sensitivity to either ultraviolet (360 nm) or green light (508 nm). The M/S-opsin ratio varies across the retina but has not been characterized functionally, preventing quantitative study of cone-mediated vision. Furthermore, physiological and behavioral measurements suggested that mouse retina supports relatively slow temporal processing (peak sensitivity, ∼ 2-5 Hz) compared to primates; however, past studies used visible wavelengths that are inefficient at stimulating mouse S-opsin. Here, we measured the M/S-opsin expression ratio across the mouse retina, as reflected by ganglion cell responses in vitro, and probed cone-mediated ganglion cell temporal properties using ultraviolet light stimulation and linear systems analysis. From recordings in mice lacking rod function (Gnat1(-/-), Rho(-/-)), we estimate ∼ 70% M-opsin expression in far dorsal retina, dropping to <5% M-opsin expression throughout ventral retina. In mice lacking cone function (Gnat2(cpfl3)), light-adapted rod-mediated responses peaked at ∼ 5-7 Hz. In wild-type mice, cone-mediated responses peaked at ∼ 10 Hz, with substantial responsiveness up to ∼ 30 Hz. Therefore, despite the small percentage of cones, cone-mediated responses in mouse ganglion cells are fast and robust, similar to those in primates. These measurements enable quantitative analysis of cone-mediated responses at all levels of the visual system.

The effect of physical effort on retinal activity in the human eye: rod and cone flicker electroretinogram studies

The aim of our study was to assess the effect of physical exercise with increasing intensity on neuroretinal activity in healthy subjects (n = 30). We analysed the amplitude and implicit time of b-wave electroretinogram (ERG) responses in two experiments: (1) for a scotopic blue 10 Hz flicker stimulus (rod-mediated responses), and (2) for a photopic white 30 Hz flicker stimulus (cone-mediated responses). Using a cycloergometer, three 10-minute effort-tests with increasing intensity were performed. Each participant was assigned individual workload values (W) below the lactate threshold (40% VO(2)max), at the lactate threshold (60-65% VO(2)max) and above the lactate threshold (80% VO(2)max). Five ERG recordings were taken: (1) before, (2-4) immediately after the three subsequent efforts and (5) 1 hour after the completion of the last effort. The right eye was selected for monocular stimulation in both experiments. After the first effort (40% VO(2)max), we observed an increased amplitude (p < 0.001) and decreased implicit time of the b-wave (p < 0.01) in cone-mediated responses, and no significant effects in rod-mediated responses. Despite the increase in effort intensity, the cone b-wave amplitude remained unchanged, whereas the rod b-wave amplitude significantly decreased after the subsequent efforts (p < 0.001). Rod-mediated responses were more susceptible to effort-induced homeostasis disruptions than the cone-mediated responses. The application of ERGs may be used as neurophysiological criteria in defining the cardiovascular status of the physical performance.

Retinitis pigmentosa and punctate cataracts in mevalonic aciduria.

Mevalonic aciduria, caused by deficiency of mevalonate kinase, was the first recognized defect in the biosynthesis of cholesterol and isoprenoids. Ophthalmic features of this potentially blinding disorder include blue sclera, cataract, uveitis, optic atrophy, and, importantly, a retinitis pigmentosa-like retinopathy. To date, ∼30 cases of this rare autosomal recessive disorder have been reported, with no full characterization appearing in the ophthalmic literature. An 11-year-old white girl with mevalonic aciduria presented with decreasing peripheral vision and night blindness. Examination revealed decreased central vision, punctate cataracts, and a retinitis pigmentosa-like retinopathy. Goldmann visual fields confirmed severe constriction in both eyes. A full-field electroretinogram was performed. A-waves, B-waves, and oscillatory potentials were all nonrecordable in both eyes, indicating severe bilateral retinopathy, affecting both cone- and rod-mediated responses. Dark adaptation testing showed severely impaired cone and rod function under dark-adapted (scotopic) conditions. Farnsworth-Munsell hue discrimination (FM-100 hue) testing was abnormal in both eyes. The ocular findings in patients with mevalonic aciduria are heterogeneous and include blue sclerae, cataracts, uveitis, retinopathy, and optic atrophy. Visual prognosis is guarded; several patients surviving to adulthood have progressed to apparent legal blindness caused by cataracts and/or retinopathy.

Predominant loss of rod-mediated electroretinogram response in a case of acute annular outer retinopathy

Predominant loss of rod-mediated electroretinogram response in a case of acute annular outer retinopathy

A method for investigating the temporal dynamics of local neuroretinal responses

Visual sensitivity improves with prolonged exposure to light. Global neuroretinal responses increase, but little is known about the dynamics of local retinal responses over brief time intervals after changes in light level. This study applies the time-slice multifocal electroretinogram (TS mfERG) paradigm for the measurement of local electrical responses of the human eye over brief time intervals. Sixty-one, localised retinal areas were assessed over 25° of the visual field. Cone-mediated contributions to the time-slice waveform were established. The time-slice mfERG waveforms were similar in shape and timing for pre- and post-photopigment bleach conditions after saturation of rod-mediated responses, suggesting there was no rod-mediated intrusion in the waveform. The temporal dynamics of the mfERG components show that N1P1 amplitudes decrease with each successive time-slice probe, with larger amplitude responses in the central retina compared to nasal and temporal retina. The time-slice mfERG waveform is a technique for assessing the temporal dynamics of cone-generated neural responses over time. The data are interpreted in terms of the vascular supplies and lower-level visual adaptation mechanisms.

Recoverin Improves Rod-Mediated Vision by Enhancing Signal Transmission in the Mouse Retina

Vision in dim light requires that photons absorbed by rod photoreceptors evoke signals that reliably propagate through the retina. We investigated how a perturbation in rod physiology affects propagation of those signals in the retina and ultimately visual sensitivity. Recoverin is a protein in rods that prolongs phototransduction and enhances visual sensitivity. It is not present in neurons postsynaptic to rods, yet we found that light-evoked responses of rod bipolar and ganglion cells were shortened when measured in recoverin-deficient retinas. Unexpectedly, the effect of recoverin on postsynaptic signals could not be explained by its effect on phototransduction. Instead, it is an effect of recoverin downstream of phototransduction in rods that prolongs signal transmission and enhances visual sensitivity. An important implication of our findings is that the recovery phase of the rod photoresponse does not contribute significantly to visual sensitivity near absolute threshold.

Impaired Channel Targeting and Retinal Degeneration in Mice Lacking the Cyclic Nucleotide-Gated Channel Subunit CNGB1

Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers composed of homologous A and B subunits. In heterologous expression systems, B subunits alone cannot form functional CNG channels, but they confer a number of channel properties when coexpressed with A subunits. To investigate the importance of the CNGB subunits in vivo, we deleted the CNGB1 gene in mice. In the absence of CNGB1, only trace amounts of the CNGA1 subunit were found on the rod outer segment. As a consequence, the vast majority of isolated rod photoreceptors in mice lacking CNGB1 (CNGB1-/-) failed to respond to light. In electroretinograms (ERGs), CNGB1-/- mice showed no rod-mediated responses. The rods also showed a slow-progressing degeneration caused by apoptotic death and concurred by retinal gliosis. Cones were primarily unaffected and showed normal ERG responses up to 6 months, but they started to degenerate in later stages. At the age of approximately 1 year, CNGB1-/- animals were devoid of both rods and cones. Our results show that CNGB1 is a crucial determinant of native CNG channel targeting. As a result of the lack of rod CNG channels, CNGB1-/- mice develop a retinal degeneration that resembles human retinitis pigmentosa.

Monitoring retinal function in early age-related maculopathy: visual performance after 1 year.

To monitor visual performance in early age-related maculopathy (ARM). We measured monocular visual function-high-contrast visual acuity (HC-VA), central visual fields (mean sensitivity, MS), colour vision (desaturated Panel D-15), Pelli-Robson (P-R), and cone- and rod-mediated multifocal electroretinograms (mfERG) in 13 ARM subjects and 13 age-matched control subjects with normal fundi at baseline and after 1 year. All had visual acuity of 6/12 or better. The mfERG data were compared to templates derived from the control group at baseline. We analysed the mfERG results by averaging the central and peripheral fields and the superior and inferior fields (CP and SI methods) and by calculating the local responses. The mean rod-mediated responses were significantly delayed in the ARM group for the CP (P=0.04) and the SI methods (P=0.03) at baseline compared to the control group. This did not change significantly after 1 year, whereas the mean cone-mediated responses were within the normal range at both times. Although the local analysis revealed lower amplitudes for the cone- and rod-mediated responses at baseline this was not found after 1 year and only the local rod-mediated latencies were delayed at both times (P<0.01). HC-VA, desaturated Panel D-15 and P-R were significantly worse in the ARM group (P< or =0.01) at baseline but did not show further significant deterioration. Progressive fundus changes were found in only two subjects (18%). Although there was significant impairment of retinal function in early ARM at baseline no further deterioration was evident after 1 year.

Rod and cone photoreceptor function in patients with cone dystrophy.

To determine the extent of rod and cone photoreceptor dysfunction in patients with cone dystrophy using psychophysical and electrophysiological tests. Ten patients with cone dystrophy participated. Rod and cone system psychophysical thresholds were measured as a function of retinal eccentricity. Bright-flash full-field electroretinograms were obtained under dark-adapted (rod-mediated) and light-adapted (cone-mediated) conditions. The a-wave data were fitted with a model based on photopigment transduction to obtain values for log Rmax (maximum response) and log S (sensitivity). b-Wave parameters were also examined by fitting a nonlinear, saturating function (the Naka-Rushton equation) to the rod-mediated responses. Oscillatory potentials were measured to the cone-mediated high-intensity flashes. On average, the rod-mediated psychophysical thresholds were elevated by 0.5 log unit. These threshold elevations did not differ significantly with retinal eccentricity. In contrast, cone-mediated psychophysical thresholds were elevated up to 3.0 log units. Threshold elevation was greatest in the central retinal locations. For rod-mediated conditions, the a-wave Rmax parameter was significantly reduced in three patients; the a-wave log S parameter was within normal limits. The rod-mediated b-wave Rmax parameter was reduced in six patients; log k was abnormal in one patient. For cone-mediated conditions, the a-wave Rmax parameter was reduced in six patients and the a-wave log S parameter was reduced in two patients. The cone system oscillatory potentials were abnormal in nine patients. Patients with cone dystrophy show different patterns of psychophysical rod versus cone system sensitivity losses with retinal eccentricity. The full-field electrophysiological data indicate that most of the patients had abnormal cone photoreceptor function. Some patients also showed rod photoreceptor abnormalities. The rod system changes were smaller than the cone system changes.

Time courses for maturation of electroretinogram responses from infancy to adulthood.

The purpose of this study was to determine how responses in the normal human electroretinogram (ERG) change with subject age. We studied 62 children, 10 days to 15 years old, and 30 subjects 15-37 years old, using the standard protocol established by the International Society for Clinical Electrophysiology of Vision, with Burian-Allen bipolar contact-lens electrodes. We measured rod response, maximal response, oscillatory potentials (OPs), cone response, flicker response, and b-wave amplitude/log intensity (V/log I) curve. A logistic growth curve was used to describe the developmental changes. Dark- and light-adapted ERG a- and b-wave amplitudes reached adult levels by three to five years of age. although b-wave amplitudes of scotopic rod-mediated responses were slower to reach maturity than mixed rod-cone mediated responses. In early infancy OPs were the most immature of the ERG responses, although the rate of development thereafter exceeded that of the other responses such that OP amplitudes were within adult levels by two years of age. Amplitudes of the ERG responses in 21 children sedated with chloral hydrate did not differ significantly from 21 who had not been sedated. ERG responses developed at varying rates, reflecting different developmental stages in photoreceptors, middle retinal layers and more proximal retina.