Yes / Congenital achromatopsia or rod monochromatism is a rare autosomal recessive condition defined by a severe loss of cone photoreceptor function in which rods purportedly retain normal or near-to-normal function. This report describes the results of electroretinography in two siblings with CNGB3-associated achromatopsia. Full field light- and dark-adapted electroretinograms (ERGs) were recorded using standard protocols detailed by the International Society for Clinical Electrophysiology of Vision (ISCEV). We also examined rod-mediated ERGs using series of stimuli that varied over a 6 log unit range of retinal illuminances (−1.9–3.5 log scotopic trolands). Dark-adapted ERGs in achromatopsia patients exhibited severely reduced b-wave amplitudes with abnormal b:a ratios (1.3 and 0.6). In comparison, the reduction in a-wave amplitude was less marked. The rod-mediated ERG took on an electronegative appearance at high-stimulus illuminances. Although the defect that causes achromatopsia is primarily in the cone photoreceptors, our results reveal an accompanying disruption of rod function that is more severe than has previously been reported. The differential effects on the b-wave relative to the a-wave points to an inner-retinal locus for the disruption of rod function in these patients.

Yes / The purpose of this paper is to demonstrate: 1) that silent substitution stimuli can be used generate electro-retinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation and 2) that this approach constitutes a viable alternative to current clinical standard testing protocols. Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary LED ganzfeld stimulator to elicit ERGs from non-dark adapted participants with normal and compromised rod function. Responses were subjected to Fourier analysis and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. ERGs elicited by rod isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30Hz. Responses are optimal between 5 – 8 Hz and between 10-100 photopic Td. There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal to noise ratios reveals significant differences between subjects with normal and compromised rod function. Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance: This method of generating rod ERGs rod isolation can be achieved without time consuming periods of dark adaptation and provides improved isolation of rod- from cone-based activity and will lead to the development of faster clinical electro-physiological testing protocols with improved selectivity.

A hallmark of retinal diseases is degeneration of neural cells, leading to subsequent vision loss. For such diseases, replenishment of functional neural cells may be an optimal therapy. Unlike humans, the adult red-spotted newt, Notophthalmus viridescens, possesses the remarkable ability to regenerate a complete retina following its removal or injury. The purpose of this study was to develop a reproducible model of retinal damage and regeneration in the newt to understand the process of retinal regeneration. Intense light, shown in other organisms to be a relevant model of visual cell loss, was tested in the newt and resulted in variable loss of retinal function, correlating with the appearance of apoptotic cells. Due to the variability of damage observed, surgical removal of the retina was used to complement the light-damage model. A novel and non-invasive protocol using full-field electroretinography was developed to assess retinal function in vivo following damage. Measures of retinal function with the electroretinogram protocol successfully showed that photoreceptor function is initially lost and subsequently restored during regeneration. These results enhance our understanding of retinal regeneration in the adult newt and serve as a starting point for further studies aimed at determining the molecular mechanisms involved in the regeneration process.

Vigabatrin (VGB) is an anti-epileptic drug used to treat children with Infantile Spasms (IS). The 3.0 flicker amplitude of the electroretinogram (ERG) is currently used to monitor visual function changes in infants on VGB. To find a more specific marker of permanent changes due to VGB, sedated ERGs were performed on 31 IS patients and 13 retinally normal controls to isolate components of the cone pathway. ERG growth curves, for each component, recorded from children with IS were generated using data recorded pre-VGB treatment and for controls. Only the cone off response (from Off bipolar cells) and cone photoreceptor sensitivity were associated with decreased flicker amplitude. Twenty nine percent of patients had an abnormal cone off response. No patient had an abnormal cone off response at baseline. No patient with an abnormal cone off response recovered normal function. The cone off response could serve as a marker VGB retinal toxicity.

Vigabatrin (VGB) is an anti-epileptic drug used to treat children with Infantile Spasms (IS). The 3.0 flicker amplitude of the electroretinogram (ERG) is currently used to monitor visual function changes in infants on VGB. To find a more specific marker of permanent changes due to VGB, sedated ERGs were performed on 31 IS patients and 13 retinally normal controls to isolate components of the cone pathway. ERG growth curves, for each component, recorded from children with IS were generated using data recorded pre-VGB treatment and for controls. Only the cone off response (from Off bipolar cells) and cone photoreceptor sensitivity were associated with decreased flicker amplitude. Twenty nine percent of patients had an abnormal cone off response. No patient had an abnormal cone off response at baseline. No patient with an abnormal cone off response recovered normal function. The cone off response could serve as a marker VGB retinal toxicity.

A hallmark of retinal diseases is degeneration of neural cells, leading to subsequent vision loss. For such diseases, replenishment of functional neural cells may be an optimal therapy. Unlike humans, the adult red-spotted newt, Notophthalmus viridescens, possesses the remarkable ability to regenerate a complete retina following its removal or injury. The purpose of this study was to develop a reproducible model of retinal damage and regeneration in the newt to understand the process of retinal regeneration. Intense light, shown in other organisms to be a relevant model of visual cell loss, was tested in the newt and resulted in variable loss of retinal function, correlating with the appearance of apoptotic cells. Due to the variability of damage observed, surgical removal of the retina was used to complement the light-damage model. A novel and non-invasive protocol using full-field electroretinography was developed to assess retinal function in vivo following damage. Measures of retinal function with the electroretinogram protocol successfully showed that photoreceptor function is initially lost and subsequently restored during regeneration. These results enhance our understanding of retinal regeneration in the adult newt and serve as a starting point for further studies aimed at determining the molecular mechanisms involved in the regeneration process.

Electroretinoraphic signals (ERGs) are affected when recorded under isoflurane anesthesia in the operating room. We explored the effect of isoflurane and propofol in ex vivo guinea pig retinal preparations using a multielectrode array to record simultaneously ERGs and retinal ganglion cell (RGC) activity. The viability and light-response characteristics of the model were documented. In the presence of isoflurane, the ERG and RGC activity was reduced in a dose-dependent manner, even at sub-clinical doses; the OFF responses were consistently more affected. Propofol had minimal effects: at subclinical doses, a small excitation was measured while a concentration a hundred times stronger than the clinical concentration was required to measure a significant decline in EGR and RGC signals. This study confirms the usefulness of the guinea pig model to study clinically relevant retinal issues and shows that propofol is a better anesthetic to use in the operating room when retinal investigations are required.

A hallmark of retinal diseases is degeneration of neural cells, leading to subsequent vision loss. For such diseases, replenishment of functional neural cells may be an optimal therapy. Unlike humans, the adult red-spotted newt, Notophthalmus viridescens, possesses the remarkable ability to regenerate a complete retina following its removal or injury. The purpose of this study was to develop a reproducible model of retinal damage and regeneration in the newt to understand the process of retinal regeneration. Intense light, shown in other organisms to be a relevant model of visual cell loss, was tested in the newt and resulted in variable loss of retinal function, correlating with the appearance of apoptotic cells. Due to the variability of damage observed, surgical removal of the retina was used to complement the light-damage model. A novel and non-invasive protocol using full-field electroretinography was developed to assess retinal function in vivo following damage. Measures of retinal function with the electroretinogram protocol successfully showed that photoreceptor function is initially lost and subsequently restored during regeneration. These results enhance our understanding of retinal regeneration in the adult newt and serve as a starting point for further studies aimed at determining the molecular mechanisms involved in the regeneration process.

A hallmark of retinal diseases is degeneration of neural cells, leading to subsequent vision loss. For such diseases, replenishment of functional neural cells may be an optimal therapy. Unlike humans, the adult red-spotted newt, Notophthalmus viridescens, possesses the remarkable ability to regenerate a complete retina following its removal or injury. The purpose of this study was to develop a reproducible model of retinal damage and regeneration in the newt to understand the process of retinal regeneration. Intense light, shown in other organisms to be a relevant model of visual cell loss, was tested in the newt and resulted in variable loss of retinal function, correlating with the appearance of apoptotic cells. Due to the variability of damage observed, surgical removal of the retina was used to complement the light-damage model. A novel and non-invasive protocol using full-field electroretinography was developed to assess retinal function in vivo following damage. Measures of retinal function with the electroretinogram protocol successfully showed that photoreceptor function is initially lost and subsequently restored during regeneration. These results enhance our understanding of retinal regeneration in the adult newt and serve as a starting point for further studies aimed at determining the molecular mechanisms involved in the regeneration process.

Studies demonstrate localized neuro-retinal dysfunction in patients with diabetes and no visible diabetic retinopathy (DR). Poor glycemic control is a strong risk factor for DR. We hypothesized that poor glycemic control predicts increased areas of localized neuro-retinal dysfunction in patients with diabetes. Forty-eight adolescents with diabetes and 45 controls were tested using the standard (103 hexagons) multifocal electroretinogram (mfERG). Negative binomial regression analysis was conducted with number of abnormal hexagons (delayed responses) as the dependent variable and glycated hemoglobin (HbA1c), disease duration, age and sex as covariates. Results indicate that a one-unit increase in HbA1c predicts an 80% (p = 0.002) increase in the number of abnormal hexagons when controlling for age. Increased areas of neuro-retinal dysfunction are predicted by worsening glycemic control in patients with no visible DR. Standard mfERG may be useful in monitoring patients with diabetes and identifying those who may be at risk of developing DR.