Retinal dystrophies with bull's-eye maculopathy along with negative ERGs.

PURPOSE: The aim of this study was to examine the ophthalmological characteristics and genotypes of patients with congenital retinal pathologies, who display a bull's-eye maculopathy in the fundus, along with a negative scotopic electroretinogram. METHODS: We analysed the results of five patients showing both a bull's-eye maculopathy, as well as a negative scotopic ERG evoked by a bright flash. Their median age was 39 years (range 11-63 years): three males and two females. All underwent a comprehensive examination with determination of distant visual acuity (ETDRS) and recording of the full-field ERG (scotopic and photopic). Fundus, OCT, and FAF images were obtained, the kinetic visual field was determined, and colour vision (D-15) was tested in most patients. Targeted gene panel sequencing was performed on peripheral blood. RESULTS: One patient carried a homozygous ABCA4 mutation and an additional heterozygous variant in CRX. Two of the five patients were shown to have a heterozygous mutation in the CRX gene, one of whom had an additional heterozygous ABCA4 mutation. Two patients had the common heterozygous mutation c.2413G>A;p.Arg838His in GUCY2D. In all of the patients, there was a reduction in the amplitude of the b-wave with a regular a-wave amplitude in the scotopic bright-flash ERG. CONCLUSIONS: The five patients with bull's-eye maculopathy along with a negative ERG had differing genotypes. Mutations were found in the CRX gene (2 patients), the ABCA4 gene (1 patient), and the GUCY2D gene (2 patients).

A case of X-linked retinoschisis with atypical fundus appearance.

PURPOSE: Mutations in the RS1 gene are known to cause retinoschisis, an X-linked hereditary retinal degeneration. Here, we present a case of atypical retinoschisis with clinical findings of retinoschisis and retinitis pigmentosa. METHODS: This report is an observational case report. The detailed ophthalmological examinations included visual field determination, multimodal imaging and electrophysiological recordings. Targeted next-generation sequencing of a retinal disease gene panel was performed. RESULTS: The 55-year-old male, highly hyperopic patient, presented with a best-corrected Snellen visual acuity of 20/100 in the right eye and 20/400 in the left eye. In the kinetic visual field, there was a superior scotoma, as well as a ring scotoma in the inferior hemisphere in the right eye and a concentric visual field constriction to 10° in the left eye. Funduscopy revealed marked pigmentary changes (i.e. bone spicules) in the mid-periphery bilaterally and symmetrically, as well as two small intra-retinal haemorrhages in the left eye. Full-field electroretinography recordings showed extinguished rod and cone responses. Diagnostic-genetic testing revealed a hemizygous missense mutation in the RS1 gene (c.305G > A; p.Arg102Gln) was identified. CONCLUSION: We present a case of atypical retinoschisis with clinical findings of retinitis pigmentosa.

The importance of electrode position in visual electrophysiology.

PURPOSE: The DTL fibre electrode is commonly used to record the electric potentials elicited by stimulation of the retina. Two positions are commonly used: it is placed either on the cornea along the lower lid or in the conjunctival fornix. The PERG and OPs have previously been examined and compared under both conditions. The aim of this study was to examine the ERG, flicker response and on-off responses with differing electrode positions. METHODS: Before recruitment, all subjects underwent an ophthalmological examination. We enrolled 13 normal control subjects into the study aged 13-64 years, all with a visual acuity of ≥1.0. We recorded scotopic and photopic ERGs, flicker and on-off responses, for both electrode positions. On the first day, one eye had the electrode placed on the cornea along the lower lid and the other eye had it positioned in the conjunctival sac. On a second day, the recordings were repeated with the alternative electrode placements. RESULTS: ERG, on-off and flicker responses were all smaller by between 20 and 25% when the DTL electrode was positioned in the conjunctival sac, compared to when it was positioned on the cornea, as did the scatter in the data points. This indicates that there is no advantage clinically for one or the other placement. CONCLUSIONS: Our results confirm other reports examining the effect of electrode position on electrophysiological potentials. When recording with the DTL electrode, it is important to ensure that it is placed at the same position in repeat recordings or in multicentre trials and that it is stable and does not move during recording.

Electrophysiology and colour: a comparison of methods to evaluate inner retinal function.

PURPOSE: Several methods are routinely used in the clinic to diagnose and monitor diseases of inner retinal function. In this study, we compare four such methods in patients with diabetes and glaucoma, to determine correlations between their results and to determine which method is most sensitive for detecting disease. METHODS: Twenty control subjects, 12 patients with early glaucoma and eight patients with diabetes mellitus, were enrolled in the study. All underwent four examinations: transient pattern electroretinogram (PERG), multifocal pattern electroretinogram (mfPERG), chromatic contrast threshold measurements (protan and tritan), and blue-on-yellow short-wavelength automated perimetry (SWAP). RESULTS: For the total cohort of 40 subjects, the results show a significant correlation between the amplitudes of the PERG and those of the mfPERG, as well as between the tritan contrast thresholds and the SWAP MD. Furthermore, ROC analyses reveal that colour contrast thresholds could significantly distinguish between the patient and the control group. Glaucoma patients alone could also be distinguished. CONCLUSIONS: We conclude that the methods compared in this study show correlations between their results if they are testing same pathway or underling cells, and that the colour contrast threshold is the most sensitive method to detect early functional deficits in diabetic and glaucoma patients.

Multimodal multidimensional imaging for visual system status assessment.

Non-invasive optical methods that enable in vivo or in situ visualization of tissue components are of particular relevance in ophthalmology, as they can provide key information about the relationship between the structure and function of the visual system. In this paper we present a semiautomated multimodal imaging tool for co-registration of images of retinal structure and its function, based on point correspondence. Decision support analysis was applied to define significant features for the multimodal mapping system, using a set of 1500 subjects who were affected by blindness associated hereditary retinal dystrophies. Additionally, the developed software was tested by two experienced observers using data from 25 subjects. Inter-observer and intra-observer reliability was determined. We conclude that semi-automated multimodal mapping could be a promising new tool for an individualized visual system status assessment that can be applied for the early diagnosis of blindness associated diseases. Moreover, this mapping approach should prove particularly appropriate for studying pathophysiology in inherited blindness associated diseases.

A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy.

UNLABELLED: This study was designed to determine whether a new form of treatment of diabetic retinopathy (DR) was acceptable to patients and whether reduction in the maximal activity of rods in diabetes could affect the progress of DR. METHODS: In 12 patients, trans-lid retinal illumination of one eye was employed during sleep to prevent the depolarisation of rods and thus reduce their metabolic activity. TECHNIQUES: A headband was used to place a source of chemical light over one eye, with its fellow as a control. MEASUREMENTS: Colour contrast thresholds were measured before and after a period of treatment in treated eyes, and the changes were compared to those in untreated fellow eyes, and areas of 'dark retinal anomalies' (microaneurysms, dot haemorrhages) were measured at the same time points. RESULTS: Patients found this intervention to be acceptable, and no adverse effects were noted. In the majority of cases, and for each outcome measure, the treated eyes improved relative to their fellows. The intervention significantly reduced the tritan thresholds in treated eyes relative to their fellows (P=0.03), and the area of dark retinal anomalies decreased in treated eyes and increased in untreated eyes, with a similar probability. CONCLUSIONS: The study showed that this intervention is safe. Although the study was not powered to study efficacy, the results are promising and consistent with other reports that indicate the retina in DR is suffering from hypoxia; however, further trials should be undertaken.

Multifocal oscillatory potentials in type 1 diabetes without retinopathy.

PURPOSE: To study multifocal recordings of oscillatory potentials (m-OPs) in diabetic (Type 1) eyes that have no visible fundus alterations, to ascertain whether topographical changes in sensitivity are evident when compared with recordings from control subjects. METHODS: The Visual Evoked Response Imaging System (VERIS; EDI, San Diego, CA) system was used to elicit m-OPs from 61 independent areas, subtending the central 30 degrees of the retina, from 24 eyes of 12 patients with diabetes without retinopathy and from 26 eyes of 14 control subjects. For each group of subjects, the mean first- and second-order (first slice) kernel components of the responses for one eye, randomly chosen from each subject, were analyzed and compared for a retinal ring analysis and for an analysis of retinal quadrants. RESULTS: Both first- and second-order kernel responses of the diabetic group show significant delays in the implicit times of some of the m-OPs, compared with those of the control group. No significant changes in amplitude were found. For the first-order component, significant differences are found for both potentials between 5 degrees and 22 degrees eccentricity, for the nasal retina, and for one of the potentials for the remaining retinal areas. In the second-order kernel responses, the differences are significant for two of the three potentials in the midperiphery between 5 degrees and 13 degrees eccentricity, with the central potential being significantly delayed in all rings and quadrants. CONCLUSIONS: Patients with diabetes without retinopathy show prolonged latencies in m-OP recordings. This indicates an alteration in inner retinal sensitivity that can be explained by an impaired rod-cone interaction.

A temporal deficit in juvenile diabetics.

BACKGROUND: In this study we examined the temporal domain of visual function in diabetics without retinopathy by examining wavelength discrimination ability at two exposure durations. The results were compared to those found by heterochromatic brightness matching and anomaloscope matches. METHODS: Wavelength discrimination was performed between 440 and 540 nm at exposure times of 1 s and 0.04 s in eight juvenile diabetic patients without retinopathy. The monochromatic stimuli were presented in Maxwellian view and were set to be equally bright prior to the experiment using heterochromatic brightness matching. In addition, Rayleigh and Moreland anomaloscope matches were performed. The results of the diabetic group were compared to those of an age-matched control group of eight subjects with normal colour vision. RESULTS: Wavelength discrimination showed no difference between the groups for an exposure time of 1 s. With an exposure duration of 0.04 s, however, the diabetics show raised thresholds for the shortest wavelengths tested. In addition, brightness matches were increased at the short wavelengths, and anomaloscope matches showed a decrease in the match range for the Moreland (blue-yellow) equation. CONCLUSION: The results indicate post-receptoral alterations in diabetic patients with no visible changes in their retinae.

Development of brightness matching and colour vision deficits in juvenile diabetics.

We studied hue discrimination and brightness matching throughout the spectrum in ten juvenile patients suffering from diabetes mellitus (Type I) with no (eight patients) or mild (two patients) retinopathy. In addition, the FM 100-Hue test was performed. The data were collected once every year over 5 years. Over the 5 years, the diabetics show a continual change in the shape of their brightness matching function. Wavelength discrimination ability remains quite stable with time at the long end of the spectrum but is variable at short wavelengths. FM-100 error scores remain similar over the period tested, at a level slightly higher than that of a control group. Additional experiments show that the sensitivity of the S-cone in the diabetic group is similar to that of controls. The results can be explained by an early relative reduction in the sensitivity of post-receptoral processes in juvenile diabetics.

Preretinopic changes in the colour vision of juvenile diabetics.

AIMS: To examine the colour vision of juvenile patients suffering from diabetes mellitus without retinopathy in relation to metabolic and ophthalmic state. METHODS: Metameric matches, both Rayleigh (red/green) and Moreland (blue/green) were used to test the colour vision yearly of 10 juvenile patients. The patients were monitored over 4 years, and during the final year, their blood glucose level was determined directly after testing colour vision. An ophthalmic examination was performed on the day of colour vision testing and blood and urine were analysed regularly throughout the 4 years. Their results are compared with an aged matched control group of 20 subjects, seven of whom were retested after 9-16 months. RESULTS: After 4 years, the colour vision results show an enlarged matching range for the Moreland match, as well as a smaller increase in the matching range for the Rayleigh match. No significant correlation was found between blood glucose at the time of testing and any of the variables measured. CONCLUSION: The pattern of colour vision deficits in metameric matching shown by juvenile diabetics is consistent with postreceptoral alterations of the inner retina, at this preretinopic stage of disease. Duration of diabetes is correlated with both colour vision changes and morphological alteration of the retina.

Influence of luminance flicker and purity on heterochromatic brightness matching and hue discrimination: a postreceptoral opponent process.

We have studied psychophysically the characteristics of the postreceptoral stage of visual processing, using heterochromatic brightness matching (HBM) between 540 and 600 nm, and hue discrimination between 565 and 585 nm, under differing luminance flicker (0-30 Hz) and excitation purity (1.0-0.1) conditions. The HBM curves exhibit deeper minima around 575 nm with decreasing purity. The minimum is generally most pronounced with a 3 Hz flicker and least pronounced with a 30 Hz flicker. Hue discrimination ability is relatively insensitive to flicker and deteriorates at the lower purities. The HBM results for low purities can be explained by the upper envelope of activities in PC- and MC-pathways.

Reversed visual motion and self-sustaining eye oscillations.

A random-dot field undergoing counterphase flicker paradoxically appears to move in the same direction as head and eye movements, i.e. opposite to the optic-flow field. The effect is robust and occurs over a wide range of flicker rates and pixel sizes. The phenomenon can be explained by reversed phi motion caused by apparent pixel movement between successive retinal images. The reversed motion provides a positive feedback control of the display, whereas under normal conditions retinal signals provide a negative feedback. This altered polarity invokes self-sustaining eye movements akin to involuntary optokinetic nystagmus.

Centrally tinted contact lenses. A useful visual aid for patients with achromatopsia.

Achromatopsia (rod monochromacy) is a congenital color-vision defect of autosomal recessive inheritance due to severely abnormal or totally absent cone function. The disease is characterized by markedly reduced visual acuity, nystagmus, and, often, ametropia. Even under normal daylight conditions, these patients are extremely handicapped by glare because of a lack of rod inhibition by the abnormal or deficient cones. Light-absorbing glasses (absorption > 90%) can ameliorate this visual impairment to a certain extent but are sometimes not accepted by the patient since they are felt to disfigure the face. Especially during the first few years of school, this can lead to psychological problems. A special contact lens (Hydroflex, Wöhlk Company, Kiel) with a centrally tinted area (absorption 80%) that is slightly greater in diameter than the pupil under daylight conditions can correct ametropia and reduce light exposure and dazzle in a cosmetically much better way. Our first experience with this kind of visual aid in a 9-year-old girl suffering from incomplete achromatopsia is presented.

Brightness matching and colour discrimination in young diabetics without retinopathy.

This study used the methods of the Farnsworth-Munsell 100-hue test (FM-100), heterochromatic brightness matching (HBM) and wavelength discrimination to test the sensitivity and colour vision of 20 juvenile diabetics with no (16) or very mild (4) retinopathy. Their results were compared to an age-matched control group. The FM-100 results showed a significant increase in error scores throughout the spectrum in comparison to the controls. This deterioration in colour vision was confirmed in the results for the wavelength discrimination task, tested between 440 and 640 nm, where the just noticeable difference in colour was, in general, larger for the diabetic group than the control group. Only at 460 nm were the results of the diabetics similar to those of the controls. The diabetic group were also less sensitive than the control group in the HBM task between 480 and 600 nm. The results show that a deficit in sensitivity and colour vision occurs in diabetics before the onset of a clinically visible retinopathy.

Dynamic noise backgrounds facilitate target fading.

With strict fixation, a small uniform target of medium contrast, placed at 10 deg eccentricity, faded much faster when presented on a dynamic random noise background than on either a static random noise background or a uniform background of the same luminance. Time to first disappearance was between 10 and 16 sec when the background was dynamic, 26 sec when it was static, and 57 sec when it was uniform. Times were shortest for temporal noise frequencies of the background between 3.5 and 15 Hz. These findings are unexpected: the frequent change of pixel contrast at the edge of the target should perceptually enhance the border, make it less susceptible to local adaptation, and prevent fading. Instead, dynamic random noise facilitates, rather than suppresses fading. Three potential mechanisms are discussed: edge perturbation, jerk effect and surround induction.

Reduced spatial sensitization on nonuniform backgrounds.

Spatial sensitivity (Westheimer) functions, when measured on nonuniform backgrounds made up of light dots of 12 min arc, were found to differ in shape, depending on the polarity of the central area on which the test spot was placed. When thresholds were measured on the dark centre between light dots, ie on the adapting-field illumination, the resulting curve was similar to the control curve, measured on a uniform background equated for flux. In comparison, thresholds measured on a central light dot, serving as a pedestal, peaked at larger background diameters and showed much less sensitization compared to the control function.