The Enhanced S Cone Syndrome: An Analysis of Receptoral and Post-receptoral Changes (original) (raw)
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Enhanced S cone syndrome: Evidence for an abnormally large number of S cones
Vision Research, 1995
The cellular basis of the hypersensitivity of the S (blue) cone system in patients with enhanced S cone syndrome was examined by analyzing ERGs from three patients. The patients had large a-waves in response to the blue and white flashes. These a-waves were shown to be driven nearly entirely by the S cones. Although these S cone a-waves were 4-6 times the size of the normal L/M cone a-wave, they are of the same form, and could be quantitatively described with the same model previously shown to fit cone a-waves. We propose that the retina of these patients has many more S cones than the normal retina and that these cones replace some of the normal L/M cones and many of the rods.
Phenotypic Variation in Enhanced S-cone Syndrome
Investigative Ophthalmology & Visual Science, 2008
To characterize the clinical, psychophysical, and electrophysiological phenotype of 19 patients with enhanced Scone syndrome (ESCS) and relate the phenotype to the underlying genetic mutation. METHODS. Patients underwent ophthalmic examination and functional testing including pattern ERG, full-field ERG, and long-duration and short-wavelength stimulation. Further tests were performed in some patients, including color contrast sensitivity (CCS), multifocal ERG, fundus autofluorescence imaging (FAI), optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). Mutational screening of NR2E3 was undertaken in 13 patients. RESULTS. The fundus appearance was variable, from normal to typical nummular pigment clumping at the level of the retinal pigment epithelium in older patients. Nine patients had foveal schisis, and one had peripheral schisis. Pattern ERG was abnormal in all patients. In all patients, ISCEV Standard photopic and scotopic responses had a similar waveform, the rod-specific-ERG was undetectable and the 30-Hz flicker ERG was markedly delayed with an amplitude lower than the photopic a-wave. Most ERG responses arose from short-wavelengthsensitive mechanisms, and a majority of patients showed possible OFF-related activity. Multifocal ERG showed relative preservation of central function, but reduced responses with increased eccentricity. Mutations were identified in NR2E3 in 12 of 13 patients including four novel variants. CONCLUSIONS. The phenotype in ESCS is variable, both in fundus appearance and in the severity of the electrophysiological abnormalities. The ERGs are dominated by short-wavelengthsensitive mechanisms. The presence, in most of the patients, of possible OFF-related ERG activity is a finding not usually asso-ciated with S-cones. (Invest Ophthalmol Vis Sci. subsequently to characterize the proportion and nature of NR2E3 mutations in this cohort.
Enhanced S-cone function with preserved rod function: a new clinical phenotype
Molecular vision, 2011
To describe the clinical findings and genetic analysis in two brothers having a novel retinal disease characterized by an enhanced S-cone phenotype with normal rod function. Both patients underwent complete ophthalmologic examinations, including fundus photography, electroretinography (ERG), fluorescein angiography and optical coherence tomography (OCT). Mutation analysis of the following candidate genes was performed: nuclear receptor subfamily 2 group E member 3 (NR2E3), neural retina leucine zipper (NRL), nuclear receptor subfamily 1 group D member 1 (NR1D1), and thyroid hormone receptor beta (THRB). Spectral photopic ERG responses demonstrated enhanced S-cone function in both patients. Their scotopic b-wave ERG amplitude responses, however, were within normal limits. Their scotopic a-wave amplitude responses were within the lower limit of normal. The a- and b-wave latencies were normal for one sibling and on the upper limit of normal for the other. Peripheral retinal findings we...
Expanded Clinical Spectrum of Enhanced S-Cone Syndrome
JAMA Ophthalmology, 2013
nhanced Scone syndrome (ESCS) is a rare, autosomal recessive inherited retinal dystrophy first described more than 2 decades ago. 1-3 Because of the variable clinical presentation, it is not unusual that patients with ESCS are misdiagnosed as having atypical retinitis pigmentosa, congenital stationary night blindness, or X-linked retinoschisis. The adult human retina typically consists of approximately 120 million rods and 6 million cones containing 3 cone subtypes: short-wavelength (S), medium-wavelength (M), and long-wavelength (L) cones. Scones are the minority (about 10%) 4 subset of cones in healthy human retinas w h e r e a s i n E S C S , S-c o n e s a r e t h e m a j o r i t y c o n e subtype. 1-3,5,6 Electroretinography (ERG) and psychophysical testing play a key role in diagnosing patients with ESCS. Characteristic ERG findings are the presence of similar waveforms in the maximum dark-adapted response and singleflash light-adapted waveform. An associated ERG feature is disproportionately reduced 30-Hz cone flicker to the singleflash cone amplitude. 7-9 The basis of these waveforms has been explored. 10 All of these findings occur in the absence of rod function. 1-3,7,8 Scone stimuli can show supernormal responses, although the relative increase in Scone function compared with Land M-cone function is diagnostic and independent of degree of disease severity. Psychophysical testing demonstrating the abnormal ratio of Scone to Land M-cone function was especially helpful in proving that ESCS and the more severe expression Goldmann-Favre syndrome were part of the same disease spectrum. 3 IMPORTANCE New funduscopic findings in patients with enhanced Scone syndrome (ESCS) may help clinicians in diagnosing this rare autosomal recessive retinal dystrophy. OBJECTIVE To expand the clinical spectrum of ESCS due to mutations in the NR2E3 gene. DESIGN Retrospective, noncomparative case series of 31 patients examined between 1983 and 2012. SETTING Academic and private ophthalmology practices specialized in retinal dystrophies. PARTICIPANTS A cohort of patients diagnosed with ESCS and harboring known NR2E3 mutations. INTERVENTION Patients had ophthalmic examinations including visual function testing that led to the original diagnosis. MAIN OUTCOMES AND MEASURES New fundus features captured with imaging modalities. RESULTS New clinical observations in ESCS include (1) torpedo-like, deep atrophic lesions with a small hyperpigmented rim, variably sized and predominantly located along the arcades; (2) circumferential fibrotic scars in the posterior pole with a spared center and large fibrotic scars around the optic nerve head; and (3) yellow dots in areas of relatively normal-appearing retina. CONCLUSIONS AND RELEVANCE Enhanced Scone syndrome has more pleiotropy than previously appreciated. While the nummular type of pigmentation at the level of the retinal pigment epithelium and cystoid or schisis-like maculopathy with typical functional findings remain classic hallmarks of the disease, changes such as circumferential fibrosis of the macula or peripapillary area and "torpedo-like" lesions along the vascular arcades may also direct the clinical diagnosis and focus on screening the NR2E3 gene for a molecular diagnosis.
S-cone function in patients with retinitis pigmentosa
Investigative ophthalmology & visual science, 1994
To determine whether short-wavelength-sensitive (S-) cones are more severely damaged in patients with retinitis pigmentosa than long-wavelength-sensitive (L-) and middlewavelength-sensitive (M-) cones. To determine whether there are differences in the amount of Scone damage in patients with dominant versus nondominant inheritance patterns. To accomplish these goals with methods that provide information not furnished by previous studies with two-color increment thresholds. Methods. Acuity mediated by the Scones was measured in 56 patients with retinitis pigmentosa, and the electroretinogram (ERG) generated by the Scones was measured in 11 of these patients. Mixed Land M-cone acuity, mixed Land M-cone ERGs, and clinical full-field rod and cone ERGs were obtained for all patients. Data for both dominant and nondominant patient groups were compared with data from age-matched normal subjects. Results. Only the nondominant group had reduced Scone acuity, and 43% of patients in this group had selective reduction of Scone acuity. In this particular sample the dominant and nondominant groups were comparable in clinical full-field ERG parameters and mixed Land M-cone acuity, so the difference in Scone acuities is not due to the dominant group having less advanced retinal degeneration. All 11 patients tested had reduced Scone ERGs, 6 with significantly greater loss in the Scone ERG than in the mixed Land M-cone ERG. Conclusions. These data provide evidence that retinitis pigmentosa can produce greater loss of Scones than Land M-cones, and that this selective loss is primarily seen in patients with nondominant forms of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1993; 34:3045-3055. L ritan color vision defects are common in patients with retinitis pigmentosa (RP), 1 but it is not certain 23 if RP causes more severe damage to the short-wavelength-sensitive (S-) cones than to the long-wavelength-sensitive (L-) or middle-wavelength-sensitive (M-) cones. It is clear that RP does not affect all types of photoreceptors equally, because one of the hallmarks of RP is greater damage to the rods than to the cones. In a number of ways the Scones are more similar to the rods than to the Land M-cones. Carbonic anhydrase is present in Land M-cones but not in Scones or rods, 4 and the S-antigen (a protein that regulates phototransduction) common to rods and Scones is different from the S-antigen in Land M-cones. 5 ' 6 The calcium metabolism of Scones may be more simi
Progress in Retinal and Eye Research, 2003
Electroretinography (ERG) is a non-invasive method that can contribute to a description of the functional organization of the human retina under normal and pathological circumstances. The physiological and pathophysiological processes leading to an ERG signal can be better understood when the cellular origins of the ERG are identified. The ERG signal recorded at the cornea is initiated by light absorption in the photoreceptors which leads to activity in the photoreceptors and in their post-receptoral pathways. Light absorption in distinct photoreceptor types may lead to different ERG responses caused either by differences between the photoreceptors or between their post-receptoral pathways. The description of contributions of the different photoreceptor types to the ERG may therefore give more detailed insight in the origins of the ERG. Such a description can be obtained by isolating the responses of a single photoreceptor type. Nowadays, careful control of differently colored light sources together with the relatively well-known cone and rod fundamentals enables a precise description and control of photoreceptor excitation. Theoretically, any desired combination of photoreceptor excitation modulation can be achieved, including conditions in which the activity in only one photoreceptor type is modulated (silent substitution). In this manner the response of one photoreceptor type is isolated without changing the state of adaptation. This stimulus technique has been used to study the contribution of signals originating in the different photoreceptor types to the human ERG. Furthermore, by stimulating two or more photoreceptor types simultaneously, the interaction between the different signals can be studied. With these new techniques results of measurements in healthy subjects and patients with retinal diseases can be compared. This approach should ultimately help to develop better diagnostic tools and result in a fuller description of the changes and the pathophysiological mechanisms in retinal disorder. Finally, data obtained with cone and rod specific stimuli may lead to a reinterpretation of the standard ERG used in a clinical setting.