Rod-cone interactions and analysis of retinal disease.

Cone flicker threshold rises as the rods dark adapt, though the cone threshold to continuous light remains constant. The rise is normally about 1 log unit, but in certain patients who complain of night blindness it may be as great as 2.5 log units. In these persons the kinetics of the rod-cone interaction are those of the recovery of rod sensitivity. The rods impose a low-pass filter on the cones. This effect is absent in congenital nyctalopia and X-linked retinoschisis. We suggest that cone flicker is maintained through a feedback system involving horizontal cells, and when the rod dark current returns in dark adaptation this feedback is altered. Rod cone interaction thus tests rod dark current, and cases of abnormal interaction in patients with retinitis pigmentosa occur, which indicate that the transduction mechanism and the membrane dark current may be differentially affected.     

EYS-Associated Sector Retinitis Pigmentosa

Graefe's Archive for Clinical and Experimental Ophthalmology - Sector retinitis pigmentosa (RP) is a rare form of rod-cone degeneration typically associated with mutations in the RHO gene. We...     

Distribution of pigment epithelium autofluorescence in retinal disease state recorded in vivo and its change over time

· Background: Recently a technique of imaging the retinal pigment epithelium (RPE) has been developed that takes advantages of its intrinsic fluorescence derived from lipofuscin. The purpose of this study was to document the distribution of fundus autofluorescence in patients with various retinal diseases and its change over time. · Methods: The intensity and spatial distribution of fundus autofluorescence was documented in 318 eyes from 159 patients with various retinal diseases using a confocal Laser Scanning Ophthalmoscope. Thirty patients with macular dystrophies and 30 with age-related macular disease underwent serial examinations over a period of 1–3 years in order to monitor the changes over time of fundus autofluorescence. · Results: Absent autofluorescence corresponded well spatially with outer retinal atrophy in eyes with retinitis pigmentosa and rod-cone dystrophy. Abnormally high background autofluorescence was seen in the macular region in some patients with dominant and recessive retinitis pigmentosa and rod-cone dystrophies. In areas of macular edema fundus autofluorescence was abnormal. Fundus autofluorescence showed changes over time in most of the eyes with retinal diseases studied. · Conclusion: Fundus autofluorescence allows documentation of areas of photoreceptor cell loss in eyes with retinitis pigmentosa and rod-cone dystrophies. If abnormal high background autofluorescence in the surviving areas occurs only in some patients with retinitis pigmentosa, the technique may serve to distinguish the regional from the diffuse type of disease. Over time, fundus autofluorescence may demonstrate change or may remain stable. Received: 14 August 1997 Revised version received: 28 January 1998 Accepted: 4 March 1998     

Retinal histopathology of an autopsy eye with advanced retinitis pigmentosa in a family with rhodopsin Glu181Lys

PURPOSE: To compare histologic findings in an autopsy eye of an 84-year-old man with advanced retinitis pigmentosa and rhodopsin, Glu181Lys, with two cases of autosomal dominant retinitis pigmentosa (one with rhodopsin, Pro23His, and one with rhodopsin, Cys110Arg) and with a normal control, all of comparable age. METHODS: All eyes were prepared for light and electron microscopy within 6 hours after death. RESULTS: Extensive photoreceptor degeneration was revealed in the eyes with retinitis pigmentosa. Some macular cones showed membranous swirls only in the eye with rhodopsin, Glu181Lys. CONCLUSION: The retinal degeneration caused by rhodopsin, Glu181Lys, can feature membranous swirls in the inner segments of cones in the macula. These swirls have not been reported in other cases of dominant retinitis pigmentosa studied so far, and their pathogenesis remains to be defined.     

Vitreous fluorophotometry in patients with cone-rod dystrophy.

Eight patients with cone-rod dystrophy were examined by means of vitreous fluorophotometry. The data in three patients with an early stage of retinitis pigmentosa (rod-cone dystrophy) served for comparison. In contrast with the abnormal findings on vitreous fluorophotometry in patients with an early stage of retinitis pigmentosa the value of vitreous fluorophotometry in cone-rod dystrophy was within the normal range in all patients except the two with advanced stages of this disease. Our results suggest that, although both diseases are based on diffuse dystrophy of photoreceptors, and the final stages of the two diseases may show several similar features, the process of breakdown of the blood retinal barrier differs greatly in the two diseases.     

Rod-cone interaction in flicker perimetry: evidence for a distal retinal locus

The luminance threshold for the detection of 25 Hz flicker was measured in nine patients with retinal disorders under stimulus conditions that have been shown previously to involve an interaction between rod and cone systems. The disorders studied included congenital stationary nightblindness, X-linked juvenile retinoschisis, hereditary dominant optic atrophy, optic atrophy found in association with neurofibromatosis, retinitis pigmentosa, choroideremia, and an acquired diffuse photoreceptor disorder, all of which involve pathologic changes that are presumed to occur primarily at specific levels of the retina. The results are consistent with a distal (outer) retinal locus for the rod-cone interaction.     

Histologic study of retinitis pigmentosa due to a mutation in the RP13 gene (PRPC8): comparison with rhodopsin Pro23His, Cys110Arg, and Glu181Lys

PURPOSE: To evaluate the retina in autopsy eyes from patients over age 60 with autosomal dominant retinitis pigmentosa and a mutation in the RP13 gene (designated as PRPC8, Arg2310Gly), rhodopsin Pro23His, rhodopsin Cys110Arg, or rhodopsin Glu181Lys. DESIGN: Histologic study of the retina. METHODS: All eyes were prepared for electron microscopy within 12 hours after death. RESULTS: All eyes showed loss of rod photoreceptors. Remaining cones showed perinuclear membranous swirls, inclusion bodies in the inner segments, and shortened or absent outer segments despite causation by various gene defects. CONCLUSION: The comparable histologic findings in these four cases suggest a final common pathway leading to photoreceptor cell death in these dominant forms of retinitis pigmentosa.     

Vision threshold profiles in X-linked retinitis pigmentosa.

Absolute thresholds for blue-green and red stimuli were measured along the horizontal and vertical meridans in two patients with X-linked retinitis pigmentosa. From these data, we deduced that cones mediate detection of both stimuli in the central 10 degrees, there is a ring scotoma in the mid-periphery, and in the far periphery rods mediate detection of both stimuli. Conclusions drawn from the psychophysical measures about rod and cone function across the retina are in point-by-point agreement with the data of a recent electron microscopic study by Szamier et al. on the retina of a 24-year-old X-linked retinitis pigmentosa patient.     

Concentric retinitis pigmentosa: clinicopathologic correlations

Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective or modify photoreceptor degeneration in concentric retinitis pigmentosa.     

Retinal pigmentary degeneration--clinical features, diagnostics and possibilities of treatment

The purpose of this study was to evaluate clinical course of retinitis pigmentosa taking into consideration models of inheritance and possible treatment. Retinitis pigmentosa belongs to heterogeneous group of hereditary disorders, which are connected with gradual loss of the photoreceptor function, firstly rod cells subsequently cones, which is accompanied by the retinal pigmentary epithelium disorder. Retinitis pigmentosa connected with X chromosome is one of the most severe form of this disease that in polish population takes place with frequency at average 10-15% which is similar to ADRP--10-20%. Course of RP, despite many similarities may differ from each other and prognosis depends on model of inheritance. Unfortunately, in spite of many efforts, nowadays medicine do not have successful treatment for patients with RP.     

Psychophysical studies of cone optical bandwidth in patients with retinitis pigmentosa

Estimates of variation in the alignment of cones with the pupil were obtained from the fovea and parafovea in normal subjects and in patients with retinitis pigmentosa known to have reduced directional sensitivity. The degree of cone disarray was inferred from differences in sensitivity between Stiles-Crawford functions obtained with a stimulus alone and with the stimulus superimposed on a background entering the pupil at a point corresponding to the peak of the Stiles-Crawford function. The magnitude of the selective effect of the background in normals was consistent with previous estimates of variations in photoreceptor alignment in the macula. In contrast, the selective adaptation effect was not present in patients with retinitis pigmentosa. These results exclude increased disarray among cones with normal optical bandwidths, but rather, suggest that morphological abnormalities increasing the optical bandwidths of individual cones underlie reduced directional sensitivity in these patients.     

Abnormalities in rod photoreceptors, amacrine cells, and horizontal cells in human retinas with retinitis pigmentosa

PURPOSE: To evaluate changes in the rods and amacrine cells and horizontal cells in human retinas with retinitis pigmentosa. METHODS: Seven retinas from patient donors with retinitis pigmentosa and 14 age- and postmortem-matched normal human retinas were processed for immunocytochemistry and confocal microscopy. The following cell-specific antibodies were used: anti-rhodopsin (rods), anti-gamma-aminobutyric acid (amacrine cells), anticalbindin (cones and horizontal cells), anti-glial fibrillary acidic protein (astrocytes and reactive Müller cells), and anti-synaptophysin and anti-SV2 (synaptic vesicles). RESULTS: In retinal regions with significant photoreceptor loss, the rods, gamma-aminobutyric acid-positive amacrine cells, and calbindin-positive horizontal cells had undergone neurite sprouting. The rod, amacrine and horizontal cell neurites were associated with the surfaces of glial fibrillary acidic protein-immunoreactive Müller cells. Most rod neurites that projected into the inner retina contacted the somata of gamma-aminobutyric acid-positive amacrine cells. CONCLUSIONS: Rods, amacrine and horizontal cells undergo neurite sprouting in human retinas with retinitis pigmentosa. These changes in the retinal neurons may contribute to the electroretinographic abnormalities and progressive decline in vision noted by patients with retinitis pigmentosa. These alterations may also complicate strategies for treatment of retinitis pigmentosa.     

Retinal histopathology of a carrier of X-chromosome-linked retinitis pigmentosa

Autopsy eyes were examined from a 79-year-old female carrier of X-chromosome-linked retinitis pigmentosa. At age 78 years, she had no visual symptoms but had intraretinal bone spicule pigmentation in the nasal and inferior periphery of both eyes. Rods, cones, and pigment epithelium in the central retina appeared normal. In the midperiphery, patches with advanced photoreceptor cell degeneration were observed overlying pigment epithelium containing melanolysosomes. Within these patches, rods and cones were reduced in number or absent, and pigment epithelial cells abutted the external limiting membrane. A precipitous decline in rod nuclei was observed in transitional zones between areas of apparently normal photoreceptors and areas of absent photoreceptors. In the far periphery, large areas lacked photoreceptors and pigment epithelium. Histopathologic findings in this elderly carrier are compared with those previously described in a 24-year-old man with X-chromosome-linked retinitis pigmentosa.     

Atypical association of Duane retraction syndrome and Bardet Biedl syndrome

Duane's retraction syndrome (DRS) includes changes in palpebral fissure width along with restriction of ocular motility. Bardet Biedl syndrome (BBS) includes presence of retinitis pigmentosa (RP) with obesity, mental retardation, polydactyly and renal abnormalities. We report a case of rare association of DRS with BBS in a seven-year-old child. The ocular motility examination revealed left DRS with esotropia. Fundus examination revealed findings characteristic of an atypical retinitis pigmentosa. The electro-retinogram waveforms were extinguished both for rods and cones. He was diagnosed as a case of BBS on the basis of the ophthalmological findings plus association with the systemic features of obesity, polydactyly, hypogonadism, mental retardation and renal abnormalities. This case gives further evidence of the fact that BBS may be associated with abnormalities of eye movements.     

Autosomal dominant retinitis pigmentosa: a log quotient analysis of the photopic and scotopic b-wave amplitude.

The relationship of the photopic and the scotopic b-wave amplitudes of the electroretinogram was studied in 85 normal subjects and 25 patients with autosomal dominant retinitis pigmentosa, in which one amplitude was at least 20 microvolts. The log quotient of their b-wave amplitudes--that is log of the photopic b-wave amplitude divided by the scotopic b-wave amplitude--was considered to represent the activity of cones relative to rods. The log quotient values had a normal gaussian distribution in the normal control eyes, while they formed two groups in the patients with autosomal dominant retinitis pigmentosa. In the first group (type 1), the scotopic b-wave was non-recordable while the photopic b-wave amplitude was larger than 20 microvolts in all cases, indicating that the log quotient is larger than 0.5 and that the rod system is much more severely affected than the cone system. The second group (type 2) had a log quotient smaller than 0.5 and its distribution almost overlapped the normal one, indicating more symmetrical damage in the cone and rod systems. The mean final rod threshold at 45 minutes for type 1 was significantly higher than that for type 2. The log quotient proved to be a useful index for analysing the cone and rod involvement and consequently provides a better understanding of autosomal dominant retinitis pigmentosa.     

Association of antiretinal antibodies and cystoid macular edema in patients with retinitis pigmentosa.

PURPOSE: To report the association of antiretinal antibodies in patients with bilateral cystoid macular edema and retinitis pigmentosa. METHODS: In a prospective study, 30 consecutive patients with bilateral cystoid macular edema and retinitis pigmentosa were tested for antiretinal antibodies. As control subjects, 30 consecutive patients with retinitis pigmentosa who did not have cystoid macular edema and 50 normal subjects without retinitis pigmentosa or cystoid macular edema were tested for antiretinal antibodies. Laboratory personnel performing the antiretinal antibody testing were masked regarding the diagnosis of each patient. RESULTS: Twenty-seven (90%) of 30 patients with retinitis pigmentosa with cystoid macular edema had antiretinal protein antibody activity, compared with three (6%) of 50 normal controls (P < .001) and only four (13%) of 30 control patients with retinitis pigmentosa (P < .001). CONCLUSIONS: We found a significant association between cystoid macular edema and the presence of circulating antiretinal antibodies in patients who presented with retinitis pigmentosa and cystoid macular edema. This study suggests that patients with retinitis pigmentosa with cystoid macular edema may have an autoimmune process that is contributing to the formation of cystoid macular edema in retinitis pigmentosa, but to date, there is no direct evidence that the cystoid macular edema is caused by the antiretinal antibodies.     

Retinitis Pigmentosa: A Review of the Tapeto-Retinal Dystrophies

ABSTRACT: The signs and symptoms, clinical course, underlying pathology, hereditary characteristics and management of retinitis pigmentosa are reviewed. Aberrant forms of retinitis pigmentosa are discussed and those syndromes in which retinitis pigmentosa feature are listed.     

视网膜色素变性的研究进展

视网膜色素变性(retinitis pigmentosa,RP)是常见的与遗传相关的致盲性眼病之一,随着人类基因图谱的成功建立,它成为近几年国内外基础医学和临床医学共同的研究热点。本文回顾十余年来国内外特别是国外相关文献,对视网膜色素变性的发病机制、治疗方法的研究进展作一综述。     

Retinitis pigmentosa and allied diseases: applications of electroretinographic testing

Electroretinograms (ERGs) have provided criteria for establishing the diagnosis of retinitis pigmentosa in early life even at a time when fundus abnormalities visible with the ophthalmoscope are minimal or absent. Patients with widespread progressive forms of retinitis pigmentosa have shown not only reduced amplitudes but also delays in cone or rod b-wave implicit times, or both, while patients with self-limited sector retinitis pigmentosa or stationary forms of night blindness have had reduced amplitudes with normal b-wave implicit times. In families with retinitis pigmentosa ERGs can be used not only to identify which patients are affected but also to establish which patients are normal as those patients, age 6 and over, with normal cone and rod amplitudes and normal cone and rod b-wave implicit times have not been observed to develop primary retinitis pigmentosa at a later time. ERGs from patients with retinitis pigmentosa and allied night blinding disorders are presented to show their usefulness in genetic typing, documenting natural histories, and defining possible pathogenetic mechanisms. The potential application of the ERG in evaluating the efficacy of therapeutic trials is also considered.Presented in part as the Alex E. Krill Memorial Lecture before The Chicago Ophthalmological Society, Chicago, Illinois, October 15, 1979.This research was supported in part by Specialized Research Center Grant EY02014 from the National Institutes of Health and in part by the National Retinitis Pigmentosa Foundation, Baltimore, Maryland and the George Gund Foundation, Cleveland, Ohio, U.S.A.     

580眼视网膜色素变性患者ERG改变的研究

统计和分析了580眼视网膜色素变性患者的视力、视野、暗适应和ERG检查结果。讨论了ERG与患者年龄、性别、视力、视野、暗适应之间的关系。指出ERG波型熄灭是视网膜色素变性的临床特征之一。ERG检查在视网膜色素变性患者的诊断(特别是早期诊断)、治疗以及预后等方面有重要意义。