Senile macular degeneration and geographic atrophy of the retinal pigment epithelium.

The case is reported of a man who had oval areas of atrophy of the retinal pigment epithelium in paracentral areas which previously had heavy concentrations of drusen OU. This supports the suggestion by others that atrophy of the RPE in senile macular disease may in some cases occur in the absence of previous serous detachment of the RPE.     

Progressive atrophy of retinal pigment epithelium after trypan-blue-assisted ILM peeling for macular hole surgery

We report a case of progressive atrophy of the retinal pigment epithelium (RPE) after trypan-blue-assisted peeling of internal limiting membrane (ILM) for macular hole surgery. A 68-year-old Caucasian female underwent a 20-g pars plana vitrectomy for a chronic stage-3 macular hole. The ILM was stained with 0.06% trypan blue (VisionBlue™, DORC Netherlands) for 2 min after fluid air exchange. Dye was reapplied for another 2 min due to poor staining. The ILM was completely removed around the macular hole with forceps. RPE atrophy was noticed at the edge of the hole 1 month after surgery. It progressively increased in intensity and enlarged over 2 years. Her final visual acuity was counting fingers, significantly worse compared to her presenting visual acuity of 20/200. Progressive atrophy of RPE in our patient was most likely due to the toxicity of trypan blue. Reapplication of the dye may increase the likelihood of toxicity.     

Geographic atrophy of the retinal pigment epithelium

We followed the clinical course of 29 eyes with geographic atrophy of the retinal pigment epithelium and identified three phases of the disease through which the eyes progressively evolved. In the initial phase, eyes showed focal discrete areas of atrophy of the retinal pigment epithelium in the parafoveal area. These eyes retained good visual acuity for many years. The second phase was characterized by foveal involvement in which there was a precipitous loss in visual acuity. Foveal involvement included coarse foveal granularity, thinning of the foveal retinal pigment epithelium, increasing encirclement of the fovea with focal areas of atrophy, and minimal macular drusen. The end stage of the disease was a confluent, usually circular, area of atrophy that involved the entire central macula.     

Senile macular degeneration. The involvement of giant cells in atrophy of the retinal pigment epithelium

Senile macular degeneration (SMD) is a leading cause of registered blindness in the United States and other Western countries. Loss of central vision develops as a result of atrophy of the retinal pigment epithelium or subretinal neovascularisation. The histopathology of the atrophic form of SMD has not been extensively studied. This paper illustrates at the light and electron microscope level the involvement the atrophic form of SMD. Additional features including pigment clumping and detachment of the retinal pigment epithelium at the advancing edge of the lesion are illustrated. Giant cells and MPS cells are typical features of granulomatous inflammation, and results suggest that they may play a role in the pathogenesis of SMD.     

Foveal congenital hypertrophy of the retinal pigment epithelium in the setting of geographic atrophy from age-related macular degeneration

PURPOSE: To report a case of presumed congenital hypertrophy of the retinal pigment epithelium in the fovea of an 88-year-old woman in the setting of geographic atrophy from age-related macular degeneration. DESIGN: Observational case report. METHODS: An 88-year-old woman was examined. RESULTS: Best-corrected visual acuity was 20/63 in the right eye and 20/50 in the left eye. Multifocal areas of geographic atrophy and large-sized drusen were seen in the maculae of both eyes. Biomicroscopic examination of the right eye showed hyperpigmentation consistent with congenital hypertrophy of the retinal pigment epithelium through the center of the macula. No prior photographic documentation of the retina was available. CONCLUSION: This case suggests that foveal congenital hypertrophy of the retinal pigment epithelium may be seen in the setting of macular geographic atrophy. Although it is theoretically possible that the hyperpigmentation is reactive rather than congenital, the pigmentation is typical for congenital hypertrophy and is unlike any reactive pigmentation in our experience or described in a MEDLINE search of features of age-related macular degeneration. The case suggests that a hypertrophic process of the retinal pigment epithelium may coexist within or immediately adjacent to the anatomic boundaries of an atrophic process such as geographic atrophy from age-related macular degeneration.     

Juvenile macular serous detachment of the retinal pigmented epithelium

Juvenile macular detachment of the retinal pigmented epithelium is a rare chorioretinal disease, more frequent in young people, with a macular or extramacular localization, single or multiple, and with a good functional prognosis. We present 9 patients (11 eyes), with a mean age 41 years. The disease presented a single localization in 8 cases, a multiple localization in 9 cases, was unilateral in 9 cases, and bilateral in 2 cases. Clinical aspects, pathogeny and functional prognosis are discussed.     

Persistent subretinal indocyanine green induces retinal pigment epithelium atrophy

PURPOSE: To describe a case of a patient with macular hole with subretinal indocyanine green (ICG) during vitrectomy. DESIGN: Interventional case report. METHODS: A 66-year-old woman with macular hole underwent a vitrectomy with ICG. RESULTS: After application of ICG into the vitreous, ICG was introduced in the subretinal space. Indocyanine green was found to be present for more than 6 months. Retinal pigment epithelium atrophy appeared at the site of the lesion. CONCLUSIONS: Although ICG may be a useful tool for distinguishing the internal limiting membrane and other tissues careful application is required to prevent side effects.     

Protecting the retinal pigment epithelium during macular hole surgery

Herein a new surgical technique used during pars plana vitrectomy with internal limiting membrane peeling for macular hole surgery is reported. Perfluorocarbon liquid is used to tamponade the macular hole in order to prevent indocyanine green contact with the retinal pigment epithelium.     

A case of acute diffuse atrophy of retinal pigment epithelium

PURPOSE: To report a case of acute bilateral visual disturbance where the ocular fundus changed like retinitis pigmentosa in a short time. PATIENT: 26-year-old man. FINDINGS: In initial examination, the patient's visual acuity was 0.01 OD and 0.02 OS with myopic correction, but his fundus did not look abnormal. Fluorescein angiogram showed marked background hyperfluorescence and dye leaking to the vitreous. After 2-3 weeks, the fundus appearance changed like retinitis pigmentosa. Best corrected visual acuity became 1.0 OD and 0.9 OS after steroid pulse therapy. We were unable to find the cause of this disease in spite of blood tests and other examinations. CONCLUSION: This case with acute diffuse atrophy of retinal pigment epithelium and damage of the function of blood-retinal barrier was considered remarkably rare.     

Delayed atrophy of the retinal pigment epithelium after submacular surgery

PURPOSE: We report a case of delayed atrophy of the retinal pigment epithelium (RPE) eighteen months after apparently successful excision of submacular choroidal new vessels (CNV) in a patient with age-related macular degeneration (AMD). METHODS: Case report. RESULTS: Submacular surgery for CNV was achieved without visible disturbance of the underlying RPE in an 83 year old man diagnosed with AMD. At the time of surgery the CNV displayed clinical features consistent with lying internal to Bruch's membrane (Type 2 configuration). There was no visible RPE defect at the fovea and vision improved during the subsequent 12 months follow-up. Eighteen months later, however, an atrophic central RPE defect appeared, with a similar shape to the CNV originally excised. CONCLUSIONS: This case demonstrates that submacular CNV with Type 2 configuration can occur in AMD and lead to an initially favourable outcome following submacular surgery. Atrophy of the RPE nevertheless did eventually occur and in a pattern consistent with damage during the original operation. It is important to consider results of longer term follow-up when interpreting success rates for surgery in AMD.     

Natural history of incomplete retinal pigment epithelial and outer retinal atrophy in age-related macular degeneration

ObjectiveTo assess the time course and risk factors for conversion of incomplete retinal pigment epithelium and outer retina atrophy (iRORA) to complete retinal pigment epithelium and outer retina atrophy (cRORA) in eyes with non-neovascular intermediate age-related macular degeneration (iAMD), using optical coherence tomography (OCT) analysis.DesignRetrospective survival study.ParticipantsTracked structural Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) volume datasets from 2 retinal specialists at the University of California–Los Angeles were retrospectively screened to identify consecutive participants with non-neovascular iAMD without signs of atrophy or macular neovascularization in either eye at baseline.MethodsIn the first stage of selection, 321 consecutive iAMD eyes were screened for onset of iRORA. Eyes that developed iRORA within the first 24 months were followed for an additional 24 months to assess the rate of conversion to cRORA. A Kaplan-Meier survival curve was formulated to illustrate the conversion from iRORA to cRORA.ResultsAmong 321 baseline participants with iAMD, 87 incident iRORA lesions (50 eyes, 42 participants) were included in the conversion analysis. Eighty-one iRORA lesions (93.1%) converted to cRORA within 24 months (median 14 months). Multivariate binary logistic regression analysis indicated that intraretinal hyperreflective foci and extrafoveal iRORA location at baseline were associated with a faster rate of progression to cRORA (model R² = 0.816, p < 0.05).ConclusionsThe majority of incident iRORA lesions progress to cRORA within a 24-month period. These findings may be of value in the design of early intervention trials for risk stratification and prognostication but need to be validated with a prospective analysis.     

Autoradiographic studies of aged primate macular retinal pigment epithelium.

The authors used 35S-sulfate and 3H-proline to trace labeled molecules in autoradiograms of aged monkey and human macular retina to detect the synthesis of extracellular matrix (ECM) components by retinal pigment epithelial (RPE) cells. Quantitative analysis of silver grains 6 hr and 3 d after intravitreal injection of 35S-sulfate in the monkey showed that secretion from the basal pole of the RPE occurs at a slower rate than from the apical pole. In vitro incubation of human maculas produced poor autoradiographs with 35S-sulfate. Good autoradiographs were obtained using 3H-proline. Human macular RPE showed uneven labeling, but densely labeled cells did not correlate with sites of basal linear deposits, ECM though to be basement membrane material, and a hallmark of age-related maculopathy. The time course of labeling in adult primate tissue showed a fairly high turnover rate for these molecules. Scant labeling of ECM at drusen sites and no labeling in basal linear deposits suggested that either (1) these structures have a slow turnover or (2) their components contain scant sulfate and proline. Alternatively, faulty degradative processes rather than enhanced synthesis may account for the accumulation of abnormal ECM at the RPE-Bruch's membrane interface in aged maculas.     

Concentric retinal pigment epithelium atrophy after a single photodynamic therapy

PURPOSE: To report a case with concentric retinal pigment epithelium (RPE) atrophy after a single photodynamic therapy (PDT). METHODS: We report a case of a 33-year-old female patient who developed RPE atrophy after a single standard PDT for treatment of a juxtafoveal, predominantly classic choroidal neovascularization (CNV). RESULTS: After a single PDT treatment, visual acuity increased from 20/50 to 20/20. Six weeks after PDT, a concentric area of RPE atrophy was clearly visible on fluorescein angiogram. This circular area corresponded to the 3500 microm diameter of the laser spot used in the PDT treatment. The visual acuity and the RPE atrophy remained stable over the follow-up period of 3 years. CONCLUSIONS: We are unable to explain the exact mechanism of the observed RPE changes; however, they did not lead to loss of visual acuity. Different reasons for the RPE atrophy such as collateral damage of the choriocapillaris with a subsequent secondary RPE atrophy, a direct photochemical effect due to the early localization of the photosensitizer in the RPE, or a depigmentation or photobleaching of the RPE, which led to a window defect in the fluorescein angiogram without loss of the major functional properties of the RPE, are possible mechanisms involved in the development of the documented lesion.     

Development of atrophy of the retinal pigment epithelium around disciform scars

BACKGROUND/AIMS: Eyes with burnt out disciform scars secondary to age related macular degeneration (AMD) are regarded as visually stable. The aim of this study is to report the subsequent development of atrophy of the retinal pigment epithelium (RPE) around the scars and discuss the possible basis. METHODS: 20 eyes from 18 patients were observed to develop atrophy around choroidal neovascularisation (CNV). A method of measuring expansion of the atrophy over time is described using the Topcon Imagenet 2000 system. An additional 10 clinicopathological examples were reviewed. RESULTS: Clinically CNV became surrounded initially by a ring of pallor that progressed to an expanding band of atrophy of the RPE. It developed most rapidly in the first 3 years after CNV became quiescent but then continued to expand slowly to more than three times the size of the scar. Histopathological specimens showed large choroidal vessels entering the scars directly and a reduced number of small choroidal vessels beneath and around the scar CONCLUSIONS: Disciform scars may become surrounded by an expanding band of atrophy of the RPE, postulated to result from remodelling of the choroidal circulation. The ongoing enlargement of the resulting scotoma may need to be considered when planning management and assessing treatment outcomes.     

Antioxidant enzymes in the macular retinal pigment epithelium of eyes with neovascular age-related macular degeneration

PURPOSE: To test the hypothesis that neovascular age-related macular degeneration is related to oxidative stress involving the macular retinal pigment epithelium. This study investigated, as a function of age, levels of enzymes that defend tissues against oxidative stress in the macular retinal pigment epithelium of human eyes with this disease. METHODS: Surgical specimens of macular choroidal neovascular membranes from eyes with age-related macular degeneration and the macular regions of whole donor eyes with neovascular age-related macular degeneration or without evident ocular disease were studied by quantitative electron microscopic immunocytochemistry with colloidal gold-labeled second antibodies. Relative levels in retinal pigment epithelium cell cytoplasm and lysosomes were determined of five enzymes believed to protect cells from oxidative stress, as well as levels of the retinal pigment epithelium marker cytoplasmic retinaldehyde-binding protein, for comparison with the enzymes. RESULTS: Copper, zinc superoxide dismutase immunoreactivity increased and catalase immunoreactivity decreased with age in cytoplasm and lysosomes from macular retinal pigment epithelium cells of normal eyes and eyes with age-related macular degeneration. Cytoplasmic retinaldehyde-binding protein immunoreactivity showed no significant relationship to age or the presence of neovascular age-related macular degeneration. Glutathione peroxidase immunoreactivity was absent from human retinal pigment epithelium cells. Both heme oxygenase-1 and heme oxygenase-2 had highly significantly greater immunoreactivity in retinal pigment epithelium cell lysosomes than in cytoplasm, differing from the much greater cytoplasmic immunoreactivity of the other proteins studied. This immunoreactivity decreased with age, particularly in the lysosomes of retinal pigment epithelium cells from eyes with neovascular age-related macular degeneration. These decreases were of borderline significance (P = .067 for heme oxygenase-1; P = .12 for heme oxygenase-2) when eyes with age-related macular degeneration were compared with normal eyes by multivariable logistic regression. CONCLUSIONS: The high heme oxygenase-1 and heme oxygenase-2 lysosomal antigen levels in macular retinal pigment epithelium cells of eyes with neovascular age-related macular degeneration suggest that oxidative stress causes a pathologic upregulation of these enzymes. Increased lysosomal disposal may indicate that the reparative functions of these enzymes are accompanied by deleterious effects, necessitating their rapid removal from the cell. The much higher heme oxygenase-1 and heme oxygenase-2 antigen levels in macular retinal pigment epithelium cells from younger individuals suggest that protective mechanisms against oxidation and, hence, presumably to the development of age-related macular degeneration, decrease with age.     

光学相干断层扫描技术诊断RPE脱离

目的:观察黄斑区视网膜色素上皮(RPE)脱离的光学相干断层扫描(OCT)图像特征。方法:并发黄斑区RPE脱离的眼底病病例共48例(52眼),进行黄斑区OCT检测,观察其图像特征,并结合FFA结果进行分析。结果:根据形态特征,RPE脱离可分为两种,浆液性RPE脱离和出血性RPE脱离。前者见于部分中心性浆液性脉络膜病例(16例)、特发性浆液性RPE脱离(7例)、部分视网膜下新生血管病变的病例(10例),后者仅见于部分视网膜下新生血管病变的病例(16例)。结论:OCT能够直观形象地显示RPE脱离的形态特征,准确地测量RPE脱离的范围大小。     

Atrophic creep of the retinal pigment epithelium after focal macular photocoagulation

To determine if enlargement of laser scars occurs in nonmyopic individuals, the authors retrospectively reviewed 126 consecutive patients with age-related macular degeneration who had been successfully treated with focal macular laser photocoagulation for subretinal neovascularization. Of the 174 laser scars in the study, 122 (70%) increased in size from 50 to 1016 microns (mean, 290 microns) as determined photographically on serial examination ranging from 2 to 81 months. There was no statistically significant difference in the number of scars which increased in size among the three laser wavelengths used. Four (3%) patients lost vision as a result of the scar extending into the fovea. Enlargement of retinal pigment epithelial (RPE) atrophy after focal macular laser photocoagulation may cause significant, delayed visual loss after successful treatment of subretinal neovascularization.     

Phenotypic variation of retinal pigment epithelium in age-related macular degeneration.

PURPOSE: To determine whether retinal pigment epithelium (RPE) in eyes with age-related macular degeneration (ARMD) express vimentin and alpha smooth muscle actin (alphaSMA), two cytoskeletal proteins associated with phenotypic variation in culture. METHODS: Six eyes with late ARMD and three age-matched control eyes were preserved in buffered 4% paraformaldehyde and cryosectioned at 10 microm. Stages of RPE morphology and pigmentation were assessed by the Alabama Age-Related Macular Degeneration Grading System. Vimentin, alphaSMA, and glial fibrillary acidic protein (GFAP) expression was detected by indirect immunofluorescence. These results were compared with regional variations in disease severity. RESULTS: RPE changes in ARMD included acquired expression of vimentin, but alphaSMA-positive cells were rare. GFAP expression increased in Müller cells in the neural retina in association with RPE changes and photoreceptor degeneration. CONCLUSIONS: The initial stages of RPE changes in eyes with ARMD mimic those reported for cultured RPE cells. The absence of alphaSMA-positive cells in regions of RPE atrophy suggests that RPE are lost rather than persist in a dedifferentiated state.     

Clinical electrophysiology of the retinal pigment epithelium

There is no ideal electrophysiological test for retinal pigment epithelial (RPE) function. The light-induced responses (EOG, c-wave, fast oscillation) that require photoreception are not pure RPE signals, and even the widely-used EOG has not been associated with any specific physiological disturbance of the RPE or retina. The discovery of non-photic RPE responses (hyperosmolarity, acetazolamide and bicarbonate) has enhanced the possibility of finding tissue-specific RPE tests, but these responses have yet to be correlated with specific RPE functional activity or pathology. We may face a dilemma in our search for RPE tests, insofar as electrophysiology measures membrane changes, but RPE membrane activity is related only indirectly to many functions of the RPE cell. These concerns notwithstanding, RPE electrophysiology can be a valuable clinical tool if one accounts for the physiological limitations and assets of the procedures.Presented at the 28th ISCEV Symposium, Guangzhou, China, 10–14 March 1990.