Retinal Pigment Epithelium Lesions Research Articles

Reduction of iatrogenic RPE lesions in AMD patients: evidence for wound healing?

Our purpose was to study retinal pigment epithelium (RPE) wound healing in patients with age-related macular degeneration (AMD). Abrasive debridement of nasal RPE was performed with a metal cannula during pars plana vitrectomy for foveal choroidal neovascularization (CNV) membrane excision combined with simultaneous autologous RPE transplantation. Fundus autofluorescence, fluorescein angiography images, and red-free pictures were taken initially within 1-2 weeks postoperatively, subsequently in 2-week intervals until 3 months, monthly until 6 months, and every 3 months thereafter. The borders of these lesions were measured; areas were calculated and compared using ArchiCad Software. Fourteen eyes of 14 patients suffering from AMD were included (nine women and four men, mean age 75.6 years +/-6.6 years). Six of 14 (42.9 %) patients showed a reduction of the RPE debrided area. The size of these lesions reduced 5.6-20% within 2 postoperative months compared with their size at first examination (from a mean of 13.7 mm2 +/- 7.2 at baseline to a mean of 12.8 mm2 +/- 6.7 at 2 months postoperatively). No further reduction of the lesions was seen after the 2 months. In eight cases, borders of the RPE debrided areas stayed stable during observation time. Wound healing of abrasively debrided RPE monolayer defects in patients with AMD occurs to a certain extent in nearly half of the cases. This process seems to stop after 2 months.

Controlling Retinal Pigment Epithelium Injury after Experimental Detachment of the Retina

Damage induced by detachment of the neural retina and the retinal pigment epithelium (RPE) can be reduced by dark adaptation. The authors evaluated the influence of the duration of dark adaptation, time of day, and modification of the melatonin-dopamine pathway on acute RPE lesions induced by mechanical detachment. BALB/c mice were studied at different times of day and different periods of dark adaptation. Some mice were treated with melatonin or sulpiride, a D2 dopamine receptor antagonist. Enucleated eyes and different saline solutions were used in experiments ex vivo. Retinal detachments in vivo were made by subretinal injections of hyaluronic acid. RPE cell damage was quantitatively evaluated with a dye exclusion procedure, and their viability was tested by preservation of tight junctions in culture. Lectin histochemistry was used to examine the interphotoreceptor matrix (IPM). Significant propidium iodide (PI) incorporation in RPE cells was detected after ex vivo separation during daytime, but it was very low when detachment took place at night after 24 to 48 hours of dark adaptation. PI exclusion was achieved during daytime after a single hour of dark adaptation when mice were pretreated with melatonin or sulpiride. Reduction of RPE cell damage was accompanied by decreased lectin binding to cone sheaths. A combination of time of day and length of dark adaptation decreased damage induced by detachment of the retina ex vivo and in vivo. Melatonin or sulpiride could replace these environmental factors. Therefore, melatonin and dopamine pathways might be involved in the control of IPM properties and retina/RPE interactions.

Three-dimensional optical coherence tomographic findings in central serous chorioretinopathy

The purpose of this study was to evaluate three-dimensional optical coherence tomographic findings at the leakage point on fluorescein angiography in central serous chorioretinopathy (CSC) with OCT-ophthalmoscope. Twenty-seven eyes of 26 patients (23 men, three women; mean age, 50 years; range, 30-72) diagnosed with CSC were examined with OCT-ophthalmoscope, and transverse and longitudinal images were compared with fundus and fluorescein angiography findings. Transverse images (C-scan) clearly showed serous retinal detachment in all eyes and irregular lesions in retinal pigment epithelium (RPE) in 26 of 27 eyes (96%). These results agreed with the location of lesions in areas of fluorescein dye leakage on fluorescein angiography. Longitudinal images (B-scan) of irregular RPE lesions in transverse images showed RPE detachment (PED) in 17 eyes (63%), small protrusion of the RPE layer in five eyes (19%), and rough RPE layer in four eyes (15%). OCT-ophthalmoscope detects morphologic changes easily and noninvasively at the point of dye leakage in eyes with CSC.

Depigmented atrophic lesions in sunset glow fundi of Vogt-Koyanagi-Harada Disease

PURPOSE: Although the depigmented, small, round to oval lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are considered to represent Dalén-Fuchs nodules, there is no histopathologic evidence to support such a consideration. An attempt is made herein to clarify the nature of the atrophic lesions and distinguish them from Dalén-Fuchs nodules seen in eyes with Vogt-Koyanagi-Harada disease. METHODS: Eyes from five individuals with clinical diagnoses of Vogt-Koyanagi-Harada disease were subjected to histopathologic examination. The retinal pigment epithelial changes from early active to convalescent and late chronic recurrent stages were evaluated. Particular attention was paid to Dalén-Fuchs nodules, depigmented lesions in the sunset glow fundi, and hyperpigmentation of the chronic recurrent stage. RESULTS: Eyes of two individuals, one in the active stage of Vogt-Koyanagi-Harada disease and the other in the convalescent stage, showed the presence of Dalén-Fuchs nodules. The depigmented small retinal pigment epithelial lesions were seen in two individuals, both of whom exhibited the sunset glow fundus of the convalescent stage. The retinal pigment epithelial lesions represented damage or disappearance of retinal pigment epithelial cells, and the sunset glow fundus appearance was from the loss of choroidal melanocytes. The heavy pigmentation seen in fundi with the chronic recurrent stage was the result of the proliferation of retinal pigment epithelial cells. CONCLUSION: The Dalén-Fuchs nodule is a specific histologic change observed at the level of retinal pigment epithelium in patients with Vogt-Koyanagi-Harada disease. There is no histologic confirmation that the depigmented small atrophic lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are Dalén-Fuchs nodules. The depigmented lesions represent localized damage or disappearance of retinal pigment epithelial cells.

Ocular findings in familial adenomatous polyposis.

Retinal pigment epithelium (RPE) lesions are predictive congenital phenotypic markers for familial adenomatous polyposis (FAP). This prospective screening study aims at assessing the incidence and significance of these lesions in FAP patients and their family members. Sixty-two members from three families including five patients with the diagnosis of FAP have been ophthalmologically surveyed. All RPE lesions were documented with fundus photography and fluorescein angiography was performed in 13 subjects. Sigmoidoscopy and/or radiological examination were performed annually in 9 family members with typical RPE lesions during 4 years to allow early diagnosis of FAP. Typical RPE lesions were present in five FAP patients and 15 family members. Telangiectatic dilatations in the retinal periphery with small dot-like hemorrhages were detected in 6 subjects from 3 families These lesions were particularly evident on fluorescein angiography. Annual colon analysis showed polyps in 3 out of 9 subjects who were positive for RPE lesions. RPE lesions are valuable as a clinical marker in predicting FAP. The co-existing peripheral vascular alterations which have not been reported before, are probably related to FAP.

Angiographic abnormalities of experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) is an invaluable animal model for studying inflammatory eye disease in humans. Indocyanine green (ICG) is a fluorescent dye that can be used to image both retinal and choroidal vessels. This study was performed to examined the retinal and choroidal vascular abnormalities of a rat model of EAU using ICG and fluorescein as the contrast media to assess the suitability of this model for studying ICG angiographic abnormalities in inflammatory eye disease in humans. Twenty-six black-hooded Lister rats were inoculated with bovine retinal S-antigen plus adjuvant with or without Bordetella pertussis antigen. Fluorescein and ICG angiograms were performed at different stages of clinical disease with a scanning laser ophthalmoscope. EAU was more severe and primarily choroidal disease in rats given Bordetella pertussis, but no animals showed evidence of dye leakage from large choroidal vessels. There was frank leakage of indocyanine green from retinal vessels. Leakage of both fluorescein and ICG retinal vessels largely correlated with disease activity. Retinal pigment epithelial lesions either corresponded to areas of hypofluorescence on the ICG angiogram alone or were represented by areas of ICG hyperfluorescence that had overlying areas of fluorescein leakage from retinal capillaries. This study has demonstrated the vascular abnormalities of this model of EAU using ICG and fluorescein as the contrast media. The suitability of this method for studying ICG angiographic abnormalities in inflammatory eye disease in humans is encouraging.

Retinal Pigment Epithelium Lesions as a Biomarker of Disease in Patients with Familial Adenomatous Polyposis: A Follow-up Report

The sensitivity of retinal pigment epithelium (RPE) lesions as a predictive congenital marker for the development of familial adenomatous polyposis (FAP) is evaluated. In a prospective study, 34 patients at 50% risk of inheriting FAP were examined. Based on the presence or absence of four or more RPE lesions, patients were categorized as those who had inherited or those who lacked the FAP genes. All patients received dilated fundus examinations with binocular indirect ophthalmoscopy and all RPE lesions were documented with fundus photography. All patients underwent annual sigmoidoscopy to determine the presence or absence of polyps. A 3-year follow-up analysis showed that 8 of 14 patients who were positive for RPE lesions later developed polyps. Of the 20 patients considered negative for FAP based on normal fundus examination, none has developed polyps. The authors urge all patient at risk of inheriting FAP to undergo dilated fundus examination with binocular indirect ophthalmoscopy and wide-angle fundus photography at the earliest age possible. All patients with 4 or more RPE lesions should undergo annual sigmoidoscopic examinations beginning before 10 years of age.

Long-term follow-up of central serous retinopathy in 150 patients.

To study the evolution of the retinal pigment epithelial lesions in the central serous retinopathy, the authors studied 150 patients with ages between 20 and 49 years at the first examination, during periods varying between 6 months and 14 years. It was found a greater incidence of the disease in the males (83.3%); bilaterality in 23.3%; only one point of leakage in 62.7%; 3 different types of diffusion (inkblot 71.4%; mushroom 23.8%; with serous pigment epithelial detachment 4.9%). The final visual acuity was < 20/40 in a quarter of the cases and the frequency of the recurrences was 30%. The laser treatment did not influence the recurrences. In 50 patients with a follow-up superior to 3 years, 8 (16%) developed lesions similar to those described as diffuse retinal pigment epitheliopathy with visual field defects and subnormal EOG. Actuarial calculus suggests that 50% of the patients may get the most severe and extensive form of the disease after 12 years of evolution. The results allow to conclude that the diffuse retinal pigment epitheliopathy is only the terminal state of the most severe cases of central serous retinopathy.

Specific eye fundus lesions in type II membranoproliferative glomerulonephritis

In three adolescents, suffering from membrano-proliferative glomerulonephritis type II, ophthalmoscopy and fluorescein angiography revealed retinal pigment epithelium lesions, referred to as basal laminar drusen. The patient with the longest renal history had the most pronounced fundus changes. These lesions, earlier described in adult patients, are believed to be specific for this particular form of chronic glomerulonephritis.

Classification of Hypertensive Fundus Changes and Their Order of Appearance

We studied the sequence of appearance of the various fundus lesions in experimentally produced renovascular malignant arterial hypertension in 60 rhesus monkeys. The earliest lesion to appear usually was focal intraretinal periarteriolar transudates (FIPTs). Some time after that, three lesions: acute focal retinal pigment epithelial lesions, macular edema and optic disk edema, developed at roughly the same time. Cotton-wool spots appeared after these lesions. Retinal lipid deposits developed relatively late. Retinal arteriolar changes were a much later phenomenon. Conspicuous retinal hemorrhages were not a common or prominent early sign. The various classifications of hypertensive fundus changes proposed in the literature are reviewed and discussed critically, and it is concluded that, instead of using the various arbitrary grades advocated in different classifications, it is more informative and clinically useful to give a descriptive account of the individual fundus lesions revealed by ophthalmoscopy and fluorescein fundus angiography; because different lesions have different degrees of significance.

Fundus Lesions in Malignant Hypertension: VI. Hypertensive Choroidopathy

Experimental renovascular malignant arterial hypertension was produced, by modified Goldblatt's procedures, in 60 rhesus monkeys, and hypertensive fundus changes were studied in detail (by serial ophthalmoscopy and fluorescein fundus angiography in all monkeys on a long-term follow-up, and pathologically in 29 eyes). In hypertensive choroidopathy, retinal pigment epithelial (RPE) lesions and serous retinal detachment (RD) were the classic ophthalmoscopic lesions, whereas fluorescein fundus angiography and histopathologic studies revealed marked abnormalities in the choroidal vascular bed, in addition to the changes in the RPE. The RPE lesions could be subdivided into (1) initial acute focal lesions (due to focal RPE infarction), and (2) degenerative lesions, which developed later and were progressive in nature, maximally involving the macular and peripheral regions of the fundus. The RD developed most commonly in the posterior pole and infrequently involved the peripheral retina. The choroidal vascular bed showed impaired circulation and extensive occlusive and ischemic changes. These studies revealed that hypertensive choroidopathy is as important a fundus change as hypertensive retinopathy. The pathogenesis of hypertensive choroidopathy is discussed in detail; the evidence indicates that it is due to choroidal ischemia, and that hypertensive choroidopathy and retinopathy are two independent and unrelated manifestations of renovascular malignant hypertension.

OCULAR INVOLVEMENT IN SYSTEMIC IDIOPATHIC FIBROSIS

Systemic idiopathic fibrosis is a rare disease characterized by a nonsuppurative inflammation of fat and connective tissue in many anatomic sites with subsequent fibrosis and sclerosis of the involved tissue. A 29-year-old patient is presented who manifested bilateral exophthalmos as the first sign of systemic idiopathic fibrosis. The patient subsequently developed fundus changes, including disc edema, retinal hemorrhages, a serous retinal detachment, and retinal pigment epithelial lesions that responded rapidly to oral prednisone therapy. She died shortly thereafter from complications of her disease.

Clinicopathologic study of blood-retinal barrier in experimental diabetes mellitus.

Rats with experimental diabetes (induced by streptozocin [Streptozotocin]) were studied by vitreous fluorophotometry and horseradish peroxidase tracer technique. Vitreous fluorescein sodium concentration notably increased four to eight days after a single dose of streptozocin. No leakage from the retinal vasculature could be demonstrated by the horseradish peroxidase tracer study, but three types of retinal pigment epithelial (RPE) lesions were observed. The RPE lesions seemed to be partially responsible for the increase of vitreous fluorescein concentration.