A clinicopathologic study of the eyes in familial adenomatous polyposis with extracolonic manifestations (Gardner's syndrome)

The eyes of a 51-year-old woman with familial adenomatous polyposis and extracolonic manifestations (Gardner's syndrome) were obtained postmortem and studied by light microscopy and by transmission and scanning electron microscopy. We found a generalized abnormality in melanogenesis of the retinal pigment epithelium and at least three types of pigmented lesions. The histologic findings in one type of lesion were consistent with congenital hypertrophy of the retinal pigment epithelium or benign pigmented nevus of the retinal pigment epithelium. The other two types of lesion were most consistent with hamartomatous malformations of the retinal pigment epithelium featuring cellular hypertrophy, hyperplasia, and rarely retinal invasion and formation of a minute mushroom-shaped tumor. These histopathologic findings indicate a generalized effect of the familial adenomatous polyposis gene on the retinal pigment epithelium. This oncogene, which is responsible for tumor formation in the gastrointestinal tract, soft tissues, bone, and other locations in patients with familial adenomatous polyposis, also leads to a generalized defect in melanogenesis and focal lesions of the retinal pigment epithelium.     

Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary nonpolyposis colorectal cancer

The authors studied pigmented ocular fundus lesions in three different forms of hereditary gastrointestinal polyposis and in hereditary nonpolyposis colorectal cancer. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was present in at least one member of 23 families with Gardner's syndrome. By contrast, CHRPE was not found in three families with familial polyposis coli, four families with hereditary nonpolyposis colorectal cancer, and three families with Peutz-Jeghers syndrome. Pigmented ocular fundus lesions of the CHRPE-type appear to be specific to Gardner's syndrome among inherited diseases with gastrointestinal polyposis.     

Ocular manifestations of familial adenomatous polyposis (Gardner syndrome)

Familial adenomatous polyposis (FAP) is a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colonic polyp become evident at a mean age of 16 years (range, 7-36 years). By age 35 years, 95% of patients have polyps. Gardner syndrome is the eponym given to a subgroup of FAP with extracolonic manifestations, such as pigmented ocular fundus lesions that resemble congenital hypertrophy of the retinal pigment epithelium, among others.     

Ocular changes in Gardner syndrome]

In hereditary adenomatosis of the large bowel (familial polyposis) extraintestinal manifestations of the disease are common: hyperostosis, dental anomalies, soft tissue tumours, desmoid tumours etc. Patients with marked extracolic signs are described as patients with Gardner's syndrome. Recently a further sign is described--foci of congenital hypertrophy of the pigmented retinal epithelium. The authors examined 22 patients with confirmed hereditary adenomatosis (Gardner's syndrome). The typical finding of pigmented foci on the fundus was recorded in 18 subjects (82%) incl. 9 subjects (50%) where the finding was bilateral. The authors examined also 25 children of these patients. In those a positive finding was recorded in 11 (44%). Ophthalmological examination can contribute in a significant way to detection of an asymptomatic subject with hereditary adenomatosis, in particular when seeking risk patients in an affected family. Evaluation of ophthalmological changes can also contribute to the solution of some special genetic problems of this disease.     

When is congenital hypertrophy of the retinal pigment epithelium (CHRPE) associated with the Gardner's syndrome? An overview with clinical examples

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) can be associated with Gardner's syndrome (GS). During childhood multiple adenomatose polyps develop in the colon ascendens (familiar-autosomal Polyposis coli [FAP]), and always become malignant until the age of 35. The tumour-suppressive FAP-gen was identified at the long arm of chromosome 5 (5q21). Ophthalmic funduscopy is very important. Patients with more than 3 CHRPE in one eye or a bilateral CHRPE, as well as patients with a positive family history and one unilateral solid CHRPE require further gastroenterological evaluation.     

Lack of association among typical congenital hypertrophy of the retinal pigment epithelium, adenomatous polyposis, and Gardner syndrome.

BACKGROUND: It has been recently documented that multiple bilateral pigmented lesions at the level of the retinal pigment epithelium may be an indicator of patients with familial adenomatous polyposis who are prone to develop intestinal cancer, particularly if there is a positive family history of these intestinal disorders. Although atypical, such lesions have been called congenital hypertrophy of the retinal pigment epithelium (CHRPE). This study was undertaken to determine whether the typical lesions of CHRPE, seen frequently by ophthalmologists, also were indicators of familial adenomatous polyposis. METHODS: Review of charts and follow-up studies were performed on all patients diagnosed and coded as having solitary CHRPE or its multifocal variant (congenital grouped pigmentation; bear tracks). Patients and their physicians were contacted by telephone to complete a detailed questionnaire designed to detect signs or symptoms of familial adenomatous polyposis or Gardner syndrome among these patients with CHRPE and their relatives. RESULTS: Of the 132 patients with previously diagnosed CHRPE, there were none with familial adenomatous polyposis, Gardner syndrome, or intestinal cancer, and only one patient had a history of intestinal polyps. Among more than 2000 of their blood relatives, only 20 had intestinal polyposis or colonic cancer (1%). This is much lower than would be expected from a survey of patients with the typical fundus lesions seen with familial adenomatous polyposis. CONCLUSIONS: It appears that solitary CHRPE and congenital grouped pigmentation differ clinically from the multiple pigmented lesions seen with familial adenomatous polyposis and that patients with these conditions, as well as their relatives, are not at a greater risk of developing intestinal cancer.     

先天性视网膜色素上皮肥大对家族性腺瘤性息肉病的筛查

对8例家族性腺瘤性息肉病(FAP)5名I级高危亲属和100例对照组作眼底色素病变研究。结果表明：先天性视网膜色素上皮肥大对FAP有筛检价值，若色素斑有晕圈、数量≥4颗、病变为双眼且位于后极部，则FAP的可能性很大。 （中华眼底病杂志，1995，11：1-3）     

Congenital hypertrophy of the retinal pigment epithelium and familial adenomatous polyposis

Congenital hypertrophy of the retinal pigment epithelium is a common eye sign in patients with familial adenomatous polyposis (FAP). FAP has autosomal dominant inheritance with virtually 100% risk of colonic malignancy in adult life. There may be other associated systemic abnormalities including extracolonic malignancy. Early detection of disease is desirable, but has in the past been reliant on regular endoscopic examination. The nature of congenital hypertrophy of the retinal pigment epithelium and its usefulness as a predictive marker of the disease are discussed     

Congenital hypertrophy of the retinal pigment epithelium: prevalence and ocular features in the optometric population

AIM: In this study we aimed to determine the prevalence, features and associations of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in the optometric population. METHOD: The Optomap imaging system uses an ultra-wide-field scanning-laser ophthalmoscope to image the fundus at the choroidal and retinal levels, non-mydriatically, capturing an image of up to 200 degrees . Optomap images of 1745 consecutive patients obtained at a recent optometric examination were examined retrospectively. RESULTS: The prevalence of CHRPE was found to be 1.20%. CHRPE was found to be most commonly located temporally to the optic disc within the peripheral fundus. All lesions found were of previously documented shapes and sizes, and divided approximately evenly between those with and without depigmented haloes and lacunae; all were monocular. The progression of the condition could not be accurately described without follow-up. The evidence found appears to support the theory that increasing atrophy is related to flat, overall enlargement of the lesion. No symptoms or associations were found, and no abnormalities were found in the fellow eye. No evidence was found to suggest a relationship between true CHRPE and familial adenomatous polyposis coli, Gardner's or Turcot's syndromes.     

The importance of congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis

We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer.     

家族性腺瘤性息肉病患者中先天性视网膜色素上皮肥厚的FFA研究

目的:研究家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)患者中双眼多灶性先天性视网膜色素上皮肥厚(congenital hypertrophy of the retinal pigment epithelium,CHRPE)患者的眼底荧光素血管造影(fundus fluoresceinangiography,FFA)的特点。方法:我们对22例有65处CHRPE病灶的FAP患者前瞻性进行FFA和眼底检查。结果:发现86%CHRPE病损面积>0.5个视盘直径,74%的CHRPE病变接近视网膜血管,视网膜血管有以下变化:46%CHRPE病变中出现毛细血管无灌注区,8%穿过病灶的视网膜血管部分阻塞,6%出现脉络膜视网膜吻合支,3%病变有毛细血管微血管瘤,5%可观察到脉络膜毛细血管,20%的脉络膜毛细血管出现在脱色素边缘晕环中。约10%的CHRPE病变眼底检查未发现,只能通过FFA观测到。结论:虽然通过眼底检查能诊断CHRPE,但有些病变仍需通过FFA确诊,其对此病变仍是非常有用的诊断方法。     

Indocyanine green angiography in congenital hypertrophy of the retinal pigment epithelium

PURPOSE: To report a case of congenital hypertrophy of the retinal pigment epithelium followed up for 7 years showing features not previously reported. METHODS: A complete fundus examination including fluorescein angiography was performed at first examination and at follow-up. RESULTS: The area of congenital hypertrophy of the retinal pigment epithelium presented morphologic changes, showing enlargement of the lesion on one side associated with partial regression on another side. In addition, the indocyanine green angiography findings revealed that this test was more useful than fluorescein angiography to delineate the real boundaries of the lesion and disclosed hypofluorescent areas inside the main lesion that were not appreciated at ophthalmoscopy or fluorescein angiography. CONCLUSIONS: Indocyanine green angiography is an useful test to understand the findings and evolution of congenital hypertrophy of the retinal pigment epithelium.     

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.     

Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis

One hundred fifty-three members of 56 kindreds with familial adenomatous polyposis (FAP) underwent funduscopic examination for congenital hypertrophy of the retinal pigment epithelium (CHRPE). All patients underwent wide-angle fundus photography to document lesions, proctosigmoidoscopy to document polyps, and examination for extracolonic manifestations. Ninety-seven patients were diagnosed as having FAP and 56 patients were offspring of FAP patients and thus at 50% risk of inheriting the disease. In two thirds of the kindreds, CHRPE could be used as a congenital phenotypic marker to predict the presence or development of polyps. In these kindreds, all patients with diagnosed FAP and 39% of the patients at risk had at least four CHRPE lesions. In one third of the kindreds, CHRPE could not be used as a predictive congenital marker, and in these kindreds all patients had zero to three total lesions of CHRPE. The presence of CHRPE did not correlate with any other extracolonic manifestations. In kindreds without any other extracolonic manifestations, CHRPE can still be present and can be used as a predictive congenital phenotypic marker.     

Selected pigmented fundus lesions of children.

BACKGROUND: Ocular cells that accumulate melanin pigment are derived from 1 of 2 sources, the optic vesicle or the neural crest. Migration and distribution of pigment containing cells may go awry during fetal development or these cells may be altered before or after birth either by local or systemic stimuli. Specific recognition patterns of pigment distribution often exist and may relate directly to a single disease process. METHODS: Records of pediatric patients with disorders of pigment distribution in the ocular fundi who had been examined by the author were reviewed. RESULTS: Five disorders with recognizable patterns of retinal pigment epithelium (optic vesicle derivation) disturbance (congenital hypertrophy of the retinal pigment epithelium, Gardner syndrome, chronic granulomatous disease, preserved para-arteriole retinal pigment epithelium in (autosomal-recessive) retinitis pigmentosa, and combined hamartoma of the retina and retinal pigment epithelium), and 5 disorders of cells originating from the neural crest (choroidal nevi, choroidal melanoma, melanocytoma, ocular melanosis, and oculodermal melanosis), were selected for illustration and discussion. CONCLUSIONS: These arbitrarily selected groups of disorders affect or involve patterns of pigment deposition in the ocular fundus. These patterns are recognizable and distinguishable one from another but have different implications for treatment and follow-up. Progress in recognizing distinguishing characteristics, diagnostic implications, understanding, and treatment of these disorders during the past 40 years is compared and contrasted between the 2 groups.     

Histopathological features of congenital fundus lesions in familial adenomatous polyposis

We report the light and electron microscopic findings for two lesions from two patients who died of complications of familial adenomatous polyposis. In the first case microscopy of a small (100 to 200 mu), uniformly dark lesion (the commonest type seen in this condition) showed enlarged retinal pigment epithelial cells with an increased number of pigment granules. This is consistent with the term "hypertrophy of the retinal pigment epithelium", currently used to describe these lesions. In the second case we sectioned a larger (1000 to 1500 mu), oval, grey lesion from the posterior pole. The pigment epithelium was normal, but between it and outer retina was an unusual choristoma consisting largely of myelinated axons and astrocytes.     

Review of optical coherence tomography for intraocular tumors

PURPOSE OF REVIEW: Optical coherence tomography has assumed an important role in the management of numerous ocular conditions. With regard to ocular oncology, optical coherence tomography can illustrate retinal changes overlying choroidal tumors. Some of these features include photoreceptor loss, intraretinal edema, and retinal thinning overlying choroidal nevus; fresh subretinal fluid with preservation of photoreceptors overlying choroidal melanoma; and intraretinal edema, retinoschisis, and retinal thinning overlying irradiated choroidal melanoma. RECENT FINDINGS: The optical coherence tomography features of tumors of the retinal pigment epithelium include typical findings of peaked vitreoretinal traction and retinal disorganization with combined hamartoma of the retina and retinal pigment epithelium, full-thickness retinal shadowing with congenital simple hamartoma, and photoreceptor loss and retinal thinning overlying congenital hypertrophy of the retinal pigment epithelium. SUMMARY: Optical coherence tomography of retinal tumors, such as retinoblastoma and astrocytic hamartoma, reveals full-thickness replacement of the retinal anatomic layers with the tumor and shadowing corresponding to the intralesional calcification. For all intraocular tumors, optical coherence tomography provides valuable information regarding the status of the retina and the retinal pigment epithelium and can be useful in ascertaining reasons for visual loss.     

Congenital retino-pigment epithelial malformation: a clinicopathological case report

An unusual unilateral fundus lesion in a 16-year-old boy is described consisting of hyperpigmentation and presumed hypertrophy of the retinal pigment epithelium combined with malformation and thickening of the overlying sensory retina. Based on its clinical and histological characteristics, this lesion is considered to be a congenital retinal pigment epithelial malformation.     

A Unique Presentation of Grouped Congenital Hypertrophy of the Retinal Pigment Epithelium

Purpose: To describe a unique presentation of grouped congenital hypertrophy of the retinal pigment epithelium (CHRPE) and to review the clinical features which differentiate grouped CHRPE from the pigmented ocular fundus lesions (POFLs) associated with familial cancer syndromes.

Methods: Report of a case.

Results: A 28-year-old asymptomatic, Caucasian female demonstrated multiple small, flat, dark brown to black clusters of retinal pigment epithelium (RPE) hypertrophy on dilated fundus examination of both eyes. These plaque-like lesions were circumferential along the peripheral fundus and were associated with smaller foci of pigmentation oriented towards the posterior pole. The appearance was consistent with grouped pigmented CHRPE. A unique, co-existing feature was the presence of non-pigmented, punctate lesions located within the maculae suggestive of grouped non-pigmented CHRPE. Fluorescein angiography demonstrated persistent hypofluorescence correlating with the clinically observed areas of hyperpigmentation and hypopigmentation.

Conclusions: The combination of both pigmented and non-pigmented lesions occurring in the same individual with grouped CHRPE is rare. It is important to distinguish grouped CHRPE lesions from the POFLs associated with familial cancer syndromes.     

Optical coherence tomography in the acute and chronic phases of Vogt-Koyanagi-Harada disease

PURPOSE: To assess the potential of optical coherence tomography (OCT) in the diagnosis and monitoring of serous retinal detachment in Vogt-Koyanagi-Harada (VKH) disease and to describe OCT characteristics of subretinal sequelae of the disease. METHODS: Six patients in the acute phase of VKH disease with serous retinal detachment were followed in our department from July 2001 to December 2003 using slit-lamp biomicroscopy, OCT, and fluorescein angiography. RESULTS: OCT was effective in objectively quantifying the amount of serous retinal detachment present and then in following the resolution of subretinal fluid accumulation. Subretinal pigmented lesions on angiography corresponded with retinal pigment epithelium hypertrophy and fibrosis on OCT. CONCLUSION: A beneficial effect of treatment was observed within days, paralleling the improvement in visual acuity. Retinal pigment epithelium hypertrophy and fibrosis in the chronic phase of the disease were analyzed with OCT for the first time.