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     

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。     

Congenital hypertrophy of the retinal pigment epithelium associated with familial adenomatous polyposis

Congenital hypertrophy of the retinal pigment epithelium is often observed in patients suffering from familial adenomatous polyposis. This paper describes a patient diagnosed with familial adenomatous polyposis where such ocular signs were present. The nature of the lesions and their use in detecting individuals at risk of developing the disease are discussed. (Clin Exp Optom 1995; 78: 4: 135–137)     

Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis

Background Familial adenomatous polyposis (FAP) results from a germline mutation in the adenomatous polypsis coli (APC) gene on chromosome 5q21. The extracolonic manifestations of FAP include pigmented ocular fundus lesions (POFLS), cutaneous cysts, osteomas, occult radio-opaque jaw lesions, odontomas, desmoids, and extracolonic cancers. POFLS are present at birth in about 80% of patients with FAP and are excellent clinical congenital markers for the disease. We studied the distribution of POFLS by number and APC mutation in families of the Johns Hopkins Polyposis Registry. Materials and methods Of the 51 families with FAP, 42 (82%) had an identifiable APC mutation. We correlated the presence/absence and distribution by number of POFLS with the type and location of the mutation in the APC gene in 21 families where an ocular examination had been performed in at least one affected member, and where a systematic search for mutations in the APC gene had been undertaken. Families were considered POFL-positive if the average number of lesions per patient was three or more, or if at least one family member had three or more lesions. Results Fifteen of the 21 families (71.4%) were POFL-positive. Mutations of the APC gene were detected in 15 of the 21 families. Of these, 12 (80%) were POFL-positive. Families with mutations at codons 215 (exon 5) and 302 (exon 8) were POFL-negative. Families with mutations at codons 541, 625, 1055, 1059, 1061, 1230, 1309, 1465, and 1546 (exons 12-15) were POFL-positive. One patient with a mutation at codon 2621 (exon 15) had no POFLS. Conclusions Mutations in exons 1-8 and the distal portion of exon 15 of the APC gene are associated with a POFL-negative phenotype, while those in exons 10 to the proximal portion of exon 15 are generally associated with a POFL-positive phenotype.     

Value of the Congenital Hypertrophy of the Retinal Pigment Epithelium in the Diagnosis of Familial Adenomatous Polyposis

BACKGROUND: Several kinds of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in patients with familial adenomatous polyposis (FAP). This study aims to assess which properties of CHRPE better predict FAP and investigate whether a relationship exists between specific CHRPE characteristics and FAP variants. METHODS: We examined 286 subjects, Group I--patients with FAP plus individuals "at risk"; n = 173; Group II--controls n = 113. Retinal lesions were classified in five types (A-E) and different characteristics (distribution, number, shape, size, pigmentation and site) were evaluated. RESULTS: The most common lesions in affected subjects were types A-D (83.4%) whilst in the "at risk" and control groups were type E. Greater numbers of lesions and bilateral distribution occurred more frequently among affected subjects than in other participants (p < 0.001). Large lesions with mixed pigmentation were associated with polyposis (p > 0.5). Controls had solitary CHRPE lesions (3.5%) and types C and E lesions (23%). The cumulative sensitivities and specificities of CHRPE were 42 and 97%, respectively. CHRPE was most common among those with classical FAP, but no specific characteristic was associated with any particular FAP variant. CONCLUSIONS: Pigmented fundal lesions are highly pleomorphic and represent the variable expression of a common genetic defect of growth regulation. No association was found between CHRPE characteristics and specific FAP variants.     

The Gardner Syndrome: Significance of Ocular Features

Gardner syndrome is a dominantly inherited familial cancer syndrome characterized by intestinal polyposis, bony hamartomata, and various soft tissue tumors. The risk of malignancy during adult life is essentially 100%, but as yet no phenotypic marker nor biochemical or serological linkage have been useful to identify the presence of the gene in early life. We studied three families in which multiple and bilateral patches of congenital hypertrophy of the retinal pigment epithelium are related uniquely to other phenotypic features of the Gardner gene. This readily identifiable characteristic may be useful to identify early in life individuals at risk for malignancy. We also suggest that the Gardner syndrome may be genetically heterogeneous.     

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.     

Documentation of Congenital Hypertrophy of the Retinal Pigment Epithelium with Wide-Field Funduscopy

Background: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) are rare hyperpigmented fundus lesions of the peripheral retina.

Methods: We evaluated CHRPE with the Optomap wide-field fundus camera.

Results: The pattern, location, and extension of the pigmented lesion were compared between the wide-field and composed digital fundus camera. The wide-field image had the same angle of the fundus image, magnification as well homogenious illumination of the entire fundus. Superimposed pattern of the lesions extended from the margin of the optic disk and radiated in sectors to the fundus periphery. Smaller lesion clusters were mainly located near the optic disk, whereas larger lesions were found in the periphery.

Conclusion: The sectorial pigmentations on the ocular fundus may reflect the stream, outgrowth and migration of RPE-cells during embryogenesis.     

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.     

Fluorescein Angiographic Features of the Congenital Hypertrophy of the Retinal Pigment Epithelium in the Familial Adenomatous Polyposis

Purpose To asses the prevalence of fluorescein angiographic features in bilateral and multifocal Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) in patients with a diagnosis of familial adenomatous polyposis. Methods We performed prospective angiographic and clinical examination of 49 CHPRE lesions in 15 patients. Results About 77.5% of CHRPE lesions were close to retinal vessels. The retinal vascular changes observed overlying and surrounding the CHRPE were: capillary non-perfusion with an area greater than 0.5 disc diameters (41%), capillary microaneurysms (4%), chorioretinal anastomoses (6.2%), attenuation of retinal vessels (4%), choriocapillary vessels inside the lacunae (6.2%) and in the depigmented marginal halo (18.4%). Depigmented streaks in contact with one or both edges of the CHRPE were observed in 79.6% of the lesions. About 9.6% of the lesions were not seen on ophthalmoscopy and could only be detected by angiography. Conclusions Even though the diagnosis of CHRPE is clinical, fluorescein angiography may be useful in confirming the diagnosis, as well as detecting additional lesions not seen by means of ophthalmoscopic examination.     

Ocular findings in incontinentia pigmenti

Incontinentia pigmenti is an uncommon disorder affecting females, and is associated with ocular, dental, skeletal, and central nervous system abnormalities. Ocular abnormalities are found in 35% of cases. The authors present an eight-month-old girl with neonatal history of skin bullae, who was noted to have esotropia, leukocoria, and a fixed pupil. Histologic examination of the enucleated globe reveals total retinal detachment with retinal neovascularization into the collapsed vitreous, reactive retinal gliosis, and scattered giant nodular proliferations of retinal pigment epithelium. It is suggested that the underlying defect is at the level of the retinal pigment epithelium and that the neurosensory retinal changes are secondary.     

先天性视网膜色素上皮肥大的研究现状

先天性视网膜色素上皮肥大(CHRPE)是一种临床上较为少见的眼底病变。由于它一般不引起严重的临床症状,多数眼科医生对它的认识很少,可能容易导致错误的诊断和治疗。本文着重介绍CHRPE的流行病学资料、临床特点、影像学特征及预后转归等,以便临床上正确地鉴别诊断和指导治疗随访。     

From an asymptomatic lesion to a vision-threatening condition: Congenital hypertrophy of the retinal pigment epithelium complicated by choroidal neovascular membrane

We reported a case of congenital hypertrophy of the retinal pigment epithelium (CHRPE) complicated by choroidal neovascular membrane (CNVM). A 41-year-old woman presented to our clinic with visual loss in the left eye. She was diagnosed as CHRPE complicated by a CNVM. The patient was treated with 2 consecutive monthly intravitreal aflibercept (IVA) injections. The best-corrected visual acuity (BCVA) improved and stabilized at 6/6. Subretinal fluid depending on CNVM resolved completely. CHRPE complicated by CNVM in the macular area is a rare condition and these cases can be treated with IVA therapy.     

Topographical distribution of typical unifocal congenital hypertrophy of retinal pigment epithelium

Purpose To describe the topographical distribution of typical congenital hypertrophy of retinal pigment epithelium (CHRPE) lesions in the ocular fundi. Methods Retrospective review of the clinical records of 52 patients with typical unifocal CHRPE. Results The 52 CHRPE lesions ranged from 2.5 mm to 11.5 mm in maximal basal diameter (mean=6.6 mm, SD=2.6 mm). The central point of the lesion was in the peripheral fundus in 44 eyes and in the intermediate fundus in eight eyes. The footprint of the lesion involved the peripheral fundus only in 25 eyes, both the intermediate and peripheral fundus in 22 eyes, and the intermediate fundus only in five eyes. The central point of the lesion was located in the temporal quadrant in 24 eyes, the inferior quadrant in 12 eyes, the nasal quadrant in nine eyes, and the superior quadrant in seven eyes. No lesion in this series involved the posterior fundus. Conclusions The most common fundus location for typical unifocal CHRPE in this series was the peripheral fundus temporally. Although posterior fundus location of CHRPE has been reported occasionally, our study suggests that such a location is very uncommon.     

Hipertrofia congénita del epitelio pigmentario de la retina asociada a retinosquisis adquirida y degeneración microquística: La importancia del estudio con imagen multimodal

We present an illustrated clinical case with multimodal representation of a congenital hypertrophy of the depigmented retinal pigment epithelium (CHRPE) associated with acquired retinoschisis and microcystic degeneration (MD) in a 64-year-old hypermetropic, asymptomatic woman. Retinography showed a whitish lesion with pigmented edges, slightly raised, accompanied by a lower area with a microcystic pattern. The complementary tests carried out allowed to determine a well-defined diagnosis of exclusion. B-mode ultrasound showed a smooth, cupuliform and cystic elevation characteristic of acquired retinoschisis, and fluorescein angiography could rule out the presence of a vascular tumor. The hypoautofluorescence of the lesion determined the depigmentation of the CHRPE, while the slight perilesional hyperautofluorescence corresponded to the associated retinoschisis and DM. This is the first case described in the literature of an acquired retinoschisis associated with CHRPE.     

Congenital Simple Hamartoma of the Retinal Pigment Epithelium

ABSTRACT

Congenital simple hamartoma of the retinal pigment epithelium (CSHRPE) is a rare tumor speculated to arise from the retinal pigment epithelium (RPE). A case of CSHRPE is presented herein along with the related literature. A healthy 20-year-old Middle-Eastern man was evaluated for an asymptomatic retinal lesion found on routine examination of his left eye. Fluorescein angiogram, spectral domain optical coherence tomography, and A and B scan ultrasonography confirmed the suspected clinical diagnosis. For the first time high-definition OCT images are shown, which have an RPE origin for this tumor.