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.

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.

Abnormal cell cycle regulation in primary human uveal melanoma cultures.

Uveal malignant melanoma is the most frequent primary intraocular tumor in adult humans. The cellular events leading to neoplasic transformation of normal uveal melanocytes are not well known when compared to other cancers. In this study, we investigated the role of G1 and G1/S regulatory proteins of the cell cycle in human uveal melanoma (UM) primary cell cultures, since these proteins are common targets in tumor development. Further, freshly established and characterized tumor cells are a better model for in vitro studies when compared to cell lines established long ago. Human primary cell cultures from eight different UM were established, as well as one primary culture from rhesus uveal normal melanocytes (UNM). Primary human UM cultures were characterized by a low establishment and growing rate. From four successful cultures, three showed a high expression of cyclin D1, cyclin E, p16NK4A, and p27KIP1 with no variations in cyclin A, cyclin-dependent kinase 2 (CDK2), and CDK4. Interestingly, in one of the cultured tumors, tumor suppressor protein retinoblastoma (Rb) did not bind E2F despite the fact that Rb was found in its hypophosphorylated form. No mutations in either RB1 or the Rb-binding pocket of E2F-1 were detected. Furthermore, we identified seven proteins co-immunoprecipitating with Rb in this tumor, including Lamin A/C and six proteins not previously reported to bind Rb: Hsc70, high mobility group protein 1 (HMG-1), hnRPN, glyceraldehyde 3 phosphate dehydrogenase (G3PDH), EF-1, and EF-2. Our results indicate that the overexpression of cyclins D1/E and CDKIs p16 and p27, together with a deregulation of the Rb/E2F pathway, may be implicated in the development of human UM.

Amniotic membrane as support for human retinal pigment epithelium (RPE) cell growth.

PURPOSE: The aim of this work was to culture human retinal pigment epithelium (hRPE) cells over human amniotic membrane (hAM). Human AM was studied for its viability as an adequate support for transplantation of an hRPE cell monolayer with preserved cell polarity to the subretinal space. METHODS: Human AM was obtained from pregnant women during caesarean section. The hAM was sectioned and the pieces were fixed to culture dishes. Human RPE cells were cultured from adult corneal donors and were seeded over hAM. Phase-contrast photographs were obtained. Selected specimens were processed by transmission electronic microscopy (TEM). RESULTS: The attachment and growth of hRPE cells over hAM was observed. Human RPE cells constituted tight colonies that maintained epithelial phenotype. Using TEM, we identified a monolayer of hRPE cells, with cuboidal to spheroidal morphology. These cells showed integration with the substrate and cell-cell contacts were detected. CONCLUSION: Amniotic membrane may be a suitable substrate for hRPE growth. Further studies are required in order to determine the viability of hRPE on hAM in the subretinal space.

Topical mitomycin C in the treatment of pigmented conjunctival lesions.

PURPOSE: To assess the clinical efficacy of topical mitomycin C (MMC) 0.04% for the treatment of patients with pigmented conjunctival lesions. Clinical efficacy was evaluated on the basis of reduction in lesion size and degree of pigmentation and histologic study. METHODS: Two patients, one with primary acquired conjunctival melanosis with atypia and another with conjunctival melanoma, were treated with topical MMC 0.04%. Before treatment, a biopsy was performed that confirmed the diagnosis and the absence of atypical melanocytes beyond the basal layer. In both patients, MMC was administered with sponges, while one patient additionally received MMC 0.04% drops. Each treatment cycle lasted 14 days, with repetition after 3 months when necessary. Follow-up was weekly, then monthly, and then every 6 months up to 3 years. RESULTS: Treatment with topical MMC 0.04% not only reduced the size and degree of pigmentation clinical lesions in both patients but also eradicated atypical conjunctival melanocytes as observed in histologic studies. In the patient with primary acquired conjunctival melanosis, adjunct cryotherapy was required, along with various cycles of MMC, to reduce the pigmented areas of skin of the internal canthus and caruncle. In the second case, only MMC was used. No severe adverse reactions to the treatment were observed. After 3 years of follow-up, no clinical relapse has been detected. CONCLUSION: Topical MMC 0.04% is an option worth considering for the treatment of pigmented conjunctival lesions, particularly as an adjunct to other forms of treatment.

Posterior vitreous findings in cases of spontaneous retinal reattachment.

PURPOSE: To describe the posterior vitreous findings in two patients with retinal detachment who experienced spontaneous retinal reattachment. DESIGN: Two observational case reports. TESTING: Biomicroscopic and high-resolution echographic evaluation of the vitreoretinal relationships. MAIN OUTCOME MEASURES: Retinal reattachment and echographic vitreoretinal relationships. RESULTS: Two patients, one with a rhegmatogenous retinal detachment and one with a tractional retinal detachment, were noted to have a partial posterior vitreous detachment with vitreoretinal adherence at the time of presentation. Spontaneous retinal reattachment occurred in both cases, with echography showing complete vitreous separation from the retina. CONCLUSIONS: Complete posterior vitreous detachment may release tractional components in retinal detachment and contribute to spontaneous retinal reattachment.