A comparative histologic study of the fibrillin microfibrillar system in the lens capsule of normal subjects and subjects with Marfan syndrome.

PURPOSE: To gain a better understanding of the pathogenesis of ectopia lentis and myopia in Marfan syndrome, studies were performed to determine the distribution and structure of fibrillin microfibrils in the lens capsule of normal subjects and of subjects with Marfan syndrome. METHODS: Frozen sections and/or flat mounts of lens capsules were prepared from six autopsy eyes, nine surgical capsulotomy specimens obtained at the time of cataract extraction, and five capsules from patients with Marfan syndrome obtained at intracapsular lens extraction. Avidin-biotin-peroxidase complex (ABC) immunoperoxidase or immunofluorescence staining with monoclonal antifibrillin antibody was used to localize fibrillin in lens capsules. Image analysis was also performed to compare the amount of fibrillin expression in normal and Marfan syndrome capsules. RESULTS: Based on fibrillin staining patterns, we identified three distinct zones in the equatorial and periequatorial regions of the normal lens capsule. Zone I, a 0.75-mm-wide peripheral ring of the anterior capsule, contained radial bundles of fibrillin fibers. In Zone II, a 1-mm-wide meshwork of fibrillin-rich fibers encircled the equator and served as an insertion platform for zonular fibers. Zone III was composed of radial, 0.1-mm-wide bands arranged in a periodic fashion in the most peripheral part of the posterior capsule. Fibrillin fibers were abnormal and disrupted in all three zones in patients with Marfan syndrome. The amount of fibrillin staining per unit area was significantly reduced in Marfan capsules compared with normal capsules (16-26% versus 49-56% per unit area, respectively; P < 0.001). CONCLUSIONS: Fibrillin was a major constituent of the peripheral and equatorial areas of the lens capsule. Zonular fibers, also rich in fibrillin, insert into the equatorial region, primarily in Zone II. Possibly, fibrillin played a role in the ability of the lens to change its configuration during accommodation. The observed qualitative and quantitative abnormalities in fibrillin expression in the lens capsule of patients with Marfan syndrome supported a causal relationship to lens abnormalities in these patients.

Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) results from a germline mutation in the adenomatous polyposis 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 condons 215 (exon 5) and 302 (exon 8) were POFL-negative. Families with mutations at condons 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 I5 are generally associated with a POFL-positive

Ocular findings in the Hermansky-Pudlak syndrome.

BACKGROUND: The Hermansky-Pudlak syndrome (HPS) is defined by the autosomal recessively inherited triad of tyrosinase-positive oculocutaneous albinism, bleeding diathesis and accumulation of ceroid in tissues. Late complications include: interstitial pulmonary fibrosis; inflammatory bowel disease; and renal failure. PATIENTS AND METHODS: We undertook a non-concurrent prospective study of 55 Puerto Rican patients with HPS (age range 1 to 54 yrs; mean = 19.7 yrs). These patients had a comprehensive ocular examination and a systemic evaluation for HPS. RESULTS: Visual acuities ranged from 20/50 to 5/200. All patients had nystagmus. Forty-three patients had strabismus; esotropia was found in 24 patients; exotropia in 18 patients; and one patient had hypertropia. Posterior embryotoxon occurred in 15 patients and Axenfeld anomaly in 4 patients. Iris pigmentation varied from minimal to almost completely normal. Three patients had cataract formation. The retina was typically albinotic with macular hypoplasia. All patients had cutaneous albinism, bleeding diathesis and various systemic manifestations as part of HPS. CONCLUSION: Ocular findings in HPS include reduced visual acuity; congenital nystagmus, strabismus and cataract. Diagnosis of the syndrome ought to be made preoperatively to help minimize the potential complications associated with bleeding diathesis at the time of extraocular muscle and intraocular surgery in patients with HPS.