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Section on Ophthalmic Clinical Genetics

Current Research

Studies by the Section on Ophthalmic Clinical Genetics have emphasized retinal degenerations and other ophthalmic involvement in systemic genetic diseases. This Section has been a world leader in studying two genetic diseases: gyrate atrophy of the choroid and retina (GA) and nephropathic cystinosis. In GA, the accumulation of long term natural history data and the work on definition of the genetic abnormalities has been unique. In collaboration with Dr. David Valle of the Johns Hopkins Medical School, evidence for biochemical, clinical, and molecular heterogeneity continue to be confirmed. There appear to be many different single point mutations in the ornithine aminotransferase (OAT) gene in GA patients. Dietary intervention studies utilizing an arginine deficient diet in young patients followed for 17 to 18 years have almost stopped the progression of retinal lesions and have markedly slowed down the progression of functional changes. Most recently, psycophysical studies in the laboratory are exploring foveal cone sensitivity (assessed by measurements of increment thresholds) and orientation (estimated with measurements of the Stiles-Crawford effect). These studies were found to be abnormal in a group of patients with gyrate atrophy. These results suggest that foveal cones are altered in their orientation and sensitivity before the encroachment on the foveal area by the atrophic lesions of gyrate atrophy.

With respect to the nephropathic cystinosis study, the use of topical cysteamine eye drops to prevent the accumulation of corneal crystals is continuing in collaboration with Dr. William Gahl of trhe National Institute of Child Health Diseases, National Institutes of Health,The results from a double-masked placebo controlled clinical trial of topically administered 0.5% cysteamine eye drops to patients with nephropathic cystinosis clearly demonstrated complete clearing of the cystine crystals from the cornea of young patients. We have now expanded our study to include older patients, with similarly striking results. Particularly important is the fact that these patients have shown dramatic relief from their ocular symptoms, with a decrease in crystals in the treated eye and a significant improvement of their quality of life. At present, we await the issuance of an NDA from the FDA to make this treatment available to all cystinosis patients.

Clinical and laboratory studies continue in patients with Albinism, Usher Syndrome, the Hermansky-Pudlak Syndrome, Alkaptonuria, Neurofibromatosis 2 (NF2), Bietti Crystallin Chorioretinal Dystrophy, Congenital Cataract and Corneal Dystrophy, the last three diseases being intensively studied in collaboration with the molecular genetics section of the Ophthalmic Genetics and Visual Function Branch.Collaboration with the InterInstitute Medical Genetics Program has continued, with active participation by the Genetics Clinic. Because of the high frequency of ocular involvement in these genetic cases, most all of these patients were evaluated by the OGVFB staff. These included the Bardet Biedl and Smith Magenis patients.


Name Title E-mail Phone
Rick Ferris, M.D. Acting Chief of OGVFB ferrisf@mail.nih.gov (301) 496-6583
Meira Rina Meltzer, MA, MS Genetic Counselor meira.meltzer@nih.gov (301) 402-4175
Delphine Blain, MBA, MSC Genetic Counselor, Contractor dblain@mail.nih.gov (301) 496-3577
Ekaterini Tsilou, MD Staff Clinician tsiloue@intra.nei.nih.gov (301) 402-2391

Selected Publications

Kaiser-Kupfer MI, Caruso RC, and Valle D: Gyrate atrophy of the choroid and retina: Long-term reduction of ornithine slows retinal degeneration. Arch Ophthalmol 109:1539-1548, 1991.

Kaiser-Kupfer MI, Chan C-C, Markello TC, Crawford MA, Caruso RC, Csaky KG, Guo J, and Gahl WA: Clinical, biochemical and pathologic correlations in Bietti’s crystalline dystrophy. Am J Ophthalmol 15;118:569-582, 1994.

Scott MH, Hejtmancik JF, Wozencraft LA, Reuter LM, Parks MM, and Kaiser-Kupfer MI: Autosomal dominant congenital cataract: Interocular phenotypic heterogeneity. Ophthalmology. 101:866-871, 1994.

Bouzas EA, Caruso RC, Drews-Bankiewicz MA, and Kaiser-Kupfer MI: Evoked potential analysis of visual pathways in human albinism. Ophthalmology 101:309-314, 1994.

Mahurkar AA, Vivino MA, Trus BL, Kuehl EM, Datiles MB, and Kaiser-Kupfer MI: Constructing retinal fundus photomontages: A new computer-based method. Invest. Ophthalmol. Vis. Sci. 37:1675-1683, 1996.

Basti S, Hejtmancik JF, Padma T, Ayyagari R, Kaiser-Kupfer MI, Murty JS, and Rao GN: Autosomal dominant zonular cataract with sutural opacities in a four-generation family. Am J Ophthalmol 121:162-168, 1996.

Gentleman S, Kaiser-Kupfer MI, Sherins RJ, Caruso R, Robison Jr WG, Lloyd-Muhammad RA, Crawford MA, Pikus A, and Chader GJ: Ultrastructural and biochemical analysis of sperm flagella from an infertile man with a rod-dominant retinal degeneration. Hum Pathol 27:80-84, 1996.

Ayyagari R, Smith RJH, Polymeropolous M, Daiger S, Pelias MZ, Wozencraft L, Kaiser-Kupfer M, and Hejtmancik JF: Localization of the Usher syndrome type 1 gene in the French Acadian population of Louisiana to chromosome 11p14-15.1 by linkage and haplotype analysis. Indian Journal of Human Genetics 1:93-103, 1996.

Gahl WA, McDowell G, Kaiser-Kupfer MI: Benign cystinosis patients. Cornea 1996 Jan;15(1):101-2

Alberti G, Oguni M, Podgor M, Sperduto RD, Tomarev S, Grassi C, Williams S, Kaiser-Kupfer M, Maraini G, Hejtmancik JF: Glutathione S-transferase M1 genotype and age-related cataracts. Lack of association in an Italian population. Invest Ophthalmol Vis Sci 1996 May;37(6):1167-73

Whitcup SM, Iwata F, Podgor MJ, Valle D, Sran PK, Kaiser-Kupfer MI: Association of thyroid disease with retinitis pigmentosa and gyrate atrophy. Am J Ophthalmol 1996 Dec;122(6):903-5

Iwata F, Patronas NJ, Caruso RC, Podgor MJ, Remaley NA, Kupfer C, Kaiser-Kupfer MI: Association of visual field, cup-disc ratio, and magnetic resonance imaging of optic chiasm. Arch Ophthalmol 1997 Jun;115(6):729-32

Magno BV, Datiles MB, Lasa MS, Fajardo MR, Caruso RC, Kaiser-Kupfer MI: Evaluation of visual function following neodymium:YAG laser posterior capsulotomy. Ophthalmology 1997 Aug;104(8):1287-93

Caruso RC, Zujewski J, Iwata F, Podgor MJ, Conley BA, Ayres LM, Kaiser-Kupfer MI: Effects of fenretinide (4-HPR) on dark adaptation. Arch Ophthalmol 1998 Jun;116(6):759-63

Rodriguez IR, Mazuruk K, Jaworski C, Iwata F, Moreira EF, Kaiser-Kupfer MI: Novel mutations in the XLRS1 gene may be caused by early Okazaki fragment sequence replacement. Invest Ophthalmol Vis Sci 1998 Aug;39(9):1736-9

Iwata F, Kuehl EM, Reed GF, McCain LM, Gahl WA, Kaiser-Kupfer MI: A randomized clinical trial of topical cysteamine disulfide (cystamine) versus free thiol (cysteamine) in the treatment of corneal cystine crystals in cystinosis. Mol Genet Metab 1998 Aug;64(4):237-42

Lee J, Jiao X, Hejtmancik JF, Kaiser-Kupfer M, Chader GJ: Identification, isolation, and characterization of a 32-kDa fatty acid-binding protein missing from lymphocytes in humans with Bietti crystalline dystrophy (BCD). Mol Genet Metab 1998 Oct;65(2):143-54

Kannabiran C, Rogan PK, Olmos L, Basti S, Rao GN, Kaiser-Kupfer M, Hejtmancik JF: Autosomal dominant zonular cataract with sutural opacities is associated with a splice mutation in the betaA3/A1-crystallin gene. Mol Vis 1998 Oct 23;4:21

Anikster Y, Lucero C, Guo J, Huizing M, Shotelersuk V, Bernardini I, McDowell G, Iwata F, Kaiser-Kupfer MI, Jaffe R, Thoene J, Schneider JA, Gahl WA: Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations. Pediatr. Res. 47(1):17-23, Jan 2000.

Iwata F, Reed GF, Caruso RC, Kuehl EM, Gahl WA, Kaiser-Kupfer MI: Correlation of visual acuity and ocular pigmentation with the 16-bp duplication in the HPS-1 gene of Hermansky-Pudlak syndrome, a form of albinism. Ophthalmology 107(4):783-789, Apr 2000.