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PubMed1999

A new model of retinal pigment epithelium transplantation with microspheres.

OBJECTIVES: To develop a 3-dimensional carrier system for subretinal transplantation of human fetal retinal pigment epithelial (HFRPE) cells and to assess their growth pattern in the rabbit subretinal space. METHODS: After a standard 3-port vitrectomy, HFRPE cells grown as microspheres on cross-linked fibrinogen were introduced into the subretinal space of rabbits. The eyes were studied at 7, 14, and 30 days after surgery by ophthalmoscopy and light microscopy. RESULTS: Ophthalmoscopically, at day 7, 11 (61%) of the 18 eyes showed radiating hyperpigmentation around the transplanted HFRPE microspheres. The results of a histological examination revealed a monolayer outgrowth of HFRPE cells, overlying host retinal pigment epithelium. The control eyes revealed a patch of chorioretinal atrophy with lymphocytic infiltration around the microspheres. CONCLUSIONS: Human fetal retinal pigment epithelial cells grown as microspheres on cross-linked fibrinogen can be successfully transplanted into the subretinal space. Cells can survive for at least 1 month and form a monolayer over the host retinal pigment epithelium cells, with a mild local inflammatory response. The difference in inflammatory responses between the eyes that underwent transplantation and the control eyes may suggest a modulating effect of the HFRPE cells on inflammation, immunity, or both. This new xenogenic model may have importance in the study of subretinal transplant cell biology and the associated immune response. CLINICAL RELEVANCE: The results of this study may be important for better understanding of the mechanisms of retinal pigment epithelium cell behavior after transplantation. The proposed model may be applicable for future clinical and experimental investigations in the area of retinal pigment epithelium transplantation.

Animals↗
PubMed2003

A peculiar autosomal dominant macular dystrophy caused by an asparagine deletion at codon 169 in the peripherin/RDS gene.

OBJECTIVE: To describe the clinical and genetic findings in a family with a peculiar autosomal dominant macular dystrophy with peripheral deposits. METHODS: All family members underwent an ophthalmic examination, and their genomic DNA was screened for mutations in the human retinal degeneration slow (peripherin/RDS) and rhodopsin genes. In selected cases, fluorescein angiography and electrophysiologic testing were performed. RESULTS: The age at onset of the disease was between the third and fourth decades of life, starting with mild visual acuity loss and periods of metamorphopsia. Clinical signs included subretinal yellowish macular deposits evolving into geographic atrophy and retinal hypopigmentation and hyperpigmentation. Electroretinography demonstrated rod dysfunction, and electro-oculograms were mildly to severely disturbed. All affected members were found to carry a 3-base pair deletion affecting codon 169 of the peripherin/RDS gene. This mutation resulted in an asparagine (Asn) deletion in the peripherin/RDS protein and was not found in 155 control individuals. CONCLUSION: A deletion of Asn169 in the peripherin/RDS protein causes a peculiar form of autosomal dominant macular dystrophy in a large family from the Netherlands. CLINICAL RELEVANCE: Characterizing the phenotype and genotype in this family may, in the long term, result in a better understanding of the precise mechanism underlying this retinal degeneration.

Adolescent↗
PubMed1976

Acute choroidal ischemia as a complication of photocoagulation.

Acute choroidal vascular insufficiency as a complication of photocoagulation has been little noticed. In 17 eyes of 16 patients photocoagulated with either xenon or argon sources for proliferative sickle cell retinopathy, gray lesions of the fundus developed peripheral to the photocoagulation sites. Histologic examination of similar gray lesions produced in monkeys showed necrosis and atrophy of the outer half of the retina. Intense photocoagulation of the human fundus, even with smaller spot sizes, may occlude a choroidal artery, producing separate gray lesions of distinctive shape. The lesions in both the patients and the monkeys progressed to granular hyperpigmentation by two to three weeks after photocoagulation.

Adolescent↗
PubMed1982

Autosomal dominant vitreoretinochoroidopathy.

Autosomal dominant vitreoretinochoroidopathy is a newly described fundus dystrophy characterized by abnormal chorioretinal hypopigmentation and hyperpigmentation, usually lying between the vortex veins and the ora serrata for 360 degrees. In this zone, there are a discrete posterior boundary, preretinal punctate white opacities, retinal arteriolar narrowing and occlusion, and, in some cases, choroidal atrophy. Most affected family members have diffuse retinal vascular incompetence, cystoid macular edema, and presenile cataracts. The vitreous is characterized by fibrillar condensation and a moderate number of cells. Electroretinograms are normal in younger affected individuals and are only moderately abnormal in older ones. Preretinal neovascularization, present in the posterior pole, is progressive in the proband. There are no identifiable systemic or skeletal abnormalities, high myopia, optically empty vitreous, lattice degeneration, areas of white-without-pressure, retinal breaks, or retinal detachment; thus, previously described vitreoretinopathies can be excluded from diagnostic consideration. Progression of this diagnostic seems to be extremely slow in most family members.

Adolescent↗
PubMed1982

Scleropachynsis maculopathy.

To our knowledge, this is the first clinicopathologic report of a previously unrecognized maculopathy in which there is thickening and mucopolysaccharide deposition in the sclera subjacent to the macula. A healthy 50-year-old man had bilateral mottling of the retinal pigment epithelium (RPE) in the macular region. The left eye was enucleated because of a choroidal melanoma. Histopathologic examination disclosed a thickened sclera with abnormal collagen fibrils with diameters up to 5,800 A and compressed choroid. The overlying RPE had areas of hypopigmentation, hyperpigmentation, and hyperplasia and contained intracytoplasmic lipofuscin.

Choroid↗
PubMed1988

Cellular proliferation induced by subretinal injection of vitreous in the rabbit.

A new experimental model of subretinal cellular proliferation, based on injection of autologous vitreous into the subretinal space of rabbits, was studied by light and electron microscopy. As early as five days after injection, proliferation of retinal pigment epithelial (RPE) and retinal glial cells was observed in the subretinal space. These morphologically distinct proliferating cells were sometimes joined by junctional complexes. Morphologically, the proliferating RPE cells resembled either RPE cells or fibroblasts. Some proliferating RPE cells also retained their epithelial characteristics (ie, basement membranes and cell junctions), while others were partially dedifferentiated and showed some embryonic features. New formation of melanin could be identified within the proliferated RPE cells, which could account, in part, for the hyperpigmentation at the site of the bleb caused by the injection of vitreous. The results demonstrated that injection of autologous vitreous into the subretinal space can lead to subretinal proliferation of retinal glial and RPE cells in the rabbit.

Animals↗
PubMed1989

Exposure to sunlight and other risk factors for age-related macular degeneration.

As some ultraviolet (UV) radiation is transmitted by the ocular media, there is a growing concern that there may be a possible relationship between long-term exposure to ultraviolet radiation and increased risk of age-related macular degeneration. To address this question, a survey was conducted of 838 Maryland watermen who had well-characterized ocular UV-A and UV-B exposure. Fundus photographs were taken and graded for presence of exudative disease, geographic atrophy, focal hyperpigmentation of the retinal pigment epithelium, and drusen that were large and/or confluent. None of the subjects in these analyses were aphakic. The results suggested that age-related macular degeneration was not associated with cumulative exposure to either UV-A or UV-B. Age and the presence of nuclear opacity were independently associated with an increased risk of macular degeneration. Thus, we found that in phakic subjects, even with high levels of sunlight exposure, there was no evidence of increased risk of age-related macular degeneration associated with UV-B or UV-A exposure.

Adult↗
PubMed1994

Are antioxidants or supplements protective for age-related macular degeneration?

OBJECTIVES: The relationships between fasting plasma levels of retinol, ascorbic acid, alpha-tochopherol, and beta-carotene and age-related macular degeneration (AMD) were studied in a population enrolled in the Baltimore Longitudinal Study of Aging (BLSA), in which most of the data were collected 2 or more years before assessment of macular status. DESIGN: A total of 976 participants in the study were scheduled for a biennial examination from January 1988 through January 1, 1990, which included taking lens and macular photographs. A total of 827 (85%) of the participants had fundus photographs taken, and most plasma data were available for 82% of those subjects with fundus photographs. Age-related macular degeneration was defined as neovascular changes, geographic and nongeographic atrophy, large or confluent drusen, or hyperpigmentation. A total of 226 cases of AMD were available for analysis. RESULTS: Logistic regression analyses suggested that alpha-tocopherol was associated with a protective effect for AMD, adjusted for age, sex, and nuclear opacity. An antioxidant index, including ascorbic acid, alpha-tocopherol, and beta-carotene, was also protective for AMD. Our conclusions must be tempered with the knowledge that the population under study was basically well nourished, and few individuals had any clinically deficient status. The study cannot exclude the possibility that quite low levels of micronutrients, lower than those observed in this study, might be risk factors for AMD. CONCLUSIONS: The data suggest a protective effect for AMD of high plasma values of alpha-tocopherol. An antioxidant index, composed of plasma ascorbic acid, alpha-tocopherol, and beta-carotene, was also protective. The use of vitamin supplements to prevent AMD is not supported by these data, which showed no protective effect of vitamin use.

Adult↗
PubMed1997

Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Macular Photocoagulation Study Group.

OBJECTIVES: To verify and quantify previously reported risk factors for development of choroidal neovascularization (CNV) in the fellow eye of patients with 1 eye affected with CNV secondary to age-related macular degeneration, to examine the value of characteristics of the pericentral macula in the quantification of risk for developing CNV, and to explore whether the presence of occult CNV in the first eye affects the development of CNV in the fellow eye. DESIGN, PATIENTS, AND SETTING: Follow-up study of fellow eyes of 670 patients enrolled in multicenter, randomized clinical trials of laser photocoagulation of juxtafoveal or subfoveal CNV. MAIN OUTCOME MEASURE: Development of CNV. RESULTS: Three characteristics of the central macula of the fellow eye and 1 systemic factor were associated independently with an increased risk of developing CNV: the presence of 5 or more drusen (relative risk, 2.1; 95% confidence interval, 1.3-3.5), focal hyperpigmentation (relative risk, 2.0; 95% confidence interval, 1.4-2.9), 1 or more large drusen (relative risk, 1.5; 95% confidence interval 1.0-2.2), and definite systemic hypertension (relative risk, 1.7; 95% confidence interval, 1.2-2.4). Estimated 5-year incidence rates ranged from 7% for the subgroup with no risk factors to 87% for the subgroup with all 4 risk factors. Characteristics of the pericentral macula were not strongly associated with the development of CNV. The presence of occult CNV in the first eye affected had no influence on the development of CNV or on the type of CNV in the fellow eye. CONCLUSIONS: The prognosis of the fellow eye is affected strongly by characteristics of its central macula and by systemic hypertension. These factors should be considered when counseling patients with unilateral neovascular age-related macular degeneration and when targeting patients for preventive interventions.

Aged↗
PubMed1992

Selective destruction of facial telangiectasia using a copper vapor laser.

Copper vapor lasers emit pulsed light at 511 and 578 nm. The 578-nm option corresponds with a peak in the absorption of oxyhemoglobin and a diminished absorption by melanin. The pulse width of this light (20 nanoseconds) is significantly shorter than the thermal relaxation time of typical facial telangiectatic vessels (20 to 100 milliseconds). This laser is therefore able to selectively destroy facial telangiectatic vessels with little damage to the overlying epidermis. Twenty patients with facial telangiectasia were treated with the 578-nm option of a copper vapor laser. Treatment was administered in an office-room setting, and no anesthesia was used. Eighteen of the 20 patients experienced satisfactory clearance of their telangiectasia. Three patients developed temporary postinflammatory hyperpigmentation, which cleared within 6 to 8 weeks, and one patient developed a small depressed scar, which was not noticeable at 3 months. Copper vapor lasers are thus safe and effective in treating facial telangiectasia.

Adult↗
PubMed2002

Berloque dermatitis mimicking child abuse.

Berloque dermatitis is a type of photocontact dermatitis. It occurs after perfumed products containing bergamot (or a psoralen) are applied to the skin followed by exposure to sunlight. Striking linear patterns of hyperpigmentation are characteristic, corresponding to local application of the scented product. In the acute phase, erythema and even blistering can be seen. We report a case of berloque dermatitis in a 9-year-old girl that was initially reported as child abuse. To our knowledge, this is the first report of berloque dermatitis mimicking child abuse. Questioning to elicit a history of perfume application coupled with sunlight exposure should help to prevent this misdiagnosis in children.

Child↗
PubMed1977

Incidence of Nelson's syndrome after adrenalectomy for Cushing's disease in children: results of a nationwide survey.

To establish the incidence of Nelson's syndrome in children treated with total bilateral adrenalectomy (TBA) for Cushing's disease, a survey was made of members of The Lawson Wilkins Pediatric Endocrine Society. Thirty-one patients aged 10 months to 16 years had been treated with TBA for Cushing's disease; one had been treated with ortho para prime isomer of dichlorodiphenyldichloroethane alone. Postadrenalectomy hyperpigmentation was reported in 18 patients. Sella enlargement was detected in eight patients (25%) after 1 to 5.5 years (mean, three years) post-TBA. Five of these patients have had documented pituitary adenomas to date. This incidence is higher than the adult figure of 10% to 16%.

Adolescent↗
PubMed1978

Cushing's syndrome and acute lymphoblastic leukemia.

Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences.

Adrenal Gland Neoplasms↗
PubMed1983

Cutaneous disease in black children.

Understanding cutaneous disease in the black races requires that the physician first be able to discern normal from abnormal pigmentary patterns and second be able mentally to add or subtract the patient's color, so that classic textbook descriptions of disease become applicable. Blacks tend to have four exaggerated pathologic reaction patterns: (1) pigment lability (frequent hyperpigmentation and hypopigmentation), (2) follicular responses and follicular diseases, (3) mesenchymal responses (fibroplastic and granulomatous), and (4) bullous responses. Social patterns in black communities aimed at masking hypopigmentation by use of emollients produce a wide spectrum of folliculitides rarely seen in whites. Methods of hair care commonly cause alopecias. Tinea capitis, which mimics four other varied scalp diseases, is now almost exclusively seen in blacks. Infesations, such as scabies and pediculosis capitis, are almost unheard of in American blacks.

Adolescent↗
PubMed1994

Skin lesions of the spinal axis and spinal dysraphism. Fifteen cases and a review of the literature.

OBJECTIVE: To catalog the paraspinal skin lesions of early childhood that are associated with occult spinal dysraphism. RESEARCH DESIGN: Retrospective review of a series of patients. SETTING: Tertiary care referral center. PATIENTS: Fifteen patients who had significant paraspinal skin lesions were identified from the personal files of the authors who saw them. RESULTS: The skin lesions included various combinations of hyperpigmentation, hypopigmentation, hypertrichosis, acrochordons, dimples, lipomas, hemangiomas, or teratomas. Not all lesions were evaluated with the same tests, which included plain roentgenography, ultrasonography, myelography, computed tomography, and magnetic resonance imaging. Of the 15 patients, six had spinal anomalies, eight had no apparent spinal dysraphism, and one had insufficient results of the evaluation to assess the spinal column. CONCLUSIONS: Early recognition of paraspinal skin lesions is essential to prevent neurologic damage. Urinary or fecal incontinence, recurrent urinary infections, muscle atrophy, foot deformities, weakness, pain, or decreased sensation in the lower extremities may eventually develop in these patients. Magnetic resonance imaging appears to be the single best screening test for dysraphism.

Back↗
PubMed1986

Hemodynamic indicators of postthrombotic sequelae.

Single or repetitive episodes of lower-extremity venous thrombosis may result in venous obstruction, valvular incompetence, and the postthrombotic syndrome. Seventy-seven patients with ileofemoral deep venous thrombosis diagnosed with biplane phlebograms received routine anticoagulant therapy and follow-up with clinical and noninvasive vascular examinations (reflux photoplethysmography, Doppler ultrasonography, and venous outflow plethysmography). The results of the final visit (mean, 25 months; range, three to 50 months) revealed that 53 patients (69%) had evidence of edema and/or hyperpigmentation and five patients (6%) had ulceration. Doppler ultrasonography was 77% sensitive (41 of 53 patients) and 95% specific (41 of 43 patients) at identifying patients with postthrombotic sequelae. We conclude that noninvasive testing throughout the rehabilitative period following acute deep venous thrombosis will identify patients at risk for postthrombotic symptoms. This information may alert the clinician toward initiating elastic compressive therapy in hopes of prolonging a disease-free interval.

Adult↗
PubMed1996

Hypertrichosis, pigmentary retinopathy, and facial anomalies: a new syndrome?

We report on a 22-month-old male with congenital hypertrichosis of the face, arms, legs, shoulders, back, and buttocks, abnormal facial appearance, dolichocephaly, and pigmentary retinopathy. Symmetrical hyperpigmentation is present on the sideburn areas of his face, and hyperpigmented streaks are seen on arms and legs. Biopsy of the hyperpigmented' skin showed many separate bundles of smooth muscles in the dermis. No relative had hypertrichosis or other birth defects. To our knowledge, the syndrome of facial anomalies, pigmentary retinopathy, and congenital hypertrichosis has not been reported previously.

Abnormalities, Multiple↗
PubMed1999

Clinical, cytogenetic, and fluorescence in situ hybridization findings in two cases of "complete ring" syndrome.

The term "ring syndrome" was proposed to describe a phenotype of growth failure without major malformations due to a ring autosome. The growth failure is thought to be caused by instability of the ring chromosome leading to aneusomy and cell death. Most previous studies of ring chromosomes were based on standard cytogenetic banding techniques and were limited to microscopically detectable deletions in the ring chromosomes. We report on two patients with complete ring (4) and ring (9) chromosomes, respectively. The first was a 15-month-old girl and the second was a 16-month-old boy. They both presented with severe, symmetrical growth failure and normal psychomotor development in the absence of malformations. Their parents had a normal phenotype. The first case had a whorled pattern of hyperpigmentation and hypopigmentation on part of the face and chest, and the second case had a patchy hyperpigmented rash on the trunk. Peripheral blood karyotype of the first patient was 46,XX, r(4)(p16.3q35.2) and of the second 45,XY,-9/46,XY,r(9)(p24q34.3). G-band analysis suggested no loss of material in the ring chromosomes. These findings were confirmed by fluorescence in situ hybridization (FISH) analysis using chromosome-specific subtelomeric probes. The common human telomeric sequences were intact in the first patient but absent in the second patient. The cytogenetic and FISH data in our two cases provide further evidence for the existence of a "complete ring" phenotype independent of the autosome involved. Pigmentary skin changes are a useful clinical sign of mosaicism caused by the ring instability.

Chromosomes, Human, Pair 4↗