Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions.

Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs. Under three diagnostic models, we have conducted linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an autosomal dominant model) and nonparametric (Sall statistic) methods. There is ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. If we treat the third set of families as a replication set, then two regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD or Sall scores > or =2.0. Within the 1q31 region, we observed an HLOD of 2.72 (genomewide P=.061) under our least stringent diagnostic model, whereas the 17q25 region contained a maximal HLOD of 3.53 (genomewide P=.007) under our intermediate diagnostic model. We have evaluated our results with respect to the findings from several new independent genomewide linkage studies and also have completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking history, and age at onset as stratifying covariates. The OSAs generate the interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region--a region implicated by four other studies.

Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions.

PURPOSE: We seek to identify genetic loci that contribute to age-related maculopathy susceptibility. METHODS: Families consisting of at least two siblings affected by age-related maculopathy were ascertained using eye care records and fundus photographs. Additional family members were used to increase the power to detect linkage. Microsatellite genotyping was conducted by the National Heart, Lung and Blood Institute Mammalian Genotyping Service and the National Institutes of Health Center for Inherited Disease Research. Linkage analyses were conducted with parametric (autosomal dominant; heterogeneity lod score) and nonparametric methods (S(all) statistic) using three diagnostic models. False-positive rates were determined from simulations using actual pedigrees and genotyping data. RESULTS: Under our least stringent diagnostic model, model C, 860 affected individuals from 391 families (452 sib pairs) were genotyped. Sixty-five percent of the affected individuals had evidence of exudative disease. Four regions, 1q31, 9p13, 10q26, and 17q25, showed multipoint heterogeneity lod scores or S(all) scores of 2.0 or greater (under at least one model). Under our most stringent diagnostic model, model A, the 1q31 heterogeneity lod score was 2.46 between D1S1660 and D1S1647. Under model C, the 17q25 heterogeneity lod score at D17S928 was 3.16. Using a threshold of 1.5, additional loci on chromosomes 2 and 12 were identified. CONCLUSIONS: The locus on chromosome 1q31 independently confirms a report by Klein and associates mapping an age-related maculopathy susceptibility gene to this region. Simulations indicate that the 1q31 and 17q25 loci are unlikely to be false positives. There was no evidence that other known macular or retinal dystrophy candidate gene regions are major contributors to the genetics of age-related maculopathy.

Corticosteroid therapy for optic disc neovascularization secondary to chronic uveitis.

PURPOSE: To report successful corticosteroid treatment of optic disc neovascularization associated with uveitis. METHODS: Retrospective review of medical records. RESULTS: Nine patients were identified with chronic uveitis and optic disc neovascularization without clinical or angiographic evidence of retinal ischemia. Ages ranged from 14 to 37 years (median age, 27). All patients were treated with either oral and/or subtenon's corticosteroids. Partial regression of the neovascularization was observed in all patients within 2 to 6 weeks (median, 5 weeks) after initiating treatment. Eight of nine patients had complete resolution of disc neovascularization at a median of 3 months (range, 2 to 42 months) after initiation of treatment and a median follow-up of 24 months (range, 7 to 144 months). Recurrence of disc neovascularization occurred in two patients, but it regressed again after further corticosteroid therapy. CONCLUSIONS: Optic disc neovascularization may occur in patients with chronic uveitis in the absence of retinal ischemia. This neovascularization can be successfully treated with corticosteroids.

A full genome scan for age-related maculopathy.

Age-related macular degeneration or age-related maculopathy (ARM) is a major public health issue, as it is the leading cause of irreversible vision loss in the elderly in the Western world. Using three diagnostic models, we have genotyped markers in 16 plausible candidate regions and have carried out a genome-wide screen for ARM susceptibility loci. A panel of 225 ARM families comprising up to 212 affected sib pairs was genotyped for 386 markers. Under our most stringent diagnostic model, the regions with the strongest evidence of linkage were on chromosome 9 near D9S301 and on 10 near D10S1230, with peak multipoint heterogeneity LOD scores (HLOD) of 1.87 and 1. 42 and peak GeneHunter-Plus non-parametric LOD scores (GHP LOD) of 1. 69 and 1.83. After expanding our initial set of families to 364 ARM families with up to 329 affected sib pairs, the linkage signal on chromosome 9 vanished, while the chromosome 10 signal decreased to a GHP LOD of about 1.0, with a SimIBD P -value of 0.008 under the broadest diagnostic model with marker D10S1236. After error filtration, the GHP LOD increased to 1.27 under our most stringent model and 1.42 under our broadest model, peaking near D10S1236. This peak was seen consistently across all three diagnostic models. Our analyses also excluded up to nine different candidate regions and identified a few other regions of potential linkage, suitable for further studies. Of particular interest was the region on chromosome 5 near D5S1480, where a reasonable candidate gene, glutathione peroxidase 3, resides.

Ocular manifestations of cat-scratch disease.

Bartonella henselae has only recently been isolated, characterized, and found to be the principal cause of cat-scratch disease (CSD). The availability of specific serologic investigations has allowed the recognition of a spectrum of ocular CSD syndromes that previously were ill defined and considered idiopathic. The primary inoculation complex causing regional lymphadenopathy is represented in the eye by Parinaud's oculoglandular syndrome; B. henselae is the most common cause. Leber's neuroretinitis has been identified for 80 years, and new data suggest that it is commonly a manifestation of CSD; the extent of the association remains to be determined. CSD optic neuritis is also described. The vitreoretinal manifestations include anterior uveitis, vitritis, pars planitis, focal retinal vasculitis, a characteristic retinal white spot syndrome, Bartonella retinitis, branch retinal arteriolar or venular occlusions, focal choroiditis, serous retinal detachments, and peripapillary angiomatous lesions. The pattern of ocular disease in AIDS-associated B. henselae infections is poorly delineated; unusual manifestations include conjunctival and retinal bacillary angiomatosis. The benefit of antimicrobial therapy for CSD in immunocompetent individuals has been difficult to establish, partly because most infections are self limited. Empirically, azithromycin, ciprofloxacin, rifampin, parenteral gentamicin, or trimethoprim-sulfamethoxazole provide the best therapeutic choices to minimize damage to the eye.

Vitreon, a new perfluorocarbon.

We evaluated a new liquid perfluorocarbon, perfluorophenanthrene (Vitreon). This material has proven to be non-toxic in vitrectomised rabbit eyes for up to six weeks. Present investigation under FDA guidelines establishes both the safety and efficacy of Vitreon in human eyes. We used Vitreon for intraoperative hydrokinetic retinal manipulation in 15 patients. In cases of proliferative vitreoretinopathy (6), rhegmatogenous retinal detachment (5), giant retinal tear (2), retinal dialysis (1), and tractional retinal detachment (1) the retina was successfully reattached. Postoperatively two patients developed proliferative vitreoretinopathy necessitating further surgery, and one patient developed hypotony. Follow-up showed 100% reattachment rate with a mean duration of 6.3 months. Postoperative visual acuity ranges from light perception to 20/30.

Surgical technique for managing rhegmatogenous retinal detachment following prosthokeratoplasty.

The authors report the successful repair of a retinal detachment following Cardona prosthokeratoplasty. The surgical technique included pars plana vitrectomy, endolaser photocoagulation, peripheral cryopexy, scleral buckling, and the use of a liquid perfluorocarbon derivative, perfluorophenanthrene, to achieve and maintain reattachment. Perfluorophenanthrene was removed 3 weeks postoperatively. Postoperative visual acuity stabilized at functional levels. No ocular complications, adverse reactions, or redetachment were observed.