Showing papers by "John H. Fingert published in 2003"

Leber's hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus.

Abstract: Purpose To describe the clinical features of two cases of Leber's hereditary optic neuropathy (LHON) precipitated by antiretroviral treatment for human immunodeficiency virus (HIV) infection. Methods Two cases of LHON (from an expected four new cases a year throughout Australia) were identified in men on treatment for HIV infection. Results Two HIV-infected men were receiving combination antiretroviral therapy that included nucleoside analogues. Both patients carried the 14 484 mitochondrial DNA mutation and were distantly related (seventh cousins). Although both men presented with sequential visual loss typical of LHON and one had a known close relative affected by LHON, the correct diagnosis was delayed in both cases. The final visual outcome was profoundly reduced in both instances and cessation of antiretroviral therapy did not result in recovery of vision in one patient. Conclusion Patients with a family history of LHON who require antiretroviral treatment should be warned of the high risk of severe visual loss. The underlying mechanism of antiretroviral side effects may help characterize the other trigger factors for LHON.

Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation.

Abstract: Objective: To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the myocilin mutation Thr377Met. Method and Design: Cross-sectional genetic study. Four unrelated pedigrees carrying the Thr377Met mutation were ascertained from more than 2000 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania and from families with glaucoma referred to the study from throughout Australia. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Thr377Met mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. Results: From the 4 pedigrees carrying the Thr377Met mutation, 23 individuals with either ocular hypertension (OHT) or POAG were found, with a mean±SD age at diagnosis of 41.2±11.5 years, and a mean peak intraocular pressure of 31.7±9.9 mm Hg. A further 9 mutation carriers older than 18 years were studied who as yet showed no signs of OHT or POAG (6 of these 9 were younger than 30 years). A single individual with POAG was identified who did not carry the Thr377Met mutation. For Thr377Met carriers, age-related penetrance for OHT or POAG was 88% at age 30 years. A positive family history of POAG was present for 3 of the 4 index cases. Thirteen (57%) of the 23 Thr377Met carriers with OHT or POAG had undergone glaucoma drainage surgery. Although the glaucoma in these families appears to be pressure dependent, 2 individuals showed optic disc cupping before detected elevation in intraocular pressure. One family was of British origin, with a different background haplotype from the other 3 families from Greece or Macedonia, who shared a common haplotype. Conclusions: The GLC1A Thr377Met mutation is associated with POAG that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common Gln368STOP mutation. In addition, patients with glaucoma with the Thr377Met mutation were more likely to have undergone glaucoma drainage surgery.