Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

PURPOSE: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. DESIGN: A national matched case-control study. PARTICIPANTS: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). METHODS: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. MAIN OUTCOME MEASURES: Extensive macular atrophy with pseudodrusen status (cases vs. controls). RESULTS: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. CONCLUSIONS: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

Dietary, environmental, and genetic risk factors of Extensive Macular Atrophy with Pseudodrusen, a severe bilateral macular atrophy of middle-aged patients.

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.106) was lower in Provence-Côte d'Azur with a Mediterranean diet (1.9/1.106), and higher in regions with intensive farming or industrialized activities (5 to 20/1.106). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina.

Idiopathic and radiation-induced ocular telangiectasia: the involvement of the ATM gene.

PURPOSE: To investigate whether individuals, with no family history of ataxia telangiectasia (AT), in whom idiopathic or radiation-induced ocular telangiectasia developed are carriers of ATM gene mutations. METHODS: The ATM cDNA from lymphoblastoid cell lines established from 16 patients with idiopathic retinal or choroidal telangiectasia and 14 patients with radiation-induced telangiectasia after radiotherapy for age-related macular degeneration (AMD) was screened using the restriction endonuclease fingerprinting technique. The frequency of each detected variant was determined in the French population by either a mass spectrometry-based technique or variant-specific endonuclease digestion. RESULTS: Twenty-one ATM missense alterations, at 10 different sites, 8 of which would result in an amino acid substitution at a conserved position in the ATM protein were found. Four were novel changes, three of which were not detected in the 128 French control subjects screened. Eleven of 16 of the individuals with either idiopathic polypoidal choroidal vasculopathy or juxtafoveolar retinal telangiectasis and 6 of 14 individuals that had choroidal telangiectasis after radiotherapy for AMD carried ATM sequence variants. These latter six individuals had a significantly shorter delay time before the presentation of this vasculopathy compared with those individuals who had a wild-type ATM (11.8 +/- 3.4 months vs. 17.5 +/- 4.5 months, P = 0.024). They had also received a lower average dose of X-rays, although this difference did not reach statistical significance (18.7 +/- 3.9 Gy vs. 23.7 +/- 5.6 Gy, P = 0.09). CONCLUSIONS: ATM missense variants could confer an AT-like phenotype and influence the formation of retinal and choroidal vascular abnormalities.

Exudative idiopathic polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin.

PURPOSE: To report two cases of exudative idiopathic polypoidal choroidal vasculopathy treated by photodynamic therapy with verteporfin. DESIGN: Interventional case reports. METHODS: Two patients, a man aged 58 years and a woman aged 57 years, with recent visual impairment in the right eye (OD) (both eyes best-corrected visual acuity: 10/50 and Pelli-Robson contrast sensitivity 1.35 and 1.20) and angiographically proved subfoveal idiopathic polypoidal choroidal vasculopathy were treated with photodynamic therapy using verteporfin (Visudyne; Novartis SA, Rueil Malmaison, France). Functional and angiographic outcomes were assessed 6 weeks and 3, 6, and 12 months after treatment. RESULTS: In Patient 1, 3 months after treatment, best-corrected visual acuity and contrast sensitivity improved (10/16 and 1.50) and then remained stable throughout the 12 months after treatment. In Patient 2, 6 weeks after treatment, vision and contrast sensitivity were 10/20 and 1.35; and at 3 months, were improved and stabilized at 10/12.5 and 1.50. Angiographically, photodynamic therapy with verteporfin was associated with nonperfusion and occlusion of the exudative polypoidal dilations. No acute recurrence was noted during the follow-up period. CONCLUSION: In subfoveal exudative idiopathic polypoidal choroidal vasculopathy, photodynamic therapy with verteporfin may be associated with beneficial functional results.