Clinical characteristics and risk factors of extensive macular atrophy with pseudodrusen The EMAP case-control national clinical trial

Aymeric Douillard (1, 2) , Marie-Christine Picot (3) , Cecile Delcourt (4, 5) , Annie Lacroux (6, 7, 8) , Xavier Zanlonghi (9, 10) , Bernard Puech (11) , Sabine Defoort-Dhelemmes (11) , Isabelle Drumare (12) , Elsa Jozefowicz (13, 14, 15) , Beatrice Bocquet (6, 7, 8) , Corinne Baudoin (6, 7, 8) , Nour Al-Dain Marzouka (6, 7, 8) , Sarah Perez-Roustit (6, 7, 8) , Sophie Arsene (16) , Valerie Gissot (17, 18) , Francois Devin (19) , Carl Arndt (20) , Benjamin Wolff (21, 22) , Martine Mauget-Faysse (21) , Maddalena Quaranta (23) , Thibault Mura (24) , Dominique Deplanque (13, 25, 15) , Hassiba Oubraham (26) , Salomon Yves Cohen (26, 27) , Pierre Gastaud (28, 29) , Olivia Zambrowsky (26) , Catherine Creuzot Garcher (30, 31, 32) , Saddek Mohand Said (33, 34, 35, 36, 37, 38) , Rocio Blanco Garavito (26) , Eric Souied (26) , José-Alain Sahel (21, 39, 40, 33, 34, 41, 36, 37, 38) , Isabelle Audo (40, 34, 34, 35, 36, 37, 38) , Christian Hamel (7, 42, 8) , Isabelle Meunier (7, 42, 8)

1 Clinical Investigation Center - Clinical Research and Epidemiology Unit
2 CIC 1411 Clinical Investigation Center
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED)
5 BPH - Bordeaux population health
6 Centre de Référence Maladies Sensorielles Génétiques
7 INM - Institut des Neurosciences de Montpellier
8 UM - Université de Montpellier
9 Eye Clinic
10 Centre Ophtalmologique de la Clinique Jules Verne
11 Service d’Exploration de la Vision et Neuro-ophtalmologie [CHU Lille]
12 Service d’Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro
13 CIC Lille - Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301
14 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
15 Université de Lille
16 Eye Clinic
17 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
18 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
19 Eye Clinic
20 Hôpital Robert Debré - Eye Clinic
21 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
22 Eye Clinic
23 Centre Ophtalmologique Rabelais
24 Clinical Investigation Center and Clinical Research and Epidemiology Unit
25 CHU de Lille - Centre Hospitalier Universitaire de Lille
26 Eye Clinic
27 Centre Ophtalmologique d'Imagerie et de Laser
28 Eye Clinic
29 CHU Nice - Centre Hospitalier Universitaire de Nice
30 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
31 UBFC - Université Bourgogne Franche-Comté [COMUE]
32 Eye Clinic - Eye Nutrition and Signaling Group
33 CIC 1423 DHU Sight Restore
34 CHNO - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
35 Institut de la Vision
36 CNRS - Centre National de la Recherche Scientifique
37 UPMC - Université Pierre et Marie Curie - Paris 6
38 SU - Sorbonne Université
39 Académie des sciences [Paris, France]
40 Institute of Ophthalmology
41 INSERM - Institut National de la Santé et de la Recherche Médicale
42 Hôpital Gui de Chauliac [CHU Montpellier]

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.

Domaines: Sciences du Vivant [q-bio]

Aymeric Douillard, Marie-Christine Picot, Cecile Delcourt, Annie Lacroux, Xavier Zanlonghi, et al.. Clinical characteristics and risk factors of extensive macular atrophy with pseudodrusen The EMAP case-control national clinical trial. Ophthalmology: Journal of The American Academy of Ophthalmology, 2016, 123 (9), pp.1865-1873. ⟨10.1016/j.ophtha.2016.05.018⟩. ⟨hal-01607011⟩