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



A national matched case-control study.



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).



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.



Extensive macular atrophy with pseudodrusen status (cases vs. controls).



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.



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.
CHRU Montpellier, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Montpellier, France; INSERM, CIC 1411, Montpellier, France.
Aymeric
A
Douillard
CHRU Montpellier, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Montpellier, France; INSERM, CIC 1411, Montpellier, France.
Marie-Christine
MC
Picot
University of Bordeaux, ISPED, Bordeaux, France; Inserm, U1219 - Bordeaux Population Health Research Center, Bordeaux, France.
Cécile
C
Delcourt
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France.
Annie
A
Lacroux
Eye Clinic, Sourdille Jules Verne, Nantes, France.
Xavier
X
Zanlonghi
Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, CHU de Lille, France.
Bernard
B
Puech
Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, CHU de Lille, France.
Sabine
S
Defoort-Dhelemmes
Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, CHU de Lille, France.
Isabelle
I
Drumare
University Lille, Inserm, CHU Lille, CIC 1403 - Centre d'Investigation Clinique, Lille, France.
Elsa
E
Jozefowicz
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France.
Béatrice
B
Bocquet
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France.
Corinne
C
Baudoin
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France.
Nour
N
Al-Dain Marzouka
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France.
Sarah
S
Perez-Roustit
Eye Clinic, Hôpital de Tours, CHRU de Tours, Tours, France.
Sophie
S
Arsène
Inserm 1415, Centre d'Investigation Clinique, CHRU de Tours, Tours, France.
Valérie
V
Gissot
Eye Clinic, Centre Paradis, Monticelli, Marseille, France.
François
F
Devin
Eye Clinic, Hôpital Robert Debré, CHRU de Reims, France.
Carl
C
Arndt
Eye Clinic, Maison Rouge, Strasbourg, France; Fondation Adolphe de Rothschild, Paris, France.
Benjamin
B
Wolff
Fondation Adolphe de Rothschild, Paris, France.
Martine
M
Mauget-Faÿsse
Centre Ophtalmologique Rabelais, Lyon, France.
Maddalena
M
Quaranta
CHRU Montpellier, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Montpellier, France.
Thibault
T
Mura
University Lille, Inserm, CHU Lille, CIC 1403 - Centre d'Investigation Clinique, Lille, France.
Dominique
D
Deplanque
Eye Clinic, Hôpital Intercommunal, Créteil, France.
Hassiba
H
Oubraham
Eye Clinic, Hôpital Intercommunal, Créteil, France; Centre d'Imagerie Laser, Rue Antoine Bourdelle, Paris, France.
Salomon Yves
SY
Cohen
Eye Clinic, Hôpital Saint Roch, CHU de Nice, France.
Pierre
P
Gastaud
Eye Clinic, Hôpital Intercommunal, Créteil, France.
Olivia
O
Zambrowsky
Eye Clinic, Hôpital Universitaire de Dijon and Eye Nutrition and Signaling Group, INRA, Dijon, France.
Catherine
C
Creuzot-Garcher
Sorborne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France; CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France.
Saddek
S
Mohand Saïd
Eye Clinic, Hôpital Intercommunal, Créteil, France.
Rocio
R
Blanco Garavito
Eye Clinic, Hôpital Intercommunal, Créteil, France.
Eric
E
Souied
Fondation Adolphe de Rothschild, Paris, France; Sorborne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France; CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France; Institute of Ophthalmology, University College of London, London, United Kingdom; Académie des Sciences, Institut de France, Paris, France.
José-Alain
JA
Sahel
Sorborne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France; CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, Paris, France; Institute of Ophthalmology, University College of London, London, United Kingdom.
Isabelle
I
Audo
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France.
Christian
C
Hamel
Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France. Electronic address: isabelannemeunier@yahoo.fr.
Isabelle
I
Meunier
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001766:Blindness; D016022:Case-Control Studies; D020256:Choroidal Neovascularization / Q000453:epidemiology; D003941:Diagnostic Techniques, Ophthalmological; D018450:Disease Progression; D005260:Female; D005602:France / Q000453:epidemiology; D057092:Geographic Atrophy / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010781:Photography; D015593:Retinal Drusen / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D017678:Sex Distribution; D041623:Tomography, Optical Coherence; D014792:Visual Acuity