Aymeric Douillard1, Marie-Christine Picot1, Cécile Delcourt2, Annie Lacroux3, Xavier Zanlonghi4, Bernard Puech5, Sabine Defoort-Dhelemmes5, Isabelle Drumare5, Elsa Jozefowicz6, Béatrice Bocquet3, Corinne Baudoin3, Nour Al-Dain Marzouka3, Sarah Perez-Roustit3, Sophie Arsène7, Valérie Gissot8, François Devin9, Carl Arndt10, Benjamin Wolff11, Martine Mauget-Faÿsse12, Maddalena Quaranta13, Thibault Mura14, Dominique Deplanque6, Hassiba Oubraham15, Salomon Yves Cohen16, Pierre Gastaud17, Olivia Zambrowsky15, Catherine Creuzot-Garcher18, Saddek Mohand Saïd19, Rocio Blanco Garavito15, Eric Souied15, José-Alain Sahel20, Isabelle Audo21, Christian Hamel3, Isabelle Meunier22. 1. CHRU Montpellier, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Montpellier, France; INSERM, CIC 1411, Montpellier, France. 2. University of Bordeaux, ISPED, Bordeaux, France; Inserm, U1219 - Bordeaux Population Health Research Center, Bordeaux, France. 3. Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University and INSERM U1051, Institute for Neurosciences of Montpellier, France. 4. Eye Clinic, Sourdille Jules Verne, Nantes, France. 5. Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, CHU de Lille, France. 6. University Lille, Inserm, CHU Lille, CIC 1403 - Centre d'Investigation Clinique, Lille, France. 7. Eye Clinic, Hôpital de Tours, CHRU de Tours, Tours, France. 8. Inserm 1415, Centre d'Investigation Clinique, CHRU de Tours, Tours, France. 9. Eye Clinic, Centre Paradis, Monticelli, Marseille, France. 10. Eye Clinic, Hôpital Robert Debré, CHRU de Reims, France. 11. Eye Clinic, Maison Rouge, Strasbourg, France; Fondation Adolphe de Rothschild, Paris, France. 12. Fondation Adolphe de Rothschild, Paris, France. 13. Centre Ophtalmologique Rabelais, Lyon, France. 14. CHRU Montpellier, Clinical Investigation Center and Clinical Research and Epidemiology Unit, Montpellier, France. 15. Eye Clinic, Hôpital Intercommunal, Créteil, France. 16. Eye Clinic, Hôpital Intercommunal, Créteil, France; Centre d'Imagerie Laser, Rue Antoine Bourdelle, Paris, France. 17. Eye Clinic, Hôpital Saint Roch, CHU de Nice, France. 18. Eye Clinic, Hôpital Universitaire de Dijon and Eye Nutrition and Signaling Group, INRA, Dijon, France. 19. 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. 20. 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. 21. 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. 22. 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.
Abstract
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.
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.
Authors: Francesco Romano; Matteo Airaldi; Mariano Cozzi; Marta Oldani; Ester Riva; Alice Ingrid Bertoni; Astrit Dautaj; Matteo Bertelli; Giovanni Staurenghi; Anna Paola Salvetti Journal: Ophthalmol Sci Date: 2021-03-19