Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights.

PURPOSE: To reappraise the autosomal dominant Martinique crinkled retinal pigment epitheliopathy (MCRPE) in light of the knowledge of its associated mutated gene mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3), an actor in the p38 mitogen-activated protein kinase pathway. DESIGN: Clinical and molecular study. PARTICIPANTS: A total of 45 patients from 3 generations belonging to a family originating from Martinique with an autosomal dominant MCRPE were examined. METHODS: Best-corrected visual acuity, fundus photographs, and spectral-domain optical coherence tomography (SD OCT) of all clinically affected patients and carriers for the causal mutation were reviewed at the initial visit and 4 years later for 10 of them. Histologic retinal lesions of Mapkapk3(-/-) mice were compared with those of the human disease. MAIN OUTCOME MEASURES: The MCRPE natural history in view of MAPKAPK3 function and Mapkapk3(-/-) mouse retinal lesions. RESULTS: Eighteen patients had the c.518T>C mutation. One heterozygous woman aged 20 years was asymptomatic with normal fundus and SD OCT (stage 0). All c.518T>C heterozygous patients older than 30 years of age had the characteristic dried-out soil fundus pattern (stages 1 and 2). Complications (stage 3) were observed in 7 cases, including polypoidal choroidal vasculopathy (PCV) and macular fibrosis or atrophy. One patient was homozygous and had a form with severe Bruch's membrane (BM) thickening and macular exudation with a dried-out soil pattern in the peripheral retina. The oldest heterozygous patient, who was legally blind, had peripheral nummular pigmentary changes (stage 4). After 4 years, visual acuity was unchanged in 6 of 10 patients. The dried-out soil elementary lesions radically enlarged in patients with a preferential macular extension and confluence. These findings are in line with the progressive thickening of BM noted with age in the mouse model. During follow-up, there was no occurrence of PCV. CONCLUSIONS: MCRPE is an autosomal dominant, fully penetrant retinal dystrophy with a preclinical stage, an onset after the age of 30 years, and a preserved visual acuity until occurrence of macular complications. The natural history of MCRPE is in relation to the role of MAPKAPK3 in BM modeling, vascular endothelial growth factor activity, retinal pigment epithelial responses to aging, and oxidative stress.

Martinique (West Indies) crinkled retinal pigment epitheliopathy: clinical description.

PURPOSE: To report a previously undescribed pattern of crinkled retinal pigment epithelium (RPE), observed in a family of black patients originating from Martinique, an island in the French West Indies. METHODS: Three generations were examined by visual acuity measurement and fundus photography. Autofluorescence photography, fluorescein and indocyanine green angiography, visual field testing, electrophysiology, and spectral domain optical coherence tomography were performed in certain patients. RESULTS: One 86-year-old grandmother, her 7 children, her nephew, and 18 of her 22 grandchildren were examined. Nine patients were affected: five children, one nephew, and three grandchildren. An unrelated patient originating from the same area was also affected. In the third generation, fundus findings were whitish deep lines located in the posterior pole. Optical coherence tomography showed a crinkled pattern of a slightly elevated RPE. In the second generation, a scalloped crinkled RPE was observed in the posterior pole and midperiphery, giving an image of dry desert land in fluorescein and indocyanine green angiography. Optical coherence tomography showed that the RPE formed ripples, giving it a crinkled appearance. Complications were observed in six cases: they included RPE atrophy (one case), subretinal and sub-RPE hemorrhages because of polypoidal choroidal vasculopathy (four cases), and fibrovascular scarring (one case). The grandmother's fundi were characterized by peripheral pigmentary changes, with severe visual loss. CONCLUSION: The observed pattern appeared different from previously described dystrophies and could be referred to as Martinique crinkled retinal pigment epitheliopathy.