Retinal Nerve Fiber Layer Thickness in Dominant Optic Atrophy Measurements by Optical Coherence Tomography and Correlation with Age Piero Barboni, MD, 1,2 Giacomo Savini, MD, 3 Vincenzo Parisi, MD, 3 Michele Carbonelli, MD, 1 Chiara La Morgia, MD, 2 Alessandra Maresca, PhD, 2 Federico Sadun, MD, 4 Anna Maria De Negri, MD, 5 Arturo Carta, MD, 6 Alfredo A. Sadun, MD, PhD, 7 Valerio Carelli, MD, PhD 2 Purpose: To measure the retinal nerve fiber layer (RNFL) thickness by means of optical coherence tomog- raphy (OCT) in patients with dominant optic atrophy (DOA). Design: Cross-sectional study. Participants: Thirty-three patients from 15 pedigrees with DOA harboring heterozygous mutations in the OPA1 gene and 43 healthy subjects were enrolled. Methods: The RNFLs of DOA patients were studied by OCT and compared with those of 43 healthy subjects matched for age and optic nerve head (ONH) size. Main Outcome Measures: Retinal nerve fiber layer thickness. Results: Dominant optic atrophy patients revealed a significant RNFL thickness reduction in all quadrants, with a preferential involvement of the temporal and inferior sectors. The progressive decline of RNFL thickness with age was similar to that observed in healthy subjects and was more evident in the 2 quadrants with higher residual amounts of fibers, that is, the superior and the inferior. The temporal quadrant was profoundly depleted of fiber so that the further rate of loss of microns per year is close to zero, whereas the nasal quadrant was spared the most by neurodegeneration. Conclusions: The present findings, taken in conjunction with the authors’ previous description of small ONH size in DOA, strongly suggest that patients with this disease are born with fewer optic nerve axons and support the hypothesis that subsequent visual loss depends on further age-related loss of fibers, which also occurs in controls. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:2076 –2080 © 2011 by the American Academy of Ophthalmology. Dominant optic atrophy (DOA), initially described by Kjer, 1 is a genetic neurodegenerative disorder affecting the retinal ganglion cells and characterized by a slowly progressive bilateral visual loss starting in childhood, ultimately leading to severe optic atrophy. 2 Approxi- mately 60% of DOA cases harbor a heterozygous muta- tion in the OPA1 gene (3q28 – q29, Online Mendelian Inheritance in Man 165500), 3 a dynamin-related guanos- ine triphosphate (GTPase) targeted to mitochondria in- volved in multiple functions, including mitochondrial fusion, cristae morphologic features, oxidative phosphor- ylation (OXPHOS) and membrane potential maintenance, and control of apoptosis. 4 Over 200 OPA1 mutations have been reported (http://lbbma.univ-angers.fr/eOPA1/, accessed January 11, 2011), and most are predicted to induce haploinsufficiency, but missense mutations also are found commonly, and a subset of these, remarkably affecting the GTPase domain, are associated with a com- plicated form of syndromic DOA (DOA plus) character- ized by the accumulation of mitochondrial DNA multiple deletions. 5–7 Clinical examination demonstrates loss of vision, impair- ments of color vision, cecocentral scotomas, and temporal or diffuse pallor of the optic disc, which often leads to optic disc excavation. Disease progression may be quite variable within the same family, ranging from mild cases with min- imal losses of visual acuity that stabilizes in adolescence, to slowly but relentlessly progressing cases, to cases with subacute severe decreases of visual acuity. This variability of clinical expression may be reflected by the different extent of optic atrophy in different patients. Dominant optic atrophy, similarly to Leber’s hereditary optic neuropathy (LHON), is characterized by the early and preferential in- volvement of the small fibers in the papillomacular bundle, a hallmark of mitochondrial optic neuropathies. 8 Optical coherence tomography (OCT) has been used successfully by the authors’ group to redefine by objective anatomic measures the features of optic neuropathy in 2076 © 2011 by the American Academy of Ophthalmology ISSN 0161-6420/11/$–see front matter Published by Elsevier Inc. doi:10.1016/j.ophtha.2011.02.027