RETINAL MANIFESTATIONS IN MITOCHONDRIAL DISEASES ASSOCIATED WITH MITOCHONDRIAL-DNA MUTATION

Purpose: To scrutinize retinal involvement associated with distinct mi tochondrial DNA (mtDNA) defects, we reviewed the records of a consecut ive series of patients with various mitochondrial diseases. Methods: C linical, laboratory and mtDNA studies were performed in: five patients with Kearns-Sayre syndrome (KSS); six patients with chronic progressi ve external ophthalmoplegia (CPEO); three patients, with mitochondrial myopathy; encephalopathy, lactic acidosis, and stroke-like episode (M ELAS); three patients with myoclonic epilepsy and ragged-red fibers (M ERRF); 20 patients,vith Leber's hereditary optic neuropathy (LOHN); 30 patients with simple diabetes mellitus. Results: All KSS patients wit h neurologic and cardiac symptoms associated with a deletion of mtDNA in muscle biopsy specimens show ed widespread retinal pigmentary chang es characterized by salt-and pepper-like appearance of the fundus, Thr ee of six patients with CPEO, a mild variant of KSS, showed subtle def ects at the level of retinal pigment epithelium of the posterior pole, although mtDNA deletion was similar to that in KSS, Of three patients with MELAS syndrome, one patient showed juvenile cataract and mild re tinal pigmentary defect in the posterior pole. Of three patients with MERRF syndrome associated with a mtDNA mutation at nucleotide position (np) 8344, one patient showed mild pigment disorder in the posterior pole in addition to optic neuropathy, Two of 20 patients with LHON ass ociated with a mtDNA mutation at np 11778 showed mild pigmentary defec t in the macula together with typical optic neuropathy. In addition, t wo of 30 patients,vith isolated diabetes mellitus showed a mtDNA mutat ion at np 3243 (MELAS mutation), but they did not present with any oth er neurologic or multisystem disorder. Conclusion: The retina, in part icular the retinal pigment epithelium, is highly vulnerable to be invo lved by mtDNA defect, and the retinopathy is phenotypically variable a nd frequently subclinical, depending to some extent on the type or sit e of mtDNA defect.