Prog Retin Eye Res. 2026 Apr 3:101466. doi: 10.1016/j.preteyeres.2026.101466. Online ahead of print.
ABSTRACT
Mitochondrial diseases are the most common group of inherited neurometabolic disorders and frequently involve multiple organ systems with high energy demands. Ophthalmic manifestations are a common occurrence in affected individuals and may be the earliest or predominant clinical feature. However, the marked clinical heterogeneity of mitochondrial eye disease often delays recognition and therefore diagnosis. Mitochondria play a central role in cellular metabolism through the process of oxidative phosphorylation. Genetic mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) can impair this key metabolic process leading to clinical disease. Diagnosing such mitochondrial diseases is however often complicated – the same genetic change can result in different symptoms (variable expressivity); different genes can cause similar conditions (allelic and locus heterogeneity); a single genetic change may affect multiple body systems (pleiotropy); and the proportion of affected mitochondrial DNA molecules can vary between tissues (mtDNA heteroplasmy). While the diagnostic process will certainly be influenced by the initial clinical presentation, perhaps more important is clinician awareness and early consideration of an underlying mitochondrial disorder. Early and accurate molecular genetic diagnosis is both available and essential, not only for prognostication and management, but also for reproductive counselling, access to appropriate clinical trials, cascade testing of relevant family members and consideration of emerging mitochondrial therapeutics(1,2). In this review, we summarise the biochemical and genetic foundations of mitochondrial eye disease, describe the spectrum of clinical phenotypes, outline diagnostic approaches and considerations, and highlight the importance of precise early diagnosis in guiding management and reproductive decision-making.
PMID:41936865 | DOI:10.1016/j.preteyeres.2026.101466