# Clinical Ophthalmic Outcomes and Impact of Single Large-Scale Mitochondrial DNA Deletions

## TL;DR

This study examines the clinical outcomes of mitochondrial DNA deletions in patients with chronic progressive external ophthalmoplegia, focusing on age-related patterns and symptoms like ptosis.

## Contribution

The study identifies age-related trends in the 'common' 4977 bp deletion and proposes ptosis and single deletions as early diagnostic indicators for mitochondrialopathy.

## Key findings

- Ptosis was observed in 56% of patients with CPEO.
- The 'common' 4977 bp deletion was more frequent in older patients (≥51 years).
- COX-deficient fibers increased with age in patients with the 4977 bp deletion.

## Abstract

Introduction/Objectives: Chronic progressive external ophthalmoplegia (CPEO) is commonly associated with mtDNA deletions. Multiple deletions result mostly due to nuclear DNA defects that lead to an autosomal mode of inheritance, whereas single mtDNA deletions are mostly sporadic events with low inheritance risk. The study focused on assessing the clinical ophthalmic outcomes and their effects on patients with mitochondrial DNA disorders. Methods: A retrospective analysis of clinical characteristics in a cohort of CPEO patients (n = 36; 11 males, 25 females; mean age of onset: 41.2 years (±SD)) was performed. The underlying genetic defects, as well as histological features and their correlation with the clinical features, were evaluated. Results: Ptosis (56% of patients) was a frequently identified clinical symptom. Single mtDNA deletions were reported in all patients, and the ‘common’ 4977 bp deletion (CD) was detected in 11 patients (30.6%). The incidence of the common deletion was higher (36.36%) in older patients (≥51 years) as compared to younger patients (18.18%). The mean age of onset in patients harboring CD was 27 years (±11.9). Furthermore, a tendency to increase the frequency of COX-deficient fibers with increasing age was observed in patients harboring the CD. Conclusions: The present study shows that CD is typically associated with elderly patients with CPEO. Moreover, ptosis and the presence of a single deletion in patients with mitochondrialopathy seem to be preliminary diagnostic criteria.