1. Corneal Disease and Mitochondrial Cytopathy: Report of Two Unrelated Individuals Jocelyn Kim, BA, Anagha Medsinge, MD, Bharesh Chauhan, PhD, Cara Wiest, BA, Will Moore, FRCOphth, Ken K. Nischal, MD, FRCOphth The authors have no financial interests to disclose

2. Purpose Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by – retinitis pigmentosa ; external ophthalmoplegia; heart block KSS is really a spectrum of disease which may not present with the classic triad above There is little in the literature about corneal involvement in KSS in the pediatric population We report two children with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10)

3. Methods Multi-center retrospective observational study involving Children’s Hospital of Pittsburgh and Great Ormond Street Hospital for Children, London

4. Results: Case 1 5 year old male in London with photophobia and poor vision following bilateral ptosis repair four months earlier Visual acuity: 0.325 uncrowned Log Mar OU Ultrasound biomicroscopy (UBM) showed small cystic like lesions with punctate epithelial erosions

5. Results: Case 1 Initially a diagnosis of Meesmann dystrophy was made, punctal plugs were placed and lubrication was given He was still symptomatic one year after presentation, review of UBM showed corneal lesions extending past the epithelium, arguing against the original diagnosis of Meesmann

6. Results: Case 1 During this time he was admitted for metabolic acidosis and was found to have myopathy, renal tubular dysfunction, decreased hearing and bilateral ptosis A clinical diagnosis of Kearns-Sayre Syndrome was made and he was started on CoQ10, potassium chloride syrup, magnesium glycophosphate, thiamine, L-carnitine, and calcium folinate Two years after presentation, his best corrected visual acuity (BCVA) improved to 0.26 Log MAR OU, 0.34 OU

7. Results: Case 1-cont. He was noted to have external ophthalmoplegia and pigmentary retinopathy confirmed by electroretinography (ERG) At 11 years of age, the diagnosis of KSS was confirmed genetically The child later developed multiorgan failure and passed away

8. Results: Case 2 8 year old male in Pittsburgh with photophobia, possible retinal dystrophy, and sensorineural hearing loss BCVA was 20/60 in the right eye and 20/100 in the left eye On slit lamp examination, both corneas showed small microcystic changes throughout the cornea

9. Results: Case 2-cont. Fundus exam showed mottling of the retinal pigment epithelium ERG revealed mixed cone and rod dysfunction UBM revealed granular deposits in the stroma Pachymetry revealed corneal thickness of 773 microns and 732 microns in the right and left eyes respectively

10. Results: Case 2-cont. After 8 weeks of treatment with bandage contact lens (BCL) and punctal plugs, his photophobia improved but corneal lesions persisted Anterior segment optical coherence tomography (AS-OCT) confirmed the lesions involved the deep stroma, including the endothelium

11. Results: Case 2-cont. A heteroplasmic large mitochondrial deletion was found and the diagnosis of KSS was confirmed He was started on CoQ10 and on subsequent follow-up the cystic changes in the cornea showed continued improvement One year after treatment with CoQ10 and BCL, BCVA was 20/70 in the right eye and improved to 20/60 in the left

12. Conclusion Corneal involvement in a clinical phenotype of mitochondrial disease has been described before However, confirmation with UBM and AS-OCT of the endothelial involvement and improvement with CoQ10 has never been reported We believe that CoQ10 may be beneficial in these patients in preventing endothelial cell failure and subsequent corneal edema