Purpose: Opoid Use Disorder (OUD) is a major worldwide health concern. Methadone Maintance Therapy (MMT) has been a recognized as an effective OUD treatment for over 40 years. Reported ocular side effects of MMT are limited, and no corneal findings have ever been reported. We document for the first time the concerrence of long term MMT with neurotrophic, microbial and florid persistent interstitial keratitis. We term this uniquely devestating clinical constellation Methadone Keratitis.

Methods: Retrospective observational case series.

Results: Two patients with a history of OUD and long term MMT were hospitalized for treatment of severe perforated infectious keratitis. Both reported several months of precedent ocular symptoms prior to acute onset of pain and vision loss. Both had been pre-referral treated with unknown antibiotics, and on admission were culture negative.

Case 1. A 33 -year-old female with a 12 year history of MMT for Oxycodone OUD presented with bilateral, central, densely infiltrated, perforated corneal ulcers. The patient was glued OU and hospitalized for 24 days, receiving intensive topical and systemic antibiotics as well as antivirals. On her last followup visit ~18 months post discharge, BCVA was CF's OU. Slit lamp exam (SLE) revealed 3-4+diffuse PEK with surface keratinization, 3+ active stromal eovascularization, and dense central scarring OU. Sequential corneal sensation testing with Cochet Bonnet Eistheisimetry (CBE) registered 0mm OU x2. MMT (79mg/day) was maintained throughout the entire pre-hospitalization, inpatient and follow-up period.

Case 2. A 42 year-old female with a 5 month history of OUD related MMT was admitted for a perforated corneal ulcer/pan ophthalmitis OS. SLE additionally revealed significant active noninfectious keratitis and evidence of previous perforation OD. The patient was hospitalized for 13 days, receiving intensive topical and systemic antibiotics along with an emergent corneal transplant and vitrectomy. OS Her last follow-up exam ~11 months later revealed BCVA of CF OD and NLP with phthisis OS. CBE measured 16mm OD. The patient had continued MMT throughout the entire period.

Conclusion: Methadone keratitis appears to represent a previously undescribed, severe, synergistically pernicious and bilaterally blinding concurrence of MMT, neurotrophic, microbial, and florid persistent interstitial keratitis.