Managing corneal epithelial downgrowth: Image-guided surgery, cryotherapy, and single-dose methotrexate

Epithelial downgrowth (EDG) is a rare but potentially sight-threatening complication characterized by migration of epithelial cells into the anterior chamber along a wound tract, where proliferation on intraocular structures leads to inflammation and progressive tissue damage.¹ Without treatment, EDG may result in corneal decompensation, secondary glaucoma, and irreversible vision loss. Management is challenging given the proliferative nature of epithelial cells within the intraocular environment and the tendency toward recurrence despite intervention. Reported approaches include surgical excision, cryotherapy, laser photocoagulation, and intraocular antimetabolite agents.¹

A case report published in Cornea Open by Haidar and colleagues at the University of California, Los Angeles, describes a patient with EDG following cataract surgery who was successfully managed with image-guided surgical excision, adjunctive cryotherapy, and a single anterior chamber methotrexate (MTX) injection, with no clinical evidence of recurrence at 10 months of follow-up.¹

Case presentation

A 69-year-old man with a history of retinal detachment repair, bilateral LASIK, cataract extraction by phacoemulsification, and YAG capsulotomy in the right eye presented with tearing. A wound leak with associated EDG was identified. At initial cornea service evaluation approximately 6 weeks after symptom onset, best-corrected visual acuity (BCVA) was 20/60 in the right eye, with a Seidel-positive wound leak and a demarcated endothelial opacity extending centrally up to 3 mm. The patient also had hypotony maculopathy. Anterior segment optical coherence tomography (AS-OCT) demonstrated a continuous hyperreflective thick layer along the posterior corneal surface extending from the wound, consistent with EDG arising from a chronic wound leak.¹

An initial wound revision with tissue adhesive did not achieve a durable seal. Over the following 2 weeks, a brisker wound leak with progressive endothelial haze and enlarging EDG led to planning for surgical excision.¹

Surgical approach

The patient underwent surgical removal of the EDG guided by intraoperative AS-OCT, adjunctive wound cryotherapy, and a single anterior chamber MTX injection (50 μL, 400 μg, 8 mg/mL). Epithelial removal was performed using Descemet stripping forceps and a Terry scraper. Cryotherapy was applied externally over the wound using a nitrous oxide–based cryoprobe at approximately −60°C, with a double freeze–thaw technique; each freeze cycle was maintained for approximately 20 seconds until an adequate ice ball formed, followed by complete passive thawing before a second freeze was applied. Intraoperative AS-OCT guided complete removal and verified the absence of residual epithelial sheet.¹

Histopathologic examination confirmed nonkeratinized stratified squamous epithelium, and immunohistochemistry demonstrated marked reactivity to anti-MUC16, confirming ocular surface origin of the epithelial cells.¹

Outcomes at 10 months

The cornea was Seidel-negative from postoperative day 1. Cystoid macular edema identified at postoperative week 2 resolved over the following month with ketorolac twice daily and retina referral, with BCVA improving to 20/40. At 10 months, BCVA was stable at 20/40 in the right eye, with resolution of hypotony, faint residual endothelial haze, and no evidence of EDG recurrence on slit-lamp examination or AS-OCT. Central corneal thickness, endothelial cell density, and cell morphology remained within normal limits, supporting preserved endothelial integrity.¹

Context and significance

The authors note that prior reports of intraocular MTX for EDG have required multiple injections to achieve remission. A multicenter case series by Hébert et al² reported that after a mean of 16 injections, 70% of eyes achieved EDG resolution, but complications were frequent: 80% developed corneal epithelial abnormalities, 50% required corneal transplantation, and 20% developed retinal detachment. The present case achieved sustained remission with a single injection following surgical debridement and cryotherapy. According to Haidar et al, targeted, image-guided intervention may reduce the need for repeated MTX dosing and, in turn, lower the cumulative risk of drug-associated ocular toxicity.¹

The authors conclude that this case demonstrates the potential for successful EDG management using a combined approach of surgical excision, cryotherapy, and single-dose intraocular MTX, and contributes to the limited literature on this rare but challenging condition.¹

References

1. Haidar AJ, Glasgow BJ, Bonnet C, Al-Hashimi S. Image-guided surgical management of corneal epithelial downgrowth with cryotherapy and single-dose intraocular methotrexate. Cornea Open. 2026;5(2):e0094. doi:10.1097/coa.0000000000000094

2. Hébert M, Kyrillos R, Snyder ME, et al. Intraocular methotrexate for epithelial downgrowth: long-term outcomes in a multicentre case series. Br J Ophthalmol. 2023;107(9):1383-1389. doi:10.1136/bjophthalmol-2022-321168