**Background:** Neurotrophic keratopathy (NK) is a degenerative corneal disease characterized by corneal hypoesthesia or anesthesia, leading to epithelial defects, ulceration, and risk of keratolysis and perforation. Common causes include damage to the trigeminal nerve (V cranial nerve), herpetic infection, diabetic neuropathy, and corneal surgery. Standard conservative treatments include withdrawal of toxic therapies, frequent unpreserved lubricants, bandage contact lenses, blood-derived products, matrix metalloproteinase inhibitors, and recombinant human nerve growth factor. Recently, insulin eye drops (1 IU/mL, 4 times daily) have shown efficacy in recalcitrant moderate-to-severe NK, possibly by restoring corneal nerves or enhancing epithelial cell migration. The therapeutic Hyper-CL (EyeYon Medical) is a novel soft contact lens with a groove and fenestrations that acts as a drug depot, increasing ocular surface drug bioavailability. This case report describes the first use of combined insulin eye drops and Hyper-CL for stage III NK.
**Methods:** A 40-year-old man with a history of adenoid cystic carcinoma of the nasal cavity treated with endoscopic resection and carbon ion radiotherapy (total dose 68.8 Gray) developed iatrogenic right V cranial nerve damage, resulting in stage III NK. Prior treatments included tear substitutes, vitamin A ointment, punctal occlusion, autologous serum drops, standard bandage contact lens, and short courses of topical fluorometholone, all without success. At presentation, Snellen best-corrected visual acuity (BCVA) was 0.01, slitlamp examination showed conjunctival hyperemia (Efron grade IV), a large epithelial defect (approximately 7 × 4 mm), diffuse corneal opacity with deep inferior neovascularization, central keratolysis (3 mm area), and stromal thinning (about one third of stroma). Blink rate was markedly reduced (6/min average), and Cochet-Bonnet esthesiometry revealed total corneal anesthesia in all quadrants with absent corneal reflex. The contralateral eye was normal. Ongoing treatments were discontinued, and insulin eye drops (1 IU/mL) were prepared by a compounding pharmacy using Humalog (insulin lispro) in a hydroxypropyl guar-based artificial tear formulation (see Table 1 for full composition). Drops were prescribed 4 times daily. A therapeutic Hyper-CL was applied to enhance drug residence time. Follow-up occurred at 10 days (T1) and 20 days (T2). The epithelial defect area was digitally analyzed using ImageJ software.
**Key Results:** At T1 (10 days), conjunctival hyperemia reduced to Efron grade III, and the epithelial defect decreased to approximately 5 × 3 mm. At T2 (20 days), conjunctival hyperemia further improved to Efron grade II, and the epithelial defect completely healed. The cornea appeared clearer, and Snellen BCVA improved to 0.05. The Hyper-CL was kept in place for an additional 10 days after healing, and insulin drops were continued. At 3-month follow-up, the corneal epithelium remained closed with unpreserved tear substitutes only. No changes in corneal sensitivity were observed during the entire course.
**Clinical Implications:** This case demonstrates that combined insulin eye drops and Hyper-CL can achieve rapid and complete healing of a severe, recalcitrant NK with total corneal anesthesia and keratolysis, avoiding progression to perforation. The Hyper-CL likely prolongs insulin residence time on the ocular surface (up to 20 minutes per drop) and provides mechanical protection, while insulin promotes reepithelialization. The approach is low-cost, easily accessible, and safe. However, the individual contribution of each component is unclear, and randomized clinical trials are needed to confirm efficacy and determine optimal protocols. This combination may be particularly valuable for NK cases at high risk of corneal perforation where other therapies have failed.