Winning The Battle Against Neurotrophic Ulcer: An Ophthalmologist Worst Nightmare

Neurotrophic ulcer is a degenerative disease of the cornea that is characterized by  damage of trigeminal innervation. Loss of sensitivity impairs corneal wound healing, leading to epithelial changes. Some of the most common conditions that can lead to neurotrophic keratopathy are herpes keratitis (simplex and zoster), chronic use of topical medications, contact lenses overuse, chemical and physical burns, and intracranial masses. 

Diagnosis is clinic, observing disruption of the epithelial layer, swelling of the epithelial cells, disorganisation of Bowman’s membrane, stromal melting, or scarring and neovascularization. When managing neurotrophic keratopathy, the main purpose is to promote corneal healing without any complications.

The management is with application of preservative-free artificial tears and lubricant ointments, also autologous serum can be used, as well as a therapeutic soft contact lens. In further stages,  an amniotic membrane graft, or tarsorrhaphy are performed in order to manage the epithelial defects. If stromal melting is present doxycycline can be prescribed. When a perforation occurs, cyanoacrylate glue can be applied, with a contact lens or a conjunctival flap or even a lamellar keratoplasty.

A 75-year-old man presented with redness, crater-shaped corneal lesion and decreased vision in the RE. 

Examination revealed a sterile oval-shaped ulcer, with smooth rolled margins, associated Dellen formation and decreased corneal sensation. His BCVA was inferior to 20/200. Based on it, neurotrophic keratitis was suspected.

The patient was treated with ample artificial tears and an antibiotic and a contact lens was placed. Meanwhile amniotic membrane extract was ordered. No oral Doxycycline was prescribed because of renal and hepatic disturbance.  He returned a few days later complaining of pain and severe loss of visual acuity (LP). The slit lamp examination revealed a 5 x1.5mm corneal ulcer. Despite treatment, the epithelial stromal defect expanded. So amniotic membrane graft transplantation was performed.

One month later, the lesion showed significant improvement and healed partially, while amniotic membrane completely reabsorbed. Patient was started on amniotic membrane extract three-four times a day. Despite the change of medical treatment, epithelialization was not achieved and in further visits corneal defect enlarged again up to 5x1.5mm.

At that point, topical insulin eye drop was started (1 IU/mL).  A fortnight after treatment initiation, epithelial defect healed to 2 x 1.5mm and a reduction in the depth of the ulcer was appreciated and 6 weeks later the defect was closed and the patient’s visual acuity improved to basal BCVA 20/200. To date the has been no recurrence.

The diagnosis and management of NK is a challenge for ophthalmologists. The currently available medical and surgical treatments aim to promote healing, prevent disease progression, and avoid corneal perforation. However, when current therapies do not improve it becomes challenging.

Nevertheless, our clinical case shows that topical insulin is promising. Even in cases non-responding to amniotic graft.

Based on it, we have added insulin as the second line treatment for persistent epithelial defects, together with autologous serum and membrane amniotic extract.

Undoubtedly clinical trials will enable to better understand insulin efficacy.