Medical and surgical management of neurotrophic keratopathy

Abstract

Neurotrophic Keratopathy (NK) is not a specific disease entity but a consequence of several conditions with varied aetiopathogenesis, of which a loss or reduction in corneal sensitivity is the hallmark. NK is clinically graded as Mild (stage1), Moderate (stage 2) and Severe (stage 3). The grading helps in understanding severity and planning treatment. Management can be considered in two parts. The first is the management of the underlying condition when active, for example herpes virus keratitis, bacterial ulcers and immune mediated ulcerative keratitis; and the second part, which deals with treatment of the non‐healing epithelial defect, stromal melting with or without vascularization and perforation that remains due to epithelial, stromal and corneal nerve pathology.Management of mild and moderate NK begins with the identification and elimination of any obvious underlying cause such as neuroleptic, antipsychotic, antihistamine and other systemic medications, preservatives in long term topical medications; and treatment of concurrent ocular surface infection. Tear substitutes and anti‐inflammatory agents both steroids and specific immunosuppressors like cyclosporin and lifitegrast should be used early. Antibiotics can be used prophylactically or to treat subclinical or overt infection. Medication with preservatives should be avoided. Prevention of progression to severe (stage 3) NK can be achieved with antiproteases such as citrate, tetracyclines and macrolides. Substrate re‐generating agents like Cacicol and promoters of epithelial regeneration like co‐enzyme Q10 target aspects of the underlying pathology. The introduction of recombinant human nerve growth factor (rh)NGF (Cenegermin/Oxervate) has provided specific therapy that addresses the basic defect related to corneal nerves. Insulin drops are proving to be useful and amniotic membrane extracts/amniotic fluid has also been tried. Autologous and pooled allo serum or plasma drops, which provide a variety of known and unknown factors have also proved useful but may at times aggravate the condition. Usually a combination of two or more of the above are required but rhNGF and insulin hold considerable promise for long term remission.Medical treatment is often augmented with non‐surgical interventions such as bandage contact lens, padding, punctal plugs, botulinum toxin, frost suture and glue. These are primarily designed to deal with exposure, dry eyes and reduce the abrasive effect of lid blinks, to promote healing. Useful surgical procedures include tarsorrhaphy, amniotic and conjunctival grafts, penetrating and lamellar keratoplasty and limbal stem cell transplants. Surgical interventions are designed to augment effects of the non‐surgical interventions, reduce scarring, deal with complications and restore sight. A key principle is that wound healing after any form of surgery or transplant, is poor if the corneal sensations remain impaired or absent.