The tear film is the interface between the eye and the environment, and it is governed in part by the underlying densely innervated cornea. Corneal nerves transduce a variety of sensations, including pain, mechanoreception, and temperature, which help regulate the blink response and tear production [1,2]. Corneal nerves are also directly responsible for the maintenance of a healthy cornea through the production of trophic factors such as nerve growth factor (NGF) [3].

Neurotrophic keratopathy (NK) arises from either the partial or complete impairment of the trigeminal nerve that innervates the cornea. Impairment can come from a variety of etiologies, including systemic disease, trauma, surgery, topical drug toxicity, herpetic infections, or contact lens wear. Persistently altered corneal sensation starts a cascade of events involving the loss or imbalance of trophic factors, secondary alterations of the lacrimal functional unit (LFU), and impaired corneal healing that can, if left untreated, lead to epithelial breakdown and visual impairment from epitheliopathy or ulceration, melting, or scarring [4].

Treatment for NK has encompassed a variety of options based on disease severity and included behavioral modification, artificial tears, serum tears, anti-inflammatory therapy, punctal occlusion, amniotic membrane transplantation, therapeutic contact lenses, cenegermin-bkbj, tarsorrhaphy, corneal neurotization, and keratoplasty.

This study's purpose was to propose an updated definition and staging system for NK to aid in refining the management of this challenging disease as additional treatments are developed. At a time when effective treatment options were more limited, one of the most cited clinical staging systems for NK was that proposed by Mackie (Table 1) [5] and later modified by Dua et al. [4], which basically clustered a number of distinct and often nonsequential phases of NK development into 3 broad categories. However, it seems evident that a more highly defined staging system that better reflects the evolution of the disease and alerts clinicians to the earlier stages of NK. For instance, the Mackie Classification categorizes superficial vascularization, as well as stromal scarring as “Mild Stage.” Many patients have significant clinical findings of NK prior to vascularization or scarring. We feel these are findings in later stages of NK; therefore, we propose a new 6-step clinical staging system (Fig. 1) in an effort to more precisely classify the signs and symptoms associated with NK, allow for earlier diagnosis, accurately monitor its progression, evolution or recurrence, and, of vital importance, to assess and evaluate its response to treatment.