Key messages

• Neurotrophic keratopathy (NK) is a rare disease of the cornea. It has no or little sensation but can progress to a deeper wound of the cornea and possibly vision loss.

• We found seven studies that looked at how medical and surgical treatments may affect the healing and sensation of the cornea and vision.

• There is uncertain evidence that recombinant human nerve growth factor (rhNGF) may help heal the corneal wound.

• Because of a lack of reliable evidence, we do not know the best treatment for NK. We need more studies with better designs that look at all NK treatments.

What is neurotrophic keratopathy?

Neurotrophic keratopathy (or keratitis) is a rare disease of the cornea, the front clear dome of the eye, and of the nerves that supply the cornea. In neurotrophic keratopathy (NK), these important nerves are damaged, which means that the cornea has reduced or no sensation, leading to a decrease in blinking and less spreading of the tears over the front of the eye. This can lead to a damaged cornea, which could progress to a deeper wound and eventual vision loss.

At different stages of NK, patients may experience tearing, redness, blurry vision, intermittent sharp or deep pain, and delayed healing of the cornea. NK can result from viral infection, chemical injury, surgery on head and neck cancers that inadvertently affect nerves that supply the cornea, long-term contact lens use or medication use, radiation, prior eye surgery, and conditions such as diabetes mellitus or multiple sclerosis.

How is NK treated?

Treatment primarily focuses on maintaining cornea health to prevent further damage or the development of a hole in the cornea. It aims to promote corneal healing and prevent vision loss. Supportive treatment in the early stages of NK can include preservative-free artificial tears and/or 'bandage' (non-prescription) contact lenses. In more advanced stages, serum blood tears (i.e. donated blood that is formulated into eye drops) can promote healing. RhNGF, a laboratory-created protein that mimics the body's growth factor, can be applied as a drop to improve NK. When the deeper layers of the cornea are involved, pills like doxycycline that work against scarring and inflammation can be considered. Surgical treatments may be necessary if the disease is not responding to medical therapies. For example, tarsorrhaphy is a surgical option where the patient's eyelid is stitched down over the damaged part of the cornea. Applying an amniotic membrane, which is a thin film that is created from the strong layer that surrounds a baby in the womb, is another surgical option that can heal a damaged cornea.

What did we want to find out?

We wanted to find out about the effectiveness and safety of several different medical and surgical treatments for NK.

What did we do?

We searched for studies known as 'randomized controlled trials' that tested medical and surgical interventions for NK against no treatment, placebo ('fake' treatment, e.g. saline), supportive treatment (e.g. artificial tears), or another active intervention. We summarized study findings and rated our confidence in them, based on factors such as the number of study participants, quality of the study methods, and consistency of findings across studies.

What did we find?

We found seven studies that involved a total of 494 people with NK. Six studies tested medical treatments and one study tested surgical intervention. The average age of participants ranged from 25 to 68 years across the studies. The duration of treatments ranged from 28 days to 18 months.

Overall, because of possible bias in the studies and lack of consistent evidence, we cannot be certain about any treatment being better than no treatment or simple supportive treatment for healing the cornea, improving the sensation of the cornea, or improving vision. Of the medications being evaluated, rhNGF may help heal the cornea. Other medical interventions (including 0.1% RGN-259) may not improve corneal healing, vision, or the risk of negative side effects, and their effect on corneal sensation is unclear.

One surgical study compared amniotic membranes to tarsorrhaphy or bandage contact lenses. It found there may be no difference between them in corneal healing or vision, but the evidence is very uncertain.

What are the limitations of the evidence?

We found only seven studies suitable for inclusion in the review, only one of which evaluated surgical treatment. We had only low or very low certainty about the results. Most of the studies had problems with the way they were designed. They also used different methods to measure patient outcomes. Some medical treatments that doctors use to treat NK were not tested at all, for example, blood serum tears and doxycycline pills.

Because of a lack of reliable evidence, we do not know the best treatment for NK. We need more studies with more participants and treatments. Future studies must be better designed in order to strengthen the evidence comparing the benefits and risks of different treatments.

How up to date is this evidence?

The evidence is based on searches conducted on 10 January 2025.