Evaluating the efficacy and safety of therapeutic interventions for corneal neuropathy: A systematic review

Rajni Rajan, Eve Makrai, Ji-Hyun Lee, Sumeer Singh, Holly R Chinnery, Laura E Downie

Research output: Contribution to journalReview articlepeer-review


Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n=6 studies), dietary supplements (n=4), anti-glycemic agents (n=3), combination therapy (n=3), supportive therapies (n=2) and systemic pain pharmacotherapies (n=2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve capacity to synthesize data to inform evidence-based based care. Protocol registration: PROSPERO ID: CRD42022348475.

Original languageEnglish
Pages (from-to)80-98
Number of pages19
JournalThe Ocular Surface
Early online date28 Apr 2024
Publication statusPublished - Jul 2024
Externally publishedYes


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