Recombinant Human Nerve Growth Factor (Cenegermin)–Driven Corneal Wound Healing Process: An Evidence-Based Analysis

Abstract

Purpose: To evaluate anterior segment optical coherence tomography (AS-OCT) to detect the wound healing process as per monitoring the effectiveness of cenegermin to treat moderate to severe neurotrophic keratoplasty.Methods: A retrospective chart review was realized to identify patients treated with cenegermin at the Clinica Oculistica, University of Genoa, Italy. All patients underwent careful examinations at baseline and follow-up visits. AS-OCT scans centered on the minimum corneal thickness (CT) area were always performed. We compared findings of AS-OCT with the findings from the slit-lamp examination. A linear regression analysis was used to evaluate factors associated with corneal healing. A further analysis, including a control group treated with 50% autologous serum (AS), was done to investigate and compare the efficacy of cenegermin.Results: Data from 16 eyes were studied. The average patients' age was 60.9 ± 21.1 years; five (31.2%) eyes experienced persistent epithelial defect and 11 (68.8%) eyes had neurotrophic corneal ulcer. The average reepithelialization time was 3.9 ± 0.5 weeks in the cenegermin group versus 5.9 ± 1.9 weeks in the AS group (p < 0.01). The AS‐OCT scans revealed an average CT at the thinnest point of 276.3 ± 74.1 μm before treatment with an average increase of 176.5 ± 60.3 μm at the end of the cenegermin treatment (B = −0.15; p = 0.035). The AS-OCT percentage increase in corneal thickness between the two groups was statistically significant (p < 0.02).Conclusion: Understanding the cascade of events involved in the nerve growth factor–driven corneal wound healing process is clinically meaningful for the clinician. AS-OCT is an effective tool for systematic anterior segment imaging, allowing the detailed detection of the front-to-back layered corneal structure for quantitative analysis and monitoring of the healing process.

Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment

“… 12 Chronic inflammation seen in DED can lead to damage in corneal sensory nerves ultimately leading to progression to NK. 7 , 8 , 9 The frequencies for the etiologies of NK in the recent studies cited 7 , 8 , 9 , 10 are generally in line with what was observed in the pivotal trials of neurotrophic growth factors to treat Stage 2 and 3 NK. There were 17/156 eyes (10.9%) in the REPARO clinical trial 13 and 6/48 eyes (12.5%) in the US clinical trial 14 that had dry eye disease listed as the underlying cause of NK.…”

“…6 More recently, it has been determined that chronic dry eye disease (DED) disease can also cause corneal nerve damage since eye lubrication and nourishment is reduced leading to corneal nerve damage. 7 , 8 , 9 In fact, any condition that can cause corneal damage may lead to NK symptoms including DED, exposure keratitis, limbal stem cell deficiency, surgical damage to the cornea, and Sjögren's syndrome. 4 , 7 , 8 , 9 , 10 A recently published retrospective study cites dry eye as the underlying cause of NK in 8/63 eyes (12.7%), including 2/63 eyes (3.2%) that were attributed to Sjögren's syndrome.…”

“… 7 , 8 , 9 In fact, any condition that can cause corneal damage may lead to NK symptoms including DED, exposure keratitis, limbal stem cell deficiency, surgical damage to the cornea, and Sjögren's syndrome. 4 , 7 , 8 , 9 , 10 A recently published retrospective study cites dry eye as the underlying cause of NK in 8/63 eyes (12.7%), including 2/63 eyes (3.2%) that were attributed to Sjögren's syndrome. Dry eye was the fourth most common etiology in this study.…”

“… 7 Another recently published retrospective chart review cites severe DED as the underlying cause of NK in 3/32 eyes (9.4%). Dry eye was tied for the fourth most common etiology in this study: “The most common cause of NK in our patients was herpes simplex keratoplasty, followed by ocular surgery, neurosurgical trigeminal damage, and severe dry eye disease.” 8 Another retrospective study cites chronic ocular surface disease as the underlying cause of NK in 62/354 eyes (17.5%), of which 3/354 eyes (0.8%) were attributed to Sjögren's syndrome. 9 Finally, a review by Labetoulle et al suggests that advanced DED may result in loss of neuronal endings, often as a consequence of inflammation, which may eventually evolve into NK.…”

Clinical observation of recombinant human nerve growth factor in the treatment of neurotrophic keratitis

“…As a neurotrophic factor and immunomodulatory factor, nerve growth factor (NGF) plays an important role in the survival, growth, and differentiation of sensory neurons, as well as in promoting wound healing [4] . Recombinant human NGF (rhNGF) has the same structure as endogenous NGF, so it can quickly promote corneal wound healing and improve the corneal perception and tear production [5] . RhNGF (cenegermin, 20 µg/mL of rhNGF) has been clinically used in Europe, United States, etc, and has been shown to aid in the recovery of corneal nerve function [6][7][8] .…”