Introduction This study aimed to investigate the impact of cenegermin (recombinant human nerve growth factor) on corneal epithelial healing, nerve regeneration, and tear secretion in patients with diabetic neurotrophic keratopathy(DNK).

Methods This study was conducted as a single-arm and open-label trial. Fourteen patients diagnosed with bilateral DNK were treated with cenegermin eye drops (20 mcg/ml) six times daily for eight weeks and followed up to twenty weeks. Clinical evaluations—including corneal fluorescein staining score, in vivo confocal microscopy, corneal sensitivity, and Schirmer I test—were conducted to assess the corneal epithelial healing time, nerve fibre regeneration, and tear secretion.

Results The corneal epithelium exhibited complete healing in week 2, with further enhancement in epithelial integrity observed in week 8 and sustained until week 20. Corneal nerve fibre density (CNFD), length (CNFL), and branch density (CNBD) exhibited a significant increase at week 8 in all patients. However, CNFD and CNFL showed a slight reduction in the peripheral zones of patients with moderate DNK by week 20. Nonetheless, corneal sensitivity demonstrated consistent improvement throughout the treatment period. Tear secretion experienced a significant increase at week 8 but returned to baseline levels by week 20. Furthermore, the best-corrected visual acuity (BCVA) improved after treatment and remained stable until the final visit.

Conclusions The administration of cenegermin effectively facilitated and sustained the healing process of corneal epithelium in cases of mild-to-moderate DNK by promoting nerve regeneration and tear secretion. Prolonged treatment is crucial for stimulating both nerve regeneration and tear secretion.

Trial Registration: Chinese Clinical Trial Registry identifier ChiCTR2200058806

What is known?

Diabetic neurotrophic keratopathy (DNK), a subtype of neurotrophic keratopathy (NK) secondary to diabetes mellitus, is characterized by peripheral epithelial defects and varying degrees of corneal hypoesthesia or anesthesia. This condition exhibits poor responsiveness to conventional therapeutic approaches, leading to persistent or progressive lesions.

The efficacy of rhNGF eye drops (cenegermin) in treating stage 2 and 3 NK has been evaluated in two prospective multicenter randomized clinical trials involving a limited number of patients with moderate and severe DNK. However, these studies do not provide sufficient evidence regarding the effects of rhNGF on tear function, corneal sensitivity and nerve density in mild and moderate DNKs.

What is new?

The study addresses a significant clinical challenge by investigating an optimized treatment approach for diabetic neurotrophic keratopathy (DNK), focusing on the complex interplay between the corneal nerve, epithelium, and lacrimal gland.

The administration of cenegermin effectively facilitated and sustained the healing process of the corneal epithelium in cases of mild-to-moderate DNK that were refractory to conventional medical treatments and amniotic membrane transplantation (AMT). Noteworthy findings included significant regeneration of corneal nerve fibers and enhanced tear function.

Prolonged administration is imperative for promoting nerve regeneration and stimulating tear secretion.

The authors have declared no competing interest.

ChiCTR2200058806

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The study was approved by the Ethics Committee of Qingdao Eye Hospital at Shandong First Medical University (2021(01)) and was conducted in compliance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients.

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