New therapeutic approaches in the treatment of diabetic keratopathy: a review

Abstract

The cornea is densely innervated, and the integrity of these nerve fibres is critical in maintaining the refractive and protective functions of the cornea. Many ocular and systemic diseases can adversely affect corneal sensory nerves and consequently impair their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatments regimens are often ineffective. Over the past three decades, the role of growth factors in maintaining the normal structure and function of the cornea, and in corneal epithelial healing, has become increasingly evident. Many preclinical and clinical trials have shown that growth factors and cytokines can significantly enhance epithelialization (epithelial proliferation and migration) and consequently accelerate wound healing. More recently, local/topical administration of insulin, naltrexone (opioid antagonist) and nicergoline (ergoline derivatives) were found to improve, and significantly increase, the corneal wound healing rate. This report reviews the major attributes of these growth factors and therapeutic agents that may be used in ameliorating impaired corneal wound healing, and presents a perspective on the potential clinical use of these agents as a new generation of ophthalmic pharmaceuticals for the treatment of diabetic keratopathy.

Risk Factors Associated With Corneal Nerve Alteration in Type 1 Diabetes in the Absence of Neuropathy

“…43 This condition is difficult to manage clinically, requires multimodal treatment approaches, may fail to respond to conventional treatment, and eventually leads to visual impairment. 44,45 By monitoring corneal nerve alterations in vivo, application of IVCM may also demonstrate efficacy of topically applied neuropeptides and neurotrophins in clinical studies to treat neurotrophic keratitis and DK.…”

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

“…Taken together, SP, secreted by corneal sensory nerve fibers, may be the key neurotransmitter and neuropeptide that mediates corneal nociception transmission and provides trophism to the corneal epithelium. Furthermore, as for the treatment of diabetic keratopathy, many growth factors, cytokines, and various agents have been evaluated for their capacity to accelerate corneal wound healing (40). However, SP and its functional derivative (FGLM-amide), with the advantages of smaller molecules and higher efficiency, have been shown to be effective for the treatment of persistent corneal epithelial defects in clinical studies (40)(41)(42).…”

“…Furthermore, as for the treatment of diabetic keratopathy, many growth factors, cytokines, and various agents have been evaluated for their capacity to accelerate corneal wound healing (40). However, SP and its functional derivative (FGLM-amide), with the advantages of smaller molecules and higher efficiency, have been shown to be effective for the treatment of persistent corneal epithelial defects in clinical studies (40)(41)(42). In addition, we found that SP promoted the regeneration of nerve fibers in diabetic corneal epithelium and accelerated trigeminal neuronal growth in vitro that was impaired by high glucose (Supplementary Fig.…”

Effect of Stem Cell Therapy on Induced Diabetic Keratopathy in Albino Rat

“…Diabetes adversely affects corneal sensory nerves and consequently impairs their function, with vision loss being the inevitable consequence of severe corneal neurotrophic ulceration. However, current standard treatment regimens are often ineffective (3).…”