Use of Topical Insulin to Treat Refractory Neurotrophic Corneal Ulcers

Wang, Angeline L.; Weinlander, Eric; Metcalf, Brandon M.; Barney, Neal P.; Gamm, David M.; Nehls, Sarah; Struck, Michael C.

doi:10.1097/ico.0000000000001297

Cited by 67 publications

(64 citation statements)

References 9 publications

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“…More recently, Wang and colleagues reported on a small case series of six human subjects with refractory corneal ulcers (59). Patients ranged in age from 2 to 73 years and all presented to clinic with non-healing neurotrophic corneal ulcers.…”

Section: Insulin and The Diabetic Corneamentioning

confidence: 99%

The IGF/Insulin-IGFBP Axis in Corneal Development, Wound Healing, and Disease

2020

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The insulin-like growth factor (IGF) family plays key roles in growth and development. In the cornea, IGF family members have been implicated in proliferation, differentiation, and migration, critical events that maintain a smooth refracting surface that is essential for vision. The IGF family is composed of multiple ligands, receptors, and ligand binding proteins. Expression of IGF type 1 receptor (IGF-1R), IGF type 2 receptor (IGF-2R), and insulin receptor (INSR) in the cornea has been well characterized, including the presence of the IGF-1R and INSR hybrid (Hybrid-R) in the corneal epithelium. Recent data also indicates that each of these receptors display unique intracellular localization. Thus, in addition to canonical ligand binding at the plasma membrane and the initiation of downstream signaling cascades, IGF-1R, INSR, and Hybrid-R also function to regulate mitochondrial stability and nuclear gene expression. IGF-1 and IGF-2, two of three principal ligands, are polypeptide growth factors that function in all cellular layers of the cornea. Unlike IGF-1 and IGF-2, the hormone insulin plays a unique role in the cornea, different from many other tissues in the body. In the corneal epithelium, insulin is not required for glucose uptake, due to constitutive activation of the glucose transporter, GLUT1. However, insulin is needed for the regulation of metabolism, circadian rhythm, autophagy, proliferation, and migration after wounding. There is conflicting evidence regarding expression of the six IGF-binding proteins (IGFBPs), which function primarily to sequester IGF ligands. Within the cornea, IGFBP-2 and IGFBP-3 have identified roles in tissue homeostasis. While IGFBP-3 regulates growth control and intracellular receptor localization in the corneal epithelium, both IGFBP-2 and IGFBP-3 function in corneal fibroblast differentiation and myofibroblast proliferation, key events in stromal wound healing. IGFBP-2 has also been linked to cellular overgrowth in pterygium. There is a clear role for IGF family members in regulating tissue homeostasis in the cornea. This review summarizes what is known regarding the function of IGF and related proteins in corneal development, during wound healing, and in the pathophysiology of disease. Finally, we highlight key areas of research that are in need of future study.

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Section: Insulin and The Diabetic Corneamentioning

confidence: 99%

The IGF/Insulin-IGFBP Axis in Corneal Development, Wound Healing, and Disease

2020

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“…1 Corneal adverse effects occur far less frequently, with only rare reports of brimonidine-related peripheral corneal neovascularization and deep stromal opacification. 2,3 To the best of our knowledge, we describe the first reported case of a brimonidine user developing multifocal corneal subepithelial infiltrates.…”

Section: Footnotes and Disclosurementioning

confidence: 93%

“…Bastion and Ling 5 suggested that 50 IU/mL topical insulin might improve the rate of epithelial wound healing, whereas Fai et al 6 found that dilutions of 25 IU/mL was associated with better healing. As discussed by Wang et al, 3 it is likely that insulin drops may benefit patients with NK of heterogeneous etiologies, other than diabetic neuropathy.…”

Section: Topical Insulin For Neurotrophic Corneal Ulcersmentioning

confidence: 99%

“…Wang et al 3 described sterile, refractory neurotrophic ulcers from various pathologies (diabetic keratitis, herpetic keratitis, and postsurgical cranial nerve injury) that re-epithelialized less than 25 days after starting topical insulin drops (1 IU/ mL) 2À3 times daily. 3 Galvis et al 4 discussed a case of exposure keratopathy that progressed to an infected, neurotrophic ulcer after acoustic neuroma resection. Topical insulin (1 IU/mL) was used as an adjuvant therapy to topical antibiotics, steroids, autologous serum drops, and bandage contact lens.…”

Section: Topical Insulin For Neurotrophic Corneal Ulcersmentioning

confidence: 99%

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Topical insulin for neurotrophic corneal ulcers

Tong

Iovieno

Yeung

2020

Canadian Journal of Ophthalmology

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“…It may be used on its own or in a combined solution with umbilical cord blood and has been shown to successfully accelerate corneal epithelial healing in animal and human corneas [74,[76][77][78][79]. Isolated cases of successful resolution of epithelial defects with topical insulin and topical coenzyme Q10 in refractory cases of NK have been reported [80,81]. The underlying mechanism remains unknown; however, topical insulin decreased the rate of sub-basal corneal plexus loss in diabetic mice and promoted epithelial cell migration in in vitro models [82,83].…”

Section: Additional Medical Therapiesmentioning

confidence: 99%

Corneal Neurotization and Novel Medical Therapies for Neurotrophic Keratopathy

Rosenblatt

Sears

Park

et al. 2020

Curr Ophthalmol Rep

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Purpose of Review Neurotrophic keratopathy (NK) is a degenerative corneal disease characterized by decreased corneal sensibility and impaired corneal healing. In this article, we review surgical techniques for corneal neurotization (CN) and novel medical therapies for the treatment of NK. Recent Findings In recent decades, there has been a paradigm shift in the treatment strategies for NK. New minimally invasive direct and indirect CN approaches have demonstrated efficacy at improving best-corrected visual acuity and central corneal sensation while decreasing surgical morbidity. In addition, several targeted medical therapies, such as recombinant human nerve growth factor (rhNGF), regenerating agents (RGTA), and nicergoline, have shown promise in improving corneal epithelial healing. Of these options, cenegermin (Oxervate®, Dompé), a topical biologic medication, has emerged as an approved medical treatment for moderate to severe NK. Summary NK is a challenging condition caused by alterations in corneal nerves, leading to impairment in sensory and trophic function with subsequent breakdown of the cornea. Conventional therapy for NK depends on the severity of disease and focuses primarily on protecting the ocular surface. In recent years, numerous CN techniques and novel medical treatments have been developed that aim to restore proper corneal innervation and promote ocular surface healing. Further studies are needed to better understand the long-term efficacy of these treatment options, their target populations, and the potential synergistic efficacy of combined medical and surgical treatments.

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Use of Topical Insulin to Treat Refractory Neurotrophic Corneal Ulcers

Cited by 67 publications

References 9 publications

The IGF/Insulin-IGFBP Axis in Corneal Development, Wound Healing, and Disease

The IGF/Insulin-IGFBP Axis in Corneal Development, Wound Healing, and Disease

Topical insulin for neurotrophic corneal ulcers

Corneal Neurotization and Novel Medical Therapies for Neurotrophic Keratopathy

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