Topical Insulin—Utility and Results in Refractory Neurotrophic Keratopathy in Stages 2 and 3

Abstract

Purpose:The purpose of this study was to evaluate the clinical outcome of patients with refractory neurotrophic keratopathy (NK) in stages 2 and 3 treated with topical insulin.Methods:Retrospective analysis of eyes with NK in stages 2 and 3 refractory to standard medical and/or surgical treatment which were treated with topical insulin (1 unit per mL). This treatment was applied 4 times per day and was continued until the persistent epithelial defect (PED) or ulcer resolved. The primary outcome of the study was the complete reepithelialization of the PED or persistent ulcer. “Best-corrected visual acuity” pretreatment and posttreatment, “days until complete reepithelialization” data, and anterior segment photographs were obtained. Outcome measures were compared before and after treatment in both groups using paired and independent samples t tests.Results:Twenty-one eyes were included in this study, and 90% achieved complete reepithelialization of the PED and/or persistent ulcer within 7 to 45 days of follow-up. The mean number of days until complete reepithelialization was significantly lower in NK stage 2 (18 ± 9 days) when compared with NK stage 3 (29 ± 11 days) (P = 0.025). The best-corrected visual acuity improved significantly in both NK stage 2 (P < 0.001) and NK stage 3 (P = 0.004). No side effects were reported during the follow-up.Conclusions:Our results suggest that topical insulin drops may be an effective therapeutic in refractory NK. This therapy may prove extremely useful because of its low cost and high accessibility.

Indications and Results of Emergency Penetrating Keratoplasty With Simultaneous Cataract Surgery (“Triple-PKP à Chaud”)

“…17 The clinical use of insulin eye drops for the treatment of resistant neurotrophic epithelial healing disorders also demonstrated promising results and offers a cost-effective alternative to nerve growth factor eye drops. 18,19 Eyelid surgery can be performed either intraoperatively or postoperatively to reduce epithelial healing disorders. Especially in the case of incomplete lid closure or neurotrophic pathogenesis, combined tarsorrhaphy is recommended.…”

“…17 The clinical use of insulin eye drops for the treatment of resistant neurotrophic epithelial healing disorders also demonstrated promising results and offers a cost-effective alternative to nerve growth factor eye drops. 18,19…”

Neurotrophic Keratopathy Treated with Topical Recombinant Human Nerve Growth Factor (Cenegermin): Case Series Study with Long-Term Follow-Up

“…Other treatment modalities reported for patients with NK with satisfactory results showing corneal defect/ulcer resolution include a combination of the neurotransmitter substance P and insulin-like growth factor 1 (IGF-1) [ 24 , 25 ], topical insulin in cases of refractory NK stages II and III [ 26 ], and eye drops of autologous serum [ 27 ] and plasma rich in growth factors [ 28 ]. None of these options, however, are addressed to the main problem of inhibition of corneal sensitivity.…”

Neurotrophic Keratitis. Etiology, Pathogenesis, Clinical Manifestations. Review. Part 2

“…Реэпителизация достигнута у 90 % пациентов в сроки от 7 до 45 дней; в последующем этих пациентов наблюдали 20 мес. Авторы объясняют действие инсулина сходством его молекулярной структуры и ИФР-1, что позволяет инсулину связываться с рецепторами ИФР-1 и активировать их [18]. Исследования показали, что ИФР-1 действует синергически с веществом П, способствуя миграции эпителиоцитов и заживлению повреждений эпителия роговицы.…”

“…Помимо этого, активируя рецепторы IGF-1R и свои собственные рецепторы, инсулин инициирует путь фосфоинозитид-3-киназы/ Akt/mTOR, что приводит к полному блокированию аутофагии (включая митофагию) в эпителиальных клетках роговицы [19]. К возможным преимуществам данной методики относятся доступность препарата, его дешевизна и отсутствие осложнений [18].…”