Neurotrophic keratitis (NK) is caused by damage to the trigeminal nerve and abolishes both tearing and blinking reflexes, causing severe dry eye disease.
Case Report
A 55-year-old gentleman presented with right eye redness, pain, and diminution of vision; which had increased in the past 15 days. He had a neurosurgery, 7 years back, details of which were not available with the patient. This was followed by right facial palsy and required permanent tarsorrhaphy. On examination, the left eye was normal. The right eye had a vision of 20/120 with permanent tarsorrhaphy, and conjunctival congestion with central corneal ulcer, thinning and surrounding corneal haze, vascularization, and absent corneal sensations (when checked with a wisp of a cotton-tipped applicator, in comparison with the other eye) with a nondilating pupil—Grade IV NK [Fig. 1a]. Patient being on lubricants/emollients was offered amniotic membrane grafting (AMG) but refused it. After informed consent, he was offered off-label therapy with insulin eye drops. Insulin eye drops were prepared by diluting 0.1 ml of 100 IU/ml of insulin aspart, fast-acting insulin in 10 ml of PEG 400-Propylene Glycol eye drops to obtain 1 IU/ml, which was added 4 times/day to current treatment. Within 12 days of treatment, patient was subjectively better, with reduction of congestion, healing of ulcer, and relenting vascularization [Fig. 1b] and healing effect further progressing by Day 25 [Fig. 1c] to achieve a best-corrected vision of 20/80p. This effect is maintained at his current last follow-up at 4 months. A similar encouraging healing effect of topical insulin has been observed by us in another patient; a 41-year-old gentleman, diabetic patient, with post COVID mucormycosis who's nonseeing eye [Fig. 2a] was structurally salvaged, but developed NK despite an initial temporary tarsorrhaphy with intense lubrication [Fig. 2b] with partial resolution after permanent tarsorrhaphy and AMG [Fig. 2c] and a good response after the introduction of insulin eye drops in 8 days [Fig. 2d]. This effect is maintained at his last current follow-up at 7 months.
Figure 1.
(a) Right eye of a 55-year-old gentleman with Grade IV neurotrophic keratitis. (b) Right eye of a 55-year-old gentleman with Grade IV neurotrophic keratitis, 12 days after use of insulin eye drops. (c) Right eye of a 55-year-old gentleman with Grade IV neurotrophic keratitis, 25 days after use of Insulin eye drops
Figure 2.
(a) Right eye of a 41-year-old gentleman, diabetic patient, with post-COVID mucormycosis at presentation. (b) Right eye of a 41-year-old gentleman, diabetic patient, with post-COVID mucormycosis that developed NK despite an initial temporary tarsorrhaphy with intense lubrication. (c) Right eye of a 41-year-old gentleman, diabetic patient, with post-COVID mucormycosis with partial resolution after a permanent tarsorrhaphy and amniotic membrane transplantation. (d) Right eye of a 41-year-old gentleman, diabetic patient, with post-COVID mucormycosis with the resolution of congestion and a stable ocular surface, after the introduction of insulin eye drops
Discussion
Wang et al. have used topical insulin (1 IU/mL) 2-3 times daily in refractory NK in diabetic keratitis, herpetic keratitis, and cranial nerve damage postsurgery to achieve re-epithelialization in <25 days.[1] Galvis et al. have used topical insulin in exposure keratopathy that had progressed to infected NK after acoustic neuroma surgery.[2] Higher concentrations of topical insulin (50 IU/mL) were used in diabetics who were at risk of NK after vitreoretinal surgery.[3] The presence of insulin receptors on the cornea and lacrimal gland, and the already known increased prevalence of keratopathy in diabetics suggests that insulin may contribute to corneal wound healing.[4] No adverse events are noted with topical insulin up to 100 IU/mL in previous publications.[5]
Conclusion
Topical insulin drops may be used to manage NK unresponsive to conventional treatments. We look forward to have further studies from other centers across our country to determine the ideal concentration of insulin drops, identify side effects, and further characterize the patients who might benefit from this therapy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
The authors wish to acknowledge Dr. Rahul Baxi, Consultant Diabetologist, Bombay Hospital, and Medical Research Centre, Mumbai, for technical help in the preparation of the drops.
References
- 1.Wang AL, Weinlander E, Metcalf BM, Barney NP, Gamm DM, Nehls SM, et al. Use of topical insulin to treat refractory neurotrophic corneal ulcers. Cornea. 2017;36:1426–8. doi: 10.1097/ICO.0000000000001297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Galvis V, Niño CA, Tello A, Grice JM, Gomez MA. Topical insulin in neurotrophic keratopathy after resection of acoustic neuroma. Arch Soc Esp Oftalmol. 2019;94:100–4. doi: 10.1016/j.oftal.2018.06.003. [DOI] [PubMed] [Google Scholar]
- 3.Bastion ML, Ling KP. Topical insulin for healing of diabetic epithelial defects: A retrospective review of corneal debridement during vitreoretinal surgery in Malaysian patients. Med J Malaysia. 2013;68:208–16. [PubMed] [Google Scholar]
- 4.Rocha EM, Cunha DA, Carneiro EM, Boschero AC, Saad MJ, Velloso LA. Identification of insulin in the tear film and insulin receptor and IGF-1 receptor on the human ocular surface. Invest Ophthalmol Vis Sci. 2002;43:963–7. [PubMed] [Google Scholar]
- 5.Bartlett JD, Turner-Henson A, Atchison JA, Woolley TW, Pillion DJ. Insulin administration to the eyes of normoglycemic human volunteers. J Ocul Pharmacol. 1994;10:683–90. doi: 10.1089/jop.1994.10.683. [DOI] [PubMed] [Google Scholar]