In vivo microscopic and optical coherence tomography classification of neurotrophic keratopathy

Abstract

Neurotrophic keratopathy (NK) is a rare degenerative corneal disorder characterized by instability of epithelial integrity with consequent epithelial defects that can worsen up to persistent epithelial defects with stromal melting and ulceration. The pathogenesis of NK springs from a variable degree of damage to the trigeminal nerve plexus, leading to a reduction or total loss of corneal sensitivity. Mackie classification (1995) distinguishes three stages of NK, based on the severity of clinical presentation. The technological innovations in corneal diagnostic imaging allow clinicians to accurately study the morphometry and morphology of corneal structure with microscopic resolution. In this study, 45 patients affected by NK at different stages underwent in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) with particular attention to analyze subbasal nerve plexus fibers and the stromal structure. At the light of IVCM and AS-OCT observations, we propose a different staging of NK with respect to the Mackie's classification that takes into account the severity of subbasal nerve fibers damage and the extension in depth of stromal ulceration; this classification better defines, at the time of diagnosis, the cellular and structural alterations in the affected corneas, with possible prognostic and therapeutic values in the management of NK.

Corneal Neurotization and Novel Medical Therapies for Neurotrophic Keratopathy

“…Neurotrophic keratopathy (NK) is a rare degenerative corneal condition with a prevalence of 1.6 to 4.2 per 10,000 persons [8]. Reduced corneal sensation, as seen in NK, can lead to recurrent and persistent corneal epithelial defects, ulcers, corneal opacification, and even perforation, posing a serious threat to vision in addition to negatively impacting the quality of life [1,7,[9][10][11][12][13].…”

Role of the Neurokinin-1 Receptor in the Promotion of Corneal Epithelial Wound Healing by the Peptides FGLM-NH2 and SSSR in Neurotrophic Keratopathy

“…17 Neurotrophic keratopathy is a degenerative disease of the cornea that results from denervation of the trigeminal nerve. 4,5,[18][19][20] It is characterized histologically by defective differentiation of corneal epithelial cells and delayed heal-ing of corneal epithelial wounds. 10 There is no specific clinical sign of neurotrophic keratopathy, for which the clinical manifestations include superficial punctate keratopathy, epithelial erosion, and persistence of epithelial defects.…”

“…21 Clinical causes of the loss or impairment of trigeminal nerve function and consequent reduced corneal sensation include herpes simplex virus infection or herpes zoster ophthalmicus; complications of surgery for acoustic neuroma or of ophthalmic surgeries such as penetrating keratoplasty, LASIK, and photorefractive keratectomy; toxic keratopathy such as that resulting from abuse of topical anesthetics or β-blockers; and congenital diseases such as Riley-Day syndrome. 19,21 To develop eyedrops containing FGLM-NH 2 and SSSR for the treatment of persistent corneal epithelial defects in individuals with neurotrophic keratopathy, we previously examined the clinical efficacy of such eyedrops in a prospective single-center open clinical study. 6 The eyedrops induced the rapid healing of such epithelial defects; however, the molecular mechanism of this effect has remained unclear.…”

“… 21 Clinical causes of the loss or impairment of trigeminal nerve function and consequent reduced corneal sensation include herpes simplex virus infection or herpes zoster ophthalmicus; complications of surgery for acoustic neuroma or of ophthalmic surgeries such as penetrating keratoplasty, LASIK, and photorefractive keratectomy; toxic keratopathy such as that resulting from abuse of topical anesthetics or β-blockers; and congenital diseases such as Riley–Day syndrome. 19 , 21 …”

Genetically Encoded Calcium Indicators for In Situ Functional Studies of Corneal Nerves

“…1,[3][4][5][6][7][8][9][10] Diseases such as dry eye syndrome and neurotrophic keratopathy, which are principally of the ocular surface, are at least partially due to abnormal corneal nerve function. [11][12][13][14][15][16] Additionally, common ocular procedures such as refractive surgery and corneal cross-linking cause damage to the corneal nerves and can result in long-term morbidities. 2,[17][18][19][20][21] These conditions and diseases collectively affect millions of people in the United States and many more worldwide.…”