A Surgical Cryoprobe for Targeted Transcorneal Freezing to Treat Corneal Endothelial Dysfunction

Program Number: 1248 Poster Board Number: D0196 Presentation Time: 3:15 PM–5:00 PM A Surgical Cryoprobe for Targeted Transcorneal Freezing to Treat Corneal Endothelial Dysfunction Alina Akhbanbetova1, Shinichiro Nakano2, Stacy L. Littlechild1, Robert D. Young1, Madara Zvirgzdina1, Nigel J. Fullwood3, Shigeru Kinoshita4, Naoki Okumura2, Noriko Koizumi2, Andrew J. Quantock1. 1Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom; 2Biomedical Engineering, Doshisha University, 1-3 Miyakodami-Tatara, Japan; 3Biomedical and Life Sciences, Lancaster University, Lancaster, United Kingdom; 4Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Purpose: To examine the effects on corneal tissue of localized freezing induced by a new surgical cryoprobe. The machine was designed to remove endothelial cells from the posterior surface of the cornea in a reproducible and targeted manner to aid the treatment of corneal endothelial dysfunction. Methods: A freezing console was designed and manufactured based on the use of nitrous oxide as a cryogen. The console was connected to one of four different cryoprobes, each with a different freezing tip (1.8 mm-diameter, flat profile; 2.4 mm-diameter, flat profile; 2.4 mm-diameter concave profile; 3.4 mm-diameter, concave profile) at which temperatures below -50°C were achieved. In vitro studies were conducted on 426 porcine corneas, followed by a small number of in vivo investigations on rabbit corneas. After treatment the epithelial basement membrane, corneal stroma, and corneal endothelium were investigated by slit-lamp microscopy, ultrasound pachymetry, and light and electron microscopy. Results: In vivo and in vitro the corneal epithelium was destroyed by freezing, but the epithelial basement membrane remained intact. In vitro, reproducible corneal endothelial damage was achieved using the 3.4 mm-diameter cryoprobe tip with the concave profile. The damage occurred after a short, 3-sec freeze, and was confined to a circular region of the endothelium located directly under the surface application position of the cryoprobe tip. Corneal edema was seen in vivo 24-hrs after freeze injury and was accompanied by alterations to the arrangement of collagen fibrils, but this resolved by 10-days and 1-month concurrent with endothelial repopulation of the wound area. Conclusions: Surface corneal freezing using a 3.4 mm-diameter concave cryoprobe induces transient stromal edema, but leaves the epithelial basement membrane intact which likely aids epithelial resurfacing. Localized destruction of the endothelial monolayer was achieved in a consistent manner, and represents a potentially useful approach to help treat corneal endothelial dysfunction. Commercial Relationships: Alina Akhbanbetova, None; Shinichiro Nakano, None; Stacy L. Littlechild, None; Robert D. Young, None; Madara Zvirgzdina, None; Nigel J. Fullwood, None; Shigeru Kinoshita, None; Naoki Okumura, None; Noriko Koizumi; Andrew J. Quantock, None Support: Ser Cymru The Life Sciences Research Network Wales UK: Research Studenship Program Number: 1249 Poster Board Number: D0197 Presentation Time: 3:15 PM–5:00 PM The use of topical insulin to treat refractory neurotrophic corneal ulcers Angeline L. Wang, Eric Weinlander, Brandon Metcalf, David M. Gamm, Michael Struck. Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI. Purpose: Refractory neurotrophic corneal ulcers are clinically challenging and potentially blinding. Current research focuses on targeted therapies to improve corneal epithelial healing in these cases. Insulin has been shown to improve corneal epithelial healing in vitro and in diabetic animal models; however, clinical experience with topical insulin in patients with non-healing corneal wounds is limited. The purpose of this study is to present three cases of refractory neurotrophic corneal ulcers that were treated with topical insulin. Methods: Retrospective chart review of patients’ exam findings, medications, and procedures. Regular insulin at a concentration of 1 unit per mL of artificial tears was prescribed topically as one drop two or three times daily. Results: The three patients included a 2-year-old girl with a history of excised orbital teratoma and proptosis; a 2-year-old boy with aniridia, congenital glaucoma status post multiple glaucoma procedures, and bilateral corneal decompensation; and a 24-year-old woman with a history of herpes zoster keratoconjunctivitis. All three patients were noted to have decreased or absent corneal sensation in one eye. Each patient developed a neurotrophic corneal ulcer with associated epithelial defect and stromal thinning. The ulcers were refractory to a range of traditional treatments, up to and including surgical management with permanent tarsorrhaphy in one patient. The addition of topical insulin resulted in complete corneal reepithelialization ranging from 13 to 25 days following initiation of treatment. One patient reported increased eye irritation and redness with the treatment; no systemic side effects were noted. Conclusions: Topical insulin may be an effective treatment for refractory neurotrophic corneal ulcers. Proposed mechanisms include increased corneal epithelial cell migration and restoration of bidirectional trophic signaling through preservation of corneal nerves. Insulin has been shown to promote cell migration and closure of artificial wounds in cultured sheets of corneal epithelial cells. In diabetic mice, topical insulin appears to slow the loss of sub-basal plexus corneal nerves. Further study is needed to determine the clinical efficacy and side effect profile of topical insulin in corneal wound healing. Commercial Relationships: Angeline L. Wang, None; Eric Weinlander, None; Brandon Metcalf, None; David M. Gamm, None; Michael Struck