Research Brief Report Toxic Keratopathy Following the Use of Alcohol-Containing Antiseptics in Nonocular Surgery Hsin-Yu Liu, MD; Po-Ting Yeh, MD; Kuan-Ting Kuo, MD; Jen-Yu Huang, MD; Chang-Ping Lin, MD; Yu-Chih Hou, MD IMPORTANCE Corneal abrasion is the most common ocular complication associated with nonocular surgery, but toxic keratopathy is rare. OBSERVATION Three patients developed severe toxic keratopathy after orofacial surgery on the left side with general anesthesia. All patients underwent surgery in the right lateral tilt position with ocular protection but reported irritation and redness in their right eyes after the operation. Alcohol-containing antiseptic solutions were used for presurgical preparation. Ophthalmic examination showed decreased visual acuity ranging from 20/100 to 20/400, corneal edema and opacity, anterior chamber reaction, or stromal neovascularization in the patients’ right eyes. Confocal microscopy showed moderate to severe loss of corneal endothelial cells in all patients. Despite prompt treatment with topical corticosteroids, these Author Affiliations: Department of Ophthalmology, National Taiwan 3 patients eventually required cataract surgery, endothelial keratoplasty, or penetrating University Hospital, College of keratoplasty, respectively. After the operation, the patients’ visual acuity improved to 20/30 Medicine, National Taiwan University, or 20/40. Data analysis was conducted from December 6, 2010, to June 15, 2015. Taipei, Taiwan (Liu, Yeh, Huang, Lin, Hou); Department of Pathology, National Taiwan University Hospital, CONCLUSIONS AND RELEVANCE Alcohol-containing antiseptic solutions may cause severe College of Medicine, National Taiwan toxic keratopathy; this possibility should be considered in orofacial surgery management. University, Taipei, Taiwan (Kuo). Using alcohol-free antiseptic solutions in the periocular region and taking measures to protect Corresponding Author: Yu-Chih the dependent eye in the lateral tilt position may reduce the risk of severe corneal injury. Hou, MD, Department of Ophthalmology, National Taiwan University Hospital, College of JAMA Ophthalmol. 2016;134(4):449-452. doi:10.1001/jamaophthalmol.2016.0001 Medicine, National Taiwan University, Published online February 25, 2016. 7 Chung-Shan South Rd, Taipei, Taiwan ([email protected]). lthough they are rare, eye injuries ranging from cor- 20/50 OD and 20/25 OS. Biomicroscopy showed an epithe- neal abrasion to serious corneal edema occur during lial defect and corneal edema in the right lower cornea with A nonocular surgery.1,2 Various ocular protective strat- a trace anterior chamber reaction, while the left eye was egies during general anesthesia have been proposed, but unremarkable. Treatment with fluorometholone and tetra- corneal injury still occurs because of incorrect placement of cycline, 0.1%, ointment was started. Thereafter, corneal tape or unwise use of surgical preparation solutions.3-5 edema increased and keratic precipitates were observed. Here, we report 3 cases of severe toxic keratopathy in the The patient was referred to a corneal specialist (Y.-C.H.) and right eye after orofacial surgery performed on the left side. was treated with prednisolone acetate, 1%, for 1 month. Alcohol-containing antiseptic preparation solution was Betamethasone sodium phosphate, 0.1%, or fluorometho- used for skin preparation with eye protection. We examined lone, 0.1%, was used for a further 3 months. Six months possible pathogenic mechanisms and describe the manage- later, a faint opacity persisted in the lower paracentral ment of this ocular complication. Data analysis was con- region of the right cornea. The patient developed a cataract, ducted from December 6, 2010, to June 15, 2015. The and BCVA decreased to 20/100 OD. Because the remaining National Taiwan University Hospital Institutional Review corneal opacity was faint and superficial and corneal endo- Board approved this study. All patients provided verbal thelial cell density was approximately 1228 cells/mm2,cata- consent. ract surgery was performed in the right eye. The patient’s BCVA improved to 20/30 OD, with a refraction of +0.25 −2.25 × 120° after surgery (Figure 1A and B). Report of Cases Case 2 Case 1 A man in his mid-40s developed redness and pain in his right A man in his 60s experienced pain and decreased vision in eye after surgery for left lower gingival cancer. Biomicros- the right eye after excision of a tumor on the left tongue. On copy revealed ciliary injection, diffuse superficial punctuate initial examination, best-corrected visual acuity (BCVA) was keratopathy, Descemet membrane folds, and anterior cham- jamaophthalmology.com (Reprinted) JAMA Ophthalmology April 2016 Volume 134, Number 4 449 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jamanetwork.com/ by Sociedad Mexicana de Oftalmologia on 08/10/2017 Research Brief Report Toxic Keratopathy by Alcohol-Containing Antiseptics in Nonocular Surgery Figure 1. Biomicroscopy Findings Key Points A Patient 1: faint corneal opacities B Patient 1: faint corneal opacities Question: Can toxic keratopathy follow the use of alcohol-containing antiseptics in nonocular surgery? Findings: Right corneal edema and opacity, associated with the use of alcohol-containing antiseptic solutions, were observed despite ocular protection in 3 patients in whom left-sided orofacial surgery was performed under general anesthesia in the right lateral tilt position. Meaning: Alcohol-containing antiseptic solutions may cause toxic keratopathy, especially in the dependent eyes. centrally along with peripheral corneal neovascularization in C Patient 2: corneal edema D Patient 2: after endothelial the lower nasal area 7 months later (Figure 1E). Lamellar kera- keratoplasty tectomy was performed to remove superficial corneal opaci- ties on the right eye. Thereafter, poor corneal reepithelializa- tion was noted because of limbal insufficiency. Despite complete reepithelialization after topical 20% autologous se- rum use every 2 hours for 2 months, vision improved only slightly because of residual corneal opacity, edema, and cata- ract. Therefore, penetrating keratoplasty and cataract sur- gery were performed on the right eye 2 years after the initial presentation. Thereafter, BCVA improved to 20/40 OD with a refraction of −0.25 −4.5 × 125°. The patient later developed pe- E Patient 3: edema with band F Patient 3: after penetrating ripheral iridocorneal synechia in the lower nasal region keratopathy keratoplasty (Figure 1F). The graft remained clear 2 years after transplant. In all patients, orofacial surgery on the left side with eye protection was performed under general anesthesia in the right lateral tilt position. The antiseptic agents used in the surgical fields in all patients contained alcohol: povidone-iodine, 10%, in 70% alcohol in patients 1 and 3 and chlorhexidine, 2%, in 70% isopropyl alcohol in patient 2. Confocal microscopy showed marked polymegathism and pleomorphism with prominent nuclei, indicating cellular stress, in right endothe- lial cells but not in the left eye in all patients (Figure 2). The A and B, Faint corneal opacities seen in patient 1. C, Corneal edema seen in initial endothelial cell density of the right eye vs the left eye patient 2. D, Clear graft after endothelial keratoplasty in patient 2. E, Corneal 2 edema with band keratopathy in patient 3. F, Clear graft after penetrating was 966 vs 3477, 1263 vs 2469, and 1909 vs 3146 cells/mm in keratoplasty in patient 3. patients 1, 2, and 3, respectively. Corneal endothelial cell den- sity in patient 3 rapidly decreased to 560 cells/mm2 three months after the initial presentation. The histopathologic find- ber reaction in the right eye. Topical betamethasone, 0.1%, was ings of the corneal button from patient 3 showed hypocellu- applied, and the symptoms gradually resolved within 1 week. lar stroma, focal edematous collagens with loosening arrange- However, corneal microcystic edema persisted and was ac- ment, intrastromal neovascularization, and markedly sparse companied by superficial corneal opacities and intrastromal endothelial cells. neovascularization in the upper nasal area (Figure 1C). The pa- tient’s BCVA decreased to 20/100 OD. Descemet stripping automated endothelial keratoplasty was performed 6 months Discussion later. Three years after endothelial keratoplasty, the corneal graft remained clear, and visual acuity was 20/30 OD with a Corneal injury is the most common perioperative eye injury refraction of +0.5 + 2.0 × 165° (Figure 1D). in nonocular surgery, especially orofacial surgery.3 Our 3 pa- tients who underwent orofacial surgery in the right lateral tilt Case 3 position developed severe corneal injuries in the dependent A man in his mid-60s presented with an irritated right eye fol- eyes. Alcohol-containing antiseptic agents were used in all pa- lowing surgery for left nasal tumor. Severe corneal edema was tients along with ocular protection during the procedure. noted, and visual acuity was 20/400 OD. Topical betametha- Povidone-iodine is considered safe for ophthalmic use, such sone, 0.1%, hypromellose, 0.32%, and sodium chloride, 5%, as conjunctival sac irrigation or instillation.6 Despite the pos- hypertonic solution were administered. Although the cor- sibility of iodine-related allergy, limited cases of povidone- neal edema slowly decreased, band keratopathy developed iodine–related allergy in nonocular fields have been reported.7 450 JAMA Ophthalmology April 2016 Volume