CLINICAL SCIENCE Corneal Fine Needle Diathermy With Adjuvant Bevacizumab to Treat Corneal Neovascularization in Children Uri Elbaz, MD, Kamiar Mireskandari, MBChB, FRCSEd, FRCOphth, PhD, Carl Shen, BMSc, and Asim Ali, MD, FRCSC orneal neovascularization (CN) in the pediatric popula- Purpose: fi To report the outcomes of corneal ne needle Ction has various etiologies including blepharokeratocon- diathermy (FND) with adjuvant intrastromal and subconjunctival junctivitis (BKC),1 bacterial ulcer, herpes keratitis, anesthetic bevacizumab injection for corneal neovascularization (CN) in cornea, and exposure keratopathy. The cornea in its native children. state is completely devoid of vascular components thereby 2,3 Methods: Medical records of all children who had undergone retaining immunoprivilege. In the event of infectious FND with adjuvant bevacizumab injection were reviewed retro- keratitis, the resulting immune response and new vessel spectively. Treatment efficacy was evaluated by changes in visual formation can help to eradicate the invading organism but can acuity, regression of CN, and clearing of lipid deposits with the cause stromal necrosis, thinning, and scarring that impair aid of slit-lamp color images that were taken before surgical vision. Additionally, irregular astigmatism, edema, haze, and intervention and at last follow-up visit. Postoperative complica- lipid deposition can also occur. Despite elimination of the tions were recorded and served to assess the safety of the inciting cause, CN may often persist. In noninfectious procedure. conditions such as BKC, corneal anesthesia, or exposure keratopathy, the mechanism of CN is poorly understood but is Results: Nine eyes of 9 patients were included in the study. The most likely related to weakness in the integrity and function of mean age of the patients was 8.4 6 4.2 years (4–15 years) and the the blood vessel barrier provided by the limbal stem cells.4 mean follow-up time was 18.7 6 12.2 months (5–35 months). Three In adults, CN has been reported to respond to numerous eyes had a history of herpes simplex keratitis (HSK), 3 eyes had treatment modalities including topical corticosteroids and complete corneal anesthesia, 2 eyes had CN following suture tract nonsteroidal anti-inflammatory drops,5 corneal argon laser infection after corneal transplant for HSK scar and limbal dermoid photocoagulation,6 photodynamic therapy,7 fine needle dia- excision, and 1 eye had blepharokeratoconjunctivitis. After treat- thermy (FND),8,9 electrolysis-needle cauterization,10 repeated ment, 8 eyes had complete CN resolution, and 1 eye with corneal bevacizumab injections (Avastin; Genentech, San Francisco, anesthesia following brain tumor resection had partial regression in CA),11 and ligation of blood vessel origin.12 No treatment vessel distribution and size. Lipid deposition clearance lagged modality has been reported to be completely effective in behind CN resolution. Mean duration of CN before treatment was eradicating blood vessels from the cornea and often, repeated 15.3 6 14.0 months (1–37 months). Mean corrected distance visual treatments are required. Recently, encouraging results of FND acuity before and after surgery was 0.66 6 0.31 and 0.50 6 0.37 and topical and/or subconjunctival bevacizumab administra- logMAR, respectively (P = 0.02). tion before planned keratoplasty were reported in adults.13 In Conclusions: contrast, there are very few reports on CN treatment in Corneal FND with adjuvant bevacizumab injection 8,14 is effective at treating sectorial corneal vessels in children. children. Bevacizumab and FND each have their own disadvan- Key Words: corneal neovascularization, bevacizumab, fine needle tages when applied separately. Bevacizumab is postulated to diathermy be ineffective in more mature chronic vessels that have already acquired a pericyte covering15 and are hence less dependent on (Cornea 2015;34:773–777) vascular endothelial growth factor. FND is thought to induce release of proangiogenic factors,16 collagen shrinkage with potential damage to surroundings of the treated vessel, and Received for publication October 1, 2014; revision received January 27, insufficient response when collateral vessels are still patent.8 It 2015; accepted February 1, 2015. Published online ahead of print March 26, 2015. also does not prevent further new vessel growth. By using From the Department of Ophthalmology and Vision Sciences, Hospital for Sick a combination therapy, we hypothesized that each modality Children, University of Toronto, Toronto, ON, Canada. would compensate for the limitation of the other. The purpose The authors have no funding or conflicts of interest to disclose. of our study was to report the outcomes of a novel combined Reprints: Uri Elbaz, MD, Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, 555 University Ave, Toronto, ON approach of corneal FND with adjuvant intrastromal and M5G 1X8, Canada (e-mail: [email protected]). subconjunctival bevacizumab injection (off-label use) in Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. a series of pediatric patients with CN. To the best of our Cornea Volume 34, Number 7, July 2015 www.corneajrnl.com | 773 Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Elbaz et al Cornea Volume 34, Number 7, July 2015 knowledge, this is the only series reporting this technique in a history of corneal anesthesia had undergone permanent children with CN and among the first reports to present an tarsorrhaphy before the combined treatment. effective treatment modality for this disorder in children. RESULTS PATIENTS AND METHODS Nine eyes of 9 patients were included in this study. The The study was approved by the Research Ethics Board mean patient age was 8.4 6 4.2 years (4–15 years) and the of The Hospital for Sick Children Toronto, Ontario, Canada. mean follow-up time was 18.7 6 12.2 months (5–35 months). We retrospectively reviewed the charts of all patients less The etiology of CN was as follows: 3 eyes had a history of than 18 years who had undergone combined FND with herpes simplex keratitis (HSK), 3 eyes had complete corneal intrastromal and subconjunctival bevacizumab injection. Data anesthesia, 2 eyes had CN following suture tract infection were collected on patient demographics, causes and indica- after lamellar corneal graft for HSK scar and for limbal tions for CN treatment, corrected distance visual acuity dermoid excision, and 1 eye had blepharokeratoconjunctivitis (CDVA), procedural details, and complications. Slit-lamp (BKC). Two of the 3 patients with corneal anesthesia had photographs before surgical intervention and at last follow-up resection of brain tumors affecting the trigeminal nerve in one visit were used to evaluate treatment efficacy. The main patient and trigeminal and facial nerves in the other. The third outcomes measures were regression of abnormal corneal patient had isolated complete corneal anesthesia with a small blood vessels, resolution of corneal lipid deposits, and trigeminal ganglion found on brain imaging and presented changes in CDVA over time. Response to treatment as with recurrent corneal ulcers with subsequent CN. measured by vessel regression and resolution of lipid deposits Patient 4 with HSK had deep anterior lamellar kerato- was graded as complete, partial, no change, or worse than plasty (DALK) performed at the same time as FND and baseline. For statistical analysis, Snellen visual acuity was adjuvant bevacizumab injection; otherwise, all procedures converted to logarithm of the minimum angle of resolution were performed in isolation. All patients presented with (logMAR) units and Student t test was used for comparison of a single (4 eyes) or double (5 eyes) vessel main trunk CDVA before surgery and at last follow-up visit. P , 0.05 involving a single corneal quadrant only. Three patients had was considered significant. multiple previous FND treatments without bevacizumab injections with recurrence of their CN. Mean duration of CN before treatment was 15.3 6 14.0 months (range, 1–37 Surgical Technique months). Lipid deposition was observed in 5 eyes before Corneal FND was performed as previously described treatment. by Pillai et al.8 Briefly, all surgeries were performed in Following treatment, 8 of 9 eyes treated (88.9%) had children under general anesthesia. The needle tip from complete CN resolution with subsequent resolution of corneal a stainless steel needle detached from a 10-0 monofilament edema within 1 month of treatment. They all maintained nylon suture was inserted intrastromally approximately 1 mm corneas devoid of vessels throughout a mean follow-up from the limbus to the level of corneal new vessels. Unipolar period of 17.0 6 11.9 months (5–35 months) after surgery. diathermy was then lightly tapped against the needle and Complete cessation of blood flow was noted on postoperative served to heat the needle in its corneal track to a degree day 1 in all these eyes. Only 1 eye (patient 3) with corneal where blanching of the vessels was noticeable with minimal anesthesia and exposure keratopathy following brain tumor stromal collagen shrinkage. An attempt was made to resection had partial regression in vessel distribution and size. cannulate the vessels or at least disrupt their integrity to Complete lipid deposition clearance was noted in 3 of 5 eyes further enhance the thermal effect. This was repeated as and this lagged behind CN resolution. In 1 patient (patient 4), needed to disrupt all the blood vessels. Once cauterization lipid deposits were removed with removal of the old DALK was complete, bevacizumab 25 mg/mL was injected into the graft. A temporary increase in lipid deposits was noted in 2 deep stroma (up to 2.5 mg in 0.1 mL per each corneal patients, patient 2 (Fig. 1B) and patient 9 (Fig. 2C) at 3 and quadrant involved) in proximity to the vessels until whiten- 3.5 months after surgery, respectively. In patient 2, lipid ing around the vessels was visible and the remainder into the deposition had resolved completely by the 13-month visit subconjunctival space adjacent to areas of CN.