Michael A. Morris, MD PGY-3 Ophthalmology Resident Scott & White Eye Institute Temple, TX Authors have no financial interests. Purpose To evaluate the effectiveness of combination treatment with corneal photodynamic therapy (PDT) using verteporfin and subconjunctival bevacizumab for deep stromal corneal neovascularization as primary treatment or in preparation for therapeutic penetrating keratoplasty. The above therapy is an off-label use of PDT with verteporfin and bevacizumab. Methods Retrospective case series performed at Scott & White Eye Institute from 2009- 2010. Six eyes of 6 patients with deep corneal neovascularization were treated with corneal PDT with verteporfin (total light dose=150 J/cm2) and subconjunctival bevacizumab (2.5 mg/0.1 ml). Methods Blood flow through the deep stromal vessels was evaluated by slit lamp examination (SLE) and corneal fluorescein angiography (FA). Examination was performed before treatment and at 1 week, 1 month, and 3 months after treatment. Repeat combination treatment was applied after the 1-month visit if reperfusion of the deep stromal vessels was observed either by SLE or corneal FA. Results Patients (eyes) 6 eyes out of 6 patients Age (years) 65 ± 22 (Range 43-87) 66% Female (n=4) Gender 33% Male (n=2) Pre-op BCVA 20/188 (Range = 20/30 - 5/200) 3 month BCVA 20/62 (Range = 20/30 – 20/100) Post-tx IOP 0 cases Results Absence of blood flow in the deep stromal vessels was observed on SLE and corneal FA in all patients (N=6 eyes) treated with corneal PDT and subconjunctival bevacizumab at the 1-week follow-up examination. In addition, all patients (5 of 6) evaluated at the 1-month follow-up examination showed persistent absence of blood flow on slit lamp evaluation and/or corneal FA. 0:15.5 Red-free (Pre-treatment) Early phase (Pre-treatment) 1:11.0 8:07.6 Mid-phase (Pre-treatment) Late phase (Pre-treatment) 0:46.9 Red-free (1 month post-treatment) Early phase (1 month post-treatment) 1:45.7 7:36.2 Mid-phase (1 month post-treatment) Late phase (1 month post-treatment) Results At 3 months, 4/6 patients (66%) were noted to have early revascularization requiring retreatment and 2/6 (33%) had no revascularization at 3 months post-treatment. Recurrences were much less prominent, and easily treated with a second treatment. One patient underwent PKP after the 3-month follow-up appointment. Of the 2 patients without revascularization at 3 mos, 1 patient had revascularization at 6 mos requiring retreatment. Pathology * A B Figure 1 PK host cornea 1 month s/p PDT and subconjunctival bevacizumab treatment. A, Erythrocytic debris in the stromal vessels (arrow) and stroma (asterisk) appears red when stained with Masson- trichrome. B, Fibrin in the stromal vessels appears blue when stained with Phosphotungstic acid hematoxylin (PTAH). Results No serious adverse events were observed. All patients had mild corneal intrastromal and subconjunctival hemorrhage at the 1-week post-treatment visit which resolved by the 1-month post-tx visit. No cases of elevated IOP throughout the duration of post-tx follow-up. Conclusions The combination of corneal PDT with verteporfin and subconjunctival injection of bevacizumab appears to be effective in closing deep stromal blood vessels as observed by SLE and corneal FA. Further study is required to examine the long-term effectiveness of this combination therapy to treat corneal neovascularization either as primary treatment or in patients anticipating corneal transplantation. Special thanks to Dr. Samuel Fulcher and Dr. Robert Rosa, Jr. at the Scott & White Eye Institute for allowing me to join them in this research project. References 1. You I, Kang I, Lee S, Yoon K. Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization. Acta Ophthalmologica. 2008: 1-6. 2. Bock F, Onderka J, Dietrich T, et al. Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. Invest Ophthalmol Vis Sci. 2007; 48:2545- 52. 3. Qian C, Bahar I, Levinger E, Rootman D. Combined Use of Superficial Keratectomy and Subconjunctival Bevacizumab Injection for Corneal Neovascularization. Cornea. 2008; 27, 9: 1090-92. 4. Bock F, Konig Y, Dietrich T, et al. Inhibition of Angiogenesis in the Anterior Chamber of the Eye. Ophthalmology. 2007;104:33-44. 5. Gerten G. Bevacizumab (Avastin) and Argon Laser to Treat Neovascularization in Corneal Transplant Surgery. Cornea. 2008; 27,10: 1195-99. 6. Bahar I, Kaiserman I, McAllum P, Rootman D, Slomovic A. Subconjunctival Bevacizumab Injection for Corneal Neovascularization. Cornea. 2008;27, 2: 142-47. 7. Amano S, Rohan R, Kuroki M, et al. Requirement for Vascular Endothelial Growth Factor in Wound- and Inflammation-related Corneal Neovascularization. Invest Ophthalmol. 1998; 39:18-22 8. Yoon K, Ahn K, Kim K, Im S, Nah H, Im W. Experimental Inhibition of Corneal Neovascularization by Photodynamic Therapy with Verteporfin. Current Eye Research. 2006; 31:215-224. 9. Framme C, Flucke B, Birngruber R. Comparison of Reduced and Standard Light Application in Photodynamic Therapy of the Eye in Two Rabbit Models. Graefe’s Arch Clin Exp Ophthalmol. 2006; 244:773-781.
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