Eyeworld

EW CORNEA 44 June 2014 C orneal surgeons are increasingly turning to antivascular endothelial growth factor (anti-VEGF) treatments for corneal neovascularization (CNV). That's because the anti-VEGF medications used primarily for age-related macu- lar degeneration (AMD) seem to work more effectively than the available treatments for CNV. Some of the available therapies include topical steroids, nonsteroidal anti-inflammatory drugs, lasers, and immunosuppressives such as methotrexate and cyclosporine, said Neema Nayeb-Hashemi, MD, assistant professor, Department of Ophthalmology, Loyola University Medical Center, Maywood, Ill. Still other therapies include fine needle diathermy and transplantation with amniotic membranes, limbal tissue, and conjunctiva, added Scott R. Anagnoste, MD, Retina Group of Florida, Fort Lauderdale, Fla. The therapies used until re- cently for CNV have varying results, compared with more favorably consistent outcomes with the anti-VEGFs bevacizumab (Avastin, Genentech, South San Francisco), ranibizumab (Lucentis, Genentech), or aflibercept (Eylea, Regeneron, Tarrytown, N.Y.). "Even with the relatively small trials published so far, it's clear that VEGF inhibitors are much more effective than other therapies avail- able," Dr. Anagnoste said. "VEGF inhibition leads to more rapid and more complete regression of neovas- cularization than any other current treatment." One approach that surgeons can use is topical therapy, such as beva- cizumab 1% on the surface of the eye 4 to 6 times a day. "It does show efficacy, but it can cause epithelial defects and thinning of the cornea," Dr. Nayeb-Hashemi said. Another approach is administer- ing the therapy subconjunctivally at the limbus. "Reports in patients with penetrating keratoplasty or deep an- terior lamellar keratoplasty [DALK] have shown that this is safe and ef- fective and causes at least partial re- gression," Dr. Nayeb-Hashemi said. Intrastromal and intraocular injections reported by surgeons in the U.S. and abroad have been effec- tive, Dr. Nayeb-Hashemi explained. In fact, patients who have both choroidal neovascularization from AMD and CNV have responded positively to intraocular injections. Some corneal specialists attempt combined therapies to treat CNV— for instance, concurrent steroids and anti-VEGF treatment or anti-VEGF with laser use—but the results appear mixed, Dr. Nayeb-Hashemi said. "As VEGF primarily causes new vessel growth but is not required for maintenance of existing neovascu- larization, combination treatments with photodynamic therapy, steroids, and platelet-derived growth factor inhibitors are being investi- gated," Dr. Anagnoste said. In their hands Generally speaking, the anti-VEGF therapies appear to target fresher vessels better than they do vessels that are a few years old. "After the vessels grow, they've become more established. Anti-VEGFs are more effective for the regression of newly formed vessels," said Mark I. Rosenblatt, MD, PhD, director, Margaret M. Dyson Vision Research Institute, and vice chairman, Depart- ment of Ophthalmology, Weill Cornell Medical College, New York. Dr. Nayeb-Hashemi typically sticks with steroids so long as there is no sign the patient will be on them for long and provided he or she is not at an elevated risk for glaucoma, infection, or poor heal- ing. "Avastin is still second-line ther- apy at this point in that it requires a procedure," he said. However, he has successfully performed a subcon- junctival injection for CNV in a pa- tient with DALK for keratoconus. One caution with the use of this treatment is evidence that shows VEGF helps corneal nerves to grow, Dr. Rosenblatt said. "By impinging upon the amount of VEGF, you might alter the corneal nerves in some way, especially in the injury setting." Epithelial defects, corneal melt- ing, and other corneal compromises have occurred occasionally. "Early studies seem to indicate the possibility of delayed corneal ep- ithelial healing and an increase in spontaneous corneal erosions with topical or subconjunctival VEGF in- hibitor use," Dr. Anagnoste said. Because of these factors, Dr. Rosenblatt said careful use of anti- VEGFs for CNV is appropriate. Although the current use of anti-VEGF medications for CNV is off-label, Dr. Rosenblatt does not necessarily see pharmaceutical com- panies rushing to get this approach approved by the U.S. FDA. Aside from the complex regulatory process, Dr. Rosenblatt cited various standard-of-care medications that are used off-label. "Approval is bene- ficial for acceptance and safety, but there are also no widespread reports of complications from anti-VEGF therapies for the cornea," he said. Future directions Going forward, researchers will ex- plore the use of anti-VEGF treatment during graft rejection vs. using steroids alone. Dr. Rosenblatt is involved with a multicenter trial that will aim to determine if beva- cizumab is effective at decreasing the likelihood of a graft rejection. Reza Dana, MD, Schepens Eye Re- search Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, is leading the trial. Based on evidence from Dr. Dana's previous single-site trial, Dr. Rosenblatt believes the multicenter trial may show that bevacizumab use both before and after corneal transplantation will have an impor- tant role in preventing graft rejec- tion. There is also ongoing research regarding the benefit of other pro- angioigenic factors to augment the efficacy of existing treatments, Dr. Nayeb-Hashemi said. Future studies should also focus on the right timing and dosage to increase patient response to anti- VEGFs, Dr. Rosenblatt said. EW Editors' note: The physicians interviewed have no financial interests related to their comments. Contact information Anagnoste: sanagnoste@rgfla.com Hashemi: jritter@lumc.edu Latkany: relief@dryeyedoctor.com Rosenblatt: mar2058@med.cornell.edu by Vanessa Caceres EyeWorld Contributing Writer Corneal specialists try anti-VEGF therapy for corneal neovascularization Soothing the eye post-injections I t's not uncommon for ophthalmologists to see some eye sensitivity after a VEGF inhibitor injection, especially for AMD. So what's the best way to handle it? Dry eye specialist Robert A. Latkany, MD, associate professor, New York Medical College, New York Eye & Ear Infirmary, instructs patients to apply cold compresses to the eye and insert a drop of Refresh Plus (carboxymethylcellulose 0.5%, Allergan, Irvine, Calif.) prior to an injection; afterward, they should use the eye drops again, he said. "The redness and discomfort is all transient, but some patients are still bothered by it," he said. "There's often focal pain in the injection area, and sometimes there's a small subconjunctival hemorrhage," Dr. Nayeb-Hashemi said. He will the check IOP as in some patients it can rise to the 40s during an injection and occasionally not dip back down to normal, causing pain. For routine post-injection redness or discomfort, he advises patients to put an ice pack on the eyelid. Over-the-counter pain relievers can also help, he added. Dr. Anagnoste, a retinal specialist, commonly sees eye sensitivity, and he said it appears to be a combination of the effect of anesthetics and povidone-iodine used in the process of preparing for injections. He also noted the sensitivity appears more common in patients with dry eye or corneal epithelial disease. Dr. Anagnoste will irrigate the eye copiously after injection, instill ophthalmic ointment after irrigation, and encourage patients to use artificial tears. "In rare cases where a frank epithelial defect is encountered, a patch or bandage contact lens is sometimes used," he said. He encourages patients to return to his office if they still have discomfort the day after an injection. EW 42-44 Cornea_EW June 2014-DL_Layout 1 6/3/14 12:34 PM Page 44

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