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EW FEATURE 122 Controversies in cataract surgery • April 2017 AT A GLANCE • Intracameral vancomycin has been associated with a rare but sight-threatening condition known as hemorrhagic occlusive retinal vasculitis (HORV). • Thought to be a Type III delayed hypersensitivity reaction, vision loss often occurs a week or more after uneventful cataract surgery in which intraocular vancomycin was admin- istered. • According to the latest published case series—36 eyes of 23 patients diagnosed with HORV—61% were 20/200 or worse. • The ASCRS/ASRS task force has made several recommendations regarding the use of intracameral vancomycin and treatment of HORV should it develop postop. by Liz Hillman EyeWorld Staff Writer The latest data on vancomycin-associated HORV and where to go from here I n July 2016, ASCRS and the American Society of Retina Specialists (ASRS) formed a joint task force and established a registry to better track, analyze, and understand hemorrhagic occlu- sive retinal vasculitis (HORV), a rare, sight-threatening condition that appears to occur after uneventful cataract surgery that included intra- ocular vancomycin prophylaxis. According to the task force's re- cent paper published in Ophthalmol- ogy, vancomycin-associated HORV has been diagnosed in 36 eyes of 23 patients. 1 The task force describes it as a "potentially devastating condi- tion that can develop after cataract surgery or intraocular injection." Kevin M. Miller, MD, chief of the cataract and refractive surgery division, David Geffen School of Medicine, University of California, Los Angeles, said the ASCRS/ASRS task force collected eyes with diffuse retinal hemorrhages after surgery— eliminating central retinal vein occlusions (CRVO), which don't classify as HORV—and collected in- formation about everything that was used at the time of cataract surgery, such as fluids, anesthetic agents, vis- enced HORV after intracameral van- comycin developed symptoms later, suggesting an immune reaction. If the second eye also has sur- gery with intraocular vancomycin, Dr. Chang, co-chair of the ASCRS/ ASRS HORV task force, noted that the onset of HORV is often earlier and more severe than it was in the first. Conversely, if the second eye did not receive vancomycin, it had a normal outcome. Seven eyes in the latest dataset received an additional bolus of vancomycin to treat what was thought at the time to be en- dophthalmitis and five of the seven ended up with no light perception. Dr. Mamalis said that the ma- jority of HORV patients also experi- enced a mild to moderate anterior chamber reaction, though not as severe as seen with TASS, in addition to mild to moderate vitritis. The hallmark of these patients, however, is a hemorrhagic occlusive vasculitis seen in a dilated fundus exam of the retina. The retinal vasculitis seems to preferentially involve the peripheral venules, Dr. Chang observed. "There are large sectoral hemor- rhages in the affected ischemic areas of retina. Diffuse blot hemorrhages, and vascular dilation and tortuosity are seen with CRVO but not HORV," Dr. Chang said, adding that early progression to neovascular glaucoma is unfortunately common with this condition. Of the 36 eyes in the latest published series that were diagnosed with HORV after receiving vancomy- cin intracamerally, intravitreally, or in the irrigation bottle, 61% (22/36) coelastic agents, artificial tears, and anything injected into the eye. "All the cases that did fit the criteria had one thing in common, and that was they all had injections of vancomycin," Dr. Miller said. What's concerning about the condition, said Nick Mamalis, MD, professor of ophthalmology, director of ocular pathology, John Moran Eye Center, Salt Lake City, is that it is delayed. "As surgeons, we will often do cataract surgery a week apart or maybe even less than that … in rare situations there is even simultane- ous bilateral surgery done," he said. "What's difficult about this issue is if there is a delay in the onset of signs and symptoms—and it can be a delay of longer than a week, even 2 weeks—then we may not know there is going to be a reaction and then proceed with the second eye. That's the part that's really scary about this condition; we don't see this right away … we may be doing surgery on the second eye before we even know if it is going to occur in the first eye." How it started The first reported cases of HORV were described between 2014 and 2015, totaling 11 eyes in 6 patients who had uncomplicated cataract surgery and received prophylactic intracameral vancomycin. 2–3 One of those patients was referred to Andre Witkin, MD, assistant professor of ophthalmology, Tufts University School of Medicine, Boston. The female patient had uncomplicated bilateral cataract surgery spaced 1 week apart. After a week, she started losing vision in her first eye and was put on steroids by another retina specialist. A week later, her second eye developed similar symptoms. By the time she was referred to Dr. Witkin, she exhibited severe bilat- eral occlusive retinal vasculitis and diffuse intraretinal hemorrhage. "At the time, we didn't know what was happening," Dr. Witkin said. The patient was admitted to the hospital where she had an extensive workup for various infectious dis- eases or inflammatory conditions— none of which were determined to be the cause of her retinal patholo- gy. None of the tests came back pos- itive. She was treated with high-dose steroids and for a presumptive viral retinitis. In the end, this patient had no light perception in one eye and was 20/200 in her other eye. At the time of this patient's discharge, Dr. Witkin said an article by Nicholson and colleagues was published describing two other cases that sounded and looked similar to this case. 2 Over time, as these cases were presented at regional and national conferences, other similar cases came out as well. "It seemed like there was mounting evidence that vanco- mycin may be associated with this disease," Dr. Witkin said. Intracameral vancomycin use is certainly not new, so why does it seem these HORV cases are occur- ring only recently? "It's so rare that I think people didn't recognize it, and I think some HORV was treated as endophthalmi- tis," Dr. Miller said. "Other HORV was probably brushed off as an unfortunate postoperative central vein occlusion. I think it's when the cases started appearing bilaterally that it became clear it wasn't these other things." Signs, symptoms, and etiology According to David Chang, MD, clinical professor, University of Cal- ifornia, San Francisco, and private practice in Los Altos, California, there is a delayed but sudden onset of painless, decreased vision, usually around 1 to 3 weeks postop, though it can occur earlier. Dr. Mamalis pointed out that unlike a toxicity reaction, which would present im- mediately, the patients who experi- Vancomycin-associated HORV: What do we know now? Stats from ASCRS/ASRS online HORV Registry 1 • 36 eyes/23 patients diagnosed with HORV • 33/36 received intracameral vancomycin, 1/36 received intravitreal, 2/36 received it through the irrigation bottle • 61% of eyes were 20/200 or worse • 22% had no light perception • Three eyes that received intravitreal corticosteroids were 20/40, 20/70, and hand movements, respectively • 56% of eyes developed neovascular glaucoma • 5/7 eyes that received additional intravitreal vancomycin ended up with no light perception

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