Eyeworld

EW NEWS & OPINION 16 January 2017 1990s EyeWorld was publishing arti- cles about bifocal diffractive lenses, these are now essentially gone from the market, Dr. Findl said. Coverage on accommodative lenses has evolved. These were orig- inally thought to have some effect on near vision, but this has proven not to be true. "If you look at the data, they don't accommodate, and we now know that," Dr. Findl said. Another emerging area is diag- nostics. "Twenty years ago, we were doing ultrasound biometry," he said, adding that the contact method was intimidating to the patient. Also, even with practitioners dedicated to good results, the precision wasn't great. "Then came optical biometry, and that revolutionized the arena of biometry and power calculation," Dr. Findl said. "Optical biometry was born in Vienna, my hometown. We did the first prototyping." In glaucoma cases, trabeculec- tomy has remained a staple, Dr. Findl observed. "The trabeculecto- my we do today is pretty much the same as we did 20 years ago," he said. "We added mitomycin, which was a game changer in the mid- or late 90s." While there has been the emergence of techniques like deep sclerectomy and viscocanalostomy, many surgeons do not favor these. "Some use it, but many don't," Dr. Findl said, adding that even with MIGS, trabeculectomy remains a mainstay. "MIGS doesn't give the final answer," he said. "It will still not replace trabeculectomy, at least for the difficult cases." Going forward, Dr. Findl hopes to continue to see a range of cov- erage in EyeWorld. "I would like to see that we have a good mix of the proper evidence showing that this device or lens works and something really innovative in technology." EW Editors' note: Dr. Braga-Mele has finan- cial interests with Alcon, Abbott Med- ical Optics (Abbott Park, Illinois), and Allergan (Dublin, Ireland). Dr. Findl has financial interests with Abbott Medical Optics and Carl Zeiss Meditec. Dr. Henderson has financial interests with Alcon, Abbott Medical Optics, Allergan, Bausch + Lomb (Bridgewater, New Jersey), Shire (Lexington, Massa- chusetts), and Sun Pharma (Mumbai, India). Dr. Chang has no financial interests related to his comments. Contact information Braga-Mele: rbragamele@rogers.com Chang: dceye@earthlink.net Findl: ofindl@googlemail.com Henderson: BAHenderson@eyeboston.com with TASS that have been linked with compounding pharmacies, Dr. Braga-Mele said. "The concern is obvious with intracamerals and making sure they're compounded correctly," she said, adding that because this has been highlighted, it has helped make practitioners aware of the potential issues with TASS involving any intraocular injection or device put into the eye. Also of note is the use of life- style IOLs, Dr. Braga-Mele said. "The advent of toric IOLs and presbyopia- correcting IOLs has made a differ- ence in being able to offer patients a range of vision or visual correction choices with more precision," she said. There have been significant changes in diagnostic cataract tech- nology. "We've moved from A-scans to optical biometry to corneal topography. What has been dis- cussed recently is the mystery of the cornea. Dr. Koch's work in posterior corneal astigmatism has been huge," Dr. Braga-Mele said, adding that this has led to EyeWorld discussions on diagnostic topography and OR suites such as Verion (Alcon, Fort Worth, Texas) and Callisto (Carl Zeiss Meditec, Jena, Germany), as well as intraoperative aberrometry. Also garnering its share of EyeWorld headlines has been the advent of MIGS devices, Dr. Braga- Mele said. In July 2012, EyeWorld ran a breaking news segment on the approval of the iStent (Glaukos, San Clemente, California), which was described as a "game changer." Over the years, other EyeWorld articles have explored this further. For glaucoma patients under- going phacoemulsification, this has made a big difference. "Now we have data that some of the current MIGS devices like the iStent and CyPass Micro-Stent [Transcend Med- ical, Menlo Park, California] help lower IOP more than phacoemulsifi- cation alone," Dr. Braga-Mele said. "I think the biggest develop- ment in glaucoma has been the shift to doing a MIGS procedure because our trabeculectomies, although they're good, are rather invasive," Dr. Braga-Mele said. "MIGS allows us to treat the glaucoma patient with cataract surgery a lot sooner with less invasive procedures, to get good outcomes and minimize the need for eye drops, thereby minimizing dry eye and compliance issues." Oliver Findl, MD, Department of Ophthalmology, Hanusch Hospi- tal, Vienna, Austria, pointed out that the emergence of multifocal lenses has been of worldwide importance. "Multifocals have gone through a lot of changes," he said. "There's more in Europe because we have models available that are not available in the U.S., like trifocals, which we use quite readily." While in the mid- HORV on the ASCRS listserv," he said, adding that HORV Task Force members responded to these ques- tions in real time on July 20 and 21. A subsequent issue of EyeWorld highlighted excerpts of the listserv discussion of HORV. "Coverage of this story illus- trates some of the unique strengths of EyeWorld as a source of news and clinical education," Dr. Chang said. "As the official voice of our society, ASCRS Clinical Committees and task forces utilize EyeWorld to dissemi- nate important new information in a timely fashion." Because the print issue of EyeWorld has a distribution of about 24,000 and the digital issue can be downloaded by anyone with internet access in any country, this breaking clinical information could potentially reach every ophthalmol- ogist worldwide—not just ASCRS members, he said. Rosa Braga-Mele, MD, profes- sor of ophthalmology, University of Toronto, views endophthalmitis prevention pieces as particularly noteworthy. These are often seen in the pages of EyeWorld highlighting ASCRS surveys spearheaded by Dr. Chang. The work may be important in obtaining FDA approv- al of a pre-compounded intraca- meral injection, such as is already available in Europe, she said. Another issue that has drawn attention over the years is problems Outstanding continued from page 14 17 EW NEWS & OPINION July 2016 by the ASCRS/ASRS HORV Task Force: David F. Chang, MD, Steve Charles, MD, Dean Eliott, MD, Richard S. Hoffman, MD, J. Michael Jumper, MD, Nick Mamalis, MD, Kevin M. Miller, MD, Andre J. Witkin, MD, and Charles C. Wykoff, MD • Surgeons desiring an alternative to vancomycin for intracameral pro- phylaxis may consider cefuroxime or moxifloxacin. 4 Recommendations for management of HORV • Consider avoiding intravitreal vancomycin if both bacterial endophthalmitis and HORV are in the differential. • Consider ocular and/or systemic work-up for other syndromes (e.g., viral retinitis). • Aggressive systemic and topical corticosteroids; consider peri- or intraocular steroids • Early anti-VEGF treatment • Early panretinal photocoagulation • If you identify a patient with HORV, please submit the clinical data to the HORV registry site (links from www.asrs.org and www.ascrs.org). Patient and surgeon names will be kept confidential. EW References 1. Nicholson LB, Kim BT, Jardon J, et al. Severe bilateral ischemic retinal vasculitis following cataract surgery. Ophthalmic Surg Lasers Imaging Retina. 2014;45:338–342. 2. Witkin AJ, Shah AR, Engstrom RE, Kron-Gray MM, et al. Postoperative hemorrhagic occlu- sive retinal vasculitis: Expanding the clinical spectrum and possible association with vancomycin. Ophthalmology. 2015;122:1438– 1451. 3. Chang DF, Braga-Mele R, Henderson BA, Mamalis N, et al. Antibiotic prophylaxis of postoperative endophthalmitis after cata- ract surgery: Results of the 2014 ASCRS member survey. J Cataract Refract Surg. 2015;41:1300–1305. 4. Braga-Mele R, Chang DF, Henderson BA, Mamalis N, et al. Intracameral antibiotics: Safety, efficacy, and preparation. J Cataract Refract Surg. 2014;40:2134–2142. This ASCRS/ASRS alert is provided for informational and educational purposes only. It is not intended to mandate or establish a specific standard of care or dictate the treatment of any particular patients. ASCRS and ASRS members must make independent judgments about the treatment of their patients based on all the facts and circumstanc- es relating to each patient's condition. Contact information Chang: dceye@earthlink.net Witkin: ajwitkin@gmail.com rare type III hypersensitivity reaction to vancomycin, rather than direct drug toxicity. This might be similar to leukocytoclastic vasculitis and He- noch-Schonlein purpura, which are type III hypersensitivity reactions in the skin that have also been rarely associated with vancomycin. Unfor- tunately, there is no current method to test for such hypersensitivity either pre- or post-HORV diagnosis. Fourteen of the 22 cases (64%) were bilateral. Because of the de- layed onset, HORV did not appear in the first eye until after surgery in the second eye in the 11 cases who un- derwent sequential bilateral cataract surgery (3 days to 3 weeks apart). In most of these 11 sequential bilateral cases, the first eye became symp- tomatic first, but bilateral HORV was diagnosed simultaneously during the initial examination. Even with a long delay between eyes in the re- maining 3 bilateral cases (9 months, 3 years, and 9 years) the second eye presented similarly to the first after the second eye underwent surgery. Use of intracameral antibiotic for endophthalmitis prophylaxis is increasing. In a 2014 ASCRS member survey, 50% of respondents were us- ing intracameral antibiotics. 3 Among those using intracameral antibiotic, vancomycin was used by 37% over- all and by 52% of American sur- geons. Many high volume practices using intracameral vancomycin have never knowingly experienced HORV, and the Task Force believes it to be extremely rare. Without knowing how many patients have received intracameral vancomycin, however, the actual rate is unknown. Considerations for intraocular vancomycin use • Because HORV appears to be ex- tremely rare, each surgeon should weigh the potential risk of HORV associated with vancomycin against the risk of endophthalmitis. • Reconsider using vancomycin with close sequential bilateral cataract surgery. • Surgeons using intraocular van- comycin with sequential cataract surgery should be aware that in addition to delayed onset, HORV may not cause symptoms in the first eye, and a dilated retinal examination may be the only way to detect it. postop day 1 • Delayed onset of sudden painless decreased vision (range 1–26 days postop; mean 8 days) • Visual acuity often poor on pre- sentation, but may be normal in mild cases • Mild to moderate anterior cham- ber and vitreous inflammation, with no hypopyon • Sectoral intraretinal hemorrhage in areas of non-perfusion (often along venules) • Peripheral retinal involvement in all cases, with macular ischemia and whitening in advanced disease • Sectoral retinal vasculitis and retinal vascular occlusion on FA, corresponding to areas of hemor- rhage • Rapid progression to neovascular glaucoma common (53%) Other associations • Intraocular vancomycin exposure during procedure • History of similar reaction in fellow eye • When both eyes involved, second eye often has faster onset and more severe course • Minimal to no corneal edema • Retinal hemorrhages are often large and/or confluent • Propensity for retinal venule involvement (although can affect both arteries and veins) • No significant increase in venous dilation or tortuosity • OCT: Hyper-reflectivity and thick- ening of the inner retinal layers; CME not a key feature • Therapy with intravitreal vanco- mycin for presumed endophthal- mitis associated with poor out- comes HORV is different from ischemic CRVO, which is unilateral, usual- ly presents on postop day 1 when associated with cataract surgery, and is associated with diffuse small intraretinal hemorrhages; converse- ly, HORV is often bilateral, has a delayed onset, and often presents with large patches of intraretinal hemorrhage only in sectors of retinal vascular occlusion. CME and severe vascular dilation and tortu- osity are key features with CRVO, but not HORV, and the rates of NLP vision and of neovascular glaucoma are higher with HORV. Consulted immunology experts hypothesize this might represent a F ollowing the first published series of hemorrhagic occlusive retinal vasculi- tis (HORV), 1,2 the Ameri- can Society of Cataract & Refractive Surgery (ASCRS) and the American Society of Retina Special- ists (ASRS) formed a joint Task Force to further analyze the prevalence, potential etiology, treatment, and outcomes of this complication associated with intraocular surgery. An HORV case registry was devel- oped and made accessible through the ASRS website, www.asrs.org, and an online surveillance survey was emailed to all ASCRS members. In addition to the first 6 cases reported, 1,2 we have identified at least 16 additional cases of HORV for a total of 22 cases. Fourteen cases were bilateral and 8 were unilater- al, for a total of 36 eyes. Twelve of the cases occurred in 2015–2016, 5 cases occurred in 2013–2014, and the other 5 cases were prior to 2013. The age range was 51–84 (mean 68 years). Although reporting and data collection are ongoing, preliminary findings from these 22 cases warrant this special Clinical Alert because of their potential impact on patient safety. HORV appears to be extremely rare, and can occur following any in- traocular procedure (usually cataract surgery). Presentation is delayed, with a mean onset of symptoms 8 days after the procedure. Although the cause of HORV is currently unproven, there is a strong asso- ciation with the use of intraocular vancomycin (including intravitreal, intracameral bolus, and irrigating solution containing vancomycin). All 36 eyes from these 22 cases received intraocular vancomycin. As of now, there has not been an association with one formulation or one manufacturer. Visual outcomes were often poor; 22/36 eyes (61%) were 20/200 or worse, and 8/36 eyes (22%) were NLP. Notably, 7 of 36 eyes (19%) received an additional bolus of intra- vitreal vancomycin for treatment of presumed bacterial endophthalmitis. These patients had particularly poor outcomes, and 5/7 eyes were NLP at most recent follow-up. HORV characteristic findings • Occurs after intraocular procedure with normal undilated exam on Clinical Alert: HORV association with intraocular vancomycin EW NEWS & OPINION 18 July 2016 by Liz Hillman EyeWorld Staff Writer the opinion this will ultimately be shown to be vancomycin-induced HORV." Neal Shorstein, MD, Kaiser Permanente, Walnut Creek, California Intracameral cefuroxime was the first line endophthalmitis prophy- laxis for Dr. Shorstein's group nearly a decade ago based on findings from the multicenter, randomized control trial by the European Society of Cat- aract & Refractive Surgeons. 3 But 15% of their patients were allergic to penicillin or cephalo- sporin, making them suboptimal candidates for cefuroxime. In these patients, Dr. Shorstein said they started using moxifloxacin. Even Dr. Shorstein said he thinks there may still be a place for intra- cameral vancomycin—such as in patients who have a history of infec- tion or colonization with MRSA— and thus, he encourages more research to better understand the mechanism behind the conditions that could be causing HORV. Overall, Dr. Shorstein said his bottom line is that injecting an in- tracameral antibiotic of some kind is more favorable than not. "Presently, I think patients incur a much higher risk of endophthalmitis if physicians don't inject any intracameral anti- biotic than of getting HORV if they inject intracameral vancomycin." Experts weigh in on recommendations regarding rare but "strong association" between HORV cases and intracameral vancomycin F ollowing the first published data showing a possible association with intraoc- ular vancomycin use and postoperative hemorrhagic occlusive retinal vasculitis (HORV), 1,2 ASCRS and the American Society of Retina Specialists (ASRS) formed a joint Task Force to investigate, make recommendations, and establish an HORV registry to collect more information. In its Clinical Alert (see page 17 of this issue of EyeWorld), the Task Force states that while the "cause of HORV is currently unproven, there is a strong association with the use of intraocular vancomycin." There are still many unknowns regarding intraocular vancomycin and rare cases of HORV. Coupled with the proven benefits of using the antibiotic to reduce risk of endophthalmitis, there are various opinions on both. EyeWorld spoke with a few physicians about the Clinical Alert and their own takes on the topic. Opinions on intracameral antibiotics and ASCRS/ASRS alert then though, 1% of patients were allergic to both classes of drugs. These patients received intracameral vancomycin. "We knew we wanted to give an intracameral antibiotic to 100% of patients so we started with cefu- roxime because that had the best evidence. That has always been our default drug; we haven't changed from that. Moxi was the second line and vanco was the third line," Dr. Shorstein said. In light of the recent informa- tion regarding rare cases of HORV and intracameral vancomycin, Dr. Shorstein said, based on the annu- al volume of cataract surgeries in Kaiser Permanente's Northern Cal- ifornia system, which is more than 38,000 a year, "we had to weigh the risks and benefits." "In a recent study, we found that the organisms that cause en- dophthalmitis in our system were most sensitive to vancomycin. On the other hand, whereas a single ophthalmologist practicing in the United States may never experience HORV if he or she continues to use vancomycin, the chances of a large group like ours finally encountering a case of HORV is higher because of our annual volume of cataract surgery," he said. As such, Dr. Shorstein said Kaiser Permanente's cataract sur- gery research group, much like the ASCRS/ASRS Task Force's recommen- dation, is advising, although not mandating, its ophthalmologists avoid vancomycin on immediately sequential bilateral cataract surgery (ISBCS) patients. For delayed sequen- tial bilateral cataract surgery, he said the recommendation is to wait at least 4 weeks. Dr. Shorstein said his local group will continue to use cefurox- ime as a first line antibiotic prophy- laxis and moxifloxacin as a second line if there is an allergy to the first. If in the rare case there is an allergy associated with both, Dr. Shorstein said physicians have 3 choices: not inject an intracameral antibiotic at all (which he does not suggest); inject vancomycin knowing there is a very small risk of HORV; or ask the patient more about his or her allergic reaction to penicillin, and without a history of anaphylaxis, ad- minister cefuroxime since the risk of cross-reactivity is extremely remote. 4 Richard Kent Stiverson, MD, Kaiser Permanente, Denver Dr. Stiverson said he has used vanco- mycin since 2006, including in more than 1,750 patients who have had ISBCS since 2013. "The data supporting intracam- eral antibiotics is impressive in my opinion," Dr. Stiverson said. Yet in light of recent data re- garding vancomycin and HORV, Dr. Stiverson said he will be changing his habits somewhat. "At first, I thought we would be in the clear as we use vancomy- cin at a lower dose in the irrigation solution, but that is not the case as HORV has been reported with this method as well," he said. As such, Dr. Stiverson said he will continue using vancomycin for unilateral cataract surgery cases with 6 weeks between surgeries. For ISBCS or patients who wish to have unilat- eral surgery within the 6-week time frame, he will use moxifloxacin. "I think the [ASCRS/ASRS] alert is informative, restrained, and as evidence-based as it can be at this time," Dr. Stiverson said, adding that there is still very much that is not known about the relationship between HORV and intracameral vancomycin, but "what we do know is profoundly disturbing. I am of Jeffrey Liegner, MD, Eye Care Northwest, Sparta Township, New Jersey Dr. Liegner said he has used intraca- meral and intravitreal vancomycin in every case he's had for the last 3 years, adding it to his practice after perceiving an increased risk of MRSA in his community. He routinely combines vancomycin with moxi- floxacin and triamcinolone, a me- dium strength steroid that remains active inside the eye for 3 weeks postoperatively. "The risk of something ver- sus the benefits of something are carefully weighed by the judicious surgeon, and decisions are made that sometimes embrace risk in exchange for benefit," he said. "In this situation, vancomycin provides protection against MRSA that is not duplicated by moxifloxacin or [cefuroxime]." Bringing the possible associa- tion between intracameral vancomy- cin use and HORV into the equation caused Dr. Liegner to weigh the risk of HORV compared to the benefit of MRSA prophylaxis. Calling the ASCRS/ASRS Clinical Alert a well-structured and well-for- mulated document, Dr. Liegner said he is not going to alter his use of vancomycin based on the current knowledge. As of right now, Dr. Liegner said he thinks far more MRSA cases can be prevented with vancomycin use compared to HORV cases that could be prevented with- out its use. "I think there is a sense of worry out there. As with any profession, there are some individuals who are more inclined to do risk analysis and take risk, and there are others who are profoundly conservative and avoid risk wherever it might be, even if it is in exchange for a differ- ent kind of adverse event," he said.

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