Although no new drug therapies entered cataract surgeons’ armamentarium in 2015, interest continues to grow in approaches for intraocular administration.
By Cheryl Guttman Krader; Reviewed by Malik Y. Kahook, MD, Nick Mamalis, MD, and Mark Packer, MD
Though cataract surgeons in 2015 had no new choices of medications to use with their patients, there appeared to be growing interest in options for intraocular administration.
Speaking to Ophthalmology Times, Malik Y. Kahook, MD, Nick Mamalis, MD, and Mark Packer, MD, discussed modalities targeting intraoperative miosis and postoperative pain, inflammation, and endophthalmitis.
Intracameral administration of antibiotic for endophthalmitis prophylaxis continues to be a hot topic in cataract surgery, said Dr. Mamalis, professor of ophthalmology, John A. Moran Eye Center, and co-director, Intermountain Ocular Research Center, University of Utah, Salt Lake City.
“There is very good evidence from studies in Europe and also from Kaiser Permanente in California showing that use of an intracameral antibiotic decreases the incidence of postoperative endophthalmitis,” Dr. Mamalis said. “Yet, adoption of this technique is still limited in the United States because there is no medication approved by the FDA for intracameral use.”
Worldwide, cefuroxime is currently the most common antibiotic given intracamerally to prevent endophthalmitis after cataract surgery.
According to findings from the most recent American Society of Cataract and Refractive Surgery (ASCRS) survey, concerns about the risks accompanying compounding of cefuroxime for intracameral use, which involves a multistep procedure, remains a major barrier to its more widespread adoption in the United States, Dr. Mamalis said.
As an alternative approach, there seems to be a growing trend for “Go Dropless” cataract surgery (Imprimis Pharmaceuticals), observed Dr. Packer, clinical associate professor of ophthalmology, Oregon Health and Science University, Portland.
This approach uses a compounded dual or triple formulation that contains triamcinolone plus moxifloxacin with or without vancomycin. The preparation is intended to be administered at the end of surgery as a transzonular injection or into the vitreous through the pars plana.
Acting as a compounding pharmacy, Imprimis can provide medications when ordered for a specific patient without having to obtain FDA approval for marketing based on studies demonstrating safety and efficacy, Dr. Packer noted.
“Clearly, some surgeons are happy with this approach,” he said. “One drawback, however, is that the material floating around in the vitreous affects vision and diminishes the ‘wow’ factor of rapid visual recovery after cataract surgery. So, that is a tradeoff for the benefit of having to use a topical medication after surgery, which also is not ideal.”
Dr. Mamalis commented, “Certainly there are advantages to having a dropless material for preventing infection and controlling pain and inflammation after cataract surgery as it eliminates the possibilities of patients not obtaining their medications and not using them.”
However, he noted the only published information about this technique is in non-peer review literature.
In addition, Dr. Mamalis expressed concerns about the ability of surgeons to successfully administer a transzonular injection so that the zonules are not disrupted and the mediation is delivered at the proper location behind the capsular bag and into the anterior vitreous.
“Intracameral cefuroxime may also need to be obtained from a compounding or hospital pharmacy,” he said. “Compared with the ‘Go Dropless’ technique, however, intracameral cefuroxime is easier to administer, and it is a clear liquid that it does not interfere with vision.”
Dr. Kahook, The Slater Family Endowed Chair in Ophthalmology and professor of ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, noted the potential for floaters with the “dropless” approach and for other complications relating to the posterior segment delivery.
“There is potential for vitreous detachment, and there have even been some reports of retinal detachment following use of ‘Go Dropless’, although a causal relationship is unclear since retinal detachment can also occur after cataract surgery,” he said.
Another drawback of going “dropless” is that the medication is not reimbursable, and so the surgeon has to absorb the cost, he said.
“The future of cataract surgery will be dropless, in my opinion, but we will have to find ways to do it in a more cost-effective manner and perhaps integrally combined with the very same IOLs we are implanting to correct vision,” Dr. Kahook added.
Dr. Packer said that there appears to be a growing number of American surgeons who are using non-preserved topical moxifloxacin (Vigamox, Alcon) right off the shelf intracamerally for endophthalmitis prophylaxis.
“This approach also presents some medicolegal concerns because it is off-label, but apparently the associated risk is acceptable to some surgeons,” he said.
Dr. Kahook said “LessDrops,” also from Imprimis, is a more appealing approach for achieving the goal of limiting the burden of postoperative medication use. “LessDrops” offers dual or triple combinations of antibiotic, corticosteroid, and nonsteroidal anti-inflammatory drug (triamcinolone-moxifloxacin, prednisolone-moxifloxacin, prednisolone-ketorolac, or prednisolone-moxifloxacin-ketorolac), and thereby simplifies the treatment paradigm to enable better patient adherence. The medication is bought by the surgery center and sold to the patient, so that any monetary loss is avoided, Dr. Kahook said.
“Currently big pharma and other smaller companies are gearing up to be in competition with ‘Dropless’ and ‘LessDrops’,” he added. “The potential disruption to a multibillion dollar postoperative topical medication business has many people paying attention.”
FDA approval for the fixed-combination phenylephrine 1%/ketorolac 0.3% injection (Omidria, Omeros) that is added to the irrigation bottle and indicated for preventing intraoperative miosis and reducing postoperative pain came at the end of May 2014. Then, in October 2014, the Centers for Medicare and Medicaid Services determined that the product met requirements to qualify for transitional pass-through reimbursement status, which became effective January 2015 and will expire at the end of December 2017.
“Without pass-through payment, surgeons might consider Omidria a hard-to-justify added expense. Pass-through payment, however, provided strong support for its adoption,” Dr. Packer said. “There are advantages for using Omidria, and with pass-through payment, surgeons can get those benefits without stressing their surgery center budget.”
Even so, Dr. Mamalis questioned how many surgeons will use the fixed-combination phenylephrine/ketorolac injection routinely.
However, he noted there is a particularly good niche for employing it in certain cases where there is increased propensity for intraoperative pupil constriction, such as in patients with uveitis or a history of alpha 1-antagonist use who are at risk for intraoperative floppy iris syndrome (IFIS).
“A lot of surgeons in the United States are injecting a combination of epinephrine and lidocaine prior to surgery to prevent intraoperative miosis in these situations,” Dr. Mamalis said. “However, the experience of surgeons in Europe shows that phenylephrine injected into the eye is much more effective for decreasing pupillary constriction and floppiness of the iris than epinephrine, which is used by surgeons in the United States.
“With the fixed combination of phenylephrine/ketorolac, surgeons have an option to use an FDA-approved, preservative- and bisulfite-free preparation of phenylephrine to reduce intraoperative miosis and get the added benefit of having intracameral ketorolac that also decreases pupil constriction and inflammation,” he said.
Dr. Mamalis added that there are no data from clinical studies of phenylephrine/ketorolac in IFIS cases, and evidence would be valuable to confirm its benefit in this subset of patients.
Though no topical nonsteroidal anti-inflammatory drug (NSAID) is approved by the FDA for preventing cystoid macular edema (CME) after cataract surgery, because of the efficacy of these medications for controlling inflammation, they are widely used in extended postoperative regimens for that purpose.
In November 2015, a report on topical NSAIDs and cataract surgery from the American Academy of Ophthalmology [Kim SJ et al. Ophthalmology. 2015;122:2159-2168] concluded “there is a lack of level I evidence that supports the long-term benefit of NSAID therapy to prevent vision loss from CME at 3 months or more after cataract surgery.”
Members of the ASCRS Cataract Clinical Committee had reservations about that conclusion, Dr. Mamalis noted.
“We think there are several more recent relevant studies, which were not included in the review of the literature, that give compelling evidence to show NSAIDs have a role in preventing CME,” he said.
The ASCRS Cataract Clinical Committee has submitted a review paper on cataract surgery and NSAIDs to the Journal of Cataract and Refractive Surgery.
Malik Y. Kahook, MD
Dr. Kahook is a consultant to Alcon Laboratories, Allergan, Aerie Pharmaceuticals, ClarVista Medical, New World Medical, Shire, Tempest Medical, Foresight Vision, and Mile High Ophthalmics. He holds patent interests with Alcon, Abbott Medic Optical MO, ClarVista Medical, Mile High Ophthalmics, Glaukos, and New World Medical.
Nick Mamalis, MD
Dr. Mamalis is a consultant to Anew Optics and Medennium and receives research grant support from these companies and ARC Laser, Aaren Scientific, Abbott Medical Optics, Alcon Laboratories, Allergan, Bausch + Lomb, Calhoun Vision, ClarVista, Genisphere, HOYA, LensGen, Mynosys, Nu-Vue Technologies, Omega, PowerVision, and Sharklet.
Mark Packer, MD
Dr. Packer is a consultant to Advanced Vision Science, Aerie Pharmaceuticals, Alcon Laboratories, Bausch + Lomb, International Biomedical Devices, i-Optics, LensAR, Oculeve, Promedica International, Rayner Intraocular Lenses, Refocus Group, SOLX, STAAR Surgical Company, Transcend Medical, and VisionCare Ophthalmic Technologies. He holds equity in Eyenovia, Iantech, International Biomedical Device,s LensAR, mTuitive, Refocus Group, Transcend Medical, TrueVision Systems, and WaveTec Vision Systems.