Cataract surgery 2016: News from the pharmaceutical front

December 1, 2016

A review of some of the most significant advances in medications for cataract surgery during the past year revealed a mix of the expected with a few surprises.

Reviewed by Eric D. Donnenfeld, MD; Robert H. Osher, MD; and Mark Packer, MD

A review of some of the most significant advances in medications for cataract surgery during the past year revealed a mix of the expected with a few surprises. For instance, though phenylephrine and ketorolac injection 1%/0.3% (Omidria, Omeros Corp.) received FDA approval for marketing in 2014, this intracameral product still earned top mention by Ophthalmology Times' Editorial Advisory Board members.

Eric D. Donnenfeld, MD, noted that use of the combination product grew substantially in 2016 and with good reason.

“There is strong and convincing evidence from clinical trials showing that adding phenylephrine/ketorolac injection to the irrigating solution is effective for preventing intraoperative miosis and reducing pain after cataract surgery. My real-world experience has been that its use reduces problems with intraoperative pupil constriction, and as a result, cataract surgery is much less traumatic,” said Dr. Donnenfeld, Clinical Professor of Ophthalmology, New York University, New York, and Founding Partner, Ophthalmic Consultants of Long Island and Connecticut, Garden City, NY.

Robert H. Osher, MD, professor of ophthalmology, University of Cincinnati School of Medicine, and Medical Director Emeritus, Cincinnati Eye Institute, Cincinnati, OH noted that phenylephrine/ketorolac is an important drug because it fulfills the need for an approved intracameral medication for preventing intraoperative miosis.

“With a commercially available intracameral product that is indicated for preventing intraoperative miosis, surgeons using medications in an off-label manner may be putting themselves at risk medicolegally, even if a complication occurs and is completely unrelated to the pupil,” he said.

Because intracameral phenylephrine/ketorolac was granted pass-through reimbursement status, there is no reason why surgeons should not be using it routinely, said Mark Packer, MD, Clinical Associate Professor of Ophthalmology, Oregon Health & Science University, Portland.

“The decision to grant pass-through reimbursement status to Omidria indicates that the reviewers at the Centers for Medicare and Medicaid Services were convinced it provides significant benefit, and it is certainly a better option than using some extemporaneously compounded formulation,” he said.

Endophthalmitis prophylaxis

 

Endophthalmitis prophylaxis

Use of intracameral antibiotics for endophthalmitis prophylaxis is also growing in the United States, albeit slowly, and Dr. Osher was hopeful that sooner or later, there would be a commercially available product approved for this indication.

“It is 8 years since Steve Lane, Sam Masket, and I wrote the first article reporting on the safe use of intracameral antibiotics in cataract surgery in the United States. There is still no FDA-approved product, but the tide is rising,” said Dr. Osher.

“The efficacy and safety of intracameral antibiotics is being supported by a growing body of research and published reports, and I think its time has come.”

Although there is no FDA-approved intracameral antibiotic, Dropless Cataract Surgery products (Imprimis Pharmaceuticals) combining antibiotics and anti-inflammatory products for transzonular administration is generating a lot of interest, Dr. Osher noted.

Dr. Packer observed that in October, 2016, Imprimis issued a press release announcing results of a fairly large retrospective study evaluating the efficacy of Dropless Cataract Surgery. The study included data from more than 1500 eyes injected with triamcinolone acetonide 3.0 mg/moxifloxacin 0.2 mg/vancomycin 2.0 mg. The results showed that for 92% of cases, no supplemental medication was needed in 92%. In addition, there was a low incidence of IOP elevation (0.9%), a 9.2% rate of breakthrough inflammation at days 14 to 21 after surgery, and visually significant cystoid macular edema developed in 2% of eyes. There were no cases of endophthalmitis.

“I think the incidence of CME in this series is concerningly high considering that a few years ago, we published a paper reporting a CME rate of only 0.1% among 2862 eyes that received topical anti-inflammatory medications for CME prophylaxis,” said Dr. Packer.

“Although a much larger series is needed to show definitively that Dropless Cataract Surgery reduces the risk of postoperative endophthalmitis, I would expect it is effective. Therefore, I think that this approach might at least have the potential to reduce the postoperative medication burden by eliminating the antibiotic drop from the regimen.”

Dr. Donnenfeld agreed that American cataract surgeons are turning increasingly to intracameral antibiotics for endophthalmitis prophylaxis. Accompanying this trend, however, hemorrhagic occlusive retinal vasculitis (HORV) was identified as a new syndrome associated with the use of intracameral vancomycin.

The first clinical series reporting on HORV were published in 2014 and 2015, and in July 2016, the American Society of Cataract and Refractive Surgery and the American Society of Retina Specialists issued a clinical alert about the complication, recognizing its potential impact on patient safety.

“Although HORV has been a rare event, it is potentially devastating as it has led to cases of bilateral blindness,” Dr. Donnenfeld said.

Simplifying surgical medication regimens

 

Simplifying surgical medication regimens

In 2016, Imprimis Pharmaceuticals also introduced a sublingual product for conscious sedation (IV Free MKO Melt). Containing midazolam, ketamine, and ondansetron, it offers an alternative to the use of intravenous medications and could open the door to in-office cataract surgery, said Dr. Packer.

In addition, Imprimis Pharmaceuticals announced plans to expand its LessDrops topical formulation line with a new product combining prednisolone acetate, moxifloxacin hydrocholoride, and nepafenac.

On the topic of minimizing the medication burden for cataract surgery patients, Dr. Donnenfeld said that he is looking forward to the eventual availability of the dexamethasone intracanalicular insert (Dextenza, Ocular Therapeutix). It was developed as a treatment for ocular pain after surgery, and in July, 2016, Ocular Therapeutix announced that it received a Complete Response Letter from the FDA regarding its NDA. The letter identified issues pertaining to manufacturing and controls but no efficacy or safety concerns.

“This punctal plug delivery system is designed to release dexamethasone for up to 30 days and would eliminate the need for using a topical corticosteroid drop after cataract surgery,” said Dr. Donnenfeld.

 

Ocular surface optimization

Another issue in cataract surgery that has been receiving increasing attention is the importance of optimizing the ocular surface preoperatively and avoiding dry eye postoperatively. Oral supplementation with omega-3 fatty acids is one strategy for improving and maintaining ocular surface health, and Dr. Donnenfeld noted he was involved in a multicenter, randomized, placebo-controlled, double-masked trial that demonstrated re-esterified omega-3 fatty acids (Physician Recommended Nutriceuticals) effectively improved the signs and symptoms of dry eye in patients with meibomian gland dysfunction. The paper reporting on the study was published in September 2016 [Epitropoulos AT, et al. Cornea. 2016;35(9):1185-1191].

“Nutritional supplementation with omega-3 fatty acids is an important way to improve the quality of the tear film. We are now including the re-esterified omega-3 product in our protocol for all patients having cataract surgery,” said Dr. Donnenfeld.

He added that he continues to be proactive in identifying dry eye preoperatively and is aggressive about treating it with anti-inflammatory medications as appropriate.

“I continue to use topical cyclosporine emulsion (Restasis, Allergan) and have begun to prescribe topical lifitegrast (Xiidra, Shire) to improve the ocular surface before cataract surgery in patients with dry eye,” Dr. Donnenfeld said.

Medical treatment for presbyopia

 

Medical treatment for presbyopia

While the huge amount of research that is ongoing to develop novel implant solutions for presbyopia correction is exciting and promising, Dr. Osher cited the idea of topical drop therapy as an interesting approach that could provide an option for risk averse individuals to reduce spectacle dependence. The concept originated by the late Lee Nordan, MD, is known as Liquid Vision and is being developed by Presbyopia Therapies. Intended for binocular use, it combines aceclidine to create miosis and tropicamide to inhibit accommodation. Together the two medications provide a pinhole effect for increased depth of focus without the accommodative blur that occurs using a miotic by itself.

“Well-respected cataract surgeons who have been involved with this project are very enthusiastic about its potential,” noted Dr. Osher.

 

Eric D. Donnenfeld, MD

E: ericdonnenfeld@gmail.com

Dr. Donnenfeld is a consultant to Abbott Medical Optics, AcuFocus, Alcon, Allergan, Aquesys, Bausch + Lomb, Beaver Visitec International, CRST, Glaukos, Novaliq, Omeros, Pfizer, and Shire Pharmaceuticals. He consults and has investment interests in Katena, Novabay Pharmaceuticals, PRN Pharmaceuticals, and RPS Diagnostics.

 

Robert H. Osher, MD

E: rhosher@cincinnatieye.com

Dr. Osher is a consultant to Alcon Laboratories, Bausch + Lomb, Beaver Visitec International, Carl Zeiss Meditec, Clarity Medical Systems, MicroSurgical Technology, Omeros, and the Video Journal of Cataract and Refractive Surgery.

 

Mark Packer, MD  

E: mark@markpackerconsulting.com

Dr. Packer is a consultant to Advanced Vision Science, Alcon, Allergan, Bausch + Lomb, Cassini BV, International Biomedical Devices, LensAR, Rayner, and STAAR Surgical, and he owns equity in Cassini BV, International Biomedical Devices, LensAR, and TrueVision.