HOT TOPICS IN REFRACTIVE SURGERY s PHARMACOLOGIC SOLUTIONS FOR PRESBYOPIA DOWN THE ROAD Several promising options are in the pipeline. BY COLMAN R. KRAFF, MD predictable, safe, consistent means of surgical correction AT A GLANCE of presbyopia has eluded cor- s neal refractive surgeons for There are at least four pharmacologic products for presbyopia in various decades. A variety of methods Afor altering the corneal shape have stages of clinical development. been attempted, but results have var- ied widely. These have included pres- s Most depend on some combination of miotic agents to increase depth byopic LASIK using an excimer laser, of focus. Ho:YAG laser thermal keratoplasty, and corneal inlays. No single method has s consistently been able to deliver pre- As these topical agents go through clinical trials and other agents dictable results to a large population are developed and become available, their indications and use in the of presbyopic patients. The reasons presbyopic population will potentially increase. are multifactorial, but they include a diverse patient population with varying presbyopic demands, the limitations of each of the available techniques, and A less invasive way of addressing others may be available in Europe and the natural aging characteristics of the presbyopia is an unmet medical elsewhere around the world. Some of human crystalline lens. need. A topical drop that could these will be discussed below. None Recently, medical device manu- restore accommodative function are commercially available in the facturers have turned their efforts would be a welcome addition to our United States at this time. Most of the to developing improved IOLs for array of treatment options for pres- agents being tested depend on com- the treatment of presbyopia. Part byopic patients. binations of compounds that induce of their motivation is the massive miosis to increase depth of focus. Data population of baby boomers now OPTIONS ON THE WAY? on these topical agents in the peer- entering their 60s and their eventual When talking with patients about review literature are limited. need for cataract surgery. treatment options for presbyopia, I’ve But patients with cataracts are not recently started mentioning that there EVO6 in the same universe as presbyopes. might someday be an eye drop avail- In an early clinical trial, EVO6 The mindset is different. Although in able to get rid of reading glasses. The (Novartis) demonstrated statistically some of these patients a presbyopia- typical response is “Wow! When can I significant improvement of near visual correcting IOL might be an option, get that?” Now I can tell them that the acuity compared with a placebo I have found that early presbyopes day may not be far off. group.1 The topical formulation of and most late presbyopes are not There are many pharmacologic lipoic acid choline ester 1.5% was ready for the discussion of a lens- products in various stages of clini- developed by Encore Vision, which based intraocular procedure. For a cal development for this indication was acquired by Novartis in 2016. It is multitude of reasons, the time has of presbyopic therapy. Three are a prodrug that breaks into lipoic acid not yet come. undergoing US clinical trials, and and choline and converts to an active MAY 2018 | CATARACT & REFRACTIVE SURGERY TODAY 37 s HOT TOPICS IN REFRACTIVE SURGERY “A TOPICAL DROP THAT COULD RESTORE the induced myopia and short dura- tion of action of pilocarpine. ACCOMMODATIVE FUNCTION WOULD BE A FOV TEARS Another topical agent is FOV Tears, WELCOME ADDITION TO OUR ARRAY OF which was developed by Luis Felipe Vejerano, MD. This drug combines pilocarpine and additional active TREATMENT OPTIONS FOR PRESBYOPIC agents, including an anticholinesterase and two alpha-agonists, to modulate PATIENTS.” the accommodation from pilocarpine and achieve near vision enhancement with good distance vision retention. It agent intraocularly. Theoretically, while also maintaining distance acu- is intended to be used binocularly. upon entering the lens, it reduces ity. Presbyopic patients could poten- The drop has received regulatory disulfide bonds, which improves lens tially use a drop like this with their approval in Colombia. Early results flexibility and restores some degree contact lenses in place to maintain suggest that, with regular use, further of accommodation. In a phase 1/2 distance acuity and gain near acu- improvement in near vision may be study, statistically significant near ity. This might be an advantage over obtained.5 Like the Liquid Vision agent, vision improvement began at day 8, multifocal contact lenses, which often this too has the potential advantage of and 82% of patients achieved 20/40 compromise quality of distance acuity immediate effect, providing improved vision or better by day 90, versus to gain near acuity. near acuity and maintaining good dis- 48% of patients receiving placebo.1 A phase 2 trial comparing PRX100 tance acuity. At this time, there are no Long-term studies with larger popu- to placebo has been completed, but active US trials of this agent. lations will be needed to establish no results have been posted or pub- safety and long-term efficacy. lished. According to Gerald Horn, CONCLUSION Chief Scientific Officer of Presbyopia As these topical agents go through LIQUID VISION Therapies, the phase 2 trial demon- the rigorous clinical trial process Liquid Vision (PRX100; Presbyopia strated safety and efficacy, with the and other agents are developed and Therapies) uses an entirely different added goal of assessing the initial become available, their indications and approach: It depends on the miotic dose of its primary active ingredi- use in the presbyopic population can effect of aceclidine alone or aceclidine ent, the miotic aceclidine. A phase only potentially increase. n combined with a low dose of the 2B masked, triple-armed, crossover 2 1. Encore Vision announces successful phase I-II study of topical EV06 for cycloplegic tropicamide. The miotic trial comparing a slightly modified the treatment of presbyopia [press release]. Encore Vision. May 5, 2016. pilocarpine, instilled alone, induces PRX100 formulation in two arms, https://www.prnewswire.com/news-releases/encore-vision-announces- successful-phase-i-ii-study-of-topical-ev06-for-the-treatment-of-presby- extreme degrees of myopia due to its aceclidine alone and aceclidine plus opia-300263690.html. Accessed March 14, 2018. powerful effect on accommodation. low-dose tropicamide (PRX100), and 2. Evaluation of the efficacy and safety of PRX-100 in the treatment of early to moderate presbyopia. clinicaltrials.gov. Last updated October 23, 2017. Aceclidine is an equally or slightly a third arm of placebo, is expected https://clinicaltrials.gov/ct2/show/NCT02554396. Accessed March 14, 2018. more powerful miotic, but it induces to be completed soon.3 3. A single-center, double-masked evaluation of the efficacy and safety of PRX-100 in the treatment of early to moderate presbyopia. clinicaltrials. a much milder degree of accom- gov. Last updated November 1, 2017. https://clinicaltrials.gov/ct2/show/ modation. Aceclidine has historically NCT03201562. Accessed March 14, 2018. ALLERGAN CANDIDATES 4. A safety, efficacy and pharmacokinetic study of AGN-199201 and AGN- been used to treat glaucoma and was, Allergan has completed a phase 2 190584 in patients with presbyopia. clinicaltrials.gov. Last updated November 17, 2017. https://clinicaltrials.gov/ct2/show/NCT02780115. Accessed March in some cases, better tolerated than safety and efficacy study of two drug 14, 2018.5. pilocarpine for that purpose. candidates, AGN-199201 and AGN- 5. Renna A, Vejarano LF, de la Cruz E, Ali JL. Pharmacological treatment of presbyopia by novel binocularly instilled eye drops: a pilot study. Ophthalmol PRX100 is intended to achieve 190584. No results have been posted Ther. 2016;5(1):63-73. improved near vision and retain on clinicaltrials.gov or published.4 distance vision by syncing two One or more of these compounds mechanisms: significant miosis and is believed to use a combination of COLMAN R. KRAFF, MD modest accommodation. A potential pilocarpine and oxymetazoline at n Director of Refractive Surgery, Kraff Eye Institute, advantage of this approach is that it various dosages. Like the Liquid Vision Chicago almost immediately improves near product, induced miosis increases the n [email protected] acuity (within 30 to 60 minutes) and user’s depth of focus. However, this n Financial disclosure: Consultant (Presbyopia allows the patient to use it selectively approach may have limits because of Therapies) 38 CATARACT & REFRACTIVE SURGERY TODAY | MAY 2018.