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- neal refractive surgeons for s 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 - - - Ophthalmol n

Like the Liquid Vision agent,Vision Liquid the Like 5 As these topical agents go through go agents topical these As Another topical agent is FOV Tears,FOV is agent topical Another regulatoryreceived has drop The . 2016;5(1):63-73. Director of Refractive Surgery, Kraff Eye Institute, Director of Refractive Surgery, Kraff Eye Institute, [email protected] Financial disclosure: Consultant (Presbyopia Chicago Therapies)   presbyopia by novel binocularly instilled eye drops: a pilot study. Ther COLMAN R. KRAFF, MD n n n obtained. ofadvantage potential the has too this improvedproviding effect, immediate dis good maintaining and acuity near noare there time, this At acuity. tance agent.this of trials US active CONCLUSION processtrial clinical rigorous the anddeveloped are agents other and andindications their available, become canpopulation presbyopic the in use increase. potentially only 1. Encore Vision announces successful phase I-II study of topical EV06 for the treatment of presbyopia [press release]. Encore Vision. May 5, 2016. https://www.prnewswire.com/news-releases/encore-vision-announces- successful-phase-i-ii-study-of-topical-ev06-for-the-treatment-of-presby opia-300263690.html. Accessed March 14, 2018. 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. https://clinicaltrials.gov/ct2/show/NCT02554396. Accessed March 14, 2018. 3. A single-center, double-masked evaluation of the efficacy and safety of PRX-100 in the treatment of early to moderate presbyopia. clinicaltrials. gov. Last updated November 1, 2017. https://clinicaltrials.gov/ct2/show/ NCT03201562. Accessed March 14, 2018. 4. A safety, efficacy and pharmacokinetic study of AGN-199201 and AGN- 190584 in patients with presbyopia. clinicaltrials.gov. Last updated November 17, 2017. https://clinicaltrials.gov/ct2/show/NCT02780115. Accessed March 14, 2018.5. 5. Renna A, Vejarano LF, de la Cruz E, Ali JL. Pharmacological treatment of the induced myopia and short dura short and myopia induced the pilocarpine. of action of tion FOV TEARS FelipeLuis by developed was which combinesdrug This MD. Vejerano, active additional and pilocarpine anticholinesterasean including agents, modulateto alpha-agonists, two and pilocarpinefrom accommodation the enhancementvision near achieve and Itretention. vision distance good with binocularly.used be to intended is results Early Colombia. in approval furtheruse, regular with that, suggest bemay vision near in improvement - - - - -

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3 Allergan has completed a phase 2 phase a completed has Allergan compounds these of more or One A phase 2 trial comparing PRX100 PRX100 comparing trial 2 phase A user’s depth of focus. However, this However, focus. of depth user’s of because limits have may approach to be completed soon. completed be to ALLERGAN CANDIDATES drug two of study efficacy and safety AGN- and AGN-199201 candidates, posted been have results No 190584. published. or clinicaltrials.gov on of combination a use to believed is at oxymetazoline and pilocarpine Vision Liquid the Like dosages. various the increases miosis induced product, lished. According to Gerald Horn, Horn, Gerald to According lished. Presbyopia of Officer Scientific Chief demon trial 2 phase the Therapies, the with efficacy, and safety strated initial the assessing of goal added ingredi active primary its of dose phase A aceclidine. miotic the ent, crossover triple-armed, masked, 2B modified slightly a comparing trial arms, two in formulation PRX100 plus aceclidine and alone aceclidine and (PRX100), tropicamide low-dose expected is placebo, of arm third a while also maintaining distance acu distance maintaining also while poten could patients Presbyopic ity. their with this like drop a use tially maintain to place in lenses contact acu near gain and acuity distance over advantage an be might This ity. often which lenses, contact multifocal acuity distance of quality compromise acuity. near gain to but completed, been has placebo to pub or posted been have results no 2018 -

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The miotic The 2 PRX100 is intended to achieve to intended is PRX100 Liquid Vision (PRX100; Presbyopia (PRX100; Vision Liquid mechanisms: significant miosis and miosis significant mechanisms: potential A accommodation. modest it that is approach this of advantage near improves immediately almost and minutes) 60 to 30 (within acuity selectively it use to patient the allows been used to treat glaucoma and was, and glaucoma treat to used been than tolerated better cases, some in purpose. that for pilocarpine retain and vision near improved two syncing by vision distance pilocarpine, instilled alone, induces induces alone, instilled pilocarpine, its to due myopia of degrees extreme accommodation. on effect powerful slightly or equally an is Aceclidine induces it but miotic, powerful more accom of degree milder much a historically has Aceclidine modation. Therapies) uses an entirely different entirely an uses Therapies) miotic the on depends It approach: aceclidine or alone aceclidine of effect the of dose low a with combined tropicamide. cycloplegic 48% of patients receiving placebo. receiving patients of 48% popu larger with studies Long-term establish to needed be will lations efficacy. long-term and safety LIQUID VISION disulfide bonds, which improves lens improves which bonds, disulfide degree some restores and flexibility 1/2 phase a In accommodation. of near significant statistically study, 8, day at began improvement vision 20/40 achieved patients of 82% and versus 90, day by better or vision PATIENTS.” PATIENTS.” Theoretically, intraocularly. agent reduces it lens, the entering upon ACCOMMODATIVE FUNCTION WOULD BE A BE A FUNCTION WOULD ACCOMMODATIVE OF TO OUR ARRAY WELCOME ADDITION OPTIONS FOR PRESBYOPIC TREATMENT “A TOPICAL DROP THAT COULD RESTORE RESTORE THAT COULD DROP “A TOPICAL CATARACT & REFRACTIVE SURGERY TODAY

38 HOT TOPICS HOT IN REFRACTIVE SURGERY s