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Carl D Regillo,1 Lisa M Nijm,2 Diana L Shechtman,3 Peter K Kaiser,4 Paul M Karpecki,5 Edwin H Ryan,6 Michael S Ip,7 Elizabeth Yeu,8 Terry Kim,9 Mohammad R Rafieetary,10 Eric D Donnenfeld11 1Mid Atlantic Retina, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA; 2Warrenville Eye Care and LASIK Center, Warrenville, IL, USA; 3Eye Centers of South Florida, North Miami Beach, FL, USA; 4Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA; 5Kentucky College of Optometry, University of Pikeville, Pikeville, KY, USA; 6Retina Consultants of Minnesota, Edina, MN, USA; 7Doheny Eye Center UCLA, Pasadena, CA, USA; 8Virginia Eye Consultants, Norfolk, VA, USA; 9Duke University, Durham, NC, USA; 10Charles Retina Institute, Germantown, TN, USA; 11Ophthalmic Consultants of Long Island, Garden City, NY, USACorrespondence: Carl D Regillo, Mid Atlantic Retina, Wills Eye Hospital, Thomas Jefferson University, 840 Walnut St # 1020, Philadelphia, PA, 19107, USA, Tel +1 (215) 928-3300, Email cregillo@midatlanticretina.comAbstract: Newly approved treatments for patients with geographic atrophy are changing the treatment paradigm, highlighting the need for eye care providers (ECPs) to have a set of recommendations on how to best manage GA patients. Here, we outline how to identify various stages of age-related macular degeneration including geographic atrophy (GA) by examining optimal management scenarios implicating various ECPs and reviewing treatment considerations for patients with GA. Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among ECPs treating patients with GA.Keywords: age-related macular degeneration, patient care, retina, treatment

Marjan Farid,1 Brandon D Ayres,2 Eric Donnenfeld,3 Ian Benjamin Gaddie,4 Preeya K Gupta,5 Edward Holland,6 Richard Lindstrom,7 Stephen C Pflugfelder,8 Paul M Karpecki,9 Kelly K Nichols,10 Christopher E Starr,11 Elizabeth Yeu12 1Gavin Herbert Eye Institute, UC-Irvine, Irvine, CA, USA; 2Wills Eye Hospital, Philadelphia, PA, USA; 3Ophthalmic Consultants of Long Island, Long Island, NY, USA; 4Gaddie Eye Centers, Louisville, KY, USA; 5Triangle Eye Consultants, Raleigh, NC and Tulane University, New Orleans, LA, USA; 6University of Cincinnati, Cincinnati, OH, USA; 7University of Minnesota, Minneapolis, MN, USA; 8Baylor College of Medicine, Houston, TX, USA; 9Kentucky Eye Institute, Lexington, KY, USA; 10University of Alabama at Birmingham, School of Optometry, Birmingham, AL, USA; 11Weill Cornell Medicine, New York, NY, USA; 12Virginia Eye Consultants, Norfolk, VA, USACorrespondence: Marjan Farid, University of California, 850 Health Sciences Road, Mail Code: 4375, Irvine, CA, 92697, USA, Tel +1 949 824-0327, Email mfarid@uci.eduPurpose: To obtain consensus on Demodex blepharitis (DB) treatment using a modified Delphi panel process.Methods: Literature search identified gaps in knowledge surrounding treatment of DB. Twelve ocular surface disease experts comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). They completed a live roundtable discussion in addition to 3 surveys consisting of scaled, open-ended, true/false, and multiple-choice questions pertaining to the treatment of DB. Consensus for scaled questions using a 1 to 9 Likert scale was predefined as median scores of 7– 9 and 1– 3. For other question types, consensus was achieved when 8 of 12 panelists agreed.Results: The experts agreed that an effective therapeutic agent for treatment of DB would likely decrease the necessity of mechanical intervention, such as lid scrubs or blepharoexfoliation (Median = 8.5; Range 2– 9). When treating DB, panelists believed that collarettes serve as a surrogate for mites, and that eliminating or reducing collarettes should be the main clinical goal of treatment (Median = 8; Range 7– 9). The panelists would treat patients with at least 10 collarettes, regardless of other signs or symptoms and agreed that DB can be cured, but there is always the possibility for a reinfestation (n = 12). There was also consensus that collarettes, and therefore mites, are the primary treatment target and the way by which clinicians can monitor patient response to therapy (Median = 8; Range 7– 9).Conclusion: Expert panelists achieved consensus on key facets of DB treatment. Specifically, there was consensus that collarettes are pathognomonic for DB, that DB patients with > 10 collarettes should be treated even in the absence of symptoms, and that treatment efficacy can be tracked by collarette resolution. By increasing awareness about DB, understanding the goals of and monitoring treatment efficacy, patients will receive better care and, ultimately, better clinical outcomes.Keywords: collarettes, cylindrical dandruff, ocular surface disease, eyelid disease

James A Katz,1 Paul M Karpecki,2 Alexandra Dorca,3 Sima Chiva-Razavi,4 Heather Floyd,4 Elizabeth Barnes,4 Mark Wuttke,4 Eric Donnenfeld5 1The Midwest Center for Sight, Des Plaines, IL, USA; 2Kentucky Eye Institute, Lexington, KY, USA; 3Favoris AG, Basel, Switzerland; 4Novartis Pharma AG, Basel, Switzerland; 5Ophthalmic Consultants of Long Island, Garden City, NY, USACorrespondence: Eric DonnenfeldOphthalmic Consultants of Long Island, 711 Stewart Avenue, Suite 160, Garden City, NY, 11530, USAEmail ericdonnenfeld@gmail.comAbstract: Presbyopia is a common age-related vision disorder characterized by a progressive inability to focus on near objects. If uncorrected or under-corrected, presbyopia can significantly impact patients’ quality of life. Presbyopia represents an area of considerable unmet need due to its rising prevalence worldwide as the population ages, the high proportion of under-treated individuals in some parts of the world, and the limitations of currently available corrective methods. Progressive or bifocal spectacles are associated with peripheral blur, a restricted visual field and impaired depth perception, which have been linked to an increased risk of falls in the elderly. Contact lens options can be difficult to maintain due to the development of age-related dry eye symptoms and reduced manual dexterity. Other corrective methods involve surgical interventions that modify the optics of the cornea, replace the crystalline lens, or attempt to restore active accommodation. While patients undergoing surgery report satisfactory outcomes post-operatively, many of them eventually require reading glasses. Non-invasive therapies with novel mechanisms of action are currently being investigated; these include miotic agents and UNR844, a lipoic acid choline ester. In this narrative review, available evidence on presbyopia prevalence, quality of life impact and risk factors are described, with a focus on observational studies in non-clinical settings. The diagnosis pathway and patient journey in presbyopia are outlined, and various treatment options are analyzed. The data reviewed herein reveals significant gaps in the provision of vision correction for this common condition, with a paucity of effective, non-invasive treatment options broadly accessible to presbyopic individuals.Keywords: presbyopia, epidemiology, patient characterization, vision correction, pharmacological therapies

Jay S Pepose,1,2 Paul J Hartman,3 Harvey B DuBiner,4 Marc A Abrams,5 Robert J Smyth-Medina,6 Sayoko E Moroi,7 Alan R Meyer,8 Mina P Sooch,8 Reda M Jaber,8 Konstantinos Charizanis,8 Seth A Klapman,8 Arin T Amin,8 Jonah E Yousif,8 Eliot S Lazar,9 Paul M Karpecki,10 Charles B Slonim,11 Marguerite B McDonald12 1Pepose Vision Institute, St. Louis, MO, USA; 2Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; 3Department of Ophthalmology, University of Rochester, Rochester, NY, USA; 4Clayton Eye Center, Morrow, GA, USA; 5Case Western Reserve University, Cleveland, OH, USA; 6North Valley Eye Medical Group, Mission Hills, CA, USA; 7The Ohio State University Wexner Medical Center, Columbus, OH, USA; 8Ocuphire Pharma Inc, Farmington Hills, MI, USA; 9elCON Medical, Buffalo, NY, USA; 10Kentucky College of Optometry, University of Pikeville, Pikeville, KY, USA; 11Oculos Development Services, LLC, Tampa, FL, USA; 12Department of Ophthalmology, New York University Langone Medical Center, New York, NY, USACorrespondence: Konstantinos CharizanisOcuphire Pharma, Inc., 37000 Grand River Ave, Farmington, MI 48335, USATel +1 (352) 328 9117Email kcharizanis@ocuphire.comPurpose: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population.Patients and Methods: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia.Results: Use of 1% PMOS did not lead to a statistically significant decrease in diurnal IOP compared to placebo (P = 0.89) but trended toward a greater decrease in patients with lower IOP baselines. PMOS produced a statistically significant mean 20% PD reduction under both photopic and mesopic conditions that was sustained for 36 hours post-dosing. A statistically significant number of patients with PMOS compared to placebo demonstrated ≥ 1 line of improvement in photopic DCNVA at day 8 (P = 0.0018), day 15 (P = 0.0072), and day 16 (P = 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo.Conclusion: Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.Keywords: IOP, presbyopia, night vision disturbances, dim light vision disturbances, pupil diameter, ORION-1

Laura M Periman,1 Francis S Mah,2 Paul M Karpecki3 1Periman Eye Institute, Seattle, WA, USA; 2Scripps Health, La Jolla, CA, USA; 3Kentucky Eye Institute, Lexington, KY, USACorrespondence: Laura M PerimanPeriman Eye Institute, Seattle, WA, USAEmail dryeyemaster@gmail.comAbstract: Dry eye disease (DED) is a multifactorial disease of the ocular surface and tear film that has gained awareness as a public health problem. Characteristics of DED include tear film instability, hyperosmolarity, and ocular surface inflammation, which can occur independently or may be a sequela of numerous ocular diseases, ocular surgery or contact lens wear. Much has been learned about the impact of the disease to help affected individuals who report symptoms of poor vision, pain, and tearing. Recently, new research highlights the importance of the role of ocular surface inflammation and damage in DED—leading to a vicious cycle of inflammation as well as loss of tear film homeostasis. DED immunopathophysiology is characterized by four stages: initiation, amplification, recruitment, and re-initiation. Cyclosporine is proven to be a valuable ophthalmic therapeutic for DED through its immunomodulatory actions and regulation of the adaptive immune response. Cyclosporine mechanism of action is well described in the published literature and the myriad of benefits in all four stages lend a broad-based immunomodulatory function particularly suitable for addressing DED. Furthermore, cyclosporine has unique goblet cell density improvement capabilities as well as anti-apoptotic properties. Topical formulations of cyclosporine are centered around addressing the highly lipophilic nature of the molecule. The poor aqueous solubility of cyclosporine traditionally presented technical challenges in drug delivery to the ocular surface. Newer formulations such as cationic emulsions and nanomicellar aqueous solutions address formulation, tissue concentration, and drug delivery challenges.Keywords: dry eye disease, cyclosporine A, emulsion, OTX-101, keratoconjunctivitis sicca

Darrell E White,1 Yang Zhao,2 Abayomi Ogundele,2 Nicole Fulcher,3 Annabel Acs,3 Laura Moore-Schiltz,3 Paul M Karpecki4 1Department of Ophthalmology, SkyVision Centers, Westlake, OH 44145, USA; 2Health Economics and Outcomes Research, Sun Pharmaceutical Industries, Princeton, NJ 08540, USA; 3Outcomes Research, IBM Watson Health, Cambridge, MA 02142, USA; 4Corneal Services and Advanced OSD Clinic, University of Pikeville Kentucky College of Optometry, Pikeville, KY 41501, USACorrespondence: Yang ZhaoHealth Economics and Outcomes Research, Sun Pharmaceutical Industries, Inc., 2 Independence Way, Princeton, NJ 08540, USATel +1 609 720 8132Email yang.zhao@sunpharma.comPurpose: To assess adherence, non-persistence, discontinuation, and switching of topical cyclosporine ophthalmic emulsion 0.05% (CYC) and lifitegrast ophthalmic solution 5% (LIF) use in the real world among patients with dry eye disease (DED).Design: Retrospective insurance claims study.Methods: Adult patients with DED and ≥1 prescription claim for CYC or LIF (first claim = index date) in the IBM® MarketScan® databases from July 2016 to February 2018 were identified. Eligible patients had continuous medical and pharmacy benefits in the 12 months pre- and post-index periods, and no prior use of the index medication. The proportion of days covered (PDC), adherence, non-persistence, discontinuation, and switching were examined over the 12-month post-index period.Results: This study included 6537 CYC and 3235 LIF patients. The adherence rate was 5.9% for CYC and 9.7% for LIF; the median PDC was 0.3 for both cohorts. Overall, 70.8% of CYC and 64.4% of LIF patients discontinued treatment with median days to discontinuation of 89 and 29, respectively. Non-persistence was 7.1% for CYC and 6.8% for LIF (median days to discontinuation: 89 and 105). In addition, 5.0% switched from CYC to LIF, and 9.6% switched from LIF to CYC over the post-index period.Conclusion: Over 60% of DED patients discontinued treatment within 12 months of initiation; the median time to discontinuation was 3 months for CYC and 1 month for LIF. Although this analysis did not capture the reasons why patients discontinued treatment, the results demonstrate there likely exists a significant unmet need amongst DED patients.Keywords: dry eye disease, adherence, persistence, cyclosporine ophthalmic emulsion, lifitegrast ophthalmic solution

Paul M Karpecki,1,2 Sidney L Weiss,3 William G Kramer,4 Patrick O’Connor,5 David Evans,6 Josh Johnston,7 April L Jasper,8 Angela Justice,9 Abayomi B Ogundele,9 Doug Devries10 1Kentucky Eye Institute, Lexington, KY, USA; 2Gaddie Eye Centers, Louisville, KY, USA; 3i-novion, Inc., Randolph, NJ, USA; 4Kramer Consulting, LLC, North Potomac, MD, USA; 5Auven Therapeutics, Delray Beach, FL, USA; 6Total Eye Care, Memphis, TN, USA; 7Georgia Eye Partners, Atlanta, GA, USA; 8Advanced Eyecare Specialists, West Palm Beach, FL, USA; 9Sun Ophthalmics, Sun Pharmaceutical Industries, Ltd., Princeton, NJ, USA; 10Eye Care Associates of Nevada, Sparks, NV, USA Purpose: To evaluate the ocular safety of OTX-101 0.09% – a novel, nanomicellar, clear, aqueous solution of cyclosporine (CsA) – and to determine the systemic exposure to CsA following ophthalmic administration. Patients and methods: Healthy volunteers ≥18 years of age were recruited for participation in this phase 1, open-label, single-center, single-arm, study. Subjects received one drop of OTX-101 0.09% in each eye every 12 hours for 7 days, and once on day 8. Blood samples were collected predose, and 0.25, 0.5, 1, 2, 4, 8, and 12 hours post-first dose on day 1 and day 8. CsA levels in whole blood samples were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (maximal whole blood concentration [Cmax, ng/mL], time to Cmax [Tmax, hours]), and area under the concentration-time curve from 0 to the last measurement [AUC(0–t), h·ng/mL]) were calculated using noncompartmental analysis. Safety assessments included subject-reported adverse events (AEs), vital signs, visual acuity, intraocular pressure measurement, biomicroscopy, and direct ophthalmoscopy. Results: A total of 16 subjects were enrolled; 15 subjects completed the study. Blood sample analysis indicated limited systemic exposure to CsA; three subjects had a CsA concentration greater than or equal to the lower limit of quantitation (LLOQ) on day 1; only four subjects had three consecutive CsA concentration measurements ≥LLOQ on day 8; the mean±SD for Cmax was 0.17±0.02 ng/mL, Tmax was 1.5±0.58 hours, and AUC(0–t) was 0.53±0.06 h·ng/mL. Three subjects reported three AEs (eye pain, eye pruritis, and eye irritation) during the study. No clinically significant changes in the safety assessments were noted. Conclusion: The OTX-101 formulation was well tolerated. Systemic exposure to CsA was negligible in healthy volunteers after twice-daily ocular administration. No evidence for systemic accumulation of CsA was observed. Keywords: dry eye disease, cyclosporine, pharmacokinetic, systemic exposure

George Ousler III,1 Douglas K Devries,2 Paul M Karpecki,3 Joseph B Ciolino41Ora, Inc, Andover, MA, USA; 2Eye Care Associates of Nevada, Sparks, NV, USA; 3Koffler Vision Group, Lexington, KY, USA; 4Massachusetts Eye and Ear, Boston, MA, USAAbstract: A single-center, open-label study consisting of two visits over the course of approximately 2 weeks was conducted to evaluate the efficacy of Retaine™ ophthalmic emulsion in improving the signs and symptoms of dry eye. Forty-two subjects were enrolled and received 1–2 drops twice daily of Retaine™ beginning at the first visit (day 1) and ending at the second visit. Subjects were instructed to complete a symptomatology diary twice daily prior to drop instillation through the morning of the second visit. Ocular sign and symptom assessments, visual acuity procedures, and comfort assessments were conducted during both visits. A statistically significant reduction was observed in mean breakup area on the second visit between the predose time and the postdose time (P=0.026). On the second visit, subjects had significantly less corneal fluorescein staining in the superior (P=0.002), central (P=0.017), corneal sum (P=0.011), and all ocular regions combined (P=0.038) than on the first visit. On the second visit, statistically significant reductions in dryness (P