5/25/2018. Advances in Ocular Drug Delivery. Compliance: Areas of Concern. Current Drug Delivery

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1 Advances in Ocular Drug Delivery COPE#54896-PH Walter O. Whitley, OD, MBA, FAAO Director of Optometric Services Virginia Eye Consultants Residency Program Supervisor PCO at Salus University Virginia Eye Consultants Tertiary Referral Eye Care Since 1963 John D. Sheppard, MD, MMSc Stephen V. Scoper, MD David Salib, MD Elizabeth Yeu, MD Thomas J. Joly, MD, PhD Dayna M. Lago, MD Constance Okeke, MD, MSCE Jay Starling, MD Samantha Dewundara, MD Rohit Adyanthaya, MD Albert Cheung, MD Walter O. Whitley, OD, MBA, FAAO Cecelia Koetting, OD, FAAO Christopher Kruthoff, OD, FAAO Jessica Schiffbauer, OD Mark Enochs, OD Kelsey Butler, OD Disclosures - Walter O. Whitley, OD, MBA, FAAO has received consulting fees, honorarium or research funding from: Compliance: Areas of Concern Alcon Allergan Bausch and Lomb Biotissue Beaver-Visitec Carl Zeiss Meditec Glaukos J&J Vision Ocusoft Science Based Health Shire Sun Pharmaceuticals TearLab Corporation Tearscience Advanced Ocular Care..Collaborative Eye Co-Chief Medical Editor Review of Optometry Contributing Editor Optometry Times Editorial Advisory Board Current Drug Delivery

2 Compliance 5/25/2018 Patient Compliance and Dosing Dosing (Times/day) Literature review of 76 studies show Compliance increases with decreased dosage regimen and complexity 1 79% compliance with QD regimen vs 51% for QID regimens (p=0.001) 1 Simpler, less-frequent dosing results in better compliance in a variety of therapeutic classes 1 Barriers to Compliance 1. Claxton et al. Clinical Therapeutics. 2001; 23: Topical Drug Delivery Considerations Strategies to Improve Topical Ocular Drug Delivery 1. Ghate D, Edelhauser HF. Ocular drug delivery. Expert Opin Drug Deliv. 2006;3(2): Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3): Coffey MJ, Decory HH, Lane SS. Development of a non-settling gel of 0.5% loteprednol etabonate for anti-inflammatory use as an ophthalmic drop. Manuscript in preparation. 4. McGhee CN. An overview of topical ophthalmic drugs and the therapeutics of ocular infection. Accessed October 25, Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002;28(5): Ghate D, Edelhauser HF. Expert Opin Drug Deliv. 2006;3(2): Shirasaki Y. J Pharm Sci. 2008;97(7): Kaur IP, Kanwar M. Drug Dev Ind Pharm. 2002;28(5): Barar J, et al. Expert Opin Drug Deliv. 2008;5(5): Key Approaches to Improve Ocular Bioavailability Prodrug strategies Excipients Cyclodextrins Penetration enhancers Dosage forms Polymeric gels Bioadhesive hydrogels Temperature induced gelation ph induced gelation Osmotically induced gelation Combination of polymers Microneedling Colloidal systems Liposomes Niosomes Cubosomes Microemulsions Nanoemulsions Nanoparticles 0.05% Emulsion Formulations Cyclosporine (Restasis) & Difluprednate (Durezol) Only 4 manufacturers with technology Excellent drop-to-drop dose uniformity compared to suspensions 1 More bioavailable than a suspension formulation of same drug 2 Oil phase Surfactant (Polysorbate 80) 100 nm Difluprednate (dissolved in oil) Water phase Achouri D., Alhanout, K., Piccerelle, P. Recent advances in ocular drug delivery. Drug Development and Industrial Pharmacy, Stringer W, Bryant R. Dose uniformity of topical corticosteroid preparations: difluprednate ophthalmic emulsion 0.05% vs. branded and generic prednisolone acetate ophthalmic suspension 1%. Clin Ophthalmol Oct 5;4: Inoue, J., et al. Preclinical pharmacokinetics of difluprednate ophthalmic emulsion. Invest Ophthalmol Vis Sci. 2007;48:ARVO E-Abstract

3 % Label Claim Mean Peak Aqueous Humor Concentration (ng/ml) 5/25/ Dose Uniformity: Difluprednate Emulsion Mucoadhesive Technology Upright, Shaken (Durezol) Upright, Not Shaken (Durezol) Inverted, Not Shaken (Durezol) Time (Days) Stringer W, Bryant R. Dose uniformity of topical corticosteroid preparations: difluprednate ophthalmic emulsion 0.05% vs. branded and generic prednisolone acetate ophthalmic suspension 1%. Clin Ophthalmol Oct 5;4: DuraSite Vehicle Multiple-Dose Rabbit: Azithromycin Conjunctiva Concentrations 1 Insite Pharmaceuticals Alameda, CA Mucoadhesive Sustained Pharmacokinetics 2,3 1. Data on file. Inspire Pharmaceuticals Inc, Study report I 04U Data on file. Inspire Pharmaceuticals Inc, NDA Study Report Data on file. Inspire Pharmaceuticals Inc, NDA Study Report Use of DuraSite Results in Increased Aqueous Humor Concentrations P= Δ2.1X BromSite Bromfenac Ophthalmic (N=29) Solution 0.09% (Bromday ) (N=29) Mucoadhesive Adaptive Viscosity: Polycarbophil Gel Matrix US National Institutes of Health. Aqueous humor concentration of InSite Vision (ISV) 303 (bromfenac in DuraSite) to Bromday once daily (QD) prior to cataract surgery. Gel at Rest; Viscous Liquid in the Eye 3

4 CMHA-S Crosslinked Hyaluronic Acid HA occurs naturally in the human body with qualities ideal for the ocular surface Promotion of wound healing and lubrication Native HA has a relatively short half-life Crosslinking HA creates a 3D structure that stabilized the molecule Adheres longer to the ocular surface (up to 90 min) Higher viscosity that thins with blinking and is non blurring Matrix protects the ocular surface CMHA-s: Animal studies Commercially available as a veterinary device; Manufactured by SentrX Animal Care Sold in the U.S. by Bayer Animal Health as Remend Corneal Repair 1 Sold world wide with 5 years experience in thousands of dogs, cats and horses, with an excellent safety profile Efficacy has been demonstrated in masked, randomized clinical studies of corneal defects in dogs and cats M O L L Y A 1 2 Y E A R O L D C AT W I T H A N O N - H E A L I N G C O R N E A L D E F E C T A T 4 2 D A Y S (A) H E A L I N G U L C E R A F T E R 12 D A Y S W I T H % C M H A - S G E L D R O P S 1. EyeGate (NASDAQ: EYEG) has human ophthalmic rights only. Visit C M H A - s : O c u l a r b a n d a g e G e l Iontophoresis Platform: A Non-Invasive Method of Propelling Charged Active Compounds Into Ocular Tissues A clear hydrogel (or liquid-gel) eye drop with a 0.75% concentration of CMHA-S Crosslinked to provide reduced degradation on the eye Exhibits significant shear thinning properties Enables better residence time with no optical blur Forms a thin layer over the ocular surface, protecting the eye May accelerate re-epithelialization of corneal epithelial defects PRK, superficial keratectomy, PKP Corneal abrasions and ulcers Neurotrophic keratitis Severe SPK Conclusions EGP-437 is safe and effective in reducing inflammation and preventing pain as early as Day 1 with 2 different iontophoretic doses. Best responses observed with 4.5 ma-min and 14.0 ma-min doses Percentage of patients with ACC count of zero greater than Durezol historical data at Day 7 and Day 28 Percentage of patients with zero pain better than Durezol historical data at Day 4, 7, and 14 Phase 2b trial initiation targeted for 1H 2017 EGP-437 effectively controls post operative pain and inflammation without the need for drop therapy VersiDoser / VRx2 Disposable/reloadable multi-dose ophthalmic delivery systems VersiDoser Liquid VRx2 Powers Packaged in unit dose blisters 4

5 Issues with Cataract Post Op Drops Cataract Considerations TriMoxi or DexMoxi Intravitreal Injection An injection of an antibiotic & steroid combination in the eye at the time of surgery. Preparation: 1. triamcinolone or dexamethasone 2. moxifloxacin One intravitreal injection Pars plana injection into the vitreous cavity. Medicine is injected after the IOL placement. Patients are still under anesthesia so it is mostly painless What Will the Doctor See??? View of the injected medication 2 hours after injection Benefits Compliance Convenience Cost 5

6 Rates of Endophthalmitis 5/25/ % 0.20% 0.15% 0.10% 0.05% Safety? 0.00% A-no antibiotic 0.23% B-intracameral cefuroxime 0.05% C-topical levofloxacin 0.17% D-intracameral & topical 0.03% Braga-Mele, R., Chang, D., Henderson, B., Mamalis, N., Talley-Rostov, A., & Vasavada, A. (2014, December). Intracameral antibiotics: Safety, efficacy, and preparation. Journal of Cataract & Refractive Surgery, 40, fold decrease in endophthalmitis with intracameral cefuroxime Kaiser Study Topical Only Some injections Topical and Injection Endophthalmitis cases per 1000 Percent of patients receiving injections of post-op meds 22 (2100%) fold decrease in endophthalmitis from Shorstein, N., Winthrop, K., & Herrinton, L. (2013, January). Decreased postoperative endophthalmitis rate after institution of intracameral antibiotics in a Northern California eye department. Journal of Cataract & Refractive Surgery, 39, Concerns with Injections 1. Cystoid Macular Edema 1. This study measured macular thickness in both arms at both 1 week and 1 month post-op 2. No statistically significant difference in macular thickness Concerns with Injections Cystoid Macular Edema Steroid response/ IOP spikes Compared at Baseline, 1 day PO, 1 week PO, and 1 month PO No statistically significant difference in IOP, no significant drift over time. Fisher, B. L., & Potvin, R. (2016). Transzonular Vitreous Injection vs. a Single Drop Compounded Topical Pharmaceutical Regimen After Cataract Surgery. Clinical Ophthalmology, 10, Fisher, B. L., & Potvin, R. (2016). Transzonular Vitreous Injection vs. a Single Drop Compounded Topical Pharmaceutical Regimen After Cataract Surgery. Clinical Ophthalmology, 10, Concerns with Injections 1. Cystoid Macular Edema 2. Steroid response/ IOP spikes 3. HORV Concerns with Injections 1. Overall experience Patient Experience Drops vs. TM 100% 80% 60% 92% 88% 40% 20% 0% TM vs. Drops Overall Experience Vision Post-Op. Fisher, B. L., & Potvin, R. (2016). Transzonular Vitreous Injection vs. a Single Drop Compounded Topical Pharmaceutical Regimen After Cataract Surgery. Clinical Ophthalmology, 10, Fisher, B. L., & Potvin, R. (2016). Transzonular Vitreous Injection vs. a Single Drop Compounded Topical Pharmaceutical Regimen After Cataract Surgery. Clinical Ophthalmology, 10,

7 Dextenza Dexamethasone 0.4mg Insert Currently under FDA Review for post-surgical ocular inflammation and pain Intracanalicular Plug Drug released over 30 days DEXTENZA successfully met the trial s two primary efficacy endpoints, absence of ocular pain on day 8 and absence of ocular inflammation on day 14 when compared to placebo Other future considerations?? INVELTYS TM (KPI-121 1%) Kala Pharmaceuticals A topical twice-a-day product candidate for the treatment of inflammation and pain in patients who have undergone ocular surgery. Utilizes Mucus Penetrating Particles (MMP) which binds to mucin in the eye and slowly release loteprednol etabonate KPI-121 Cataract Prevention Drug? Gemini Refractive Capsule Omega Ophthalmics Drug delivery Biometric sensors Lens technology 7

8 TRUETEAR : PRODUCT INNOVATION First-ever neurostimulation device in eye care An easy-to-use and drug-free option to temporarily increase tear production during neurostimulation in adult patients Provides small electrical pulses to stimulate production of your own natural tears First smart device in eye care with Bluetooth enabled and connected application LFU REGULATES TEAR PRODUCTION 1-4 BY COMMUNICATING WITH CENTRAL NERVOUS SYSTEM (CNS) Lacrimal Functional Unit (LFU) maintains a healthy environment for the eye by regulating tear production In response to any external and internal stimuli, LFU communicates with Central Nervous System (CNS) Sensory signals are carried via afferent neurons from LFU to CNS Parasympathetic and sympathetic signals are carried via efferent neurons from CNS to LFU This afferent and efferent signaling and communication occurs via the trigeminal nerve Neurostimulation in the nasal cavity targets the trigeminal nerve to trigger the nasolacrimal reflex to emulate the normal neural signals to create a natural tear 1. Kossler et al. Ophthal Plast Reconstr Surg. 2015; 2. Beuerman et al. In: Pflugfelder et al, eds. Dry Eye and Ocular Surface Disorders. 2004; 3. Dartt. Ocul Surf Freidman et al. A nonrandomized, open-label study to evaluatethe effects of nasal stimulation on tear production in subjects with dry eye disease CLINICAL DATA In Study 1, patients saw an approximate 2.5x greater increase in tear production with intranasal stimulation on study day compared to sham or external stimulation 1 Results of a randomized, controlled, double-masked, cross-over clinical trial conducted at two sites in patients with Aqueous Deficient Dry Eye ( 22 yo; baseline OSDI score 13 with no more than three responses of N/A; At least one eye: baseline Jones Schirmer test with anesthetic of 10 mm/5 min and cotton swab nasal stimulation Jones Schirmer test 7 mm higher in the same eye). Participants underwent 3 applications in random order: active intranasal, active extranasal (control), and sham device intranasal (control). Primary endpoint was the difference between the Schirmer test score during active stimulation and the 2 control applications in the study eye. The direct clinical benefit of temporarily increasing tear production as a therapy for Dry Eye Disease patients was not assessed as part of the clinical trial. 1 CLINICAL DATA (CONTINUED) In Study 2, clinically and statistically significant increase in tear production was seen at 180 days 1 Results of a 6-month single-arm, open-label clinical trial conducted at three sites in patients with Aqueous Deficient Dry Eye ( 22 yo; baseline OSDI score 23 with no more than three responses of N/A; At least one eye: baseline Jones Schirmer test with anesthetic of 10 mm/5 min and cotton swab nasal stimulation Jones Schirmer test 7 mm higher in the same eye; corneal fluorescein staining score of 2 in at least one corneal region and sum of 4 for all corneal regions in the same eye; no contact lens wear for 7 days prior to screening and during the study). Participants used the TrueTear device at least 2 times/day, and no more than 3 minutes/use. The primary endpoint was tear production increase in the study eye during the TrueTear device use compared to unstimulated tear production as assessed by the Schirmer test at day 180. The analysis used a one-sided paired t- test. The direct clinical benefit of temporarily increasing tear production as a therapy for Dry Eye Disease patients was not assessed as part of the clinical trial Data on file, Allergan; OCUN Data on file, Allergan; OCUN-010 OTX-101 Sun Pharmaceuticals A nanomicellar formulation of cyclosporine 0.09% In this 12 week, multicenter, randomized, double-masked, vehicle controlled Phase 3 confirmatory study, 744 dry eye patients were treated either with OTX-101 or its vehicle. Met primary endpoint of Schrimer s Score (p<0.0001) The demonstration of efficacy at 12 weeks is earlier than other drugs approved for dry eye in the same class. NovaTears / EvoTears Innovative mode of action due to the patented EyeSol -Technology Made in Germany Forms a protective layer over the tear film Long-lasting effect for greater patient satisfaction clinically proven¹ Extremely well tolerated as free from preservatives, phosphates and emulsifiers 8

9 Neuropathic Dry Eye Pain Role of cannabis EyeSol, Novaliq a novel semifluorinated alkane drug delivery technology Low surface tension No water Metabolically inert Refractive index similar to H20 What About Glaucoma??? Steven, P. Realm of dry eye therapy expanding. Ophthalmology Times. November 15, 2017 How Adherent are Glaucoma Patients with QD Medication? Nordstrom, Friedman, et al. Ophthalmology 2005 Glaucoma Considerations Ocular Science Glaucoma Drops When COMPLIANCE with drops is low When MEDICAL THERAPY FAILS When the PROGRESSION continues to WORSEN Treatment options More medications Laser therapy Surgical intervention $25.00/ 1 month supply $30.00/ 1 month Supply $35.00/ 1 month supply 180 day shelf life 0.02% BAK preservative Ships directly to patient 9

10 Glaucoma Drops On the Horizon New Drug Company Type Latanoprostene bunod*** Bausch + Lomb Nitric oxide donating prostaglandin F2-a-analogue Rhopressa*** Arie Inhibits Rho kinase and norepinephrine transporter Roclatan Arie Rhopressa + latanoprost Trabodenoson Inotek Highly selective adenosine mimetric acting only at A1 receptor subtype OTX-TP Ocular therapeutix Sustained release travoprost punctal plug Bimatoprost Sustained Release Allergan Intracameral sustained release bimatoprost What Do You Get When You Add? + Great Candidate for MIGS/PHACO Concomitant Cataract & Glaucoma Patients - US Significant Treatment Opportunity One in five Cataracts Eyes on OHT 20.5% Medication Cataract + 3.5M US Cataract Procedures Minimum of 1 OHT Med 718K Centers for Medicare and Medicaid Services Medicare Standard Analytical File. Baltimore, MD Cataract Pts. Cataract Pts w/ Glaucoma 79.5% Cataract Only 57 Pathway for Trabecular Bypass Devices Shunting the canal Express MiniShunt (Alcon) Stenting the canal istent (Glaukos Corp) Reduce aqueous production Endocyclophotocoagulation Dilating the canal Visco 360 / Ab-Interno Canaloplasty (ABIC) Divert aqueous into the suprachoroidal space Cypass Microshunt (Alcon) Divert aqueous into the subconjunctival space Xen Gen Stent (Allergan) MIGS ADVANTAGES Safer Gentler Reduction of IOP Faster recovery Combined with cataract sx Good for contact lens wearers Avoids serious complications Less OR time Less glaucoma meds Decreased IOP fluctuations Spares the conjunctiva Fewer follow-up appointments No Bleb Are Patients Interested in MIGS? 28pts 79% did not mind instilling drops 64% did not mind wearing glasses 86% were interested in reducing their need for topical medications 10

11 Istent Video Courtesy of Constance Okeke, MD, MSCE Percent of Patients With IOP 21 mm Hg Without Medication Use Cataract Surgery istent istent + Phaco Ferguson, Berdahl, Schweitzer et. Al istent + Phaco Ferguson, Berdahl, Schweitzer et. Al. Retrospective Case Series IOP reduction higher with higher baseline IOP Ferguson TJ, Berdahl JP, Schweitzer JA, Sudhagoni RG. Clinical evaluation of trabecular microbypass stents with phacoemulsification in patients with open-angle glaucoma and cataract. Clinical Ophthalmology 2016: Ferguson TJ, Berdahl JP, Schweitzer JA, Sudhagoni RG. Clinical evaluation of trabecular microbypass stents with phacoemulsification in patients with open-angle glaucoma and cataract. Clinical Ophthalmology 2016: The XEN Gel Stent The XEN Procedure A glaucoma implant designed to reduce intraocular pressure in eyes suffering from refractory glaucoma 1 6-mm length, 45-micron inner diameter about the length of an eyelash 1,2 Composed of gelatin, cross-linked with glutaraldehyde 1 1. XEN Directions for Use; 2. Vogt et al. In: Blume-Peytavi et al, eds. Hair Growth and Disorders In the clinical investigation, standard ophthalmic surgery techniques, 1. viscoelastic, XEN Directions for and Use. mitomycin C (0.2 mg/ml) were used before injection. 1 11

12 Established Effectiveness at 12 Months Cypass Microstent 76.3% (95% CI = 65.8%, 86.8%); using observed data and failures for subjects with glaucomarelated secondary surgical intervention and multiple imputations for missing data (N = 65) XEN Directions for Use ± 1.1 (95% CI = -8.7, -4.2); using observed data and worst within-eye IOP for subjects with glaucomarelated secondary surgical intervention and multiple imputations for missing data (N = 65). 1 Ab-interno insertion into the supraciliary space Fenestrated microstent made of biocompatible polyimide material Magnetic resonance safe CyPass Micro-Stent: Enhanced Aqueous Outflow The supraciliary space has a negative pressure gradient that drives aqueous outflow and reduction of intraocular pressure 1 The uveoscleral pathway bypasses Schlemm s canal and collector channels, which may be atrophic in glaucoma patients 2 The CyPass Micro-Stent utilizes the same outflow pathway as first line prostaglandin analogues 3 Clinical Data Delivers superior, longterm IOP-lowering efficacy Two-year COMPASS Trial is the largest MIGS randomized controlled trial completed to date Landmark FDA study with two-year follow-up on >500 patients with baseline/terminal washout 72.5% of eyes achieved a 20% reduction in unmedicated diurnal IOP at 2 years* 61.2% of eyes maintained an unmedicated diurnal IOP range between 6 and 18 mmhg at 24 months (a 41% increase)* 1. Saheb H, Ianchulev T, Ahmed I. Optical coherence tomography of the suprachoroid after CyPass Micro-Stent implantation for the treatment of open-angle glaucoma. Br J Ophthalmol. 2012;98: Fellman. Episcleral venous fluid wave correlates with the type and extent of canal-based surgery. AGS 2014 abstract. 3. Weinreb RN, Toris CB, Gabelt BT, et al. Effects of prostaglandins on the aqueous humor outflow pathways. Surv Ophthalmol. 2002;47(Suppl 1):S53 S64. *Prospective, randomized, multicenter clinical trial in patients (n=505) with open-angle glaucoma undergoing cataract surgery randomized to microstent (n=374) or phacoemulsification (n=131). Primary outcome measure was unmedicated diurnal IOP reduction at 24 months versus cataract surgery alone at baseline. Secondary outcomes measures included mean change in 24 month DIOP from baseline and 24 month unmedicated mean IOP (between 6 mmhg to 18 mmhg) versus cataract surgery alone. Medication use at 24 months was also analyzed. The primary and secondary effectiveness analyses were performed using intent to treat (ITT) population. And There s More Ocular Therapeutix Canaloplasty Glaukos Istent Supra Glaukos Istent Inject Allergan Bimatoprost SR Ocular Therapeutix SR Travaprost Solx Gold Shunt Sustained-release travoprost in an intracanalicular depot composed of polyethylene glycol hydrogel and drug-containing microparticles Drug elutes over 90 day period In Phase 3 Clinical Trials Kahook Dual Blade Ocular Therapeutix. Sustained release travoprost. 12

13 IOP mm Hg IOP Reduction 5/25/2018 Travoprost Punctum Plug (OTX-TP, Ocular Therapeutix) Bimatoprost Sustained Release Implant mm Hg mm Hg OTX-TP timolol No hyperemia in OTX-TP Retention Rates 91, 88, days 60, 75, 90 Phase 2 trial comparable to topical bimatoprost qd dosing (for 4-6 months) Inserted into the anterior chamber Biodegradable Allergan is currently performing phase 3 clinical trials Ocular Therapeutix, Inc. Ocular Therapeutix TM reports on topline results of phase 2b glaucoma clinical trial. Press Release. 22 October investors.ocutx.com/phoenix.zhtml?c=253650&p=irol-newsarti- cle&id= [Accessed 6 September 2016] 24 Month Phase I/II Clinical Trial 24 Month Phase I/II Clinical Trial Bimatoprost pellet (6, 10, 15, or 20 micrograms) Bimatoprost pellet (6, 10, 15, or 20 micrograms) Topical bimatoprost 0.03% 75 Patients Topical bimatoprost 0.03% 4 months IOP reduction 7.2, 7.4, 8.1, 9.5 mm Hg 92% of patients 4 months IOP reduction of 8.4 mm Hg Sustained at 6 mos. in 71% % Conjunctival Hyperemia Safety Bimatoprost Ring n = 49 eyes Side Effects 52% Implant group 30.7% Topical group 5 0 Baseline 1 mo 6 mo Month Goldberg I, Laganovska G, Baumane K, et al. The novel topical ocular insert (Helios) for sustained delivery of bimatoprost in glaucoma and ocular hypertension. Poster presented at: American Academy of Ophthalmology Annual Meeting; October 20, 2014; Chicago, IL. 13

14 Bimatoprost Ring Bimatoprost Ring Retention Rate 89% Ophthalmology , DOI: ( /j.ophtha ) Ophthalmology , DOI: ( /j.ophtha ) Brandt J, Sall K, DuBiner H, et al. Six-month intraocular pressure reduction with a topical bimatoprost ocular insert. Ophthalmology. 2016;123(8): Copyright 2016 American Academy of Ophthalmology Terms and Conditions Brandt J, Sall K, DuBiner H, et al. Six-month intraocular pressure reduction with a topical bimatoprost ocular insert. Ophthalmology. 2016;123(8): Copyright 2016 American Academy of Ophthalmology Terms and Conditions Latanoprost-Eluting Contact Lens Attractive option secondary to large residence time in the eye. Latanoprost-Eluting Contact Lens Patient Compliance Comfort of Lens Vision with Lens Dry Eye/Ocular Surface Disease Replacement Schedule Preclinical Trial and Results Preclinical Trial and Results CLHI (149g latanoprost) CLLO (97g latanoprost) VS Topical latanoprost ~ 1 week Ciolino JB, Ross AE, Tulsan R, et al. Latanoprost-eluting contact lenses in glaucomatous monkeys. Ophthalmology 2016; 123: Ciolino JB, Ross AE, Tulsan R, et al. Latanoprost-eluting contact lenses in glaucomatous monkeys. Ophthalmology 2016; 123:

15 CL Drug Delivery - Advantages Over 50% of the drugs released from a CL can diffuse into the cornea, which is at least 35 times more efficient than eye drops Ability to deliver drugs over extended time periods CL Drug Delivery - Barriers Still no commercial products available since 1960s Silicon hydrogel CL addressed hypoxia-related complications Rapid release kinetics May differ based on CL material / drug combos Rate of drug release is not constant over time.li CC, Chauhan A (2006) Modeling ophthalmic drug delivery by soaked contact lenses. Ind Eng Chem Res 45: Li CC, Chauhan A (2006) Modeling ophthalmic drug delivery by soaked contact lenses. Ind Eng Chem Res 45: CL Drug Delivery What does the future hold? Molecular imprinting - Creates specific drug recognition sites within the polymer through the use of molecular templates Conclusion Opportunity to address compliance issues Vitamin E coatings - Form diffusion barriers within the lens, which forces the target drug to take long complex paths to diffuse from the lens Nanoparticles - Encapsulated with the target drug can be loaded and released from the CL, and the extended release is controlled by the degradation of the nanoparticles Concerns - Frequent lens application?? Non-CL wearers?? Cost?? Opportunity to improve efficacy while maintaining safety profile Numerous drugs in the pipeline so be ready to practice at the highest level of our great profession!! wwhitley@vec2020.com.li CC, Chauhan A (2006) Modeling ophthalmic drug delivery by soaked contact lenses. Ind Eng Chem Res 45: