1/3/18

Believe It...or Not! Disclosures A Peek Behind the Curtain at the Future of Eye Care • No financial interest in any product discussed • Some past lecturing and/or paid research for Alcon,

Allergan, Bausch & Lomb/Valeant, Pfizer, & Inspire • Mention of these products in no way implies endorsement by the presenter

• (mention of these products in no way implies expertise on Chris Wroten, O.D. behalf of the presenter either!) [email protected]

Believe It or Not...

• Alternative Health Care Technologies • Contact Lenses Alternave Healthcare Technologies • Traditional Technology Advances • Non-Traditional Healthcare Delivery • Scope of Practice/Scope of Payment Contact Lenses... • Registries • Medicare Payment Reform • Implantable Technologies • Cataract Surgery Advances • Presbyopia Management Options • Lesion Removal & Cosmetic Therapies • Miscellaneous Therapeutic Advances

NaturalVue from Visioneering Technologies 3-D Prinng • Richard Griffin, O.D. Ophthalmic applicaons • NEI Grant to develop • Contact Lenses? • 14 patents • So, daily disposable mulfocal, etafilcon A • “Neurofocus Opcs” • Center distance, extended depth of focus design • Single add power • Myopia progression control?...regression?!?!

1 1/3/18

Triggerfish (Sensimed) Hyper-CL (EyeYon Medical)

FDA-approved in U.S. March 2016 • Israeli Company Connuous IOP-monitoring from silicone CL • Hyperosmoc CL to treat K edema (with hypertonic g) • FDA-approved 2016

Telescopic Contact Lenses (for AMD)

• Swiss Researchers (Defense Advanced Research Projects Agency) • Contains miniscule mirrors arranged to mimic Galilean telescope, acng like built-in binoculars; can be paired with receiving specs • Challenge is thickness (1.55mm vs normal 0.35mm) Courtesy: cnn.com Also adjustable focus MF CL, too?

Night Vision Contacts?!?! Alternave Health Care Technologies

“Tradional” Technology Advances

2 1/3/18

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Horus • Similar product • Assesses paent's visual needs & facial features • Advanced soware calculates ideal lens posion in relaon to the eyes, then designs frame based on those unique parameters • 3D prinng allows further customizaon of the frame according to paent’s visual, comfort & aesthec needs

Other “Smart” Specs...

Will wearable technology also change the way we • Carl Zeiss SmartOpcs correct refracve disorders & interact with the world?

• Google Glass • Mad Glass • Senth IN1 • Sound Glasses • iGlass? • others

3 1/3/18

Other “Smart” Specs... OAKLEY

• CTRL Eyewear • Oakley Prizm Lenses • Polarized • Color-opmized (Green=Golf, Blue=Fishing, etc.) • Oakley Radar Pace • $495 • AI Sunglasses • Biometrics + “Coach”

Other “Smart” Specs... Project Blaid (Toyota)

• Amblyz (XPAND)- digital LCD • Wearable device that scans the amblyopia “patch” glasses environment • Programmable • Uses cameras & recognion soware • “Good” eye lens alternates • Will integrate: clear to opaque x 30 secs • Mapping • Study of 33 kids, age 3-8 yrs • Object ID (doors, Exit signs, stairs, with moderate amblyopia escalator, restroom signs, etc.) (20/40-20/100): 4 hrs of • Facial recognion technologies Amlbyz = 2 hrs patching • Users can request locaon of certain things & feedback audibly or by vibraon

Proximity Hat MyEye (OrCam)

• For visually impaired & those in poor lighng condions • Already successfully tested in Germany • Scans environment 50 x’s/sec • Applies pressure to wearer’s head in direcon of obstacle

4 1/3/18

Horus

• Samsung • Lan “return back to the light” • Uses image processing • Modes: • Regular (enhances outlines) • Color Invert • Paral Vision • Scotoma Relocator • Tunnel Vision • Display Color Filter

Digital Vision Opmizer (DigitalVision Systems) Digital Vision Opmizer (DigitalVision Systems) • Virtual refracng plaorm to dx vision disorders & procure customized, digital, free-form lenses/glasses • Paents interacvely choose & opmize design of their correcve lenses under natural, real-world viewing condions • Provides “beer vision and viewing comfort than convenonal eyewear procured using error-prone phoropter measurements” • Vision tesng & fing info xmied to lab • Partners: Essilor, Zeiss, Hoya, Transions, Ga. Tech, others

3-D Prinng: Surgical Applicaons?

Alternave Health Care Technologies Australian Co. Anatomics/Lab 22 @ CSIRO Non-Tradional Technology Advances 3-D printed Ti sternum/rib cage successfully implanted in cancer paent in Spain

5 1/3/18

3-D Prinng: Surgical Applicaons? 3-D Prinng: Surgical Applicaons?

Wake Forest Bapst Medical Center: • EpiBone Integrated Tissue & Organ Prinng System (ITOP) • Employs 3-D bioprinng to produce living human ssues & bone

3-D Prinng: Surgical Applicaons? 3-D Prinng: Surgical Applicaons?

Corneal Confocal Microscopy (CCM)

• Examines unmyelinated corneal nerve fibers @ high mag, using Lens Autofluorescence laser-scanning CCM to image corneal sub-basal nerve plexus New possible • Using Lens Fluorescence Biomicroscope calibrated with standards indicaon for • Predicts insipient peripheral neuropathy in Type 1 DM traceable to Naonal Instute of Standards and Technology (NIST): diagnosing MS (63% Sensive; 74% Specific) • Type 2 DM Detecon (via AGEs on lens) • Reduced Corneal NFL length & Corneal sensivity = increased • Sensivity = 67%, Specificity = 94% severity diabec peripheral neuropathy (Hemoglobin A1C: Sens.= 44%, Spec.= 79%) • Previous studies demonstrate ulity for CCM in other neuropathies (Fasng Plasma Gluc.: Sens.=50%, Spec.= 95%) • Takes 6 secs, non-invasive, doesn’t require fasng

6 1/3/18

Lens Autofluorescence my Vision Track (a.k.a. mVT) from Vital Art and Science • FDA-approved • Rx only, free download* • Home monitor • AMD & DR

*Charge to share FDA Market Clearance 2013 data with doctor

Epigenecs... 23andME • FDA-approved • Direct-to-consumer genotyping • 36 condions currently(Sjogren’s, Sickle Cell) • Glaucoma?, AMD?, RP?, Color Deficiency? • Salivary sample

7 1/3/18

Color Vision Deficiency...

Color Vision Deficiency

• App-based products • Diagnosc? • Daily use...

enchroma

8 1/3/18

Red-Green Color Blindness

Colorblind Cure.flv - YouTube

New Test for Color Blindness Regenerave Medicine: Stem Cells

• Shinya Yamanaka (Japan) • 2006 discovered pluripotent stem cells (iPSCs) • Nobel Prize • Allows sciensts to regenerate any type of cell into an embryonic cell • Companies now developing treatments to “replace damaged corneas” (expected to launch in Japan in 2018) & AMD...who?

9 1/3/18

Stem Cells: Ocata Therapeucs/Astellas Stem Cells: Ocata Therapeucs/Astellas

Skin-to-Eye Stem Cells Transplant? Sept. 2014 • Luxturna (voregene neparvovec-ryzl) Yasuo Kiromoto, M.D., Ph.D, @ Kobe City Medical Center Gen. Hosp. st • Gene therapy for inherited renal dystrophies Performed 1 -ever human skin cell xplant in 70-yr old Japanese female • Succeeded in late-stage clinical trial • Paent’s skin cells used to generate induced Pluripotent Stem Cells • 1st gene therapy for genec disorders to win FDA approval in U.S. (iPSCs) (Dec. ‘17) • iPSCs then used to create Renal Pigment Epithelium (RPE) sheet • 2 gene therapies for cancer have also been approved • RPE sheet then implanted in paent’s eye • Cost? • 1 year later: no rejecon & subjecve improvement in sight

Skin-to-Eye Stem Cells Transplant? Stem Cells...for Cataracts!?!?

03/09/16 Journal Nature: Sep. 2016: Another team at Japan’s RIKEN Center for Developmental Biology... “Stem Cells were Successfully Used To Treat Congenital Cataracts In 12 Babies” • Used major histocompability complex (MHC) matching to grow RPE cells from induced pluripotent stem cells (iPSCs) in skin cells with no • Univ. California-San Diego sciensts, in conjuncon with Shiley Eye Instute & rejecon researchers in China, used stem cells &... • • Reported the infants “regrew lenses” that are “funconal and appear to act Could allow “RPE banks” normally in the infants, who are now toddlers”

10 1/3/18

• Kiosks? Alternave Health Care Delivery Models • Telemedicine

Arficial Intelligence in Eye Care?...

Google’s IBM Watson

• Google’s Arficial Intelligence Computer Program • IBM Researchers in Australia have trained Watson to detect abnormalies (e.g. • Taught itself how to play 49 different video games with only raw pixel input AMD, diabec renopathy, & glaucoma) in renal photographs • Plans to use >1M anonymized eye scans to “teach computers how to • Able to measure C/D & determine signs of glaucoma with up to 95% accuracy diagnose eye disease”

11 1/3/18

App-Based Technologies...

Opternave Simple Contacts PUPIL 20/20 Now

Evolving Trends in Eye Care

Scope of Pracce Needs

12 1/3/18

Physician Extenders/Replacers? • Rena study...can nurses safely administer intra-vitreal injecons?

Disposable Intravitreal Injecon Speculum

Physician Extenders/Replacers? • Nurses provided 3,355 hospital- based intravitreal injecons • No complaints from paents • Only 0.3% minor adverse events (subconj. heme & k abrasion) • Conclusion: Appropriately trained non-medical staff can improve efficiency & access

New & Emerging Ocular Technology PRO-IOP (Implandata Ophthalmic Products)

• Implantable Microsensor Implantable Technology • Capable of Measuring Absolute IOP connuously or on-demand • Sends data via GSM/modem to Paent & Doctor with IOP ALERT

13 1/3/18

Implantable Telescope: CentraSight Implandata Ophthalmic Products “PRO-IOP”

Iris II Epirenal Implant (Pixium Vision) Argus II Renal Prosthesis System (Second Sight)

• For advanced RP paents • CE Mark & FDA-approved for advanced RP • 150 mini-electrodes • Implanted in worse-seeing eye • CE Mark applied for

Orion I: Visual Corcal Prosthesis (Second Sight)

• Wireless, Mulitchannel Neurosmulaon System (Visual Cortex New & Emerging Ocular Technology Smulator) • First implantaon & acvaon in human subject completed • UCLA – successful proof of concept Cataract Surgery & IOLs • 30 yr old blind paent • Could perceive & localize light with no adverse effects (4 million procedures in U.S. in 2015) • Inial FDA applicaon pending

14 1/3/18

MKO Melt

Verion Image-Guided Cataract Surgery Suite (Alcon) Conscious Sedaon (Imprimis)

• Novel proprietary formulaon (midazolam-ketamine-ondansetron) • Sedaon + anesthesia/analgesia • Can be used in place of IV sedaon for cat sx in 85% of paents • Specifically for ophthalmic use (as well as other procedures) • 2-pack=$25 (usually only need 1) • Sublingual • Available as of 2016

Drop Compliance ReSure (Ocular Therapeux) • >90% of paents non-compliant with ocular meds (from glaucoma studies; & • Hydrogel corneal wound sealant with blue visualizaon aid ~50% stop taking glaucoma meds before 6 mos of therapy ends) • Indicaon for Cataract Surgery Incision Closure (& others?) • 41% of those admit challenges in paying for their meds • Applied to dried cornea x 20 secs; study = signif. beer than suture • 1 in 4 glaucoma paents admits to missing at least one drop per week

Dropless Cataract Surgery (www.godropless.com) “Less Drops” Cataract Surgery Intracameral Trans-zonular • 3 ml = $30.00 Tri-Mox • 6 ml = $60.00 3x ê CME 3x ê Endophthalmis (22x êwith Cephalosporin!)

15 1/3/18

B&L Trulign Toric

Tecnis Symfony (Abbo Medical Opcs) • Only “accommodave” toric IOL approved in U.S. (toric Crystalens) • Reportedly good distance & intermediate vision • Some post-op surprises?

FDA Approval July 2016; CE Mark 2014 No glare/halos (corrects chromac aberraon) Monofocal-like DVA?

Lenstec Tetraflex SmartIOL (Medennium)

• CE Mark received • “Accommodave” IOL • More stable post-op refracon than Crystalens?

Thermodynamic hydrophobic acrylic; Pre-Clinical Trials

IC-8 (AcuFocus)

LiquiLens IOL (Vision Soluon Technologies)

Contains 2 immiscible fluids & relies on agravity-dependent juxtaposion in downward gaze to add power in visual axis

Alan Glazier, O.D.

In Clinical Trials

Approved Europe late ‘14; US clinical trials to come

16 1/3/18

In Clinical Trials NuLens IOL (Dynacurve)

2-pc Accommodang IOL Out of the bag Sulcus-based 5.00D Accommodaon In Clinical Trials

CE Mark Oct. 2015; In Clinical Trials In Phase III Clinical Trials

• IOL powered by own power cell & computer chip embedded inside. Rechargeable & fully programmable, allowing adjustment of opcal power as visual needs change. Expect ~2018

Far vision-mydriasis Near vision-miosis Working on in situ customizaon via femtosecond laser to modify Source: Eyemaginaons/ELENZA refracve index of IOL

17 1/3/18

Topical Cataract Prevenon & Treatment?!?! Topical Cataract Prevenon & Treatment?!?!

• Drops to prevent/treat Drops to prevent Cataracts?!?! Cataracts?!?! • Unspecified... • Nanoparcles infused with • “Nonsurgical Cataract Treatment” Lutein • In conjuncon with UMASS • Rodent studies show • Protein aggregaon interceptor reducon in cataract size within 1 wk of tx

New & Emerging Ocular Technology

Presbyopia Reversal?

>1 Billion Presbyopes Worldwide

Presbyopia Reversal: Laser Ablaon of Cornea Presbyopia Reversal: Laser Ablaon of Cornea

PresbyLASIK • Mulfocal LASIK = advanced laser vision correcon to IIntracor change corneal shape & create diff. power zones for seeing varying distance • Just completed U.S. clinical trials (in other countries x several yrs) • Promising results?

Presbyond • Modified monovision correcon (dominant eye for distance, non-dominant eye with wavefront- No flap (enrely intrastromal); quick recovery; stable; opmized, slightly myopic ablaon) disadvantages: k stability, glare, loss of mesopic contrast

18 1/3/18

Presbyopia (& Myopia) Reversal: Presbyopia (& Myopia) Reversal: Laser “Keratectomy” SMall Incision Lencule Extracon ReLEx SMILE: Uses Zeiss Visumax Femtosecond Laser

• FDA-approved September 2016 • >500K Procedures Worldwide since 2011 • Monovision or Distance Only Correcon • Create thin disc-shaped lencule within cornea which is then removed thru small, surface LASER incision

Presbyopia Reversal: Corneal Inlays Presbyopia Reversal: Corneal Inlays

• In general, inserted on Non-Dominant eye • Mechanisms: • Small Aperture Opcs (KAMRA) >1000 • Change Corneal Curvature (Raindrop) now done; • Change Index of Refracon (Flexivue Microlens, Icolens) Near VA • Techniques: stable 3 & • Lamellar (under LASIK flap) 5 years • Pocket post-op

Presbyopia Reversal: Corneal Inlays Presbyopia Reversal: Corneal Inlays

Flexivue Microlens (Presbia) = refracve inlay Raindrop Near Vision Inlay (ReVision Opcs) • Microscopic hydrogel inlay to correct presbyopia • Previously the Presbylens, then Vue+

Not yet FDA-approved but CE mark FDA Approval July 2016

19 1/3/18

Presbyopia Reversal: Corneal Inlays Presbyopia Reversal: Scleral Procedures

Mulfocal Refracve Inlay • Scleral Spacing Procedure; recently completed Phase III; results improved x me

Presbyopia Reversal: Scleral Procedures Presbyopia Reversal: Laser Ablaon of Lens

Lensar Laser Lens Soening • Uses Femtosecond Laser to soen lens nucleus • Trials underway with encouraging inial results?

Presbyopia Reversal: Pharmacologic Presbyopia Reversal: Pharmacologic

The Benozzi Method Liquid Vision (Presbyopia Therapies) • 1% Pilocarpine Parasympathec smulaon generates ciliary muscle • Topical BID dosing & Reversible contracon & increased lens thickness = increased depth of • Short-term treatment for presbyopia focus (beer NVA, poorer DVA) • Miosis without accommodave spasm • + 0.1% Diclofenac • Clinical Trial Presbyopes in Mexico (avg age 51): Avg NVA = 20/22 Reduces intensity of pupillary & ciliary muscle contracons for • Phase II trials ’15 good vision @ all distances • 100 emmetrope study: DVA remained 20/20 with enhanced accommodaon/improved NVA x 5 yrs (only 4% pref. specs)

20 1/3/18

Presbyopia Reversal: Pharmacologic Presbyopia Reversal: Pharmacologic

Other formulaons in study, including: EVO6/Diopn? (Encore Vision) • Presbeyedrops

• 2 parasympathomimecs + 1 NSAID • Proposed mech. acon for Presbyopia = intracellular redox (lens • PresbyPlus proteins x-link = harden) • 2 Parasympathomimecs + 1 Parasympatholyc • Topical drop to “break” cross links & restore accommodaon • BID dosing x 30 days = ~ 2.0 D Accommodave Recovery • May 2016: Met Primary Safety & Efficacy Outcomes for Phase I-II • 75 paents b/t 45-55 yrs old with 20/20 BCDVA & worse than 20/40 DCNVA • Dosed BID • 1st Improvement @ Day 15, connuing thru the 90-Day Study Period

Second Skin

• Clear Siloxane cream spread over skin, then planum catalyst applied which transforms into cross-linked polymer layer • Result = invisible material Other Non-Tradional Therapeuc/Surgical Updates with very similar elasc properes to young skin

Corneal Collage Crosslinking (CXL) Corneal Collage Crosslinking (CXL) • Invented in Germany in 1998 to strengthen cornea (Keratoconus, • FDA-Approved April 18, 2016 post-LASIK ectasia, etc.) & prevent progression, not necessarily improve vision • Pre-tx topical anesthec & mild sedave (e.g. Valium); Epithelium prepped (may do epi-off or trans-epi/epi-on if thick enough K) • Vitamin B2 (riboflavin) g inslled & paent looks at UV Light • Outpaent procedure; OU Tx = 90 minutes; Monoc. Tx = 60 minutes • Now FDA-approved; pre-approval trial website (www.cxlusa.com) • Studies show: may prevent further vision loss in >98% of paents & improves vision in >50%; Epi-on beer than epi-off?; if performed with hyperopic LASIK, reduces regression?; also for advanced k-conus

21 1/3/18

Corneal Collage Crosslinking (CXL): Corneal Collage Crosslinking (CXL) Treatment of Myopia? • Clin Ophthalmol. 2014; 8: 697–702. • Published online 2014 Apr 7. doi: 10.2147/OPTH.S59934 • Therapy for microbial keras? • PMCID: PMC3984063 • Novel myopic refracve correcon with transepithelial very high- • Used in conjuncon with Orthokeratology? fluence collagen cross-linking applied in a customized paern: early clinical results of a feasibility study - Anastasios John Kanellopoulos • Can/should ODs do? • 4 cases; treated transepithelially in a myopic paern, total = 12 J/cm2 • Avg = 2.3 D myopic correcon achieved wk 1, with slight regression to 1.44 D @ 1 mo post-op (stable to 6 mo post-op) • Mean keratometry Δ = 44.90 D to 43.46 D, no signif Δ endothelial cell counts or k clarity; mild Δ epi thickness distribuon (mean = 8 μm)

TrueTear™: Intranasal Tear Neurosmulator?!?!.... LT-300 Photobiomodulator (LumiThera, Inc.)

• LIGHTSITE Study For Dry AMD Filed for FDA Approval • 42 eyes in 24 paents & Expected 4Q17 • 3-wk course of tx • LED light comprising red (670 nm), yellow (590 nm), & infrared (790 nm) applied to subjects’ eyes • Significantly improved Visual Acuity, Contrast Sensivity, & Renal Drusen Volume • Improvements maintained x 3 mos

Not yet FDA-Approved

Surgical Glaucoma Updates Iray Radiotherapy System (Oraya) TUG (EyeSonix) • For Wet AMD • Therapeutic Ultrasound for Glaucoma  • Low power, low frequency x-rays voltage Low • • One me non-invasive treatment • Enhances outflow • Reduces # Intravitreal Injecons • In Clinical Trials Prelim: 20% IOP ê x 1 yr in 74% with elevated IOP

French co. Eye Tech Care developing same technology

22 1/3/18

New Glaucoma Theory/Therapy?

• SECO & ASCRS 2016 PAN-9086 (PanOpca) • John Berdahl, M.D.: Glaucoma not just an ocular condion, • Potent & selecve inhibitor of VEGF rather an imbalance between IOP & ICP • Preclinical trials completed by Wilmer Eye Instute at Johns Hopkins • His research revealed paents with glaucoma have lower ICP, (i.e. larger pressure gradient between IOP & ICP), producing • Completed Phase I/II Clinical Trials opc nerve damage • Effecve in 50% of treated individuals • Proposed Treatment: “Balance Goggles” manufactured by • Treatment of: Wet AMD, Diabec Renopathy & Macular Edema Equinox to equilibrate pressure across the opc nerve • It’s TOPICAL

Regenerave Medicine? BIIB033 (Biogen) Opna (Ampio Pharmaceucals) • Invesgaonal monoclonal anbody, administered intravenously • An-LINGO agent (LINGO-1 is a CNS-specific membrane • Ultra low-dose danazol (synthec derivave of testosterone) glycoprotein that suppresses oligodendrocyte differenaon & • Enhances endothelial cell barrier funcon for tx of DME myelinaon) • Early results: improved opc nerve latency in affected eye of acute • Oral opc neuris, as well as fellow eye • Large, late-stage clinical trials underway in U.S. • VEP latency improved post-tx, indicang remyelinaon • Poss. 1st true neuroprotecve agent for this? • IV administraon & now in Phase II

Regenerave Medicine? From Nature Neuroscience, 7/11/16: • Andrew Huberman & fellow Stanford researchers “...Help Mice With Technology in the Destroyed Opc Nerves To See Again” • Combined visual smulaon & viral acvaon of the mammalian target of Optometric Classroom? rapamycin (mTOR) led renal ganglion cells in blind mice to regenerate, restoring paral vision • In 70% of mice, axons regrew all the way to chiasm & “reconnected to their correct targets in the brain”

23 1/3/18

Take Homes...

• Today’s success, does not guarantee tomorrow’s “People tell me, ‘You're such an opmist.’ Am I an opmist? An opmist says the glass is half full. • Sir Winston Churchill: A pessimist says the glass is half empty. “To improve is to change; to be perfect is to change oen.” A survivalist is praccal. He says, ‘Call it what you want, but just fill the glass.’ I believe in filling the glass.” - Louis Zamperini (subject of bestselling book & major moon picture Unbroken)

THANK YOU!!!

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