“ Corneal Augmentation: Is SMILE the Gate Opener? “ from Hoopes Vision

9/14/2019

Majid Moshirfar, MD

• Hoopes Vision Corneal Augmentation: • Director of Clinical Research – Hoopes, Durrie, Rivera Research • Fellowship Director SMILE – The Gate Opener • University of California San Francisco • Professor UOA Mega CE 09/14/2019 • Co‐Director of Cornea and Refractive Surgery • Co‐Medical Director of Ophthalmology Clinics Majid Moshirfar, MD • Fellowship Director Hoopes Vision • University of Utah | John Moran Eye Center MORAN • Director of Cornea and Refractive Surgery EYE CENTER • Fellowship Director • Full Tenured Professor

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STEP 1 Lenticule Creation

What is SMILE? A refractive lenticule and small Majid Moshirfar, MD incision are created inside intact Small cornea, all in one step • FINANCIAL DISCLOSURES Incision • NONE STEP 2 Lenticular Lenticule Removal

The lenticule is removed through Extraction the incision with only minimal disruption to the corneal biomechanics

STEP 3 Corneal Curve Change

Removing the lenticule changes the shape of the cornea, thereby achieving the desired refractive correction

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What is SMILE? SMILE (Small Incision Lenticular Extraction) Small Incision • History Lenticular • Designed from developmental needs? • Could help with less epi‐ingrowth Extraction • Could decrease nerve disruption compared to LASIK • Increased Refractive Correction Range • Etc. • Advantages • No flap complications, less invasive, possibly less dry eye due to less nerve disruption • Disadvantages • Greater surgical skill needed, some may have slower recovery

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SMILE (Small Incision Lenticular Extraction) SMILE (Small Incision Lenticular Extraction)

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What do we do with these tissues?: We throw them out. SMILE

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The Safety and Predictability of Implanting LASIK & HYPEROPIA Autologous Lenticule Obtained by SMILE for Hyperopia • 14 million Americans have hyperopia Ling Sun, Peijun Yao, Meiyan Li, Yang Shen, Jing Zhao, Xingtao Zhou • For hyperopia > +5.0 D, LASIK is • 5 patients (10 eyes) with 1 EYE MYOPIC and 1 EYE HYPEROPIC imperfect. • Hyperopic ablations commonly result in worse optical regressions than myopic corrections due to epithelial hyperplasia. • Complications of HOAs, loss of BCVA Myopic SMILE Hyperopic LIKE • Two possible improvements: LIKE and sLIKE

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The Safety and Predictability of Implanting The Safety and Predictability of Implanting Autologous Lenticule Obtained by SMILE for Autologous Lenticule Obtained by SMILE for Hyperopia Hyperopia Ling Sun, Peijun Yao, Meiyan Li, Yang Shen, Jing Zhao, Xingtao Zhou Ling Sun, Peijun Yao, Meiyan Li, Yang Shen, Jing Zhao, Xingtao Zhou • 5 patients (10 eyes) with 1 EYE MYOPIC and 1 EYE HYPEROPIC • Results MYOPIC EYES • Performed SMILE procedure in MYOPIC EYE Patient POSTOP UCVA • Used +LENTICULE removed from MYOPIC EYE and re‐implanted into 01 20/20 HYPEROPIC EYE under femtosecond flap. 02 20/20 • HYPEROPIC EYE did receive some treatment of excimer laser to 03 20/16 compensate for what the implanted lenticule could not correct. 04 20/16 05 20/20 • Patients followed for 12 months

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The Safety and Predictability of Implanting What is LIKE? Autologous Lenticule Obtained by SMILE for Lenticular Hyperopia Ling Sun, Peijun Yao, Meiyan Li, Yang Shen, Jing Zhao, Xingtao Zhou Intrastromal • Results HYPEROPIC EYES KEratoplasty Patient PREOP PREOP PREOP POSTOP POSTOP POSTOP UCVA Refraction BCVA UCVA Refraction BCVA 01 20/400 +3.00 ‐0.25 x __ 20/100 20/100 ‐2.00 ‐1.25 x ___ 20/50 02 20/100 ‐4.75 ‐0.75 x __ 20/32 20/63 ‐1.00 ‐0.75 x ___ 20/32 03 20/200 +5.25 ‐0.75 x __ 20/50 20/32 ‐0.75 ‐0.00 x ___ 20/20 04 20/400 +8.25 ‐2.00 x __ 20/63 20/100 ‐2.00 ‐0.50 x ___ 20/50 05 20/20 +2.50 ‐0.25 x __ 20/20 20/20 +1.50 ‐0.75 x ___ 20/20

• Lenticules were well centered • Transparent with no haze • No complications

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What is LIKE? What is LIKE? Lenticular Lenticular Intrastromal Intrastromal KEratoplasty KEratoplasty

HARLI Hyperopic Allogenic Refractive Lenticule Implantation

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LIKE (Lenticular Intrastromal KEratoplasty) LIKE (Lenticular Intrastromal KEratoplasty)

• Theo Seiler (Germany) • 7 eyes of 6 patients treated with LIKE • Hyperopia up to +6.50 D and Astigmatism up to ‐2.50 D • 3 eyes received Excimer Laser treatment on Lenticule at 1 month • 1 lenticule was replaced at 1 month due to undercorrecxtion • Developed by • No eyes lost more than 1 line of BCVA Dr. Theo Seiler • 3 eyes gained 2 lines or more of BCVA • First conceived of • 4 eyes showed transient haze in the lenticule by Dr. Jose Barraquer • 2 eyes had decentered lenticule which were recentered

Image: Gebauer Medical https://www.gebauermedical.com/refractive/ 19 20

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LIKE – Hoopes Vision Case Report (1st in U.S.) LIKE – Hoopes Vision Case Report (1st in U.S.)

PREOP 6 MO POSTOP PREOP 6 MO POSTOP K‐Readings Flat 39.9 46.2 PREOP K‐Readings Steep 41.4 47.6 UCVA 20/25 20/40 Refraction +6.00 ‐1.00 x 040 0.00 ‐1.25 x 071 BCVA 20/20 20/20 Corneal Thickness 597 (OCT) 816 (OCT)

2 Day Postop

Lenticule Information: Diameter: 7.0 mm Thickness: 157 microns 6 Mo Postop Estimated Power: +7.00 D

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LIKE – Hoopes Vision Case Report (1st in U.S.) sLIKE (small incision LIKE)

• Eye Comfort normal • Patient does experience some nighttime • Slight modification of LIKE glare • Small incision access to stromal pocket • Patient wearing soft CL for residual refractive error • Lenticule inserted into pocket • Residual Rx may be enhanced with Lift Flap excimer enhancement or PRK when stable

2 Months Postop

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sLIKE (small incision LIKE) Procedure

Femtosecond Dissect Pocket LASER Pocket Mark lenticule with spatula with “S” Soak lenticule Diameter: 8‐9 mm in 0.06% Depth: 120 um Tryptan Blue Align to visual Incision: 5 mm Insert with axis and special forceps pupillary center delivery

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Comparison of LIKE vs sLIKE for High Corneal Augmentation Hyperopia Treatment • Hyperopia ADVANTAGES DISADVANTAGES • Presbyopia • Surgical approach similar to LASIK • Increased risk for epithelial ingrowth LIKE • Easier centration • Higher risk for dry eyes • Keratoconus • Simple & Straightforward enhancement • Significant weakening of corneal biomechanics (flap re‐lift), if needed • Higher risk for DLK • Corneal Wounds • Preliminary evidence shows efficacy and • Other flap‐related complications safety • Flap size of at least 10 mm is difficult to create • Etc. on most FS platforms • Less weakening of cornea biomechanics • More challenging surgically sLIKE • Less dry eye symptoms • More difficult centration • Less risk for epithelial ingrowth • Use of dye • Less risk for DLK • Converting cap‐to‐flap for enhancement • No flap purposes can be more challenging

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Corneal Reaction to Foreign Substances (inlays) Corneal Healing Response

• MAN MADE MATERIALS • DONOR CORNEAL TISSUE • PMMA inlays • Stroma • Hydrogel inlays (HEMA/MMA) • Bowman’s Membrane • PVDF (polyvinylidene fluoride) inlay • Full‐Thickness Cornea

Post removal of presbyopic corneal inlay

14% of patients developed corneal haze. Post removal of presbyopic Post removal of presbyopic corneal inlay corneal inlay 29 30

Corneal Augmentation for Keratoconus “The use of biological inlays could be a method to address the problems related to the tissue reaction resulting from the insertion of synthetic inlays.” Soosan Jacobs, MS, FRCS, DNB

Types of Tissue: • Autogenic: tissue from the same individual • Allogenic: tissue from the same species • Xenogenic: tissue from a different species

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• Bowman layer prevents excessive bulging of the cornea. Keratoconus • In keratoconic eyes, it suffers multiple changes that can be seen under electronic microscopy. • Discontinuities, sharply edged defects, ruptures, gaps, and scars were all found in the Bowman layer of keratoconic eyes. • A difficult condition to treat • Penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) for advanced cases come with difficulties and complications. • Wound‐healing problems, allograft rejection, and persistent irregular astigmatism are a few problems with the current treatment paradigm. • LIKE or sLIKE using a minus‐shaped lenticule with collagen cross‐ linking could be less a troublesome therapeutic alternative.

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Bowman layer transplantation using a Bowman layer transplantation using a femtosecond laser femtosecond laser Gonzalo García de Oteyza, Laura A. Gonzalez Dibildox, Kristian A. Vazquez‐Romo, Andre Tapia Vazquez, Jesus H. Davila Gonzalo García de Oteyza, Laura A. Gonzalez Dibildox, Kristian A. Vazquez‐Romo, Andre Tapia Vazquez, Jesus H. Davila Alquisiras, Blanca E. Martínez‐Baez, Ana M. García‐Albisua, Manuel Ramírez, Everardo Hernandez‐Quintela Alquisiras, Blanca E. Martínez‐Baez, Ana M. García‐Albisua, Manuel Ramírez, Everardo Hernandez‐Quintela • For progressive and advanced keratoconus • Study / Procedure • Hypothesis: • Transplantation of an isolated donor Bowman layer within the mid‐stroma of a keratoconic (KCN) cornea • Flatten corneal curvature • 2 patients, stage IV KCN • Halt progression • Donor cornea prepared by removing epithelium • Increase Contact Lens tolerance • 360 degree dissection of Bowman’s layer with a 30‐gauge needle • Mechanical removal of Bowman’s layer with forceps • Femtosecond creation of stromal pocket in KCN cornea at 50% depth • Pocket dissection and Bowman’s layer insertion and unfolding

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Bowman layer transplantation using a femtosecond laser Gonzalo García de Oteyza, Laura A. Gonzalez Dibildox, Kristian A. Vazquez‐Romo, Andre Tapia Vazquez, Jesus H. Davila Alquisiras, Blanca E. Martínez‐Baez, Ana M. García‐Albisua, Manuel Ramírez, Everardo Hernandez‐Quintela

• Bowman’s layer removal from donor cornea PRE PRE

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PREOP 3 Month Postop

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Bowman’s Intrastromal Transplant for Keratoconus

What about sLIKE for Keratoconus?

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sLIKE for Keratoconus sLIKE for Keratoconus

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sLIKE for Keratoconus OCT sLIKE for Keratoconus OCT

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Intacs for Keratoconus‐ made of PMMA sLIKE for Keratoconus Possible Complications: • Flattens cornea • Segment migration • Reinforces periphery • Stromal thinning • Corneal melt • Refractive outcomes unknown • Infectious keratitis • Preliminary trials necessary to measure outcomes • Neovascularization

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Corneal Allogenic Intrastromal Ring Segments Corneal Allogenic Intrastromal Ring Segments (CAIRS) Combined With Corneal Cross‐linking for (CAIRS) Combined With Corneal Cross‐linking for Keratoconus Keratoconus Soosan Jacobs, Shaila Patel, Amar Agarwal, Arvind Ramalingam, John Michael Raj Soosan Jacobs, Shaila Patel, Amar Agarwal, Arvind Ramalingam, John Michael Raj

• Study / Procedure • The segments were not visible on naked eye • 24 eyes of 20 patients, stage 1‐4 KCN examination in any patient. • Donor cornea cut into ring with double trephine • All segments remained well positioned and no case • Divided into 2 equal half segments, then soaked in riboflavin of melt or corneal necrosis was encountered. • Receiving cornea channels made by femtosecond laser @ 50% depth • No other major intraoperative or postoperative 2 WK • Segments then implanted into receiving cornea using complication were seen. PMMA intacs segment as “threading needle” • Corneal Cross‐Linking performed

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Corneal Allogenic Intrastromal Ring Segments (CAIRS) Combined With Corneal Cross‐linking for Keratoconus Soosan Jacobs, Shaila Patel, Amar Agarwal, Arvind Ramalingam, John Michael Raj AVERAGES PREOP POSTOP Allogenic UDVA 20/100 20/50 Intrastromal CDVA 20/30 20/25 Ring Segments for Keratoconus Spherical Equivalent (SE) ‐5.35 ‐1.28 Steepest K value 57.61 D 52.55 D 2 WK

*12 Month Follow‐up *24 eyes of 20 patients 1 MO 51 52

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Biological corneal inlay for presbyopia, derived Biological corneal inlay for presbyopia, derived from small incision lenticule extraction (SMILE) from small incision lenticule extraction (SMILE) Yu‐Chi Liu, Ericia Pei Wen Teo, Heng Pei Ang, Xin Yi Seah, Nyein Chan Lwin, Gary Hin Fai Yam, Jodhbir S. Mehta Yu‐Chi Liu, Ericia Pei Wen Teo, Heng Pei Ang, Xin Yi Seah, Nyein Chan Lwin, Gary Hin Fai Yam, Jodhbir S. Mehta • Study Design: • Study Results: • 10 primate eyes • “In this study, the implanted lenticule, derived from a SMILE procedure, acted • Received Autogenic & Xenogenic lenticules as a shape‐altering inlay to induce a corneal hyper‐prolate change, by • Removed ‐3.00 D convex‐shaped lenticule from myopic SMILE procedure increasing the central corneal radius of curvature.” using femtosecond laser. • “The procedure had good biocompatibility and was not associated with • 3 mm diameter stroma section cut from central portion of lenticule adverse effects such as corneal haze or keratolysis.” • 7.5 mm intrastromal pocket was created in receiving eye at 120 micron depth using a femtosecond laser.

Donor Cornea – SMILE created lenticule Lenticule cut to size Presbyopic Lenticule implanted into recipient

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Soosan Jacobs, MS, FRCS, DNB

Soosan Jacobs, MS, FRCS, DNB 55 56

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Excimer Laser Shaped Allograft Corneal Inlay for Excimer Laser Shaped Allograft Corneal Inlay for Presbyopia: Initial Clinical Results Presbyopia: Initial Clinical Results Aylin Kihc, Merve Ozbek, Burcu Nurozler Tabakci, David Muller, Michael Mrochen Aylin Kihc, Merve Ozbek, Burcu Nurozler Tabakci, David Muller, Michael Mrochen • Study Design: • Study Results: • 12 eyes of 12 patients (average age 52) • 9 out of 12 were satisfied with outcome • Received allogenic lenticules in non‐dominant eye. • Average Uncorrected NEAR VA increase by 5 lines • Tissue buttons from Eyebank were cut with 3 mm trephine • 2 eyes lost 1 line of Uncorrected Distance VA • Button was then formed by excimer laser to desired shape. • 2 eyes lost 2 lines of Uncorrected Distance VA • Dia: 3mm Thickness: 20 microns • Mild corneal haze was seen in 2 patients but disappeared after 3 months • Femtosecond created flap was created in receiving eye at 110 micron depth • Stromal inlay was placed and centered over pupil, then flap replaced • Patients were followed for 3 months.

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Conclusion THANK YOU

• Corneal augmentation with allogenic QUESTIONS? tissue is a promising method for corneal reshaping and strengthening. • Prophylactic corneal collagen cross‐linking of lenticule/segments after implantation may help reinforce cornea, reduce optical regression, and improve visual outcomes.

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