Minimally Invasive Glaucoma Surgery MIGS: Minimally Invasive Glaucoma Surgery Ilya Rozenbaum, MD Matossian Eye Associates June 2014 Copyright Matossian Eye Associates, 2014

Disclosures Speaker/Consultant: Allergan Alcon Copyright Matossian Eye Associates, 2014

Understanding Glaucoma 3 Human Cost of Glaucoma Glaucoma is the second leading cause of blindness worldwide Global estimates of glaucoma cases exceeded 60M in 2010 and are estimated to grow to 78M by 2020 Bilateral blindness is occurring at an alarming 7.5% of OAG cases globally, growing from 4.4M to 6M patients between 2010 and 2020 In the US, there are an estimated 2.2M cases of OAG, growing to more than 3M cases by 2020, with more than 88,000 of these patients going blind Notes: Primary Open-angle glaucoma affects approximately 66 million people in the world and is the second leading cause of blindness. According to Dr. Quigley’s research, of the 66 million people with glaucoma, just under 6 million will go blind. In the US, the estimates are 2.2 million cases of primary open-angle glaucoma with 87,800 expected to go blind as a result. The incidence is expected to increase to just under 3 million cases by 2020. In the United States, approximately 2% of the population has the disease, and the probability of undergoing conventional filtration surgery is 23% in one eye after 20 years of having the disease. As surgery is usually done at a late stage in the disease after medical and laser treatments have failed, an earlier, more aggressive treatment is warranted. 1.Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol. 2006 March; 90(3): 262–267. 2.Congdon NG, De Jong PT, Klein BE et al.Glaucoma as a cause of blindness in the United States. American Glaucoma Society Annual Meeting 2003; abstract. 3.Friedman DS, De Jong PT, Klein BE, et al. Glaucoma prevalence in the United States: results of a meta-analysis. American Glaucoma Society Annual Meeting 2003; Abstract. Reference Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996;80:389-393. Congdon NG, De Jong PT, Klein BE et al. Glaucoma as a cause of blindness in the United States. American Glaucoma Society Annual Meeting 2003; Abstract. Friedman DS, De Jong PT, Klein BE, et al. Glaucoma prevalence in the United States: results of a meta-analysis. American Glaucoma Society Annual Meeting 2003; Abstract.

Problems with Glaucoma Meds Future surgery success rate may be lower Quality of life Cost Compliance Side effects: Death from beta-blockers Fatal aplastic anemia (CAIs) Severe allergic reactions Retinal detachment (pilocarpine) Irritation, redness, etc Copyright Matossian Eye Associates, 2014

Glaucoma: Surgical Disease 5 Understanding Glaucoma Glaucoma: Surgical Disease CIGTS: Glaucomatous optic disc progression is higher in patients on medical treatment than surgical patients Notes: Primary Open-angle glaucoma affects approximately 66 million people in the world and is the second leading cause of blindness. According to Dr. Quigley’s research, of the 66 million people with glaucoma, just under 6 million will go blind. In the US, the estimates are 2.2 million cases of primary open-angle glaucoma with 87,800 expected to go blind as a result. The incidence is expected to increase to just under 3 million cases by 2020. In the United States, approximately 2% of the population has the disease, and the probability of undergoing conventional filtration surgery is 23% in one eye after 20 years of having the disease. As surgery is usually done at a late stage in the disease after medical and laser treatments have failed, an earlier, more aggressive treatment is warranted. Five-year Follow-up Optic Disc Findings of the Collaborative Initial Glaucoma Treatment Study. Am J Ophthalmol 2009;147:717–724. Copyright Matossian Eye Associates, 2014 Reference Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996;80:389-393. Congdon NG, De Jong PT, Klein BE et al. Glaucoma as a cause of blindness in the United States. American Glaucoma Society Annual Meeting 2003; Abstract. Friedman DS, De Jong PT, Klein BE, et al. Glaucoma prevalence in the United States: results of a meta-analysis. American Glaucoma Society Annual Meeting 2003; Abstract.

Glaucoma: Surgical Disease Surgical options Trabeculectomy or ExPress Tube shunts Ahmed, Baerveldt, Molteno Laser trabeculoplasty Trans-scleral laser Canaloplasty MIGS Copyright Matossian Eye Associates, 2014

Glaucoma: Surgical Disease Trabeculectomy 2014 Advantages Still the gold standard surgery No device needed - available, cost-effective Can achieve low IOPs Disadvantages Less standardized (hasn’t significantly changed in 50 years) Complications in up to 40% Failure in up to 50% at 5 years Cataract in 50% at 5 years Gedde SJ, Schiffman JC, Feuer WJ, et al. Am J Ophthalmol. 2012;153:789-803 e2.

Glaucoma: Surgical Disease TVT study: complications Early postoperative complications: 21% (tube) and 37% (trab) Late postoperative complications (up to 5 years after surgery): 34% (tube) and 36% (trab) Cataract surgery: 54% of phakic tube eyes and 43% of phakic trab eyes Reoperation for surgical complications: 22% (tube) and 18% (trab) Gedde SJ, Herndon LW, Brandt JD, et al. Am J Ophthalmol. 2012;153:804-814 e1.

Bleb Leak Evaluation must be done with high concentration fluorescein Cascading darker/clear fluid with fluorescent edges is a leak

Endophthalmitis Copyright Matossian Eye Associates, 2014

Tube Erosion Copyright Matossian Eye Associates, 2014

Plate Erosion Copyright Matossian Eye Associates, 2014

Ideal glaucoma surgery? As effective as trabeculectomy but safer Reproducible/Predictable No bleb Easy to perform Less post-operative effort Cost-effective Copyright Matossian Eye Associates, 2014

Cataract surgery vs. controls from OHTS: 16.5% reduction in IOP sustained for 36 months Mansberger SL, et al. Reduction in intraocular pressure after cataract extraction: the ocular hypertension treatment study. Ophthalmology. 2012 Sep;119:1826-31.

Concomitant Cataract & Glaucoma (US) 1 in 5 Cataract Eyes on OHT Medication Centers for Medicare and Medicaid Services. 2002 – 2007. Medicare Standard Analytical File. Baltimore, MD. 2007 . Copyright Matossian Eye Associates, 2014

SITA-Standard HVF 24-2 Copyright Matossian Eye Associates, 2014

MIGS Minimally Invasive Glaucoma Surgery Copyright Matossian Eye Associates, 2014

Minimally Invasive Glaucoma Surgery (MIGS) Ab interno microincisional approach Minimally traumatic to the target tissue Safe and (at least modest) IOP reduction Rapid recovery with minimal impact on the patient’s quality of life Typically indicated for mild to moderate POAG Curr Opin Ophthalmol 2012, 23:96–104 Copyright Matossian Eye Associates, 2014

iStent Trabecular Micro-Bypass Stent (Glaucos) 1 mm x 0.33 mm Snorkel: 0.25 mm x 120 µm (bore diameter) Weight: 60 µg Surgical grade nonferromagnetic titanium Heparin-coated to promote self- priming and facilitate outflow Snorkel 0.3 mm Open Half Pipe Retention Arches Lumen 120 µm Self-Trephining Tip The iStent was designed to be as small as possible in order to require a micro- invasive surgical procedure. It is the smallest device known to be implanted in humans. The iStent is 1.0 mm in length and 0.33 mm in height, with a snorkel length of 0.25 mm and diameter of 120 µm. has an “L”- shaped structure with a snorkel (inlet) on the short side (which sits in the anterior chamber) and an open half-pipe lumen. The convex side of the iStent sits against the inner wall of Schlemm’s canal and the open half-pipe against the outer wall. The snorkel of the device is designed to extend slightly into the anterior chamber to allow aqueous to exit from the anterior chamber. The size of the lumen (120µm) has more than adequate capacity to accommodate flow of aqueous humor produced. The iStent is manufactured from titanium (Ti6Al4V ELI), a material commonly used in medical implants with proven biocompatibility in the body. It is non- ferromagnetic for safety in magnetic resonance imaging. The heparin coating is used to ensure wetting ability of the lumen for self-priming. iStent® is FDA approved in the U.S., C.E. marked in the E.U., and has Medical Device Approval in Canada 19

iStent Copyright Matossian Eye Associates, 2014

For patients with OAG/OHTN who also need cataract surgery iStent: Indication In conjunction with cataract surgery Mild to moderate open- angle glaucoma Currently treated with ocular hypotensive medication For patients with OAG/OHTN who also need cataract surgery The iStent was designed to be as small as possible in order to require a micro-invasive surgical procedure. It is the smallest device known to be implanted in humans. The iStent is 1.0 mm in length and 0.33 mm in height, with a snorkel length of 0.25 mm and diameter of 120 µm. has an “L”-shaped structure with a snorkel (inlet) on the short side (which sits in the anterior chamber) and an open half-pipe lumen. The convex side of the iStent sits against the inner wall of Schlemm’s canal and the open half-pipe against the outer wall. The snorkel of the device is designed to extend slightly into the anterior chamber to allow aqueous to exit from the anterior chamber. The size of the lumen (120µm) has more than adequate capacity to accommodate flow of aqueous humor produced. The iStent is manufactured from titanium (Ti6Al4V ELI), a material commonly used in medical implants with proven biocompatibility in the body. It is non-ferromagnetic for safety in magnetic resonance imaging. The heparin coating is used to ensure wetting ability of the lumen for self-priming. iStent® is FDA approved in the U.S., C.E. marked in the E.U., and has Medical Device Approval in Canada 21

Done with cataract surgery iStent Done with cataract surgery Copyright Matossian Eye Associates, 2014

iStent: Mechanism Designed to improve aqueous outflow thru the natural physiologic pathway Creates a bypass thru trabecular meshwork to Schlemm’s canal iStent® is FDA approved in the U.S., C.E. marked in the E.U., and has Medical Device Approval in Canada

iStent Copyright Matossian Eye Associates, 2014

iStent Surgical Video Copyright Matossian Eye Associates, 2014

At 12 months: 68% of iStent subjects with IOP ≤ 21 mm Hg without medication vs. 50% with cataract surgery alone (p=0.004) Ophthalmology. 2011 Mar;118(3):459-67. Copyright Matossian Eye Associates, 2014

35% cataract group on medication (p=0.001) At 12 months: 15% of iStent vs. 35% cataract group on medication (p=0.001) Ophthalmology. 2011 Mar;118(3):459-67. Copyright Matossian Eye Associates, 2014

iStent + Cataract Surgery N = 111 Complication iStent + Cataract Surgery N = 111 Cataract Surgery N = 122 Anticipated early postoperative event 14(13%) 15(12%) Stent obstruction by iris, vitreous, fibrous overgrowth, fibrin, blood, and so forth 4(4%) 0(0%) Posterior capsular opacification 3(3%) 8(7%) Stent malposition Subconjunctival hemorrhage 2(2%) Elevated IOP, other 1(1%) Epiretinal membrane Iris atrophy Blurry vision or visual disturbance 6(5%) Iritis Dry eye Elevated IOP requiring treatment with oral or intravenous medications or with surgical intervention Macular edema Foreign body sensation 3(2%) Allergic conjunctivitis Mild pain Rebound inflammation from tapering steroids

iStent Lower IOP Fewer medications No bleb!! Copyright Matossian Eye Associates, 2014

What's in the Pipeline? 2 “iStent inject” vs latanoprost/timolol Copyright Matossian Eye Associates, 2014

Endoscopic Cyclo Photocoagulation (ECP) - EndoOptiks Copyright Matossian Eye Associates, 2014

ECP Copyright Matossian Eye Associates, 2014

ECP ECP is the selective ablation of aqueous producing ciliary processes via an ab interno approach Inhibits aqueous production, therefore reducing IOP and medication use ECP has been performed globally for over 12 years More than 50,000 patients treated to date Copyright Matossian Eye Associates, 2014

ECP Indications Mild to moderate glaucoma (any type) or Refractory glaucoma (after multiple failed glaucoma surgeries) Copyright Matossian Eye Associates, 2014

Phaco-ECP: Combined ECP and Cataract Surgery Lindfield D, Ritchie RW, Griffith MF. BMJ Open 2012 Copyright Matossian Eye Associates, 2014

ECP COLLABORATIVE STUDY GROUP SAFETY STUDY: COMPLICATIONS 5824 PATIENTS IOP Spike 14.5% Hemorrhage 3.8% Serous Choroidal Effusion 0.36% IOL Dislocation 0.36% CME 1.03% RD 0.27% Massive Choroidal Hemorrhage 0.09% Hypotony or Phthisis 0.12% NLP Vision 0.12% Cataract 24.5% Acute Graft Rejection 5.3% Chronic Graft Rejection 0 Chronic Inflammation 0 Flat AC 0 Endophthalmitis 0 Diplopia 0 Wound Leak 0 Bleb Complications 0

Trabectome (Neomedix) Copyright Matossian Eye Associates, 2014

Surgical Treatment Trabectome Ablates and removes a strip of trabecular meshwork and re- establishes access to the eye’s natural drainage pathway Notes: Trabectome (developed by NeoMedix) ablates and removes a strip of trabecular meshwork and re-establishes access to the eye’s natural drainage pathway. HOW IT WORKS It all happens at the tip. The Trabectome handpiece is positioned across the anterior chamber and the tip enters the Schlemm’s canal. At the tip, the Trabectome handpiece incorporates a bipolar micro-electrocautery which ablates and removes a strip of trabecular meshwork. Simultaneous irrigation and aspiration washes away the debris and provides a stable anterior chamber while protecting the adjacent tissues. The main difficulty is identifying Schlemm’s canal. Trabectome has an excellent operative and post operative safety profile and has not resulted in any of the following postoperative conditions: Flat or shallow anterior chamber, Persisting corneal edema, Iris injury, Hypotony or hypotony maculopathy, Infection, Cataract progression, Wound leak, Bleb formation and infection, Choroidal effusion; choroidal hemorrhage, Visual acuity decrease (>2 Lines) Trabectome Tip is bent to create the triangular Protective Footplate. The Protective Footplate:   provides protection from heat injury to adjacent structures.  is coated with a smooth insulating material.  easily penetrates the trabecular meshwork.  acts as a guide and glide inside Schlemm's canal to protect the collector channels, outer wall of Schlemm's canal and adjacent tissues. Feeds trabecular and juxtacanalicular tissues into the ablative bipolar electrodes as the instrument tip is advanced. Complications (49 patients) from latest study   • Intraoperative blood reflux when instrument removed in majority of cases   • Hyphema cleared by 6.4 + 4.1 days •20% hyphema largest in this series •Minimized by wound suture/air tamponade/ Intra-operative Iopidine  •2% Pilocarpine pre-op & 2 – 6 weeks post-op   • Transient Corneal injuries: 6/49 (12.2%) •Epithelial defect: 3/49(6%) •Decemet’s hemorrhage: 1/49(2%) •Decemet’s scroll/detach: 1/49 (2%) •Persisting Decemet’s injury: 1/49(2%)   • Partial PAS/goniosynechiae: 14/49(28.5%) Copyright Matossian Eye Associates, 2014 38 38

Review of 115 Trabectome patients vs. 102 trab-MMC patients. Success rates (IOP<21 mmHg or >20% reduction) at 2 years: 22.4% for trabectome and 76.1% for trab (P=0.001) Ophthalmology. 2012 Jan;119(1):36-42. Copyright Matossian Eye Associates, 2014

Trabectome had 100% hyphema POD #1, plus 4 Trabectome had 100% hyphema POD #1, plus 4.3% other complications, compared to 35.3% complication rate for trabeculectomy (P=.001) Ophthalmology. 2012 Jan;119(1):36-42. Copyright Matossian Eye Associates, 2014

Trabectome Side Effects and Complications Descemet’s injury Surgical Treatment Trabectome Side Effects and Complications Descemet’s injury Ciliary body injury Reflux bleeding, hyphema Zonule injury Notes: Trabectome (developed by NeoMedix) ablates and removes a strip of trabecular meshwork and re-establishes access to the eye’s natural drainage pathway. HOW IT WORKS It all happens at the tip. The Trabectome handpiece is positioned across the anterior chamber and the tip enters the Schlemm’s canal. At the tip, the Trabectome handpiece incorporates a bipolar micro-electrocautery which ablates and removes a strip of trabecular meshwork. Simultaneous irrigation and aspiration washes away the debris and provides a stable anterior chamber while protecting the adjacent tissues. The main difficulty is identifying Schlemm’s canal. Trabectome has an excellent operative and post operative safety profile and has not resulted in any of the following postoperative conditions: Flat or shallow anterior chamber, Persisting corneal edema, Iris injury, Hypotony or hypotony maculopathy, Infection, Cataract progression, Wound leak, Bleb formation and infection, Choroidal effusion; choroidal hemorrhage, Visual acuity decrease (>2 Lines) Trabectome Tip is bent to create the triangular Protective Footplate. The Protective Footplate:   provides protection from heat injury to adjacent structures.  is coated with a smooth insulating material.  easily penetrates the trabecular meshwork.  acts as a guide and glide inside Schlemm's canal to protect the collector channels, outer wall of Schlemm's canal and adjacent tissues. Feeds trabecular and juxtacanalicular tissues into the ablative bipolar electrodes as the instrument tip is advanced. Complications (49 patients) from latest study   • Intraoperative blood reflux when instrument removed in majority of cases   • Hyphema cleared by 6.4 + 4.1 days •20% hyphema largest in this series •Minimized by wound suture/air tamponade/ Intra-operative Iopidine  •2% Pilocarpine pre-op & 2 – 6 weeks post-op   • Transient Corneal injuries: 6/49 (12.2%) •Epithelial defect: 3/49(6%) •Decemet’s hemorrhage: 1/49(2%) •Decemet’s scroll/detach: 1/49 (2%) •Persisting Decemet’s injury: 1/49(2%)   • Partial PAS/goniosynechiae: 14/49(28.5%) Copyright Matossian Eye Associates, 2014 41

The ICE Procedure Cataract Extraction iStent ECP Copyright Matossian Eye Associates, 2014

What is ICE? 16.5% IOP lowering at 3 years Mansberger. Ophthal. 2012; 119:1826-31. 33% IOP lowering with cataract extraction Samuelson. Ophthal. 2011;118:459-67. 43% IOP lowering with cataract extraction Kahook; J Glaucoma. 2007;16:527-30.

Mechanisms of ICE? ? Angle widening ? Decreased aqueous production Increased trabecular outdlow Decreased aqueous production

Preoperative vs. Month 3-6 IOP Reduction (n=48) % of eyes Preoperative vs. Month 3-6 IOP Reduction (n=48) From Glaukos Panel Executive Summary pgs. 58-59 Copyright Matossian Eye Associates, 2014 45

Preoperative vs. Month 3-6 IOP % of eyes Preoperative vs. Month 3-6 IOP From Glaukos Panel Executive Summary pgs. 58-59 Copyright Matossian Eye Associates, 2014 46

What about Cost? Projected cost savings at 6 years in $: 1 drop 2 drops 3 drops iStent -20.77 1272.55 2124.71 ECP 779.23 2072.55 2924.71 Trabectome 279.23 1572.55 2424.71 Copyright Matossian Eye Associates, 2014 Iordanous Y et al. J Glaucoma. 2014 Feb;23(2):e112-8.

Summary Appreciation for the risks and complications associated with traditional glaucoma surgery has ignited the MIGS revolution MIGS, combined with cataract surgery, provides safe new options for IOP reduction Lots of options, data is forthcoming Trabeculectomy and tube shunt surgery for significant IOP reduction Copyright Matossian Eye Associates, 2014

Thank you! Hopewell office 609-882-8833 Doylestown office 215-230-9200 Cell 646-263-3045 Copyright Matossian Eye Associates, 2014