Safety and Efficacy of Oculus Gen Biodegradable Collagen

Safety and Efficacy of Oculus. Gen Biodegradable Collagen Matrix Implant in Phacotrabeculectomy Surgery Satinder Pal Singh Grewal MD Rajeev Jain, MD Dilraj Grewal MBBS Gagandeep S Brar MD v GREWAL EYE INSTITUTE CHANDIGARH, INDIA

Financial Disclosures None of the authors have any financial interest in this presentation v

Purpose To present the preliminary results of a pilot study that evaluating the safety and efficacy of Oculus. Gen Biodegradable Collagen Matrix Implant designed to improve the regenerating tissue-remodeling in glaucoma patients with cataract undergoing combined phacotrabeculectomy surgery. v This study was registered with Clinical. Trials. gov: Identifier NCT 00477685

Introduction Long-term intraocular pressure (IOP) control following trabeculectomy may be limited by filtration failure, due to scarring at the level of the conjunctiva. Tenon’s-episcleral interface, the scleral flap or its overlying episclera, or the internal ostium v Clinically, mitomycin-C (MMC), 5 -fluorouracil, and corticosteroids have all been used to inhibit fibroblast proliferation to prevent scar development after glaucoma surgery. However they are associated with the risk for late postoperative complications, including wound leakage, hypotony, and maculopathy. 1, 2, 3 1. Sinnreich Z, Barishak R, Stein R. Leaking filtering blebs. Am J Ophthalmol. 1978; 86: 345– 349. 2. Stamper RL, Mc. Menemy MG, Lieberman MF. Hypotonous maculopathy after trabeculectomy with subconjunctival 5 -fluorouracil. Am J Ophthalmol. 1992; 114: 544– 553 3. Sinnreich Z, Barishak R, Stein R. Leaking filtering blebs. Am J Ophthalmol. 1978; 86: 345– 349.

Introduction The use of tissue bioengineering to prevent scar prevention has been described. 4, 5, 6, 7 The application of three-dimensional, collagenglycosaminoglycan copolymers can lead to random and relatively loose reorganization of regenerating myofibroblasts, and the secreted extracellular matrix (i. e. , collagen), reducing scar formation. These biodegradable implants may simultaneously provide physical resistance to overfiltration in the early stages and progressively may reduce this resistance as the implant degrades and a random connective tissue matrix permeates the spaces within the implant to create a loosely organized bleb structure. v 4. 5. 6. 7. 8. Yannas IV, Lee E, Orgill DP, Skrabut EM, Murphy GF. Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. Proc Nat Acad Sci USA. 1989; 86: 933– 937. Yannas IV. Studies on the biological activity of the dermal regeneration template. Wound Repair Region. 1998; 6: 518– 524. Chen HS, Ritch R, Krupin T, Hsu WC. Control of filtering bleb structure through tissue bioengineering: An animal model. Invest Ophthalmol Vis Sci. 2006 Dec; 47(12): 5310 -4. Young MJ, Borras T, Walter M, Ritch R (2005) Potential applications of tissue engineering to glaucoma. Arch Ophthalmol 123: 1725– 173 Hsu WC, Ritch R, Krupin T, Chen HS. Tissue bioengineering for surgical bleb defects: an animal study. Graefes Arch Clin Exp Ophthalmol. 2008 Feb 12 [Epub ahead of print]

Structure: Biodegradable Collagen Matrix Implant In this study a three-dimensional biodegradable collagen matrix was placed in the subconjunctival space and on top of the scleral flap to achieve better postoperative IOP control and to reduce the risk for early shallow anterior chamber. v Scanning electron microscopic image of collagen matrix. A drug-free, biodegradable, porous collagen matrix of 1% collagen/C-6 -S copolymer (Olo. Gen) with a 7 -mm diameter and a 4 -mm thickness was used.

Methods 5 patients underwent combined trabeculectomy with the Oculus. Gen Biodegradable Collagen Matrix Implant in one eye for refractory glaucoma Refractory glaucoma was defined as having previously failed medical, laser or surgical treatment, and phacoemulsifcation with Acrylic IOL impant (AMO AR-40). The Oculus. Gen was implanted on the top of the scleral flap at the limbus before closing the conjunctival wound during trabeculectomy operations. v Intraocular pressure (IOP), bleb characteristics and post-operative complications were assessed before and after surgery. Bleb photographs were analyzed at all post-operative visits according to the Moorfields Bleb-Grading System for the parameters of area (grades 1 -5), height (grades 1 -4) and vascularity (grades 1 -5).

Methods Inclusion Criteria: v • Age 30 years or older • No previous intraocular surgery • Uncontrolled glaucoma, with failed medical and laser treatment, requiring trabeculectomy. Exclusion Criteria: • Known allergic reaction to porcine collagen. • Subject is on warfarin and discontinuation is not recommended. • Patients with: • Normal tension glaucoma, • Uveitic glaucoma, • Sphakic or pseudophakic glaucoma, • Neovascular glaucoma • Secondary glaucoma. • Ocular infection within 14 days prior to trabeculectomy. • Pregnant or breast-feeding women

Surgical Method of Implantation v Graphics from www. oculusgen. com

Surgical Method of Implantation v • Positioning of implant in respect to the scleral flap and the conjunctival wound. • Double arrow points to Conjunctival defect over the area above the implant. 1. Hsu WC, Ritch R, Krupin T, Chen HS. Tissue bioengineering for surgical bleb defects: an animal study. Graefes Arch Clin Exp Ophthalmol. 2008 Feb 12 [Epub ahead of print] Graphics from www. oculusgen. com

Results The study population included 4 Males and 1 Female Average was 56. 3 ± 9. 6 yrs The mean preoperative IOP was 35. 7 ± 7. 8 mm. Hg. v Postoperatively, the mean IOP at 4 months follow-up for all eyes had a 54. 3% reduction (p < 0. 05) to 16. 3 ± 2. 1 mm. Hg. There were no significant intraoperative or post-operative complications in any patients.

Conclusions The short-term preliminary results of this study indicate that the Oculus. Gen implantation in combined phaco-trabeculectomy could potentially provide a safe and effective therapeutic preventing wound failure following trabeculectomy surgery. The Oculus. Gen helps to modulate wound healing response following glaucoma filtering surgery. v However a larger study with a longer follow-up period is required to confirm these observations. Biodegradable Collagen Matrix implants can help in achieving a successful trabeculectomy without antifibrotic medication, controlling both the physical and physiologic aspects of wound healing.