ologen® implants in revision filtering surgery: two-year results Augenklinik Mülheim ologen® implants in revision filtering surgery: two-year results Zaher Sbeity M.D, FEBO1,2, B.B. Bestges M.D1, C.C. Lösche M.D1 1Mülheim Eye Hospital, Teaching Hospital University of Düsseldorf, Germany 2 New York Medical College, Valhalla, USA

Bleb survival only 40-60% of all successful blebs survive in 10 yrs 1,2,3 Late bleb failure occurs in 23-51% of all blebs 5 yrs after surgery (with MMC/5-FU) 24-74% of all blebs 4 yrs after surgery (w/o MMC/FU) Bleb failure is NOT uncommon Jampel HD et al: Am J Ophthalmol. 2005;140:16-22. Suzuki R et al. Ophthalmology. 2002;109:1921-1924 Chen TC et al. Ophthalmology. 1997;104:1120-1125.

Bleb failure Early bleb failure Late bleb failure Flat bleb syndrome Excessive wound healing Encapsulated blebs Scarred flat blebs Scarred flat bleb Encapsulated bleb

Flat bleb syndrome Causes: Early bleb leaks Hypofiltration blocked sclerostomy bleb hemorrhage tight flap sutures Extraocular causes: tight orbit syndrome1(asians) 1Lee GA et al. Acta Ophthalmol. 2010 ;88:120-4.

Late bleb failure Excessive bleb wound healing is commonly seen in: hypervascular & inflammed conjunctiva (allergies, drop intolerance, ocular surface disease) previous ocular surgeries (RD & CE) ocular pathologies: uveitis, ICE syndrome,XFS, etc. Other risk conditions: african race, juvenile age group, systemic autoimmune diseases

Rescuing failing blebs Early bleb failure: subconjunctival injections or topical use of antimetabolites or anti-angiogenesis agents digital massage, repair of bleb leaks suture lysis, release of adjustable sutures Late bleb failure needling/revisions ab externo/ or ab interno with or w/o antimetabolite adjuvants All approaches are till date still suboptimal 1.Ghoneim EM et al. J Glaucoma. 2011;20:528-32 2. Anand N et al.J Glaucoma. 2009;18:513-20 3. Kahook MY wt al. Ophthalmic Surg Lasers Imaging. 2006 ;37:148-50

Adjuvants in filtering surgery Several adjuvants has been used in trabeculectomies to improve bleb success rate: antimetabolites (MMC,5-FU) has been used as adjuvants since early 1980s1 antiangiogenesis agents (Avastin) has been used as adjuvant in Trabeculectomy since 20062 amnion membrane and ant lens capsule as an adjuvants were used3,4 collagen matirx implants (ologen®) as an adjuvant since 20065 1. Chen CW et al. J Ocul Pharmacol. 1990;6:175-82. 2. Kahook MY et al.Ophthalmic Surg Lasers Imaging. 2006;37:148-50 3. Emarah AM et al. J Glaucoma. 2011;20:514-8 4. Sheha H et al. J Glaucoma. 2008 ;17:303-7 5. Hsu WC et al.Graefes Arch Clin Exp Ophthalmol. 2008;246:709-17

What is an ologen® implant? Porous matrix implant consists of porcine Type I Atelo- Collagen (90% ) and glycosaminoglycan (10%) pore diameter between 10 ~ 300μm a biodegradable ( 6-12 months) dry disc scaffold of different sizes

Why ologen® implants for primary trabeculectomy? It occupies the area over scleral flap preventing collapse of the subconjuctival space (avoids early flat bleb syndrome) It guides fibroblasts to grow through the matrix pores preventing scar formation (modified wound healing) act as an aqueous reservoir by creating a buffer milieu ( avoids hyperfiltration, flat AC )

ologen® vs MMC in primary filtration surgery Filtration surgery with ologen® had similar success rate to that with MMC1,2 (1Cillino et al. Trab w ologen : randomized prospective comparative trial, 24 months follow-up, n= 40),2 Primary trabeculectomies with ologen® has lower success rate (40%) at 12 months than that with MMC (93%) in POAG (prospective n=15+15)3 1 Cillino S et al. Eye . 2011;25:1598-606. 2 Johnson MS, Sarkisian JR. J Glaucoma, Nov 2013, Epub. 3 Rosentreter A et al. Ophthalmologica. Ophthalmologica. 2013 Dec, Epub.

ologen® implants for failing blebs We evaluated the efficacy of ologen® implants as an adjuvant wound modulator in bleb revision and compared the results to revisions with antimetabolites up to two years

Methods retrospective, comparative case series All bleb revisions done between 2010- 2011were analyzed and compared Two groups: Bleb revisions/needling with MMC or 5-FU Bleb revisions with ologen® implants All primary trabeculectomies and bleb revisions were performed by two surgeons ( CCL and ZS) between 01-2009 till 11.2011 Assessment of surgical outcome up to two years after surgery IOP number of medications

Results Adjuvant MM C/ 5FU ologen® ologen® + MMC Total Trabeculectomy Revision/Needling MM C/ 5FU 102 15 ologen® 3 13 ologen® + MMC 1 2 Total 105 30

Results Mean Age M / F Diagnosis 72,5 +10.3 6/9 POAG 8, XFG 6 Revision/needling (MMC/5FU) 15 72,5 +10.3 6/9 POAG 8, XFG 6 uveitic 1 Revision with ologen® 66,8 +11.9 5/10 POAG 7, XFG 3, uveitic 3, PG 1 , CACG 1 Revision Group Ologen Group

Results Period Revision/needling mean IOP n No Meds Revision ologen® P-value Pre-op 28.6 + 4.9 15 1.5+1.4 31.1+ 8.4 3 .0+ 1.0 1 month 17.3 + 7.7 14.3 + 4.9 3 months 17.8 + 5.9 14.8 + 3.9 6 months 18.7 + 4.9 0.8+ 1.0 14.4 + 4.7 0.7 +0.1 0.058 12 months 16.4 + 7.1 14 1.4 18.8 10 1.0 24 months 17.5 + 5.6 11 2.0 + 1.3 7 1.0 + 1.3 P >0.05 15.0 + 5.1

Results: IOP and Medications Meds

Additional Glaucoma revision surgeries within 2 years % 26.7% 18,2 % implants

Bleb revisions with ologen® 3 months Preop 1 week 6 months 6 weeks 24 months

Discussion: Limitations: retrospective, non randomized cases series groups with small numbers (n=15) selectivity bias: ologen® was chosen for younger patients with encapsulated blebs and more tendency of bleb scarring and failure

Ologen Implants in bleb revision Advantages Disadvantages/Limitations avoid early flat bleb syndrome (preoperated less mobile conj) modifies wound healing: increases survival rate? reduces number of subsequent revision surgeries tendency for more IOP reduction and less meds limited effect of postologen needling and digital massage. Conjunctival mobility over flap restricted Incomplete resorption Post-op laser suture lysis extremly difficult

Conclusion ologen® Collagen Matrix implants are effective adjuvants in revision filter surgery to rescue failing blebs and to control intraocular pressure

Disclosure of the Conflict of interest Zaher Sbeity, M.D., FEBO In relation to this presentation, I declare that there are no conflicts of interest.