1. Evidence-Based Target Pressures Paul Palmberg, MD, PhD Bascom Palmer Eye Institute University of Miami School of Medicine How to Achieve Low Target Pressures Safely with MMC or 5-FU

2. Advanced Glaucoma Intervention Study All < 18 mmHg 75%-99% < 18 50%-74% < 18 < 50% < 18 The AGIS Investigators. Am J Ophthalmol. 2000;130:429-440.

3. Can MMC or 5-FU give us the low IOP we want without too many complications? nWe could reduce post-op healing nWhat would be the cost? nHow could we get a discount?

4. How to use MMC or 5-FU Safely nThe use of Mitomycin C or 5-Fluorouracil never causes hypotony. nBUT, the use of MMC or 5-FU will preserve any hypotony you create! nAntimetabolites allow one to use a new strategy: 1) set the IOP by adjusting the scleral resistance 2) use antimetabolites to prevent the formation of additional resistance in the conjunctiva-Tenons

5. Highlights of Ophthalmology 1993

10. Primary Filtering Surgery with 5-FU or Mitomycin: Intraocular Pressure Control and Visual Field Data mm Hg # (IOP) MD PSD # fields Pre-OP26.1 212 -14.3 7.58 181 1 Year10.7183-13.67.59 117 2 Years10.8161-12.47.67 96 3 Years10.8143-13.38.18 92 4 Years10.5125-13.68.05 71 5 Years11.8123-11.97.68 65 6 Years10.6 99-13.08.70 47 7 Years11.0 81-12.69.34 42 8 Years11.0 63-12.78.79 22 9 Years10.4 46-10.77.42 19 10 Years11.0 30-12.18.71 13 Ishida K, E Escalona, J Schiffman, Palmberg P, ARVO 2003 Technique: Suner, et al, Ophthalmology 1997:104:207-214.

11. Mean MD over time Mean change of MD over time MD(dB) ⊿ MD(dB) -6 -4 -2 0 2 4 6 ⊿ 1yMD ⊿ 2yMD ⊿ 3yMD ⊿ 4yMD ⊿ 5yMD ⊿ 6yMD ⊿ 7yMD ⊿ 8yMD ⊿ 9yMD ⊿ 10yMD Mean±S.E. N=181 116 96 91 72 65 47 42 22 29 13 N=109 86 85 68 59 44 35 21 23 9 > 0 = deterioration There was no statistical difference between baseline and each year’s value ( Wilcoxon signed ranks test ).

12. Improve tissue function? Hypothesis Occleston et al Invest Ophthalmol Vis Sci 1997, Daniels et al 1999 Exp Eye Res  Growth arrested cells  Release stimulatory factors  Stimulate normal fibroblasts  Ring of scar tissue  “ring of steel”  + Anterior drainage jet  Thinned area

13. System to prevent complications of filtration surgery (trabeculectomy) Infusion Khaw

14. Results Results DiscomfortDiscomfort LeakageLeakage HypotonyHypotony BlebitisBlebitis EndophthalmitisEndophthalmitis

15. Results Results Bleb related problems inc leaks / blebitis / endoph 0% 20% 0% 20% After change Fornix based Large Area MMC 0.5 mg/ml Ophthalmology 2003 in press Before Change Limbus based Small Area MMC 0.4 mg/ml

16. IOP vs 5 Yr Risk of Progression