Biomedical papers, 2014 (vol. 158), issue 1

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014, 158(1):138-143 | 10.5507/bp.2012.066

Progression of macular atrophy after PDT combined with the COX-2 inhibitor Nabumetone in the treatment of neovascular ARMD

Martin Sina, Oldrich Chrapeka, Marta Karhanovaa, Zuzana Pracharovaa, Katerina Langovab, Jiri Rehaka
a Department of Ophthalmology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
b Department of Medical Biophysics, Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc

Aim: To evaluate photodynamic therapy (PDT) combined with the preferential the cyclooxygenase-2 (COX-2) inhibitor, nabumetone in the treatment of the neovascular age-related macular degeneration (ARMD).

Methods: A prospective, double-blind, randomized study on 60 patients with subfoveal CNV secondary to ARMD without any previous treatment. Patients were divided into a nabumetone or placebo group. The main endpoints were the change of best-corrected visual acuity (BCVA), central macular thickness (CRT) and number of required PDT treatments.

Results: In the nabumetone group, 27 patients (90%) and 28 (93%) in the placebo group completed the follow-up of 12 months. In the nabumetone group, the mean CRT decreased from 332 μm (SD 68 μm) to 220 μm (SD 46 μm). In the placebo group, CRT decreased from 331 μm (SD 72 μm) to 254 μm (SD 61 μm). The mean BCVA was 0.68 log MAR (SD 0.22 log MAR) in the nabumetone group and 0.62 log MAR (SD 0.23 log MAR) in the placebo group at baseline. This stabilised in the placebo group to 0.66 log MAR (SD 0.33) but deteriorated in the nabumetone group to 0.86 logMAR (SD 0.41 log MAR). There was a significant reduction in the number of required PDTs in the nabumetone group, but significant progression of the RPE atrophy area.

Conclusion: Combined PDT with oral intake of the COX-2 inhibitor, nabumetone reduced the number of required PDT retreatments, but worsening BCVA caused by macular atrophy progression. Therefore the combination of the PDT with the nabumetone is not recommended.

Keywords: age-related macular degeneration, cyclooxygenase-2, CD36 metabolic pathway, combination therapy, nabumetone, macula atrophy progression, choroidal atrophy

Received: March 1, 2012; Accepted: June 20, 2012; Published: November 6, 2012; Published: April 1, 2014


References

  1. Treatment of age-related macular degeneration with photodynamic therapy (TAP) study group: photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials. TAP report 1. Arch Ophthalmol 1999;117:1329-45. Go to PubMed...
  2. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 2003;44:4473-80. Go to original source... Go to PubMed...
  3. Tatar O, Adam A, Shinoda K, Stalmans P, Eckardt C, Lüke M, Bartz-Schmidt KU, Grisanti S. Expression of VEGF and PEDF in choroidal neovascular membranes following verteporfin photodynamic therapy. Am J Ophthalmol 2006;142:95-104. Go to original source... Go to PubMed...
  4. Tatar O, Shinoda K, Adam A, Eckert T, Eckardt C, Lucke K, Deuter C, Bartz-Schmidt KU, Grisanti S. Effect of verteporfin photodynamic therapy on endostatin and angiogenesis in human choroidal neovascular membranes. Br J Ophthalmol 2007;91:166-73. Go to original source... Go to PubMed...
  5. Shah GK, Sang DN, Hughes MS. Verteporfin combination regimens in the treatment of neovascular age-related macular degeneration. Retina 2009;29:133-48. Go to original source... Go to PubMed...
  6. Rajakariar R, Yaqoob MM, Gilroy DW. COX-2 in inflammation and resolution. Mol Interv 2006;6:199-207. Go to original source... Go to PubMed...
  7. Davies NM, Good RL, Roupe KA, Yáñez JA. Cyclooxygenase-3: axiom, dogma, anomaly, enigma or splice error? - Not as easy as 1, 2, 3. J Pharm Pharm Sci 2004;7:217-26. Go to PubMed...
  8. Wilkinson-Berka JL. Vasoactive factors and diabetic retinopathy: vascular endothelial growth factor, cycoloxygenase-2 and nitric oxide. Curr Pharm Des 2004;10:3331-48. Go to original source... Go to PubMed...
  9. Maloney SC, Fernandes BF, Castiglione E, Antecka E, Martins C, Marshall JC, Di Cesare S, Logan P, Burnier MN Jr. Expression of cyclooxygenase-2 in choroidal neovascular membranes from age-related macular degeneration patiens. Retina 2009;29:176-80. Go to original source... Go to PubMed...
  10. Hu W, Criswell MH, Ottlecz A, Cornell TL, Danis RP, Lambrou GN, Ciulla TA. Oral administration of lumiracoxib reduces choroidal neovascular membrane development in the rat laser-trauma model. Retina 2005;25:1054-64. Go to original source... Go to PubMed...
  11. Chan CK, Pham LN, Zhou J, Spee C, Ryan SJ, Hinton DR. Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization. Lab Invest 2005;85:721-33. Go to original source... Go to PubMed...
  12. Ferrario A, Von Tiehl K, Wong S, Luna M, Gomer CJ. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Cancer Res 2002;62:3956-61. Go to PubMed...
  13. Castro MR, Lutz D, Edelman JL. Effect of COX inhibitors on VEGF-induced retinal vascular leakage and experimental corneal and choroidal neovascularization. Exp Eye Res 2004;79:275-85. Go to original source... Go to PubMed...
  14. Wilkinson-Berka JL, Alousis NS, Kelly DJ, Gilbert RE. COX-2 inhibition and retinal angiogenesis in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 2003;44:974-9. Go to original source... Go to PubMed...
  15. Takahashi H, Yanagi Y, Tamaki Y, Uchida S, Muranaka K. COX-2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model. Biochem Biophys Res Commun 2004;325(2):461-6. Go to original source... Go to PubMed...
  16. Hedner T, Samulesson O, Währborg P, Wadenvik H, Ung KA, Ekbom A. Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. Drugs 2004;64:2315-43. Go to original source... Go to PubMed...
  17. Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, Taylor RS. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess 2008;12:1-278. Go to original source... Go to PubMed...
  18. Dewi NA, Yuzawa M, Tochigi K, Kawamura A, Mori R. Effects of photodynamic therapy on the choriocapillaris and retinal pigment epithelium in the irradiated area. Jpn J Ophthalmol 2008;52(4):277-81. Go to original source... Go to PubMed...
  19. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44. Go to original source... Go to PubMed...
  20. Lux A, Llacer H, Heussen FM, Joussen AM. Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions. Br J Ophthalmol 2007;91:1318-22. Go to original source... Go to PubMed...
  21. Adjunctive diclofenac with verteporfin (ADD-V) study group. Effect of adjunctive diclofenac with verteporfin therapy to treat choroval neovascularisation due to age-related macular degeneration. Phase II study. Retina 2007;27:693-700. Go to PubMed...
  22. Ranchod TM, Guercio JR, Ying GS, Brucker AJ, Stoltz RA. Effect of aspirin therapy on photodynamic therapy with verteporfin for choroidal neovascularization. Retina 2008;28:711-6. Go to original source... Go to PubMed...
  23. Debefve E, Pegaz B, Ballini JP, Konan YN, van den Bergh H. Combination therapy using aspirin-enhanced photodynamic selective drug delivery. Vascul Pharmacol 2007;46:171-80. Go to original source... Go to PubMed...
  24. van Kraaij DJ, Hovestad-Witterland AH, de Metz M, Vollaard EJ. A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers. Br J Pharmacol 2002;53:644-647. Go to original source... Go to PubMed...
  25. Houssier M, Raoul W, Lavalette S, Keller N, Guillonneau X, Baragatti B, Jonet L, Jeanny JC, Behar-Cohen F, Coceani F, Scherman D, Lachapelle P, Ong H, Chemtob S, Sennlaub F. CD36 Deficiency Leads to Choroidal Involution via COX2 Down-Regulation in Rodents. PLoS Med 5(2):e39. doi:10.1371/journal.pmed.0050039 Go to original source... Go to PubMed...
  26. Nishijima K, Ng YS, Zhong L, Bradley J, Schubert W, Jo N, Akita J, Samuelsson SJ, Robinson GS, Adamis AP, Shima DT. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol 2007;171:53-67. Go to original source... Go to PubMed...