Intravitreal Aflibercept Application in Patients with Type 1 Choroidal Neovascular Membrane Resistant to Ranibizumab Treatment Results

Öz

Aim: To research efficacy of intravitreal aflibercept injection treatment in patients who are resistant to ranibizumab treatment and having type 1 choroidal neovascular membranes. Material and Methods: Twenty four eyes of 22 patients having neovascular age related macular degeneration (AMD) diagnosed as type 1 choroidal neovascular membrane were identified by optical coherence tomography (OCT) and fundus fluorescein angiography at Haydarpasa Numune Research and Training Hospital between Dec’12 and Jan’16 and were analyzed retrospectively. Baseline and post-ranibizumab treatment of best-corrected visual acuity (BCVA), fundus findings and central retinal thickness with OCT of patients were recorded. In order to assess efficacy of intravitreal aflibercept treatment the mean numbers of injections, BCVA and the mean central retinal thickness were statistically compared with baseline and post- treatment figures. NCSS program (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) was used for statistical analysis. Descriptive analyses were presented using means and standard deviations for normally distributed variables. The Mann Whitney U test was used for the comparison of the quantitative data and the comparison of the parameters that did not show normal distribution between the two groups. Kruskal Wallis test was used for comparisons of groups of three or more that did not show normal distribution. Wilcoxon Signed Ranks test was used for in-group comparisons of parameters that did not show normal distribution. Significance was evaluated at p<0.05 levels. Results: The mean follow-up time was 35.32±13.36 months. The mean central retinal thickness decreased 80.25±76.32 μm as a result of aflibercept treatment compared to ranibizumab treatment and the outcomes were statistically significant (p=0.001; p<0.01). No significant difference was observed in BCVA between aflibercept and ranibizumab treatment (p>0.05). No significant difference was observed with respect to the location of retinal fluid or existence of PED in the efficacy of aflibercept (p>0.05). Conclusion: Anatomic improvement was confirmed in all patients who were resistant to ranibizumab. Retinal fluid location and existence of PED may not be a decisive factor at efficacy of aflibercept in patients resistant to ranibizumab.

Anahtar Kelimeler

• aflibercept
• age-related macular degeneration
• best corrected visual acuity
• ranibizumab
• type 1 choroidal neovascularization

Ranibizumab Tedavisine Dirençli Tip 1 Koroidal Neovasküler Membranlı Olgularda İntravitreal Aflibercept Uygulaması Sonuçlarımız

Öz

Amaç: Ranibizumab tedavisine dirençli tip 1 koroidal neovasküler membranlı olgularda intravitreal aflibercept tedavisinin etkinliğini araştırmak. Gereç ve Yöntemler: Haydarpaşa Numune Eğitim ve Araştırma Hastanesi Göz Kliniği’ne Aralık 2012- Ocak 2016 tarihleri arasında başvurup, neovasküler tip yaşa bağlı makula dejenerasyonu (YBMD) tanısı alan, optik koherens tomografi (OKT) ve fundus floresein anjiografi (FFA) ile tip 1 koroidal neovasküler membranı (KNV) olduğu tespit edilen 22 hastanın 24 gözü geriye dönük olarak incelendi. Olguların ilk başvurularındaki ve ranibizumab tedavisi sonrasındaki en iyi düzeltilmiş görme keskinlikleri (EİDGK), fundus muayene bulguları ve OKT ile yapılan makula kalınlığı ölçümleri kaydedildi. İntravitreal aflibercept tedavisinin etkinliğini değerlendirmek için tedavi öncesi ve sonrasındaki EİDGK’leri, ortalama enjeksiyon sayıları ve ortalama makula kalınlıkları istatistiksel olarak karşılaştırıldı. İstatistiksel analizler için NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) programı kullanıldı. Çalışma verileri değerlendirilirken tanımlayıcı istatistiksel metodların (Ortalama, Standart Sapma, Medyan, Frekans, Oran, Minimum, Maksimum) yanı sıra; niceliksel verilerin karşılaştırılmasında normal dağılım göstermeyen parametrelerin iki grup karşılaştırmalarında ise Mann Whitney U testi kullanıldı. Normal dağılım göstermeyen üç ve üzeri grupların karşılaştırmalarında ise Kruskal Wallis test kullanıldı. Normal dağılım göstermeyen parametrelerin grup içi karşılaştırmalarında ise Wilcoxon Signed Ranks test kullanıldı. Anlamlılık p<0.05 düzeylerinde değerlendirildi. Bulgular: Olgular kliniğe ilk başvurudan itibaren ortalama 35,32±13,36 ay takip edildi. Ranibizumab tedavisi sonrası ortalama makula kalınlığı ölçümlerine göre aflibercept tedavisi sonrası ortalama makula kalınlığı ölçümlerinde 80,25±76,32 μm’luk düşüş saptandı ve istatistiksel olarak anlamlı bulundu. (p=0,001; p<0,01) Ranibizumab tedavisi sonrası EİDGK ölçümleri ile aflibercept tedavisi sonrası EİDGK ölçümleri arasında istatistiksel olarak anlamlı bir farklılık saptanmadı. (p>0,05) Retinal sıvının lokasyonuna göre (subretinal, intraretinal, her ikisi birden ya da kistoid dejenerasyon) ya da pigment epitel dekolmanı (PED) mevcudiyetine göre aflibercept tedavisi başarısında anlamlı bir farklılık görülmedi (p>0,05). Sonuç: Çalışmamızda ranibizumab tedavisine dirençli neovasküler YBMD’nin intravitreal aflibercept enjeksiyonu ile tedavisinde anatomik iyileşme sağlandı. Retinadaki sıvı lokasyonunun, PED mevcudiyetinin, tedaviye dirençli vakalarda aflibercept etkinliğinde belirleyici faktör olmayabileceği düşünüldü.

Anahtar Kelimeler

• aflibercept
• görme keskinliği
• ranibizumab
• tip 1 koroid vaskülarizasyonu
• yaşa bağlı makula dejenerasyonu

Kaynakça

1. 1. Karaçorlu M, Karaçorlu S, Bürümcek ve ark. Yaşa bağlı makula dejenerasyonunda fotodinamik tedavi uygulamasının klasik koroid neovaskülarizasyonlu olgular ile klasik+gizli koroid neovaskülarizasyonlu olgulardaki 6 aylık takip sonuçları. T Oft Gaz 2002;32:832-837
2. 2. Haab, O. Erkrankungen der Macula Lutea. Centralbhat Augenheilkd 1985; 9:384-391.
3. 3. Thompson W: Classification of Age-Related Macular Degeneration. In: Alfaro DV III, Liggett PE, Mieler WF, Mercado HQ et al. Age-Related Macular Degeneration. Philadelphia: Lippincott William & Wilkins; 2006:44-52.
4. 4. Karaçorlu Arf S: Non-Neovasküler (Kuru Tip) Yaşa bağlı Makula Dejeneresansı. Tıbbi Retina (Türk Oftalmoloji Derneği Eğitim yayınları No:10) İstanbul: Epsilon; 2009:63-72.
5. 5. Age-Related Macular Degeneration. In: Bandella F,ed. Loures: Ondagrafe-Artes Graficas, 2010.
6. 6. Stewart MW. Clinical and Differential Utility of VEGF inhibitors in wet age-related macular degeneration: Focus on Aflibercept. Clin Ophthalmol:2012;4:1178-86.
7. 7. Ehlken C, Jungmann S, Böhringer D, et al. A. Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD. Eye (Lond). 2014;28:538-45..
8. 8. Moisseiev E, Katz G, Moisseiev J, et al. Switching treatment for neovascular age-related macular degeneration from bevacizumab to ranibizumab: who is likely to benefit from the switch? Retina. 2015;35:1323-30.


9. 9. Küçükerdönmez C, Gelisken F, Yoeruek E, et al. Switching intravitreal anti-VEGF treatment in neovascular age-related macular degeneration. Eur J Ophthalmol. 2015;25:51-6.
10. 10. Pinheiro-Costa J, Costa JM, Beato JN, et al. Switch to Aflibercept in the treatment of Neovascular AMD: one-year results in clinical practice. Ophthalmologica. 2015;233:155-61.
11. 11. Bakall B, Folk JC, Boldt HC, et al. Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol. 2013;156:15-22.
12. 12. Singh RP, Srivastava S, Ehlers JP, et al. A single- arm, investigator-initiated study of the efficacy, safety and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration, previously treated with ranibizumab or bevacizumab: 6-month interim analysis. Br J Ophthalmol. 2014;98:22-27.
13. 13. Hall LB, Zebardast N, Huang JJ, et al. Aflibercept in the treatment of neovascular age-related macular degeneration in previously treated patients. J Ocul Pharmacol Ther. 2014;30:346-52.
14. 14. Friedman DS, O’Colmain BJ, Munoz B, et al. Prevalance of age-related macular degeneration in the United States. Archieves of Opthtalmology 2004;122:564-72.
15. 15. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, Fine SL, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration:two-year results. Ophthalmology. 2012;119:1338-1398.
16. 16. Semeraro F, Morescalchi F, Duse S, et al. Aflibercept in wet AMD: specific role and optimal use. Drug Des Devel Ther 2013;7:711-22.
17. 17. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537-2548.
18. 18. Sarwar S, Clearfield E, Soliman MK, et al. Aflibercept for neovascular age-related macular degeneration. Cochrane Database of Systematic Reviews 2016, Issue 2. Art. No: CD011346.
19. 19. Yonekawa Y, Andreoli C, Miller JB, et al. Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol.2013;156:29-35.
20. 20. Suzuki M, Nagai N, Izumi-Nagai K, et al. Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration. Br J Ophthalmol 2014;98:1186-91.
21. 21. Hirakata T., Fujinami K., Watanabe K., et al. One-year outcome of intravitreal aflibercept injection for age-related macular degeneration resistant to ranibizumab: rapid morphologic recovery and subsequent visual improvement. Clin Ophthalmol 2016:10, 969-77.
22. 22. Nagai N., Suzuki M., Uchida A, et al. Non-responsiveness to intravitreal aflibercept treatment in neovascular age related macular degeneration: implications of serous pigment epithelial detachment. Scientific Reports. 2016;6:29619.
23. 23. Kim JH, Lee DW, Chang YS, et al. Twelve-month outcomes of treatment using ranibizumab or aflibercept for neovascular age-related macular degeneration: a comparative study. Graefes Arch Clin Exp Ophthalmol 2016;254:2101-9.
24. 24. Muftuoglu İ., Arcinue C., Tsai FF, et al. Long-term results of Pro Re Nata regimen of aflibercept treatment in persistent neovascular age-related macular degeneration. Am J Ophthalmol 2016;167:1-9.
25. 25. Singh RP, Srivastava S, Ehlers JP, et al. A single-arm, investigator-initiated study of the efficacy, safety and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration, previously treated with ranibizumab or bevacizumab: 6-month interim analysis. Br J Ophthalmol 2014;98,22-27.