DİYABETİK MAKULA ÖDEMİNİN FARMAKOLOJİK YÖNETİMİNDE GÜNCEL GELİŞMELER: İNTRAVİTREAL ENJEKSİYON UYGULAMALARI VE SÜREKLİ İLAÇ SALINIM SİSTEMLERİ

Diyabetik makula ödemi, diyabet hastalarında görme kaybının başlıca sebeplerinden biridir. Lazer fotokoagülasyon tedavisi çok uzun yıllardır standart tedavi olmasına rağmen, önemli bir grup hastada lazer fotokoagülasyon tedavisine yanıt alınamamaktadır. Vasküler endotelyal büyüme faktörü inhibitörü ilaçların intravitreal olarak uygulanması diyabetik makula ödemi tedavisinde günümüzde yaygın olarak kullanılmaktadır. Diyabetik retinopatide de artan vasküler endotelyal büyüme faktörü sonucunda retinal vasküler geçirgenlik artar ve bu da kan-retina bariyerinin yıkılmasına ve retinal ödeme neden olmaktadır. Bugüne kadar diyabetik makula ödemi tedavisinde ranibizumab, bevasizumab, pegabtanib sodyum gibi çok sayıda farklı vasküler endotelyal büyüme faktörü inhibitörü üzerinde çalışılmıştır. Pegaptanib sodyum, sentetik olarak üretilmiş, vasküler endotelyal büyüme faktörü-A 165 izomerine bağlanan bir ribonükleik asit aptameridir. Seçici olarak vasküler endotelyal büyüme faktörü-A’nın heparin bağlama alanına bağlanarak ve vasküler endotelyal büyüme faktörü-A 165 ve daha büyük izomerlerin vasküler endotelyal büyüme faktörü reseptörüne bağlanmasını engeller. Vasküler endotelyal büyüme faktörü için yüksek seçicilik gösterir. Bevasizumab ve ranibizumab vasküler endotelyal büyüme faktörü A’nın tüm izoformlarına karşı etki eden rekombinan insanlaştırılmış antikorlarıdır. Daha sonraları, vasküler endotelyal büyüme faktörü A ve B’nin tüm izoformlarına bağlanan ve inhibe eden rekombinan füzyon proteini olan aflibersept kullanıma sunulmuştur. T üm vasküler endotelyal büyüme faktörü proteinlerini bloke ettiği için vasküler endotelyal büyüme faktörü tuzağı olarak da bilinmektedir. Vasküler endotelyal büyüme faktörü mesajcı RNA’sını azaltmak ve inaktif hale getirmek üzere tasarlananan bevasiranib ve yine vasküler endotelyal büyüme faktörü tarafından tetiklenen anjiogenez gibi büyüme faktörü ilişkili sinyalleri birleştiren bir kinaza etki ederek faaliyet gösteren sirolimus da son dönemlerde kullanılmaya başlanmıştır.Bu derlemede, günümüzde diyabetik makula ödemi tedavisinde uygulanan intravitreal enjeksiyon uygulamaları ve sürekli ilaç salınım sistemleri tartışılmıştır.

INTRAVITREAL INJECTION APPLICATIONS AND SUSTAINED DRUG DELIVERY SYSTEMS

Diabetic macular edema is the leading cause of vision loss in diabetic patients. Although laser photocoagulation is used for standart therapy for many years, it is unresponsive in a significant group of patient. Nowadays, intravitreal injection of vascular endothelial growth factor inhibitors has been widely used in diabetic macular edema treatment. As a result of the increase in vascular endothelial growth factor in diabetic retinopathy, retinal vascular permeability increases and this leads to destroy of blood-retina barrier and retinal edema. Many vascular endothelial growth factor inhibitors such as bevacizumab, ranibizumab and pegabtanib sodium are studied on the treatment of diabetic macular edema. Pegabtanib sodium is a ribonucleic acid aptamer which binds to the vascular endothelial growth factor A 165 isomer. It binds selectively to the heparine binding area of vascular endothelial growth factor A and inhibits the binding of vascular endothelial growth factor A 165 and greater isomers to the vascular endothelial growth factor receptor. Pegabtanib sodium demonstrates a great selectivity for vascular endothelial growth factor A. Bevacizumab and ranibizumab are humanized anticor which effect on all isomers of vascular endothelial growth factor A. More recently, aflibercept a recombinant fusion protein binds and inhibits to all isoforms of vascular endothelial growth factor A and B aflibercept was presented for usage. It is also known as vascular endothelial growth factor-trap for blocking the whole vascular endothelial growth factor proteins. Bevasiranib is designed for reducing and inactivating vascular endothelial messanger RNA and sirolimus effects by growth factor induced angiogenesis related with combining signals effect of kinase activity are also used recently. In this review, current use of intravitreal injection applications and sustained drug delivery systems in diabetic macular edema is discussed.

Kaynakça

34. Krishnadev N, Forooghian F, Cukras C, et al: Subconjunctival sirolimus in the treatment of diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2011;249(11):1627-1633.

33. Dedania VS, Bakri SJ. Novel pharmacotherapies in diabetic retinopathy. Middle East Afr J Ophthalmol. 2015;22(2):164-173.

32. Nguyen QD, Schachar RA, Nduaka CI, et al: Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study). Invest Ophthalmol Vis Sci 2012;53(12):7666-7674.

31. Callanan DG, Gupta S, Boyer DS, et al. Ozurdex PLACID Study Group.Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema. Ophthalmology. 2013 Sep;120(9):1843-1851.

30. Lim JW, Lee HK, Shin MC: Comparison of intravitreal bevacizumab alone or combined with triamcinolone versus triamcinolone in diabetic macular edema: a randomized clinical trial. Ophthalmologica 2012;227(2):100-106.

29. Gillies MC, McAllister IL, Zhu M, et al: Intravitreal triamcinolone prior to laser treatment of diabetic macular edema: 24-month results of a randomized controlled trial. Ophthalmology 2011;118(5):866-872.

28. Agarwal A, Sarwar S, Sepah YJ, Nguyen QD. What have we learnt about the management of diabetic macular edema in the antivascular endothelial growth factor and corticosteroid era? Curr Opin Ophthalmol. 2015;26(3):177-183.

27. Do DV, Nguyen QD, Boyer D, et al: One-year outcomes of the Da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 2012;119(8):1658-1665.

26. Heier JS, Brown DM, Chong V, et al: Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology 2012;119(12):2537-2548.

25. Sultan MB, Zhou D, Loftus J, Dombi T, Ice KS: A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology 2011;118(6):1107-1118.

24. Sivaprasad S, Crosby-Nwaobi R, Heng LZ, Peto T, Michaelides M, Hykin P: Injection frequency and response to bevacizumab monotherapy for diabetic macular oedema (BOLT report 5). Br J Ophthalmol 2013;97(9):1177-1180.

23. Soheilian M, Ramezani A, Obudi A, et al: Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology 2009;116(6):1142-1150.

22. Lam DS, Lai TY, Lee VY, Chan CK, et al: Efficacy of 1. 25 mg versus 2. 5 mg intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial. Retina 2009;29(3):292-299.

21. Arevalo JF, Sanchez JG, Wu L, et al: Primary intravitreal bevacizumab for diffuse diabetic macular edema: the Pan-American Collaborative Retina Study Group at 24 months. Ophthalmology 2009;116(8):1488-1497.

20. Brown DM, Nguyen QD, Marcus DM, et al: Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 2013;120(10):2013-2022.

19. Nguyen QD, Brown DM, Marcus DM, et al: Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 2012;119(4):789-801.

18. Nguyen QD, Shah SM, Heier JS, et al: Primary end point (six months) results of the Ranibizumab for Edema of the Macula in Diabetes (READ-2) study. Ophthalmology 2009;116(11):2175-2181.

17. Mitchell P, Bandello F, Schmidt-Erfurth U, et al: The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011;118(4):615-625.

16. Massin P, Bandello F, Garweg JG, et al: Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010;33(11):2399-2405.

15. Ferrara N, Damico L, Shams N, Lowman H, Kim R: Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 2006;26(8):859-870.

14. Iacono P, Battaglia Parodi M, Bandello F: Antivascular endothelial growth factor in diabetic retinopathy. Dev Ophthalmol 2010;46(1):39-53.

13. Stewart MW. Anti-VEGF therapy for diabetic macular edema. Curr Diab Rep. 2014;14(8):510.

12. Campochiaro PA, Brown DM, Pearson A, et al: Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology 2012;119(10):2125-2132.

11. Boyer DS, Faber D, Gupta S, et al: Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina 2011;31(5):915-923.

10. Funatsu H, Noma H, Mimura T, Eguchi S, Hori S: Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 2009;116(1):73-79.

9. Beck RW, Edwards AR, Aiello LP, et al. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation andintravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009;127(3):245-251.

8. Gillies MC, Simpson JM, Gaston C, et al: Five-year results of a randomized trial with open-label extension of triamcinolone acetonide for refractory diabetic macular edema. Ophthalmology 2009;116(11):2182-2187.

7. Jonas JB: Intravitreal triamcinolone acetonide: a change in a paradigm. Ophthalmic Res 2006;38(4):218-245.

6. Audren F, Erginay A, Haouchine B, et al: Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial. Acta Ophthalmol Scand 2006;84(5):624-630.

5. Lee SS, Hughes PM, Robinson MR: Recent advances in drug delivery systems for treating ocular complications of systemic diseases. Curr Opin Ophthalmol 2009;20(6):511-519.

4. Beck RW, Edwards AR, Aiello LP, et al: Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 2009;127(3):245-251.

3. Bandello F, Battaglia Parodi M, Lanzetta P, et al: Diabetic macular edema. Dev Ophthalmol 2010;47(1):73-110.

2. Lee CM, Olk RJ: Modified grid laser photocoagulation for diffuse diabetic macular edema. Long-term visual results. Ophthalmology 1991;98(10):1594-1602.

1. Frank RN. Diabetic retinopathy and systemic factors. Middle East Afr J Ophthalmol. 2015;22(2):151-156.

Kaynak Göster