Yaşa bağlı maküla dejenerasyonunun yaş tipinde intravitreal ranibizumab enjeksiyonun etkinliğinin araştırılması

Yıl 2018, Cilt: 15 Sayı: 3, 166 - 175, 12.12.2018

Müslüm Toptan , Ahmet Satıcı Ayhan Sağlık

Öz

Amaç: Yaşa bağlı maküla dejenerasyonunun yaş tipinde intravitreal ranibizumab enjeksiyonun etkinliğinin araştırılması.

Materyal ve Metod: Haziran 2009 ile Haziran 2011 tarihleri arasında Harran Üniversitesi Tıp Fakültesi Göz Hastalıkları Anabilim Dalında yaş tip yaşa bağlı maküla dejenerasyonu tanısıyla intravitreal ranibizumab uygulanan ve en az 12 ay izlenen 60 hastanın 60 gözü retrospektif olarak incelenmiştir. Hastalara ranibizumab tedavisi öncesi ve sonrası her kontrolde en iyi düzeltilmiş görme keskinliği ölçümü ve detaylı oftalmolojik muayene yapılmıştır. Tedavi öncesi hastaların renkli fundus fotoğrafları ve fundus floresein anjiografi çekimleri yapılmıştır. Daha sonra fundus floresein anjiografi çekimleri 2 ayda bir gerçekleştirilmiştir. Tedavi şeması olarak ilk 3 ay, ayda bir kez ranibizumab intravitreal olarak uygulanmıştır. 3. aydan sonra en az bir Snellen sırası görme azalması olan, intraretinal veya preretinal hemorajisi bulunan, fundus floresein anjiografide orta derece veya artmış sızıntısı olan olgularda koroid neovaskülarizasyonu aktif olarak kabul edilmiş ve tedavi tekrarlanmıştır. Hastalar her ay kontrole çağrılmıştır. Tedavi sonrası en iyi düzeltilmiş görme keskinliği, ranibizumab enjeksiyon sayısı araştırılmıştır.

Bulgular: Hastaların ortalama yaşı 72,0±7.13 (56-84) idi. Olguların % 53 ü kadın, % 47 si erkek idi. Ortalama takip süresi 16.81±7.34 (12-30) ay idi. Hastaların fundus floresein anjiografide bulgularına göre 60 gözün 32 (% 53) sinde gizli tip, 20 (% 33) sinde baskın klasik tip ve 8 (% 13) inde minimal klasik tip koroid neovaskülarizasyon saptanmıştır. Tedavi öncesi en iyi düzeltilmiş görme keskinliği ortalama logMAR değerleri 0.67±0.29 iken tedavi sonrası 12. ayda 0.59±0.30 olarak saptanmıştır. Gözlerin % 83 ünde görmenin aynı kaldığı veya arttığı saptanmıştır. 3 logMAR sırası ve üzeri kazanımı olan 10 (% 16,6) hasta, 3 sıradan az kazancı olan 16 (% 26,6) hasta, 3 sıradan az kaybı olan 7 (% 11,6) hasta, 3 sıradan fazla kaybı olan 3 (% 5) hasta olduğu saptanmıştır. Ranibizumab uygulanan gözlerde görme keskinliğinde istatistiksel olarak anlamlı düzeyde artış saptanmıştır (p < 0.01). Lezyon tipine göre subgruplar arasında görme artışı bakımından istatistiksel açıdan anlamlı düzeyde bir farklılık saptanmamıştır ( p > 0.05). Takip süresi boyunca ortalama 4.54±1.32 intravitreal ranibizumab enjeksiyonu yapılmıştır. Enjeksiyon sonrası 1. günde 2 gözde GİB değerlerinin 40 mmHg nın üzerinde olduğu saptanmış olup bir hastada akut açı kapanması glokomu, 2 gözde üveitik reaksiyon görülmüştür. Hastalarımızın hiçbirinde sistemik yan etkiye rastlanmamıştır.

Sonuç: Yaşa bağlı maküla dejenerasyonunun yaş tipinde intravitreal ranibizumab enjeksiyonu ile görme keskinliği artmıştır. Sabit uygulama aralığından farklı olarak hastalığın aktivasyon bulgularına göre tedavi uygulanması maliyet bakımından daha yararlı olacaktır. Gerektiğinde tekrarlanan ranibizumab enjeksiyonu her ay uygulananlara göre ilaca ve enjeksiyona bağlı yan etkileri azaltacaktır.

Anahtar Kelimeler

Ranibizumab, maküla dejenerasyonu, neovaskülarizasyon

To evaluate the efficacy of intravitreal ranibizumab injection in wet type age- related macular degeneration

Öz

Background: To evaluate the efficacy of intravitreal ranibizumab injection in wet type age-related macular degeneration.

Material and Methods: Sixty eyes of 60 patients treated with intravitreal ranibizumab injection for wet type age-related macular degeneration that were followed up for at least 12 months were evaluated retrospectively between june 2009 with june 2011 in Harran University Medical School Ophthalmology Department. Before and after ranibizumab treatment, in each control, measurement of best-corrected visual acuity and detailed ophthalmological examination were done to patients. Before treatment, color fundus photographs and fundus fluorescein angiography of patients were performed. Later, fundus fluorescein angiography was realized once in 2 months bimonths. First three months all patients were treated with intravitreal ranibizumab monthly in the treatment protocol. After the third month, chroidal neovascularization was regarded as active on the phenamenans with at least on Snellen line decrease in visual acuity, intraretinal or preretinal hemorrhage, moderate or increased leakage of fundus fluorescein angiography, and the treatment was repeated. Patients were called up to control every month. After treatment, best-corrected visual acuity, ranibizumab injection number was investigated.

Results: Thirty-two patients were female (53 %) and 28 (47 %) were male. Mean age was 72.0±7.13 (56-84) years. The mean follw-up period was 16.81±7.34 (12-30) months. According to fundus fluorescein angiography findings of patients out of 60 eyes 32 (53 %) of them were determined as occult type, 20 (33 %) of them were determined as predominantly classic type and 8 (13 %) of them were determined as minimally classic type choroidal neovascularization. While the average rates of logMAR were 0.67±0.29 before the treatment, on the 12th month after the treatment they were 0.59±0.30. On the 83 % of the eyes , the visual acuity was determined as the some or incresed. It was determined that there were 10 (16.6 %) patiens with 3 logMAR sequens and over acquisition, 16 (26.6 %) patients with a less acquisition of 3 sequences, 7 (11.6 %) patients with a less loss of 3 sequences, 3 (5 %) patients with a more loss of 3 sequences. The mean best-corrected visual acuity was significantly improved (p < 0.01) in all eyes with treatment ranibizumab but there was no statistical difference between the subgroups (p > 0.05). During follow-up period, about 4.54±1.32 intravitreal ranibizumab injection was performed. The first day after injection in both eyes intraocular pressure values were determined over 40 mmHg and acute angle-closure glaucoma in a patient and reaction was observed uveitis in both eyes. None of the patients with systemic side effects were seen.

Conclusion: Intravitreal ranibizumab injection was effective in increasing significantly in patients with wet type age-related macular degeneration. Unlike a fixed range of toolkid, a treatment according to the findings of activation of the disease will be more useful in terms of costs. Considering the ones applied every month, ranibizumab injection repeated as needed will reduce the side effects of drug and injection.

Anahtar Kelimeler

Intravitreal ranibizumab, Macular degeneration, Neovascularization

Kaynakça

• Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992;99(6):933-43.
• Schmidt-Erfurth U, Pruente C. Management of neovascular age-related macular degeneration. Prog Retin Eye Res. 2007;26(4):437-51.
• Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD de Jong PT, Klaver CC, Klein BE, Klein R. An in-ternational classification and grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol. 1995 ;39(5):367-74. Ferris FL, Fine SL, Hyman L. Age-related macular degenera-tion and blindness due to neovascular maculopathy. Arch Oftalmol . 1984;102(11):1640-2.
• Van Leeuwen R, Klaver CC, Vingerling JR, et al. Epidemiol-ogy f age-related maculopathy. Eur J Epidemiol. 2003;18(9):845-54.
• Lin RC, Rosenfeld PJ. Antiangiogenic therapy in neovascular age-related macular degeneration. Int Ophthalmol Clin. 2007;47(1):117-37.
• Rosenfeld PJ, Schwartz SD, Blumenkranz MS. Maximum tolerated dose of a humanized anti-vasculer endothelial growth factor antibody fragment for treating neovaskular age-related maculer degeneration. Ophthalmology 2005;112(6):1048-53.
• Ferrara N, Mass RD ve ark Targeting VEGF A to Treat Can-cer and Age Related Macular Degeneration. Annu Rev Med. 2007;58:491-504.
• Rosenfield PJ, Schwartz SD, Blumenkranz M, et al. Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovaskular age-related maculer degeneration. Ophthalmology. 2005;112(6):1048-53.
• Krzystolik MG, Afsari MA, Adamis PA et al. Prevention of experimental choroidal neovascularization with intravitreal an-ti-vasculer endothelial growth factor antibody fragment. Arch Ophthalmol. 2002;120(3):338-46.
• Hogan MI, Alvaro A, Weddell JE. Histology of the Human Eye An Atlas and Textbook. Philadelphia: WB Saunders Company, 1971;508-519.
• Klein R, Klein BE, Knudston MD, Meuer SM, Swift M, Gag-non RE. Fifteen year cumulative incidence of age-related macular degeneration. The Beaver Dam Eye Study. Oph-thalmology, 2007;114(2):253-62.
• Rosenfeld PJ, Brown DM, Heiser, JS, et al. for MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-31.
• Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degenera-tion. ANCHOR Study Group. N Engl J Med. 2006;355(14): 1432-44.
• Smith W, Assink J, Klein K, Mitchell P, Klaver CCW, Klein BEK, Hofman A, Jensen S. Risk factors for age-related mac-ular degeneration. Pooled findings from three continents. Ophthalmology, 2001;108(4):697-704.
• Altan T, Kapran Z, Yalçın O, et al. Yaşa bağlı Maküla De-jenerasyonunda Subfoveal koroidal Neovaskülarizasyonun verteporfin ile Fotodinamik Tedavisinin Orta ve Uzun Dönem Sonuçları. Retina-Vitreus, 2006;14:169-174.
• Klein R, Peto T, Tod A, Vannewkirk M. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004;137(3):486-95.
• Age-Related Eye Disease Study Research Group. Risk factors for the incidence of advanced age related macular degeneration in the Age-Related Eye Disease Study: AREDS report no. 19 Ophthalmol. 2005; 112(4): 533-539.
• H A Moeini, H Masoudpour, H Ghanbari. A study of the relation between body mass index and the incidence of age related macular degeneration. Br J Ophthalmol. 2005;89(8):964-6.
• M Miyazaki, H Nakamura, M Kubo ve ark. Risk factors for age-related maculopathy in a japanese population: The Hisayama study. Br J Ophthalmol. 2003; 87(4): 469-72.
• Bell S, Klein R, Azen A ve ark. Cardiovasculer risk factors and age-related macular degeneration: The Los Angeles La-tino Eye Study. Am J Ophthalmol. 2008; 145(2):308-16.
• Regillo DC, Brown DM, Abraham P. Randomized, double-masked, shamcontrolled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 1. Am J Ophthalmol. 2008;145(2):239-248.
• Mantel I, Zografos L, Ambresin A. Early clinical experience with ranibizumab for occult and minimally classic neovascular membranes in age-related macular degeneration. Ophthal-mologica. 2008;222(5):321-3.
• Querques G, Azrya S, Martinelli D, et al. Ranibizumab for exudative age-related macular degeneration: 24 months outcomes from a single-center institutional setting. Br J Oph-thalmol. ;94(3):292-6.
• Cohen SY, Dubois L, Tadayoni R, et al. Result of one-year’s treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting. Am J Ophthalmol. 2009;148(3):409-13.
• Dadgostar H, Ventura AA, Chung JY,et al. Evaluation of injection frequency and visual acuity outcomes for ranibi-zumab monotherapy in exudative age-related macular de-generation. Ophthalmology. 2009;116(9): 1740-7.
• Wykrota H, Gierek-Lapifska A, Trzciakowski K, Gajdzik-Gajdecka U. Ranibizumab for treatment of exudative age-related macular degeneration-own experience. Klin Oczna. 2007; 109(10-12):402-9.
• Sorensen TL, Kemp H. Intravitreal ranibizumab for age-related macular degeneration. Ugeskr Laeger. 2010;172(22):1685-9.
• Rothenbuehler SP, Waeber D, Brinkmann CK, et al. Effects of ranibizumab in patients with subfoveal choroidal neovas-cularization attributable to age-related macular degeneration. Am J Ophthalmol. 2009;147(5):831-7.
• Aslankara H, Öner H, Yaman A, Ergin M, Saatci O. Yaş tip yaşa bağlı maküla dejenerasyonunda intravitreal ranibi-zumab enjeksiyonu. Ret-Vit. 2010;18:134-138.
• Kocak N, Kaya M, Selver Ö, Ayhan Z, Kaynak S. Koroid neovaskülarizasyonunda ranibizumab monoterapisinin erken dönem sonuçları. Turk J Ophthalmol. 2011;41:10-5.
• Hughes MS, Sang DN. New combination approaches ex-plored for AMD management. Retina Today, 2007;6:14-18.