Abstract
Purpose
The purpose of the present study was to evaluate the long-term incidence and timing of reactivation in patients with type 3 neovascularization who were treated with three monthly anti-vascular endothelial growth factor (VEGF) injections.
Methods
A total of 179 patients (179 eyes) diagnosed with type 3 neovascularization with dry macula after three monthly anti-VEGF loading injections were included in this retrospective study. After the initial treatment, patients were followed up without further injection until the first reactivation. The incidence and timing of the first reactivation after the initial treatment were recorded, and factors predictive of early reactivation (≤ 6 months after the third anti-VEGF injection) were investigated.
Results
During a mean follow-up of 37.5 ± 18.8 months, the first reactivation was noted in 145 patients (81.0%) at a mean of 6.6 ± 4.1 months after the third injection. In 94 eyes (64.8%), reactivation was noted 2–6 months after the third injection, while in 37 eyes (25.5%) it was noted 7–12 months after the third injection. In the remaining 14 eyes (9.7%), the reactivation was noted after this period. The incidence of early reactivation was higher in women (P = 0.014) and patients with thicker choroid (P = 0.026).
Conclusions
In patients with type 3 neovascularization, almost all reactivation was noted within 15 months of the third anti-VEGF injection, suggesting the need for close follow-up and detailed examination during this period. Female patients with thick choroid should be monitored more frequently during this early period.
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References
Congdon N, O’Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P (2004) Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 122:477–485
Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431
Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548
Fauser S, Muether PS (2016) Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br J Ophthalmol 100:1494–1498
Okada M, Kandasamy R, Chong EW, McGuiness M, Guymer RH (2018) The treat-and-extend injection regimen versus alternate dosing strategies in age-related macular degeneration: a systematic review and meta-analysis. Am J Ophthalmol 192:184–197
Hatz K, Prunte C (2016) Changing from a pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related macular degeneration. Br J Ophthalmol 100:1341–1345
Smiddy WE (2009) Economic implications of current age-related macular degeneration treatments. Ophthalmology 116:481–487
Senra H, Ali Z, Balaskas K, Aslam T (2016) Psychological impact of anti-VEGF treatments for wet macular degeneration-a review. Graefes Arch Clin Exp Ophthalmol 254:1873–1880
Kuroda Y, Yamashiro K, Miyake M, Yoshikawa M, Nakanishi H, Oishi A, Tamura H, Ooto S, Tsujikawa A, Yoshimura N (2015) Factors associated with recurrence of age-related macular degeneration after anti-vascular endothelial growth factor treatment: a retrospective cohort study. Ophthalmology 122:2303–2310
Kim JH, Chang YS, Lee DW, Kim CG, Kim JW (2017) Incidence and timing of the first recurrence in neovascular age-related macular degeneration: comparison between ranibizumab and aflibercept. J Ocul Pharmacol Ther 33:445–451
Kim JH, Chang YS, Kim JW, Kim CG, Lee DW (2017) Recurrence in patients with type 3 neovascularization (retinal angiomatous proliferation) after intravitreal ranibizumab. Retina 37:1508–1515
Freund KB, Ho IV, Barbazetto IA, Koizumi H, Laud K, Ferrara D, Matsumoto Y, Sorenson JA, Yannuzzi L (2008) Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina 28:201–211
Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, Freund KB, Sorenson J, Orlock D, Borodoker N (2001) Retinal angiomatous proliferation in age-related macular degeneration. Retina 21:416–434
Nagiel A, Sarraf D, Sadda SR, Spaide RF, Jung JJ, Bhavsar KV, Ameri H, Querques G, Freund KB (2015) Type 3 neovascularization: evolution, association with pigment epithelial detachment, and treatment response as revealed by spectral domain optical coherence tomography. Retina 35:638–647
Su D, Lin S, Phasukkijwatana N, Chen X, Tan A, Freund KB, Sarraf D (2016) An updated staging system of type 3 neovascularization using spectral domain optical coherence tomography. Retina 36(Suppl 1):S40–S49
Xu L, Mrejen S, Jung JJ, Gallego-Pinazo R, Thompson D, Marsiglia M, Freund KB (2015) Geographic atrophy in patients receiving anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Retina 35:176–186
Grunwald JE, Daniel E, Huang J, Ying GS, Maguire MG, Toth CA, Jaffe GJ, Fine SL, Blodi B, Klein ML, Martin AA, Hagstrom SA, Martin DF (2014) Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology 121:150–161
Holz FG, Strauss EC, Schmitz-Valckenberg S, van Lookeren Campagne M (2014) Geographic atrophy: clinical features and potential therapeutic approaches. Ophthalmology 121:1079–1091
Daniel E, Shaffer J, Ying GS, Grunwald JE, Martin DF, Jaffe GJ, Maguire MG (2016) Outcomes in eyes with retinal angiomatous proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Ophthalmology 123:609–616
Mrejen S, Jung JJ, Chen C, Patel SN, Gallego-Pinazo R, Yannuzzi N, Xu L, Marsiglia M, Boddu S, Freund KB (2015) Long-term visual outcomes for a treat and extend anti-vascular endothelial growth factor regimen in eyes with neovascular age-related macular degeneration. J Clin Med 4:1380–1402
Abdelfattah NS, Zhang H, Boyer DS, Sadda SR (2016) Progression of macular atrophy in patients with neovascular age-related macular degeneration undergoing antivascular endothelial growth factor therapy. Retina 36:1843–1850
Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW Jr, Esquiabro M (2007) An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 143:566–583
Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Hykin P, Staurenghi G, Wittrup-Jensen K, Altemark A, Nilsson J, Kim K, Sivaprasad S (2016) Key drivers of visual acuity gains in neovascular age-related macular degeneration in real life: findings from the AURA study. Br J Ophthalmol 100:1623–1628
Kim YK, Park SJ, Woo SJ, Park KH (2016) Choroidal thickness change after intravitreal anti-vascular endothelial growth factor treatment in retinal angiomatous proliferation and its recurrence. Retina 36:1516–1526
Nickla DL, Wallman J (2010) The multifunctional choroid. Prog Retin Eye Res 29:144–168
Barthelmes D, Nguyen V, Walton R, Gillies MC, Daien V (2018) A pharmacoepidemiologic study of ranibizumab and aflibercept use 2013-2016. The Fight Retinal Blindness! Project. Graefes Arch Clin Exp Ophthalmol 256(10):1839–1846. https://doi.org/10.1007/s00417-018-4061-2
Cho HJ, Hwang HJ, Kim HS, Han JI, Lee DW, Kim JW (2017) Intravitreal aflibercept and ranibizumab injections for type 3 neovascularization. Retina 38(11):2150–2158. https://doi.org/10.1097/IAE.0000000000001862
Konstantinidis L, Mameletzi E, Mantel I, Pournaras JA, Zografos L, Ambresin A (2009) Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP). Graefes Arch Clin Exp Ophthalmol 247:1165–1171
Gross NE, Aizman A, Brucker A, Klancnik JM Jr, Yannuzzi LA (2005) Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation. Retina 25:713–718
Chang YS, Kim JH, Yoo SJ, Lew YJ, Kim J (2016) Fellow-eye neovascularization in unilateral retinal angiomatous proliferation in a Korean population. Acta Ophthalmol 94:e49–e53
Kim JH, Chang YS, Kim JW, Kim CG, Lee DW, Kim HS (2018) Long-term visual changes in initially stronger fellow eyes in patients with unilateral type 3 neovascularization. Retina doi: https://doi.org/10.1097/IAE.0000000000002239
Funding
Kim’s Eye Hospital (Seoul, South Korea) provided financial support in the form of funding for English editing support. The sponsor had no role in the design or conduct of this research.
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The study was approved by the Institutional Review Board of Kim’s Eye Hospital (Seoul, South Korea). This study was conducted in accordance with the tenets of the Declaration of Helsinki.
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Informed consent was not obtained in this study. Identifying information about participants was not presented in this study.
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This study was supported by Kim’s Eye Hospital Research Center.
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Kim, J.H., Chang, Y.S., Kim, J.W. et al. Long-term incidence and timing of reactivation in patients with type 3 neovascularization after initial treatment. Graefes Arch Clin Exp Ophthalmol 257, 1183–1189 (2019). https://doi.org/10.1007/s00417-019-04306-1
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DOI: https://doi.org/10.1007/s00417-019-04306-1