Treat-and-extend Using Aflibercept for Type 3 Neovascularization

Description

Type 3 neovascularization also called retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (AMD) that is characterized by intraretinal neovascularization.

The incidence of type 3 neovascularization is relatively lower than other subtypes of neovascular AMD, constituting 10 to 20% of entire neovascular AMD. However, it is a very important disorder because it often leads bilateral visual deterioration. The high risk of bilateral involvement is characteristic of type 3 neovascularization. In some cases, the visual prognosis of the initially uninvolved eye with better vision, is poorer than the initially involved eye. In addition, profound visual loss may occur during the treatment course, especially in undertreated cases. Thus, preserving vision is particularly important in type 3 neovascularization, which subsequently highlights the importance of investigating more effective treatment strategies. Previous study suggested the need for proactive treatment in type 3 neovascularization to reduce the risk of abrupt visual loss.

Treat-and-extend (TAE) regimen is a widely-used, effective anti-vascular endothelial growth factor treatment regimen for neovascular age-related macular degeneration (AMD), regardless of subtypes of AMD. However, since type 3 neovascularization is at high risk of GA, there has been some debate regarding the benefit of TAE, when compared to the as-needed regimen, for treating type 3 neovascularization. Despite some controversy, reports indicated that increased injection frequency is associated with development or progression of GA. Thus, it is important to balance efficacy and efficiency when treating type 3 neovascularization.

Type 3 neovascularization is a disorder in which the treatment outcome of TAE regimen was first reported. Nevertheless, only limited evidence has been available regarding the efficacy of TAE using aflibercept in this disorder. In addition, all the previous studies were retrospective, based on relatively small study population. Moreover, results of extending the injection interval to 4 months have not yet been reported. Recently, ALTAIR study provides a scientific evidence that injection interval can be extended to 4 months when using TAE regimen. In type 3 neovascularization, extending the injection interval is not only decreases treatment burden of the patient, but also may improve long-term visual outcomes because it may decrease the injection frequency. If this regimen is found to be effective in type 3 neovascularization, it may contribute to more widespread use of TAE regimen using aflibercept for type 3 neovascularization.

In addition, there are two questions which have not been addressed in previous TAE studies for type 3 neovascularization. The first question is "Is the treatment using TAE regimen can impede the fundamental progression of the disorder?". Since visual loss in type 3 neovascularization usually develops in stage 3 disorder (eyes exhibits serous pigment epithelial detachment on OCT, it will be a very meaningful result if TAE can impede stage progression. The second question is "Is there any clues to predict the recurrence of fluid?" Since avoiding under-treatment is very important in type 3 neovascularization, it is very important to identify any factor predictive of recurrence. To address this question, it is necessary to evaluate the serial changes in vascular morphology of type 3 neovascularization lesion. Previously, however, this kind of approach cannot be performed because it requires frequent, serial indocyanine-green angiography examination. Fortunately, recent advent of OCT-angiography provides simple and safe evaluation of vascular morphology. By using OCT-angiography, any vascular morphologic changes preceding the recurrence of fluid during the TAE treatment can be evaluated.

The purpose of the present study is to investigate the 18-month treatment outcome of TAE in type 3 neovascularization. The maximum injection interval was set as 4 months. Since the ALTAIR study nicely show how to extend the interval to 4 months, the study protocol of ALTAIR study was partly adopted in the present study.

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