Outcomes of Tolerating Subretinal Fluid in Type 1 MNV and PCV

Study Overview
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Brief Summary
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The purpose of the present study was to evaluate the outcomes of type 1 macular neovascularization (MNV), including polypoidal choroidal vasculopathy in patients treated tolerating subretinal fluid (SRF) using Aflibercept in a clinical setting. Approximately 150 patients are anticipated to be enrolled in this study. SRF is a primary type of fluid compartment prevalent in type 1 aneurysmal MNV. In a recent study, the prevalence of SRF during 24-month follow-up period was 36.7% to 38.8% in type 1 MNV and polypoidal choroidal vasculopathy (PCV), 20.0% in type 2 MNV, and 7.7% in type 3 MNV. In addition, patients with SRF showed better visual prognosis in type 1 MNV/PCV. For this reason, type 1 MNV is an appropriate candidate for evaluating the influence of tolerating SRF.

Detailed Description
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Tolerating subretinal fluid (SRF) is one of the current major issues in the field of neovascular age-related macular degeneration. Previous post-hoc analysis studies have demonstrated that SRF is not associated with poor visual acuity as well as poor visual outcome. In addition, previous studies showed that tolerating small amount of SRF may not influence visual outcome when using treat-and-extend regimen. Based on these observations, it is generally accepted that small stable amounts of SRF can be tolerated. To date, several clinical trials evaluated association of residual SRF with visual outcome. In these clinical trials, treatment was performed based on strict study protocol. In addition, strict rescue treatment criteria impeded definite under-treatment. However, in a clinical setting, non-scientific factors such as financial or time burden, fear to injection and compliance can influence treatment decisions. As a result, in some patients, more intensive treatment cannot be performed despite substantial amount of persistent retinal fluid. Unlike clinical trials, in real-world practice it is difficult to precisely measure and tolerate fluid in strict amounts. As a result, large degree of fluctuation of fluid volume can occur in some patients. In addition, large amounts of fluid, which may not be tolerated in clinical trials, can persist for a relatively long period. Such cases are usually difficult to encounter in clinical trials because these patients are either treated more intensively or are dropped from the trial. Investigating the outcomes in these cases can provide useful information that cannot be obtained from clinical trials. The purpose of the present study was to evaluate the outcomes of type 1 macular neovascularization (MNV), including polypoidal choroidal vasculopathy in patients treated tolerating SRF using Aflibercept in a clinical setting. Approximately 150 patients are anticipated to be enrolled in this study. SRF is a primary type of fluid compartment prevalent in type 1 aneurysmal MNV. In a recent study, the prevalence of SRF during 24-month follow-up period was 36.7% to 38.8% in type 1 MNV and PCV, 20.0% in type 2 MNV, and 7.7% in type 3 MNV. In addition, patients with SRF showed better visual prognosis in type 1 MNV/PCV. For this reason, type 1 MNV is an appropriate candidate for evaluating the influence of tolerating SRF. This study may contribute to the better understanding the influence of tolerating SRF on treatment outcomes in patients diagnosed with this subtype of neovascular age-related macular degeneration (AMD). In addition, it may also contribute to the evolution of aflibercept T&E therapy, and provide evidence for physicians to guide treatment decisions.

Official Title
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Tolerating Subretinal Fluid in Type 1 Macular Neovascularization and Polypoidal Choroidal Vasculopathy Treated Using Aflibercept

Conditions
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Polypoidal Choroidal Vasculopathy, Choroidal Neovascularization, Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Intravitreal aflibercept injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient who were diagnosed with type 1 MNV or PCV Patients who were treated using aflibercept between January 2021 and December 2022 Patients underwent continuous aflibercept injections with tolerating subfoveal retinal fluid more than 6 months. Exclusion Criteria: Less than 6 months of tolerating-fluid phase Patients without indocyanine green angiography (ICGA) result Patients who received other treatment for neovascular age-related macular degeneration (AMD), except for aflibercept (eg. ranibizumab, bevacizumab, or PDT) History of intraocular or periocular steroid injection History of vitreoretinal surgery or glaucoma surgery History of intraocular inflammation Uncontrolled glaucoma (IOP ≥ 25mmHg)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Type 1 Macular Neovascularization and Polypoidal Choroidal Vasculopathy<br>Patients with type 1 macular neovascularization and polypoidal choroidal vasculopathy who underwent continuous aflibercept injections with tolerating subfoveal retinal fluid more than 6 months | Drug: Intravitreal aflibercept injection<br>* Intravitreal injection of aflibercept (0.2 mg / 0,05 ml; Bayer Co. Ltd.,)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in visual acuity | Change in best-corrected visual acuity (BCVA) between the start and the end of treatment tolerating subretinal fluid | Through study completion, an average of 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who exhibited deterioration of ≥0.3 logMAR BCVA | Proportion of patients who exhibited deterioration of ≥0.3 logMAR BCVA between the start and the end of treatment tolerating subretinal fluid | Through study completion, an average of 20 months | 
| Difference in the BCVA change, according to MNV subtype | Difference in the BCVA change, according to MNV subtype (type 1 MNV vs PCV) | Through study completion, an average of 20 months | 
| Degree of visual deterioration according to the treatment period | Degree of visual deterioration according to the treatment period | Through study completion, an average of 20 months | 
| Degree of visual deterioration according to the height of SRF | Degree of visual deterioration according to the height of SRF | Through study completion, an average of 20 months | 
| Degree of visual deterioration according to the fluctuation of SRF height | Degree of visual deterioration according to the fluctuation of SRF height | Through study completion, an average of 20 months | 
| Comparison of visual outcomes between the following three groups (mean SRF height <100 µm vs ≥100 µm, <200 µm vs ≥200 µm) | Comparison of visual outcomes between the following three groups (mean SRF height <100 µm vs ≥100 µm, <200 µm vs ≥200 µm) | Through study completion, an average of 20 months | 
| Risk factor of developing deterioration of ≥0.2 logMAR BCVA | Risk factor of developing deterioration of ≥0.2 logMAR BCVA | Through study completion, an average of 20 months | 
| Proportion of patients in whom the intraretinal fluid (IRF) developed during treatment tolerating SRF | Proportion of patients in whom the IRF developed during treatment tolerating SRF | Through study completion, an average of 20 months | 
| Difference in visual outcome between patients with and without IRF development | Difference in visual outcome between patients with and without IRF development | Through study completion, an average of 20 months | 
| Risk factors of IRF development | Risk factors of IRF development | Through study completion, an average of 20 months | 
| The incidence of vision-threatening event such as large submacular hemorrhage or tear of retinal pigment epithelium | The incidence of vision-threatening event such as large submacular hemorrhage or tear of retinal pigment epithelium | Through study completion, an average of 20 months | 
| The incidence of SRF resolution without shortening injection interval | The incidence of SRF resolution without shortening injection interval | Through study completion, an average of 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 macular neovascularization, Polypoidal Choroidal Vasculopathy, Subretinal fluid, Aflibercept, Age-related macular degeneration