Clinical trial NCT05662943: Outcomes of Tolerating Subretinal Fluid in Type 1 MNV and PCV
Official title: Tolerating Subretinal Fluid in Type 1 Macular Neovascularization and Polypoidal Choroidal Vasculopathy Treated Using Aflibercept
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Polypoidal Choroidal Vasculopathy
Choroidal Neovascularization
Age-Related Macular Degeneration
Keywords: Type 1 macular neovascularization
Polypoidal Choroidal Vasculopathy
Subretinal fluid
Aflibercept
Age-related macular degeneration
Lead sponsor: Kim's Eye Hospital
Sponsor class: OTHER
First posted: 2022-12-23
Enrollment: 135
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients were diagnosed with type 3 MNV or PCV and underwent continuous aflibercept injections with tolerating subfoveal retinal fluid more than 6 months

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Changes in visual acuity
timeFrame: Through study completion, an average of 20 months
Secondary outcomes:
measure: Proportion of patients who exhibited deterioration of ≥0.3 logMAR BCVA
timeFrame: Through study completion, an average of 20 months
measure: Difference in the BCVA change, according to MNV subtype
timeFrame: Through study completion, an average of 20 months
measure: Degree of visual deterioration according to the treatment period
timeFrame: Through study completion, an average of 20 months
measure: Degree of visual deterioration according to the height of SRF
timeFrame: Through study completion, an average of 20 months
measure: Degree of visual deterioration according to the fluctuation of SRF height
timeFrame: Through study completion, an average of 20 months
measure: Comparison of visual outcomes between the following three groups (mean SRF height <100 µm vs ≥100 µm, <200 µm vs ≥200 µm)
timeFrame: Through study completion, an average of 20 months
measure: Risk factor of developing deterioration of ≥0.2 logMAR BCVA
timeFrame: Through study completion, an average of 20 months
measure: Proportion of patients in whom the intraretinal fluid (IRF) developed during treatment tolerating SRF
timeFrame: Through study completion, an average of 20 months
measure: Difference in visual outcome between patients with and without IRF development
timeFrame: Through study completion, an average of 20 months
measure: Risk factors of IRF development
timeFrame: Through study completion, an average of 20 months
measure: The incidence of vision-threatening event such as large submacular hemorrhage or tear of retinal pigment epithelium
timeFrame: Through study completion, an average of 20 months
measure: The incidence of SRF resolution without shortening injection interval
timeFrame: Through study completion, an average of 20 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Jae Hui Kim
Study officials:
affiliation: Kim's Eye Hospital
name: Jae Hui Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharma A, Parachuri N, Kumar N, Bandello F, Kuppermann BD, Loewenstein A, Regillo CD, Chakravarthy U. Notion of tolerating subretinal fluid in neovascular AMD: understanding the fine print before the injection pause. Br J Ophthalmol. 2021 Feb;105(2):149-150. doi: 10.1136/bjophthalmol-2020-317933. Epub 2020 Sep 26. No abstract available.
citation: Chaudhary V, Matonti F, Zarranz-Ventura J, Stewart MW. IMPACT OF FLUID COMPARTMENTS ON FUNCTIONAL OUTCOMES FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Systematic Literature Review. Retina. 2022 Apr 1;42(4):589-606. doi: 10.1097/IAE.0000000000003283.
citation: Mitchell P, Holz FG, Hykin P, Midena E, Souied E, Allmeier H, Lambrou G, Schmelter T, Wolf S; ARIES study investigators. EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The ARIES Study: A Randomized Clinical Trial. Retina. 2021 Sep 1;41(9):1911-1920. doi: 10.1097/IAE.0000000000003128.
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citation: Cheng CK, Chen SJ, Chen JT, Chen LJ, Chen SN, Chen WL, Hsu SM, Lai CH, Sheu SJ, Wu PC, Wu WC, Wu WC, Yang CM, Yeung L, Chen TC, Yang CH. Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan. BMC Ophthalmol. 2022 Jan 15;22(1):25. doi: 10.1186/s12886-021-02231-8.
citation: Kim JH, Kim JW, Kim CG. Difference Between the Incidence of Retinal Fluid Subtypes and Their Association with Visual Outcomes According to the Types of Macular Neovascularization in a Korean Population. J Ocul Pharmacol Ther. 2022 Apr;38(3):261-268. doi: 10.1089/jop.2021.0103. Epub 2022 Feb 3.