Novel volumetric imaging biomarkers for assessing disease activity in eyes with PCV.

The aim of this study was to evaluate influence of baseline imaging features on visual and anatomical outcomes in eyes with PCV treated with anti-VEGF monotherapy. In this prospective study we enrolled participants with treatment-naïve PCV who followed a treat-and-extend protocol using intravitreal aflibercept (IVA) monotherapy. Baseline clinical features evaluatedincluded best corrected visual acuity (BCVA), traditional features such as lesion size, fluid-related OCT parameters and novel parameters using automated software. This included quantitative and qualitative pigment epithelium detachment (PED) parameters [height, volume]; and choroidal parameters. [choroidal thickness (CT), choroidal volume (CV) and choroidal vascularity index (CVI). We evaluated the predictive value of each parameter on visual and anatomical outcome at month 12. We additionally evaluated initial treatment response after 3 monthly injections with respect to month 12 outcomes. Fifty-two eyes from 52 participants were included in the study. The BCVA increased from 61.1 ± 13.2 to 69.6 ± 13.2 early treatment diabetic retinopathy study (ETDRS) letters (p < 0.01) and CRT reduced from 455.7 ± 182.4 µm to 272.7 ± 86.2 (p < 0.01) from baseline to month 12. The proportion of eyes with PED decreased significant from 100% at baseline to 80% at month 12 (p < 0.01). Reduction in the mean maximum height of PED (from 381.3 ± 236.3 µm to 206.8 vs ± 146.4 µm) and PED volume (from 1322 ± 853 nl to 686 ± 593 nl) (p < 0.01) was also noted from baseline to month12. Baseline features associated with better month 12 BCVA included baseline BCVA (ß = - 0.98, 95%CI - 3.38 to - 1.61, p = 0.02) and baseline CRT (ß = - 0.98, 95%CI - 1.56 to - 0.40, p = 0.04) while the disease activity at month12 was significantly associated with lower baseline CRT (366.0 ± 129.5 vs 612.0 ± 188.0 , p < 0.001), lower baseline PED height (242.0 ± 150.0 vs 542.0 ± 298.0 µm, p < 0.01), lower baseline PED volume (0.6 ± 0.3 mm3 vs 2.2 ± 1.3 mm3 vs, p < 0.01), lower proportion with marked CVH (17.9% vs 46.2%, p = 0.02) and lower mean CVI (61.8 ± 1.4 vs 63.0 ± 1.4, p < 0.02). Additionally, a larger decrease in CRT (per 100 nm) and larger PED volume reduction (per 100 nl) at month 3 from baseline were associated with greater BCVA gain and inactive disease. PED-related volumetric parameters have an additional predictive value to traditional biomarkers of disease activity in eyes with PCV undergoing anti-VEGF monotherapy. With increasingly precise quantification, PEDs can be a crucial biomarker in addition to traditional parameters and may aid in retreatment decisions.

OPTICAL COHERENCE TOMOGRAPHY FEATURES OF POLYPOIDAL LESION CLOSURE IN POLYPOIDAL CHOROIDAL VASCULOPATHY TREATED WITH AFLIBERCEPT.

PURPOSE: To evaluate whether optical coherence tomography (OCT) can determine polypoidal lesion (PL) perfusion in polypoidal choroidal vasculopathy eyes after 12 months of aflibercept monotherapy. Polypoidal lesion perfusion status, assessed by indocyanine green angiography, is an important anatomical outcome in polypoidal choroidal vasculopathy management. METHODS: Post hoc data from a prospective randomized, open-label, study in eyes with polypoidal choroidal vasculopathy undergoing monotherapy with aflibercept evaluated PL perfusion status based on indocyanine green angiography (gold standard) and OCT features from baseline to 12 months. RESULTS: Individual PLs (110 in total) from 48 eyes (48 patients) showed at 12 months; 57/110 PLs (51.8%) were closed on indocyanine green angiography. At 12 months, eyes with closed PLs were more likely to have the following OCT features: 1) no subretinal fluid (67.1% vs. 32.9%), 2) smaller pigment epithelial detachment height (67.2 [±43.8] vs. 189.2 [±104.9] µm), 3) densely hyperreflective pigment epithelial detachment contents (84.0% vs. 16.0%), 4) an absence of a hyperreflective ring(64.0% vs. 36.0%), and a 5) indistinct overlying retinal pigment epithelial (71.4% vs. 28.6%) (all P < 0.05). The three highest performing OCT features that differentiated perfused from closed PLs were (1), (3), and (4) (area under the receiver operating characteristic curve 0.85, 0.73, and 0.70, respectively). A combination of these three features achieved an area under the receiver operating characteristic curve of 0.90. CONCLUSION: Polypoidal lesion closure, an important anatomical treatment outcome in polypoidal choroidal vasculopathy typically defined by indocyanine green angiography, can be accurately detected by specific OCT features.

Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study. TRIAL REGISTRATION NUMBER: NCT03941587.