Short-term response to anti-VEGF as indicator of visual prognosis in refractory age-related macular degeneration.

BACKGROUND: Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections. Their short-term response between injections was investigated for extent and visual prognosis. SUBJECTS/METHODS: Monocentric retrospective observational study. 45 eyes from 41 patients with refractory nAMD (who previously received at least 12 months of anti-VEGF treatment), evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric measurements performed by an automated algorithm based on artificial intelligence. RESULTS: A significant improvement was found at week 1 in terms of CRT (p < 0.0001), intraretinal (IRF) (p = 0.007), subretinal fluid (SRF) (p < 0.0001), and pigment epithelium detachment (PED) volume (p < 0.0001). Volumetric fluid measures revealed a >50% reduction at week 1 for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF + SRF) (p = 0.003), larger PED (p = 0.007), lower visual acuity (p = 0.004) and less anatomic changes at treatment initiation (p < 0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later was significantly worse with weaker short-term responsiveness (p = 0.005), with the presence of atrophy (p = 0.01) and larger PED volumes (p = 0.002). CONCLUSIONS: Incomplete responders to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis.

In Vivo Retinal Pigment Epithelium Imaging using Transscleral Optical Imaging in Healthy Eyes.

Objective: To image healthy retinal pigment epithelial (RPE) cells in vivo using Transscleral OPtical Imaging (TOPI) and to analyze statistics of RPE cell features as a function of age, axial length (AL), and eccentricity. Design: Single-center, exploratory, prospective, and descriptive clinical study. Participants: Forty-nine eyes (AL: 24.03 ± 0.93 mm; range: 21.9-26.7 mm) from 29 participants aged 21 to 70 years (37.1 ± 13.3 years; 19 men, 10 women). Methods: Retinal images, including fundus photography and spectral-domain OCT, AL, and refractive error measurements were collected at baseline. For each eye, 6 high-resolution RPE images were acquired using TOPI at different locations, one of them being imaged 5 times to evaluate the repeatability of the method. Follow-up ophthalmic examination was repeated 1 to 3 weeks after TOPI to assess safety. Retinal pigment epithelial images were analyzed with a custom automated software to extract cell parameters. Statistical analysis of the selected high-contrast images included calculation of coefficient of variation (CoV) for each feature at each repetition and Spearman and Mann-Whitney tests to investigate the relationship between cell features and eye and subject characteristics. Main Outcome Measures: Retinal pigment epithelial cell features: density, area, center-to-center spacing, number of neighbors, circularity, elongation, solidity, and border distance CoV. Results: Macular RPE cell features were extracted from TOPI images at an eccentricity of 1.6° to 16.3° from the fovea. For each feature, the mean CoV was < 4%. Spearman test showed correlation within RPE cell features. In the perifovea, the region in which images were selected for all participants, longer AL significantly correlated with decreased RPE cell density (R Spearman, Rs = -0.746; P < 0.0001) and increased cell area (Rs = 0.668; P < 0.0001), without morphologic changes. Aging was also significantly correlated with decreased RPE density (Rs = -0.391; P = 0.036) and increased cell area (Rs = 0.454; P = 0.013). Lower circular, less symmetric, more elongated, and larger cells were observed in those > 50 years. Conclusions: The TOPI technology imaged RPE cells in vivo with a repeatability of < 4% for the CoV and was used to analyze the influence of physiologic factors on RPE cell morphometry in the perifovea of healthy volunteers. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Fluid dynamics between injections in incomplete anti-VEGF responders within neovascular age-related macular degeneration: a prospective observational study.

BACKGROUND: The purpose of the study was to investigate the short-term response profile after an intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in patients with neovascular age-related macular degeneration (nAMD) and incomplete response to anti-VEGF. METHODS: In this monocentric prospective observational study, we recruited patients with incomplete response to anti-VEGF, defined as presence of subretinal fluid (SRF) and/or intraretinal fluid (IRF) on optical coherence tomography (OCT) for at least 6 months despite monthly anti-VEGF treatment. Each patient underwent complete ophthalmic exam and imaging study (including OCT, fluorescein angiography, indocyanine green angiography, OCT-angiography) the day of their scheduled monthly IVI. Intermediate visits were performed weekly thereafter (comprising ophthalmic exam and OCT), until week 4. Fluid metrics were quantified using an artificial intelligence-based algorithm at baseline and at each subsequent weekly visit. Main outcomes were residual fluid volumes of SRF and IRF for each time point, and its relative change after treatment. Particular interest was given to each patients' nadir point, which was used for association analysis with imaging parameters. RESULTS: A total of 28 eyes of 26 patients were included into the study. The maximal response was reached at 1.93 weeks on average. The relative fluid resolution at nadir point was 66 ± 36.7%, with quartile limits at 49.1%, 83%, and 96.1%, respectively. Mean residual fluid volume was 64.9 ± 128.8 µl at nadir point. Residual fluid was positively correlated with baseline SRF (r = 0.76, p < 0.0001) and larger pigment epithelium detachment (r = 0.65, p = 0.0001). Polypoidal choroidal vasculopathy was associated with larger residual fluid (p = 0.0013). CONCLUSIONS: Incomplete anti-VEGF responders in nAMD showed significant mean fluid resolution between injections, typically after 2 weeks. However, complete resolution was the exception, and the amount of residual fluid varied greatly. To understand the role of the unresponsive fluid, further studies are needed.