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.

INDOCYANINE GREEN ANGIOGRAPHY OF TYPE 1 MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION AND CENTRAL SEROUS CHORIORETINOPATHY REVEALS DIFFERENT DISEASE MECHANISMS.

PURPOSE: To assess the rate of late phase hyperfluorescent plaque (LPHP) in Type 1 macular neovascularization (MNV) in central serous chorioretinopathy (CSCR) and age-related macular degeneration (AMD) and to evaluate its prognostic value. METHODS: Retrospective study including Type 1 MNV in AMD and CSCR, from 2012 to 2020. Eyes with a late indocyanine green angiography image (>20 minutes) and clear visualization of MNV on optical coherence tomography angiography (OCTA) were included. Quantitative and qualitative parameters on optical coherence tomography and best-corrected visual acuity were recorded at baseline and after three monthly antivascular endothelial growth factor injections. RESULTS: Eighty-three eyes were included, 35 with CSCR and 48 with AMD. Patients in the CSCR group were significantly younger than in the AMD group (61.3 ± 10.4 vs. 80.2 ± 6.8 years, respectively, P < 0.001), predominantly male (68.6% CSCR vs. 35.4% AMD; P = 0.003), and with a thicker choroid (379 ± 93.3 µ m vs. 204.2 ± 93.2 µ m; P < 0.001). Type 1 MNV in CSCR showed fewer LPHP compared with AMD (31.4% vs. 77.1%; P < 0.001). The baseline visual acuity was lower in patients with LPHP (0.37 ± 0.22 vs. 0.27 ± 0.28 logarithm of the minimum angle of resolution, P = 0.03). On multivariate analysis, AMD was associated with the presence of LPHP ( P < 0.001). No significant difference in the response to antivascular endothelial growth factor was observed. CONCLUSION: Leakage of macromolecules from MNV and accumulation in the retinal pigment epithelium and/or in the stroma imaged by the LPHP is less common in eyes with Type 1 MNV in CSCR than in AMD. Late phase indocyanine green angiography imaging offers an insight into the metabolism of the dye and the environment surrounding the neovascular membrane.

SOIN - MI Data Lab: Personalized Ophthalmology Through Collaborative Data Collection and Dynamic Patient Consent.

The Swiss Ophthalmic Image Network (SOIN) is part of the Swiss Personalized Health Network (SPHN). SOIN contains a collaborative, clinical research environment, MI Data Lab, which allows privacy-preserving, data-driven, research. Personalized care of chronic ocular disease, based on Machine Learning (ML) and medical imaging, can dramatically improve quality of life and reduce the burden on health and social care systems. MI Data Lab allows research partners to consolidate their data in a space where doctors and data scientists cooperate to design novel ML algorithms, on curated datasets. To date, we have created several algorithms to detect ocular biomarkers automatically, and applied such tools to 100k+ retinal images. MI Data Lab enables the development of predictive models, the extraction novel traits to be explored in terms of -omic associations, treatment outcome, and priors for disease progression.

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.

Type one macular neovascularization in central serous chorioretinopathy: Short-term response to anti-vascular endothelial growth factor therapy.

PURPOSE: The aim of this study was to assess the short-term effect of anti-vascular endothelial growth factor (VEGF) treatment on type 1 macular neovascularization (MNV) secondary to central serous chorioretinopathy (CSCR) and to identify potential predictive factors for treatment response using multimodal imaging. METHODS: Retrospective, multicentre study in CSCR patients with MNV detected by OCT-angiography and treated with anti-VEGF injections. Clinical and multimodal imaging data before and after anti-VEGF injections was reviewed. Univariate and multivariate linear regression analyses were performed to evaluate associations between the change in central macular thickness (CMT) after anti-VEGF therapy and other factors. RESULTS: Forty patients were included. One month after receiving a mean number of 2.7 anti-VEGF intravitreal injections, visual acuity increased significantly from 0.46 ± 0.3 logMAR at baseline to 0.38 ± 0.4 logMAR (p = 0.04). The CMT and foveal serous retinal detachment (SRD) decreased significantly from 330 ± 81.9 µm at baseline to 261.7 ± 63.1 µm after treatment (p < 0.001) and from 145.1 ± 98.8 µm at baseline to 52.6 ± 71.3 µm (p < 0.001), respectively. Subretinal fluid and/or intraretinal fluid were still present in 18 eyes (45%) one month after treatment. In the multivariate analysis, a higher SRD height was associated with a greater CMT change (p = 0.002) and a lower CMT change with the presence of subretinal hyperreflective material (SHRM) (p = 0.04). CONCLUSION: Fluid resorption was incomplete in about half of the patients with MNV secondary to CSCR after anti-VEGF injections. Shallower SRD or the presence of SHRM were predictors of poor response to anti-VEGF.

TREATMENT DEFERRAL DURING COVID-19 LOCKDOWN: Functional and Anatomical Impact on Patients With Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate the visual and anatomical impact of intravitreal injection treatment deferral because of the COVID-19 lockdown on patients affected by neovascular age-related macular degeneration. METHODS: We retrospectively reviewed 314 patients (394 eyes) who were scheduled to receive the impact of intravitreal injections during the Swiss lockdown. We compared patients who continued to receive scheduled impact of intravitreal treatment without clinical consultation (Group Continue ?C"; n = 215) and patients for whom the impact of intravitreal treatment was completely deferred (Group Stop, ?S"; n = 179). Functional and anatomical parameters were collected at four time points before and after the lockdown. RESULTS: In Group C, the visual acuity at baseline and after the lockdown did not differ significantly. In Group S, the visual acuity deteriorated significantly compared with baseline and then improved slightly after the resumption of treatment, but it did not recover to baseline values. The mean central subfield thickness remained stable in Group C, whereas it increased in Group S and then returned to prelockdown values after the resumption of treatment. CONCLUSION: An "injection-only" approach was effective in managing patients with neovascular age-related macular degeneration during the pandemic lockdown, whereas patients who deferred their scheduled treatment showed partially irreversible deterioration of visual function. We recommend treatment continuation in patients with neovascular age-related macular degeneration during a lockdown.

Automated Quantification of Pathological Fluids in Neovascular Age-Related Macular Degeneration, and Its Repeatability Using Deep Learning.

Purpose: To develop a reliable algorithm for the automated identification, localization, and volume measurement of exudative manifestations in neovascular age-related macular degeneration (nAMD), including intraretinal (IRF), subretinal fluid (SRF), and pigment epithelium detachment (PED), using a deep-learning approach. Methods: One hundred seven spectral domain optical coherence tomography (OCT) cube volumes were extracted from nAMD eyes. Manual annotation of IRF, SRF, and PED was performed. Ninety-two OCT volumes served as training and validation set, and 15 OCT volumes from different patients as test set. The performance of our fluid segmentation method was quantified by means of pixel-wise metrics and volume correlations and compared to other methods. Repeatability was tested on 42 other eyes with five OCT volume scans acquired on the same day. Results: The fully automated algorithm achieved good performance for the detection of IRF, SRF, and PED. The area under the curve for detection, sensitivity, and specificity was 0.97, 0.95, and 0.99, respectively. The correlation coefficients for the fluid volumes were 0.99, 0.99, and 0.91, respectively. The Dice score was 0.73, 0.67, and 0.82, respectively. For the largest volume quartiles the Dice scores were >0.90. Including retinal layer segmentation contributed positively to the performance. The repeatability of volume prediction showed a standard deviations of 4.0 nL, 3.5 nL, and 20.0 nL for IRF, SRF, and PED, respectively. Conclusions: The deep-learning algorithm can simultaneously acquire a high level of performance for the identification and volume measurements of IRF, SRF, and PED in nAMD, providing accurate and repeatable predictions. Including layer segmentation during training and squeeze-excite block in the network architecture were shown to boost the performance. Translational Relevance: Potential applications include measurements of specific fluid compartments with high reproducibility, assistance in treatment decisions, and the diagnostic or scientific evaluation of relevant subgroups.

Refractory neovascular age-related macular degeneration: time-dependent changes of central retinal thickness with anti-VEGF treatment.

PURPOSE: To assess the influence of time interval since last injection and time from baseline on central retinal thickness (CRT) in neovascular age-related macular degeneration (nAMD) with fluid refractory to monthly anti-VEGF treatment. METHODS: This retrospective study included nAMD eyes with incomplete response to anti-VEGF defined by the presence of intra- or subretinal fluid on optical coherence tomography despite maximal (monthly) anti-VEGF dosing. The outcome measure was CRT, and two time variables (time from last injection ant time from baseline) were the independent factors included in the individual correlation analyses. In addition, an association analysis was performed. RESULTS: Sixty eyes of 56 patients (67.9% females, mean age: 78.7 ± 6.8 years) were included with a mean included time period of 35.6 months. A significant positive correlation between CRT and the time from last injection occurred in 24 (40%) and 25 (42%) eyes by univariate and multivariate analysis, respectively. Time from baseline was significantly correlated with CRT in 29 (48.3%) and 30 (50%) eyes by univariate and multivariate analysis, respectively. This correlation was positive in 12 (20%) and negative in 18 eyes (30%). No association with such correlation was found. CONCLUSION: So-called refractory nAMD frequently shows a correlation of CRT with the interval in days from the preceding anti-VEGF injection, revealing that there is a subgroup of short-term responsiveness of the residual fluid. Moreover, slower CRT changes may occur over the years, either decrease or increase. In case of a slow CRT increase, this might require a diagnostic workup and therapeutic change.

Beneficial switch from aflibercept to ranibizumab for the treatment of refractory neovascular age-related macular degeneration.

PURPOSE: The aim of this study was to evaluate the effects of switching to ranibizumab in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept treatment and to identify predictive factors for switch response. METHODS: A retrospective chart review was conducted including 32 eyes from 26 patients with refractory nAMD, who switched from monthly intravitreal aflibercept treatment (≥ 6 months) to ranibizumab. Outcome measures included changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central retinal thickness (CRT), evaluated at 6 months before switch (T1), at the time of switch (T2), and 3 months post-switch (T3). RESULTS: There was an increase in CRT from T1 to T2, which decreased after switch from T2 to T3. Regression analysis of the changes per month observed between time points showed significant differences in PED height (p = 0.02), SRF (p = 0.01), and neuroretinal thickness as a measure for IRF (p = 0.03). No significant change was found for VA. Predictive factors for better switch response included an exacerbation between T1 and T2, thicker measurements at T2, male sex, shorter treatment duration before switch, and fewer preceding injections. No association with preceding switch was found. CONCLUSION: Patients with nAMD refractory to aflibercept benefit from switching to ranibizumab, particularly those whose condition worsened prior to the switch. This may be explained by drug tolerance to aflibercept. Our findings may facilitate making appropriate treatment decisions, potentially improving patient outcomes.

Predictors of treatment response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for choroidal neovascularisation secondary to chronic central serous chorioretinopathy.

PURPOSE: The aim of this study was to evaluate the effect of anti-vascular endothelial growth factor (VEGF) therapy on choroidal neovascularisation (CNV) complicating central serous chorioretinopathy (CSC) using multimodal imaging, and to identify possible predictive factors of the treatment response. DESIGN: Retrospective study. METHODS: Data of 27 eyes with CNV complicating CSC treated with anti-VEGF therapy (either ranibizumab or aflibercept) were reviewed. Response to anti-VEGF treatment was evaluated by change in visual acuity, intra/subretinal fluid modifications and CNV changes on optical coherence tomography angiography (OCTA). Univariate and multivariate analyses were performed to identify predictive factors for central retinal thickness (CRT) change and for the relative degree of treatment response (complete, incomplete or absent fluid reduction). RESULTS: CRT was significantly reduced at 32±15 days after 2.8±1.3 injections (p=0.0004) as was the subretinal fluid (p=0002). Complete fluid resorption was observed in 45% of cases. Best corrected visual acuity did not significantly improve (p=0.18). CNV area (p=0.09) and CNV flow area (p=0.07) did not significantly decrease. No changes in CNV pattern were noted. Univariate analysis identified greater CRT at baseline (p<0.0001), greater amount of subretinal fluid (p<0.0001), a shorter period of retinal fluid (p=0.04) and female gender (p=0.04) as predictors for CRT reduction. After multivariate analysis the factor of greater CRT at baseline (p<0.0001) proved independent. The degree of treatment response was dependent on the size of CNV surface (p=0.05) and flow area (p=0.05) on OCTA in the univariate analysis, and the latter independent after multivariate analysis. In addition, a shorter time period of retinal fluid appeared to play a role (p=0.01 multivariate, p=0.19 univariate). CONCLUSION: The anti-VEGF response was highly variable and often incomplete, suggesting that CNV was not solely responsible for the fluid accumulation. Predictive factors may guide indication for anti-VEGF in CNV associated with CSC.

Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.

Choroidal neovascularization (CNV) is a major cause of visual impairment in patients suffering from wet age-related macular degeneration (AMD), particularly when refractory to intraocular anti-VEGF injections. Here we report that treatment with the oral mineralocorticoid receptor (MR) antagonist spironolactone reduces signs of CNV in patients refractory to anti-VEGF treatment. In animal models of wet AMD, pharmacological inhibition of the MR pathway or endothelial-specific deletion of MR inhibits CNV through VEGF-independent mechanisms, in part through upregulation of the extracellular matrix protein decorin. Intravitreal injections of spironolactone-loaded microspheres and systemic delivery lead to similar reductions in CNV. Together, our work suggests MR inhibition as a novel therapeutic option for wet AMD patients unresponsive to anti-VEGF drugs.

MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Risk Factor Evaluation for Individualized Treatment Need of Ranibizumab or Aflibercept According to an Observe-and-Plan Regimen.

PURPOSE: To investigate factors associated with macular atrophy (MA) incidence in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept in an Observe-and-Plan variable dosing regimen. METHODS: Information was obtained from two identical prospective treatment protocols using ranibizumab or aflibercept in a variable dosing regimen termed "Observe and Plan." Eyes without MA at baseline were included. New atrophy at the final 2-year visit was investigated with univariate and multivariate analysis to identify associated risk factors, focusing on treatment factors. RESULTS: De novo MA developed in 63 (42%) of 149 eyes/patients (mean age 79.0 years), in 70 eyes treated using aflibercept and 79 eyes using ranibizumab. The univariate analysis showed multiple associations of MA with baseline factors, of which the following were confirmed as independent risk factors after multivariate stepwise logistic regression: lower number of anti-vascular endothelial growth factors injections (P = 0.011), depigmentation (P = 0.0004), reticular pseudodrusen (P = 0.0005), lower baseline visual acuity (P = 0.0006), and retinal angiomatous proliferation (P = 0.001). The drug type showed no significant association with MA incidence (P = 0.21). CONCLUSION: Within the variable dosing regimen, MA incidence was higher when fewer injections were required. More injections, if required by disease activity, did not increase the risk for MA.

Antidepressant medication and ocular factors in association with the need for anti-VEGF retreatment in neovascular age-related macular degeneration.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a key player in the pathogenesis of neovascular age-related macular degeneration (nAMD) and is also involved in the final common pathway of antidepressant medication. This study investigated the relationship between the need for anti-VEGF retreatment in patients with nAMD and antidepressant medication, and the potential impact of ocular structural factors. METHODS: Data from two identical prospective 2-year treatment protocols using ranibizumab or aflibercept in a variable-dosing regimen ('Observe-and-Plan') were analysed. Retreatment requirement was compared with antidepressant medication intake (primary outcome) and a variety of ocular factors from baseline and from month 3 response (secondary outcomes), using univariate and multivariate analyses. RESULTS: Of the 206 included patients (227 eyes), 19 were on antidepressant medication. Their nAMD eyes significantly more often had pigment epithelium detachment (PED, p=0.04). Multivariate analysis revealed a significant association between anti-VEGF retreatment requirement and antidepressant medication use (p=0.027), as well as thicker central retinal thickness at month 3 (p<0.0001) and month 3 PED height (p=0.001). CONCLUSION: This study provides evidence that treatment with antidepressant medication increases the anti-VEGF retreatment requirement in patients with nAMD, possibly through the interplay of antidepressant medication, depression status and VEGF levels.

Factors influencing macular atrophy growth rates in neovascular age-related macular degeneration treated with ranibizumab or aflibercept according to an observe-and-plan regimen.

BACKGROUND/AIMS: To investigate the factors associated with macular atrophy (MA) growth rates in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept. METHODS: We obtained data from two identical prospective studies using ranibizumab or aflibercept under observe-and-plan variable dosing regimens. We analysed eyes that presented MA within 2 years. After applying square root transformations to MA sizes, we calculated MA growth rate from baseline to the year 2 endpoint and used univariate and multivariate analyses to detect ocular and treatment factors associated with the MA growth rate. RESULTS: Included were 109 eyes from 101 patients (mean age 80.6 years). The mean square-root-transformed MA growth rate was 0.54±0.34 mm/year. The univariate analyses revealed that MA growth rates were significantly associated with lower baseline visual acuities (p=0.001) and thicker subretinal tissue complexes (p=0.006) and near-significantly associated with the presence of pigment epithelium detachment (p=0.057) and choroidal neovascularisation subtypes (p=0.069). Our multivariate analysis confirmed the significance of lower baseline visual acuities (p=0.008) and pigment epithelium detachments higher than 200 µm (p=0.035). Furthermore, MA growth rates in neovascular eyes significantly correlated with MA growth rates in non-neovascular fellow eyes (n=61; p=0.003). CONCLUSION: MA growth rates were associated with ocular factors in the study eyes and the fellow eyes but not with the drug or the number of injections within this variable dosing regimen.

Switching between ranibizumab and aflibercept for the treatment of neovascular age-related macular degeneration.

The introduction of antivascular endothelial growth factor agents such as ranibizumab and aflibercept has revolutionized the management of neovascular age-related macular degeneration. A number of randomized clinical trials have shown that ranibizumab and aflibercept produce similar efficacy and safety outcomes. Most of the switching studies published to date show that efficacy benefits are uncontrolled, retrospective trials with limitations in terms of their selection, monitoring, numbers, and assessment criteria. Based on the published literature to date, we propose arguments for and against switching antivascular endothelial growth factor agents, provide our own perspective on this topic, and suggest a focus for future research.

GOOD VISUAL OUTCOME AT 1 YEAR IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH PIGMENT EPITHELIUM DETACHMENT: Factors Influencing the Treatment Response.

PURPOSE: To evaluate baseline and treatment factors influencing the response of pigment epithelial detachment (PED) in patients with treatment-naive neovascular age-related macular degeneration after 1 year of intravitreal anti-vascular endothelial growth factor treatment. METHODS: This retrospective consecutive case series study included 104 eyes (94 patients) with treatment-naive neovascular age-related macular degeneration and associated PED >150 µm treated with aflibercept (n = 41) or ranibizumab (n = 63) for at least 1 year. Stepwise linear regression was used to assess factors influencing best-corrected visual acuity and PED response. RESULTS: At 1 year, the best-corrected visual acuity improved from 20/63 (60.8 ± 15.9 Early Treatment of Diabetic Retinopathy Study letters) at baseline to 20/40 (69.0 ± 15.0 letters) (P = 0.001), and PED maximal height decreased from 370.8 ± 205.6 µm to 238.8 ± 178.5 µm (P = 0.001). Multivariate analysis revealed an association of the visual improvement with lower best-corrected visual acuity at baseline (P = 0.001), the presence of foveal subretinal fluid (P = 0.001), and female gender (P = 0.047). Pigment epithelial detachment height reduction was dependent on higher baseline PED height (P = 0.001) and treatment drug (P = 0.008). CONCLUSION: Visual improvement in neovascular age-related macular degeneration with PED was equally achieved with ranibizumab and aflibercept, influenced mainly by baseline best-corrected visual acuity and foveal subretinal fluid. Pigment epithelial detachment height reduction was influenced by baseline height and the treatment drug, favoring aflibercept for a stronger effect. The clinical significance of this result warrants further studies.

EFFICACY OF INTRAVITREAL AFLIBERCEPT IN MACULAR TELANGIECTASIA TYPE 1 IS LINKED TO THE OCULAR ANGIOGENIC PROFILE.

PURPOSE: To evaluate intravitreal aflibercept in macular telangiectasia Type 1 (MacTel 1) patients and measure their ocular angiogenic profile. METHODS: Eight subjects with MacTel 1 refractory to bevacizumab, ranibizumab, or laser therapy and switched to aflibercept were included. Best-corrected visual acuity, central macular thickness, and cystic areas quantified on optical coherence tomography B-scans were assessed during 12 months. Perifoveal capillary densities were measured on optical coherence tomography angiography. Aqueous humor was sampled from six patients and eight control subjects undergoing cataract extraction. Growth factors were quantified using a multiarray immunoassay. RESULTS: Over 12 months, patients received 6.6 ± 1.4 (range, 5-8) intravitreal aflibercept injections. Twelve months after switching to aflibercept, best-corrected visual acuity increased by ≥5 letters in 5 of 8 patients, compared with preaflibercept levels. Mean best-corrected visual acuity improved from 79.6 (∼20/50) to 88.0 (∼20/35) Early Treatment Diabetic Retinopathy Study letters (P = 0.042), and central macular thickness decreased from 434 ± 98 µm to 293 ± 59 µm (P = 0.014). Compared with control subjects, the profile of angiogenic factors in MacTel 1 eyes revealed no difference in vascular endothelial growth factor-A levels but significantly higher levels of placental growth factor (P = 0.029), soluble vascular endothelial growth factor receptor-1 (sFlt-1; P = 0.013), vascular endothelial growth factor-D (P = 0.050), and Tie-2 (P = 0.019). Placental growth factor levels inversely correlated with both superficial and deep capillary plexus densities on optical coherence tomography angiography (P = 0.03). CONCLUSION: The clinical response to aflibercept coupled to the angiogenic profile of MacTel 1 eyes support the implication of the placental growth factor/Flt-1 pathway in MacTel 1.

PIGMENT EPITHELIAL DETACHMENT RESPONSE TO AFLIBERCEPT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION REFRACTORY TO RANIBIZUMAB: Time Course and Drug Effects.

PURPOSE: To investigate the time course of pigment epithelium detachment (PED) height and its change after anti-vascular endothelial growth factor switch from ranibizumab to aflibercept in neovascular age-related macular degeneration. METHODS: This retrospective study included 60 eyes of 50 consecutive patients with neovascular age-related macular degeneration who showed refractory intraretinal or subretinal fluid (≥9 months) despite monthly ranibizumab treatment and an associated PED (height ≥150 µm). The treatment was switched to aflibercept, and patients were followed-up for at least 9 months. Data on the height and type of PED, exudative fluid, and best-corrected visual acuity were collected at four different time points (two before and two after the drug switch). RESULTS: The maximal PED height was significantly decreased over time, both under ranibizumab and aflibercept treatment. However, the reduction was significantly greater during the 3 months after the switch to aflibercept, due to two outliers. Visual acuity remained stable. Complete resolution of intraretinal or subretinal fluid was observed in 9 cases (15%) at 3 months after switch, allowing for treatment interval extension. CONCLUSION: Maximal PED height continuously decreased over time. Switching the intravitreal anti-vascular endothelial growth factor medication from ranibizumab to aflibercept had a significantly stronger short-term effect on PED height reduction, without changes in visual acuity.