Treatment-resistant Neovascular Age-related Macular Degeneration Research Articles

Visual and Anatomic Responses in Patients With Neovascular Age-Related Macular Degeneration and a Suboptimal Response to Anti-VEGF Therapy Switched to Faricimab

Purpose: To determine the efficacy of switching to intravitreal (IVT) faricimab in patients with treatment-resistant neovascular age-related macular degeneration (nAMD) and determine the rates of reversion to original antivascular endothelial growth factor (anti-VEGF) therapy. Methods: A retrospective chart review was performed of patients with nAMD and persistent fluid on optical coherence tomography previously treated with anti-VEGF injections who received at least 1 IVT faricimab injection between March 1, 2022, and January 31, 2023. Results: The study comprised 135 eyes of 119 patients. Before switching to IVT faricimab, the mean number of anti-VEGF injections in the previous 12 months was 10.7 ± 2.6 (SD) with a mean interval of 4.8 ± 1.3 weeks (range, 2-8). The mean follow-up was 11.6 ± 2 months. Thirty eyes (22.2%) switched to IVT faricimab returned to the original therapy. Of 105 eyes remaining on IVT faricimab, 66 (62.9%) had no fluid at the last follow-up. Compared with the original treatment, there was a significant improvement in logMAR visual acuity at the last follow-up in eyes on IVT faricimab (0.42 vs 0.38; P < .01) and in central subfield thickness (286 µm vs 246 µm; P < .0001). There was also a significant increase in the dosing interval after the third injection vs before IVT faricimab was prescribed (4.8 weeks vs 5.5 weeks; P < .001). Conclusions: Faricimab has a potent drying effect and potential for increasing the injection interval in many eyes with nAMD and persistent fluid on other anti-VEGF agents. Although nearly 25% of eyes reverted to the original therapy because of an insufficient response or adverse events, the majority did not achieve fluid resolution after reversion.

Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab

PurposeWhile previous studies have demonstrated the efficacy of Faricimab in treatment-naïve nAMD patients, its outcomes in patients switched from Aflibercept are less understood. This study aimed to assess real world anatomical and functional outcomes of switching to Faricimab in patients undergoing Aflibercept intravitreal injections for nAMD with sub-optimal response. DesignRetrospective case series. SubjectsPatients with nAMD at a single tertiary care center who were switched from Aflibercept to Faricimab due to persistent suboptimal response. MethodsPatients had received a minimum of 6 consecutive intravitreal injections of aflibercept and showed persistent presence of intraretinal or subretinal fluid on OCT despite receiving aflibercept at 4 or 6-weekly intervals at the time of the switch. Patients receiving 4-weekly aflibercept were either switched with 2 or 3 loading doses of 4-weekly Faricimab injections.. Regression models were used to identify predictors of clinical outcomes. Main Outcome MeasuresVisual acuity, central macular thickness, and OCT parameters were assessed pre- and post-switch ResultsEighty-one eyes of 68 patients were included. The mean age was 79.1 years (SD: 8.9), and females constituted 53% of cases. A statistically significant reduction in central macular thickness was observed post-switch (p<0.0001). The proportion of cases with intraretinal (p=0.0219) and subretinal fluid (p<0.000) decreased significantly. Overall clinical improvement on OCT was noted in 80% of patients. No significant improvement in ETDRS vision was observed. There was no evidence that switching regimen (2 vs. 3 loading doses) had an independent effect on clinical outcomes. ConclusionAmongst patients with treatment-resistant nAMD, switching from Aflibercept to Faricimab may serve as a safe and effective option. Significant anatomical improvements were observed, with a trend towards visual stability. The loading regimen with two Faricimab injections appeared to be sufficient for non-naïve patients. However, a longer follow-up and larger studies are warranted to confirm these findings.

One-Year Outcomes of Faricimab Treatment for Aflibercept-Resistant Neovascular Age-Related Macular Degeneration.

To assess the 12-month outcomes of intravitreal faricimab (IVF) in treatment-resistant neovascular age-related macular degeneration (nAMD) subjects recalcitrant to intravitreal aflibercept (IVA). This study was conducted as a retrospective interventional case series of nAMD patients receiving treatment at a single private practice institution. All included patients at baseline had undergone six or more IVA injections over the previous 12 months, four or more IVA injections over the previous 6 months, had a central macular thickness (CMT) ≥320 µm on optical coherence tomography (OCT), and were observed to have intraretinal and/or subretinal fluid on OCT assessment. The baseline exam for the purpose of this study was considered the visit in which the patient was switched from IVA to IVF. Patients were managed with a real-world treat-and-extend protocol and followed over a 12-month study period. A total of 54 eyes of 54 subjects were analyzed. Overall, 31.5% (17/54) of subjects attained a treatment interval ≥8 weeks and had a fluid-free macula on OCT at 12 months. The CMT on OCT decreased from 395.4 (383.5-407.3) µm at baseline to 350.0 (335.1-364.8) µm at the end of the 12-month study interval (p<0.01). There were 16.7% (9/54) of subjects who gained three or more lines of Snellen visual acuity at the end of the study. Visual acuity improved from 0.72 (0.67-0.77) logMAR (Snellen 20/105) at baseline to 0.59 (0.55-0.64) logMAR (Snellen 20/78) at the end of the study (p<0.01). A clinically significant minority of aflibercept-resistant nAMD subjects may attain longer treatment intervals and improved outcomes at 12 months after switching to IVF when a treat-and-extend treatment protocol is utilized. IVF use may be considered whenever resistance to IVA is encountered in this patient population.

Initial Real-World Experience with Faricimab in Treatment-Resistant Neovascular Age-Related Macular Degeneration.

To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD). A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up. A total of 190 eyes were included. Patients received a mean of 34.2±23 anti-VEGF injections over 182.41±128 weeks prior to switching to faricimab. Patients then received a mean of 6.99±2.3 faricimab injections with an average 34.88±8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33±0.32 logMAR ≈20/43 to 0.27±0.32 logMAR ≈20/37 (P=0.0022). The central subfield thickness (CST) improved from 312±87μm to 287±71μm (P<0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64±6.2 weeks) was significantly longer than that for ranibizumab (5.16±2.0 weeks, P<0.001) or aflibercept (5.57±3.6 weeks, P<0.001). No patients developed idiopathic intraocular inflammation. Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.

Intravitreal Faricimab for Aflibercept-Resistant Neovascular Age-Related Macular Degeneration.

To evaluate the short-term effects of intravitreal faricimab (IVF) in treatment-resistant neovascular age-related macular degeneration (nAMD) subjects previously treated with intravitreal aflibercept (IVA). A retrospective review was conducted on nAMD patients undergoing IVA therapy at a single private practice institution. Subjects were divided into Study and Control groups. Both Study and Control subjects had undergone ≥6 IVA treatments during the previous 12 months, ≥4 IVA treatments during the previous 6 months, had a central macular thickness (CMT) on optical coherence tomography (OCT) of ≥300 microns, and had observable intraretinal and/or subretinal fluid on OCT prior to group assignment. Study subjects were switched from IVA to IVF and received 3 treatments within 4 months. Control subjects remained on IVA during the same time period and received 3 treatments within 4 months. There were a total of 55 subjects analyzed. There were 39.3% (11/28) in the Study Group and 7.4% (2/27) in the Control Group attaining a CMT of less than 300 microns without retinal fluid on OCT at the end of the 4-month study period (p = 0.004). There were 35.7% (10/28) in the Study Group and 7.4% (2/27) in the Control Group gaining 2 or more lines of visual acuity at the end of the 4-month study period (p = 0.008). IVF can improve the visual and anatomic outcomes in a significant minority of treatment-resistant nAMD subjects previously managed with IVA. A greater follow-up period is needed to determine if such improvements can be maintained.

Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration.

To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3mg aflibercept, 0.75mg or 1.0mg ranibizumab, and 1.8mg or 2.5mg bevacizumab. The eyes were analyzed at standardized time points up to 48months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate. There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point (p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents (p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 (p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group (p < 0.05). Mean absolute CRT was similar at month 6 for all agents (p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7-6.4weeks). Mean follow-up was 22.8months. Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents.

Intraocular pressure decreases in eyes with glaucoma-related diagnoses after conversion to aflibercept for treatment-resistant age-related macular degeneration.

To understand intraocular pressure (IOP) response after switching from intravitreal bevacizumab (IVB) and/or ranibizumab (IVR) to intravitreal aflibercept (IVA) for treatment-resistant neovascular age-related macular degeneration (nAMD) in patients with and without coexisting glaucoma-related diagnoses. Retrospective, cross-sectional comparative case series of 62 eyes of 58 patients treated with intravitreal injection for nAMD from March 2010 to April 2018. Patients with glaucoma-related diagnoses, defined here as open-angle glaucoma or suspicion of open-angle glaucoma, ocular hypertension, and/or narrow-angle glaucoma, were compared to those without glaucoma. IOP data were collected at baseline, at the three visits where patients received loading doses of IVB/IVR, and at all of the visits following the switch to IVA through the end of follow-up. 19 eyes with pre-existing glaucoma-related diagnoses were compared to 43 eyes without such diagnoses. Baseline IOP was similar for glaucoma and non-glaucoma patients. The loading doses of IVB/IVR did not impact IOP; however, a small, sustained rise in IOP was noted among patients with glaucoma-related diagnoses by the final IVB/IVR injections before the switch to IVA (∆IOP 1.61 ± 0.52 mmHg, P < 0.002). After conversion to IVA, pre-injection IOP declined in eyes both with (-1.59 ± 0.54 mmHg, P < 0.001) and without (-0.99 ± 0.28 mmHg, P < 0.001) glaucoma-related diagnoses. IOP in patients with glaucoma-related diagnoses appears to be more sensitive to intravitreal injections than it is in patients without glaucoma-related diagnoses. It rises with IVB/IVR and declines after the switch to IVA. Switching patients with nAMD to IVA may present an opportunity to lower IOP in patients with glaucoma.

The prognostic value of total macular external limiting membrane and ellipsoid zone damage for clinical outcome in treatment-resistant neovascular age-related macular degeneration.

To examine the prognostic value of the extent of damage to the ellipsoid zone (EZ) and external limiting membrane (ELM) in response to the treatment of age-related macular degeneration (AMD) eyes switched from ranibizumab to aflibercept. This is a retrospective study of patients with neovascular AMD resistant to ranibizumab defined as having persistent intra- or subretinal fluid on OCT scans despite at least 6-month treatment and switched to aflibercept. Clinical data was collected and quantitative measurements of the area of EZ and ELM damage were obtained, on en-face optical coherence tomography images, at the time of switch to aflibercept (baseline) and up to 6months of follow-up. The study included 71 eyes (52.1% right eye) of 71 patients. At baseline, there was a correlation between the size of the EZ and ELM damaged area and BCVA (R=-0.39, p=0.001 and R=-0.47, p<0.001, respectively). The EZ and ELM damaged areas maintained correlation with BCVA at 6months (R=-0.28, p=0.01 and R=-0.39, p=0.001, respectively). Central retinal thickness did not correlate with BCVA at the time of switch (p=0.38) or at 6months (p=0.36). The extent of damage to the EZ and ELM correlates with BCVA following a switch in treatment.

Long‐term outcomes of switching to aflibercept for treatment‐resistant neovascular age‐related macular degeneration

To report 4-year outcomes following the switch to aflibercept in treatment-resistant neovascular age-related macular degeneration (nAMD). In this prospective, open-label, non-controlled, clinical trial, 49 patients with treatment-resistant nAMD received 2mg intravitreal aflibercept as three loading doses every 4weeks, followed by injections every 8weeks for the first 48weeks, then an individualized regimen for a further 36months, following previous treatment with ranibizumab and/or bevacizumab. Outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) height and geographic atrophy (GA) surface area. Of the 49 patients who were initially recruited, data from 39 eyes of 39 patients were available at 48-month follow-up. Mean age was 76.7±7.2years. Over the 48months, these eyes received a mean of 32.1±5.6 injections. The mean BCVA improved significantly following 12months of treatment (4.9±9.0 ETDRS letters, p<0.001); however, this was not maintained and was similar to baseline after 48months (mean difference -0.4±13.3 letters between baseline and 48months, p<0.001). The reduction in CRT from baseline was 170.3±143.3μm (p<0.001) with absence of macular fluid in 56% of the 39 eyes at the end of month 48. PED height reduced by a mean 77.5±20.0μm, and geographic atrophy increased by a mean of 4.1±3.4mm2 (p<0.01) over the 48months. Aflibercept is an effective alternative therapy for treatment-resistant nAMD. Good anatomical and stable functional responses are achievable with continued therapy. The lack of continued visual improvement may be representative of GA progression, reflecting the progression of late-stage nAMD in these patients.

OUTCOME OF INTRAVITREAL AFLIBERCEPT FOR REFRACTORY PIGMENT EPITHELIAL DETACHMENT WITH OR WITHOUT SUBRETINAL FLUID AND SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

To investigate the outcomes of intravitreal aflibercept in refractory pigment epithelial detachment (PED) with or without subretinal fluid (SRF) in patients with neovascular age-related macular degeneration. A prospective, nonrandomized, interventional case series involved 40 patients with persistent vascularized PED previously treated with at least 3 injections of intravitreal bevacizumab or ranibizumab. Intravitreal aflibercept was administered as 3 initial loading doses every 4 weeks, followed by pro re nata retreatment every 8 weeks over 48 weeks. Pigment epithelial detachment was classified into solid-, hollow-, or mixed-type according to the reflective properties visualized using optical coherence tomography. The mean changes in best-corrected visual acuity, central subfield thickness, and the volumes of SRF and PED were analyzed. The PED volume (baseline: 0.43 ± 0.55 mm) significantly reduced to 0.23 ± 0.32 mm at Week 8 (P = 0.003) and increased to 0.36 ± 0.41 mm at Week 48 (P = 0.345). The SRF volume (baseline: 0.52 ± 0.64 mm) significantly reduced to 0.24 ± 0.43 mm at Week 48 (P = 0.021). The mean baseline best-corrected visual acuity was 20/75 (47.5 letters); it showed no significant difference at Week 48 (+4.4 letters; P = 0.125). The baseline central subfield thickness was 323.2 ± 92.3 μm; it significantly reduced to 281.2 ± 90.7 μm at Week 48 (P = 0.001). In solid-type PEDs, there were poorer improvements in central subfield thickness, best-corrected visual acuity, and the volumes of the SRF and PED, with newly developed intraretinal cysts. Intravitreal aflibercept in treatment-resistant neovascular age-related macular degeneration led to significant reduction in PED and SRF volume, central subfield thickness, and best-corrected visual acuity preserved, over 12 months. However, solid-type PED showed less improvement than hollow- or mixed-type PED.

One-Year Outcomes of Intravitreal Conbercept for Treatment-Resistant Neovascular Age-Related Macular Degeneration

Purpose: To evaluate the efficacy of intravitreal conbercept injections in patients with treatment-resistant neovascular age-related macular degeneration (nvAMD). Methods: Retrospective review of patients with resistance (persistent exudation) to ranibizumab (0.5 mg) that were switched to treatment with 3 monthly intravitreal injections of conbercept (0.5 mg), followed by dosing on an as-needed basis. The demographic data, visual acuities, central retinal thickness (CRT), and the maximum pigment epithelial detachment (PED) height were reviewed. Results: Outcomes observed in 34 eyes from 26 patients with a mean of 7.68 (range 6–14) previous ranibizumab injections were compiled. Twelve months after switching to conbercept, there were significant reductions of CRT (402.59 ± 163.85 vs. 473.18 ± 164.84 μm, p = 0.002) and maximum PED height (218.59 ± 106.89 vs. 295.32 ± 179.80 μm, p = 0.006) compared with the baseline. No statistical change in visual acuity logarithm of the minimal angle of resolution occurred after 12 months (0.68 ± 0.48 vs. 0.78 ± 0.63 letters, p = 0.17) despite 27 of 34 eyes (79.41%) remaining stable or having improvement visual acuity. Conclusions: Intravitreal injections of conbercept appear to be beneficial in patients with nvAMD who exhibit persistent fluid despite previous treatment with ranibizumab.

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis.

PurposeTo systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD).DesignSystematic review and meta-analysis.MethodsMedline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs).ResultsOf 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI −0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI −0.26 to 1.52, P=0.17, respectively). There was a significant improvement in mean CRT following switching (−61.90 µm, 95% CI −77.10 to −46.80, P<0.001 and −50.00 µm, 95% CI −63.20 to −36.80, P<0.001 at 6 and 12 months, respectively).ConclusionPooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.

Vision-related quality of life: 12-month aflibercept treatment in patients with treatment-resistant neovascular age-related macular degeneration

To assess changes in vision-related quality of life (VR-QoL) among patients with treatment-resistant neovascular age-related macular degeneration (nAMD) following intravitreal aflibercept treatment over 48weeks. We conducted a prospective study in which 49 patients with nAMD resistant to anti-vascular endothelial growth factor therapy were switched to intravitreal aflibercept. Patients were treated with three loading doses every 4 weeks followed by injections every 8 weeks, for a total of 48weeks. Ophthalmic examinations performed at each visit included best-corrected visual acuity (BCVA) and central macular thickness (CMT) measurement. The National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) was used to assess VR-QoL at baseline and weeks 24 and 48. Changes in NEI VFQ-25 composite and subscale scores were analyzed using paired t tests. The relationship between the change in VR-QoL and changes in BCVA and CMT, and the impact of the better-seeing eye (BSE, defined as the eye reading the greater number of letters at baseline) vs. the worse-seeing eye (WSE, the fellow eye to the BSE) were assessed. Mean NEI VFQ-25 composite scores improved significantly at weeks 24 and 48 compared to baseline (4.5 ± 9.2 and 4.4 ± 11.8, respectively, all p < 0.01). Among subscales, general vision and near and distance activities showed significant improvements at weeks 24 and 48 (all p < 0.05). Improvement in the NEI VFQ-25 composite score was significantly associated with increased BCVA at week 48 (β coefficient = 0.43, p = 0.029), but not with change in CMT (β coefficient = -0.007, p = 0.631). There was no association between VR-QoL changes and BSE or WSE. Despite previous anti-VEGF treatment in this cohort, overall VR-QoL improved following aflibercept therapy over 48weeks. This improvement was related to improved vision in treatment eyes regardless of whether they were the BSE or WSE.

Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-Related Macular Degeneration: 12-Month Safety and Efficacy Outcomes

Purpose: To prospectively assess the safety and efficacy of intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). Methods: This prospective, non-randomized clinical trial included 49 patients with treatment-resistant nAMD who received 2 mg intravitreal aflibercept as 3 monthly loading doses, followed by injections every 2 months over 12 months. Inclusion criteria included active nAMD on fluorescein angiography at baseline and persistent intra- or subretinal fluid on optical coherence tomography (OCT) for ≥6 months prior to baseline with a minimum of 4 injections of bevacizumab and/or ranibizumab. Patients were assessed monthly for best-corrected visual acuity (BCVA), central retinal thickness (CRT) measured with OCT and occurrence of adverse events. Retinal pigment epithelium atrophy (RPEA) was assessed at baseline and at 12 months. Results: Mean BCVA improved by 4.7 letters (95% CI: 2.1-7.3, p < 0.001) and CRT decreased by 97.2 µm (95% CI: 54.4-140.1, p < 0.001) at 12 months compared to baseline. Median RPEA area increased by 0.48 mm² (range = -0.1 to 19.9, p < 0.001). There was 1 arterial thromboembolic event and 2 cases of submacular haemorrhage. Conclusion: In this cohort of treatment-resistant nAMD patients, intravitreal aflibercept was effective in improving vision and reducing exudation. Early visual and anatomic outcomes may predict longer-term response to treatment, but further assessment is required.

Correlation Between Hyperreflective Foci and Clinical Outcomes in Neovascular Age-Related Macular Degeneration After Switching to Aflibercept.

To assess the correlation between hyperreflective foci (HF) and visual and anatomical outcomes in treatment-resistant neovascular age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). This was a prospective interventional case series. Thirty-three eyes of 30 consecutive patients with treatment-resistant neovascular AMD were enrolled. Intravitreal aflibercept injections were performed at week 0 (baseline), week 4, and week 8. Spectral-domain OCT images were obtained before each injection and 4 weeks after the third injection. The main focus was on the measurement of choroidal neovascularization (CNV) size in the cross-sectional area in the B-scan through the fovea, and HF number along line segments of 1- and 3-mm length passing through the fovea. Mean number of HF in the radius of 500 μm decreased from 8.36 ± 7.58 to 4.15 ± 3.39 (P = 0.02). Mean number of HF in the radius of 1500 μm was reduced from 21.30 ± 12.47 to 10.45 ± 6.34 (P < 0.001). Mean CNV area decreased from 0.35 ± 0.22 to 0.22 ± 0.16 mm2 (P < 0.001). There was a significant positive correlation between HF reduction in the radius of 500 μm and decrease in central subfield thickness (CST) (r = 0.43, P = 0.01), but no statistically significant correlation was found between HF decline in the radius of 1500 μm and other parameters. Switching from ranibizumab to aflibercept caused significant decrease in the number of HF 1 month after aflibercept upload, and HF decrease in the radius of 500 μm was correlated positively with the reduction in CST.

Rescue effects of intravitreal aflibercept in the treatment of neovascular age-related macular degeneration

We report the rescue results of intravitreal aflibercept in patients with treatment-resistant neovascular age-related macular degeneration (AMD). We retrospectively analyzed eyes with neovascular AMD resistant to posterior subtenon triamcinolone, intravitreal ranibizumab, and/or bevacizumab treatment in a tertiary medical center in middle Taiwan between December 2013 and October 2014. We then switched treatment to 2.0 mg aflibercept. The main outcome included changes in best-corrected visual acuity and central foveal thickness measured by optical coherence tomography during monthly follow-up. There were 204 patients with neovascular AMD, and the percentage of refractory cases was 1.96% (4 of 204 cases). Our study included five eyes of four patients that were resistant to multiple treatments and subsequently switched to aflibercept. The mean age was 71.25 ± 11.09 years (range 57–83 years). Treatments were on average 6.6 times previously. Upon switching to aflibercept treatment, the average central foveal thickness on optical coherence tomography was 505.6 ± 270.86 μm (range 150–815 μm). After aflibercept treatment, the average central foveal thickness was 192 ± 51.76 μm (range 149–274 μm). All patients showed anatomic improvement, and 80% of the eyes (4 of 5 eyes) had improved best-corrected visual acuity and 20% of the eyes (1 of 5 eyes) had stable visual acuity. Patients tolerated the treatment well without serious adverse events. This short-term study showed that intravitreal aflibercept was effective and safe in treatment-resistant neovascular AMD cases. However, analysis of more cases and long-term follow-ups are mandatory.

Response of pigment epithelial detachments to intravitreal aflibercept among patients with treatment-resistant neovascular age-related macular degeneration.

To assess the effect of intravitreal aflibercept on pigment epithelial detachment (PED) in patients with treatment-resistant neovascular age-related macular degeneration. Forty-six patients with vascularized PEDs participating in a wider, prospective clinical trial of treatment-resistant neovascular age-related macular degeneration received 2-mg aflibercept as 3 loading doses 1 month apart, followed by further 2-monthly doses over a total 12-month period. Change in PED dimensions and reflective properties were assessed by optical coherence tomography. Reflectivity was subclassified as solid (hyperreflective), hollow (hyporeflective), or mixed (elements of both). Aflibercept reduced PED height, width, and length at 48 weeks compared with baseline values (P ≤ 0.01 for all). Reductions in PED height were correlated with reductions in central macular thickness at 48 weeks (R = 0.36, P < 0.001). There was no significant correlation between PED height decrease and visual acuity changes at 48 weeks. Solid PEDs were less likely to experience reductions in all three dimensions than either hollow or mixed PEDs. Aflibercept is effective in reducing PED dimensions in treatment-resistant patients and is most effective in PEDs demonstrating some hyporeflective optical coherence tomography characteristics. Reduction in PED dimensions correlated with central macular thickness, but not with visual acuity changes. The role of PEDs as markers of disease requires further investigation; however, lesions should be monitored for retinal fluid recurrence.

Biweekly Bevacizumab for Refractory Neovascular Age-related Macular Degeneration

Purpose: To evaluate the effectiveness of biweekly (twice-permonth) bevacizumab for treatment-resistant neovascular agerelated macular degeneration (nAMD). Methods: The charts of nAMD subjects treated with biweekly bevacizumab injections because of persistent retinal edema on optical coherence tomography (OCT) despite consecutive monthly anti-vascular endothelial factor (VEGF) therapy were retrospectively

Treating the untreatable patient: current options for the management of treatment-resistant neovascular age-related macular degeneration.

Anti-vascular endothelial growth factor (anti-VEGF) agents represent the current standard of care for neovascular age-related macular degeneration (nAMD). Although effective in a majority of cases, a significant proportion of patients have persisting retinal exudation despite regular anti-VEGF therapy. This exudation is considered to produce poorer visual outcomes in these patients. Some of these patients may have misdiagnosed nAMD variants such as polypoidal choroidal vasculopathy; however, the majority of these eyes have what has been termed treatment-resistant nAMD. Currently, the best way to care for these patients is uncertain. Here, we review the evidence for different approaches to the management of treatment-resistant nAMD, including high-dose anti-VEGF therapy, combination regimes and switching of anti-VEGF agents, and discuss possible therapeutic approaches for patients with treatment-resistant nAMD.

Visual and anatomical outcomes of intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration.

A retrospective chart review of patients with persistent subretinal and/or intraretinal fluid, despite previous treatment with intravitreal ranibizumab (0.5 mg), who were switched to aflibercept injections, was performed. Treatment was three monthly aflibercept (2 mg) injections followed by dosing on pro re nata basis. Main outcome measures included changes in best corrected visual acuity (BCVA), 1 mm central subfield (CSF) retinal thickness, the height of the pigment epithelial detachment (PED), and subfoveal choroidal thickness on optical coherence tomography at 6 months. Thirty-one eyes of 30 patients were analyzed. The mean number of injections before aflibercept conversion was 34.4 ± 11.9. After an average of 4.5 aflibercept injections (range 3 to 6) over 6 months, no significant change in BCVA was observed (P > 0.05). Compared with baseline, there was a significant reduction of the CSF retinal thickness (449 ± 179 versus 269 ± 145 μm, P < 0.001), maximum PED height (262 ± 134 versus 183 ± 100 μm, P < 0.001), and choroidal thickness (192 ± 67 versus 167 ± 51 μm, P < 0.01). Stable visual acuity and anatomical improvement were obtained for up to 6 months after aflibercept conversion. However, choroidal thinning related to treatment was observed.