Refractory Neovascular Age-related Macular Degeneration Research Articles

Short-term outcomes of intravitreal faricimab for refractory neovascular age-related macular degeneration.

To assess the short-term outcomes of intravitreal faricimab (IVF) for previously treated refractory neovascular age-related macular degeneration (nAMD) in a real-world setting. A retrospective monocentric study including 44 eyes treated with an upload of 4 × monthly intravitreal injections (IVI) of faricimab 6 mg/0.05 mL and followed for 4 weeks after last IVI (16 W). Patients were switched to IVF after treatment with at least three other anti-vascular endothelial growth factors (anti-VEGF). Main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and retinal fluid distribution. 44 eyes of 44 patients with previously treated refractory nAMD (63% males) were included. Mean age was 79 ± 7 years. The total number of previous anti-VEGF before switching to IVF was 32 ± 15 IVIs/eye. BCVA (logMAR) improved significantly from 0.65 ± 0.26 to 0.50 ± 0.23 at 16 W (p < 0.01). CMT (µm) decreased significantly from 422 ± 68 to 362 ± 47 at 16 W (p < 0.01). SFCT did not change significantly at 16 W (p = 0.06). The number of eyes with subretinal fluid (SRF) decreased significantly from 29 (65%) to 13 (29%) at 16 W (p = 0.001). There were no significant changes regarding the distribution of intraretinal fluid or pigment epithelial detachment (p > 0.05). A complete fluid resolution was achieved in 8 eyes (18%). No adverse events were noticed. In the short term, IVF led to a significant decrease in CMT as well as a significant improvement of BCVA and thus appears to be an effective treatment option for previously treated refractory nAMD without relevant adverse effects.

First-Year Real-Life Experience with Intravitreal Faricimab for Refractory Neovascular Age-Related Macular Degeneration.

Background: To evaluate the outcomes of intravitreal faricimab (IVF) for refractory neovascular age-related macular degeneration (nAMD) and investigate the impact of baseline optical coherence tomography, biomarkers for total IVF injections are needed. Methods: A retrospective analysis of 33 eyes of patients who completed one year (52 W) of treatment with IVF. The eyes received four IVF injections (6 mg/0.05 mL) as the upload phase. Thereafter, the treatment interval was extended to 8 or 12 weeks if disease activity was not recorded. The outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal fluid distribution. Results: A total of 33 eyes were included. CMT decreased significantly at 52 W (p < 0.01). BCVA and SFCT did not change significantly at 52 W (p > 0.05). The number of eyes with subretinal fluid decreased significantly at 52 W (p < 0.01). Complete fluid resolution was achieved in 20 eyes (60%). The total number of injections was significantly negatively correlated with the presence of hyperreflective dots at baseline (HRDs, p < 0.01) and SFCT at baseline (p < 0.01). Conclusions: IVF led to a significant reduction in CMT with stabilization of BCVA. The total number of injections was lower in eyes with HRDs and increased SFCT at baseline. This might provide clues regarding response to IVF for future studies.

Real-world study to evaluate the efficacy and safety of intravitreal brolucizumab for refractory neovascular age-related macular degeneration

This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (− 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy.

Sustained Biweekly Aflibercept For Refractory Neovascular Age-Related Macular Degeneration: The Prospective TRISTAR Study.

To assess the safety and efficacy of biweekly (every 2 week) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD). A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual SRF at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52. Enrolled eyes (n=22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. BCVA improved significantly from baseline to week 14 (2.52 letters, p<0.001). Mean CST was also significantly improved at week 14 (-31.9µm, p<0.001) with 8 of 22 eyes achieving complete SRF resolution. Only 2 of 8 eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7µm compared with week 14. By week 52, improvements in BCVA and CST were lost. In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomic improvements during biweekly dosing. These gains, however, were lost upon return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.

Short-term Effect and Safety of a Single Intravitreal Brolucizumab in Refractory Neovascular Age-related Macular Degeneration

Minjae Kang, Christopher Seungkyu Lee, Ye Ji Kim, Hae Rang Kim, Jay Jiyong Kwak, Sun Young Ryu, Do Wook Kim, Hyo Song Park, Jae Yong Han, Yong Joon Kim, Eun Young Choi, Suk Ho Byeon, Sung Soo Kim. J Retin 2022;7:113-20. https://doi.org/10.21561/jor.2022.7.2.113

Automatic quantification of retinal photoreceptor integrity to predict persistent disease activity in neovascular age-related macular degeneration using deep learning.

Using deep learning (DL)-based technique, we identify risk factors and create a prediction model for refractory neovascular age-related macular degeneration (nAMD) characterized by persistent disease activity (PDA) in spectral domain optical coherence tomography (SD-OCT) images. A total of 671 typical B-scans were collected from 186 eyes of 186 patients with nAMD. Spectral domain optical coherence tomography images were analyzed using a classification convolutional neural network (CNN) and a fully convolutional network (FCN) algorithm to extract six features involved in nAMD, including ellipsoid zone (EZ), external limiting membrane (ELM), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal hyperreflective material (SHRM). Random forest models were probed to predict 1-year disease activity (stable, PDA, and cured) based on the quantitative features computed from automated segmentation and evaluated with cross-validation. The algorithm to segment six SD-OCT features achieved the mean accuracy of 0.930 (95% CI: 0.916-0.943), dice coefficients of 0.873 (95% CI: 0.847-0.899), a sensitivity of 0.873 (95% CI: 0.844-0.910), and a specificity of 0.922 (95% CI: 0.905-0.940). The six-metric model including EZ and ELM achieved the optimal performance to predict 1-year disease activity, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.980, the accuracy of 0.930, the sensitivity of 0.920, and the specificity of 0.962. The integrity of EZ and ELM significantly improved the performance of the six-metric model than that of the four-metric model. The prediction model reveals the potential to predict PDA in nAMD eyes. The integrity of EZ and ELM constituted the strongest predictive factor for PDA in nAMD eyes in real-world clinical practice. The results of this study are a significant step toward image-guided prediction of long-term disease activity in the management of nAMD and highlight the importance of the automatic identification of photoreceptor layers.

First Year Real Life Experience With Intravitreal Brolucizumab for Treatment of Refractory Neovascular Age-Related Macular Degeneration.

Purpose: To assess the morphological and functional outcomes within the first year of treatment with intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 21 eyes from 19 patients with refractory nAMD followed for 12 months. All patients were switched to brolucizumab after treatment with at least two other anti-vascular endothelial growth factors (VEGF). All eyes received 3x brolucizumab 6 mg/0.05 ml intravitreal injections (IVI) monthly as an upload phase. Then eyes received an IVI every 8 weeks with interval adjustment to every 12 weeks if disease activity was not present. Main outcome measures: best corrected visual acuity (BCVA), central macular thickness (CMT) and retinal fluid distribution. In addition, we reported the adverse event rate. Results: The number of previous anti-VEGF IVIs/eye was 36 ± 22 before switching to brolucizumab. BCVA (ETDRS) was 51 ± 16 before treatment and 50 ± 19 at week 52 (p = 0.6). CMT was 374 ± 158 μm before treatment and 298 ± 92 μm at week 52 (p = 0.01). The number of IVIs/eye decreased from 9.6 ± 1.9 IVIs in the last year before switching to 6.4 ± 0.9 IVIs in the first year after switching to brolucizumab (p < 0.001). The rate of eyes with subretinal fluid and pigment epithelial detachment decreased at week 52. Finally, two cases of intraocular inflammation were observed as adverse events. Conclusion: In the first year of treatment, intravitreal brolucizumab was able to stabilize visual acuity with significantly less IVIs in patients with refractory nAMD. It also improved anatomic outcomes in these patients, particularly reducing subretinal fluid and pigment epithelial detachment and subsequently central macular thickness. However, two cases of intraocular inflammation were observed as adverse events.

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration.

To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. Retrospective observational study. Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. A total of 48 eyes of 48 patients were reviewed. At 4 to 7weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4µm to 241.9 ± 92.5µm (P < 0.001) and CCT from 182.6 ± 89.3µm to 169.7 ± 82.6µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1month. At 16weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8weeks. Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

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

PurposeTo 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.MethodsThis 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.ResultsSixty 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.ConclusionSo-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

PurposeThe 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.MethodsA 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).ResultsThere 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.ConclusionPatients 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.

Bevacizumab dosing every 2 weeks for neovascular age-related macular degeneration refractory to monthly dosing.

To evaluate intravitreal bevacizumab every 2 weeks (biweekly) in refractory neovascular age-related macular degeneration (nAMD). Retrospective study. A retrospective study of consecutive nAMD patients unresponsive to monthly intravitreal anti-vascular endothelial growth factor (VEGF) switched to 3-4 biweekly injections. Twenty-seven eyes of patients aged 82.08 ± 6.85 years were included. Prior to the 2-week interval bevacizumab injections, 74.1% (n=20) were treated with both bevacizumab and ranibizumab, 11.1% (3 eyes) also received aflibercept and 14.8% (4 eyes) had received prior treatment of monthly bevacizumab (average number of injections 21.5 ± 6.7). Best corrected visual acuity (BCVA) remained stable between baseline (logMAR 0.72± 0.60) and follow-up (0.76± 0.66) (p=0.41). Mean central macular thickness and macular volume did not change significantly between baseline and follow-up (p=0.35 and p=0.60, respectively). Six eyes (22.2%) showed morphologic anatomic improvements, while 19 eyes (70.4%) were stable and two eyes (7.4%) deteriorated from baseline. Subretinal fluid completely resolved in 3 of the eyes and improved in the other 3 eyes and in this group (22.2%) both central macular thickness (326.2 ± 101.4 versus 297.5 ± 97.2, p=0.002) and macular volume (8.69 ± 1.69 versus 8.22 ± 1.43, p=0.03) were significantly reduced. No adverse events were observed in any of the treated eyes. This study demonstrates that biweekly bevacizumab injections are effective in nearly one-quarter of nAMD non-responders with no adverse events reported. Switching earlier, rather than later, to this low cost modality may be of benefit for a portion of non-responders to conventional treatment.

Switching Anti-Vascular Endothelial Growth Factors in Refractory Neovascular Age-Related Macular Degeneration.

Anti-vascular endothelial growth factor (VEGF) therapy is the treatment of choice for cases with neovascular age-related macular degeneration (AMD). Switching to an alternate anti-VEGF has been suggested as a possible option for resistant cases. The purpose of this review is to evaluate whether the timing of switching affects treatment outcomes. A review of published literature was performed looking at all studies where patients with refractory neovascular AMD were switched to an alternative anti-VEGF. Studies were then stratified based on the timing of switching into early (< 12 previous injections) and late (> 12 previous injections). A total of 38 studies were identified: 18 where patients were switched early and 20 where they were switched late. Both subgroups showed anatomic improvement after switching, with limited visual gains. There are insufficient data to recommend early versus late switching. However, both groups showed a reduction of fluid on optical coherence tomography and visual gains in 25% to 30% of patients. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:166-170.].

Refractory Neovascular Age-related Macular Degeneration

Refractory Neovascular Age-related Macular Degeneration

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To determine the efficacy of monthly (0.1 mL/4 mg) aflibercept for refractory neovascular age-related macular degeneration (wet age-related macular degeneration). This was a retrospective interventional case series in which patients with wet age-related macular degeneration were treated with stepwise dose escalation. Nonvitrectomized patients resistant to monthly (Q4W) ranibizumab/bevacizumab were switched to 2 mg aflibercept every 8 weeks. With resistance, they were escalated to Q4W 2 mg aflibercept, then Q4W 4 mg (high dose high frequency, 4Q4W) aflibercept. Resistance was defined as ≥2 recurrences after being dry following ≥3 injections or persistent exudation on treatment of ≥5 injections. Thirty-three eyes of 28 patients were treated with 4Q4W aflibercept and followed for a mean of 16 months. A dry retina (no intraretinal or subretinal fluid) was achieved after initiating 4Q4W aflibercept treatment at a mean of 3.8 months. Central foveal thickness, maximum foveal thickness, intraretinal fluid, subretinal fluid, and retinal pigment detachment height decreased significantly at 1 month after initiating the 4Q4W aflibercept, and the morphologic therapeutic effect was sustained until the last visit. Forty-five percent of eyes had one or more lines of vision improvement. New geographic atrophy developed in 9% of eyes during follow-up. No ocular or systemic adverse events occurred after initiating 4Q4W aflibercept. Intravitreal high-dose high-frequency aflibercept is an effective treatment for patients with refractory wet age-related macular degeneration.

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review.

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward.

The recent introduction of anti-VEGF drugs has widely changed the prognosis of exudative age-related macular degeneration (AMD), even if a variable percentage of patients showed an insufficient response. Aflibercept is a new anti-VEGF drug approved by FDA for the treatment of exudative AMD with a wider binding capacity than either bevacizumab or ranibizumab. Therefore, the purposes were as follows: (i) to report anatomical and functional outcomes of switching from bevacizumab/ranibizumab to aflibercept previously described in the scientific literature, (ii) to hypothesize the possible pathophysiological mechanisms of the resistance and tachyphylaxis to anti-VEGF drugs, and (iii) to suggest possible clinical actions to increase the chances of success for such difficult cases. We reviewed the available scientific literature in Medline, Cochrane database, Current Contents, PubMed, and cross-referencing from identified articles, regarding the treatment of exudative AMD patients refractory to bevacizumab and/or ranibizumab and switched to aflibercept monotherapy. We included in this review all the cases in which the diagnosis of refractory or resistant exudative AMD was properly made, and the results of at least one aflibercept injection were described. We reported the outcomes of 21 papers for a total of 1066 eyes affected by exudative AMD resistant to previous anti-VEGF drug injections and switched to aflibercept. Enrolled reports were divided into two groups: 5 prospective reports and 16 retrospective reports. All the reported papers conclude their analysis, stating that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. Analysis of the papers reported in this review demonstrates that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. The mechanism for these effects is not yet completely understood.

Alternating Bi-Weekly Intravitreal Ranibizumab and Bevacizumab for Refractory Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment

Objective: To describe visual and anatomical outcomes following bi-weekly intravitreal ranibizumab/bevacizumab injections in eyes with refractory neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED). Design: Retrospective, consecutive, interventional case series. Participants: Eighteen patients diagnosed with neovascular AMD that were refractory to anti-VEGF therapy and received alternating biweekly ranibizumab/bevacizumab injections were included. Methods: Patients with neovascular AMD and PED that were refractory to at least 11 monthly ranibizumab or bevacizumab injections were included in this study at a large, single retina practice. Following inclusion, patients received four bi-weekly alternating ranibizumab/bevacizumab intravitreal injections. After completing a course of four bi-weekly injections, patients were treated with variable regimens of intravitreal anti-vascular endothelial growth factor (VEGF) therapy. The primary outcomes of the study included change in visual acuity (VA) and central foveal thickness (CFT) at eight weeks follow-up. Results: Study eyes had previously received a mean of 22 intravitreal anti-VEGF injections. At enrollment, mean VA was 20/95 and mean CFT was 455 µm. After four bi-weekly anti-VEGF injections, mean VA improved to 20/65 (p < 0.001), and mean CFT decreased to 387 µm (p = 0.029). In patients with PED, there was a mean 27.9% reduction in height (p = 0.046) at eight weeks’ follow-up. Conclusions: Four injections of bi-weekly alternating ranibizumab/bevacizumab improved visual acuity and reduced macular thickness in a number of patients with refractory neovascular AMD and PED.

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

Refractory Neovascular Age-related Macular Degeneration Secondary to Polypoidal Choroidal Vasculopathy

To describe a neovascular pattern associated with treatment-refractory neovascular age-related macular degeneration (AMD). A retrospective observational case series. Clinical practice. Twelve eyes of 12 patients with neovascular AMD in which a poor anatomic response to anti-vascular endothelial growth factor (VEGF) therapy was related to polypoidal choroidal vasculopathy (PCV). Slit-lamp biomicroscopy, optical coherence tomography, fluorescein and indocyanine green angiography. Snellen visual acuity (VA), anatomic response to therapy including presence or absence of retinal edema, hemorrhage, and lipid exudates. New or persistent PCV was identified in a cohort of patients demonstrating increasing macular exudation despite regular intravitreal ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) or bevacizumab (Avastin; Genentech Inc) injections for a minimum of 6 months. Treatment with verteporfin photodynamic therapy (PDT), PDT/anti-VEGF combination therapy, or continued anti-VEGF monotherapy resulted in complete resolution of exudation in 9 of 12 patients and partial resolution of exudation in the remaining 3 patients. Treatment-refractory neovascular AMD may harbor vascular abnormalities such as PCV. Modifications in therapeutic protocols may be indicated in order to improve visual and anatomic outcomes in this population.