Treatment Of Polypoidal Choroidal Vasculopathy Research Articles

Evaluating photodynamic therapy versus brolucizumab as a second-line treatment for polypoidal choroidal vasculopathy.

To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy. This case-control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders. Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: -36.3 ± 99.4μm vs. -114.7 ± 181.4μm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42-2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44. Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.

Predicting treatment outcomes of intravitreal brolucizumab for polypoidal choroidal vasculopathy through noninvasive assessment of polypoidal lesion blood flow with optical coherence tomography angiography

We investigated the assessment of blood flow within polypoidal lesions using optical coherence tomography angiography (OCTA) to determine intravitreal brolucizumab (IVBr) efficacy for treating polypoidal choroidal vasculopathy (PCV). We retrospectively studied 46 eyes with PCV that completed 1-year IVBr treatment. Blood flow signals within polypoidal lesions were evaluated using OCTA after loading-phase treatment, and 1-year outcomes were compared between eyes in which blood flow signals disappeared versus persisting. After loading-phase treatment, blood flow signals within polypoidal lesions disappeared in 31 eyes and persisted in 15. In the former group, visual acuity improved significantly throughout the year (P < 0.01), while in the latter there was no significant difference between baseline and after 1 year. The total number of injections was significantly lower with than without disappearance of blood flow signals (6.0 vs. 6.9, P < 0.01). The intended injection interval at the last visit was significantly longer in the former than in the latter group (15.7 weeks vs. 12.5 weeks, P < 0.01). These results indicate that PCV cases showing disappearance of blood flow signals within polypoidal lesions by OCTA after loading-phase treatment had favorable 1-year outcomes of IVBr. Therefore, evaluating blood flow within polypoidal lesions by OCTA may allow noninvasive prediction of PCV treatment outcomes.

Advances in multi-modal non-invasive imaging techniques in the diagnosis and treatment of polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a disease characterized by subretinal pigment epithelium (RPE) orange-red polypoidal lesions and abnormal branching neovascular networks (BNNs). In recent years, various non-invasive imaging technologies have rapidly developed, especially the emergence of optical coherence tomography angiography (OCTA), multi-spectral imaging, and other technologies, which enable the observation of more features of PCV. In addition, these technologies are faster and less invasive compared to indocyanine green angiography (ICGA). Multi-modal imaging, which combined multiple imaging techniques, provides important references for the diagnosis and treatment of PCV with the assistance of regression models, deep learning, and other algorithms. In this study, we reviewed the non-invasive imaging techniques, multi-modal imaging diagnosis, and multi-scene therapeutic applications of PCV, with the aim of providing a reference for non-invasive multi-modal diagnosis and treatment of PCV.

Polypoidal Choroidal Vasculopathy: Updates on Risk Factors, Diagnosis, and Treatments.

There have been recent advances in basic research and clinical studies in polypoidal choroidal vasculopathy (PCV). A recent, large-scale, population-based study found systemic factors, such as male gender and smoking, were associated with PCV, and a recent systematic review reported plasma C-reactive protein, a systemic biomarker, was associated with PCV. Growing evidence points to an association between pachydrusen, recently proposed extracellular deposits associated with the thick choroid, and the risk of development of PCV. Many recent studies on diagnosis of PCV have focused on applying criteria from noninvasive multimodal retinal imaging without requirement of indocyanine green angiography. There have been attempts to develop deep learning models, a recent subset of artificial intelligence, for detecting PCV from different types of retinal imaging modality. Some of these deep learning models were found to have high performance when they were trained and tested on color retinal images with corresponding images from optical coherence tomography. The treatment of PCV is either a combination therapy using verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF), or anti-VEGF monotherapy, often used with a treat-and-extend regimen. New anti-VEGF agents may provide more durable treatment with similar efficacy, compared with existing anti-VEGF agents. It is not known if they can induce greater closure of polypoidal lesions, in which case, combination therapy may still be a mainstay. Recent evidence supports long-term follow-up of patients with PCV after treatment for early detection of recurrence, particularly in patients with incomplete closure of polypoidal lesions.

Commentary: Biosimilars in the treatment of retinopathy of prematurity.

The Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity study established the superiority of intravitreal bevacizumab monotherapy over conventional laser therapy in infants with Zone I disease.[1] The current indications for the use of intravitreal antivascular endothelial growth factor (VEGF) injection include aggressive posterior ROP (APROP); Stage 3 ROP with plus disease in Zone I or Zone II posterior; sick or small child not expected to tolerate laser therapy; progression despite laser therapy; and conditions where performing laser is difficult like poorly dilating pupil, cataract, and vitreous haze or hemorrhage. Other anti-VEGF drugs like ranibizumab, aflibercept, and conbercept have also been shown to be efficacious and safe for the treatment of eyes with ROP.[2-4] However, the high cost of these drugs has contributed to reduced patient compliance. Several biosimilars have been developed to help reduce this financial burden. The World Health Organization has defined biosimilars as “biotechnological products comparable in pharmacokinetics, pharmacodynamics, safety, and efficacy to the already approved innovator biologic product.”[5] The cost of a biosimilar is considerably less compared to the innovator molecule as the cost to develop the former is considerably less (US $120–150 million) than the latter ((US $1.2–1.5 billion).[6] This is due to the reduced need for research and development required to develop the biosimilar drug as well as the lower number of clinical trials required to obtain regulatory approval. Razumab is a biosimilar of ranibizumab that has been developed by Intas Pharmaceuticals, India. It received approval from the Drug Controller General of India in 2015 for the treatment of eyes with neovascular age-related macular degeneration. Currently, it has been approved for myopic choroidal neovascularization (CNVM), polypoidal choroidal vasculopathy (PCV), diabetic macular edema (DME), and retinal vein occlusion (RVO). With the expiry of the patents for bevacizumab and ranibizumab in the United States in 2019 and 2020, respectively, as well as in 2022 in Europe, the use of biosimilars is set to increase multifold.[5] Multiple studies have shown that the efficacy as well as the safety profile of the biosimilar drug for the treatment of CNVM, PCV, DME, and RVO is similar to the innovator drug.[5,6] However, none of the studies have evaluated the drug for the treatment of ROP, even though around 5% of members of the Indian ROP Society use biosimilars for the treatment of ROP.[7] We congratulate the authors for their study showing that monotherapy with biosimilar ranibizumab is effective for the treatment of posterior severe ROP.[8] One of the major apprehensions about the use of biosimilars is the high incidence of adverse drug reactions. Several clusters of sterile endophthalmitis were reported in India from 2015–19 with multiple batches of razumab. As a result, the Vitreoretinal Society of India had to issue an advisory that halted its use for a certain period. The inflammation was hypothesized to occur secondary to the immunogenicity against the molecule.[9,10] However, the incidence reported by the authors in the current study is <0.01%.[8] Similarly, other authors have also reported that they are increasingly becoming satisfied with the safety profile of razumab.[11] Further large sample studies are required to study the safety profile of the biosimilar drug for the treatment of ROP. Treatment with anti-VEGF injections leads to regression of the acute phase of ROP as well as enables the normal development of the retinal vasculature. However, a significant number of eyes show disease recurrence. The third edition of the International Classification of Retinopathy of Prematurity has highlighted that the signs of reactivation may range from a new self-limiting demarcation line to stage 3 with plus disease. They also proposed that the reactivated disease may not follow the normal sequence of stages as seen in the acute-phase disease.[12] Reactivation has been seen to occur most commonly at 37–60 weeks postmenstrual age.[13] Similarly, the authors also reported a recurrence rate of 35%.[8] The various reported risk factors for disease reactivation include low gestational age, birth weight or Apgar score; the presence of APROP, Zone I disease, extensive retinal neovascularization or preretinal hemorrhage; multiple births; the use of supplemental oxygen; and longer duration of hospitalization.[13] Currently, there is no clear consensus on the treatment of reactivated disease. While some authors prefer treatment with laser photocoagulation, others support repeat anti-VEGF injection. The authors treated eyes with the recurrent disease with repeat anti-VEGF injection followed by laser photocoagulation, and eyes with peripheral avascular retina in the absence of recurrence with laser photocoagulation.[8] Tandon et al. proposed performing laser 6–8 weeks after anti-VEGF injection in all the eyes irrespective of disease recurrence.[14] Martinez-Castellanos et al. suggested a treatment algorithm according to which the treatment modality is selected depending on the features of reactivation.[15] Further studies are required standardize the treatment protocol for proper management of the reactivated disease.

Current Trends in Clinical Characteristics, Diagnosis, and Treatment of Polypoidal Choroidal Vasculopathy: A Perspective from Vietnam.

Polypoidal choroidal vasculopathy (PCV) is a common choroidal disease in the Asian population including Vietnam and is characterized by subretinal red-orange nodules, pigmented epithelium detachment, and massive subretinal hemorrhage. The recent focus on PCV in Vietnam can be attributed to advancements in PCV diagnosis and treatment. However, there is a scarcity of published literature and clinical data on PCV in the Vietnamese population, highlighting a key knowledge gap in this region. In order to address this gap, we gathered the opinions of experienced clinicians and retinal experts in Vietnam and reviewed available medical literature with the aim of: (i) providing an overview of PCV in the Vietnamese population—in terms of epidemiology, clinical characteristics, and management; (ii) tailoring international/national guidelines for the diagnosis and management of PCV, in line with available resources and medical equipment in Vietnam; and (iii) identifying gaps in clinical data in order to guide future PCV research in Vietnam and other countries with similar clinical conditions. The present review will enable healthcare providers and researchers to gain insight into current clinical practices and the limitations of PCV management in Vietnam and provide optimal and effective solutions.

Analysis of the aqueous humor lipid profile in patients with polypoidal choroidal vasculopathy

This study aimed to investigate the lipid profiles of aqueous humor from polypoidal choroidal vasculopathy (PCV) patients and identify potential biomarkers to increase the understanding of PCV pathomechanism. An ultra-high performance liquid chromatography-tandem mass spectrometry based untargeted lipidomic analysis was performed to acquire lipid profiles of aqueous humor of PCV patients and control subjects. Differentially expressed lipids were identified by univariate and multivariate analyses. A receiver operator characteristic curve (ROC) analysis was conducted to confirm the potential of identified lipids as biomarkers. Sixteen PCV patients and twenty-eight control subjects were enrolled in this study. In total, we identified 33 lipid classes and 639 lipid species in aqueous humor using the LipidSearch software. Of them, 50 differential lipids were obtained by combining univariate and multivariate statistical analyses (VIP>1 and P < 0.05), and 19 potential lipid biomarkers were identified by ROC analysis. In addition, significant alterations were found in several metabolic pathways, including glycerophospholipid, glycerolipid, and glycosylphosphatidylinositol-anchor biosynthesis. This study is the first to systematically characterize the alterations in lipid profiles in aqueous humor of PCV patients and screen for the potential lipid biomarkers for PCV diagnosis and treatment intervention. The results of this study are likely to broaden our understanding of the pathogenesis of PCV and contribute to improvements in the diagnosis and treatment of the disease.

Rethinking about the treatment of polypoidal choroidal vasculopathy

Polypoidal Choroidal Vasculopathy (PCV) is now categorized as a subtype of neovascular Age-related Macular Degeneration (nAMD), though the ocular manifestation and prognosis of PCV patients are quite distinct from nAMD. Due to its high prevalence in Asian population, retina specialists have implemented multiple randomized control trials (RCT) in recent years, aiming at providing grade 1 clinical evidence for current therapies and exploring efficient and affordable regimens for long-term management of PCV. Here we summarised current problems existed in available RCTs and prognostic biomarkers, and presented our thoughts based on previous clinical experiences which may be helpful for clinical management of PCV.

Quantitative analysis of branching neovascular networks in polypoidal choroidal vasculopathy by optical coherence tomography angiography after photodynamic therapy and anti-vascular endothelial growth factor combination therapy.

To study serial changes in branching neovascular networks (BNN) by using optical coherence tomography angiography (OCTA) in patients with polypoidal choroidal vasculopathy (PCV) who underwent combined photodynamic therapy (PDT) and anti-vascular endothelial growth factor (anti-VEGF) therapy. In this retrospective study of 30 PCV patients who underwent combined therapy, OCTA images obtained at baseline and 1, 3, and 6months after treatment were collected. The vessel area, vessel percentage area, average vessel length, and presence of polypoidal lesions on OCTA images as well as best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT) were recorded at each time point. The BNN- and polypoidal lesion-detection rates on baseline OCTA images were 100% and 71%, respectively. The vessel area decreased during the first 3months, and increased 6months post-treatment, showing significant differences from baseline (p = 0.031). The vessel percentage area also reduced 1 and 3months post-treatment (p = 0.025) and increased 6months post-treatment. Continuous polypoidal lesion regression was observed from 1 to 3 and 6months post-treatment (p = 0.031, p = 0.004, p = 0.002, respectively, in comparison with baseline). Patients with a decreasing vessel area over 6months showed greater choroidal thickness than those with increasing vessel area (p = 0.004). The BNN showed initial regression but were enlarged at 6months after therapy. Patients showing continuous BNN regression showed a thicker choroid at baseline. This difference should be considered during treatment for PCV, and OCTA could be used for follow-up evaluations of PCV patients.

Updated guidelines for the management of polypoidal choroidal vasculopathy: Recommendations from the Indian Polypoidal Choroidal Vasculopathy Panel and the Vitreoretinal Society of India.

In Asians, polypoidal choroidal vasculopathy (PCV) is becoming more widely recognized as a significant cause of exudative maculopathy. The previous set of Indian guidelines on the management of PCV were published in 2018, with a literature search updated up to November 2015. As the treatment of PCV evolves, retinal physicians must constantly modify their current practice. The current guidelines are based on the most up-to-date information on PCV and are an update to the previous set of guidelines. These guidelines were developed by a panel of Indian retinal experts under the aegis of the Vitreoretinal Society of India (VRSI), based on a comprehensive search and assessment of literature up to September 2021. The final guidelines i) provide the updated nomenclature in PCV; ii) discusses the newer diagnostic imaging features of PCV, especially in the absence of indocyanine green angiography (ICGA); and iii) recommends the best possible therapeutic approach in the management of PCV, including the choice of anti-vascular endothelial growth factor (anti-VEGF) agents, treatment regimen, and the role of switching between the anti-VEGF agents. In the face of non-availability of photodynamic therapy (PDT) in India, we constructed practical recommendations on anti-VEGF monotherapy in PCV. The current updated recommendations would provide a broader framework to the treating retinal physician for the diagnosis and management of PCV for optimal therapeutic outcomes.

Real-world cost-effectiveness of anti-VEGF monotherapy and combination therapy for the treatment of polypoidal choroidal vasculopathy.

For patients with polypoidal choroidal vasculopathy (PCV), intravitreal anti-vascular endothelial growth factor (anti-VEGF) combination therapy has been shown to be cost-saving relative to monotherapy in a clinical trial setting. However, whether this also applies to real-world settings is unclear. We aim to compare the real-world functional outcomes and cost-effectiveness of intravitreal anti-VEGF combination therapy relative to monotherapy, to investigate whether combination therapy is truly cost-saving. We used a Markov model to simulate a hypothetical cohort of PCV patients treated at Singapore National Eye Centre. Model parameters were informed by coarsened exact matched estimates of a two-year retrospective study of patients who initiated treatment in 2015. Treatment options included intravitreal aflibercept, bevacizumab, or ranibizumab, as monotherapy or in combination with full-fluence verteporfin photodynamic therapy. The two-year logMAR letters gains were significant for combination therapy ( + 10.6, P = 0.006) but not monotherapy (-2.2, P = 0.459). Over 20 years, a PCV patient would cost the health system SGD 48,790 under monotherapy and SGD 61,020 under combination therapy. Quality-adjusted life-years (QALYs) were estimated to be 7.41 for monotherapy and 7.80 for combination therapy. The incremental cost-effectiveness ratio of combination therapy was SGD 31,460/QALY, which is less than the common willingness-to-pay threshold of per capita gross domestic product of Singapore (SGD 88,990/QALY). Sensitivity analysis showed that combination therapy remained incrementally cost-effective, but not cost-saving. Our study shows that combination therapy is good value for money but is likely to increase costs when applied in real-world settings.

Evolution of Polypoidal Lesions after Treatment of Polypoidal Choroidal Vasculopathy.

PurposeTo evaluate the status and evolution of polypoidal lesions during the course of treatment of patients with symptomatic macular polypoidal choroidal vasculopathy (PCV).DesignComparative cohort study of randomly selected patients from a multicenter, randomized controlled clinical trial.ParticipantsThirty randomly selected patients from the EVEREST II study who were treated with combination ranibizumab and verteporfin photodynamic therapy (n = 15) or ranibizumab monotherapy (n = 15).MethodsAll patients were randomized at baseline and treated with a standardized treatment protocol. Indocyanine green angiography (ICGA) images were graded at the central reading center at baseline and months 3, 6, 12, and 24. Polypoidal lesions present at baseline were overlaid on ICGA images at subsequent visits to determine if these remained perfused or had regressed completely. New polypoidal lesions occurring at subsequent visits were similarly tracked to detail the evolution of each polypoidal lesion.Main Outcome MeasuresComplete polypoidal lesion regression over time.ResultsComplete polypoidal lesion regression was higher in the combination therapy group compared with the monotherapy group at all visits (month 12, 12 of 15 patients [80%] vs. 5 of 14 patients [35.7%]; P = 0.016). Persistence of baseline polypoidal lesions was lower in the combination therapy group: 1 of 15 patients (6.7%) versus 7 of 14 patients (50%) in the monotherapy group at month 12. Recurrences of polypoidal lesions that had regressed completely at an earlier time point were uncommon: 0% in the combination therapy group and 1 patient each at months 6 and 12 in the monotherapy group. Fewer new polypoidal lesions (arising after the baseline visit) were found in the combination therapy group at all visits (combination therapy: 2 of 15 [13.3%] vs. monotherapy: 4 of 14 eyes [28.6%] at month 12). Total polypoidal lesion area was significantly smaller in the combination therapy group compared with the monotherapy group throughout the study (0.013 mm2 vs. 0.110 mm2; P < 0.01 at month 12).ConclusionsCombination therapy was associated with higher rates of complete polypoidal lesion regression and fewer persistent polypoidal lesions compared with monotherapy. Closed polypoidal lesions rarely reopened, regardless of the treatment.

Cost-Utility Analysis of Drug Treatments in Patients with Polypoidal Choroidal Vasculopathy in Thailand.

PurposeThe aim of this study was to estimate the cost-utility and budget impact of pharmacological treatments for the eye with polypoidal choroidal vasculopathy (PCV) in Thailand.MethodsA Markov model-based cost-utility analysis (CUA) and budget impact analysis were conducted. The lifetime cost and outcomes of PCV treatments were estimated. We discounted costs and outcomes at 3% per annum. Parameters were estimated using data from published literatures, local cost and utility data, and epidemiology data among Thai patients. Univariate and probabilistic sensitivity analyses were performed to account for parameter uncertainty.ResultsIntravitreal bevacizumab (IVB) resulted in the lowest lifetime cost, followed by IVB plus verteporfin photodynamic therapy (IVB+vPDT) and intravitreal aflibercept (IVA). The combination of IVB or intravitreal ranibizumab (IVR) and verteporfin photodynamic therapy (IVB+vPDT or IVR+vPDT) yielded the highest quality-adjusted life-years (QALY). When compared with IVB from a societal perspective, the incremental cost-effectiveness ratio for patients with PCV receiving IVB+vPDT, IVR+vPDT, IVA were 10,304; 54,135; and 82,738 the United States dollar (USD) per QALY gained, respectively. At the Thai societal willingness to pay threshold of 4884 USD, IVB had the highest probability of being cost-effective (99%) followed by IVB+vPDT (1%). IVB+vPDT could be a cost-effective strategy and required a budget of 12.61 million USD over five fiscal years when the price of verteporfin reduced by approximately 45%.ConclusionNone of the drug treatments for PCV was cost-effective in the Thai context. The decreased price of verteporfin is required to support the inclusion of IVB+vPDT in the Thai National List of Essential Medicines for the treatment of PCV.

Combination of half-dose photodynamic therapy and anti-VEGF versus anti-VEGF monotherapy for polypoidal choroidal vasculopathy

Introduction: Polypoidal choroidal vasculopathy (PCV) is an abnormality of the inner choroidal vasculature. The recommended treatment for PCV is a combination of standard verteporfin photodynamic therapy (PDT) with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). There have been reports ofsuccess with combination of half-dose PDT (hd-PDT) and anti-VEGF in the treatment of PCV. hd-PDT might be a cost-effective method with favourable outcome in the treatment of PCV and fewer side effects.Purpose: To explore the efficacy of hd-PDT combined with anti-VEGF and anti-VEGF monotherapy in PCV.Study design: Retrospective nonrandomized comparative study.Material and methods: We conducted a retrospective nonrandomized comparative records review of all patients with PCV received a combination of hd-PDT and anti-VEGF vs anti-VEGF monotherapy from November 2017 to November 2019 at Hospital Tengku Ampuan Afzan, Pahang, Malaysia. Patients received a half-dose of verteporfin over 10 minutes and were irradiated by the standard fluence combined with intravitreal ranibizumab or aflibercept injections. The monotherapy group received either intravitreal ranibizumab or aflibercept. Primary outcome measures were best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 6 months post-treatment. Secondary outcome measure was documentation of sideeffects.Results: The study included a total of 16 patients, with 8 patients (8 eyes) in the combination group and 8 patients (10 eyes) in the monotherapy group. At 6 months post-treatment, the BCVA changes in logarithm of the minimum angle of resolution (logMAR) were -0.06 in the combination group and +0.02 in the monotherapy group (p = 0.928). The average CST reduction was 51.6 μm in the combination group and 106.1 μm in the monotherapy group (p = 0.214). One eye developed subretinal haemorrhage after hd-PDT and one eye developed retinal atrophy in the monotherapy group.Conclusion: hd-PDT combined with anti-VEGF was able to produce similar functional outcomes in terms of BCVA when compared to anti-VEGF monotherapy. However, monotherapy is shown to be superior to combination treatment for anatomical improvement.

Long-term outcomes of focal laser photocoagulation for the treatment of polypoidal choroidal vasculopathy.

To evaluate the long-term effect and safety of focal laser photocoagulation treatment in eyes with polypoidal choroidal vasculopathy (PCV). Medical records of 13 eyes of 13 patients with PCV were followed-up for more than 2y after focal laser photocoagulation treatment. The patients were diagnosed with PCV using indocyanine green angiography, and eyes with other comorbid ocular diseases were excluded. The measurement outcomes of the study were the post-treatment regression and recurrence of polyps, complications, and changes in visual acuities. Paired t-test was performed to compare visual outcome before and after the treatment. The mean age of the 13 patients was 70.2±5.5y, and the follow-up period was 72.3±31.0 (range, 25-118)mo. Three eyes had juxtafoveal polyps and 10 eyes had extrafoveal polyps. Of the 13 eyes, 9 eyes (69.2%) had regression of polyps 1.7±1.2 (range, 0.9-4)mo after focal laser photocoagulation. Five eyes (55.6%) showed recurrence of polyps during the follow-up periods, and the recurrence period was 12.8±18.9 (range, 1.9-48)mo. Mild subretinal hemorrhage occurred in two eyes (15.4%) 27 and 72d after laser treatment, respectively. There were no statistically significant differences in visual acuities at baseline; 1, 2, 3y post-treatment (all P>0.05); and last follow-up (0.63±0.5, 0.73±0.70, 0.67±0.57, 0.75±0.7, and 0.95±0.8 logMAR, respectively). Focal laser photocoagulation is beneficial for early regression of polyps in eyes with PCV and does not result in significant submacular hemorrhage during the long-term follow-up. Furthermore, it can be primarily considered in eyes with PCV with extrafoveal or juxtafoveal polyps to regress risky polyps as well as to maintain visual acuity without serious hemorrhagic complications.

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial

Importance: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. Methods: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). Results: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2–12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7–9) injections, with a significant reduction of −93.0 [−154.0, −44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2–11] vs. 5 [2–13] letters (p = 0.98)), number of IVAIs (8.5 [7–9] vs. 8 [7–9] (p = 0.21)), change in CRT (−143 [−184; −47] vs. −89 [−123; −41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. Conclusions and Relevance: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. Trial Registration: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

Comparison of Polypoidal Choroidal Vasculopathy Lesion Sizes Measured on Multicolor Imaging and Indocyanine Green Angiography.

PurposeTo evaluate the areas of lesion components of polypoidal choroidal vasculopathy (PCV) measured using multicolor imaging compared to indocyanine green angiography (ICGA).MethodsIn a prospective study of 50 consecutive treatment-naïve PCV patients, multicolor imaging and ICGA were performed. The images were independently graded by reading center-certified retinal specialists to confirm the diagnosis of PCV and identify lesion components. The areas of the respective lesion components were compared.ResultsThe mean age of the participants was 67.8 years. PCV was diagnosed in 96% of eyes using multicolor imaging. The mean numbers of polypoidal lesions identified using ICGA and multicolor were 4.0 and 2.1, respectively (P < 0.001), with mean total polypoidal lesion areas of 0.32 mm2 versus 0.30 mm2 (P = 0.727). The area of the branching vascular network (BVN) on ICGA was 7.8 mm2 compared to 5.7 mm2 on multicolor imaging (P = 0.289). Patients with four or more polypoidal lesions on ICGA had larger differences in total lesion area between ICGA and multicolor imaging (4.07 vs. –0.70 mm2, p = 0.039). Those with total lesion area ≥ 2.0 mm2 on ICGA had larger differences in mean polypoidal lesion number compared to those with smaller areas (2.2 vs. 0.5; P = 0.026).ConclusionsMulticolor imaging is a useful, noninvasive adjunct for detecting PCV lesion components, revealing lesion areas similar to but generally smaller than those seen on ICGA. This is important to consider when making treatment decisions with different imaging modalitiesTranslational RelevanceNew features seen on multicolor imaging can aid in the diagnosis and treatment of PCV.

One-year Results of Aflibercept Treatment for Polypoidal Choroidal Vasculopathy with Good Visual Acuity.

PurposeTo evaluate the one-year efficacy of intravitreal aflibercept injection in polypoidal choroidal vasculopathy (PCV) with best-corrected visual acuity (BCVA) of 20 / 40 or better.MethodsThis was a multicenter retrospective study. The medical records of patients diagnosed with treatment-naïve PCV were retrospectively reviewed. Patients with an initial BCVA of 20 / 40 or better and who had undergone intravitreal aflibercept injection were included. Patients were treated with three consecutive monthly injections, followed by pro re nata regimen according to the clinician’s discretion at variable interval visits. The proportions of eyes for which BCVA was maintained (≤ 0.2 logarithm of the minimum angle of resolution change) or improved at 12 months were evaluated. The changes of BCVA, central subfield macular thickness (CSMT), pigment epithelial detachment, and subretinal fluid also were assessed.ResultsA total of 86 eyes were included. The mean number of injections for 12 months of treatment was 5.4 ± 1.7. BCVA was maintained or improved in 94.2% (81 / 86) of cases. Mean BCVA (logarithm of the minimum angle of resolution) had changed from the baseline (0.23 ± 0.09) at 3 months (0.21 ± 0.14), 6 months (0.24 ± 0.22), and 12 months (0.20 ± 0.18), but with no statistical significance. CSMT had improved significantly from the baseline (336.1 ± 97.3 μm) at 3 months (223.6 ± 47.22 μm), 6 months (239.6 ± 64.2 μm), and 12 months (223.8 ± 47.9 μm). Pigment epithelial detachment was observed in 93% of cases at the baseline, 72.1% at 3 months, and 69.8% at 12 months, showing a significant decrease at all observation points. Subretinal fluid was observed in 91.9% of cases at the baseline, 20.9% at 3 months, and 29.1% at 12 months, showing a significant decrease at all observation points.ConclusionsIn cases of PCV with good visual acuity, intravitreal aflibercept injections decreased CSMT and were effective in maintaining visual acuity.

Systematic review with network meta-analysis of antivascular endothelial growth factor use in managing polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) is a vision-threatening disease common in Asian populations. However, the optimal treatment for PCV remains under debate. We searched the databases with optimal searching strategy. The study included randomized clinical trials and prospective studies that recruited patients with active PCV who had received interventions, including PDT, anti-VEGF, or a combination of PDT and anti-VEGF. The Grading of Recommendations Assessment, Development, and Evaluation methodology was used for rating the quality of evidence. Our study included 11 studies involving 1277 patients. The network meta-analysis of RCTs revealed the anti-VEGF group, early combination group, and late combination group had significant BCVA changes compared with the PDT group. Early combination therapy led to a significant decrease in CRT compared with PDT, anti-VEGF, and late combination therapy. Additionally, the early combination group had a significantly higher complete polyp regression rate than the anti-VEGF group. No significant differences were detected in the analysis of the number of anti-VEGF injections and safety profile. This network meta-analysis revealed that early combination therapy exhibited better efficacy related to anatomical outcomes than other therapies. Nonetheless, no significant differences related to BCVA change could be detected between anti-VEGF and late combination therapy.

Comparison of visual outcomes between therapy choices and subtypes of polypoidal choroidal vasculopathy (PCV) in Taiwan: a real-world study

Polypoidal choroidal vasculopathy (PCV) is a distinctive type of neovascular age-related macular degeneration prevalent in many Asian countries. However, there is still some controversy in how the subtypes of PCV are classified. This post-hoc study redefined the branching vascular network (BVN) and PCV subtypes through retrospective review of indocyanine green angiography (ICGA) and fluorescein angiography images from two observational studies (RENOWNED/REAL). Of the visual outcomes for each angiographic subtype and treatment pattern investigated, BVN was identified in 56.3% of PCV patients. The proportions and features of the re-defined PCV subtypes were 43.8%, 10.4%, and 45.8% for subtype A (without distinctive features of BVN), B (with BVN but no leakage), and C (with BVN and leakage), respectively. Subtype A had better visual outcomes when compared to subtype C. This possibly resulted from a better baseline visual acuity in subtype A. Moreover, combination therapy [photodynamic therapy plus anti-vascular endothelial growth factor (VEGF)] may lead to better visual improvement than mono-anti-VEGF treatment alone. This study provides the prevalence of PCV subtypes in Taiwan and may serve as a reference for PCV treatment strategies in a real-world setting, especially for the combination therapy and patients without distinctive features of BVN.