Verteporfin Photodynamic Therapy Research Articles

Factors for recurrence in acute central serous chorioretinopathy patients underwent one-third dose verteporfin photodynamic therapy

PurposeTo investigate the factors for recurrence in acute central serous chorioretinopathy (aCSC) for patients who underwent one-third dose verteporfin photodynamic therapy (PDT). Materials and methodsA retrospective study was performed in aCSC patients treated with one-third dose PDT and followed up for 36 months. Demographic information and clinical features were compared. A logistic regression model was used to evaluate the associated factor of aCSC recurrence. ResultsThere were 162 patients with aCSC included in current study. 36-month after one-third dose PDT, good recovery was identified in 131 patients (80.86%), whereas 31 cases (19.14%) developed recurrence. Significant between-group differences were observed in baseline age, the right, left and both eyes, best-corrected visual acuity (BCVA), presenting with pigment epithelium detachment (PED), retinal pigment epithelium (RPE) damage and subfoveal choroidal thickness (SCT) level (P = 0.005, P < 0.001, P < 0.001, P < 0.001, P = 0.006, and P < 0.001, respectively). The recurrence of aCSC was associated with presenting with PED (odds ratio = 1.78; 95% CI, 1.45–1.98; P < 0.001), RPE damage (OR = 1.13; 95%CI: 1.08–1.23; P < 0.001), baseline BCVA (OR = 0.96; 95%CI: 0.95 - 0.99; P = 0.001), and SCT level (OR = 1.18; 95%CI: 1.02–1.20; P < 0.001). ConclusionIn acute CSC after treatment of one-third dose PDT, recurrence is associated with RPE damage, baseline BCVA and SCT level. Our findings will assist clinicians to evaluate aCSC in clinical practice and provide insights into the prevention of recurrence.

Rescue photodynamic therapy for age-related macular degeneration refractory to anti-vascular endothelial growth factor monotherapy

BackgroundTo evaluate the 3-year outcome in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor monotherapy or rescue therapy using standard verteporfin photodynamic therapy (PDT), and corroborate efficacy of rescue PDT. MethodsPatients were administered aflibercept injections once a month for 3 months followed by once every 2 months in the first year. After year 1, treatment with aflibercept monotherapy as indicated or in combination with PDT at the retinal specialist's discretion. Only cases completing the three-year follow-up were included. Regression analysis with visual acuity and macular atrophy at year 3 was performed for the dependent variable. ResultsOf the 292 eyes, 15 eyes underwent rescue PDT following year 1. The best-corrected visual acuity (logarithm of minimal angle of resolution, mean/Snellen equivalent ± SD) was 0.35 (20/45) ± 0.38, 0.23 (20/30) ± 0.36, 0.26 (20/35) ± 0.38, and 0.31 (20/40) ± 0.42 at baseline, year 1, year 2, and year 3, respectively. Multiple regression analysis revealed that the rescue PDT was significantly associated with macular atrophy and poor visual outcome at year 3 (odds ratio = 1.2, p < 0.001; β = 0.23, p = 0.0029, respectively). ConclusionsThe visual outcome in eyes with nAMD retained baseline levels at year 3; however, patients treated with rescue PDT developed macular atrophy more frequently and poor visual outcomes.

Evaluation of the choriocapillaris after photodynamic therapy for chronic central serous chorioretinopathy. A review of optical coherence tomography angiography (OCT-A) studies.

Emerging evidence suggests that choroidal microcirculation and microstructural changes after verteporfin photodynamic therapy (vPDT) for chronic central serous chorioretinopathy (CSC) can be shown in detail using OCT-Angiography (OCT-A). The use of OCT-A for the examination of choriocapillaris (CC) has attracted significant attention as the technique offers potential explanations for the effects of vPDT on choroidal tissue. A meticulous literature search was performed in the PubMed database without restriction on year of publication until June 2021. The reference list of all electronically retrieved articles was carefully reviewed for potentially relevant articles that had not been identified. We identified and reviewed 11 studies reporting a comprehensive update on microvasculature and morphologic changes of the CC layer as seen on OCT-A in chronic CSC. The reviewed articles extensively analyze both the qualitative and quantitative characteristics of the CC flow pattern after applying vPDT safety-enhanced protocols. The changes in the CC plexus indicate the potential of beneficial or deleterious treatment effect on choroidal tissue remodeling. The reviewed series have revealed variability of flow pattern, vessel density, and perfusion of the CC over time. The CC plexus alterations during the post-vPDT period in chronic CSC may imply the treatment effect on choroidal tissue, indicating the potential of anatomical or functional recovery over time. The reviewed literature may confirm the diagnostic value of OCT-A in the assessment of the pathophysiology of eyes with CSC.

Risk factors of persistent subretinal fluid after half-dose photodynamic therapy for treatment-naïve central serous chorioretinopathy.

To investigate the prognostic factors on spectral domain optical coherence tomography (SD-OCT) associated with incomplete subretinal fluid (SRF) absorption in treated-naïve eyes with central serous chorioretinopathy (CSC) after the half-dose verteporfin photodynamic therapy (vPDT). Patients with CSC who underwent half-dose vPDT with a follow-up period of more than 3months were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with the SRF persistence at 3months after the treatment. A total of 143 patients with 150 eyes were enrolled in this study (102 male and 41 female patients). The rate of complete SRF resolution was 82.7% at 3months for all cases. The duration of symptoms > 6months (odds ratio [OR] = 3.135, 95% confidence interval [95% CI] (1.147-8.573), p = 0.026), larger SRF area with base diameter > 3mm (odds ratio (OR) = 4.051, 95% CI: 1.336-12.284, p = 0.013), and larger flat irregular pigment epithelium detachment (FI-PED) area with base diameter > 1mm (OR = 3.311, 95% CI: 1.249-8.780, p = 0.016) on OCT B-scans were risk factors for incomplete SRF absorption after half-dose vPDT, while outer nuclear layer (ONL) thickness was not significantly associated with the anatomical outcome (OR = 1.015, 95% CI: 0.995-1.036, p = 0.145). The duration of symptoms, baseline SRF, and FI-PED base diameter on SD-OCT were important predictors for the anatomical outcome at 3months after half-dose vPDT. Further studies are needed to establish a better therapeutic strategy for patients with poor response to half-dose vPDT.

Abstract P044: Real-time visualization of tumor cell phenotype and microenvironmental heterogeneity enabled by a hyperspectral fluorescence microendoscope

Abstract Tumor microenvironmental heterogeneity is a major driver of treatment resistance and variability in clinical response to therapy. This heterogeneity arises from variations in cellular phenotypes populating the tumor microenvironment (TME), their spatio-temporal localization and expression of surface markers, often associated with specific biological function – stemness, metabolism, proliferation, immune activation and others. Such features are usually studied through ex vivo immunofluorescence and cytometry to identify cellular phenotypes in TME; however, they cannot be applied in vivo for real time TME analysis. Moreover, current in vivo imaging techniques fail to provide real-time high-resolution visualization of the TME. Routinely employed biopsy tissue sampling through fine needle aspirates is limited by its invasive nature and inability to provide a global and dynamic overview of the TME, thus limiting our ability to study spatiotemporal TME dynamics and identify possible features leading to potentially resistant tumor phenotypes. In this study, we demonstrate the use of a hyperspectral fluorescence microendoscope (HFME) to monitor cellular phenotypes in TME with real-time visualization and high video imaging capability (~17 fps). Current fluorescence video microscopy is limited to simultaneous imaging of no more than 2 molecular markers with potential to be expanded to ~4 markers using dichroic mirrors and point detectors; the HFME demonstrated in this study can currently resolve 6 different molecular markers, simultaneously, using a multichannel linear array detector with potential to expand to 10 or more markers. Using a cocktail of near infra-red fluorophore-antibody conjugates targeted against key molecular (surface) markers of different cells in the TME, we are able to capture real-time TME dynamics at cellular resolution in two pre-clinical models; 1) a xenograft orthotopic mouse model of peritoneal carcinomatosis (disseminated metastases within the abdominal cavity) and imaging epidermal growth factor receptor (EGFR), CD44, CA125 (MUC16), transferrin receptor, Thomsen-Friedenreich carbohydrate antigen (T antigen), and CD45, 2) A syngeneic immunocompetent KPC cell line implanted mouse model of pancreatic ductal adenocarcinoma and imaging CD3, CD4, CD8a and CD45. Imaging on these tumor models was performed pre- and post-sub-therapeutic verteporfin (benzoporphyrin derivative monoacid A) photodynamic therapy (PDT, a cytotoxic light-based therapy). PDT treatment resulted in reduction of cancer cell burden, immune cell infiltration and alterations in their relative spatial localization. The results were confirmed by histopathological validation and ex vivo immunofluorescence staining of tumor tissue sections. Collectively, these results demonstrate the capability of HFME to image cancer cell phenotypes and the tumor microenvironment, in real time in live mice. With the ability to monitor cancer growth and treatment effects at a cellular level, HFME can potentially assist in customizing therapies in a patient-specific manner. Citation Format: Mohammad A. Saad, Bryan Q. Spring, Akilan Palanisami, Eric M. Kercher, Ryan T. Lang, Jason Sutin, Zhiming Mai, Tayyaba Hasan. Real-time visualization of tumor cell phenotype and microenvironmental heterogeneity enabled by a hyperspectral fluorescence microendoscope [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P044.

The Choroid after Half-Dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

To characterize choroidal structure and vasculature after half-dose verteporfin photodynamic therapy (hd-vPDT) in eyes with chronic central serous chorioretinopathy using Enhanced Depth Imaging Optical Coherence Tomography (EDI OCT) and Optical Coherence Tomography Angiography (OCT-A). This prospective case-control study included 10 eyes. Choroid was examined before and at 1 month following hd-vPDT. We measured choroidal thickness (CT) at subfoveal area and at 750 μm nasal and temporal of fovea and thickness of Haller and choriocapillaris/Sattler layers. Whole (WA), luminal (LA) and interstitial area (IA) at EDI-OCT, and perfusion density at OCT-A were analyzed. The unaffected fellow eyes were used for comparisons. Mean CT at subfoveal area and at 750 μm nasal and temporal of fovea, values of Haller and choriocapillaris/Sattler layers and those of WA, LA and IA were reduced, while PD increased at 1 month after hd-vPDT (all p < 0.001). There was a significant (p < 0.05) negative correlation (ρ = -0.658) between PD and post-treatment logMARVA. None of analyzed parameters reached values of unaffected fellow eye. Following hd-vPDT, choroidal thickness with both luminal and interstitial components markedly decreased, while perfusion of choriocapillaris improved.

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.

ITVT-02. Elucidating the pleiotropic effects of verteporfin photodynamic therapy in preclinical glioblastoma models

Abstract Glioblastoma (GBM) ranks the highest in mortality rate, incidence, and aggressiveness of primary brain tumor types. The highly malignant nature of GBM makes it difficult for mainstay treatments to have an effect beyond stabilizing the disease. Deregulation of receptor tyrosine kinase (RTKs), such as EGFR and PI3K, have been implicated in GBM tumorigenesis. The expression of EGFR has been linked to hippo pathway transcriptional co-activators YAP and TAZ that bind to TEAD co-factors to drive the transcription of target genes. The convergence of EGFR signaling and the hippo pathway regulates stem cell programs, including proliferation, survival, and self-renewal. Verteporfin (VP), an FDA-approved macular degeneration therapy, has antitumor effects in in vitro and in vivo GBM preclinical models and phase I/II clinical trials for patients with EGFR mutated/amplified GBM by abrogating YAP/TAZ-TEAD interactions. As a porphyrin derivative, VP can exert therapeutic and photodynamic effects in the presence of 689 nm light; however, the efficacy of VP-PDT has not been explored in GBM. Our results indicate that VP-PDT reduces cell viability to a greater extent than solitary VP treatment (viability — 0.7 uM VP: 97%, 0.7 uM VP-PDT: 46%). The antitumor effects of VP-PDT are two pronged involving 1) inhibition of live cell dynamics, including migration and intravasation, by downregulating hippo pathway constituents YAP, TAZ and TEAD and transcriptional target EGFR and 2) induction of programmed cell death by reactive oxygen species. Our results suggest that VP-PDT can be a potential avenue for treating these incurable tumors.

Acute Central Serous Chorioretinopathy Subtypes as Assessed by Multimodal Imaging.

PurposeTo differentiate acute central serous chorioretinopathy (CSC) subtypes by multimodal imaging.MethodsThe research was designed as a prospective, interventional study. Naive patients with acute CSC were followed for 24 months. Overall, 96 CSC patients (96 eyes) and 210 controls (210 eyes) were included. Multimodal imaging allowed the study to classify CSC into retinal pigment epithelium-related CSC (RPE-CSC) and choroidal-related CSC (choroidal-CSC) subtypes. The RPE-CSC type was characterized by normal choroidal thickness (CT) in association with disseminated RPE alterations. The choroidal-CSC type was distinguished by identifying a pachychoroid. All the patients underwent eplerenone or verteporfin photodynamic therapy (PDT). Patients developing macular neovascularization (MNV) underwent anti-VEGF injections. Quantitative measurements included central macular thickness (CMT), choroidal thickness (CT), Sattler layer thickness (SLT) and Haller layer thickness (HLT).ResultsConsidering the CSC patients as a whole, baseline BCVA was 0.18 ± 0.25 LogMAR, increasing to 0.13 ± 0.21 LogMAR after 24 months (P < 0.01), whereas baseline CMT improved from 337 ± 126 µm to 244 ± 84 µm after 24 months (P < 0.01).We found the following subdivision of CSC eyes: RPE-CSC type (45%) and choroidal-CSC type (55%). Overall, MNV were detected in 18 eyes (19%), 13 eyes (72%) in the RPE-CSC subgroup and five eyes (28%) in the choroidal-CSC subgroup.Forty eyes responded to eplerenone (57% of RPE-CSC and 47% of choroidal-CSC), whereas 38 eyes required PDT (43% of RPE-CSC and 53% of choroidal-CSC).ConclusionsAcute CSC includes two main clinical manifestations, displaying differing features concerning retinal and choroidal involvement.Translational RelevanceThis study identified two clinically different acute CSC subtypes on the basis of quantitative pachychoroid cutoff values.

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.

Subfoveal choroidal thickness as a potential predictor of treatment response after intravitreal ranibizumab injections for polypoidal choroidal vasculopathy

ObjectiveTo evaluate the impact of subfoveal choroidal thickness (SFCT) and other clinical biomarkers in intravitreal anti-vascular endothelial growth factor response in treatment-naive Caucasian patients diagnosed with polypoidal choroidal vasculopathy (PCV/AT1). DesignCross-sectional study. ParticipantsTreatment-naive patients diagnosed with PCV/AT1 recruited in a single centre from January 2013 to December 2020. MethodsEligibility was determined in treatment-naive PCV patients who received a loading dose of 3 injections of 0.5 mg ranibizumab. A diagnosis of PCV/AT1 was made based on the diagnostic criteria in the efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with sumptomatic macular polypoidal choroidal vasculopathy study. Choroidal thickness was manually measured by enhanced depth imaging technology in Spectralis spectral domain optical coherence tomography. ResultsEighty-three eyes of 83 patients were included in this study, 47 patients diagnosed with PCV/AT1 with a good response to 3 intravitreal injections of ranibizumab and 36 with a poor response. The receiver operating characteristic curve of treatment effect against the SFCT revealed that the area under the curve was 0.85 (range, 0.74–0.96). Based on the Youden index, the optimal SFCT cut-off point for predicting a poor response to anti-vascular endothelial growth factor is 257 µm. In the multivariate analysis, the SFCT remained statistically significant (odds ratio 1.02 [range, 1.01–1.04]; P = 0.008). The combined effect of treatment effect against clinical biomarkers produced an area under the curve of 0.90 (range, 0.82–0.98). ConclusionSFCT is a risk factor for a poor response to the 3 loading injections of ranibizumab in treatment-naive PCV/AT1 Caucasian patients. A cut-off point of 257 µm could be a valuable parameter for defining the population at risk for an inadequate response to ranibizumab.

Combined verteporfin- mediated photodynamic therapy and catheter- based 192Ir- mediated brachytherapy for neoatherosclerosis inhibition after laser angioplasty

Abstract Background and aims The laser atherectomy methods that are currently in use, cause to inflammation and subsequent restenosis. The aim of this study was to evaluate the effect of combined verteporfin photodynamic therapy and catheter-based 192Ir-mediated β-brachytherapy on inflammation and neoatherosclerosis reduction after laser angioplasty of the animal occluded femoral artery, wherein diagnostic ultrasound is adjuncted with laser angioplasty system and combination therapy system, with a goal of increased safety. Methods Briefly, New Zealand white rabbits were submitted to femoral artery advanced atherosclerotic occlusion by primary perivascular severe cold injury followed by a 2% cholesterol- rich diet for fourteen weeks. Histopathology results showed the formation of stable advanced atherosclerosis with lipid and neovessel-rich plaque, resulted in occlusion in all of the rabbits' arteries. Then treatment group underwent B- mode ultrasound-guided argon laser (488 nm) angioplasty followed by catheter- based β-brachytherapy (192Ir, 15 Gy) in combination with verteporfin (10mg/kg)-mediated low level red laser (λ=635 nm, E=130 J/cm2) photodynamic therapy. Results Results from ultrasonography and histopathology showed a significant reduction in the mean value for immune cells and smooth muscle hyperplasia cells density after angioplasty in the treatment group compared with the other groups (p&amp;lt;0.05). Conclusions Apoptotic effect of catheter-based 192Ir-mediated β-brachytherapy in combination with toxicity effect of verteporfin, can cause to reduce the density of macrophage cells and smooth muscle hyperplasia cells in the intimal layer. These findings provide the basis for developing of combined β-brachytherapy and verteporfin- mediated photodynamic therapy for a successful clinical application in the treatment of neoatherosclerosis after laser angioplasty. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab

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.

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.

3-year follow-up of half-dose verteporfin photodynamic therapy for central serous chorioretinopathy with OCT-angiography detected choroidal neovascularization

To assess the 3-year outcome of half-dose verteporfin photodynamic therapy (PDT) in central serous chorioretinopathy (CSC) with optical coherence tomography angiography (OCT-A) detected choroidal neovascularization (CNV), we performed a retrospective, interventional study. Patients were divided into 2 groups according to the fluorescein angiography: point source leakage in group 1 and diffuse oozing in group 2. Data were collected from patients including changes of best-corrected visual acuity (BCVA), size of CNV, central macular thickness (CMT), choroidal thickness (CT), reabsorption of subretinal fluid (SRF), sessions of half-dose PDT, and the number of intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF). There was a total of 34 eyes in 32 patients included. The mean sessions of half-dose PDT was 1.50 ± 0.75. The mean number of IVI of anti-VEGF was 1.38 ± 3.34. BCVA improved from 0.38 ± 0.33 to 0.20 ± 0.22 (p < 0.001). Mean CMT was significantly reduced along with reduced CT and increased size of CNV. SRF was totally reabsorbed in 31 eyes. Patients in group 1 had significant less sessions of PDT and better final BCVA. In conclusion, half-dose PDT treatment was effective for CSC with CNV. Patients with diffuse oozing in FA may fare less well with half-dose PDT.

Decrease in choroidal blood flow after half and one-third dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy

BackgroundThe effect of various reduced doses of verteporfin photodynamic therapy (PDT) on choroidal blood flow in chronic central serous chorioretinopathy (CSC) remains unclear. Therefore, this study aimed to evaluate choroidal blood flow after half-dose PDT (1/2PDT) and one-third dose PDT (1/3PDT) with verteporfin for chronic CSC using laser speckle flowgraphy and spectral-domain optical coherence tomography.MethodsTwenty-seven eyes of 27 patients with serous retinal detachment (SRD) caused by chronic CSC for more than 6 months were included in this study. Patients were divided into the 1/2PDT (n = 12; January 2018 to July 2019) and 1/3PDT (n = 15; August 2016 to December 2017) groups based on the treatment period. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), and mean blur rate in the macular area (m-MBR) and optic nerve head (ONH-MBR) were obtained using laser speckle flowgraphy and evaluated at baseline (pre-treatment), and 2 weeks, 1 month, 3 months, and 6 months after treatment.ResultsWe found that SRD disappeared after 1 month in 92 and 93% of patients’ eyes in the 1/2PDT and 1/3PDT groups, respectively. Recurrence of SRD was observed in one eye at the 6-month follow-up after 1/2PDT and two eyes at the 3-month follow-up after 1/3PDT. No significant improvement was observed in baseline BCVA in the 1/3PDT and 1/2PDT groups. The average m-MBR against baseline significantly decreased at 2 weeks and 1, 3, and 6 months in the 1/2PDT group. The average m-MBR against baseline decreased significantly only at the 2 weeks follow-up in the 1/3PDT group. The average rate of change in the CCT against baseline decreased significantly throughout for up to 6 months in the 1/2PDT group and for up to 3 months in the 1/3PDT group. No significant fluctuation was observed in the ONH-MBR.Conclusions: Here, PDT significantly affected choroidal blood flow depending on the verteporfin dose in chronic CSC.Trial registrationThis trial was retrospectively registered (UMIN000026850; Approval date 03/04/2017).

Pachychoroid diseases

The aim of this study is to present our knowledge about pachychoroid diseases using case reports, literature review and our own clinical experiences. A summary flow chart of treatment options for the subgroups was prepared, too. Pachychoroid diseases include the following: central serous chorioretinopathy (CSCR), pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), peripapillary pachychoroid syndrome (PPS), focal choroidal excavation (FCE). A common feature of pachychoroid diseases is the quantitative or qualitative abnormality of the choroidea, which is often associated with subretinal fluid accumulation. The disease group does not currently have a standard treatment protocol; some of the multiple treatments prove to be more effective, however, there are significant differences between the subgroups. We summarize which subgroup benefits from eplerenone tablet therapy, micropulse laser therapy, verteporfin photodynamic therapy or intravitreal anti-VEGF injection therapy. Orv Hetil. 2020; 162(20): 770-781.

Timing of Complete Polypoidal Regression after Intravitreous Aflibercept Treatments in Polypoidal Choroidal Vasculopathy

To understand timing of complete polypoidal regression on indocyanine green angiography (ICGA) after aflibercept injections for polypoidal choroidal vasculopathy (PCV). Multicenter prospective study. Adults with treatment-naïve PCV. After institutional review board approval, participants were enrolled and followed up for 1 year, from Apr 1, 2016, through Dec 30, 2018, at 2 university-based centers in Thailand. Diagnosis of PCV was based on the Efficacy and Safety of Verteporfin Photodynamic Therapy in Combination with Ranibizumab or Alone versus Ranibizumab Monotherapy in Patients with Symptomatic Macular Polypoidal Choroidal Vasculopathy criteria. Eligible eyes received fixed-dose aflibercept injections (3 monthly then every 8 weeks), or monthly if fluid persisted on OCT. Photodynamic therapy (PDT) was administered when fluid persisted despite 6 consecutive injections. Indocyanine green angiography was performed at baseline and then every 8 weeks. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was administered at baseline, 6 months, and 1 year. Two retina specialists reviewed posttreatment ICGA, categorized into: complete regression (complete disappearance of polypoidal lesions), partial regression (reduced in size or number), or no regression. Disagreements were resolved through open adjudication. Timing of complete regression over 1 year. Final analysis included 40 eyes (39 participants; 100% Thai, 59% women; mean age±standard deviation, 64 ± 8.3 years). At baseline, 90% had 5 or more polypoidal lesions. Ninety-five percent received aflibercept monotherapy, and 5% received rescue PDT per protocol. Polypoidal statuses at 1 year were 55% complete, 40% partial, and 5% no regression. Cumulative rates of complete regression at 2, 4, 6, and 12 months were 28%, 33%, 43%, and 55%. Of 22 eyes with complete regression at 1 year, complete regression was identified first at 2, 4, 6, 8, 10, 12 months in 50%, 9%, 18%, 5%, 9%, and 9%, respectively. Cumulative rates of complete regression among these eyes at 2, 6, and 12 months were 50%, 77%, and 100%, respectively. Median duration of complete regression was 3 months (interquartile range, 2-6 months). Median visual acuity improved from 20/125 (Snellen equivalent) to 20/50; median NEI VFQ-25 scores improved from 80 to 93 from baseline to 1 year. Complete polypoidal regression could occur as early as 2 months after aflibercept injections. Most PCV eyes with complete polypoidal regression at 1 year already showed complete regression within the first 6 months. These findings support consideration of aflibercept for PCV to achieve both anatomic and visual outcomes.

Choroidal and Retinal Changes After Systemic Adrenaline and Photodynamic Therapy in Non-Human Primates.

PurposeTo determine the tomographic, angiographic, and histologic changes in the choroid and retina of cynomolgus monkeys after systemic adrenaline and verteporfin photodynamic therapy (vPDT).MethodsSix cynomolgus monkeys (12 eyes) were treated with vPDT only (n = 2), adrenaline only for eight weeks (n = 2), adrenaline for eight weeks with vPDT at week 4 (n = 4), and adrenaline for 12 weeks and vPDT at week 8 (n = 4). Spectral-domain optical coherence tomography, angiography, and autofluorescence were performed at baseline and every 14 days thereafter until 28 days after adrenaline therapy or vPDT. Choroid parameters included choroidal thickness (CT) changes and structural changes using semiautomated image binarization. Histology with light and electron microscopy was performed.ResultsAdrenaline resulted in subfoveal CT increase at week 4 compared with baseline (3.4%, P = 0.010), with further increase at week 8 (3.9%, P = 0.007). This correlated with choroidal luminal area increase (16.0% at week 8 compared with baseline, P = 0.030). Outer retinal changes included subretinal fluid, ellipsoid zone (EZ) disruption, photoreceptor elongation, and sub/intraretinal bright dots. Hypocyanescent spots surrounded by leakage was observed. Histology showed dilated choroidal vessels, intracytoplasmic vacuoles, and retinal pigment epithelium (RPE) enlarged basal infoldings. The vPDT decreased subfoveal CT at four weeks after vPDT (−7.5%, P = 0.007). This correlated with choroidal stromal area decrease (−18.0%, P < 0.010). Within the treatment spot, there was outer retinal atrophy, EZ disruption, irregular RPE thickening, intense hypoautofluorescence, hyperfluorescence, and hypocyanescence. On histology, there were outer retina, RPE, and choroid changes.ConclusionsAdrenaline induces choroidal vessel dilation and CT increase. The vPDT decreases CT because of a reduction in choroidal stromal component.