Polypoidal Choroidal Vasculopathy Patients Research Articles

Responsiveness of anti-VEGF treatment for polypoidal choroidal vasculopathy based on aqueous humour proteomics: A preliminary study.

Patients with polypoidal choroidal vasculopathy (PCV) exhibit variability in response to anti-VEGF therapy. This study aimed to analyse the aqueous humour proteomic profiles of PCV patients and provide preliminary insights for the identification of biomarkers associated with anti-VEGF drug responsiveness. PCV patients who were treatment-naïve or untreated for more than 3 months were prospectively recruited from two hospitals in Beijing and Tianjin. Based on the relative changes in central macular thickness (ΔCMT/baseline-CMT) before and after anti-VEGF treatment, the PCV patients were divided into a good response (GR) group (≤-25%) and a poor response (PR) group (>-25%). Aqueous humour proteomics was performed by the Data-independent Acquisition-Mass Spectrometry (DIA-MS) method, and differentially expressed proteins (DEPs) analysis between the different PCV groups and the control group was conducted. Key DEPs were selected for preliminary validation in the aqueous humour using the Luminex method retrospectively. A total of 31 PCV patients (31 eyes) were included, 13 in the GR group and 18 in the PR group. A total of 414 DEPs were identified, including 36 significantly upregulated proteins, such as G protein regulatory factor 10 (RGS10), podocin (PODN) and epidermal growth factor (EGF), and 32 downregulated proteins, including RAB11FIP4 (Rab11 family-interacting protein 4), α-synuclein (SNCA), haemoglobin subunit δ (HBD) and interleukin 6 (IL6). Compared to the cataract control group (10 eyes), 134 proteins were significantly upregulated, and 72 were downregulated. KEGG pathway enrichment analysis revealed that the GR and PR groups differ in terms of cell communication, and cell signal transduction. Protein-protein interaction analysis revealed interactions between EGF and various DEPs. Validation of aqueous humour proteins using the Luminex method revealed that changes in the levels of EGF were associated with the anti-VEGF treatment response in PCV patients. PCV patients with good or poor anti-VEGF responses exhibit distinct aqueous humour proteomic profiles. Aqueous EGF may serve as a biomarker for the 'precise treatment' of PCV.

Exploring and identifying the imaging biomarkers for predicting anti-VEGF treatment response in polypoidal choroidal vasculopathy: aprospective multicenter study.

Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation. This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making. The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The 'Good responder' exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 μm, p < 0.001), lower choroidal vascularity index (CVI) (0.31 ± 0.08 vs. 0.36 ± 0.05, p = 0.006), fewer choroidal vascular hyperpermeability (CVH) (31.0 vs. 62.2%, p = 0.012), and more intraretinal fluid (IRF) (58.6 vs. 29.7%, p = 0.018). SFCT (OR 0.990; 95% CI 0.981-0.999; p = 0.033) and CVI (OR 0.844; 95% CI 0.732-0.971; p = 0.018) were ultimately included as the optimal predictive biomarkers and presented in the form of a nomogram. The model demonstrated AUC of 0.837 (95% CI 0.738-0.936), 0.891 (95% CI 0.765-1.000), and 0.901 (95% CI 0.824-0.978) for predicting 'Good responder' in the training set, internal validation set, and external test set, respectively, with excellent sensitivity, specificity, and practical utility. Thinner SFCT and lower CVI can serve as imaging biomarkers for predicting good treatment response to anti-VEGF monotherapy in PCV patients. The nomogram based on these biomarkers exhibited satisfactory performances.

Development and validation of optical coherence tomography (OCT) and OCT angiography prediction model for short-term vitreous haemorrhage secondary to polypoidal choroidal vasculopathy

AimsTo construct and validate an optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) image model for predicting the occurrence of short-term vitreous haemorrhage (VH) in polypoidal choroidal vasculopathy...

Comparison of One-Year Outcome of Intravitreal Aflibercept with or without Photodynamic Therapy for Polypoidal Choroidal Vasculopathy.

Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

Initial Factors Associated with Resistance to Intravitreal Aflibercept Injection in Polypoidal Choroidal Vasculopathy

Purpose: To identify initial factors contributing to the resistance against intravitreal aflibercept treatment in polypoidal choroidal vasculopathy (PCV) patients.Methods: This study included PCV patients initially treated with aflibercept. Resistance was defined when treatment did not reduce subretinal fluid (SRF) or intraretinal fluid (IRF) by 100 μm or more after three consecutive 4-week intervals, and the treatment interval could not be extended beyond 8 weeks. To identify initial factors associated with resistance to aflibercept treatment, we examined visual acuity and central choroidal thickness before initial treatment and after three treatments. Choroidal thickness was divided into the thickness of the large choroidal vessel layer and the layer that includes choriocapillaris and medium choroidal vessel thickness (termed medium choroidal vessel/choriocapillaris layer thickness, MCCT). Additionally, the volume of SRF, IRF, subretinal hyperreflective material, and pigment epithelial detachment in optical coherence tomography (OCT) images was investigated. The statistical significance of each factor was assessed through logistic regression analysis.Results: The study included 39 eyes showing no resistance to aflibercept and 37 eyes that exhibited resistance. Multiple logistic regression analysis, adjusted for age and sex, indicated that a lower initial ratio of MCCT to choroidal thickness at the fovea was associated with resistance to aflibercept.Conclusions: In patients with PCV treated with aflibercept, early OCT anatomical structures, such as the initial MCCT-choroidal thickness ratio at the fovea, may predict response to treatment injections.

Polypoidal choroidal vasculopathy versus neovascular age related macular degeneration: a comparison of demographics, clinical presentation, and treatment outcomes in Nigerians

PurposeTo compare the demographics, clinical presentation, and outcomes of intravitreal (IV) anti-VEGF monotherapy in the management of treatment-naïve polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) in Nigerians. MethodsThis is a retrospective, interventional, comparative study. Data obtained from consecutively treated PCV and nAMD patients include age, sex, laterality, symptom duration, LogMAR visual acuity (pre- & post-treatment), occurrence of vitreous hemorrhage, optical coherence tomography central macular thickness (CMT), and duration of clinic visits. Data was analyzed using IBM SPSS version 22.0, P < 0.05. ResultsThe sample population was 162 patients/191 eyes (nAMD 85 patients/106 eyes, and PCV 77 patients/85 eyes). The nAMD patients were older than the PCV patients (72.48 +/− 8.81 years versus 62.04 +/− 10.50 years) p = 0.000. Females constituted 45.9% of the nAMD and 57.1% of the PCV patients, p = 0.1. Symptom duration: nAMD 11 months and PCV 12 months. Bilaterality: nAMD > PCV (38% versus 19%) p = 0.036. Vitreous hemorrhage: more common in PCV (42% versus 19%) p = 0.001. nAMD patients had poorer baseline vision (LogMAR 1.4 versus LogMAR 1.2) p = 0.2, thicker maculae (361 microns versus 331 microns), and received more mean intravitreal anti-VEGF injections (4 versus 3). Visual and anatomical outcomes were better for PCV; final vision (LogMAR 0.89 versus LogMAR 1.04), p = 0.064, final CMT (247 microns versus 331 microns), p = 0.05. nAMD patients had higher rate of >12 months follow-up (57.6% versus 35.0%) p = 0.002. ConclusionDemographic and clinical differences exist between PCV and nAMD. Though chronic presentation for both diseases is common, treatment improves vision and anatomy in most patients, moreso in PCV. Earlier treatment will likely yield better outcomes.

One-year outcomes and safety assessment of faricimab in treatment-naïve patients with neovascular age-related macular degeneration in Japan

This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 μm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications.

Efficacy of Brolucizumab in Polyp Regression of Treatment-Naïve Polypoidal Choroidal Vasculopathy and Its Effect on One-Year Treatment Outcome.

To evaluate the efficacy of intravitreal brolucizumab in polyp regression of treatment-naïve polypoidal choroidal vasculopathy (PCV) patients and its effect on one-year treatment outcome. Medical records of 31 treatment-naïve PCV patients, who received three monthly intravitreal brolucizumab injections followed by as-needed injections for at least a year, were retrospectively reviewed. Visual and anatomical outcomes were evaluated at 3-month, 6-month, and 12-month. Complete polyp regression rate and percentage change of vascular lesion and polyp area were evaluated after three monthly injections of brolucizumab. The effect of complete polyp regression and the impact of vascular lesion and polyp reduction rate on one-year treatment outcome were also evaluated. Additionally, the incidence of brolucizumab-related intraocular inflammation (IOI) and its clinical course were examined. In terms of visual outcome, best-corrected visual acuity(BCVA) significantly improved after 12 month follow-up (p<0.001). In terms of anatomical outcome, central macular thickness(CMT) and central choroidal thickness(CCT) significantly decreased after 12 month follow-up (p<0.001). Complete polyp regression was observed in 74.2% (23/31) after three monthly injections. Group with complete polyp regression had a higher rate of achieving dry macula at 3-month(p=0.026) and fewer number of injections(p<0.001) compared to the group without complete polyp regression. Higher polyp reduction rate was significantly associated with higher CMT change from baseline at 3-month (p=0.048) while higher vascular lesion reduction rate was significantly associated with higher CMT change from baseline at 12-month(p=0.031) and fewer number of injections(p=0.012). Brolucizumab related IOI occurred in one eye (1/31, 3.2%). Intravitreal brolucizumab injection effectively improved visual and anatomical outcomes and achieved significant polyp regression in treatment-naïve PCV patients. Complete polyp regression and the reduction rate of vascular lesion size and polyp size after loading injection significantly influence the treatment outcome of PCV patients. However, careful monitoring and preoperative warning is warranted due to occurrence of brolucizumab-related IOI.

Differences between young and elderly polypoidal choroidal vasculopathy patients with and without pachychoroid phenotypes.

To investigate the distinct characteristics between young and elderly polypoidal choroidal vasculopathy (PCV) patients based on the pachy- or non-pachychoroid phenotypes. PCV patients treated with intravitreal injections of Conbercept based on the 3 + PRN regimen from 27 centers of China PCV Research Alliance were included. Patients were categorized into the young and the elderly aged group based on the cut-off point determined using the Youden method according to the pachychoroid phenotypes. The characteristics of past medical history, lifestyle factors, fundus manifestations, and treatment response between the subgroups were analyzed. Three hundred eight eligible patients were included. Multivariate logistic regression showed a significant association between age and PCV subtype classification (OR = 0.921, P = 0.002). A cutoff age of 64.5 effectively distinguished between pachychoroid PCV and non-pachychoroid PCV (P < 0.001). Elderly PCV patients had a higher incidence of hypertension history (P = 0.044) but a lower incidence of diabetes history (P = 0.027). In terms of lifestyle, smoking history (P = 0.015) and staying up late (P = 0.004) were more significant in the young group of PCV patients. For clinical characteristics, the proportion of hemorrhagic PCV in the young group was significantly higher (P = 0.038), with a higher proportion of sharp-peaked PED (P = 0.049), thicker choroid (P < 0.001) but a lower portion of double-layer sign (P = 0.023) in OCT. Both groups showed significant anatomical changes compared to baseline in each follow-up period (P < 0.05), with the young group having a higher proportion of good anatomical response after the first injection (P = 0.009). PCV patients stratified by subtype exhibit distinct characteristics between the young and elderly groups.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis

Introduction: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. Methods: We retrospectively reviewed patients’ medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. Results: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. Conclusion: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Genetic associations of central serous chorioretinopathy subtypes, neovascular age-related macular degeneration, and polypoidal choroidal vasculopathy

PurposeTo evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV). DesignA case-control genetic association study. MethodsThis study enrolled 217 CSCR, 341 nAMD, 288 PCV patients, and 1380 controls. The CSCR patients were classified into those with focal or diffuse leakage, with or without pigment epithelial detachment (PED), and with or without macular neovascularization (MNV). Associations between 11 variants from 8 genes, ADAMTS9, ANGPT2, ARMS2, CFH, NR3C2, PGF, TNFRSF10A and VIPR2, and diseases/subtypes were analyzed by logistic regression analysis adjusted for age and sex, and inter-phenotype comparison by heterogeneity test. ResultsThe CFH rs800292-A conferred a protective effect for CSCR with MNV (OR=0.44, P = 0.002) and a risk effect for CSCR without MNV (OR=1.31, P = 0.023). CSCR patients carrying rs800292-G had a 3.23-fold of increased risk towards developing secondary MNV (P = 1.45 ×10-4). CFH rs3753394, rs800292 and rs1329428 showed similar effects among CSCR with MNV, nAMD and PCV, but opposite effects on CSCR without MNV. TNFRSF10A rs13278062-T was associated with overall CSCR but not with CSCR subtypes, nAMD or PCV. Moreover, CFH and ARMS2 SNPs showed heterogeneous effects in CSCR without MNV against CSCR with MNV, nAMD and PCV. ConclusionsGenetic associations of CSCR with MNV resembled nAMD and PCV compared to CSCR without MNV, indicating differential genetic effects on neovascularization and choroidopathy. Further investigation of the functional roles of CFH, ARMS2, and TNFRSF10A in CSCR, nAMD and PCV should help elucidate the mechanisms of these maculopathies.

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel (P , < , 1.19times {10}^{-8}). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; P=1.05times {10}^{-6}) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

RISK OF EXUDATION IN EYES WITH NONEXUDATIVE POLYPOIDAL CHOROIDAL VASCULOPATHY.

To investigate the characteristics and natural history of treatment-naive nonexudative polypoidal choroidal vasculopathy (PCV) and to determine biomarkers predicting exudative conversion. Patients diagnosed with nonexudative PCV based on indocyanine green angiography and optical coherence tomography were included. Incidence of exudative conversion in nonexudative PCV patients and cumulative estimates for overall risk were assessed. Indocyanine green angiography and optical coherence tomography imaging-based features were analyzed to identify risk factors for exudative conversion. The study included 42 eyes of 40 patients with nonexudative PCV. The mean follow-up duration was 54.3 ± 35.5 months. Of the 42 eyes with nonexudative PCV, exudative conversion developed in 23 eyes (54.8%) after 42.2 ± 28.3 months (range, 8-103 months). Kaplan-Meier analysis showed that the exudation-free survival at 5 years after baseline was estimated to be 53.6%. Multivariate regression analysis showed that sequentially increased protrusion of retinal pigment epithelium in the polyp area was a significant risk factor for exudation in nonexudative PCV (odds ratio = 10.16; 95% CI 1.78-57.81; P = 0.01). Exudative conversion has been noted in nearly half of the nonexudative PCV cases in 5 years. The progressive protrusion of polypoidal lesions on optical coherence tomography examination may be a significant biomarker for predicting the near-term onset of exudation.

Clinical variations of polypoidal choroidal vasculopathy: A cohort study from Japan and the USA

We describe the clinical characteristics of treatment-naïve polypoidal choroidal vasculopathy (PCV) in three tertiary clinic settings in 2 cities (Chicago in the USA and Nishinomiya in Japan). This cohort study was a retrospective, multicenter, consecutive case series. A total of 126 patients with treatment-naïve PCV—46 in Chicago and 80 in Nishinomiya—were identified. The proportion of PCV in patients with neovascular age-related macular degeneration was lower in Chicago (10.8% vs. 36.9%). Patients in Chicago had a significantly higher prevalence of soft drusen (50.0% vs 25.0%, p = 0.006) and intra-retinal cyst (37.0% vs 15.0%, p = 0.008), and a significantly lower prevalence of pachyvessels (41.3% vs 62.5%, p = 0.03). At baseline, presenting vision for patients in Chicago was worse than in Nishinomiya (mean log MAR: 0.609 vs. 0.312, p < 0.001). Ninety-five eyes were followed for more than one year. The Nishinomiya group received a higher rate of combination therapy (61.0%) compared to the Chicago group (5.3%). Vision and central foveal thickness at month 12 were significantly improved from baseline in both Chicago (p = 0.009 and p = 0.01) and Nishinomiya groups (both p < 0.001). Our study highlights interesting differences in the proportion of PCV, clinical findings and treatment responses of PCV, that need to be further evaluated in larger, epidemiologic cohorts.

Photodynamic and Anti-VEGF Therapy for Polypoidal Choroidal Vasculopathy - ‘Real World’ Outcomes in a Caucasian Population

Background: The prevalence of polypoidal choroidal vasculopathy (PCV) is significantly higher amongst Asian populations compared to Caucasian, and evidence regarding the clinical outcomes of Caucasian patients is limited. Objective: This retrospective study sought to investigate real-world clinical outcomes of Caucasian PCV patients treated with polypoidal verteporfin photodynamic therapy (PDT) in combination with anti-VEGF therapy up to 36 months post-treatment. Methods: Consecutive PCV patients who received PDT between 2011 and 2017 were included. Mean change in visual acuity (VA) measured by ETDRS letter score and mean change in central subfield thickness (CST) were the main outcome measures. Data were collected at baseline, 3, 12, 24 and 36 months. Regression analyses were carried out on pre-treatment clinical features to determine if there were any factors associated with a good visual outcome (better than or equal to 70 ETDRS letters at 12 months). Results: Seventy six patients (96% Caucasian) and seventy eight eyes were included in the analysis. Mean change in VA was -1, -4, and 0 ETDRS letters at 12, 24, and 36 months, respectively. CST was reduced by a mean of -51, -54, and -55 microns at 12, 24, and 36 months, respectively. Better pre-treatment VA was the only pre-treatment clinical feature associated with a good visual outcome at 12 months (OR 1.16, p&lt;0.001). Conclusion: PDT, in combination with anti-VEGF therapy, maintains VA and may reduce the anti-VEGF therapy burden in Caucasian patients with PCV. Better pre-treatment VA is associated with a good visual outcome.

Three-dimensional heads-up system assisted pars plana vitrectomy and subretinal recombinant tissue plasminogen activator injection for submacular hemorrhage

BackgroundTo evaluate the outcomes of three-dimensional (3D) heads-up system assisted pars plana vitrectomy (PPV) and subretinal injection of recombinant tissue plasminogen activator (rt-PA) for submacular hemorrhage (SMH).MethodsMedical records of SMH patients who underwent 3D heads-up system assisted-PPV and subretinal injection of rt-PA from June 2021 to January 2022 were reviewed. The main outcomes included best-corrected visual acuity (BCVA), SMH absorption, and perioperative complications.ResultsWe finally included 18 SMH eyes, most of which happened secondary to polypoidal choroidal vasculopathy (PCV) (10, 55.56%), followed by retinal arterial microaneurysm (RAM) (5, 27.78%), traumatic retinopathy (2, 11.11%) and neovascular age-related macular degeneration (nAMD) (1, 5.56%). The greatest linear dimension (GLD) and height of SMH were 6538.17 ± 2533.11 μm and 937.36 ± 420.21 μm, respectively. After an average postoperative follow-up period of 131.06 ± 38.96 days, patients’ BCVA improved significantly from 1.85 ± 0.62 to 1.14 ± 0.82 logMAR (P < 0.05). SMH was completely and partially absorbed in 9 (50.00%) and 6 (33.33%) eyes, with no occurrence of iatrogenic retinal break. However, 4 additional PPVs were performed to manage the postoperative SMH and/or vitreous hemorrhage (VH) recurrence (2, 11.11%) and retinal detachment (RD) occurrence (2, 11.11%). Preoperative BCVA was significantly correlated with postoperative BCVA in multiple linear regression analysis (P < 0.05), and hemorrhagic pigment epithelial detachment (PED) was significantly correlated with SMH and VH recurrence in univariate binary logistic regression analysis (P < 0.05).ConclusionsThe 3D heads-up system assisted-PPV and subretinal injection of rt-PA were efficacious in eliminating SMH and improving visual prognosis with satisfactory safety profile, while caution should be taken for PCV patients with hemorrhagic PED and massive SMH.

Clinical features and outcomes of breakthrough vitreous hemorrhage secondary to polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) with hemorrhagic complications is at higher risk for breakthrough vitreous hemorrhage (VH). This study aimed to evaluate the clinical features and outcomes of breakthrough VH secondary to PCV. Data of patients receiving pars plana vitrectomy for breakthrough VH secondary to PCV (VH group) were evaluated retrospectively and compared statistically to data of age and sex-matched PCV patients without breakthrough VH (control group). Among PCV patients, 36 eyes with breakthrough VH and 62 eyes without VH were included. Compared with baseline, best corrected visual acuity (BCVA) was worse in the VH group (P < 0.001), and improved postoperatively (P < 0.001). Percentages of pigmented epithelial detachment (PED), hemorrhagic PED, massive subretinal hemorrhage, hemorrhagic retinal detachment (RD), and hemorrhagic choroidal detachment (CD) (P = 0.007) were higher in the VH group (P < 0.001). Incidence of choroidal vascular hyperpermeability (P < 0.001), massive subretinal hemorrhage (P = 0.001), hemorrhagic retinal detachment (P = 0.001) and hemorrhagic type PCV (P = 0.001) was higher in patients with pachychoroid PCV, while fibrovascular type had lower incidence (P < 0.001). Better initial BCVA (P < 0.001), higher frequency of anti-VEGF treatment (P = 0.009), and previous photodynamic therapy (P = 0.017) showed better visual outcomes. Breakthrough VH risk is higher in PCV patients with massive subretinal hemorrhage, hemorrhagic PED and hemorrhagic RD. BCVA and hemorrhagic complications improve significantly postoperatively. Higher frequency of anti-VEGF treatment and previous photodynamic therapy are associated with better visual prognosis in PCV patients with breakthrough VH.

Determination of Vascular Endothelial Growth Factor-B Concentrations in Aqueous Humor and Plasma of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy Patients Before and After Anti-VEGF Therapy.

Anti-vascular endothelial growth factor (anti-VEGF) injection was widely used in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV); however, the systemic and local levels of vascular endothelial growth factor (VEGF)-B were seldom detected before. This study was conducted to detect and compare the aqueous humor and plasma VEGF-B levels in nAMD and PCV before and after anti-VEGF therapy. Concentrations of VEGF-B in aqueous humor and plasma of individuals with nAMD (n = 10), PCV (n = 22), and age-related cataract controls (n = 12) were measured by enzyme-linked immunosorbent assay. Ranibizumab was injected intravitreally in patients monthly for three consecutive months. Before each injection in patients and at the baseline of controls, blood and aqueous humor samples were collected. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were collected before each injection in patient groups. The differences of BCVA, CRT, and VEGF-B levels in aqueous humor and plasma between groups before and after anti-VEGF therapy were compared. VEGF-B was overexpressed in aqueous humor and plasma of nAMD and PCV groups compared with control group (P < 0.05), but no statistically significant difference existed across nAMD and PCV groups (P > 0.05). Moreover, there were no obvious difference in levels of VEGF-B in aqueous humor and plasma within the treatment groups after anti-VEGF treatment (P > 0.05). The mean CRT in the nAMD group was thinner than that in the PCV group at baseline (P < 0.01). After injections, the CRT obviously declined in both groups (P < 0.05). There was no correlation between CRT reduction and high VEGF-B expression in aqueous humorand plasma of treatment groups. Overexpression of VEGF-B locally and systemically in patients with nAMD and PCV indicated that elevated VEGF-B concentrations were relevant to the disease processes. Ranibizumab did not influence the levels of VEGF-B in the real world. CRT might help to distinguish PCV from nAMD.

Polypoidal choroidal vasculopathy—characteristics and response to treatment with bevacizumab in caucasian patients

PurposeTo investigate the features and treatment response in Caucasian patients with polypoidal choroidal vasculopathy (PCV), initially treated with bevacizumab.Methods45 eyes of 43 treatment-naïve patients with PCV were included in this retrospective study, all uniformly initially treated with three bevacizumab injections monthly. OCT characteristics and clinical parameters were recorded and analyzed at presentation, after the initial 3 bevacizumab injections and at the final follow up period.ResultsFollowing 3 monthly bevacizumab injections visual acuity significantly improved with a mean gain of one line of vision. Central macular thickness (CMT) significantly improved from a mean of 402.1 ± 130.8 μm at presentation to 322.0 ± 96.8 μm (p < 0.01). Subretinal fluid, intraretinal fluid and submacular hemorrhage significantly improved. 53% were later switched to aflibercept and showed better response in the central macular thickness in comparison to those in which bevacizumab injections were continued. No correlation was found between the presence of pachyvessels or increased choroidal thickness and the improvement in VA or CMT.ConclusionFixed first-line treatment with intravitreal bevacizumab monotherapy in non-Asian PCV patients achieves satisfactory visual and anatomical outcomes.

Plasma Cytokine Profiles in Patients With Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration.

The concentrations of cytokines in plasma may be different between neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). We studied plasma levels of cytokines in patients with nAMD and PCV and compared them with control individuals. This was a prospective, clinic-based, case-control study of treatment-naive participants (n=49) with PCV (n=24), nAMD (n=11), and cataract controls (n=14). We sampled fresh venous blood and isolated plasma for analysis. Plasma concentrations of 34 angiogenic and inflammatory cytokines were determined by Luminex bead-based multiplex array. After adjusting for gender and age using multivariate logistic analysis, we found that the plasma concentrations of monocyte chemoattractant protein-1, vascular endothelial growth factor (VEGF)-A, and VEGF-D significantly higher in both nAMD and PCV patients than those in controls (all P<0.05, times in nAMD: 3.5, 4.3, and 13.8, respectively, times in PCV: 4.1, 4.0, and 11.5, respectively). In contrast, the plasma concentration of platelet-derived growth factor-BB was significantly lower in nAMD and PCV patients than those in controls (all P<0.05, times in nAMD: 1.6, times in PCV: 1.7). The plasma levels of leukemia inhibitory factor in nAMD group were significantly higher compared with PCV group (P<0.0167). Multiple cytokines involved in systemic inflammation and angiogenesis including monocyte chemoattractant protein-1, platelet-derived growth factor-BB, VEGF-A, and VEGF-D may contribute to the pathogenesis of nAMD and PCV. Measurement of leukemia inhibitory factor in the plasma may help differentiate nAMD from PCV. This finding suggests that the 2 disorders may have different molecular mechanisms, and additional longitudinal studies will be needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy.