Positive association of CD36 gene variants with the visual outcome of photodynamic therapy in polypoidal choroidal vasculopathy.
ABSTRACT: PURPOSE: To clarify the association between cluster of differentiation 36 (CD36) gene polymorphisms and the response to photodynamic therapy (PDT) in polypoidal choroidal vasculopathy (PCV). METHODS: One hundred and thirty-seven patients with PCV were enrolled. The patients were treated with PDT and followed up for more than 6 months. Retreatments were performed every 3 months as needed based on findings from angiography. Patients who showed an improvement in their best-corrected visual acuity at 6 months post-PDT were classified as PDT responders, and the others were defined as non-responders. For the 73 responders and 64 non-responders, 19 single nucleotide polymorphisms (SNPs) across the CD36 region were genotyped using the TaqMan assay. We analyzed the association between these variants and the visual outcomes of PDT. RESULTS: The allelic frequencies of the SNPs rs3211851, rs3173798, and rs3211908 showed nominally significant differences between the PDT responders and non-responders. Genotype association analysis revealed a significant association of SNP rs3173798 with the visual outcome of PDT in a dominant model. The presence of the C allele in rs3173798 was significantly associated with a poor response to PDT after multivariate logistic regression analysis with clinical pre-PDT parameters. The mean best-corrected visual acuity in the group with the TT genotype of rs3173798 was significantly improved over 12 months of follow-up after the initial PDT. CONCLUSIONS: The coding variants in CD36 are possibly associated with the visual outcome of PDT in patients with PCV.
Project description:PURPOSE: To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the phenotype of typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) and the effects of photodynamic therapy (PDT). METHODS: The single nucleotide polymorphisms at rs10490924 (A69S) in ARMS2 of 68 tAMD and 119 PCV patients who underwent PDT were genotyped using the TaqMan assay. The baseline best corrected visual acuity (BCVA) and lesion size were compared among the three genotypes at rs10490924. A multivariate regression analysis was performed to evaluate the influence of the baseline BCVA, greatest linear dimension (GLD), and lesion phenotype (tAMD or PCV) on the association of rs10490924 with the BCVA 12 months after the first PDT. RESULTS: The mean lesion size was significantly different among the GG, GT, and TT genotypes at rs10490924 in the PCV group, although no significant differences were detected in the tAMD group. PCV patients with a G allele had significantly better vision at 3 months after the initial PDT. tAMD patients with a TT genotype had significantly poorer vision at 12 months after the first PDT. In the multivariate regression analysis, the additive model of the G allele at rs10490924 was associated with a significantly better BCVA 12 months after the first PDT in tAMD and PCV patients. CONCLUSIONS: ARMS2 variants are likely associated with the phenotype and the effects of PDT in tAMD and PCV.
Project description:PURPOSE: To clarify the association of cluster of differentiation 36 (CD36) variants with polypoidal choroidal vasculopathy (PCV) and compare them with those in typical neovascular age-related macular degeneration (tAMD). METHODS: We included 349 Japanese AMD patients (210 PCV, 139 tAMD) and 198 age-matched controls. Four tag single-nucleotide polymorphisms (SNPs)-rs10499862, rs3173798, rs3211883, and rs3173800-in the CD36 region were genotyped using the TaqMan assay. Allelic and genotypic frequencies of the SNPs were tested. RESULTS: Although none of the SNPs tested were associated with PCV, the allelic frequencies of rs3173798 and rs3173800 were significantly different between PCV and tAMD patients. Genotype association analysis demonstrated different associations of these two SNPs between PCV and tAMD in the genotype model. Haplotype analysis revealed that the association of the major haplotype (T-T-T-T) at four selected SNPs in CD36 differed significantly between PCV and tAMD patients. CONCLUSIONS: The CD36 region may be associated with the difference in genetic susceptibility for PCV and tAMD.
Project description:BACKGROUND:To evaluate 5-year outcomes of anti-vascular endothelial growth factor (VEGF) monotherapy and combination therapy of anti-VEGF agents and photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) in a real-world Chinese population. METHODS:Retrospective study. Fifty-three eyes of 46 patients with subtype 1 and 2 PCV followed up for at least 60?months were grouped into three regimens: anti-VEGF monotherapy, PDT combining with anti-VEGF therapy initially, and PDT combining with deferred anti-VEGF therapy. Main outcome measure was best-corrected visual acuity (BCVA) using logarithm of minimal angle of resolution (logMAR). RESULTS:The mean BCVA of eyes with subtype 1 PCV (n?=?28) deteriorated from 0.69 logMAR at baseline to 1.25 logMAR at months 60 (P?=?0.001), while the mean BCVA of eyes with subtype 2 PCV (n?=?25) sustained stable from 0.62 logMAR at baseline to 0.57 at months 60 (P?=?0.654). No significant differences of visual outcomes were found between the 3 treatment regimens for subtype 1 PCV. Anti-VEGF monotherapy and initial combination treatment had better visual outcomes in eyes with subtype 2 PCV than deferred combination group during part of follow-up significantly. Initial combination group needed a less number of PDT than deferred combination group (P?<?0.001). CONCLUSIONS:Compared with subtype 1 PCV, subtype 2 PCV has a more favorable visual outcome in real world. All the regimens presented unfavorable visual outcomes for subtype 1 PCV. Anti-VEGF monotherapy and initial combination therapy should be superior to deferred combination therapy in the long-term management of subtype 2 PCV. Prospective randomized studies of larger size are needed to determine the long-term efficacy and safety of various treatment for PCV in real world.
Project description:Photodynamic therapy (PDT) combined with intravitreal anti-vascular endothelial growth factor (VEGF) agents is currently the first-line treatment for polypoidal choroidal vasculopathy (PCV), along with anti-VEGF monotherapy. In this study, 100 eyes with treatment-naïve PCV were initially treated with PDT combined with intravitreal ranibizumab (IVR; n?=?57) or aflibercept (IVA; n?=?43). We compared two-year outcomes between these two groups and investigated factors associated with visual improvement and retreatment over 24 months. Best-corrected visual acuity (BCVA) was significantly improved in both groups (P?<?0.001) at 24 months. Multiple regression analysis revealed that visual improvement at 24 months was associated with female (P?=?0.030), worse baseline BCVA (P?=?3.0?×?10-6), smaller greatest linear dimension (GLD; P?=?2.0?×?10-4), and treatment with IVA rather than IVR (P?=?0.016). Multiple logistic regression analysis revealed that absence of retreatment was associated with younger age (P?=?2.2?×?10-4), female (P?=?1.2?×?10-3), and the non-risk variants of ARMS2 A69S (P?=?6.0?×?10-4). Although there were no significant differences in the retreatment rate between the two groups, PDT/IVA may be superior to PDT/IVR in terms of visual improvement at 24 months.
Project description:Importance:Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV. Objective:To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV. Design, Setting, and Participants:A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017. Interventions:Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n?=?168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n?=?154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. Main Outcomes and Measures:Step 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12. Results:Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 ?m, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P?=?.01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P?<?.001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]). Conclusions and Relevance:After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV. Trial Registration:clinicaltrials.gov Identifier: NCT01846273.
Project description:BACKGROUND:To investigate the one-year visual and anatomical outcomes of combination therapy with intravitreal aflibercept (IVA) and photodynamic therapy (PDT) for treating polypoidal choroidal vasculopathy (PCV). METHODS:This was a retrospective case-series study, including 30 eyes from 30 patients with treatment-naïve PCV treated by combination therapy with IVA and PDT. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), complete polyp regression rate, and dry macula rate were recorded every 3 months during 12-month follow-up. Clinical factors associated with final visual outcome and retreatment were investigated. RESULTS:The mean LogMAR BCVA was significantly improved from 0.73 ± 0.65 at baseline to 0.51 ± 0.60 (p = 0.01), and the mean CRT was also significantly improved from 339 ± 96 μm at baseline to 244 ± 43 μm at 12-month follow-up (p < 0.001). Complete regression of polypoidal lesions was 76.7%, and dry macula rate was 100% at 12 months. Better final BCVA was associated with younger age and better baseline BCVA (p = 0.02 and p < 0 001). The patients without complete polyp regression at 3-month follow-up were associated with retreatment (p = 0.03). CONCLUSION:In this study, combination therapy with IVA and PDT had significant visual and anatomical improvements to PCV patients during one-year follow-up. Better baseline BCVA and younger age were found to be associated with better visual outcome.
Project description:We report 5-year visual and anatomical outcomes after combination therapy of photodynamic therapy (PDT) and intravitreal injection of ranibizumab or aflibercept for polypoidal choroidal vasculopathy (PCV) and predictive factors for visual outcomes at 5-year and time to recurrence. Medical charts were retrospectively reviewed for 43 consecutive eyes with PCV treated with combination therapy of PDT and intravitreal injection of ranibizumab(n = 13) or aflibercept(n = 30) and completed 5-year follow-up. The variants of ARMS2 A69S and CFH I62V were genotyped using TaqMan assay. Best corrected visual acuity (BCVA) significantly improved at 5-year (P = 0.01) with 20% reduction of subfoveal choroidal thickness irrespective of presence or absence of recurrence. Visual improvement was associated with baseline shorter greatest linear dimension (GLD) (P = 1.0×10-4). Mean time to recurrence was 28.6±23.1 months (95% CI: 21.5-35.7, Median:18.0) and time to recurrence was associated with G allele (protective allele) of ARMS2 A69S and GLD (P = 4.0×10-4 and 1.0×10-2, respectively). Multiple regression analysis revealed that time to recurrence extended by 15.5 months when the G allele of ARMS2 A69S increased by one allele (TT: 15.7±17.0, TG: 30.8±23.5, GG: 41.1±22.6 months). The combination therapy resulted in a favorable visual outcome for PCV during 5-year follow-up.
Project description:PURPOSE:To describe treatment outcomes in a cohort of Caucasian patients with polypoidal choroidal vasculopathy (PCV). METHODS:Clinical charts from 48 eyes of 45 Caucasian patients with PCV were retrospectively reviewed. All cases were diagnosed with indocyanine green angiography. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) imaging were analyzed at baseline and final follow-up. RESULTS:Eyes were treated with a combination of verteporfin photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) (n = 24), or PDT monotherapy (n = 9), or anti-VEGF monotherapy (n = 8), or no treatment (n = 7). Aflibercept was the anti-VEGF agent in 30 out of 32 eyes. Sixteen out of 24 eyes in the combination treatment group received initial PDT at diagnosis. All treatments led to stabilization of BCVA at final visit with a trend for better visual acuity in the anti-VEGF monotherapy group. There was a substantial reduction in central retinal thickness associated with resolution of subfoveal fluid and improvement in retinal pigment epithelial detachment in all treatment groups. BCVA and OCT findings remained stable in eyes which received no treatment. The use of PDT was associated with 0.5 fewer intravitreal injections per annum, which was not statistically significant. CONCLUSIONS:In the largest series of Caucasian patients with PCV presented to date, anti-VEGF monotherapy, PDT, or their combination preserved visual acuity and improved subfoveal exudative changes. Combination treatment was not superior to anti-VEGF monotherapy.
Project description:We investigated whether response to photodynamic therapy (PDT) with intravitreal aflibercept injection (IAI) for polypoidal choroidal vasculopathy (PCV) differs depending on fellow eye condition. A retrospective review was conducted for consecutive 60 eyes with PCV treated with PDT combined with IAI as well as 2-years of follow-up data. Fellow eyes were divided into 4 groups; Group 0: no drusen, Group 1; pachydrusen, Group 2; soft drusen, Group 3: PCV/fibrovascular scarring. Best-corrected visual acuity improved at 24-months irrespective of groups and there were no significant differences in visual improvement among treated eyes among the 4 groups. Within 2-years, 35 (58.3%) required the retreatment. The need for retreatment including additional injection and the combination therapy was significantly less in Group 1(12.5%) compared to the others (P = 0.0038) and mean number of additional IAI was also less in Group 1 compared to the others (P = 0.017). The retreatment-free period from the initial combination therapy was longest in Group 1 (23.6±1.1 months) (P = 0.0055, Group 0: 19.1±6.9, Group 2: 12.8±7.9, Group 3: 11.5±9.9). The need for retreatment was significantly different according to fellow-eye condition. Among PCV patients, pachydrusen in fellow eyes appear to be a predictive characteristic for a decreased treatment burden at 2 years.
Project description:Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like choroidal neovascularization and a branching vascular network. Intravitreal aflibercept injection (IAI) or photodynamic therapy (PDT) is used for treatment. We retrospectively compared the 1-year outcomes of IAI monotherapy and its combination with initial PDT for PCV. Twelve eyes with naïve PCV received three IAIs and a single PDT after the first IAI and as needed injection (combination group); 11 eyes with naïve PCV received three IAIs and as needed injections (IAI group). Significant improvements in visual acuity after 2 months and in CRT after 1 month were maintained at 12 months in both groups (both P < 0.05); groups did not differ significantly at any time point. CCT significantly reduced after 3 and 12 months in the combination group (both P < 0.05) but not in the IAI group. A mean of 3.7 ± 0.9 and 5.6 ± 2.0 injections was administered to the combination and IAI groups, respectively (P = 0.013). Within a 1-year period, combination therapy was found to yield similar visual acuity and retinal structure improvements and maintenance as IAI monotherapy while requiring fewer IAIs.