Clinical Features Of Polypoid Choroidal Vasculopathy, Therapy And Gene Polymorphism

Part I A preliminary study on single nucleotide polymorphisms of polypoidal choroidal vasculopathy patientsPurpose:To investigate whether polymorphisms in the LOC387715/HTRA1, PEDF, ELN, TIMP3, LIPC and CETP genes are associated with polypoidal choroidal vasculopathy(PCV)in a Chinese population.Methods:A case-control association study of153unrelated Chinese patients with PCV and221control subjects matched in ethnicity and gender was undertaken. Genomic DNA was prepared from peripheral blood. All SNPs were genotyped using the MassArray platform and MALDI-TOF analysis. Genotypic distribution was tested for Hardy-Weinberg equilibrium. Statistical analyses were performed on computer using the SPSS (version170:SPSS Science, Chicago, IL) software. The genotype and allele frequencies were evaluated using the x2tests. Bonferroni corrections for multiple comparisons were performed. The significance of the differences in the estimated haplotype frequencies between case and control groups were examined on Haploview4.2using the x2tests.Results:Three SNPs for LOC387715/HTRA1, rs10490924, rs3793917and rs11200638, showed significant differences in allele frequencies between PCV and control groups (P=3.46×10-10,3.40×10-9,8.31×10-11, respectively). The significant differences remained after Bonferroni correction. The genotype frequencies of rs10490924, rs3793917and rs11200638in LOC387715/HTRA1were also found to be significantly different between PCV and control groups(P=8.926X10-9,3.408X10-8,1.099X10-9, respectively). The differences for rs10490924, rs3793917and rs11200638were still significant among the PCV cases after adjustment for age. Three SNPs for LOC387715/HTRA1, rs10490924, rs3793917and rs11200638, showed high linkage (r2=0.95,0.89,0.85, respectively). The haplotypes TC A and GGG of rs10490924, rs3793917and rs11200638were also associated with PCV (P=1.80X10-9,1.92X10-10, respectively). No significant association was noted with PEDF (rs1136287), ELN (rs2301995), TIMP3(rs8136803, rs2283883, rs242089, rs1962223, rs242082, rs80272,rs135025,rs715572,rs242076),LIPC(rs6078,rs6083,rs1800588,rs3829462, rs1077834), CETP (rs4783961, rs1800775, rs17245715, rs1801706, rs5882) among the PCV cases(P>0.05). Evaluation of common haplotypes across TIMP3, LIPC and CETP did not reveal any association with PCV(P>0.05).Conclusions:We found no evidence to support the polymorphisms of PEDF、ELN、 TIMP3、LIPC and CETP in the susceptibility to PCV in a Chinese population. The SNPs rs10490924, rs3793917and rs11200638of LOC387715/HTRA1are significantly associated with the risk of PCV. Part II Clinical characteristics of polypoidal choroidal vasculopathyObjective:To observe the clinical characteristics of polypoidal choroidal vasculopathy (PCV) and to explore the possible risk factors associated with the development and progression of PCV.Methods:This is a retrospective, uncontrolled case series study. One hundreds fifty-three PCV patients(185eyes)were enrolled in this study. All the patients were underwent stardard questionnaire survey by one trained person. Uniform questionnaires were administered to obtain information such as gender, age, occupation, hypertension, diabetes, hyperlipemia, coronary heart disease, smoking, diet, height, and weight etc. All the patients were examined for best corrected visual acuity(BCVA)testing, slit—lamp microscope, indirect ophthalmoscopy, fundus photography, fluorescein angiography, indocyanine green angiography and optic coherence tomography.Results:The patients included82males(53.59%)and71females(46.41%); the age was from44to84years, with a mean age of(64.94±9.49)years. The body mass index(BMI) was from15.82to32.19, with a mean BMI of (24.74±2.37). There were fifty-one patients with a history of hypertension(33.33%), seventy-three patients with a history of hyperlipemia (47.71%), and fourty-eight patients with a history of smoking (31.37%). Bilateral lesions were observed in32patients(20.92%)and unilateral lesions were observed in121patients(79.08%). In121patients with unilateral PCV lesions, drusen can be observed in the contralateral eyes of39patients(32.23%), Vitreous hemorrhage was observed in30eyes(16.22%).There were five patients with a histoty of central serous chorioretinopathy(3.27%). PCV lesions located at macula area in123eyes(66.49%), under the temporal retinal vascular arcade in23eyes(12.43%), and peripapillary in8eyes(4.32%). PCV lesion formation was single in72eyes(38.91%), cluster in96eyes (51.89%), string in2eyes(1.08%), branch in3eyes(1.62%), and both single and cluster polyps in12eyes(6.49%). There were108eyes(58.38%)with sub-neuroretinal fluid,94eyes(50.81%)with hemorrhagic pigment epithelium detachment, and22eyes(11.89%)with serous pigment epithelium detachment.Conclusion:PCV patients have higher bilateral incidence and female prevalence, higher serous or hemorrhagic PED incidence, and higher rate of macula area lesions. Age and race factor may be the most important risk factor for PCV, smoking, hypertension, and hyperlipemia may have some contact with PCV. Part Ⅲ Efficacy evaluation of photodynamic therapy and intravitreal anti-vegf injection for polypoidal choroidal vasculopathy:systematic reviewObjectives:To compare the efficacy of photodynamic therapy (PDT) alone, intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone, and the combination of the two therapies for polypoid choroidal vasculopathy (PCV).Methods:A computerized search was conducted in Pubmed, Biosis Preview, Cochrane Library, and Embase. Studies comparing any two of the above three treatment strategies were enrolled in the study. Meta-analysis of pairwise comparisons of the three approaches were conducted. The primary endpoint was the proportion of patients with complete regression of polyps. Other endpoints included best corrected visual acuity(BCVA), central retinal thickness(CRT), number of treatments.Results:A total of13comparative studies were obtained, including1randomized controlled trials (RCT) and12retrospective comparative study (RCS). Four studies compared anti-VEGF monotherapy with PDT monotherapy. Seven studies compared PDT monotherapy with combination therapy. Four studies compared anti-VEGF monotherapy with combination therapy. Considering the RCT and RCS results:PDT was superior to anti-VEGF in achieving complete regression of polyps at month6(P=0.0037), although BCVA and CRT showed no significant difference at12-month follow-up. There was no significant difference in BCVA, CRT, and the proportion of patients with complete regression of polyps between PDT and combination group at12months follow-up. However, combination therapy showed more promising result in improving visual acuity at24months (P=0.05), with fewer PDT needed than in PDT monotherapy.Combination therapy was superior to anti-VEGF in achieving complete regression of polyps and the number of injections needed tended to be fewer.BCVA improvement and CRT reduction showed no significant difference at12-month follow-up.Conclusions:PDT with or without anti-VEGF therapy is superior to anti-VEGF monotherapy in achieving complete polyp regression, and combination therapy appeared toresult in better visual outcome than PDT monotherapy in the long term(2years). PartⅣ Three-year follow-up results of photodynamic therapy for polypoidal choroidal vasculopathyObjective:To evaluate the3-year efficacy of photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV).Method:This is a retrospective, uncontrolled case series study. Thirty-two eyes of29patients wih PCV were enrolled. All patients were primarily treated with the first conventional PDT. For the eye with active polypoida, residual or exudative lesions in6month after PDT, PDT combined with intravitreal anti vascular endothelial growth factor (VEGF) or simple vitreous injection of anti VEGF therapy were used. All the patients were followed up for at least3years with the mean follow-up duration of43.64±10.84months. The best-corrected visual acuity (BCVA) in1,3,6,12,24and36months after the primary PDT, PCV recurrence rates and number of treatments were followed and analyed. The BCVA was converted into a logarithm of the minimal angle of resolution (logMAR) for statistical analysis.Results:During the1,3,6,12months after the primary PDT, the mean BCVA were all improved with statistically significant difference (t=2.27,4.57,3.77,2.37; P<0.05). During the24and36months after PDT, the mean BCVA was decreased without statistically significant difference (t=-1.29,-0.81;P>0.05). On the final evaluation at36months, the mean BCVA was improved in6eyes (18.75%), stable in14eyes (43.75%), and decreased in12eyes (37.50%). During the follow-up time, recurrence of PCV in24eyes (75.00%), no recurrence in8eyes (25.00%). There was1recurrence in12eyes(50.00%),2recurrences in9eyes(37.50%),3recurrences in3eyes(12.50%). Initial recurrences were noted in4eyes (16.67%) within12months of baseline PDT treatment; in11eyes (45.83%) between13and24months; in9eyes (37.50%) between25and36months. The mean number of PDT and anti-VEGF was1.86±1.04and4.95±3.92in all patients, respectively.Conclusions:The3-year efficacy of PDT in patients with PCV was poor with low improvement of visual acuity and high recurrence rate of PCV.