Mechanism And Clinical Study Of Age-related Macular Degeneration

Chapter 1 Pharmacogenetics of genes associated with outcome of conbercept treatment for age-related macular degeneration in a Chinese populationAim:To investigate the Pharmacogenetic associations between the genetic risk variants of age-related macular degeneration(AMD)and the outcomes of neovascular AMD by conbercept in Chinese patients.To make clear whether there is a genetic variation in the patients with poor curative effect in conbercept.To provide the clinical evidence for the precision medical model and clinical indicidualized therapy.Methods:We enrolled 184 neovascular AMD patients from the AURORA and PHOENIX trials,and participants were administrated with conbercept.For each patient,baseline best corrected visual acuity(BCVA)letter score was recorded,and the BCVA score at each subsequent visit,age,sex and the number of injections were also recorded.Patients with a gain of>5 Early Treatment Diabetic Retinopathy Study(ETDRS)letters from baseline at 6 and 12 months were defined as responders,and those who gained ≤5 letters were designated as nonresponders.Seven candidate single-nucleotide polymorphisms(SNP)were selected,complement factor H(CFH),interleukin 8(IL8),vascular endothelial growth factor A(VEGFA),age-related maculopathy susceptibility 2(LOC387715/ARMS2),high-temperature requirement A-1(HTRA1)and complement component C3(C3)genes.The SNP genotyping was performed using the TaqMan SNP genotyping assays.Single-locus analysis and haplotype analysis were used to determine the influence of each SNP on treatment outcome at 6 months and 12 months.Results:We found that,both in single-locus analysis and haplotype analysis,rs10490924 and rs11200638 were significantly associated with patient response to conbercept treatment for neovascular AMD in Chinese population.The χ2 test revealed the distribution of genotypes for each genetic variant was consistent between responders and nonresponders,with the exception of SNPs rs10490924 and rs11200638(p = 0.018 and 0.008,respectively)at 6 months.Patients carrying the GG or GA genotype for HTRA1 rs 1120063 8 and the GG or GT genotype for LOC387715/ARMS2 rs10490924 are more likely to be responders compared with AA or TT genotypes carriers.Conclusion These findings suggest that SNPs rs 10490924 and rs 1120063 8 could be used as genetic biomarkers for the estimation of visual outcomes in response to conbercept treatment for neovascular AMD,an effective and reasonable therapeutic plan with conbercept can be formulated if we have knowledge of genetic variations of AMD patients.Chapter 2 The efficacy of subthreshold micropulse 577nm laser for dry age-related macular degeneration with Retinal pigment epithelium detachmentAim To investigate the visual and morphological outcome in eyes with Retinal pigment epithelium detachment(PED)secondary to dry age-related macular degeneration(AMD)treated with subthreshold micropulse 577nm laser.Methods This is a prospective case-series study.The clinical data of 17 patients 20 eyes of dry AMD with PED were analyzed.All of 20 eyes were treated with subthreshold micropulse 577nm laser.The best corrected visual acuity(BCVA),Central retinal thickness(CRT),PED height,PED surface area,and PED volume were measured before and after treatment during the 18 months follow-up visit.We analyzed the changes in baseline and 1 months,3 months,6 months,12 months and 18 months after treatment.Results Preoperative the mean of the BCVA was(60.85±6.52)letter,PED Height was(434±273.22)μm.1,3,6,12,18 months after treatment the average BCVA were 62.15±6.26,62.95±5.03,63.55±5.81,63.85±4.87,64.4±5.67;the average height of PED were(411.1 ±289.05)μm、(385.55±303.84)μm、(249.95±170.41)μm、(213.95±182.74)μm、(177.65±147.10)μm.Compared with before treatment,1,3,6,12,18 months after treatment,statistically differences of BCVA,PED height,PED surface area,and PED volume were found(F=4.107,P=0.002;F=15.267,P=0.000;F=10.238,P=0.00 和 F=8.611,P=0.000).Each record index has a difference from baseline to 6 months..After 18 months of treatment,no new drusen were found.20 eyes were repeated micro pulse laser treatment.The number of repetitions:2,3,4,5 times were 1,3,4,2 and 1 eyes,respectively.Conclusions Our data confirmed that subthreshold micro-pulse 577nm laser was a good treatment method for PED in dry AMD,with a good maintain in BCVA and a reduction in retinal thickness,PED height,PED surface area,and PED volume.