Complement factor B polymorphism (rs641153) and susceptibility to age-related macular degeneration:evidence from published studies

AIM

To determine whether single nucleotide polymorphism (SNP) rs641153 is associated with the risk of age-related macular degeneration (AMD), we performed a systematic meta-analysis of 15 eligible studies. SNP in the complement factor B (CFB) gene is considered to have significant association with AMD susceptibility, but there is great discrepancy in these results.

METHODS

The eligible studies were identified by searching the databases of PubMed, EMBASE, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. All data were analyzed using Stata software.

RESULTS

The association between rs641153 and AMD risk was statistically significant under the homozygous model (AA vs GG:OR=0.26, 95%CI=0.15-0.45, P_h=0.973, I²=0.0%, fixed effects), dominant model (AA+GA vs GG:OR=0.49, 95%CI=0.40-0.59, P_h=0.004, I²=56.4%, random effects) and recessive model (AA vs GA+GG:OR=0.30, 95%CI=0.17-0.51, P_h=0.983, I²=0.0%, fixed effects). The same results were also observed in the stratified analyses by ethnicity, source of control and sample size.

CONCLUSION

Our meta-analysis suggests that rs641153 in the CFB gene may play a protective role in AMD susceptibility, the late AMD in particular, both in Caucasians and in Asians.     

SERPING1基因rs2511989多态性与年龄相关性黄斑变性相关性研究的Meta分析

目的:探讨经典通路SERPING1基因rs2511989基因多态性与年龄相关性黄斑变性(age-related macular degeneration,AMD)的相关性.方法:检索中国学术期刊网(CNKI)、PubMed、Cochrane、Embase以及Web of Science数据库,使用随机效应模型,使用OR值及其95％可信区间评价SERPING1 rs2511989基因多态性与AMD易感性的关联程度,同时对入选文献异质性,敏感性以及发表偏倚等进行评估.结果:共纳入15项病例对照研究,收集8657例AMD患者,对照组5393例.各个遗传模型中均未发现SERPING1基因多态性与AMD发病具有相关性.(显性模型:OR=0.960,95％ CI:0.918 ～1.003,P=0.009;隐性模型:OR=0.898,95％ CI:0.791 ～1.019,P=0.035;共显性纯合模型:OR=0.881,95％ CI:0.770 ～1.008,P=0.003;共显性杂合模型:OR=0.962,95％ CI:0.917 ～1.010,P=0.050).但进一步研究发现SERPING1基因多态性与新生血管型AMD显著相关.(显性模型:OR=0.691,95％ CI:0.547～0.872;共显性纯合模型:OR=0.661,95％ CI:0.450 ～0.971;共显性杂合模型:OR=0.754,95％ CI:0.589～0.964).亚组分析未发现种族与国家对rs2511989基因多态性与AMD有影响.结论:通常情况下SERPING1 rs2511989基因多态性与AMD无相关性,但在新生血管类型AMD可能与其存在相关性.期待更多研究来证实该假说.     

The association between matrix metalloprotease-9 gene polymorphisms and primary angle-closure glaucoma in a Chinese Han population

AIM:To examine the association between the single nucleotide polymorphisms (SNPs) of matrix metalloprotease-9 (MMP-9) gene and primary angle-closure glaucoma (PACG) in a Chinese Han population.METHODS: DNA samples were extracted from peripheral-blood mononuclear cells of 214 PACG patients and 224 healthy controls. Genotyping of rs3918249, rs3918254, rs17577 and rs3787268 in MMP-9 was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis and the direct sequencing technique. The association between these genetic polymorphisms and risk of PACG was estimated by χ² test.RESULTS: The distributions of rs3918249, rs3918254, rs17577 and rs3787268 genotypes among cases and healthy controls were compatible with that from Hardy-Weinberg equilibrium (HWE, P>0.05).The increased frequency of CC and CT genotypes of rs3918254 were observed in PACG patients compared to healthy controls [P=0.006, Pcorrected (Pcorr)=0.048]. The haplotype analysis showed that the CCGG haplotype was nominal associated with PACG (P=0.015), however, the significant was lost when the Bonferroni correction was used (Pcorr=0.105).CONCLUSION:Our results revealed that rs3918254 in MMP-9 may be a susceptible locus to PACG in China, people with the CC and CT genotypes of rs3918254 are more susceptible to PACG. The susceptibility to PACG in Chinese Han patients may be not influenced by SNPs rs3918249, rs3787268 and rs17577 in MMP-9.     

FPR1 interacts with CFH,HTRA1 and smoking in exudative age-related macular degeneration and polypoidal choroidal vasculopathy

Purpose

To determine the genetic association of an inflammation-related gene, formyl peptide receptor 1 (FPR1), in exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).

Methods

The coding region of FPR1 gene was sequenced in 554 unrelated Chinese individuals: 155 exudative AMD patients, 179 PCV patients, and 220 controls. Interactions and combined effects of FPR1 with complement factor H (CFH), high temperature requirement factor A1 (HTRA1), and smoking were also investigated.

Results

A total of 28 polymorphisms in FPR1 were identified. Single nucleotide polymorphisms (SNP) rs78488639 increased the risk to exudative AMD (P=0.043) and PCV (P=0.016), whereas SNP rs867229 decreased the risk to exudative AMD (P=0.0026), but not PCV. Homozygous G allele of rs1042229 was associated with exudative AMD (P=0.0394, odds ratio (OR)=2.27, 95% confident interval: 1.08–4.74), but not with PCV. Exudative AMD, but not PCV, was associated with the heterozygous genotypes of rs2070746 (P=0.019, OR=0.57) and rs867229 (P=0.0082, OR=0.54). Significantly, interactions were identified among FPR1 rs78488639, CFH rs800292, and HTRA1 rs11200638 in both exudative AMD and PCV. Combined heterozygous risk alleles of CFH rs800292 GA and FPR1 rs78488639 CA were posed to PCV (P=2.22 × 10⁻⁴, OR=10.47), but not exudative AMD. Furthermore, FPR1 rs78488639 CA combining with HTRA1 rs11200638 and smoking was also predisposed risks to exudative AMD and PCV.

Conclusion

FPR1 is associated with exudative AMD and PCV in a Hong Kong Chinese cohort. FPR1 rs78488639 interacted with CFH rs800292, HTRA1 rs11200638, and smoking, enhancing risk to exudative AMD and PCV.     

Genetic and clinical factors associated with reticular pseudodrusen in exudative age-related macular degeneration

Backgrounds

Reticular pseudodrusen (RPD) is considered to be a distinct entity from soft drusen and a risk factor for age-related macular degeneration (AMD). In the present study, we investigate the genetic and clinical factors associated with reticular pseudodrusen (RPD) in patients with exudative AMD, including polypoidal choroidal vasculopathy (PCV), typical neovascular AMD, and retinal angiomatous proliferation (RAP).

Methods

The presence or absence of RPD was studied among 408 patients with exudative AMD in at least one eye, and the clinical characteristics of those with RPD were investigated as well as genetic polymorphisms of ARMS2 A69S (rs10490924) and CFH I62V (rs800292). Subfoveal choroidal thickness was also evaluated in a limited number of subjects using the EDI mode of spectral-domain optical coherence tomography.

Results

The prevalence of RPD was significantly higher in RAP eyes than in typical neovascular AMD or in PCV eyes (38.2 % of 26 eyes, 13.6 % of 132 eyes and 0 % of 250 eyes respectively, P?P?P?P?ARMS2 A69S was significantly higher in eyes with RPD than in those without RPD (85.7 % vs 63.8 %, P?=?0.0009), although the frequency of CFH I62V was not significantly different between those with and without RPD. Logistic regression analysis revealed that age (odds ratio [OR]:1.10; 95 % confidence interval [CI]: 1.04–1.18; p?=?0.002), female gender (OR:4.26; 95%CI: 1.72–10.4; p?=?0.002), T-allele at ARMS2 A69S (OR: 3.23; 95%CI: 1.36–7.68; p?=?0.008) and RAP (OR: 4.25; 95%CI:1.49–12.1; p?=?0.007) were risk factors for RPD.

Conclusions

Among eyes with exudative AMD, RPD is more common in eyes with RAP having a thin choroid at the fovea, especially in old, female patients with the risk variant of ARMS2 A69S.     

Complement factor B polymorphism (rs641153) and susceptibility to age-related macular degeneration:evidence from published studies

AIM:To determine whether single nucleotide polymorphism (SNP) rs641153 is associated with the risk of age-related macular degeneration (AMD), we performed a systematic meta-analysis of 15 eligible studies. SNP in the complement factor B (CFB) gene is considered to have significant association with AMD susceptibility, but there is great discrepancy in these results.METHODS: The eligible studies were identified by searching the databases of PubMed, EMBASE, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. All data were analyzed using Stata software.RESULTS:The association between rs641153 and AMD risk was statistically significant under the homozygous model (AA vs GG:OR=0.26, 95%CI=0.15-0.45, Ph=0.973, I²=0.0%, fixed effects), dominant model (AA+GA vs GG:OR=0.49, 95%CI=0.40-0.59, Ph=0.004, I²=56.4%, random effects) and recessive model (AA vs GA+GG:OR=0.30, 95%CI=0.17-0.51, Ph=0.983, I²=0.0%, fixed effects). The same results were also observed in the stratified analyses by ethnicity, source of control and sample size.CONCLUSION:Our meta-analysis suggests that rs641153 in the CFB gene may play a protective role in AMD susceptibility, the late AMD in particular, both in Caucasians and in Asians.     

Reconsidering the connection between vitamin D levels and age-related macular degeneration

Purpose

Recent evidence has suggested a correlation between reduced vitamin D levels and delayed angiogenesis and reduced inflammatory response, which are known to have a major role in the development and progression of age-related macular degeneration (AMD).

Design

Cross-sectional study.

Participants

Members of the Maccabi Healthcare Services (MHS, one of the four largest Israeli Health Maintenance Organization) aged ≥60 years, whose vitamin D levels were taken as part of routine examinations between 2000 and 2008.

Methods

All data for this study were obtained from MHS databases that include medical information on 1.8 million subscribers.

Main outcome measures

Serum 25-OH vitamin D levels.

Results

The total study population comprised of 1045 members diagnosed as having AMD, and 8124 as non-AMD, for whom there was information on vitamin D levels. The mean±SD level of 25-OH vitamin D was 24.1±9.41 ng/ml (range 0.8–120) for the AMD patients and 24.13±9.50 ng/ml (range 0.0–120) for the controls (P=ns). One-third (33.6%) of the AMD patients and 32.86% of the controls had a 25-OH vitamin D level <16 ng/ml, and the proportions of tests in which the 25-OH vitamin D level was >74 ng/ml were 0.19 and 0.14%, respectively (P=ns)

Conclusions

No association was detected between vitamin D levels and the presence of AMD in this cross-sectional study. These results raise some doubt about an association between reduced vitamin D levels and the prevalence of AMD.     

Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma:a meta-analysis

AIM: To study the associations between lysyl oxidase-like 1 (LOXL1) polymorphisms and primary open angle glaucoma (POAG) remain inconsistent. In this study, we have performed a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk.METHODS: Published literature from PubMed and other databases were retrieved. All studies evaluating the association between LOXL1 polymorphisms (rs2165241, rs1048661, rs3825942) and POAG risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.RESULTS: Twelve studies were identified as eligible articles, with thirteen (2098 cases and 16 473 controls), thirteen (1795 cases and 2916 controls) and sixteen population cohorts (2456 cases and 2846 controls) for the association of rs2165241, rs1048661 and rs3825942 with POAG risk respectively. Overall analyses showed no association between each LOXL1 polymorphism and POAG risk, and the negative associations were remained when the subjects were stratified as Caucasian and Asian. The heterozygote of rs2165241 was associated with reduced POAG risk in hospital-based populations (TC vs CC:OR, 0.79, 95%CI:0.63-0.99), and rs1048661 was associated with increased POAG risk in hospital-based populations in a dominant model (TT vs CC+CT:OR, 1.23, 95%CI:1.01-1.50); however, these associations were not found in population-based subjects.CONCLUSION: This meta-analysis suggests that LOXL1 polymorphisms are not associated with POAG risk. Given the limited sample size, the associations of LOXL1 polymorphisms with POAG risk in hospital-based populations await further investigation.     

Association of polymorphisms of angiotensin I converting enzyme 2 with retinopathy in type 2 diabetes mellitus among Chinese individuals

Aims

To examine the association of Angiotensin I converting enzyme 2 (ACE2) gene polymorphisms and retinopathy in a Chinese type 2 diabetes mellitus (T2DM) cohort.

Methods

A total of 743 T2DM participants were involved in this study including 408 female and 335 male cases. Female cases were divided into two groups: diabetes without retinopathy (DNR group, n=171) and with retinopathy (DR group, n=237), the latter was further subclassified into nonproliferative DR (NPDR group, n=121) and proliferative DR (PDR group, n=116). Male cases were assigned to DNR group (n=153) and DR group (n=182) which was further grouped into NPDR group (n=86) and PDR group (n=96). Two single nucleotide polymorphisms (SNPs; rs2074192 and rs714205) in ACE2 gene were genotyped.

Results

In female cases, the frequency of genotypes TT in rs2074192 and CC in rs714205 were higher in DR and PDR group than in DNR group (P<0.05). The frequency of alleles T in SNP rs2074192 and C in SNP rs714205 was higher in DR group (P<0.05) and PDR group (P<0.05) than in DNR group. The frequency of allele T in SNP rs2074192 was higher in PDR group (P=0.04) than in NPDR group. The frequency of haplotype TC and CG was higher in DR and PDR groups, respectively (P<0.05). No positive results were found in male cases.

Conclusions

Our results revealed that SNPs rs2074192 and rs714205 in ACE2 gene were associated with the susceptibility of DR and PDR.     

Comparing fixation location and stability in patients with neovascular age-related macular degeneration treated with or without Ranibizumab

Purpose

To compare fixation location and stability in patients with neovascular age-related macular degeneration (AMD) treated with or without ranibizumab.

Methods

Patients were recruited from the Macular Clinic of the King''s College Hospital in London. Two groups of patients with neovascular AMD with at least 12 months of follow-up were included in the study. The treated group was treated with ranibizumab while the untreated group did not have any treatment. Best corrected visual acuity (BCVA) with modified ETDRS chart, fixation location and stability as measured with Nidek MP1, central retinal thickness as measured by Zeiss Cirrus SD-optical coherent tomography (OCT), and lesion size as measured by Topcon TRC-50IX camera were analysed and correlated.

Results

In total, 102 eyes were included in the study with 76 in the ranibizumab-treated group and 26 in the untreated group. There were no significantly demographic differences between the two groups. However, as expected, the treated group has significantly better vision (48.5 vs15.5 letters, P<0.0001) and smaller lesions (10.8 vs18.3 mm², P=0.004), the central macular thickness as measured by OCT also showed a trend of normalised macular thickness (252 vs282 microns, P=0.07). The location of fixation was significantly more central in the ranibizumab-treated group (χ² 17.9, P<0.0001) with over 50% of eyes with predominantly central fixation. Majority (84.6%) of the patients in the untreated group had predominantly eccentric fixation. Fixation stability was significantly better in the ranibizumab-treated group as compared with the untreated group, using both the software provided by the MP1 machine (χ² 21.8, P<0.0001) and the mean log bivariate contour ellipse area calculated from the raw data obtained from the machine (3.64 vs4.39 in treated and untreated group respectively, P<0.0001).

Conclusion

Low vision rehabilitation strategy for this group of patients in the ranibizumab era will be very different from those used in untreated patients with dense central scotoma. Further studies on the visual rehabilitation in the ranibizumab-treated patients should consider fixation characteristics of the patients.     

Retinal Vessel Functionality Is Linked With ARMS2 A69S and CFH Y402H Polymorphisms and Choroidal Status in AMD Patients

PurposeWe aimed to investigate the reactivity of retinal vessels to a flickering stimulus in patients with age-related macular degeneration (AMD) and healthy participants. We also assessed whether the parameters of retinal vessels are dependent on genetic predisposition.MethodsA total of 354 patients with AMD and 121 controls were recruited for the study. All participants underwent thorough ophthalmologic examination and static and dynamic retinal vessel analysis. AMD risk polymorphisms were genotyped in the CFH and ARMS2 genes.ResultsWe found no differences between the AMD group and controls in central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriovenous ratio (AVR), dynamic analysis of arteries (DAAs), or dynamic analysis of veins (DAVs). Eyes with early AMD presented with significantly higher AVR values than eyes with late AMD. In the AMD group, DAA correlated positively with both choroidal thickness (Rs = 0.14, P = 0.00096) and choroidal volume (Rs = 0.23, P < 0.0001), and no such associations were observed in the controls. We found significantly lower DAA (1.47 ± 1.50) in TT homozygotes for the ARMS2 A69S polymorphism in comparison with GG homozygotes (2.38 ± 1.79) and patients with GG + GT genotypes (2.28 ± 1.84). We also observed less prominent DAV (3.24 ± 1.71) in patients with TC + CC genotypes in the CFH Y402H polymorphism compared with TT homozygotes (3.83 ± 1.68).ConclusionsOur findings suggest that retinal microcirculation appears to be associated with the genetic background, choroidal parameters, and clinical features of the patients with AMD.     

Low-fluence photodynamic therapy combinations in the treatment of exudative age-related macular degeneration

AIM: To compare the efficacy of low-fluence photodynamic therapy (PDT) combinations in the treatment of age-related macular degeneration (AMD). METHODS: Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity (BCVA) was ≥0.3 (Snellen) were enrolled. 15 patients in Group I underwent low-fluence PDT (25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination, 15 patients in Group II underwent PDT (50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while, 15 patients in Group III underwent intravitreal pegaptanib monotherapy. Complete ophthalmologic examinations were performed in pre and post treatment visits, and the results were statistically analised. A clinical activity score (CAS) was calculated by using changes in lesion size, amount of hemorrhage, staining pattern in FA and OCT measurement of intra/subretinal fluid. ≤ 3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment. RESULTS: The mean age of 19 female (42.2%) and 26 male (57.8%) patients was 72.82±8.02 years. Mean follow-up was 13.93±5.87 months. Lesion type was occult in 28 eyes (62.2%). Treatment success rates according to BCVA assessments were 86.7%, 80%, 60% and mean BCVA decrease were 0.3, 1.0, 2.2 logMAR lines in Group I, II and III, respectively (P>0.05). According to the changes in central macular thickness and CAS, no difference was found among the study groups (P=0.850 and P=0.811, respectively). Patients treated with combination regimens had lower intravitreal injection frequencies (P=0.015). CONCLUSION: Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.     

Cigarette smoking, body mass index associated with the risks of age-related cataract in male patients in northeast China

AIM: To determine the association between cigarettes smoking, body mass index (BMI) and the risk of age-related cataract (ARC) in middle-aged and elderly men in Northeast China. METHODS: A hospital-based case control study was conducted. Cases (n =362) were men who had surgically treated ARC, 45-85 years old; controls frequency-matched (n =362) were men who had been admitted to the same hospital as cases for other diseases not related with eye diseases. Cases and controls were matched with 1:1. The cases and controls were interviewed during their hospital stay, using a structured interviewer-administrated questionnaire that included information on sociodemographic characteristics, socioeconomic, lifestyle habits (tobacco smoking and alcohol consumption, etc.), anthropometric measures, personal medical history, and family history of ARC in first-degree relatives, and simultaneously BMI was calculated. The odds ratios (OR) and 95% confidence intervals (CI) of ARC were estimated using multiple logistic regression models. RESULTS: After adjusting for age and multiple potential confounders, higher BMI was associated with an increased risk of ARC. Cigarette smoking, years smoking or moderate cigarette smoking (1-29 cigarettes per day) had no relation with the risk of ARC (P >0.05), although patients smoking ≥30 cigarettes per day had an elevated risk of ARC as compared with the non-smokers (OR =1.55, 95% CI; 1.16-2.85, P =0.026). Higher BMI was associated with an increased risk of ARC. Both overweight and obesity was associated with an obviously increased risk for surgically ARC (OR=1.55, 95% CI: 1.02-1.98, P=0.015 and OR=1.71, 95% CI: 1.32-2.39, P=0.013 respectively) compared to normal BMI. Then participants were grouped into quartiles of BMI (Q1 to Q4), compared to controls in the lowest quartile, the OR for cases in the highest quartile of BMI was 1.54 (OR=1.54, 95% CI: 1.08-2.46, P=0.022). The results of univariate analysis showed cigarette smoking was not associated with ARC formation for men with lower or normal BMI (P >0.05). Compared to the non-smokers, for men of overweight or obesity, cigarette smoking was associated with a significantly increased risk for surgically ARC (OR=2.00, 95% CI: 1.49-6.65, P =0.003 and OR =1.66, 95% CI: 1.63-13.21, P =0.002 respectively). Similarly, smokers in the highest quartile of BMI had approximately 1.5 times the risk of ARC as non-smokers in the lowest quartile (OR=1.46, 95% CI: 1.06-5.29, P <0.001). Followed multivariate models revealed that the association had never changed. CONCLUSION: Current cigarette smoking is positively related to ARC only among those who smoking 30 or more cigarettes per day. For men who are both overweight and obesity, cigarette smoking is associated with a significantly increased risk for ARC.     

Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension:a systematic review and meta-analysis

AIM:To assess the effects of the fixed combination of 0.005% latanoprost and 0.5% timolol (FCLT) vs their individual components for primary open angle glaucoma (POAG) and ocular hypertension (OHT).METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials (RCTs) and cross-over studies were included. The control groups were the mono therapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure (IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:The post-intervention mean IOP of FCLT was significantly lower compared to timolol [mean difference (MD) -2.92, 95%CI -3.28 to -2.55, P<0.00001] and latanoprost (MD -1.11, 95%CI -1.51 to -0.72, P＜0.00001). The post-intervention IOP fluctuation was also significantly lower compared to timolol (MD -0.88, 95%CI -1.23 to -0.53, P<0.00001) and latanoprost (MD -0.63, 95%CI -1.04 to -0.22, P=0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol (UFCLT) (MD 1.10, 95%CI 0.81 to 1.39, P<0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT (MD 0.34, 95% CI -0.01 to 0.69, P=0.06). There was no statistical difference for the incidence of visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the mono therapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.     

Influence of seasonal sunlight intensity and iris color on the anti-VEGF therapy for neovascular age-related macular degeneration

Purpose

To investigate the influence of seasonal light intensity and patients'' iris color on the visual recovery after anti-vascular endothelial growth factor (VEGF) therapy with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).

Methods

The visual acuity of 555 eyes (529 patients) with neovascular AMD was evaluated after intravitreal injections of either ranibizumab or bevacizumab in respect to global radiation intensity and iris color.

Results

The functional results during anti-VEGF therapy revealed a seasonal oscillation with a negative correlation between visual recovery and global radiation intensity (R²=−0.756, P=0.004). Although the influence of the sunlight intensity on the visual recovery was significant after the first injection, this effect vanished within the continuous course of treatment. Regarding the improvement of functional recovery depending on iris color, dark-colored eyes (16.0%) gained 8.5±10.0 letters after the first injection and 9.9±12.8 letters after the second injection, compared with 3.4±8.6 letters and 4.4±11.0 letters in light-colored eyes (84.0%), respectively (P=0.005 and P=0.019).

Conclusions

Our results indicate that seasonal sunlight intensity and iris color might influence the visual recovery of neovascular AMD patients undergoing anti-VEGF therapy. Our findings may be used as suggestions to refine individual anti-VEGF therapy regimens, especially in patients with light-colored eyes.     

Complement factor H and LOC387715 gene polymorphisms in a Greek population with age-related macular degeneration

Background

Age-related macular degeneration (AMD) is the leading cause of severe visual loss among people over 60 years old. The lack of a broadly effective treatment for AMD underscores the need to identify causative biomarkers that could serve as preventive targets. Thus far, two major susceptibility loci for AMD have been identified, CFH T1277C and LOC387715 G270T. The primary goal of the present study was to elucidate whether these polymorphisms are major genetic determinants of AMD in a Greek population.

Patients and methods

A clinic-based, case-control association study was conducted, comprising 100 Greek patients with early and late-stage AMD and 115 independent controls of Caucasian origin. All participants underwent clinical examination including best-corrected visual acuity, intraocular pressure, and dilated fundus examination. Moreover, they were genotyped for CFH T1277C and LOC387715 G270T polymorphisms, by direct sequencing and ARMS PCR, respectively.

Results

The frequency of the CFH 1277C allele was significantly higher in AMD patients in comparison with controls while the odds ratios (ORs) for AMD were 4.4–5.5. Statistical comparison of early and advanced AMD patients, on the basis of CFH genotype, revealed that the CFH 1277C allele was associated with both subgroups when compared with the controls (P?<?0.001). When statistical comparison was performed between early and advanced patients on the basis of CFH genotypic frequencies, the CC genotype was found to be more prevalent in advanced AMD patients (P?=?0.008, OR?=?2.3). The frequency of the LOC387715 270 T allele was higher in AMD patients in comparison with controls (P?<?0.04) while the ORs for AMD were 1.4–2. No statistically significant differences were located between the early AMD patients and controls, on the basis of LOC387715 genotype (P?=?0.189). On the contrary, the T270G polymorphism was associated with advanced AMD (P?=?0.04). Moreover, the TT genotype was more prevalent in patients with advanced AMD (P?=?0.011, OR?=?1.7) when compared with early AMD patients. Assessment of the combined contribution of CFH T1277C and LOC387715 G270T SNPs showed an independent manner of action of these polymorphisms in the development of the disease.

Conclusions

The replication of the reported associations of CFH T1277C polymorphism with AMD suggest that the 1277C allele could serve as a high-risk genetic marker for the development of AMD and the progression of the disease to the advanced clinical stage in the Greek population.     

C-reactive protein and complement factor H polymorphism interaction in advanced exudative age-related macular degeneration

Purpose

To determine the association of C-reactive protein (CRP) and complement factor H (CFH) gene with exudative age-related macular degeneration (AMD) and any possible interaction among these factors.

Methods

In this case–control study, 139 unrelated patients with exudative AMD and 123 non-AMD controls were recruited. Blood sample was taken for analysis of the CRP levels and DNA testing. DNA fragments of CFH gene variants containing 4 single nucleotide polymorphisms including rs800292, rs1061170, rs2274700, and rs3753395 were assessed. A CRP level of ≥3 mg/L was considered as elevated. The association of elevated CRP and CFH gene variants polymorphism with exudative AMD was compared between the groups.

Results

Mean age was 72.6 ± 6.4 for controls and 74.9 ± 7.4 for case group (P = 0.006). The difference between CRP levels in cases and controls was not statistically significant (P = 0.055). However, Y402H variant of CFH in both homozygous and heterozygous carriers C allele was significantly more frequent among exudative AMD patients than controls, 32.1 versus 6.5 % (P < 0.001). Evaluating various CRP levels in patients with CC and non-CC genotypes disclosed that in CC genotype group, higher CRP level (>3 mg/L) was associated with higher risk of developing exudative AMD (OR = 12.0, CI: 1.5–98.8) compared with the control group.

Conclusion

This study disclosed no difference in CRP levels per se between exudative AMD patients with control group. However, higher levels of CRP in the presence of C allele of Y402H might confer more risk for the development of exudative AMD.

     

Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005–2008

Purpose

To determine the association of hydroxymethylglutarylcoenzyme A (HMG Co-A) reductase inhibitor (statin) use with the prevalence of age-related macular degeneration (AMD).

Methods

This cross-sectional study included 5604 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008, ≥40 years of age, who were ascertained with regard to the diagnosis of AMD, the use of statins, and comorbidities and health-related behaviors such as smoking.

Results

The mean age of participants denying or confirming a history of AMD was 68 (SEM 0.90) and 55 (SEM 0.36) years, respectively. Individuals 68 years of age or older who were classified as long-term users of statins had statistically significant less self-reported AMD (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.49–0.84; P=0.002), after adjusting for potential confounding variables. No significant association was found between the prevalence of AMD and statin consumption among subjects between 40 and 67 years of age (OR 1.61, 95% CI 0.85–3.03; P=0.137).

Conclusions

Our results suggest a possible beneficial effect of statin intake for the prevention of AMD in individuals 68 years of age or older.     

Variability of subfoveal choroidal thickness measurements in patients with age-related macular degeneration and central serous chorioretinopathy

Purpose

To evaluate the variability in subfoveal choroidal thickness measurements in patients with age-related macular degeneration (AMD) and central serous chorioretinopathy using enhanced depth imaging optical coherence tomography (EDI-OCT).

Methods

One hundred and sixty eyes of 160 patients who were diagnosed with early AMD (N=40), exudative AMD (N=40), polypoidal choroidal vasculopathy (PCV, N=40), or central serous chorioretinopathy (CSC, N=40) were included in this retrospective observational study. In addition, we included 40 normal eyes of 40 subjects. Subfoveal choroidal thickness was measured manually by two masked observers based on EDI-OCT images. The correlation of choroidal thickness with the absolute value of the difference in the choroidal thickness measurement was estimated for all 200 eyes. Intraobserver and interobserver coefficients of repeatability (CRs) were calculated.

Results

There was a significant positive correlation between subfoveal choroidal thickness and both intraobserver (P<0.001) and interobserver (P<0.001) difference in choroidal thickness measurements. The mean intraobserver CRs in nonexudative AMD, exudative AMD, PCV, CSC, and normal eyes were ∼15–21, 23–29, 24–35, 32–38, and 19–25 μm, respectively. The mean interobserver CRs were ∼24–28, 30–36, 39–45, 46–57, and 26–35 μm, respectively.

Conclusions

Relatively great measurement variability should be considered when investigating eyes with pathologic conditions related to a thick choroid, including PCV or CSC.     

HTRA1多态性与汉族人群湿性年龄相关性黄斑变性遗传易感性的关系

目的：探讨高温必需因子A-1(HTRA1)多态性与汉族人群湿性年龄相关性黄斑变性(AMD)遗传易感性的关系。

方法：选取本院2014-05/2017-01收治的汉族湿性AMD患者201例,汉族正常健康者201例,分别设为病例组和健康组。采集研究对象外周静脉血样并提取基因组DNA,利用Sequenom质谱分析平台对HTRA1基因的rs11200638、rs2248799位点进行基因型检测,分析HTRA1多态性与湿性AMD遗传易感性的关系。

结果：两组研究对象rs11200638、rs2248799位点的基因型等级分布比较,差异均有统计学意义(P<0.01),病例组AA、TT的频率分别为51.2%、57.7%,健康组AA、TT的频率分别为20.9%、28.4%,前者均明显高于后者,差异均有统计学意义(P<0.01); 病例组rs11200638位点危险性等位基因A与rs2248799位点危险性等位基因T分布的频率分别为69.7%、73.6%,健康组分别为45.8%、52.5%,前者均明显高于后者,差异均有统计学意义(P<0.01)。rs11200638基因型AA、AG的OR值分别为5.36与3.45,是湿性AMD发病的危险因素(P<0.01); rs2248799 基因型TT、TC的OR值分别为2.36与1.98,是湿性AMD发病的危险因素(P<0.01)。

结论：HTRA1基因rs11200638和rs2248799多态性与湿性AMD发病关系显著,基因型AA、TT与汉族人群湿性AMD患病风险关系密切,其频率增高可增加湿性AMD患病风险。