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.

     

Complement factor H variant Y402H and basal laminar deposits in exudative age-related macular degeneration

Background Complement factor H (CFH) polymorphism Y402H has been shown to be significantly associated with age-related macular degeneration (AMD). Furthermore, histopathological studies in AMD have implicated basal laminar deposits (BLD) in the development of choroidal neovascularization (CNV) membranes. The purpose of this study was to correlate CFH staining in BLD with the CFH genotype at the tyrosine 402 histidine (Y402H) polymorphism. Patients and methods During macular translocation, 21 angiographically confirmed CNV membranes were extracted in 21 patients. The specimens were analysed histologically for BLD. The presence of CFH, complement proteins, and vitronectin was determined by immunohistochemistry. Finally, the CFH Y402H genotype was established by direct sequencing analysis. Results Histological examination demonstrated BLD in all of the excised CNV membranes. By immunostaining CFH was detected in the peripheral aspect at the inner and outer surface of BLD, which colocalized with other proteins of the complement cascade (C3, C5b-9). Similarly, vitronectin was detected in all of the BLD investigated. Four patients were noncarriers of CFH Y402H polymorphism, nine patients were heterozygous and eight patients homozygous for the CFH Y402H polymorphism. Conclusions BLD are composed of different complement factors (factor H, C3, C5b-9) and extracellular matrix proteins such as vitronectin. The prevalence of homozygous carriers in regard to CFH Y402H polymorphism, which is suspicious for AMD, might be associated with increased secretion of vitronectin in response to dysregulation of the complement cascade.     

补体因子H基因单核苷酸多态性与渗出型老年性黄斑变性易感性的相关性研究

目的 探讨渗出型老年性黄斑变性(AMD)易感性与补体因子H(CFH)基因单核苷酸(SNP)多态性的相关性。方法 病例对照研究。136例渗出型AMD患者（AMD组）和年龄、性别与之匹配的140名正常健康者（对照组）纳入研究。取得所有受检者的知情同意后,抽取晨起空腹肘静脉血4 ml,提取基因组DNA。采用多聚酶链反应和特异性限制内切酶消化法检测CFH Y402H(rs1061170)、CFH-257C＞T(rs3753394)及CFH IVS15(rs1329428)的基因型和等位基因。采用SHEsis软件构建单倍型,对比分析两组CFH基因SNP不同单倍型的频率。分析CFH基因SNP不同等位基因、基因型和单倍型与渗出型AMD的相关性。结果 CFH Y402H(rs1061170)存在TT、TC、CC 3种基因型,等位基因位于位点T、C;CFH-257C＞T(rs3753394)存在CC、CT、TT 3种基因型,等位基因位于位点C、T;CFH IVS15(rs1329428)存在AA、AG、GG 3种基因型,等位基因位于位点A、G。AMD组、对照组CFH基因型和等位基因频率比较,差异均有统计学意义(P＜0.05)。CFH Y402H (rs1061170)的杂合子基因型TC、CFH-257C＞T(rs3753394)的纯合子基因型TT及CFH IVS15(rs1329428)的纯合子基因型GG均与渗出型AMD有相关性(OR=4.11,2.55,3.11;P＜0.05);等位基因T、C、G为风险等位基因(OR=3.14,1.72,1.79;P＜0.05)。AMD组和对照组单倍型TCG、CTG及CTA频率间差异有统计学意义(X2=10.53,6.60,32.82;P＜0.05);其余单倍型频率间差异无统计学意义(P＞0.05)。结论 CFH基因SNP多态性与渗出型AMD易感性有关。     

Chlamydia pneumoniae is not detectable in subretinal neovascular membranes in the exudative stage of age-related macular degeneration

PURPOSE: Age-related macular degeneration (AMD) is the most frequent cause of severe visual impairment in western countries, but its aetiology remains unclear. A growing body of evidence suggests that inflammation contributes to the pathogenesis of AMD, similarly to that shown for atherosclerosis. In view of a number of shared risk factors between the two entities and the hypothesized link between Chlamydia pneumoniae infection and atherosclerosis, we investigated whether C. pneumoniae might be involved in exudative AMD. METHODS: To examine whether C. pneumoniae contributes to the development of subretinal neovascular (SRNV) membranes in AMD, 13 consecutive SRNV membranes surgically excised from patients with exudative AMD were collected and assayed for the presence of C. pneumoniae or other bacterial pathogens by means of polymerase chain reaction (PCR). RESULTS: The age of patients ranged from 68 to 85 years (median 73.5 years). In all 13 SRNV membranes, no DNA of either C. pneumoniae or other pathogens was found by PCR. CONCLUSIONS: These findings indicate that C. pneumoniae is not associated with the development of SRNV membranes in exudative AMD.     

光动力疗法治疗渗出性年龄相关性黄斑变性

目的观察光动力疗法(photodynamic therapy,PDT)治疗渗出性年龄相关性黄斑变性(age-related macular degeneration,AMD)的疗效。方法回顾分析经荧光素眼底血管造影(fundus fluorescein angiography,FFA)、吲哚菁绿血管造影(indocyanine green angiography,ICGA)以及光学相干断层扫描(optical coherence tomography,OCT)检查确诊的21例(31眼)渗出性AMD患者PDT治疗前及治疗后的临床资料,主要以视力、FFA及(或)ICGA、OCT的改变为观察指标,评价PDT对渗出性AMD的治疗效果。结果治疗后13眼视力明显改善(视力提高≥2行),占41.9%;14眼视力稳定不变(视力波动在1行以内),占45.2%;4眼视力下降2行,占12.9%。大部分患眼于PDT治疗后眼底出血和渗出减轻;ICGA检查显示:PDT治疗后1周,16眼CNV的渗漏明显减少或完全停止,8眼渗漏完全停止。OCT检查显示:CNV周围视网膜脉络膜水肿以及神经上皮脱离好转。5例6眼患者在PDT治疗过程中及治疗后发生视网膜神经上皮脱离范围变大,1例1眼发生黄斑部再次大面积出血,所有病例均未发生任何全身不良反应。结论单次和重复PDT治疗可以部分或完全封闭渗出性AMD的CNV,PDT治疗对病灶周围的正常视网膜和脉络膜组织短期内有轻度影响,对视力无损害。     

重视抗血管内皮生长因子疗法在渗出型老年性黄斑变性治疗应用中的问题

抗血管内皮生长因子疗法的应用是渗出型老年性黄斑变性治疗中的重大突破,但作为一种新兴疗法,其疗效持久性、药物副作用、药物选择等方面存在的问题也正逐步显现。充分认识该疗法的局限性以及应用过程中可能发生的副作用,加强临床监测,提倡个体化治疗,以提高其疗效和安全性是值得关注和重视的问题。     

Use of a macular buckle in the treatment of exudative age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To evaluate a macular buckle for exudative choroidal neovascularization secondary to age-related macular degeneration (ARMD). PATIENTS AND METHODS: Forty-two eyes with choroidal neovascular membranes (CNVM) secondary to ARMD underwent surgical placement of a macular buckle. A Gore-Tex strip (2.0-2.5 mm wide) was button-holed through a 5 mm diameter silicone sponge (9 mm long) and placed behind the macula underneath the CNVM by the same surgeon (Dr Peyman) in all cases. Follow-up ranged from 7-76 months (mean, 20.9 months). RESULTS: Of 12 eyes with classic subfoveal CNVM: 4 (33%) gained 2 or more lines of Snellen visual acuity; 3 (25%) gained 1 line, remained the same, or lost 1 line; and 5 (42%) lost 2 or more lines (range + 6 to - 6 lines). Of 22 eyes with ill-defined subfoveal CNVM: 12 (54%) gained 1 line, remained the same, or lost 1 line; and 10 (46%) lost 2 or more lines (range + 1 to - 8 lines). Eight eyes with ill-defined juxtafoveal CNVM had the following visual acuity outcomes: 5 eyes (62%) maintained the same level of Snellen visual acuity (gained 1, 0, or lost 1 line); and 3 (38%) got worse (lost 2 or more lines of Snellen visual acuity, range + 1 to - 6 lines). Ten eyes (24%) bled subretinally during the follow-up period (average 11.5 months, range 14 days to 27 months), all outside the area of indentation of the macular buckle. CONCLUSIONS: The macular buckle treatment for exudative subretinal choroidal neovascular membranes in ARMD stabilized visual decline and displaced significant subfoveal hemorrhage.     

Practical guidance for imaging biomarkers in exudative age-related macular degeneration

We provide an overview of current macular imaging techniques and identify and describe biomarkers that may be of use in the routine management of macular diseases, particularly exudative age-related macular degeneration (AMD). This perspective includes sections on macular imaging techniques including optical coherence tomography (OCT) and OCT angiography (OCTA), classification of exudative AMD, and biomarkers in structural OCT and OCTA.Fluorescein angiography remains a vital tool for assessing the activity of neovascular lesions, while indocyanine green angiography is the preferred option for choroidal vessel imaging in neovascular AMD. OCT provides a non-invasive three-dimensional visualization of retinal architecture in vivo and is useful in the diagnosis of many imaging biomarkers of AMD-related neovascular lesions, including lesion activity. OCTA is a recent advance in OCT technology that allows accurate visualization of retinal and choroidal vascular flow. OCT and OCTA have led to an updated classification of exudative AMD lesions and provide several biomarkers that help to establish a diagnosis and the disease activity status of neovascular lesions.Individualization of therapy guided by OCT and OCTA biomarkers has the potential to further improve visual outcomes in exudative AMD. Moving forwards, integration of technologically-advanced imaging equipment with AI software will help ophthalmologists to provide patients with the best possible care.     

Clinical characteristics of exudative age-related macular degeneration in Taiwan

PurposeTo describe the clinical features of exudative AMD of patients in Taiwan.MethodsA retrospective case series consisting of 235 eyes in 211 patients, with a male/female ratio of 7:3, mean age 70.36 ± 8.98 years (range 50–86), with exudative AMD, was reviewed at Changhua Christian Hospital, Taiwan.ResultsAmong the 211 patients, 77 (36.5%) had bilateral involvement of exudative AMD; and of the 235 eyes, 117 (49.7%) were diagnosed with idiopathic PCV, 111 (47.2%) with typical AMD, and seven eyes (2.9%) with retinal angiomatous proliferation. PCV is predominant in patients younger than 70 years (71.8%), whereas typical AMD is prevalent in patients 70 years or older (59.4%). After treatment, mean visual acuity improved in 154 eyes, as reflected in the decreasing logarithm of minimal angle of resolution (log Mar VA)—from 0.95 ± 0.60 to 0.84 ± 0.55, whereas in the other 81 eyes without treatment visual acuity deteriorated—log Mar VA increased from 0.85 ± 0.60 to 1.22 ± 0.53.ConclusionMale predominance, higher ratio of PCV, and lower ratio of retinal angiomatous proliferation are common features of exudative AMD in Taiwan.     

Retina transplantation in exudative form of age-related macular degeneration

The paper presents different techniques of macular translocation in exudative form of AMD, including particularly retinal detachment followed by retinotomy, limited macular translocation with chorioscleral infolding and outfolding by scleral imbrication.     

经瞳孔温热疗法治疗渗出型老年性黄斑变性的临床疗效观察

目的
评价经瞳孔温热疗法(transpupillary thermotherapy,TTT)治疗渗出型老年性黄斑变性（age-related macular degeneration, AMD）的临床疗效。
方法
回顾分析62例确诊为AMD的患者的62只患眼TTT治疗的临床资料。62例AMD患眼中，行荧光素眼底血管造影(fundus fluorescein angiography，FFA)检查者58例，吲哚青绿血管造影(indocyanine green angiography ,ICGA)检查者42例，光相干断层成像术(optic coherence tomography, OCT)检查者56例。激光治疗机波长为810 nm，光斑0.5～3.0 mm,能量60～400 mW,照射时间60 s。62例患者治疗后随访观察1～10个月，平均随访观察时间4.8个月，分析末次随访视力与治疗前视力以及OCT复查资料。
结果
视力不变者43例，占69.4%；进步者15例，占24.2%；下降者4例，占6.5%。51例OCT复查者中，黄斑水肿不变者29例，占56.96%；好转者18例，占38.3%；恶化者4例，占7.8%。视力改善与OCT黄斑水肿的形态改善相一致者38只眼，占OCT检查者的74.5%；视力改善滞后于黄斑水肿形态改善者13只眼，占25.5%。再次行TTT治疗者18只眼，占接受TTT治疗者的29.0%。治疗随访期间无明显治疗副作用。
结论
TTT治疗能使大部分渗出性AMD患眼视力稳定或提高，使用安全，但激光治疗参数尚需进一步探索。
(中华眼底病杂志, 2002, 18: 180-183)     

中国人群渗出性年龄相关性黄斑变性与线粒体基因A4917G多态性的相关性分析

目的研究线粒体基因A4917G多态性改变与中国人群渗出性年龄相关性黄斑变性（AMD）的相关性,寻找中国人群渗出性AMD发病的易感基因。设计病例对照研究。研究对象来自北京同仁医院的渗出性AMD患者158例和健康对照者117例。方法应用聚合酶链反应（PCR）并结合限制性内切酶酶切分析和DNA序列测定方法对线粒体基因A4917G多态性改变进行检测。主要指标线粒体基因A4917G多态性。结果AMD患者组与对照组比较,两组间年龄（P=10．614）与性N（P=0．427）差异无统计学意义。AMD患者及对照人群线粒体基因4917位点的碱基全部为A,两组中均未见变异型4917G。在本研究人群中线粒体基因A4917G多态性改变与渗出性AMD不存在相关性。结论线粒体基因A4917G多态性在中国人中罕见,与中国人群渗出性AMD发病无明显相关性。