中国汉族人群SOX2基因与高度近视的关联研究

目的　研究SOX2是否可作为中国汉族人群高度近视的候选基因,寻找与高度近视关联的致病基因位点。方法　采用病例-对照关联分析法。将同意参加本研究的83例（160眼）正视者作为对照组,117例（211眼）高度近视患者作为病例组,所有患者均进行详细的眼部检查,并提取外周血白细胞基因组DNA。在中国汉族北京居民的基因型数据库中选取3个标签单核苷酸多态性（single nucleotide polymorphism,SNP）位点,采用SNP直接测序法进行基因分型检测。根据所有样本所得各标签SNP的基因型,计算其基因型和等位基因频率,并使用Bonferroni法进行多重检验矫正;采用χ²检验比较病例组和对照组之间等位基因频率及基因型频率分布是否有差异。结果　3个标签SNP位点（rs11915160、rs4575941、rs4459940）的基因型结果在病例组和对照组中都符合Hardy-Weinberg平衡,本研究人群具有一定的代表性。rs4575941位点的基因型频率和等位基因频率在病例组和对照组间的差异均具有统计学意义（P=0.04、0.03）,但经Bonferroni法矫正后,两组等位基因频率差异无统计学意义（Pc=0.09）;病例组rs4575941位点的等位基因G的频率明显高于对照组,OR值为1.58,等位基因G可能是高度近视的一个危险基因。结论　中国汉族人群SOX2基因SNP位点rs4575941与高度近视之间的关联存在可疑性,为了明确相关性,需要进一步扩大样本量,选择合适的多重检验方法,并结合其他手段进行大数据分析。     

Eales病与人类白细胞抗原-DRB、DQB基因位点的关联

目的 分析Eales病与人类白细胞抗原（HLA）DRB和DQB基因位点的相关性，探讨Eales病可能的免疫遗传学机制。 方法 采用聚合酶链反应-序列特异性引物法（PCR-SSP）检测27例北方汉族Eales病患者以及30名正常对照者HLA-DRB、DQB基因位点，用SPSS 12.0统计软件分析两组人群HLA-DRB、DQB1等位基因频率的分布特点。 结果 与正常对照组比较，Eales病患者HLA-DRB1*04等位基因频率明显增高（P=0.047,OR=3.20,OR 95% 可信区间为1.00～10.21）, 两组间其他DRB 和DQB1等位基因频率的分布差异均无显著性(P>0.05)。 结论 中国北方汉族人群中，DRB1*04等位基因与Eales病呈正相关，可能是Eales病的遗传易感基因。Eales病患者可能因其特定的HLA遗传素质而易受致病因子攻击出现免疫功能紊乱，从而促成Eales病的发生与发展。 (中华眼底病杂志, 2006, 22: 90-93)     

血清中性激素水平与视网膜静脉周围炎的关系

探讨血清中性激素水平与视网膜静脉周围炎（ Eales病）发病的关系。方法回顾分析经临床表现、眼底检查及荧光素眼底血管造影（ FFA）确诊为Eales病的76例患者的临床资料。同时选取与Eales病患者年龄、性别相匹配的76例体检健康者作为对照组。抽取两组受试者肘静脉血,用化学发光法检测Eales例患者及对照组血清中部分性激素：促黄体生成素（ LH）、促卵泡生成素（ FSH）、睾酮（ T）含量。采用t检验对检测结果进行统计学处理。结果与对照组相比,Eales病组患者血清中性激素值均升高,其差异有统计学意义。结论性激素水平与Eales病的发病是有关联的,血清LH、FSH、T指标的变化可作为Eales病患者的一个参考指标。     

Eales病与人类白细胞抗原-A/B、-DRB/DQB的相关性研究

目的 26例临床确诊为Eales病的遵义市汉族患者作为研究组,选取与研究组患者年龄、性别、民族等因素无差异的100名健康人为对照组。抽取外周静脉血,提取DNA,采用聚合酶链式反应特异序列引物法（PCR-SSP）检测HLA-A/B,HLA-DRB/DQB等位基因频率分布,计算两组优势比（OR）。结果 Eales病患者HLA-A*01 （P=0.041,OR=20.5）A*02（P=0.00;OR=54.667;OR95%CI为11.837-252.473）、B*55（P=0.047;OR=4.524;OR95%CI为1.200-17.047）,HLA-DRB*01（P=0.048;OR=5.879;OR95%CI为1.227-28.169）,DQB*05（P=0.021,OR=2.769,OR95%CI为1.145-6.692）其分布频率明显高于对照组,差异有统计学意义(P＜0.05),HLA-A*11（P=0.031,OR=0.383,OR95%CI为0.158-0.930）明显低于对照组,差异有统计学意义(P＜0.05)。结论 Eales病可能存在遗传易感性,HLA-A*01,-A*02,-B*55,-DRB*01,-DQB*05可能是遵义市汉族Eales病患者的遗传易感基因,而HLA-A*11可能是该病的保护基因。     

HLA与Eales病相关性研究

目的探讨北方汉族HLA-DRB和-DQB1基因位点与Eales病及病情严重性的相关性。方法应用病例-对照相关分析方法,采用PCR-序列特异性引物基因分型技术对北方汉族30名健康个体和21例Eales病患者(均无血缘关系)进行HLA-DRB和-DQB1进行遗传相关分析。结果Eales病患者中DRB1*04的频率为(0.57)显著高于对照组(0.02),χ2=7.46,P<0.01,比数比(OR)为5.33。DRB1*11的频率(0.05)显著低于对照组(0.30),χ2=4.99,P〈0.05,OR为0.17。DRB1*04阳性患者最终平均视力明显低于DRB1*4阴性患者,并且DRB*04阳性患者行玻璃切割手术治疗的频率高于DRB*04阳性患者,但二者没有统计学差异(P>0.05)。结论北方汉族HLA-DRB等位基因与Eales病相关,DRB1*04可能与Eales病易感相关;DRB1*11可能在发病中有保护作用。     

遵义市汉族居民Eales病人类白细胞抗原基因多态性和结核感染的相关性研究

目的 探讨遵义市汉族Eales病与人类白细胞抗原(HLA)-A/B、HLA-DRB/DQB基因多态性和结核感染的相关性.方法 采用聚合酶链反应序列特异引物法(PCR-SSP)检测Eales病组、肺结核组、正常对照组HLA-A/B、HLA-DRB/DQB共59个等位基因分布频率,计算各组间优势比(OR)及95%可信区间(CI);对Eales病组与肺结核组的HLA-A*02基因分布频率做相关分析.Eales病组为临床确诊的Eales病患者47例;肺结核组为痰结核菌培养确诊肺结核并排除眼部疾病的患者36例;正常对照组为与研究组患者年龄、性别、民族等因素无差异的100名健康人.Easle病组中,资料完整的39例Eales病患者根据病史及纯结核菌素试验(PPD)检查结果分为4组,a组为既往或现在患肺结核患者,12例;b组为无结核感染患者,27例;c组为PPD检查阳性者,27例;d组为PPD阴性者,12例.结果 Eales病组HLA-A*02(OR=9.719,OR 95%CI为4.377～21.580,P=0.000)、HLA-B*07(OR=11.605,OR 95%CI为2.397～56.191,P=0.001)基因分布频率高于正常对照组,差异有统计学意义,HLA-A*11基因分布频率低于正常对照组,差异有统计学意义(OR=0.495,OR 95%CI为0.245～1.000,P=0.048).肺结核组HLA-DRB*16(OR=5.215,P=0.049)、HLA-A*02(OR=18.87,P=0.000)基因分布频率高于正常对照组,差异有统计学意义,HLA-A*24基因分布频率低于正常对照组,差异有统计学意义(OR=5.690,P=0.015).a组与b组,c组与d组比较:HLA-A*02、HLA-A*11、HLA-B*07基因分布频率差异无统计学意义.在Eales病组、肺结核组、正常对照组间,HLA-A*02、HLA-A*24、HLA-B*07、HLA-DRB*16基因总体分布频率比较,差异均有统计学意义,进一步行x2分割法在Eales病组、肺结核组间两两比较,肺结核组HLA-A*24基因分布频率低于Eales病组,差异有统计学意义(x2=7.289,P=0.007),而HLA-A*02基因分布频率无统计学意义(OR=0.515,P=0.202).Eales病组与肺结核组HLA-A*02基因相关性比较,差异无统计学意义(列联系数0.412,P=0.064).结论 Eales病可能存在遗传易感性,HLA-A*02和HLA-B*07可能是遵义市汉族Eales病患者的遗传易感基因,而HLA-A*11可能是保护基因;HLA-DRB*16和HLA-A*02可能是遵义市汉族肺结核病的易感基因,而HLA-A*24可能是保护基因.HLA-A*02可能是遵义市汉族人群中Eales病和肺结核病共同的易感基因.

Abstract：

Objective To analyze the relationship of human leukocyte antigen alleles (HLA-A/B,HLA-DRB/DQB) polymorphism and Eales disease, tuberculosis infection in a Han population in Zunyi city of China. Methods The subjects were analyzed by case-control study, which consisted of three groups including Eales disease group (47 patients), pulmonary tuberculosis group (36 patients) and normal control group (100 healthy people). Thirty-nine patients in Eales disease group who had complete history were divided into 4 subgroups according to the history and tuberculin PPD test. Twelve patients with past or present pulmonary tuberculosis were in group A, 27 patients without pulmonary tuberculosis were in group B, 27 patients with positive PPD test were in group C, and 12 patients with negative PPD test were in group D. Fifty-nine alleles of HLA-A/B and HLA-DRB/DQB were analyzed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in all subjects. Odds ratios between each group (OR) and 95%confidence interval (CI) were calculated; Frequency distribution of HLA-A * 02 gene were analyzed for the group A and the TB group. Results The frequency distribution of HLA-A* 02 (OR=9. 719, OR 95% CI:4. 377-21. 580, P=0. 000) and HLA-B* 07 (OR= 11. 605, OR 95% CI: 2. 397-56. 191, P=0. 001) alleles in Eales disease group were obviously higher than that in normal control group, but frequency distribution of HLA-A * 11 (OR = 0. 495, OR 95% CI: 0. 245-1. 000, P= 0. 048) in Eales disease group was obviously lower than that in normal control group. There was no significant difference in frequency distribution of HLA-A * 02, HLA-A * 11 and HLA-B* 07 alleles between groups A and B, and between groups C and D (P＞0. 05). The distribution frequency of HLA-A * 02, HLA-A * 24, HLA-B * 07 and HLA-DRB * 16alleles among Eales disease group, pulmonary tuberculosis group and control group was statistically different (P＜0. 05). The frequency distribution of HLA-A * 24 alleles in pulmonary tuberculosis group was lower than that in Eales disease group (x2 = 7. 289, P = 0. 007), but the frequency distribution of HLA-A * 02 alleles had no significant difference (OR=0. 515, P=0. 202) between two groups. Conclusions The alleles of HLA-A * 02 and HLA-B * 07 may be genetic predisposing genes of Eales disease, but HLA-A * 11 alleles may be protective gene in population of Han nationality from Zunyi city. The alleles of HLA-DRB * 16 and HLA-A * 02 may be genetic predisposing genes of pulmonay tuberculosis. The alleles of HLA-A * 02 may be a common susceptible gene for Eales disease and pulmonary tuberculosis. HLA-A * 11 and HLA-A * 24 alleles were protective genes of Eales disease and pulmonary tuberculosis respectively.     

碳酸酐酶Ⅱ基因多态性与原发性开角型青光眼遗传易感性的关系

目的：分析碳酸酐酶Ⅱ基因多态性与原发性开角型青光眼遗传易感性的关系。方法：选取2012－01／2014－12在丽水市人民医院进行诊治的原发性开角型青光眼患者（观察组）50例与在丽水市人民医院门诊部体检的健康人（对照组）50例进行试验观察,常规肘静脉取血,使用聚合酶链反应和限制性片段长度多态性技术测试碳酸酐酶Ⅱ基因多态性的特点。结果：两组患者在和rs10504813位点rs3758078位点的分布符合哈迪－温伯格平衡定律（ Hardy －Weinberg equilibrium）,且试验结果显示在rs10504813位点中,两组的基因型频率的差异无统计学意义（P＞0．05）,但在等位基因频率分布之间的差异具有统计学意义（P＜0．05）;两组在rs3758078位点的基因型频率以及等位基因频率的差异无统计学意义（ P＞0．05）。两组患者在碳酸酐酶Ⅱ基因多态性进行单倍型分析发现, TAC单倍型携带者出现原发性开角型青光眼的风险较小。结论：碳酸酐酶Ⅱ基因多态性与原发性开角型青光眼的患病风险存在一定的关联,rs3758078位点基因平衡可能是患病风险低的主要原因;TAC单倍型携带者出现原发性开角型青光眼的风险较小。     

CRLR基因单核苷酸多态性与原发性前房角关闭人群的关联研究

目的：探讨降钙素受体样受体（ calcitonin receptor－like receptor,CRLR）基因单核苷酸多态性（ single nucleotide polymorpnism ,SNP）与汉族原发性前房角关闭人群的关联性。方法：以流行病学人群为研究对象,采用病例对照设计。收集江苏省阜宁县流行病学调查中筛查出的原发性前房角关闭（ primary angle closure ,PAC）患者232例,正常对照306例。血样经DNA提取后采用TaqMan－MGB荧光探针法检测CRLR基因的rs1157699（ C／T ）位点SNP基因型,比较两组等位基因及基因型频率的分布。结果：病例组的基因型分布（ CC 67．4％, CT 30．0％, TT 2.6％）,对照组的基因型分布（CC 71．3％,CT 27．0％,TT 1．7％）,两组之间差异无统计学意义（P＞0．05）。结论：中国汉族人群的CRLR rs1157699位点SNP与原发性前房角关闭无相关性。     

脂联素基因SNP＋276多态性与糖尿病性视网膜病变的关系

目的 分析重庆地区汉族人群脂联素基因SNP＋276 G／T、的基因型分布,探讨该多态性与糖尿病性视网膜病变的相关关系方法在重庆地区汉族人群中选取100例2型糖尿病患者、98例糖尿病性视网膜病变患者和69例正常对照组,采用聚合酶链式反应-限制性内切酶长度多态性（PCR-RFLP）方法检测脂联素基因SNP＋276的多态性位点,比较各组基因型及等位基因频率分布结果①脂联素基因SNP＋276在重庆地区汉族人群中存在三种基因型（G／G、G／T、T/T），对照组的分布频率分别为42．0％、47．8％、10．1％，糖尿病无视网膜病变组的分布频率分别为53．0％、39．0％、8．0％,糖尿病性视网膜病变组的分布频率分别为42．9％、37．8％、19．4％。②对照组、糖尿病无视网膜病变组及糖尿病性视网膜病变组三组脂联素基因SNP＋276基因型分布频率比较差异无统计学意义。③对照组、糖尿病无视网膜病变组及糖尿病性视网膜病变组的G等位基因频率分别为65．9％、72．5％、61．7％；三组脂联素基因SNP＋276等位基因的分布频率比较差异无统计学意义，结论脂联素基因SNP＋276多态性位点与重庆地区汉族人群中糖尿病性视网膜病变的发生无明显相关性。     

染色体15q14、15q25和13q12.12区域单核苷酸多态性与宁夏回族、汉族高度近视的相关性研究

背景 目前认为高度近视是多基因遗传性眼病,其发病受遗传因素及环境因素的共同作用,具有显著的遗传异质性.已有研究报道了高度近视相关的候选基因,但后续的研究中一些候选基因与高度近视的关系仍存在争议. 目的 研究已有报道的染色体15q14、15q25和13q12.12区域单核苷酸多态性（SNPs）与中国宁夏地区回族、汉族高度近视人群的关联性.方法 纳入2011年10月至2013年1月在宁夏眼科医院及宁夏医科大学总医院眼科就诊的高度近视患者487例进入前瞻性队列研究,包括汉族患者380例,回族患者107例,同期收集488名屈光状态和眼轴长度在正常范围的正常受检者作为对照,包括汉族受检者361例,回族受检者127例.收集所有受检者的外周血各5 ml,提取全血DNA,选取染色体15q14、15q25和13q12.12区域的rs634990、rs524952、rs8027411、rs9318086、rs9510902、rs3794338、rs1886970、rs7325450和rs7331047共9个标签SNPs,通过Sequenom质谱平台对受检者的各SNPs基因型进行测定,并对汉族高度近视组与正常对照组、回族高度近视组与正常对照组、汉族患者与回族患者间的基因型和等位基因分布进行比较,分析其与高度近视的相关性. 结果 汉族高度近视组与正常对照组位于染色体15q25区段的rs8027411SNPs基因型频率及等位基因频率的比较差异均有统计学意义（P=0.003、0.001）,GT和TT基因型优势比（OR）值分别为1.794（95％CI∶1.198 ～ 2.687）和1.697（95％ CI∶1.214～2.372）.回族与汉族高度近视患者间15q25区段的rs8027411位点等位基因频率的比较差异有统计学意义（P=0.038）,T等位基因OR值为0.725（95％CI∶0.534 ～0.983）.回族高度近视患者与正常对照者间在上述9个SNPs中的基因型频率及等位基因频率分布差异均无统计学意义（P＞0.05）. 结论 染色体15q25区段的rs8027411 SNPs可能与宁夏地区汉族高度近视的发病关联性较强.在rs8027411位点,携带GT和TT基因型的个体患高度近视的风险明显增加.本研究未发现上述9个SNPs与宁夏地区回族高度近视患者发病有关联.     

Profiling of human leukocyte antigens in Eales‘ disease

Eales' disease is a primary retinal perivasculitis of an undetermined etiology seen predominantly in the Indian sub-continent and rarely in the West. Strong HLA association has been proven in retinal vasculitis of Behcet's disease. HLA association of Eales' disease is unknown and therefore the present study was undertaken to determine the same. The frequency of 30 HLA antigens (9 HLA-A antigens, 10 HLA-B antigens, 3 HLA-C antigens, 7 HLA-DR antigens and 1 HLA-DQ antigen) was studied by standard micro-lymphocytotoxicity test in 57 patients with Eales' disease and 50 age and sex-matched normal persons as controls. Both the patients and controls underwent complete ocular and clinical examinations and laboratory investigations. Inflammatory diseases similar to Eales' disease were ruled out in the patients before they were enrolled. Statistically significant higher phenotype frequencies of HLA B5 (B51), DR1 and DR4 were observed among patients with Eales‘ disease as compared to controls. The gene frequency of HLA B5 (B51) in our group of patients and controls was comparable with other earlier studies in the Indian population. The finding of significant association of Eales' patients with positive disequilibrium (Δ)haplotypes A3-B44 and A11-B12 may be related to the development of this disease. The presence of the above HLA antigens may be indicative of predisposition to Eales' disease. This revised version was published online in July 2006 with corrections to the Cover Date.     

Determination of carbonyl group content in plasma proteins as a useful marker to assess impairment in antioxidant defense in patients with Eales' disease

PURPOSE: Formation of protein carbonyl groups is considered an early biomarker for the oxidant/antioxidant barrier impairment in various inflammatory diseases. We evaluated the intensity of free radical reactions in patients with Eales' disease, an idiopathic inflammatory condition of the retina. METHODS: Twenty patients with Eales' disease in active vasculitis stage, 15 patients with Eales' disease in healed vasculitis stage and 20 healthy control subjects were recruited for the study. Plasma protein carbonyl groups,plasma glutathione (GSH) superoxide dismutase (SOD) activity and thiobarbituric acid reactive substances (TBARS) were determined in erythrocytes. RESULTS: Plasma protein carbonyl content was elevated by a factor of 3.5 and 1.8 respectively in active and healed vasculitis stages. The increase of carbonyl group content in active and healed stage of patients with Eales' disease correlated with diminished SOD activity and GSH content. There was also increased accumulation of TBARS in active and healed vasculitis stages of Eales' disease, and this correlated with diminished SOD activity. CONCLUSION: Our results showed that protein carbonyl group content increases with severity of Eales' disease. The increase in carbonyl content correlated with diminished antioxidant status. This confirms an earlier report that free radical mediated tissue damage occurs in Eales' disease. The determination of protein carbonyl content may be used as a simple biomarker to monitor the efficacy of antioxidant supplementation in controlling retinal vasculitis in patients with Eales' disease.     

Further investigations on the association of Mycobacterium tuberculosis with Eales' disease

PURPOSE: To apply polymerase chain reaction (PCR) on vitreous fluid (VF) from Eales' disease to further confirm its association with Mycobacterium tuberculosis. METHODS: Sixty nine VF samples from 69 patients (24 Eales' disease and 45 Non-Eales' as controls) were processed by conventional methods for detection of mycobacteria. Polymerase chain reaction (PCR) specific for IS 6110 and nested PCR (nPCR) using primers coding for MPB 64 gene were applied on all 69 VF. PCR based dot-blot hybridisation was applied on the IS 6110 amplified products of n PCR-positive VFs. RESULTS: Conventional methods (direct smear and culture) did not detect mycobacteria in any of the 69 VF samples. Five (20.8%) of 24 VF from Eales' and 2 (4.2%) of 45 VF from control patients tested positive for M. tuberculosis DNA by nPCR. This difference was statistically significant (P < 0.05). All 69 VF were negative by PCR for IS 6110. Two VF of Eales' patients positive by nPCR were also positive by DNA probe dot-blot hybridisation for IS 6110. CONCLUSION: Detection of M. tuberculosis DNA by PCR in a significant number of VF of Eales' disease patients reemphasizes the association of this bacterium with Eales' disease.     

Eales' disease: increased oxidation and peroxidation products of membrane constituents chiefly lipids and decreased antioxidant enzymes and reduced glutathione in vitreous.

PURPOSE. To measure the levels of oxidation and peroxidation products of membrane constituents chiefly lipids produced by oxygen and lipid free radicals as thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH) and the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GP) in vitreous samples from patients with Eales' disease and estimate GSH, SOD, GP in the erythrocytes of patients with Eales' disease with active perivasculitis and healed perivasculitis. METHODS. Vitreous samples on vitrectomy from 11 patients with Eales' disease and 11 patients with diabetic vitreous hemorrhage were used for comparison. For study on erythrocytes, 30 patients of Eales' disease at the active vasculitis stage (group-I), 33 of healed vasculitis stage (group-II) and 25 controls (group-III) were used. The male female ratio was kept the same among the patients and the controls. Oxidation and peroxidation products of membrane constituents chiefly lipids were estimated as TBARS, SOD by its activity to inhibit auto-oxidation of epinephrine, GP by estimating the reduction in the level of GSH and GSH by its colour reaction with 5,5'-dithio bis (2-nitro) benzoic acid (DTNB). RESULTS. TBARS were increased 6 fold in the vitreous of Eales' patients compared to the samples from those with diabetic vitreous hemorrhage while there was a reduction of 95.9% of SOD and 84.2% of GSH. Activity of SOD, GP and the levels of GSH in the erythrocytes were reduced (%) by 81.6, 65 and 56.5 respectively in group I and 22,46.4 and 29.2% respectively in group II. The values are statistically significant. CONCLUSIONS. Increased levels of TBARS and decreased levels of SOD and GSH in the vitreous could explain inflammation, retinal damage and neovascularization in patients with Eales' disease. Decrease of SOD, GP and GSH is found in erythrocytes both in the active perivasculitis stage and the healed perivasculitis stage. Treatment of Eales' disease with antioxidants vitamin E, C as also vitamin A may have a beneficial effect.     

Polymerase chain reaction for detection of Mycobacterium tuberculosis in epiretinal membrane in Eales' disease

PURPOSE: Tuberculous etiology has been suggested in Eales' disease. Because epiretinal membrane (ERM) is formed on the inner surface of the retina in Eales' disease, it could be the most appropriate intraocular specimen for investigation. Therefore, a nested polymerase chain reaction (nPCR), which detects MPB64 gene of Mycobacterium tuberculosis on the archival specimens of ERM of well-documented Eales' and non-Eales' patients, was applied and the results compared. METHODS: nPCR technique was standardized, and the sensitivity and specificity of the primers were determined. nPCR technique was applied to tissue sections obtained from formalin-fixed and paraffin-embedded tissues of ERM from 23 patients with Eales' disease and 27 noninfective and non-Eales' disease patients as controls. RESULTS: nPCR technique was specific for M. tuberculosis genome and sensitive enough to detect 0.25 fg (corresponding to the presence of a single bacillus). Eleven (47.8%) ERM of 23 Eales' disease and 3 (11.1%) of 27 controls were positive for M. tuberculosis genome. The difference between the two groups was statistically significant (P = 0.001), indicating association of this bacterium with Eales' disease. CONCLUSIONS: The demonstration of the presence of M. tuberculosis DNA by nPCR technique in significant number of ERM of Eales' disease compared with the controls further emphasizes the probable role of this bacterium in the pathogenesis of this enigmatic clinical condition.     

A comparative study of epiretinal membranes associated with Eales' disease: a clinicopathologic evaluation

AIM: To study the histopathologic features and clinical correlation of epiretinal membranes (ERM) obtained from patients of Eales' disease and compare with other vasoproliferative disorders. METHODS: Retrospective analysis of epiretinal membranes submitted for histological evaluation between January 1995 and June 2001, from the patients of diabetic retinopathy and vascular occlusions (Group 1; vaso-occlusive disorders) and of Eales' disease (Group 2; vasoinflammatory disorders). Demographics, pre and postoperative visual acuity, and anatomic and histologic characteristics of membranes were studied. Histopathologic features and clinical outcomes were correlated between the groups. The results were analysed statistically by Student's t-test, Fisher's exact test and Kruskal-Wallis test. RESULTS: This study consisted of 42 patients, 24 in Group 1 and 18 in Group 2. Patients in Group 2 (33.0+/-9.2 years) were significantly younger than the patients in Group 1 (49.9+/-7.6 years) (P< or =0.0001). Final visual acuity of >20/400 was attained in 79.2% (19/24) patients in Group 1 and 83.3% (15/18) in Group 2 (P=1.0). Inflammatory membranes were significantly associated with presumed Eales' disease (94.4 vs 0%) (P< or =0.0001) and fibrovascular membranes with Group 1 (70.8% vs 33.3%) (P=0.028). Mast cells and eosinophils were observed as special features in epiretinal membranes of patients with Eales' disease. CONCLUSIONS: Histological features of ERM in Eales' disease are comparable to other vasoproliferative disorders except for features of inflammation. Presence of mast cells and eosinophils in epiretinal membranes of Eales' disease needs further investigation.     

Eales' disease in Inuit: report of four cases

PURPOSE: To report four cases of Eales' disease in Inuit from Greenland diagnosed within a 6.5-year period. There are no previous reports on Eales' disease among Greenlanders. METHODS: Four younger Inuit, three males and one female, were diagnosed with Eales' disease based on fundus changes and exclusion of possible differential diagnoses. Several studies point to a possible relation between Eales' disease and tuberculosis (TB); examination of possible exposure to TB was part of the clinical investigation. RESULTS: Retinal changes made panretinal laser photocoagulation necessary in all cases. Four eyes in three patients were vitrectomized. Three patients received oral corticosteroid treatment. The final visual outcome was relatively good, with a visual acuity below 6/60 (3/36) in only one vitrectomized eye. All patients had been exposed to TB. CONCLUSION: Eales' disease seems to be rather common in the small population of Inuit (56,000) in Greenland. Attention is required to ensure diagnosis and appropriate treatment, including laser photocoagulation, leading to a reasonably good prognosis.     

Immunolocalization and quantification of advanced glycation end products in retinal neovascular membranes and serum: a possible role in ocular neovascularization

PURPOSE: Earlier studies have revealed the association of advanced glycation end products (AGE) with the pathogenesis of various micro and macro vascular complications. The purpose of the present study is to localize AGEs, namely carboxy methyl lysine (CML-AGE) and methyl glyoxal-derived AGEs (MG-AGE), in retinal neovascular membranes and to quantify them in serum samples. METHODS: Surgically excised retinal neovascular membranes and serum samples obtained from patients with diabetic retinopathy, Eales' disease and nondiabetics were studied. Immunolocalization of AGEs namely CML-AGE and MG-derived AGEs was done using avidin biotin complex method and quantification was done by enzyme linked immunosorbent assay (ELISA). RESULTS: CML-AGE immunoreactivity was detected in all cases of Eales' disease and 61% cases of diabetic retinopathy and none in idiopathic epiretinal membrane (ERM). MG-AGE immunoreactivity was observed in approximately 15% of diabetic retinopathy and none in Eales' disease and and idiopathic ERM. Quantification of AGEs in serum samples revealed statistically significant increased levels of MG-AGE in diabetes, in relation to nondiabetics with idiopathic ERM and CML-AGE in Eales' disease, in relation to diabetics and nondiabetics with idiopathic ERM. CONCLUSION: Results from this study suggest that AGEs formed through glycation and glycoxidation may play an important role in the development of retinal neovascularization. The immunoreactivity of CML-AGEs in neovascular membrane and its increased levels in serum suggest that inspite of the normoglycemic status, glycoxidation and lipid peroxidation due to oxidative stress may trigger retinal neovascularization in Eales' disease, while MG-AGEs in diabetic membrane and serum suggest the role of glycation. Thus the mechanism of neovascularization in different pathological conditions could be different.     

Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease

BACKGROUND: Platelets are an elective site for oxidative stress owing to their high content of polyunsaturated fatty acid. Increased lipid peroxidation and elevated platelet thiobarbituric acid-reacting substances (TBARS) signal oxidative stress. This possibly leads to retinal neovascularization in Eales' disease. METHODS: TBARS levels were estimated in consecutive cases of Eales' disease with neovascularisation (n = 26), Eales' disease without neovascularisation (n = 17) and healthy controls (n = 17). RESULTS: Platelet TBARS levels in the cases of Eales' disease with neovascularisation, Eales' disease without neovascularisation, and healthy controls were 0.66 +/- 0.1, 0.57 +/- 0.11 and 0.42 +/- 0.14 n moles TBARS formed/hour/10(8) platelets respectively. Student's t-test showed a significant increase in platelet TBARS levels in cases with neovascularisation as compared to cases without neovascularization (p < 0.05) and healthy controls (p < 0.01). CONCLUSION: The increase in platelet TBARS levels in proliferative Eales' disease is consistent with an emerging view that lipid peroxides may be associated with retinal neovascularisation.     

New classification system-based visual outcome in Eales' disease

PURPOSE: A retrospective tertiary care center-based study was undertaken to evaluate the visual outcome in Eales' disease, based on a new classification system, for the first time. MATERIALS AND METHODS: One hundred and fifty-nine consecutive cases of Eales' disease were included. All the eyes were staged according to the new classification: Stage 1: periphlebitis of small (1a) and large (1b) caliber vessels with superficial retinal hemorrhages; Stage 2a: capillary non-perfusion, 2b: neovascularization elsewhere/of the disc; Stage 3a: fibrovascular proliferation, 3b: vitreous hemorrhage; Stage 4a: traction/combined rhegmatogenous retinal detachment and 4b: rubeosis iridis, neovascular glaucoma, complicated cataract and optic atrophy. Visual acuity was graded as: Grade I 20/20 or better; Grade II 20/30 to 20/40; Grade III 20/60 to 20/120 and Grade IV 20/200 or worse. All the cases were managed by medical therapy, photocoagulation and/or vitreoretinal surgery. Visual acuity was converted into decimal scale, denoting 20/20=1 and 20/800=0.01. Paired t-test / Wilcoxon signed-rank tests were used for statistical analysis. RESULTS: Vitreous hemorrhage was the commonest presenting feature (49.32%). Cases with Stages 1 to 3 and 4a and 4b achieved final visual acuity ranging from 20/15 to 20/40; 20/80 to 20/400 and 20/200 to 20/400, respectively. Statistically significant improvement in visual acuities was observed in all the stages of the disease except Stages 1a and 4b. CONCLUSION: Significant improvement in visual acuities was observed in the majority of stages of Eales' disease following treatment. This study adds further to the little available evidences of treatment effects in literature and may have effect on patient care and health policy in Eales' disease.