Risk factors for flat anterior chamber after glaucoma filtration surgery.

AIM: To investigate the incidence rate and risk factors for grade III flat anterior chamber (FAC) after glaucoma filtration surgery based on 5-year data. METHODS: Patients who underwent glaucoma filtration surgery in Daping hospital from January 2009 to December 2013 were enrolled in this retrospective study. The incidence of grade III FAC following glaucoma filtration surgery was determined. Regression analysis was performed to investigate the influence of glaucoma type, surgical approach, age, and preoperative intraocular pressure (IOP) on the risk of postoperative FAC. RESULTS: A total of 2179 eyes receiving anti-glaucoma surgery were included. Ninety-one eyes suffered from postoperative FAC, with an overall incidence rate of 4.18%. Of 471 eyes with primary open angle glaucoma (POAG), grade III FAC occurred in only 3 eyes (0.64%). Primary angle-closure glaucoma (PACG) was diagnosed in 1076 eyes, 39 (3.62%) of which developed grade III FAC, including 12 eyes (12/300, 4%) with acute PACG (aPACG) and 27 eyes (27/776, 3.48%) with chronic PACG (cPACG). Six of 259 eyes (2.32%) with secondary glaucoma, 28 of 186 eyes (15.05%) with neovasular glaucoma, 1 of 66 eyes (1.52%) with congenital glaucoma, and 14 of 115 eyes (12.17%) with remnant glaucoma suffered from grade III FAC. Of 6 eyes with mixed glaucoma, none developed grade III FAC after surgery. When stratified by surgical approach, 24 of 766 eyes (3.13%) undergoing trabeculectomy, 21 of 924 eyes (2.27%) treated by trabeculectomy plus mitomycin C (MMC), 18 of 109 eyes (16.51%) undergoing Ahmed glaucoma valve implantation, 23 of 201 eyes (11.44%) managed by Ahmed implantation plus MMC, and 5 of 133 eyes (3.76%) treated by Ahmed implantation plus lens extraction or vitrectomy developed grade III FAC. Logistic regression analysis revealed that factors including neovasular glaucoma, remnant glaucoma, glaucoma valve implantation, glaucoma valve implantation+MMC, glaucoma valve implantation+vitrectomy, age>60y, and IOP at admission >50 mm Hg were significantly associated with an increased risk for grade III FAC. CONCLUSION: The overall incidence of grade III FAC after glaucoma filtration surgery is 4.18%. Patients with neovasular glaucoma and remnant glaucoma are at a higher risk of developing FAC. Ahmed glaucoma valve implantation is associated with a higher risk for grade III FAC compared with trabeculectomy. No significant correlation was observed between the use of MMC in glaucoma filtration surgery and the risk of postoperative FAC. Higher IOP at admission (>50 mm Hg) and old age (>60y) are risk factors for grade III FAC.

Clinical relevance of the glucocorticoid receptor gene polymorphisms in glucocorticoid-induced ocular hypertension and primary open angle glaucoma.

AIM: To avoid the side effects of ocular hypertension of glucocorticoid (GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all primary open angle glaucoma (POAG) patients show this phenotype. Glucocorticoid receptor (GR) regulates C responsiveness in trabecular meshwork (TM) cells. In this study, single nucleotide polymorphism (SNP) genotyping was used to determine whether there are differences in the BclI (rs41423247) and N363S (rs6195) polymorphisms of the GR gene in healthy and POAG patients, and glucocorticoid-induced ocular hypertension (GIOH) populations. METHODS: Three hundred and twenty-seven unrelated Chinese adults, including 111 normal controls, 117 GIOH subjects and 99 POAG patients, were recruited. DNA samples were prepared and the BclI and N363S polymorphisms were screened using real-time polymerase chain reaction (RT-PCR)-restriction fragment length polymorphism (RFLP) analysis. Frequencies of the BclI and N363S polymorphisms were determined and compared using Fisher's exact test and the Chi-squared test. RESULTS: Only the BclI polymorphism was identified in the Chinese Han population. The frequency of the G allele was 21.6 % in normal controls, 18.3% in GIOH patients, and 13.64% in the POAG patients. There was no significant difference in polymorphism or allele frequency in the 3 groups. Furthermore, no N363S polymorphism was found in the study subjects. CONCLUSION: The BclI polymorphisms in GR gene had no association with GIOH and POAG patients, and N363S polymorphism might not exist in the Chinese Han population. Therefore, the BclI polymorphism might not be responsible for the development of GC-induced ocular hypertension or POAG.

Prevalence of open-angle glaucoma in southwestern China: the Yongchuan Glaucoma study.

This study examined the prevalence of primary open-angle glaucoma (POAG) among residents aged ≥50 years living in Yongchuan district of Chongqing. Stratified cluster sampling was employed in random selection to estimate the prevalence of glaucoma from April to June, 2005. Twenty-nine villages or neighborhood communities were randomly selected in urban area (Zhongshan Road), suburban area (Shanjiao Town) and exurban area (Zhutuo Town) of this district. All the respondents underwent detailed ophthalmic examinations. The examinations included questionnaire investigation, visual acuity test, naked-eye examination, measurement of peripheral anterior chamber depth (Van Herrick's technique), detection of intraocluar pressure (IOP) with a Perkins hand-held applanation tonometer (HA-2) and examination of the optic disc by using a 78 diopters (D) lens (including the cup-disc ratio, cup/disc ratio asymmetries, horizontal and vertical diameter, notching and optic disc hemorrhages). A total of 5938 residents were actually examined, and the response rate was 85.19%. The crude prevalence of POAG was 0.86% (n=51/5938, 95% CI 0.64%-1.11%). There were 24 males and 27 females in the glaucoma group. The glaucoma prevalence was not significant different in case number between the male and female subjects (P=0.4900). Furthermore, no association between age or schooling and POAG was noted (P=0.8030, 0.0734). Out of 51 subjects with POAG, unilateral glaucoma-related blindness occurred in 38 subjects (74.5%) and bilateral glaucoma-related blindness was found in 7 subjects (13.7%). This study exhibited that the prevalence of POAG was 0.86% among residents aged ≥50 years living in Yongchuan District of Chongqing. The vision loss caused by POAG in this population was obviously higher than that previously reported in other studies. Glaucoma management, detection of affected persons and handling of the burden of glaucoma should be the priorities of the agenda of local health authorities of Western China.

[Challenge and treatment strategy for ocular surface damage in patients with long term use of antiglaucoma drugs].

Long term use of topical anti-glaucoma drugs has been shown to induce chronic conjunctivitis, superficial punctate keratitis (SPK) and dry eye symptom. Under these conditions, a loss of goblet cells in conjunctiva, epithelial squamous metaplasia and apoptosis were morphologically revealed. Benzalkonium Chloride (BKC), a most frequently used preservative in eye drops, has been found to be an important factor causing ocular surface damage. Furthermore, a big challenge for ophthalmologists is that toxic damage of medication to ocular surface tissues is mild, poor specificity, and delayed manifestation in patients, especially when coexisting with other ocular surface diseases. Impairment of ocular surface tissues greatly impacts the life quality of patients and subsequently influences compliance with glaucoma therapy. This paper emphasizes to take measures to prevent ocular surface tissue damage resulted from chronic use of topical anti-glaucoma drugs and further discusses the treatment strategy. Effective and long-lasting action drugs should always be selected for glaucomatous patients in order to decrease the frequency of topical instillation or at a more expensive medication, a fixed combination formula can be considered for glaucoma therapy. An early surgery or laser treatment is also proposed for the patients who require an IOP reduction with an existing ocular surface impairment. Future investigation and development of new medications with long-term efficacy and appropriate BKC are suggested and preservative-free or drugs with new preservative materials recommended.

[Effect of Nogo-66 on retinal microglia in chronic ocular hypertension rats].

OBJECTIVE: To study the effect of protein Nogo-66 on the expression of CD11b and MHC-II in retinal microglia of chronic ocular hypertension SD rats and the effects of protein Nogo-66 on the immunogenicity of injured retinal tissues. METHODS: It was a control experimental study. Chronic ocular hypertension rat model was established by laser photocoagulation on the anterior chamber angle and superficial vein of the sclera. One ml of Nogo-66 (0.01%) in PBS was injected subcutaneously on the day of laser treatment and 0.005% Nogo-66 PBS solution was injected into the vitreous 7 days and 1 month latter. PBS without Nogo-66 was injected in the control group. The expression of cell surface antigen CD11b and MHC-II were detected by immunohistochemistry 1 month and 1 day after the establishment of hypertension model. The difference of average IOP among groups was analyzed by variance analysis. The difference of expression of CD11b and MHC-II between the experimental and control groups was analyzed by t-test. RESULTS: The intraocular pressure (IOP) of experimental groups rised from the seventh day after model-building and the highest IOP was (24.16 ± 2.70) mm Hg (1 mm Hg = 0.133 kPa) 1 month later while that in the control groups was (15.93 ± 3.28) mm Hg. The difference between them was statistically significant (F = 2.10, P < 0.05). Expression of CD11b was (1.78 ± 0.63)% and MHC-II was (3.92 ± 1.03)% in Nogo-66 with hypertension groups, these results was significantly lower than those in Nogo-66 with normal intraocular pressure groups in which the expression of CD11b was (8.15 ± 1.97)% (t = 2.35, P < 0.05) and MHC-II was (11.45 ± 1.97)% (t = 2.14, P < 0.05). CONCLUSIONS: Protein Nogo-66 activated the cell surface antigen CD11b in nerve fiber layer of retina and induced antigen presenting molecules (MHC-II). This indicates that Nogo has the center immunogenicity and this protein could activate antigen-presenting cells to present injury antigen.

[Efficacy and safety in treatment of ocular neovascularization by Bevacizumab versus Ranibizumab: a meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety in treatment of ocular neovascularization by Bevacizumab versus Ranibizumab. METHODS: It was a systematic review and meta-analysis. According to evaluation guidelines of Cochrane collaboration, clinical controlled trials (CCTs) comparing Bevacizumab and Ranibizumab in treatment of ocular neovascularization were searched using Medline, EMbase, the Cochrane Library and CBM. Methodology qualities of literatures were performed by experienced researchers according to the Jadad Score. RevMan 4.2 offered by Cochrane was used to do the meta-analysis. The differences of efficacy and safety in treatment of ocular neovascularization by Bevacizumab versus Ranibizumab were analyzed through statistical test for incorporative effect (the test results were shown by Z value). RESULTS: Only 7 literatures came into meta-analysis (1620 eyes). The result of analysis showed that Bevacizumab could improve the BCVA and cut down the CFT in treatment of ocular neovascularization, and that Bevacizumab did not display any statistically difference in improving best-corrected visual acuity (converted to logMAR, Bevacizumab group, from -0.9031 + or - 0.0323 to -0.7635 + or - 0.0214, improving by 0.1396 + or - 0.0225; Ranibizumab group, from -0.9345 + or - 0.0194 to -0.8050 + or - 0.0221, improving by 0.1295 + or - 0.0203, Z = 0.56, P = 0.57), and cutting down the central foveal thickness [Bevacizumab group, from (325.4 + or - 52.3) microm to (269.1 + or - 21.3) microm, cutting down by (56.3 + or - 18.5) microm; Ranibizumab group, from (342.0 + or - 45.1) microm to (277.2 + or - 35.5) microm, cutting down by (67.8 + or - 23.2) microm, Z = 1.13, P = 0.26] and safety [inflammation at injection site, Bevacizumab group, 4.1% (34/823 eyes); Ranibizumab group, 3.8% (30/797 eyes), Z = 0.74, P = 0.46; subconjunctival hemorrhage, Bevacizumab group, 3.3% (27/823 eyes); Ranibizumab group, 3.4% (27/797 eyes), Z = 0.98, P = 0.33; total complications, Bevacizumab group, 10.2% (84/823 eyes); Ranibizumab group, 9.5% (76/797 eyes), chi(2) = 0.21, P = 0.65] compared with Ranibizumab. CONCLUSIONS: Meta-analysis shows that Bevacizumab has equal efficacy and safety to Ranibizumab in treatment of ocular neovascularization. However, a high quality perspective study is still required for further analysis.

[Expression of CD11b in the retinal microglia in chronic hypertension rat].

OBJECTIVE: To study the expression of CD11b in the retinal microglia in laser induced ocular hypertension (OHT) SD rat. METHODS: It was an experimental study. OHT was induced by the coagulation of trabecular meshwork using 532-laser in sixty SD rats. Intraocular pressure (IOP) was measured by Tonopen-XL, the expression of CD11b in retinal microglia detected by immunohistochemistry, and retinal ganglion cells (RGCs) were labeled with Dextran Tetramethyl Rhodamine (DTR) and counted by Image-Pro Plus Version 6.0 image analysis software at 2 weeks, 1, 2, 3, 4, 5, and 6 months, respectively. All the numerical data were statistically analyzed by SPSS 13.0 software. RESULTS: Although the IOP of experimental groups are still the similar level at 2w after coagulation (t = 1.124, P = 0.287), Compared to control eyes, IOP in lasered eyes was significantly (t = 2.487, P = 0.036) increased at 1 month, lasting for 3 months and returned to normal from 5 to 6 months (t = 1.103, P = 0.290). The expression of CD11b in the retinal microglia in the lasered eyes was significantly more intensive than that in control eyes at 1 month (t = 3.333, P = 0.008) and faded after 5 months, a similar pattern to IOP response, that two group data shows significant dependability (r = 0.891, P = 0.014). The number of RGC was significantly reduced from 1 month to 6 months (t = 3.316, P = 0.009), the velocity of reducing seems dependability to the advancing of IOP (r = 0.757, P = 0.021). CONCLUSIONS: The expression of CD11b in retinal microglia is fluctuated with chronic OHT pattern and RGCs injury level indicating that the injury antigens by microglia are presented in the retina with the increase of IOP and activate the immunologic process leading to glaucomatous RGCs damage. It suggests that it is important to effectively control the IOP in order to reduce the risk of immune induced retinal damage by microglia.

Bietti crystalline dystrophy with bilateral macular holes.

OBJECTIVE: Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. DESIGN: Case report and literature review. RESULTS: Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. CONCLUSION: Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear.

[Meta-analysis on the association of Myocilin Q368X mutation and primary open angle glaucoma].

OBJECTIVE: To study the association between Myocilin (MYOC) Gln368STOP mutation and primary open angle glaucoma (POAG) by means of Meta-analysis. METHODS: Odds ratios (OR) of MYOC Gln368STOP genotype distributions in POAG patients verse the controls were analyzed. All the relevant reported studies were identified. Poor-qualified studies were eliminated, and the risk of publication bias was excluded. Meta-analysis software, RevMan 4.2, was applied for investigating heterogeneity among individual studies and summarizing the effects across studies. RESULTS: A total of 3077 POAG cases and 2063 controls from 11 studies were included. No heterogeneity among these studies was noticed (P = 0.79). The pooled OR (with 95% CI) of MYOC Gln368STOP in POAG cases versus that in the controls was 6.01 (2.57 - 14.04, P < 0.01). CONCLUSION: MYOC Gln368STOP mutation might be associated with the increased risk of POAG and is one of its risk factors.

[Meta-analysis of diagnostic capability of frequency-doubling technology (FDT) for primary glaucoma].

OBJECTIVE: To evaluate the overall diagnostic capabilities of frequency-doubling technology (FDT) in patients of primary glaucoma, with standard automated perimetry (SAP) and/or optic disc appearance as the gold standard. METHODS: A comprehensive electric search in MEDLINE, EMBASE, Cochrane Library, BIOSIS, Previews, HMIC, IPA, OVID, CNKI, CBMdisc, VIP information, CMCC, CCPD, SSreader and 21dmedia and a manual search in related textbooks, journals, congress articles and their references were performed to identify relevant English and Chinese language articles. Criteria for adaptability were established according to validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests. Quality of the included articles was assessed and relevant materials were extracted for studying. Statistical analysis was performed with Meta Test version 0.6 software. Heterogeneity of the included articles was tested, which was used to select appropriate effect model to calculate pooled weighted sensitivity and specificity. Summary Receiver Operating Characteristic (SROC) curve was established and the area under the curve (AUC) was calculated. Finally, sensitivity analysis was performed. RESULTS: Fifteen English articles (21 studies) of 206 retrieved articles were included in the present study, with a total of 3172 patients. The reported sensitivity of FDT ranged from 0.51 to 1.00, and specificity from 0.58 to 1.00. The pooled weighted sensitivity and specificity for FDT with 95% confidence intervals (95% CI) after correction for standard error were 0.86 (0.80 - 0.90), 0.87 (0.81 - 0.91), respectively. The AUC of SROC was 93.01%. Sensitivity analysis demonstrated no disproportionate influences of individual study. CONCLUSIONS: The included articles are of good quality and FDT can be a highly efficient diagnostic test for primary glaucoma based on Meta-analysis. However, a high quality perspective study is still required for further analysis.

[Cloning and screening of retina damage related genes in experimental rabbit chronic ocular hypertension].

OBJECTIVE: To construct the subtractive differentially expressed genes cDNA library of retina in rabbits with chronic ocular hypertension then to clone and screen the genes that related with retina damage. METHODS: Rabbit chronic ocular hypertension model was Established by injecting 1% methylcellulose into anterior chamber once a week for 5 weeks. Total RNA was extracted from retina of experimental and control rabbit eyes. Differentially expressed cDNAs libraries between chronic ocular hypertension eyes and control eyes were constructed using suppression subtraction hybridization (SSH) and then the preliminary data was screened for gene expression. One of upregulation expressed sequence tags (ESTs) was labeled with biotin as a probe. Cellular location of the interested genes in retina was identified by in situ hybridization. RESULTS: The constructed subtractive cDNA library that related to retina damage of chronic ocular hypertension was established and sixteen effective sequences were obtained. Two known expressed sequence tags (similarity over 98%) were found by BLAST Analyze in NCBI. The EST(number F9) was 99% similar to Ras genes family. Through ISH cellular location it was found the gene highly expressed in retina ganglion cells and inner nuclear layer of experimental retina but not in controls. CONCLUSIONS: There was abnormal gene expression in rabbit retina in response to chronic ocular hypertension. Our result suggests EST F9 may play an important role in retina damage under chronic ocular hypertension. The subtractive differentially expressed genes cDNA library could provide valuable information in the research of optical neuro damage and protection in glaucoma.

[Study on the gene mutation of TIGR in primary open angle glaucoma, their relatives and normal controls in Chongqing].

OBJECTIVE: To study trabecular meshwork induced glucocorticoid response protein (TIGR) gene mutation in primary open angle glaucoma (POAG), their relatives and normal controls in Chongqing. METHODS: (1) The coding sequence of TIGR was screened for sequence alterations using polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP). (2) Samples corresponding to bands of altered mobility were sequenced. (3) The sequence alterations were analyzed by bioinformatics. RESULTS: (1) In 15 POAG, TIGR gene mutation was found in 5 cases. In 10 POAG relatives, 2 TIGR gene mutations were found. No TIGR gene mutation was found in 20 normal persons in Chongqing. (2) The mutation sites Ser55Thr, Asp247Stop and in 49021 c-t alteration discovered in the present study have not been reported previously. The 63155 c-t alternation has been reported as a polymorphism site previously. (3) Bioinformatics analysis indicated that the mutations in structural domain could lead to the changes in the amino acid sequence coded, second structure of protein, isoelectric point and antigen binding site. CONCLUSIONS: We found that the TIGR gene mutations is closely related to the occurrence of JOAG in Chongqing. The relatives of POAG patients may have a higher incidence of TIGR gene mutation as compared with the controls. Furthermore, after analyzed by bioinformatics, we found that the alteration of structure and biological activity of TIGR protein resulted from gene mutation may be one of the important changes that leading to the occurrence of POAG.