Neuroprotective effect of mesenchymal stem cell-derived extracellular vesicles on optic nerve injury in chronic ocular hypertension.

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors, and which may be mediated by extracellular vesicles (or exosomes) released by mesenchymal stem cells. To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma, we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma. One week after injury, extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity. We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage, increased the number of retinal ganglion cells, and inhibited the activation of caspase-3. These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension, and this effect is achieved by inhibiting cell apoptosis.

Safety profile of 0.0015% tafluprost eye drops in China: a post-marketing observational study.

AIM: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China. METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected. RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), ß-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500). CONCLUSION: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances.

Formation of DNA:RNA hybrid G-quadruplex in bacterial cells and its dominance over the intramolecular DNA G-quadruplex in mediating transcription termination.

DNA with four guanine tracts can fold into G-quadruplexes that are targets of transcription regulation. We recently found that hybrid DNA:RNA G-quadruplexes (HQs) can form during in vitro transcription. However, it is unclear whether they can form in cells. Evidence is presented supporting their formation in plasmids in bacterial cells. The formation of the HQs is indicated by a unique pattern of prematurely terminated transcripts under two conditions where the RNA transcripts do or do not participate in G-quadruplex assembly and further supported by a number of chemical and biochemical analysis. HQs dominate over the intramolecular DNA G-quadruplexes (DQ) in mediating the transcription termination when both structures are able to form. These findings provide the first evidence of HQ formation in cells and suggest that the competition/conversion between HQ and DQ may regulate transcription and serve as drug target in pharmaceutical applications.

Formation of DNA:RNA hybrid G-quadruplexes of two G-quartet layers in transcription: expansion of the prevalence and diversity of G-quadruplexes in genomes.

G-quadruplexes are implicated in important cellular processes. Previous studies mostly focused on intramolecular G-quadruplexes of three or more G-quartets. Those composed of two G-quartets were only shown to form in single-stranded oligonucleotides. On the basis of electrophoresis, DMS footprinting, fluorescence labeling, and photo-cross-linking, we detected the formation of DNA:RNA hybrid G-quadruplexes (HQs) of two G-quartets during the transcription of DNA duplexes. These HQs have a lifetime on the minute scale and are stabilized by a stabilizing ligand. They are far shorter-lived than the HQs of three G-quartets, which last for hours. The occurrence of putative formation motifs of such HQs shows a transcription-dependent strand-biased selection, thus supporting their formation and function in genomes. They are present in almost all human genes in large amounts. We speculate that the two-G-quartet HQs may be a distinct type of G-quadruplexes that may play a role in timely responsive processes and for purposes of fine-tuning.

A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the mitochondrial transcription termination at the DNA replication priming site.

Human mitochondrial DNA contains a distinctive guanine-rich motif denoted conserved sequence block II (CSB II) that stops RNA transcription, producing prematurely terminated transcripts to prime mitochondrial DNA replication. Recently, we reported a general phenomenon that DNA:RNA hybrid G-quadruplexes (HQs) readily form during transcription when the non-template DNA strand is guanine-rich and such HQs in turn regulate transcription. In this work, we show that transcription of mitochondrial DNA leads to the formation of a stable HQ or alternatively an unstable intramolecular DNA G-quadruplex (DQ) at the CSB II. The HQ is the dominant species and contributes to the majority of the premature transcription termination. Manipulating the stability of the DQ has little effect on the termination even in the absence of HQ; however, abolishing the formation of HQs by preventing the participation of either DNA or RNA abolishes the vast majority of the termination. These results demonstrate that the type of G-quadruplexes (HQ or DQ) is a crucial determinant in directing the transcription termination at the CSB II and suggest a potential functionality of the co-transcriptionally formed HQ in DNA replication initiation. They also suggest that the competition/conversion between an HQ and a DQ may regulate the function of a G-quadruplex-forming sequence.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Lack of association between primary angle-closure glaucoma susceptibility loci and the ocular biometric parameters anterior chamber depth and axial length.

PURPOSE: Three susceptibility loci for primary angle-closure glaucoma (PACG) were recently identified: PLEKHA7 rs11024102, COL11A1 rs3753841, and rs1015213 located in the intergenic region between PCMTD1 and ST18. The purpose of this study was to investigate the associations of these loci with the ocular biometric parameters anterior chamber depth (ACD) and axial length (AL). METHODS: Genotype and ocular biometric data were available for four population-based studies, including three from Singapore (Singapore Chinese Eye Study, Singapore Malay Eye Study, and Singapore Indian Eye Study) and one from China (Beijing Eye Study), exceeding 7000 participants. ACD and AL were measured using the IOLMaster for the Singapore cohorts and optical low-coherence reflectometry (Lenstar 900 Optical Biometer) for the Beijing cohort. Five readings were obtained for each participant and the average was computed. Analysis excluded any eye that was pseudophakic or aphakic. RESULTS: ACD measurements and genotype data of the three loci were available for 7245, 7243, and 7239 subjects, respectively. We noted nominal evidence of association between single nucleotide polymorphism (SNP) rs1015213 (PCMTD1-ST18) and a shallower ACD when all data were meta-analyzed (ß = -0.033, P = 0.021). When multiple testing was considered, the observation was nonsignificant. There was no association between ACD and rs11024102 (PLEKHA7) or rs3753841 (COL11A1). We did not observe significant associations between AL and any of the three SNPs. CONCLUSIONS: The lack of association between the PACG susceptibility loci with ACD or AL suggests that predilection to PACG may be mediated by factors other than shallow anterior chamber or short eyeball length.

Effect of cAMP on short-circuit current in isolated human ciliary body.

BACKGROUND: Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change. METHODS: In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied. RESULTS: Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP. CONCLUSIONS: cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

Differential associations of myopia with major age-related eye diseases: the Singapore Indian Eye Study.

PURPOSE: To determine the associations of myopia and axial length (AL) with major age-related eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), age-related cataract, and primary open-angle glaucoma (POAG). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 3400 Indians (75.6% response rate) aged 40 to 84 years in Singapore. METHODS: Refractive error was determined by subjective refraction, and AL was determined by noncontact partial coherence laser interferometry. Age-related macular degeneration and DR were defined from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System and Airlie House classification system, respectively. Age-related cataract was diagnosed clinically using the Lens Opacity Classification System (LOCS) III system. Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. MAIN OUTCOME MEASURES: Age-related macular degeneration, DR, age-related cataract, and POAG. RESULTS: Myopic eyes (spherical equivalent [SE] <-0.5 diopter [D]) were less likely to have AMD (early plus late AMD) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.79) or DR (OR, 0.68; 95% CI, 0.46-0.98) compared with emmetropic eyes; each millimeter increase in AL was associated with a lower prevalence of AMD (OR, 0.76; 95% CI, 0.65-0.89) and DR (OR, 0.73; 95% CI, 0.63-0.86). Myopic eyes were more likely to have nuclear (OR, 1.57; 95% CI, 1.13-2.20) and posterior subcapsular (OR, 1.73; 95% CI, 1.10-2.72) cataract, but not cortical cataract (P = 0.64); each millimeter increase in AL was associated with a higher prevalence of posterior subcapsular cataract (PSC) (OR, 1.29; 95% CI, 1.07-1.55), but not nuclear (P = 0.77) or cortical (P = 0.39) cataract. Eyes with high myopia (SE <-6.0 D) were more likely to have POAG (OR, 5.90; 95% CI, 2.68-12.97); each millimeter increase in AL was associated with a higher prevalence of POAG (OR, 1.43; 95% CI, 1.13-1.80). CONCLUSIONS: Myopic eyes are less likely to have AMD and DR but more likely to have nuclear cataract, PSC, and POAG. The associations of myopia with AMD, DR, and POAG are mostly explained by longer AL. However, the association between myopia and nuclear cataract is explained by lens refraction rather than AL.

Telomere- and telomerase-interacting protein that unfolds telomere G-quadruplex and promotes telomere extension in mammalian cells.

Telomere extension by telomerase is essential for chromosome stability and cell vitality. Here, we report the identification of a splice variant of mammalian heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), hnRNP A2*, which binds telomeric DNA and telomerase in vitro. hnRNP A2* colocalizes with telomerase in Cajal bodies and at telomeres. In vitro assays show that hnRNP A2* actively unfolds telomeric G-quadruplex DNA, exposes 5 nt of the 3' telomere tail and substantially enhances the catalytic activity and processivity of telomerase. The expression level of hnRNP A2* in tissues positively correlates with telomerase activity, and overexpression of hnRNP A2* leads to telomere elongation in vivo. Thus, hnRNP A2* plays a positive role in unfolding telomere G-quadruplexes and in enhancing telomere extension by telomerase.

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Variation in prevalence of myopia between generations of migrant indians living in Singapore.

PURPOSE: To assess the influence of factors related to migration and acculturation on myopia in migrant Indians in Singapore. DESIGN: Population-based cross-sectional study. METHODS: A total of 3400 Singaporean Indians (75.6% response rate) aged over 40 years participated in this study. Information regarding country of birth, migration age, and language of interview were collected from interviews. Indians born outside of Singapore were defined as "first-generation" immigrants, while Indians born in Singapore were defined as "second-generation (or higher)" immigrants. Refraction was determined by autorefraction and refined by subjective refraction. Ocular biometry including axial length (AL), anterior chamber depth (ACD), and corneal radius (CR) were measured by partial coherence interferometry. Myopia and high myopia were defined as spherical equivalents (SE) of less than -0.5 diopter (D) for myopia, and < -5 D for high myopia, respectively. RESULTS: The prevalence of myopia (30.2% vs 23.4 %) and high myopia (4.8% vs 2.5%) were higher in second-generation immigrants compared with first-generation immigrants. Second-generation immigrants had longer AL (23.50 mm vs 23.37 mm, P = .004) than first-generation immigrants after multivariate adjustment. The excess prevalence of myopia was reduced by 37.5% but remained statistically significant (P = .02) after further controlling for educational level. Among first-generation immigrants, those migrating to Singapore before the age of 21 had significantly higher prevalence of myopia (odds ratio [OR]: 1.85; 95% confidence interval [CI]: 1.32, 2.59) and longer AL (regression coefficient: 0.27; 95% CI: 0.11, 0.43) than those migrating after 21 years of age. Also, first-generation immigrants interviewed in English had higher prevalence of myopia (OR: 1.46; 95% CI: 1.00, 2.17) than their non-English-interviewed counterparts. CONCLUSIONS: The prevalence of myopia among second-generation (or higher) Indian immigrants in Singapore is higher than first-generation immigrants. Country-specific environmental factors may be important for the increasing prevalence of myopia in Asia.

Expression of nitric oxide synthase and guanylate cyclase in the human ciliary body and trabecular meshwork.

BACKGROUND: The role played by the nitric oxide (NO) signaling pathway in the aqueous humor dynamics is still unclear. This study was designed to investigate the expression and distribution of NO synthase (NOS) isoforms and guanylate cyclase (GC) in human ciliary body, trabecular meshwork and the Schlemm's canal. METHODS: Twelve eyes after corneal transplantation were used. Expression of three NOS isoforms (i.e. neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS)) and GC were assessed in 10 eyes by immunohistochemical staining using monoclonal or polyclonal antibody of NOS and GC. Ciliary bodies were dissected free and the total proteins were extracted. Western blotting was performed to confirm the protein expression of 3 NOS isoforms and GC. RESULTS: Expression of 3 NOS isoforms and GC were observed in the ciliary epithelium, ciliary muscle, trabecular meshwork and the endothelium of the Schlemm's canal. Immunoreactivity of nNOS was detected mainly along the apical cytoplasmic junction of the non-pigmented epithelium (NPE) and pigmented epithelial (PE) cells. Protein expressions of 3 NOS isoforms and GC were confirmed in isolated human ciliary body by Western blotting. CONCLUSIONS: The expression of NOS isoforms and GC in human ciliary body suggest the possible involvement of NO and cyclic guanosine monophosphate (cyclic GMP, cGMP) signaling pathway in the ciliary body, and may play a role in both processes of aqueous humor formation and drainage.

Ocular biometry in an urban Indian population: the Singapore Indian Eye Study (SINDI).

PURPOSE. To describe the distribution and determinants of ocular biometric parameters in adult Singapore Indians. METHODS. A population-based, cross-sectional study was conducted on 3400 Indians aged 40 to 83 years residing in Singapore. Ocular components including axial length (AL), anterior chamber depth (ACD), and corneal radius (CR) were measured by partial coherence interferometry. Refraction was recorded in spherical equivalent (SE). RESULTS. After 502 individuals with previous cataract surgery were excluded, ocular biometric data on 2785 adults were analyzed. The mean AL, ACD, and CR were 23.45 ± 1.10, 3.15 ± 0.36, and 7.61 ± 0.26 mm, respectively. The mean AL/CR ratio was 3.08 ± 0.13. The mean AL was 23.53, 23.49, 23.35, and 23.25 mm in 40- to 49-, 50- to 59-, 60- to 69-, and 700 to 83-year age groups, respectively (P < 0.001). Men had significantly longer ALs than women (23.68 mm versus 23.23 mm, P < 0.001). In multivariate linear regression models, AL was found to be longer in adults who were taller (P < 0.001), better educated (University, P < 0.001), and more apt to spend time reading (P < 0.001). Increasing CR was associated with increasing height (P = 0.008). AL was the strongest determinant for refraction in all age groups, whereas lens nuclear opacity was a predictor in adults aged 60 to 83 years. CONCLUSIONS. The AL in Indians living in Singapore was similar to that of Malays in Singapore, but longer than that of Indians living in India. Time spent reading, height, and educational level were the strongest determinants of AL. AL was the strongest predictor of SE in all age groups.

Influence of refractive error on optic disc topographic parameters: the singapore malay eye study.

PURPOSE: To examine the relationship between refractive error and optic disc topographic parameters and retinal nerve fiber layer (RNFL) thickness. DESIGN: Population-based cross-sectional study. METHODS: All 3,280 (78.7% response rate) persons of Asian Malay ethnicity 40 to 80 years of age underwent a standardized interview, ocular examinations, and optic disc imaging with the Heidelberg Retina Tomography II (HRT; Heidelberg Engineering). Associations between spherical equivalent (SE) and HRT parameters were evaluated by partial correlation analysis. RESULTS: There were 2,457 (74.9%) right eyes with good-quality HRT images for analyses. When compared with emmetropic eyes, highly myopic eyes (SE < -6.0 diopters) had greater disc area, rim area, rim volume, whereas hyperopic eyes (SE > 0.5 diopters) had significantly smaller disc area, rim area, and cross-sectional RNFL area (all P < .005). In partial correlation after adjustment for age, sex, body mass index, intraocular pressure, and optic disc area, increase of SE (toward hyperopia) was related significantly with greater cup area (partial correlation coefficient, r = 0.058; P = .004) and cup-to-disc area ratio (r = 0.058; P = .004) and with smaller optic disc area (r = -0.058; P = .004), rim area (r = 0.058; P = .004), and rim volume (r = -0.091; P < .001). CONCLUSIONS: This population-based study shows that refractive error is significantly (but weakly) associated with HRT parameters of disc area, cup area, rim area, cup-to-disc area ratio, and rim volume. The clinical significance of these associations need to be determined in further studies.

Association of narrow angles with anterior chamber area and volume measured with anterior-segment optical coherence tomography.

OBJECTIVES: To describe the measurement of anterior chamber area and anterior chamber volume by anterior-segment optical coherence tomography and to investigate the association of these parameters with the presence of narrow angles. METHODS: This was a cross-sectional study of subjects aged at least 50 years without ophthalmic symptoms recruited from a community clinic. All participants underwent standardized ocular examination and anterior-segment optical coherence tomography. Customized software was used to measure anterior chamber area (cross-sectional area bounded by the corneal endothelium, anterior surface of iris, and lens within the pupil) and anterior chamber volume (calculated by rotating the anterior chamber area 360° around a vertical axis through the midpoint of the anterior chamber area). An eye was considered to have narrow angles if the posterior pigmented trabecular meshwork was not visible for at least 180° on gonioscopy with the eye in the primary position. RESULTS: A total of 1922 subjects were included in the final analyses, 317 (16.5%) of whom had narrow angles. Mean anterior chamber area (15.6 vs 21.1 mm(2); P < .001) and anterior chamber volume (97.6 vs 142.1 mm(3); P < .001) were smaller in eyes with narrow angles compared with those in eyes without narrow angles. After adjusting for age, sex, anterior chamber depth, axial length, and pupil size, smaller anterior chamber area (odds ratio, 53.2; 95% confidence interval, 27.1-104.5) and anterior chamber volume (odds ratio, 40.2; 95% confidence interval, 21.5-75.2) were significantly associated with the presence of narrow angles. CONCLUSION: Smaller anterior chamber area and anterior chamber volume were independently associated with narrow angles in Singaporeans, even after controlling for other known ocular risk factors.

Prevalence and risk factors for refractive errors in Indians: the Singapore Indian Eye Study (SINDI).

PURPOSE: To determine the prevalence and risk factors for refractive errors in middle-aged to elderly Singaporeans of Indian ethnicity. METHODS: A population-based, cross-sectional study of Indians aged over 40 years of age residing in Southwestern Singapore was conducted. An age-stratified (10-year age group) random sampling procedure was performed to select participants. Refraction was determined by autorefraction followed by subjective refraction. Myopia was defined as spherical equivalent (SE) < -0.50 diopters (D), high myopia as SE < -5.00 D, astigmatism as cylinder < -0.50 D, hyperopia as SE > 0.50 D, and anisometropia as SE difference > 1.00 D. Prevalence was adjusted to the 2000 Singapore census. RESULTS: Of the 4497 persons eligible to participate, 3400 (75.6%) were examined. Complete data were available for 2805 adults with right eye refractive error and no prior cataract surgery. The age-adjusted prevalence was 28.0% (95% confidence interval [CI], 25.8-30.2) for myopia and 4.1% (95% CI, 3.3-5.0) for high myopia. There was a U-shaped relationship between myopia and increasing age. The age-adjusted prevalence was 54.9% (95% CI, 52.0-57.9) for astigmatism, 35.9% (95% CI, 33.7-38.3) for hyperopia, and 9.8% (95% CI, 8.6-11.1) for anisometropia. In a multiple logistic regression model, adults who were female, younger, taller, spent more time reading and writing per day, or had astigmatism were more likely to be myopic. Adults who were older or had myopia or diabetes mellitus had higher risk of astigmatism. CONCLUSIONS: In Singapore, the prevalence of myopia in Indian adults is similar to those in Malays, but lower than those in Chinese. Risk factors for myopia are similar across the three ethnic groups in Singapore.

Determinants of corneal biomechanical properties in an adult Chinese population.

PURPOSE: To investigate variations in corneal hysteresis (CH) and corneal resistance factor (CRF) and their ocular and systemic associations in Chinese adults. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 1136 subjects of Chinese origin from an ongoing population-based study. METHODS: All subjects in this population-based study underwent a standardized ocular examination including keratometry (corneal radius of curvature), intraocular pressure (IOP) measurement with Goldmann applanation tonometry, central corneal thickness (CCT), and axial length (AL) assessments. The CH and CRF were measured with the Ocular Response Analyzer. Participants underwent a detailed interview and laboratory investigations that included estimation of nonfasting serum glucose, glycosylated hemoglobin, and lipid profile. MAIN OUTCOME MEASURES: We assessed CH, CRF, and their associations with demographic, ocular, and systemic factors. RESULTS: The mean age of study subjects was 55.3±8.4 years and 51.2% were females. The mean CH and CRF were 10.6±1.5 and 10.1±1.6 mmHg, respectively. Women had higher mean CH (10.8 vs 10.4 mmHg; P<0.001) and CRF (10.4 vs. 9.8 mmHg; P<0.001) than men. After adjusting for age, gender, IOP, CCT, keratometry, AL, and diabetes, CH was negatively associated with age (ß = -0.034; P<0.001), IOP (ß = -0.037; P = 0.01), corneal radius of curvature (ß = -0.963; P<0.001), and AL (ß = -0.106; P = 0.001); and positively associated with female gender (ß = 0.308; P<0.001) and CCT (ß = 0.020; P<0.001). The CRF showed a negative association with age (ß = -0.023; P<0.001) and corneal radius of curvature (ß = -0.771; P<0.001), and was positively associated with female gender (ß = 0.368; P<0.001), IOP (ß = 0.134; P<0.001) and CCT (ß = 0.024; P<0.001). Subjects with diabetes had a higher CH (ß = 0.324; P<0.001) and CRF (ß = 0.396; P = 0.002) compared with those without diabetes. CONCLUSIONS: With advancing age, the CH and CRF in adult Chinese decreased. Women and subjects with diabetes had greater CH and CRF. Corneal biomechanical properties of hysteresis and resistance factor are significantly influenced by IOP, CCT, corneal radius of curvature, and AL.

Relationship of central corneal thickness with optic disc parameters: the Singapore Malay Eye Study.

PURPOSE: To examine the relationship of central corneal thickness (CCT) with optic disc parameters measured by confocal scanning laser ophthalmoloscopy in a Malay population. METHODS: This was a population-based cross-sectional study of Asian Malay adults aged 40-80 years living in Singapore. Participants had a standardized interview, examination, and imaging at a study clinic. CCT was measured with an ultrasound pachymeter. Confocal scanning laser imaging was performed on all participants to obtain optic disc parameters. Multivariate regression analyses controlling for age, sex, intraocular pressure, and other potentially confounding factors were conducted separately for disc area, rim area, cup-to-disc ratio, and mean cup depth. RESULTS: Of the 3280 participants in the study, 2525 (77.0%) right eyes with reliable confocal scanning laser tomography images were included in this analysis, with 48 eyes defined to have primary open-angle glaucoma (POAG). In POAG subjects, CCT was positively correlated with rim area (regression coefficient of 0.372 mm(2) per 100 µm CCT increase; P = 0.035) and negatively correlated with cup-to-disc area ratio (-0.160 per 100 µm CCT increase; P = 0.024). There was no relationship between CCT and disc size (P = 0.088). In the 2468 subjects without glaucoma, there were no associations between CCT and confocal scanning laser tomography parameters. CONCLUSIONS: In this population-based study, decreased CCT was associated with lower rim area and greater cup-to-disc area in subjects with POAG, but not in subjects without glaucoma.

[The diagnostic value of double-balloon enteroscopy in 67 cases with obscure abdominal pain].

OBJECTIVE: To evaluate the diagnostic valve of double balloon enteroscopy in patients with obscure abdominal pain and analyze the etiology of chronic abdominal pain resulted from enteral diseases. METHODS: Sixty-seven cases with chronic abdominal pain underwent a previous negative gastroscopy, colonoscopy, gastrointestinal barium, B ultrasound and electrocardiogram were received double balloon enteroscopy during June 2005 to June 2008. RESULTS: Thirty-six of 67 patients was done by enteroscopy via anus, and 19 cases via oral, and 12 cases via both anus and oral. The lesions were found in 41 of the 67 patients, with overall diagnostic yield of 61.19%. Among 41 cases of abdominal pain resulted from small bowel diseases, Crohn's disease were found in 15 cases (36.59%), non-specific small enteritis in 10 cases (24.39%), tumors in 8 cases (19.51%), other enteral diseases in 8 cases (19.51%). CONCLUSIONS: Double balloon enteroscopy was a diagnostic modality with a high diagnostic value for obscure abdominal pain resulted from small bowel diseases. The most common causes of obscure abdominal pain were Crohn's disease, non-specific small enteritis and tumors.