Peripapillary Arterial Circle of Zinn-Haller: Location and Spatial Relationships with Myopia

Purpose

To measure histomorphometrically the location of the peripapillary arterial circle of Zinn-Haller (ZHAC) and assess its associations with axial length.

Methods

Using a light microscope, we measured the distance from the ZHAC to the peripapillary ring (optic disc border), the merging point of the dura mater with the posterior sclera (“dura-sclera point”), and the inner scleral surface. In the parapapillary region, we differentiated between beta zone (presence of Bruch''s membrane, absence of retinal pigment epithelium) and gamma zone (absence of Bruch''s membrane). The peripapillary scleral flange as roof of the orbital cerebrospinal fluid space was the connection between the end of the lamina cribrosa and the posterior full-thickness sclera starting at the dura-sclera point.

Results

The study included 101 human globes (101 patients) with a mean axial length of 26.7±3.7 mm (range: 20.0–39.0 mm). The distance between the ZHAC and the peripapillary ring increased significantly with longer axial length (P<0.001; correlation coefficient r = 0.49), longer parapapillary gamma zone (P<0.001;r = 0.85), longer (P<0.001;r = 0.73) and thinner (P<0.001;r = −0.45) peripapillary scleral flange, and thinner sclera posterior to the equator (P<0.001). ZHAC distance to the peripapillary ring was not significantly associated with length of parapapillary beta zone (P = 0.33). Including only non-highly myopic eyes (axial length <26.5 mm), the ZHAC distance to the disc border was not related with axial length (P = 0.84). In non-highly myopic eyes, the ZHAC was located close to the dura-sclera point. With increasing axial length and decreasing thickness of the peripapillary scleral flange, the ZHAC was located closer to the inner scleral surface.

Conclusions

The distance between the ZHAC and the optic disc border is markedly enlarged in highly myopic eyes. Since the ZHAC is the main arterial source for the lamina cribrosa blood supply, the finding may be of interest for the pathogenesis of the increased glaucoma susceptibility in highly myopic eyes.     

Subfoveal Choroidal Thickness and Glaucoma. The Beijing Eye Study 2011

Purpose

To examine subfoveal choroidal thickness (SFCT) in eyes with glaucoma, using enhanced depth imaging spectral domain optical coherence tomography.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of SFCT, and assessment of fundus photographs for presence of glaucoma. In addition, the group of patients with chronic angle-closure glaucoma (ACG) from the Beijing Eye Study (n = 37) was merged with a group of patients with chronic ACG from the Tongren hospital (n = 52).

Results

Assessments of SFCT and glaucoma were available for 3232 (93.2%) subjects. After adjusting for age, axial length, gender, anterior chamber and lens thickness, SFCT was not significantly associated with presence of glaucoma (P = 0.08; regression coefficient B:−15.7). As a corollary, in logistic regression analysis with adjustment for age, axial length and intraocular pressure, presence of glaucoma was not significantly associated with SFCT (P = 0.20). If only open-angle glaucoma was considered, multivariate analysis revealed no significant association between SFCT and presence of open-angle glaucoma (P = 0.44). As a corollary, in logistic regression analysis, open-angle glaucoma was not significantly associated with SFCT (P = 0.91). In a similar manner if only ACG was taken into account, SFCT was not significantly associated with the presence of ACG (P = 0.27) in multivariate analysis. As a corollary in binary regression analysis, presence of ACG was not significantly associated with SFCT (P = 0.27).

Conclusions

In multivariate analysis with adjustment for age, axial length, gender, anterior chamber and lens thickness, neither OAG nor ACG was associated with an abnormal SFCT.     

Macular Bruch′s Membrane Length and Axial Length. The Beijing Eye Study

Purpose

To assess whether macular Bruch´s membrane gets lengthened in axial myopia.

Methods

Using the enhanced depth imaging mode of spectral-domain optical coherence tomography and examining a subgroup of participants of the population-based cross-sectional Beijing Eye Study, we measured the length of Bruch´s membrane (“MacBMLength”) from the fovea to the temporal edge of parapapillary gamma zone, and the distance between the fovea and the temporal optic disc border. Parapapillary gamma zone was defined as the parapapillary region without Bruch´s membrane. We additionally measured ocular biometric parameters and assessed non-ophthalmologic variables.

Results

Measurements of MacBMLength were performed on 322 individuals. MacBMLength (mean: 3.99±0.33 mm; range: 3.17–4.93 mm) was not significantly associated with any systemic parameter or ocular biometric parameter. Gamma zone width (mean: 0.18±0.30mm; range: 0.00–2.61mm) was associated (multivariate analysis; correlation coefficient r:0.80) with longer axial length (P<0.001; standardized correlation coefficient beta: 0.60; non-standardized correlation coefficient B:0.11; 95%CI: 0.09,0.14) and with longer fovea-optic disc border distance (P<0.001; beta:0.28; B:0.19; 95%CI:0.14,0.25), but not with MacBMLength (P = 0.42). Fovea-temporal disc border distance (mean: 4.16±0.44mm; range: 3.17–5.86mm) was associated (overall correlation coefficient: 0.68) with longer axial length (P<0.001; beta: 0.36; B: 0.10; 95%CI: 0.06, 0.13), after adjusting for flatter anterior chamber depth (P = 0.003; beta:-0.14; B:-0.14; 95%CI: -0.23,-0.05) and wider parapapillary gamma zone (P<0.001; beta:0.42; B:0.62; 95%CI:0.44,0.81).

Conclusions

In contrast to parapapillary gamma zone width and fovea-disc border distance, MacBMLength was not significantly associated with axial length. Axial elongation associated increase in fovea-disc distance may predominantly occur through development or elongation of parapapillary gamma zone, while macular Bruch´s membrane may mostly be independent of axial elongation.     

Comparison of Optic Disc Morphology of Optic Nerve Atrophy between Compressive Optic Neuropathy and Glaucomatous Optic Neuropathy

Objectives

To compare the optic nerve head (ONH) structure between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc.

Methods

We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method.

Results

The mean and maximum cup depths of CON were significantly smaller than those with GON (P<0.001 and P<0.001, respectively). The distance between Bruch''s membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P<0.001 and P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P = 0.005, P = 0.003, and P = 0.001, respectively).

Conclusions

Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON.     

The Whole Macular Choroidal Thickness in Subjects with Primary Open Angle Glaucoma

Purpose

We investigated the whole macular choroidal thickness in subjects with glaucoma in order to evaluate the effects of glaucoma and glaucoma visual field damage on the choroidal thickness.

Subjects and Methods

We examined 40 primary open angle glaucoma patients with only superior visual field defects and 48 normal controls. The macular choroidal thickness was measured using swept-source optical coherence tomography according to the three-dimensional raster scan protocol (6×6 mm). We used the choroidal thickness within a 1.0-mm circle measured on ETDRS grids as the central sector and then used a 6×6 rectangular grid to divide the area into six sectors.

Results

No significant differences were found in the choroidal thickness values between the glaucoma and normal subjects in any of the sectors after adjusting for the age and axial length (all P>0.4, ANCOVA). According to a stepwise analysis of the glaucoma subjects performed using the parameters of age, axial length, central corneal thickness and mean deviation (MD value) obtained by static perimetry, age was the most predictive and significant factor in all sectors (coefficient  = −3.091 to −4.091 and F value  = 15.629 to 22.245), followed by axial length (coefficient  = −10.428 to −23.458 and F value  = 2.454 to 6.369). The central corneal thickness and MD values were not significant predictive factors in any of the sectors. No significant predictive factors were found for the differences in the choroidal thickness values observed between the superior and inferior field sectors.

Conclusions

Neither the glaucoma-related visual field damage nor glaucoma itself have any apparent associations with the whole macular choroidal thickness.

Trial Registration

Japan Clinical Trials Register (http://www.umin.ac.jp/ctr/ number, UMIN 000012527).     

Association of Aminoacyl-tRNA Synthetases Gene Polymorphisms with the Risk of Congenital Heart Disease in the Chinese Han Population

Aminoacyl-tRNA synthetases (ARSs) are in charge of cellular protein synthesis and have additional domains that function in a versatile manner beyond translation. Eight core ARSs (EPRS, MRS, QRS, RRS, IRS, LRS, KRS, DRS) combined with three nonenzymatic components form a complex known as multisynthetase complex (MSC).We hypothesize that the single-nucleotide polymorphisms (SNPs) of the eight core ARS coding genes might influence the susceptibility of sporadic congenital heart disease (CHD). Thus, we conducted a case-control study of 984 CHD cases and 2953 non-CHD controls in the Chinese Han population to evaluate the associations of 16 potentially functional SNPs within the eight ARS coding genes with the risk of CHD. We observed significant associations with the risk of CHD for rs1061248 [G/A; odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.81–0.99; P = 3.81×10⁻²], rs2230301 [A/C; OR = 0.73, 95%CI = 0.60–0.90, P = 3.81×10⁻²], rs1061160 [G/A; OR = 1.18, 95%CI = 1.06–1.31; P = 3.53×10⁻³] and rs5030754 [G/A; OR = 1.39, 95%CI = 1.11–1.75; P = 4.47×10⁻³] of EPRS gene. After multiple comparisons, rs1061248 conferred no predisposition to CHD. Additionally, a combined analysis showed a significant dosage-response effect of CHD risk among individuals carrying the different number of risk alleles (P _trend = 5.00×10⁻⁴). Compared with individuals with “0–2” risk allele, those carrying “3”, “4” or “5 or more” risk alleles had a 0.97-, 1.25- or 1.38-fold increased risk of CHD, respectively. These findings indicate that genetic variants of the EPRS gene may influence the individual susceptibility to CHD in the Chinese Han population.     

The Tumor-Educated-Macrophage Increase of Malignancy of Human Pancreatic Cancer Is Prevented by Zoledronic Acid

We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as “tumor-educated-macrophages” (Edu) and macrophages harvested from mice without tumors as “naïve-macrophages” (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naïve. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naïve-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naïve in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.     

Pattern of Pseudoexfoliation Deposits on the Lens and Their Clinical Correlation- Clinical Study and Review of Literature

Purpose

To study the clinical correlates of pattern of deposits over the lens in patients with pseudoexfoliation syndrome (PXF) or pseudoexfoliation glaucoma.

Methods

This retrospective observational study screened 346 patients with PXF seen in glaucoma clinic of a tertiary hospital from 2011–2013. Details like pattern of deposits, location on the lens surface and pupillary abnormalities in slit lamp photographs and their correlation with clinical and demographic variables, were analysed.

Results

A total of 84 eyes of 42 patients with bilateral PXF were included for the study. Glaucoma was seen in 30 eyes with baseline IOP of 24+3.8 mm Hg. Comparing the type of deposits, namely classical (n = 39 eyes), radial pigmentary (RP) form (n = 39 eyes) and combined classical and radial pigmentary (CR) forms (n = 6 eyes) of deposits, pupillary ruff atrophy was common in all forms while poor dilatation was rare in the RP type (n = 5 vs n = 25 in classical forms, p<0.001). Mean deviation (MD) was worse in the classical and CR form as compared to RP type with the latter presenting much earlier, 43±3.2 years vs 48±4.1 years in CR and 56±5.7 years in classical form, p<0.001. The baseline IOP in the RP group (18±2.3 mm Hg) was significantly lower than the other two forms (CR 20±3.2 mm Hg, classical 28±2.3 mm Hg), p<0.001, with only 2 eyes on anti-glaucoma drugs at presentation.

Conclusion

Pattern of exfoliation deposits may indicate the stage and severity of the disease process in evolution with the RP representing an earlier/less severe form of pseudoexfoliation syndrome.     

Trans-Lamina Cribrosa Pressure Difference and Open-Angle Glaucoma. The Central India Eye and Medical Study

Purpose

To assess associations of the trans-lamina cribrosa pressure difference (TLCPD) with glaucomatous optic neuropathy.

Methods

The population-based Central India Eye and Medical Study included 4711 subjects. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44 Body Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]−0.18×Age[Years] −1.91. TLCPD was IOP–CSFP.

Results

Mean TLCPD was 3.64±4.25 mm Hg in the non-glaucomatous population and 9.65±8.17 mmHg in the glaucomatous group. In multivariate analysis, TLCPD was associated with older age (P<0.001; standardized coefficient beta:0.53; regression coefficient B:0.18; 95% confidence interval (CI):0.17, 0.18), lower body mass index (P<0.001; beta: −0.28; B: −0.36; 95%CI: −0.38, −0.31), lower diastolic blood pressure (P<0.001; beta: −0.31; B: −0.12; 95%CI: −0.13, −0.11), higher pulse (P<0.001; beta:0.05; B:0.02; 95%CI:0.01,0.2), lower body height (P = 0.02; beta: −0.02; B: −0.01; 95%CI: −0.02,0.00), higher educational level (P<0.001; beta:0.04; B:0.15; 95%CI:0.09,0.22), higher cholesterol blood concentrations (P<0.001; beta:0.04; B:0.01; 95%CI:0.01,0.01), longer axial length (P = 0.006; beta:0.03; B:0.14; 95%CI:0.04,0.24), thicker central cornea (P<0.001; beta:0.15; B:0.02; 95%CI:0.02,0.02), higher corneal refractive power (P<0.001; beta:0.07; B:0.18; 95%CI:0.13,0.23) and presence of glaucomatous optic neuropathy (P<0.001; beta:0.11; B:3.43; 95%CI:2.96,3.99). Differences between glaucomatous subjects and non-glaucomatous subjects in CSFP were more pronounced for open-angle glaucoma (OAG) than for angle-closure glaucoma (ACG) (3.0 mmHg versus 1.8 mmHg), while differences between glaucomatous subjects and non-glaucomatous subjects in IOP were higher for ACG than for OAG (8.5 mmHg versus 3.0 mmHg). Presence of OAG was significantly associated with TLCPD (P<0.001; OR:1.24; 95%CI:1.19,1.29) but not with IOP (P = 0.08; OR:0.96; 95%CI:0.91,1.00). Prevalence of ACG was significantly associated with IOP (P = 0.04; OR:1.19; 95%CI:1.01,1.40) but not with TLCPD (P = 0.92).

Conclusions

In OAG, but not in ACG, calculated TLCPD versus IOP showed a better association with glaucoma presence and amount of glaucomatous optic neuropathy. It supports the notion of a potential role of low CSFP in the pathogenesis of open-angle glaucoma.     

Higher Landing Accuracy in Expert Pilots is Associated with Lower Activity in the Caudate Nucleus

The most common lethal accidents in General Aviation are caused by improperly executed landing approaches in which a pilot descends below the minimum safe altitude without proper visual references. To understand how expertise might reduce such erroneous decision-making, we examined relevant neural processes in pilots performing a simulated landing approach inside a functional MRI scanner. Pilots (aged 20–66) were asked to “fly” a series of simulated “cockpit view” instrument landing scenarios in an MRI scanner. The scenarios were either high risk (heavy fog–legally unsafe to land) or low risk (medium fog–legally safe to land). Pilots with one of two levels of expertise participated: Moderate Expertise (Instrument Flight Rules pilots, n = 8) or High Expertise (Certified Instrument Flight Instructors or Air-Transport Pilots, n = 12). High Expertise pilots were more accurate than Moderate Expertise pilots in making a “land” versus “do not land” decision (CFII: d′ = 3.62±2.52; IFR: d′ = 0.98±1.04; p<.01). Brain activity in bilateral caudate nucleus was examined for main effects of expertise during a “land” versus “do not land” decision with the no-decision control condition modeled as baseline. In making landing decisions, High Expertise pilots showed lower activation in the bilateral caudate nucleus (0.97±0.80) compared to Moderate Expertise pilots (1.91±1.16) (p<.05). These findings provide evidence for increased “neural efficiency” in High Expertise pilots relative to Moderate Expertise pilots. During an instrument approach the pilot is engaged in detailed examination of flight instruments while monitoring certain visual references for making landing decisions. The caudate nucleus regulates saccade eye control of gaze, the brain area where the “expertise” effect was observed. These data provide evidence that performing “real world” aviation tasks in an fMRI provide objective data regarding the relative expertise of pilots and brain regions involved in it.     

Mitochondrial Genome Analysis of Primary Open Angle Glaucoma Patients

Primary open angle glaucoma (POAG) is a multi-factorial optic disc neuropathy characterized by accelerating damage of the retinal ganglion cells and atrophy of the optic nerve head. The vulnerability of the optic nerve damage leading to POAG has been postulated to result from oxidative stress and mitochondrial dysfunction. In this study, we investigated the possible involvement of the mitochondrial genomic variants in 101 patients and 71 controls by direct sequencing of the entire mitochondrial genome. The number of variable positions in the mtDNA with respect to the revised Cambridge Reference Sequence (rCRS), have been designated “Segregating Sites”. The segregating sites present only in the patients or controls have been designated “Unique Segregating Sites (USS)”. The population mutation rate (θ = 4N_eμ) as estimated by Watterson’s θ (θ_w), considering only the USS, was significantly higher among the patients (p = 9.8×10⁻¹⁵) compared to controls. The difference in θ_w and the number of USS were more pronounced when restricted to the coding region (p<1.31×10⁻²¹ and p = 0.006607, respectively). Further analysis of the region revealed non-synonymous variations were significantly higher in Complex I among the patients (p = 0.0053). Similar trends were retained when USS was considered only within complex I (frequency 0.49 vs 0.31 with p<0.0001 and mutation rate p-value <1.49×10⁻⁴³) and ND5 within its gene cluster (frequency 0.47 vs 0.23 with p<0.0001 and mutation rate p-value <4.42×10⁻⁴⁷). ND5 is involved in the proton pumping mechanism. Incidentally, glaucomatous trabecular meshwork cells have been reported to be more sensitive to inhibition of complex I activity. Thus mutations in ND5, expected to inhibit complex I activity, could lead to generation of oxidative stress and favor glaucomatous condition.     

Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10⁻⁸), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10⁻¹¹) and 8q12 (minimum p value 1.82×10⁻¹¹) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. “Replication-level” association was also seen between hyperopia and 12 of Kiefer et al.''s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.     

Retinal Nerve Fiber Layer Thickness. The Beijing Eye Study 2011

Purpose

To measure retinal nerve fiber layer (RNFL) thickness in a population-based setting.

Methods

In the population-based Beijing Eye Study 2011 with 3468 individuals, RNFL thickness was measured in a subgroup of 1654 (47.7%) study participants by spectral domain optical coherence tomography (iVue SD-OCT).

Results

Mean RNFL thickness was significantly (P<0.001) higher in the inferior sector (131.4±20.6 µm) than the superior sector (126.1±19.1 µm), where it was higher than in the temporal sector (79.8±12.2 µm;P<0.001), where it was higher than in the nasal sector (75.1±12.6 µm;P<0.001). In multivariate analysis, mean global RNFL thickness (103.2±12.6 µm) increased significantly with younger age (standardized correlation coefficient beta:−0.30;P<0.001), larger neuroretinal rim area (beta:0.26;P<0.001), shorter axial length (beta:−0.21;P<0.001), thicker subfoveal choroidal thickness (beta:0.15;P<0.001), larger optic disc area (beta:0.10;P<0.001), less refractive lens power (beta:0.10;P<0.001), flatter anterior cornea (beta:0.07;P = 0.01) and female gender (beta:0.05;P = 0.03). In this population with an age of 50+ years, the age-related decline in RNFL thickness was 0.5 µm per year of life or 0.36% of an original RNFL thickness of 137 µm at baseline of the study at 50 years of age. Mean global RNFL thickness decreased by 2.4 µm for each mm enlargement of axial length.

Conclusions

The RNFL profile shows a double hump configuration with the thickest part in the inferior sector, followed by the superior sector, temporal sector and nasal sector. Factors influencing global RNFL thickness were younger age, larger neuroretinal rim, shorter axial length, thicker subfoveal choroid, larger optic disc, less refractive lens power, flatter anterior cornea and female gender. Beyond an age of 50+ years, RNFL decreased by about 0.3% per year of life at an age of 50+ years and by 2.4 µm per mm of axial elongation. These findings may be of interest for the knowledge of the normal anatomy of the eye and may be of help to diagnose diseases affecting the RNFL.     

Ten-Year Cumulative Incidence of Diabetic Retinopathy. The Beijing Eye Study 2001/2011

Objective

To assess the cumulative 10-year incidence of diabetic retinopathy (DR) and its associated factors in a population living in Greater Beijing.

Methods

The population-based longitudinal Beijing Eye Study, which included 4439 subjects (age in 2001: 40+years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). The study participants underwent a detailed ophthalmic examination. Fundus photographs were examined for the new development of DR.

Results

After excluding individuals with DR at baseline (n = 87) or no sufficient fundus photographs in 2011 (n = 6), the study included 2602 subjects with a mean age of 64.6±9.7 years (median: 64.0 years; range: 50 to 93 years). In the 10-year period, 109 subjects (39 men) developed new DR with an incidence of 4.2% (95% confidence interval (CI): 3.45,5.03). In multiple logistic regression analysis, incident DR was significantly associated with higher HbA1c value (P<0.001; Odds Ratio (OR): 1.73; 95% Confidence Interval (CI): 1.35,2.21), longer duration of diabetes mellitus (P<0.001; OR: 1.16; 95% CI: 1.10,1.22), higher serum concentration of creatinine (P = 0.02; OR: 1.01; 95% CI: 1.002,1.022), lower educational level (P = 0.049; OR: 0.74; 95% CI: 0.55,0.99), higher estimated cerebrospinal fluid pressure (P = 0.038; OR: 1.10; 95% CI: 1.01,1.22), and shorter axial length (P<0.001; OR: 0.48; 95% CI: 0.33,0.71).

Conclusions

The cumulative 10-year incidence (mean: 4.2%) of DR in a North Chinese population was significantly associated with a higher HbA1c value, longer known duration of diabetes mellitus, higher estimated CSFP and shorter axial length (P<0.001). Shorter axial length (or hyperopia) and, potentially, higher CSFP may be additional risk factors to be taken into account when counseling and treating patients with diabetes mellitus.     

Depressive Symptoms Are Not Associated with Leukocyte Telomere Length: Findings from the Nova Scotia Health Survey (NSHS95), a Population-Based Study

Background

Premature shortening of leukocyte telomere length has been proposed as a novel mechanism by which depression may confer increased risk of adverse cardiovascular events. Prior studies demonstrating associations of depression and depressive symptoms with shorter leukocyte telomere length were small, included selected psychiatric outpatients, were based on convenience samples, and/or adjusted for a limited number of possible confounding factors.

Methods and Findings

We examined the associations of depressive symptoms, probable depressive disorder, and specific depressive symptom clusters, as assessed by the Center for Epidemiological Studies—Depression (CES-D) scale, with leukocyte telomere length, measured by using a real-time PCR method, in 2,225 apparently healthy participants from the 1995 Nova Scotia Health Survey population-based study. The mean age was 48.2±18.9 years; 49.9% of participants were female; and the mean CES-D score was 7.4±7.9. The mean telomere length was 5,301±587 base pairs. In an unadjusted model, depressive symptoms were significantly associated with longer leukocyte telomere length (B = 27.6 base pairs per standard deviation increase in CES-D, 95% confidence interval [CI] = 3.1–52.1, p = 0.027). This association was no longer significant after adjustment for age and sex (B = 9.5, 95% CI = −14.6–33.6, p = 0.44) or after further adjustment for body mass index, Framingham risk score and previous history of ischemic heart disease (all p''s≥0.37). Neither probable depressive disorder nor specific depressive symptom clusters were independently associated with leukocyte telomere length.

Conclusions

Concurrent depressive symptoms were not associated with leukocyte telomere length in a large, representative, population-based study.     

IOL Tilt and Decentration Estimation from 3 Dimensional Reconstruction of OCT Image

Purpose

To evaluate intraocular lens (IOL) tilt and decentration by anterior segment optical coherence tomography (AS-OCT) using 3-dimensional (3D) reconstruction method.

Design

Prospective observational case series.

Participants

Thirty-nine patients (39 eyes) were included.

Methods

The IOL positions of all eyes were examined by AS-OCT. Images were obtained in 4 axes (0–180 degrees, 45–225 degrees, 90–270 degrees, and 135–315 degrees) using the quadrant-scan model. The cross-sectional images were analyzed with MATLAB software.

Main Outcome Measures

The angle (θ) between the reference pupillary plane and the IOL plane, the distances between the center points of the pupil circle and the IOL on the x-axis (dx) and y-axis (dy) and the spatial distance (ds) were calculated after 3D-reconstruction.

Results

The mean angle (θ) between the pupillary plane and the IOL plane was 2.94±0.99 degrees. The mean IOL decentration of dx and dy was 0.32±0.26 mm and 0.40±0.27 mm, respectively. The ds of the IOL decentration was 0.56±0.31 mm. There was no significant correlation between the ocular residual astigmatism (ORA) and the tilted angle or the decentration distance. There was a significant correlation between the ORA and total astigmatism (r = 0.742, P<0.001). There was no significant correlation between the postoperative best corrected visual acuity (BCVA) and the ORA (r = 0.156; P = 0.344), total astigmatism (r = 0.012; P = 0.942), tilted angle (θ; r = 0.172; P = 0.295) or decentration distance (dx: r = 0.191, P = 0.244; dy: r = 0.253, P = 0.121; ds: r = 0.298, P = 0.065).

Conclusions

AS-OCT can be used as an alternative for the analysis of IOL tilt and decentration using 3D-reconstruction.     

Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Purpose

To investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia.

Methods

A total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure β-peripapillary atrophy (PPA) lengths with and without Bruch''s membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well.

Results

LC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P<0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P<0.001), and larger vertical/horizontal tilt angles (vertical, P<0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P<0.001) and vertical tilt angle (P<0.001) were identified as significant.

Conclusions

The presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.     

Analysis of Quality of Clinical Practice Guidelines for Otorhinolaryngology in China

Objective

To evaluate the quality of clinical practice guidelines (CPGs) for otorhinolaryngology in China.

Materials and Methods

A systematic search of relevant literature databases (CBM, WANFANG, VIP, CNKI, China Guideline Clearinghouse) published between 1978 and March 2012 was undertaken to identify and select CPGs related to otorhinolaryngology. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Their degree of agreement was evaluated using the intraclass correlation coefficient (ICC).

Result

From 170 citations, 21 relevant guidelines were included. The overall agreement among reviewers was moderate (ICC = 0.87; 95% confidence interval [CI], 0.78–0.91). The scores for each of the AGREE domains were the following: “scope and purpose” (mean ± standard error [SE] = 45.4±4.4; ICC = 0.92), “stakeholder involvement” (mean ± SE = 30.4±3.1; ICC = 0.81), “rigor of development” (mean ± SE = 20.9±2.8; ICC = 0.87), “clarity of presentation” (mean ± SE = 48.8±3.7; ICC = 0.80), “applicability” (mean ± SE = 12.6±1.7; ICC = 0.72), and “editorial independence” (mean ± SE = 6.2±0.8; ICC = 0.76). Three guidelines (14%) mentioned updates, and the average update frequency was 7 years. None used the GRADE system.

Conclusion

The quality of otorhinolaryngology guidelines in China is low. Greater efforts are needed to provide high-quality guidelines that serve as a useful and reliable tool for clinical decision-making in this field.     

Localized Retinal Nerve Fiber Layer Defects Detected by Optical Coherence Tomography: The Beijing Eye Study

Objective

To assess the prevalence of localized retinal nerve fiber layer defects (LRNFLD) and associated factors in adult Chinese.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals (mean age: 64.6±9.8 years (range: 50–93 years)). The study participants underwent a detailed ophthalmological examination including spectral-domain optical coherence tomography (Spectralis^R-OCT) assisted measurement of the RNFL. A LRNFLD was defined as a sector in which the RNFL contour line dipped into the red zone for a length of <180°.

Results

Readable OCT images were available for 3242 (93.5%) subjects. LRNFLDs were detected in 640 eyes (9.9±0.4%) of 479 subjects (14.8±0.6%). In the age groups of 50–59 years, 60–69 years, 70–79 years, and 80+ years, the prevalence of LRNFLD per person increased from 9.9±0.9%, 11.6±1.0% and 20.6±1.4% to 33.0±3.2%, respectively. In multivariate analysis, prevalence of LRNFLDs was significantly associated with older age (P = 0.001; Odds Ratio (OR): 1.03; 95% Confidence Interval (CI): 1.01,1.05), myopic refractive error (P<0.001;OR:0.79;95%CI:0.74,0.85), larger beta zone of parapapillary atrophy (P<0.001; OR:1.34;95%CI:1.20,1.50), presence of glaucomatous optic neuropathy (P<0.001;OR:7.02;95%CI:3.87,12.7), presence of non-glaucomatous optic nerve damage (P = 0.001;OR:43.3;95%CI:8.24,227.1), and presence of diabetic retinopathy (P = 0.003;OR:2.79;95%CI:1.43,5.44).

Conclusions

OCT-defined LRNFLDs were present in a prevalence of 14.8±0.6% in a population-based study sample of subjects aged 50+ years. Prevalence of LRNFLDs increased with higher age, myopic refractive error, and larger parapapillary beta zone. Major ocular diseases associated with LRNFLs were glaucoma, non-glaucomatous optic nerve damage and diabetic retinopathy. These data may be helpful for a semiautomatic assessment of the RNFL.