Mani Baskaran

Lens Vault, Thickness, and Position in Chinese Subjects with Angle Closure

PURPOSE To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure. DESIGN Prospective, comparative study. PARTICIPANTS One hundred two Chinese subjects with angle closure (consisting of primary angle closure, primary angle-closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study. METHODS All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs, on horizontal AS OCT scans. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth [ACD] +1/2 LT) and relative LP (RLP; defined as LP/axial length [AL]). MAIN OUTCOME MEASURES Lens parameters and angle closure. RESULTS Significant differences between angle-closure and normal eyes were found for LV (901±265 vs. 316±272 μm; P<0.001), LT (4.20±0.92 vs. 3.90±0.73 mm; P = 0.01), LT-to-AL ratio (0.18±0.04 vs. 0.16±0.03; P<0.001), ACD (2.66±0.37 vs. 2.95±0.37 mm; P<0.001), and AL (22.86±0.93 vs. 23.92±1.37 mm; P<0.001), but no significant differences were found for LP (4.76±0.51 vs. 4.90±0.54 mm; P = 0.34) or RLP (0.21±0.02 vs. 0.20±0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio [OR], 48.1; 95% confidence interval [CI], 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearsons correlation coefficient [PCC], 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2). CONCLUSIONS Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT.

Ocular biometry in occludable angles and angle closure glaucoma: a population based survey

Aim: To compare ocular biometric values in a population based sample of eyes with occludable angles, angle closure glaucoma, and normal subjects. Method: 2850 subjects from a population based glaucoma prevalence study underwent complete ocular examination including indentation gonioscopy. Ocular biometry was performed in all subjects classified to have occludable angles (n = 143); angle closure glaucoma (n = 22), and a random subgroup of 419 normal subjects. Ocular biometry readings between the groups were compared and statistically analysed using “t,” “z,” and Mann-Whitney U tests. Results: The mean age among subjects with occludable angles (54.43 (SD 9.53) years) and angle closure glaucoma (57.45 (8.5) years) was significantly higher (p<0.001) than normal subjects (49.95 (9.95) years). Axial length was shorter (p<0.001) in the occludable angle group (22.07 (0.69) mm) compared to the normal group (22.76 (0.78) mm). Anterior chamber depth (ACD) was shallower (p<0.001) among subjects with occludable angles (2.53 (0.26) mm) than normal subjects (3.00 (0.30) mm). Lens thickness (LT) was greater (p<0.001) in people with occludable angles (4.40 (0.53) mm) compared to normal subjects (4.31 (0.31) mm). No significant difference was noted in axial length, ACD (p = 0.451), and LT (p = 0.302) between angle closure glaucoma and occludable eyes. Conclusion: South Indian eyes with angle closure glaucoma and occludable angles seem to have significantly shorter axial lengths, shallower anterior chambers and greater lens thickness compared to the normal group.

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.

Effect of corneal parameters on measurements using the pulsatile ocular blood flow tonograph and Goldmann applanation tonometer

Aims: To investigate the effect of central corneal thickness and corneal curvature on intraocular pressure measurements using the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer, and to assess the agreement between the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer in intraocular pressure measurement. Methods: 479 subjects underwent intraocular pressure measurements with the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph. Of these, 334 patients underwent additional measurement of central corneal thickness with an ultrasonic pachymeter and corneal curvature measurement with a keratometer. Results: The intraocular pressure measurements obtained with both the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph varied with central corneal thickness and mean keratometric reading. Intraocular pressure measured using the Goldmann applanation tonometer increased by 0.027 mm Hg per µm increase in central corneal thickness. Intraocular pressure measured using the pulsatile ocular blood flow tonograph increased by 0.048 mm Hg per μm increase in central corneal thickness. For an increase of 1 mm of mean corneal curvature there was rise in intraocular pressure of 1.14 mm Hg measured by the Goldmann applanation tonometer and of 2.6 mm Hg measured by the pulsatile ocular blood flow tonograph. When compared to the Goldmann applanation tonometer, the pulsatile ocular blood flow tonograph underestimated at low intraocular pressure and overestimated at higher intraocular pressure. Conclusion: Central corneal thickness and corneal curvature affected measurements obtained with the pulsatile ocular blood flow tonograph more than they affected measurements obtained with the Goldmann applanation tonometer.

Diagnostic Performance of Anterior Chamber Angle Measurements for Detecting Eyes With Narrow Angles: An Anterior Segment OCT Study

OBJECTIVE To assess the diagnostic performance of angle measurements from anterior segment optical coherence tomography (AS-OCT) images for identifying eyes with narrow angles. METHODS We conducted a community-based cross-sectional study of individuals 50 years or older who had phakic eyes and who underwent AS-OCT imaging in the dark by a single operator and gonioscopy by an ophthalmologist masked to AS-OCT findings. An eye was considered to have narrow angles if the posterior pigmented trabecular meshwork was not visible for at least 180° on gonioscopy. Horizontal AS-OCT images were analyzed for the following measurements using customized software: angle opening distance (AOD) at 250, 500, and 750 μm from the scleral spur; trabecular-iris space area (TISA) at 500 and 750 μm; and angle recess area (ARA) at 750 μm. Areas under the receiver operating characteristic curves (AUCs) were generated for AOD, TISA, and ARA to assess the performance of these measurements in detecting eyes with narrow angles. RESULTS Of 2047 individuals examined, 582 were excluded mostly because of poor image quality or inability to locate the scleral spur. Of the remaining 1465 participants, 315 (21.5%) had narrow angles on gonioscopy. Mean (SD) age was 62.7 (7.7) years, 54.1% were women, and 90.0% were Chinese. The AUCs were highest for AOD750 in the nasal (0.90 [95% confidence interval, 0.89-0.92]) and temporal (0.91 [0.90-0.93]) quadrants. CONCLUSIONS The AOD750 is the most useful angle measurement for identifying individuals with gonioscopic narrow angles in gradable AS-OCT images. Poor definition of the scleral spur precludes quantitative analysis in approximately 25% of AS-OCT images.

Pseudoexfoliation in south India

Aim: To study the profile of pseudoexfoliation in a population based study. Method: 2850 consecutive subjects aged 40 years or older from a population based survey in a rural area of southern India underwent complete ophthalmic evaluation including history, visual acuity testing, refraction, slit lamp examination, applanation tonometry, gonioscopy, and dilated examination of the lens (including LOCS II grading of cataract), fundus, and optic disc. Patients with pseudoexfoliation syndrome were identified and their data were analysed with respect to age, sex, intraocular pressure, gonioscopic grading, cataract, and optic neuropathy. Results: 108 subjects had pseudoexfoliation syndrome (3.8 %). There was a significant increase in prevalence with age but no sex predilection. The condition was unilateral in 53 cases (49.1%) and bilateral in 55 cases (50.9%). 18 cases with pseudoexfoliation (16.7%) had high intraocular pressure (>21 mm Hg), 16 cases (14.8%) had occludable angles, and 14 cases (13%) had pseudoexfoliation glaucoma. There was a significantly higher prevalence of cataract among people with pseudoexfoliation compared to those without pseudoexfoliation (p = 0.014). Conclusion: The prevalence of pseudoexfoliation syndrome in the rural population of south India was 3.8%. Raised intraocular pressure was seen in 16.7% of people with pseudoexfoliation and glaucoma was present in 13%.

Evaluation of tonometric correction factors.

To investigate the efficacy of currently available correction factors in correcting intraocular pressure (IOP) measurements for the errors induced by the normal variations in corneal structural characteristics. Materials and Methods:Central corneal thickness (CCT) and corneal radius of curvature were measured on 324 individuals (175 normal: group 1 and 149 had either open angle glaucoma or ocular hypertension: group 2). IOP was measured in all normal subjects with the Goldmann applanation tonometer and the highest recorded IOP was obtained from patient charts for subjects with either open angle glaucoma or ocular hypertension. Regression analysis was performed on IOP, CCT, and corneal radius of curvature. The corrected IOP was also calculated using the models proposed by Ehlers and Orssengo & Pye. Linear regression analysis was used to calculate the residual association between corneal parameters and corrected IOP. Results:There was a significant positive correlation between IOP measured using Goldmann applanation tonometer and the CCT in both groups. There was no significant correlation between corneal radius of curvature and IOP in either group. There was a significant negative correlation in both the groups between CCT and corrected IOP calculated using the models of Ehlers and Orssengo & Pye. This indicates that the Ehlers and Orssengo & Pye models may significantly overestimate the effect of CCT on IOP measurement. Conclusion:The effect of CCT and IOP as observed in the present study and by other studies in literature is less than predicted by both the Ehlers formula and the Orssengo & Pye model. Correcting IOP for the effect of CCT using these models could be erroneous and lead to overcorrection of IOP, thus resulting in erroneously low corrected IOP eyes with thicker cornea and erroneously high corrected IOP in eyes with thinner cornea.

Comparison of anterior chamber depth measurements using the IOLMaster, scanning peripheral anterior chamber depth analyser, and anterior segment optical coherence tomography

Aim: To compare anterior chamber depth measurements by three non-contact devices—the IOLMaster, scanning peripheral anterior chamber depth analyser (SPAC), and Visante anterior segment optical coherence tomography (AS-OCT) Methods: Prospective, cross sectional study of 497 phakic subjects over 50 years of age attending a community clinic in Singapore. Anterior chamber depth of the right eye was measured using all three techniques by the same investigator. Depth measurements were made from the corneal epithelium to the anterior lens surface. The values obtained were compared using Bland–Altman analysis. Results: 232 men and 265 women were examined (mean (SD) age, 63.4 (7.9) years). Mean anterior chamber depth was 3.08 (0.36) mm with IOLMaster, 3.10 (0.44) mm with SPAC, and 3.14 (0.34) mm with AS-OCT. A significant difference was present between the anterior chamber depth measurements recorded by the three devices (p<0.0001). Mean differences between the measurements were: AS-OCT v IOLMaster, 0.062 (0.007) mm (95% limits of agreement, −0.37 to 0.25 mm) (p<0.0001); AS-OCT v SPAC, 0.035 (0.011) mm (−0.44 to 0.51 mm) (p = 0.0001); SPAC v IOLMaster, 0.027 (0.012) mm (−0.57 to 0.50 mm) (p = 0.027). Conclusions: AS-OCT gave systematically deeper anterior chamber measurements than SPAC and IOL-Master. However, as the differences found were small they are unlikely to be clinically important.

Determinants of ganglion cell-inner plexiform layer thickness measured by high-definition optical coherence tomography.

PURPOSE To determine the distribution, variation, and determinants of ganglion cell-inner plexiform layer (GC-IPL) thickness in nonglaucomatous eyes measured by high-definition optical coherence tomography (HD-OCT). METHODS Six hundred twenty-three Chinese adults aged 40 to 80 years were consecutively recruited from a population-based study. All subjects underwent a standardized interview, ophthalmic examination, and automated perimetry. HD-OCT with macular cube protocol was used to measure the GC-IPL thickness. Univariate and multiple linear regression analyses were performed to examine the relationship between GC-IPL thickness with ocular and systemic factors. RESULTS The mean (±SD) age of study subjects was 52.84 ± 6.14 years, 50.1% were male, and all subjects had normal visual fields with no signs of glaucoma or glaucoma suspect. The mean overall, minimum, superior, and inferior GC-IPL thicknesses were 82.78 ± 7.01 μm, 79.67 ± 9.17 μm, 83.30 ± 7.89 μm, and 80.16 ± 8.31 μm, respectively. In multiple linear regression analysis, GC-IPL thickness was significantly associated with age (β = -0.202, P < 0.001), female sex (β = -2.367, P < 0.001), axial length (β = -1.279, P = 0.002), and mean peripapillary retinal nerve fiber layer (RNFL) thickness (β = 0.337, P < 0.001). IOP, central corneal thickness, disc area, serum glucose level, and history of diabetes mellitus had no significant influence on GC-IPL thickness. CONCLUSIONS Thinner GC-IPL was independently associated with older age, female sex, longer axial length, and thinner RNFL thickness. These factors should be taken into account when interpreting GC-IPL thickness measurements with HD-OCT for glaucoma assessment.

Determinants of Quantitative Optic Nerve Measurements Using Spectral Domain Optical Coherence Tomography in a Population-Based Sample of Non-glaucomatous Subjects

PURPOSE To evaluate the ocular and systemic factors influencing measurements of optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thickness with spectral-domain optical coherence tomography (SD-OCT) in healthy Chinese adults. METHODS Adults ranging in age from 40 to 80 years were consecutively recruited from the population-based Singapore Chinese Eye Study. A SD-OCT instrument was used to measure ONH and RNFL parameters. A total of 542 eyes from 542 non-glaucomatous Chinese subjects were analyzed. Univariable and multiple linear regression analyses were performed to examine the effects of a range of ocular (e.g., intraocular pressure [IOP], axial length [AL], disc area) and systemic (e.g., blood pressure, serum glucose) factors on ONH and RNFL parameters. RESULTS In multiple regression analyses, neuroretinal rim area was independently associated with age (β = -0.006, P < 0.001), disc area (β = 0.183, P < 0.001), IOP (β = -0.009, P = 0.008), AL (β = -0.023, P = 0.004), and lens nuclear color (β = 0.042, P = 0.001). Vertical cup-to-disc ratio was independently correlated with age (β = 0.003, P < 0.001), disc area (β = 0.207, P < 0.001), IOP (β = 0.004, P = 0.014), AL (β = 0.010, P = 0.008), and lens nuclear color (β = -0.017, P = 0.006). Average RNFL thickness was independently related to age (β = -0.204, P = 0.001), disc area (β = 4.218, P < 0.001), signal strength (β = 1.348, P < 0.001), and AL (β = -1.332, P < 0.001). Disc area had the strongest effect on measurements of ONH parameters and RNFL thickness. CONCLUSIONS In a non-glaucomatous population, optic nerve measurements with SD-OCT vary with disc area, age, IOP, AL, lens nuclear color, and signal strength, but systemic parameters have little influence. This information may be useful for interpretation of SD-OCT measurements.