Baskaran Mani

Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma

We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10−8) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10−6). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10−19 for rs2487032 representing ABCA1 and P = 5.77 × 10−10 for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.

Follow-up of primary angle closure suspects after laser peripheral iridotomy using ultrasound biomicroscopy and A-scan biometry for a period of 2 years.

AimTo determine the morphologic changes in the anterior segment of primary angle closure suspects (PACS) who underwent laser peripheral iridotomy (LPI) for a period of 2 years. MethodsPACS (n=82 eyes) of Asian Indian origin who attended the Glaucoma clinic of tertiary eye hospital underwent A-scan biometry and ultrasound biomicroscopy. Anterior chamber depth, anterior chamber angle (ACA), axial length, lens thickness, relative lens position, central corneal thickness, angle opening distance 500, trabecular-ciliary process distance, iris-ciliary process distance, and iris thickness were measured before LPI and after LPI at 1 week, 6 months, 1 year, 1.5 years, and 2 years. Variation in the parameters measured over a period of 2 years was analyzed. ResultsFifteen eyes out of 52 eyes developed into primary angle closure (PAC) with synechial changes. Univariate analysis for the predictive factors of PAC showed no significant association for age, sex, narrow angle, ultrasound biomicroscopy parameters, and vertical cup-disc ratio. When analyzed as continuous variables, decreasing ACA was significant risk factor (95% confidence interval: 0.703, 0.989, P=0.037). Iris-ciliary process distance, ACA, lens thickness, and angle opening distance 500 were the parameters that varied significantly (P<0.05) between “before LPI group” and “after LPI groups.” None of the subjects developed increased intraocular pressure after laser iridotomy. ConclusionsIn this hospital-based study on the course of PACS subjects after LPI, as many as 28% progressed to PAC. Decreasing ACA was the predictive factor for the progression of PACS to PAC. There was no increase in intraocular pressure, history, or symptoms of acute attack of glaucoma among the study subjects after LPI.

Neural rim characteristics of healthy South Indians: the Chennai Glaucoma Study.

PURPOSE To report neural rim dimensions for South Indians and examine rim shape with relevance to clinical evaluation. METHODS Healthy phakic participants (n = 623) of the Chennai Glaucoma Study with normal frequency-doubling perimetry underwent complete eye examinations including optic disc digital stereophotography. Planimetry was performed under stereoviewing conditions using custom software. Rim area, shape, and associations were examined. Rim area asymmetry was studied in a subgroup of 565 subjects. RESULTS Mean neuroretinal rim area was 2.29 +/- 0.39 mm(2). Disc area (P < 0.001) and type of cupping (P < 0.001) were associated with rim area. Mean rim area asymmetry was 0.18 +/- 0.15 mm(2); 95% of subjects had asymmetry < 0.5 mm(2). Disc area asymmetry (0.359, P < 0.0001) and intraocular pressure (IOP) asymmetry (P = 0.004) were related to rim area asymmetry. On average, the inferior rim was thickest and the temporal was thinnest. Mean inferior by superior rim width was 1.18 +/- 0.17; 2.5 percentile, 0.9. Thirty-eight (7.1%) subjects had the superior rim thicker than the inferior rim, the occurrence of which was associated with disc torsion (P = 0.002) and male sex (P = 0.04). Of the clinically relevant rim width measures in glaucoma (i.e., inferior, superior, and temporal) the temporal rim was thinnest in 469 (87.8%) eyes. Horizontally oval disc shape (P < 0.0001), type of cupping (P = 0.006), and astigmatism (P = 0.001) were associated with the presence of thicker temporal than superior/inferior rims. CONCLUSIONS The report provides hitherto unreported neural rim measurements among healthy South Indians. The ISNT rule (inferior rim thicker than superior rim, thicker than nasal rim, thicker than temporal rim) was violated in a significant minority. Physiological associations with such violations are described.

Change in iris parameters with physiological mydriasis.

Purpose. A pilot study to analyze the association of change in iris parameters with physiological mydriasis in angle closure eyes compared with normal control eyes among south Indian participants. Methods. Sixteen eyes diagnosed with primary angle closure and 14 age, gender-matched open-angle control eyes were selected. All participants underwent anterior segment imaging using anterior segment optical coherence tomography in dim and bright illumination. The iris area (IA), iris volume (IV), and pupillary diameter were calculated using customized image processing software. Results. The IA and IV were found to be lesser in angle closure compared with normal controls. Average IA (dim and bright) was found to be 3.4 and 3.7 mm2 in normals and 3.03 and 3.35 mm2 in angle closure, and average IV (dim and bright) was found to be 24.28 and 26.09 mm3 in normals and 21.38 and 22.6 mm3 in angle closure. The IA and IV decreased significantly with pupillary dilation in normals and in angle closures. However, decrease in the IA (slope = 0.52 and 0.42; p = 0.012) and IV (slope = 1.97 and 1.41; p = 0.014) with pupillary dilation was significantly higher in normals compared with angle closures, respectively. Conclusions. IA and IV were found to decrease as pupil dilates in normal and angle closure eyes among South Indians. Loss in the IV was found to be lower in angle closure eyes.

Optic disc dimensions and cup-disc ratios among healthy South Indians: The Chennai Glaucoma Study.

Purpose: To present optic disc and cup dimensions, cup-disc ratios (CDRs) and asymmetry among healthy South Indians, and their associations with ocular and systemic variables. Methods: A total of 623 healthy phakic participants of the Chennai Glaucoma Study underwent complete eye examinations including optic disc stereo-photography. Planimetry was performed under stereo-viewing conditions. The morphological type of cupping (no cups, steep cups, partly sloping and fully sloping cups) was identified based on a modification of the classification by Jonas et al.[11] The associations of planimetric measures (optic disc area, cup area and vertical cup-disc ratio [VCDR]) with age, gender, height, intraocular pressure, refraction, astigmatism, axial length and corneal thickness as explanatory variables were examined. The associations of asymmetries in the above planimetric measures with age, gender and asymmetries of the above explanatory variables were examined. Results: Mean optic disc and cup areas were 2.82 ± 0.52 mm2 and 0.53 ± 0.39 mm2. Mean CDR was 0.36 ± 0.18. Men had larger discs (P = 0.03). Cup area and VCDR revealed significant associations with disc area (P <0.0001) and type of cupping (P < 0.0001). Mean disc and cup area asymmetries were 0.19 ± 0.16 mm2 and 0.15 ± 0.15 mm2. Mean VCDR asymmetry was 0.07 ± 0.08 mm2. Cup area and VCDR asymmetries showed significant associations with disc area asymmetry (P < 0.0001, both) and asymmetry in the presence or absence of physiological cupping, i.e. subjects with physiological cupping in one eye and no cupping in the other (P < 0.0001, both). Conclusions: We present normative optic disc, cup and VCDR measures and asymmetries among healthy South Indians. We demonstrated the dependence of VCDR on the morphological type of cupping.

Axial Alignment for Anterior Segment Swept Source Optical Coherence Tomography via Robust Low-Rank Tensor Recovery

We present a one-step approach based on low-rank tensor recovery for axial alignment in 360-degree anterior chamber optical coherence tomography. Achieving translational alignment and rotation correction of cross-sections simultaneously, this technique obtains a better anterior segment topographical representation and improves quantitative measurement accuracy and reproducibility of disease related parameters. Through its use of global information, the proposed method is more robust compared to using only individual or paired slices, and less sensitive to noise and motion artifacts. In angle closure analysis on 30 patient eyes, the preliminary results indicate that the proposed axial alignment method can not only facilitate manual qualitative analysis with more distinct landmark representation and much less human labor, but also can improve the accuracy of automatic quantitative assessment by 2.9 %, which demonstrates that the proposed approach is promising for a wide range of clinical applications.

Diagnostic accuracy of macular ganglion cell-inner plexiform layer thickness for glaucoma detection in a population-based study: Comparison with optic nerve head imaging parameters

Aims To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) for glaucoma detection in a Chinese population in comparison with optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters measured by both SD-OCT and Heidelberg Retina Tomography 3 (HRT-3). Methods Adults aged 40 to 80 years were recruited from the population-based study (n = 3353, response rate 72.8%). Macular cube 200x200 scan was performed with Cirrus SD-OCT (version 6.0, Carl Zeiss Meditec Inc, Dublin, CA) for GCIPL thickness measurement. ONH and RNFL imaging was performed with Cirrus SD-OCT and HRT-3 (Heidelberg Engineering, Heidelberg, Germany). Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. Results In total, 86 eyes of 60 subjects with glaucoma and 1709 eyes of 1001 non-glaucoma participants were included. The best performing parameters for Cirrus SD-OCT GCIPL, Cirrus SD-OCT ONH and HRT-3 were minimum GCIPL thickness (Area under receiver-operating curve [AUC] = 0.89, 95% CI 0.83–0.95), vertical cup-disc ratio (CDR) (AUC = 0.94, 0.91–0.98) and vertical CDR (AUC = 0.86, 0.81–0.92), respectively. At 85% specificity, vertical CDR measured using Cirrus OCT ONH scan showed the highest sensitivity (88.64%, 95% CI 75.4–96.2) compared to minimum GCIPL thickness with sensitivity of 60.53% (95% CI 46.4–73.0) (p<0.001). Inferior RNFL thickness (AUC = 0.84, 95% CI 0.91–0.97) measured by Cirrus SD-OCT was also superior to Cirrus SD-OCT GCIPL (p<0.007). Conclusions The diagnostic performance of macular GCIPL scan is inferior compared to vertical CDR measured by Cirrus OCT ONH scan. Cirrus OCT ONH scan showed the best ability in detecting glaucoma in a Chinese population, suggesting it could be a good glaucoma screening tool in an Asian population.

Agreement between clinical estimates and planimetric measures of vertical cup:disc ratio.

Clinical estimates and planimetric measurement of cup:disc ratio (CDR) are made under very different conditions. In the clinic, decisions are made under constraints of patient discomfort under bright lights, eye movement and limited time. Planimetry, on the other hand, permits comfortable and accurate measurement without time constraints. We examined the relationship between clinical estimates and planimetrically measured vertical CDR (VCDR) as part of the Chennai Glaucoma Study, a population-based survey of glaucoma in southern India. The methodology of the Chennai Glaucoma Study has been described earlier. The urban component included five random clusters in Chennai. Persons examined from two clusters were included here. Participants underwent a complete eye examination including frequency doubling perimetry (C-20-1 screening; Carl Zeiss Meditec, CA, USA), and dilated stereobiomicroscopic optic disc examination with a +78 D lens. Clinical VCDR (CVCDR) was assessed by one of two glaucoma specialists (HA and RG, each with 5 years’ experience in glaucoma). Subjects with clear media underwent fundus photography (Zeiss FF450-plus fundus camera) – one stereo-pair (non-simultaneous) of 20° optic disc photographs for each eye. Subjects with normal FDP were included. Patients with cataract, other ocular abnormality, media haze, aphakia, pseudophakia, nonavailable keratometry, poor quality photographs, unreliable/ abnormal FDP and myopia >-8.0 D were excluded. Planimetry was performed by one of the glaucoma specialists (HA), using custom planimetry software developed using MATLAB version 7 (Mathworks Inc, MA, USA). Stereo pairs of photographs were displayed together on a 15′ monitor. Optic disc and cup margins, vertical and horizontal disc and cup diameters were marked with the computer mouse under direct stereovision using a stereo viewer. When blood vessels obscured the cup margin, it was marked in continuation with the clearly visible areas on both sides of that vessel. Planimetric VCDR (PVCDR) was calculated as vertical cup diameter/vertical disc diameter. Corrections for ocular magnification were based on keratometry and refraction (Littmann’s correction). Right eye data of 531 persons with physiological cupping were analysed (Table 1 and Fig. 1). Good agreement between CVCDR and PVCDR was noted (intraclass correlation coefficient 0.65). Mean clinical minus planimetric VCDR was 0.04 0.11 (range -0.31 to 0.45). Altman–Bland plots (Fig. 1a) revealed that differences between the two methods increased with their average. Figure 1b presents the same data grouped into class intervals. At average VCDR of 0.3–0.4, there was negligible difference between the methods. At lower average VCDRs, PVCDR was greater than CVCDR. At