Comparison of Lamina Cribrosa Thickness in Normal Tension Glaucoma Patients With Unilateral Visual Field Defect

Comparison of Lamina Cribrosa Thickness in Normal Tension Glaucoma Patients With Unilateral Visual Field Defect YOUNGKYO KWUN, JONG CHUL HAN, AND CHANGWON KEE


PURPOSE:

To compare the lamina cribrosa thickness, measured by swept-source optical coherence tomography (SS OCT), between each eye of normal tension glaucoma (NTG) patients with unilateral visual field (VF) defect and to investigate the correlation between lamina cribrosa thickness and VF loss.
DESIGN: Prospective, cross-sectional study.
METHODS: Optic nerve heads were scanned using SS OCT, and laminar thickness was measured on midsuperior, central, and mid-inferior regions of vertical midline of the optic disc. The inter-eye differences of lamina cribrosa thickness in NTG patients with unilateral VF defect and the intra-eye difference of lamina cribrosa thickness in VF-affected eyes were analyzed using the paired t test. We evaluated the correlation between lamina cribrosa thickness and mean deviation, measured using standard automated perimetry, in NTG patients.
RESULTS: This study included 102 eyes in 51 NTG patients with unilateral VF defect and 47 eyes in 47 normal subjects without glaucomatous change in either eye. The mean lamina cribrosa thickness of normal fellow eyes was thicker than VF-affected eyes in NTG patients (P < .001), but thinner than normal subject eyes (P < .001). Within VF-affected eyes, lamina cribrosa thickness of regions correlated with visual field defect was thinner than horizontally contralateral locations (P < .001). The mean deviation was statistically correlated with inter-eye difference of lamina cribrosa thickness in NTG patients (n [ 51; r2 [ 0.12; P [ .01).
CONCLUSIONS: The lamina cribrosa was thinner in VF-unaffected eyes of NTG patients than in normal subject eyes, in VF-affected eyes than in normal fellow eyes of NTG patients, and in regions correlated with visual field loss than in horizontally contralateral ones in VF-affected eyes. (Am J Ophthalmol 2015;159: 512–518. Ó 2015 by Elsevier Inc. All rights reserved.) Accepted for publication Nov 26, 2014. From the Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Inquiries to Changwon Kee, Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, South Korea; e-mail: ckee@ skku.edu

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LAUCOMA IS THE MOST COMMON CAUSE OF IRRE-

versible blindness worldwide.1 However, the pathophysiology of glaucomatous optic atrophy remains unclear. Many studies have confirmed that elevated intraocular pressure (IOP) is one of the most important risk factors for glaucoma development and progression.2–6 However, even when IOP is maintained within the normal range, glaucomatous optic neuropathy such as normal tension glaucoma (NTG) can develop. Conversely, ocular hypertension with a high IOP can have normal functional and structural configurations. Therefore, non-IOP-related risk factors such as biomechanical, autoimmune, or blood flow issues must be considered and studied, especially in NTG. In regard to biomechanical factors, the optic nerve head (ONH) is considered a weak region owing to discontinuity in the corneoscleral shell.7 This discontinuity concentrates the stress or strain on the optic nerve. Therefore, the ONH, especially the lamina cribrosa, has come into focus as a key pathophysiologic site in glaucomatous optic neuropathy. The emergence and advancement of optical coherence tomography (OCT) has facilitated lamina cribrosa morphology and thickness evaluation. Studies performed using enhanced-depth imaging (EDI) OCT have shown that glaucoma patients have a thinner lamina cribrosa than glaucoma suspects or normal subjects, and that lamina cribrosa thickness is significantly correlated with the mean deviation (MD) in standard automated perimetry (SAP).8–10 However, there is little knowledge about the factors that could affect lamina cribrosa biomechanics and thickness, such as age or sex. Furthermore, biomechanical, vascular, and immunologic factors could contribute to glaucomatous optic neuropathy development. Human patients can have similar or identical blood flow, autoimmunity, cerebrospinal fluid (CSF) pressure, and extracellular matrix properties in both eyes. If 1 eye is diagnosed with NTG and the other has a normal configuration, many of the contributing factors would be controlled, and these patients could serve as an ideal model to assess the relationship between lamina cribrosa and NTG. Recently, swept-source OCT (SS OCT) became commercially available, and this instrument uses a longer wavelength and a higher scanning speed compared with currently used OCT. SS OCT was suitable for evaluating

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deeper structures such as the choroid and lamina cribrosa. Therefore, we measured lamina cribrosa thickness using SS OCT in both eyes of NTG patients with unilateral visual field (VF) defect to test the following hypotheses. First, when compared intra-individually, the lamina cribrosa would be thinner in the VF-affected eyes than in the normal fellow eyes. Second, when analyzed by intra-eye comparison in VF-affected eyes, the lamina cribrosa would be thinner in locations corresponding to the VF defect than in horizontally contralateral locations.

METHODS THIS

PROSPECTIVE,

CROSS-SECTIONAL

STUDY

WAS

approved by the Institutional Review Board of the Samsung Medical Center. All participants provided informed consent, and the study was carried out in accordance with the tenets of the Declaration of Helsinki. Fifty-one NTG patients with unilateral VF defect and 47 normal subjects were included in this study. The subjects were evaluated using SS OCT between May 2013 and April 2014 in the Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University in Seoul, South Korea. All participants underwent comprehensive ophthalmologic examinations including slit-lamp biomicroscopy, best-corrected visual acuity (BCVA), refractive error, central corneal thickness, and Goldmann applanation tonometry. An automated VF test was evaluated using the 30-2 Swedish interactive threshold algorithm standard program on a Humphrey 740 Visual Field Analyzer (HFA 30-2; Carl Zeiss Meditec, Dublin, California, USA). To identify glaucomatous ONH, retinal nerve fiber layer (RNFL) defect, and retinal pathology, a dilated stereoscopic examination of the optic disc and fundus and red-free fundus photography (TRC-50IX; Topcon Corp, Tokyo, Japan) were performed and reviewed for all participants. A single well-trained operator performed all SS OCT (DRI OCT1 Atlantis; Topcon Corp) and Cirrus OCT (Carl Zeiss Meditec Inc) and screened all the OCT scans during imaging. Rescanning was performed if the image was determined to be poor quality or to have off-center locations on ONH, or if there were scans with missing data. NTG with unilateral VF defect was defined as having 1 eye diagnosed with NTG, and the fellow eye showing no VF defect, glaucomatous ONH, or RNFL defect. Normal subjects were defined when they did not have any VF defect, glaucomatous optic disc, or significant eye disease in either eye. Randomly selected eyes in normal subjects were assigned as normal control group. NTG was diagnosed using the following criteria: glaucomatous ONH or RNFL defects with corresponding VF loss, open angle configura_21 mm Hg during tion on gonioscopy, and IOP recordings < the follow-up period. Glaucomatous ONH was defined as VOL. 159, NO. 3

neural rim thinning, focal notching, excavation, and cupto-disc ratio difference of greater than 0.2 determined by color stereoscopic photography. A localized RNFL defect was defined as a defect wider than the width of a major retinal vessel at 1 disc diameter distance from the edge of the disc, which widened into an arcuate or wedge shape and reached the edge of the disc as determined by redfree fundus photography. Glaucomatous VF defects were defined as the presence of a cluster of 3 or more contiguous non-edge points on the pattern deviation probability plot with a probability less than 5% and with at least 1 of these points having a probability less than 1%. This was confirmed on 2 consecutive tests. Test results were considered unreliable and excluded if the fixation loss was more than 30% or the false-positive or false-negative was greater than 33%. All examinations were evaluated and recorded by 2 experienced observers (Y.K., J.C.H.) in a masked fashion. Exclusion criteria were as follows: (1) older than 80 years old or younger than 20 years old, (2) BCVA less than 20/ 40, (3) refractive error less than -6 diopters or more than þ6 diopters, (4) history of intraocular surgery including laser treatment and refractive surgery, (5) media opacity that reduced image quality, (6) non-glaucoma conditions that affect VF, (7) glaucomatous VF defect in both eyes, or (8) an invisible lamina cribrosa posterior border in the scanned images.
SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY OF THE OPTIC NERVE HEAD: We used SS OCT with a

1050-nm wavelength and a 100 nm tuning range swept source to scan the ONH in each patient. The scans yielded an approximately 8 mm depth and a 20 mm transverse resolution. The tunable laser source allowed for quick scans through the range of relevant frequencies, and the longer wavelength could visualize deep fundus structures, including the choroid and lamina cribrosa.11–15 This technique provided high-quality images with constant signal strength of the posterior pole, even in eyes with cataracts that affected image quality because of light scattering.16 The instrument provided up to 100 000 A-scans per second and an invisible scanning line owing to the long wavelength, which could reduce an eye movement and provide more successful scans. The lamina cribrosa was captured using the 3-dimensional (3D) optic disc scan protocol that covered a 3 3 3-mm area with a depth of 2.6 mm centered on the ONH. Each dataset consisted of 256 cross-sectional B-scan images of 512 3 256 pixels. The total data acquisition time for a 3D optic disc scan was 0.9 seconds. An internal nasal fixation light was used to center the ONH in the rectangle imaging mode.
MEASUREMENT OF LAMINA CRIBROSA THICKNESS:

The lamina cribrosa thickness was defined as the distance between the anterior and posterior borders of the highly reflective region visible beneath the ONH in a

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FIGURE 1. Disc photographs and horizontal cross-sectional B-scan images of the optic nerve head collected using swept-source optical coherence tomography (SS OCT). Lamina cribrosa thickness was measured along 3 lines: the mid-superior (Top), central (Middle), and mid-inferior lines (Bottom) of the optic nerve head. Mid-superior and mid-inferior lines were identified as the horizontal line located at the halfway point on the vertical line that connects the optic disc center to the margin. At each line, the laminar thickness was measured at 3 locations along a line perpendicular to the reference line that connected the ends of the Bruch membrane (white glyph): at the center of the reference line, located 50 mm temporally, and 100 mm temporally.

cross-sectional B-scan SS OCT image. For identifying the anterior and posterior borders of the lamina cribrosa, horizontal SS OCT B-scans were assessed in Adobe Photoshop CS2 (version 9.0; Adobe Systems, Inc, San Jose, California, USA). A quantitative lamina cribrosa thickness measurement was performed on 3 lines including the mid-superior, central, and mid-inferior lines of the optic disc using the manual caliper tool in DRI OCT Viewer 9.01 (Figure 1). Mid-superior and mid-inferior lines were identified as the horizontal line on the middle of the vertical line connecting the center to the margin of the optic disc. At each line, laminar thickness was measured at 3 locations along a perpendicular line from the reference line connecting the end of the Bruch membrane: the center of the reference line, 50 mm temporally, and 100 mm temporally. Laminar thickness was the average of those 3 measurements. In this 514

study, beta, ‘‘b,’’ was defined as the average laminar thickness measured on the vertical center of the optic disc. Alpha, ‘‘a,’’ was defined as the average laminar thickness measured at the halfway point of a vertical line connecting the optic disc center to the margin in the direction of the VF defect in VF-affected eyes or the corresponding location in fellow eyes. Gamma, ‘‘g,’’ was defined as the average laminar thickness measured at points horizontally contralateral to ‘‘a.’’ For evaluating the inter-observer reproducibility of our measurements, lamia cribrosa thickness from 30 randomly selected SS OCT cross-sectional B-scans was independently measured by both observers (Y.K., J.C.H.) without clinical information.
STATISTICAL

ANALYSIS: Statistical analyses were performed using SPSS (version 21.0; SPSS Inc, Chicago,

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TABLE 1. Demographic Data of the Visual Field-Affected Eyes and Contralateral Normal Eyes in Normal Tension Glaucoma Patients With Unilateral Visual Field Defect, and Eyes in Normal Subjects NTG (n ¼ 51) Affected Eyes

Unaffected Eyes

P Valuea

Controls (n ¼ 47)

P Valueb

.661 .124

57.4 6 12.1 23/24 536.0 6 31.0 1.2 6 2.2

.605 .417 .013 .975

.093 .274

17.1 6 3.1 16.7 6 3.1

.059 <.001

0.1 6 1.6 2.0 6 0.6 87.9 6 10.4 219.5 6 28.4

.884 .635 .174 <.001

56.2 6 11.3 30/21 519.6 6 36.3 518.7 6 35.3 1.3 6 2.3 1.2 6 2.1

Age (y) Male/female Central corneal thickness (mm) Refractive error (diopters) Intraocular pressure (mm Hg) Initial visit At scanning disc Automated perimetry (dB) MD PSD RNFL average thickness (mm) Mean LCT (mm)

16.4 6 2.9 14.0 6 2.3

15.9 6 2.7 14.3 6 2.7

5.7 6 5.3 10.8 6 12.0 71.5 6 11.3 178.9 6 28.3

0.1 6 1.5 2.0 6 0.7 84.6 6 10.4 196.4 6 28.6

<.001 <.001 <.001 <.001

LCT ¼ lamina cribrosa thickness; MD ¼ mean deviation; NTG ¼ normal tension glaucoma; PSD ¼ pattern standard deviation; RNFL ¼ retinal nerve fiber layer. Values are expressed as mean 6 standard deviation. a Paired t test between VF-affected eyes with fellow normal eyes of NTG patients with unilateral visual field defect. b t test between VF-unaffected eyes of NTG patients with eyes of normal subjects.

TABLE 2. Comparisons of Lamina Cribrosa Thickness Between the Visual Field–Affected Eyes and Contralateral Normal Eyes in Normal Tension Glaucoma Patients, and Between Visual Field–Presenting Locations in the Visual Field–Affected Eyes Measured Locationsa

Affected eye, mm Unaffected eye, mm P valueb

P Valueb

a

b

g

a vs b

b vs g

a vs g

169.1 6 24.0 192.1 6 29.3 <.001

185.1 6 29.1 202.0 6 30.5 <.001

180.4 6 29.0 192.1 6 31.5 <.001

<.001 <.001

.012 <.001

<.001 1.000

N ¼ 47; 4 patients with both hemifield defects in the normal tension glaucoma eye are excluded. Values are expressed as mean 6 standard deviation. a b is defined as the average laminar thickness measured on vertical center of the optic disc. a is defined as the average laminar thickness measured at the halfway point of a vertical line connecting the optic disc center to the margin in the direction of the VF defect in VF-affected eyes or the corresponding location in fellow eyes. g is defined as the average laminar thickness measured at points horizontally contralateral to ‘‘a.’’ b Paired t test is corrected by Bonferroni method.

Illinois, USA). A paired t test was used to compare related data values measured from both eyes of NTG patients. In cases of multiple comparisons, Bonferroni correction was applied to control the family-wise error rate. The interobserver reproducibility of lamina cribrosa thickness measurements was evaluated by calculating the intraclass correlation coefficient (ICC). We used the t test to compare the means of data from VF-unaffected NTG patient eyes and normal control eyes. A linear regression analysis was performed to evaluate the statistical correlation between MD measured by SAP and lamina cribrosa thickness. P values less than .05 were considered statistically significant. VOL. 159, NO. 3

RESULTS THE OPTIC DISC OCT IMAGES WERE COLLECTED FOR 180 EYES

from 120 patients (120 eyes in 60 NTG patients and 60 eyes in 60 normal subjects). In 11 of the eyes, vascular shadowing prevented clear lamina cribrosa structure imaging. In 21 of the eyes, the posterior borders of the highly reflective region beneath the optic disc cup were unresolvable. Images from these eyes were excluded from analyses. If 1 eye of an NTG patient was excluded then data from both eyes were excluded from the analysis. The remaining 149 eyes in 98 subjects were evaluated and analyzed. The NTG group included 102 eyes in 51 patients who had

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FIGURE 2. The correlation between lamina cribrosa thickness and mean deviation (MD) in normal tension glaucoma (NTG) patients with unilateral visual field defect. The MD was measured by standard automated perimetry using the 30-2 Swedish interactive threshold algorithm standard program. (Left) The linear regression analysis scatterplot indicated that MD was significantly correlated with the mean lamina cribrosa thickness in VF-affected eyes (n [ 51; r2 [ 0.08; P [ .04). (Right) The inter-eye lamina cribrosa thickness difference between VF-affected eyes and normal fellow eyes was statistically correlated with MD (n [ 51; r2 [ 0.12; P [ .01).

been treated with IOP-lowering eye drops for VF-affected eyes. The average age of the NTG group was 56.2 6 11.3 years (range: 27–79 years; 30 men and 21 women). The normal control group included 47 eyes in 47 subjects with an average age of 57.4 6 12.1 years (range: 23–80 years; 23 men and 24 women). There was no statistically significant difference in age or sex between the 2 groups (Table 1). Within the NTG group, there was no difference in central corneal thickness (P ¼ .661), refractive error (P ¼ .124), or intraocular pressure at baseline (P ¼ .093) between VF-affected and fellow eyes. Mean lamina cribrosa thickness was 178.9 6 28.3 mm in VF-affected eyes and 196.4 6 28.6 mm in fellow eyes; therefore, lamina cribrosa in VF-affected eyes were significantly thinner than in fellow eyes (P < .001). The mean lamina cribrosa thickness for the normal control group was 219.5 6 28.4 mm, which was significantly thicker than the VF-unaffected eyes of the NTG group (P < .001). The lamina cribrosa thickness measurement reproducibility was excellent (ICC ¼ 0.831, 95% confidence interval, 0.812–0.847). Intra-eye comparisons of lamina cribrosa thickness in the VF-affected eyes of the NTG group showed a statistically significant difference between the VF defect–presenting locations (Table 2). Four patients with both hemifield defects in the VF-affected eye were excluded, and 47 patients were included in the analyses. The lamina cribrosa thicknesses of ‘‘b,’’ ‘‘a,’’ and ‘‘g’’ were 185.1 6 29.1 mm, 169.1 6 24.0 mm, and 180.4 6 29.0 mm in VF-affected eyes and 202.0 6 30.5 mm, 192.1 6 29.3 mm, and 192.1 6 31.5 mm in fellow eyes, respectively. The lamina cribrosa thickness of ‘‘b,’’ center of the lamina cribrosa, was the thickest location regardless of group. The lamina cribrosa thickness of ‘‘a’’ was significantly thinner than ‘‘g’’ in VFaffected eyes (P < .001) but not in fellow eyes (P ¼ 1.000). Linear regression analyses revealed that the MD values in SAP were correlated with the mean lamina cribrosa 516

thickness of VF-affected eyes (r2 ¼ 0.08; P ¼ .04) and inter-eye difference of mean lamina cribrosa thickness in both eyes of NTG patients with unilateral VF defect (r2 ¼ 0.12; P ¼ .01; Figure 2).

DISCUSSION IN THIS STUDY, WE DEMONSTRATED THAT LAMINA

cribrosa thickness was associated with VF defect and glaucomatous optic neuropathy. In NTG patients with unilateral VF defect, VF-affected eyes had a thinner lamina cribrosa than fellow eyes with normal configuration. Although the normal fellow eyes of NTG patients did not have any VF defects, glaucomatous ONH, or RNFL defects, the lamina cribrosa was thinner than in normal control subject eyes. The results of our study agree with previous experimental and clinical studies. Jonas and associates17 evaluated the lamina cribrosa in eyes that were enucleated because of malignant choroidal melanoma without optic nerve involvement (control group) or because of painful absolute secondary angle-closure glaucoma (glaucoma group). This study determined that the lamina cribrosa was significantly thinner in the glaucoma group compared with the control group. Recently, several studies performed using EDI OCT to investigate the ONH have shown that lamina cribrosa thickness is associated with VF defect. Other studies have shown that lamina cribrosa thickness was significantly correlated with VF defects as determined by MD in SAP,8 and those results agreed with our study. Furthermore, we showed that the MD of VF-affected eyes had a stronger relationship with the inter-eye difference of lamina cribrosa thickness than with lamina cribrosa thickness in VF-affected eyes. This study was conducted using intraindividual comparison, which ensures that both eyes have

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similar risk factors for glaucoma and avoids confounding factors that are known as risk factors for glaucoma, such as age, race, sex, family history of glaucoma, diabetes mellitus, and hypertension. Therefore, inter-eye differences of lamina cribrosa thickness in NTG patients with unilateral VF defects could be correlated with retinal ganglion cell axon loss and, consequently, a VF defect. The inter-eye thickness difference had a greater correlation than the individual lamina cribrosa thickness measurements in VFaffected eyes. Previous studies have shown that the lamina cribrosa was thinner in the glaucoma group than in the normal control group.9,10 Recently, Park and Park18 reported that the lamina cribrosa was thinner in eyes with NTG than in those with primary open-angle glaucoma despite similar visual loss severity, and that laminar thickness was comparable to peripapillary RNFL thickness for diagnosing glaucoma. Finite element models of the ONH have predicted that the peripheral location of the lamina cribrosa exposes it to relatively high strain.7,19–22 This suggested that when the lamina cribrosa is deformed by IOP, some areas could experience more strain while others remain largely unaffected. As a result, the biological effects on cells would depend more on the local strain or stress than the global levels.23 In this study, lamina cribrosa locations corresponding to the VF defect were thinner than the horizontally contralateral locations. This susceptibility could be caused by differences in the laminar pore size,24,25 anatomic relationships with the cerebrospinal space,17 and retinal vascular diameter.26,27 Many groups hypothesized that IOP-related deformations could cause anterior laminar beam failure, which in turn would transfer the load to adjacent beams, causing a damage cascade that results in glaucomatous optic disc cupping and thinning of the entire lamina cribrosa.19,28–31 In this study, the central locations of the lamina cribrosa in VFaffected eyes were significantly thinner than in the fellow eyes in NTG patients with unilateral VF defect. This study

also determined that the normal subject eyes had thicker lamina cribrosa than the VF-unaffected eyes of NTG patients. Similarly, Kim and associates32 showed that the RNFL thicknesses of VF-unaffected eyes of NTG patients were thinner than normal controls that did not have any VF defects in both eyes; this may indicate that RNFL thickness reductions were already present in the VF-unaffected eyes of NTG patients. Our study suggests that NTG patients might have thinner lamina cribrosa, regardless of VF defect, and that could make the ONH susceptible even within a normal IOP range. However, a cohort study examining the risk of developing VF defects based on lamina cribrosa thickness should be performed to confirm this hypothesis. There were several limitations to our study. First, because this study was cross-sectional, it is unclear whether the NTG patients originally had thinner lamina cribrosa than normal subjects, or whether thinner lamina cribrosa resulted from IOP stress or strain. However, because the VF-unaffected eyes of NTG patient had thinner lamina cribrosa compared with normal subject eyes, a thin lamina cribrosa could contribute to glaucomatous changes. Longitudinal studies are needed to clarify this temporal ambiguity. Second, we defined the posterior border of the lamina cribrosa as posterior borders of the highly reflective area; however, these borders have not been confirmed by histology. Strouthidis and associates33 demonstrated that, in histologic sections, the anterior laminar border matched the anterior border of the highly reflective region in OCT cross-sectional B-scans; however, the posterior surface was not detectable. In conclusion, the laminar thickness was thinner in the VF-unaffected eyes of NTG patients compared with normal subject eyes, in the VF-affected eyes of NTG patients compared with the contralateral VF-unaffected eyes, and in locations corresponding to VF defect compared with horizontally contralateral locations within VF-affected eyes. Therefore, thinner lamina cribrosa could contribute to the development of normal tension glaucoma.

ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and none were reported. The authors indicate no funding support, and have no financial conflicts of interest. Contributions of authors: involved in conception, design, and conduct of the study (Y.K., J.C.H., C.K.); collection, management, and interpretation of data (Y.K., J.C.H., C.K.); data analysis (Y.K., J.C.H., C.K.); and preparation, review, and approval of the manuscript (Y.K., J.C.H., C.K.).

REFERENCES 1. Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82(11):844–851. 2. 7 TAGISA. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol 2000;130(4):429–440. 3. Anderson DR, Drance SM, Schulzer M. Natural history of normal-tension glaucoma. Ophthalmology 2001;108(2):247–253.

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4. Bengtsson B, Heijl A. A long-term prospective study of risk factors for glaucomatous visual field loss in patients with ocular hypertension. J Glaucoma 2005;14(2):135–138. 5. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120(10):1268–1279. 6. Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol 2003;121(1):48–56.

LAMINA CRIBROSA THICKNESS IN NORMAL TENSION GLAUCOMA

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7. Bellezza AJ, Hart RT, Burgoyne CF. The optic nerve head as a biomechanical structure: initial finite element modeling. Invest Ophthalmol Vis Sci 2000;41(10):2991–3000. 8. Inoue R, Hangai M, Kotera Y, et al. Three-dimensional highspeed optical coherence tomography imaging of lamina cribrosa in glaucoma. Ophthalmology 2009;116(2):214–222. 9. Lee EJ, Kim TW, Weinreb RN, Park KH, Kim SH, Kim DM. Visualization of the lamina cribrosa using enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2011;152(1):87–95 e1. 10. Park HY, Jeon SH, Park CK. Enhanced depth imaging detects lamina cribrosa thickness differences in normal tension glaucoma and primary open-angle glaucoma. Ophthalmology 2012; 119(1):10–20. 11. Hirata M, Tsujikawa A, Matsumoto A, et al. Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52(8):4971–4978. 12. Ohno-Matsui K, Akiba M, Moriyama M, et al. Acquired optic nerve and peripapillary pits in pathologic myopia. Ophthalmology 2012;119(8):1685–1692. 13. Srinivasan VJ, Adler DC, Chen Y, et al. Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head. Invest Ophthalmol Vis Sci 2008;49(11):5103–5110. 14. Takayama K, Hangai M, Kimura Y, et al. Three-dimensional imaging of lamina cribrosa defects in glaucoma using sweptsource optical coherence tomography. Invest Ophthalmol Vis Sci 2013;54(7):4798–4807. 15. Schuman JS. Spectral domain optical coherence tomography for glaucoma (an AOS thesis). Trans Am Ophthalmol Soc 2008;106:426–458. 16. Esmaeelpour M, Povazay B, Hermann B, et al. Three-dimensional 1060-nm OCT: choroidal thickness maps in normal subjects and improved posterior segment visualization in cataract patients. Invest Ophthalmol Vis Sci 2010;51(10): 5260–5266. 17. Jonas JB, Berenshtein E, Holbach L. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest Ophthalmol Vis Sci 2003;44(12):5189–5195. 18. Park HY, Park CK. Diagnostic capability of lamina cribrosa thickness by enhanced depth imaging and factors affecting thickness in patients with glaucoma. Ophthalmology 2013; 120(4):745–752. 19. Edwards ME, Good TA. Use of a mathematical model to estimate stress and strain during elevated pressure induced lamina cribrosa deformation. Curr Eye Res 2001;23(3): 215–225.

518

20. Sigal IA. Interactions between geometry and mechanical properties on the optic nerve head. Invest Ophthalmol Vis Sci 2009;50(6):2785–2795. 21. Sigal IA, Flanagan JG, Ethier CR. Factors influencing optic nerve head biomechanics. Invest Ophthalmol Vis Sci 2005; 46(11):4189–4199. 22. Sigal IA, Flanagan JG, Tertinegg I, Ethier CR. Predicted extension, compression and shearing of optic nerve head tissues. Exp Eye Res 2007;85(3):312–322. 23. Tan JC, Kalapesi FB, Coroneo MT. Mechanosensitivity and the eye: cells coping with the pressure. Br J Ophthalmol 2006;90(3):383–388. 24. Quigley HA, Addicks EM. Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthalmol 1981;99(1):137–143. 25. Radius RL. Regional specificity in anatomy at the lamina cribrosa. Arch Ophthalmol 1981;99(3):478–480. 26. Chang M, Yoo C, Kim SW, Kim YY. Retinal vessel diameter, retinal nerve fiber layer thickness, and intraocular pressure in Korean patients with normal-tension glaucoma. Am J Ophthalmol 2011;151(1):100–105.e1. 27. Mitchell P, Leung H, Wang JJ, et al. Retinal vessel diameter and open-angle glaucoma: the Blue Mountains Eye Study. Ophthalmology 2005;112(2):245–250. 28. Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res 2005;24(1):39–73. 29. Jonas JB, Berenshtein E, Holbach L. Lamina cribrosa thickness and spatial relationships between intraocular space and cerebrospinal fluid space in highly myopic eyes. Invest Ophthalmol Vis Sci 2004;45(8):2660–2665. 30. Ren R, Wang N, Li B, et al. Lamina cribrosa and peripapillary sclera histomorphometry in normal and advanced glaucomatous Chinese eyes with various axial length. Invest Ophthalmol Vis Sci 2009;50(5):2175–2184. 31. Sigal IA, Ethier CR. Biomechanics of the optic nerve head. Exp Eye Res 2009;88(4):799–807. 32. Kim DM, Hwang US, Park KH, Kim SH. Retinal nerve fiber layer thickness in the fellow eyes of normal-tension glaucoma patients with unilateral visual field defect. Am J Ophthalmol 2005;140(1):165–166. 33. Strouthidis NG, Grimm J, Williams GA, Cull GA, Wilson DJ, Burgoyne CF. A comparison of optic nerve head morphology viewed by spectral domain optical coherence tomography and by serial histology. Invest Ophthalmol Vis Sci 2010;51(3):1464–1474.

AMERICAN JOURNAL OF OPHTHALMOLOGY

MARCH 2015

Biosketch Youngkyo Kwun, MD, is a glaucoma fellow at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. After graduating from Sungkyunkwan University School of Medicine he completed internship and residency at Samsung Medical Center, Sungkyunkwan University School of Medicine. His interests are progression of normal tension glaucoma and imaging of the lamina cribrosa.

VOL. 159, NO. 3

LAMINA CRIBROSA THICKNESS IN NORMAL TENSION GLAUCOMA

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