Glaucoma
Optic Disc Tilt Direction Determines the Location of Initial Glaucomatous Damage Jin A. Choi,1 Hae-Young Lopilly Park,2 Hye-Young Shin,3 and Chan Kee Park2 1
St. Vincent’s Hospital, Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul, Korea Seoul St. Mary’s Hospital, Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul, Korea 3Uijeongbu St. Mary’s Hospital, Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul, Korea 2
Correspondence: Chan Kee Park, Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, Catholic University of Korea, #505 Banpodong, Seocho-ku, Seoul, 137-701, Korea; [email protected]. Submitted: April 25, 2014 Accepted: June 17, 2014 Citation: Choi JA, Park H-YL, Shin H-Y, Park CK. Optic disc tilt direction determines the location of initial glaucomatous damage. Invest Ophthalmol Vis Sci. 2014;55:4991–4998. DOI:10.1167/iovs.14-14663
PURPOSE. To explore differences in optic disc tilt and torsion between normal control and glaucoma subjects, and to determine whether the direction of optic disc tilt is consistent with the initial location of glaucomatous visual field (VF) defect. METHODS. Glaucoma patients with isolated superior or inferior hemifield loss (n ¼ 136) and normal controls (n ¼ 99) were analyzed. Disc ovality index and torsion degree were measured on retinal photographs. Imaging of optic disc was obtained using Heidelberg retinal tomography (HRT) III and Cirrus spectral-domain optical coherence tomography (OCT). The degree of temporal disc tilt was assessed using horizontal topographic images and vertical (upward or downward) disc tilt using vertical topographic images, respectively. RESULTS. In all subjects, disc ovality was significantly associated with HRT- and OCT-measured temporal disc tilt and axial length (AL) (all P < 0.001), whereas disc torsion degree was associated with HRT- and OCT-measured vertical disc tilt and AL (all P < 0.05). Association of AL with disc ovality and torsion became more evident as the mean deviation increased. When data on glaucoma patients with superior and inferior hemifield defects were compared, the vertical disc tilt (HRT- and OCT-assessed, P < 0.001 and 0.030, respectively) and the torsion degree (P ¼ 0.002) differed significantly. Upon multivariate logistic regression analysis, the HRT-measured vertical disc tilt was an independent factor determining initial location of the VF defect (P ¼ 0.012). CONCLUSIONS. Measurement of vertical disc tilt may give valuable information about the superior versus inferior regional susceptibilities of glaucoma. Keywords: optic disc, disc torsion, susceptibility, retinal nerve fiber layer defect, disc tilt
vidence indicates that particular optic disc morphologic parameters, including peripapillary atrophy (PPA), disc torsion, and tilt, are associated with regional susceptibility to glaucomatous damage.1–4 Beta-zone PPA, which occurs more commonly in glaucomatous eyes, is associated with both glaucoma development and subsequent disease progression.1,2 In a recent study, the location of the largest beta-zone PPA was found to predict rapid deterioration of the visual field (VF).3 In addition, the disc torsion direction is associated with the location of the glaucomatous damage (superior versus inferior) in patients with myopic normal-tension glaucoma.4 These findings suggest that optic disc characteristics are relevant to glaucoma pathogenesis. Advances in imaging techniques have enabled high-level axial resolution of optic disc anatomy, in turn allowing precise examination of the optic disc. New imaging techniques and novel methods of direct optic disc tilt determination have been described.5–7 The optic disc tilt direction was divided into horizontal (disc tilt in the temporal direction) and vertical (disc tilt in the upward or downward direction) planes using horizontal and vertical height profiles in confocal scanning laser ophthalmoscopy, and the degree of the disc tilt in each plane was determined.5 The degree of disc tilt in the temporal direction has also been evaluated using a new approach to spectral-domain optical coherence tomography (OCT), known
E
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
as enhanced depth imaging.6 In both of these studies, the degree of temporal disc tilt was significantly associated with disc ovality, which has been used as a surrogate index of tilt.5,6 However, little is known about the clinical significance of vertical disc tilt. Disc tilt is thought to result from posterior scleral expansion, particularly in myopic eyes.8 There has recently been considerable interest in understanding the anatomy of the posterior sclera in relation to glaucoma, because the peripapillary sclera of glaucomatous eyes may have different biomechanics compared to healthy eyes. 9–11 Therefore, a comprehensive evaluation of the optic disc tilt in glaucomatous eyes will help elucidate glaucoma pathophysiology. In the present study, we investigated differences in optic disc tilt and torsion between normal control and glaucoma subjects. In addition, we determined whether the direction of the optic disc tilt is consistent with the location of the initial glaucomatous VF defect.
PATIENTS
AND
METHODS
Study Subjects The medical records of all consecutive patients with primary open-angle glaucoma (POAG) with isolated superior or inferior 4991
IOVS j August 2014 j Vol. 55 j No. 8 j 4992
Impact of Upward or Downward Disc Tilt on Glaucoma hemifield defects, examined by a glaucoma specialist (CKP) between August 2010 and September 2011 at the glaucoma clinic of Seoul St. Mary’s Hospital (Seoul, Korea), were reviewed retrospectively. When both eyes of a patient met the inclusion criteria, one eye was randomly selected for evaluation. Each initial patient visit featured a review of medical history; measurement of best-corrected visual acuity and refraction; slit-lamp biomicroscopy; gonioscopy; Goldmann applanation tonometry; dilated stereoscopic examination of the optic disc; disc and red-free fundus photography (Canon, Tokyo, Japan); standard automated perimetry (SAP; 24-2 Swedish Interactive Threshold Algorithm, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc., Dublin, CA, USA); and measurement of central corneal thickness and axial length (AL) (Tomey Corporation, Nagoya, Japan). Optical coherence tomography using a Cirrus HD-OCT (Carl Zeiss Meditec, Inc.) and confocal scanning laser ophthalmoscopy using Heidelberg Retina Tomograph III (HRT III; Heidelberg Engineering, Heidelberg, Germany) were performed. Patients were followed up in an identical manner, usually at 6- to 12-month intervals. The study was performed in strict accord with the tenets of the Declaration of Helsinki after approval by our Institutional Review Board. All included subjects had a best-corrected visual acuity ‡ 20/40 on two or more consecutive VF tests, and normal anterior chamber angles in both eyes on slit-lamp biomicroscopy and gonioscopy. Patients with a neurologic or intraocular disease that could cause a VF defect, eyes yielding consistently unreliable VF results (defined as > 25% false-negative results, > 25% false-positive results, or > 20% fixation losses), and eyes with high myopia (a spherical equivalent [SE] 10 diopters [D], thus outside the focal range of the HRT III [SE ‡ þ12 D]), were excluded. Subjects with an intraocular pressure (IOP) 21 mm Hg, a normal optic disc appearance upon examination of color stereoscopic photographs (an intact neuroretinal rim without peripapillary hemorrhage, thinning, or localized pallor), absence of any retinal nerve fiber layer (RNFL) abnormality visible on red-free fundus photographs, and normal VF test results were included in the normal group. A normal VF presentation was defined as a glaucoma hemifield test result within normal limits and mean and pattern standard deviation values associated with probabilities of normality greater than 5%. Glaucoma was defined by the presence of glaucomatous optic neuropathy associated with typical reproducible VF defects evident on SAP. A glaucomatous VF change was defined as a glaucoma hemifield test result outside normal limits and the presence of at least three contiguous points in the pattern deviation plot with P values < 5%, with at least one point associated with a P value < 1% (excluding points directly above or below the blind spot), on two consecutive reliable SAP examinations. Consecutive eyes with VF defect clusters within or outside the central 108 of an isolated hemifield were selected and designated as a central and a peripheral subgroup, respectively. These two VF regions were divided into the superior and inferior sectors, as in a previous study.12 Patients with overlapping VF defect clusters in both sectors were excluded from the study. To minimize false-positive results, a VF loss had to be apparent on at least two consecutive examinations.
Measurement of Disc Ovality and Torsion Color disc and red-free RNFL photographs were obtained using standard settings of a nonmydriatic retinal camera (Nonmyd 7; Kowa, Tokyo, Japan). The photographs and red-free images
were evaluated independently, in random order and in a masked fashion, by two of the authors (JAC and H-YLP), who thus lacked knowledge of all clinical information. Disc ovality and torsion were measured on photographs using National Institutes of Health image analysis software (ImageJ version 1.40; available at http://rsb.info.nih.gov/ij/index.html [in the public domain]; developed by Wayne Rasband, National Institutes of Health, Bethesda, MD, USA). Disc ovality index was determined using the tilt ratio, which is the ratio between the longest and shortest disc diameter.13,14 Disc torsion was defined as the deviation of the long disc axis from the vertical meridian, which was a vertical line perpendicular to a reference line connecting the fovea and the center of the disc.4 The angle between the vertical meridian and the long axis of the disc was termed the degree of torsion. Positive and negative angles indicated the presence of inferotemporal and supranasal torsion, respectively.
Definitions of Temporal and Vertical Disc Tilt The degrees of temporal and vertical disc tilt were measured using both HRT III and Cirrus HD-OCT. First, topographic analysis of the optic disc was performed using HRT III. Topographic images were obtained through dilated pupils. The intrascan standard deviation was required to be
Optic Disc Tilt Direction Determines the Location of Initial Glaucomatous Damage Jin A. Choi,1 Hae-Young Lopilly Park,2 Hye-Young Shin,3 and Chan Kee Park2 1
St. Vincent’s Hospital, Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul, Korea Seoul St. Mary’s Hospital, Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul, Korea 3Uijeongbu St. Mary’s Hospital, Department of Ophthalmology, College of Medicine, Catholic University of Korea, Seoul, Korea 2
Correspondence: Chan Kee Park, Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, Catholic University of Korea, #505 Banpodong, Seocho-ku, Seoul, 137-701, Korea; [email protected]. Submitted: April 25, 2014 Accepted: June 17, 2014 Citation: Choi JA, Park H-YL, Shin H-Y, Park CK. Optic disc tilt direction determines the location of initial glaucomatous damage. Invest Ophthalmol Vis Sci. 2014;55:4991–4998. DOI:10.1167/iovs.14-14663
PURPOSE. To explore differences in optic disc tilt and torsion between normal control and glaucoma subjects, and to determine whether the direction of optic disc tilt is consistent with the initial location of glaucomatous visual field (VF) defect. METHODS. Glaucoma patients with isolated superior or inferior hemifield loss (n ¼ 136) and normal controls (n ¼ 99) were analyzed. Disc ovality index and torsion degree were measured on retinal photographs. Imaging of optic disc was obtained using Heidelberg retinal tomography (HRT) III and Cirrus spectral-domain optical coherence tomography (OCT). The degree of temporal disc tilt was assessed using horizontal topographic images and vertical (upward or downward) disc tilt using vertical topographic images, respectively. RESULTS. In all subjects, disc ovality was significantly associated with HRT- and OCT-measured temporal disc tilt and axial length (AL) (all P < 0.001), whereas disc torsion degree was associated with HRT- and OCT-measured vertical disc tilt and AL (all P < 0.05). Association of AL with disc ovality and torsion became more evident as the mean deviation increased. When data on glaucoma patients with superior and inferior hemifield defects were compared, the vertical disc tilt (HRT- and OCT-assessed, P < 0.001 and 0.030, respectively) and the torsion degree (P ¼ 0.002) differed significantly. Upon multivariate logistic regression analysis, the HRT-measured vertical disc tilt was an independent factor determining initial location of the VF defect (P ¼ 0.012). CONCLUSIONS. Measurement of vertical disc tilt may give valuable information about the superior versus inferior regional susceptibilities of glaucoma. Keywords: optic disc, disc torsion, susceptibility, retinal nerve fiber layer defect, disc tilt
vidence indicates that particular optic disc morphologic parameters, including peripapillary atrophy (PPA), disc torsion, and tilt, are associated with regional susceptibility to glaucomatous damage.1–4 Beta-zone PPA, which occurs more commonly in glaucomatous eyes, is associated with both glaucoma development and subsequent disease progression.1,2 In a recent study, the location of the largest beta-zone PPA was found to predict rapid deterioration of the visual field (VF).3 In addition, the disc torsion direction is associated with the location of the glaucomatous damage (superior versus inferior) in patients with myopic normal-tension glaucoma.4 These findings suggest that optic disc characteristics are relevant to glaucoma pathogenesis. Advances in imaging techniques have enabled high-level axial resolution of optic disc anatomy, in turn allowing precise examination of the optic disc. New imaging techniques and novel methods of direct optic disc tilt determination have been described.5–7 The optic disc tilt direction was divided into horizontal (disc tilt in the temporal direction) and vertical (disc tilt in the upward or downward direction) planes using horizontal and vertical height profiles in confocal scanning laser ophthalmoscopy, and the degree of the disc tilt in each plane was determined.5 The degree of disc tilt in the temporal direction has also been evaluated using a new approach to spectral-domain optical coherence tomography (OCT), known
E
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
as enhanced depth imaging.6 In both of these studies, the degree of temporal disc tilt was significantly associated with disc ovality, which has been used as a surrogate index of tilt.5,6 However, little is known about the clinical significance of vertical disc tilt. Disc tilt is thought to result from posterior scleral expansion, particularly in myopic eyes.8 There has recently been considerable interest in understanding the anatomy of the posterior sclera in relation to glaucoma, because the peripapillary sclera of glaucomatous eyes may have different biomechanics compared to healthy eyes. 9–11 Therefore, a comprehensive evaluation of the optic disc tilt in glaucomatous eyes will help elucidate glaucoma pathophysiology. In the present study, we investigated differences in optic disc tilt and torsion between normal control and glaucoma subjects. In addition, we determined whether the direction of the optic disc tilt is consistent with the location of the initial glaucomatous VF defect.
PATIENTS
AND
METHODS
Study Subjects The medical records of all consecutive patients with primary open-angle glaucoma (POAG) with isolated superior or inferior 4991
IOVS j August 2014 j Vol. 55 j No. 8 j 4992
Impact of Upward or Downward Disc Tilt on Glaucoma hemifield defects, examined by a glaucoma specialist (CKP) between August 2010 and September 2011 at the glaucoma clinic of Seoul St. Mary’s Hospital (Seoul, Korea), were reviewed retrospectively. When both eyes of a patient met the inclusion criteria, one eye was randomly selected for evaluation. Each initial patient visit featured a review of medical history; measurement of best-corrected visual acuity and refraction; slit-lamp biomicroscopy; gonioscopy; Goldmann applanation tonometry; dilated stereoscopic examination of the optic disc; disc and red-free fundus photography (Canon, Tokyo, Japan); standard automated perimetry (SAP; 24-2 Swedish Interactive Threshold Algorithm, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc., Dublin, CA, USA); and measurement of central corneal thickness and axial length (AL) (Tomey Corporation, Nagoya, Japan). Optical coherence tomography using a Cirrus HD-OCT (Carl Zeiss Meditec, Inc.) and confocal scanning laser ophthalmoscopy using Heidelberg Retina Tomograph III (HRT III; Heidelberg Engineering, Heidelberg, Germany) were performed. Patients were followed up in an identical manner, usually at 6- to 12-month intervals. The study was performed in strict accord with the tenets of the Declaration of Helsinki after approval by our Institutional Review Board. All included subjects had a best-corrected visual acuity ‡ 20/40 on two or more consecutive VF tests, and normal anterior chamber angles in both eyes on slit-lamp biomicroscopy and gonioscopy. Patients with a neurologic or intraocular disease that could cause a VF defect, eyes yielding consistently unreliable VF results (defined as > 25% false-negative results, > 25% false-positive results, or > 20% fixation losses), and eyes with high myopia (a spherical equivalent [SE] 10 diopters [D], thus outside the focal range of the HRT III [SE ‡ þ12 D]), were excluded. Subjects with an intraocular pressure (IOP) 21 mm Hg, a normal optic disc appearance upon examination of color stereoscopic photographs (an intact neuroretinal rim without peripapillary hemorrhage, thinning, or localized pallor), absence of any retinal nerve fiber layer (RNFL) abnormality visible on red-free fundus photographs, and normal VF test results were included in the normal group. A normal VF presentation was defined as a glaucoma hemifield test result within normal limits and mean and pattern standard deviation values associated with probabilities of normality greater than 5%. Glaucoma was defined by the presence of glaucomatous optic neuropathy associated with typical reproducible VF defects evident on SAP. A glaucomatous VF change was defined as a glaucoma hemifield test result outside normal limits and the presence of at least three contiguous points in the pattern deviation plot with P values < 5%, with at least one point associated with a P value < 1% (excluding points directly above or below the blind spot), on two consecutive reliable SAP examinations. Consecutive eyes with VF defect clusters within or outside the central 108 of an isolated hemifield were selected and designated as a central and a peripheral subgroup, respectively. These two VF regions were divided into the superior and inferior sectors, as in a previous study.12 Patients with overlapping VF defect clusters in both sectors were excluded from the study. To minimize false-positive results, a VF loss had to be apparent on at least two consecutive examinations.
Measurement of Disc Ovality and Torsion Color disc and red-free RNFL photographs were obtained using standard settings of a nonmydriatic retinal camera (Nonmyd 7; Kowa, Tokyo, Japan). The photographs and red-free images
were evaluated independently, in random order and in a masked fashion, by two of the authors (JAC and H-YLP), who thus lacked knowledge of all clinical information. Disc ovality and torsion were measured on photographs using National Institutes of Health image analysis software (ImageJ version 1.40; available at http://rsb.info.nih.gov/ij/index.html [in the public domain]; developed by Wayne Rasband, National Institutes of Health, Bethesda, MD, USA). Disc ovality index was determined using the tilt ratio, which is the ratio between the longest and shortest disc diameter.13,14 Disc torsion was defined as the deviation of the long disc axis from the vertical meridian, which was a vertical line perpendicular to a reference line connecting the fovea and the center of the disc.4 The angle between the vertical meridian and the long axis of the disc was termed the degree of torsion. Positive and negative angles indicated the presence of inferotemporal and supranasal torsion, respectively.
Definitions of Temporal and Vertical Disc Tilt The degrees of temporal and vertical disc tilt were measured using both HRT III and Cirrus HD-OCT. First, topographic analysis of the optic disc was performed using HRT III. Topographic images were obtained through dilated pupils. The intrascan standard deviation was required to be
