September 2016
Volume 57, Issue 11
Open Access
Glaucoma  |   September 2016
Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma
Author Affiliations & Notes
  • Masoud Aghsaei Fard
    Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Marjan Afzali
    Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Parisa Abdi
    Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Rebecca Chen
    Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
    Department of Ophthalmology, University of California-San Francisco, San Francisco, California, United States
  • Mehdi Yaseri
    Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
    Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, Iran
  • Ebrahim Azaripour
    Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Sasan Moghimi
    Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
    Department of Ophthalmology, University of California-San Francisco, San Francisco, California, United States
  • Correspondence: Sasan Moghimi, Farabi Eye Hospital, Eye Research Center, Qazvin Square, Tehran 13352, Iran; sasanimii@yahoo.com
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4632-4640. doi:10.1167/iovs.16-19442
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      Masoud Aghsaei Fard, Marjan Afzali, Parisa Abdi, Rebecca Chen, Mehdi Yaseri, Ebrahim Azaripour, Sasan Moghimi; Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(11):4632-4640. doi: 10.1167/iovs.16-19442.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To compare optic nerve head (ONH) morphology of optic nerve atrophy between eyes with primary open-angle glaucoma (POAG) and eyes with a history of nonarteritic anterior ischemic optic atrophy (NAION) using enhanced depth imaging (EDI) with spectral-domain optical coherence tomography (SD-OCT).

Methods: In this cross-sectional study, 121 eyes of 91 patients consisted of moderate to severe POAG (n = 32 eyes), visual field mean deviation–matched NAION (n = 30 eyes) and their fellow eyes (n = 30 eyes), and healthy controls (n = 29). The optic discs were scanned using SD-OCT and measurements were obtained using HEYEX software 6.0. Lamina cribrosa (LC) thickness and anterior lamina cribrosa depth (ALD) at three scans (midsuperior, central, and midinferior) were determined and compared. In addition, prelaminar tissue thickness was measured at three points of a single central scan.

Results: There was no significant difference in the visual field mean deviation (MD) between the NAION and POAG groups (P > 0.99), but both groups had a significantly worse MD than the healthy group (P < 0.001). The NAION and POAG groups had similar peripapillary retinal nerve fiber layer (pRNFL) thickness (P < 0.99). Eyes with POAG had greater ALD and thinner LC than control eyes and NAION eyes in all regions of the ONH (P < 0.001 for both). There was a marked prelaminar tissue thinning in POAG eyes compared to control and NAION eyes (P < 0.001). Lamina cribrosa thickness and ALD of NAION eyes were not different from their fellow eyes and control eyes. Although prelaminar thickness was thinner in NAION eyes compared to their fellow eyes (P = 0.005), it was thicker than in control eyes (P < 0.001).

Conclusions: Despite profound thinning and posterior displacement of LC in POAG, the thickness and position of LC in NAION eyes are similar to those seen in healthy control and their fellow eyes.

Both open-angle glaucoma (OAG) as chronic progressive optic neuropathy and nonarteritic anterior ischemic optic neuropathy (NAION) as acute optic neuropathy with inflammation-associated axonal loss cause irreversible damage to the optic nerve.13 In contrast to NAION, which presents with disc pallor after an ischemic event, OAG results in the enlargement of the optic disc cup.2 
Optic nerve head (ONH) morphologic features differ in NAION and OAG. While a small disc area and smaller cupping are predisposing risk factors for the development of NAION,35 IOP is the primary risk factor in the pathogenesis of OAG.6,7 
Nonetheless, other risk factors also have been suggested to explain the development and progression of glaucoma. These factors include abnormal blood flow,8 systemic hypotension,9 and low cerebral spinal fluid pressure.10 In addition, lamina cribrosa (LC) defects or thinning is associated with glaucoma.1116 The LC stabilizes intraocular pressure (IOP) by forming a barrier between the intraocular space and the extraocular space, and it has been considered the principal site of retinal ganglion cell mechanical axonal injury in glaucomatous damage.17 Burgoyne18 has proposed that only “laminar” or “deep” forms of ONH cupping are pathognomonic for glaucoma and that laminar deformation in nonglaucomatous optic neuropathy, such as that induced by experimentally reduced cerebrospinal fluid pressure in monkeys, might be minimal.1921 However, histologic studies may be prone to the effects of tissue swelling or shrinkage from fixation processes. Investigations in enucleated eyes suffer from postmortem changes in connective tissue and lack of vascular supply. 
Spectral-domain optical coherence tomography (SD-OCT) using enhanced depth imaging (EDI) can reliably capture high-resolution images of the deep optic nerve and allow for the characterization of the laminar component of cupping in different forms of optic neuropathy. Although both glaucoma and NAION have been shown to cause thinning of the peripapillary retinal nerve fiber layer (pRNFL), the ONH morphology and LC deformation may be unique in these two diseases22,23 and warrant further study. Recent studies show that the LC is posteriorly located and significantly thinner in patients with glaucoma than in healthy controls.1115 Recently, one study evaluated deep optic nerve structures in NAION eyes after an ischemic attack compared to normal-tension glaucoma eyes. The authors found a striking difference in the deep ONH configuration between glaucoma and NAION.24 
Using SD-OCT technology, we compared morphologic features between NAION and primary open-angle glaucoma (POAG) eyes, which were matched by visual field defect and pRNFL thinning. 
In this cross-sectional study, we evaluated ONH anatomic features in patients with chronic unilateral NAION, those with moderate to severe glaucoma, and healthy normal subjects using EDI functionality of SD-OCT. 
Methods
Subjects
Patients with moderate to severe POAG and visual field mean deviation (MD)-matched chronic unilateral NAION, as well as healthy control subjects who visited the outpatient clinic of Farabi Eye Hospital between July 2014 and March 2015, were enrolled in this cross-sectional study. The study was approved by the local ethics committee of the Tehran University of Medical Science and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients. All subjects underwent a thorough ophthalmic evaluation including slit-lamp biomicroscopy, best-corrected visual acuity (BCVA) using a logMAR chart, refractive error examination with an autorefractometer, IOP by Goldman applanation tonometry (GAT), fully dilated fundus examination, gonioscopy, and axial length measurement with ocular biometry (IOLMaster; Carl Zeiss Meditec, Dublin, CA, USA). Perimetry was performed with standard Swedish Interactive Thresholding Algorithm (SITA) with the 24-2 pattern on the Humphrey Field Analyzer (Carl Zeiss Meditec). Only reliable results were included (fixation loss < 20%, false-positive error < 15%, and false-negative error < 15%). 
Patients also underwent ONH imaging with EDI SD-OCT (Spectralis, HEYEX software 6.0; Heidelberg Engineering, Heidelberg, Jena, Germany). Peripapillary RNFL thickness was also measured. 
Inclusion criteria for unilateral NAION were (1) optic disc atrophy with a history of sudden, painless visual loss in one eye together with optic disc swelling and/or superficial hemorrhage on the border of the disc or adjacent retina that took place >3 months ago (which was confirmed by objective signs or by the referring ophthalmologists); and (2) a healthy fellow eye. At the time of the study, optic disc swelling had to have subsided, and disc borders had to be sharp and discrete. The exclusion criteria for NAION patients were (1) having an ocular or neurologic disease other than NAION, especially those with possible evidence of glaucoma (an IOP of >21 mm Hg in either eye, or glaucomatous optic disc or glaucomatous visual field results in the contralateral eye); (2) bilateral NAION; (3) acute NAION; and (4) evidence of arteritic AION (systemic manifestations of giant cell arteritis, an erythrocyte sedimentation rate >50 mm/h, and elevated C-reactive protein) or inflammatory optic neuritis. 
In the present study, POAG was defined as present in an eye with past history of documented IOP > 21 mm Hg, an open iridocorneal angle on gonioscopy, a typical glaucomatous optic disc appearance (enlargement of the vertical cup-to-disc ratio, apparent difference in the vertical cup-to-disc ratio between both eyes, diffuse or focal thinning of the neuroretinal rim, and visible nerve fiber layer defect), and glaucomatous visual field defects correlating with the area of optic disc damage. All the patients received medication in order to have controlled IOP before EDI-OCT imaging. 
A visual field defect was considered to be present if both of the following criteria were met: Glaucoma Hemifield Test outside normal limits and four abnormal points with P < 0.05 on the pattern deviation plot, both confirmed at least once. We used the Hodapp-Parrish-Anderson criteria for diagnosis and staging of glaucomatous visual field.25 To make the POAG and NAION groups more similar in terms of severity, only patients with a MD score less than −6.00 dB (i.e., moderate to severe defects) were recruited in this study. 
Healthy controls were refractive error–matched subjects with best-corrected visual acuity of ≥20/30, IOP of ≤21mm Hg, an open angle, normal optic disc appearance on fundus examination, and no visual field or pRNFL defects. 
In all groups, patients with age below 18 years, refractive error of ≥+6.00 or ≤−6.00 diopters (D) or more than ±3.00 D astigmatism, a history of ocular surgery other than uncomplicated cataract extraction, or history of ocular or neurologic disease other than glaucoma were excluded. Diagnoses of any type of secondary glaucoma, angle-closure glaucoma, and early glaucoma were also excluded. 
Spectral-Domain Optical Coherence Tomography Measurements
Scans were obtained using EDI-OCT after pupil dilation, and the images were analyzed via the Heidelberg Eye Explorer software (version 6.0, Heidelberg Engineering). Images with poor centration, segmentation errors, or poor quality (<15 dB) were excluded from analysis. Two sets of scans were obtained for each eye: pRNFL and ONH. 
Peripapillary RNFL measurement was performed using the standard 360°, 3.4-mm peripapillary circle centered around the optic disc, and the obtained thickness values were recorded in seven sectors: global, superonasal, nasal, inferonasal, inferotemporal, temporal, and superotemporal. 
For the ONH scan, the EDI-OCT device was set to image a 15°×15° square on the optic disc. This area was divided into approximately 65 sections, each of which had average of 42 OCT frames. From these horizontal B-scans, three frames that passed through the ONH (central, midsuperior, and midinferior) were selected. The anatomic parameters were measured in each of these frames and labeled “Cen,” “Sup,” and “Inf,” respectively. Figure 1 depicts the LC borders and Bruch's membrane opening (BMO) in an ONH OCT image. The BMO was defined as the innermost termination of the Bruch's membrane/retinal pigment epithelium complex, and the line that connects both ends of the Bruch's membrane/retinal pigment epithelium complex was defined as the BMO distance. Other parameters were measured as close as possible to the line perpendicular from the midpoint of BMO distance and as close as possible to the vertical center of the ONH. When a vessel trunk made the measurement impossible, the measurements were taken at its temporal side. The anterior and posterior borders of the highly reflective region at the vertical center of the ONH in the horizontal SD-OCT cross section were defined as the borders of the LC, and the distance between these two borders was defined as LC thickness. Anterior laminar cribrosa depth (ALD) was measured at the anterior LC surface as the perpendicular distance from BMO distance. Anterior lamina cribrosa depth and LC thicknesses were measured at central, midsuperior, and midinferior sections of the ONH. The prelaminar tissue thickness was defined as the distance between the internal limiting membrane (anterior surface) of the ONH or optic cup and the anterior border of the LC. In a single central B-scan, the distance from the anterior surface of the optic nerve to the level of anterior border of LC was measured at three points: the maximally depressed point of the anterior surface of LC and two additional points (100 and 200 μm apart from the maximally depressed point in a temporal direction). Only the temporally adjacent points were selected.26 The mean of three measurements was defined as average prelaminar tissue thickness. All images were analyzed by two specialists (SM, MA) in two different sessions. 
Figure 1
 
Upper row, left: An EDI-OCT of a glaucomatous optic nerve shows Bruch's membrane opening (BMO), anterior and posterior border of lamina cribrosa (arrows) and anterior laminar depth (ALD), prelaminar thickness (A), and lamina cribrosa (LC) thickness (B) in a raster line across the center of the optic nerve. ALD is deeper and LC and prelaminar thickness are thinner than in nonarteritic anterior ischemic optic neuropathy (NAION) and controls. Upper row, right: Circular circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 58 μm). Middle row, left: an EDI-OCT of an optic nerve with a history of NAION 8 months before. Lamina cribrosa is not thin and is not located posteriorly. Middle row, right: Circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 53 μm). Lower row: an EDI-OCT of a normal optic nerve head with normal circumpapillary retinal nerve fiber layer thickness (Global = 103 μm).
Figure 1
 
Upper row, left: An EDI-OCT of a glaucomatous optic nerve shows Bruch's membrane opening (BMO), anterior and posterior border of lamina cribrosa (arrows) and anterior laminar depth (ALD), prelaminar thickness (A), and lamina cribrosa (LC) thickness (B) in a raster line across the center of the optic nerve. ALD is deeper and LC and prelaminar thickness are thinner than in nonarteritic anterior ischemic optic neuropathy (NAION) and controls. Upper row, right: Circular circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 58 μm). Middle row, left: an EDI-OCT of an optic nerve with a history of NAION 8 months before. Lamina cribrosa is not thin and is not located posteriorly. Middle row, right: Circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 53 μm). Lower row: an EDI-OCT of a normal optic nerve head with normal circumpapillary retinal nerve fiber layer thickness (Global = 103 μm).
Statistical Methods
Data are presented as mean and standard deviation. To compare demographic characteristics of the patients, we compared the NAION, POAG, and control groups by independent samples 2-tailed t-test and χ2 test. To evaluate the intraobserver and interobserver reproducibility of ONH measurements, 20 randomly selected EDI-OCT B-scans from 20 eyes were evaluated. Analysis was based on two independent series of reevaluations made by two independent observers. The absolute agreement of a single observer's measurements and the mean of the measurements conducted by the two observers were calculated with the intraclass correlation coefficient (ICC) from a 2-way mixed effects model. 
A linear mixed model was used to compare the ONH parameters among groups along with Bonferroni correction to account for multiple comparisons. In the last step, to simultaneously compare ONH parameters between POAG and NAION groups with statistical correction for age, sex, axial length, and pRNFL, multivariate analysis of covariance (MANCOVA) was performed. All statistical analysis was performed on SPSS software (IBM SPSS Statistics for Windows, Version 22.0, released 2013; IBM Corp., Armonk, NY, USA). A P value less than 0.05 was considered statistically significant. 
Results
One hundred thirty-seven eyes of 102 subjects were initially enrolled in this study. Laminar measurements were not possible in 5 NAION eyes and their unaffected fellow eyes, 2 POAG eyes, and 4 healthy control eyes, and these 16 eyes were excluded due to poor image quality. In most of the excluded eyes, visualizing the LC layer was difficult due to the shadow from neuroretinal tissue. Therefore, 60 eyes of 30 patients with chronic unilateral NAION, 32 eyes of 32 patients with moderate to severe treated POAG, and 29 eyes of 29 healthy normal subjects (a total of 91 patients) were included in the final analysis. When both eyes were eligible in patients with POAG and in normal subjects, one eye was chosen at random. 
The basic demographic and clinical characteristics of the study participants are listed in Table 1. There were no statistically significant differences in sex, refractive error (spherical equivalent), IOP, and axial length between NAION, POAG, and healthy controls. Best-corrected visual acuity (logMAR) was significantly worse in NAION eyes (P < 0.001) compared to POAG and control groups. Although POAG and normal subjects were age matched, the participants in the POAG group were significantly older than those in the NAION group (P = 0.01). The acute event of NAION had taken place 4 months to 2 years before the examination, with a mean of 6.5 months. 
Table 1
 
Baseline Demographics and Presenting Clinical Features of All Subjects
Table 1
 
Baseline Demographics and Presenting Clinical Features of All Subjects
The MD of the visual field was −16.47 ± 9.05, −1.02 ± 2.8, −16.28 ± 9.98, and −1.0 ± 2.09 dB in the NAION, their fellow eyes, POAG, and healthy control groups, respectively. There was no significant difference in the MD between the NAION and glaucoma groups (P > 0.99), but both groups had a significantly poorer MD than the healthy group (P < 0.001). There was no significant difference in pRNFL thickness between the NAION and POAG groups. However, both groups showed thinner pRNFL when compared to control eyes (Table 2). 
Table 2
 
Comparison of Retinal Nerve Fiber Layer Thickness Among the Groups Using Linear Mixed Model
Table 2
 
Comparison of Retinal Nerve Fiber Layer Thickness Among the Groups Using Linear Mixed Model
Optic nerve head measurements showed an excellent intraobserver and interobserver reproducibility that ranged from an ICC of 0.827 to 0.998 for the various parameters (Table 3). Linear mixed model analysis showed statistically significant differences in prelaminar depth and thickness, ALD, and LC thickness (central, midsuperior, and midinferior areas) among POAG, NAION, and control eyes. There was no statistically difference in BMO distance among the three groups (Table 4). 
Table 3
 
Interclass Coefficient Correlation (ICC) for Optic Nerve Head Measurements
Table 3
 
Interclass Coefficient Correlation (ICC) for Optic Nerve Head Measurements
Table 4
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Among the Groups Using Linear Mixed Model and Multivariate Analysis of Covariance
Table 4
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Among the Groups Using Linear Mixed Model and Multivariate Analysis of Covariance
Anterior laminar depth and LC thickness in NAION eyes were similar to those seen in healthy controls in all central, midsuperior, and midinferior regions. Although prelaminar tissue demonstrated thinning in NAION eyes compared to their fellow eyes, both groups had significantly thicker average prelaminar tissue compared to healthy control eyes (Tables 4, 5). 
Table 5
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Between NAION and Their Fellow Eyes
Table 5
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Between NAION and Their Fellow Eyes
Eyes with POAG had deeper central laminar depth and thinner central lamina than control eyes. Thinning of LC and deepening of laminar depth were also apparent in the midsuperior and midinferior regions of the optic disc. There was marked prelaminar tissue thinning in POAG eyes compared to control eyes (Table 4). 
Anterior laminar depth was greater and LC thickness was thinner in POAG eyes compared to NAION eyes (at all central, midinferior, and midsuperior disc regions) after adjusting for age, sex, axial length, and pRNFL (all P < 0.001) (Table 3). Despite similar peripapillary nerve fiber loss in both groups, prelaminar tissue thickness was greater in NAION eyes compared to POAG eyes (P < 0.001). 
Discussion
Although there are some similarities in optic disc cupping and loss of neuroretinal rim in glaucomatous and nonglaucomatous optic neuropathies, most nonglaucomatous optic neuropathies do not show clinical, morphologic, and histopathologic characteristics of glaucomatous optic neuropathy. Studies in both conditions have attempted to identify the mechanism of optic nerve damage with the goal of protecting retinal ganglion cells; however, there is little overlap.1,27 In the present study, we compared changes in optic nerve structure that occurred in glaucoma and NAION after resolution of the acute phase. We demonstrate that LC is thinner and located more posteriorly in eyes with glaucomatous optic neuropathy than in NAION and control healthy eyes. Although the laminar depth and LC thickness were not significantly different between NAION and control groups, NAION eyes have thicker prelaminar tissue than normal and glaucoma eyes. 
Considerable research in recent years has focused on the biomechanical properties of the ONH to explain the pathophysiology of glaucoma. Laminar stress, thinning, and deformation can lead to axonal dysfunction via several mechanisms, including increased translaminar pressure gradient,17,28 mechanical damage,11,29 and compromised vascular supply.30 
In our POAG cases with moderate to severe glaucomatous damage, we showed that laminar tissue was thinner and more posteriorly located compared to healthy controls. This is in agreement with previous animal and human studies that found LC thickening in early disease with subsequent thinning, posterior displacement, and disruption. Response of IOP to LC has been reported in the literature. Although temporary moderate IOP elevation does not result in significant posterior displacement of the LC in normal humans,31,32 experimental models have shown that with more chronic IOP elevation, the LC is displaced posteriorly compared to its baseline position.18,33 Anterior displacement of the optic disc surface resulting from acute IOP reduction has been observed in glaucoma patients after surgical or medical IOP reduction.26,34 
In the present study, we showed that LC in NAION eyes and their fellow eyes was neither thinner nor posteriorly displaced compared to the normal controls or glaucomatous eyes. In order to understand the presentations of various optic neuropathies, Burgoyne18 suggested that we should understand ONH connective tissue and the diverse biomechanical factors affecting the ONH. He also proposed that profound laminar deformation and remodeling resulting from connective tissue changes are present in eyes with as little as 12% to 14% optic nerve axon loss.18,21 Our finding that mild ischemic assault like NAION does not have a prominent effect on LC thickness and depth supports the theory of Burgoyne. In a recent study comparing eyes with compressive optic neuropathy and eyes with POAG, Hata et al.35 found that despite having the same cup-to-disc ratios in both groups, ALD was smaller in compressive optic neuropathy than in POAG eyes but similar to that in control healthy eyes. In line with our results, in an experimental animal study, Ing et al.36 showed that while RNFL thickness demonstrated profound thinning, ALD was not displaced posteriorly approximately 50 days following optic nerve transection. As these findings are in contrast to OCT detection of significant laminar deformation after chronic IOP elevation,33 the authors proposed that posterior laminar deformation following connective tissue damage should be included in the definitions used to distinguish glaucomatous and nonglaucomatous optic neuropathy in the monkey eye.18 However, assessment of ONH changes and laminar anatomy has not been made in the monkey model of NAION.3 In their recent study, Lee et al.24 compared ONH morphology between NAION and normal-tension glaucoma eyes. Similar to what was seen in our study, they found that the ALD was larger in glaucomatous eyes than in healthy control subjects while it was comparable between NAION patients and healthy controls.24 
In our study, glaucomatous eyes also had the smallest prelaminar thickness. In vivo assessment of ONH structures in glaucomatous patients demonstrated that eyes with deeper ONH cup and thinner RNFL presented with less prelaminar tissue15,37 (Vessani R, et al. IOVS 2013;54:ARVO E-Abstract 76). Surprisingly, in our NAION eyes with prominent optic atrophy and the same RNFL loss as in the POAG eyes, prelaminar tissue was thicker than in POAG eyes and healthy controls. Lee et al.24 also found that prelaminar thickness was less in glaucomatous patients than in NAION patients. Similarly, Ing et al.36 found prelaminar tissue thinning following experimental optic nerve transaction. Lack of optic disc excavation and changes in optic rim in atrophic optic nerve due to NAION have been described in previous studies.1,38 However, Heyreh and Jonas,39 in their series of 29 patients, revealed that arteritic AION resulted in profound rim loss and optic disc cupping. They proposed that in arteritic AION there is permanent thrombotic occlusion of the posterior ciliary arteries and total infarction of the involved part of the ONH, leading to massive loss of not only axons but also connective tissue and supporting cells of the ONH. In contrast, in patients with NAION, ischemia is mild, and fluorescein angiography has shown evidence of only transient hypoperfusion or nonperfusion of the ONH during sleep in most cases. It was noted that another difference is that NAION eyes have no excavation and have crowded optic nerve before the attack. While we detected a thinner prelaminar tissue of NAION eyes compared to their healthy fellow eyes, this tissue was significantly thicker than in healthy control eyes. No enrollment and assessment of unaffected fellow eyes of NAION patients were performed in the Lee et al.24 study. In addition, in contrast to our study, Lee et al.24 showed that prelaminar tissue thickness was thinner in NAION patients than in healthy controls. The source of this interstudy discrepancy might be different methods of measuring prelaminar tissue thickness. Lee et al.24 measured prelaminar tissue area on the radial B-scan, and average prelaminar tissue thickness was calculated by dividing the prelaminar tissue area by half of the BMO distance. We measured the prelaminar tissue thickness in the horizontal central scan after averaging three measurements (Fig. 2). In addition, Lee et al.24 included only patients who had been diagnosed at least 6 months earlier, and prelaminar swelling might not have been fully resolved after 3 months of disease occurrence in our study. 
Figure 2
 
Prelaminar thickness (PLT) measurement in a single central B-scan of the fellow eye of a patient with unilateral ischemic optic neuropathy. Distance from the anterior surface of the optic nerve to the level of anterior border of lamina cribrosa (LC) (upper arrowheads) was measured at three points: the maximally depressed point of anterior surface of LC and two additional points (100 and 200 μm apart from the maximally depressed point in a temporal direction). The mean of three measurements was defined as average prelaminar tissue thickness. Posterior border of LC was also marked (lower arrowheads).
Figure 2
 
Prelaminar thickness (PLT) measurement in a single central B-scan of the fellow eye of a patient with unilateral ischemic optic neuropathy. Distance from the anterior surface of the optic nerve to the level of anterior border of lamina cribrosa (LC) (upper arrowheads) was measured at three points: the maximally depressed point of anterior surface of LC and two additional points (100 and 200 μm apart from the maximally depressed point in a temporal direction). The mean of three measurements was defined as average prelaminar tissue thickness. Posterior border of LC was also marked (lower arrowheads).
A recent study by Burgoyne18 may offer more insight into our findings. Burgoyne defined “prelaminar thinning” as the portion of cup enlargement that results from thinning of the prelaminar tissues due to physical compression and/or the loss of retinal ganglion cell axons and “laminar deformation or laminar cupping” as the portion of cup enlargement that results from permanent, IOP-induced deformation of the LC following damage and/or remodeling. We speculate that in NAION eyes, mild/transient ischemia mostly affects RNFL in prelaminar tissue and not connective tissue in the laminar portion, precluding cupping. Nonetheless, in our glaucomatous cases, LC change and prelaminar thinning induced by IOP might result in optic nerve cupping. In line with this study, Danesh-Meyer et al.1 compared ONH of POAG and NAION eyes using Heidelberg retina tomography (HRTII), and showed that discs affected by OAG had significantly less disc rim tissue and a dramatically deeper cup than NAION and concluded that POAG affects the laminar connective tissues much more than either NAION. 
This study has some limitations that should be kept in mind. First, ONH parameters were measured at three standard scans. Although this method has been used in previous studies, more scan sections may increase the accuracy of the ONH measurement with considerable variations. Although we have a better visualization of the LC with the EDI technique than with conventional imaging, it does not provide satisfactory visualization of the LC in all eyes. Nevertheless, we had excellent intraobserver and interobserver variability for ONH measurement, and we believe that the reliability of our data is acceptable for final analysis. Second, although the observer was masked to the clinical characteristics and disease status of each eye, the shape of the optic nerve, especially in glaucomatous eyes, could possibly have given the observer some clues and affected the observer's evaluation of depth or thickness measurements. Finally, we did not measure ONH parameters in the matched affected sectors between NAION and POAG eyes. However, we measured ALD of the central, midsuperior, and midinferior scans in all eyes, and all of these scans were compared between groups. 
In conclusion, we found that atrophic optic nerves after an attack of NAION have similar laminar thickness and depth as do control eyes. Prelaminar tissue of NAION eyes was thicker than in glaucomatous and healthy control eyes, even with obvious clinical pallor. The glaucomatous eyes with the same severity of visual field damage have a thinner and more posteriorly located LC. These findings may give insight into pathophysiological changes of glaucomatous and nonglaucomatous optic atrophy and may elucidate different clinical findings related to ischemic and glaucomatous optic nerve damage. 
Acknowledgments
The authors thank Nassim Khatibi, Somayeh Heidarzadeh, and Sepideh Heydarzadeh for gathering data and biometric measurements. 
The protocol of the study was approved by the institutional review board of Farabi Eye Hospital, Tehran, Iran. 
Disclosure: M.A. Fard, None; M. Afzali, None; P. Abdi, None; R. Chen, None; M. Yaseri, None; E. Azaripour, None; S. Moghimi, None 
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Figure 1
 
Upper row, left: An EDI-OCT of a glaucomatous optic nerve shows Bruch's membrane opening (BMO), anterior and posterior border of lamina cribrosa (arrows) and anterior laminar depth (ALD), prelaminar thickness (A), and lamina cribrosa (LC) thickness (B) in a raster line across the center of the optic nerve. ALD is deeper and LC and prelaminar thickness are thinner than in nonarteritic anterior ischemic optic neuropathy (NAION) and controls. Upper row, right: Circular circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 58 μm). Middle row, left: an EDI-OCT of an optic nerve with a history of NAION 8 months before. Lamina cribrosa is not thin and is not located posteriorly. Middle row, right: Circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 53 μm). Lower row: an EDI-OCT of a normal optic nerve head with normal circumpapillary retinal nerve fiber layer thickness (Global = 103 μm).
Figure 1
 
Upper row, left: An EDI-OCT of a glaucomatous optic nerve shows Bruch's membrane opening (BMO), anterior and posterior border of lamina cribrosa (arrows) and anterior laminar depth (ALD), prelaminar thickness (A), and lamina cribrosa (LC) thickness (B) in a raster line across the center of the optic nerve. ALD is deeper and LC and prelaminar thickness are thinner than in nonarteritic anterior ischemic optic neuropathy (NAION) and controls. Upper row, right: Circular circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 58 μm). Middle row, left: an EDI-OCT of an optic nerve with a history of NAION 8 months before. Lamina cribrosa is not thin and is not located posteriorly. Middle row, right: Circular OCT (C) scan shows thinning of the circumpapillary retinal nerve fiber layer (Global = 53 μm). Lower row: an EDI-OCT of a normal optic nerve head with normal circumpapillary retinal nerve fiber layer thickness (Global = 103 μm).
Figure 2
 
Prelaminar thickness (PLT) measurement in a single central B-scan of the fellow eye of a patient with unilateral ischemic optic neuropathy. Distance from the anterior surface of the optic nerve to the level of anterior border of lamina cribrosa (LC) (upper arrowheads) was measured at three points: the maximally depressed point of anterior surface of LC and two additional points (100 and 200 μm apart from the maximally depressed point in a temporal direction). The mean of three measurements was defined as average prelaminar tissue thickness. Posterior border of LC was also marked (lower arrowheads).
Figure 2
 
Prelaminar thickness (PLT) measurement in a single central B-scan of the fellow eye of a patient with unilateral ischemic optic neuropathy. Distance from the anterior surface of the optic nerve to the level of anterior border of lamina cribrosa (LC) (upper arrowheads) was measured at three points: the maximally depressed point of anterior surface of LC and two additional points (100 and 200 μm apart from the maximally depressed point in a temporal direction). The mean of three measurements was defined as average prelaminar tissue thickness. Posterior border of LC was also marked (lower arrowheads).
Table 1
 
Baseline Demographics and Presenting Clinical Features of All Subjects
Table 1
 
Baseline Demographics and Presenting Clinical Features of All Subjects
Table 2
 
Comparison of Retinal Nerve Fiber Layer Thickness Among the Groups Using Linear Mixed Model
Table 2
 
Comparison of Retinal Nerve Fiber Layer Thickness Among the Groups Using Linear Mixed Model
Table 3
 
Interclass Coefficient Correlation (ICC) for Optic Nerve Head Measurements
Table 3
 
Interclass Coefficient Correlation (ICC) for Optic Nerve Head Measurements
Table 4
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Among the Groups Using Linear Mixed Model and Multivariate Analysis of Covariance
Table 4
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Among the Groups Using Linear Mixed Model and Multivariate Analysis of Covariance
Table 5
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Between NAION and Their Fellow Eyes
Table 5
 
Comparison of Optic Nerve Head and Lamina Cribrosa Parameters Between NAION and Their Fellow Eyes
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