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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 106  |  Issue : 4  |  Page : 253-258

Retinal nerve fiber layer versus optic nerve head evaluation in the diagnosis of glaucoma and glaucoma suspect patients


Mansoura Ophthalmic Center, Mansoura University, Mansoura, Egypt

Date of Submission10-Jul-2013
Date of Acceptance05-Nov-2013
Date of Web Publication28-Apr-2014

Correspondence Address:
Amal M Elbendary
MD, Mansoura Ophthalmic Center, Mansoura University, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2090-0686.131608

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  Abstract 

Purpose
To evaluate the role of retinal nerve fiber layer (RNFL) versus optic disc parameters in the diagnosis of glaucoma and glaucoma suspect using spectral domain optical coherence tomography (SD-OCT).
Patients and methods
Forty-five normal, 51 glaucoma suspect, and 54 glaucomatous eyes were examined. Complete ophthalmic examination, white-on-white perimetry, and SD-OCT were performed for all patients. RNFL thickness of quadrants and clock hours and optic disc parameters were recorded. Area under receiver operating characteristic curves (AUC) were used to assess the performance of OCT.
Results
RNFL thickness and optic head parameters were used discriminate the three groups for all comparisons. Inferior, average, and superior RNFL thickness were the best parameters that discriminated normal from glaucoma (AUC: 0.96-0.99), suspect from glaucoma (AUC: 0.84-0.91), and normal from suspect (AUC: 0.71-85). Rim area and vertical cup/disc ratio were the best parameters that discriminated normal from glaucoma (0.87-0.90), suspect from glaucoma (AUC: 0.82-0.83), and normal from suspect (0.76).
Conclusion
The ability of SD-OCT to differentiate between normal and glaucoma suspect eyes from glaucomatous eyes is better for RNFL thickness than optic nerve head parameters. The ability of both RNFL thickness and optic disc parameters is less in differentiating normal from glaucoma suspect eyes.

Keywords: Discrimination, glaucoma, optical coherence tomography, perimetry


How to cite this article:
Mokbel TH, Elbendary AM, El Sharkawy HT, El Desouky WM. Retinal nerve fiber layer versus optic nerve head evaluation in the diagnosis of glaucoma and glaucoma suspect patients. J Egypt Ophthalmol Soc 2013;106:253-8

How to cite this URL:
Mokbel TH, Elbendary AM, El Sharkawy HT, El Desouky WM. Retinal nerve fiber layer versus optic nerve head evaluation in the diagnosis of glaucoma and glaucoma suspect patients. J Egypt Ophthalmol Soc [serial online] 2013 [cited 2020 Sep 24];106:253-8. Available from: http://www.jeos.eg.net/text.asp?2013/106/4/253/131608


  Introduction Top


Glaucoma is an optic neuropathy associated with progressive loss of retinal ganglion cells and their axons [1]. Evaluation of retinal nerve fiber layer (RNFL) and optic nerve head (ONH) is an essential step in the diagnosis and monitoring of glaucoma [2]. Early detection and treatment of glaucomatous optic neuropathy may reduce the incidence of blindness from glaucoma [3].

Longitudinal and histologic studies of early glaucomatous optic neuropathy proved that structural injury precedes detectable visual field loss using standard automated perimetry (SAP) [4],[5]. Postmortem studies showed that up to 40% axonal loss may occur before detectable visual field changes [6]. Similarly, optic disk structural damage without coexisting visual field changes on SAP had been documented in 55% of ocular hypertensive eyes that converted to glaucoma [7].

Sommer et al. [8] reported that 60% of patients with ocular hypertension had evidence of RNFL loss that occurred up to 6 years before a detectable change on SAP. Advanced imaging technology enabled the detection of structural changes before the development of SAP abnormality [4],[9].

The recently introduced spectral domain optical coherence tomography (SD-OCT) systems had shown good performance in discriminating healthy eyes from those with glaucomatous visual field loss [10],[11]. It is particularly valuable in glaucoma detection and monitoring through identification of subtle RNFL or ONH changes over time [2],[9]. However, the role of OCT remains less certain in eyes with early damage [12]. Although early detection of damage in eyes with preperimetric glaucoma by advanced imaging and psychophysical testing has been documented, limited data exist on the characteristics of such eyes by a comprehensive diagnostic approach [3].

The aim of this study is to evaluate the role of RNFL versus optic disc parameters in the diagnosis of glaucoma using SD-OCT.


  Patients and methods Top


This was a prospective cross-sectional study involving 150 eyes of 100 patients during the period from May 2010 to October 2012. All eyes were subjected to a complete ophthalmic examination including best-corrected visual acuity, dilated fundoscopic examination, slit-lamp biomicroscopy, gonioscopy, Goldmann applanation tonometry, SAP, and SD-OCT. Eyes with myopic refraction of more than -5.0 D, retinal disease, uveitis, or nonglaucomatous optic neuropathy were excluded from the study.

Participants in the study included individuals with normal eyesight, those suspected to have glaucoma, and patients with eyes with definite glaucomatous damage.

Normal eyes: All eyes had intraocular pressure of less than 21 mmHg, normal optic disc appearance, and normal visual field. Glaucoma suspect eyes were defined as eyes showing the presence of an abnormal disc appearance suspicious of glaucoma with a normal visual field. Suspicious disc appearance included asymmetry of more than 0.2, cup disc ratio of more than 0.6, and neuroretinal rim thinning, notching, excavation, RRNFL defect, and deviation from the ISNT (inferior, superior, nasal, temporal) rule for normal distribution of quadrant thickness.

Visual field testing was performed using a Humphrey field analyzer (Carl Zeiss Meditec Inc.). Eyes were considered glaucomatous if they had two consecutive abnormal visual field test results irrespective of the ONH and RNFL appearance to avoid potential bias in the evaluation of the sensitivity and specificity of RNFL measurement for glaucoma detection.

A visual field defect was defined as having at least three nonedge contiguous points showing a threshold sensitivity loss on the pattern deviation plot with P less than 5%, with at least one of the points depressed at P less than 1%, or at least 10dB difference across the nasal horizontal midline at two or more adjacent locations. In addition, an abnormal glaucoma hemifield test was required.

A three-dimensional (3D), Fourier-Domain OCT system with a nonmydriatic retinal camera, 3D OCT 2000 (Topcon Corp, Tokyo, Japan), was used in this study. This system has ˜5 μm axial resolution and 20 μm horizontal resolution, and acquires 18 700 axial scans per second, corresponding to about 36 images of commercially available stratus generation (512 axial scans per image). Three-dimensional data were obtained using the raster scanning technique centered on the ONH covering a square area 6 mm (horizontal) × 6 mm (vertical). The raster pattern acquires 128 horizontal scans, and each scan is composed of 512 axial scans; thus, it provides comprehensive topographic and cross-sectional image information because full 3D data are available at a large number of transverse points across the ONH. The total acquisition time is about 3.7 s. RNFL thickness maps and a 3.4-mm diameter circumpapillary OCT image can be generated from the 3D OCT data. The circumpapillary OCT image can be reposited manually to provide accurate centration around the ONH.

The disc margin is detected automatically without the need for operator intervention. The edge of the cup is determined by the intersection of the retinal surface with a plane parallel to the RPE and offset by 120 μm. The contours defining the cup and disc are then computed and displayed as an en-face map. RNFL measurements was expressed over four quadrants, 12 o'clock hours, 36 sectors, and mean thickness of the total circumpapillary scanning. On the basis of the instrument's normative database, any RNFL measurement beyond 95% normal limits that were confirmed on at least two of three repeat scans was considered abnormal.

Statistical analysis

Analysis was carried out using SPSS v16 (SPSS Inc. Chicago, Illinois, USA). The mean values of peripapillary RNFL thickness and ONH parameters were compared between normal, suspect, and glaucomatous eyes using one-way analysis of variance, followed by the post- hoc test for multiple comparisons. Receiver operating characteristic curves were used to describe the ability of each parameter to differentiate between normal, glaucoma, and suspect eyes. P value less than 5% was considered statistically significant.

Areas under receiver operating characteristics (AUCs) measures a test's diagnostic ability, that is, its power to correctly classify those with and without the disease. An AUC of 1 (100% sensitivity and 100% specificity) represents a perfect test, whereas an AUC of 0.5 indicates a completely worthless test. For this study, the AUC was classified as follows: [13] 0.9-1 = excellent, 0.80-0.89 = good, 0.70-0.79 = fair, 0.60-0.69 = poor, and 0.50-0.59 = worthless test.


  Results Top


A total of 100 patients, 150 eyes, were enrolled in this study. 45 eyes were normal, 51 eyes were glaucoma suspect, and 54 eyes had definite glaucomatous damage. Sixty-five patients were men whereas 35 were women. The mean age of the patients was 45.7 ± 16.2 years (range 38-70). [Table 1] summarizes the baseline characteristics of the study population. There was no difference between the groups in age, intraocular pressure refractive error, and sex. A statistically significant difference (P = 0.000) in the mean deviation and pattern standard deviation existed between the three groups.

The mean superior, inferior, and average RNFL thickness values were significantly different (P = 0.000) between the three groups. All comparisons between the groups were significantly different: Normal versus glaucoma suspect, normal versus glaucoma, and glaucoma suspect versus glaucoma (one-way analysis of variance with a post-hoc test). No significant difference in the mean nasal RNFL thickness was detected between normal and glaucoma suspect eyes. No significant difference in the mean temporal RNFL thickness was detected between glaucoma suspect and glaucoma groups [Table 2].

Different disc parameters were compared between the study groups [Table 3]. There was a significant difference (P < 0.05) in the mean cup area, rim area, cup/disc area, linear cup disc ratio, and vertical cup disc ratio. All comparisons between the groups were significantly different, except for cup area, which showed no difference between normal and glaucoma suspect eyes (one-way analysis of variance with a post-hoc test).
Table 1: Baseline data of the study population

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Table 2: Comparison of the mean retinal nerve fiber layer thickness among the study groups

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Table 3: Comparison of optic disc parameters among the study groups

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Receiver operating characteristic curves in differentiating groups

To detect the most sensitive OCT parameters that can discriminate between different groups, AUC were calculated [Table 4] and [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5] and [Figure 6]. Excellent retinal RNFL parameters that could distinguish normal from glaucomatous eyes irrespective of the stage of the disease were inferior RNFL thickness, followed by average, 5, and 11 o'clock hours and superior RNFL thickness (AUC: 0.99-0.96). The best optic disc parameters were rim area and vertical cup disc ratio (AUC: 0.90, 0.87).
Figure 1:

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Figure 2:

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Figure 3:

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Figure 4:

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Figure 5:

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Figure 6:

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Table 4: Discriminating ability of optical coherence tomography parameters between the three groups using area under receiver operating characteristic curves

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The best RNFL parameters that distinguished glaucoma from glaucoma suspect eyes were 1 o'clock hour, inferior RNFL thickness, followed by superior RNFL, 5 o'clock, and average thickness (AUC: 0.94-0.84). The best optic disc parameters were rim area and vertical cup disc ratio (AUC: 0.83, 0.82).

The best RNFL parameters that distinguished normal from glaucoma suspect eyes were inferior RNFL, 7 o'clock hour, followed by average and superior RNFL thickness with lower AUC areas (0.85-0.71, respectively). The best optic disc parameters were rim area and vertical cup disc ratio with lower AUC areas (AUC: 0.76, 0.76).


  Discussion Top


In the present study, OCT-derived measures of RNFL thickness were significantly different between the three groups for all comparisons. Excellent RNFL discriminators between the normal and the glaucoma group were inferior RNFL thickness, followed by average, 5, and 11 o'clock hours and superior RNFL thickness (AUC: 0.99-0.96). Several studies have reported that the average and inferior average RNFL thickness are the best discriminators between normal and glaucomatous eyes with variable AUC areas. Budenz et al. [14], using Stratus OCT, reported AUCs of 0.97, 0.97, and 0.95 for inferior, average, and superior RNFL thickness, respectively. Mwanza et al. [2], using SD-OCT, reported slightly lower values, whereas Schuman [15], using both Stratus and SD-OCT, reported much lower values. The best discriminators between glaucoma suspect and glaucoma were 1 o'clock hour, inferior RNFL thickness, followed by superior RNFL, 5 o'clock, and average thickness (AUC: 0.94-0.84).

Studies have shown that OCT-derived measurements of optic disc topography are highly reproducible and well correlated with topographic measurements derived by scanning laser tomography [16]. In the present study, the best disc discriminators between both normal and glaucoma and the suspect versus glaucoma group were rim area and vertical cup disc ratio. The AUC ranges were lower than RNFL (0.82-0.90). Mwanza et al. [2], using Cirrus ONH parameters, reported AUCs between 0.90 and 0.96. The prevalence of mild-stage and moderate-stage glaucoma (51%) in our sample may explain the lower AUC values.

The ability of RNFL and optic disc parameters to discriminate between normal and suspect eyes appeared to be much less. Inferior, 7 o'clock hour, average, and superior RNFL thickness provided good to fair values (AUC: 0.85-0.71). Rim area and vertical cup disc ratio provided fair discrimination (AUC 0.76). Contradictory results have been published on the role of OCT in eyes with early damage. In a study carried out by Mok et al. [9] on glaucoma suspect eyes with normal SAP, lower RNFL thickness was detected in the superotemporal and inferotemporal peripapillary area. Mwanza et al. [2] found that no significant differences between AUCs that best differentiate between normal eyes and glaucomatous eyes or between normal eyes and eyes with mild glaucoma. Nouri-Mahdavi et al. [12] reported that RNFL thickness measurement performed well in discriminating early perimetric glaucoma from normal eyes whereas its discriminating ability in glaucoma suspect with suspicious optic disk cupping and normal achromatic visual fields was less adequate. Mansoori et al. [17] found that glaucomatous eyes could be differentiated from normal and ocular hypertensive eyes in most quadrants. However, ocular hypertensive eyes could not be differentiated from normal eyes, except in temporal quadrants.

These contradictory results in eyes with early glaucoma may be because of variable inclusion criteria, which depend on the definition of early glaucoma. Early damage may include ocular hypertensive eyes or eyes with optic disc changes with normal SAP and or normal short wave automated perimetry. The mild stage of perimetric glaucoma may also be included. In addition, the generation of OCT used and the treatment that may or may not be used are other factors. Therefore, inclusion criteria of population samples may differ across different studies.


  Conclusion Top


In conclusion, the ability of SD-OCT to differentiate between normal and glaucoma suspect eyes from glaucomatous eyes is better for RNFL thickness than ONH parameters. The ability of both RNFL thickness and optic disc parameters is less in differentiating normal from glaucoma suspect eyes.

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Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Sehi M, Pinzon-Plazas M, Feuer WJ, Greenfield DS. Relationship between pattern electroretinogram standard automated perimetry and optic nerve structural assessments. J Glaucoma 2009; 18 :608-617.  Back to cited text no. 1
    
2.Mwanza JC, Oakley JD, Budenz DL, Anderson DR, Cirrus optical coherence tomography normative database study group. Ability of Cirrus HD-OCT optic nerve head parameters to discriminate normal from glaucomatous eyes. Ophthalmology 2011; 118 :241-248.  Back to cited text no. 2
    
3.Bagga H, Feuer WJ, Greenfield DS. Detection of psychophysical and structural injury in eyes with glaucomatous optic neuropathy and normal standard automated perimetry. Arch Ophthalmol 2006; 124 :169-176.  Back to cited text no. 3
    
4.Bagga H, Greenfield DS. Quantitative assessment of structural damage in eyes with localized visual field abnormalities. Am J Ophthalmol 2004; 137 :797-805.  Back to cited text no. 4
    
5.Johnson CA, Adams AW, Casson EJ, Brandt JD. Progression of early glaucomatous visual field loss as detected by blue-on-yellow and standard white-on white automated perimetry. Arch Ophthalmol 1993; 111 :651-656.  Back to cited text no. 5
    
6.Quigley HA, Addicks EM, Green RW. Optic nerve damage in human glaucoma. III: Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol 1982; 100 :135-146.  Back to cited text no. 6
    
7.Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120 :701-713.  Back to cited text no. 7
    
8.Sommer A, Katz J, Quigley HA, et al. Clinically detectable nerve fiber layer atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol 1991; 109 :77-83.  Back to cited text no. 8
    
9.Mok KH, Lee VW, So KF. Retinal nerve fiber layer measurement by optical coherence tomography in glaucoma suspects with short-wavelength perimetry abnormalities. J Glaucoma 2003; 12 :45-49.  Back to cited text no. 9
    
10.Rao, HL, Zangwill, LM, Weinreb, RN, et al. Comparison of different spectral domain optical coherence tomography scanning areas for glaucoma diagnosis. Ophthalmology 2010; 117 :1692-1699.  Back to cited text no. 10
    
11.Sehi M, Grewal DS, Sheets CW, Greenfield DS. Diagnostic ability of Fourier-domain vs time domain optical coherence tomography for glaucoma detection. Am J Ophthalmol 2009; 148 :597-605.  Back to cited text no. 11
    
12.Nouri-Mahdavi K, Hoffman D, Tannenbaum DP, Law SK, Caprioli J. Identifying early glaucoma with optical coherence tomography. Am J Ophthalmol 2004; 137 :228-235.  Back to cited text no. 12
    
13.Tape TG. Interpreting diagnostic tests. Available at: http://gim.unmc.edu/dxtests/Default.htm. [Last accessed on 2012 Mar 11].  Back to cited text no. 13
    
14.Budenz DL, Michael A, Chang RT, McSoley J, Katz J. Sensitivity and specificity of the stratus OCT for perimetric glaucoma. Ophthalmology 2005; 112 :3-9.  Back to cited text no. 14
    
15.Schuman JS. Spectral domain optical coherence tomography for glaucoma (an AOS thesis). Trans Am Ophthalmol Soc 2008; 106 :426-458.  Back to cited text no. 15
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16.Schuman JS, Wollstein G, Farra T, Hertzmark E, Aydin A, Fujimoto JG. Comparison of optic nerve head measurements obtained by optical coherence tomography and confocal scanning laser ophthalmoscopy. Am J Ophthalmol 2003; 135 :504-512.  Back to cited text no. 16
    
17.Mansoori T, Viswanath K, Balakrishna N. Quantification of retinal nerve fiber layer thickness in normal eyes, eyes with ocular hypertension, and glaucomatous eyes With SD-OCT. Ophthalmic Surg Lasers Imaging 2010; 41:S50-S55.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
Acknowledgements
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