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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 111  |  Issue : 1  |  Page : 7-14

Correlation of retinal nerve fiber layer thickness and perimetric changes in primary open-angle glaucoma


1 Department of Ophthalmology, Ministry of Health, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Ophthalmology, Mansoura Ophthalmic Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Web Publication26-Jul-2018

Correspondence Address:
Hossam Y Abouelkheir
Department of Ophthalmology, Mansoura Ophthalmic Center, Faculty of Medicine, Mansoura University, Mansoura 35516
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejos.ejos_5_18

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  Abstract 

Purpose This study aims at evaluating the relation between retinal nerve fiber layer (RNFL) thickness evaluated by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma and visual field sensitivity.
Patients and methods A total of 20 normal and 60 glaucomatous eyes were included in this study. Glaucomatous eyes were graded into early, moderate and severe stages according to Hodapp, Parrish, and Anderson classification. Complete ophthalmic examination, white-on-white perimetry and spectral-domain OCT were done for all patients. RNFL thickness of quadrants and average thickness were recorded. Area under receiver operating characteristic curves were used to assess the performance of OCT parameters.
Results Average RNFL thickness was the best parameter to discriminate normal from early glaucoma, early from moderate and moderate from severe. Average RNFL loss was 14.9% in early glaucoma, 25.1% in moderate glaucoma and 37.2% in severe glaucoma. A significant correlation was detected between mean deviation and average RNFL thickness.
Conclusion The present study found that average RNFL thickness has a good diagnostic value for diagnosis of glaucoma and for differentiating between glaucoma stages according to its severity.

Keywords: open-angle glaucoma, perimetry, retinal nerve fiber layer thickness


How to cite this article:
El-Naby AE, Abouelkheir HY, Al-Sharkawy HT, Mokbel TH. Correlation of retinal nerve fiber layer thickness and perimetric changes in primary open-angle glaucoma. J Egypt Ophthalmol Soc 2018;111:7-14

How to cite this URL:
El-Naby AE, Abouelkheir HY, Al-Sharkawy HT, Mokbel TH. Correlation of retinal nerve fiber layer thickness and perimetric changes in primary open-angle glaucoma. J Egypt Ophthalmol Soc [serial online] 2018 [cited 2018 Nov 12];111:7-14. Available from: http://www.jeos.eg.net/text.asp?2018/111/1/7/237609


  Introduction Top


Optical coherence tomography (OCT) is an innovative diagnostic tool in tomographic imaging of tissues. In the field of ophthalmology, its ease of access to different areas in the eye allows its use as an excellent diagnostic technology [1].

Spectral-domain optical coherence tomography (SD-OCT) is superior to time-domain OCT in performing scanning with higher axial resolution, faster speed and better reproducibility [2].

Chronic progressive optic neuropathy is the descriptive pathogenesis of primary open-angle glaucoma (POAG), which is associated with optic disc cupping and visual field (VF) changes with no obvious systemic or ocular cause [3].

As glaucoma is listed as the second leading cause of blindness among population, its early diagnosis is crucial. Standard VF examinations is used in the diagnosis and follow-up of glaucoma, but one of its drawbacks is that the abnormalities do not appear until 20–40% of ganglion cells are lost. Earlier defects in the retinal nerve fiber layer (RNFL) measured by OCT provide an excellent objective and quantitative method in the diagnosis and management of glaucoma [3].

The use of low coherence interferometry in recording the echo time delay and intensity of backscattered light from various layers of the retina allows OCT to achieve an accurate measurement of the peripapillary RNFL thickness [4].


  Patients and methods Top


In this study, all cases were examined in Mansoura Ophthalmology Center in the period extending from December 2013 to January 2015, including 80 eyes of 80 patients. The eyes were classified into the following:
  1. Normal age-matched patients included 20 patients.
  2. Patients with POAG classified according to disease severity into 22 patients experiencing early glaucoma, 20 patients with moderate glaucoma and 18 patients having severe glaucoma according to Hodapp, Parrish and Anderson classification ([Table 1]).
    Table 1 Hodapp, Parrish, and Anderson classification

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All patients underwent assessment regarding medical and family history, best-corrected visual acuity, intraocular pressure (IOP) measurement, gonioscopy, slit lamp biomicroscopy using 78 D lens, Humphrey 24-2 VF test and OCT examination.

Inclusion criteria

  1. Normal eyes: no history or evidence of ocular pathology, surgery or laser; IOP of 21 mmHg or less; normal appearance of the nerve head; and no abnormal VF defects.
  2. Glaucomatous eyes: glaucomatous optic neuropathy was defined as either cup-disc asymmetry between the two eyes of more than 0.2, rim thinning, notching, excavation or RNFL defect on clinical stereoscopic fundus examination.


Minimal criteria for glaucomatous VF abnormality:
  1. Three or more adjacent points in an expected location of the central 24° field that have P less than 5% on the pattern deviation plot, one of which must have P less than 1%.
  2. Glaucoma Hemifield test outside normal limits.
  3. Corrected pattern SD, with P less than 5%.


If any of the three criteria for minimal abnormality is met, the defect is considered significant.

Exclusion criteria

Patients with any ocular pathology, intraocular operation, trauma, secondary glaucoma, unreliable VFs (defined as a false negative >33%, false positive >33% and fixation losses >20%) and a possible neurological field loss were excluded from the study.

Visual field examination

All patients were tested using central 24-2 full threshold automated static perimetry by Humphrey (Carl Zeiss Meditec, Germany).

Optical coherence tomography examination

Optical coherence tomographic examination was performed using Topcon 3D OCT-1000 mark II (Topcon, Tokyo, Japan). RNFL measurements were recorded as an average over four quadrants, 12 clock hours and mean thickness of the total circumpapillary scan. Depending on the instrument’s normative database, any RNFL measurements outside 95% normal limits that were confirmed on at least two of three repeat scans were highlighted as abnormal thinning in red or yellow according to the severity of thinning.

In this study, we evaluated the ability of the OCT to discriminate non-glaucomatous eyes from glaucomatous eyes in their various stages of functional damage using the average peripapillary RNFL thickness. Specifically, we compared the average RNFL thickness between patients with mild, moderate, and severe glaucomatous VF loss based on the Hodapp–Anderson–Parish criteria and normal age-matched controls. We also determined the correlation between the visual field parameter mean defect (VFMD) of automated perimetry and the average peripapillary RNFL thickness as measured by the OCT.

Lastly, we determined the level of RNFL percentage loss in mild, moderate, and severe glaucoma.

Statistical analysis

The received data in the current research were analyzed by SPSS program versions 17 using Microsoft Windows 7. Continuous variables were illustrated in the form of mean±SD and categorical variables were shown in the form of count and percent. Comparison among continuous data was done using Student’s t-test, whereas categorical data were analyzed using χ2-test. Pearson’s correlation coefficient was used to investigate the relation between variables. We used receiver operator characteristic to determine test reliability. P value less than 0.05 was considered statistically significant.


  Results Top


Descriptive statistics of age and gender in studied groups

Comparison between glaucoma patients and healthy controls regarding the age and gender distribution illustrated no statistically significant differences ([Table 2]).
Table 2 Comparison between patients and controls regarding the age and sex revealed no statistically significant differences

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Basic data in the studied groups

Comparison between patients and controls regarding the basic data [spherical equivalent, best-corrected visual acuity (BCVA) in logMar, IOP in mmHg, VFMD in db] shows that patients had significantly lower BCVA when compared with controls, with P value of 0.038, and significant decrease in VFMD when compared with controls, with P value less than 0.001 ([Table 3]).
Table 3 Comparison between patients and controls regarding the basic data

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Retinal nerve fiber layer thickness in normal controls and glaucoma subgroups

Results showed that patients with early disease had significantly higher average RNFL measurements when compared with patients with moderate and severe disease. Moreover, patients with moderate disease had significantly higher RNFL measurements when compared with patients with severe disease. In addition, normal controls had significantly higher RNFL measurements when compared with all degrees of glaucoma, as shown in [Table 4] and [Table 5] and [Figure 1].
Table 4 Comparison between normal and glaucoma subgroups regarding retinal nerve fiber layer measurements

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Table 5 Post-hoc analysis

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Figure 1 Retinal nerve fiber layer measurements in normal and glaucoma subgroups.

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Correlation between average retinal nerve fiber layer measurements and visual field mean deviation

There was a significant direct correlation between average RNFL and VFMD ([Table 6] and [Figure 2]).
Table 6 Correlation between average retinal nerve fiber layer measurements and visual field mean deviation

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Figure 2 Correlation between average retinal nerve fiber layer and visual field mean deviation (VFMD).

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Retinal nerve fiber layer thinning at various stages of glaucoma

Compared with normal controls, patients with early glaucoma had a 14.9% thinning, whereas patients with moderate glaucoma had 25.1% thinning and patients with severe glaucoma had 37.2% thinning ([Table 7] and [Figure 3]).
Table 7 Retinal nerve fiber layer thinning in different stages of glaucoma

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Figure 3 Retinal nerve fiber layer thinning in different stages of glaucoma.

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Diagnostic reliability of average retinal nerve fiber layer thickness in diagnosis of glaucoma and its different grades

It was shown that average RNFL has a good diagnostic value for diagnosis of glaucoma and for differentiating subgroups into early, moderate and severe) by receiver operator characteristic curve and area under the curve as shown in [Table 8] and [Figure 4],[Figure 5],[Figure 6].
Table 8 Average retinal nerve fiber layer in diagnosis of glaucoma and its different grades

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Figure 4 The receiver operator characteristic (ROC) curve of the average retinal nerve fiber layer for discriminating between normal and early stages of glaucoma.

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Figure 5 The receiver operator characteristic (ROC) curve of the average retinal nerve fiber layer for discriminating between early and moderate stages of glaucoma.

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Figure 6 The receiver operator characteristic (ROC) curve of the average nerve fiber layer for discriminating between moderate and severe stages of glaucoma.

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At cutoff of 94.5 μm, average RNFL can differentiate normal from early glaucoma with 100% sensitivity and 76.2% specificity.

At cutoff 82.5 μm, average RNFL can differentiate early glaucoma from moderate with 95.2% sensitivity and 68.4% specificity.

At cutoff of 68.5 μm, average RNFL can differentiate severe from moderate glaucoma with 100% sensitivity and 65% specificity.

Sample of the recruited patients

Case no. 1

This was a 48-year-old female patient with 8-year history of glaucoma, with the following data upon examination ([Table 9] and [Figure 7]).
Table 9 Data of patient number 1

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Figure 7 (a) Case no. 1 perimetry. (b) Case no. 1 optical coherence tomography.

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Case no. 2

This was a 49-year-old male patient with 10-year history of glaucoma, with the following data upon examination ([Table 10] and [Figure 8]).
Table 10 Data of patient number 2

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Figure 8 (a) Case no. 2 perimetry. (b) Case no. 2 optical coherence tomography.

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  Discussion Top


The present study aimed to evaluate the role of RNFL thickness measurement by SD-OCT in the diagnosis of glaucoma progression. The study included 60 patients with glaucoma and 20 age-matched and sex-matched healthy individuals as a control group. They underwent history taking, ophthalmological assessment and imaging using SD-OCT.

Comparison between patients and controls regarding the basic data showed that patients had significantly lower BCVA (0.4±0.27 vs. 0.3±0.13; P=0.038) and VFMD (−9.45±5.57 vs. 0.3±0.65; P=0.0001) than the control individuals. The same results were shown in the study of Hasegawa et al. [5]. In their study, glaucomatous patients had significantly more deteriorated VFMD when compared with healthy controls. Moreover, the significant worsening of visual acuity in patients with POAG was noted by the study of Chan et al. [6] who studied the influence of visual acuity deterioration on patients with glaucoma.

In our study, it was shown that patients with glaucoma had significantly lower RNFL quadrant measurements when compared with controls in microns (65.1±4.03 vs. 77.4±6.87; P=0.0001 for temporal quadrant; 73.7±8.8 vs. 88.5±4.7; P=0.0001 for nasal quadrant; 91.06±18.86 vs. 124.55±6.95; P=0.0001 for superior quadrant; and 94.16±19.17 vs. 129.25±6.65; P=0.0001 for inferior quadrant). This in accordance with the study of Elbendary and Mohamed Helal [7] who evaluated the role of SD-OCT in different stages of glaucoma and found similar results.

Regarding the comparison between average retinal nerve fiber measurements in patients with different stages of glaucoma and controls, the present study found that patients with early disease had significantly thicker average RNFL thickness measurements when compared with patients with moderate and severe disease (90.8±7.2, 78.8±6.6 and 66.9±7.2 µm, respectively). Moreover, patients with moderate disease had significantly thicker RNFL thickness measurements when compared with patients with severe disease. In addition, normal controls had significantly thicker RNFL thickness measurements when compared with all degrees of glaucoma.

This is in harmony with the study of Mansoori et al. [4] who assessed the utility of SD-OCT to differentiate normal eyes from those with early glaucoma in Asian Indian eyes. The study recruited 178 eyes (83 patients with glaucoma and 95 age-matched healthy persons). The mean RNFL thickness in healthy controls and patients with glaucoma was 105.7±5.1 and 90.7±7.5 µm, respectively (P=0.001).

In addition, Kaw et al. [8] in their study aimed to compare SD-OCT evaluation of RNFL thickness in normal controls and POA glaucoma of various stages and found that normal patients had the thickest RNFL thickness when compared with patients; moreover, increased glaucoma severity was associated with thinner RNFL.

Moreover, the study of Firat et al. [9] measured RNFL thickness in POAG, normal tension glaucoma and normal healthy individuals using SD-OCT. RNFL thickness measurements were significantly higher in normal persons, followed in order by the normal tension glaucoma and POAG (P<0.05).

Furthermore, our data are in accordance with the former study of Elbendary and Mohamed Helal [7] who noted that normal controls had significantly higher RNFL thickness when compared with patients with glaucoma, and those with more severe disease had significantly thinner RNFL.

We are also in agreement with the study of Golzan et al. [10] who assessed RNFL thickness in patients with glaucoma and healthy patients. In their study, patients with glaucoma had significantly lower RNFL thickness when compared with normal patients (87±26 vs. 111±15 µm, P<0.0001).

In the study of Nakatani et al. [11] who evaluated the diagnostic ability of peripapillary RNFL measurements for early glaucoma, the authors found significant differences between early glaucoma and normal patients in all parameters except fovea in macular scans and in the superior and inferior quadrants at 12, 3, 6, 7, and 11 o’clock positions.

In this study, there was a significant correlation found between VF loss and RNFL thickness. Moreover, nerve thinning was more significant in cases with severe glaucoma when compared with patients with mild and moderate glaucoma.

This is in accordance with the study by Sehi et al. [12] that compared prospectively the detection of progressive RNFL loss using time-domain OCT with VF progression using standard automated perimetry in glaucoma suspect and in patients with glaucoma with and without perimetric changes. They found that structural progression is accompanied with functional progression in glaucoma suspect and glaucomatous eyes. Average and superior RNFL thickness may give the clue for further standard automated perimetry loss.

This is in agreement with the study of Alasil et al. [13] who studied 108 patients with glaucoma in addition to 78 healthy controls. The participants were subjected to perimetry analysis and RNFL OCT scans aiming to detect the RNFL thickness threshold at which VF loss begins to be clinically detectable. The study revealed a statistically significant correlation between RNFL thickness and corresponding VF loss.

In addition, the study of Miki et al. [14] used RNFL thickness measurements by OCT to predict VF loss in patients with glaucoma. In their study, 454 eyes from 294 glaucoma suspects were included. The study found that the rate of RNFL loss was more than double as fast in eyes that developed VF defects in comparison with eyes that did not develop field defects. They concluded that assessment of the rate of SD-OCT RNFL loss may be a useful indicator in patients who are at a high risk of developing VF loss.

In the current study, it was reported that in comparison with normal controls, patients with early glaucoma had a 14.9% thinning, whereas patients with moderate glaucoma had 25.1% thinning and patients with severe glaucoma had 37.2% thinning. This agrees with the former study of Kaw et al. [8]. They found that in comparison with healthy controls, patients with mild glaucoma had 12.2% thinning whereas patients with moderate glaucoma had 22.1 thinning and patients with severe glaucoma had 42.7% thinning.

Finally, the present study found that RNFL thickness has a good diagnostic value for diagnosis of glaucoma and for differentiating mild glaucoma from normal controls and moderate from mild glaucoma and severe from moderate glaucoma. This is in agreement with the study of Elbendary and Mohamed Helal [7] and with a recent meta-analysis performed by Michelessi et al. [15]. The authors illustrated the accuracy of OCT for diagnosing glaucoma. They reported that RNFL had a high accuracy for diagnosing glaucoma.

A larger multicenter nationwide study is needed to clarify and establish the role of OCT in follow-up of patients with POAG.

Average RNFL thickness assessed with SD-OCT can differentiate the three stages of glaucoma. Structural damage owing to RNFL loss can be correlated with functional damage shown in VF loss. This finding may be the cornerstone for upcoming OCT-based staging of glaucoma, combined to automated perimetry.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

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