|Year : 2018 | Volume
| Issue : 2 | Page : 117-121
Correlation of peripapillary retinal nerve fiber layer thickness and ganglion cell complex thickness with the severity of diabetic retinopathy
Doaa A Mahmoud, Adel M Abdulwahab, Doaa A Ali
Department of Ophthalmology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
|Date of Submission||20-Sep-2017|
|Date of Acceptance||21-Dec-2017|
|Date of Web Publication||7-Jun-2018|
Doaa A Mahmoud
Department of Ophthalmology, Faculty of Medicine for Girls, Al-Azhar University, Al-Zahraa University Hospital, Abbasia, Cairo
Source of Support: None, Conflict of Interest: None
Purpose The aim of this study was to verify the role of peripapillary retinal nerve fiber layer thickness (RNFLT) and ganglion cell (GC) complex thickness in early detection of diabetic retinopathy (DR) using spectral domain optical coherence tomography (SD-OCT).
Patients and methods This was a cross-sectional, case–control study. Twenty-nine eyes of patients with type 2 diabetes mellitus, either with no DR (16 eyes, group 1) or mild nonproliferative DR (13 eyes, group 2), and 14 eyes of healthy controls (group 3) were enrolled in the present study. All participants had a complete ophthalmic examination, including SD-OCT. Ganglion cell inner plexiform layer (GCIPL) and RNFLT values were calculated after automated segmentation of SD-OCT scans.
Results Significantly reduced GCIPL and RNFLT values were demonstrated in both diabetic patients’ groups compared with healthy controls. Mean GCIPL thickness was 97.5 µm in group 1, 96.9 µm in group 2, and 107.9 µm in group 3 (P=0.04 and 0.04 compared with healthy controls, respectively). Average RNFLT was 104.12±9.6 µm in diabetes patients with no DR (group 1), 100.46±12.86 µm in group 2, and 111.35±6.15 µm in controls (P=0.02 and 0.009 compared with healthy controls, respectively).
Conclusion Significantly reduced GCIPL and RNFLT values were demonstrated in both no DR and mild nonproliferative DR groups compared with healthy controls. This indicates that retinal neuronal degeneration occurs in the early stages of DR, even before microvascular abnormalities are visible.
Keywords: diabetic retinopathy, ganglion cell thickness, optical coherence tomography, retinal nerve fiber layer, type 2 diabetes
|How to cite this article:|
Mahmoud DA, Abdulwahab AM, Ali DA. Correlation of peripapillary retinal nerve fiber layer thickness and ganglion cell complex thickness with the severity of diabetic retinopathy. Delta J Ophthalmol 2018;19:117-21
|How to cite this URL:|
Mahmoud DA, Abdulwahab AM, Ali DA. Correlation of peripapillary retinal nerve fiber layer thickness and ganglion cell complex thickness with the severity of diabetic retinopathy. Delta J Ophthalmol [serial online] 2018 [cited 2018 Nov 16];19:117-21. Available from: http://www.djo.eg.net/text.asp?2018/19/2/117/233934
| Introduction|| |
Diabetic retinopathy (DR) is one of the major complications in patients with diabetes mellitus (DM) that can lead to blindness. However, the precise mechanisms leading to the onset and the progression of the retinopathy remain unclear .
For a long period of time, DR has been considered primarily a retinal microvascular disorder caused by the direct effects of hyperglycemia and by the metabolic pathways it activates . Nevertheless, some recent studies have demonstrated that retinal neurodegeneration (the result of a negative balance between neurotoxic and neuroprotective factors) is present even before the development of clinically detectable microvascular damage. Retinal neurodegeneration may therefore represent an early event in the pathophysiology of DR and may anticipate the onset of microvascular changes .
Recent studies have shown that not only vascular abnormalities but also neuronal abnormalities, including retinal ganglion cell (RGC) death, accompany the pathogenic changes at the early stage of DR . Thus, these two factors should be considered in investigating the pathogenesis of DR, and examination of these abnormalities at the early stage of DR may provide clues to help determine the mechanisms that lead to DR . Numerous studies have evidenced that alteration of different metabolic pathways in diabetes induces functional deficits and loss of different types of retinal cells including ganglion cells (GCs), bipolar cells, and eventually photoreceptors .
The main purpose of this study was to identify in vivo, by spectral domain optical coherence tomography (SD-OCT), the changes in thickness of selected retinal layers both in the macula and the peripapillary area in diabetic patients without DR or with early stages of DR (mild and moderate nonproliferative DR) compared with normal participants.
| Patients and methods|| |
This cross-sectional, case–control study was performed at Al-Zahraa University Hospital, Department of Ophthalmology from October 2016 to March 2017. It included 43 eyes divided into three groups: 16 eyes of diabetic patients with no DR proved by clinical examination and fluorescein angiography (group 1), 13 eyes of diabetic patients with mild or moderate nonproliferative diabetic retinopathy (NPDR) proved by clinical examination and fluorescein angiography  (group 2), and 14 eyes of normal persons with no DM of the same age group as a control group proved by clinical examination and blood sugar test (group 3).
Patients were selected on the basis of the following criteria:
- Patients who were diagnosed clinically and by laboratory investigations as diabetic patients.
- Type 2 DM with NPDR (mild or moderate) according to the international clinical DR disease severity scale .
- Age between 30 and 50 years.
- Clear view of the retina.
The exclusion criteria were as follows:
- Patients with type 1 diabetes or proliferative diabetic retinopathy (PDR).
- Eyes with macular edema.
- Eyes with a history of treatment that could potentially affect the retinal nerve fiber layer (RNFL), including intraocular laser, intravitreal triamcinolone acetonide injection, and vitrectomy.
- Eyes with any unsatisfactory SD-OCT image.
- Eyes with a history of intraocular pressure (IOP) greater than or equal to 22 mmHg or treatment for glaucoma or with optic disc not following the inferior–superior–nasal–temporal rule or showing RNFL defect.
- Other associated ocular problems (e.g. uveitis, optic neuritis, or severe peripapillary atrophy).
- Eyes with a refractive error exceeding ±5.00 D.
The patients, after detailed history taking (especially duration and control of diabetes), underwent a full ophthalmic examination, including the following:
- Measurement of visual acuity, both aided and unaided visual acuity, by the Landolts’ broken ring chart expressed in a decimal fraction.
- Anterior segment examination using slit-lamp biomicroscopy to detect any opacity of the media.
- IOP measurement using Goldman applanation tonometer.
- Fundus examination by using a slit-lamp biomicroscopy with +90 D lens.
- Fundus photography: color stereoscopic fundus photographs (seven early treatment DR study fields) were taken after an adequate dilatation using Topcon fundus camera (TOPCON, TRC.50EX 35° fundus camera, TOPCON, Tokyo, Japan). DR was graded as no DR and as nonproliferative mild or moderate DR (NPDR) according to the international clinical DR severity scale .
- OCT was done by NIDEK SD-OCT machine (RS-3000.OCT Retina Scan Lite; Nidek, Fremont, California, USA). All scans were obtained in a dark room with pupil dilation by a single retina specialist. SD-OCT automatic segmentation of the retinal layers was performed in the macula and in the peripapillary area. In the macula, the segmentation was performed on the linear scan and in the peripapillary area on the circular scan around the optic disc ([Figure 1] and [Figure 2]).
|Figure 1 Optical coherence tomography (retinal nerve fiber layer) of left eye for case no. 28, group 3 shows normal nerve fiber thickness (left photo), and optical coherence tomography (retinal nerve fiber layer) of right eye for patient no. 21, group 2 Shows lower temporal nerve fiber thinning (right photo).|
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|Figure 2 Optical coherence tomography (ganglion cell complex) of left eye for patient no. 9, group I shows diminished ganglion cell complex of both upper and lower quadrant.|
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All participants signed a written informed consent and the study was approved by the Local Ethics Committee.
Statistical analyses were performed with SPSS software, versions 17.00 (SPSS Inc., Chicago, Illinois, USA). P value of less than 0.05 was considered statistically significant. One-way analysis of variance (f) was used to compare the continuous variables.
| Results|| |
The demographic characteristics of the study participants are shown in [Table 1].
|Table 1 Comparison between (age and sex) in patients with no diabetic retinopathy, patients with nonproliferative diabetic retinopathy and normal participants|
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There was no significant difference in best corrected visual acuity and IOP between the three groups ([Table 2]). There was a significant difference in the duration of DM between the two diabetic groups ([Table 3]), as group 2 had a longer duration of DM than group 1.
|Table 2 Comparison between visual acuity, best corrected visual acuity, and intraocular pressure in the three groups|
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|Table 3 Comparison between patients with no diabetic retinopathy and nonproliferative diabetic retinopathy patients in duration of diabetes mellitus|
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group 1, the mean retinal nerve fiber layer thicknesses (RNFLT) were as follows: superior, 129.5±17.28µm; inferior, 135.62±17.41 µm; temporal, 68.5±10.77 µm; nasal, 81.0±16.43 µm; and mean, 104.12±9.6 µm. The mean retinal ganglion cell complex thicknesses (GCCT) were as follows: superior, 104.12±9.61 µm; and inferior, 90.87±23.55 µm. In group 2, the mean RNFLTs were as follows: superior, 125.23±18.26 µm; inferior, 127.30±22.68 µm; temporal, 63.46±17.37 µm; nasal, 85.61±11.16 µm; and mean, 100.46±12.86 µm. The mean GCCTs were as follows: superior, 100.46±12.86 µm; and inferior, 93.38±9.43 µm. In group 3, the mean RNFLTs were as follows: superior, 137.42±10.07 µm; inferior, 145.0±16.98 µm; temporal, 69.78±8.82 µm; nasal, 89.57±8.97 µm; and mean, 111.35±6.15 µm; The mean GCCTs were as follows: superior, 111.35±6.15 µm; and inferior, 104.64±4.41 µm. There was a significant reduction in the mean RNFLT in patients with diabetes compared with the normal participants ([Table 4]). In addition, there was a significant reduction in the superior GCCT and inferior GCCT in the diabetic group compared with the normal participants ([Table 5]). Thus, significantly reduced GCCT and RNFLT values were demonstrated in both diabetic patients’ groups compared with healthy controls.
| Discussion|| |
DR is one of the leading causes of blindness in the developed countries. Although it has long been considered to be a microvascular abnormality, several studies have reported neuronal degeneration as an early event in DR .
Peripapillary RNFLT and GCCT assessment in diabetic patients was performed to confirm this neurodegenerative process. The affected quadrants in RNFL, whether superior, inferior, nasal, or temporal, are still a matter of controversy .
In the current study, the thickness of the peripapillary RNFL and GCC was assessed in diabetic patients who already had DR, and their fundus showed microvascular changes in different stages of DR (mild and moderate NPDR), and diabetic patients who had no DR or any microvascular changes. There was a significant reduction in the mean RNFLT in patients with diabetes compared with normal participants.
Regarding the RNFL thinning, the results of the present study were consistent with those of Takis et al. , who reported that the mean inferior average RNFLT was statistically significantly lower in eyes with no DR and those with mild-NPDR compared with the age-matched controls. In addition, Oshitari et al.  found that the mean RNFLT, superior and inferior RNFLT in eyes with no DR, as well as in eyes with mild and moderate NPDR, was thinner than the age-matched controls, and in eyes with mild and moderate NPDR compared with those with no DR. Chen et al.  and Demir et al.  demonstrated that the thicknesses of the RNFL and ganglion cell inner plexiform layer (GCIPL) were lower in type 2 diabetic patients than in healthy controls, but the results were not statistically significant.
On the other hand, Takahashi et al. , when they compared the average RNFLT and the RNFLT in the superior and inferior quadrants only, they found no significant differences between age-matched healthy controls and diabetic eyes (with mild and moderate NPDR, combined). Using a Topcon 3D OCT-1000, van Dijk et al.  found that the pericentral area of the GCL and the peripheral area of the RNFL were significantly thinned in patients with mild DR, but not in diabetic patients with no DR.
In the present study, the GCC (superior and inferior) showed statistically significant reduction in both diabetic groups in comparison with the normal group. In addition, we found that GCC in the NPDR group was thinner than the diabetic group with no DR, but the reduction was not statistically significant. Chhablani et al.  reported early thinning of GC complex thickness using the Cirrus HD-OCT, and Zhu et al.  found that the macular GCC thickness in the non-DR eyes was significantly reduced by 6.8% in the superior region, whereas no significant difference was found in the inferior area in comparison with control eyes. Demir et al.  concluded that GCC and RNFL were thinner in patients with DM (without DR and with mild or moderate NPDR) compared with control patients, but this difference was not statistically significant. Recently, Tavares Ferreira et al.  found a thinner retina, with decreased thickness particularly in the inner layers, in diabetic patients without DR after 1 year of follow-up. This agreement between the results of the current study about GCC and other studies’ results may give good evidence about neuronal degeneration that may help in the early detection of DR especially in the early stages of DR and diabetic cases without any features of DR.
In conclusion, the data of the present study revealed a significantly reduced GCIPL and RNFLT values in both no DR and mild-NPDR groups compared with healthy controls. Therefore, retinal neuronal degeneration may occur in the early stages of DR even before microvascular abnormalities are visible.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]