• Users Online: 175
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 17  |  Issue : 3  |  Page : 162-166

Effect of diabetic retinopathy on retinal nerve fiber layer thickness


Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

Date of Submission25-May-2016
Date of Acceptance03-Aug-2016
Date of Web Publication6-Dec-2016

Correspondence Address:
Mohammad A.M. El-Hifnawy
Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria 21521
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-9173.195262

Rights and Permissions
  Abstract 

Purpose
The objective of this study was to assess the effect of diabetic retinopathy (DR) on the retinal nerve fiber layer (RNFL) thickness.
Patients and methods
This study included 30 diabetic patients having nonproliferative diabetic retinopathy (NPDR) without macular edema, 20 diabetic patients without DR, and 20 healthy nondiabetic age-matched individuals as a control group. In each patient one eye was included. Patients were evaluated for RNFL thickness by Heidelberg Spectralis optical coherence tomography.
Results
The global (G), the superior, and the temporal RNFL thickness in the diabetic patients without DR was significantly less than that of the control group and that of the patients with NPDR. However, there was no statistically significant difference between the patients with NPDR and the control group. It was noted that there was no statistically significant difference in the RNFL thickness of the inferior and nasal quadrants between the three studied groups.
Conclusion
Early retinal neurodegeneration can occur before retinal microvascular diabetic changes can be observed.

Keywords: diabetic retinopathy, heidelberg spectralis, optical coherence tomography, retinal nerve fiber layer


How to cite this article:
El-Hifnawy MA, Sabry KM, Gomaa AR, Hassan TA. Effect of diabetic retinopathy on retinal nerve fiber layer thickness. Delta J Ophthalmol 2016;17:162-6

How to cite this URL:
El-Hifnawy MA, Sabry KM, Gomaa AR, Hassan TA. Effect of diabetic retinopathy on retinal nerve fiber layer thickness. Delta J Ophthalmol [serial online] 2016 [cited 2017 Oct 20];17:162-6. Available from: http://www.djo.eg.net/text.asp?2016/17/3/162/195262


  Introduction Top


Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population [1].

Clinically detectable characteristics of DR have focused on damage to the retinal vasculature. On the basis of vascular changes, DR is subdivided into an early nonproliferative stage (NPDR) and a more advanced, proliferative, or neovascular stage [2]. In addition, macular edema (i.e. retinal edema involving or threatening the macula) can occur in both stages [3].

NPDR can affect visual function through two mechanisms: (a) increased intraretinal vascular permeability, resulting in macular edema, and (b) variable degrees of intraretinal capillary closure, resulting in macular ischemia [4].

Diabetes can also damage nonvascular cells of the retina. In autopsy samples, retinal ganglion cells are lost, at least in part, through apoptosis [5],[6],[7],[8],[9],[10],[11],[12]. Histological studies of neural components of the retina have revealed that diabetes-induced biochemical mechanisms can potentially cause neural cell degeneration [13]. In addition, 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, bipolar cells, and eventually photoreceptors [14].

Optical coherence tomography (OCT) has been proposed as a powerful tool for retinal measurement, and it provides detailed information with a high resolution [15],[16],[17]. It also allows direct measurement of retinal nerve fiber layer (RNFL) thickness by in-vivo visualization of the retina and RNFL [18].

The Spectralis (Heidelberg Engineering, Heidelberg, Germany), one of the newest spectral (or Fourier) domain OCT machines, uses a significantly faster, nonmechanical technology. It is 100 times faster than time-domain OCT and acquires 40 000 A-scans per second. The increased speed and number of scans translates into higher resolution and a better chance of observing disease. In addition, it has an axial resolution of 7 µm, transverse resolution of 14 µm, and a scan depth of 1.9 mm [19].

RNFL is often shown to be affected in the early pathogenesis of DR. Several studies have reported RNFL thinning or defects in patients with diabetes [20],[21],[22],[23],[24]. However, it is not yet known whether ganglion cell loss in diabetic patients is severe enough to contribute to impaired vision [25].

The aim of this study was to assess the effect of DR on RNFL thickness.


  Patients and methods Top


This comparative study was conducted on 30 diabetic patients having NPDR without macular edema, 20 diabetic patients without DR, and 20 healthy nondiabetic age-matched individuals as a control group. In each patient, one eye was included in the study. Participants were recruited from the Ophthalmology Outpatient Clinic in Alexandria Main University Hospital. Age ranged from 30 to 65 years. Eyes with glaucoma, media opacity precluding OCT imaging, previous ocular surgery in the past 6 months, previous macular laser photocoagulation, traction affecting the macular or peripapillary zone, previous intravitreal injections, spherical error of at least ±6 D or cylindrical error of at least 2 D, macular degeneration, retinal vein occlusion, hypertensive retinopathy, or uveitis were excluded.

All participants provided an informed consent before their enrollment in the study after explanation of the procedure, and the study was approved by the local ethics committee. All participants were subjected to detailed history taking regarding age, duration of diabetes, drugs used for treatment, hypertension, previous ocular surgery, and its timing if present. Complete ophthalmological examination was performed, including slit-lamp biomicroscopy, refraction, intraocular pressure measurement, dilated fundus examination, fundus fluorescein angiography for patients with NPDR, and OCT imaging using Heidelberg Spectralis (software version 5.1; Heidelberg Engineering). RNFL scan protocol was used to measure the peripapillary RNFL, producing a circular scan manually positioned at the optic disc center (768 A-scans) with circle diameter of 12°. RNFL thickness was measured and reported as an overall mean (G, global) and by quadrants, whereby quantitative maps of the retina were obtained. Macular scan was performed, to exclude macular edema. The images were generated by the fast volume scan: 20×20° (6×6 mm) raster scans consisting of 25 horizontal lines (B-scan sections) that were spaced 240 μm apart with 512 A-scans per B-scan. A mean macular thickness map of four quadrants was measured automatically.

All data were tabulated in Microsoft Excel worksheet (Microsoft office system 2007; Microsoft Corporation, Redmond, Washington, USA).

Statistical analysis was carried out using SPSS statistics software version 20 (IBM Corporation, Armonk, New York, USA).


  Results Top


The mean age of the subjects in the three groups was 52.33±8.82, 52.90±5.11, and 47.80±10.47 years, respectively. The mean duration of diabetes was 9.67±7.31 years in group I and 6.25±3.64 years in group II. The mean SE of the three groups was −0.68±2.01, −0.51±2.06, and −0.65±2.47 D, respectively. All study groups showed a statistically insignificant difference.

[Table 1] illustrates the RNFL thickness in the three groups. There was a statistically significant difference in RNFL thickness of global (G), superior, and temporal quadrants between the three studied groups (P=0.014, 0.004, and 0.001, respectively). In the global (G) thickness, the mean RNFL thickness in the diabetic patients without DR (93.35±10.05 µm) was significantly less than that of the control group (104.80±9.96 µm) (P=0.012) and that of the patients with NPDR (104.30±17.96 µm) (P=0.009). However, there was no statistically significant difference between the patients with NPDR and the control group (P=0.902). In the superior quadrant, the mean RNFL thickness in the diabetic patients without DR (110.13±13.93 µm) was significantly less than that of the control group (124.80±14.57 µm) (P=0.013) and that of the patients with NPDR (127.57±22.41 µm) (P=0.001). However, there was no statistically significant difference between the patients with NPDR and the control group (P=0.601). In the temporal quadrant, the mean RNFL thickness in diabetic patients without DR (61.40±12.00 µm) was significantly less than that of the control group (71.75±9.37 µm) (P=0.003) and that of the patients with NPDR (85.73±19.40 µm) (P=0.001). However, there was no statistically significant difference between patients with NPDR and the control group (P=0.751).
Table 1 Comparison between the different study groups according to retinal nerve fiber layer thickness

Click here to view


It was noted that there was no statistically significant difference in RNFL thickness of the inferior and nasal quadrants between the three studied groups (P=0.097 and 0.414, respectively).

The macular thickness in all quadrants in the diabetic patients, whether with NPDR or without retinopathy, was not statistically significantly different from the control group except for the superior quadrant where the macular thickness in the diabetic patients without DR was significantly less than that of the control group. The mean macular thickness of the superior, inferior, temporal, and nasal quadrants in patients with NPDR was significantly more than that of the diabetic patients without DR ([Table 2]).
Table 2 Comparison between the different study groups according to macular thickness

Click here to view



  Discussion Top


The majority of published work on the retina in diabetes has investigated the effect of vascular changes on visual function [26],[27],[28]. However, Della Sala et al. [29] and Sokol et al. [30] reported functional deficits in eyes that have normal visual acuity and minimal evidence of DR.

Bresnick argued strongly that retinopathy should not be viewed as a vascular pathology in isolation and that a similar argument can be applied to neuropathy; it should not be considered as an isolated neural disease. Anatomical and physiological changes to the retina in diabetes highlight the importance of considering neural and vascular complications as potentially linked processes [31].

In the present study, it was found that the global (G), the superior, and the temporal quadrant RNFL thicknesses in the diabetic patients without DR were significantly less than those of the control group and those of the patients with NPDR. However, there was no statistically significant difference between patients with NPDR and the control group. In addition, there was no statistically significant difference in RNFL thickness of the inferior and nasal quadrants between the three studied groups.

Paul et al. [32] used HRA-OCT Spectralis machine to assess RNFL in patients with type 2 diabetes mellitus and reported that most of their patients with RNFL thinning had temporal quadrant lesions.

Lopes de Faria et al. [21], using the nerve fiber analyzer (GDx), reported significant nerve fiber layer loss in the superior segment of the retina in patients with type 1 diabetes mellitus without DR.

Sugimoto and colleagues used Stratus OCT to assess RNFL during glycemic control in patients with type 2 diabetes mellitus. All patients were examined at initial visit, 1 month, 2 months, and 4 months after the initial examination. On each occasion, glycosylated hemoglobin (HbA1c) levels and OCT scanning for RNFL thickness were evaluated. No significant RNFL change was seen between the initial and 1-month or 2-month examinations. A significant decrease was seen in the superior quadrant between the initial and 4-month examinations. No significant change was found in the other quadrants [23].

The findings of the present study corroborate with an experimental study conducted by Kern and Engerman [33] in two animal models of DR, showing that the early events of diabetic retinal disease (microaneurysms and acellular capillaries) were not uniformly distributed across the retina and both lesions were significantly more prevalent in the superior temporal retina rather than in inferior nasal areas.Among other studies, an experimental study was conducted by Chung et al. [34] to evaluate the blood flow response to hyperoxia and hypercapnia in peripapillary retinal tissue superior and inferior to the optic nerve head using confocal scanning laser Doppler flowmetry. Their results revealed that the superior temporal regions were more responsive to vasoconstriction and less responsive to vasodilatation, and thus more prone to develop oxidative damage and nerve cell loss.

In the present study, it was noted that there was no statistically significant difference in RNFL thickness of any quadrant in eyes with early NPDR when compared with healthy age-matched control group. This is in accordance with other studies conducted by Tekeli et al. [35] and Takahashi et al. [22].

In the present study, the macular thickness in all quadrants in the diabetic patients, whether with NPDR or without retinopathy, was not statistically significantly different from the control group except for the superior quadrant where the macular thickness in the diabetic patients without DR was significantly less than that of the control group. The macular thickness in patients with NPDR was significantly more than that of the diabetic patients without retinopathy in all quadrants, which may indicate subclinical and sub-OCT macular edema. This may explain why RNFL thickness in patients with NPDR was thicker than that of the diabetic patients without DR.


  Conclusion Top


The present study showed that the RNFL thickness was significantly less in diabetic patients without DR than in the control group and the patients with NPDR in the global (G), superior, and temporal quadrants, which could be explained by more vascular insult on the superior quadrant as compared with the inferior quadrant.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103:137–149.  Back to cited text no. 1
    
2.
Davis MD, Kern TS, Rand LI. Diabetic retinopathy. In: Alberti KGMM, Zimmet P, DeFronzo RA, editors. International textbook of diabetes mellitus. 2nd ed. New York: John Wiley & Sons; 1997. 1413–1446.  Back to cited text no. 2
    
3.
Kohner EM, Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am J Ophthalmol 1970; 69:403–414.  Back to cited text no. 3
    
4.
Chew EY, Ferris FL III. Non proliferative diabetic retinopathy. In: Ryan SJ, Hinton DR, Schachat AP, Wilkinson CP, editors. Retina. 4th ed. Philadelphia: Elsevier/Mosby; 2006. 1271–1284.  Back to cited text no. 4
    
5.
Wolter JR. Diabetic retinopathy. Am J Ophthalmol 1961; 51:1123–1141.  Back to cited text no. 5
    
6.
Bloodworth JMJr. Diabetic retinopathy. Diabetes 1962; 11:1–22.  Back to cited text no. 6
    
7.
Bloodworth JMJr, Molitor DL. Ultrastructural aspects of human and canine diabetic retinopathy. Invest Ophthalmol 1965; 4:1037–1048.  Back to cited text no. 7
    
8.
Kerrigan LA, Zack DJ, Quigley HA, Smith SD, Pease ME. Tunl-positive ganglion cells in human primary open-angle glaucoma. Arch Ophthalmol 1997; 115:1031–1035.  Back to cited text no. 8
    
9.
Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 1998; 102:783–791.  Back to cited text no. 9
    
10.
Abu-El-Asrar AM, Dralands L, Missotten L, Al-Jadaan IA, Geboes K. Expression of apoptosis markers in the retinas of human subjects with diabetes. Invest Ophthalmol Vis Sci 2004; 45:2760–2766.  Back to cited text no. 10
    
11.
Abu El-Asrar AM, Dralands L, Missotten L, Geboes K. Expression of antiapoptotic and proapoptotic molecules in diabetic retinas. Eye 2007; 21:238–245.  Back to cited text no. 11
    
12.
Oshitari T, Yamamoto S, Hata N, Roy S. Mitochondria and caspase dependent cell death pathway involved in neuronal degeneration in diabetic retinopathy. Br J Ophthalmol 2008; 92:552–556.  Back to cited text no. 12
    
13.
Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, Jefferson LS et al. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 2006; 55:2401–2411.  Back to cited text no. 13
    
14.
Ly A, Yee P, Vessey KA, Phipps JA, Jobling AI, Fletcher EL. Early inner retinal astrocyte dysfunction during diabetes and development of hypoxia, retinal stress, and neuronal functional loss. Invest Ophthalmol Vis Sci 2011; 52:9316–9326.  Back to cited text no. 14
    
15.
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WC, Chang W et al. Optical coherence tomography. Science 1991; 254:1178–1181.  Back to cited text no. 15
    
16.
Hee MR, Izatt JA, Swanson EA, Huang D, Schuman JS, Lin CP, Puliafito CA, Fujimoto JG. Optical coherence tomography of the human retina. Arch Ophthalmol 1995; 113:325–332.  Back to cited text no. 16
    
17.
Fujimoto JG, Brezinski ME, Tearney GJ, Boppart SA, Bouma B, Hee MR, Southern JF, Swanson EA. Optical biopsy and imaging using optical coherence tomography. Nat Med 1995; 1:970–972.  Back to cited text no. 17
    
18.
Zangwill LM, Bowd C, William J, William J, Blumenthal EZ, Sanchez-Galeana CA, Weinreb RN. Discriminating between normal and glaucomatous eyes using the Heidelberg retinal tomography, GDx nerve fibre analyzer and optical coherence tomography. Arch Ophthalmol 2001; 119:985–993.  Back to cited text no. 18
    
19.
Spectralis. Spectral domain optical coherence tomography. 2 October 2013. Available at: http://www.heidelbergengineering.com/us/products/spectralis-models/technology/spectral-domain-oct/. [Last accessed on 2016 Mar 10].  Back to cited text no. 19
    
20.
Chihara E, Matsuoka T, Ogura Y, Matsaumura M. Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy. Ophthalmology 1993; 100:1147–1151.  Back to cited text no. 20
    
21.
Lopes de Faria JM, Russ H, Costa VP. Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. Br J Ophthalmol 2002; 86:725–728.  Back to cited text no. 21
    
22.
Takahashi H, Goto T, Shoji T, Tanito M, Park M, Chihara E. Diabetes-associated retinal nerve fiber damage evaluated with scanning laser polarimetry. Am J Ophthalmol 2006; 142:88–94.  Back to cited text no. 22
    
23.
Sugimoto M, Sasoh M, Ido M, Wakitani Y, Takahashi C, Uji Y. Detection of early diabetic change with optical coherence tomography in type 2 diabetes mellitus patients without retinopathy. Ophthalmologica 2005; 219:379–385.  Back to cited text no. 23
    
24.
Verma A, Raman R, Vaitheeswaran K, Pal SS, Laxmi G, Gupta M, Shekar SC, Sharma T. Does neuronal damage precede vascular damage in subjects with type 2 diabetes mellitus and having no clinical diabetic retinopathy? Ophthalmic Res 2006; 47:202–207.  Back to cited text no. 24
    
25.
Kern T, Tang J, Berkowitz B. Validation of structural and functional lesions of diabetic retinopathy. Mol Vis 2010; 16:2121–2131.  Back to cited text no. 25
    
26.
Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs-an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 1991; 98:786–806.  Back to cited text no. 26
    
27.
Larsen M, Godt J, Larsen N, Lund-Andersen H, Sjolie AK, Agardh E et al. Automated detection of fundus photographic red lesions in diabetic retinopathy. Invest Ophthalmol Vis Sci 2003; 44:761–766.  Back to cited text no. 27
    
28.
Early Treatment of Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology 1991; 98:823–833.  Back to cited text no. 28
    
29.
Della Sala S, Bertoni G, Somazie L, Stubbe F, Wilkins AJ. Impaired contrast sensitivity in diabetic patients with and without retinopathy: a new technique for rapid assessment. Br J Ophthalmol 1985; 69:136–142.  Back to cited text no. 29
    
30.
Sokol S, Moskowitz A, Skarf B, Evans R, Molitch M, Senior B. Contrast sensitivity in diabetics with and without background retinopathy. Arch Ophthalmol 1985; 103:51–54.  Back to cited text no. 30
    
31.
Bresnick GH. Diabetic retinopathy viewed as a neurosensory disorder. Arch Ophthalmol 1986; 104:989–990.  Back to cited text no. 31
    
32.
Paul R, Ghosh AK, Chakraborty B, Dan S. Study of retinal nerve fiber layer thickness in type II diabetes mellitus by 3-dimensional optical coherence tomography from Eastern India. J App Pharm Sci 2014; 4:34–38.  Back to cited text no. 32
    
33.
Kern TS, Engerman RL. Vascular lesions in diabetes are distributed non uniformly within the retina. Exp Eye Res 1995; 60:545–549.  Back to cited text no. 33
    
34.
Chung HS, Harris A, Halter PJ, Kagmann L, Roff EJ, Garzozi HJ, Hosking SL, Martin BJ. Regional differences in retinal vascular reactivity. Invest Ophthalmol Vis Sci 1999; 40: 2448–2453.  Back to cited text no. 34
    
35.
Tekeli O, Turaçli ME, Atmaca LS, Elhan AH. Evaluation of the optic nerve head with the Heidelberg retina tomograph in diabetes mellitus. Ophthalmologica 2008; 222:168–172.  Back to cited text no. 35
    



 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed368    
    Printed3    
    Emailed0    
    PDF Downloaded47    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]