|Year : 2021 | Volume
| Issue : 1 | Page : 9-13
Study of peripapillary retinal nerve fiber layer thickness in patients of type 2 diabetes mellitus and its correlation with glycemic control
Valerie Menezes, Ugam P S. Usgaonkar, Akshaya Nagvenkar
Department of Ophthalmology, Goa Medical College, Bambolim, Goa, India
|Date of Submission||03-Oct-2019|
|Date of Decision||12-Oct-2020|
|Date of Acceptance||27-Oct-2020|
|Date of Web Publication||10-Apr-2021|
Siddarth Apartments-2/S-2, P.O, Caranzalem - 403 002, Goa
Source of Support: None, Conflict of Interest: None
Context: The retina of diabetic patients undergoes neurodegenerative changes, in addition to the vascular changes. Aims: The aim of this study is to evaluate the peripapillary retinal nerve fiber layer (RNFL) thickness in type 2 diabetes mellitus (DM) patients compared to healthy controls, using optical coherence tomography (OCT) and to correlate it with glycemic control. Settings and Design: Prospective study. Subjects and Methods: A total of 90 patients were enrolled in the study. The study group included 120 eyes of 60 type 2 DM patients. Sixty eyes of 30 healthy participants served as the control group. All patients underwent an OCT scan for peripapillary RNFL thickness measurement. Metabolic control of DM was assessed using glycosylated hemoglobin (HbA1c). Statistical Analysis Used: Independent sample t-test was used for normally distributed variables. Pearson's correlation analysis was used to assess the correlation between HbA1c and RNFL thickness. Results: Right eye RNFL thickness was thinner in diabetic patients than controls, with a statistically significant P value (P = 0.002) in the superior quadrant and inferior quadrant (P = 0.019). The average, superior, and inferior RNFL thickness in the left eye was significantly thinner in diabetic patients as compared to controls (P < 0.001, P = 0.001, and P < 0.001 respectively). No significant correlation was found between HbA1c and RNFL thickness. Conclusions: The peripapillary RNFL is thinner in diabetic patients as compared to controls. This is the first study of its kind, among diabetic patients in Goa, which makes this study unique.
Keywords: Diabetic retinopathy, optical coherence tomography, retinal nerve fiber layer thinning
|How to cite this article:|
Menezes V, S. Usgaonkar UP, Nagvenkar A. Study of peripapillary retinal nerve fiber layer thickness in patients of type 2 diabetes mellitus and its correlation with glycemic control. J Clin Ophthalmol Res 2021;9:9-13
|How to cite this URL:|
Menezes V, S. Usgaonkar UP, Nagvenkar A. Study of peripapillary retinal nerve fiber layer thickness in patients of type 2 diabetes mellitus and its correlation with glycemic control. J Clin Ophthalmol Res [serial online] 2021 [cited 2022 Jan 27];9:9-13. Available from: https://www.jcor.in/text.asp?2021/9/1/9/313477
| Introduction|| |
Diabetic retinopathy (DR) is a leading cause of visual loss globally.
Despite advances in the treatment of DR, such as laser photocoagulation, intravitreal anti-vascular endothelial growth factor, or vitreous surgery, vision does not improve significantly in many patients, and in some patients, vision continues to decline. The most commonly accepted pathophysiological model for this visual loss is attributed to vascular change (microvascular theory) in the retina, particularly in the retinal capillaries. The other pathophysiological model, somewhat less investigated is the neurodegenerative theory.
Several studies have shown that neurodegeneration precedes clinically detectable microvascular damage in diabetes., Any loss of neural tissue will lead to a decrease in the retinal thickness.
Optical coherence tomography (OCT) is the most precise method to measure retinal thickness. Spectral-domain OCT has the advantages of high-speed data acquisition, three-dimensional reconstruction of acquired retinal images, and improved visualization of retinal architecture, layer by layer.
Spectral-domain OCT allows detailed quantitative measurement of peripapillary retinal nerve fiber layer (RNFL) thickness. The objective of this study was to identify the changes in the peripapillary RNFL thickness in patients of type 2 diabetes mellitus (DM) and to compare it with healthy controls, using OCT. Correlation between peripapillary RNFL thickness and glycemic control was assessed.
To the best of our knowledge, no such prior study has been done among diabetic patients from Goa which makes this study uniquely valuable.
An examination for alterations in the thickness of the RNFL may provide additional evidence about the alternate pathogenic mechanisms in DR that is neurodegenerative damage. The data obtained in this study could be used as a reference for larger studies and might pave the way for novel therapeutic approaches such as neuroprotective treatment, so that a preventive approach can be used in managing diabetic retinopathy.
| Subjects and Methods|| |
It was a prospective study consisting of patients attending the ophthalmology outpatient department, at a tertiary care center in Goa over a period of 6 months. Using appropriate statistical formula, power of 80% and 5% significance level, minimum sample size calculated was 49 patients. There were two groups: study group and control group. The inclusion criteria for the study group were type 2 DM patients of Goan ethnicity, whose fundus examination showed no DR or mild nonproliferative diabetic retinopathy (NPDR) or moderate NPDR without macular edema.
The inclusion criteria for the control group were healthy controls of Goan ethnicity, with no systemic diseases, having a best-corrected visual acuity of 6/6 and a normal fundus examination.
The exclusion criteria consisted of patients with media opacities such as dense cataract and corneal opacities, preexisting glaucoma, patients with refractive errors of myopia >5 D or hypermetropia >3 D or astigmatism >2 D, optic disc anomalies, previous history of laser or vitreoretinal surgery, and retinopathy due to hypertension or other vascular diseases.
Informed consent was obtained from all the participants of the study. Ethical clearance from the Institutional Ethics Committee was obtained before the study.
While selecting patients, the Goan ethnicity of the patient population was verified by the details given on the case paper, made at the time of outpatient department registration.
All participants underwent a comprehensive ophthalmological examination including visual acuity assessment using Snellen's chart (best-corrected visual acuity was applied according to refraction), anterior segment examination, intraocular pressure assessment using Goldman applanation tonometer, and fundus examination using 78 diopter (D) lens at the slit lamp.
An OCT scan was done in both eyes of all patients by using spectral-domain OCT. The Primus 200 (Carl Zeiss Meditec) was used for the spectral-domain OCT scan. Average RNFL was analyzed using the “optic-disc cube” scan protocol. The peripapillary RNFL thickness within a circular scan of 3.46 mm centered on the optic disc was measured automatically. The reproducibility limit of the Primus 200 in measuring the average RNFL thickness is 7 (±2.5) μm.
Metabolic control of DM was assessed using the reports of glycosylated hemoglobin (HbA1c) and fasting blood sugar level (FBSL) available with the patient at the time of examination. HbA1c was measured by the high-performance liquid chromatography method.
It was performed using the commercially available Statistical Package for Social Sciences (SPSS 14.0, SPSS Inc, Chicago, Illinois, USA). Independent sample t-test was used for normally distributed variables. Pearson's correlation analysis was applied to find the correlation between HbA1c and RNFL thickness. P < 0.05 was considered to be statistically significant.
| Results|| |
There were 90 patients included, of which 51 were male and 39 were female. There were two groups.
- Group 1 (study group) – included 120 eyes of 60 patients of type 2 DM
- Group 2 (control group) – included 60 eyes of 30 healthy participants.
[Figure 1] shows the flow diagram of enrolled patients
|Figure 1: Flow diagram showing enrolled patients. DR: Diabetic retinopathy|
Click here to view
The mean age of the control group was 47.03 years (SD 9.231). Mean HbA1c of the control group was 5 (SD 0.2586).
In the study group, diabetic patients were divided into two groups based on the fundus examination:
- Patients without DR. This group had 80 eyes of 40 patients
- Patients with DR (mild or moderate NPDR without diabetic macular edema). This group had 40 eyes of 20 patients. 27 eyes had mild NPDR and 13 eyes had moderate NPDR.
There was no diabetic patient with unilateral DR.
Baseline characteristics of the study group are shown in [Table 1]. The independent sample t-test was used to analyze the baseline characteristics such as age, duration of DM, mean HbA1c level, and FBSL. No statistically significant difference was found between the two groups (patients without DR and with DR) with respect to age (P = 0.401) and duration of DM (P = 0.734). Similarly, there was no statistically significant difference in HbA1c and FBSL between the two groups (P = 0.666 and P = 0.847, respectively)
|Table 1: Baseline characteristics of diabetic patients in the study group|
Click here to view
[Table 2] shows the comparison of the RNFL thickness measured by OCT in both the study and the control groups. The RNFL thickness was found to be thinner in diabetic patients as compared to normal healthy controls. Right eye RNFL thickness was found to be thinner in diabetic patients than in controls with a statistically significant P value in the superior quadrant (P = 0.002) and inferior quadrant (P = 0.019)
|Table 2: Comparison of retinal nerve fiber layer thickness in the study and control groups|
Click here to view
The average, superior, and inferior RNFL thickness in the left eye was statistically significantly thinner in diabetic patients as compared to the control group (P < 0.001, P = 0.001, and P < 0.001 respectively). Both eyes were analyzed separately to see if there was any clinically significant difference in RNFL thickness between the right and left eyes. There was no significant difference in RNFL thickness between eyes in this study.
Pearson's correlation co-efficient was calculated to assess the relationship between the RNFL thickness and parameters of metabolic control. No statistically significant correlation was found between the HbA1c and RNFL thickness [Table 3].
|Table 3: Correlation between glycemic control (glycosylated hemoglobin) and peripapillary retinal nerve fiber layer thickness|
Click here to view
| Discussion|| |
DR is a common and specific microvascular complication of diabetes and remains the leading cause of preventable blindness in working aged people. Several recent publications have shown that retinal neurodegeneration precedes clinically detectable microvascular damage.,
In DM, thinning of the RNFL can occur in the absence of glaucoma and other optic nerve diseases. Increased apoptosis, glial cell reactivity, and microglial and altered glutamate mechanism are some neurodegenerative changes that have been proposed to occur in DR. Decreased RNFL thickness in diabetics without DR or early DR occurs due to alterations is the inner retina. On the contrary, the outer retina is not affected in the early stage of DM.
Exact mechanisms for inner retinal loss are not clear but have been implicated to lower perfusion and higher metabolic demands of the inner retina which make it more vulnerable to the metabolic stress induced by DM. Reduced RNFL thickness can be explained by the progressive ganglion and astrocytes loss induced by diabetes. It may depend on a direct toxicity of hyperglycemia or Muller's cell dysfunction which are unable to maintain an adequate osmotic equilibrium between the intracellular and extracellular matrices with consequent apoptosis of the neuronal cells and progressive axonal degeneration. The selective thinning of the RNFL suggests that retinal neurodegeneration is an early event in DM, representing a preclinical stage of DR.
Loss of RNFL with changes in the inner retina and their association with metabolic control has been studied with varying results in diabetic patients. Some studies have shown that the RNFL thickness using OCT in diabetics, with or without DR is thinner as compared to controls.,,, A few studies have showed that only the superior quadrant RNFL thickness was thinner in patients with DR than healthy controls.,,,
In our study, it was found that the RNFL thickness was thinner in diabetic patients as compared to normal healthy controls. Right eye RNFL thickness was thinner in diabetic patients as compared to controls, with a statistically significant P value (P = 0.002) in the superior quadrant as well as in the inferior quadrant (P = 0.019). Average, superior, and inferior left eye RNFL thickness was also significantly thinner in diabetic patients with a statistically significant P value of P < 0.001, P = 0.001, and P < 0.001, respectively [Table 2].
In this study, no statistically significant correlation was found between HbA1c and RNFL thickness by the Pearson's correlation co-efficient [Table 3]
The results were in concordance with a similar study by Dhamsana et al. Some studies, have shown a negative correlation between HbA1c and RNFL thickness. It was concluded that the RNFL thinning is associated with poor glycemic control and progression of DR.
In this study, no significant correlation was found between the HbA1c and RNFL thickness probably because the glycemic control of majority of the diabetic patients (both without DR and with DR) was good [Table 1]. HbA1c level of <8 gm% was considered as good metabolic control in diabetic patients.
Our study shows that the RNFL thickness measured by OCT is significantly thinner in diabetics as compared to normal controls. The results indicate an early neurodegenerative effect on the RNFL even when the vascular component of DR remains minimal. This supports the theory that neurodegenerative changes in the inner retinal layers precede the microvascular damage in DR. OCT is an objective, noninvasive, rapid, and reliable method that allows quantitative assessment of peripapillary RNFL thickness. Further, larger studies are required to ascertain, if peripapillary RNFL thickness measurement at baseline, in newly diagnosed diabetics, may be used as a predictive marker for the development of DR. Thus, by identifying the newly diagnosed diabetic patients with RNFL thinning, a preventive rather than an interventional approach can be applied in managing DR. Newer therapeutic treatment (neuro-protective treatment) can help prevent the vision-threatening complications of DR.
To the best of our knowledge, this is the first study of its kind, among diabetic patients from Goa, and it may be used as a reference point for future large scale studies.
Limitation of the study was that the sample size was small. Only the average, superior and inferior quadrant RNFL thickness could be measured using the OCT machine used in this study.
| Conclusions|| |
The present study positively concluded that the peripapillary RNFL thickness measured by OCT is thinner in diabetic patients, as compared to normal controls. Peripapillary RNFL thickness assessment in diabetics by OCT could prove to be an objective and valuable predictive tool in identifying early neurodegenerative changes in the retina, even before the onset of DR.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond) 2015;2:17.
Verma A, Rani PK, Raman R, Pal SS, Laxmi G, Gupta M, et al
. Is neuronal dysfunction an early sign of diabetic retinopathy? Microperimetry and spectral domain optical coherence tomography (SD-OCT) study in individuals with diabetes, but no diabetic retinopathy. Eye (Lond) 2009;23:1824-30.
Villarroel M, Ciudin A, Hernández C, Simó R. Neurodegeneration: An early event of diabetic retinopathy. World J Diabetes 2010;1:57-64.
Biallosterski C, van Velthoven ME, Michels RP, Schlingemann RO, DeVries JH, Verbraak FD. Decreased optical coherence tomography-measured pericentral retinal thickness in patients with diabetes mellitus type 1 with minimal diabetic retinopathy. Br J Ophthalmol 2007;91:1135-8.
Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010;376:124-36.
Simó R, Hernández C, European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR). Neurodegeneration is an early event in diabetic retinopathy: Therapeutic implications. Br J Ophthalmol 2012;96:1285-90.
Vujosevic S, Midena E. Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and Müller cells alterations. J Diabetes Res 2013;2013:905058.
Barber AJ. A new view of diabetic retinopathy: A neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:283-90.
van Dijk HW, Kok PH, Garvin M, Sonka M, Devries JH, Michels RP, et al
. Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. Invest Ophthalmol Vis Sci 2009;50:3404-9.
Demir M, Oba E, Sensoz H, Ozdal E. Retinal nerve fiber layer and ganglion cell complex thickness in patients with type 2 diabetes mellitus. Indian J Ophthalmol 2014;62:719-20.
] [Full text]
Cabrera DeBuc D, Somfai GM. Early detection of retinal thickness changes in diabetes using optical coherence tomography. Med Sci Monit 2010;16:MT15-21.
Oshitari T, Hanawa K, Adachi-Usami E. Changes of macular and RNFL thicknesses measured by stratus OCT in patients with early stage diabetes. Eye (Lond) 2009;23:884-9.
Rodrigues EB, Urias MG, Penha FM, Badaró E, Novais E, Meirelles R, et al
. Diabetes induces changes in neuroretina before retinal vessels: A spectral-domain optical coherence tomography study. Int J Retina Vitreous 2015;1:4.
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;219:379-85.
Dhasmana R, Sah S, Gupta N. Study of retinal nerve fibre layer thickness in patients with diabetes mellitus using fourier domain optical coherence tomography. J Clin Diagn Res 2016;10:NC05-9.
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. [Full text]
Park HY, Kim IT, Park CK. Early diabetic changes in the nerve fibre layer at the macula detected by spectral domain optical coherence tomography. Br J Ophthalmol 2011;95:1223-8.
Fahmy RM, Bhat RS, Al-Mutairi M, Aljaser FS, El-Ansary A. Correlation between glycemic control and peripapillary retinal nerve fiber layer thickness in Saudi type II diabetics. Clin Ophthalmol 2018;12:419-25.
Srivastav K, Saxena S, Ruia S, Mahdi AA, Khanna VK. Correlation of retinal nerve fibre layer thinning and central subfield thickness with type 2 diabetic retinopathy on spectral domain optical coherence tomography. Open Sci J Clin Med 2015;3:194-8.
[Table 1], [Table 2], [Table 3]