|Year : 2018 | Volume
| Issue : 3 | Page : 150-154
Central macular thickness in diabetics without retinopathy
Sindhuja Murugesan1, Kirti Nath Jha1, Srikanth Krishnagopal1, G Ezhumalai2
1 Department of Ophthalmology, Mahatma Gandhi Medical College and Research Institute, (Sri Balaji Vidyapeeth), Pondicherry, India
2 Department of Research, Mahatma Gandhi Medical College and Research Institute, (Sri Balaji Vidyapeeth), Pondicherry, India
|Date of Web Publication||23-Oct-2018|
Dr. Kirti Nath Jha
Department of Ophthalmology, Mahatma Gandhi Medical College and Research Institute, Pillaiyarkuppam, Puducherry - 607 402
Source of Support: None, Conflict of Interest: None
Background: Diabetic maculopathy is the major cause for blindness in type 2 diabetics. Slit-lamp biomicroscopy with +90 D lens has been the traditional method for diagnosis. Neurodegenerative changes precede clinical retinopathy. Optical coherence tomography (OCT) is a newer tool for diagnosis of such subtle changes in the macula. Aim: This study aimed to compare the central macular thickness (CMT) in type 2 diabetics without clinical retinopathy and normal controls. Subjects and Methods: This prospective case–control study was conducted at a rural tertiary care center after obtaining clearance from the Institutional Human Ethics Committee. CMT was measured using spectral-domain OCT among the type 2 diabetics without clinical retinopathy and control group. CMT was correlated with duration of diabetes and glycemic control using Pearson's correlation. Results: This study included 170 patients (85 cases and 85 controls). The average age in cases and controls was 52 ± 10.2 years and 51 ± 8.1 years, respectively; this difference was statistically not significant. Duration of diabetes ranged from newly diagnosed to 15 years. Mean glycosylated hemoglobin (HbA1c) in the study and control groups were 8.93 ± 2.54% and 4.57 ± 0.56% respectively. Mean CMT in type 2 diabetics without clinical retinopathy was 198.47 ± 17.98 μm and in control group, it was 235.68 ± 11.25 μm (P = 0.00). CMT among male diabetics was thicker than that of female diabetics (P = 0.00). CMT did not correlate with duration of diabetes (r = 0.54) or with the glycemic control (r = 0.09). Conclusion: CMT was thinner among type 2 diabetics without clinical retinopathy than healthy controls. CMT did not correlate with duration of diabetes or with the glycemic control.
Keywords: Central macular thickness and glycemic control, diabetic maculopathy, type 2 diabetes mellitus
|How to cite this article:|
Murugesan S, Jha KN, Krishnagopal S, Ezhumalai G. Central macular thickness in diabetics without retinopathy. TNOA J Ophthalmic Sci Res 2018;56:150-4
|How to cite this URL:|
Murugesan S, Jha KN, Krishnagopal S, Ezhumalai G. Central macular thickness in diabetics without retinopathy. TNOA J Ophthalmic Sci Res [serial online] 2018 [cited 2019 Oct 14];56:150-4. Available from: http://www.tnoajosr.com/text.asp?2018/56/3/150/243768
| Introduction|| |
In India, the prevalence of diabetes is increasing at a rapid rate. Hence, the prevalence of associated complications has also increased exponentially, and diabetic retinopathy (DR) is one such microvascular complication resulting in preventable blindness.
Nearly all patients with type 1 diabetes and more than 60% of patients with type 2 diabetes develop some form of retinopathy by the first decade of incidence of diabetes.
The major causes of visual impairment in DR are proliferative DR and diabetic maculopathy including macular edema and ischemia. Type 2 diabetics are at more risk for diabetic maculopathy. Their visual acuity depends on the foveal involvement, perifoveal capillary blood flow velocity, severity of perifoveal capillary occlusion, and central foveal thickness.
Timely diagnosis with screening and referral facilities, strict control of systemic parameters, and timely intervention can delay the sight-threatening complications of DR.
The traditional approach to diagnosis of diabetic maculopathy is by slit-lamp biomicroscopy and fundus fluorescein angiography. Although useful clinically, these methods do not contribute much to the evaluation of retinal morphology and thickness and volume profile of the retina.
Newer noninvasive imaging modalities such as optical coherence tomography (OCT) produce an “in vivo” optical biopsy of the retinal layers and are highly reproducible in measuring the macular thickness and volume. Spectral-domain-OCT (SD-OCT) is a newer third-generation high-resolution OCT with the advantages of high-speed data acquisition, three-dimensional (3D) reconstruction of acquired retinal images, improved visualization of retinal architecture, and can also detect the subtle changes in the macula that are not clinically evident. It also aids in the treatment and follow-up of diabetic macular edema (DME).
In this study, central macular thickness (CMT) was assessed in type 2 diabetics without clinical retinopathy and healthy age- and gender-matched controls by SD-OCT with an aim to find any early neurodegenerative changes. Among the diabetics, we also compared CMT with duration of diabetes and glycemic control.
| Subjects and Methods|| |
A prospective case–control study was conducted in a rural tertiary care eye hospital after the approval from the Institutional Human Ethics Committee. Patients above 40 years of age with type 2 diabetes mellitus attending ophthalmology outpatient department from January 2016 to June 2017 were included in the study. Informed consent was obtained from each participant. Patients with previous intraocular surgery, medical treatment to retina, type 1 diabetes mellitus, hypertension, chronic kidney disease, hyperlipidemia, gestational diabetes mellitus, signs of DR changes, and other ocular diseases such as glaucoma, macular disorders, uveitis, and media opacities were excluded from the study. Duration of diabetes was noted, and fasting blood glucose (FBS), postprandial blood glucose, and glycosylated hemoglobin (HbA1c) were also done. According to the American Diabetes Association, glycemic control was considered good if HbA1c was <7% and HbA1c ≥7% was considered poor glycemic control.
All patients underwent recording of best-corrected visual acuity, intraocular pressure measurement by Goldmann applanation tonometry, and anterior- and posterior-segment examination by slit-lamp biomicroscopic examination with +90 diopter lens was carried out after pupillary dilatation with tropicamide 0.8% and phenylephrine 5% (Tropac-P eye drops) 3 applications at an interval of fifteen minutes in all cases.
Type 2 diabetic patients with normal fundus without any evidence of clinical retinopathy were taken for CMT measurement by SD-OCT (OCT SLO Combination Imaging system, Optos Miami, Florida, USA). CMT was measured for healthy age- and gender-matched controls who visited the ophthalmology outpatient department for routine master health checkup. All measurements were taken by a single experienced examiner.
All participants were subjected to macular imaging using the SD-OCT version 4.0 following pupillary dilatation. The 3D retinal topography uses the fast macular scan protocol to measure the macular thickness. Each eye was scanned with the patient in sitting position with the head of the patient stabilized on the chin- and forehead- rest. The patient was asked to fix at the internal fixation target so that the center of the fovea was mapped. The OCT image was displayed as a real-time video to aid in alignment. Only scans with signal strengths more than 7 and without artifacts were taken for the study.
First, line scan was done and taken for subjective analysis with fovea centered at 0° angle. Then, macular cube scan 200 × 200 was taken and the macula was mapped on fast macular thickness map [Figure 1]. It comprises three concentric circles centered on the fovea; the fovea (<1 mm diameter), the inner macula (1–3 mm), and the outer macula (3–6 mm). These zones were further divided into nine Early Treatment Diabetic Retinopathy study regions [Figure 2]. Since CMT was highly correlated between the right and left eyes among the 170 participants, the average CMT between both eyes was taken as the value.
|Figure 1: Macular thickness scan in type 2 diabetics without diabetic retinopathy|
Click here to view
|Figure 2: Early Treatment Diabetic Retinopathy study zone for fast macular thickness map|
Click here to view
The HbA1c, duration of diabetes, and CMT of 85 patients in both the groups were compared. All statistical analyses were carried out using SPSS software version 19.0 (IBM Corporation, NY, USA.) with regression modules installed.
The demographic profiles such as age and gender were described in terms of percentages and mean. Duration of diabetes, HbA1c, and CMT was summarized as mean with standard deviation, range, and 95% confidence interval. The CMT between type 2 diabetics and controls was compared by paired t-test. The CMT between gender distribution and the glycemic control was compared by the paired t-test. The correlation of CMT and duration of diabetes and HbA1c levels was done using Pearson's correlation. P < 0.05 was considered statistically significant.
| Results|| |
This prospective study comprised of 170 (340 eyes) participants: 85 cases with type 2 diabetes mellitus without DR and 85 controls with no diabetes mellitus. The study population included 98 (57.6%) females and 72 (42.4%) males. [Table 1] summarizes the demographics of cases and controls. Difference of age among the groups was statistically not significant. In the study group, the duration of diabetes mellitus ranged from newly diagnosed (<1 year) to more than 15 years. Fifteen (17.6%) patients were newly diagnosed, 33 (38.8%) patients had been diagnosed for 1–5 years, 25 (29.4%) patients had been diagnosed for 6–10 years, 6 (7%) patients had been diagnosed for 11–15 years, and 6 (7%) patients had been diagnosed for more than 15 years.
The HbA1c values ranged from 4.9% to 15.9% in the study population. The average HbA1c among the study population was 8.93 ± 2.54% and in the control group, it was 4.57 ± 0.56%. The mean level of HbA1c was statistically higher in the study group than in the control group [Table 2] (P = 0.00). Nineteen (22.3%) patients had good glycemic control, whereas 66 (77.6%) patients had poor glycemic control.
|Table 2: Comparison of diabetic control (glycosylated hemoglobin) and central macular thickness among cases and controls|
Click here to view
The mean CMT in type 2 diabetics without clinical retinopathy was estimated to be 198.47 ± 17.98 μm, ranging from 149 to 240 μm. In the control group, the mean CMT was 235.68 ± 11.25 μm, ranging from 190 to 258 μm. The CMT was thinner in the study group than in the control group and this difference was statistically significant [Table 2] (P = 0.00). Among the cases and controls, males had thicker CMT than females; this difference was statistically significant (P = 0.00). [Table 3] summarizes the difference in mean CMT among genders in cases and controls.
|Table 3: Comparison between central macular thickness in males and females in both the groups|
Click here to view
Mean CMT in type 2 diabetics with good glycemic control (19 patients) was 196.15 ± 15.63 μm and mean CMT in patients with poor glycemic control (66 patients) was 199.14 ± 18.65 μm. This difference was statistically not significant (P = 0.52). We did not find a correlation between the HbA1c level and the CMT among the cases (r = 0.09) (P = 0.39) and control group (r = −0.06) (P = 0.55). Furthermore, duration of diabetes had no correlation with CMT (r = 0.54) (P = 0.62).
| Discussion|| |
Diabetic maculopathy is the major cause for visual loss in patients with type 2 diabetes mellitus. OCT can detect early neurodegenerative changes even before the onset of clinical retinopathy. It also aids in follow-up and also establishes quantitative and qualitative measurements in response to therapy in established retinopathy.
Time-domain OCT produces lowest CMT; the SD-OCT namely the Copernicus [Reichert/ Optopol Technology, Inc., Depew, NY], Spectral OCT/SLO [Opko/OTI, Inc., Miami, FL], and RTVue-100 [Optovue Corp., Fremont, CA], showed mid-range CMT; and the Spectralis® high-resolution OCT [Heidelberg Engineering, Inc., Heidelberg, Germany], and Cirrus HD-OCT [Carl Zeiss Meditec, Inc.] produced highest CMT values. This significant difference between each instrument is due to different scan acquisition methods, different sampling measurement points, and the different retinal segmentation algorithms used. In addition, the inner retinal border does not vary among instruments and is taken as the internal limiting membrane, but the outer retinal border varies among different machines. Therefore, comparing our results with other studies may not be useful.
In this study, we found that the CMT in patients with type 2 diabetes without DR was reduced in comparison with the controls. This provided evidence that neuronal damage possibly precedes clinical DR. Previous studies have noted mixed results when comparing the macular thickness in type II diabetic participants with no retinopathy and control nondiabetic participants. Few studies showed that there was increased macular thickness in diabetics when compared to control,, whereas some studies showed no correlation. Evidences suggest that there is gradual loss of neurons resulting from ganglion cell apoptosis and degeneration of the inner nuclear, inner plexiform, photoreceptor layer, and retinal pigment epithelium layers in diabetics, leading to thinning of central macula. These changes are not discernible on ophthalmoscopy.
In this study, we also found that males have thicker CMT than females both in type 2 diabetics without clinical retinopathy and in controls. Other studies have also shown similar difference among normal population., However, others have found no significant difference between the macula thickness in males and females in normal population.,
Subgroup analysis of CMT, HbA1c level, and duration of diabetes in type 2 diabetics without clinical retinopathy found no relationship between the Hb1Ac level and the CMT. This is similar to the observation of Demir et al., who stated that CMT did not get affect by the glycemic control or FBS. However, Yeung et al. found a positive correlation of HbA1c level with macular thickness and volume in diabetic patients with DME of more than 10 years' duration. They concluded that strict glycemic control can prevent the deterioration of macular function. Similarly, a study by Chou et al. stated that there was increased macular thickness in patients with HbA1c level more than 8%. Since our study involved a limited population, larger study sample may provide different observation in the future.
Lack of correlation between CMT and duration of diabetes noted by us also finds support from other studies who concluded similar results.
Limited sample size and the duration of diabetes limited to 15 years are the limitations of this study. Comparison of changes in the central foveal region in the cases and controls also forms a limitation since the inner retinal layers are absent in the fovea. Further studies would be required for assessing changes in all the regions of the macula.
Lack of correlation of anatomical changes in the retina with functional loss by microperimetry is another requirement that may unravel changes in retinal function preceding clinical retinopathy.
| Conclusion|| |
The CMT in type 2 diabetics without clinical retinopathy was thinner than the CMT in the normal population, suggesting that neuronal damage precedes clinical retinopathy. Our results may add to further evidence about the alternate pathogenesis in DR, that is, neurodegenerative damage.
CMT in type 2 diabetics without clinical retinopathy shows no correlation with the duration of diabetes and with glycemic control.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gadkari SS, Maskati QB, Nayak BK. Prevalence of diabetic retinopathy in India: The all India Ophthalmological Society Diabetic Retinopathy Eye Screening Study 2014. Indian J Ophthalmol 2016;64:38-44.
] [Full text]
Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology 1984;91:1464-74.
Bowling B. Kanski's Clinical Ophthalmology: A Systematic Approach. 8th
ed. Elsevier Limited; 2016. p. 917.
Gardner TW, Larsen M, Girach A, Zhi X; Protein Kinase C Diabetic Retinopathy Study (PKC-DRS2) Study Group. Diabetic macular oedema and visual loss: Relationship to location, severity and duration. Acta Ophthalmol 2009;87:709-13.
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al.
Optical coherence tomography. Science 1991;254:1178-81.
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.
Lattanzio R, Brancato R, Pierro L, Bandello F, Iaccher B, Fiore T, et al.
Macular thickness measured by optical coherence tomography (OCT) in diabetic patients. Eur J Ophthalmol 2002;12:482-7.
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.
Wolf-Schnurrbusch UE, Ceklic L, Brinkmann CK, Iliev ME, Frey M, Rothenbuehler SP, et al.
Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments. Invest Ophthalmol Vis Sci 2009;50:3432-7.
Pierro L, Giatsidis SM, Mantovani E, Gagliardi M. Macular thickness interoperator and intraoperator reproducibility in healthy eyes using 7 optical coherence tomography instruments. Am J Ophthalmol 2010;150:199-2040.
Chalam KV, Bressler SB, Edwards AR, Berger BB, Bressler NM, Glassman AR, et al.
Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg spectralis optical coherence tomography. Invest Ophthalmol Vis Sci 2012;53:8154-61.
Demir M, Oba E, Dirim B, Ozdal E, Can E. Central macular thickness in patients with type 2 diabetes mellitus without clinical retinopathy. BMC Ophthalmol 2013;13:11.
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;102:783-91.
Song WK, Lee SC, Lee ES, Kim CY, Kim SS. Macular thickness variations with sex, age, and axial length in healthy subjects: A spectral domain-optical coherence tomography study. Invest Ophthalmol Vis Sci 2010;51:3913-8.
Appukuttan B, Giridhar A, Gopalakrishnan M, Sivaprasad S. Normative spectral domain optical coherence tomography data on macular and retinal nerve fiber layer thickness in Indians. Indian J Ophthalmol 2014;62:316-21.
] [Full text]
Grover S, Murthy RK, Brar VS, Chalam KV. Normative data for macular thickness by high-definition spectral-domain optical coherence tomography (spectralis). Am J Ophthalmol 2009;148:266-71.
Tewari HK, Wagh VB, Sony P, Venkatesh P, Singh R. Macular thickness evaluation using the optical coherence tomography in normal Indian eyes. Indian J Ophthalmol 2004;52:199-204.
] [Full text]
Yeung L, Sun CC, Ku WC, Chuang LH, Chen CH, Huang BY, et al.
Associations between chronic glycosylated haemoglobin (HbA1c) level and macular volume in diabetes patients without macular oedema. Acta Ophthalmol 2010;88:753-8.
Chou TH, Wu PC, Kuo JZ, Lai CH, Kuo CN. Relationship of diabetic macular oedema with glycosylated haemoglobin. Eye (Lond) 2009;23:1360-3.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]