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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 111  |  Issue : 1  |  Page : 25-32

Ganglion cell complex changes with long-standing diabetic macular oedema among Egyptian diabetic patients: an optical coherence tomography study


Ophthalmology Department, Research Institute of Ophthalmology, Giza, Egypt

Date of Web Publication26-Jul-2018

Correspondence Address:
Tamer A Refai
Ophthalmology Department, Research Institute of Ophthalmology, Giza, 12211
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejos.ejos_9_18

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  Abstract 

Introduction Optical coherence tomography (OCT) is a valuable tool for imaging retinal thickness and structure as well as performing good evaluation for the ganglion cell complex (GCC) parameters, reflecting the status of retinal nerve fiber layer, the ganglion cell layer and the inner-plexiform layers. In this study, these parameters were evaluated in eyes with long-standing diabetic macular oedema, thus emphasising the importance of seriously treating macular oedema.
Patients and methods Sixty eyes of 38 patients were included in the study. There were 38 eyes of 25 male patients and 22 eyes of 13 female patients. These 60 eyes were divided into two groups: group A (30 eyes) included eyes of patients with long-standing diabetic macular oedema (>1 year duration) and group B (30 eyes) included eyes of patients without apparent ocular pathology as a control. The age range was 23–73 years (mean 56.57±11.42) in group A and 30–74 years (mean 53.33±12.10) in group B. The duration of diabetes ranged from 1 to 25 years (mean 15.2±5.97) in group A. The patients were examined by an ocular response analyser (OCT-Optovue) that performs different GCC studies in addition to macular map analysis (EMM5). Best-corrected visual acuity in Snellen lines was also reported. Collected data were arranged and subjected to analysis using suitable statistical methods.
Results In this study, a highly significant difference (P<0.01) was found with higher mean values for the diabetic macular oedema group for the GCC average (116.95±21.14 μm), GGC superior (121.80±28.36 μm), GCC inferior (116.16±25.52 μm) and focal loss volume (FLV=5.55±2.50%) compared with the control group, with GCC average of 97.29±6.32 μm, GCC superior of 96.49±7.90 μm, GCC inferior of 97.77±6.44 μm and the FLV of 1.26±0.90%. In addition, a statistically significant difference (P<0.05) was found with higher mean values for the global loss volume in diabetic macular oedema group [global loss volume (GLV=7.40±3.90%)] versus control group (GLV=5.49±3.27%). For the diabetic macular oedema group, the central macular thickness (μm) showed a highly significant correlation (<0.01) with the thickness (μm) of GCC average, GCC superior and GCC inferior and a statistically significant correlation (<0.05) with both of the GLV% and FLV%. For the diabetic macular oedema group, the duration of diabetes mellitus showed a statistically significant correlation (<0.05) with the FLV%, with a nonsignificant correlation (>0.05) with the other studied GCC parameters. Compared with normative data, FLV% was abnormal in 70% of eyes, borderline in 6.67% of eyes and normal in 23.33% of eyes in diabetic macular oedema group compared with the control group, which showed values of 0, 6.67 and 93.33% for abnormal, borderline and normal values respectively, with χ2-test showing a highly significant difference (χ2=30.718 P<0.001) between both the groups.
Conclusion Compared with normal group, patients with long-standing diabetic macular oedema showed higher mean values for all GCC parameters, which were strongly correlated with the central macular thickness. The FLV% values in particular was abnormal in ∼70% of eyes with diabetic macular oedema in comparison with normative data, and it correlated strongly with the duration of diabetes, so we recommend considering this parameter (FLV%) for seriously treating diabetic macular oedema before permanent GCC damage occurs.

Keywords: diabetic macular oedema, focal loss volume, ganglion cell complex parameters, ocular coherence tomography


How to cite this article:
Refai TA, Hassan AA. Ganglion cell complex changes with long-standing diabetic macular oedema among Egyptian diabetic patients: an optical coherence tomography study. J Egypt Ophthalmol Soc 2018;111:25-32

How to cite this URL:
Refai TA, Hassan AA. Ganglion cell complex changes with long-standing diabetic macular oedema among Egyptian diabetic patients: an optical coherence tomography study. J Egypt Ophthalmol Soc [serial online] 2018 [cited 2018 Aug 21];111:25-32. Available from: http://www.jeos.eg.net/text.asp?2018/111/1/25/237644


  Introduction Top


Background and statement of the problem

Diabetic retinopathy is the chief cause of vision loss in working-age individuals all over the world, primarily owing to macular oedema [1]. Optical coherence tomography (OCT) has the potential of measuring retinal thickness and structure, thus producing cross-sectional and three-dimensional optical images of the macula. It provides objective and quantitative assessment of macular oedema. Optical coherence tomography is also a useful tool for following up the effects of treatment of clinically significant macular oedema quantitatively [2]. Recently, OCT has detected loss of ganglion cell complex (GCC) [3],[4] consisting of three retinal layers: (a) the retinal nerve fiber layer (RNFL), the ganglion cell layer, and the inner-plexiform layer, which become thinner as the ganglion cells die from glaucoma [5] and could be an early indicator of this disease [6]. GCC evaluation yielded better results than RNFL evaluation in detecting early glaucoma in some studies [7], and when added to RNFL data, it enhanced detection of glaucoma in both pre-perimetric and perimetric stages [8]. In this research, GCC parameters in cases with long-standing diabetic macular oedema were studied to find out if these structures, namely, the RNFL, the ganglion cell layer and the inner-plexiform layer, were affected with long-standing diabetic macular oedema to emphasize the need for seriously treating these cases before irreversible damage happens ([Figure 1]).
Figure 1 Different ganglion cell complex (GCC) parameters studied in both eyes with relatively normal right eye and abnormal left eye parameters.

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Objective

The aim of this work was to evaluate the changes in the GCC parameters in eyes with long-standing diabetic macular oedema compared with otherwise normal eyes, thus emphasizing the need for seriously treating these cases.


  Patients and methods Top


Sixty eyes of 38 Egyptian patients were included in the study. There were 38 eyes of 25 male patients and 22 eyes of 13 female patients. The study was performed in the Research Institute of Ophthalmology, Giza, Egypt, between September 2016 and May 2017. The eyes were divided into two groups: group A (30 eyes) included eyes of patients with long-standing diabetic macular oedema (>1 year duration), and group B (30 eyes) included eyes of patients without apparent ocular pathology as a control. Both groups were examined by ocular coherence tomography (Optovue; Incorporated, Fremont, California, USA) focusing on GCC parameters, including overall average thickness (GCC-AVG, average); average thickness for superior hemisphere (GCC-superior); inferior hemisphere (GCC-inferior); global loss volume (GLV), which is the sum of fractional deviation (FD) showing the percentage of GCC loss in areas where FD is negative; focal loss volume (FLV), which is the sum FD in the region where there is significant focal loss in GCC; and macular thickness in microns. Macular oedema was confirmed by OCT showing diffuse thickening, flattening of foveal depression or intraretinal hyporeflective cystic spaces (cystoid macular oedema). Best-corrected visual acuity in Snellen lines was also reported. Collected data were arranged and analysed using the suitable statistical methods. We calculated the mean values and SD for quantitative data. Comparison tests (t-test) and correlation tests (Pearson) were also performed. χ2-Test for categories of data was also performed as necessary.

The significance of the data was determined using the probability (P). P value greater than 0.05 was considered nonsignificant, P value of less than 0.05 was considered significant, and P value of less than 0.01 was considered highly significant.

The following were set as the exclusion criteria: (a) gross retinal pathology like degenerative myopia, retinitis pigmentosa, retinal and choroidal dystrophies and degenerations; (b) significant macular ischemia; (c) previous retinal surgeries or laser treatment (ttt); (d) glaucomatous patients; (e) previous vascular occlusions; and (f) macular oedema less than 1-year duration.


  Results Top


General findings

Sixty eyes of 38 patients were included in the study. There were 38 eyes of 25 male patients and 22 eyes of 13 female patients. These 60 eyes were divided into two groups: group A (30 eyes) included eyes of patients with long-standing diabetic macular oedema (>1 year duration) and group B (30 eyes) including eyes of patients without apparent ocular pathology as a control. The age range was 23–73 years (mean 56.57±11.42) in group A and 30–74 years (mean 53.33±12.10) in group B. The duration of diabetes ranged from 1 to 25 years (mean 15.2±5.97) in group A. The central macular thickness (µm) (i.e. average thickness in the central 1 mm circle of the retinal thickness map) ranged from 217 to 778 μm (mean 426.33±177.43) in group A and 211 to 282 μm (mean 243.37±18.26) in group B. The best-corrected visual acuity in Snellen lines ranged from 0.1 to 0.5 (mean 0.27±0.11) in group A and from 0.5 to 1 (mean 0.68±0.22) in group B ([Table 1]).
Table 1 Demographic data

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The GCC average thickness in microns showed a mean value of 116.95±21.14 μm in diabetic macular oedema group (group A) and 97.29±6.32 μm in control group (group B), with t-test showing a value of 4.88 (P<0.01) denoting a highly significant difference. The GCC superior thickness in microns showed a mean value of 121.80±28.36 μm in diabetic macular oedema group (group A) and 96.49±7.90 μm in control group (group B), with t-test showing a value of 4.70 (P<0.01) denoting a highly significant difference. The GCC inferior thickness in microns showed a mean value of 116.16±25.52 μm in diabetic macular oedema group (group A) and 97.77±6.44 μm in control group (group B), with t-test showing a value of 3.76 (P<0.01) denoting a highly significant difference ([Table 2] and Chart 1)

. The FLV% in percentage showed a mean value of 5.55±2.50 in diabetic macular oedema group (group A) and 1.26±0.90 in control group (group B), with t-test showing a value of 8.84 (P<0.01) denoting a highly significant difference. The GLV% in percentage showed a mean value of 7.40±3.90 in diabetic macular oedema group (group A) and 5.49±3.27 in control group (group B), with t-test showing a value of 2.06 (P<0.05) denoting a statistically significant difference ([Table 2] and Chart 2)

.
Table 2 The mean±SD value for ganglion cell complex parameters for both diabetic macular oedema group (group A) and control group (group B) and their comparison by t-test and significance among patients under study

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The central macular thickness in microns showed a mean value of 426.33±177.43 μm in diabetic macular oedema group (group A) and 243.37±18.26 μm in control group (group B), with t-test showing a value of 5.62 (P<0.01) denoting a highly significant difference ([Table 3] and Chart 3)

.
Table 3 The mean±SD value for central macular thickness for both diabetic macular oedema group (group A) and control group (group B) and their comparison by t-test and significance among patients under study

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For the diabetic macular oedema group

A highly significant correlation (r=0.78, P<0.01) existed between the GCC average thickness (μm) and central macular thickness (μm). A highly significant correlation (r=0.58, P<0.01) existed between the GCC superior thickness (μm) and central macular thickness (μm). A highly significant correlation (r=0.50, P<0.01) existed between the GCC inferior thickness (μm) and central macular thickness (μm). A statistically significant correlation (r=−0.38, P<0.05) existed between the GLV% and central macular thickness (μm). A statistically significant correlation (r=−0.22, P<0.05) existed between the FLV% and central macular thickness (μm) ([Table 4]).
Table 4 Correlation (Pearson test) between ganglion cell complex parameters and central macular thickness for both diabetic macular oedema group and control group among patients under study

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For the control group

A nonsignificant correlation (r=0.08, P>0.05) existed between the GCC average thickness (μm) and central macular thickness (μm). A nonsignificant correlation (r=0.09, P>0.05) existed between the GCC superior thickness (μm) and central macular thickness (μm). A nonsignificant correlation (r=0.12, P>0.05) existed between the GCC inferior thickness (μm) and central macular thickness (μm). A nonsignificant correlation (r=−0.14, P>0.05) existed between the GLV% and central macular thickness (μm). A nonsignificant correlation (r=−0.05, P>0.05) existed between the FLV% and central macular thickness (μm) ([Table 4]).

For the diabetic macular oedema group

A nonsignificant correlation (r=−0.03, P>0.05) existed between the GCC average thickness (μm) and the duration of diabetes in years. A nonsignificant correlation (r=−0.02, P>0.05) existed between the GCC superior thickness (μm) and the duration of diabetes in years. A nonsignificant correlation (r=0.15, P>0.05) existed between the GCC inferior thickness (μm) and the duration of diabetes in years. A nonsignificant correlation (r=−0.06, P>0.05) existed between the GLV% and the duration of diabetes in years. A statistically significant correlation (r=−0.27, P<0.05) existed between the FLV% and the duration of diabetes in years ([Table 5]).
Table 5 Correlation (Pearson test) between ganglion cell complex parameters and duration of diabetes for diabetic macular oedema group among patients under study

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In our study, compared with a normative database, GCC parameters that showed borderline or abnormal values were the FLV% and to a much lesser extent GLV% (i.e. the significance Map is colour coded where green represents values within the normal range (P=5–95%), yellow indicates borderline results (P<5%), and red represents results with outside normal limits (P<1%)). Regarding the FLV%, of 30 eyes in the diabetic macular oedema group, 21 (70%) eyes showed abnormal values, two (6.67%) eyes showed borderline values and seven (23.33%) eyes showed normal values, whereas for the control group, of the 30 studied eyes, no eyes (0%) showed abnormal values, two (6.67%) eyes showed borderline values, and 28 (93.33%) eyes showed normal values. Comparison of the results in both groups by χ2-test revealed a highly significant difference (χ2=30.718 P<0.001) ([Table 6] and Chart 4)

.
Table 6 The number and relative percentage of abnormal, borderline and normal values for focal loss volume for both diabetic macular oedema group (group A) and control group (group B) and their comparison by χ2-test among patients under study

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Regarding the GLV%, of the 30 eyes in the diabetic macular oedema group, two (6.67%) eyes showed abnormal values, two (6.67%) eyes showed borderline values, and 26 (86.67%) eyes showed normal values, whereas for the control group, of the 30 studied eyes, one (3.33%) eyes showed abnormal values, no eye (0%) showed borderline values, and 29 (96.67%) eyes showed normal values. Comparison of the results in both groups by χ2-test revealed a nonsignificant difference (χ2=2.50 P>0.05) ([Table 7] and Chart 5)

.
Table 7 The number and relative percentage of abnormal, borderline and normal values for global loss volume both for diabetic macular oedema group (group A) and control group (group B) and their comparison by χ2-test among patients under study

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  Discussion Top


Diabetic patients particularly of disease duration of 20 years or more frequently experience macular oedema as a main cause for visual loss [9]. Not infrequently, treatment modalities for macular oedema do not result in significant improvement of visual acuity probably owing to the damage in the macular structure caused by chronic macular oedema [10]. OCT is commonly used to diagnose macular oedema by different scans as well as detecting retinal thickness for planning treatment as well as in follow-up [11],[12],[13]. In addition to providing different scanning methods for the macular area and providing thickness map, OCT can perform diagnostic parameters for studying the GCC parameters like average, superior, and inferior GCC thicknesses as well as two pattern-based diagnostic parameters, namely, FLV and GLV. These parameters have been used to detect early damage in patients with glaucoma as well as in patients with pre-perimetric glaucoma [14],[15]. Oli et al. [15] studied the average GCC thickness in 33 patients with glaucoma (age 58.54±13.78 years), 45 patients with pre-perimetric glaucoma (age 53.71±17.55 years), and 30 controls (age 52±14.88 years), and they found that GCC was 69.19 μm in patients with glaucoma, 71 μm in patients with pre-perimetric glaucoma and 85.16 μm in controls. The difference of mean for GCC by analysis of variance was statistically significant for controls, patients with glaucoma and patients with pre-perimetric glaucoma. Similarly, Kim et al. [14] studied GCC parameters in 241 eyes of 241 patients, of which 103 were of normal controls (mean age 55.10±12.76 years), and 138 eyes were of patients with glaucoma (mean age: 58.54±15.44 years). The mean values for the mean GCC, superior GCC, inferior GCC (μm), FLV% and GLV% were 95.08±7.88, 94.52±8.33, 95.28±9.26, 2.21±3.21 and 8.33±5.87, respectively, in normal controls and 78.89±10.66, 82.66±12.69, 77.16±11.85, 7.79±5.42 and 21.62±9.27, respectively, for patients with glaucoma, with statistically significant differences between both groups for all parameters (<0.001). In our study, which evaluates the GCC parameters in long-standing diabetic macular oedema, a highly significant difference (P<0.01) was found with higher mean values for the diabetic macular oedema group for the GCC average (116.95±21.14 μm), GGC superior (121.80±28.36 μm), GCC inferior (116.16±25.52 μm) and the FLV (5.55±2.50%) compared with the control group, which showed GCC average of 97.29±6.32 μm, GCC superior of 96.49±7.90 μm, GCC inferior of 97.77±6.44 μm and the FLV of 1.26±0.90%. Moreover, a statistically significant difference (P<0.05) was found with higher mean values for the diabetic macular oedema group for the GLV (7.40±3.90%) compared with the control group where the GLV was 5.49±3.27%. The higher mean values for the average, superior and inferior GCC thicknesses in the diabetic group appeared to be just related to the higher values for central macular thickness rather than being abnormal, particularly that they are graded as normal according to normative data. For the diabetic macular oedema group, the central macular thickness (μm) showed a highly significant correlation (<0.01) with the average, GCC superior and GCC inferior thickness (μm) and a statistically significant correlation (<0.05) with both of the GLV% and FLV% whereas for the control group, no such correlation was found. For the diabetic macular oedema group, the duration of diabetes mellitus showed a statistically significant correlation (<0.05) with the FLV% but a nonsignificant correlation (>0.05) with the other studied GCC parameters which arouse the importance of this parameter (FLV%) as a strong indicator of the structural damage to the macula in long-standing diabetic macular oedema. Compared with normative data, FLV% was abnormal in 70% of eyes, borderline in 6.67% of eyes and normal in 23.33% of eyes in diabetic macular oedema group compared with control group, which showed values of 0, 6.67 and 93.33% for abnormal, borderline and normal values, with a highly significant difference (<0.001) between both groups, which again highlights the importance of considering the FLV% as the most important indicator of damage. The GLV%, however, showed a nonsignificant difference (>0.05) for the normative values between both groups. Zhang et al. [16], on follow-up of 513 eyes (of 309 patients), showed 55 eyes (46 patients) experienced VF conversion during a follow-up duration of 41±23 months, where the GCC FLV was the best single predictor of conversion (AUC=0.753, P<0.001). Thus, there appears to be agreement between glaucoma and long-standing macular oedema, in which the FLV% is the single most useful indicator of potential damage. Both diseases are characterized by chronic progressive retinal damage. From this research, we strongly recommend evaluating cases with long-standing macular oedema with ganglion cell parameters, particularly FLV%, in addition to the traditional retinal scanning and retinal thickness map on OCT to detect potential structural damage as early as possible and manage it accordingly before permanent visual damage occurs.


  Conclusion Top


Compared with the normal group, patients with long-standing diabetic macular oedema showing higher mean values for all GCC parameters, which were strongly correlated with the central macular thickness. The FLV% values in particular was abnormal in ∼70% of eyes with diabetic macular oedema in comparison with normative data, and it correlated strongly with the duration of diabetes, so we recommend considering this parameter (FLV%) for seriously treating diabetic macular oedema before permanent GCC damage occurs.

Acknowledgements

This paper was prepared from the authors’ postgraduate thesis in Refractive Unit in the Research Institute of Ophthalmology, Giza, Egypt, providing valuable funding deserving acknowledgement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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