|Year : 2021 | Volume
| Issue : 1 | Page : 13-18
Difference between diabetic macular edema and pseudophakic macular edema using optical coherence tomography
Mostafa Kamel Abdelfattah1, Omar Mohamed Ali2, Gamal-Eldin Rashed Othman2, Mohamed Shehata Hussein2
1 Department of Ophthalmology, Sohag Teaching Hospital, Sohag, Egypt
2 Department of Ophthalmology, Assiut University Hospital, Assiut, Egypt
|Date of Submission||22-Mar-2021|
|Date of Acceptance||14-Sep-2021|
|Date of Web Publication||27-Jan-2022|
Dr. Mostafa Kamel Abdelfattah
41th Nour Al-Islam St., Nasser City, Sohag
Source of Support: None, Conflict of Interest: None
Context: Macular edema (ME) is a common pathologic condition causing vision impairment. Diabetic retinopathy is a common cause of ME which can also develop after cataract surgery. Optical coherence tomography (OCT) is a noninvasive diagnostic technique that provides imaging of fine retinal details. Proper diagnosis of the underlying etiology shall affect the management. Aims: This study aims to differentiation between diabetic and pseudophakic ME (DME and PME) using OCT. Settings and Design: Cross-sectional study of 2 Groups; A: 30 eyes with DME and B: 20 eyes with PME. Subjects and Methods: Full clinical evaluation, OCT scanning, and data analysis were done for both groups. Statistical Analysis Used: SPSS software v. 16 was used for: Descriptive statistics, mean, range, and standard deviation. Student's t-test was used for comparison between means. Pearson correlation coefficient was used to assess correlation between variables. Results: Maximum macular thickness and central macular thickness were elevated in both groups but were higher in PME group (P = 0.042 and P = 0.00001, respectively). Macular thickness/volume ratio (TVR) was higher in PME group (P = 0.00001). Cystic changes had different distribution patterns; ganglion cell layer and retinal nerve fiber layer layers were free in PME(Pseudophakic macular edema) while inner nuclear layer and outer nuclear layer were affected in both groups (P = 0.0061). Epiretinal membranes were found much more in DME group (P = 0.0452). Dome-shaped macula was frequently noticed in PME group (P = 0.043). Conclusions: PME and DME have different OCT features; higher TVR, dome-shaped macula, absence of ERM suggest PME while lower TVR, presence of inner retinal cysts and/or ERM suggest DME.
Keywords: Diabetic macular edema, diabetic retinopathy, IrvineGass syndrome, optical coherence tomography, pseudophakic macular edema
|How to cite this article:|
Abdelfattah MK, Ali OM, Othman GER, Hussein MS. Difference between diabetic macular edema and pseudophakic macular edema using optical coherence tomography. Egypt Retina J 2021;8:13-8
|How to cite this URL:|
Abdelfattah MK, Ali OM, Othman GER, Hussein MS. Difference between diabetic macular edema and pseudophakic macular edema using optical coherence tomography. Egypt Retina J [serial online] 2021 [cited 2022 Jul 5];8:13-8. Available from: https://www.egyptretinaj.com/text.asp?2021/8/1/13/336669
| Introduction|| |
Prevailing among 9.3% of the adult population, diabetes mellitus (DM) is a major cause of macular edema (ME)., Limited recovery after cataract surgery due to chronic and recurrent ME is also common.,,, Proper diagnosis can prevent macular degenerative changes.,,, Optic disc leakage in fluorescein angiography (FA) is not conclusive besides being limited in patients susceptible to renal subclinical damage.,,, Optical coherence tomography (OCT) sensitively detects minor structural changes, reveals different ME patterns, and accurately measures retinal thickness which has a better correlation with visual acuity than FA. This study aimed to differentiate pseudophakic from diabetic ME using OCT.
| Subjects and Methods|| |
A cross-sectional study included 50 eyes of 43 patients between December 2015 and March 2019. Subjects were recruited from the Retina Clinic of Sohag Teaching Hospital. Informed written consent was obtained from each participant after explaining the nature of the study. The study was approved by the Ethics Committee of the Faculty of Medicine of Assiut University. Subjects were classified into two groups:
- Group A: DME (30 eyes of 23 patients)
- Group B: PME (20 eyes of 20 patients).
- DME group: Diabetic patients having diabetic retinopathy with ME
- PME group: Patients having ME within 4 months after cataract surgery by phacoemulsification done by a single surgeon.
- Retinal diseases causing ME such as vitreomacular traction, retinal vein occlusion, or sensory detachment
- History of intraocular inflammation; uveitis
- Media opacities; dense corneal opacity or dense cataract interfering with clear tomographic imaging (signal/noise ratio >30)
- Previous intravitreal injections or retinal laser photocoagulation
- Previous intraocular surgery within the preceding 4 months (except cataract surgery in PME group)
- Diabetic patients were excluded from PME group.
- Personal history including name, age, race, residency, and occupation
- History and duration of associated systemic diseases; hypertension and DM
- Ophthalmic history including a detailed visual complaint
- Past ocular history including intraocular surgeries, injections, laser therapy, or chronic inflammation
- Random blood glucose measurement
- Complete ophthalmic examination including: Measurement of intraocular pressure by Goldmann Applanation tonometer, best-corrected visual acuity, ocular examination using Haag Streit slit lamp, and fundus examination using indirect ophthalmoscopy and slit-lamp biomicroscopy using 90D volk lens
- OCT examination was performed by a single examiner using Optovue RTvue model RT100-1 FD-OCT (manufacturer: Optovue incorporated 2800 Bayview Drive Fremont, CA 94538 USA), using application RTVue 100, software version 126.96.36.199. including:
- Radial scans: Twelve scans traversing foveal center, each of 8 mm length
- Grid-line scans: Ten vertical and horizontal raster lines with 8 mm length and 2 mm spacing width
- Enhanced macular mapping: Macular topographic representation into an organized thickness map of 9 zones in 3 concentric circles. The inner one is 1 mm diameter representing the fovea, the middle and outer circles are 3 and 5 mm diameter respectively and are subdivided into 4 quadrants (upper, lower, nasal, and temporal parafovea and perifovea)
- Macular three-dimensional scan.
Central macular thickness (CMT) is defined as the average thickness for the central 1 of the fovea and is automatically calculated. Maximum macular thickness (MMT) is obtained at the point of maximum thickness in the thickness map. Macular volume (MV) in is automatically calculated, which is defined as the volume occupied within the central 6 mm of the macula from retinal pigment epithelium (RPE) to the inner limiting membrane (ILM).
Data were statistically analyzed using SPSS software v. 16 (developer: International Business Machines IBM Corporation, Armonk, New York, USA) for descriptive statistics, mean, range, and standard deviation (SD). Student's t-test was used for comparison between means. Pearson correlation coefficient was used to assess the correlation between variables. The calculated P value (the probability of occurrence) indicated the level of significance as follows:
- P < 0.001 = highly significant
- P < 0.05 = significant.
| Results|| |
The study included 50 eyes of 43 patients subdivided into. Group A: 30 eyes of 23 patients with DME. Group B: 20 eyes of 20 patients with PME. Descriptive data of both groups are shown in [Table 1]. The following findings were noticed: The mean values of CMT and MMT were found to be significantly higher in Group B than in Group A [P = 0.00001 and P = 0.042 respectively; [Table 2]]. The mean MV was higher in Group A than in Group B [P = 0.23; [Table 3]].
A thickness/volume ratio (TVR) was calculated for each case between CMT in microns and MV in mm3. The mean TVR was lower in Group A than in Group B: (37.3 ± 5.6 [range: 26.23–56.37] vs. 56.6 ± 13.2 [range: 31.91–90.16]. The difference was statistically highly significant [P = 0.0001; [Figure 1]].
|Figure 1: A scatter plot chart showing values of thickness/volume ratio in both groups. DME: Diabetic macular edema, PME: Pseudophakic macular edema|
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Retinal cystic changes were found in both groups; 93.3% in Group A (28 of 30) and 95% in Group B (19 of 20). However, a statistically significant difference was found in the distribution of cysts [[Figure 2]; P = 0.0061]. DME cysts were scattered in both inner and outer retinal layers, In contrast, PME cysts were confined to inner nuclear layer (INL) and outer nuclear layer (ONL) [Figure 3], [Figure 4], [Figure 5], [Figure 6].
|Figure 2: Multiple bar chart showing the differential distribution of cystic changes. ONL: Outer nuclear layer. INL: Inner nuclear layer. GCL: Ganglion cell layer. RNFL: Retinal nerve fiber layer|
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|Figure 3: Optical coherence tomography radial scan for a 59 years old diabetic male showing diabetic macular edema. Cystic spaces are scattered in the outer nuclear, inner nuclear, and ganglion cell layers|
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|Figure 4: Macular optical coherence tomography radial scan showing pseudophakic macular edema 32 days after cataract surgery. Cysts are confined to the inner and outer nuclear layers with central distribution. Ganglion cell and nerve fiber layers are not involved|
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|Figure 5: Macular optical coherence tomography radial scan 50 days after cataract surgery showing pseudophakic macular edema with central large cysts in outer nuclear layer, small cysts in inner nuclear layer, subretinal fluid, and preserved inner retina|
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|Figure 6: Macular optical coherence tomography radial scan for a 69 years-old diabetic male with small cystic spaces and scattered hard exudates mainly in outer plexiform layer and outer nuclear layer. Foveal depression is preserved|
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In DME group, scattered hard exudates (HE) (small hyperreflective intraretinal lesions) were found in 24 of 30 of cases scattered in most retinal layers, OPL was the most involved (18) then the INL (10), ganglion cell layer (GCL), and ONL (7 each) followed by retinal nerve fiber layer (RNFL) (5) (P = 0.00001). In PME group, only one case had HE (5%) [Figure 3], [Figure 4], [Figure 5], [Figure 6].
Morphologically, there was a variant distribution of contour morphology; dome-shaped foveal contour was a prominent finding in PME as shown in [Figure 7] (P = 0.04).
|Figure 7: Multiple bar chart showing morphologic changes in macular contour in both groups. DME: Diabetic macular edema PME: Pseudophakic macular edema|
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Regarding vitreoretinal interface (VRI), the presence of epiretinal membranes (ERM) in DME group was statistically significant (P = 0.045). Details are shown in [Table 4].
Homogenous hyporeflective space between RPE and inner/outer segments junctions (IS-OS) representing subretinal fluid (SRF) collections were found in 12 cases of DME group (40%) and 13 cases of PME group (65%) [P = 0.043; [Figure 3], [Figure 4], [Figure 5]. IS-OS and external limiting membrane (ELM) did not witness significant differences (P = 0.4).
| Discussion|| |
Few studies tried to assess the difference between PME and DME. Munk's cross-sectional study used an automatic classifier for differentiation, whereas Jo EB's cross-sectional study compared evaluation parameters using an hierarchical approach.,, According to the results of our cross-sectional study, we notice that TVR was found to provide a reliable differentiation parameter (P = 0.0001). Among 30 cases in Group A, TVR exceeded 50 in only 10% of cases while 83% of cases had values <40 with a mean of 37.3 ± 5.6. In Group B, 50% of PME cases had values higher than 50 and the mean was 56.6 ± 13.2 with a range from 31.91 up to 90.16 and only one case had a ratio value <40. The same was found in Munk's study; a higher TVR was related to PME compared to DME (54 ± 8 vs. 37 ± 11).
PME was reported to show central cystic fluid accumulation in contrast to DME that tends to have higher MV, diffuse or focal retinal thickening, and preserved foveal depression. These observations are compatible with our results. A probable explanation may be related to the mechanism of disease progression. The chronicity in diabetic patients facilitates a relatively concomitant increase in MV along with CMT, keeping a TVR lower than that in PME, where an acute increase in CMT occurs due to the acute inflammatory reaction before the MV gains a parallel value. Besides, the leaking microaneurysms contribute to DME pathogenesis but not to PME. Since the micro-aneurysms are located away from the central foveal avascular zone (FAZ), the expected increase in MV in DME does not necessitate a concomitant CMT increase, thus lowering the TVR in DME.
The distribution of cystic spaces was also found to be valid for differentiation:
1. Outer retinal cystic changes had a high prevalence in both groups. However, in PME, INL was most affected while ONL was frequently affected in DME. In Munk's study, the presence of solely INL cysts was suggestive for PME. Furthermore, the outer/total retinal thickness in DME was more than in PME. These findings are compatible with our results
Previous studies showed that DME cysts present predominantly in the outer retina even before foveal involvement. Small inner layer cysts were also occasionally found occupying the full retinal thickness. A recent study of IrvineGass syndrome showed a directional progression of cystic changes beginning with INL then outward to OPL and may continue to SRF. Inner layers remained uninvolved while isolated INL cysts were found in the phakic fellow eyes. An explanation can be based on the pathophysiological fact that PME is caused by pro-inflammatory cytokine release leading to blood-retinal barrier (BRB) breakdown. As the intermediate and the deep vascular plexuses are located around INL, it seems expected that INL is initially frequently affected in PME. In DME, outer BRB breakdown, impaired RPE pumping function, and glial cell dysfunction are likely to disturb fluid homeostasis by changes in hydrostatic pressure; molecular extravasal shift and decreased oncotic pressure due to hypoalbuminemia, making ONL in diabetics more prone to fluid accumulation.
2. The inner retina was less affected in both groups. However, the absence of cysts in GCL and RNFL in all cases of PME was found to be statistically significant (P = 0.0061) because in DME cases, cystic changes in both layers were found in 47.7% and 33.3% respectively (P = 0.0003 and P = 0.004 respectively). The presence of RNFL and GCL cysts was mentioned as an indicator for DME over PME in Munk's study. Jo also has reported that the inner retina tends to remain preserved in PME, unlike DME where reduction of inner/total retinal thickness occurs. A possible explanation may be related to the MAs of the superficial vascular plexus which leak into the respective inner retina, making DME more prone to inner retinal fluid accumulation than PME where no microangiopathic changes are expected.
Regarding CMT, values were higher in both groups than the average normative data, but PME values were higher than in DME (482 ± 122 μm vs. 342.2 ± 74 μm) (P = 0.042). In Jo's study, results differed and CMT was higher in DME than in PME. That might be explained by the individual variation in the severity of each case. Furthermore, in Munk's study, no definite period range between cataract surgery and OCT imaging was mentioned in PME group inclusion parameters; producing a probable greater variability.
Regarding VRI, the prevalence of ERM in DME group (33.3% compared to 5% of PME) is compatible with Munk's study (22%–25% vs. 7%). Theories of ERM pathogenesis can help the explanation. Idiopathic ERM is hypothesized to be related to anomalous PVD causing cellular vitreous segments containing hyalocytes to transdifferentiate into myofibroblasts on the retinal surface forming ERM. In ERM secondary to diabetic retinopathy, hyperglycemia was found to cause Müller cells activation with reactive gliosis and proliferation of glial fibrillary acidic protein; strengthening Müller cells-ILM bonds.,,
Regarding macular contour, the prevalence of dome-shaped fovea in PME group (80%) compared to (33.3%) in DME group is compatible with another study suggesting that PME represents a central ME pattern, unlike the focal or diffuse thickening in DME. The inflammation-mediated reaction in PME makes the fovea get the prominent effect. In contrast, DME is likely to be presented by microfoci related to leaking micro-aneurysms (normally absent in FAZ). Another explanation can be based on the severity of ME. DME might vary according to the stage of DR, the duration of DM, and blood glucose control; producing a wider range of severity than PME producing variable morphological outcomes.
SRF was found in PME (65%) more than DME (40%). The difference is consistent with Munk's study (26% in DME vs. 76% in PME). Breakdown of the outer BRB, impaired RPE and ELM functions, subretinal diffusion of proteins and a positive oncotic pressure gradient may lead to SRF accumulation. Furthermore, Müller cells traction on the foveal photoreceptors' IS and OS might initiate SRF development. The different underlying pathomechanisms may be the major cause of the uneven prevalence of SRF. Diabetics suffer chronic hyperglycemia associated with advanced glycation end products, activation of protein-kinase C and hexosamine pathways, leading to a breakdown of intercellular junctions, pericyte loss, basement membrane thickening, and increased oxidative stress. PME in contrast is induced by an acute release of variable proinflammatory cytokines, prostaglandins, proteases, and complement; causing acute profound RPE dysfunction and acute breakdown of the inner and/or outer BRB contrasting the sustained chronic inflammation and degenerative processes in diabetes.
The presence of HE (P = 0.0001) was expected in DME group due to the microangiopathic changes of diabetes causing leakage and lipoprotein deposition. Since no basic microvascular pathology is evident in PME, the presence of HE is not likely to exist. OPL being most commonly affected by HE followed by ONL, can be explained on anatomical and pathophysiologic bases; OPL represents a shed-like area between the two circulations supplying the retina as the DVP lies just deep to INL facing OPL. HE are known to surround leaking MA where chronic localized edema results in exudation at the junction of normal and edematous retina making OPL more prone to HE deposition.
The main limitations of our work were the technical difficulties in generating much more parameters for differentiation, requiring accurate automatic measurement for finer retinal details. Hence, developing more complex OCT softwares capable of much detailed data analysis and segmentation might help to assess more parameters or to find a sharper exclusive feature applicable for a wider variety of cases. These criteria are significantly reliable in suggesting the proper diagnosis. However, further studies may consider using other OCT devices and larger samples to enhance these results.
| Conclusion|| |
DME can be differentiated from PME using SD-OCT. The efficacy of OCT in such a differentiation shall positively affect the management strategy and makes OCT superior to other investigative tools. It might be particularly valuable in diabetic patients who were found to have ME after recent cataract surgery because neither the clinical assessment nor the other diagnostic tools can rule out the underlying pathology.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4]