|Year : 2016 | Volume
| Issue : 3 | Page : 632-636
Assessment of diabetic macular edema by fundus autofluorescence and optical coherence tomography
Khaled E. El-Kotb Said Ahmad1, Asmaa M Ahmad Ibrahim1, Yasmeen A Abd El-Razag El-Ghazaly2
1 Department of Ophthalmology, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||13-Aug-2015|
|Date of Acceptance||27-Sep-2015|
|Date of Web Publication||23-Jan-2017|
Yasmeen A Abd El-Razag El-Ghazaly
Ashohada, Menoufia, 32958
Source of Support: None, Conflict of Interest: None
The objective of this study was to evaluate the role of fundus autofluorescence (FAF) in the diagnosis of diabetic macular edema (DME) and to compare it with optical coherence tomography findings.
FAF imaging is a new technology that can be used to characterize eyes with macular disease. Specific FAF patterns observed in patients with DME seem to correlate with various optical coherence tomography patterns rather than with visual acuity.
Patients and methods
This study included a total of 51 eyes (26 right and 25 left eyes) of 27 patients (12 male and 15 female) with a mean age of 56.5 years. Main outcome measurements included best corrected visual acuity (BCVA), central macular thickness (CMT), the integrity of photoreceptors inner/outer segment junction (IS/OS), and the presence or absence of increased FAF (iFAF) at the foveola.
Among the 51 eyes, 37 (72.5%) eyes had no FAF, eight (15.7%) eyes had single-spot iFAF, and six (11.8%) eyes had multispot iFAF; only three (5.8%) eyes of 51 eyes showed the presence of iFAF at the foveola. There was a significant association between grades of FAF regarding intact IS/OS layer (P = 0.003) and significant association between grades of FAF regarding partly interrupted IS/OS layer (P = 0.04). There was a significant association between grades of FAF and the mean CMT (P = 0.002). There was a nonsignificant association between grades of FAF and the mean values of BCVA (P = 0.27), and there was a highly significant positive correlation between BCVA and CMT (P < 0.001).
FAF might reflect the damage of the retina and had a relationship with the integrity of photoreceptors, as well as CMT, which gives new insight into the evaluation of DME, but it cannot reflect the severity of DME and cannot help us to evaluate the visual function of the patients.
Keywords: diabetic macular edema, fundus autofluorescence, optical coherence tomography, photoreceptor integrity
|How to cite this article:|
Said Ahmad KE, Ahmad Ibrahim AM, Abd El-Razag El-Ghazaly YA. Assessment of diabetic macular edema by fundus autofluorescence and optical coherence tomography. Menoufia Med J 2016;29:632-6
|How to cite this URL:|
Said Ahmad KE, Ahmad Ibrahim AM, Abd El-Razag El-Ghazaly YA. Assessment of diabetic macular edema by fundus autofluorescence and optical coherence tomography. Menoufia Med J [serial online] 2016 [cited 2020 Apr 3];29:632-6. Available from: http://www.mmj.eg.net/text.asp?2016/29/3/632/198745
| Introduction|| |
Diabetic macular edema (DME) is a common complication of diabetic retinopathy and is known to be the leading cause for visual impairment of the diabetic patient  .
The pathophysiology of DME is not completely understood. Biochemical changes are supposed to lead to endothelial damage with altered leukocyte function with a consecutive breakdown of the blood-retinal barrier, dilated capillaries, microaneurysms, and loss of pericytes. Resulting vascular leakage of fluid and serum proteins, plasma constituents, and lipids into the intraretinal space lead to increased retinal thickness and DME  .
Early diagnosis of DME is vital to the preservation of visual acuity  . Assessment of DME can be done by slit-lamp biomicroscopy or by stereoscopic macular photographs. Noninvasive imaging techniques such as optical coherence tomography (OCT) are of high value for diagnosis of DME and provide qualitative and quantitative data that are useful as progression parameters  .
Fundus autofluorescence (FAF) imaging is a relatively new technology that can be used to characterize eyes with macular disease. FAF is mainly based on lipofuscin in the Retinal Pigment Epithelium (RPE), which is a residue of phagocytosed photoreceptor outer segments  .
The Heidelberg Retinal Angiography system is a system that can obtain FAF images. This confocal scanning laser ophthalmoscope uses an excitation wavelength of 488 nm and a barrier filter of 500 nm to provide FAF imaging in vivo  .
Specific FAF patterns observed in diabetic patients with DME seem to correlate with various OCT patterns rather than with visual acuity. Recent works assume a more accurate FAF analysis of pathological changes at the RPE level. If confirmed, FAF might help in screening for DME  .
| Patients and methods|| |
This cross-sectional study included cases of untreated DME. They were recruited from the ophthalmology clinic of Menoufia University Hospital. The eyes that were included had DME for which OCT and FAF were obtained. The study was approved by the ethics committee of the faculty. Informed consent was taken from each participant.
The inclusion criteria were as follows:
- Any type of DME.
- No previous treatment was performed.
Exclusion criteria were as follows:
- Previous laser treatment or surgery in the study eye
- Significant media opacities
- Eyes with vitreoretinal pathology other than diabetic retinopathy
- Macular edema caused by other etiologies such as retinal vascular occlusions and postoperative or inflammatory cystoid macular edema
- Eyes with tractional retinal detachment.
All patients will undergo a full ophthalmologic evaluation, including slit-lamp examination and biomicroscopy. Best corrected visual acuity (BCVA) was measured with Snellen's Chart and converted to logarithm of the minimum angle of resolution using visual acuity conversion . Indirect ophthalmoscopy and fundus photography were performed, followed by OCT and FAF.
Optical coherence tomography measurements
A 6 × 9 mm area of the macular region centered on the fovea was examined using SD-OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). Volume scans of 25 sections (each with a distance of 240 μm) were performed, centered on the fovea.
Each obtained cross-sectional OCT scan from each study eye was evaluated for the integrity of inner/outer segment (IS/OS) layer of the photoreceptors (0 = continuous, 1 = partly interrupted, 2 = completely interrupted) ([Figure 1]).
|Figure 1: Completely interrupted (a) and partially interrupted (b) inner/outer segment (IS/OS) layer band in patients with cystoid diabetic macular edema (DME) compared with continuous (c) IS/OS layer band in patients without DME in cross-sectional optical coherence tomography scans.|
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Each diabetic study eye with OCT-based diagnosis of DME [central macular thickness (CMT) measured with SD-OCT >200 μm] was subdivided into the following:
- Focal DME (locally defined retinal thickening)
- Diffuse DME (extensive retinal thickening within at least two OCT subfields)
- Cystoid DME (the presence of cysts within the outer retinal layers seen on cross-sectional scans through the central subfield)
- Mixed DME (diffuse and cystoid DME).
Fundus autofluorescence measurements
Because the fluorescence intensity emitted by the RPE at ∼500 nm is extremely low, an scanning laser ophthalmoscope (HRA2, Heidelberg, Germany) was used with both excitation illumination (488-nm laser) and barrier filters in place. The degree of FAF is graded as follows:
Grade 1: samples with no or barely visible FAF
Grade 2: samples with single-spot increased FAF (iFAF)
Grade 3: samples with multispot iFAF ([Figure 2]).
|Figure 2: Normal (a), single-spot (b), and multispot (c) increased fundus autofluorescence pattern of included patients with diabetic macular edema.|
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The presence or absence of iFAF at the foveola was also determined for the analysis of the correlation with the SD-OCT parameters ([Figure 3]).
|Figure 3: Presence of increased fundus autofluorescence at foveola of a patient with diabetic macular edema.|
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The collected data were analyzed using SPSS IBM, New York, USA (statistical package for the social science).
χ2 was used to study the association between two qualitative variables.
Kruskal -Wallis test was used for comparison between three or more groups of not normally distributed quantitative variables.
Spearman's correlation coefficient (r) was used to measure the association between two quantitative variables not normally distributed or one quantitative and other qualitative variables. A P value less than 0.05 was considered statistically significant.
| Results|| |
This study included a total of 51 eyes (26 right and 25 left eyes) of 27 patients (12 male and 15 female) with a mean age 56.5 years (range: 30-74 years). All patients had non-insulin-dependent diabetes mellitus with a mean duration of diabetes of 11.5 years (range: 2-25 years). The mean BCVA was 0.81and the mean CMT was 361.4 μm.
Among the 51 eyes, 37 (72.5%) eyes had no FAF, eight (15.7%) eyes had single-spot iFAF, and six (11.8%) eyes had multispot iFAF; only three (5.8%) eyes of 51 eyes showed the presence of iFAF at the foveola. According to the FAF morphology, patients were categorized into three grades: normal (no FAF), single-spot iFAF, and multispot iFAF.
There was a significant difference between grades of FAF and the mean CMT ([Table 1]) and the integrity of photoreceptors IS/OS ([Table 2]). There was a significant difference between the subclassification of DME by OCT regarding grade 1 FAF ([Table 3]).
|Table 1 Comparison between grades of fundus autofluorescence regarding central macular thickness |
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|Table 2 Comparison between grades of fundus autofluorescence regarding integrity of photoreceptors inner/outer segment junction |
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|Table 3 Comparison between subclassification of diabetic macular edema regarding fundus autofluorescence intensity |
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According to the comparison on the visual function and grades of FAF, there was a nonsignificant difference between grades of FAF and the mean values of BCVA ([Table 4]). There was a highly significant positive correlation between BCVA and CMT ([Table 5]).
|Table 4 Comparison between grades fundus autofluorescence regarding visual acuity |
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|Table 5 Spearman's correlation between central macular thickness and visual acuity |
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| Discussion|| |
The classification of diabetic macular edema (DME) was extensively studied. The Early Treatment Diabetic Retinopathy Study introduced the term clinically significant macular edema (CSME). Others have divided DME into focal and subtypes  . As time went by, others included fluorescein angiographic findings in the definition of diffuse or focal DME. When OCT was used, several OCT patterns of morphological macular changes associated with DME were described  .
FAF is a recent technique that is used mostly for the structural evaluation of AMD, retinitis pigmentosa, inherited macular dystrophies (such as Stargardt disease, Best disease), and so on  .
In our study, there were only three patients with iFAF at the foveola; OCT showed increased retinal thickness, and it was shown to be associated with the presence of Cystoid macular edema (CME). At the foveola, FAF is very weak or almost absent in normal eyes because lutein and zeaxanthin are especially dense in the axons of the cone photoreceptors (Henle's fiber) at the foveola blocking the FAF signal from lipofuscin in the RPE layer. Thus, iFAF at the foveola could indicate significant damage to cone photoreceptors cells  .
McBain et al.  observed that luteal pigments are found at the outer nuclear layer, outer plexiform layer, Henle's fiber, and the inner nuclear layer, and that cystic spaces in CME mainly occur in the outer plexiform layer and inner nuclear layer. More of the excitatory light may pass through cysts within the foveal area such that the RPE under the cyst is more easily exposed to light and is more fluorescent. This is in agreement with our study in which the patients with iFAF at the foveola were shown to be associated with the presence of CME.
In this study, some patients had normal FAF, and OCT showed increased retinal thickness without obvious cystic changes. It is inferred that the distribution of MP was relatively normal in these kinds of patients, and therefore their FAF was close to normal. For those who had iFAF, OCT showed cysts-like change. It is possible that cysts might displace MP preventing the normal blockage of foveal FAF signal  .
Our study also showed that there was a significant association between the subclassification of DME by OCT regarding grade 1 FAF. There was a nonsignificant association between the subclassification of DME by OCT regarding grade 2 FAF and nonsignificant association between the subclassification of DME by OCT regarding grade 3 FAF. Among the patients with mixed DME (cystoid and diffuse edema), 25% had single-spot iFAF and 50% had multispot iFAF. Among the patients with cystoid DME, 28% had single-spot iFAF and 8% had multispot iFAF. On the other hand, only 13.3% of patients with diffuse DME had multispot iFAF, and none of the cases with diffuse DME had single-spot iFAF; 100% of patients with focal DME showed no FAF (normal FAF).
This is supported by Bessho et al.  , who proposed that autofluorescence from CME may be 'pseudo' or 'relative' autofluorescence owing to macular stretching after CME, which may result in a lateral displacement of MPs and subsequent reduction in MP density.
Pece et al.  also reported that iFAF during CME in diabetic patients was not abnormal FAF but, instead, was the normal fluorescence of the RPE as observed through a defect in the xanthophyll pigment.
Vujosevic et al.  has proposed an 'oxidative theory' indicating that the iFAF areas in DME are caused by accumulation of oxidative product induced by activated microglia because of ongoing DM.
Uji et al.  reported that there is an association between FAF characteristics and the integrity of IS/OS. This is in agreement with the results of our study in which there was a significant association between grades of FAF regarding intact IS/OS layer and significant association between grades of FAF regarding partly interrupted IS/OS layer.
This study showed that there was a significant association between grades of FAF and the mean CMT. This is in agreement with the study by Pece et al.  , who reported that FAF increases as macular thickness increases.
This study revealed that there was a highly significant positive correlation between BCVA and CMT. Patients with good BCVA showed less CMT. This is in agreement with the study by Shrestha et al.  , who found that there was a high correlation between vision status and CMT (P = 0.0001).
This study showed that there was a nonsignificant association between grades of FAF and the mean values of BCVA. This is in disagreement with the study by Chung et al.  , who reported that the visual acuity of DME patients with iFAF was worse than that of patients without iFAF. This disagreement may be because of the inclusion of a relatively small number of patients. In the study by Chung et al.  , they included 165 patients, whereas in this study we included 51 patients. Another explanation may be the presence of another possible visual prognostic factor. This may explain the different results between this study and that of Chung et al.  .
| Conclusion|| |
FAF might reflect the damage of the retina and had a relationship with the integrity of photoreceptors, as well as CMT, which gives new insight into the evaluation of DME but it cannot reflect the severity of DME and cannot help us to evaluate the visual function of the patients.
The mechanism of FAF in DME is still unclear, and further studies are needed to confirm the results of our study and to determine the exact mechanism of FAF changes in DME.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Moss SE, Klein R, Klein BE. The 14-year incidence of visual loss in a diabetic population. Ophthalmology 1998; 105
Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH et al.
Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 2005; 6
Wagdy FM, Sarhan ARE, Elmorsy OA, Galal MAZ, Nassar MK. Optical coherence tomography as a prognostic tool for visual improvement after management of diabetic macular edema. Menoufia Med J 2014; 27
Kook D, Wolf A, Kreutzer T, Neubauer A, Strauss R, Ulbig M et al.
Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema. Retina 2008; 28
Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo
fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci 1995; 36
Holz FG, Bellmann C, Margaritidis M, Schütt F, Otto TP, Völcker HE. Patterns of increased in vivo
fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1999; 237
Vujosevic S, Casciano M, Pilotto E, Boccassini B, Varano M, Midena E. Diabetic macular edema: fundus autofluorescence and functional correlations. Invest Ophthalmol vis Sci 2011; 52
Bresnick GH. Diabetic macular edema. A review. Ophthalmology 1986; 93
Browning DJ, Fraser CM. Regional patterns of sight-threatening diabetic macular edema. Am J Ophthalmol 2005; 140
Greenstein VC, Duncker T, Holopigian K, Carr RE, Greenberg JP, Tsang SH, et al
. Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa. Retina 2012; 32
Charbel Issa P, van der Veen RL, Stijfs A. Quantification of reduced macular pigment optical density in the central retina in macular telangiectasia type 2. Exp Eye Res 2009; 89
McBain VA, Forrester JV, Lois N. Fundus autofluorescence in the diagnosis of cystoid macular oedema. Br J Ophthalmol 2008; 92
Pece A, Isola V, Holz F, Milani P, Brancato R. Autofluorescence imaging of cystoid macular edema in diabetic retinopathy. Ophthalmologica 2010; 224
Bessho K, Gomi F, Harino S. Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm excitation but not with 580 nm-excitation. Graefes Arch Clin Exp Ophthalmol 2009; 247
Uji A, Murakami T, Nishijima K, Akagi T, Horii T, Arakawa N et al
. Association between hyperreflective foci in the outer retina, status of photoreceptor layer, and visual acuity in diabetic macular edema. Am J Ophthalmol 2012; 153
Shrestha A, Maharjan N, Shrestha A, Thap R, Poudyal G. Optical coherence tomographic assessment of macular thickness and morphological patterns in diabetic macular edema: prognosis after modified grid photocoagulation. Nepal J Ophthalmol. 2012; 4
Chung H, Park B, Shin HJ, Kim HC. Correlation of fundus autofluorescence with spectral-domain optical coherence tomography and vision in diabetic macular edema. Ophthalmology 2012; 119
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]