Spectral Domain Optical Coherence Tomography Features and Classification Systems For Diabetic Macular Edema - A Review APO.0000000000000218
Spectral Domain Optical Coherence Tomography Features and Classification Systems For Diabetic Macular Edema - A Review APO.0000000000000218
Spectral Domain Optical Coherence Tomography Features and Classification Systems For Diabetic Macular Edema - A Review APO.0000000000000218
Copyright © 2016 Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
Asia-Pacific Journal of Ophthalmology • Volume 5, Number 5, September/October 2016 SD-OCT Features and Classification Systems for DME
Type 1 (sponge-like swelling) Thickening of the fovea with homogeneous optical reflectivity
Type 2 (cystoid macular edema) Thickening of the fovea with markedly decreased optical reflectivity in outer layers
Type 3 (serous retinal detachment) Thickening of the fovea with subfoveal fluid accumulation and distinct outer border
of detached neurosensory retina
Type 3A Without vitreofoveal traction
Type 3B With apparent vitreofoveal traction
Several studies have correlated retinal sensitivity with visual 3 patterns of fluid accumulation as follows: sponge-like retinal
acuity and retinal thickness at the fovea in patients with DME.13,14 swelling, cystoid macular edema, and serous retinal detachment.
Fundus-monitored microperimetry determines the retinal sensitiv- Initially, the fluid accumulates in the outer retinal layers, with fur-
ity, and retinal thickness is obtained by OCT. The retinal sensitiv- ther cystoid cavity formation correlating with histopathological
ity within the central 2 and 10 degrees of the macula was observed finding of Muller cell necrosis. Persistent edema engages the inner
to be significantly lower in eyes with DME in comparison with retinal layers, leading to atrophy and appearance similar to retinos-
normal eyes. A negative correlation was found between retinal chisis. Serous retinal detachment was interpreted on OCT as de-
sensitivity and foveal retinal thickness. Retinal sensitivity supple- tachment of the neurosensory retina with the presence of
ments the predictive value of OCT in DME.14 underlying fluid (nonreflecting space) above the hyperreflective
line of the retinal pigment epithelium (RPE). Otani et al15 further
observed a significant correlation between visual acuity and reti-
OCT-BASED MORPHOLOGICAL CLASSIFICATION nal thickness regardless of the different tomographic features. In
SYSTEMS FOR DME 2004, Panozzo et al16 classified the morphological pattern in DME,
Otani et al15 proposed the first time domain OCT (TD-OCT) taking into account the size of the cysts (Table 2).
classification for DME based on retinal morphological changes In 2004, Kang et al correlated OCT and FA findings (focal
in 1999 (Table 1). Accumulation of intraretinal fluid leads to in- leakage, diffuse, diffuse cystoid leakage) in DME and inferred a
creased retinal thickness and reduced reflectivity. They described significant correlation between them. Kang et al classified DME
TABLE 2. Classification of DME by Panozzo et al16 Based on Retinal Thickness, Volume, Morphology of Retina, and Macular Traction
Retinal Thickness
Fixation Point Central Zone Perifoveal and Peripheral Areas Volume
Normal 150 + 20 μm 170 + 20 μm 230 + 20 μm 6.5 mm3 ± 1
Borderline 170–210 μm 190–230 μm 250–290 μm Up to 8.0 mm3
Edema >210 μm >230 μm >290 μm ≥8.0 mm3
Morphology
E1 E2 E3
Simple: compact retinal thickening, Cystoid thickening: retinal thickening Neuroepithelial detachment:
no clinically visible cystoid with cysts isolated or associated with
spaces E2A simple or cystoid retinal
Mild: 2–4 central small cysts each with thickening
horizontal diameter 150–200 μm,
vertical diameter 400 μm
E2B
Intermediate: cysts with petaloid
configuration or central cysts with
horizontal diameter less than
300 μm, vertical diameter less
than 600 μm
E2C
Severe: coalescence of cysts with
appearance similar to retinoschisis
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Ruia et al Asia-Pacific Journal of Ophthalmology • Volume 5, Number 5, September/October 2016
TABLE 3A. OCT-Based Classification of DME by Koleva-Georgieva TABLE 4. SD-OCT–Based Classification of DME by Helmy et al19
and Sivkova18
CME I Cysts less than 30% of macular thickness
Mild Small cysts predominantly in the outer retinal layers CME II Cysts between 30% and 60% of macular thickness
Moderate Cysts mainly located in the outer layers CME III Cysts between 60% and 90% of macular thickness
Severe Cysts mainly located in the outer layers predominantly CME IV Cysts more than 90% of the macular thickness
in the fovea A Cysts without any disruption to the ELM or EZ
B Cysts with ELM disruption
into 4 morphological types. Type 1 was described as thickening of C Cysts with EZ disruption
the fovea with homogeneous optical reflectivity throughout the
D Cysts with disruption of both the ELM and EZ
whole layer of the retina, whereas type 2 referred to thickening
of the fovea with markedly decreased optical reflectivity in the CME indicates cystoid macular edema.
outer retinal layers. Type 3 represented foveolar detachment with-
out traction, and type 4 constituted foveolar detachments with ap-
parent vitreofoveal traction. They observed that the morphological QUANTITATIVE ANALYSIS OF DME ON OCT
type of DME on OCT and the type of leakage on FA correlated
with visual acuity.17 In 2008, Koleva-Georgieva and Sivkova clas- Time domain OCT was widely used in clinical practice and
sified DME in terms of the size of cystoid spaces and evaluated was the principal instrument used in numerous studies conducted
the progression of macular edema (Tables 3A and 3B). They by the DRCR.net until 2011. Retinal thickness was measured as
found a correlation between the size of cystoid spaces, retinal the value in microns of the distance between the OCT layers, the
thickness, and visual acuity.18 Recently, Helmy et al19 classified RPE, and the internal limiting membrane. The center point thick-
patients with cystoid macular edema into 4 groups based on the ra- ness was defined as the average of the thickness values at the in-
tio of the vertical height of the largest macular cyst in relation to tersection of the 6 radial scans of the fast macular thickness
the maximum macular thickness, with the use of OCT (Table 4). protocol. The central subfield was defined as the circular area
TABLE 3B. Classification by Koleva-Georgieva With Retinal Thickness, Morphology, Topography, Presence and Severity of Macular
Traction, and Photoreceptor Inner Segment EZ Integrity
Retinal Thickness
No Macular Edema Early Subclinical Macular Edema Established Macular Edema
Normal macular morphology and No clinically detected retinal thickening on Retinal thickening and evident
thickness not reaching the criteria ophthalmoscopy, OCT measured retinal thickness morphological characteristics
for subclinical DME exceeding normal + 2 SD for central fixation of edema
point and fovea
Retinal Morphology
Simple Noncystoid Macular Edema Cystoid Macular Edema Serous Macular Detachment
Increased retinal thickness, intraretinal (a) Mild: cystoid spaces with horizontal
reduced reflectivity, irregularity of the diameter < 300 μm
layered structure, flattening of the foveal (b) Intermediate: cystoid spaces with horizontal
depression without presence of diameter of 300–599 μm
cystoid spaces (c) Severe: cystoid spaces with horizontal
diameter ≥ 600 μm, or large confluent cavities
with retinoschisis appearance
Retinal Topography
Nonsignificant macular edema CSME, as defined by ETDRS and evaluated on
the OCT retinal topography map
Presence and Severity of Macular Traction (PVD and/or ERM)
No Macular Traction Questionable Macular Traction Definite Macular Traction
Presence of complete PVD (Weiss ring Incomplete PVD with perifoveal or peripapillary Incomplete PVD with perifoveal
detected on ophthalmoscopy), or no adhesion and/or globally adherent ERM adhesion and/or focal ERM with
PVD (no visible posterior hyaloid line), without detectable distortion of retinal surface detectable distortion of retinal
and no ERM contour at the points of adhesion contour at the points of adhesion
Retinal Outer Layer Integrity (EZ and ELM)
EZ and ELM intact EZ and ELM with disrupted integrity
*Koleva-Georgieva DN. Optical coherence tomography findings in diabetic macular edema. In: Ola MS, ed. Diabetic Retinopathy. Vienna, Austria:
InTech; 2012.
ERM indicates epiretinal membrane; PVD, posterior vitreous detachment.
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Asia-Pacific Journal of Ophthalmology • Volume 5, Number 5, September/October 2016 SD-OCT Features and Classification Systems for DME
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Ruia et al Asia-Pacific Journal of Ophthalmology • Volume 5, Number 5, September/October 2016
TABLE 6. SD-OCT–Based Classification of Retinal Photore- TABLE 8. SD-OCT–Based Classification of Retinal Photoreceptor
ceptor Inner Segment EZ Disruption in Diabetes Mellitus by ELM and Inner Segment EZ Disruption in Diabetes Mellitus by
Maheshwary et al42 Jain et al44
Maheshwary et al graded the severity of EZ disruption in At present, clinical decision making about DME manage-
eyes with DME in 2010. Grades from each patient’s horizontal ment is mostly based on simple qualitative evaluation of baseline
and vertical SD-OCT scans were added to yield a global disrup- and follow-up OCT scans and thickness measurements.20 Various
tion scale (Table 6).42 The percentage of disruption along the EZ previously mentioned physician-friendly classification systems
band, measured 500 μm in either direction from the foveal center, provide in vivo retinal structural alterations with regard to patho-
was recorded. They demonstrated that the percentage of disrup- physiology of the disease process. These structural alterations cor-
tion of the photoreceptor EZ band was an important predictor of relate with changes in visual acuity. These classification systems
visual acuity in patients with DME. Sharma et al43 in 2014 gave provide a systematic approach to the diagnosis and management
a simplified, comprehensive, and physician-friendly approach to of DME and are useful for execution and analysis of clinical stud-
grading EZ disruption based on SD-OCT findings (Table 7). ies. The recent focus has been on outer retinal structural alter-
The EZ was studied using horizontal and vertical SD-OCT scans ations and integrity of inner retinal layers.42,44,48,49 Changes in
through the fovea. The study also illustrated a significant decrease these parameters correlate with changes in visual acuity and facil-
in visual acuity correlated with an increase in the grade of disrup- itate treatment decision making.
tion of the EZ in patients with DR, and a marked decrease in visual
acuity was found to be associated with global disruption.43
In 2013, Jain et al44 showed for the first time that ELM dis-
MACULAR ISCHEMIA IN DME
ruption occurred earlier than disruption of the EZ (Table 8, Fig. 1). Macular ischemia has been suggested to be associated with
This was based on the observation that the ELM has tight junc- poor visual outcomes in patients with DME.50 Studies have docu-
tions similar to those between RPE cells. Therefore, the ELM acts mented macular ischemia to have a limiting effect on visual out-
like the third outer BRB and its disruption contributes to fluid comes after intravitreal bevacizumab injections in patients
accumulation in DME.45 The disruption of the EZ is secondary with DME.51
to disrupted ELM. This was observed in experimental mice where Fluorescein angiography has been used to identify macular
a mutation leading to disruption of the ELM was found to cause ischemia. The size of the foveal avascular zone (FAZ) and its out-
shortening of the photoreceptor inner segment.46 A significant line, on FA, correspond to the ischemic state of the macula.52 Sev-
positive correlation was found between logMAR visual acuity eral recent reports suggested that OCT can detect the structural
and grade of disruption.44 Helmy et al19 also took into consider- changes in the retina due to ischemic changes. Byeon et al53
ation the presence of photoreceptor ELM and EZ disruption in assessed foveal ganglion cell layer damage in ischemic diabetic
their classification of DME (Table 4). In another study, Murakami maculopathy and postulated that OCT provides objective results
et al overcame the limitation of variability in the reflectivity levels and might be a good noninvasive substitute for FA. Further studies
of continuous EZ bands seen on SD-OCT. Relatively homoge- documented a significant correlation of ganglion cell layer dam-
neous and continuous ELM bands were described as intact, age with duration of diabetes.54 In patients with severe non-
whereas absent or discontinuous ELM bands were described as proliferative and proliferative DR without DME, no significant
disrupted. Quantification of the status of the transverse length of association of FAZ outline or size was found with retinal volume,
each segment of disrupted EZ and ELM band was performed. total retinal thickness, and thickness of the outer and inner retina
Statistical analysis demonstrated that the total additive transverse and ganglion cell layer. There is a contradictory association be-
length of disrupted EZ and ELM within the fovea correlated tween the FAZ outline and continuity of the ELM and EZ. Certain
more closely with logMAR visual acuity than did foveal thickness studies mention foveal ischemia in DME to cause EZ disruption
measurements.47 resulting in outer retinal layer atrophic changes and subsequent
Classifications based on OCT have proved to be useful in visual loss. Studies correlating choroidal thickness and FAZ en-
monitoring disease progression and in clinical trials for the treat- largement in patients with DME have also documented contradic-
ment of DME. Trials on anti-VEGF have recommended the in- tory results.52
itiation of anti-VEGF therapy for foveal center-involving DME In most of the OCT studies in DR, the effects of macular is-
with visual impairment but laser photocoagulation for noncenter- chemia are masked by coexisting DME. Fluorescein angiography
involving cases. Vitrectomy for DME has been found to have remains the gold standard for evaluating the retinal perfusion sta-
good visual outcome in cases with traction over the retina.30 tus and for detecting macular ischemia in patients with DR. Re-
cently, OCT angiography was found to be useful for quantifying
retinal ischemia in diabetic DR. The parafoveal and perifoveal
TABLE 7. SD-OCT–Based Classification of Retinal Photore- vessel density are significantly reduced and low-perfusion areas
ceptor Inner Segment EZ Disruption in Diabetes Mellitus by are significantly increased in eyes with DR. Areas of low perfu-
Sharma et al43 sion in OCT angiogram corresponded to ischemic areas in FA.55
Grade 0 Intact EZ
HYPERREFLECTIVE SPOTS
Grade 1 Focal disruption (localized, subfoveal EZ disruption)
Grade 2 Global disruption (generalized EZ disruption
Bolz et al described the distribution of hyperreflective spots
throughout the macular cube) throughout all the retinal layers in eyes with DME. They hypoth-
esized that the hyperreflective spots represent subclinical features
Copyright © 2016 Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
Asia-Pacific Journal of Ophthalmology • Volume 5, Number 5, September/October 2016 SD-OCT Features and Classification Systems for DME
of lipoprotein extravasation that act as precursors of hard exu- treatment modality, whether medical or surgical. With various
dates.56 Uji et al documented that the hyperreflective spots were clinical trials on anti-VEGF pharmacotherapy, SD-OCT has be-
located in the outer retina and were closely associated with dis- come an indispensable tool in clinical practice.
ruption of the ELM and EZ. The hyperreflective spots were also
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Everything you see or hear or experience in any way at all is specific to you. You create a universe by perceiving it,
so everything in the universe you perceive is specific to you.
— Douglas Adams
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