OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography

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Uvea OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography Kirti Jaisingh MS Kirti Jaisingh MS, Yashpal Goel* MS, Kshitij Aditya** DO * Guru Nanak Eye Centre, New Delhi **

remains the leading cause of blindness in working-age populations of industrialized countries.

It affects central vision from the early stages of retinopathy, and it is the most frequent sight-threatening complication of diabetic retinopathy, particularly in older type 2 diabetic patients.

Until few years, assessment of the macular status was subjective, relying on slit lamp biomicroscopy. Other traditional methods detect intraretinal leakage in these patients.

1 Uvea OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography Kirti Jaisingh MS Kirti Jaisingh MS, Yashpal Goel* MS, Kshitij Aditya** DO * Guru Nanak Eye Centre, New Delhi ** Baba Saheb Ambedkar Hospital, Delhi Diabetic retinopathy, one of the most frequent complications of diabetes, remains a major implications, affecting approximately 50% of diabetic subjects, and remains the leading cause of blindness in working-age populations of industrialized countries. Diabetic macular edema (DME) is the largest cause of visual acuity loss in non proliferative diabetic retinopathy 1. It affects central vision from the early stages of retinopathy, and it is the most frequent sight-threatening complication of diabetic retinopathy, particularly in older type 2 diabetic patients. Its frequency increases with both the duration and of macular edema is therefore of major importance in evaluation of any diabetic patient. Until few years, assessment of the macular status was subjective, relying on slit lamp biomicroscopy. Other traditional methods detect intraretinal leakage in these patients. However, FA is only used as a guide for focal or grid laser treatment of thickened retina. Moreover, it is the amount and type of edema that determines the modality of treatment employed the emergence of optical coherence tomography (OCT) in the diagnosis and management of DME. Roles of OCT in DME thickening not visible on slit lamp biomicroscopy (especially within μm). 3) Estimation of macular volume. 4) Classifying the macular edema morphologically. 6) Both quantitative and qualitative response to treatment and follow up. 7) Determining the prognosis. 8) Research tool. like cystoid macular edema, spongiform swelling etc. correlating with the physiological abnormalities causing edema. Definition The Early Treatment Diabetic Retinopathy Study (ETDRS) retinal thickening at macula using slit lamp biomicroscopy 2. or presence of hard exudates within 1 disc diameter of the centre of macula. as: a) Retinal thickening at or within 500μm of the centre of the macula and/or b) Hard exudates at or within 500μm of the centre of macula if associated with retinal thickening and/or c) A zone or zones of retinal thickening 1 disc area in size, at least part of which is within 1 disc diameter of the centre of macula. Pathophysiology The pathogenesis is not completely understood. It is believed to result from the breakdown of inner blood retinal barrier. Hyperglycemia induced changes in tight junctions, pericyte loss, endothelial cell loss, increased permeability of retinal vasculature and vitreoretinal traction are all implicated in its development. The retina is a compact www. dosonline.org l 43

Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography Fiure 1: tissue composed of neural element and glial cells.

2 Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography Fiure 1: tissue composed of neural element and glial cells. Because glial cells occupy all the interneural space, extracellular space is virtually absent. Ischemia causes intracytoplasmic swelling of Muller cells, constituting cytotoxic edema. The cytotoxic edema may progress to vasogenic edema with the later release of permeability substances such as prostaglandins and vascular endothelial growth factor from layer is markedly swollen in macular edema. Prominent space in the outer retinal layers may represent the swollen liquefaction and necrosis of the Muller cells ensues. Necrosis of the Muller cells and adjacent neural cells leads to cystoid cavity formation in the retina. The external progression of hypoxia, there is breakdown of outer blood retinal barrier also leading to a defective retinal pigment causing serous macular detachment (SMD). DME may also be exacerbated due to persistent vitreomacular traction by the residual cortical vitreous on the macula after PVD, thickened and taut posterior hyaloid that may or may not be adherent to ILM, macular traction due to tractional proliferative membranes, or loculation of cytokines in the pre-macular vitreous pocket. A diabetic retina compromised due to microvascular abnormalities may be vulnerable to increased exudation in the presence of any macular traction. OCT: Principle and Techniques OCT is a non contact, non invasive diagnostic technique that provides highly reliable, reproducible and objective in a way that is analogous to the ultrasound B-scan. It can achieve 2- or 3-dimensional cross-sectional imaging of tissue by measuring the echo delay and intensity of back- second generations of commercial OCT instrument were time domain (TD) (OCT1, OCT2) and had an axial resolution of 10 15μm. Third generation OCT (OCT3, Stratus; Carl Zeiss Meditec, Dublin, California, USA) provided an axial resolution of 8 10μm. The recently available spectraldomain OCT (SD-OCT) has an axial resolution of 5 6μm, providing highly detailed anatomical description of retinal layers (Figure 1). Besides the qualitative analysis, OCT is capable of measuring the retinal thickness at a particular location quite accurately. Mean macular retinal thickness (RT) is displayed as a two-dimensional false color-coded map, where bright colors (e.g. red and white) represent thick areas and dark colors (e.g., blue and black) represent thin areas, and as a numerical map, for nine ETDRS-type areas (Figure 2). Clinically, it is important to recognize that TD- for retinal thickness, with SD-OCT giving larger values ranging from 30 to 55 μm compared to TD-OCT. This is based on reference points i.e. retinal pigment epithelium in Cirrus SD-OCT and IS/OS junction of the photoreceptors in Stratus TD-OCT. Patterns of DME on OCT al in 1999, which divided it into 3 types 4 : 1) Sponge like thickening (88%). 2) Cystoid macular edema (47%) (CME). 3) Serous macular detachment (15%) (SMD). No component of vitreomacular traction was included in 5 : 44 l DOS Times - Vol. 20, No. 3 September, 2014

Uvea Figure 4: Cystoid macular edema Figure 2: Retinal Thickness Map Figure 5: Serous macular detachment

markedly decreased optical 3) Type 3a: foveolar detachment without traction.

This divided type 3 (SMD) with respect to tractional forces seen at the vitreoretinal interface.

Few authors have described a 5th class also depicting focal macular edema.

areas of Increased retinal thickness but no cystoid spaces.

Later these septae dissolve and the cystoids spaces involve whole of the retina.

3 Uvea Figure 4: Cystoid macular edema Figure 2: Retinal Thickness Map Figure 5: Serous macular detachment Figure 3: Spongiform swelling 1) Type 1: thickening with homogenous optical 2) Type 2: thickening with markedly decreased optical 3) Type 3a: foveolar detachment without traction. 4) Type 3b: foveolar detachment with apparent vitreofoveal traction. This divided type 3 (SMD) with respect to tractional forces seen at the vitreoretinal interface and many others all of which included vitreomacular traction as one of the types of macular edema 6. Few authors have described a 5th class also depicting focal macular edema. The characteristic changes in DME appear on OCT as follows: 1) Sponge like thickening (Figure 3): expanded areas of Increased retinal thickness but no cystoid spaces. 2) CME (Figure 4): intraretinal cystoid spaces involving outer layers initially with intervening septae. Later these septae dissolve and the cystoids spaces involve whole of the retina. Figure 6: Vitreomacular traction Figure 7: 3) SMD anterior boundary. Associated with increased macular thickness. 4) Tractional retinal detachment: foveovitreal traction causing peak shaped detachment of fovea. 5) Taut posterior hyaloid membrane (Figure 6): highly and extending towards the optic nerve or periphery. www. dosonline.org l 45

Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography 2 RT (μm) ± SD Fovea Central area (1mm) Perifoveal and peripheral areas Normal 150±20 170±20 230±20 Borderline

7) Haemorrhages: layers 8) Epiretinal Membrane thickening at the level of internal limiting membrane, It can be focally adherent or globally adherent.

4 Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography 2 RT (μm) ± SD Fovea Central area (1mm) Perifoveal and peripheral areas Normal 150±20 170±20 230±20 Borderline Edema Figure 8: Retinal thickness is greatly increased with intraretinal 6) Hard exudates backscattering, located in the outer layers or the subretinal space. 7) Haemorrhages: layers 8) Epiretinal Membrane thickening at the level of internal limiting membrane, It can be focally adherent or globally adherent. quantitative data from various studies 7,8 : Retinal thickness 1. No macular edema normal macular morphology and thickness not reaching the criteria for subclinical DME; 2. Early subclinical macular edema no clinically detected retinal thickening on ophthalmoscopy, OCT measured retinal thickness exceeding normal +2SDs 3. Established macular edema retinal thickening and evident morphological characteristics of edema. Retinal morphology Simple non-cystoid macular edema increased retinal depression, without presence of cystoid spaces; Cystoid macular edema the above criteria, associated spaces. Mild cystoid macular edema cystoid spaces with Intermediate cystoid macular edema cystoid 3 Instrument CRT Stratus OCT 212±19 Cirrhus OCT 277±19 Spectral OCT 243±25 Spectralis HRA OCT 289±16 RTvue ±28 Severe cystoid macular edema cystoid spaces Serous macular detachment any of the above, associated with serous macular detachment Retinal topography ETDRS and evaluated on the OCT retinal topography map. Presence and severity of macular traction (incomplete PVD and/or ERM) 1. No macular traction presence of complete PVD (Weiss ring detected on ophthalmoscopy), or no PVD (no visible posterior hyaloid line on SD OCT), and no ERM; 2. Questionable macular traction incomplete PVD with perifoveal or peripapillary adhesion and/or globally adherent ERM without detectable distortion of retinal surface contour at the points of adhesion; perifoveal adhesion and/or focal ERM with detectable distortion of retinal contour at the points of adhesion. Retinal outer layers integrity (IS/OS and ELM) 1. IS/OS and ELM intact; 2. IS/OS and ELM with disrupted integrity. 46 l DOS Times - Vol. 20, No. 3 September, 2014

Uvea Figure 9: Cystic changes in the OPL correspond to few micro aneurysms on the early

effective. laser or drugs and need posterior vitrectomy.

vascular leakage qualitatively in macular edema, OCT can offer highresolution

5 Uvea Figure 9: Cystic changes in the OPL correspond to few micro aneurysms on the early phase frame Figure 10: needed to reduce the thickness before any laser treatment would be effective. laser or drugs and need posterior vitrectomy. to remove the traction, take away the scaffold for present in vitreous and improve the oxygenation of retina. Comparison Between OCT and Flourescein Angiography Although FA has been used to assess vascular leakage qualitatively in macular edema, OCT can offer highresolution cross-sectional images of the retina and quantitative measurement of the retinal thickness. angiography, and the anatomical features of clinically thickening and the retinal layer involved can be assessed www. dosonline.org l 47

Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography Figure 11: Figure 12: with OCT.

Furthermore, FA is an invasive test, with side effects ranging from nausea in up to 20% of cases to its rare complications of anaphylaxis and death.

OCT is non-invasive, comfortable, safe and fast and can be repeated as often as is required and offers an alternative to the FA in follow-up of

However, FA is still essential for the assessment of foveal perfusion state which can not be demonstrated with OCT.

6 Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography Figure 11: Figure 12: with OCT. FA is known to be a sensitive method for the edema, however, actual macular thickening is better correlated with loss of visual acuity. Furthermore, FA is an invasive test, with side effects ranging from nausea in up to 20% of cases to its rare complications of anaphylaxis and death. The information it provides is qualitative and the interpretation of the results may be subjective. OCT is non-invasive, comfortable, safe and fast and can be repeated as often as is required and offers an alternative to the FA in follow-up of changes in retinal thickness after laser photocoagulation and intravitreal steroid injections. However, FA is still essential for the assessment of foveal perfusion state which can not be demonstrated with OCT. Considering the appearance of new therapeutic modalities such as intravitreal corticosteroid injection or vitrectomy to make correlations between them. Several studies have been conducted to achieve the same and their observations are as follows 9 (Figures 9-14): Henle s layer in OCT. 48 l DOS Times - Vol. 20, No. 3 September, 2014

Uvea Figure 13: Figure 14: The late-phase FA (A): pattern in the foveal area (small circle) and honeycomb pattern in

shown to correspond to cystoid macular edema on OCT. corresponded to a petaloid appearance in the foveal region in FA.

outer nuclear, inner nuclear and even ganglion cell layers, they begin in outer layers.

As the severity of edema and number of cysts in the outer nuclear layer increases. detachment occurs on FA.

7 Uvea Figure 13: Figure 14: The late-phase FA (A): pattern in the foveal area (small circle) and honeycomb pattern in the perifoveal area (B, C): show that the mostly sponge like swelling appearance of DME on OCT. shown to correspond to cystoid macular edema on OCT. corresponded to a petaloid appearance in the foveal region in FA. honeycomb cystoid appearance in perifoveal region on FA. outer nuclear, inner nuclear and even ganglion cell layers, they begin in outer layers. cystic or edematous changes are more likely to expand toward the outer nuclear layer. As the severity of edema and number of cysts in the outer nuclear layer increases. detachment occurs on FA. detachment and their location anterior to these neurosensory detachments may prevent us from seeing them in FA. very early intraretinal morphological changes in DME when leakage occurs, which do not show a change in intra retinal morphology in OCT. By contrast, OCT www. dosonline.org l 49

Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography seems to be superior to FA in detecting more advanced stages of DME, especially foveal serous detachment.

pass through the external limiting membrane and therefore does not cause a build-up of proteins.thus there is no thickening or changes in intra retinal morphology in OCT.

8 Uvea: OCT in Diabetic Macular Edema and its Correlation with Flourescein Angiography seems to be superior to FA in detecting more advanced stages of DME, especially foveal serous detachment. morphological abnormalities in OCT, although some focal leaking points are evident in FA has been explained as modest damage to the inner blood retinal barrier, which allows only small molecules to pass through the external limiting membrane and therefore does not cause a build-up of proteins.thus there is no thickening or changes in intra retinal morphology in OCT. Another explanation for this is that the active retinal pigment epithelium may remove excess not cause thickening of the retinal layers. thickening on OCT which was not detectable clinically or angiographically. corresponds to areas of capillary non perfusion on FA. But this can also be seen in retinas with cicatricial areas distinguish between these 2, the photoreceptor layer s to be preserved in SDOCT images with capillary non perfusion, whereas this line is typically lost in areas of Thus, a judicious use of FA and OCT combined can be highly useful in deciding the appropriate management of diabetic macular edema and its follow up. References 1. L.P. Aiello, T.W. Gardner, G.L. King, G. Blankenship, J.D. Cavallerano, F.L.I.I.I. Ferris, R. Klein, Diabetic retinopathy. Technical review. Diabetes Care 1998;21: Early Treatment Diabetic Retinopathy Study Research Group. ETDRS Report No.1: Phtocoagulation for diabetic macular edema. Arch Ophthalmol 1985;103: Wolf-Schnurrbusch U, Ceklic L, Brinkmann CK, Iliev M, et al. Macular Thickness measurements in healthy eyes using six different optical coherence tomography instruments. Invest. Ophthalmol. Vis. Sci. 2009;7: Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol 1999;6: angiographic and optical coherence tomographic features in 2004;2: Kim BY, Smith SD, Kaiser PK. Optical coherence tomographic patterns of diabetic macular edema. Am J Ophthalmol 2006;3: diabetic macular edema, in Diabetic Retinopathy, M. S. Ola, Ed., InTech, Vienna, Austria, D.The diagnostic Function of OCT in Diabetic Maculopathy. 9. Yeung L, Lima VC, Garcia P, Landa G, et al. Correlation between Ophthalmology. 2009;6: Reputed, well furnished and Running Kawatra eye hospital situated at a prime location (Near Bus Stand) in Hisar (Haryana) is available for independent practice. An experienced ophthalmologist preferred Terms & Conditions Negotiable details at: ashakawatra@gmail.com , (Dr. Asha Kawatra) (Dr. Narinder Taneja) 50 l DOS Times - Vol. 20, No. 3 September, 2014

OCT Assessment of the Vitreoretinal Relationship in CSME

December 2007 Sonia Rani John et al. - IFIS 375 ORIGINAL ARTICLE OCT Assessment of the Vitreoretinal Relationship in CSME Dr. Manoj S. DNB FRCS, Dr. Unnikrishnan Nair MS DO FRCS, Dr. Gargi Sathish MS Introduction