1. A Comparison between Fluorescein Angiography and Optical Coherence Tomography Findings in Patients with Clinically Significant Macular Edema KoriAnne Elkins Galler, M.D. Resident’s Day May 30 th, 2008

2. Introduction Macular edema is the most common cause of decreased visual acuity and quality of life in diabetic patients Slit lamp biomicroscopy is the gold standard for diagnosis based on the ETDRS criteria Laser photocoagulation is the mainstay of treatment for CSME

3. Vascular leakage can be qualitatively measured with fluorescein angiography (FA) –Provides guidance for application of focal laser –Leakage can be present without clinical evidence of edema Optical coherence tomography (OCT) is a non-invasive way to calculate macular thickening and demonstrate retinal swelling Introduction

4. Several authors have established a correlation between FA leakage and abnormal macular thickness or retinal swelling on OCT However, these studies have several limitations –Timing of FA and OCT data –Inclusion of only horizontal and vertical meridians for comparison Introduction Otani T, Kishi S. Correlation between Optical Coherence Tomography and Fluorescein Angiography Findings in Diabetic Macular Edema. Ophthalmology 2007;114  Kang SW, Park CY, Ham DI: The correlation between fluorescein angiographic and optical coherence tomographic features in clinically significant diabetic macular edema. Am J Ophthalmol 2004;137:313–322. Özdek SC, Erdinç MA, Gürelik G, Aydın B, Bahçeci U, Hasanreisog B. Optical Coherence Tomographic Assessment of Diabetic Macular Edema: Comparison with Fluorescein Angiographic and Clinical Findings. Ophthalmologica 2005;219:86–92

5. OCT has the potential to improve clinic efficiency In some places, OCT is being used in placed of FA In order for OCT to supplant FA, it must be able to reliably detect leakage and provide valuable information for treatment and follow-up Introduction

6. Purpose To evaluate the correlation between fluorescein leakage and optical coherence tomography (OCT) abnormalities in diabetic patients with clinically significant macular edema (CSME) 1. When CSME is present on clinical examination, how often do both the FA and OCT show abnormalities? 2. How often does one imaging modality miss leakage when it is present on the other? 3. How often is the OCT thickness recorded as normal when FA leakage is present?

7. Methods Retrospective review of 74 eyes of 48 patients with a diagnosis of CSME All patients that had fluorescein angiography (FA) and OCT testing on the same day were reviewed

8. Methods Treatment-naïve and treated patients (laser, intravitreal injection, or vitrectomy) were included in this study

9. Methods Fluorescein angiograms were graded by a single physician in a masked fashion OCTs were read independently of the FAs by a second masked physician

10. Methods: Fluorescein Angiography For each eye, digitized early-phase and late-phase FA images were reviewed –Early: 1-2 minutes post-injection –Late: 5-10 minutes post-injection Images were overlain with a modified ETDRS grid and type of leakage recorded

11. Methods: Fluorescein Angiography

12. Grades of FA leakage FA Leakage Types Grade 1Normal Grade 2Focal Grade 3Mixed Focal & Diffuse Grade 4Diffuse Grade 5Cystoid Macular Edema

13. Methods: OCT Analysis OCT was performed on a Zeiss OCT3 –6.0-mm scans in 6 meridians (every 30 degrees) for each study eye A digitized grid was created for the radial OCT scans to correspond to the same areas as the ETDRS grid

14. Methods: OCT Analysis

15. Methods: OCT Types OCT Abnormality Types Type 1Swelling without cysts Type 2Swelling with cysts Type 3A Neurosensory detachment without VMT Type 3B Neurosensory detachment with VMT

16. Methods: Comparison of FA’s to OCT’s

17. Methods: OCT Map Analysis The standard macular thickness map was used to record the thickness in 9 standard subfields Values of > 250 microns for central foveal thickness and > 300 microns for other subfields were considered abnormal

18. Results: Baseline Characteristics NumberPercentage Men2347.9 Women2552.1 Age 58 (Range 39-75) DM I613.0 DM II4287.0 Treatment-naïve eyes 4664.8 74 eyes of 48 patients the study

19. Results: Patterns of Leakage Normal Focal Mixed Diffuse CME

20. 2. How often does one imaging modality miss leakage when it is present on the other? 3. How often is the OCT thickness recorded as normal when FA leakage is present?

21. FA/OCT Correlation OCT Abnormality Negative Positive FA Leakage Positive Negative 106 (16%)47 (7.1%) 233 (35%)280 (42%) Only 42% of zone-by-zone comparisons had both an abnormal FA and OCT 74 Eyes x 9 zones per eye = 666 zones

22. Results: Abnormal OCT’s by FA Grade Percentage of OCT Types FA Leakage Type NormalType 1Type 2Mixed 1 (Normal)69.311.114.45.2 2 (Focal)51.921.913.912.2 3 (Mixed)32.128.221.817.9 4 (Diffuse)41.713.929.814.6 5 (Cystic)020.040.0 Percentage of OCT Types FA Leakage Type NormalType 1Type 2Mixed 1 (Normal)69.311.114.45.2 2 (Focal)51.921.913.912.2 3 (Mixed)32.128.221.817.9 4 (Diffuse)41.713.929.814.6 5 (Cystic)020.040.0

23. Concordance of FA & OCT A total of 666 comparisons were made between FA and OCT zones –386 (58%) showed consistent findings –233 (35%) had an abnormal FA with a normal OCT in all 3 subscans –47 (7.1%) resulted in a normal FA with an abnormal OCT in at least one scan Cohen’s kappa of 0.1673 (poorly concordant)

24. 1. When CSME is present on clinical examination, how often do both the FA and OCT show abnormalities? 2. How often does one imaging modality miss leakage when it is present on the other?

25. Macular Thickness Correlation & Distribution FA Leakage Pattern Abnormal OCT Thickness Measurements Inner + outer zones (67 eyes)46 eyes (64.8 %) Inner zone only (2 eyes)1 eye (50%) Outer zone only (2 eyes)0 eyes (0 %) No leakage (0 eyes)0 eyes (0 %)

26. Discussion Of the 280 (42%) comparisons that resulted in a mis-match between FA and OCT –233 (35%) with abnormal FA and a normal OCT –Only 47 (7.1%) instances with a normal FA but some abnormality detected on the OCT Additionally, in 35% of patients OCT thickness measurements were normal despite FA leakage

27. This suggests that there is a large subset of patients that will have leakage detected on FA but no comparable OCT changes or increased macular thickness Discussion

28. Two possibilities to account for this difference –First, these patients may still have a relatively healthy retinal pigment epithelium Able to pump out the additional fluid without leading to retinal swelling or increased thickness –Secondly, these patients may have preexisting retinal thinning that creates a falsely normal OCT

29. Limitations Small number of Type 1 diabetics, results may not generalize Treated vs. untreated patients not controlled for and comparison between groups was not made

30. In Conclusion Fluorescein is still a useful clinical tool for assessment of leakage and guiding treatment Although OCT is a less invasive testing modality for detection of DME, up to 1/3 rd of patients with active leakage will be missed OCT not surrogate for clinical exam or FA and cannot be used as a guide for placement of laser photocoagulation

31. Acknowledgements Rohan J. Shah, M.D. Franco Recchia, M.D.