June 2014, Issue 70

Enhanced Depth Imaging of Spectral Domain
Optical Coherence Tomography in Age-Related
Macular Degeneration

Samuel Yun, MD Ophthalmology and Visual Science Yale School of Medicine New Haven, CT

Ron A. Adelman, MD, MPH, MBA Professor of Ophthalmology and Visual Science Director, Yale Retina Service Yale School of Medicine New Haven, CT

Optical coherence tomography (OCT) technology has been of tremendous value in evaluating patients with age-related macular degeneration (AMD). Spectral domain OCT (SD-OCT) utilizes light waves to create interference signals from the posterior pole; these signals then undergo Fourier transformation to create a high resolution retinal image. With the added technology of confocal scanning laser ophthalmoscopy (cSLO), SD-OCT has enhanced ability to penetrate through dense media such as cataract. Images obtained using SD-OCT, however, fail to show choroidal structures in detail owing to the shadow cast by the retinal pigment epithelium (RPE). Since many retinal pathologies may be associated with choroidal pathology, a new technology has been developed to image the choroid without an invasive procedure such as indocyanine green (ICG) angiography.

Enhanced depth imaging OCT (EDI-OCT) is a relatively new technology developed to provide higher resolution images of the choroid. Currently, several machines, including the Heidelberg Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) and the Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA), may be used for EDI-OCT. EDI-OCT modifies the standard technique of SD-OCT, and moves the instrument closer to the eye to image deeper layers. When the instrument is moved closer to the eye, the retinal image is inverted (the choroid faces up and the inner retina faces down), and zero delay, which is the point of maximal focus in the interference signal, is focused on the choroid.¹

In 2009, Spaide studied pigment epithelial detachment (PED) in patients with AMD. Using EDI-OCT, the author was able to demonstrate choroidal neovascularization within PED, which was frequently seen as a hyperreflective tissue on the back surface of the RPE, contiguous with the choroidal neovascularization.²

There have been several studies looking at the reliability of EDI-OCT. Chhablani et al. studied the choroidal volume in 32 patients with and without choroidal pathology and showed high reproducibility of the choroidal volume measurements.³ Lee et al. studied automated measurement of subfoveal choroidal thickness in eyes with non-exudative AMD and compared the measurements taken by two observers; he reported high reproducibility of the automated measurements and the intra-observer measurements, but noted substantial differences in the inter-observer measurements.⁴ Kim et al. studied 40 eyes in each of the following groups: normal eyes, early AMD, exudative AMD, polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). The investigators compared the intra-observer and inter-observer measurement variability for each group, and reported greater intra- and inter-observer variability with pathologic conditions with increased choroidal thickness such as PCV and CSC.⁵

Choroidal thickness is defined as the distance between the outer border of the RPE and the inner scleral border. Margolis et al. reported a mean choroidal thickness of 287µm (the choroidal thickness is lower on both the nasal and temporal sides of the fovea) in 54 eyes of 30 individuals with no ocular disease.⁶

Data concerning the association between choroidal thickness and AMD is inconclusive. Several studies have reported the choroidal thickness in eyes with non-exudative AMD. In a series of 176 eyes of 114 patients with non-exudative AMD, Lee et al. found that a thinner subfoveal choroidal thickness is associated with a poorer best-corrected visual acuity and an increased rate of progression of geographic atrophy (GA).⁷ In addition, increased drusen load appears to be associated with a thinner choroid.^8,9 Sigler et al. studied eyes of normal (n=51) and early AMD (n=99) patients. They observed that eyes with early AMD and no GA had a thinner choroidal thickness compared to normal eyes, and that a single subfoveal choroidal thickness measurement is highly correlated with the mean macular choroidal thickness.¹⁰

The choroidal thickness in eyes with exudative AMD can be variable. Jirarattanasopa et al. and Koizumi et al. studied the relationship between AMD and PCV, and both groups of investigators concluded that the subfoveal choroidal thickness is increased in eyes with PCV compared to eyes with AMD.^11,12 In studying 24 eyes with typical exudative AMD and 20 eyes with retinal angiomatous proliferation (RAP), Kim et al. found a thinner choroidal thickness and a greater extent and density of drusen in eyes with RAP; based on these data, the investigators hypothesized that compromised choroidal perfusion may play a role in the development of RAP.¹³ Jonas et al. studied 204 eyes with nonexudative or exudative AMD and compared them to normal (non-AMD) eyes; the investigators found no significant association between choroidal thickness and the presence of AMD.¹⁴

Anti-VEGF therapy may be associated with decreased choroidal thickness. Although one study showed no effect of intravitreal ranibizumab on choroidal thickness in short follow-up (one month),¹⁵ Yamazaki et al. found a linear decrease in choroidal thickness after intravitreal ranibizumab therapy for neovascular AMD over one year of follow-up.¹⁶

In conclusion, EDI-OCT provides an exciting new technology to investigate choroidal pathology. There are conflicting data that suggest that thinner choroidal thickness may be associated with non-exudative AMD. The clinical implication of this technology is not yet certain.

References
1. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008 Oct;146:496-500.
2. Spaide RF. Enhanced depth imaging optical coherence tomography of retinal pigment epithelial detachment in age-related macular degeneration. Am J Ophthalmol. 2009 Apr;147:644-52.
3. Chhablani J, Barteselli G, Wang H, et al. Repeatability and reproducibility of manual choroidal volume measurements using enhanced depth imaging optical coherence tomography. Invest Ophthalmol Vis Sci. 2012 Apr 24;53:2274-80.
4. Lee S, Fallah N, Forooghian F, et al. Comparative analysis of repeatability of manual and automated choroidal thickness measurements in nonneovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013 Apr 23;54:2864-71.
5. Kim JH, Kang SW, Kim JR, Kim SJ. Variability of subfoveal choroidal thickness measurements in patients with age-related macular degeneration and central serous chorioretinopathy. Eye (Lond). 2013 Jul;27:809-15.
6. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol. 2009 May;147:811-5.
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9. Ko A, Cao S, Pakzad-Vaezi K, et al. Optical coherence tomography-based correlation between choroidal thickness and drusen load in dry age-related macular degeneration. Retina. 2013 May;33:1005-10.
10. Sigler EJ, Randolph JC. Comparison of macular choroidal thickness among patients older than age 65 with early atrophic age-related macular degeneration and normals. Invest Ophthalmol Vis Sci. 2013 Sep 19;54:6307-13.
11. Jirarattanasopa P, Ooto S, Nakata I, et al. Choroidal thickness, vascular hyperpermeability, and complement factor H in age-related macular degeneration and polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2012 Jun 14;53:3663-72.
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13. Kim JH, Kim JR, Kang SW, Kim SJ, Ha HS. Thinner choroid and greater drusen extent in retinal angiomatous proliferation than in typical exudative age-related macular degeneration. Am J Ophthalmol. 2013 Apr;155:743-9, 9 e1-2.
14. Jonas JB, Forster TM, Steinmetz P, Schlichtenbrede FC, Harder BC. Choroidal thickness in age-related macular degeneration. Retina.
15. Ellabban AA, Tsujikawa A, Ogino K, et al. Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization. Clin Ophthalmol. 2012;6:837-44.
16. Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S. Subfoveal choroidal thickness after ranibizumab therapy for neovascular age-related macular degeneration: 12-month results. Ophthalmology. 2012 Aug;119:1621-7.