The choroid is a highly dynamic structure that not only supplies oxygen to the outer retina, but also adjusts the eye’s refractive state and plays a pivotal role in the development of many ocular diseases.1 However, visualisation of the choroid is challenging because the overlying pigmented layers of the retina obscure all but the large choroidal vessels on slit lamp examination.
Better visualisation of the choroid, particularly in disease states such as polypoidal choroidal vasculopathy, became possible in the late 1980s and early 1990s with improvements in indocyanine green angiography (ICGA).2 Despite this, conventional angiography is invasive and cannot be repeated frequently to assess longitudinal changes. Furthermore, there is limited scope for studying features within individual choroidal sub-layers, i.e., the choriocapillaris, Sattler’s and Haller’s layers, using conventional angiography.
Going deeper with OCT
Recent advances in spectral-domain optical coherence tomography (SD-OCT) technology have enabled non-invasive evaluation of the cross-sectional structure of the choroid, which we now know is a key feature in many chorioretinal diseases. Reliable and convenient cross-sectional imaging of the choroid has become possible with the advent of enhanced depth imaging (EDI) OCT.3 Using the Heidelberg Spectralis OCT instrument, Spaide and colleagues described a method to obtain high resolution images of the choroid and choroid-sclera interface.4, 5
These initial studies showed dramatic differences in choroidal thickness between normal eyes and disease states such as central serous chorioretinopathy (CSCR), and high myopia. Subsequent studies further established that age is a significant factor that can influence choroidal thickness – there is a 30% decrease in choroidal thickness from age 20 years to the age of 80.6 Thin choroid may also be seen in age-related macular degeneration (AMD), particularly in patients with reticular pseudodrusen and type 3 neovascularisation.
In addition to evaluating thickness of the choroid, more recent studies have attempted to evaluate morphological features within the sub-layers of the choroid based on EDI-OCT. Some investigators have described methods to quantify the ‘vascularity’ of the choroid by evaluating the ratio between its luminal and stromal components using binarised EDI-OCT images.
More recently, pathologically dilated outer choroidal vessels (pachyvessels) have been the focus of studies that suggest a role in the attenuation and thinning of the choriocapillaris. Indeed, this ‘pachychoroid’ phenotype may play an important etiologic role in several conditions, including CSCR and polypoidal choroidal vasculopathy (PCV).
AMD and thin choroid
Histological studies show a loss of choriocapillaris density in both early and late AMD, suggesting that choroidal ischaemia may play a significant role in the pathogenesis of AMD. Using EDI-OCT, a wide range of choroidal thicknesses has been reported in exudative AMD.7
Thin choroid has been consistently associated with type 3 neovascularisation.8, 9 EDI-OCT has also demonstrated that eyes with exudative AMD have reduced choroidal vessel lumen size and vascularity compared with their fellow eyes. In addition, in eyes receiving anti-vascular endothelial growth factor (VEGF) therapy for exudative AMD, a reduction in choroidal thickness has been observed.
Thinner subfoveal choroid at baseline is also associated with a higher incidence of macular atrophy.10 However, no cause-and-effect relationship between anti-VEGF therapy and macular atrophy has been established. Choroidal thinning involving all vascular sublayers occurs in eyes with geographic atrophy.11
Polypoidal choroidal vasculopathy and thick choroid
PCV is considered by many as a subtype of AMD and is characterised by aneurysmal dilatations at the termini of a branching vascular network (BVN). The characteristic features including ‘polyps’ and branching vascular networks are best seen on ICGA.
SD-OCT studies have now clarified that the BVN is typically located in a plane between the retinal pigment epithelium (RPE) and Bruch’s membrane, similar to type 1 neovascularisation. This can be seen as the “double layer” sign. Additionally, a peak-like elevation of the RPE and notched PEDs are also suggestive signs of PCV and are useful for screening purposes, especially if ICGA is not routinely performed.12, 13
There is great interest in choroidal changes in PCV. Early work using EDI-OCT imaging for PCV eyes revealed a substantially thicker choroid than normal eyes.14, 15 However, significant inter-individual variability exists, with choroidal thickness ranging from 40 to >600 μm having been reported.
Subsequently, a bimodal distribution with peaks at 170 μm and 390 μm was reported.16 However, regardless of choroidal thickness, abnormally dilated Haller’s layer choroidal vessels (pachyvessels) were observed in the majority of cases. In these areas, there is evidence from OCT that suggests attenuation of the inner choroid overlying these pachyvessels.16
Reduction in choroidal thickness after anti-VEGF therapy has also been observed in eyes with PCV. Some investigators have attempted to further examine the longitudinal changes in the detailed sub-components of the choroid using image binarisation to understand the mechanism of action of various therapies.
One study reported that in the inner choroid, the reduction was most marked in the stroma, whereas in the outer choroid, the reduction was greatest in the luminal area.17 Another study based on binarised EDI-OCT reported that reduction in choroidal luminal area was more prominent in eyes with high baseline vascularity, whereas reduction in stromal area was more marked in eyes with lower baseline vascularity.18 These studies suggest a degree of choroidal remodelling may result from therapies for AMD.
Central serous chorioretinopathy and thick choroid
CSCR typically presents as serous detachment of the neurosensory retina and is accompanied by one or more focal points of vascular leakage at the level of the retinal pigment epithelium. Conventional OCT imaging of the macula typically shows a well-defined area of serous detachment in acute CSCR, which may be accompanied by PED.
Following resolution, visual recovery is highly correlated with extent of disruption of the ellipsoid zone, which can be clearly evaluated using SD-OCT.19 The significance of the choroid in CSCR is clearly demonstrated by EDI-OCT findings of thickened choroid in eyes with CSCR, which may be up to 2–3 times thicker than in normal eyes.5, 14, 20, 21
Elevated choroidal hydrostatic pressure in these eyes may render them susceptible to vascular leakage,5 leading to the serous detachments typical of CSCR. Increased choroidal vascularity has also been demonstrated using binarised EDI-OCT.
In addition to luminal dilation in the outer choroid vessels, increased hyperreflectivity in the inner choroid may represent inflammation and oedema of the choroidal stroma. Increased choroidal thickness and vascularity also occurs in the fellow eyes of patients with CSCR.
Most cases of CSCR show spontaneous resorption of subretinal fluid within 6–8 months, though treatment with focal laser or photodynamic therapy (PDT) may be used to treat patients with persistent fluid or the need for rapid return to normal vision (e.g., only-eyed patients, high visual requirements). However, while both thermal laser and PDT are effective in resolving subretinal fluid, choroidal thickness and choroidal hyperpermeability (seen on ICGA) are significantly reduced only following PDT.
Interestingly, using binarised EDI-OCT, the reduction in choroidal thickness following PDT may be attributed to decreases in exudative changes of the inner choroidal stroma and reduced dilation of the outer choroidal vessels.22 It is likely that these hitherto unknown choroidal changes are central to the pathogenesis of CSCR.
The use of OCT instruments to image the posterior segment has become almost ubiquitous, and now it is convenient for practitioners to image not only the retina, but also the choroid with a high level of reproducibility and detail. The benefits of this method in disease diagnosis, prognosis and research are now becoming apparent, especially in the area of age-related retinal degenerative diseases.
New insights gained by this method have begun to improve our understanding of common retinal diseases like AMD and PCV, and we anticipate it will continue to shape developments in therapy during the coming years.
Dr Beau J Fenner, MD, PhD
E: [email protected]
Dr Beau J Fenner is a resident at the Singapore National Eye Centre. He has no interests to declare.
Dr Gemmy CM Cheung, MBBS, FRCOphth
E: [email protected]
Dr Cheung is currently deputy head and senior consultant of the medial retina service, Singapore National Eye Centre. Her research interests include the study of risk factors and clinical features of macular diseases which may be unique in Asian populations. Dr Cheung has published over 150 articles, mostly in age-related macular degeneration, including polypoidal choroidal vasculopathy. She has conducted several clinical trials in anti-vascular endothelial growth factor therapies. Dr. Cheung is a consultant for Topcon, Zeiss, Novartis, Bayer, Allergan, Roche, Boehringer Ingelheim and Samsung.
1. Nickla DL and Wallman J. The multifunctional choroid. Prog Retin Eye Res. 2010;29:144-168.
2. Owens SL. Indocyanine green angiography. Br J Ophthalmol. 1996; 80:263-266.
3. Spaide RF, Koizumi H and Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146:496-500.
4. Fujiwara T, et al. Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes. Am J Ophthalmol. 2009;148:445-450.
5. Imamura Y, et al. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009;29:1469-1473.
6. Margolis R and Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol. 2009;147:811-815.
7. Yiu G, et al. Relationship of central choroidal thickness with age-related macular degeneration status. Am J Ophthalmol. 2015;159:617-626.
8. Yamazaki T, et al. Subfoveal choroidal thickness in retinal angiomatous proliferation. Retina. 2014;34:1316-1322.
9. Tsai ASH, et al. Retinal angiomatous proliferation. Surv Ophthalmol. 2017;62:462-492.
10. Fan W, et al. Subfoveal choroidal thickness predicts macular atrophy in age-related macular degeneration: results from the TREX-AMD trial. Graefes Arch Clin Exp Ophthalmol. 2018;256:511-518.
11. Adhi M, et al. Analysis of the thickness and vascular layers of the choroid in eyes with geographic atrophy using spectral-domain optical coherence tomography. Retina. 2014;34:306-312.
12. Cheung CMG, et al. Polypoidal Choroidal Vasculopathy: Definition, Pathogenesis, Diagnosis, and Management. Ophthalmology. 2018.
13. Wong CW, et al. Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians. Prog Retin Eye Res. 2016;53:107-139.
14. Kim SW, et al. Comparison of choroidal thickness among patients with healthy eyes, early age-related maculopathy, neovascular age-related macular degeneration, central serous chorioretinopathy, and polypoidal choroidal vasculopathy. Retina. 2011;31:1904-1911.
15. Koizumi H, et al. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol. 2013;155:305-313 e301.
16. Lee WK, et al. Choroidal Morphology in Eyes with Polypoidal Choroidal Vasculopathy and Normal or Subnormal Subfoveal Choroidal Thickness. Retina. 2016; 36 Suppl 1:S73-S82.
17. Daizumoto E, et al. Changes of choroidal structure after intravitreal aflibercept therapy for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2017;101:56-61.
18. Ting DSW, et al. Choroidal Remodeling in Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy: A 12-month Prospective Study. Sci Rep 2017; 7:7868.
19. Eandi CM, et al. Optical coherence tomography in unilateral resolved central serous chorioretinopathy. Retina. 2005;25:417-421.
20. Kuroda S, et al. Choroidal thickness in central serous chorioretinopathy. Retina. 2013;33:302-308.
21. Maruko I, et al. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology. 2010;117:1792-1799.
22. Kinoshita T, et al. Changes in Choroidal Structures in Eyes with Chronic Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy. PLoS One 2016; 11:e0163104.