What is the cause of this macular finding?
- Vitelliform deposits
Answer: b The cause of this macular finding is non-exudative choroidal neovascularisation.
A 52-year-old Asian male presented for an assessment of pigmentary changes at the left macula. He denied any visual or ocular symptoms and was in good general health. On examination, best-corrected visual acuities were 6/7.5-1 R and 6/7.5 L. Amsler grid was normal and contrast sensitivity was within the normal range at 1.68 log units R and L using the Mars test.
Anterior segment examination was unremarkable and intraocular pressures were within the normal range. Dilated fundus examination showed an unremarkable macula in the right eye and mottled hypopigmentation at the central and temporal macula in the left eye. Fundus autofluorescence imaging revealed corresponding stippled hypoautofluorescence at the left macula (Figure 1).
Optical coherence tomography (OCT) revealed a subfoveal irregular and shallow pigment epithelium detachment (PED). Subfoveal choroidal thickness measured 250µm. The underlying choroid showed large dilated vessels with compression of the overlying choriocapillaris. OCT angiography of the choroidal slab revealed a tangled network of increased flow signal suggestive of Type I choroidal neovascularisation (CNV).
Diagnosis: Pachychoroid neovasculopathy in the left eye
Figure 1: Case images from the patient’s left eye, which indicate hypopigmentary abnormalities at the macula (A). Autofluorescence imaging (B) reveal stippled hypoautofluorescent areas around the macula. En face OCT (C) show dilation of the large choroidal vessels (pachyvessels). OCT-B scans (D) reveal a double layer sign that corresponds to a tangled neovascular network located beneath the RPE in the choriocapillaris slab on OCT angiography (E).
The pachychoroid spectrum of diseases was first described in 2013 and was defined as a group of diseases unified by a thick choroid.1 Since then, the focus has shifted toward choroidal alterations including dilated choroidal vessels in Haller's layer (known as pachyvessels) with compression of the overlying choriocapillaris.2 On funduscopy, this often corresponds with reduced fundus tessellation.3 Several conditions reside within this spectrum including (among others), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSCR), polypoidal choroidal vasculopathy (PCV) and, as seen in our patient, pachychoroid neovasculopathy (PNV).2 These conditions are thought to result from the same choroidal morphological alterations but represent different clinical manifestations.2
PNV is a relatively new term described by Pang and Freund in 20153 and is thought to develop secondary to PPE or CSCR. The underlying pathogenesis of this condition is speculated to involve microtrauma to Bruch's membrane from the dysfunctional choroidal vessels.3 This eventually allows the growth of a choroidal neovascular membrane into the sub-RPE space. The presence of Type I choroidal neovascularisation that coincides with focal areas of dilated choroidal vessels is characteristic of PNV.3
CNV in this condition can be relatively slow growing compared to neovascular AMD and may not present with as many exudative signs such as intraretinal fluid that would usually signify the presence of neovascularisation. Instead, an important anatomical feature that can be seen on structural OCT imaging is a shallow irregular PED, also known as the double layer sign.4 This sign is characterised by two hyper-reflective bands where the upper band represents the RPE and the lower band represents Bruch's membrane.5 The material that resides between the two bands may represent neovascularisation.5, 6 PNV may be misdiagnosed as neovascular age related macular degeneration (AMD) but should be distinguished using other features including greater choroidal thickness and a younger age of onset.7 Although drusen can be an overlapping sign in both conditions, the drusen in PNV are often large, non-extensive and isolated in the posterior pole.89
Until further evidence evolves, cases of asymptomatic and non-exudative CNV should be monitored closely every 3-6 months as the lesions can grow over time and eventually become clinically active.10 In cases of intraretinal/subretinal exudation and active leakage, the current first line of treatment involves intravitreal anti-VEGF injections with a treat and extend regimen.11 Studies have suggested that PNV responds favourably to treatment and often require less injections compared to neovascular AMD.11 Another line of treatment includes photodynamic therapy which may be considered in persistent or recurrent cases.12
Although there were no signs of active exudation, given the presence of choroidal neovascularisation, this patient was referred to a retinal specialist.
What is known on this topic
· Pachychoroid disease is characterised by morphological choroidal alterations including increased choroidal thickness, dilated choroidal vessels and attenuation of the overlying choriocapillaris.2
· PNV presents with Type I CNV overlying areas of dilated choroidal vessels.3
· PNV can progress to polypoidal choroidal vasculopathy (also known as type 1 aneurysmal neovascularisation) with the development of polypoidal lesions.3
What this case highlights:
· The double layer sign is an anatomical feature on structural OCT imaging and should raise suspicion for Type I CNV even without active exudation.4
· Neovascularisation in PNV can be detected noninvasively using OCT angiography which shows a tangled vascular network with distinct margins residing between the RPE and Bruch’s membrane. 6
· PNV can masquerade as neovascular AMD but should always be suspected in cases of dilated choroidal vasculature and non-extensive drusen.7, 8
What evidence gaps remain
· The pathophysiology of PNV is not completely understood but the angiogenic factors involved may be different to neovascular AMD.12
· Further research into the natural history, appropriate methods/indications for treatment, as well as prognostic factors will be useful for managing these patients in the future.12
· The role of genetic and environmental factors e.g. predisposing lifestyle factors in this condition should be further explored.2, 13
1. Warrow DJ, Hoang QV, Freund KBJR. Pachychoroid pigment epitheliopathy. 2013;33(8):1659-72.
2. Cheung CMG, Lee WK, Koizumi H, Dansingani K, Lai TY, Freund KBJE. Pachychoroid disease. 2019;33(1):14-33.
3. Pang CE, Freund KBJR. Pachychoroid neovasculopathy. 2015;35(1):1-9.
4. Sheth J, Anantharaman G, Chandra S, Sivaprasad SJIjoo. ” Double-layer sign” on spectral domain optical coherence tomography in pachychoroid spectrum disease. 2018;66(12):1796.
5. Sato T, Kishi S, Watanabe G, Matsumoto H, Mukai RJR. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. 2007;27(5):589-94.
6. Dansingani KK, Balaratnasingam C, Klufas MA, Sarraf D, Freund KBJAjoo. Optical coherence tomography angiography of shallow irregular pigment epithelial detachments in pachychoroid spectrum disease. 2015;160(6):1243-54. e2.
7. Miyake M, Ooto S, Yamashiro K, Takahashi A, Yoshikawa M, Akagi-Kurashige Y, et al. Pachychoroid neovasculopathy and age-related macular degeneration. 2015;5(1):1-11.
8. Spaide RFJR. Disease expression in nonexudative age-related macular degeneration varies with choroidal thickness. 2018;38(4):708-16.
9. Lee J, Byeon SHJR. Prevalence and clinical characteristics of pachydrusen in polypoidal choroidal vasculopathy: multimodal image study. 2019;39(4):670-8.
10. Carnevali A, Capuano V, Sacconi R, Querques L, Marchese A, Rabiolo A, et al. OCT Angiography of treatment-naïve quiescent choroidal neovascularization in pachychoroid neovasculopathy. 2017;1(4):328-32.
11. Matsumoto H, Hiroe T, Morimoto M, Mimura K, Ito A, Akiyama HJJjoo. Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration. 2018;62(2):144-50.
12. Sartini F, Figus M, Casini G, Nardi M, Posarelli CJIO. Pachychoroid neovasculopathy: a type-1 choroidal neovascularization belonging to the pachychoroid spectrum—pathogenesis, imaging and available treatment options. 2020:1-13.
13. Yamashiro K, Hosoda Y, Miyake M, Ooto S, Tsujikawa AJJoCM. Characteristics of Pachychoroid Diseases and Age-Related Macular Degeneration: Multimodal Imaging and Genetic Backgrounds. 2020;9(7):2034.
Sophia Zhang, BOptom (Hons.),BSc
Staff Optometrist, Centre for Eye Health
Sophia graduated from the University of New South Wales with a Bachelor of Optometry (Hons) and Bachelor of Vision Science. During her undergraduate degree, she was the recipient of academic and clinical awards. She joined the Centre for Eye Health in 2017 to pursue her interests in ocular disease. She is currently involved in the clinical aspect of the Centre but also supervises the placement of final year optometry undergraduate students.
The author would like to acknowledge Dr Simon Chen (FRANZCO), Dr Angelica Ly (PhD) and Pauline Xu for reviewing the manuscript.
The Centre for Eye Health receives funding from Guide Dogs NSW/ACT.