OCT in Age Related Macular Degeneration (ARMD) and Polypoidal Choroidal Vasculopathy (PCV)

Dr. Vishal Gowindhari, Dr. Jay Chhablani
Published Online: April 5th, 2020 | Read Time: 30 minutes, 59 seconds

Optical Coherence tomography (OCT) has revolutionized the way we look at retinal disorders. The earliest version of OCT was the time domain OCT following which spectral domain OCT arrived. Advances such as enhanced depth imaging and swept source OCT have furthered our understanding of retinal disorders. Beginning from the early 90s , OCT has vastly improved the way we diagnose, prognosticate , treat and follow-up retinal disorders.(1)

Why OCT?

OCT has established itself as one the main imaging modalities in retinal conditions or macular disorders to be more specific. OCT is the most précised method measuring retinal thickness in-vivo.(1) Let us take age related macular degeneration (ARMD) as an example. Understanding the location of the neovascular membrane and its consequences such as intra/subretinal fluid can be clearly understood with the help of an OCT.(2) Prognostic factors such as integrity of the outer retinal layer , RPE alterations such as thickening or fragmentation and the presence/type of pigment epithelial detachment (PED) are also well delineated by an OCT. (3) Some of the landmark trials such as PrONTO (prospective OCT imaging of patients with neovascular AMD treated with intraocular lucentis) have included OCT features as their retreatment criteria ( 3/5 retreatment criteria in the PRONTO were based on OCT )(4).

Our chapter aims to look at the OCT features of two important macular disorders- age related macular degeneration (ARMD) and polypoidal choroidal vasculopathy (PCV).

Age-related macular degeneration (ARMD)

Age-related macular degeneration is emerging as one of the leading causes of blindness in India. The INDEYE study reported the prevalence of early ARMD with respect to age and grade. Grade 1 (soft distinct drusen or pigment irregularities) had a prevalence of around 40%, grade 2 (soft distinct drusen with pigment irregularities or soft indistinct/reticular drusen) prevalence was around 6-8% and grade 3 (soft indistinct drusen/reticular drusen with pigment abnormalities) had a prevalence of 0.2-0.5%. The prevalence of late AMD which included choroidal neovascular membrane (CNVM) and geographic atrophy (GA) was 1.2%. (5) Other population based studies such at the Andhra Pradesh eye disease study (APEDS) and the Aravind comprehensive eye study (ACES) reported the prevalence of late AMD at 3.4% and 1.4% in 60-69 years age group and 3.7% and 2% in the 70+ age group respectively.(6,7)

The age-related eye disease study (AREDS)(8) classified ARMD into 4 stages-

Table 1 – AREDS classification of ARMD

No AMD – Category 1

No or few small (<63 microns) drusen

Early AMD – Category 2

Combination of multiple small and a few intermediate (63-124 microns) or RPE abnormalities

Intermediate AMD – Category 3

Any of the following:

  • Multiple intermediate drusen
  • At least 1 large druse (>/= 125 microns)
  • Geographic atrophy (GA) sparing center of the fovea

Advanced AMD – Category 4

One or more of the following in one eye:

  • GA involving the foveal center
  • Choroidal neovascular membrane (CNVM)
  • Serous or hemorrhagic detachment of the neurosensory retina/RPE
  • Retinal hard exudates
  • Subretinal and sub-RPE fibrovascular proliferation
  • Subretinal fibrosis – disciform scar

An alternate classification(9) proposed by the international ARM (age-related maculopathy) epidemiological study group included-

Table 2 – ARM classification

Early ARM

Soft drusen >/= 63 microns and RPE hyper/hypopigmentation

Late ARM

  • Dry AMD – Geographic atrophy
  • Neovascular AMD- RPE and neurosensory detachments, hemorrhages and scarring.

OCT features – Drusen

Age-related drusen are extracellular material deposited between the basement membrane of the retinal pigment epithelium (RPE) and in the inner collagenous zone of the bruch’s membrane. They must be contrasted from basal laminar deposits (best seen on light microscopy) which occur between the plasma membrane and the basement membrane of the RPE and are considered secretory products of the RPE and basal linear deposits which are membranous debris (best noted on electron microscopy) between the RPE basement membrane and inner collagenous zone of bruch’s .Basal linear deposits create a cleavage plane between the RPE and bruchs and hence predispose to formation of a CNVM.

Drusen can be clinically classified into

  • Small hard drusen
  • Soft drusen – which are subdivided into granular, membranous and fluid( serous) with drusenoid pigment epithelial detachment (PED) (fig 4)
  • Pseudosoft (clustered hard) drusen
  • Reticular or pseudodrusen (fig 5)
  • Regressing or fading drusen(10)

A study on SD –OCT has classified the OCT patterns of drusen into 3 types

  1. RPE excrescences overlying moderately reflective material – clinically soft drusen (fig 1)
  2. Saw-toothed configuration of RPE with multiple excrescences in series (bunching up of RPE )with underlying moderately reflective material- clinically soft and cuticular drusen (fig 2)
  3. Focal, nodular and discrete pattern with moderate to high reflective material – clinically hard drusen (fig 3)

Associated changes include compression and thinning of the outer retinal layers, pigment epithelial detachments , RPE clumping and migration.(11)

Fig 1 – Swept source OCT (SS-OCT) image depicting RPE excrescences(white arrow). Note the subtle variability in the reflectivity of the underlying material.

Fig 2 – SS-OCT image depicting saw-tooth appearance of the RPE with underlying cuticular drusen. The overlying photoreceptors show small areas of discontinuity (white arrow)

Fig 3- SS-OCT depicting high reflective focal, nodular druse with overlying hyperreflectivity suggestive of RPE migration (white arrow).

Fig 4- Large drusenoid PED with altered outer retinal integrity (thick white arrow) overlying the PED . Note the tiny hyporeflective spaces in the outer retinal layers which are degenerative pseudocysts (thin white arrow)

Fig 5- Horizontal OCT scan across the macula shows hyperreflective accumulation above the level of the RPE suggestive of reticular or pseudo-drusen (thick white arrow). Also seen is a cyst-like lesion with a hyprereflective wall and hyporeflective core signifying an outer retinal tubulation (ORT – thin white arrow). The fovea show atrophy of the RPE and outer retinal layers while the choroid is thinned out.

Spaide and group divided the extracellular deposits into soft drusen, cuticular drusen and subretinal drusenoid debris (reticular drusen). All these lesion are made of up primarily lipid (esterified and unesterified cholesterol) along with carbohydrates, zinc and proteins. The location,morphology and the optical filtering properties of each of these accumulations gives rise to a varied clinical and imaging presentations. (12)

OCT feature –Geographic atrophy

It is the dry form advanced ARMD which is defined as sharply delineated oval or round hypo/depigmented area in which the choroidal vessels are more visible compared to the surroundings with a minimum dimension of 175 micron. The Indian epidemiological studies have a divided opinion of the incidence of GA with the APEDS and ACES study reporting a higher incidence of GA at a younger age group. The INDEYE study reports a higher incidence of CNVM compared to GA among patients with advanced ARMD.(5–7) GA accounts for a significant vision loss among patients with ARMD especially with increasing age. Among the multimodal imaging modalities, fundus photography and autofluorescence are used to follow-up patients with GA with respect to increase in size of pre-existing lesions and occurrence of new areas of GA.

The OCT features of GA are quite characteristic. There is a well-demarcated area of loss of outer retinal layers starting from RPE – ellipsoid zone- interdigitation zone – external limiting membrane and the outer nuclear layer. This outer retinal loss leads to collapse of the inner retina and better visualization of the bruch’s membrane and the choriocapillaris.(13)

Fig 6 – Fundus photo (A) depicting well defined depigmented area involving the macula with prominent choroidal vessels. The corresponding autofluorescence (B) defines the lesion better and show a few small islands of RPE loss temporal to the lesion which are not well appreciated on fundus photography. The OCT (vertical scan- C) shows clear cut area (marked by white arrows) of outer retinal loss along with inner retinal collapse. Note the grossly thinned out choroid and the increased transmittance in the area of GA.

Some of the other features of non-exudative ARMD on SD-OCT include:

  1. Pseudocysts (fig 4&7)
  2. Outer retinal tabulations(fig 5)
  3. Acquired vitelliform lesion associated with large drusen
  4. Retinal pigment epithelial migration (fig 3&7)
  5. Small subretinal fluid (SRF)/space between large drusen (13)

Fig 7- Horizontal OCT scan of a patient with dry ARMD. Note the shallow RPE detachment secondary to drusen. The thin white arrows point at hyporeflective spaces in the outer nuclear layer which are suggestive of pseudocysts while the thick white arrow points at the hypereflective outer retinal lesion above the drusen suggestive of an RPE migration.

OCT feature – Wet ARMD

Wet ARMD is a one of the significant causes of vision loss with advancing age. The INDEYE study reported the prevalence of late AMD as 1.2% in people aged 60 year and above with an increasing trend with age. They further went on to state that wet AMD accounted for as high as 83% of the late AMD cases.

Wet ARMD has a wide gamut of clinical and SD-OCT presentations. The hallmark of wet ARMD is the presence of a CNVM which takes origin from the choriocapillaris, penetrated the bruch’s membrane and comes lie to below or above the RPE. Clinically the present as grey green dirty membrane below the retina (colour is due to the hyperplastic RPE), subretinal or intraretinal fluid/blood and RPE detachments which can be serous , hemorrhagic or fibrovascular. The less common presentations of a CNVM include massive subretinal hemorrhage, RPE rip and break through vitreous hemorrhage.(10)

The macular photocoagulation study classified CNVM into classic and occult based on findings on fluorescein angiography (FA). Classic CNVM typically presents as well-defined early choroidal hyperfluorescence which goes on to leak in the late phase whereas the occult CNVM presents as an ill-defined hyperfluorescence in the mid-phase of FA with late leakage or presents as a late leakage of indeterminate source. (14) Gass and group had then classified neovascular membranes into type 1 membranes which predominantly lie below the RPE and type 2 membranes which enter the subretinal space.(15) Indocyanine green angiography helped in better anatomical delineation of the CNVM and added a type 3 CNVM which is anatomically begins as an intraretinal neovascularisation.(16) Freund et al gave a more inclusive classification of CNVM which looked at features on multimodal imaging –

Table 3 - Classification of choroidal neovascular membrane in ARMD(17)

Type of CNVM




Response to anti-VEGF

Type 1(fig 8)

Occult CNVM

Low intensity hyperfluorescence

Fusiform serous or fibrovascular PED, SRF may be noted



Type 2(fig 9)

Classic CNVM

Difficult to delineate against background choroidal fluorescence

Lesion noted between the RPE and photoreceptors. Intraretinal and subretinal fluid noted

Complete response

Type 3- retinal angiomatous proliferation

(fig 10)

Ill defined hyperfluorescence with leakage depending on stage

Hot spot, retino-retinal and retino-choroidal anastamosis depending on stage

Intra /subretinal hypereflective lesion, intra/subretinal fluid, serous or fibrovascular PED- depends on stage

Sensitive in the early stages

Fig 8- FA image (A-late phase) ill defined leakage (thick white arrow) surrounded by multiple hyperfluorescent spots (due to surrounding drusen). The corresponding SD-OCT(B) shows a fusiform fibrovascular PED (thin white arrow) with overlying SRF(white star).

Fig 9- FA image (A-late venous ) shows a classic CNVM with typical well defined hyperfluorescence in the early stages of FA. Corresponding SD-OCT(B) shows a irregular hyperreflective lesion (thick white arrow) in the subretinal space with associated intraretinal (thin white arrow) and subretinal fluid(white star). Note the variable reflectivity of the subretinal lesion.

Fig 10 – ICG (A- early phase) shows a central hyperfluorescent structure denoting the abnormal retinal vessel vessel dipping down into the subretinal space. Note a hyperfluorescent structure at a deeper plane and a large surrounding hypoflorescent halo denoting the abonormal vascular network in the subretinal plane. The corresponding FA image (late phase- B) shows leakage from the retinal and subretinal vascular network. The vertical OCT scan shows intraretinal fluid (thick white arrow), subretinal fluid (white star) and hypreflectivity at the intraretinal (outer nuclear layer) and subretinal levels (thin white arrow). The above multiomodal imaging suggests a stage 2 retinal angiomatous proliferation .

Fig 11- SD-OCT image depicting RPE rip (white arrow denotes the location of the RPE rip) in case of wet ARMD. Note the location of the rip at the margin of the fibrovascular PED. The RPE rip occurred after a single intravitreal anti-VEGF injection in this case.

Fig 12- Right eye colour fundus photo (A) depicting a scarred CNVM with subretinal hemorrhage. SD-OCT (B) passing through the scar shows a hyperreflective subretinal well-defined fusiform lesion (thick white arrow) with associated areas of hyporeflectivity intra and subretinally (thin white arrows). Note the less hyperreflective subretinal lesion (white star) corresponding to subretinal heam temporal to the scar. FA showed staining in late phase with no leakage suggestive of no activity. The hyporeflective areas represent degeneration rather than activity in this case (as was proven by FA) and hence this highlights the importance of multimodal imaging in wet ARMD.

CNVMs are usually accompanied by some element of fibrous tissue. Fibrous tissue may be associated with (fibrovascular) or without (fibroglial) a CNVM and may be located above or below the RPE. A clinically evident fibrous tissue –CNVM complex is defined as a disciform scar. It represents end-stage disease. They are yellow-white in colour with variable pigmentation. They may be associated with recurrence of the neovascular tissue at the edge of the scar, variable degrees of lipid exudation and subretinal hemorrhage as well a retino-choroidal anastamosis. FA and SD-OCT are crucial in establishing the activity status of a disciform scar. (10,18,19)

OCT is a key diagnostic modality in cases of wet ARMD. It helps assess activity in wet ARMD and hence current day practice considers activity on OCT as benchmark for treatment. Activity is represented by well –circumscribed hyporeflective spaces in the inner retina, subretinally and in the sub-RPE space. (20) Traditionally FA has been used to assess CNVM activity, but the invasive nature and the lack of inter-observer agreement especially in differentiating leakage from staining in treated cases of wet ARMD have been the points against routine use of FA.(21) OCT in comparison is non-invasive, more objective and more quantitative compared to FA. OCT differentiates leakage on FA into intra and subretinal fluid.(22) These features also make OCT the investigation of choice with respect to therapeutic response. The PrONTO and CATT (comparison of age-related macular degeneration treatments trial) are two landmark trials which used OCT-based features to assess activity and decide on retreatment (and hence therapeutic response) with various anti-VEGF agents. Another advantage of SD-OCT in ARMD is the detection of structural changes on OCT which serve as prognostic factors in both forms of ARMD.(23)


Fig 13- The horizontal OCT scan above (A) represents a classic CNVM represented by a spindle shaped flat structure (thin white arrow) in the subretinal plane with overlying subretinal hyperreflective material (thick white arrow) and intraretinal edema(white star). After a single intravitreal anti-vegf injection, the OCT (B) shows resolution of the hyperreflective material as well as the intraretinal edema. The subretinal spindle shaped lesion is better defined and more hyperreflective (thin white arrow) suggesting scarring which was clinically correlated. Note the altered structure and reflectivity of the RPE under the spindle in both scans.

Polypoidal choroidal vasculopathy

Described by Yanuzzi et al in 1982 , polypoidal choroidal vasculopathy(PCV) is primarily a disorder of the choroidal vasculature characterized by the presence of dilated branching inner choroidal vessels and orange-red terminal aneurismal dilatations which were defined as “polyp-like”.(24) The disease in known to have a predilection to the pigmented races and asians. The age group of presentation is generally around the 6th and 7th decade. The disease in general has bilateral involvement though the presentation is asymmetrical.

PCV is considered to be a part of the AMD spectrum (type 1 CNVM) by some schools of thought while thickened choroid in PCV suggest a relationship with the pachychoroid spectrum by others. The prevalence of PCV in a study conducted in Beijing reports an incidence of around 0.3%.(25) More importantly 20-60% of patients with neovascular AMD turned out to have PCV based on ICG.(26)

Clinical features include the presence of orange-red nodules subretinally associated with subretinal fluid, submacular hemorrhage and serous or hemorrhagic PEDs. Sequelae of the disease include RPE atrophy and subretinal fibrosis. Indocyanine green angiography has been considered the gold standard for diagnosing PCV. Polyps appear as focal hyperfluorescent lesion located at a deeper plane surrounded by hypofluorescent halo. The branching vascular network (BVN) which is a relatively larger network of abnormal choroidal vessels and the fine vascular network (FVN) which are finer capillary-like abnormal vasculature which correspond to disease activity are best seen on ICG ( better on confocal scanning laser systems compared to fundus camera systems). (27) Fundus fluorescein angiography shows stippled hyperfluorescence (occult CNVM) pattern in general and rarely a classic CNVM (well-defined early hyperfluorescence) pattern can be noted.

Table 4 - EVEREST study criteria for diagnosis of PCV(28)

Focal hyperfluorescent lesions (polyps) on ICG appearing prior to 6 minutes + one of the following :

  1. BVN on ICG
  1. Pulsatility of polyps on dynamic ICG
  1. Nodular appearance on stereoscopic viewing of ICG
  1. Hypofluorescent halo on ICG
  1. Orange subretinal nodule on colour fundus photography
  1. Associated massive subretinal hemorrhage

OCT features of PCV

Fig 14 – SS-OCT show an M-shaped or notched PED (thick arrow) with an adjoining double layer sign (RPE hypereflective band seen separated from sub-RPE layer- thin arrow) and subretinal fluid. Note the hypereflective content of the PED.

Fig 15- Large serous PED with notching and underlying hyperereflectivity (arrow) noted at the nasal end of the PED.

Fig 16- ICG image (left) shows large PED (hypofluorescent) immediately temporal to disc with a some hyperfluorescence within the PED and a bunch of grapes (polyps-thin arrow) at the temporal end. Note the diffuse network of hyperfluorescence temporal to the PED. Horizontal OCT scan (left) shows a hemorrhagic PED (white star-note the backshadowing) corresponding to the PED on ICG temporal to disc with a hypereflective material in the roof. Also note a fibrovascular PED (thick arrow) and subretinal fluid suggesting an active PCV lesion.

Fig 17- Swept source OCT scan depicting a subtle split (white arrow) of the RPE from the underlying sub-RPE hypereflective band (considered to be the outer layer of the bruchs membrane). The double layer sign has been colocalised with the fine vascular network on ICG.

Fig 18 – Colour fundus photo (left) depicting sequelae of PCV in the form of subretinal fibrosis (arrow) and hard exudates (white star) with activity persisting as depicted by intraretinal fluid on OCT (right).

Like ARMD , some of the landmark trials in PCV ,which include the PLANET and EVEREST studies(28) , used OCT features of activity as a part of their rescue or retreatment criteria. The presence of subretinal fluid and/or intraretinal fluid is considered as a sign of active PCV and till date remains the standard for considering treatment in cases of PCV.(26)

Newer Horizons

  1. En Face Imaging

The en-face imaging technique gives us a horizontal view across a given layer of the retina or choroid at a given level. Making more accurate measurements, visualizing a diffuse pathology in one image and detection of microstrucutral changes are a few advantages of this mode of imaging. This mode of imaging has a wide spectrum of utility in ARMD and PCV. A review article by Lau et al enumerated them as follows:

  1. ARMD – a) Correlation of with multimodal imaging like FA and ICG

b) Integrity of the ellipsoid zone and its correlation to visual acuity

c) Imaging and characterization of pigment epithelial detachments

d) Quantification of drusen

e) Imaging choroidal vasculature including imaging of choriocapillaris and quantification of flow in choroidal neovascular membranes

  1. PCV- Detection and qualitative assessment of polyps along with their branching vascular networks. The use of high-penetration swept source OCT improved the detection rate of the above mentioned lesions.(29)

The non-invasive nature, depth –resolved imaging at a given level of the retina or choroid and wider view of a diffuse pathology in a single image are features which make en-face imaging an exciting tool in following-up and prognosticating cases of ARMD and PCV. The addition of newer variants like the en-face doppler OCT and en-face phase-variance OCT have greatly improved our understanding of the choroidal vascular changes in ARMD and PCV and hence contributed to better comprehension of the pathogenesis of these diseases.

  1. OCT angiography

This is a non-invasive novel modality which recreates en-face images of the vasculature or the lack of it at different levels starting from the inner retina and going as deep as the larger choroidal vessels. The basic principle of OCT angiography is motion contrast imaging. Repeated OCT scans are acquired at a given location and the variance of amplitude, phase or both which occur due to the movement of RBCs is reconstructed into vasculature at that given level using a decorrelation algorithm.(30)

Fluorescein and indocyanine green angiography are invasive, time-consuming and two dimensional investigative modalities. The dynamic nature of thethese angiograms can sometimes hinder accurate assessment of pathologies such as a diffuse leak on fluorescein angiogram obscuring the underlying neovascular membranes. The use of dye , though considered relatively safe, has its own set of relative and absolute contraindications. OCT angiography on the other hand is non-invasive, less time intensive and provides us with three dimensional volumetric angiographic imaging. This allows for better delineation of size and location of the lesion in question.(30)

OCT angiography does have a few drawbacks such a smaller field of view, poor resolution on increasing the field of view, presence of different types of artifacts such as motion artifacts, inability to pick up slow flow structures like microaneurysms and inability to assess dynamic phenomena like leakage. The use of newer softwares and better image acquisition techniques is helping us overcome a few of these drawbacks. (30)

Detecting areas of reduced choriocapillaris flow in cases of dry ARMD, locating and delineating neovascular networks in wet ARMD, recognition of branching vascular networks and their terminal polyps in PCV, response to anti-VEGF therapy of the above mentioned conditions and detecting recurrences at a very early stage are a few advantages of OCT angiography in ARMD and PCV. (31) (32)

  1. Adaptive Optics

This is an additive technology which enhances the imaging quality of various modalities one of which is the OCT. It works mainly by reducing the optical aberrations of a given system like the eye. Add this to imaging with a dilated pupil, thereby reducing the blurring effect due to diffraction, and one can achieve high levels of lateral resolution (2-3 microns). Such high lateral resolution in conjunction with the high axial resolution of OCT (<3 microns) gives rise tremendously resolved images and better understanding of pathology in the eye .

Adaptive optics, apart from increasing lateral resolution, reduces the speckle size (granularity) in the OCT images which are noticed on magnifying the regular OCT images and increases the sensitivity weaker reflection from retinal structures. Imaging of the photoreceptor mosaic in disease such as ARMD can help us quantify the damage and correlate visual structure and function in a more comprehensive manner.(33)

Dr. Vishal Gowindhari, Dr. Jay Chhablani
Jay Chhablani is a faculty-clinician at the University of Pittsburgh Eye Center. He completed clinical vitreo-retina fellowship from Sankara Nethralaya, Chennai, India. He was an International Council of Ophthalmology (ICO) fellow at Jules Gonin Eye Hospital, Switzerland, in 2009 and a Clinical Instructor at the Jacobs Retina Center at Shiley Eye Center, University of California, San Diego, USA (2010 to 2012) before he joined L V Prasad Eye Institute, Hyderabad, India as faculty (2012-19). His areas of interest are macular disorders and recent imaging techniques. He published more than 300 articles in peer-reviewed journals with specific emphasis in field of choroid. He is editor of books titles “Choroidal Disorders” and “Central Serous Chorioretinopathy”. He is on the reviewing boards of all high impact Ophthalmology journals. He is on the editorial board of several journals including American Journal of Ophthalmology. He is a member of Global ONE network committee of American Academy of Ophthalmology. He has won several national and international awards. He has delivered inaugural Ian Constable lecture at Asia-Pacific Vitreo-Retina Society in 2016. He received Inaugural Namperumalsamy Young Researcher Award in 2018 by Vitreo-Retina Society of India.
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