SS-OCTA in RAP Lesions
SS-OCT is extremely effective for monitoring flow reduction following intravitreal anti-VEGF treatment of RAP lesions.
Retinal angiomatous proliferation (RAP) or type 3 neovascularization, is a subtype of age-related macular degeneration (AMD) characterized by intraretinal new vessels that can penetrate in the subretinal space and then eventually grow into the subretinal pigment epithelium (RPE) space. Currently, multimodal imaging, including fluorescein angiography (FA), indocyanine green angiography (ICGA), and cross-sectional optical coherence tomography (OCT) offer well-defined clinical findings for the diagnosis of RAP lesions.
Until recently, ICGA was considered the gold standard diagnostic method for this condition. Swept source-OCT (SS-OCT), however, is growing in use because it allows for accurate analysis of the choroid due to the use of a longer wavelength in comparison to that which is used in spectral-domain (SD) OCT. This is especially important in RAP lesions, in which the choroid is thinner compared with other AMD subtypes. In addition, the typical RAP findings consisting of RPE detachment, intraretinal cysts, drusen, and hyperreflective dots can be easily identified with SS-OCT.
In addition to being a useful tool for RAP diagnosis, SS-OCT is extremely effective for monitoring flow reduction following intravitreal anti-VEGF treatment of RAP lesions. SS-OCT provides a significant improvement over conventional OCT due to its long wavelength scanning light (1050 nm) and because of its superior penetration of the deeper layers of the eye. In clinical use, I also find SS-OCT’s En Face imaging modality to be ideal for observing RAP associated cysts. En Face imaging allows for independent dissection of the vitreoretinal interface, retina, RPE, and choroid. It also uniquely projects these layers so that macular pathology throughout the posterior pole can be studied and correlated with a patient’s symptoms, their abnormality, and their progression. I find that En Face technology is easy to use and helpful on a daily basis to clearly visualize segmentations of these diseased vessels.
OCT angiography (OCTA) is also quite effective in our efforts to diagnose and monitor RAP with its capability to demonstrate flow when these lesions are in the early stages of growth. Moreover, OCTA is valuable for its ability to quantify flow reduction following intravitreal therapy. These findings are more apparent in the deep retinal plexus of the OCTA. On the other hand, in some cases neovascularization is clearly shown in the outer retina of the OCTA. Likewise, a reduction in the lesion area can be monitored with OCTA following intravitreal therapy.
RAP lesions typically evolve through three clinical vasogenic stages, as described by Yannuzzi and colleagues.1 In stage 1, intraretinal neovascularization (IRN) involves proliferation of intraretinal capillaries originating from the deep retinal complex; this is associated with some moderate staining or leakage but is not very significant on FA. In stage 2, subretinal neovascularization (SRN) involves growth of the retinal vessels into the subretinal space. This is the stage when these lesions are diagnosed as pigmented epithelial detachment and cystoid macular edema. Stage 3 occurs when CNV can clearly be determined clinically or angiographically.
In many cases, RAP is not distinguishable from other retinal conditions. In the CATT trial investigators observed that more than 10% of the study cohort were diagnosed as having RAP lesions in a study comparing visual acuity and morphologic outcomes in eyes of patients with neovascular age-related macular degeneration (NVAMD) treated with anti-VEGF therapy.2
RAP lesions are different from ordinary wet AMD in that they tend to have less macular fluid, less leakage on FA and less scarring. They are, however, more likely to develop geographic atrophy. In polipoidal lesions, the choroid is very thick in comparison to RAP lesions where the choroid is typically thinner. OCTA, as well as En Face technology, can be used effectively in these cases to observe patchy vessel atrophy to aid in precise diagnosis, treatment, and monitoring. I find that En Face technology is easy to use and helpful on a daily basis to clearly visualize segmentations of these diseased vessels.
RAP Imaging Developments
As imaging technology improvements develop, new suggestions and recommendations regarding the most effective way to diagnose RAP are emerging as well. For instance, Kim and colleagues propose that RAP can be diagnosed without the assistance of ICG angiography. They say that if at least three of the following five features are present, a diagnosis of RAP can be made: sub-foveal choroidal thickness less than 200 microns; presence of intraretinal fluid; absence of subretinal fluid; a gently sloping dome-shaped RPE detachment or trapezoid-shaped RPE detachment without an obvious peak; and intra-retinal mass lesion.3
Ravera and colleagues have proposed a multi-imaging approach to diagnosing these lesions.4 Their retrospective study utilized FA, ICGA, spectral domain OCT, and infrared confocal scanning laser ophthalmoscopy (IRcSLO) imaging to evaluate markers for RAP. These included the presence of shunting of blood flow, the presence of light leakage on ICG angiography, and with the spectral domain OCT, the presence of intraretinal cysts, and RPE interruption or a break in the RPE on reticular pseudodrusen with infrared autofluorescence and spectral domain OCT. They concluded that all the signs investigated were strongly associated with RAP lesions. A multimodal imaging approach may help differentiate subtypes of neovascularization.
In addition to new diagnosis methods and criteria, a new classification system for type 3 neovascularization has been proposed.5 Investigators retrospectively analyzed 34 eyes with new-onset type 3 neovascularization using SD-OCT. The new classification defines the following three stages of type 3 neovascularization. Stage 1 consists of a larger intra-retinal hyper-reflective lesion associated with CME, but without outer retinal disruption; stage 2 comprises outer retinal disruption that occurs with RPE disruption in most of the cases; and stage 3 is defined by an intra-retinal hyper-reflective lesion that extends through the RPE to vascularize a drusenoid pigment epithelial detachment creating a serous component of the pigment epithelial detachment.
We, too, are performing our own studies aimed at gathering additional information regarding imaging and diagnosis of type 3 neovascularization – RAP – including our current trial, which is open and enrolling patients. We have enrolled 33 eyes from 26 patients diagnosed as having RAP lesions so far. We have more female than male participants, which is not surprising because this disease predominantly affects women. The mean age of participants is 79; this condition affects more elderly people than other subtypes of wet AMD. All participants were imaged with fundus photography, SS-OCT, En face, and OCTA. All of this multimodal technology is available in a single device – Triton (Topcon).
Imaging from selected cases of these 33 eyes illustrates Triton’s wide range of options and their value in the diagnosis and treatment of RAP. For instance, this 76-year-old male patient presented with 20/200 visual acuity, and an intra-retinal mass was clearly imaged with OCTA, En Face, and SS-OCT. En face presented a perfect map of the intra-retinal cyst and its evolution over time. The patient received three injections of Aflibercept, and we saw a clear reduction in the intra-retinal mass (Figure).
As we continue to enroll patients in this study, we expect our findings to reflect what we have seen anecdotally. SS-OCT is helpful in the diagnosis of RAP lesions; OCTA is an effective aid in monitoring flow reduction following anti-VEGF therapy in RAP lesions; and En Face is excellent for monitoring intra-retinal cyst reduction, among other things.
1. Yannuzzi LA1, Negrão S, Lida T, et al, Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416-434.
2. Daniel E, Shaffer J, Ying GS, et al, Outcomes in eyes with retinal angiomatous proliferation in the comparison of Age-related macular degeneration treatments trials (CATT). Ophthalmology. 2016;123(3):609-616.
3. Kim, JH; Chang, YS, Kim, JW, et al. Diagnosis of type 3 neovascularization base on optical coherance tomography images. Retina. 2016;36(8):1506-1515.
4. Ravera V, Bottoni F, Giani A, et al. Retinal angiomatous proliferation diagnosis; a multiimaging Approach. Retina. 2016;36(12):2274–2281.
5. Su D, Lin S, Phasukkijwatana N, et al. An Updateed Staging System of Type 3 Neovascularization using Spectral Domain Coherence Tomography. Retina. 2016;36:S40-S49.
Luis Arias Barquet, MD
• head of retina department, Bellvitge University Hospital, Barcelona
• financial disclosures: Alcon; Alimera; Allergan; Bayer; and Novartis (advisory boards)