Retinal angiomatous proliferation (RAP), also termed type 3 choroidal neovascularization (CNV), is a distinct neovascular lesion type in age-related macular degeneration (AMD) whose intraretinal pathologic characteristics differentiate it from type 1 and type 2 CNV.1,2 With improvement in imaging techniques, the incidence of RAP has been reported to be up to 34.2% among eyes with neovascular AMD.3 RAP has a very poor functional prognosis because it is more likely to develop geographic atrophy than other types of CNV.4,5 Based on the natural course of this form of neovascularization, patients with RAP are classified into three stages.1,6 Stage I involves proliferation of intraretinal neovascularization (IRN). The involved vessels extend beneath the neurosensory retina to become subretinal neovascularization (SRN), termed stage II, and eventually merge with the choroidal circulation proliferating beneath the retinal pigment epithelium to form a retinal-choroidal anastomosis (stage III). The distinct anatomic association introduces the possibility of different treatment strategies and visual prognosis during progression.1,7 To diagnose RAP precisely and to evaluate the efficacy of treatment, determining the composition of the lesion and its location in different stages is essential.
Multimodal imaging techniques, including fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT), are important tools for detecting and evaluating RAP in clinical practice.1,8–10 However, both FA and ICGA are invasive and cannot dissociate the different networks, whereas SD-OCT cannot discriminate vascular tissue from surrounding tissues. Hence, RAP lesions are delineated in a limited way by conventional multimodal approaches. Optical coherence tomography angiography (OCTA) noninvasively provides depth-resolved images of blood flow and structural changes in the retina and choroid at the same time, which is a significant improvement for monitoring the CNV and developing insights into pathogenesis.11–15 This technology may be particularly useful for studying detailed microvascular lesions of RAP in different stages.
Limited information is available regarding characterization of microvascular lesions in treatment-naïve patients with different stages of RAP. In 2015, Dansingani et al.16 first described flow within lesions by OCTA in two cases of RAP. Miere et al.17 reported a high-flow, tuft-shaped retinal proliferation in early type 3 neovascularization, and Kuehlewein et al.18 demonstrated that the intraretinal neovascular complexes communicated with the deep capillary. However, until now, no studies have characterized in detail microvascular lesions in different stages of RAP. Moreover, the origins of the vasogenic sequence in RAP lesions remains controversial.
The purpose of this study was to analyze abnormal microvascular lesions with stages from type 3 CNV secondary to AMD using OCTA. Further, we evaluated the association of OCTA features with findings from conventional angiography and SD-OCT.
Patients and Methods
This prospective study recruited patients with RAP from the Affiliated Eye Hospital of Wenzhou Medical University from January 2016 to January 2018. This project was approved by the Ethics Committee of the Wenzhou Medical University and was performed in accordance with the tenets of the Declaration of Helsinki. Informed consent was obtained from the patients and subjects after explanation of the nature and possible consequences of the study.
All patients underwent a thorough ocular examination, including slit-lamp examination, intraocular pressure by Goldman applanation tonometry, measurement of best-corrected visual acuity (BCVA) with a Snellen chart, fundus photography, FA, ICGA, and SD-OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). Diagnosis of RAP and grading of the disease stage were made as described in the literature1,6,9,10: a focal area of intense intraretinal hyperfluorescence (termed hot spot) in the FA or ICGA, along with one or more of the following signs: focal intraretinal superficial hemorrhage; lipid, serous, or fibrovascular pigment epithelial detachment (PED), and retinal vascular abnormality, such as an anastomosis between retinal vessels or between retinal and choroidal vessels or retinal vessels with the underlying CNV complex. Two trained physicians (JM and DC) joined to identify RAP, and discrepant results were arbitrated by a senior ophthalmologist (LS).
Exclusion criteria were eyes with type 1 or type 2 CNV, pathologic myopia, infectious or inflammatory chorioretinal disease, tumors, hereditary disorders or trauma, macular telangiectasia, diabetic retinopathy, other marked complications, and any previous treatment without baseline OCTA, such as laser photocoagulation, photodynamic therapy, intravitreal injections, or intraocular surgery. We excluded microaneurysms from diabetic disease (no history of diabetic disease or high levels of blood sugar; no microaneurysm in the periphery area), macular telangiectasia (no change in focal retinal vascular density, no distinct lesion in temporal retina, no degenerative changes in OCT), or perifoveal exudative vascular anomalous complex with progression and active response to anti-VEGF therapy. Patients with poor OCTA images having significant defects (motion artifacts, projection artifacts, vessel doubling, stretching defects, and signal strength index less than 40) were also excluded.19
Patients also underwent OCTA imaging using RTVue-XR Avanti (Optovue, Fremont, CA), a 70-kHz SD-OCT system with a center wavelength of 840 nm. Orthogonal registration and merging of two consecutive scans were used to obtain OCTA volume scans of a central 3 mm × 3 mm area. Split-spectrum amplitude decorrelation technology was used to improve the signal-to-noise ratio by splitting the spectrum to generate multiple repeat OCT frames from two original repeat OCT frames.11 Automated layer segmentation boundaries were adjusted to best visualize microvascular abnormalities on the enface projection angiography images. When involving multiple retinal layers, we applied contract mode to create composite enface angiograms of the inner retina and neovascular membrane; the inner retina angiogram was overlaid on the expert-graded contoured CNV.
Twelve eyes of 12 patients were included in the current study. Of the 12 patients, eight (67%) were male. The mean age of the patients was 66.08 years ± 7.23 years (range: 57 years to 82 years) (Table 1). Two (17%) eyes were treatment-naïve, 10 (83%) eyes had at least one anti-VEGF injection (mean: 1.75 ± 1.06 injections). Of all 12 eyes diagnosed with RAP, six and four eyes (50% and 33%, respectively) were in stage I and stage II, respectively, and the remaining two eyes (17%) were in stage III. Four patients had multiple and variable hot spot lesions (Figure 1), which were located on the outer retina layer, deep layer, or superior retinal layer. Of note, some superior hot spot lesions were fed by surrounding vessels (supraretinal layer), whereas some emerged from the deep vascular network and then went upward. OCTA showed a clearer location and relationship with the feeder vessels than FA or ICGA. Meanwhile, moderate or severe PED was detected in all stage II and stage III patients. Other manifestations, such as retinal-retinal anastomosis, retinal-choroidal anastomosis, focal retinal edema, and focal supraretinal or intraretinal hemorrhage, were detected to some extent.
Summary of Patient Information
Fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography angiography (OCTA) images in four patients with different patterns of retinal angiomatous proliferation lesions. Patient 10 (A1, A2). Patient 1 (B1, B2). Patient 3 (C1, C2). Patient 2 (D1, D2). High hot spots (yellow dotted circle) revealed on A1, C1, D1 (mid-FA image), and B1 (early ICGA image) were clearly detected on A2, B2, C2, and D2 (OCTA enface image), along with their feeder vessels. Hot spot lesions showed variable patterns: A2, loop-like; B2, C2, dot-like; D2, mulberry-like.
In all cases, the hot spot lesions found on late FA or ICGA images were clearly detected on OCTA images in the same areas (12 of 12, 100%). When levels were adjusted on the OCTA enface image, all hot spots along with their feeder vessels were revealed. On the OCTA B-scan image, by setting the same section line with OCT, the hot spot lesion was detected with high blood flow signal on the suspected area.
A 71-year-old man (Patient 2) had RAP in his left eye. The initial BCVA of the left eye was 20/25. Upon examination of his left eye, focal supraretinal hemorrhage (red arrow), several hard exudations, and irregular lesions on the macular area were detected with fundus photography (Figure 2A; yellow circle). The mid-FA image (Figure 2B) showed four hot spot lesions (yellow circle), which made it hard to distinguish the layers from feeder vessels to determine their relationship with surrounding vessels. To get a cross-structure image of each lesion, two section lines were set to obtain the corresponding OCT and OCTA B-scan images for further observation (Figures 2B, 2D, and 2E; yellow dotted line 1, 2). On OCT images (Figures 2C1 and 2C2), the hot spot lesions corresponded to lumen-like structures (red arrow). Meanwhile, next to the hot spot lesions (temporal) was the focal retinal edema (green arrow). On the OCTA images (Figures 2D, 2E, 2F, 2G1, 2G2, 2H), the hot spot lesions, corresponding to the OCT images, were detected as high blood flow signal spots. On the enface images (Figures 2D and 2E), all lesions were nodule-like and located on different layers from the superficial to the outer retina (red arrow). When levels were adjusted, the lesions and their relationships to the surrounding vessels were revealed (Figures 2F and 2H). All lesions emerged from the deep vascular network. On the B-scan images (Figures 2G1 and 2G2), high blood flow signals were detected in the lumen-like structures, corresponding to the OCT images (yellow arrow). The left eye received three anti-VEGF injections. After each injection, an OCTA scan was performed, and the result was compared with previous findings. Comparing the final OCTA images with the baseline images (Figure 3), we found that the retinal edema (green arrow) and one hot spot lesion were undetectable, whereas the other three lesions remained resistant (yellow arrow), with a lesser blood flow signal and smaller size. The final visual outcome of the left eye was 20/25.
Case 1. Patient 2, a 71-year-old man, left eye. (A) Fundus photography showed focal supraretinal hemorrhage (red arrow), several hard exudations, and irregular lesions on the macular area (yellow circle). (B) Mid-fluorescein angiography (FA) image showed four hot spot lesions (yellow circle). (C1, C2) Optical coherence tomography (OCT) images, which corresponded to section line 1, 2 (yellow dotted line) in Figure 1B, respectively, showed multiple lumen-like structures (red arrow) and focal retinal edema (green arrow). (D, E) OCT angiography (OCTA) en face images (superficial layer and deep layer) showed four nodule-like hot spots: two on the superficial layer and two on the deep layer (red arrow). (F, H) Adjusted OCTA enface images (superficial layer) showed the hot spot lesions (green circle) and their relationship to surrounding vessels. All lesions emerged from the deep vascular network. (G1, G2) OCTA B-scan images, which correspond to section line 1, 2 (yellow dotted line) in Figures 1B, 1D, and 1E, respectively, showed high blood flow signals in the lumen-like structures (yellow arrow).
Case 1. Patient 2, a 71-year-old man, left eye. The left eye received three anti-vascular endothelial growth factors injections. (A1, A2, C1, C2) Baseline superficial and deep images, respectively. (B1, B2, D1, D2) Final images. Optical coherence tomography angiography (OCTA) B-scan images correspond to the section line (yellow dotted line) in the OCTA enface images. Comparing the final images with the baseline, OCTA enface images show that two hot spots were smaller (red arrow). OCTA B-scan images show that the retinal edema (green arrow) and one hot spot disappeared, whereas three hot spots became smaller with less blood flow signal (yellow arrow).
A 64-year-old woman (Patient 4) had RAP in her left eye. The initial BCVA of the left eye was 20/100. Upon examination of her left eye, focal supraretinal hemorrhage, several hard exudations, and macular edema were detected using fundus photography (Figure 4A). The mid-ICGA image (Figure 4B) showed two irregular vessel structure lesions (yellow circle). Two section lines were set (Figure 4B; yellow dotted line 1, 2) on OCT and OCTA B-scan images to obtain a cross-structure image of each lesion (Figures 4C1, 4C2, 4H1, 4H2). On OCT images (Figures 4C1 and 4C2), PED and retinal edema made the image unclear. The images showed suspicious lumen-like structures (red circle) and the rupture of the pigment membrane (red arrow). On the OCTA images (Figures 4D, 4E, 4F, 4G, 4H1, 4H2), the lesions, which correspond to the OCT images, were detected as high blood flow signal spots. When examining the different layers of the enface images (Figures 4D, superficial; 4E, deep; 4F, outer retina; 4G, choroidal cap), the lesions were initially detected only on the deep layer as independent loop-like structures. The other parts of the irregular vessel structure shown on the ICGA image (Figure 4B) were supposed to be on the deeper layer: as the hot spots moved downward, they spread and became correlated with each other. On the B-scan images (Figures 4H1 and 4H2), high blood flow signals were detected in the lumen-like structures, corresponding to OCT images (red arrow). The rupture of pigment membrane was covered by the projection of the blood flow signal. The left eye had received one anti-VEGF injection. The OCTA scan and visual acuity had not yet been performed.
Case 2. Patient 4, a 64-year-old woman, left eye. (A) Fundus photography showed focal supraretinal hemorrhage (red arrow) and several hard exudations on the macular area (yellow circle). (B) The mid-indocyanine green angiography (ICGA) image showed two irregular vessel structure lesions (yellow circle). (C1, C2) Optical coherence tomography (OCT) images, which correspond to section line 1, 2 (yellow dotted line) in Figure 4B, respectively, showed two unclear lumen-like structures (red circle) and rupture of pigment membrane (red arrow). (D-G) OCT angiography (OCTA) en face images correspond to superficial, deep, outer retina, and choroidal cap, respectively. (H1, H2) OCTA B-scan images, which correspond to section line 1, 2 (yellow dotted line) in Figure 4B, respectively, showed high blood flow signals in the lumen-like structures (double red line). The rupture of the pigment membrane was covered by the projection of the blood flow signal.
An 82-year-old man (Patient 8) had RAP in his right eye. The initial BCVA of the left eye was 20/100. Upon examination of his right eye, fundus photography showed no significant abnormality (Figure 5A). The late FA image (Figure 5B) showed CNV (red arrow) and feeder vessels in the macular area. The OCT image (Figure 5C) showed a clear lumen-like structure (red arrow), beneath which was the rupture of pigment membrane (green arrow). Meanwhile, beneath the moderate PED, the irregular signal was obscure. On different layers of the enface images (Figures 5D1, superficial; 5D2, deep; 5D3, outer retina; 5D4, choroidal cap), two sharply cut off superficial retinal vessels (Figure 5D) were observed moving downward, intersecting within the deep retinal layer (Figure 5E; red circle) and feeding a CNV (Figure 5E, red circle) beneath a PED together. The enface images clearly show each layer and relative structure of the lesion. The left eye had received three anti-VEGF injections, one of which was combined with photodynamic therapy. The final OCTA images (Figures 5E1, 5E2, 5E3, 5E4) show the obscure initial feeder retinal vessels, including the pathway, terminal, and CNV. The final visual outcome of the left eye was 20/67.
Case 3. Patient 8, an 82-year-old man, right eye. The right eye had received two anti-vascular endothelial growth factor injections. (A) Fundus photography. (B) The late indocyanine green angiography image showed choroidal neovascularization (CNV) (red arrow) and feeder vessels in the macular area. (C) Optical coherence tomography (OCT) image showed a clear lumen-like structure (red arrow) and the rupture of the pigment membrane (green arrow). (D14, E14) OCT angiography (OCTA) enface images were the superficial, deep, outer retina, and choroidal layer, respectively. (D1–D4) Baseline images. The OCTA enface images showed two superficial feeder vessels, afflux of feeder vessels (red circle), CNV with pigment epithelial detachment (red circle), and CNV (red circle), respectively. (E1–E4) Final images. The OCTA enface images showed a nearly normal image at the same location (green circle).
In the current study, we characterized the features of OCTA as well as other multimodal imaging in patients with RAP of three vasogenic stages. In 2001, Yannuzzi et al.1 proposed the term “retinal angiomatous proliferation” to represent this kind of neovascular AMD and concluded that there are three stages with different manifestations. RAP may present simply as IRN or progress to be complicated by SRN or RCA. Different courses, visual prognoses, and treatments may be preferable for each stage of this neovascular disorder. Relying only on FA, ICGA, and OCT, it is hard to detect the extension of neovascularization and determine the progression of disease. With imaging of high-resolution microvascular detail for differential layer analysis of retina and choroid, OCTA shows a great advantage over traditional imaging modalities in the diagnosis and management of RAP. With simultaneous signal of blood flow on OCT B-scan images, neovascularized lesions could be demonstrated and located within a precise layer. We detected all RAP lesions in the current study. Dansingani et al.,16 Miere et al.,17 and Tan Anna et al.18 also reported that the sensitivity of OCTA in diagnosing RAP was as high as 62% to 100%. However, limited information is available regarding the multiple characterizations of the three stages. In our study with OCTA, we confirmed that six and four eyes with RAP had IRN and SRN, respectively. Moreover, two eyes had RCA and progressed to stage III, indicating a poor visual prognosis.
In the current study, we demonstrated that all of the RAP lesions originated from the retinal vessels, although previous theories that RAP stems from the deep vascular plexus or choroidal vessels are controversial.1,2 However, interestingly, in eyes with RAP, we demonstrated some intraretinal vascular lesions in the superficial plexus in the early stage. Based on Case 1 (Patient 2) in the study, which showed an example of RAP that went upward from deep vessels to the superficial layer, we speculate that the superficial lesion we found may also have a deep structure that we missed. Nonetheless, we still question whether this superficial hot spot would be a subtype of RAP, somehow caused by focal retinal oxygen deficiency, in addition to the deep one.20 Up-regulated VEGF induced by the ischemia may reflect the superficial retina in vascular anastomoses.21 In Case 1, multiple lesions were detected simultaneously in the different layers, which has been seldom reported. Further clinical observation with a large sample size and additional research mechanisms are required.
Our study fully demonstrates that one of the advantages of OCTA is to provide more-detailed information about the location and the precise layer of lesions, which is hard to acquire from FA or ICGA. Our study is the first to rely on OCTA to report multiple lesions in different layers and variable patterns of hot spots (Figure 1). All hot spot lesions were shown on FA or ICGA images, and the RAP lesions actually had variable patterns: loop-like, dot-like, mulberry-like, etc.
In recent reports, anti-VEGF therapy appeared to be a very powerful method for clinical management of RAP.4 In this study, we obtained results (reduction of exudation, improvement of final visual outcomes, little change of the lesion) similar to those of Miere et al.,22 in which eight of 15 cases had residual areas of flow in the initial lesions. We propose that the goal of RAP management may be to maintain a “dry” retina and closely observe the patient to prevent recurrence of intraretinal fluid. On the other hand, both our study and previous studies18,23 provide a reasonable example that OCTA would be a great choice during the follow-up observation as a substitute for FA or ICGA. Although the dye may induce allergic reactions, most are moderate.24
In conclusion, this study included 12 RAP patients who underwent multimodal imaging modalities. Morphological characteristics of different stages of RAP and changes after anti-VEGF therapy on OCTA images were illustrated. Compared to other modalities, OCTA provides clearer images of hot spots, including the exact locations, as well as their surrounding vessel structures. In this way, OCTA could serve as a powerful tool in the diagnosis and the follow-up observation of RAP.
- Yannuzzi LA, Negrão S, Iida T, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416–434. doi:10.1097/00006982-200110000-00003 [CrossRef] PMID:11642370
- Freund KB, Ho IV, Barbazetto IA, et al. Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina. 2008;28(2):201–211. doi:10.1097/IAE.0b013e3181669504 [CrossRef] PMID:18301024
- Jung JJ, Chen CY, Mrejen S, et al. The incidence of neovascular subtypes in newly diagnosed neovascular age-related macular degeneration. Am J Ophthalmol. 2014;158(4):769–779.e2. doi:10.1016/j.ajo.2014.07.006 [CrossRef] PMID:25034111
- Daniel E, Shaffer J, Ying GS, et al. Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group. Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Ophthalmology. 2016;123(3):609–616. doi:10.1016/j.ophtha.2015.10.034 [CrossRef] PMID:26681392
- Viola F, Massacesi A, Orzalesi N, Ratiglia R, Staurenghi G. Retinal angiomatous proliferation: natural history and progression of visual loss. Retina. 2009;29(6):732–739. doi:10.1097/IAE.0b013e3181a395cb [CrossRef] PMID:19516115
- Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina. 2008;28(3):375–384. doi:10.1097/IAE.0b013e3181619c55 [CrossRef] PMID:18327130
- Gross NE, Aizman A, Brucker A, Klancnik JM Jr, Yannuzzi LA. Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation. Retina. 2005;25(6):713–718. doi:10.1097/00006982-200509000-00005 [CrossRef] PMID:16141858
- Rouvas AA, Papakostas TD, Ntouraki A, Douvali M, Vergados I, Ladas ID. Angiographic and OCT features of retinal angiomatous proliferation. Eye (Lond). 2010;24(11):1633–1642. doi:10.1038/eye.2010.134 [CrossRef] PMID:21068770
- Matsumoto H, Sato T, Kishi S. Tomographic features of intraretinal neovascularization in retinal angiomatous proliferation. Retina. 2010;30(3):425–430. doi:10.1097/IAE.0b013e3181bd2d95 [CrossRef] PMID:19952990
- Ravera V, Bottoni F, Giani A, Cigada M, Staurenghi G. Retinal angiomatous proliferation diagnosis: a multiimaging approach. Retina. 2016;36(12):2274–2281. doi:10.1097/IAE.0000000000001152 [CrossRef] PMID:27870798
- Jia Y, Bailey ST, Hwang TS, et al. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. Proc Natl Acad Sci USA. 2015;112(18):E2395–E2402. doi:10.1073/pnas.1500185112 [CrossRef] PMID:25897021
- Min W. Better understanding retinal and choroidal vascular diseases and optical tomography angiography. Chin J Ocul Fundus Dis. 2016;32(4):353–356.
- Kuehlewein L, Bansal M, Lenis TL, et al. Optical coherence tomography angiography of type 1 neovascularization in age-related macular degeneration. Am J Ophthalmol. 2015;160(4):739–48.e2. doi:10.1016/j.ajo.2015.06.030 [CrossRef] PMID:26164826
- El Ameen A, Cohen SY, Semoun O, et al. Type 2 neovascularization secondary to age-related macular degeneration imaged by optical coherence tomography angiography. Retina. 2015;35(11):2212–2218. doi:10.1097/IAE.0000000000000773 [CrossRef] PMID:26441269
- Wang M, Zhou Y, Gao SS, et al. Evaluating polypoidal choroidal vasculopathy with optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57(9):OCT526–OCT532. doi:10.1167/iovs.15-18955 [CrossRef] PMID:27472276
- Dansingani KK, Naysan J, Freund KB. En face OCT angiography demonstrates flow in early type 3 neovascularization (retinal angiomatous proliferation). Eye (Lond). 2015;29(5):703–706. doi:10.1038/eye.2015.27 [CrossRef] PMID:25744441
- Miere A, Querques G, Semoun O, El Ameen A, Capuano V, Souied EH. Optical coherence tomography angiography in early Type 3 neovascularization. Retina. 2015;35(11):2236–2241. doi:10.1097/IAE.0000000000000834 [CrossRef] PMID:26457399
- Kuehlewein L, Dansingani KK, de Carlo TE, et al. Optical coherence tomography angiography of type 3 neovascularization secondary to age-related macular degeneration. Retina. 2015;35(11):2229–2235. doi:10.1097/IAE.0000000000000835 [CrossRef] PMID:26502007
- Spaide RF, Fujimoto JG, Waheed NK. Image artifacts in optical coherence tomography angiography. Retina. 2015;35(11):2163–2180. doi:10.1097/IAE.0000000000000765 [CrossRef] PMID:26428607
- Hartnett ME, Weiter JJ, Garsd A, Jalkh AE. Classification of retinal pigment epithelial detachments associated with drusen. Graefes Arch Clin Exp Ophthalmol. 1992;230(1):11–19. doi:10.1007/BF00166756 [CrossRef] PMID:1547961
- Shimada H, Kawamura A, Mori R, Yuzawa M. Clinicopathological findings of retinal angiomatous proliferation. Graefes Arch Clin Exp Ophthalmol. 2007;245(2):295–300. doi:10.1007/s00417-006-0367-6 [CrossRef] PMID:16738855
- Miere A, Querques G, Semoun O, et al. Optical coherence tomography angiography changes in early type 3 neovascularization after anti-vascular endothelial growth factor treatment. Retina. 2017;37(10):1873–1879. doi:10.1097/IAE.0000000000001447 [CrossRef] PMID:28079756
- Tan AC, Dansingani KK, Yannuzzi LA, Sarraf D, Freund KB. Type 3 neovascularization imaged with cross-sectional and en face optical coherence tomography angiography. Retina. 2017;37(2):234–246. doi:10.1097/IAE.0000000000001343 [CrossRef] PMID:27749497
- Hope-Ross M, Yannuzzi LA, Gragoudas ES, et al. Adverse reactions due to indocyanine green. Ophthalmology. 1994;101(3):529–533. doi:10.1016/S0161-6420(94)31303-0 [CrossRef] PMID:8127574
Summary of Patient Information
|Patient No.||Age, Years||Sex||Eye||Stage||Treatment|