Retinal angiomatous proliferation: association with clinical and angiographic features

AIM: It was the aim of this study to evaluate the frequency of retinal angiomatous proliferation (RAP) and its association with specific clinical and angiographic characteristics in age-related macular degeneration (AMD). METHODS: A consecutive series of 126 newly diagnosed patients with exudative AMD was reviewed retrospectively. All underwent a complete ophthalmic examination, a red-free photograph and fluorescein angiography. Most patients (85/126) underwent indocyanine green choroidal angiography (ICGA). RAP was diagnosed when a connection between the retinal vasculature and the neovascular complex was recognized angiographically. RESULTS: Out of 126 patients with recent neovascular AMD, 17 had RAP (13.5%; 95% CI 8.1-20.7). The study eye of patients with RAP had more frequent hemorrhages (88.2 vs. 59.6%; p = 0.027), hard exudates (82.4 vs. 26.6%; p < 0.001), pigment epithelium detachment (64.7 vs. 23.8%; p = 0.001) and a hot spot in ICGA (70.6 vs. 22.1%; p < 0.001) with respect to the other forms of exudative AMD. Hemorrhages were more frequently superficial, multiple and within the edge of the lesion in the RAP group. Bilateral AMD was more common in the RAP group (70.6 vs. 38.0%; p = 0.011). No statistically significant differences were found regarding sex, age and visual acuity. CONCLUSION: RAP represents a common lesion in patients with neovascular AMD referred to a tertiary care clinic. The recognition of hemorrhages, hard exudates, pigment epithelium detachment or a hot spot in ICGA can assist a correct diagnosis.     

视网膜血管瘤样增生的研究概况

视网膜血管瘤样增生(RAP)是年龄相关性黄斑变性的一种特殊类型,它起源于黄斑旁视网膜深层毛细血管网,并能不断增殖突破视网膜下间隙最终与脉络膜血管吻合.本文就视网膜血管瘤样增生的研究历程、分期、临床表现、诊断及治疗现状作一综述.     

Retinal angiomatous proliferation occurring after radiotherapy

Purpose

To describe two cases of retinal angiomatous proliferation (RAP)-like lesion following radiation therapy for primary tumor.

Patients and methods

Retrospective evaluation of two patients with previous irradiation treatment for a pleomorphic adenoma of the lacrimal gland and a vocal cord carcinoma, respectively. Visual acuity (VA), fluorescein angiography and optical coherence tomography were performed and demonstrated a RAP-like lesion in both cases. Treatment with intravitreal injections of Ranibizumab was performed with a follow-up of 19 and 10 months, respectively.

Results

Both the patients had a positive response to the treatment with improvement in VA and reduction of intraretinal fluid.

Conclusion

RAP-like lesions can develop following radiation treatment for a primary tumor. In patients presenting with idiopathic RAP, a history of prior radiotherapy should be considered.     

Retinal angiomatous proliferation and intravitreal bevacizumab injection

PURPOSE: To evaluate the short-term efficacy and safety of intravitreal bevacizumab injection (IVBI) in patients with retinal angiomatous proliferation (RAP). METHODS: Seven eyes of 5 patients with RAP were included in this study. All of the eyes evidenced stage 2 RAP lesions, except for one eye with a stage 3 lesion. IVBI (1.25 mg/0.05 cc) were conducted at 4 or 6-week intervals. Complete ocular examinations, angiographic results and optical coherence tomographic findings before and after the IVBI were analyzed at baseline and upon the follow-up visits. RESULTS: Seven eyes were studied in 5 patients who had undergone IVBI. Partial (3 eyes) or complete (4 eyes) regression of RAP was noted after IVBI in all of the studied eyes. Visual acuity improved in 5 of the eyes, and was stable in 2 of the eyes. One eye evidenced severe intraocular inflammation after IVBI and a subsequent development of new RAP, which was controlled with vitrectomy and repeat IVBI. CONCLUSIONS: This treatment was effective over 6 months, stabilizing or improving visual acuity and reducing angiographic leakage. These short-term results suggest that IVBI may constitute a promising therapeutic option, particularly in the early stages of RAP.     

Retinal angiomatous proliferation in age-related macular degeneration

BACKGROUND: It is known that choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) may erode through the retinal pigment epithelium, infiltrate the neurosensory retina, and communicate with the retinal circulation in what has been referred to as a retinal-choroidal anastomosis (RCA). This is extremely common in the end stage of disciform disease. In recent years, the reverse also seems to be possible, as angiomatous proliferation originates from the retina and extends posteriorly into the subretinal space, eventually communicating in some cases with choroidal new vessels. This form of neovascular ARMD, termed retinal angiomatous proliferation (RAP) in this article, can be confused with CNV. PURPOSE: The purpose of this article is 1) to review the clinical and angiographic characteristics of a series of patients with RAP and 2) to propose a theoretical sequence of events that accounts for the neovascularized process. METHODS: In this retrospective clinical and angiographic analysis, 143 eyes with RAP (108 patients) were reviewed and classified based on their vasogenic nature and course. Clinical biomicroscopic examination, fluorescein angiography, and indocyanine green angiography were used to evaluate patients. RESULTS: The results of this series suggest that angiomatous proliferation within the retina is the first manifestation of the vasogenic process in this form of neovascular ARMD. Dilated retinal vessels and pre-, intra-, and subretinal hemorrhages and exudate evolve, surrounding the angiomatous proliferation as the process extends into the deep retina and subretinal space. One or more dilated compensatory retinal vessels perfuse and drain the neovascularization, sometimes forming a retinal-retinal anastomosis. Fluorescein angiography in these patients usually revealed indistinct staining simulating occult CNV. Indocyanine green angiography was useful to make an accurate diagnosis in most cases. It revealed a focal area of intense hyperfluorescence corresponding to the neovascularization ("hot spot") and other characteristic findings. Based on understanding of the nature and progression of the neovascularized process, patients with RAP were classified into three vasogenic stages. Stage I involved proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization [IRN]). Stage II was determined by growth of the retinal vessels into the subretinal space (subretinal neovascularization [SRN]). Stage III occurred when CNV could clearly be determined clinically or angiographically. A vascularized pigment epithelial detachment and RCA were inconsistent features of this stage. CONCLUSIONS: Retinal angiomatous proliferation appears to be a distinct subgroup of neovascular ARMD. It may present in one of three vasogenic stages: IRN, SRN, or CNV. Whereas ICG angiography is helpful in diagnosing RAP and in documenting the stage of the neovascularized process, it is frequently difficult to determine the precise nature and location of the new vessel formation. It is important for clinicians to recognize the vasogenic potential and the associated manifestations of this peculiar form of neovascular ARMD so that a proper diagnosis can be made, and when possible, an appropriate management administered.     

Retinal angiomatous proliferation in age-related macular degeneration

BACKGROUND: Angiomatous proliferation in ARMD originates from the retina and extends into the subretinal space. Retinal angiomatous proliferation (RAP) is diagnosed with angiography. This study investigates the characteristics of RAP in optical coherence tomography (OCT) and correlates them with clinical and fluorescein angiographic findings. METHODS: 327 consecutive patients with age-related macular degeneration (ARMD) were retrospectively examined using a standardised protocol. The protocol included best corrected visual acuity (BCVA), binocular ophthalmoscopy, fundus photography, fluorescein angiography (FAG) and OCT. The OCT and angiographic findings were graded in 3 RAP stages. RESULTS: 32 of 327 (9.79 %) patients (45 eyes) had RAP. The age ranged from 56 to 90 years (median: 79 years). 9 eyes presented RAP stage I, 23 stage II and 13 stage III. BCVA ranged from 0.01 to 0.7 (median: 0.2). OCT foveal minimum was 136 to 722 microns (median: 327). 33 (73 %) eyes showed a detachment of retinal pigment epithelium (RPE). Macular oedema was found in 43 (96 %) eyes. Cystoid macular oedema was seen in 36 (80 %) eyes. In stage II, 22 eyes (96 %) showed an RPE detachment, in stage III 11 eyes (85 %). 11 (85 %) eyes in stage III showed retinal-choroidal anastomosis. CONCLUSIONS: RAP was found in 9.79 % of the patients with ARMD. The OCT is helpful in detection of RPE detachment, macular oedema and cystoid changes in RAP. RAP and retinal-choroidal anastomosis should be identified because of the possibly poor prognosis.     

Retinal angiomatous proliferation with a cilioretinal artery anastomosis: an unusual presentation

Purpose To report an unusual phenotype of retinal angiomatous proliferation (RAP) in age-related macular degeneration (AMD) and its short-term response to laser photocoagulation.Methods Case report.Results An 85-year-old woman was found to have an unusual RAP with a major feeder vessel originating from a cilioretinal artery and associated with a cilioretinal–retinal anastomosis (C-RRA). Diffuse cystoid macular edema (CME), intraretinal hard exudates in a circinate pattern, and a fibrovascular pigment epithelial detachment (PED) were present. Laser photocoagulation was performed and led to occlusion of the cilioretinal feeder vessel and angiomatous lesion, with less CME. The other (retinal) arm of the C-RRA became more engorged and a new cilioretinal feeder developed, and both were associated with intraretinal hemorrhages. Visual acuity was stable and the PED persisted throughout follow-up.Conclusions We report an unusual phenotype of RAP that is associated with a major cilioretinal feeder vessel and comment on the possible effect of such an association on the response to laser treatment.     

视网膜血管瘤样增生的诊断与治疗

视网膜血管瘤样增生(retinal angiomatous proliferation,RAP)是湿性老年性黄斑变性(age-related macular degeneration,AMD)隐匿性新生血管的另一种病变形式,起源于黄斑旁视网膜深层毛细血管层,以多发性小灶状视网膜内出血、视网膜色素上皮脱离(pigment epithelial detachment,PED)、视网膜-脉络膜血管吻合(retinal-choroidal anastomosis,RCA)为特点,对视力损害严重。本文对近年来的有关文献进行复习,并就RAP的发病机制、临床分期、诊断特点、治疗及预后进行综述。     

Retinal angiomatous proliferation treated by intravitreal triamcinolone and photodynamic therapy with verteporfin

Purpose To examine combined treatment of intravitreal triamcinolone acetonide (IVT) and photodynamic therapy (PDT) for retinal angiomatous proliferation (RAP).Methods Ten eyes of eight consecutive patients with RAP underwent a single injection (about 20 mg) of IVT followed 1 month later by PDT. Best-corrected visual acuity (BCVA) was measured by standardized protocol refraction.Results Median BCVA was 20/160, 20/64, 20/98, 20/89, 20/89, 20/125 at baseline and 1, 3, 6, 9 and 12 months, respectively. Of ten eyes, six (60%) improved BCVA of at least 3 lines at 1, 3, 6 and 9 months. Four (40%) eyes improved BCVA of at least 3 lines at 12 months. Three eyes (30%) lost >3 lines at 12 months. In all patients intraocular pressure was well controlled. No endophthalmitis, retinal detachment or vitreous haemorrhage developed.Conclusions Improvement of BCVA suggests that combination treatment with IVT and PDT for RAP merits further investigation.The authors do not have any proprietary interests.     

Retinal angiomatous proliferation: combined therapy of intravitreal triamcinolone acetonide and PDT versus PDT alone

BACKGROUND: The objective of the study was to investigate whether combined treatment with photodynamic therapy (PDT) and triamcinolone acetonide intravitreally applied is superior to PDT alone in eyes with retinal angiomatous proliferation (RAP). METHODS: Between July 2004 and June 2005 eyes with RAP in age-related macular degeneration were included in a prospective study and were treated with 4 mg of triamcinolone acetonide followed by PDT (group 1). Eyes with RAP treated with PDT alone before June 2004 were retrospectively reviewed (group 2). Distance visual acuity (VA) with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, greatest diameter of the lesion (measured by fluorescein angiography), and retinal thickness (measured by optical coherence tomography) were performed at baseline and at 6 weeks, 3 months, 6 months and 12 months thereafter. RESULTS: Fifty-eight eyes in 58 patients were included: 27 eyes in the combined treatment group and 31 eyes in the PDT monotherapy group. The groups were comparable with regard to age, gender and RAP stage. VA decreased from 65.6 to 52.0 and from 60.7 to 44.0 letters, and lesion size increased from 3.2 mm to 3.5 mm and from 3.3 mm to 3.5 mm in the combined and monotherapy groups respectively. There was a trend towards a better outcome in the combined group. Significantly (p = 0.01) fewer complications occurred in the combined group (22.2%) than in the monotherapy group (54.8%). CONCLUSION: No significant differences could be found in the time course of distance VA, retinal thickness, and lesion size between the PDT monotherapy group and the combined PDT and IVTA group. However, significantly fewer complications occurred in the combined treatment group. New therapeutic strategies might be required in RAP lesions, probably including therapy with anti-angiogenic agents.     

Successful treatment of retinal angiomatous proliferation by photodynamic therapy.

PURPOSE: The purpose of this study is to describe a patient with retinal angiomatous proliferation (RAP) treated successfully by photodynamic therapy. METHODS: A 74-year-old white woman was referred to our clinic for evaluation as a result of progressive decrease of vision in the right eye. Visual acuity was 20/100 in the affected right eye. The findings of fluorescein and indocyanine green angiography were consistent with a diagnosis of RAP, and cystoid macular edema was also revealed by optical coherence tomography (OCT). Photodynamic therapy (PDT) was carried out because of visual deterioration and localization of the RAP. RESULTS: The RAP was treated with PDT, and an improvement in visual acuity to 20/60 was noted 4 months after treatment and 20/40 after 6 months. The resolution of the lesion was confirmed by fluorescein angiography, indocyanine green angiography, and OCT. CONCLUSIONS: Photodynamic therapy can be effective for the treatment of RAP when it is associated with visual acuity decrease and is located near the fovea.     

Intravitreal ranibizumab treatment of retinal angiomatous proliferation

Purpose: To determine the efficacy of intravitreal injections of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) in neovascular age‐related macular degeneration. Methods: Retrospective, consecutive case series of 26 eyes (26 patients) treated with intravitreal injections of 0.5 mg ranibizumab for RAP. Patients received intravitreal injections at monthly intervals during upload phase for a 3‐month period. Results: Mean visual acuity before treatment was 0.75 ± 0.38logMAR (mean ± SD, n = 26). In the upload phase, mean visual acuity improved 4 weeks after the initial injection to 0.6 ± 0.37logMAR (n = 26) and to 0.53 ± 0.34logMAR (n = 26) 4 weeks after the third monthly intravitreal injection of ranibizumab. The mean optical coherence tomography (OCT) central foveal thickness reduced from 345 ± 55 μm at baseline to 215 ± 87 μm at 3 months. In the maintenance phase, mean visual acuity after 6 months was 0.66 ± 0.38logMAR (n = 12) and 0.7 ± 0.37logMAR after 9 months (n = 6). The mean OCT central foveal thickness was 259 ± 59 μm (n = 13) at 6 months and 280 ± 127 μm (n = 6) at nine‐month follow‐up. Conclusion: Intravitreal ranibizumab resulted in an improvement of visual acuity 4 weeks after the first injection but was more pronounced after 3 months. A reduction in leakage and OCT central foveal thickness was seen 3 months after the commencement of treatment.     

Retinal angiomatous proliferation not associated with age-related macular degeneration. Favourable outcome after photodynamic therapy

CASE: A 55-year-old male was diagnosed with exudative-hemorrhagic maculopathy, with no signs observed of drusen or pigmentary epithelium defects suggestive of age-related macular degeneration (ARMD). Fluorescein angiography (FA) and indocyanine green choroidal angiography (ICGA) showed retinal angiomatous proliferation (RAP). Afferent arteriole and retinal drainage venule connection was also observed. Treatment with a single Photodynamic Therapy provided an optimal outcome. DISCUSSION: RAP is a form of neovascular ARMD described in recent years; it consists of an angiomatous proliferation that originates from the retinal capillary system and extends posteriorly into the subretinal space. Our patient showed typical RAP findings without any sign of ARMD     

视网膜血管瘤增殖一年龄相关性黄斑变性的特殊类型

本文总结了年龄相关性黄斑变性的特殊类型—视网膜血管瘤增殖(RAP)的临床和造影表现及分期。RAP是起源于黄斑旁视网膜深层毛细血管的、以伴发多灶小片视网膜内出血及盘变前期即有视网膜-脉络膜血管吻合(RCA)形成为特征的新生血管性AMD。     

Retinal angiomatous proliferation reactivation 6 months after high-dose intravitreal acetonide triamcinolone and photodynamic therapy

PURPOSE: To describe the incidence of retinal angiomatous proliferation (RAP) reactivation after combined treatment with a high-dose intravitreal triamcinolone acetonide (IVTA) and photodynamic therapy (PDT) at 1-year follow-up. METHODS: All patients had undergone a full ophthalmic examination. High-dose IVTA (20 mg) was injected via pars plana. Four to 7 days later, PDT was delivered. RESULTS: Fourteen eyes of 13 patients were included. Eight lesions (57%) reopened and needed retreatment with combined therapy at 6 months follow-up. At 1-year follow up, the lesion was obliterated in nine cases (64.2%) and best-corrected visual acuity improved from 0.87 logMar (range, 0.7-1) to 0.79 logMar (range, 0.5-1). CONCLUSIONS: Combined therapy using high-dose IVTA and PDT is beneficial in stabilizing RAP. However, a high incidence of RAP reactivation has been observed at 6 months, even with a high-dose IVTA injection.     

视网膜血管瘤样增生治疗进展

视网膜血管瘤样增生(retinal angiomatous proliferation,RAP)是新生血管性年龄相关性黄斑变性(neovascular age-related macular degeneration,nARMD)的一种特殊病变类型,又称"3型新生血管".其基本病变为新生血管形成,目前认为其新生血管起源于视网膜深层毛细血管.主要临床特征包括视网膜色素上皮层脱离(PED)和网状假性玻璃膜疣,分别与视网膜色素上皮层撕裂和地图样萎缩相关,最终可致严重的不可逆性视力损伤.其病程进展迅猛,多数早期患者可在6 mo内发展至视力丧失.而传统治疗措施如激光疗法,疗效有限,预后较差.近年来,OCT血管造影(OCTA)等新技术从新的角度对RAP展开了探索,尤其在RAP的分期、基于分期的疗效观察等方面有了一定进展.大量有关玻璃体腔注射抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物治疗RAP的研究也证实了这种新兴疗法的安全性、有效性和优越性.这些均为临床选择治疗方案提供了依据.