Treatment of Bilateral Retinal Angiomatous Proliferation with Anti-vascular Endothelial Growth Factor: 12-Month Outcome

PURPOSE: To evaluate the 12-month outcome of intravitreal anti-vascular endothelial growth factor therapy in eyes with bilateral retinal angiomatous proliferation (RAP). METHODS: This retrospective observational study included 38 eyes of 19 patients with stage 1 or 2 bilateral RAP at diagnosis. The eyes of patients who exhibited different baseline best-corrected visual acuity (BCVA) values in both eyes were assigned to one of two groups—the better (n=13) and worse (n=13) visual acuity groups. The BCVA values in both groups were compared to those at baseline and at 12 months. In addition, the 12-month changes in BCVA were compared between the two groups. The association between the optical coherence tomography findings at diagnosis and the 12-month BCVA was also analyzed. RESULTS: The values of mean baseline and 12-month BCVA in the better visual acuity group (13 eyes) were 0.48 ± 0.19 and 0.58 ± 0.29, respectively, and those in the worse visual acuity group (13 eyes) were 0.83 ± 0.20 and 0.90 ± 0.31. The 12-month changes in BCVA were not significantly different between the two groups (p=0.786). Among the six patients with equivalent baseline BCVA in both eyes, four patients (66.7%) exhibited 1 to 2 lines or ≥3 lines of difference in BCVA between eyes at 12 months. Eyes without pigment epithelial detachment (PED) at diagnosis exhibited significantly better BCVA at 12 months than eyes with PED (p=0.021). CONCLUSIONS: Better baseline visual acuity was associated with better BCVA at 12 months posttreatment in patients with bilateral RAP. However, equivalent baseline visual acuity in both eyes might not guarantee similar treatment outcomes. In addition, the absence of PED is predictive of better visual outcome.

Advances in the treatment of retinal angiomatous proliferation / 国际眼科杂志(Guoji Yanke Zazhi)

·Retinal angiomatous proliferation ( RAP) , also known as"type 3 neovascularization", is a well - recognized variation of neovascular age - related macular degeneration ( nARMD ) . Neovascularization is the basic pathological characteristic. Current view on the origin of the neovascularization is the deep retinal capillaries. The main clinical features include retinal pigment epithelium detachment( PED) and reticular pseudodrusen. These two features have close relation to the retinal pigment epithelium ( RPE ) tear and geographic atrophy ( GA ) , respectively, which may ultimately result in severe irreversible visual impairment. The disease has a rapid natural course and the majority of patients in early stage can develop into vision loss within 6mo. However, classical therapeutic managements, such as laser therapy, have limited efficacy and poor prognosis. Recently, RAP has been further understood with the application of OCT angiography and other new technologies in diagnosing, staging and monitoring RAP. Varieties of research on intravitreal injection of anti -vascular endothelial growth factor ( VEGF ) treatment to RAP have also revealed its promising results and proved its safety as well as effectiveness. All these have provided new knowledge on choosing the optimal treatment regimen in clinical.

Comparison of Optical Coherence Tomography Characteristics among Three Subtypes of Exudative Age-related Macular Degeneration

PURPOSE: To compare the characteristics of optical coherence tomography in eyes with treatment-naïve typical neovascular age-related macular degeneration (typical nAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). METHODS: One hundred fifty-three eyes newly diagnosed with exudative AMD were retrospectively collected. All study eyes were classified into three subtypes: typical nAMD, PCV, and RAP. Subfoveal choroidal thickness (SFCT) was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Central macular thickness (CMT) and other OCT features including intraretinal cystoid fluid and subretinal fluid were also evaluated in all eyes. SFCT, CMT and other OCT features were compared among the three subtypes of exudative AMD. RESULTS: Seventy-four eyes with typical nAMD, 55 eyes with PCV, and 24 eyes with RAP were included. SFCT was significantly thickest in PCV and thinnest in RAP (p < 0.001). RAP showed the thickest CMT and the highest frequency of intraretinal cystoid fluid (p = 0.004, p < 0.001, respectively). CONCLUSIONS: In patients with exudative AMD, different characteristics of OCT were observed according to the three subtypes. Identification of OCT characteristics could help differentiate the subtypes of exudative AMD.

Comparison of Short-Term Clinical Outcomes between Intravitreal Ranibizumab and Aflibercept in Retinal Angiomatous Proliferation

PURPOSE: To evaluate the 6-month outcomes of intravitreal ranibizumab and aflibercept treatment for patients with retinal angiomatous proliferation (RAP). METHODS: A retrospective review of medical records of 28 patients (31 eyes) diagnosed with RAP was performed. All patients were initially treated with 3 consecutive intravitreal ranibizumab or aflibercept injections after diagnosis. Additional treatment was performed when exudation recurred. The best-corrected visual acuity (BCVA) and central foveal thickness were measured before the first injection and 3 and 6 months after the first injection. The values measured before the treatment were compared with those after treatment. RESULTS: Sixteen eyes were treated with ranibizumab and 15 eyes with aflibercept. The logarithm of minimal angle of resolution (log MAR) values of BCVA before the first injection and 3 and 6 months after the first injection were 0.78 +/- 0.50, 0.47 +/- 0.30 and 0.59 +/- 0.41 in the ranibizumab group and 0.96 +/- 0.52, 0.83 +/- 0.52 and 0.74 +/- 0.56 in the aflibercept group, respectively. Central foveal thickness was 315.75 +/- 115.44, 188.38 +/- 57.33 and 218.50 +/- 96.49 microm in the ranibizumab group and 249.00 +/- 74.88, 143.73 +/- 32.73 and 196.73 +/- 94.08 microm in the aflibercept group, respectively. BCVA was significantly improved and central foveal thickness was significantly reduced at 6 months (p < 0.05) compared to measurements before the first injection in both groups. However, BCVA improvement and central foveal thickness were not significantly different between the 2 groups. CONCLUSIONS: Both intravitreal ranibizumab and aflibercept treatments were beneficial for both normalizing macular thickness and improving visual acuity in patients with RAP. The efficacy of the 2 drugs was not noticeably different.

Intravitreal Anti-Vascular Endothelial Growth Factor for Retinal Pigment Epithelial Tear in Retinal Angiomatous Proliferation

PURPOSE: To evaluate the treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) therapy for retinal pigment epithelial (RPE) tear in retinal angiomatous proliferation (RAP). METHODS: In the present study we retrospectively analyzed the medical records of 14 patients (14 eyes) diagnosed with RPE tear secondary to RAP treated with intravitreal anti-VEGF. Best-corrected visual acuity (BCVA) when the RPE tear developed was compared with BCVA at 6 months and at the final follow-up. RESULTS: The mean age of the study patients was 75.1 +/- 7.0 years and the mean follow-up period was 23.7 +/- 13.7 months. During the follow-up period, patients were treated with a mean of 2.8 +/- 1.3 intravitreal anti-VEGF injections. The mean logarithm of minimal angle of resolution BCVA when the RPE tear developed, at 6 months and at the final follow-up was 1.25 +/- 0.44, 1.44 +/- 0.56, and 1.65 +/- 0.39, respectively. The BCVA at 6 months was not different from the baseline value (p = 0.258), whereas the BCVA at the final follow-up was significantly worse than the baseline value (p = 0.002). CONCLUSIONS: The prognosis of RPE tear in RAP is poor despite anti-VEGF therapy. This result suggests further investigations regarding the prevention of RPE tear or more effective treatment method for this condition are necessary.

Multimodality imaging in macular telangiectasia 2: A clue to its pathogenesis.

Macular telangiectasia type 2 also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A is an acquired bilateral neurodegenerative macular disease that manifests itself during the fifth or sixth decades of life. It is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right‑angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV). Our understanding of the disease has paralleled advances in multimodality imaging of the fundus. Optical coherence tomography (OCT) images typically demonstrate the presence of intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic (FA) finding is a deep intraretinal hyperfluorescent staining in the temporal parafoveal area. With time, the staining may involve the whole parafoveal area but does not extend to the center of the fovea. Long‑term prognosis for central vision is poor, because of the development of SRNV or macular atrophy. Its pathogenesis remains unclear but multimodality imaging with FA, spectral domain OCT, adaptive optics, confocal blue reflectance and short wave fundus autofluorescence implicate Müller cells and macular pigment. Currently, there is no known treatment for this condition.

Characteristic Findings of Optical Coherence Tomography in Retinal Angiomatous Proliferation

PURPOSE: To identify the unique pathologic findings of retinal angiomatous proliferation (RAP) in optical coherence tomography (OCT). METHODS: Retrospectively, 29 eyes of 25 patients with age-related macular degeneration and complicated RAP were analyzed. All 29 eyes had choroidal neovascularization (CNV) in the area of pigment epithelial detachment (PED) or adjacent to it, which was visible with fluorescein angiography or indocyanine green angiography. Cross-sectional images were obtained by OCT scanning through the CNV lesions. RESULTS: Six distinctive findings of OCT included drusen (100%), inner retinal cyst (80%), outer retinal cyst (68%), fibrovascular PED (84%), serous retinal detachment (40%), and PED (68%). CONCLUSIONS: Through analysis of OCT findings, we revealed six different types of lesions distinctive of RAP which may provide helpful diagnostic information for subsequent treatment and predicting the prognosis of RAP.

Twelve-Month Outcomes of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy for Retinal Angiomatous Proliferation

PURPOSE: To evaluate the 12-month outcomes of anti-vascular endothelial growth factor (VEGF) treatment for patients with retinal angiomatous proliferation (RAP). METHODS: Retrospective review of medical records was performed for 33 patients (33 eyes) who were diagnosed with RAP. All patients were initially treated with three consecutive intravitreal anti-VEGF injections after diagnosis. Additional treatment was performed when the recurrence of exudation was noted. The best-corrected visual acuity (BCVA) was measured before the first injection and at 3, 6, and 12 months after the first injection. The value measured before the treatment was compared with those measured after treatment. RESULTS: The patients received an average of 4.2 +/- 1.7 intravitreal anti-VEGF injections during the 12-month follow-up period. The logarithm of minimal angle of resolution (log MAR) values of BCVA before the first injection and at 3, 6, and 12 months after the first injections were 0.76 +/- 0.49, 0.55 +/- 0.35, 0.67 +/- 0.41, and 0.70 +/- 0.50, respectively. BCVA was significantly improved at 3 and 6 months (p or =2 log MAR lines of improvement) BCVA. CONCLUSIONS: Anti-VEGF therapy was found to be beneficial in both normalizing macular thickness and in improving or maintaining visual acuity in the majority of patients with RAP.

A study on retinal angiomatous proliferation and its mechanism in apolipoprotein E-deficient mouse with dyslipidemia / 中华实验眼科杂志

Background Retinal angiomatous proliferation (RAP) is a subtype of neovascular age-related macular degeneration (AMD).There are currently very few studies on RAP.Objective This study was to explore the pathogenic mechanism of RAP in apolipoprotein E-deficient (ApoE-/-) mice with dyslipidemia.Methods Twenty-four 2-month-old SPF ApoE-/-mice were randomly divided into the high fat diet group and the normal diet group,and twelve 2-month-old C57BL/6 mice received the normal diet as controls.A diet with a higher content of fat was given for 4 consecutive months in the high fat diet group,and normal diet was given in the same way in the mice of the normal diet group.The mice were sacrificed at 6 months of age.The expression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelial (RPE) cells,the expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in the outer plexiform layer (OPL),microvascular density (MVD) and microvascular area (MVA) in the OPL were examined by immunohistochemistry and semi-quantitatively by histopathology with the Mias 2000 Imaging Analyzer System.The expression of VEGF protein in the retina was examined by Western blot.Results The MVD in the retinal OPL were (20.67±3.20) and (19.50± 1.87),respectively,in the ApoE-/-mice of the high fat diet group and the normal diet group,which were significantly higher than that (12.50±1.87) of the C57BL/6 normal diet group (all at P＜0.01).MVA in the retinal OPL were (626.49± 120.99) μm2 and (514.06±88.83) μm2 in the ApoE-/-mice of the high fat diet group and the normal diet group,respectively,showing a significant increase in comparison with the (336.52±84.96) μm2 of the C57BL/6 normal diet group (P＜0.01).The staining area of VEGF in RPE cells was (21 048±1849) μm2 in the ApoE-/-mice of the high fat diet group,showing a significant increase in comparison with the (17 116±2023) μm2 of the C57BL/6 normal diet group.However,no significant difference was found in the staining area of VEGF between the ApoE-/-mice with normal diet group and the C57BL/6 normal diet group ([17 854±2967] μm2 vs.[17 116±2023] μm2) (P＞0.05).Significant elevation was also seen in the staining area of VEGFR-2 in the retinal OPL of the ApoE-/-mice of the high fat diet group (12 193±3806)μm2 and the ApoE-/-mice of the normal diet group (11 969± 3616)xm2 compared with C57BL/6 mice of the normal diet group (5387±2225)μm2(all at P＜0.01).The relative expression values (VEGF/β-actin) of VEGF in the retinas were (1.51 ±0.32) and (1.17±0.39) in the ApoE-/-mice of the high fat diet group and the normal diet group,respectively,showing a significant increase in comparison with (0.28±0.14) of the C57BL/6 normal diet group (P＜0.01).Conclusions The expression of VEGF and VEGFR-2 in the retinas increases in the ApoE-/-mouse,which leads to the enlargement of MVD and MVA in the retinal OPL and subsequent RAP occurrence.

The fundus findings and treatment option of retinal angiomatous proliferation / 中华实验眼科杂志

Retinal angiomatous proliferation(RAP) is a special type of age-related macular degeneration (AMD) with a pathological process of neovascularization.Different with several types of neovascular AMD,the new blood vessel in RAP is believed to originate from the inner retinal circulation.Because of inadequate knowledge,there still exist some limited understanding for this disease,such as its clinical diagnosis,therapy effectiveness and its poor prognosis.The newest interpretation about RAP was based on the findings of indocyanine green angiography(ICGA) and the first generation of optical coherence tomography (OCT) imaging system.The stage,histogenesis,histopathology,nature process,fundus findings,differentiating diagnosis and treatrnent of RAP were reviewed.

Treatments of Stage 1 Retinal Angiomatous Proliferation

PURPOSE: To evaluate the results of single or combined treatment methods administered to patients with stage 1 retinal angiomatous proliferation (RAP). METHODS: A retrospective clinical study was performed in 9 eyes of 8 patients with stage I RAP. According to fundus angiography findings taken regularly after treatment, the results were categorized as closure of stage 1, recurrence of stage 1, or progress to stage 2. RESULTS: The mean follow-up period was 25 (14~40) months. In two eyes treated with laser photocoagulation only, the lesions progressed to stage 2. In two eyes treated with laser photocoagulation and intravitreal triamcinolone injection, the lesions also progressed to stage 2. In four eyes treated with photodynamic therapy and intravitreal triamcinolone injection, stage 1 lesions recurred in 3 eyes, and the lesion progressed to stage 2 in one eye. In one eye treated with photodynamic therapy, intravitreal triamcinolone injection, and laser photocoagulation, the stage 1 lesion recurred. Final visual acuity was stable in the case of stage 1 recurrence but was lower than the pretreatment level when the lesion progressed to stage 2. CONCLUSIONS: With either single or combined therapy, temporary closure of the stage 1 RAP lesion was possible, but complete closure could not be achieved for a long period because the lesion either recurred or progressed.

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.

Neovascularizations Associated with Large Serous Retinal Pigment Epithelial Detachment: Classification According to the Angiographic Features

PURPOSE: To differentiate serous pigment epithelial detachment (PED) according to angiographic features in elderly Korean patients. METHODS: The fluorescein and indocyanine green angiograms of 72 eyes of 67 consecutive patients with a serous PED of at least 1 disc diameter were evaluated retrospectively RESULTS: Polypoidal choroidal vasculopathy (PCV) and typical choroidal neovascularization (CNV) associated with PEDs were identified in 18 eyes (25%) and 19 eyes (26.4%), respectively. In 10 eyes (13.9%), it could not be determined whether the exact type of neovascularzation was PCV or CNV. Pure serous PEDs were identified in 7 eyes (10%). The remaining 18 eyes (25%) of 13 patients were classified as retinal angiomatous proliferation (RAP) associated with PED, based on the angiographic findings of anastomosis of the retinal vasculature with neovascular lesion, as well as clinical features such as diffuse soft drusen, extrafoveal location, preretinal or superficial retinal hemorrhage, and bilateral tendency. CONCLUSIONS: In Asian patients with neovascularized, age-related macular degeneration (AMD), the incidence of PCV is known to be high, whereas the incidence of RAP is very low. However, the results of this study suggest that RAP is as common as PCV and CNV in a subset group of neovascularized AMD that is accompanied by serous PED.

Progression of Retinal Angiomatous Proliferation after Surgical Ablation

PURPOSE: To describe the clinical course of three eyes of three patients that underwent surgical ablation as treatment of retinal angiomatous proliferation (RAP). METHODS: Surgical lysis of the retinal feeding arteriole and draining venule was done in two eyes that had stage 2 RAP with serous pigment epithelial detachment (PED). It was done as the first treatment modality in one eye, and after failure of laser photocoagulation in the other. It was also performed in another eye presumed to have very early stage RAP that showed only retinal-retinal anastomosis without any definite intraretinal or subretinal angiomatous lesion. RESULTS: PED decreased within 1 month after ablation in the two eyes with stage 2 RAP, but new anastomoses eventually developed after 1 month, followed by progression of the lesions. In the eye with presumed early stage RAP, successful lysis of retinal-retinal anastomosis was maintained and initially showed no signs of further proliferation at the original lesion site; however, four months later, hemorrhagic PED developed distally and progressed further to retinal pigment epithelial tear and massive subretinal hemorrhage. CONCLUSIONS: Surgical ablation may be unable to halt the progressive nature of neovascular proliferations in RAP.

Photodynamic Therapy Results of Retinal Angiomatous Proliferation with Pigmented Epithelial Detachment in Age-related Macular Degeneration

PURPOSE: To evaluate the incidence of retinal angiomatous proliferation (RAP) and retinal pigmented epithelial detachment (PED) in Korean age-related macular degeneration (ARMD) patients and results of photodynamic therapy (PDT) with verteporfin. METHODS: Between May 2001 and December 2004, two hundred fifty-eight patients diagnosed of ARMD were evaluated and nine eyes of seven patients were as having RAP with PED. All patients underwent two or more sessions of PDT. Best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography and ICG angiography were performed before and after treatment. RESULTS: The incidence of RAP with PED was 2.8%. The mean age of onset was 71.7 and five of seven patients were female. After 17 months and mean 2.3 PDT treatments, mean BCVA decreased from 0.2 to 0.04. In two eyes, additional Transpupillary thermotherapy was undertaken. Occlusion of RAP and flattening of PED was observed in one eye, and four evolved toward stage 3 RAP. Three eyes with PDT developed tear of retinal pigmented epithelium. CONCLUSIONS: Korean ARMD patients showed a low incidence of RAP and poor visual outcomes even with treatment.

Retinal Angiomatous Proliferation

PURPOSE: To report the cases of retinal angiomatous proliferation (RAP) which has been known to be rare in Asian populations, and to describe the characteristic clinical and angiographic findings of RAP. METHODS: Six eyes of 3 patients were diagnosed as having RAP, and 5 eyes had extensive soft drusen. The first case showed intraretinal neovascularization (RAP stage 1) and subretinal neovascularization with a retinal-retinal anastomosis and an associated serous pigment epithelial detachment (RAP stage 2). The second case showed choroidal neovascularization with a retinal choroidal anastomosis (RAP stage 3) and RAP stage 1. In the third case, RAP stage 2 and severe fibrous scarring, resulting from RAP, could be found. RESULTS: RAP seems to have the tendency for bilateral involvement and extrafoveal location, and a high index of suspicion may be required in the eyes having large serous pigment epithelial detachment accompanied by soft drusen. Fundus findings, such as intraretinal or preretinal hemorrhage, intraretinal reddish nodule, macular edema and indocyanine green angiogram findings of retinal-retinal anastomosis or retinal-choroidal anastomosis, have diagnostic values.