SEARCH

SEARCH BY CITATION

Keywords:

  • age-related macular degeneration;
  • intravitreal injection;
  • Lucentis;
  • ranibizumab;
  • retinal angiomatous proliferation

Abstract.

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

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.


Introduction

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Retinal angiomatous proliferation (RAP) is a variant of neovascular age-related macular degeneration (AMD) and has recently been discovered to be present in approximately 10–15% of eyes with exudative AMD (Yannuzzi et al. 2001). According to Yannuzzi et al. (2001), RAP arises from the retina rather than from the choroidal circulation. Retinal angiomatous proliferation has been reported to have an especially poor prognosis and limited response to treatment (Bottoni et al. 2005; Bressler 2005). Moreover, the fellow eye is at high risk of developing RAP (Gross et al. 2005). Various treatments for RAP, such as conventional laser photocoagulation (Slakter et al. 2000; Johnson & Glaser 2006), photodynamic therapy (PDT) (Boscia et al. 2004; Panagiotidis et al. 2006; Silva et al. 2007), surgical therapy (Borrillo et al. 2003; Sakimoto et al. 2005; Shiragami et al. 2007) or combined therapies (Boscia et al. 2005; Nakata et al. 2006), have been discouraging or showed limited success with recurrent exudation. Recent studies showed that combined therapy of intravitreal triamcinolone and PDT effectively reduced angiographic leakage and had a positive effect on visual acuity (Freund et al. 2006; van de Moere et al. 2007). However, intravitreal triamcinolone is associated with the potential complications of elevation of intraocular pressure, endophthalmitis and development of posterior subcapsular cataract (Spaide et al. 2003; Bhavsar et al. 2007).

More recently, promising results with off-label intravitreal bevacizumab have been reported (Joeres et al. 2007; Meyerle et al. 2007; Ghazi et al. 2008). Combined intravitreal bevacizumab and PDT for RAP had a positive effect on RAP lesions (Saito et al. 2008). Intravitreal injection of ranibizumab also was effective in the treatment of RAP in a case review of four consecutive patients (Lai et al. 2007).

The purpose of this study was to determine the outcome after intravitreal injections of ranibizumab in a larger series of patients with RAP lesions in the three-month upload phase and in the following maintenance period.

Methods

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

We report a consecutive case series of 26 eyes (26 patients) with RAP because of neovascular macular degeneration treated with intravitreal injections of ranibizumab (dose 0.5 mg in 0.05 ml, Lucentis®; Novartis Pharma, Nürnberg, Germany). Patients with RAP stages I-III in which intravitreal therapy of ranibizumab was indicated for the first time and completed at least three-month follow-up were evaluated. The diagnosis of RAP was based on clinical and angiographic findings according to Yannuzzi et al. (2001). During the upload phase in the first 3 months, patients received intravitreal injections of ranibizumab at baseline, 1 and 2 months, in the following maintenance phase in case of progression (vision loss of at least one line, worsening of macular oedema of >100 μm, persistence of leakage).

Baseline ocular examination included determination of best corrected distance visual acuity [BCVA, EN ISO 8596, BCVA was converted into logarithm of the minimum angle of resolution (logMAR) for statistical analysis], slit lamp examination, binocular biomicroscopy, fundus colour photography, optical coherence tomography (OCT) (fast macular thickness acquisition protocol, StratusOCT, Zeiss Jena GmbH, Jena, Germany), fluorescein angiography (FA, HRA II, Heidelberg Engineering, Heidelberg, Germany) and, if needed, indocyanine green angiography (ICGA, HRA II, Heidelberg Engineering, Heidelberg, Germany).

Before therapy, written informed consent was obtained from all patients after the potential risks and benefits of the intravitreal injections were explained in detail.

All patients underwent intravitreal injections of ranibizumab via pars plana under topical anaesthesia under strict aseptic conditions. Light perception and intraocular pressure were tested after the injections.

Patients were rescheduled for follow-up visits every 4 weeks. Best corrected visual acuity, slit lamp and binocular examination were performed at monthly intervals, and OCT, FA and ICGA were performed at least every 3 months.

All eyes completed at least the three-month follow-up after the first injection. None of the patients had undergone prior treatment or received additional treatment for neovascular AMD during follow-up.

Statistical analysis was performed using spss statistical software (version 14.0, SPSS Inc., Chicago, IL, USA). The primary question was if there was a difference in visual acuity between baseline and follow-up at 3 months. The significance level was fixed at α = 0.05. All other p-values were considered as explorative.

A paired t-test was performed for analysis of mean visual acuity at baseline and each follow-up visit. The change of central retinal thickness over time was evaluated using the Wilcoxon signed rank test. For each paired statistical test, casewise deletion of missing data was performed if a variable had a missing value.

An unpaired t-test was used to assess the influence of RAP stages I-III on visual acuity and change in central retinal thickness at the end of the upload phase.

Results

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Twenty-six eyes of 26 consecutive patients were included in the study. Patient age ranged from 61–94 years (mean 77 years), 18 patients were women. All eyes had 3 or more months of follow-up after the first injection of ranibizumab (this equals 1 month after the third monthly injection in the upload phase). Twelve eyes completed a 6-month follow-up, and six eyes completed a 9-month follow-up after the first injection. None of the eyes had prior treatment for neovascular AMD.

The mean number of intravitreal injections per eye was 3.46 (range 3–6). Eighteen (69%) eyes received three injections, 5 (19%) eyes received four injections, 2 (8%) eyes received five injections and 1 (4%) eye received six injections.

At baseline, nine eyes (35%) had pigment epithelium detachment and seven eyes had a stage I lesion (27%), 17 eyes a stage II lesion (65%) and two eyes a stage III lesion (8%).

At baseline, mean logMAR BCVA (EN ISO 8596) was 0.75 ± 0.38 (mean ± SD, n = 26). During the upload phase, after the first injection of ranibizumab, visual acuity improved to 0.6 ± 0.37 (p = 0.014, n = 26), after the first three injections of ranibizumab in 3-month follow-up, mean logMAR BCVA further statistically significantly improved to 0.53 ± 0.34 (p = 0.002, n = 26). In the maintenance period, at the 6-month follow-up, available for 12 eyes, mean logMAR BCVA was 0.66 ± 0.38 (p = 0.793) and 0.7 ± 0.37logMAR (p = 0.922 n = 6) 9 months after the initial ranibizumab injection (Fig. 1).

image

Figure 1.  Change in best corrected visual acuity (BCVA) (LogMAR) from baseline over time (baseline, 1, 3, 6 and 9 months follow-up), [at 1 and 3 months n = 26, at 6 months n = 12, at 9 months n = 6; y-axis BCVA (LogMAR) x-axis months of follow-up].

Download figure to PowerPoint

The BCVA in five eyes (19%) improved by three or more lines at 4 weeks, 20 eyes (77%) had stable visual acuity and one eye (4%) had a decreased BCVA of three or more lines at 4 weeks. At three-month follow-up, eight eyes (31%) had increased BCVA compared to baseline by three or more lines, 17 eyes (65%) had stable BCVA and one eye (4%) had decreased BCVA of three or more lines. At 6 months, four eyes (33%) improved by three or more lines compared to baseline, six eyes (50%) had stable BCVA and two eyes (17%) had a decreased BCVA of three or more lines. At nine-month follow-up, BCVA improved one eye (17%) by three or more lines, four eyes (67%) had stable BCVA and one eye (17%) had a decreased BCVA of three or more lines (Fig. 2).

image

Figure 2.  Percentage of patients with stable best corrected distance visual acuity (BCVA), decreased BCVA by three or more lines or improved BCVA by three or more lines at 1, 3, 6 and 9 months follow-up (at 1 and 3 months n = 26, at 6 months n = 12, at 9 months n = 6; y-axis follow-up after baseline (months), x-axis percentage of patients).

Download figure to PowerPoint

The reduction in mean central foveal thickness was largest in the first 3 months during upload phase, mean OCT central foveal thickness improved from 345 ± 55 μm at baseline to 215 ± 87 μm at 3 months (p < 0.001, n = 26). In the maintenance phase, mean OCT central foveal thickness was 259 ± 59 μm (p = 0.001, n = 13) at 6 months and 280 ± 127 μm (p = 0.31, n = 6) at nine-month follow-up after the initial ranibizumab injection (Fig. 3).

image

Figure 3.  Change in central foveal thickness from baseline over time (baseline, 3, 6 and 9 months follow-up (at 1 and 3 months n = 26, at 6 months n = 13, at 9 months n = 6; y-axis central retinal thickness in μm, x-axis months of follow-up).

Download figure to PowerPoint

The change in visual acuity was related to the stage of the RAP lesion at month 3. Eyes with RAP stage II showed the most improvement of BCVA (unpaired t-test, p = 0.017) compared to baseline compared to eyes with RAP stage I.

The change in central foveal retinal thickness at month 3 compared to baseline was also more pronounced in eyes with RAP II (mean 155.2 μm reduction) compared to eyes with RAP I (mean 110.8 μm reduction); this was not statistically significant (unpaired t-test, p = 0.191).

Because of the small number of eyes with RAP stage III (n = 2), the statistical tests did not have the power to detect differences in change in BCVA or change in central foveal thickness compared to baseline.

No ocular or systemic adverse events were observed during the upload or maintenance period.

Discussion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

Retinal angiomatous proliferation is a common subtype of AMD. In contrast to choroidal neovascularization (CNV) in AMD, the angiomatous proliferation originates from the retina and extends posteriorly into the subretinal space.

In 2001, three different stages were identified by Yannuzzi et al. (2001): intraretinal neovascularization in stage I, subretinal neovascularization in stage II and CNV with a vascularized pigment epithelium detachment and retinal-choroidal anastomosis in stage III (Yannuzzi et al. 2001). Recently, the term ‘Type 3 neovascularization’ was introduced to emphasize the intraretinal location of the vascular complex and to distinguish neovascularization in RAP from the Gass CNV Type 1 and Type 2 anatomical classification (Freund et al. 2008).

Retinal angiomatous proliferation has been identified to have a poor prognosis, and therapy appears to be most challenging, as most of the established treatments for exudative AMD have limited success for RAP (Slakter et al. 2000; Borrillo et al. 2003; Boscia et al. 2004, 2005; Sakimoto et al. 2005; Johnson & Glaser 2006; Nakata et al. 2006; Panagiotidis et al. 2006; Shiragami et al. 2007; Silva et al. 2007).

In our study, we found that at the end of the upload phase all but one eye had stable visual acuity. In eight eyes, visual acuity improved by three or more lines compared to baseline. The reduction in mean central foveal thickness was largest in the first 3 months during upload phase (Fig. 4). No adverse events were observed.

image

Figure 4.  Retinal angiomatous proliferation (RAP) lesion in an 88-year-old man at baseline (upper row). Early and late fluorescein angiography (FA) shows leakage and intraretinal oedema. Indocyanine green angiography (ICGA) shows the RAP lesion. Optical coherence tomography (OCT) shows cystoid macular oedema. After three intravitreal injections of ranibizumab, at 3-month follow-up (lower row), no leakage on FA can be observed. The hot spot on ICGA resolved and OCT shows normalization.

Download figure to PowerPoint

Antivascular endothelial growth factor (anti-VEGF) therapy has been established as an effective treatment for subfoveal CNV in exudative AMD (Gragoudas et al. 2004; Brown et al. 2006; Rosenfeld et al. 2006). Ranibizumab is an antibody fragment derived from a murine antibody to VEGF and binds all active isoforms of VEGF, it is approved for the treatment of neovascular AMD and intravitreal use. Results from large, prospective clinical trials have shown that intravitreal injections of ranibizumab can inhibit CNV and improve visual acuity in approximately 40% of patients (Brown et al. 2006; Rosenfeld et al. 2006). Transgenic mice with increased expression of VEGF demonstrated new vessel formation proliferation originating from the deep retinal capillary plexus (Tobe et al. 1998). Reports on the efficacy of ranibizumab treatment for RAP lesions are limited but the results in the use of ranibizumab for RAP lesions so far are promising. In the PrONTO study, Fung et al. (2007) reported that 10 of the 40 patients included had RAP lesions and that patients with RAP required a higher mean number of intravitreal injections of ranibizumab compared to patients with other types of neovascular CNV. However, in the PrONTO study, visual acuity and OCT outcomes were not published separately for patients with RAP lesions, and therefore, efficacy of therapy in patients with RAP lesions remained unclear.

Rouvas et al. (2009) treated 13 eyes with RAP with 3 monthly injections of ranibizumab, 13 eyes with PDT followed by 3 monthly injections of ranibizumab and 11 eyes with PDT and one injection of 4 mg triamcinolone. Eight eyes in the group treated with ranibizumab alone had stable or better visual acuity at the end of follow-up. They observed a significant trend towards better functional and anatomical results in the PDT and triamcinolone group (Rouvas et al. 2009).

Lai et al. (2007) showed that three injections of ranibizumab at monthly intervals for RAP in four consecutive patients resulted in a gain in visual acuity and reduction in central macular thickness. One patient in their series developed recurrence of RAP 8 months after commencement of therapy but responded well to retreatment.

Freund et al. (2008) treated three patients with RAP lesions with a single injection of intravitreal ranibizumab that resulted in resolution of the intraretinal oedema and neovascular lesion.

Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA, USA) is a humanized monoclonal VEGF antibody, which is Food and Drug Administration approved for intravenous use in patients with colorectal cancer.

Meyerle et al. (2007) reported in a retrospective review of consecutive patients with RAP treated with intravitreal bevacizumab during a 3-month period similar short-term visual acuity and anatomical responses compared to our study. After intravitreal bevacizumab therapy, at 3-month follow-up, 29.4% (compared to 30.8% in our series) had improved visual acuity and 64.7% (compared to 65.4% in our series) remained stable. Noteworthy of their review is the small percentage of RAP III lesions (Meyerle et al. 2007). This is also the case in our study.

Ghazi et al. (2008) also reported their short-term experience with intravitreal bevacizumab of RAP. They found stabilization of visual acuity and central retinal thickness after a single injection for at least 8 weeks, suggesting that an injection frequency of less than one per month may be sufficient (Ghazi et al. 2008).

Wolf et al. (2008) retrospectively evaluated 82 eyes with RAP treated with intravitreal bevacizumab. They reported a significant improvement of visual acuity after the upload phase, but a decrease in visual function five to twelve months after completion of the upload phase (Wolf et al. 2008). In our study, we also found an improvement of visual acuity compared to baseline after 9 months in only in 16.7% compared to 30.77% at the end of the upload phase. In contrast to the three and 6 months anatomical response, change in central retinal thickness after 9 months was not statistically different to baseline.

The difficulty in treatment of RAP may be because of the high-flow nature of the lesions, an anastomotic connection between the retinal and choroidal circulation and associated detachment of the retinal pigment epithelium. In our series, retreatment after the 3-month upload phase was needed in 30.8% of patients. Joeres et al. (2007) also found in a prospective case series that after intravitreal injections of bevacizumab in eyes with RAP, a complete occlusion of feeder vessels within a three-month period could not be achieved.

We found the most improvement of BCVA and change in central foveal retinal thickness in eyes with RAP II. We presume that this might be explained by the fact that in RAP I, visual function often is only slightly reduced as it constitutes the earliest manifestation of RAP. Growth of retinal vessels in RAP II into the subretinal space then leads to a further decrease in visual function and increase in macular oedema. In RAP III eyes, retinal changes are more pronounced and might be irreversible, because of the small percentage of RAP III eyes in our review this cannot be concluded from the current observation.

This study has some limitations that must be recognized: we had no control group, all eyes completed the 3-month follow-up but less than half of the eyes included in the study could be evaluated six or 9 month after baseline. The short-term results obtained with intravitreal ranibizumab in eyes with RAP in this study appear promising. However, disease recurrence in the maintenance period suggests that patients with RAP must be monitored closely to permit early retreatment. Our results suggest that further large and long-term prospective randomized studies are needed to determine the efficacy and safety of intravitreal ranibizumab treatment of eyes with RAP and to determine the optimal dosing strategy.

Acknowledgement

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References

The authors have no commercial, proprietary or financial interest in any of the products or companies described in this article. This article has not been presented at a meeting. The authors have not received funding for research on the topic of this article. The study was performed at the Department of Ophthalmology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany.

References

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgement
  8. References
  • Bhavsar AR, Ip MS & Glassman AR (2007): The risk of endophthalmitis following intravitreal triamcinolone injection in the DRCRnet and SCORE clinical trials. Am J Ophthalmol 144: 454456.
  • Borrillo JL, Sivalingam A, Martidis A & Federman JL (2003): Surgical ablation of retinal angiomatous proliferation. Arch Ophthalmol 121: 558561.
  • Boscia F, Furino C, Sborgia L, Reibaldi M & Sborgia C (2004): Photodynamic therapy for retinal angiomatous proliferations and pigment epithelium detachment. Am J Ophthalmol 138: 10771079.
  • Boscia F, Furino C, Prascina F, Delle Noci N, Sborgia L & Sborgia C (2005): Combined surgical ablation and intravitreal triamcinolone acetonide for retinal angiomatous proliferation. Eur J Ophthalmol 15: 513516.
  • Bottoni F, Massacesi A, Cigada M, Viola F, Musicco I & Staurenghi G (2005): Treatment of retinal angiomatous proliferation in age-related macular degeneration: a series of 104 cases of retinal angiomatous proliferation. Arch Ophthalmol 123: 16441650.
  • Bressler NM (2005): Retinal anastomosis to choroidal neovascularization: a bum rap for a difficult disease. Arch Ophthalmol 123: 17411743.
  • Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP & Schneider S (2006): Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355: 14321444.
  • Freund KB, Klais CM, Eandi CM, Ober MD, Goldberg DE, Sorenson JA & Yannuzzi LA (2006): Sequenced combined intravitreal triamcinolone and indocyanine green angiography-guided photodynamic therapy for retinal angiomatous proliferation. Arch Ophthalmol 124: 487492.
  • Freund KB, Ho IV, Barbazetto IA et al. (2008): Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina 28: 201211.
  • Fung AE, Lalwani GA, Rosenfeld PJ et al. (2007): An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 143: 566583.
  • Ghazi NG, Knape RM, Kirk TQ, Tiedeman JS & Conway BP (2008): Intravitreal bevacizumab (avastin) treatment of retinal angiomatous proliferation. Retina 28: 689695.
  • Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M & Guyer DR (2004): Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351: 28052816.
  • Gross NE, Aizman A, Brucker A, Klancnik JM Jr & Yannuzzi LA (2005): Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation. Retina 25: 713718.
  • Joeres S, Heussen FM, Treziak T, Bopp S & Joussen AM (2007): Bevacizumab (Avastin) treatment in patients with retinal angiomatous proliferation. Graefes Arch Clin Exp Ophthalmol 245: 15971602.
  • Johnson TM & Glaser BM (2006): Focal laser ablation of retinal angiomatous proliferation. Retina 26: 765772.
  • Lai TY, Chan WM, Liu DT & Lam DS (2007): Ranibizumab for retinal angiomatous proliferation in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 245: 18771880.
  • Meyerle CB, Freund KB, Iturralde D et al. (2007): Intravitreal bevacizumab (Avastin) for retinal angiomatous proliferation. Retina 27: 451457.
  • van de Moere A, Kak R, Sandhu SS & Talks SJ (2007): Anatomical and visual outcome of retinal angiomatous proliferation treated with photodynamic therapy and intravitreal triamcinolone. Am J Ophthalmol 143: 701704.
  • Nakata M, Yuzawa M, Kawamura A & Shimada H (2006): Combining surgical ablation of retinal inflow and outflow vessels with photodynamic therapy for retinal angiomatous proliferation. Am J Ophthalmol 141: 968970.
  • Panagiotidis D, Karagiannis DA & Baltatzis S (2006): Photodynamic therapy in retinal angiomatous proliferation stage I. Eur J Ophthalmol 16: 326329.
  • Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY & Kim RY (2006): Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355: 14191431.
  • Rouvas AA, Papakostas TD, Vavvas D, Vergados I, Moschos MM, Kotsolis A & Ladas ID (2009): Intravitreal ranibizumab, intravitreal ranibizumab with PDT, and intravitreal triamcinolone with PDT for the treatment of retinal angiomatous proliferation: a prospective study. Retina 29: 536544.
  • Saito M, Shiragami C, Shiraga F, Nagayama D & Iida T (2008): Combined intravitreal bevacizumab and photodynamic therapy for retinal angiomatous proliferation. Am J Ophthalmol 146: 935941. e1.
  • Sakimoto S, Gomi F, Sakaguchi H & Tano Y (2005): Recurrent retinal angiomatous proliferation after surgical ablation. Am J Ophthalmol 139: 917918.
  • Shiragami C, Iida T, Nagayama D, Baba T & Shiraga F (2007): Recurrence after surgical ablation for retinal angiomatous proliferation. Retina 27: 198203.
  • Silva RM, Cachulo ML, Figueira J, de Abreu JR & Cunha-Vaz JG (2007): Chorioretinal anastomosis and photodynamic therapy: a two-year follow-up study. Graefes Arch Clin Exp Ophthalmol 245: 11311139.
  • Slakter JS, Yannuzzi LA, Schneider U et al. (2000): Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration. Ophthalmology 107: 742753. discussion 753-4.
  • Spaide RF, Sorenson J & Maranan L (2003): Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization. Ophthalmology 110: 15171525.
  • Tobe T, Okamoto N, Vinores MA, Derevjanik NL, Vinores SA, Zack DJ & Campochiaro PA (1998): Evolution of neovascularization in mice with overexpression of vascular endothelial growth factor in photoreceptors. Invest Ophthalmol Vis Sci 39: 180188.
  • Wolf A, Kook D, Kreutzer T, Gandorfer A, Haritoglou C, Kampik A & Ulbig M (2008): [Anti-VEGF treatment for retinal angiomatous proliferation]. Ophthalmologe 105: 845851.
  • Yannuzzi LA, Negrao S, Iida T et al. (2001): Retinal angiomatous proliferation in age-related macular degeneration. Retina 21: 416434.