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Intravitreal Vascular Endothelium Growth Factor Inhibitors for Retinal Macroaneurysms | OMICS International
ISSN: 2155-9570
Journal of Clinical & Experimental Ophthalmology

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Intravitreal Vascular Endothelium Growth Factor Inhibitors for Retinal Macroaneurysms

Carlos Menezes* and Carla Teixeira

Department of Ophthalmology, Pedro Hispano Hospital, Matosinhos, Portugal

*Corresponding Author:
Carlos Menezes
Rua Arménio Reis
lote B4, 4700-267 Real
Braga, Portugal
Tel: 00351 91625593
E-mail: [email protected]

Received date: January 27, 2016; Accepted date: June 23, 2016; Published date: June 27, 2016

Citation: Menezes C, Teixeira C (2016) Intravitreal Vascular Endothelium Growth Factor Inhibitors for Retinal Macroaneurysms. J Clin Exp Ophthalmol 7:563. doi:10.4172/2155-9570.1000563

Copyright: © 2016 Menezes C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Last year our group published the case of a foveal longstanding retinal macroaneurysm successfully treated with intravitreal ranibizumab. A few previous and subsequent studies also reported the safety and effectiveness of intravitreal vascular endothelium growth factor inhibitors (anti-VEGF) in other more common cases of retinal macroaneurysms. In this commentary we proposed to make a brief review of this entity, particularly of its complications and its management with emphasis on anti-VEGF therapy


Retinal arterial macroaneurysm; Intravitreal vascular endothelium growth factor inhibitors; Anti-VEGF


Retinal arterial macroaneurysms (RAM) are uncommon, acquired, focal dilatations of the arterial wall (fusiform or saccular). They occur most often in the macular or post-equatorial regions, in the first three orders of the arterial tree, where the perfusion pressure is higher and the arterial sac is easily perforated [1-3]. Arteriovenous crossings are at increased risk of aneurysm formation due to absence of the adventitial layer in this location, which lessens the structural support [3].

RAM is associated with age over 60 years, female gender and systemic vascular pathology as arterial hypertension, dyslipidemia and atherosclerosis [1-3].

Since 1987, RAM have been classified as exudative, hemorrhagic or quiescent, according to their clinical behavior [3]: exudative RAM cause macular edema and hard exudates leading to vision loss, if they are close to the fovea; hemorrhagic RAM bleed to subretinal, intraretinal, retrohyaloidal or vitreal spaces; quiescent RAM are usually asymptomatic but they can complicate with both exudates and hemorrhage.

There is a recent article about clinical, angiographic and tomographic description of a series of 14 cases of RAM and their therapeutic management [4]. Multimodal imaging is important for the initial assessment, being angiography [fluorescein (FA) and indocyanine green (ICGA)] and optical coherence tomography (OCT) the most important imaging modalities for the diagnosis and classification of RAM. In exudative cases FA shows dye exudation around the lesion, but in hemorrhagic cases ICGA is sometimes necessary to avoid the shadow effect of the blood and identify the aneurysm. Videoangiography shows the pulsatility of the RAM. OCT allows the monitoring of RAM occlusion [either spontaneous or after treatment with laser photocoagulation or intravitreal vascular endothelium growth factor inhibitors (anti-VEGF)], monitoring of macular edema and central macular thickness and shows complications such as atrophy and fibrosis.

The majority of RAM resolves spontaneously with spontaneous thrombosis and fibrosis. There is no established treatment protocol when RAM complicate. The most popular therapeutic intervention is laser photocoagulation directed to RAM or around it, to induce thrombosis and prevent both bleeding and exudation or to promote exudates reabsorption, respectively [1,5,6]. However, laser results are controversial and some patients show a decrease in visual acuity due to laser-induced retinal damage, caused by an early increase in exudates from selective reabsorption of fluid, arteriovenous shunts, macular pucker and scotomas [3,7]. In spite of these risks, laser treatment should be considered in patients with RAM to seal it and leaky peri- RAM vessels.

Multilevel retinal hemorrhage is a non-infrequent complication of hemorrhagic RAM [1,5]. Subretinal hemorrhage severely damages the overlying retina. Blood toxicity is the result of the reduction of metabolic exchange between the retinal pigment epithelium (RPE) and the outer retina, iron-related toxicity and fibrin-mediated retinal damage [7]. Irreversible damage of photoreceptors and RPE cells is responsible for the permanent loss of visual acuity. Retinal degeneration is established within two weeks after the development of a subretinal hemorrhage [7]. Patients with vitreous hemorrhage or premacular hemorrhage have a better visual prognosis than those with macular edema, intraretinal or submacular hemorrhage [5]. Bleeding to retrohyaloidal space may be treated with a hyaloidotomy with Nd: YAG (Neodymium: yttrium-aluminum-garnet) laser or vitrectomy, if there is a persistent retrohyaloidal or vitreous hemorrhage [1,5]. Submacular hemorrhage can be treated with vitrectomy with pneumatic displacement and intravitreal or subretinal injection of recombinant tissue plasminogen activator (rtPA) [1,5].

Exudative RAM with chronic macular edema and foveal involvement may decrease visual acuity and treatment is important to reestablish foveal anatomy and vision. Argon laser photocoagulation and anti-VEGF therapy are the major weapons to combat this complication. RAM can occlude with laser but as previously said there is a risk of laser induced retinal damage, which can limit the visual gains [6,7].

Anti-VEGF therapy, such as bevacizumab or ranibizumab, has recently been reported in the treatment of patients with exudative or hemorrhagic RAM, showing encouraging results (Table 1) [8]. We presented a case of a patient with an enormous exudative RAM within the avascular perifoveal zone successfully treated with six ranibizumab intravitreal injections [9].

Antiangiogenic intravitreal therapy is effective in closing RAM and improving macular edema and visual acuity [10,11]. The role of VEGF and the mechanism of action of anti-VEGF therapy in RAM neither are nor fully understood. These drugs seem not to act directly on the RAM itself, but rather through vasoconstriction, through which they can treat or prevent exudation and promote thrombosis without locally destructive side effects [7,10]. Anti-VEGF reduce the edema by blocking the VEGF-induced vasopermeability and can alter the coagulation process, also allowing a faster reabsorption in the case of subretinal hemorrhage [4,12]. They have a very good potential to treat perifoveal exudative RAM, just like we claimed at our case report. The use of anti-VEGF agents has been suggested as a mean of achieving rapid resolution of RAM with limited rate of complications. However, bevacizumab or ranibizumab are off-label intravitreal injections in this indication and the risk-benefit ratio must be explained to patients.

The majority of patients with RAM has a favorable visual outcome, even without treatment and can be observed with close follow-up. The most common causes of decreased vision are prolonged macular edema or subretinal hemorrhage and visual prognosis depends on severity and disease´s duration. In exudative RAM the poorest outcomes are observed when macular edema and exudates persist for several months or even years [5] (just like happened with our patient [9]). As a consequence we propose a prompt intervention in the case of an active RAM causing macular edema or threatening the fovea, either with laser or anti-VEGF therapy, according to each particular case.

Several case reports showed promising results of intravitreal anti- VEGF therapy for RAM (Table 1): significant visual and anatomical recovery of serous detachment, resolution of macular edema within two months (our case was the exception due to its chronicity) and visual acuity improvement by three or more lines in all cases. Anti- VEGF injections seem to improve visual acuity and macular edema in RAM. Future prospective randomized studies are necessary to identify the real effects of anti-VEGF as a treatment for symptomatic RAM [8,13].

Article´s first author Year of publication Anti-VEGF molecule Number of patients Pre-BCVA Post-BCVA CRT improvement (µm) Mean number of injections Follow-up (months)
Chanana[14] 2009 Bevacizumab 1 20/400 20/50 607 → 173 2 1.5
Jonas [18] 2010 Bevacizumab 1 20/400 20/200 “Completely absorbed” 1 3
Javey [16] 2010 Bevacizumab 1 20/400 20/20 - 2 12
Wenkstern [15] 2010 Ranibizumab + laser 1 20/50 20/25 510 → 148 2 5
Golan [19] 2011 Bevacizumab 1 20/160 20/20 364 → 242 2 13
Tsakpinis [17] 2011 Bevacizumab 1 20/60 20/25 - 2 39
Zweifel [20] 2013 Bevacizumab + ranibizumab 10 20/100 20/50 366 → 266 3 6
Cho [21] 2013 Bevacizumab 23 20/80 20/60 384 → 265 1.4 11
Pichi [10] 2013 Bevacizumab 38 20/75 20/25 520 → 214 3 3
Leung [8] 2015 Bevacizumab + laser 1 20/60 20/30 312 → 241 6 20
Menezes [9] 2015 Ranibizumab 1 20/200 20/50 310 → 233 6 12
Erol [12] 2015 Ranibizumab 7 20/245 20/30 427 → 208 2 19
Goel [22] 2015 Bevacizumab 1 20/200 20/30 “Normalization of the foveal contour” 2 24
Cahuzac [4] 2016 Ranibizumab or ranibizumab + laser 6 20/400 20/40 869 → 255 - 6

Table 1: Literature actualization of anti-VEGF therapy in RAM [6].


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Review summary

  1. Zach
    Posted on Jul 18 2016 at 4:57 pm
    The authors presented an up-to-date review of anti-VEGF treatment in RAM. The commentary is well written and clear. This article has interesting discussions. It is well sourced and has strong evidence for the claims made.

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