|Ahead of print publication
Retinal vasoproliferative tumor regression after intravitreal aflibercept
Ting-Wen Chu1, Shawn H Tsai2, Lee-Jen Chen1
1 Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan
2 Department of Ophthalmology, Mackay Memorial Hospital; Department of Optometry, Mackay Junior College of Medicine, Nursing, and Management; Department of Medicine, Mackay Medical College, Taipei, Taiwan
|Date of Submission||21-Feb-2022|
|Date of Acceptance||17-Mar-2022|
|Date of Web Publication||30-May-2022|
Shawn H Tsai,
Department of Ophthalmology, Mackay Memorial Hospital, No. 92, Section 2, Zhongshan N. Road, Taipei 10449
Source of Support: None, Conflict of Interest: None
Retinal vasoproliferative tumors (RVPTs) are rare benign retinal lesions typically located in the inferotemporal peripheral retina. Several treatment options exist for the management of RVPTs, but no consensus has been proposed. There are only a few reports on the use of anti-vascular endothelial growth factor with bevacizumab to treat exudative or neovascular retinal changes secondary to RVPTs. This report describes a 68-year-old female with a history of systemic hypertension that presented with a 2-week history of gradual loss of visual acuity in the right eye. Fundoscopic examination showed a RVPTs with atypical location that had a favorable response to two-intravitreal aflibercept injections 1 month apart, with resulting subretinal fluid absorption and tumor regression.
Keywords: Aflibercept, angiogenesis inhibitors, retinal neoplasms
| Introduction|| |
Retinal vasoproliferative tumors (RVPTs) are uncommon benign retinal lesions that typically emerge in the fourth and fifth decades of life. Men and women appear to be equally affected. These tumors appear yellowish-red on fundoscopy and are primarily located in the inferotemporal peripheral retina. In contrast to retinal capillary hemangiomas, RVPTs generally lack dilated and tortuous feeder vessels. They can be primary or secondary to preexisting ocular conditions, such as intermediate uveitis, retinitis pigmentosa, coats disease, neurofibromatosis, or other inflammatory diseases.
Several treatment options are available for the management of RVPTs. Clinical observation alone is suitable for patients with good visual acuity, small and stable tumors, and no subretinal fluid. For those who require treatment, photodynamic therapy, and surgical resection have caused tumors regression; however, subretinal fluid and exudate might increase due to inflammation. Laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) or dexamethasone might improve visual acuity, subretinal fluid, or neovascular retinal changes but cannot change the tumor's size. The treatments above can be used alone or in combination, but no consensus on treatment has been proposed.,,,,
There are three main types of injectable anti-VEGF drugs used in the eye: aflibercept (Regeneron Pharmaceuticals, Inc., Tarrytown, NY), bevacizumab (Genentech, Inc., South San Francisco, CA), and ranibizumab (Genentech, Inc., South San Francisco, CA). They reduce VEGF activity and decrease angiogenesis and vascular permeability. Ranibizumab is a recombinant humanized antibody fragment that binds to and inhibits all active isoforms of VEGF-A and their active degradation products. Bevacizumab is a full-length monoclonal antibody against all isoforms of VEGF-A. Aflibercept is a glycosylated recombinant fusion protein that acts as a VEGF receptor decoy. It is composed of a combination of a fusion of the second immunoglobulin domain of VEGF-1, and the third immunoglobulin binding domain of human VEGF-2 with the constant fragment crystallizable portion of the human immunoglobulin G. Aflibercept binds all isoforms of VEGF-A with a higher affinity than ranibizumab and bevacizumab and also binds to VEGF-B and placental-like growth factor; it can fully penetrate all retinal layers.,
There are only a few reports on the use of anti-VEGF with bevacizumab for exudative or neovascular retinal changes secondary to RVPTs., Our patient with RVPT had a favorable response to intravitreal aflibercept (IVA) injection alone, resulting in subretinal fluid absorption and tumor regression.
| Case Report|| |
A 68-year-old female presented to our hospital with controlled systemic hypertension. She denied previous ocular history and complained of progressively decreasing visual acuity in her right eye for 2 weeks. The best-corrected visual acuity was 20/66 in the right eye and 20/28 in the left eye.
The anterior segment showed one plus nuclear sclerosis in both eyes. Funduscopic examination of the right eye showed a 2.3 mm yellowish-red intraretinal mass at the temporal upper arcade, which was surrounded by hard exudates and retinal hemorrhages [Figure 1]a. Optic coherent tomography revealed a marked mass with an epiretinal membrane, with subretinal fluid surrounding the mass extending to the subfoveal area [Figure 1]b and [Figure 2]a. Fluorescein angiogram showed initial hyperfluorescence with tortuous and telangiectatic vessels within the tumor with slight late leakage corresponding to the tumor [Figure 1]c and [Figure 1]d. There was no abnormal feeding vessel surrounding the mass lesion. Based on these clinical findings, RVPT was diagnosed in the patient's right eye.
|Figure 1: Photographs of the right eye at the initial visit. (a) Fundus photography. A retinal vasoproliferative tumor at the superior temporal arcade, encircled by hard exudates and a retinal hemorrhage. (Green line indicating the location of the tumor on optical coherence tomography). (b) Optical coherence tomography. A marked intraretinal mass with an epiretinal membrane, with subretinal fluid surrounding the mass. (c) The early phase of fluorescein angiography shows hyperfluorescence with tortuous and telangiectatic vessels within the tumor. (d) The late phase of fluorescein angiography shows dye leakage|
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|Figure 2: Optical coherence tomography scan of the macula during follow-up. (a) Initial visit: subretinal macular fluid and epiretinal membrane. (b) One month after the first intravitreal aflibercept injection: decreased subretinal fluid. (c) Three years after the initial visit: no subretinal fluid|
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The patient received IVA injection (2 mg/0.05 mL), and the exudative retinal detachment rapidly regressed after 1 month [Figure 2]b. An additional IVA injection (2mg/0.05mL) was then administered, and the tumor cleared with no residual subretinal fluid [Figure 3]. At 3 years of follow-up, her best-corrected visual acuity was over 20/25 in the right eye. A fibrotic mass was left and the macula remained dry with no recurrence of exudation or subretinal fluid [Figure 2]c and [Figure 4].
|Figure 3: Photographs of the right eye 1 month after the second intravitreal aflibercept injection. (a) Fundus photography. Tumor regression after intravitreal aflibercept. (b) Optical coherence tomography. Tumor regression with epiretinal membrane and there was no subretinal fluid. (c) The early phase of fluorescein angiography shows regressed tumor with only mild vessel tortuosity. (d) The late phase of fluorescein angiography shows no dye leakage|
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|Figure 4: Photographs of the right eye at 3 years of follow-up. (a) Fundus photography. A fibrotic mass remains where the retinal vasoproliferative tumor regressed. (b) Optical coherence tomography angiography. There was no recurrence of retinal vasoproliferative tumor. (Orange circle indicating the previous location of vasoproliferative tumor)|
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| Discussion|| |
We present a case of a unilateral primary RVPT with macular complications and an atypical location in the supratemporal arcade. The diagnosis was made with fundoscopy, which revealed a fibrous solid tumor with telangiectasias, retinal hemorrhages, exudates, and serous retinal detachment. The differential diagnosis of RVPTs includes other vascular or tumorous lesions of the ocular fundus, such as macroaneurysm and retinal capillary hemangiomas., Fluorescein angiography may be the most informative diagnostic study to identify these tumors. Fluorescein angiogram shows the characteristics of RVPTs due to initial hyperfluorescence with tortuous and telangiectatic vessels within the tumor. RVPTs generally lack dilated and tortuous feeder vessels in contrast to hemangiomas. Macroaneurysms differ from RVPTs because the fluorescein dye should fill up uniformly in the early phase, revealing a fusiform dilation of the arteriole. Shields et al. reported that RPVTs are rare benign tumors usually located in regions between the equator and ora serrata (73%) followed by areas between the macula and equator (24%). Tumor location in the inferotemporal quadrant is also the most common (67%). The diagnosis is usually based on the clinical appearance of fundoscopy. These tumors can be classified as primary or secondary, with the former being more common than the latter.
Our patient had an RVPT with an exudative retinal detachment that resulted in a gradual decline in visual acuity. There are many management for RVPTs with macular complications, but none of them is conclusive.,,,, Due to the atypical location near the supratemporal arcade, laser photocoagulation might not be the suitable choice. We administered IVA to treat the subretinal fluid secondary to the tumor, and both the tumor and subretinal fluid rapidly regressed.
On histopathological observation, RVPTs are vascularized glial tumors with marked hyalinization, believed to result from the proliferation of blood vessels with thickened vessel walls, glial tissue, and retinal pigment epithelium. Immunoreactivity for VEGF was detected in the hyalinized vessels. The ideal treatment scheme for RVPTs is yet to be determined. Aflibercept, which reduces VEGF activity and leads to decreased angiogenesis and vascular permeability was approved by the United States Food and Drug Administration to treat wet age-related macular degeneration, macular edema following retinal vein occlusion, diabetic retinopathy, and diabetic macular edema. Aflibercept can fully penetrate all retinal layers and has a higher connection with VEGF than other anti-VEGF drugs, such as bevacizumab and ranibizumab., The expression of VEGF and the benefits of intravitreal injection of anti-VEGF have already been reported in other retinal vascularized tumors, such as hemangioblastoma and astrocytic hamartoma., There are only a few reports on the use of anti-VEGF for exudative or neovascular retinal changes secondary to RVPTs.,
To the best of our knowledge, this is the first report of successful treatment of RVPT-associated exudative and neovascular changes, solely with intravitreal injection of aflibercept. It not only improved the patient's vision but also promoted tumor regression. This suggests that VEGF may be involved in the proliferative pathway of RVPT formation and is a potential candidate for first-line treatment for RVPTs with prominent subretinal fluid. More case reports or studies with controlled variables on patients with these types of tumors are needed to confirm this.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
The authors declare that there are no conflicts of interests of this paper.
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