Successful Aflibercept Treatment for Choroidal Neovascularization in a Rare Case of Optic Disc Melanocytoma

Introduction

Optic disc melanocytoma (also called magnocellular nevus of the optic disc) is a hamartoma, a specific variant of melanocytic nevus located on the optic disc, which is benign, brownish or dark-colored, and occasionally encompassing adjacent choroid and retina with well-defined borders. However, melanocytoma can be located on each part of the uveal tract (iris, ciliary body, and choroid). It is supposedly due to a congenital lesion that grows and pigments over time [1–3]. Most of time, melanocytoma is unilateral. There is no ethnic predominance, but it is slightly more common in women, and median age at diagnosis is 50 years. There is no association with systemic disease; however, some cases of meningiomas are described [4,5]. Melanocytoma is diagnosed in a routine fundus examination, as it is often asymptomatic. Sometimes, it is difficult to differentiate from juxta-papillary melanoma, and multimodal imaging and observation are essential to make the differential diagnosis. A few complications are associated with melanocytoma and can cause decreased visual acuity: central artery or vein occlusion, anterior ischemic optic neuropathy secondary to necrosis of the tumor, and epiretinal membrane and neovascular membrane. Malignant transformation is a rare event, occurring in 1% to 2% of cases. To diagnose these complications, melanocytoma of the optic disk requires lifelong monitoring [6,7]. Even in the absence of these complications, some patients can present an afferent pupillary defect and blind spot enlargement on the central visual field [8,9].

Aflibercept is a recombinant fusion protein composed by VEGF-binding segments and human VEGF 1 and 2 receptors. It inhibits vascular endothelial growth factor A and B (anti-VEGFA/B), leading actors of angiogenesis, but also placenta growth factor. Aflibercept is officially used on exudative age-related macular degeneration, macular edema secondary central retinal vein occlusion, diabetic macular edema, and myopic-associated choroidal neovascularization [10,11]. All of these diseases are due to choroidal neovascularization, characterized by pathological blood vessels emerging from the choriocapillaris. Others treatments of choroidal neovascularization include photodynamic therapy and surgery of subretinal hemorrhage [12].

Here, we describe a 54-year-old man who received a diagnosis of optic disc melanocytoma complicated by choroidal neovascularization, which was treated with vitreous injection of aflibercept (anti-VEGF) according to a “treat and extend” protocol in an intermittent follow-up.

Case Report

In 2015, a 54-year-old man visited his ophthalmologist for a routine examination, with no symptoms. He had no medical or ophthtalmological history. His best corrected visual acuity was 10/10 on the Monoyer scale and 2 on the Parinaud scale in his right and left eye (OU). His slit lamp examination was unremarkable. His fundus examination was unremarkable in his left eye (OS), whereas in his right eye (OD), there was a dark-pigmented and bulging mass encompassing the optic disc (Figure 1).

On fluorescein angiography (FA), the lesion border was staining from the early phase, with no leakage even in the late phase, whereas the body of the lesion was hypofluorescent in all the sequences, and there were a few intratumoral blood vessels (Figure 2). On indocyanin green angiography (ICG), the lesion was hypofluorescent from the early to the late phase, raised from the retina and optic disc, and a few intratumoral blood vessels were seen in the intermediate phase. On optical coherence tomography (OCT), the lesion was a bulky hyperreflective lesion located on the optic disc, with intravitreal pigment, but no macular involvement (Figure 3). On B-scan ultrasonography, the lesion was hyperechogenic, borders were well limited, and it was measured at 2.70×4×5 mm. We diagnosed an optic disc melanocytoma and decided to observe the patient every 6 months.

One year after diagnosis, the lesion was growing and vitreous seeding was more prominent; therefore, we decided to discuss the case with our colleagues from the Curie Institute in Paris, a center specialized in eye tumor diagnosis and treatment. We decided to perform brain magnetic resonance imaging in search of orbital and optic nerve involvement, which are signs of malignant transformation. This examination was normal, so we continued to follow the patient every 6 months.

Unfortunately, the patient stopped his follow-ups in 2019 and returned starting 2021. In 2021, 6 years after diagnosis, the patient was still asymptomatic, his best corrected visual acuity was 10/10 OU, but in the fundus examination, the lesion was growing up to inferior vascular branches. There was more vitreous seeding and a lot of exudates appeared in the inter-papillomacular region, threatening the fovea, without macular edema (Figures 4, 5). On B-scan ultrasonography, the lesion had stable thickness (2.6 mm); optical coherence tomography angiography (OCT-A) and FA failed to find a neovascular membrane, because of a blocking effect related to pigments, and it was ICG that showed an interpapillomacular lesion compatible with neovascular membrane (Figure 6).

With our Curie Institute colleagues, we diagnosed a neovascular membrane complicating optic disc melanocytoma, and we decided to treat the patient with 3 vitreous injections of Aflibercept monthly, with good clinical response demonstrated by a decrease of interpapillomacular exudates. Therefore, we decided to continue according to the “treat and extend” protocol. In January 2023, with the week 10 injection, inter-papillomacular exudates resolved. During the last follow-up, in November 2023, spacing the injection, there was still no exu-dates (Figures 7, 8). The last injection was performed in May 2024, and we decided to stop vitreous injection and closely monitor the patient.

Discussion

Our patient did not have any symptoms nor decreased visual acuity, unlike other case reports in the literature; therefore, the diagnosis of a new and beginning neovascular membrane was very difficult because of the low contribution of multimodal imaging, particularly OCT-A, which failed, and low contribution of FA and ICG. Intensive and early treatment, according to the “treat and extend” protocol of intravitreal injection of anti-VEGF, in close monitoring, prevented any anatomical and functional sequelae. This case report confirms the importance of lifetime monitoring in the case of optic disc melanocytoma, in search of malignant transformation, but also potential vascular complications, like choroidal neovascularization; it confirms the efficacy of intravitreal injection of anti-VEGF for the treatment of neovascular membranes.

As we have seen in our case report, multimodal imaging (including FA and ICG, OCT and OCT-A, B scan, and colored fundus photographs) is important to diagnose optic disc melanocytoma and its complications. However, all of these examinations can be insufficient and can even fail to recognize neovascular membrane, because of a densely pigmented lesion.

On FA, the lesion is hypofluorescent from the early to the late phase, due to a blocking effect caused by pigmentation. Nevertheless, a neovascular membrane can result in staining in the early and intermediate phase and leaking in the late phase if located next to the melanocytoma. On OCT, melanocytoma is a hyperreflective dome-shaped lesion with an heterogeneous nodular and hyperreflective surface with posterior shadow or multiple hyperreflective nodule in its surface [13]. On OCT-A, melanocytoma vascularization is heterogeneous, irregular, and made of thin blood vessels. Choriocapillaris underlying the lesion is often not visible because of a blocking effect caused by pigmentation, too [14]. It is probably the reason why OCT-A was not informative concerning the neovascularization in our case report.

Less than 1% of optic disc melanocytoma cases are complicated by neovascular membrane. There are a few cases reported in the literature. In the case reports of Pinheiro et al [15], Hamza et al [16], Kamisasanuk et al [17], and Guirou et al [18], optic disc melanocytoma was symptomatic, with decreased visual acuity, and there were peripapillary hemorrhages associated with serous retinal detachment in the macula/ fovea. Evolution was favorable after treatment by 3 intravit-real injections of anti-VEGF (ranibizumab, aflibercept, bevacizumab) monthly. Al-Halafi [19] reported a case of an optic disc melanocytoma, newly diagnosed with peripapillary neovascular membrane well-visible on FA, associated with serous retinal detachment and macular thickening, which was treated by only 1 intravitreal injection of anti-VEGF, without recurrence after 1 year. Finally, Yu et al [20] reported a presumed choroidal neovascularization with subretinal hemorrhage associated with optic disc melanocytoma successfully treated by 6 injections of aflibercept in 10 months. However, in all these case reports, after authors ruled out malignant transformation, neovascularization was easily diagnosed clinically by the presence of hemorrhages in fundus examination and serous retinal detachment on OCT; whereas in our case report, there was no hemorrhage nor serous retinal detachment, only exudates without macular thickening. Finally, FA and ICG, in our case, was more important to diagnose neovascularization than was OCT-A. Before the era of anti-VEGF, we noted 2 similar cases: the first [21] reported treatment with dynamic phototherapy with complete anatomical response and resolution of macular exudation but partial functional response, and the second [22] reported good anatomical and functional responsiveness after surgical treatment by vitrectomy and peeling of the neovascular membrane.

Conclusions

Because it is a very pigmented lesion, we need multimodal imaging (fundus examination, FA), ICG, OCT, and OCT-A to diagnose choroidal neovascularization associated with optic disc melanocytoma. Choroidal neovascularization associated with magnocellular nevus of the optic disc can be successfully treated by intravitreal VEGF-A in a “treat and extend” protocol. In the literature, options of treatment also include submacular surgery and photodynamic therapy.