Anti-vascular endothelial growth factors for choroidal neovascularization secondary to choroidal osteoma: Long-term results.

Choroidal osteoma is an uncommon benign osseous intraocular tumor typically seen unilaterally in young women. Visual loss can occur due to choroidal neovascularization (CNV) complicating osteoma. We report a rare case of bilateral choroidal osteoma with secondary CNV in a young male and the long-term results following anti-vascular endothelial growth factor (VEGF) therapy. A 30-year-old male with history of defective vision in both eyes since several years and recent worsening in the right eye (RE) since 2 months was found to have bilateral macular osteoma with CNV in the RE based on clinical evaluation, fluorescein angiography, optical coherence tomography, and ultrasonography. Intravitreal injection of ranibizumab at monthly intervals for three doses resulted in resolution of CNV and remained stable for 5 years. Recurrent CNV detected 6 years later responded to an injection of intravitreal bevacizumab and has remained stable till date. Anti-VEGF therapy stabilized the secondary CNV in our patient for 7 years with satisfactory structural and functional outcome, demonstrating the long-term efficacy of this modality of treatment.

Introduction

Choroidal osteoma is an ossifying tumor within the choroid of unknown etiology, first described by Gass et al., in 1978.[1] It is an uncommon tumor comprising only 4% of choroidal mass lesions.[2] It has a female preponderance with 89% reported in young women and the majority (75%) presentation is unilateral.[34] It is described as yellowish white to orange-red tumor, slightly and irregularly elevated with distinct geographic borders, located at juxtapapillary or peripapillary region but may extend to macula also.[345] Development of choroidal neovascularization (CNV) is the major cause for the sudden visual loss in this benign tumor. Various modalities are described for treatment of CNV secondary to osteoma.[34678910] We report a young male with bilateral macular choroidal osteoma which is a very rare presentation. We also present the 7-year follow-up results of anti-vascular endothelial growth factor (VEGF) therapy for the secondary CNV in this patient. To our knowledge, this is the longest follow-up reported for anti-VEGF therapy in CNV complicating osteoma.

Case Report

A 30-year-old healthy male presented to us in September 2007 with complaints of gradual painless diminution of vision in both eyes (BE) since several years, which has worsened over the past 2 months in the right eye (RE). On examination, his visual acuity was counting finger (CF) at one meter in the RE and 20/200, N.18 in the left eye. Anterior segment examination and intraocular pressures were normal in BE. Fundus examination showed yellowish to orange, slightly elevated sub retinal lesion with well-defined geographic margins over the posterior pole in BE [Figure 1a and b]. RE had a small sub-foveal grayish lesion suggestive of CNV with overlying sub retinal hemorrhage. Fundus fluorescein angiography (FFA) showed patchy hyperfluorescence and late staining in BE. RE also showed blocked fluorescence due to sub retinal hemorrhage and minimal leakage from CNV [Figure 2a]. Ultrasonography showed minimally elevated lesion over the posterior pole with high reflectivity and orbital shadowing in BE confirming the diagnosis of osteoma [Figure 2b]. Optical coherence tomography (OCT) showed diffuse thickening of retinal pigment epithelium (RPE) and choroid with intact inner retinal layers in BE and CNV subfoveally in the RE [Figure 3a]. After written consent, he was treated by intravitreal injection of ranibizumab (0.5 mg in 0.05 ml) in the RE at monthly intervals for 3 months. Following treatment sub retinal hemorrhage disappeared, OCT showed resolution of CNV with the restoration of foveal contour and visual acuity improved to 20/200 [Figure 3b]. He was under regular follow-up and remained stable. At his regular visit in January 2013, he complained of a recent decrease in vision in the RE, which was found to be reduced to CF at 3 m. Fundus examination of BE revealed enlargement of osteoma with zones of decalcification and no visible CNV [Figure 4a and b]. FFA of the RE showed patchy hyperfluorescence without leakage [Figure 4 c and d] while OCT showed subretinal fluid (SRF) subfoveally suggestive of recurrent CNV [Figure 5a]. Following an injection of intravitreal bevacizumab (1.25 mg in 0.05 ml), SRF resolved completely, restoring vision to 20/200 and has remained stable for the past 1 year [Figure 5b].

Figure 1

(a and b) Color fundus photographs of both eyes in September 2007 showing macular choroidal osteoma and subfoveal choroidal neovascularization with hemorrhage in the right eye (black arrow)

Figure 2

(a) Fundus fluorescein angiography of the right eye (RE) showing blocked fluorescence due to sub retinal hemorrhage and minimal leakage from the choroidal neovascularization (white arrow). (b) Ultrasonography of the RE showing the echo dense lesion with orbital shadowing

Figure 3

(a) Stratus optical coherence tomography (OCT) of the right eye (horizontal line scan) showing the high reflective irregular thickening of retinal pigment epithelium and choroid with a subfoveal choroidal neovascularization, distorting the foveal contour. (b) OCT after three injections of ranibizumab showing resolution of the choroidal neovascularization and restoration of the foveal contour

Figure 4

(a and b) Colour fundus of the right eye and left eye in January 2013 showing growth of osteoma with zones of decalcification and no visible choroidal neovascularization. (c and d) Early and late phase of fundus fluorescein angiography in January 2013 showing only patchy hyperfluorescence with no leakage

Figure 5

(a) Spectral domain optical coherence tomography (OCT) (5 line raster scan) of the right eye in January 2013 showing subfoveal detachment suggestive of recurrent choroidal neovascularization. (b) OCT showing complete resolution of subretinal fluid after a single injection of bevacizumab

Discussion

Visual loss in eyes with choroidal osteoma can result from the macular location of the tumor, development of CNV or serous detachment, decalcification, and overlying RPE atrophy.[56] Shields et al., have reported evidence of tumor growth in 51%, decalcification in 50% and development of CNV in 31% of eyes over a period of 10 years.[5] Irregular surface of tumor and presence of sub retinal hemorrhage have been identified as predictive factors for CNV. Disruption of RPE and thinning or loss of Bruch's membrane overlying the osteoma facilitates the growth of neovascular fronds from the choroid. Treatment options described for these CNV include thermal laser photocoagulation, photodynamic therapy, and trans pupillary thermotherapy, but have shown poor outcome due to lack of pigmentation within the tumor and the thin, degenerated RPE overlying the tumor. Moreover, it can result in tumor decalcification with the further visual loss.[346] Intravitreal anti-VEGF injections such as ranibizumab and bevacizumab have been proved as successful therapeutic options for CNV secondary to age-related macular degeneration and other etiologies. Ahmadieh and Vafi first reported the efficacy of anti-VEGF agent bevacizumab in the treatment of CNV due to osteoma in a young female.[7] Osteoma being a slowly growing tumor can lead to mild ischemia and inflammation with up-regulation of VEGF which in turn stimulates the growth of abnormal vessels through a degenerated RPE.[56] Anti-VEGF therapy thus may be a more viable alternative in this situation. Favorable effects of anti-VEGF drugs could also be due to the degenerated RPE overlying the osteoma which facilitates better penetration of the drug into the sub retinal space.[8] In our patient with bilateral macular osteoma and a subfoveal CNV in one eye, anti-VEGF therapy was the preferred option. The three primary injections of ranibizumab resulted in both structural and functional improvement, which was sustained for more than 5 years. Similar improvements have been reported by other authors, but follow-up period is relatively small.[810] Kubota-Taniai et al., have reported a case of a young female with unilateral CNV secondary to osteoma treated with two injections of bevacizumab at 4 months intervals and followed up for 4 years, with no recurrence.[6] Our patient remained stable for more than 5 years and the recurrent CNV developed in the 6th year responded to a single injection of bevacizumab. The fact that recurrence occurred in the 6th year points to the need for continued follow-up in these patients. Surprisingly, during the entire period of 7 years, the fellow eye never developed CNV. To our knowledge, this is the longest follow-up reported for anti-VEGF therapy in CNV complicating osteoma. Moreover, as our patient and the case reported by Kubota-Taniai et al., were successfully managed with few injections of anti-VEGF drugs (4 and 2 respectively) over a long period, it may be believed that monotherapy with anti-VEGF drugs would suffice for the treatment of CNV secondary to osteoma. However, only a long-term study involving a larger number of patients (pooled from multiple centers) can provide more definitive guidelines regarding the treatment of CNV in these eyes.