General considerations

The presence of bone within the eye is unusual and can develop in several clinical settings.¹ Calcification can occur in tissues that are accessible to body fluids.² The process of ossification occurs when an abundant blood supply is present to deliver osteoblasts to organize the architecture of Haversian systems.^2,3 The choroid and the retinal pigment epithelium are the most common sites for bone formation within the eye. Intraocular ossification most often occurs as a dystrophic process in association with phthisis bulbi and in cyclitic membranes in the setting of chronic intraocular inflammation.^2,4,5

The choroidal osteoma is an unusual form of benign intraocular ossification.^1,6,7 In contrast to other types of intraocular ossification, it is found in otherwise healthy eyes. Interest in this tumor was stimulated by the observations of Dr Henry Van Dyk and associates who had the opportunity to study the clinical and histopathologic features of a case of an idiopathic osseous tumor of the choroid in 1975.⁸ The eye had been enucleated because of the clinical suspicion of an atypical malignant melanoma in a 26-year-old woman. In 1978, Gass and coworkers⁹ correlated the typical clinical manifestations and angiographic features of the choroidal osteoma in a series of four affected patients. Gass subsequently reported new observations in 15 patients with choroidal osteomas.¹⁰ Later, Shields and associates provided a comprehensive review on the subject of choroidal osteoma, including their own personal experiences with this tumor and Aylward and associates provided long-term follow-up of patients.^1,11 Over nearly four decades, numerous clinical case descriptions of the choroidal osteoma have appeared in the literature.^11–51

Definition and incidence

Choroidal osteoma is a benign tumor of the choroid composed of mature bone. It is typically found in healthy young females in the second or third decades of life (Fig. 152.1). However, some males,^{10,16,35,37,46,52} young children,^{21,23,24,34,38,40} and adults over age 30 years^{12,15,21,32,46,50} have been diagnosed with choroidal osteoma. There is no predilection for race. Most reported patients with this lesion are Caucasian, but several patients of African American^24,31 and Oriental descent^{26,32,34,38,46,50,51} have been reported. The tumor generally occurs as a sporadic trait; however, a few cases of familial choroidal osteoma have been reported.^21,23,40 The familial cases have been described in a mother and daughter,²¹ in a brother and sister,⁴⁰ and in three siblings.²³

Fig. 152.1 Clinical spectrum of choroidal osteoma. (A) Unilateral osteoma in a young woman. (B) Unilateral osteoma in a young man. (C) Calcified choroidal osteoma with bone excavation in the macula. (D) Macular choroidal osteoma with decalcification in a young woman.

In our practice of ocular oncology, we have seen nearly 14,000 patients with uveal melanoma and only 85 patients with choroidal osteoma. Therefore, it is presumed that choroidal osteoma is extremely rare.

Clinical features

Patients with a choroidal osteoma can be asymptomatic. Symptoms can include mild to severe visual blurring, metamorphopsia, and visual field defects corresponding to the location of the tumor.^1,10 In one report, total blindness of both eyes was found in a young girl with bilateral choroidal osteomas.⁴³

Choroidal osteoma is unilateral in approximately 75% of reported cases. In bilateral cases, the tumors can appear relatively symmetric or can be asymmetric, in different stages of development, growth, or decalcification (Fig. 152.2).¹⁰ Rarely, patients with initially unilateral choroidal osteoma, can later develop bilateral disease.³⁰

Fig. 152.2 Bilateral choroidal osteoma. (A,B) Small calcified osteomas in macula of young man. (C,D) Larger partially calcified osteomas in a young woman. (E,F) Partially decalcified choroidal osteoma in right eye with subretinal hemorrhage and completely calcified osteoma in the left eye of a young woman.

The choroidal osteoma tends to be located in the juxtapapillary or peripapillary area, often with extension into the macula (Fig. 152.1). Rarely, this tumor is confined to the macular region only, without involvement of the juxtapapillary area.^{10,16,32,35,52} Choroidal osteoma is rarely seen in other locations of the eye and, to our knowledge, it has not been known to occur as a solitary lesion anterior to the retinal vascular arcades. Quite often choroidal osteoma is confused with idiopathic sclerochoroidal calcification, a benign, often multifocal, bilateral process that typically occurs anterior to the retinal vascular arcades, near the equator of the eye.^53,54

The choroidal osteoma appears yellow-orange in color, particularly when the tumor is fully calcified. Over time, as decalcification occurs, the tumor becomes more pale yellow with overlying retinal pigment epithelial thinning and clumping. Choroidal osteoma ranges in size from approximately 2–22 mm in basal dimension and approximately 0.5–2.5 mm in elevation.^1,10,11,20 In some cases, the bony tumor surface is irregularly excavated (Fig. 152.1) or elevated. The tumor shape is generally oval or round with characteristic well-defined scalloped or geographic margins. The margins can have blunt pseudopod-like projections. In some instances the tumor can be bilobed with two large plaques joined together by an isthmus.^10,30

The vasculature within the choroidal osteoma is sometimes visible. Tufts of short branching vessels that originate deep within the tumor and emerge onto the tumor surface can be seen. They are especially prominent over the pale yellow portion of the tumor where the retinal pigment epithelium is thinned and depigmented.⁹ These large-caliber vessels are not neovascular tissue and are not associated with subretinal exudation or hemorrhage, or retinal pigment epithelial alterations.^1,10 The overlying retinal vasculature and optic disc is characteristically unaffected by the osseous tumor and there are no associated vitreous or anterior segment abnormalities.

Many choroidal osteomas show evidence of slight enlargement in basal dimensions over several months to years (Fig. 152.3).^{11,38,41,44,48,55} Aylward and associates found tumor growth in 41% of 22 cases over a mean follow-up of 10 years.¹¹ Shields and associates found tumor growth of 74 choroidal osteomas at 22% by 5 years and 51% by 10 years.⁵⁶ In some cases, the tumor has doubled in size.^10,41 Others have observed the development of a new choroidal osteoma in a previously unaffected eye.^1,10

Fig. 152.3 Documented enlargement (A,B) of choroidal osteoma over 6 years. (A) November 1986; (B) September 1992.

Trimble et al. reported a case of a choroidal osteoma in a 23-year-old woman, whose tumor enlarged slowly over 5 years.⁴⁷ She developed a choroidal neovascular membrane that was treated with photocoagulation. Later, the tumor gradually decalcified over 18 months, leaving a bed of atrophy. Partial or complete decalcification of choroidal osteoma has been found to occur in 28% of cases by 5 years and 46% by 10 years.^{18,28,44,49,56} Subtle, gradual alterations in tumor color, surface pigmentation, and surface contour have also been observed.

Serous subretinal fluid can occur overlying choroidal osteoma.¹⁰ Subretinal fluid usually occurs over the macular portion of the osteoma. Careful ophthalmoscopy and fluorescein angiography should be performed for detection of choroidal neovascular membrane (CNVM) if symptoms or signs warrant.²⁷

Choroidal neovascular membrane overlying osteoma has been found in 31% of cases by 5 years, 31–47% by 10 years, and 46–56% by 20 years (Fig. 152.4, Table 152.1).^11,56 The CNVM is usually associated with subretinal fluid or hemorrhage, but it can be detected prior to vascular leakage as a slightly elevated gray-green subretinal tissue.^15,37 Factors that predict the development of CNVM include irregular tumor surface and subretinal hemorrhage (Table 152.2).⁵⁶ If the CNVM is extrafoveal then it can be treated with laser photocoagulation or photodynamic therapy.^11,27 If the CNVM is in the fovea, the potential for subfoveal hemorrhage and disciform scarring often leads to a poor visual outcome.^33,56 For subfoveal (and most extrafoveal) CNVM, we prefer antivascular endothelial growth factor (anti-VEGF) therapy monthly to resolve the membrane and then consolidation for extrafoveal CNVM with laser or photodynamic therapy.

Fig. 152.4 Choroid osteoma with (A) choroidal neovascularization, showing (B–D) increasing fluorescence on angiography.

CNVM should be distinguished from the branching vascular tufts seen on the inner surface of the tumor. The latter are not associated with subretinal fluid, hemorrhage, or disciform scar and do not leak fluorescein on angiography as do the former. The reason for the occurrence of CNVM in eyes with choroidal osteoma is speculative. It is postulated that the thinned, degenerated retinal pigment epithelium – Bruch’s membrane complex overlying the osteoma develops breaks and neovascular fronds from the choroid grow beneath the sensory retina.²⁷

Differential diagnosis

The ophthalmoscopic features of choroidal osteoma are classic. The most important lesions in the differential diagnosis include amelanotic choroidal melanoma, amelanotic choroidal nevus, metastatic carcinoma to the choroid, circumscribed choroidal hemangioma, disciform macular degeneration, posterior scleritis, idiopathic sclerochoroidal calcification, and choroidal cartilage.^{1,43,44,56–59}

Amelanotic choroidal melanoma differs from choroidal osteoma in that it has a yellow-brown color, more elevation and a less well-defined margin. An amelanotic choroidal nevus can be relatively flat like a choroidal osteoma but a nevus differs in that it has less distinct margins and can have drusen on its surface. Choroidal metastasis tends to have indistinct margins and is often associated with a serous retinal detachment out of proportion to the size of the tumor.⁶⁰ Furthermore, metastatic carcinoma usually occurs in middle age or older patients who have a prior history of malignancy (especially breast carcinoma). An irradiated choroidal metastasis may more closely resemble a choroidal osteoma because the irradiated metastasis appears flatter and atrophic and lacks appreciable subretinal fluid. Choroidal hemangioma can occasionally have overlying fibrous and osseous metaplasia that resembles osteoma.^61,62 However, choroidal hemangioma is characteristically dome-shaped with smooth regular margins and overlying serous fluid with cystoid degeneration of the retina.

Macular degeneration is typically seen in older patients when it occurs in the spectrum of age-related macular degeneration or it is seen with other fundus findings of histoplasmosis when it occurs in the presumed ocular histoplasmosis syndrome. Macular degeneration is usually centered in the macular area and is less commonly in a juxtapapillary location. Posterior scleritis has a typical orange-brown color with indistinct margins.¹⁷ The symptom of pain and the findings of uveitis, choroidal folds, cloudy subretinal fluid, and ultrasonographic evidence of thickened sclera and choroid with retrobulbar edema aid in differentiating this entity from the choroidal osteoma.

Idiopathic sclerochoroidal calcification clinically appears as an irregular calcific plaque within the choroid (Fig. 152.5).^54,59 The overlying retina and vitreous are normal. These findings resemble the clinical appearance of the choroidal osteoma. However, idiopathic sclerochoroidal calcification is not typically juxtapapillary and more often occurs outside the retinal vascular arcades, is usually multifocal, and can rarely occur in patients with other systemic diseases.⁵³ The linear nevus sebaceous syndrome can manifest calcification within the choroid, with an appearance similar to choroidal osteoma, but histopathology has shown calcified scleral cartilage, not bone.^58,63

Fig. 152.5 Sclerochoroidal calcification demonstrating multifocal equatorial calcific choroidal lesions in an older woman. This condition is distinct from choroidal osteoma.

Pathology and pathogenesis

The histopathologic features of the choroidal osteoma were first defined in the case of Van Dyk and reported by both Gass and coworkers⁹ and Williams and coworkers.⁸ The mass is composed of dense bony trabeculae with endothelial-lined large cavernous spaces and small capillary blood vessels (Fig. 152.6). Osteoblasts, osteocytes, and osteoclasts are present. The intertrabecular marrow spaces contain loose fibrovascular elements, mast cells, and foamy vacuolated mesenchymal cells. The involved choriocapillaries are narrowed or obliterated in most areas. The choroidal melanocytes are displaced inwards towards the choriocapillaries and outwards towards the sclera. The overlying retinal pigment epithelium is focally depigmented and flat in some areas while clumps of pigment granules within melanophages are seen along Bruch’s membrane in other areas.

Fig. 152.6 Optical coherence tomography over calcified choroidal osteoma in two patients (A,B and C,D) showing preservation of retinal architecture.

The pathogenesis of the choroidal osteoma is unknown. The speculated pathogeneses include possible choristomatous, inflammatory, traumatic, hormonal, metabolic, environmental, or hereditary etiology. Noble suggested that there might be a congenital, possibly inherited, abnormality of the juxtapapillary choroid that predisposes the patient to the development of this tumor.⁴⁰

Choroidal osteoma resembles a choristoma in its tissue composition, onset in youth, and absence of other preceding ocular disease processes. Osseous choristomas are well known to occur in the epibulbar region of the eye. The embryologic development of the region of the optic nerve head is complicated and several congenital hamartomas are found in this region such as the astrocytic hamartoma, combined retinal–retinal pigment epithelial hamartoma, retinal capillary hemangioma, and others. Features of this tumor atypical for a choristoma are the sexual preponderance in females and the new development and growth of the tumor during adulthood. Bone throughout the body is constantly being remolded and reshaped in adulthood; thus, the apparent change of this osseous tumor during adulthood does not completely exclude its being a choristoma.

Intraocular inflammation has been known to cause dystrophic intraocular calcification and ossification.^64,65 A focal peripapillary choroiditis could possibly lead to dystrophic calcium deposition and eventually to a lesion compatible with a choroidal osteoma.⁴⁸ Choroidal osteomas have been reported in children after eosinophilic granulomatosis,³⁵ sclerouveitis with optic nerve edema,⁴⁸ and orbital inflammatory pseudotumor.³¹ Although these three cases are well documented, the majority of choroidal osteomas develop in otherwise clinically normal eyes.

Several reports have noted ocular trauma preceding choroidal osteoma.^10,30 Osseous metaplasia of the retinal pigment epithelium may have occurred in these cases; however the relationship to trauma is speculative.

The occurrence of this tumor predominantly in young adult women raises the question of a hormonal influence.^1,11 Most of the women are diagnosed after puberty but several cases of prepubertal girls have been documented.^10,24,31 Also several male patients have been reported.^{14,16,35,37,46,50,52} No endocrinologic work-up has been revealing in these patients.

There have been no consistently abnormal serum calcium, phosphorus, or alkaline phosphatase levels detected in patients with choroidal osteomas. Katz and Gass³¹ reported a patient with transient mild secondary hypoparathyroidism (decreased serum calcium and increased serum phosphorus and increased alkaline phosphatase) and multiple choroidal osteomas, but classically parathyroid abnormalities cause a picture of sclerochoroidal calcification, not choroidal osteomas.

Choroidal osteomas were not reported or at least recognized in the older literature. The possibility that recent environmental toxins, exposures, or drugs may cause this tumor has been suggested. No consistent drug use or geographic location has been found. Choroidal osteomas have been misdiagnosed in the earlier literature as one prominent textbook, Tumors of the Eye, showed an ossified choroidal hemangioma in 1947 that actually proved to be a choroidal osteoma upon later review.^8,66 It is possible that several cases in the older literature may have been misdiagnosed prior to the description of the choroidal osteoma in 1978.

Cunha in 1984 reported a familial case of choroidal osteomas seen in a 37-year-old mother and her 5-year-old daughter.²¹ The mother had poor vision from 11 years old. Eting and Savir in 1992 reported an atypical fulminant course of bilateral choroidal osteomas in a 5-year-old boy and his 7-year-old sister and both siblings developed severe bilateral visual loss.²³ Noble in 1990 reported bilateral choroidal osteomas in 9-year-old twin brothers and their 11-year-old sister.⁴⁰ The mother had a yellow mottled fundus but no clear evidence of osteoma. These three occurrences seem to be more than coincidental for this rare tumor and may indicate a possible hereditary or environmental component for some choroidal osteomas.

Diagnostic approaches

Ultrasonography

Ultrasonography is useful for differentiating choroidal osteomas from other clinically similar lesions. A-scan ultrasonography demonstrates a high-intensity echo spike from the inner surface of the tumor with decreased amplitude of the orbital soft tissue echoes immediately posterior to the tumor. B-scan ultrasonography demonstrates a slightly elevated, highly reflective choroidal mass which persists at lower scanning sensitivity after the other soft tissue echoes have disappeared (Fig. 152.7). Acoustic shadowing of the orbit occurs just posterior to the choroidal mass, giving the appearance of a pseudo-optic nerve.^1,7

Fig. 152.7 Bilateral choroidal osteoma. Optical coherence tomography over decalcified (A,B) osteoma in the right eye showing loss of outer retinal architecture and poor vision and over calcified (C,D) osteoma in the left eye showing preservation of overlying retina and good vision.

Optical coherence tomography and autofluorescence

Optical coherence tomography (OCT) is a high-resolution imaging method for the retina with cross-sectional resolution under 10 µm. OCT reveals only minor choroidal details. Choroidal osteoma shows dense, abrupt reflection of light on OCT and the overlying choroidal neovascularization, subretinal fluid, retinal edema, and retinal thinning can be clearly visualized on OCT (Fig. 152.6).^26,67 The retina shows profound outer-layer thinning and photoreceptor loss over decalcified osteoma whereas these features are not as advanced over the calcified portion (Fig. 152.8).⁶⁷ Recently, the SD-OCT features have been illustrated,^68,69 as well as the fundus autofluorescence findings.⁷⁰

Fig. 152.8 Bilateral choroidal osteoma (from Fig. 152.7) showing computed tomography (A) with visibility of calcified plaque in the choroid of both eyes. The T1-weighted (B) and T2-weighted (C) magnetic resonance images show the flat plaque as bright on T1 and dark on T2.

Management

The management of choroidal osteoma includes prevention of tumor growth, induction of decalcification of tumor, and treatment of choroidal neovascularization. There is currently no known systemic metabolic or hormonal method for altering the growth of the choroidal osteoma. For choroidal osteoma in the subfoveal region, the goal is to maintain calcification of the mass so that the outer retinal structures remain intact.⁶⁷ Some have advocated oral calcium supplements in these cases but there is no confirmatory study. For osteoma in the extrafoveal region, the goal is to decalcify it so that it cannot grow towards the foveola. Decalcified osteoma does not grow in the direction of decalcification. Decalcification can be achieved with ablative laser photocoagulation or photodynamic therapy.^{1,14,19,27,29,39,42,71} Our current preferred treatment for extrafoveal osteoma is photodynamic therapy, as has been published, with decalcification occurring slowly over 1 year.⁷¹

Management of related CNVM has previously been somewhat successful with laser photocoagulation, but it often requires several treatments and visual acuity can decline.^{14,19,27,29,39,67} Subretinal surgical removal of subretinal neovascular membrane has been performed, but visual acuity may not be retained.²⁵ Photodynamic therapy using verteporfin has been found successful for management of CNVM over osteoma (Fig. 152.9).^16,52 In one case, transfoveal photodynamic therapy allowed for resolution of subretinal fluid and visual acuity stabilization of 20/30 at 6 months follow-up.^16,52 More recently, anti-VEGF medications have been used for CNVM over osteoma with some success and visual preservation, but long-term reinjection might be necessary.^72,73

Fig. 152.9 Small, calcified juxtapapillary choroidal osteoma with choroidal neovascular membrane (CNVM) and subretinal hemorrhage (A,B) treated with photodynamic therapy. The tumor appeared to decalcify both clinically and echographically and the CNVM resolved (C,D).

Prognosis

The visual prognosis is quite varied and unpredictable. Most patients with extrafoveal choroidal osteoma maintain good visual acuity. Some patients with a subfoveal choroidal osteoma retain good visual acuity for months to years. In an analysis of 74 affected eyes, visual loss of three or more lines occurred in 26% by 5 years, 45% by 10 years, and 59% by 20 years. Poor visual acuity of 20/200 or worse was found in 14% at 1 year, 45% at 5 years, and 56% at 10 years (Table 152.1).⁶⁷ The reason for visual loss includes subretinal fluid, subretinal blood, retinal pigment epithelial atrophy or mottling, and photoreceptor atrophy, particularly over decalcified osteomas. Factors that statistically predict poor vision include symptoms and decalcification (Table 152.2).⁶⁷ The prognosis for life in the patient with choroidal osteoma is no different from the general population.¹

Conclusion

Choroidal osteoma is a benign ossified tumor of the choroid typically found in healthy young females in the second or third decade of life. It has been reported to exist in males and in children. Choroidal osteoma is unilateral in 75% of cases, tends to be located in the juxtapapillary area, and ranges in size from 2 to 22 mm in basal dimension. It is minimally elevated and may have associated subretinal fluid and choroidal neovascularization.

Choroidal osteoma should be differentiated from choroidal melanoma, choroidal nevus, choroidal metastasis, choroidal hemangioma, idiopathic and sclerochoroidal calcification. Ultrasonography can demonstrate calcium within the lesion. Fluorescein angiography can demonstrate neovascular tissue. Optical coherence tomography can delineate the status of the other retina with an estimate of visual potential.

The pathogenesis of choroidal osteoma is unknown and there is no known systemic modification to benefit resolution of this tumor. Related choroidal neovascularization can been treated with laser photocoagulation, photodynamic therapy, surgical excision, and anti-VEGF therapy. The visual prognosis is variable but the systemic prognosis is good.