26.2.1 Demographics

Choroidal nevus is the most common fundus tumor. It arises from the melanocytes in the choroidal stroma. ^{1 ,​ 2} According to a population-based study, the prevalence of choroidal nevus in United States persons older than 40 years is 5% or greater. ³ Although it may arise from a congenital nest of melanocytes, a choroidal nevus may not become pigmented or clinically evident until puberty or young adulthood. In some instances, a choroidal nevus can undergo transformation and develop into a malignant melanoma. ^{4 ,​ 5 ,​ 6 ,​ 7}

26.2.2 Clinical Features

Choroidal nevus, which is generally visible ophthalmoscopically, can assume several clinical variations. The most common is a flat, homogeneous, slate gray lesion with a slightly ill-defined border. With time, a nevus can develop fine drusen on the surface (Fig. 26-1 and Fig. 26-2). In some instances, a nevus may be entirely amelanotic. Most nevi are less than 2 mm in thickness. Findings that suggest a nevus could be evolving into a malignant melanoma include a thickness greater than 2 mm, presence of orange pigment on the surface of the lesion, and localized secondary retinal detachment (Fig. 26-3 ).

The clinical features of choroidal nevus differ slightly depending on patient age. Young patients tend to show little overlying retinal pigment epithelial (RPE) changes or drusen. With increasing age, choroidal nevus demonstrates slightly increased thickness, greater chance for multifocality, and more obvious overlying drusen. ⁸

Most choroidal nevi are asymptomatic, but 10to 11% of cases can become symptomatic with decreased visual acuity. ⁹ The causes of decreased visual acuity include secondary serous foveal detachment (50%), photoreceptor degeneration (42%), and subretinal choroidal neovascularization overlying the nevus (8%). Decreased visual acuity is more common in patients with subfoveolar nevus. Analysis of visual acuity in 3,422 eyes with choroidal nevi revealed the Kaplan–Meier estimates at 5, 10, and 15 years for vision loss of 3 or more logarithm of the minimum angle of resolution lines at <1, 1, and 2% of eyes with extrafoveolar nevus compared to 15, 20, and 26% of eyes with subfoveolar nevus. ⁹

Choroidal nevus can show minimal growth (<1 mm base) over many years of follow-up. This does not indicate melanoma transformation. In one large study, about 40% of patients showed growth when comparing images over 7 to 10 years. ¹⁰ In about 5% of cases, choroidal nevus demonstrates a surrounding halo, termed “halo nevus” (Fig. 26-4). Patients with halo nevus show low risk for transformation to choroidal melanoma. ¹¹ Occasionally, they give a history of skin melanoma and the halo is believed to be an autoimmune response. In about 5% of cases, choroidal nevus can be giant in basal diameter, occupying 10 mm or greater. The giant nevus often has overlying drusen and RPE abnormalities, but has an approximate 15% risk for transformation into melanoma. ¹²

26.2.3 Diagnosis

The best way to diagnose a choroidal nevus is with indirect ophthalmoscopy, which reveals the typical ophthalmoscopic features described above. Certain ancillary studies can be employed to facilitate the diagnosis.

Fluorescein angiography of a typical choroidal nevus reveals hypofluorescence of the pigmented portion of the lesion in the vascular filling phases (Fig. 26-5). Amelanotic nevus shows less hypofluorescence and even some hyperfluorescence in the late angiograms. This contrasts with choroidal melanoma, which is generally more hyperfluorescent. Drusen on the surface of a choroidal nevus usually show hyperfluorescence throughout the angiogram sequence as a result of transmission of fluorescence from the choroid. Indocyanine green angiography also generally demonstrates hypofluorescence of most choroidal nevi.

Ultrasonography is of little diagnostic value for choroidal nevus, except to document lesions that are greater than 1 mm in thickness (Fig. 26-6). When a nevus measures greater than 2 mm in thickness on ultrasonography, it should be followed more closely for evolution into malignant melanoma. Optical coherence tomography (OCT) can assist in demonstrating the choroidal nevus arising in the outer choroid and compressing the choriocapillaris inward ¹³ (Fig. 26-7). Occasionally there is overlying outer retinal atrophy with photoreceptor loss, subretinal fluid, subretinal cleft, RPE detachment, and retinal edema. On autofluorescence imaging, a choroidal nevus tends to be hypoautofluorescent and the overlying RPE is hypoautofluorescent from chronic atrophy. ¹⁴

26.2.4 Management and Course

A choroidal nevus generally requires no treatment. A choroidal nevus that has produced visual loss through a serous detachment of the fovea can sometimes be managed by anti-vascular endothelial growth factor medications, delimiting photocoagulation, surface photocoagulation directed at leaks, or transpupillary thermotherapy (TT). The patient with a choroidal nevus should be followed periodically on an annual basis, and if growth of the lesion is documented, then evolution into early malignant melanoma should be suspected and the lesion managed accordingly.

The risk factors predictive of transformation of choroidal nevus into melanoma include greater thickness (>2 mm), subretinal fluid, symptoms (decreased vision, visual field defect, flashes, floaters), orange pigment, margin near disc, ultrasonographic hollowness, and absence of halo or drusen. ^{4 ,​ 5 ,​ 7} A mnemonic (TFSOM UHHD) to recall risk factors of ocular melanoma is “To find small ocular melanoma using helpful hints daily,” representing thickness, fluid, symptoms, orange pigment, margin, ultrasonographic hollowness, halo absence, and drusen absence ⁷ (Table 26-1). Tumors that display one factor have a 38% chance for growth and those with two or more factors show growth in over 50% of cases at 5 years. The most dangerous combination of factors with a 69% risk for growth include thickness greater than 2 mm, symptoms, and tumor margin at disc. The median hazard ratio for choroidal nevus growth into melanoma for those with 1 to 2 risk factors is 3; for 3 or 4 risk factors is 5; for 5 to 6 risk factors is 9; and for all 7 risk factors is 21. Choroidal nevus with any of the above features should be followed every 6 months or sooner. Most of those tumors with two or more risk factors probably represent small choroidal melanoma and early treatment is indicated.

26.2.5 Differential Features of Choroidal Nevus versus Melanoma

It is important to differentiate choroidal nevus from a small choroidal melanoma. A small choroidal melanoma generally has a tumor thickness of =2 or 3 mm and exhibits signs of activity including subretinal fluid and/or orange pigment, while a choroidal nevus generally has a thickness <2 mm and displays signs of chronicity (drusen, RPE atrophy, RPE hyperplasia, RPE detachment, or fibrous metaplasia). On ultrasonography, choroidal nevus exhibits high internal reflectivity and acoustic solidity in contrast to small choroidal melanoma that exhibits medium to low internal reflectivity and acoustic hollowness. Hot spots and leakage on fluorescein angiography are suggestive of growth and transformation of nevus to melanoma. The OCT features of small choroidal melanoma compared with choroidal nevus include increased tumor thickness, subretinal fluid, subretinal lipofuscin deposition, retinal irregularities, and shaggy photoreceptors ^{13 ,​ 15} (Fig. 26-8). The other differential diagnosis of pigmented choroidal nevus includes congenital hypertrophy of RPE, RPE hyperplasia, combined hamartoma of the retinal epithelium and RPE, and subretinal hemorrhage. The amelanotic choroidal nevus must be differentiated from choroidal metastasis, choroidal granuloma, and choroidal lymphoma. Careful fundus examination by an experienced clinician in conjunction with imaging techniques of OCT and fluorescein angiography can differentiate choroidal nevus from other simulating lesions.

26.2.6 Histopathology

Choroidal nevus is a tumor composed of benign uveal melanocytes. Several types of nevus cells have been recognized, but most are composed of spindle-shaped or round to oval cells with benign cytologic features. Choroidal nevi that are composed predominantly of large, ovoid to round cells with densely packed cytoplasmic melanosomes are called melanocytomas, and these cells are identical to cells that comprise the better-known melanocytomas of the optic disc.

26.3.1 Demographics

Choroidal melanoma is the most common primary intraocular malignant tumor among white patients. ^{16 ,​ 17} In North America, it is estimated that approximately 2,500 persons develop uveal melanoma annually. ¹⁸ It is estimated that there are 7,095 new cases of uveal melanoma worldwide on an annual basis and 4,747 occur in White, 738 in Hispanic, 1,286 in Asian, and 316 in African patients. ¹⁸

The mean age-adjusted incidence of uveal melanoma is 4.3 per million. ¹⁹ This figure has remained relatively stable over the past 5 decades. In an analysis of 2,493 cases of uveal melanoma from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, uveal melanoma at all ages was more common in men at 4.9 per million compared with women at 3.7 per million. ¹⁹ The mean age at presentation was 60 years and there was a range of 6 to 100 years. The age-specific incidence per million population (male/female) differs depending on age and includes 0 to 4 years (0/0), 10 to 14 years (0.2/0), 20 to 24 years (0.4/0.6), 30 to 34 years (1.7/1.7), 40 to 44 years (3.9/2.4), 50 to 54 years (10.5/6.5), 60 to 64 years (14.9/11.7), 70 to 74 years (24.5/17.8), and 80 to 84 years (23.2/16.1).

In an analysis of 8,033 patients with uveal melanoma from a single tertiary referral center over a 4-decade period, Shields and coworkers reported melanoma primarily involving the choroid (90%), ciliary body (6%), or iris (4%). ²⁰ The tumor affected males (51%) or females (49%) and primarily occurred in Caucasians (98%) compared to African American (<1%), Hispanic (1%), and Asian, Native American, Middle Eastern, and Asian Indian (each <1%). In this clinic-based study, the mean patient age at detection was 58 years with a range from 3 to 99 years. ²⁰ The tumor was detected in children 20 years or younger (1%), mid-adults 21 to 60 years (53%), and older adults over 60 years (45%).

26.3.2 Symptoms

Choroidal melanoma usually manifests with symptoms of photopsia (flashes), floaters, visual field loss, or visual acuity loss. ²⁰ Some patients have no symptoms. If the tumor involves the ciliary body, sentinel vessels can be noted. Rarely this tumor can cause pain from secondary glaucoma or tumor-related inflammation or necrosis. ²¹ The importance of annual eye examination is underscored by the fact that uveal melanoma can be asymptomatic and detected on routine eye examination.

26.3.3 Predisposing Factors

Factors related to the development of uveal melanoma involve both host and environmental factors. Weis and coworkers provided a meta-analysis of all published reports on host factors for uveal melanoma and found that light eye color, fair skin color, and inability to tan were risk factors for development of uveal melanoma. ²² Shah and colleagues investigated environmental factors and found that intermittent ultraviolet exposure to arc welding was a significant risk factor. ²³ Chronic ultraviolet exposure and occupational sunlight exposure were borderline factors. Factors such as geographic birth latitude and outdoor leisure sunlight exposure were not significantly related to the development of uveal melanoma.

Two important factors for development of uveal melanoma are the presence of a preexisting choroidal nevus and the presence of congenital ocular/oculodermal melanocytosis, also termed “Nevus of Ota.” Oculodermal melanocytosis manifests as gray episcleral and cutaneous pigmentation, often with related uveal hyperpigmentation. This condition carries a 1 in 400 lifetime risk for uveal melanoma in Caucasians. ²⁴ The other risk, choroidal nevus, is generally detected in pre-teenage or teenage patients as a pigmented choroidal mass that gradually acquires chronic overlying drusen. In a population-based study, the prevalence of choroidal nevus was 4% in Caucasians, 1% in Hispanics, <1% in Blacks, and <1% in Chinese. ²⁵ Singh and associates estimated transformation in 1 in 8,845 in the white population. ⁶

Shields and coworkers further investigated the clinical risk factors for transformation of choroidal nevus into melanoma. ^{4 ,​ 5 ,​ 7} They identified eight clinical features that predicted transformation including thickness over 2 mm, subretinal fluid, symptoms, orange pigment, tumor proximity within 3 mm of the optic disc, ultrasound hollowness, halo absent, and drusen absent. ⁷ Each feature imparted approximately three times greater risk for transformation compared to a tumor without the feature.