Case Series: Retinal Pigment Epithelial Detachments Over Choroidal Nevi – What Is the Clinical Significance?

Choroidal nevus is a common benign intraocular tumor, with a reported prevalence of 2–25% in the general population [1‒4]. These melanocytic tumors, originating from the neural crest, classically present as pigmented lesions with overlying drusen and retinal pigment epithelial (RPE) alterations, such as RPE hyperplasia and atrophy, which suggest chronicity [5]. Choroidal nevi are often discovered incidentally during routine fundoscopy and are typically asymptomatic [1]. Although choroidal nevi are common, their association with retinal pigment epithelial detachment (PED) is uncommon, occurring in only 1–3% of patients diagnosed with choroidal nevi on ophthalmoscopic examination [5‒7]. In this case series, we describe 4 patients with PED overlying a choroidal nevus, 2 of whom were referred due to concerns about nevus growth. This case series is reported following the CARE guidelines [8].

A patient in their forties was found to have a choroidal lesion in the left eye during a routine eye examination. Upon presentation, the patient had a visual acuity (VA) of 20/20 in both eyes. An elevated pigmented choroidal lesion with an overlying PED and multiple drusen was seen in the superior periphery on fundoscopy of the left eye (Fig. 1a).

Fundus autofluorescence showed mottled hypo-autofluorescence over the area corresponding to the nevus, and inferior to this was a patch of hyper-autofluorescence (Fig. 1b). Optical coherence tomography (OCT) showed a choroidal mass with overlying multilobular PED and trace subretinal fluid (Fig. 1c). B-scan ultrasound of the left eye showed a choroidal lesion measuring 6.6 mm × 6.7 mm in basal diameter and 1.4 mm in thickness, although the PED was difficult to distinguish from nevus on B-scan (Fig. 1d). The lesion remained stable over 8 years of follow-up.

An adult in their sixties was referred for a left choroidal nevus. They reported intermittent blurred vision, without any flashes orfloaters. On examination, VA was 20/25 and 20/30 in the right and left eyes, respectively. Slit lamp exam showed 1+ nuclear sclerosis in both eyes; the rest of the anterior segment exam was normal. Fundoscopy of the left eye revealed a slightly elevated pigmented choroidal mass temporal to the macula with overlying drusen. A large PED was seen in the nasal aspect of the lesion, with a collection of orange pigment inferiorly (Fig. 2a).

Fundus autofluorescence showed hyper-autofluorescent dots corresponding to drusen as well as a small arc of hyper-autofluorescence in the area of the orange pigment. The area of the PED was delineated by a hypo-autofluorescent ring (Fig. 2a, b). On ultrasonography, the choroidal mass had solid echogenicity and intermediate reflectivity. The mass was 1.5 mm thick and 7.3 mm × 8.4 mm in basal diameter. An anterior hyperechoic band was seen overlying lesion (Fig. 2c). OCT confirmed the presence of a large PED (Fig. 2d). The clinical presentation was most consistent with choroidal nevus with overlying PED. The appearance and size of the choroidal nevus and PED did not change after 1.5 years.

A patient in their late sixties was referred for evaluation of an enlarging choroidal nevus in their left eye. The lesion had been monitored for several years by a local ophthalmologist. On examination, VA was 20/20 in both eyes. Dilated fundus examination of the left eye was notable for a minimally elevated pigmented choroidal nevus with a central PED. There was no associated orange pigment, hemorrhage, exudation, subretinal fluid, or sign of choroidal neovascularization (Fig. 3a).

B-scan ultrasound of the left eye demonstrated a choroidal mass measuring 4.8 mm by 4.4 mm in basal dimensions and 1.5 mm in thickness (Fig. 3b). The lesion had intermediate reflectivity on A-scan ultrasonography. OCT confirmed a fibrovascular PED over the center of the choroidal lesion (Fig. 3c). The patient was diagnosed with choroidal nevus and was observed. The lesion remained stable over the 5 years of follow-up, as demonstrated in Figure 3d.

An elderly patient in their late seventies with a previously diagnosed choroidal nevus of the left eye was referred due to concern for transformation of the lesion to choroidal melanoma. The patient was diagnosed with choroidal nevus in the same eye more than 20 years prior. On examination, VA was 20/25 in both eyes. Dilated fundus exam of the left eye was notable for a flat-pigmented choroidal lesion with a round central PED and multiple overlying drusen (Fig. 4a).

The choroidal lesion in the left eye was flat on B-scan ultrasonography, but a dome-shaped hyperechogenic band was seen anterior to the lesion (Fig. 4b). OCT scans over of the lesion showed compression of the choriocapillaris and a dome-shaped PED (Fig. 4c). Photos and scans were compared to baseline images which confirmed stability of the lesion over 26 years (Fig. 4a, d).

This report describes 4 cases of choroidal nevi associated with overlying PEDs visible on fundoscopy. Each PED measured at least one disc diameter in circumference and exhibited notable elevation. In cases 3 and 4, these findings were significant enough to warrant a more comprehensive evaluation by optometrists or ophthalmologists, particularly due to the potential for malignant transformation indicated by changes in tumor thickness. Multimodal imaging confirmed that the dome-shaped elevations observed on fundoscopy were indeed retinal PEDs and not tumor elevation. Throughout follow-up periods ranging from 1.5 to 26 years, both the nevi and the overlying PEDs remained stable.

Choroidal nevi are benign, yet over time these may transform into malignant melanoma. Characteristics that indicate an increased risk for transformation to melanoma include: thickness >2 mm, subretinal fluid, symptomatic vision loss of 20/50 or worse, orange pigment, hollow acoustic zone by ultrasonography, diameter greater than 5 mm [2, 9‒11]. If four or more factors are present, the risk of malignant transformation can be as high as 50% [10, 11].

Choroidal nevi can undergo changes that do not necessarily signify malignant transformation, such as enlargement or a decline in visual acuity. Enlargement of long-standing choroidal nevi without malignant transformation is seen in nearly one-third of patients [12]. A nevus may contribute to reduced visual acuity over time, especially if located in the subfoveal region. This is more likely when the nevus is associated with features such as orange pigment, subretinal fluid, PED, or choroidal neovascularization [13, 14]. In one study, overlying PED carried a relative risk of 22.2 for loss of three or more logMAR lines of vision among patients with choroidal nevi [13].

Retinal pigment epithelial (RPE) detachment refers to the separation of the RPE from the innermost layer of Bruch’s membrane. Depending on the contents within the space between the RPE and Bruch’s membrane, PEDs can be classified as drusenoid, serous, vascularized, or mixed [15]. This classification is crucial for determining the prognosis. The development of CNV in association with PED increases the risk of significant vision loss and RPE tears [15]. Additionally, CNV can complicate the monitoring of choroidal nevi growth, making it essential to identify any neovascularization associated with a PED for accurate assessment and management [16].

Given the potential for malignant transformation, growth, and effects on visual acuity, choroidal nevi should be monitored over time. Regular and comprehensive fundoscopic examination, supplemented by imaging techniques such as B-scan ultrasonography, OCT, and fundus autofluorescence, are essential for assessing these lesions over time. Ultrasound allows the determination of basal dimensions, thickness, internal reflectivity, and acoustic characteristics of the nevus. Large PEDs can also be detected through B-scan, as demonstrated in Cases 2 (Fig. 2c) and 4 (Fig. 4b). OCT demonstrates compression of choriocapillaris, which is a finding associated with choroidal nevi [17]. Additionally, it detects subretinal fluid, cystoid retinal edema, and orange pigment which helps identify the risk for conversion to melanoma. Furthermore, associated PED are more likely evident on OCT versus clinical examination. In one observational case series of 3,422 consecutive eyes with choroidal nevus, PED was reported in just 1.2% of cases clinically and 12% of cases with OCT [5]. Clinically visible PEDs may be perceived as elevation or thickening of the choroidal nevus, suggesting possible growth that may be concerning for melanoma. In this setting, both ultrasonography and OCT are useful in delineating the choroidal nevus from the PED.

Fundus autofluorescence is also typically utilized to detect changes in overlying orange pigment, which may be a risk factor for malignant transformation [18]. Orange pigment is hyper-autofluorescent, while drusen may be faintly hyper-autofluorescent [19]. Decreased or absent autofluorescence indicates disturbances of the RPE-photoreceptor complex [20]. Fluorescein angiographic features of choroidal nevi are variable. Smaller and darker lesions may appear hyperfluorescent, while larger, and less pigmented nevi may appear hypo-autofluorescent [18]. Fluorescein angiography may be useful in identifying choroidal neovascularization and vascularized PEDs, which are both risk factors for vision loss in choroidal nevi, especially those that are located in the macula [21].

A PED overlying choroidal nevus may develop secondary to degenerative changes in Bruch’s membrane [5, 22]. Typically, overlying PED implies stability and chronicity of the nevus and does not impart a higher risk for malignant transformation. However, PED can complicate the monitoring of the underlying nevus and can lead to the impression of enlargement, causing concern for transformation of the nevus into melanoma. Qureshi et al. [22] described a case with PED overlying a choroidal nevus imparting a pseudo-growth appearance. The authors concluded that overlying PED is not associated with transformation into melanoma and in fact implies stability and chronicity of the nevus [22]. PED can completely obscure the underlying nevus, leading to a delay in identification of the PED etiology [23].

Generally, stable choroidal nevi with overlying PED do not require active intervention. Fundus photography, fundus autofluorescence, OCT, and ultrasonography may be performed every 6–12 months as part of monitoring for malignant transformation [18]. In the presence of visual symptoms attributable to choroidal neovascularization or subretinal fluid, treatment options may be explored. Modalities such as photodynamic therapy, laser photocoagulation, transpupillary thermotherapy, and VEGF inhibitors have been used to treat neovascularization associated with choroidal nevus [24‒26]. Photodynamic therapy can also be considered for an enlarging PED that becomes visually significant [26]. Given the benign nature of extramacular choroidal nevi with overlying PED and without active neovascularization, all patients in this case series continue to be observed without intervention. None of the patients demonstrated vision loss attributable to the choroidal nevus or PED, owing to the extramacular location of the lesions.

This case series describes 4 patients each with choroidal nevus with overlying PED, a relatively uncommon clinical finding. PED does not increase risk of progression to melanoma but may complicate evaluation of the underlying choroidal nevus and may lead to decreased visual acuity. As a result, choroidal nevi with overlying PED should be monitored over time with particular attention paid to the development of secondary choroidal neovascularization.

This manuscript complies with the Declaration of Helsinki. This case series was reviewed and determined to be exempted from requiring ethics approval by the Emory University Institutional Review Board.

This is a retrospective case series using standard clinical data, and any potential indirect identifiers were removed. The original intent of the review was retrospective in nature, however, due to the limited number of patients identified, the study has evolved into a case series. As such, we were unable to obtain written informed consent from the patients for publication of the details of their medical case and any accompanying images, as they presented at Emory at different times. The information provided is very limited and would not lead to patient identification.

The authors have no financial interests, conflicts of interests, or disclosures related to this study.

There are no funding sources to declare.

J.M.S.: data gathering and data analysis, writing, editing and revising the manuscript. J.R.W.: conceptualization, data gathering and data analysis, editing and revising the manuscript, and supervision. H.E.G.: data analysis, editing and revising the manuscript, and supervision. C.P.A.: Data gathering and data analysis, writing, editing and revising the manuscript, and supervision.

Relevant data that support the findings in the study are included in the report. Additional information is not publicly available to protect the confidentiality of the included patients but may be requested from the corresponding author (C.P.A.) upon reasonable request.