Historical review

Early reports on combined hamartomas describe lesions that were clinically mistaken for choroidal malignancy. Histopathologically, these lesions were described as hyperplastic retinal pigment epithelium and were located juxtapapillary, in the posterior pole or peripherally.^2,3 In 1961, the term “hamartoma” was used to describe a large lesion of the posterior pole in a child.⁴ In 1973, Gass⁵ reported lesions in five children and two young adults, and used the term “combined hamartoma.” In 1984, Schachat et al.,¹ described 60 patients with combined hamartomas in a collaborative effort of the Macula Society Research Committee. Gass⁶ reported an additional 35 patients in his discussion of the Macula Society’s report. Additionally, there have been more recent reports of combined hamartomas, including a review of visual acuity outcomes of 77 patients from a single institution.⁷

Epidemiology

In the Macula Society’s report¹ of 60 patients with combined hamartomas, the mean age at the time of diagnosis was 15 years, with a range of 10 months to 66 years. The number of males and females was equal, and three patients were black. In a recent report by Shields et al.⁷ which evaluated 77 patients with CHRRPE, the mean age of diagnosis was 11.9 months with a range of 0.4–60 months. There is no apparent predilection based on sex or race.

Clinical manifestations

Ophthalmoscopic appearance

Combined hamartomas may be located on the optic disc and juxtapapillary region, in the macula, and in the mid-periphery. The ophthalmoscopic appearance varies depending on the location of the tumor. Lesions of the posterior pole have varying amounts of retinal pigment epithelial, vascular, and glial components, and one tumor type tends to predominate (Fig. 137.1). Clinical features include an elevated pigmented mass involving the RPE, retina and overlying vitreous with extension of fanlike projections towards the periphery. This lesion may blend imperceptibly with the surrounding RPE with an absence of RPE or choroidal atrophy. The lesion may be covered by a thickened gray-white retinal and preretinal tissue which may show contraction of the inner surface. There is generally absence of retinal detachment, hemorrhage, and vitreous inflammation.⁵ The Macula Society¹ reported retinal vascular tortuosity within the lesion in 93% of patients, hyperpigmentation in 87%, slight elevation in 80%, epiretinal membrane formation in 78%, and exudation in 7%. Peripheral lesions¹⁴ appear as an elevated ridge concentric with the disc. Adjacent to the lesion, larger retinal vessels appear stretched, and there are few smaller vessels (Fig. 137.2). A dragged disc appearance has been described in patients with peripheral lesions.^5,15 Combined hamartomas are almost always solitary, unilateral tumors; however, a few cases of bilateral involvement have been reported in association with neurofibromatosis.^9,16–18

Fig. 137.1 (A) Combined hamartoma of the left optic nerve head and juxtapapillary region. Peripapillary hyperpigmentation extends from the 3 o’clock position to 11 o’clock position and is intraretinal inferiorly and at the level of the retinal pigment epithelium nasally. Gliosis is most striking inferiorly and is associated with retinal striae involving the fovea. Retinal vascular tortuosity and telangiectasis are evident. Scattered exudate is present temporally. (Reproduced from Eliott D, Schachat AP. Combined hamartoma of the retina and retinal pigment epithelium. Semin Ophthalmol 1993;8:265–9. ©1993. With permission of Taylor & Francis Inc.). (B) Mid-phase fluorescein angiogram demonstrating numerous small, irregular blood vessels throughout the lesion. There is blocked fluorescence from the pigmentation. (C) Late-phase fluorescein angiogram showing marked hyperfluorescence as a result of leakage from small vessels.

Fig. 137.2 (A) Peripheral combined hamartoma. (B) Fluorescein angiogram demonstrates telangiectatic vessels within the lesion, blocked choroidal fluorescence surrounding the lesion, and peripheral straightening of retinal vessels.

Diagnostic evaluation

The diagnosis of CHRRPE is based upon clinical appearance of the lesion. However, fluorescein angiography (FA) and optical coherence tomography (OCT) are useful for characterizing lesion type. In the early phase of the angiogram, the degree of hypofluorescence parallels the degree of hyperpigmentation. Tractional distortion of the retina may result in marked vascular tortuosity and telangiectasia. The mid-phase of the angiogram may highlight vascular anomalies. It is not uncommon to note vascular straightening. In the late phase of the angiogram the tortuous vessels usually leak, causing late hyperfluorescence. If there is associated choroidal neovascularization, deep leakage is evident.

Optical coherence tomography is an important modality for diagnosing and characterizing CHRRPE lesions. Early generation OCT images demonstrated an elevated lesion with high reflectivity of the inner retina, hyporeflective shadowing of the underlying tissue, and obscuration of the normal retinal layers.^30,31 High-resolution spectral domain OCT imaging shows characteristic findings, including: peaked vitreoretinal traction, retinal disorganization, thickening of the retina at the level of the RPE and preretinal vitreoretinal interface abnormalities.³² OCT imaging can delineate the transition between the abnormal retinal interface and can guide surgical intervention. OCT is an important tool used to aid in the differential diagnosis and management of CHRRPE lesions. Ultrasonography is not useful in diagnosis of these minimally elevated lesions.