Figure 1. This fundus image of our 16-year-old patient’s right eye shows multiple lesions scattered across the retina.
Figure 2. On fundus exam, clinicians discovered a solitary juxtapapillary retinal lesion in the patient’s left eye.
Figure 3. Optical coherence tomography helped identify the lesion was arising from the nerve fiber layer and the presence of mild subretinal fluid.
Figure 4. This B-scan ultrasonography measured a 2.1 mm-thick juxtapapillary lesion.
A 16-year-old girl was referred to our institution for retinal lesions in both eyes and decreased vision in her left eye. Her best-corrected visual acuities were 20/20 OD and 20/25 OS. Her intraocular pressures (IOPs) were 16 mm Hg OU. An anterior segment examination was within normal limits, but a fundus exam of her right eye showed multiple retinal lesions scattered throughout the fundus (Figure 1). Her left fundus demonstrated a solitary juxtapapillary retinal lesion (Figure 2). Optical coherence tomography (OCT) confirmed that the lesion was arising from the nerve fiber layer. It was associated with mild subretinal fluid (Figure 3). B-scan ultrasonography showed that the juxtapapillary lesion measured 2.1 mm in thickness (Figure 4).
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The patient had a history of infantile spasms beginning at age 7 months, hypopigmented macules on her skin, cardiac rhabdomyomas, and facial angiofibromas. The constellation of clinical findings was diagnostic for tuberous sclerosis complex (TSC). Genetic testing was confirmatory and revealed a frameshift mutation in the TSC2 gene, which encodes the protein tuberin. This protein, along with hamartin, regulates cell growth and division. The retinal lesions were consistent with the retinal astrocytic hamartomas associated with TSC.
TSC, also known as Bourneville disease, is an autosomal dominant genetic disorder with an incidence of 1 in 6,000 to 10,000. The genes primarily responsible for this disease include TSC1 and TSC2, both of which are tumor suppressor genes, mutation of which leads to unregulated cellular proliferation through the mechanistic target of rapamycin (mTOR) pathway. TSC is a phakomatosis (neurocutaneous disorder); it can affect multiple organ systems, including the skin (facial angiofibroma, shagreen or ash leaf patch), kidneys (angiomyolipomas), lungs (lymphangioleiomyomatosis), heart (rhabdomyomas), neurological system (subependymal nodules, cortical tubers), and eyes.1
The ocular findings of tuberous sclerosis complex include retinal astrocytic hamartomas (a major diagnostic criterion) and retinal achromatic patches (a minor diagnostic criterion).2 Astrocytic hamartomas are benign glial tumors that arise in an estimated in 36% to 50% of individuals with TSC, although they can also be associated with other systemic conditions (neurofibromatosis), or they can arise sporadically. These lesions appear yellow-gray in color and may be sessile or slightly elevated.3 Astrocytic hamartomas can have glistening intrinsic calcification and have been described as having a “tapioca” or “mulberry” appearance. On OCT, these tumors are located in the nerve fiber layer of the retina and often demonstrate “moth-eaten” optically empty spaces.4 Retinal astrocytic hamartoma can in rare cases appear similar to retinoblastoma, especially when calcification is present; however the presence of other typical systemic manifestations suggested the diagnosis of TSC in this case. Retinal achromatic patches appear in only 12% of affected individuals, but consist of focal regions of retinal pigment epithelial loss, appearing as a punctate or small punched out patch.3
The majority of retinal astrocytic hamartomas are asymptomatic, and can be simply observed. However, a rare subset exhibits aggressive growth and can develop vision-threatening intraretinal or subretinal fluid. Complications include amblyopia in young children, exudative retinal detachment, retinal traction, choroidal neovascular membrane formation, and vitreous hemorrhage. Therapies that have been used to treat symptomatic lesions include anti-vascular endothelial growth factor (anti-VEGF) agents, ablative therapy with various forms of laser, and the use of oral mTOR inhibitors.5–7
This case was contributed by Karen M. Wai, MD, a resident physician at Massachusetts Eye and Ear and Harvard Medical School, Boston.
The case was edited by Grayson W. Armstrong, MD, MPH, an instructor of ophthalmology at Massachusetts Eye and Ear and Harvard Medical School and Director of Ophthalmology Emergency Service.
Drs Wai and Armstrong wish to thank Mary Beth Aronow, MD, for her expertise with this case.
1. Islam MP, Roach ES. Tuberous Sclerosis Complex. Vol 132. 1st ed. Elsevier B.V.; 2015. doi:10.1016/B978-0-444-62702-5.00006-8
2. Northrup H, Aronow ME, Bebin EM, et al. Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol. 2021;123:50-66. doi:10.1016/j.pediatrneurol.2021.07.011
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4. Shields CL, Say EAT, Fuller T, Arora S, Samara WA, Shields JA. Retinal astrocytic hamartoma arises in nerve fiber layer and shows “moth-eaten” optically empty spaces on optical coherence tomography. Ophthalmol. 2016;123(8):1809-1816. doi:10.1016/j.ophtha.2016.04.011
5. Nallasamy N, Seider MI, Gururangan S, Mruthyunjaya P. Everolimus to treat aggressive retinal astrocytic hamartoma in tuberous sclerosis complex. J AAPOS. 2017;21(4):328-331. doi:10.1016/j.jaapos.2017.04.012
6. Zhang ZQ, Shen C, Long Q, et al. Sirolimus for retinal astrocytic hamartoma associated with tuberous sclerosis complex. Ophthalmology. 2015;122(9):1947-1949. doi:10.1016/j.ophtha.2015.03.023
7. Wu F, McGarrey MP, Geenen KR, et al. Treatment of aggressive retinal astrocytic hamartoma with oral mechanistic target of rapamycin inhibition. Ophthalmol Retin. 2022;2:1-10. doi:10.1016/j.oret.2022.01.003