Tuberous sclerosis complex (TSC) is a dominantly inherited hamartomatous disorder affecting the brain, skin, eye and other organs.1 The clinical manifestations and severity can vary widely with this disease, occasionally making diagnosis challenging. The Tuberous Sclerosis Consensus Conference established diagnostic criteria requiring the presence of 2 major features, or 1 major and 2 minor features of TSC for definitive diagnosis.1 The ophthalmic major features are retinal astrocytic hamartoma and eyelid angiofibroma.1 Other ophthalmic manifestations of TSC include iris atrophy, uveal coloboma, and disturbances of the retinal pigment epithelium (RPE), referred to as “punched-out” lesions.23 only recently have these RPE lesions been defined as a clear marker of TSC.2,4

Case report

A 16-year-old male was referred our medical center with a diagnosis of tuberous sclerosis complex since age 2 years. Ocular examination disclosed visual acuity of 20/20 in the right eye and 20/60 in the left eye. Fundoscopy showed multiple astrocytic hamartomas bilaterally (arrowheads in Figures 1 and 2), as well as bilateral multifocal RPE “punchedout” lesions (arrows in Figures 1 and 2), which were confirmed by the presence of transmission defect on fluorescein angiography (arrows in Figure 2B).

Discussion

The association of RPE depigmented lesions with TSC is often unrecognized. One minor feature of TSC is the retinal achromatic patch, which is not clearly described, but could represent a flat astrocytic hamartoma or could be a description of an RPE depigmented lesion. In 1975, Shelton reported on the presence of depigmented lesions in the retina of a TSC patient but attributed them to ocular histoplasmosis rather than an additional TSC finding.3

Rowley et al4 and Shields et al2 demonstrated the diagnostic importance of “punched-out” RPE lesions, describing them in 39% (n=39) and 21% (n=12) of TSC patients, respectively, significantly more common than in age matched controls (P < .001).2,4 Shields et al further described a significant relationship of RPE lesions with definitive TSC, seizure history, mental retardation, cutaneous adenoma sebaceum, ash leaf macule, and increasing number of retinal astrocytic hamartomas per eye.2

Summary

In summary, we illustrate a patient with definitive TSC showing classic retinal astrocytic hamartomas, a well-established major diagnostic marker of TSC. In addition, we portray the less well-known minor features of RPE “punched-out” lesions. These RPE lesions are often overlooked but could represent an important diagnostic ophthalmologic finding of tuberous sclerosis complex (TSC).

Support provided by Eye Tumor Research Foundation, Philadelphia, PA (CLS, JAS). The funders had no role in the design and conduct of the study, in the collection, analysis and interpretation of the data, or in the preparation, review or approval of the manuscript. Carol L. Shields, MD, has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Anne Hutchinson, BA, is an MD candidate, class of 2014 at Jefferson Medical College, Thomas Jefferson University in Philadelphia.

Duangnate Rojanaporn, MD, FICO, is a fellow in the Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA and with the Ophthalmology Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Carol L. Shields, MD, is the Co-Director of the Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University. She is a Retina Today Editorial Board member. Dr. Shields can be reached at +1 215 928 3105; fax: +1 215 928 1140; or via email at carol.shields@ shieldsoncology.com.

No conflicting relationship exists for any author.

  1. Roach ES, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol. 2004;19(9):643-649.
  2. Shields CL, Reichstein DA, Bianciotto C, Shields JA. Retinal pigmented epithelium depigmented lesions associated with tuberous sclerosis complex. Arch Ophthalmol. 2012; 130:387-390.
  3. Shelton RW. The incidence of ocular lesions in tuberous sclerosis. Ann Ophthalmol. 1975;7:771-774.
  4. Rowley SA, O'Callaghan FJ, Osborne JP. Ophthalmic manifestations of tuberous sclerosis: a population based study. Br J Ophthalmol. 2001; 85:420-423.