Journal of Clinical Ophthalmology and Research

: 2019  |  Volume : 7  |  Issue : 3  |  Page : 130--134

Ophthalmic manifestations of tuberous sclerosis: A diagnostic clue

Richa Dhiman, Aditi Prashar, RK Sharma, Mandeep Tomar, Nishita Yadav 
 Department of Ophthalmology, Dr. Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India

Correspondence Address:
Richa Dhiman
Department of Ophthalmology, Dr. Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh


A 22-year-old female with severe headache was referred to eye outpatient department for fundus examination with a possibility of intracranial space-occupying lesion. On fundus examination, we found bilateral disc edema with creamy white elevated lesion in the left eye suggestive of retinal astrocytoma which was confirmed by spectral-domain optical coherence tomography. Hence, the patient underwent magnetic resonance imaging brain, ultrasonography abdomen, and dermatological workup which confirmed it to be the case of tuberous sclerosis. This case report exemplifies the systemic manifestations of tuberous sclerosis complex and its specific expression in the eye. Hence, in turn, to establish an appropriate diagnosis, retinal manifestations of the disorder must not be overlooked.

How to cite this article:
Dhiman R, Prashar A, Sharma R K, Tomar M, Yadav N. Ophthalmic manifestations of tuberous sclerosis: A diagnostic clue.J Clin Ophthalmol Res 2019;7:130-134

How to cite this URL:
Dhiman R, Prashar A, Sharma R K, Tomar M, Yadav N. Ophthalmic manifestations of tuberous sclerosis: A diagnostic clue. J Clin Ophthalmol Res [serial online] 2019 [cited 2022 Jul 1 ];7:130-134
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Full Text

Tuberous sclerosis complex (TSC), also referred to as Bourneville–Pringle's disease, is a rare autosomal dominant neurocutaneous disorder that causes benign tumors in multiple organs, including the eye, brain, skin, kidney, heart, and lung.[1],[2] The epidemiological study shows that the incidence of TSC is approximately 1/6000.[3] The first description of TSC is usually attributed to Bourneville in 1880,[4] and in 1908, Vogt described the classic triad of epilepsy, mental retardation, and adenoma sebaceum (now called angiofibromatosis).[5] TSC is caused by mutations of the TSC1 or TSC2 genes, which code for the tumor growth suppressors hamartin and tuberin, respectively.[3],[6],[7] Retinal hamartomas are glial tumors of the retinal nerve fiber layer that arises from retinal astrocytes. They occur in 40%–50% of patients with TSC.[8] Since TSC is a multiorgan disorder which usually presents with neurological or skin manifestations, and retinal findings are often missed or misdiagnosed. Hence, fundus examination is very important in a patient suspected of TSC.

 Case Report

A 22-year-old female presented in medicine outpatient department with fever (undocumented) and severe headache in the frontal and retro-orbital region associated with nausea and dizziness for the past 3 days with no history of seizures or mental retardation. An urgent computed tomography scan head [Figure 1] was done, which showed features suggestive of well-defined large hyperdense lesion near foramen of Monro causing obstructive hydrocephalus with multiple subependymal calcifications. She was referred to us for fundus examination to rule out papilledema with a possibility of intracranial space-occupying lesion.{Figure 1}

On ophthalmic examination, her best-corrected visual acuity was 20/20, N/6. The anterior segment in both eyes was within normal limits. On fundus examination [Figure 2], the right eye had disc edema with blurred margins and multiple dot hemorrhages in all quadrants.{Figure 2}

The left eye fundus [Figure 3] showed disc edema, dot hemorrhages along with a creamy white, well-circumscribed, slightly elevated, nodular lesion just inferior to the disc obscuring the retinal vessels. Another lesion was present along the superotemporal arcade which was flat, translucent, and grayish in color which was visible clearly in red-free fundus photograph [Figure 4]. Both the lesions were suggestive of retinal astrocytic hamartomas.{Figure 3}{Figure 4}

Spectral-domain optical coherence tomography [Figure 5] and [Figure 6] was also done which revealed abnormal thickening of the retinal nerve fiber layer, round contour of hamartoma with gradual transition to adjacent normal retina. Hence, a possibility of tuberous sclerosis was kept based on retinal findings, and magnetic resonance imaging (MRI) brain was advised to confirm it.{Figure 5}{Figure 6}

On general physical examination of the patient [Figure 7], multiple well-defined, brown sessile nodular growths were noted on the nose and cheeks in a characteristic “butterfly pattern,” which were symmetrical on both sides, avascular, and flesh colored with multiple hypomelanotic macules on the lumbosacral region, with one hypermelanotic patch showing an orange peel appearance indicative of shagreen patch. A well-defined hypomelanotic macule was present on the posterior aspect of leg giving ash-leaf appearance.{Figure 7}

MRI brain [Figure 8] was done, which confirmed the presence of subependymal giant cell astrocytoma in the right lateral ventricle.{Figure 8}

Ultrasound of the kidney was carried out, which revealed multiple variable-sized (1–3 mm) hyperechoic foci in bilateral renal cortices suggestive of renal angiomyolipomas. Echocardiography was also done which came out to be normal.

Based on all these features, a diagnosis of TSC was confirmed. The patient had also the symptoms of raised intracranial tension because of the subependymal giant cell astrocytoma at the foramen of Monro, hence, she was given symptomatic treatment and was referred to a higher center for neurosurgical intervention.


The knowledge of ophthalmic manifestations in tuberous sclerosis is important because it can aid in the diagnosis of the patient and hence better management if diagnosed at an early stage. Ophthalmic features associated with TSC can be divided into retinal and nonretinal. The retinal associations of TSC were first noted by Van der Hoeve in 1921,[9] and he introduced the concept of phakomatosis. These retinal lesions are now known to be astrocytic hamartomas.[10] Nonretinal findings include angiofibromas of the eyelids, coloboma of the iris, lens and choroid, strabismus, poliosis of eyelashes, papilledema,[11] and sector iris depigmentation.[12]

TSC is an autosomal dominant disorder with nearly complete penetrance but variable expressivity. In our case, we found that though her father also had similar hypomelanotic macules over his back, he never became symptomatic in contrast to her daughter (patient) who presented with above-mentioned symptoms. She has one brother who is clinically healthy. [Figure 9] shows the family pedigree of the proband.{Figure 9}

The severity of manifestations in TSC varies from patient to patient, and the prognosis of the patient depends on the time of accurate diagnosis when the patient is least affected.

Diagnostic criterion for TSC put forth in 1998 was modified by International Tuberous Sclerosis Consensus Conference in 2012 [Table 1], according to which two major or one major with two minor features have to be present in the patient for diagnosing it as TSC.[13]{Table 1}

Our case presented with five major features: facial angiofibromas, shagreen patch, subependymal giant cell astrocytoma, retinal hamartomas, and renal angiomyolipomas.

The management of these patients is often multidisciplinary involving the neurosurgeon, neurologist, nephrologist, pulmonologist, cardiologist, ophthalmologist, and the genetic counselor. Therapeutic options for TSC patients revolve mainly around symptomatic management. Vigabatrin is an irreversible GABA inhibitor that has been shown to quell infantile spasms in more than 90% of TSC patients. Older children with particularly epileptogenic focal tubers have been treated by surgical resection.[14]

Surgery including dermabrasion and laser treatment may be useful for the treatment of skin lesions. For retinal astrocytic hamartomas, treatment is almost never required since they are benign lesions. On rare occasions, retinal astrocytomas can show progressive growth and have associated features such as vitreous seeds, vitreous hemorrhage, and exudative retinal detachment, which can simulate retinoblastoma or choroidal melanoma. In such cases, photodynamic therapy can be effective.


The prognosis of TSC depends on the severity or multiplicity of organ involvement. About a quarter of severely affected infants are thought to die before the age of 25 years. In the case of individuals diagnosed late in life with few cutaneous signs, prognosis depends on the associated internal tumors and cerebral calcifications. This case report exemplifies the systemic manifestations of TSC and its specific expression in the eye. Hence, in turn, to establish an appropriate diagnosis, retinal manifestations of the disorder must not be overlooked.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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