Purpose
To describe and correlate the features of astrocytic hamartomas using multimodal imaging.
Design
Prospective, noncomparative, observational case series.
Methods
This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared.
Results
In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots.
Conclusions
Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.
Tuberous sclerosis complex is an autosomal dominant disorder with an incidence of 1:10 000 to 1:25 000 births. More than half of patients have retinal astrocytic hamartomas, which are predominantly composed of well-differentiated glial astrocytes. Astrocytic hamartomas are usually stable over time, though a giant-cell variant has been reported and is associated with a more aggressive disease course.
Ophthalmoscopically, retinal astrocytic hamartomas demonstrate considerable heterogeneity. Some lesions appear elevated and distinct from the surrounding normal retina, while others are more subtle, with a color similar to the fundus background. Identifying these more subtle lesions is important during pediatric fundus examination, where identification of multiple retinal lesions can help in diagnosing tuberous sclerosis. Therefore, imaging modalities that offer enhanced visualization of subtle lesions would be clinically useful. In this study, we compare the appearance of astrocytic hamartomas on fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) to fundus examination and photography.
Methods
Between October 1, 2010 and January 31, 2011, 4 patients with diagnosed tuberous sclerosis were examined at the Edward S. Harkness Eye Institute, Columbia University. Each patient underwent a complete ophthalmic examination, including measurements of best-corrected visual acuity (BCVA), dilated ophthalmoscopy, and color fundus photography. FAF, infrared imaging, and SD-OCT of all patients was performed with the Spectralis confocal scanning laser ophthalmoscope (SLO)-OCT (Heidelberg Engineering, Heidelberg, Germany). This instrumentation allows for infrared or FAF scans to be obtained simultaneously with registered SD-OCT images. Standard methods of image acquisition were employed for all imaging modalities. To improve signal-to-noise ratio, each FAF image was composed of at least 9 single 30-degree × 30-degree images. Protocols for SD-OCT scans included 40 high-resolution frames per B-scan for volume scans and 100 high-resolution frames for 9-mm line scans. However, settings for resolution, the number of frames per B-scan, and the number of B-scans per volume scan were adjusted depending on patient cooperation and fixation.
Results
Four patients with tuberous sclerosis (2 male, 2 female) were examined. No patients reported a family history of tuberous sclerosis, and all patients were treated in the past with vigabatrin for infantile spasms refractive to other treatments. Their case histories are presented below.
Case 1
A 12-year-old white boy with BCVA of 20/25 +1 and 20/25 −2 presented with a large astrocytic hamartoma in the left eye. FAF and SD-OCT of this lesion demonstrated numerous hyperautofluorescent spots and hyperreflective dots, respectively. Infrared imaging and SD-OCT imaging of the right eye revealed a subtle retinal astrocytic hamartoma that was not visible on clinical examination or color fundus photography. FAF imaging failed to identify this lesion ( Figure 1 ) .
Case 2
A 13-year-old white boy presented with bilateral astrocytic hamartomas. BCVA was 20/20 bilaterally. Clinical examination of the right eye identified a lesion superficial to the inferior arcade and a more subtle lesion further inferotemporally. Infrared imaging and FAF offered enhanced visualization of the more subtle lesion (greater contrast compared to the retinal background). The SD-OCT scans of both eyes revealed hyperreflective dots and discrete hollow cavities (optically empty spaces) at varying depths of the tumors. The optically empty spaces co-localized with hyperautofluorescent spots seen in FAF ( Figure 2 ) .
Case 3
A 9-year-old white girl presented with bilateral astrocytic hamartomas. BCVA was 20/20 −1 and 20/25 −2 . Clinical examination of the left eye revealed multiple lesions around the optic nerve and a subtle lesion over the inferotemporal arcade. Both FAF and infrared imaging allowed greater visualization of the subtle lesion. FAF also revealed 2 distinct areas of hypoautofluorescence around the optic nerve. SD-OCT revealed optically empty spaces at varying tumor depths in the left eye and hyperreflective dots in the lesion in the right eye ( Figure 3 ) .
Case 4
An 11-year-old Hispanic girl presented with an astrocytic hamartoma in the left eye. BCVA was 20/20 −1 and 20/30 −1 . Clinical examination and color fundus images of the right eye revealed no obvious abnormality, but infrared imaging, FAF, and SD-OCT revealed an occult lesion in the superior macula. Following localization with infrared imaging, FAF, and SD-OCT, the lesion was retrospectively identified on the color photograph as a very faint discoloration and slight obscuration of the vessel ( Figure 4 ) .
