Optical coherence tomography (OCT) imaging of ophthalmoscopically visible retinoblastoma was first reported in 2014.1 OCT detection of nonophthalmoscopically visible, or “invisible,” retinoblastoma has also been reported.2,3 We present one patient who developed multiple manifestations of active retinoblastoma that were detected or confirmed by portable OCT.
Design and Methods
Clinical examination, portable hand-held OCT, and color photography was used to document findings in a patient with bilateral retinoblastoma. This deidentified, retrospective case report was considered exempt from review by the Duke University Institutional Review Board.
A 2-week-old girl with a strong family history of retinoblastoma underwent examination under anesthesia (EUA) to screen for retinoblastoma. Examination revealed both a moderate-sized macular tumor as well as small, peripheral retinoblastoma tumors in the left eye and no disease in the right eye. The patient underwent six cycles of systemic chemotherapy (carboplatin, etoposide, and topotecan [Hycamtin; Novartis, Basel, Switzerland]), as well as adjunct laser photocoagulation and cryotherapy in the left. One month after completing chemotherapy, repeat EUA revealed no visible tumor but the suggestion of a very mild alteration in the reflectivity of the internal limiting membrane along the superotemporal arcade of the right eye. Hand-held spectral-domain OCT (Envisu; Bioptigen, Morrisville, NC) scanning of the right macula in the area of concern showed hyperreflective disorganization and thickening of the inner retina, confirming the presence of a retinoblastoma tumor that could not be confirmed by clinical examination alone (Figures 1a and 1b). This tumor underwent two treatments with laser photocoagulation and was rendered inactive (Figures 1c and 1d). At EUA 1 month later, all tumors appeared inactive ophthalmoscopically. OCT was performed over both maculae without the expectation of finding any new disease, but revealed multiple small circular hyperreflectivities in the inferotemporal posterior vitreous in the left eye that were concerning for new dust-like vitreous seeds (Figure 1e). These hyperreflectivities appeared to become less prominent on OCT following two intravitreal melphalan (Alkeran; ApoPharma, North York, Ontario, Canada) injections (Figures 1f and 1g) with serial examination/imaging. Five months later, a new recurrence of the left macular tumor was noted ophthalmoscopically, although review of the previous OCT images showed that tumor growth could be seen on imaging as a hyperreflective thickening of retina before it was identified clinically (Figure 2). Treatment of this tumor is ongoing.
(a) Color photograph of the right eye showing no clearly visible retinoblastoma tumor. Arrow indicates scan location in (b). (b) Portable optical coherence tomography (OCT) image corresponding to (a) showing nonophthalmoscopically confirmed retinoblastoma tumor. Color fundus photograph (c) and portable OCT image (d) 2 months later, after laser photocoagulation to tumor, revealing inactive scar. (e) Portable OCT image and corresponding OCT-simulated fundus image revealing small, hyperreflective lesions in posterior vitreous. Green line in simulated fundus image reveals scan location. (e) One week later, following one intravitreal melphalan injection, the hyperreflectivities appear less prominent in the vitreous. (f) Following three weekly intravitreal melphalan injections, the hyperreflectivities appear largely stable.
(a) Color photograph reveals inactive macular retinoblastoma. Corresponding portable optical coherence tomography (OCT) through lesion reveals disorganized retinal layers, retinal thinning, and choroidal atrophy in area of treated retinoblastoma tumor. (b) Color photograph 1 month after (a) reveals stable, inactive macular retinoblastoma. Corresponding portable OCT through lesion reveals trace thickening at the nasal edge of the retinoblastoma tumor (arrow). (C) Color photograph 3 months after (a) reveals recurrence of macular tumor (arrow). Corresponding portable OCT through lesion reveals significant tumor thickening suggestive of reactivation.
This case emphasizes the importance of obtaining OCT images of children with retinoblastoma. In this case, hand-held OCT under anesthesia was used to confirm or detect tumor activity, including a new retinal tumor, new vitreous seeds, and a new retinal tumor recurrence that were unable to be confirmed via ophthalmoscopic examination alone. OCT also aided in monitoring tumor response to treatment. Most children with retinoblastoma are too young to sit for standard clinic-based OCT imaging. As such, OCT systems with the ability to image anesthetized, usually supine, patients are useful.
Cao et al. has described retinoblastoma involvement by OCT in the inner and outer retina.1 Detection of tumor activity by OCT may be limited in thicker tumors, in the setting of exudative retinal detachment, or in regressed tumors with residual calcium that can block signal penetration. It is unclear if the small foci of hyperreflectivity detected on OCT in our patient (Figures 1e, 1f, and 1g) are truly invisible, active vitreous seeds or instead more chronic, calcified seeds and/or vitreous debris (secondary to inflammation or other cause). In this case, treatment with intravitreal chemotherapy appeared to decrease the prominence of these hyperreflectivities on imaging, although it is possible that this difference is secondary to differential imaging between examinations. This portable OCT is hand-held and does not contain the tracking software present in many table-top systems, so images are more susceptible variability between imaging sessions. However, one advantage of hand-held OCT is that its scan location may be adjusted relatively easily by tilting the probe, which may permit improved visualization of peripheral retina.
This case suggests that there is a role for an OCT-based screening protocol in retinoblastoma. We propose performing baseline macular volume scan in both eyes to document tumor and foveal morphology. Sequential volume scans should be repeated during active treatment and for several months after treatment is completed when new development of small and recurrent tumors are most common. We recommend volume cube scans centered at the macular center, optic nerve, superotemporal and inferotemporal arcades, and over areas of posterior tumor activity. Such scans permit documentation of the foveal status, change in macular morphology over time, and possible detection of ophthalmoscopically invisible retinal tumors, vitreous seeds, and early retinal tumor recurrence. Future advancements in widefield OCT scan patterns may help improve the visualization of the retinal periphery and aid in the early detection of tumor activity.
- Cao C, Markovitz M, Ferenczy S, Shields CL. Hand-held spectral-domain optical coherence tomography of small macular retinoblastoma in infants before and after chemotherapy. J Pediatr Ophthalmol Strabismus. 2014;51(4):230–234. doi:10.3928/01913913-20140603-01 [CrossRef]
- Saktanasate J, Vongkulsiri S, Khoo CT. Invisible retinoblastoma. JAMA Ophthalmol. 2015;133(7):e151123. doi:10.1001/jamaophthalmol.2015.1123 [CrossRef]
- Berry JL, Cobrinik D, Kim JW. Detection and intraretinal localization of an ‘invisible’ retinoblastoma using optical coherence tomography. Ocul Oncol Pathol. 2016;2(3):148–152. doi:10.1159/000442167 [CrossRef]