Jeffrey F McMahon, Pascal Jabbour, Carol L Shields
Intra-arterial chemotherapy (IAC) continues to provide a globe-sparing alternative as primary treatment for retinoblastoma with few adverse events. While there is growing evidence to highlight the utility of IAC in children with retinoblastoma, adult cases treated with primary IAC have not previously been characterized. We describe a rare case of Group D retinoblastoma in a 23-year-old adult treated successfully with IAC and intravitreal chemotherapy. This is a retrospective case report of a single patient. Subsequent to IAC and intravitreal chemotherapeutic treatments, at last follow-up 14 months following initial presentation and 8 months since last treatment, the retinoblastoma demonstrated complete regression into a partially calcified scar, with complete resolution of intravitreal and subretinal seeds and no evidence of tumor recurrence. Visual acuity improved to 20/30 in the left eye. There were no adverse events from therapy. Despite its rarity, it is important to consider retinoblastoma in the differential diagnosis of a white mass, even in an adult. Furthermore, this case highlights the utility of IAC for retinoblastoma, despite older patient age.
Fairooz P Manjandavida, Christina Stathopoulos, Jing Zhang, Santhosh G Honavar, Carol L Shields
Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary treatment modalities for intraocular retinoblastoma worldwide. Following the introduction of the technique in 1998, IAC has evolved over the past decades to be safer and more effective. Accumulated evidence shows that IAC is more effective in providing eye salvage in group D and E retinoblastoma as compared to conventional systemic intravenous chemotherapy (IVC). In contrast to IVC, IAC has the added benefits of reduced overall treatment duration and minimal systemic toxicity. This review provides a comprehensive update on the history, technique, indications, contraindications, and outcome of IAC. We have also identified the strengths, weaknesses, opportunities and threats (SWOT analysis) of the technique in this review.
Amar Pujari, Neiwete Lomi, Siddhi Goel, Saumya Yadav, Ritika Mukhija, Prashant Kumar, Atul Kumar
Recent ophthalmic innovations have shown that smartphones are able to capture the fundus images with  or without  any attachments. The presence of a near coaxial arrangement in smartphones, i.e., the close proximity of its camera with the light source, is the primary reason that makes the same possible. It is noteworthy that in routinely used direct ophthalmoscope, the light source and the aperture to visualize the fundus findings are also in close proximity, and hence the presence of this simple feature among the newer generation smartphones can be effectively utilized by the ophthalmologist to capture fundus images with great ease. However, this feature is currently present in a few models only, namely, iPhone X and higher version smartphone cameras, making fundus visualisation with other smartphones difficult, as the greater distance between the light source and visualization aperture obviates the coaxial functioning. In addition, the inherent optical qualities of the smartphone camera and features such as wider lens apertures, better pixel quality, optical image stabilisation, and others also play a crucial role in imaging…..
MB Thirumalesh, Raksha Rao, Gagan Dudeja
An 18-month-old male child presented with right eye white reflex for about 2 months. On fundoscopy, the patient was noted to have right eye retinoblastoma. In addition, there was posterior lens capsular opacity [Figure 1]a with a prominent posterior tunica vasculosa lentis (PTVL) dipping into the tumour located at the optic nerve head, confirmed on ultrasound B scan [[Figure 1]a, inset]. After 3 cycles of systemic chemotherapy, the tumour shrinkage resulted in posterior traction by the vasculature causing radial capsular folds [Figure 1]b. PTVL normally starts regressing in the second trimester. In this case, the continued blood supply from these primitive vessels to the retinoblastoma possibly inhibited the regular vascular endothelial growth factor (VEGF)-induced angiogenic mechanisms that take place during vascular regression, leading to persistent fetal vasculature.
Amit Khedekar, Bharanidharan Devarajan, Kim Ramasamy, Veerappan Muthukkaruppan & Usha Kim
To improve and validate the smartphone-based leukocoria detection application so that non-ophthalmologists could make use of the smartphone for early detection of Retinoblastoma (RB) in young children without anesthesia and pharmacological dilatation of the pupil.
Two apps, MDEyeCare and CRADLE, developed for red reflex based leukocoria detection were used in iPhone 6s. MDEyeCare methodology was modified with respect to ambient lighting, the distance between camera and eye and different gazes for better performance. We analyzed totally 34 eyes of 23 RB patients and four normal children. Each of the RB patients was confirmed with clinical examination and radiological investigations.
Modification in the methodology of MDEyeCare app could detect the leukocoria in early stages of RB (50% of Group B, 83% of Group C). In late stages (Group D and E), 100% of tumors were detected. The CRADLE app failed to provide adequate leukocoria detection except four late stage RB eyes. Among the 14 normal eyes (6 from unilateral RB and eight from normal children), pseudo-leukocoria was observed in three eyes only at lateral gaze even with MDEyeCare app.
Improved methodology in smartphone-based app enhanced the detection of RB and this may translate into better outcome after treatment with respect to vision salvage.
Sameh E Soliman, Cynthia VandenHoven, Leslie D Mackeen, Brenda L Gallie
Background/aims To assess tumour control, vision and anatomical visual potential in eyes with perifoveal retinoblastoma treated by sequential photocoagulation from the antifoveal tumour edge inwards, avoiding treatment near the fovea. Patients were monitored for tumour control, foveal and perifoveal anatomy at each treatment session by optical coherence tomography (OCT) and treated for amblyopia when the other eye had better vision.
Methods Eyes with perifoveal retinoblastoma treated between 1 January 2011 and 31 May 2017 with laser therapy after chemotherapy for juxtafoveal (fovea clear of tumour but <3000 µm from tumour edge) or foveolar retinoblastoma (tumour underlying fovea) were retrospectively reviewed for tumour control without recurrence, anatomical success (foveal pit preservation and/or restoration with ≥500 µm perifoveal retina free of tumour and scar) and functional success (acceptable (>0.1 decimal) or good (>0.3 decimal) visual acuity (VA)).
Results Twenty-two eyes (14 juxtafoveal, 8 foveolar tumours) of 20 patients (19 bilateral, 1 familial and 11 females) were included. No juxtafoveal tumour had tumour recurrence, and 13/14 patients showed foveal pit preservation with ≥500 µm of perifoveal retina tumour free. Foveolar tumours had significant worse anatomical outcomes: failure to restore foveal pit or perifoveal retina (8/8, p=0.001) and tumour recurrences (5/8, p=0.001). Functional success with acceptable VA was achieved in 12/14 juxtafoveal and 5/8 foveal tumours eyes (p=0.01). Amblyopia therapy data were insufficient to evaluate impact on VA.
Conclusions Anatomical visual potential and functional vision were better in juxtafoveal than foveolar retinoblastoma treated with foveal-sparing laser photocoagulation guided by OCT. The role of amblyopia therapy requires a prospective study.
Christina Stathopoulos, Alexandre Moulin, Marie-Claire Gaillard, Maja Beck-Popovic, Francesco Puccinelli, Francis L Munier
Background/aims To report conservative therapy in diffuse infiltrating retinoblastoma (DIR) and describe specific optic coherence tomography (OCT) features of the tumour.
Methods Retrospective review of all DIR cases treated conservatively between 1998 and 2012.
Results Three patients (three eyes) were included, cases 1 and 3 with previous enucleation of the contralateral eye and case 2 with unilateral retinoblastoma referred after prior pars plana vitrectomy with silicone oil. Mean age at diagnosis was 7 years (range 14 months–14 years). Globe and vision preservation (Snellen visual acuity of 12.5/10) was achieved in case 3 with a recurrence-free follow-up of 33 months after first-line thermotherapy followed by salvage intra-arterial chemotherapy (IAC) plus focal treatments. Cases 1 and 2 were enucleated for progressive disease, case 1 after first-line intravenous chemotherapy (IVC) consolidated by focal therapies and salvage treatments given over 8 years of partial remission and case 2 after IAC, brachytherapy and intracameral chemotherapy. Neither showed any high-risk histopathological features, and no adjuvant chemotherapy was necessary. Both patients are alive without metastasis (mean follow-up of >10 years). Pathognomonic features of the tumour were revealed by OCT in all cases, showing infiltration of the ganglion cell layer and horizontal growth over the inner plexiform layer. Complete restoration of the retinal microanatomy was documented after retraction of the tumour following IVC in case 2 and IAC in case 3.
Conclusion This is the first report of successful conservative management in DIR. OCT enabled diagnosis, delimitation of the tumour margins and monitoring of the treatment response in this context.
John T Lucas, Rose McGee, Catherine A Billups, Ibrahim Qaddoumi, Thomas E Merchant, Rachel C Brennan, Jiangrong Wu, Matthew W Wilson
Background/aims Non-irradiative local therapies have shown promise in delaying or supplanting external beam radiotherapy (EBRT) and enucleation in patients with retinoblastoma. We hypothesised that prior focal therapy does not compromise the efficacy of delayed episcleral plaque brachytherapy (epBRT).
Methods We performed an institutional review board-approved medical record review of patients with retinoblastoma who were treated with I-125 epBRT prior to (primary) or following chemoreduction (delayed), alone and in combination with non-irradiative focal therapy. Clinical and treatment characteristics were retrieved. Treatment failure was defined as the need for subsequent EBRT and/or enucleation. Event-free and ocular survival rates were calculated from the date of plaque placement. The cumulative incidences (CIs) of treatment failure and enucleation were compared across strata using Gray’s test.
Results We identified 50 patients with retinoblastoma (54 eyes), who received a total of 56 plaques between January 1986 and December 2010, with a median follow-up of 8.3 years (range, 0.8–21.2 years). The median time from diagnosis to plaque placement was 12.7 months (range, 0.1–128 months). The CI and 95% CI of treatment failure and enucleation following epBRT at 5 years was 37%±7.2% and42.2%±7.3%, respectively. The lack of prior diode or green laser therapy was predictive of increased risk for treatment failure (p=0.02 and 0.03). International Classification group C or D was predictive of decreased time to enucleation (p=0.004). The use of any focal therapy was not predictive of time to treatment failure (p=0.33).
Conclusions The use of non-irradiative focal therapies prior to or following epBRT does not decrease the time to enucleation or treatment failure.
Ancona-Lezama D.A. · Dalvin L.A. · Lucio-Alvarez J.A. · Jabbour P. · Shields C.L.
Purpose: Intra-arterial chemotherapy (IAC) has become a mainstay in the management of retinoblastoma, especially in advanced or refractory disease. However, IAC is not without complications, and chemotherapy toxic effects can lead to partial or complete choroidal ischemia, often causing vision loss. Methods: This is a case report. Results: A 4-month-old girl with bilateral retinoblastoma was treated with secondary IAC (melphalan 5 mg) for recurrent tumor following intravenous chemotherapy. One month later, complete tumor control was achieved. However, she demonstrated broad choroidal ischemia in the nasal and temporal quadrants but sparing of the watershed zone superior and inferior to the optic disc and in the papillomacular region. Fluorescein angiography revealed poor perfusion of the choriocapillaris with visibility of the large choroidal vessels in the nasal and temporal areas but preserved perfusion of the watershed zone. The watershed zone remained intact on the 10-month follow-up, and the final visual acuity was fix and follow without strabismus. Conclusion: The pathophysiology of choroidal ischemia is not well understood, but the fortuitous watershed zone preservation in this case could represent uneven distribution of the chemotherapeutic drug, resulting in partial chemo-dilution of the medication in the watershed region, which represents the final downstream overlapping choroidal perfusion from both medial and lateral posterior ciliary arteries.
Rita Laiginhas, MD; Manuel Falcão, MD, PhD
To determine the incidence of retinoblastoma in the United States from 1973 to 2012 (40 years) and characterize the 5-year overall survival rate of the included patients.
Cases of retinoblastoma were derived from the Surveillance, Epidemiology, and End Results (SEER) Program (National Cancer Institute, Rockville, MD). Incidence rates were calculated using U.S. Census Bureau data as the standard population, and trends over time were determined using the chi-square test. Hazard ratios with a 95% confidence interval (CI) were estimated for variables associated with mortality using Cox regression models. Survival rates were calculated using the Kaplan–Meier method and compared among different clinical and demographic categories.
A total of 879 cases of retinoblastoma were derived from the SEER databases. The annual incidence rates of retinoblastoma for a period of 40 years were 12.14 (95% CI: 11.32 to 12.96) cases per 1 million children 4 years or younger and 0.49 (95% CI: 0.36 to 0.65) cases per 1 million children between the ages of 5 and 9 years. There was no significant trend for children 4 years or younger (P = .6324) or between the ages of 5 and 9 years (P = .7695). The 5-year overall survival rates were 97.6%, 92.7%, 91.1%, and 96.4% for children diagnosed at the first, second, third, and after the third year of life, respectively (P = .0136). The 5-year overall survival rates were 92.5% for bilateral and 96.3% for unilateral cases (P = .0116). The 5-year overall survival rates were 90.8%, 92.5%, 97.6%, 97.3% for increasing time intervals (1973 to 1979, 1980 to 1989, 1990 to 1999, and 2000 to 2012, respectively; P = .0017).
The incidence rate of retinoblastoma in the United States has remained stable for the past 40 years. Survival rate analysis indicates a significant effect of laterality of tumor, age at diagnosis, and decade of diagnosis.