Aloysius Abraham, Kannan Thirumalairaj, Namrata Gaikwad, Veerappan Muthukkaruppan, Alla G Reddy, Kumarasamy Thangaraj, Usha Kim, Ayyasamy Vanniarajan
Retinoblastoma has an increased inheritance risk of germline RB1 mutations in offspring and siblings, especially twins. Three families, each having one retinoblastoma-affected twin, were selected for genetic analysis and DNA profiling. Germline RB1 mutations were found in all probands. DNA profiling carried on similar-looking twins of families I and II, proved them to be fraternal. This study demonstrates the importance of genetic analysis of RB1 gene for risk prediction in retinoblastoma families. It also emphasizes that DNA profiling is a mandate for genetic screening of families with twins, thus adding a new dimension in counseling of retinoblastoma.
Stacey A.W. · Clarke B. · Moraitis C. · Fabian I.D. · Smith V. · Sagoo M.S. · Reddy M.A.
Purpose: The study aimed to assess the incidence of and risk factors leading to visual impairment and legal blindness in children with retinoblastoma. Procedures: This is a single-center, retrospective case series of all patients with bilateral retinoblastoma presenting from 2010 to 2014. Results: A total of 44 patients were included in the study. Visual impairment was present in 14 (38%) children, legal blindness was present in 7 (19%) children. Bilateral macular tumors (BMT) were associated with visual impairment (12 of 18 patients with BMT, 2 of 19 patients without BMT, p = 0.0006) and legal blindness (7 of 18 patients with BMT, 0 of 19 patients without BMT, p = 0.003).The International Intraocular Retinoblastoma Classification (IIRC) of the better eye also predicted visual impairment (16% in IIRC Group A–C, 75% in IIRC Group D, E, p = 0.004) and blindness (3% eye in IIRC Group A–C, 50% in Group D, E, p = 0.005). Various non-Snellen visual acuity measures were able to predict visual impairment in pre-verbal children, providing them with early assistance. Conclusions: The rates of visual impairment and blindness reported in this paper can be used to counsel families regarding the risk of binocular visual impairment. Early detection and support for visually impaired infants are essential as development can be affected by severe visual impairment.
Damato B. · Afshar A.R. · Everett L. · Banerjee A. · Hetts S.W.
Background/Aims: Current retinoblastoma staging systems do not adequately describe the disease, especially in eyes with multiple tumors. The aims of this study were to develop methods for documenting individual tumors and to score disease burden over time. Methods: A coding system was devised to describe each tumor according to affected eye, meridian, anteroposterior location, activity, growth pattern, type of seed, and treatment. A scoring system for quantifying disease burden was developed, taking account of tumor number, size, spread, and secondary effects on the eye. Results: Our coding system allowed contemporaneous tumor documentation, producing datasets that enabled generation of fundus diagrams, Kaplan-Meier curves, and tables summarizing disease progression in individual tumors and eyes. Our data showed disparities between ocular and tumor documentation, e.g., indicating earlier tumor development in the left eye but younger age at presentation if disease was worse in the right eye. Actuarial rates of local treatment failure were lower when individual tumors were analyzed than when data were reported in terms of whole eyes. Conclusion: Our methods for documenting individual retinoblastomas have facilitated the review of patients’ progress in our routine practice and may provide data that could be used to refine retinoblastoma classifications in the future.
Dalvin L.A. · Kumari M. · Essuman V.A. · Shohelly Shipa S. · Ancona-Lezama D. · Lucio-Alvarez J.A. · Jabbour P. · Shields C.L.
Purpose: To report our 5-year experience with intra-arterial chemotherapy (IAC) in the intravitreal chemotherapy (IvitC) era. Methods: Retrospective review of retinoblastoma treated with primary unilateral IAC in the IvitC era (2012–2017). Results: There were 34 eyes treated with IAC alone versus 20 eyes treated with IAC plus IvitC for vitreous seeds. IAC (IAC alone vs. IAC plus IvitC) consisted of melphalan (41 vs. 10%) or melphalan plus topotecan (59 vs. 90%, p = 0.03). IvitC consisted of melphalan (60%) or melphalan plus topotecan (40%). Tumor control and globe salvage were achieved in 100% of group B and C eyes without IvitC. Despite more extensive vitreous seeds in the IvitC group (p < 0.01), comparison of IAC alone versus IAC plus IvitC revealed no difference in tumor control for group D (88 vs. 69%, p = 0.36) or group E (67 vs. 100%, p = 0.25) and no difference in globe salvage for group D (88 vs. 69%, p = 0.36) or group E (58 vs. 57%, p = 0.39). Conclusions: IAC is effective as primary therapy for unilateral group B, C, D, and E retinoblastoma. IvitC is an important adjuvant therapy to achieve comparable globe salvage rates for group D and E eyes with persistent active vitreous seeds.
Berry J.L. · Shah S. · Kim F. · Jubran R. · Kim J.W.
Background: Intravitreal injection of melphalan (IVM) is safe and effective for the treatment of seeding in retinoblastoma. Current protocols require weekly injections during examination under anesthesia (EUA). To avoid additional anesthesia exposure for these children, IVM was initiated at the EUA concurrent with the 4th cycle of systemic chemoreduction in a series of 6 patients with persistent seeding. Methods: A retrospective review was completed to assess treatment response compared to all patients at our center treated with IVM and systemic chemotherapy. Overall, 6 eyes of 6 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin and IVM for persistent seeding. Results: IVM was initiated in all eyes at cycle 4 of their chemotherapy. Success in eradicating vitreous seeds was 100%; overall salvage rate was 67%. Anterior toxicity was observed in 2 out of 6 eyes and posterior toxicity in 4 out of 6 eyes. Conclusion: The concurrent chemoreduction and IVM protocol demonstrated a similar efficacy of globe salvage while sparing children additional EUAs. However, the increased rates of observed melphalan-related toxicities for concurrent therapy are concerning. Further clinical experience is necessary to define the best initiation time and dosing schedule for IVM.
Vrushali Athavale, Vikas Khetan
Retinoblastoma, the most common primary intraocular malignancy of the young, is a prototype hereditary cancer. Due to its fairly predictable Mendelian inheritance, easily examinable tumors, and early age of presentation, RB has served as the most extensively studied model for genetics in cancer. The genetic strides in RB have progressed at an exponential rate since the 1970s. The highly morbid, reasonably curable and distinctly predictable inheritance pattern of RB; not to mention its propensity to affect our young, forms the basis of aggressively encouraging genetic diagnosis in all patients of RB. In this article, we present the basic and clinically relevant concepts of the genetics retinoblastoma.
Ahmad S. Alfaar, Guillermo Chantada, Ibrahim Qaddoumi
To the Editor: We read with interest the article by Shehata and colleagues, which suggests that measuring serum and aqueous humor levels of survivin and TGF-B1 may be beneficial for detection and follow-up in patients with retinoblastoma (RB).1 Targeting survivin does improve chemosensitivity in patients with RB.2,3 Nevertheless, survivin is not cancer specific and is involved in many essential physiological processes, which makes it a poor choice for targeted therapy.4
Jari Radros, Charlotta All‐Eriksson, Niklas Pal, Stefan Holm, Stefan Seregard, Michael Söderman, Fabian Arnberg, Staffan Holmin
No abstract available
Francesco Klinger, Luca Maione, Valeriano Vinci, Andrea Lisa, Federico Barbera, Laura Balia, Fabio Caviggioli & Alessandra Di Maria
Autologous fat grafting has been extensively and successfully adopted in a number of pathologic conditions in regenerative surgery especially on irradiated fields in order to improve pain symptoms and tissue trophism promoting scar release. In the present study, we report our experience with autologous fat grafting for the treatment of postirradiation fibrosis and pain on three consecutive patients undergoing orbital enucleation for locally advanced retinoblastoma (RB) and subsequent radiotherapy. We selected three consecutive patients who underwent orbital enucleation for locally advanced RB and subsequent local radiotherapy showing severe reduction in orbital volume and eyelid length and retraction due to fibrosis, spontaneous local pain exacerbated after digital pressure with no possibility to place an ocular implant. They underwent autologous fat grafting in the orbital cavity and results were evaluated by clinical examination at 5 and 14 days, and 1, 3, 6 months, and 1 year after surgery. A significant release of scar retraction, reduction of fibrosis and orbital rim contraction together with an important improvement of pain symptoms was observed in all patients. The local changes observed enabled an ease placement of an ocular prosthetic implant (implant). No local or systemic complication occurred. Fat grafting is a promising treatment for patients showing radiotherapy related complication in the orbital area and it should be adopted by all oculoplastic surgeon in order to improve pain syndrome creating the ideal local conditions for the placement of an ocular prosthetic implant.
Purnima R Sthapit, Raksha Rao, Santosh G Honavar
Purpose: Refractory or recurrent vitreous seeds account for a large proportion of failure of eye salvage in retinoblastoma. The purpose of this study is to evaluate the efficacy of periocular topotecan (POT) in the management of vitreous seeds in retinoblastoma. Methods: Retrospective, interventional study of patients with retinoblastoma with vitreous seeds who received POT concurrent with intravenous chemotherapy (IVC). Results: Thirty-eight eyes of 35 patients received POT. Five eyes (13%) belonged to International Classification of Retinoblastoma group C, 23 eyes (61%) belonged to group D, and 10 eyes (26%) belonged to group E. Primary treatment included IVC with a combination of carboplatin, etoposide, and vincristine for a mean of 6 cycles (median 6; range 6–9). Concurrent to IVC from the fourth cycle onward, all patients received POT. Focal vitreous seeds were present in 20 eyes (53%) which received a mean of 3 injections (median 3; range 1–7). Diffuse vitreous seeds were present in 18 eyes (47%) which received a mean of 4 injections (median 5; range 1–7). At a mean follow-up of 8.5 months (median 5 months; range 1–15 months), regression of focal and diffuse vitreous seeds was achieved in 16 eyes (80%) and 8 eyes (44%), respectively. In all, 24 eyes (63%) had complete remission of vitreous seeds with POT given concurrently with IVC. Eye salvage was possible in 19 eyes (95%) with focal vitreous seeds and 12 eyes (68%) with diffuse VS. Enucleation was necessary for persistent vitreous seeds and viable tumor in five eyes (13%), viable tumor alone in one eye (0.02%), and recurrent vitreous seeds in one eye (0.02%). None of the patients developed systemic metastasis. Conclusion: POT administered concurrent with IVC is safe and effective in the initial management of vitreous seeds.
Minal Sharma, Vikas Khetan