Retinoblastoma and vision.

The assessment of vision has a growing importance in the management of retinoblastoma in the era of globe-conserving therapy, both prior to and after treatment. As survival rates approach 98-99% and globe salvage rates reach ever-higher levels, it is important to provide families with information regarding the visual outcomes of different treatments. We present an overview of the role of vision in determining the treatment given and the impact of complications of treatment. We also discuss screening and treatment strategies that can be used to maximise vision.

Changing trends in pseudoretinoblastoma diagnoses: A 10 year review from the United Kingdom.

AIM: To study the different types and frequency of pseudoretinoblastoma (pseudoRB) lesions who present to a retinoblastoma centre due to concern that the condition may be retinoblastoma. METHODS: A retrospective chart review of 341 patients presenting sporadically to the Royal London Hospital from January 2009 to December 2018. RESULTS: 220 patients (65%) were confirmed to have retinoblastoma, while 121 (35%) had pseudoRB. There were 23 differential diagnoses in total. The top 3 differential diagnoses were Coats' disease (34%), Persistent Foetal Vasculature (PFV) (17%) and Combined Hamartoma of Retina and Retinal Pigment Epithelium (CHR-RPE) (13%). PseudoRBs differed with age at presentation. Under the age of 1 (n = 42), the most likely pseudoRB conditions were PFV (36%), Coats' disease (17%) and CHR-RPE (12%). These conditions were also the most common simulating conditions between the ages of 1 and 2 (n = 21), but Coats' disease was the most common in this age group (52%), followed by CHR-RPE (19%) and PFV (14%). Between the ages of 2 and 5 (n = 32), Coats' disease remained the most common (44%) pseudoRB lesion followed by CHR-RPE (13%), or PFV, Retinal Astrocytic Hamartoma (RAH), familial exudative vitreoretinopathy (FEVR) (all 6.3%). Over the age of 5 (n = 26), pseudoRBs were most likely to be Coats' disease (35%), RAH (12%), Uveitis, CHR-RPE, FEVR (all 7.7%). CONCLUSION: 35% of suspected retinoblastoma cases are pseudoRB conditions. Overall, Coats' disease is the most common pseudoRB condition, followed by PFV. Hamartomas (CHR-RPE & RAH) are more prevalent in this cohort, reflecting improvements in diagnostic accuracy from referring ophthalmologists.

Adjuvant use of laser in eyes with macular retinoblastoma treated with primary intravenous chemotherapy.

BACKGROUND: Adjuvant use of laser with systemic chemotherapy for treatment of retinoblastoma may reduce recurrence rates while also causing local side effects. Information is lacking on the effect of laser on visual outcomes. METHODS: A retrospective review of two retinoblastoma centres in the United Kingdom was conducted. Patients were included if there was a macular tumour in at least one eye. Eyes that received chemotherapy alone were compared with eyes that received chemotherapy plus adjuvant laser. RESULTS: A total of 76 patients and 91 eyes were included in the study. Systemic chemotherapy alone was used in 71 eyes while chemotherapy plus laser was used in 20 eyes. Demographic characteristics of both groups were similar. Macular relapse rates were similar between groups: 22/71 (31%) eyes in chemotherapy group and 9/20 (45%) eyes in laser group (p=0.29). There was no increase in vitreous relapses in the laser group (2/20 eyes), compared with the chemotherapy group 10/71 eyes (p=0.99). Survival analysis demonstrated similar time to first relapse between groups. Final visual acuity was equal between groups with 6/15 or better present in 31.1% of eyes in the chemotherapy group and 37.5% of eyes in the laser group (p=0.76). Presence of tumour at the fovea was predictive of final visual acuity, regardless of treatment group. CONCLUSION: Adjuvant laser in the treatment of retinoblastoma is safe and does not lead to increased rate of vitreous recurrence. Final visual acuity is determined by the presence of tumour at the fovea and not the use of laser.

Sclero-conjunctival ischaemia secondary to intra-arterial chemotherapy for retinoblastoma.

PURPOSE: Intra-arterial chemotherapy (IAC), delivered directly to the globe via the internal carotid artery is now an established treatment for retinoblastoma. We report a case of anterior segment ischaemia following treatment with multiple intra-arterial chemotherapy (IAC) infusions. OBSERVATIONS: A 5 month old female presented with bilateral retinoblastoma and was treated with 12 infusions of IAC. Her right eye was enucleated at diagnosis. After her seventh IAC treatment, she developed ipsilateral sixth and third cranial nerve palsies. After the twelfth IAC, she developed an area of conjunctival and scleral ischaemia between 12 and 3 o'clock meridians in her left eye. However, she maintained visual acuity of LogMAR 0.34. CONCLUSIONS AND IMPORTANCE: The median number of IAC treatments in large studies is three. It is possible that repeated doses of IAC have an accumulative negative effect on the ocular blood supply, risking anterior segment and neurologic sequelae. This case highlights the significant challenge of balancing the salvage of eyes and vision with the potentially significant morbidity associated with IAC.

Number, frequency and time interval of examinations under anesthesia in bilateral retinoblastoma.

PURPOSE: Current practice in retinoblastoma (Rb) has transformed this malignancy into a curable disease. More attention should therefore be given to quality of life considerations, including measures related to examinations under anesthesia (EUAs). We aimed to investigate EUA measures in bilateral Rb patients and compare the findings to EUAs in unilateral Rb. METHODS: A retrospective analysis of bilateral Rb patients that presented to the London Rb service from 2006 to 2013, were treated and had long-term follow-up. RESULTS: A total of 62 Rb patients, 15 (24.2%) of which had International Intraocular Retinoblastoma Classification (IIRC) group A/B/no Rb at presentation, 26 (41.9%) C/D, and 21 (33.9%) were E in at least one eye. The mean number of EUAs was 35.8 ± 21.5, mean time from first to last EUA was 50.6 ± 19.9 months, and mean EUA frequency was 0.715 ± 0.293 EUAs/month. IIRC group was found not to correlate with any of the EUA measures. Age at presentation inversely correlated with time interval from first to last EUA and to EUA frequency (p ≤ 0.029). Rb family history correlated with the latter measure (p = 0.005) and intraophthalmic artery chemotherapy and brachytherapy correlated with all EUA measures (p ≤ 0.029). Mean follow-up time was 80.1 ± 24.3 months. When compared with a previously reported cohort of unilateral Rb, the present group underwent 3× more EUAs (p < 0.001) over nearly double the time (p < 0.001). CONCLUSIONS: Families should be counselled on anticipated EUA burden associated with bilateral Rb. In this respect, age at presentation and family history were found to have a predictive role, whereas IIRC group did not.

Examinations under anaesthesia as a measure of disease burden in unilateral retinoblastoma: the London experience.

BACKGROUND: Early diagnosis strategies and advances in retinoblastoma (Rb) management have resulted in nearly 100% survival. More attention should, therefore, be given to quality of life considerations. We aimed to quantify the number of examinations under anaesthesia (EUAs) in a cohort of patients with Rb, as a measure of disease burden. METHODS: A retrospective analysis of patients with unilateral Rb that presented to the London Rb service from 2006 to 2013, were treated and had long-term follow-up. Correlations of clinical variables to number of EUAs were investigated. RESULTS: A total of 107 patients with Rb were included that presented at a mean age of 26.51 ± 22.68 months. The International Intraocular Retinoblastoma Classification (IIRC) was group B in 5 (5%), C in 13 (12%), D in 48 (45%) and E in 41 (38%) of the cases. Primary treatment was intravenous chemotherapy in 36 (34%) and enucleation in 71 (66%) of the cases. Mean number of EUAs was 20.67 ± 6.62, 12.52 ± 6.23 and 11.15 ± 6.91 for combined groups B/C, group D and group E patients (p < 0.001), respectively. On analysis, early age atpresentation and conservative treatments were found to significantly correlate with increased number of EUAs (p < 0.001). Mean follow-up time was 74.42 ± 25.16 months and no metastasis or death were reported. CONCLUSION: Families should be counselled regarding the number of EUAs associated with the patient's IIRC group, with B/C eyes undergoing twice the number as compared with D/E eyes. For group D cases, where both enucleation and conservative therapy are valid options, treatment choice has a significant impact on the number of EUAs.

Strabismus in retinoblastoma survivors with long-term follow-up.

PURPOSE: To report the long-term strabismus rate in salvaged retinoblastoma (Rb) patients and investigate possible risk factors leading to strabismus. METHODS: The medical records of patients with Rb presenting at a single institution over a 9-year period were reviewed retrospectively with regard to ocular alignment outcomes after long-term follow-up. RESULTS: A total of 64 eyes of 42 patients (22 bilateral cases [52%]) were included, presenting with International Intraocular Retinoblastoma Classification (IIRC) in the worse eye as follows: group A (n = 1), B (n = 16), C (n = 12), D (n = 11), no Rb (n = 2). Fifteen patients (36%) were initially referred because of family history of Rb. Mean age at presentation was 8.2 months (range, 0.3-58.3 months). Overall treatments included intravenous chemotherapy (62 eyes), intraophthalmic artery chemotherapy (10 eyes), brachytherapy (11 eyes), transpupillary thermotherapy (22 eyes), cryotherapy (47 eyes), and external beam radiotherapy (4 eyes). At final follow-up (mean, 93.7 months), 69% of patients had strabismus, with exotropia being the most common type (n = 18), followed by esotropia (n = 8), and alternate exotropia/esotropia (n = 3). On univariate analysis, the worse eye group IIRC and cTNMH, sporadic cases, strabismus, and foveal tumor at presentation were found to be significantly associated with strabismus at final follow-up (P ≤ 0.043). On multivariate analysis, only foveal involvement was found to be significant (P < 0.001). CONCLUSIONS: Strabismus, exotropia in particular, is a common adverse sequela following successful conservative treatment for Rb, with 69% of the present cohort having some type of deviation after long-term follow-up, for which foveal tumor at presentation was found to be a significant risk factor.

Long-term Visual Acuity, Strabismus, and Nystagmus Outcomes Following Multimodality Treatment in Group D Retinoblastoma Eyes.

PURPOSE: To analyze the long-term visual acuity, strabismus, and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral center. DESIGN: Retrospective interventional case series. METHODS: A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analyzed, and rate of strabismus and nystagmus at last follow-up visit were calculated. RESULTS: One hundred and four Group D eyes (92 patients) presented to our center during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 ± 0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT, and tumor-foveola distance (at last visit) were found to be significant risk factors for worse VA (P < .026). On multivariate analysis, however, only TTT was found to be significant (P = .010). At last visit, 6 of 27 (22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had strabismus (n = 10 exotropia and n = 2 esotropia). CONCLUSIONS: After multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision; 60% had strabismus; and 22% had nystagmus.

Reduction of severe visual loss and complications following intra-arterial chemotherapy (IAC) for refractory retinoblastoma.

BACKGROUND: Intra-arterial chemotherapy (IAC) for retinoblastoma has been documented as causing visual loss and ocular motility problems. A lack of safety data has precluded its acceptance in all centres. METHODS: Retrospective cohort study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola and relapsed following systemic chemotherapy. All required IAC. The correlation of complications with doses of melphalan +/- topotecan used and putative catheterisation complications was assessed. Ocular complications were determined using vision, macular (including pattern visual evoked potentials (PVEPs)), retinal electroretinograms (ERGs) and ocular motility functions. Efficacy (tumour control) was also assessed. RESULTS: All eyes had age appropriate doses of melphalan with five having additional doses of topotecan. Severe physiological reactions requiring adrenaline were seen in six patients during the catheterisation procedure. Difficulty was documented in accessing the ophthalmic artery in 7/27 catheterisations. The median/mean number of courses of chemotherapy was three. No child had severe visual loss as assessed by age appropriate tests (median follow-up 20.9 months, range 3.7-35.2 months). One child had nasal choroidal ischaemia and a sixth nerve palsy. Post-IAC PVEPs were performed in eight and reported as normal. All post-IAC ERGs were normal apart from one (total dose 20 mg melphalan 0.8 mg topotecan). Tumour control was achieved in six of nine cases. CONCLUSION: The proportion of visual and ocular motility complications may be reduced by providing age-adjusted doses of melphalan. Dose rather than complications from catheterisation is the most important risk factor for ocular injury.