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The present study was an open-label, prospective, uncontrolled and multicenter clinical trial to investigate the safety and effectiveness of bevacizumab (Lumiere ® ) administered by the intravitreal route for the treatment of neovascular age-related macular degeneration (nAMD). A total of 22 patients without previous treatment with anti-vascular endothelial growth factor were recruited. Monthly therapy with 1.25 mg intravitreal bevacizumab was applied. Adverse events (AE), visual acuity (VA) and central retinal thickness (CRT) were assessed at baseline, day 1 and day 28 after each injection. A total of 87 AEs were reported; most of them were not serious (96.6%), expected (65.5%) and occurred after the third injection (56.3%). The most frequent AE was 'conjunctival hemorrhage' (29.9% of AEs), attributed to the injection procedure. Treatment was not suspended due to safety reasons in any case. After six months, a statistically significant gain of +8.2 (SD±8.8) letters and a CRT reduction of -75.50 µm (SD±120.3) were achieved with unilateral therapy. VA improvement and CRT reduction were also achieved with bilateral therapy, although to a lesser extent. The results of the present study suggested that therapy with a minimum of 3 doses of bevacizumab over a 6-month period was well tolerated and resulted in a sustained response regarding VA improvement and CRT reduction from the beginning of therapy compared with the baseline value. The study protocol was registered at clinicaltrials.gov (ref. no. NCT03668054)., (Copyright: © Benisek et al.)

Background: The feasibility and results of intraarterial chemotherapy, also termed ophthalmic artery chemosurgery (OAC), for retinoblastoma in less developed countries have seldom been reported., Procedure: A retrospective evaluation of a program of OAC in Argentina from 2010 to 2015., Results: Ninety-seven eyes from 81 patients (61 bilateral) were analyzed. In 35 eyes, OAC was given as primary therapy and in 62 it was used for the treatment of tumors with partial response or those relapsing after systemic chemoreduction with focal therapy or external-beam radiotherapy. Twenty-two primarily treated eyes had group D and 13 groups B/C. A total of 400 procedures were carried out. Chemotherapy used included combinations of melphalan, carboplatin, and topotecan. There was no mortality associated with OAC. Toxicity included fever and neutropenia in five (1.25%), hypotension and bradycardia during anesthesia in two and femoral thrombosis in one, eyelid edema in nine, and neutropenia or thrombocytopenia in 28 cycles. With a median follow-up of 48.7 months (range 12-79), the 3-year probability of event-free survival (pEFS) (enucleation and/or radiotherapy were considered events) was comparable for patients who received first-line therapy and those treated at relapse (0.65 vs. 0.63, P = 0.5). In the former, the pEFS was 0.91 and 0.43 for groups B/C and D, respectively (P = 0.01). Two patients died of extraocular dissemination after refusal of enucleation., Conclusions: OAC was feasible with low toxicity. pEFS improved in all groups compared to the previous experience with systemic chemotherapy reducing the use of radiotherapy. The overall mortality associated with OAC is comparable to our previous experience with systemic chemoreduction., (© 2018 Wiley Periodicals, Inc.)

Retinopathy of prematurity (ROP) is a largely avoidable cause of blindness in children worldwide, requiring high-quality neonatal care, early detection and treatment. In middle-income countries throughout Latin America, Eastern Europe and South Asia, there has been a rise in ROP blindness due to a combination of increased survival of preterm infants, resource-scarce medical environments and lack of policies, training and human resources. However, Argentina is an example of country where rates of ROP blindness have declined and ROP programmes have been successfully and effectively embedded within the health and legal system. The purpose of this study is to describe the activities and stakeholders, including Ministry of Health (MoH) and UNICEF, involved in the process, from recognition of an epidemic of ROP blindness to the development of national guidelines, policies and legislation for control. Using a retrospective mixed methods case study design, data on rates of severe ROP was collected from 13 neonatal intensive care units from 1999 to 2012, and on the proportion of children blind from ROP in nine blind schools in seven provinces. Legislative document review, focus group discussions and key informant interviews were conducted with neonatologists, ophthalmologists, neonatal nurses, parents, MoH officials, clinical societies, legislators and UNICEF officials in seven provinces. Results are presented combining the stages heuristic policy framework and Shiffman including: agenda setting, policy formulation, implementation and evaluation. By 2012, ROP had declined as a cause of blindness in children in schools for the blind as had rates of severe ROP needing treatment in the NICUs visited. Multiple factors played a role in reducing blindness from ROP in Argentina and successfully coordinating its control including national advocacy, leadership, legislation and international collaboration. Lessons learned in Argentina can potentially be scaled to other LMICs in Latin America and beyond with further context-specific research.

Background: Few studies were reported from developing countries regarding patient outcome and ocular survival in children with bilateral retinoblastoma treated with chemoreduction compared to external beam radiotherapy (EBRT)., Procedure: We undertook a retrospective study of three treatment eras: (1) (1988-1995) n = 68 when EBRT was used as primary conservative therapy; (2) (1995-2003) n = 46 when carboplatin-based systemic chemoreduction was introduced and (3) (2003-2009) (n = 83) when additional periocular chemotherapy was added for advanced tumors and pre-enucleation chemotherapy was given for those with massive buphthalmia., Results: The probability of 5-year disease-free survival was 0.94 (95% confidence interval [CI] 0.91-0.98%) without significant differences among the three eras. Chemoreduction reduced the use of EBRT from 84.6% to 68.7% in eras 1 and 3, respectively (P = 0.008), which was more evident in cases with less advanced disease. Chemoreduction also significantly improved the 5-year probability of preservation of eyes with advanced disease from 0.13 (95% CI 0.04-0.27) during era 1 to 0.49 (95% CI 0.34-0.62) in era 3 (P < 0.0001). Chemoreduction was not associated with changes in the probability of extraocular relapse, which was reduced after the introduction of pre-enucleation chemotherapy. Second malignancies occurred in nine cases, acute myeloid leukemia being the most fatal one. Trilateral retinoblastoma occurred in three cases and all of them had been exposed to chemotherapy., Conclusions: Chemoreduction reduced the need for EBRT in eyes with less advanced disease and improved the preservation of eyes with advanced disease while its effects on secondary malignancies or trilateral disease remain unclear., (© 2013 Wiley Periodicals, Inc.)

Background: Few prospective studies about the management of unilateral retinoblastoma with pathology risk factors (PRFs) have been published., Methods: Patients (n = 114) were divided into four groups: Group 1 (initial chemoreduction) (n = 17). Groups 2 and 3, included patients initially enucleated with no, or lower risk PRFs: (n = 65) and with higher risk PRFs (n = 30), respectively. The later included postlaminar optic nerve involvement (PLONI) (n = 23), tumor at resection margin of optic nerve (n = 5) or isolated scleral invasion (n = 2). Group 3 received adjuvant chemotherapy including a total eight cycles of carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Orbital radiotherapy (45 Gy) was given to patients with invasion to the resection margin. Group 4 included patients with metastatic disease (n = 2). They were given neoadjuvant therapy followed by surgery and high-dose chemotherapy and autologous stem cell rescue., Results: Five-year event-free survival is 0.94 (1 for Group 1, 0.94 for Group 2, 0.96 for Group 3, and 0 for Group 4). Events included. Group 2: Systemic relapse (n = 2) and combined orbital and CNS relapse (n = 1). Relapsing patients had PLONI (n = 2) and isolated focal choroidal invasion (n = 1). Group 3: CNS relapse (n = 1) in a patient with tumor at the resection margin of optic nerve. Group 4: CNS relapse (n = 2). Only one relapsed patient survived. Eight of 17 eyes treated conservatively were preserved., Conclusions: The survival of patients with unilateral retinoblastoma was excellent and 60% were spared from adjuvant treatment. Our intensive regimen was likely to be effective for prevention of metastasis in patients with higher risk PRFs.

Introduction: Retinopathy of prematurity may lead to partial loss of vision and blindness; laser photocoagulation is the elective treatment, but universal access to it is not yet guaranteed in Argentina., Objectives: To estimate prevalence of children requiring laser for retinopathy, their clinical and demographic characteristics, place of origin and place of treatment. POPULATION, MATERIAL AND METHOD: Observational, descriptive and retrospective study., Population: premature newborns who required treatment at public services during 2008., Variables: Birth weight and gestational age, prognosis, unusual cases and missed opportunities., Source: 27 public services from 18/24 provinces., Results: 235 patients who required treatment were recorded (Garrahan Hospital: 86; Gutiérrez Hospital: 45, and 104 from 25 other hospitals) from 77 public services and 13 private services from 22/24 provinces, where 210,720 babies born at the same period. Cases from Buenos Aires Province were referred mainly to Garrahan Hospital, all cases from Buenos Aires City and 2/3 from the rest of the country were treated in situ. Prognosis was defined as reserved at 15% and 5 missed opportunities occurred all in referred babies. Unusual cases were 27% of the total reported., Conclusion: In this population retinopathy prevalence was 1/900 birth in 2008. The proportion of unusual cases, reserved prognosis and missed opportunities was high. A national record and improved access to treatment in situ are urgently needed.

Introduction: Increasing survival of preterm newborns and current care deficits result in high rates of retinopathy of prematurity (ROP), affecting patients with higher birth weight (BW) and gestational age (GA) than those at developed countries; unusual cases (UC) and missed opportunities (MO) are reported., Objective: To describe epidemiology of ROP during 2008 compared with the previous year. POPULATION, MATERIAL AND METHOD: Observational, descriptive and retrospective study., Population: Preterm babies with BW < 1,500 g and/or < or = 32 w GA and > or = 1,500 g and/or 33-36 w who received oxygen therapy., Source: 31 public services from 20/24 Provinces., Variables: BW, GA, ophthalmologic screening, age at 1st control, ROP Grade, treatment requirement, place of treatment and time of complete ROP screening., Results: Responses were obtained from 24/31 services from 16 Provinces (84,200 newborns) identifying 3,371 newborns at risk, 956 < 1,500 g BW. Screening was done in 90%; it was late in 6%. Neonatal discharge before complete ROP screening occurred in 93%. ROP rate was 11.93%; 26.25% in < 1,500 g BW. Treatment was required at 2.60%; of them, 7% were < 1,500 g BW; 20.3% were UC, one infant was a MO. Treatment need increased 20% at 2008 vs. 2007, without significant difference. Changes were not observed at median BW and GA and UC. Treatment in situ was 75% in 2008, similar to 2007., Conclusions: Incidence of ROP in public hospitals of Argentina is worrisome. Rates in 2008 have not improved compared with 2007, expressing that criteria for prevention are not yet consolidated. Screening and access to treatment must improve.

Purpose: To identify the maximum tolerated dose and dose-limiting toxicity of periocular topotecan in patients with relapsed or resistant intraocular retinoblastoma who are facing imminent enucleation., Methods: For this phase I study, a starting dose of 0.5 mg of periocular topotecan administered through a 25-gauge needle was given with intrapatient escalation at a rate of 0.5 mg/cycle according to toxicity, up to a maximum dose of 2 mg. Two courses separated by 2 weeks were scheduled. Plasma levels of topotecan were measured by high-performance liquid chromatography in patients with available intravenous catheters., Results: Seven eyes of five patients were treated with a total of 14 courses of periocular topotecan. Only mild orbital edema occurred, and grade 1 vomiting developed in the first patient that was controlled with ondansetron for the following courses. Dose-limiting toxicity was not reached and the maximum tolerated dose was set at the target dose of 2 mg (n=5 eyes). Lactone topotecan systemic exposure was lower than 55 ng/mL x h and it correlated linearly with dose in this small cohort. Even though the study was not designed to assess response, one eye was preserved after a partial response, but the remaining six were enucleated, either after a short period of disease stabilization followed by further therapy with other agents in five patients or by rapidly progressive disease in one., Conclusions: The dose limiting toxicity was not reached. Up to 2 mg of periocular topotecan could be given safely, but further studies are necessary to determine its effect on retinoblastoma (ClinicalTrials.gov number, NCT00460876).

Purpose: To evaluate the outcome of patients with retinoblastoma and postlaminar optic nerve invasion (PLONI)., Design: Retrospective interventional case series., Participants: Sixty-one consecutive patients included in 3 successive protocols were analyzed., Methods: Pathologic review was done in each case. Patients were stratified into 2 risk groups: the high-risk group included those with concomitant full choroidal and/or scleral invasion and were given adjuvant chemotherapy. Those without these features were considered low risk and chemotherapy was withheld after 1994., Main Outcome Measures: Extraocular relapse and survival according to stratification., Results: The probability of event-free survival (pEFS) was 0.91 and the probability of overall survival (pOS) was 0.94 at 5 years. Patients in the high-risk group (n = 22) had pEFS of 0.86. Three had extraocular relapse (involving the central nervous system; all died of disease). Microscopic scleral invasion was associated to extraocular relapse (P = 0.05). Lower risk patients (n = 39) had a pEFS of 0.94 and pOS of 1. Eighteen received postenucleation chemotherapy and none relapsed. Twenty-one received no adjuvant therapy and 2 had a systemic relapse but were successfully retrieved. Relapsing patients had a higher ratio of affected optic nerve (>25% of it overall length; P = 0.02)., Conclusions: Patients with PLONI have an excellent outcome with current therapy. Risk stratification according to the presence of concomitant choroidal and/or scleral invasion may help in the decision of giving adjuvant therapy.

Introduction: Retinopathy of prematurity (ROP) is the first cause of childhood blindness in Argentina and is reaching epidemic proportions. To gain greater insight into the issues involved in this epidemic, we analyzed the characteristics of the infants referred for treatment of very severe ROP to the Dr. Juan P. Garrahan Pediatric Hospital, located in the city of Buenos Aires., Methods: We performed a retrospective study of patients referred for ROP from 01/01/96 to 12/31/03. Very severe ROP was defined as threshold disease or worse in both eyes, plus disease in zones 1 or 2, or Rush disease. Unusual patients were defined as those with very severe ROP with a gestational age (GA) of > 31 weeks or birth weight (BW) > 1500 g. Patients were divided into two groups according to the distance between the referring center and our hospital: group A consisted of those from nearby areas ( 70 km from the hospital., Results: During the study period, the number of cases progressively increased while the proportion of "unusual" patients slightly decreased. The total number of infants referred was 809 and 14 % were unusual patients; 55 % had very severe ROP, 89 % were treated, and 7 % were referred too late and lost the opportunity for treatment. Group B comprised 61 % of the infants referred. Very severe ROP was present in 53 % of patients in group A and in 56 % of those in group B. The mean GA was 29.5 +/- 3.1 weeks in group A and 30.8 +/- 2.6 in group B (p < 0.001); 90.5 % of the patients in group A and 64 % of those in group B required mechanical ventilation (p < 0.001). No predictors for very severe ROP were found in multifactorial analysis., Conclusions: We report a childhood epidemic of blindness in which the prevalence of very severe ROP increased during the study period and the disease occurred in large, fairly mature newborns. The differences found in relation to the referring center and the lack of correlation between very severe ROP and prematurity or the use of mechanical ventilation suggests substantial disparity in healthcare, which should be taken into account when planning prevention strategies.

Background: Chemoreduction is used for the treatment of retinoblastoma in industrialized nations; however, there are fewer data from developing countries. Before the implementation of this program, radiotherapy was used in almost all preserved eyes., Methods: Retrospective evaluation from 1995 to 2001 at the Hospital Garrahan (Argentina). Carboplatin 18.7 mg/kg/day 1 and vincristine (0.05 mg/kg/day 1) were offered to patients with Reese-Ellsworth (RE) groups I-III and all unilateral cases. Etoposide (3.3 mg/kg/day 1 and 2) was added for groups IV and V. The number of cycles was tailored according to response., Results: Fifty-eight patients (78 eyes) were evaluated (39 bilateral, 19 unilateral). With a median follow-up of 47 months, 40 patients had unilateral enucleation, 14 were not enucleated, and 4 had bilateral enucleation. Nineteen patients had unilateral initial enucleation. Eye preservation at 5 years was: RE groups I-III (n = 24 eyes), 0.9 (SE: 0.095) IV-V (n = 54), 0.45 (SE 0.07). Patients received a median of four cycles of chemotherapy. Acute toxicity was mild. External beam radiotherapy was avoided in 41% of eyes with groups I-III. Etoposide was avoided in 24 patients. Two patients died of metastasis. No secondary malignancy occurred., Conclusions: Compared to our previous experience, eye preservation was better and even though less radiotherapy was used, it was prescribed more often than currently recommended in eyes with less advanced disease because of limited availability of sophisticated local therapy., (2004 Wiley-Liss, Inc.)

Purpose: To report our experience with topotecan in children with relapsed/refractory metastatic and intraocular retinoblastoma., Patients and Methods: Topotecan was administered intravenously as a 30-min infusion at a dose of 2 mg/m2/d for five consecutive days and repeated after three weeks. If obvious progression was detected by physical examination in patients with overt extraocular disease or if progressive disease was noted after fundoscopic examination in patients with intraocular disease, a second cycle was not administered. Response was evaluated at Week 6., Results: Nine patients (6 extraocular, 3 intraocular) were treated from November 1998 to March 2002. A total of 16 cycles were administered. In patients with extraocular disease, there were three partial responses, two cases of stable disease, and one case of progressive disease. Two patients with relapsed/resistant intraocular disease had partial response. allowing local therapy to be performed, and the third patient had progressive disease. The drug was well-tolerated. No patient developed fever or documented infections. No other serious toxicity was found., Conclusion: Topotecan is active in extraocular and relapsed/resistant intraocular retinoblastoma. The role of this drug in the treatment of retinoblastoma should be explored in further studies.

Background: The objectives of this prospective study were to avoid adjuvant treatment for patients with intraocular disease and patients with postlaminar optic nerve invasion (PL-ONI) without full choroidal or scleral invasion. Adjuvant chemotherapy (Regimen 1) was given to patients with scleral invasion, PL-ONI without cut section, and full choroidal and/or scleral invasion. A more intensive regimen of higher dose intravenous chemotherapy (Regimen 2) and local radiotherapy was given to patients with PL-ONI and compromise at the cut end and to patients with overt extraocular disease., Methods: Six-month intravenous chemotherapy included carboplatin plus etoposide alternating with cyclophosphamide plus vincristine (Regimen 1) and the same drugs at higher dosage plus idarubicin (Regimen 2). Chemoreduction with carboplatin and vincristine with or without etoposide was given to selected patients (n = 39 patients)., Results: From 1994 to 2001, 169 patients were evaluable at the Hospital Garrahan (Buenos Aires, Argentina). One hundred eighteen patients with intraocular disease had a 5-year disease free survival (DFS) rate of 0.98, including 54 patients with choroidal invasion. None of 22 patients with isolated PL-ONI developed recurrent disease, whereas 2 of 8 patients with concomitant risk factors had tumor recurrences and died. Three of 5 patients with scleral invasion survived, and 7 of 10 patients with cut-end ONI survived. The only patient with metastatic disease that survived (n = 6) had only lymph node invasion., Conclusions: Adjuvant therapy can be avoided in patients with intraocular and isolated PL-ONI. Patients with PL-ONI who also had other risk factors required intensive adjuvant therapy, such as patients with cut-end and overt extraocular disease. Metastatic disease was not found to be curable with this approach., (Copyright 2003 American Cancer Society.)

Background: Overt extraocular retinoblastoma is common in developing countries and little information about its treatment is available. The aim of this study is to report our experience in the treatment of these cases using a uniform approach., Procedure: Patients with overt extraocular retinoblastoma including orbital extension, preauricular lymph node invasion and/or metastatic disease on diagnosis or after extraocular relapse admitted to the Hospital JP Garrahan from August 1987 to December 2000 were retrospectively reviewed. Patients were treated according to two different protocols (1987-1993 and 1994-2000). Treatment included: neoadjuvant combination chemotherapy followed by limited surgery in case of orbital extension (enucleation or resection of residual orbital mass) and adjuvant chemotherapy and radiotherapy. Chemotherapy included cyclophosphamide, vincristine, etoposide, doxorubicin (in protocol 87), idarubicin (in protocol 94), cisplatin (in protocol 87), and carboplatin (in protocol 94)., Results: Forty-one patients were included. Fifteen of them had orbital or preauricular disease and had a 5-year event-free survival (pEFS) of 84%. Twenty-six had distant metastatic disease and non survived 5-years. One patient died of toxicity and one died in complete remission. One patient had a secondary leukemia. The remaining adverse events included CNS and/or systemic relapse., Conclusions: This treatment strategy was highly efficacious for patients with orbital and/or lymph node extension. Orbital exenteration is not necessary for these patients. Those patients with distant metastatic or CNS disease were not curable with this approach., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To define a subgroup of patients with retino-blastoma and low risk of extraocular relapse through histopathological and clinical variables., Patients and Methods: Inclusion criteria consisted of stage I (intraocular disease), stage IIb1 (without concomitant choroid and/or scleral invasion), and nonenucleated patients (according to the Grabowski-Abramson classification). A total of 112 consecutive patients admitted to Hospital JP Garrahan from 1987 to 1997 were evaluable. Treatment included enucleation or local therapy and no chemotherapy., Results: Forty-one patients had stage Ia (intraretinal), 8 stage Ib (prelaminar optic nerve invasion), 40 stage Ic (uveal invasion), and 12 stage IIb1 (postlaminar optic nerve invasion and cut end free of tumor). Eleven patients had neither eye enucleated. Median follow-up was 60 months. Only two events occurred: one patient had progressive disease in the contralateral globe and died of CNS metastasis and another had an orbital relapse that was successfully treated. Both had choroidal invasion. Five-year pEFS and pOS were 0.97 and 0.98, respectively. Neither length of the optic nerve stump, tumor size, anterior chamber invasion, degree of differentiation, nor degree of ocular coat invasion correlated with increased risk of metastasis., Conclusions: A subset of patients with retinoblastoma with low risk of relapse can be determined using histopathological evaluation of the invasion of ocular coats. Adjuvant chemotherapy is not warranted for patients with intraretinal extension and prelaminar optic nerve invasion. It is also probable that those patients with isolated choroidal invasion and those with postlaminar optic nerve extension with surgical margins clear of tumor do not need chemotherapy.

Purpose: The purpose of this study is to determine the clinical, chromosomal, and molecular characteristics of Argentine patients with unilateral and bilateral retinoblastoma., Study Design: Eighty-six patients belonging to 82 families were studied; 59% of them were examined during the first year of life. Leukocoria was the most common reason for consultation. Other presenting signs were strabismus and glaucoma. Enucleation of the affected eye was performed in 85% of the cases and the complication rate was 13%., Results: An appropriate therapy allowed the survival of 84 of the 86 patients. Two children with malformations and growth retardation had an abnormal karyotype with a deletion in 13q14. Segregation analysis of polymorphic sites within the retinoblastoma gene and the parental origin of the allele lost in the tumor were analyzed in 30 of the 82 families. Five mutant alleles transmitted through the germline and six de novo germline mutant alleles were identified in 12 patients with hereditary retinoblastoma. Most de novo germline mutant alleles were paternally derived. Molecular analysis of nonhereditary retinoblastoma showed loss of heterozygosity in three of eight cases. From these, two maternal alleles and one paternal allele were lost, thus not indicating a significant difference in the parental origin for the lost allele., Conclusions: These data are useful for deoxyribonucleic acid diagnosis of susceptibility to retinoblastoma in relatives of hereditary patients, even if mutations have not been identified.

Background: The Retinoblastoma International Collaborative Study is a multinational prospective clinical and pathologic registry designed to collect baseline clinical information, data on methods of treatment, and information on the subsequent clinical course of children with retinoblastoma., Methods: 206 children with newly diagnosed retinoblastoma were evaluated in the participating clinical centers between 1 July 1987 and 31 December 1989. All of the children underwent comprehensive baseline assessment of multiple clinical variables prospectively according to a standard protocol. The recorded values were tabulated and analyzed., Results: The 206 children with retinoblastoma included 99 boys (48.1%) and 107 girls (51.9%). The mean age at diagnosis was 21.2 mo in the total study group. One hundred twenty-seven of the 206 children (61.7%) had unilateral disease, while 79 (38.3%) had bilateral involvement. The mean age at diagnosis in the bilateral cases (14.6 mo) was substantially less than in the unilateral ones (23.5 mo). The great majority of patients (approximately 75%) had advanced disease (group V in both Reese-Ellsworth and Essen prognosis classifications) in the affected eye (unilateral cases) or the more severely affected eye (bilateral cases)., Conclusions: This study shows that there is a dedicated group of international ophthalmologists and other physicians who are willing to participate in multicenter cooperative clinical studies of retinoblastoma and that a relatively large group of children with this ocular malignancy can be enrolled within this framework during a reasonably short time for the purposes of future studies.

Thirty-seven patients with retinoblastoma were evaluated prospectively by clinical examination, lumbar puncture, and CT. Eight (22%) of the 37 were found to have meningeal dissemination. The tumor was bilateral in three patients. Two cases showed no CT signs of local recurrence. Headache, nausea/vomiting, and restlessness were the most common symptoms. CT scans in these patients showed diffuse meningeal contrast enhancement, nodular masses, ependymal-subependymal enhancement, and ventricular dilatation. Our series of eight patients with meningeal spread illustrates a considerable range of dissemination patterns referable to retinoblastoma. One case illustrated the CT finding of multiple epidural metastases.