Ophthalmology

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

To evaluate the outcome of children with different degrees of choroidal invasion, to compare different systems for grading the extent of choroidal invasion, and to assess the role of concomitant prelaminar optic nerve and anterior segment invasion as predictors of extraocular relapse. Design: Retrospective analysis of children included in 4 prospective protocols (January 1, 1989, through June 31, 2010). Children with postlaminar optic nerve or scleral involvement and overt extraocular disease were excluded. Adjuvant chemotherapy was not scheduled. All slides were reviewed, and massive involvement was classified according to 3 definitions: (1) extending at least 3 mm in any dimension,(2)throughthechoroid'swholethickness,and(3)more than 50% of the thickness and/or more than 1 cluster. Results: One hundred sixty-seven children (35 with massive invasion) were studied (136 did not receive adjuvant therapy). The probability of 5-year event-free survival was 98.1% and the probability of overall survival was 98.7% because 1 patient relapsed. Children with massive invasion had a significantly lower event-free survival probability (94.2%) compared with those with focal invasion (99.2%) (P=.04). However, no significant difference was found in overall survival probability (98.7% vs 99.2%; P=.29). No significant effect of other risk factors was found. Conclusions: Survival was excellent without adjuvant therapy, and no other factors correlated with survival. Children with massive invasion have a higher relapse rate but comparable survival to those with focal invasion provided that aggressive therapy for extraocular relapse is available with adequate safety conditions.

BackgroundFew prospective studies about the management of unilateral retinoblastoma with pathology risk factors (PRFs) have been published.MethodsPatients (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.ResultsFive‐year event‐free...

BackgroundFew 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).ProcedureWe 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.ResultsThe 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 th...

Purpose: To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) subsequent to superselective artery catheterization and to compare it with periocular injection (POI). Methods: The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a period of 30 minutes. The contralateral eye was subsequently used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples collected and assayed for total and lactone topotecan. Results: Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL [112.9-138.7] vs. 13.6 ng/mL [5.5-15.3], respectively; P , 0.005). Median vitreous exposure calculated as area under the curve for total topotecan attained after OAI was significantly higher than after POI (299.8 ngÁhour/mL [247.6-347.2] and 48.9 ngÁhour/mL [11.8-63.4], respectively; P , 0.05). The vitreous to plasma exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total topotecan was low after both modalities of administration, with a trend to be lower after OAI compared with

Different staging systems for extraocular retinoblastoma have been published, but to date they have not been validated in large cohorts. To review 533 patients (and pathology slides) with retinoblastoma included in 4 protocols (January 1, 1988, to December 31, 2009) who received uniform treatment. Retrospective review in a hospital setting. A critical analysis for detecting inconsistencies and omissions was performed. Patients were reclassified according to the modified St Jude Children's Research Hospital staging system, Grabowski-Abramson staging system, International Retinoblastoma Staging System (IRSS), and American Joint Committee on Cancer TNM staging system. The main outcome measure was disease-free survival (DFS), considering only extraocular relapse as an event. In the IRSS and the St Jude system, higher stages correlated with poorer DFS. For intraocular disease, only the TNM system and the IRSS included pathological definitions, and all systems except for the IRSS incl...

Retinoblastoma is a highly curable neoplasm in the developed world. 1 In less-developed countries, however, survival figures are lower mostly because of delayed diagnosis and poor treatment compliance. 2 During the past decades, in middleincome countries, disease-free survival of children with retinoblastoma has improved gradually, but there are many challenges related with advanced disease at diagnosis that introduce specific considerations for management. 3,4 In that setting, children present with more advanced intraocular disease that frequently needs enucleation and systemic treatment to prevent extraocular dissemination; occasionally, they present with metastatic disease that needs high-dose therapy. 2 Unlike many other pediatric malignancies, medical evidence needed for the treatment of these children is not available from cooperative groups from higher-income countries (HICs), simply because this condition is virtually nonexistent in HICs and because limited results have been reported by cooperative groups. Thus, evidence is left to be generated in less-developed countries. In addition, eye-conservative treatment is a challenge in this setting, not only because more patients present with more advanced disease but also because of the relatively low availability of sophisticated therapies and training of specialized personnel to use local treatments. 5

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 co...

Intravitreal injection of chemotherapy in retinoblastoma eyes with vitreous seeds may lead to a risk of extraocular tumour dissemination that has not been assessed so far. To develop a sensitive and clinically feasible technique to assess for potential retinoblastoma cell reflux after intravitreal injection of melphalan. Filter papers were cut in 6 mm diameter circles and sterilised before use. Eyes with retinoblastoma vitreous seeds (group D, International Classification) received weekly intravitreal melphalan injections (20 µg or 30 µg/dose) followed by cryotherapy as part of local treatment. Immediately after finishing the injection and cryotherapy, filter papers were placed on the injection site and on the cryoprobe tip to assess for the expression of the cone-rod homeobox gene (CRX) by real-time qPCR as a surrogate of retinoblastoma RNA. The assay was developed and validated to determine sensitivity, linearity, recovery, repeatability and reproducibility. The assay for quantita...

The feasibility and results of intraarterial chemotherapy, also termed ophthalmic artery chemosurgery (OAC), for retinoblastoma in less developed countries have seldom been reported. A retrospective evaluation of a program of OAC in Argentina from 2010 to 2015. 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...

Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divide...

Global Retinoblastoma Study Group IMPORTANCE Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. OBJECTIVES To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTS A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. MAIN OUTCOMES AND MEASURES Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTS The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). CONCLUSIONS AND RELEVANCE This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.