Improving survival of retinoblastoma in Uganda.

BACKGROUND: Diagnostic delay results in relatively high mortality among children with retinoblastoma in Uganda, where treatment was limited to surgery and, for some, radiotherapy. In order to improve outcomes, a simple programme of neoadjuvant and adjuvant chemotherapy was introduced. Here we report survival before and after this change to medical practice. METHODS: Affordable standard off-patent chemotherapy agents were administered by trained paramedical staff to groups of patients at the same time. Survival before and after the introduction of chemotherapy was monitored. Between 2006 and 2013 a total of 270 patients with retinoblastoma were included, 181 treated prior to chemotherapy and 89 after (beginning in 2009). We had 94% follow-up and 249 had histological verification of diagnosis. RESULTS: Using a proportional hazards model adjusted for age, sex and laterality, children treated after chemotherapy was introduced had a 37% lower risk of dying (HR 0.63, 95% CI 0.41 to 0.99) compared with children treated before. Prior to the introduction of chemotherapy only 15% of children who survived bilateral disease retained vision after treatment compared with 71% after chemotherapy. CONCLUSIONS: The introduction of chemotherapy proved safe and cost-effective in non-specialist hands and was associated with significant improvements in survival and, among bilateral cases, in preserving vision.

Clinical features and survival among children with retinoblastoma in Uganda.

AIMS: To characterise the clinical features, treatment and outcome of children diagnosed with retinoblastoma in Uganda. METHODS: The study comprised a 6-year nationwide enrolment with follow-up. RESULTS: In total, 282 cases were enrolled, 26% (72) were bilateral; 6% were lost to follow-up. Almost all diagnoses in the first affected eye were International Classification of Retinoblastoma group E or worse. Histology was available for 92%; of those, 45%, had extraocular tumour at diagnosis. Enucleation of the first eye was done for 271; 94 received radiotherapy to the socket and in the last 2 years, 70 children received chemotherapy. At close of study, 139 children had died. Survival, as determined in a proportional hazards model adjusted for age, sex, laterality and treatment era (pre or post introduction of chemotherapy), varied by extent of the tumour (p<0.001); children with only intraocular involvement were 80% less likely to die (HR=0.21, 95% CI 0.12 to 0.35) compared with children with extraocular involvement. CONCLUSIONS: Diagnostic delay results in relatively high mortality among children with retinoblastoma in Uganda. There is an urgent need for more effective treatment modalities, particularly chemotherapy, and nationwide efforts to encourage earlier access to medical care.

Replication of the recessive STBMS1 locus but with dominant inheritance.

PURPOSE: Strabismus is a common eye disorder with a prevalence of 1% to 4%. Comitant strabismus accounts for approximately 75% of all strabismus, yet more is known about the less common incomitant disorders. Comitant strabismus is at least partly inherited, but only one recessive genetic susceptibility locus, on chromosome 7p, has been identified in one family. The purpose of this study was to determine the frequency of STBMS1 as a cause of primary nonsyndromic comitant esotropia (PNCE). METHODS: Twelve families were recruited within the UK Hospital Eye Service as children attended for treatment of PNCE. All consenting persons were clinically assessed, and DNA was sampled. Chromosome 7 microsatellite markers were genotyped in all 12 families, and LOD scores were calculated under recessive and dominant models. RESULTS: One family was linked to STBMS1; in three, linkage was significantly excluded; and the remainder were uninformative. Twenty-six members from three generations of the linked family were analyzed further. Five family members were defined as affected; two had esotropia with an accommodative element; and three underwent strabismus surgery and appeared to have had an infantile/early-onset esotropia. A maximum LOD score of 3.21 was obtained under a dominant mode of inheritance; a recessive model gave an LOD score of 1.2. CONCLUSIONS: This study confirms that PNCE can result from sequence variants in an unknown gene at the STBMS1 locus. However, this locus accounts for only a proportion of cases, and other genetic loci remain to be identified. In contrast with the previously reported family, the pedigree described in this study is consistent with dominant rather than recessive inheritance at the STBMS1 locus.

Retinopathy of prematurity treatment and vitreous hemorrhage.

Two cases of hemorrhagic retinopathy of prematurity associated with thrombocytopenia are presented. The negative prognosis of vitreous hemorrhage in retinopathy of prematurity and the option of platelet transfusions are discussed.