Author, year Country
Type of Study
Population
Intervention
Results
Public assistance
Hill, 2016 Kenya
Cross-sectional study.
Mean of ~ 60 delegates per meeting.
A nationally coordinated multidisciplinary (health workers, academics, retinoblastoma survivors and families, members of government) drawing input and expertise of professionals to optimize the cure of children with retinoblastoma. The program was based on the following principles: (1) Set the agenda together; (2) Interact with stakeholders; (3) Clarify responsibilities; (4) Account to beneficiaries; (5) Promote mutual learning; (6) Enhance capacities; (7) Share data and networks; (8) Disseminate results; (9) Pool profits and merits; (10) Apply results; (11) Secure outcomes. The program fulfilled 9/11 of its objectives, with the last two (applying results and securing outcomes) in progress. They produced consensus national guidelines for care and supported capacity-building initiatives to facilitate their implementation. Outcomes of children with retinoblastoma will be evaluated in the long term.
Surveillance
Ademola-Popoola, 2017 Nigeria
Cross-sectional study.
12 (2 RB cases).
Retinal imaging from a smartphone compared to traditional fundoscopy.
In cases of retinoblastoma with a highly reflective tumor mass, the images were not as clear as with a traditional fundus camera.
Bernard, 2022 Ethiopia
Cross-sectional study.
1200 individuals screened.
The EyeScreen® software, a smartphone application designed for use with Android® devices, as an effective, easy-to-perform, community-based screening tool.
Photographs obtained with inexpensive Android smartphones running the EyeScreen® application were used to train an ImageNet (ResNet®) machine learning model and to measure the performance of the app. Eighty percent of the images were used in training the model, and 20% were reserved for testing. The model showed a sensitivity of 87% and a specificity of 73%.
Kaliki, 2019 India Prospective nonrandomized observational/ interventional case series.
262 parents and 23 siblings of 131 patients.
Routine ophthalmic examination of families (parents and siblings) in a setting of the absence of genetic testing.
Spontaneously regressed RB in 8% of parents and active RB in 2% of siblings indicate that routine fundus screening of siblings allows for early detection of RB in otherwise asymptomatic children and detection of spontaneously regressed RB in parents may act as a surrogate marker for germline RB1 mutation.
Khedekar, 2019 India
Cross-sectional study.
34 eyes of 23 RB patients and 4 controls.
Two iPhone® apps (MDEyeCare® and CRADLE®) with modifications for early detection of RB without anesthesia or pharmacological dilatation of the pupil.
The modified MDEyeCare® app could detect the leukocoria in the early stages of RB (50% of Group B, 83% of Group C, but none of Group A). In the late stages (Group D and E), 100% of tumors were detected. The CRADLE® app failed to provide adequate leukocoria detection except for four late-stage RB eyes.
Vargas-Cuentas, 2019 Peru
Cross-sectional study.
35 participants: 15 RB cases 20 controls.
The use of a mobile app (Retino App®) associated with an algorithm for imaging processing for the detection of RB.
The system correctly identified 93.33% of the cases and 95% of the controls.
Yousef, 2020 Jordan
Retrospective, clinical case series.
32 families, 76 children. 34 presented signs of RB; 42 were enrolled in the screening program.
Screening routine with examination under anesthesia and non-sedated exams. The frequency of evaluations was scheduled based on a clinical assessment of pre-test risk for relatives to carry the mutant RB1 allele, in the absence of genetic testing.
Out of the 76 children enrolled, 46 children were diagnosed with Rb (12 by screening and 34 had signs of Rb). Patients diagnosed by screening were younger (mean: 2.4 months vs 15.8 months), had significantly earlier tumor stage at diagnosis (p = .0001), had higher eye salvage rate (p = .0001), less need for systemic chemotherapy (p = .022), and better visual outcome (p = .0017). None of the eyes were group D or E, enucleated or irradiated. Six patients were cured without chemotherapy, and the visual acuity was 0.5 or better in 55% of eyes.
International partnership
Al-Haddad, 2019 Lebanon
Retrospective case series.
40 (after) and 20 (before) RB cases.
The formalization of a multidisciplinary RB program (monthly meetings, centralization of care, clinical nurse) with associated financial support.
Reduced enucleation after the institution of the program (5% after versus 13% before); increased number of diagnostics (52 after versus 20 before); increased reception of patients from neighboring countries. However, even within a multidisciplinary setting, most patients with retinoblastoma still presented with advanced intraocular disease, and eye salvage rates were poor for patients with Group D and E tumors.
Chantada, 2016 Argentina
Public policy study.
(mean/year) 1987-1994: 18. 1995-2002: 35. 2003-2008: 30. 2009-2015: 36 2016-2020: 40 (estimated).
20-year cooperation between Garrahan Hospital in Argentina with Memorial Sloan Kettering Cancer Center in New York. The program initially concentrated on medical education and facilitated the research and treatment protocol for retinoblastoma in Latin America, incorporation of the first center capable of performing intra-arterial chemotherapy.
Improvement in the survival and ocular preservation of patients (3y probability of disease-free survival from 0.84 to 0.97), centralization of care, and participation in clinical studies and publications of the group.
Howard, 2018 10 index countries (Venezuela, Honduras, Ukraine, Egypt, Morocco, Senegal, Tanzania, Philippines, Vietnam, Bangladesh). 32 additional countries.
Public policy study.
201 RB cases.
The My Child Matters program supported diverse projects. Among them, the African Retinoblastoma Network, which had as its goals to raise awareness about retinoblastoma and childhood cancers with public campaigns to promote early diagnosis; to train oncologists and ophthalmologists to manage retinoblastoma; to create infrastructure and expertise for vision conservation in children diagnosed at early stages; to provide ocular prostheses, rehabilitation, and psychosocial support to patients with advanced disease.
Decrease in patients presenting with extraocular disease from 17 (65%) of 26 in 2011 to 19 (42%) of 45 in 2016; 1-year survival for patients with the unilateral intraocular disease increased from 3 (43%) of 7 in 2011 to 10 (71%) of 14 in 2016; 1-year survival for patients with bilateral intraocular disease increased from 0 (0%) of 2 in 2011 to 5 (42%) of 12 in 2016; eye preservation for patients increased from 0 (0%) of 4 in 2011 to 5 (21%) of 24 in 2016.
Qaddoumi, 2008 Jordan
Prospective cohort.
36 patients, 58 eyes.
A collaborative RB program was established with the International Outreach Program at St. Jude Children’s Research Hospital in Memphis, Tennessee. Mentoring included Internet consultations, videoconferences, and exchange visits.
Twinning has positively impacted survival and ocular salvage in Jordan. Thirty-three children with retinoblastoma (20 bilateral) were treated. A total of 66 consultations with 29 patients were analyzed. New cases were compared to previously treated cases. The success of the program was evident in bilateral cases, with low enucleation (25%) and irradiation rates (17%).
Wilimas, 2009 Central America (Guatemala, Honduras, El Salvador)
Public policy study.
196 (after) and 167 (before).
A RB program focused on developing early diagnosis strategies, treatment protocols suited to local conditions, building local networks of oncologists and ophthalmologists, training local healthcare providers, using the modern donated equipment for diagnosis and treatment, and teleconsultation to further education and share expertise.
Patients abandoning/refusing treatment decreased in Guatemala from 21% to 11% and in Honduras from 35% to 19%.
Yousef, 2020b Jordan
Cross-sectional study.
478 patients 813 eyes.
Implementing a telemedicine-based program with St. Jude Children’s Research Hospital compared to before implementation.
After the program implementation, the mortality rate decreased from 38% to 5% (P < 0.0001), and the overall eye salvage rate increased from 4% to 61% (98% for group A, 93% for group B, 81% for group C, and 48% for group D; P < 0.0001). Initially, all cases were discussed via telemedicine, but as knowledge transfer increased, the proportion of cases that required discussion decreased to less than 3% 10 years later. Similarly, treatment changes based on consultations decreased from 70% to 7% after 10 years. Both survival and eye salvage rates were comparable at the early and later stages of implementing the twinning program.
Education
Al-Nawaiseh, 2017 Jordan
Retrospective, clinical case series.
Seventy six eyes of 44 consecutive familial RB.
Screening for RB and raising awareness in non-probands versus probands.
The eye salvage rate was significantly higher in the non-probands than in the probands in this series (p = 0 002). Patients diagnosed by screening (38%) had excellent visual outcomes, and both eyes were saved. The authors concluded that awareness of families of the possibility of retinoblastoma and adequate screening led to a significantly higher rate of eye salvage in patients with familial retinoblastoma.
Antoneli, 2004 Brazil
Cross-sectional study.
105 patients (before the educational program) and 152 (after).
Educational campaigns: articles in non-medical magazines and billboards placed at strategic points in the city. The medical population received training through courses and publications in a medical journal.
Patients who were referred within a period of less than 6 months had a higher frequency of intraocular disease when compared to patients with a referral time longer than six months (75% vs. 25% p< .001). There was no statistically significant difference for extraocular tumors. The mean referral time was 7.5 months (SD 7.79) before the educational program versus 5.3 months (SD 6.84) after the intervention.
Elfalah, 2022 Jordan
Cross-sectional study.
289 medical students.
Implementing modifications on teaching curriculum of medical students on ophthalmology rotation that focuses on the red flags of RB.
Most participants considered leukocoria an abnormal sign. Medical students of the control group had significantly lower knowledge about the diagnosis of RB (p = .0001), while the intervention group scored higher in tests about critical questions, such as knowing that RB is a fatal disease (p = .041) that needs urgent treatment (p = .042). Only 2% of students adopted the “watch and wait” strategy in the intervention group, compared to 12% in the control group. Proficiency score in the test (≥ 90%) was achieved by 8% of students in the intervention group versus 2% in the control group. In the intervention group 27% of students, compared to 65% of students in the control group, failed to obtain a sufficiency score (≥70%) in the questionnaire.
Hill, 2015 Kenya
Cross-sectional study.
38 health workers.
A workshop for RB genetics education. Attendees: ophthalmologists, pathologists, oncologists, ophthalmic clinical officers, and nurses.
Knowledge increased significantly post-workshop, driven by increased knowledge of RB causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients and had integrated more genetic counseling into patient interactions.
Leander, 2007 Honduras
Cross-sectional study.
23 patients diagnosed after the campaign 59 patients (before).
RB education program linked to a national vaccination campaign in Honduras. Posters and flyers accessible to poorly educated readers, to convey the severity of RB, and to provide contact information.
Extraocular disease at diagnosis was 73% before versus 35% after the campaign (p = .002). Leukocoria was the presenting symptom in 54% of patients before versus 83% after the campaign (p = .02). The median age at diagnosis and the median time between the first sign or symptom and diagnosis were 3.8 (p = .26) and 1.7 (p = .6) months after the campaign.
Genetic counseling
Joseph, 2004 India
Cross-sectional study.
25 patients.
Presymptomatic genetic screening (RB1) compared to the clinical screening of RB proband and relatives.
The cost of genetic testing and clinical examination for a proband was $US152.27 and 535.60, respectively, while for the nuclear family, it was $US174.51 and $US1071.20, respectively.
Joseph, 2006 India
Diagnostic model proposal.
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An efficient diagnostic model with a logical and practical flow of various genetics tests (karyotyping, loss of heterozygosity analysis, molecular deletion, linkage analysis (familial cases), mutation screening of - CGA exons first and then non-CGA exons, methylation screening of RB1 and essential promoter regions screening in a laboratory) to reduce the overall health care costs.
In the proposed model, LOH analysis costs around US$ 9.72 (5.3%), RB1 gene mutational screening US$ 146.46 (79.88%), methylation analysis US$ 3.67 (2.0%), and cytogenetic analysis US$ 22.37 (12.8%). Assuming the patient did not exit until the last step in the genetic testing algorithm and did the entire spectrum of the tests with some of them being carried out simultaneously, about 84 days are required to exit from the diagnostic model.
Thirumalairaj, 2015 India
Cross-sectional study.
21 patients (13 bilateral and 8 unilateral RB).
Rapid genetic screening strategy by prioritizing the order of exons to be analyzed, based on the frequency of nonsense mutations, deletions, and duplications reported in the RB1-Leiden Open Variation Database and published literature on Indian patients.
Mutations were identified in 76% of patients in half the usual time and one-third of the cost.