Background: Retinoblastoma is the most common intraocular cancer in childhood in the Philippines. Most data though on demographics, clinical profile, treatment options, and outcomes in the country are from the National Capital Region. Objectives: This study aimed to describe the demographics, clinical profile, treatment done, and outcomes of retinoblastoma patients seen in a public tertiary referral center in Davao from 2011-2020 to make available literature more representative of the status of retinoblastoma in the Philippines. Methods: An analytical cross-sectional study was conducted using the records of retinoblastoma patients seen in a tertiary government hospital located in Davao Region from January 2011 to December 2020. Results: There were 157 patients included in the analysis. Seventy-three (46%) were female with 44% coming from the Davao Region. One hundred seven (69%) patients had unilateral disease. Median age at initial consultation for patients with unilateral disease was significantly older than those with bilateral disease (p<0.003). Tumors were extraocular in 82 (40%) eyes. In the intraocular group, 36% of the eyes belonged to International Classification of Retinoblastoma (ICRB) Groups D and E. Enucleation was the most commonly performed treatment. Survival rate was 28%. This is the first report to provide epidemiologic and clinical data on retinoblastoma in the literature, including survival data, from Mindanao. Advanced stages and extraocular cases of retinoblastoma remain high. Delay of consultation contributed to the prognosis and clinical outcome of the disease. Conclusion. Advanced stages and extraocular cases of retinoblastoma remain significantly high in the country, even in Mindanao.
Retinoblastoma ; Therapeutics ; Survival Rate

Background and Objective: Retinoblastoma is one of the most common intraocular cancers among children usually caused by the loss of retinoblastoma protein function. Despite being a highly heritable disease, conventional diagnostic and prognostic methods depend on clinical examination, with limited consideration of cancer genetics in the standard of care. CD133, KRT19, and MUC1 are commonly explored genes for their utility in liquid biopsies of cancer including lung adenocarcinoma. To date, there are few extensive molecular studies on retinoblastoma in Filipino patients. To this end, the study aimed to describe the copy number of CD133, KRT19, and MUC1 in retinoblastoma samples from a Filipino patient and quantitate the respective expression level of these genes. Methods: Hematoxylin & Eosin (H&E) staining was utilized to characterize the retinoblastoma tissue while fluorescence in situ hybridization (FISH) using probes specific to CD133, KRT19, and MUC1 was performed to determine the copy number of genes in retinoblastoma samples from a Filipino patient (n = 1). The gene expression of CD133, MUC1, and KRT19 was quantitated using RT-qPCR. Results: The H&E staining in the retinoblastoma tissue shows poorly differentiated cells with prominent basophilic nuclei. CD133 was approximately 1.5-fold overexpressed in the retinoblastoma tissue with respect to the normal tissue, while MUC1 and KRT19 are only slightly expressed. Multiple intense signals of each probe were localized in the same nuclear areas throughout the retinoblastoma tissue, with high background noise. Conclusion These findings suggest that CD133 is a potential biomarker for the staging and diagnosis of retinoblastoma in Filipino cancer patients. However, further optimization of the hybridization procedures is recommended.
Retinoblastoma ; Biomarkers ; In Situ Hybridization

OBJECTIVE

This study compared the demographics, clinical profile, treatment, and outcomes of retinoblastoma patients seen at medical institutions in the Philippines between two time periods: 2010 to 2015 and 2016 to 2020.

This was a multicenter, analytical, cohort study using review of medical charts and databases of retinoblastoma patients seen in 11 medical institutions from 2010 to 2020.

There were 636 patients (821 eyes) included in this study: 330 patients were seen in 2010 to 2015 while 306 in 2016 to 2020. More cases per annum were seen in the latter timeline. The number of patients with unilateral disease was not significantly different between the two time periods (p=0.51). Age at onset of symptom, age at initial consultation, and delay in consult were also not significantly different between the two time periods (p > 0.05). Patients had significantly different distributions of intraocular grades (p < 0.0001) and systemic staging (p < 0.0001) between the two time periods. Enucleation was the most common surgical treatment performed in both timelines. There was significant difference in the status of patients based on the need for systemic chemotherapy (p < 0.01). There was significant difference in outcome between the two time periods, including the proportions of living and deceased patients.

This study compared the most comprehensive data on retinoblastoma patients in the country. There was no improvement in early health seeking behavior based on similar age at initial consult and delay in consult. Enucleation remained the most common treatment mode as opposed to chemotherapy due to similar percentage of patients with unilateral disease, an indication for enucleation rather than chemotherapy.

Objective: This study determined the treatment outcomes of patients with retinoblastoma seen at a Philippine tertiary government hospital from January 2000 to January 2020. Method: This is a cohort study. Medical records of patients with histopathologic-proven retinoblastoma were reviewed and pertinent information on clinical profile and presentation, treatment and outcomes were recorded. Results: This study included 118 patients (146 eyes) with mean age at symptom onset of 7.4 + 6.6 months and mean age at consult of 11.5 + 13.7 months. There were 69 (47%) eyes with International Classification of Retinoblastoma (ICRB) stage E. The most common primary treatment was enucleation (n=137, 94%). The most common high-risk histopathologic feature was involvement of the optic nerve at the cut-end section (n=27, 34%). Only 14 patients (11%) completed treatment with median follow-up of 30.5 months (range 4- 122). Conclusion The rate of overall survival of patients with retinoblastoma is low in this study, similar to other developing countries. This can be due to higher proportion of patients with advanced stage at presentation and lower percentage of treatment completion. Early diagnosis and treatment may lead to better survival rate, visual outcome and quality of life. Due to limited data on follow-up, globe preservation could not be determined.
Retinoblastoma ; Survival Rate

Objective: This study determined the capacity to treat retinoblastoma (RB) in the Philippines. Method: This was a cross-sectional study which included all Department of Health (DOH) hospitals and all government and private tertiary hospitals in the Philippines. An online modified questionnaire taken from the St. Jude Children’s Research Hospital study on RB assessment was emailed to 143 hospitals in all 17 regions. Primary outcome measures were human resources capacity, treatment capacity and education and network capacity. Availability, frequency and confidence of use were assessed for treatment capacity. An asset-based tier classification of hospitals was created based on the human resources capacity and treatment capacity. Results: This assessment survey had a 49% response rate. There were 3 regions that had zero correspondence. A general ophthalmologist, a subspecialized ophthalmologist, and a general pathologist were the most available physicians in the management of RB. Almost all respondents had the necessary diagnostic technology in their hospitals, but frequency and confidence of use were low. A quarter of the respondents (23%) used a standardized treatment protocol, while only 26% had established a referral network in their area. Tier classification was able to differentiate capacities for particular resources only. Only 23% of the participating hospitals have the capacity to treat RB through its trained human resources, available diagnostic and treatment technology, and education and network programs. Distribution of hospitals identified as tier I, II and III were 18%, 8%, and 41%, respectively. Conclusion Capacity to treat RB in the Philippines is evident only in a few hospitals, majority of which are located in the National Capital Region. However, tier 3 hospitals were identified in 10 other regions, making accessibility to RB care possible to patients in the provinces. Although human resource and technology are made available, utilization of these resources is low in many hospitals for the management of RB. Clinical practice guidelines for RB is still lacking. Connecting the different tiers in each region as a form of referral network can improve capacity and management of RB.
Retinoblastoma ; Therapeutics ; Surveys and Questionnaires

Objective: This study reported the demographic profile, clinical presentation, treatment, and outcomes of retinoblastoma (RB) patients seen at Jose R. Reyes Memorial Medical Center (JRRMMC) from January 2011 to December 2020. Methods: This was a single-center, retrospective study. Medical records of patients diagnosed with RB at JRRMMC from January 2011 to December 2020 were reviewed. Descriptive statistics were used to summarize the characteristics of the participants. Results: A total of 31 confirmed RB cases were seen, with almost half residing outside Metro Manila (52%). The median age at diagnosis was 2 years, with a slight male predominance (55%). Majority (81%) of patients had unilateral presentation, with leukocoria as the most common sign (19%) prompting consult. Nearly half (43%) of 37 eyes were diagnosed as Group E using the International Classification of Retinoblastoma (ICRB) system. Majority were in the advanced stage; 57% of eyes underwent enucleation and 29, 3 and 3% of patients required additional treatments such as chemotherapy, laser, and radiotherapy, respectively. RB was confirmed in 20 eyes (54%) through histopathology. Survival outcomes showed that 4 patients (13%) were alive, with either completed or ongoing treatment, and 19 (61%) did not complete prescribed management or were lost to follow-up. There were 8 (26%) known deaths. Conclusion Majority of cases were unilateral and at an advanced stage needing enucleation which may indicate low levels of awareness and screening efforts. Survival rates are difficult to ascertain due to patients abandoning treatment that may be attributed to limited social service support. The study reflects the 10-year data prior to the establishment of a collaborative, multispecialty RB team in the institution and exposes various areas that need to be addressed to improve clinical outcomes.
Retinoblastoma ; Enucleation ; Chemotherapy ; Epidemiology

Background: Intravitreal chemotherapy has been an effective addition in treating vitreous seeding in retinoblastoma. However, it was only in 2020 that it was used in the Philippines. There is no literature on its use in multiple Filipino retinoblastoma patients. Objectives: To describe the clinical course of the four patients who are the first to undergo intravitreal chemotherapy for vitreous seeding of retinoblastoma in the Philippine tertiary hospital. Methods: A case series of four eyes of four patients with retinoblastoma who underwent intravitreous injection of melphalan and topotecan for vitreous seeding at the Department of Ophthalmology and Visual Sciences of a Philippine tertiary hospital. Results: Two eyes, with International Intraocular Retinoblastoma Classification (IIRC) Group C with vitreous seeding, responded well to intravitreous melphalan and topotecan. One eye had recurrent vitreous seeding despite 10 intravitreal injections. One eye with IIRC Group E, did not respond to intravitreous chemotherapy and was eventually enucleated. This is the first case series on the local use of intravitreous chemotherapy in the country for vitreous seeding in retinoblastoma. The control of 50% achieved in this case series is lower than in other series due to longer treatment interval from poor follow-up and the presence of advanced disease. Conclusion The use of intravitreous melphalan and topotecan can be an effective adjuvant for systemic chemotherapy in controlling vitreous seeding in eyes with IIRC Group C. It is not effective in controlling IIRC Group E disease.
intravitreous ; melphalan ; topotecan ; retinoblastoma ; Philippines

Objectives: To evaluate the prevalence, etiologies, demographics, and clinical presentation of enucleated pseudoretinoblastoma. Methods: This retrospective study reviewed ocular pathology records of enucleated globes with clinically diagnosed or suspected retinoblastoma submitted to a public university ocular pathology laboratory from 2013 to 2018. Hematoxylin-eosin-stained sections of pseudoretinoblastoma cases were reevaluated, and additional clinical data were taken from hospital charts. Results: Of the 211 enucleated eyes with clinically diagnosed or suspected retinoblastoma, 202 (95.7%) had histologically confirmed retinoblastoma, while 9 (4.3%) had pseudoretinoblastoma. The most common ocular conditions mimicking retinoblastoma were retinal dysplasia (2 eyes) and persistent fetal vasculature (2 eyes). The pseudoretinoblastoma group consisted of 4 females and 5 males, and enucleated were 6 right eyes and 3 left eyes. The mean age at the time of enucleation was 3.65 years, and the mean symptom duration was 17.36 months. Leukocoria, which was noted in 4 patients, was the most frequent initial symptom. No significant difference between the pseudoretinoblastoma group and the retinoblastoma group were found in terms of sex, laterality of the enucleated eye, age at the time of enucleation, and symptom duration. Conclusion In this retrospective review, the prevalence of pseudoretinoblastoma in enucleated globes clinically suspected or diagnosed with retinoblastoma was 4.3%. Persistent fetal vasculature and retinal dysplasia were the most common pseudoretinoblastomas. Clinicians should perform a thorough clinical evaluation and judiciously utilize the available diagnostic means to differentiate retinoblastoma from pseudoretinoblastoma.
eye enucleation ; retinal dysplasia ; retinoblastoma

Objective: To explore the effect of lncRNA ADPGK-AS1 on the proliferation and apoptosis of retinoblastoma cells and its possible mechanism. Methods: The tumor tissues of 31 patients with retinoblastoma admitted to Henan Provincial Eye Hospital from February to June 2020 and their corresponding normal tissues adjacent to the cancer were collected. The expression levels of lncRNA ADPGK-AS1 and miR-200b-5p in retinoblastoma tissues and normal adjacent tissues were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Human retinal epithelial cell ARPE-19, human retinoblastoma cell Y-79 and WERI-Rb-1 were cultured in vitro. The expression levels of lncRNA ADPGK-AS1 and miR-200b-5p were detected by qRT-PCR. Y-79 cells were randomly divided into si-con group, si-lncRNA ADPGK-AS1 group, miR con group, miR-200b-5p group, si-lncRNA ADPGK-AS1+ anti-miR con group, and si-lncRNA ADPGK-AS1+ anti-miR-200b-5p group. The proliferation, cloning and apoptosis of cells in each group were detected by tetramethylazol blue method, plate cloning test and flow cytometry, respectively. The targeting relationship between lncRNA ADPGK-AS1 and miR-200b-5p was detected by double luciferase report test, and the expression level of cleaved-caspase-3 protein was detected by western blot. Results: Compared with the adjacent tissues, the expression of lncRNA ADPGK-AS1 in retinoblastoma tissues was increased (P<0.05), while the expression of miR-200b-5p was decreased (P<0.05). Compared with ARPE-19 cells, the expression of lncRNA ADPGK-AS1 in Y-79 and WERI-Rb-1 cells was increased (P<0.05), while the expression of miR-200b-5p was decreased (P<0.05). Compared with the si-con group, the cell viability of the si-lncRNA ADPGK-AS1 group was reduced (1.06±0.09 vs 0.53±0.05, P<0.05), the number of cell clone formation was reduced (114.00±8.03 vs 57.00±4.13, P<0.05), while the apoptosis rate [(7.93±0.68)% vs (25.43±1.94)%] and the protein level of cleaved-caspase-3 were increased (P<0.05). Compared with the miR-con group, the cell viability of the miR-200b-5p group was decreased (1.05±0.08 vs 0.57±0.05, P<0.05), the number of cell clone formation was decreased (118.00±10.02 vs 64.00±5.13, P<0.05), while the apoptosis rate [(7.89±0.71)% vs (23.15±1.62)%] and the protein level of cleaved-caspase-3 were increased (P<0.05). lncRNA ADPGK-AS1 could target the expression of miR-200b-5p. Compared with the si-lncRNA ADPGK-AS1+ anti-miR-con group, cell viability of the si-lncRNA ADPGK-AS1+ anti-miR-200b-5p group was increased (0.53±0.04 vs 1.25±0.10, P<0.05), and the number of cell clones was increased (54.00±4.39 vs 125.00±10.03, P<0.05), while the rate of apoptosis [(25.38±1.53)% vs (9.76±0.71)%] and the protein level of cleaved-caspase-3 were decreased (P<0.05). Conclusion: Interfering with the expression of lncRNA ADPGK-AS1 could inhibit the proliferation and clone formation and induce apoptosis of retinoblastoma cells by targeting the expression of miR-200b-5p.
Humans ; MicroRNAs/metabolism* ; Retinoblastoma/pathology* ; Caspase 3/metabolism* ; RNA, Long Noncoding/metabolism* ; Antagomirs/pharmacology* ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis/genetics* ; Retinal Neoplasms/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Movement/genetics*

Background: India has the highest incidence of retinoblastoma globally and is one of the six Asian countries identified to contribute 43% to the global retinoblastoma cases. Data on clinical presentation, treatment, and outcomes were reviewed which can serve as basis in the creation of clinical guidelines, policies and programs, and resource allocation in the diagnosis and management of retinoblastoma in India. Methodology: Articles on retinoblastoma in India gathered from different databases were reviewed for clinical features, treatment, and outcomes. Result: Fourteen articles with 3,666 patients involving around 4,945 eyes seen from 1983-2017 were reviewed. The median age at consult ranged from 14-48 months. The median delay of consult ranged from 2-9 months. Majority of the patients were males (59%) and unilateral disease was present in 63%. Family history was reported in 4%. Retinoblastoma was intraocular in at least 75% of eyes. Systemic chemotherapy was the most used treatment option given to >2,042 eyes. Enucleation was done in >1,695 eyes. The mean follow-up period ranged from 4-50 months. Three hundred fifty six (356) patients were lost to follow-up. The functional vision was retained in 134 eyes. The globe salvage rate for Group A was 100%, 94-100% for Group B, and 50-100% in Group C. The highest globe salvage rate for Group D eyes was 85% and 58% for group E. The overall survival rate was 75% (2,233 patients). Conclusion Common among the articles was the relatively high proportion of extraocular disease attributed to delay in consult attributed to financial factors and lack of knowledge on the disease.
Retinoblastoma ; Therapeutics ; India ; Asia