Google Gemini and Bard artificial intelligence chatbot performance in ophthalmology knowledge assessment.

PURPOSE: With the popularization of ChatGPT (Open AI, San Francisco, California, United States) in recent months, understanding the potential of artificial intelligence (AI) chatbots in a medical context is important. Our study aims to evaluate Google Gemini and Bard's (Google, Mountain View, California, United States) knowledge in ophthalmology. METHODS: In this study, we evaluated Google Gemini and Bard's performance on EyeQuiz, a platform containing ophthalmology board certification examination practice questions, when used from the United States (US). Accuracy, response length, response time, and provision of explanations were evaluated. Subspecialty-specific performance was noted. A secondary analysis was conducted using Bard from Vietnam, and Gemini from Vietnam, Brazil, and the Netherlands. RESULTS: Overall, Google Gemini and Bard both had accuracies of 71% across 150 text-based multiple-choice questions. The secondary analysis revealed an accuracy of 67% using Bard from Vietnam, with 32 questions (21%) answered differently than when using Bard from the US. Moreover, the Vietnam version of Gemini achieved an accuracy of 74%, with 23 (15%) answered differently than the US version of Gemini. While the Brazil (68%) and Netherlands (65%) versions of Gemini performed slightly worse than the US version, differences in performance across the various country-specific versions of Bard and Gemini were not statistically significant. CONCLUSION: Google Gemini and Bard had an acceptable performance in responding to ophthalmology board examination practice questions. Subtle variability was noted in the performance of the chatbots across different countries. The chatbots also tended to provide a confident explanation even when providing an incorrect answer.

Diagnostic Imaging for Retinoblastoma Cancer Staging: Guide for Providing Essential Insights for Ophthalmologists and Oncologists.

Retinoblastoma is the most common cause of all intraocular pediatric malignancies. It is caused by the loss of RB1 tumor suppressor gene function, although some tumors occur due to MYCN oncogene amplification with normal RB1 genes. Nearly half of all retinoblastomas occur due to a hereditary germline RB1 pathogenic variant, most of which manifest with bilateral tumors. This germline RB1 mutation also predisposes to intracranial midline embryonal tumors. Accurate staging of retinoblastoma is crucial in providing optimal vision-, eye-, and life-saving treatment. The AJCC Cancer Staging Manual has undergone significant changes, resulting in a universally accepted system with a multidisciplinary approach for managing retinoblastoma. The authors discuss the role of MRI and other diagnostic imaging techniques in the pretreatment assessment and staging of retinoblastoma. A thorough overview of the prevailing imaging standards and evidence-based perspectives on the benefits and drawbacks of these techniques is provided. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

THE ABILITY OF ARTIFICIAL INTELLIGENCE CHATBOTS ChatGPT AND GOOGLE BARD TO ACCURATELY CONVEY PREOPERATIVE INFORMATION FOR PATIENTS UNDERGOING OPHTHALMIC SURGERIES.

INTRODUCTION: To determine whether the two popular artificial intelligence chatbots, ChatGPT and Bard, can provide high-quality information concerning procedure description, risks, benefits, and alternatives of various ophthalmic surgeries. METHODS: ChatGPT and Bard were prompted with questions pertaining to the description, potential risks, benefits, alternatives, and implications of not proceeding with various surgeries in different subspecialties of ophthalmology. Six common ophthalmic procedures were included in the authors' analysis. Two comprehensive ophthalmologists and one subspecialist graded each response independently using a 5-point Likert scale. RESULTS: Likert grading for accuracy was significantly higher for ChatGPT in comparison with Bard (4.5 ± 0.6 vs. 3.8 ± 0.8, P < 0.0001). Generally, ChatGPT performed better than Bard even when questions were stratified by the type of ophthalmic surgery. There was no significant difference between ChatGPT and Bard for response length (2,104.7 ± 271.4 characters vs. 2,441.0 ± 633.9 characters, P = 0.12). ChatGPT responded significantly slower than Bard (46.0 ± 3.0 vs. 6.6 ± 1.2 seconds, P < 0.0001). CONCLUSION: Both ChatGPT and Bard may offer accessible and high-quality information relevant to the informed consent process for various ophthalmic procedures. Nonetheless, both artificial intelligence chatbots overlooked the probability of adverse events, hence limiting their potential and introducing patients to information that may be difficult to interpret.

Association Between Vision Difficulty and Sociodemographic Factors in Children: A Population-Based Analysis.

PURPOSE: To determine sociodemographic predictors of poor vision in children and adolescents less than 18 years of age in a large, nationally representative sample of the US population. DESIGN: Retrospective, population-based cross-sectional study. METHODS: Using data from the 2021 National Health Interview Survey (NHIS), participants less than 18 years of age for whom data were available on vision difficulty were included in our analysis. Our primary outcome was vision difficulty. Sociodemographic variables were investigated as predictors of vision difficulty. Logistic regression models were performed using Stata version 17.0. An odds ratio (OR) and 95% CI were reported for analyses. RESULTS: The 2021 NHIS reported on 8261 children and adolescents, of whom 7373 had data pertaining to vision difficulty and were included in our sample. Vision difficulty was associated with being unable to afford medical care (OR = 2.60, 95% CI = 1.17, 5.80, P = 0.02) and having public health insurance (OR = 1.52, 95% CI = 1.09, 2.12, P = .01). Compared to children less than 5 years of age, children ranging from 5 to 8 years (OR = 4.29, 95% CI = 2.26, 8.15, P < .01) and adolescents ranging from 16 to 17 years (OR = 6.06, 95% CI = 3.17, 11.58, P < .01) had a higher odds of vision difficulty. Compared to participants for whom the highest level of education of adults in their family was grade 1 to 11, the odds of vision difficulty were lower in those whose parents had a professional school or doctoral degree (OR = 0.30, 95% CI = 0.11, 0.84, P = .02). CONCLUSIONS: Multiple sociodemographic factors are associated with vision difficulty in young persons. In working toward achieving equity in vision health, it is imperative that disparities mediated by sociodemographic factors be addressed through public health policies.

Orbital Complications and Cost Analysis of Enucleation by Myoconjunctival versus Conventional Techniques for Retinoblastoma.

Introduction: The aim of the study was to compare complication rates and hospital costs of myoconjunctival versus conventional enucleation techniques in retinoblastoma. Methods: This retrospective cohort and cost analysis reviewed patients with retinoblastoma treated by primary or secondary enucleation between 2003 and 2021 and a minimum 6-month follow-up. Cases were reviewed for three postsurgical complications: chronic conjunctivitis, implant exposure/extrusion, and cellulitis. Cases were excluded if surgery was performed elsewhere or documentation was incomplete. Treatment costs were estimated based on two sample cases billed in 2021 that manifested the studied complications and represented each of the two surgical techniques. Univariate and multivariate analyses were applied to compare complication rates and treatment costs. Results: Included were 180 eyes (179 patients); 239 eyes (227 patients) were excluded. Patients had median age of 18.9 (0-104.4) months at diagnosis, the majority were male (94, 52%), with unilateral (115, 64%) group D or E (163, 91%) eyes. Enucleation was performed by conventional techniques in 107 eyes (59%) and by myoconjunctival approach in 73 (41%). Orbital complications occurred in 61 eyes (34%) during a median follow-up of 7.9 (0.5-33.7) years, more frequently in the conventional technique group (p = 0.014). The myoconjunctival technique had significantly lower costs for implant price (p < 0.001) and estimated treatment cost, including complication management (p < 0.001). Conclusion: Enucleation by myoconjunctival technique showed significantly less complication burden and treatment cost, indicating advantages over conventional approaches. Study limitations include the retrospective nature, confounders' complexity, and follow-up time variations.

Social Determinants of Health in Pediatric Ophthalmology Patients: Availability of Data in the Electronic Health Record and Association With Clinic Attendance.

Purpose: To characterize the availability of social determinants of health data in the electronic health record of pediatric ophthalmology patients and to examine the association of social determinants of health with attendance at scheduled operating room and clinic visits. Methods: This was a retrospective cohort study of pediatric ophthalmology patients seen at The Hospital for Sick Children between June 1, 2018, and May 23, 2022. Data were collected on demographics, diagnosis, and management-plan. The χ2 tests and multivariable regression were used to examine associations between social determinants of health and attendance at scheduled operating room and clinic visits. Results: The cohort consisted of 26,102 study subjects with 31,288 unique eye-related diagnoses representing 57 unique ICD-10 codes. Availability of data in the electronic health record ranged from 100% for sex, age and postal code to 0.1% for ethnic group. Female sex (P = 0.004) and urbanicity (P = 0.05) were associated with higher operating room visit cancellations. Female sex (P = 0.002), age group 0-13 (P ≤ 0.001), low-medium neighborhood income quintile (P ≤ 0.001), residence of Northern Ontario (P ≤ 0.001), and urbanicity (P ≤ 0.001) were associated with higher clinic visit cancellations and no-shows. Conclusions: At a major tertiary-care hospital in Canada, key social determinant data such as ethnicity are not consistently available in the electronic health record of pediatric ophthalmology patients. Female sex, younger age, and living in a rural area or neighborhood with low-medium income quintile may be predictors of missed visits and require further study. Translational Relevance: This study highlights a need for improved documentation of social determinants of health variables in electronic health records.

Depleted hexokinase1 and lack of AMPKα activation favor OXPHOS-dependent energetics in retinoblastoma tumors.

Lack of retinoblastoma (Rb) protein causes aggressive intraocular retinal tumors in children. Recently, Rb tumors have been shown to have a distinctly altered metabolic phenotype, such as reduced expression of glycolytic pathway proteins alongside altered pyruvate and fatty acid levels. In this study, we demonstrate that loss of hexokinase 1(HK1) in tumor cells rewires their metabolism allowing enhanced oxidative phosphorylation-dependent energy production. We show that rescuing HK1 or retinoblastoma protein 1 (RB1) in these Rb cells reduced cancer hallmarks such as proliferation, invasion, and spheroid formation and increased their sensitivity to chemotherapy drugs. Induction of HK1 was accompanied by a metabolic shift of the cells to glycolysis and a reduction in mitochondrial mass. Cytoplasmic HK1 bound Liver Kinase B1 and phosphorylated AMP-activated kinase-α (AMPKα Thr172), thereby reducing mitochondria-dependent energy production. We validated these findings in tumor samples from Rb patients compared to age-matched healthy retinae. HK1 or RB1 expression in Rb-/- cells led to a reduction in their respiratory capacity and glycolytic proton flux. HK1 overexpression reduced tumor burden in an intraocular tumor xenograft model. AMPKα activation by AICAR also enhanced the tumoricidal effects of the chemotherapeutic drug topotecan in vivo. Therefore, enhancing HK1 or AMPKα activity can reprogram cancer metabolism and sensitize Rb tumors to lower doses of existing treatments, a potential therapeutic modality for Rb.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

A typical anterior retinoblastoma: diagnosis by aqueous humor cell-free DNA analysis.

BACKGROUND: Aqueous humor from eyes with active retinoblastoma contains tumor-derived cell-free DNA. MATERIALS AND METHODS: Single retrospective case report. RESULTS: A 13-year-old girl with acute right eye pain and redness was diagnosed with hypertensive anterior uveitis. Following initial management, she was referred to ocular oncology for an atypical clinical picture. Multiple seeds were noted 360 degrees in the anterior chamber, at the equator of the lens and canal of Petit, and ultrasound biomicroscopy identified a temporal pars plana lesion. While aqueous humor cytology was inconclusive for malignancy, targeted next-generation sequencing of aqueous cell-free DNA identified biallelic RB1 full gene deletion, confirming the diagnosis of retinoblastoma. Partial regression followed three cycles of systemic carboplatin, etoposide, and vincristine and three intracameral melphalan injections. Four months later, she had recurrence of the primary tumor and increase in seeding and received the investigational sustained release episcleral topotecan chemoplaque. Stable regression was achieved to 28-month follow-up, with no detectable aqueous cell-free DNA. CONCLUSIONS: RB1 sequencing analysis of tumor-derived cell-free DNA from aqueous humor can confirm the diagnosis of retinoblastoma in cases of diagnostic uncertainty.

Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a.

Advanced retinoblastoma (Rb) tumors display high metastatic spread to distant tissues, causing a potent threat to vision and life. Through transcriptomic profiling, we discovered key upregulated genes that belonged to the epithelial-mesenchymal transition (EMT) and chemotherapy resistance pathways in advanced Rb tumors. Through in vitro models, we further showed that Rb null tumor cells under prolonged chemo drug exposure, acquires a metastasis-like phenotype through the EMT program mediated by ZEB1 and SNAI2 and these cells further acquires chemotherapeutic resistance through cathepsin-L- and MDR1-mediated drug efflux mechanisms. Using a miRNA microarray, we identified miR-181a-5p as being significantly reduced in advanced Rb tumors, which was associated with an altered EMT and drug-resistance genes. We showed that enhancing miR-181a-5p levels in Rb null chemo-resistant sublines reduced the ZEB1 and SNAI2 levels and halted the mesenchymal transition switch, further reducing the drug resistance. We thus identified miR-181a-5p as a therapeutically exploitable target for EMT-triggered drug-resistant cancers that halted their invasion and migration and sensitized them to low-dose chemotherapy drugs.

A White Retinal Lesion With Calcification in an 11-Year-Old Boy.

An 11-year-old boy was referred to assess a retinal mass in the left eye found on his first routine ophthalmic evaluation. A white, translucent solid lesion with calcification was noticeable in the inferonasal quadrant of the left eye. What would you do next?

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors.

Retinoblastoma (Rb) is a pediatric intraocular malignancy that is proposed to originate from maturing cone cell precursors in the developing retina. The molecular mechanisms underlying the biological and clinical behaviors are important to understand in order to improve the management of advanced-stage tumors. While the genetic causes of Rb are known, an integrated understanding of the gene expression and metabolic processes in tumors of human eyes is deficient. By integrating transcriptomic profiling from tumor tissues and metabolomics from tumorous eye vitreous humor samples (with healthy, age-matched pediatric retinae and vitreous samples as controls), we uncover unique functional associations between genes and metabolites. We found distinct gene expression patterns between clinically advanced and non-advanced Rb. Global metabolomic analysis of the vitreous humor of the same Rb eyes revealed distinctly altered metabolites, indicating how tumor metabolism has diverged from healthy pediatric retina. Several key enzymes that are related to cellular energy production, such as hexokinase 1, were found to be reduced in a manner corresponding to altered metabolites; notably, a reduction in pyruvate levels. Similarly, E2F2 was the most significantly elevated E2F family member in our cohort that is part of the cell cycle regulatory circuit. Ectopic expression of the wild-type RB1 gene in the Rb-null Y79 and WERI-Rb1 cells rescued hexokinase 1 expression, while E2F2 levels were repressed. In an additional set of Rb tumor samples and pediatric healthy controls, we further validated differences in the expression of HK1 and E2F2. Through an integrated omics analysis of the transcriptomics and metabolomics of Rb, we uncovered a significantly altered tumor-specific metabolic circuit that reduces its dependence on glycolytic pathways and is governed by Rb1 and HK1.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

Pediatric Cataract Surgery Following Treatment for Retinoblastoma: A Case Series and Systematic Review.

PURPOSE: To determine the visual and refractive outcomes and the ocular and systemic complications of cataract surgery in eyes treated for retinoblastoma. DESIGN: Retrospective consecutive case series and systematic review. METHODS: Children <18 years of age with retinoblastoma who underwent surgery for secondary cataract between 2000 and 2020 were reviewed. Medline (OVID), Embase, Web of Science, and the Cochrane database were searched from inception to August 2020. RESULTS: A total of 15 eyes of 15 children were included. The mean age at retinoblastoma diagnosis was 12 months (median, 14; interquartile range [IQR], 4-19). Cataract developed at a mean age of 39 months (median, 31; IQR, 20-52), secondary to multiple treatments (n = 7), pars-plana vitrectomy (n = 3), external-beam radiotherapy (n = 2), laser (n = 2), and retinal detachment (n = 1). The mean preoperative quiescent interval was 44 months (median, 28; IQR, 15-64). Primary intraocular lens implantation was performed in 93%, posterior capsulotomy in 40%, and anterior vitrectomy in 33% of participants. Postoperatively, 100% had improved fundus visibility and 73% had improved vision. Complications included visual axis opacification (11 of 15), capsular phimosis (5 of 15), and zonulopathy (3 of 15). No patient developed intraocular recurrence, extraocular extension, or metastasis at a mean of 76 months (median, 78; IQR, 29-128) follow-up. The systematic review identified 852 studies, with 18 meeting inclusion criteria. Across all studies (n = 220 children), intraocular recurrence occurred in 6%, globe salvage in 91%, and extraocular extension and metastasis in <1%. CONCLUSIONS: Modern retinoblastoma therapies, including intravitreal chemotherapy and vitrectomy, cause secondary cataract. Following cataract surgery, intraocular recurrence risk is low and extraocular spread is rare. Although surgery improves tumor visualization, visual prognosis may be limited by several factors. Challenges include biometry limitations and a high incidence of zonulopathy.

Retinoblastoma genetics screening and clinical management.

BACKGROUND: India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. METHODS: Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. RESULTS: Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. CONCLUSIONS: We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

A survey of visual impairment and blindness in children attending eight schools for the blind in Myanmar: An update.

Purpose: To determine the causes of visual impairment (VI) and blindness among children in schools for the blind in Myanmar; to identify the avoidable causes of VI and blindness; to provide spectacles, low-vision aids, and ophthalmic treatment where indicated; to provide an update of the 2007 survey performed and identify any major epidemiological changes. Methods: Two hundred and ninety children under 16 years of age from all eight schools for the blind in Myanmar were examined and the data entered into the World Health Organization Prevention of Blindness Examination Record for Childhood Blindness. Results: In total, 271 children (93.4%) were blind (visual acuity [VA] <3/60 in the better eye) and 15 (5.17%) had severe visual impairment (SVI = VA <6/60 to 3/60 in the better eye). Most children had whole globe as the major anatomical site of SVI or blindness (105, 36.6%). The cause was unknown in the majority of these (155, 54.0%). One hundred and twelve children had avoidable causes of blindness and SVI (39.0%). Forty children (13.9%) required an optical device and 10.1% required surgical or medical attention, with a potential for visual improvement through intervention in 3.48%. Conclusion: In all, 39.0% of children had potentially avoidable causes of SVI and blindness with cataracts and measles being the commonest causes. This follow-up survey performed after the first one completed in Myanmar in 2007 demonstrates a change in the major site of abnormality from the cornea to whole globe and a reduction in avoidable blindness but highlights the ongoing burden of measles.

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

PURPOSE: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. METHODS: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). CONCLUSIONS: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.