Differences in Childhood Growth Parameters Between Patients With Somatic and Heritable Retinoblastoma.

Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb. Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005. Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile. Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study.

BACKGROUND/OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.

Risk factors associated with abandonment of care in retinoblastoma: analysis of 692 patients from 10 countries.

BACKGROUND: Rates of care abandonment for retinoblastoma (RB) demonstrate significant geographical variation; however, other variables that place a patient at risk of abandoning care remain unclear. This study aims to identify the risk factors for care abandonment across a multinational set of patients. METHODS: A prospective, observational study of 692 patients from 11 RB centres in 10 countries was conducted from 1 January 2019 to 31 December 2019. Multivariate logistic regression was used to identify risk factors associated with higher rates of care abandonment. RESULTS: Logistic regression showed a higher risk of abandoning care based on country (high-risk countries include Bangladesh (OR=18.1), Pakistan (OR=45.5) and Peru (OR=9.23), p<0.001), female sex (OR=2.39, p=0.013) and advanced clinical stage (OR=4.22, p<0.001). Enucleation as primary treatment was not associated with a higher risk of care abandonment (OR=0.59, p=0.206). CONCLUSION: Country, advanced disease and female sex were all associated with higher rates of abandonment. In this analysis, enucleation as the primary treatment was not associated with abandonment. Further research investigating cultural barriers can enable the building of targeted retention strategies unique to each country.

A Multidisciplinary Thyroid Eye Clinic: A One-stop Shop.

BACKGROUND: Little is known about the success of multidisciplinary thyroid eye disease (TED) clinic. OBJECTIVES: To present the characteristics, treatments, and outcomes of patients treated in a multidisciplinary TED clinic. METHODS: A medical record review of all patients who attended a TED clinic was performed. Data included demographics, medical history, laboratory tests, visual function tests, ocular examinations, clinical activity score (CAS), and assessment of quality-of-life (QOL). RESULTS: Clinic visits included 132 patients seen during 385 appointments at a TED clinic (mean 12 appointments per patient). Management of TED included medical treatments for 48 patients (36.3%) and surgical treatment for 56 (42.4%). There was a positive significant correlation between the CAS and thyroid-stimulating immunoglobulin (TSI) activity at the first visit and at the last follow-up visit (P < 0.01 and P < 0.02, respectively). However, no correlation was found between the CAS and the thyroid-stimulating hormone levels or between the free triiodothyronine (fT3) and fT4 levels at the first or last visit. There was a significant negative correlation between the CAS and color vision (-0.347, P < 0.01, Pearson correlation) at the first visit, but not between the CAS and visual acuity and visual field at either the first or last visit. Changes in the QOL and the CAS scores were significantly negatively correlated (-0.240, P < 0.01). CONCLUSIONS: Treatment and management decisions for TED should be based on multiple parameters including clinical examinations by ophthalmologists and endocrinologists, laboratory tests, and CAS and QOL scores.

The Effects of Breastfeeding on Retinoblastoma Development: Results from an International Multicenter Retinoblastoma Survey.

The protective effects of breastfeeding on various childhood malignancies have been established but an association has not yet been determined for retinoblastoma (RB). We aimed to further investigate the role of breastfeeding in the severity of nonhereditary RB development, assessing relationship to (1) age at diagnosis, (2) ocular prognosis, measured by International Intraocular RB Classification (IIRC) or Intraocular Classification of RB (ICRB) group and success of eye salvage, and (3) extraocular involvement. Analyses were performed on a global dataset subgroup of 344 RB patients whose legal guardian(s) consented to answer a neonatal questionnaire. Patients with undetermined or mixed feeding history, family history of RB, or sporadic bilateral RB were excluded. There was no statistically significant difference between breastfed and formula-fed groups in (1) age at diagnosis (p = 0.20), (2) ocular prognosis measures of IIRC/ICRB group (p = 0.62) and success of eye salvage (p = 0.16), or (3) extraocular involvement shown by International Retinoblastoma Staging System (IRSS) at presentation (p = 0.74), lymph node involvement (p = 0.20), and distant metastases (p = 0.37). This study suggests that breastfeeding neither impacts the sporadic development nor is associated with a decrease in the severity of nonhereditary RB as measured by age at diagnosis, stage of disease, ocular prognosis, and extraocular spread. A further exploration into the impact of diet on children who develop RB is warranted.

COVID-19's Influence on Ocular Emergency Visits at a Tertiary Referral Center and Its Relationship to Emergency Indications by the American Academy of Ophthalmology.

PURPOSE: To examine the trends of ocular emergency admissions during the COVID-19 pandemic at a tertiary care center. METHODS: The study's sample consisted of all patients who were seen in the ophthalmic emergency room (OER) between March 15 and April 15, 2020 (during the COVID-19 pandemic) and in the same time frame of the previous year. The cases were categorized as urgent vs. nonurgent according to the AAO urgency guidelines during the coronavirus period, and the ability to treat the case with telemedicine was evaluated retrospectively. RESULTS: A total of 553 patients were admitted to the OER during the pandemic period, whereas in the same time frame of the previous year, 1,069 were admitted. The female/male proportion was 526/543 (49.2%/50.8%) in 2019 and 258/259 (46.7%/53.3%) the following year. Age (years, average ± SD) was 44.7 ± 24.5 in 2019 and 47.9 ± 23.4 in 2020. There were more self-referrals in 2020 compared to 2019 (41.1% vs. 32.6%; p=0.0004). The time spent in the OER was reduced from 109 ± 74 (minutes, average ± SDV) in 2019 to 73 ± 51 in 2020 (p < 0.0001). The most common cause of OER examinations in 2020 was related to the posterior segment of the eye (23.9%), whereas infection and inflammation of the anterior segment were the most common causes in 2019 (35.5%). Urgency by AAO standards was in agreement in 26.7% admissions in 2019 and 35.6% in 2020 (p=0.0002). CONCLUSION: The COVID-19 pandemic has influenced several aspects of the OER, including the number of referrals, type of ophthalmic emergency, the time spent in the OER, and the need for emergent treatment. Our change in the treatment algorithm was in agreement with the AAO recommendations during the pandemic.

Lag Time between Onset of First Symptom and Treatment of Retinoblastoma: An International Collaborative Study of 692 Patients from 10 Countries.

BACKGROUND: The relationship between lag time and outcomes in retinoblastoma (RB) is unclear. In this study, we aimed to study the effect of lag time between onset of symptoms and diagnosis of retinoblastoma (RB) in countries based on their national-income and analyse its effect on the outcomes. METHODS: We performed a prospective study of 692 patients from 11 RB centres in 10 countries from 1 January 2019 to 31 December 2019. RESULTS: The following factors were significantly different among different countries based on national-income level: age at diagnosis of RB (p = 0.001), distance from home to nearest primary healthcare centre (p = 0.03) and mean lag time between detection of first symptom to visit to RB treatment centre (p = 0.0007). After adjusting for country income, increased lag time between onset of symptoms and diagnosis of RB was associated with higher chances of an advanced tumour at presentation (p < 0.001), higher chances of high-risk histopathology features (p = 0.003), regional lymph node metastasis (p < 0.001), systemic metastasis (p < 0.001) and death (p < 0.001). CONCLUSIONS: There is a significant difference in the lag time between onset of signs and symptoms and referral to an RB treatment centre among countries based on national income resulting in significant differences in the presenting features and clinical outcomes.

A novel EyePhone© App for improving adherence to glaucoma therapy.

PURPOSE: Despite advances in glaucoma treatment options, patient adherence and compliance remain very low. The EyePhone© App is a free non-commercial reminder application designed specifically for the needs of glaucoma patients. In this study, we evaluated its usefulness in improving adherence to medical treatment among glaucoma patients. METHODS: This is a prospective multicenter interventional study. Glaucoma patients were recruited from a tertiary center and a large community glaucoma service center. After a short explanation, the EyePhone© App was installed on their smartphone device, and the notifications for the current medical treatment were entered. After enrollment and at 1-month follow-up, subjects completed the Morisky Medication Adherence Scale (MMAS-8) and the Quality of Life and Glaucoma 17-item (GlauQOL-17) questionnaires for evaluation of adherence and QOL, respectively. RESULTS: In the study, 133 patients (71 men and 62 women) aged 62±15.5 years and using 2.0±0.9 IOP-lowering drugs participated. The proportion of highly adherent subjects improved from 29.3% (39/133) at baseline to 42.1% (56/133) at follow-up (P < 0.001), and the proportion of poorly adherent subjects decreased from 29.3 (39/133) to 20.3% (27/133) at follow-up (P = 0.012). QOL also improved, as evidenced by a significant increase in the GlauQOL-17 score (P < 0.05). In a subgroup of patients for whom IOP measurements were available, IOP reduced by 0.92 mmHg (P = 0.069). CONCLUSIONS: Significant improvements in glaucoma adherence and QOL were achieved among poorly adherent glaucoma patients after 1 month of using the EyePhone© App.

Quality of life of patients with thyroid eye disease: 3-year follow-up in a multidisciplinary clinic in Israel.

BACKGROUND: Changes in the quality of life (QOL) of patients with thyroid eye disease (TED) were examined during a 3-year follow-up in a multidisciplinary eye clinic, and factors that may improve QOL were identified. METHODS: A retrospective review of medical records of all patients who attended the TED clinic at Sheba Medical Center, Israel, from May 2016 to May 2019 was performed. The retrieved data included demographics, comprehensive ophthalmic examination findings, clinical activity scores (CAS), laboratory test results, and QOL assessments by the Graves' Orbitopathy QOL (GO-QOL) questionnaire. RESULTS: One hundred thirty-two TED clinic patients were examined. Thirty patients (22.72%) received medical treatment consisting of steroids according to the European Group on Graves' Orbitopathy (EUGOGO) protocol, high-dose steroids, or immunosuppressive drugs. Twenty-eight patients (21.21%) underwent surgical rehabilitation (decompression, strabismus, or eyelid surgery). There was a significant increase in total QOL score after steroid treatment according to the EUGOGO protocol, after decompression surgery, and after strabismus surgery compared to pre-treatment total QOL (p=0.04, p=0.021, and p=0.042, respectively, matched pairs). In addition, there were significant positive correlations between the changes in the total QOL score and the change in thyroid-stimulating immunoglobulin (TSI) as well as the change in CAS among the patients who underwent medical and surgical interventions. CONCLUSIONS: QOL improved significantly after medical/surgical treatments. A change in the CAS and in the TSI may also correlate with change in QOL. Periodic evaluation of TED patients' QOL is recommended for enhanced and more comprehensive management.

Ocular injuries incurred by Israeli defense forces during low-intensity conflicts.

BACKGROUND: To describe ocular injuries sustained by Israeli Defense Forces (IDF) soldiers during low-intensity conflicts from 1998 to 2017, and to evaluate the use of protective eyewear. METHODS: Retrospective analysis of data retrieved from two tertiary Israeli medical centers and the military trauma registry. The analysis included all IDF soldiers with ocular injuries who were referred to these centers between 1998 and 2017. Data on injury type, the use of protective eyewear, and interventions were retrieved and analyzed. Additional data regarding the use of protective eyewear and ocular injuries in 108 patients with head and neck injuries in one operation was analyzed. RESULTS: A total of 126 soldiers, all males, mean age 22 (SD 5.3) years, sustained ocular injuries during low-intensity conflicts and treated at one of the two participating medical centers. Blast was the most common type of injury (n = 70/126, 56%), followed by shrapnel (n = 37/126, 29%) and gunshot wound (n = 12/126, 9%). The Birmingham Eye Trauma Terminology System (BETTS) injury pattern disclosed lamellar laceration (n = 34/126, 27%), intraocular foreign body (n = 27/126, 21%), penetrating (n = 10/126, 8%), and perforating (n = 7/126, 6%) injuries. Average VA improved from 20/140 at presentation to 20/60 after surgical or conservative intervention, the median VA improved from 20/40 to 20/30 (P < 0.001). Forty-nine patients (49/126, 39%) had poor visual outcome. The mean follow-up lasted 22 (SD 31) months. The use of protective eyewear was correlated with better initial VA(20/30 vs 20/217, P = 0.07). Among 108 patients with head and neck injuries, there was a higher rate of ocular injuries in the group of patients who did not use protective eyewear (n = 26/73, 36% vs n = 4/35, 11%, P = 0.016). CONCLUSIONS: Ocular injuries are common occurrences in low-intensity conflicts. The use of protective eyewear significantly reduces these injuries and should be mandatory. LEVEL OF EVIDENCE: III, prognostic.

Gender differences in clinical presentation and prognosis of thyroid eye disease.

OBJECTIVE: To examine the clinical differences in manifestation, treatment, and prognosis of thyroid-eye-disease (TED) between men and women. METHODS: This is a longitudinal cohort study. Men and women, who diagnosed with TED and treated at a multidisciplinary TED clinic, were compared regarding differences in demographics, eye examination, disease activity, and quality of life evaluation. RESULTS: TED was diagnosed in 132 patients during the study period, and they included 38 men (28.78%) and 94 women (71.21%). There were six men and 20 women with active disease (Clinical-Activity-Score (CAS) ⩾ 3) during the entire follow-up period (p < 0.01). The mean time from TED diagnosis to CAS ⩾ 3 was 4.50 years for men and 2.35 years for women (p = 0.05). There were no significant differences in mean total Graves' Orbitopathy-Quality-of-Life questionnaire (GO-QOL) score. However, mean GO-QOL subtotal score of external appearance of women was significantly lower compare to men in the first and last visit (p = 0.04, 0.03, respectively). CONCLUSION: Active disease was more common in women and the time-from-diagnosis of TED to CAS ⩾ 3 was shorter among women. Moreover, the appearance QOL score of women was poorer. These findings should be taken into consideration when planning the timing of treatment and when choosing the best treatment for TED patients.