Apparent Diffusion Coefficient (ADC) Differentiates Retinoblastoma from Coats Disease on MRI.

PURPOSE: Coats' disease can be difficult to differentiate from retinoblastoma. While MR imaging of retinoblastoma and Coats' disease have been examined for differentiating features such as eye size, vitreous seeding, and shape of retinal detachment, there is a lack of data on apparent diffusion coefficient (ADC). ADC is a measure of the diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI. DESIGN: Retrospective cross-sectional study. METHODS: Patient or study population: Children < 18 diagnosed with Coats disease or Retinoblastoma between January 1, 2018 and January 8, 2022 who had MRI imaging that was reviewable. MAIN OUTCOME MEASURE: Apparent diffusion coefficient (ADC) of the intraocular lesion. Retrospective brain MRIs were obtained from records of 5 eyes of 5 Coats' patients and 29 eyes of 23 patients with retinoblastoma. All MRIs were obtained prior to treatment. The eyedropper tool in Epic's default viewer (Ambra DICOM) was used to measure the ADC of five to eight randomly sampled points within the eye lesions seen on MRI. Average ADC was calculated for each affected eye. Internal reliability was confirmed by re-measuring mean ADC for a random sample of patients masked to their diagnosis and prior measurements. T-test was used to determine if ADC values differ between groups. RESULTS: The mean ADC for retinoblastoma patients (442 +/- 210 mm2/s) differed significantly from the mean for Coats' patients (1364 +/- 309 mm2/s), (P < .001). T-test between baseline and repeat measurements was not significantly different. Since ADC values can differ between different scanners and DW MRI pulse sequences, an ADC threshold may be difficult to generalize across institutes, in our data set a threshold of 900 mm2/s was useful in separating the two diagnoses with a high degree of accuracy. CONCLUSIONS: Clinical features of retinoblastoma and Coats' disease often resemble each other and can lead to misdiagnosis. Since ADCs are derived from diffusion-weighted MRI as an objective parameter, it has the potential to aid in establishing or confirming the diagnosis when retinoblastoma and/or Coats' disease are suspected.

Laser interstitial thermal therapy followed by consolidation stereotactic radiosurgery (LITT-cSRS) in patients with newly diagnosed brain metastasis.

INTRODUCTION: The efficacy and safety of laser interstitial thermal therapy followed by consolidation radiosurgery (LITT-cSRS) was previously studied in brain metastasis that recurs locally after initial radiosurgery (BMRS). Here, we characterize the clinical outcome of LITT-cSRS in patients with newly diagnosed brain metastasis. METHODS: Between 2017 and 2023, ten consecutive cancer patients with newly diagnosed brain mass of unclear etiology who underwent stereotactic needle biopsy (SNB) and LITT in the same setting followed by consolidation SRS (cSRS) with > 6 months follow-up were identified retrospectively. Clinical and imaging outcomes were collected. RESULTS: The histology of the BM were: breast cancer (n = 3), melanoma (n = 3), non-cell cell lung cancer (n = 3), colon (n = 1). There were no wound or procedural complications. All patients were discharged home, with a median one-day hospital stay (range: 1-2 days). All patients were off corticosteroid therapy by the one-month follow-up. cSRS were carried out 12-27 days (median of 19 days) after SNB + LITT. There were no subsequent emergency room presentation, 30-day or 90-day re-admission. The Karnofsky Performance Score (KPS) remains stable or improved at the 3 months-follow-up. With a median follow-up of 416 days (13.8 mo; range: 199-1,096 days), there was one local recurrence at 384 days (12.8 mo) post-LITT-cSRS. With exception of this patient with local recurrence, all patients showed decreased FLAIR volume surrounding the LITT-cSRS treated BMRS by the six-month follow-up. CONCLUSIONS: To our awareness, this case series represent the first to describe LITT-cSRS in the setting of newly diagnosed BM. The results presented here provide pilot data to support the safety and efficacy of LITT-cSRS and lay the foundation for future studies.

Dosimetric evaluation and treatment planning considerations for GammaTile permanent brain implants - a pilot, institutional experience.

PURPOSE: GammaTile® (GT) is a brachytherapy platform that received Federal Drug Administration (FDA) approval as brain tumor therapy in late 2018. Here, we reviewed our institutional experience with GT as treatment for recurrent glioblastomas and characterized dosimetric parameter and associated clinical outcome. METHODS AND MATERIALS: A total of 20 consecutive patients with 21 (n = 21) diagnosis of recurrent glioblastoma underwent resection followed by intraoperative GT implant between 01/2019 and 12/2020. Data on gross tumor volume (GTV), number of GT units implanted, dose coverage for the high-risk clinical target volume (HR-CTV), measured by D90 or dose received by 90% of the HR-CTV, dose to organs at risk, and six months local control were collected. RESULTS: The median D90 to HR-CTV was 56.0 Gy (31.7-98.7 Gy). The brainstem, optic chiasm, ipsilateral optic nerve, and ipsilateral hippocampus median Dmax were 11.2, 5.4, 6.4, and 10.0 Gy, respectively. None of the patients in this study cohort suffered from radiation necrosis or adverse events attributable to the GT. Correlation was found between pre-op GTV, the volume of the resection cavity, and the number of GT units implanted. Of the resection cavities, 7/21 (33%) of the cavity experienced shrinkage, 3/21 (14%) remained stable, and 11/21 (52%) of the cavities expanded on the 3-months post-resection/GT implant MRIs. D90 to HR-CTV was found to be associated with local recurrence at 6-month post GT implant, suggesting a dose response relationship (p = 0.026). The median local recurrence-free survival was 366.5 days (64-1,098 days), and a trend towards improved local recurrence-free survival was seen in patients with D90 to HR-CTV ≥ 56 Gy (p = 0.048). CONCLUSIONS: Our pilot, institutional experience provides clinical outcome, dosimetric considerations, and offer technical guidance in the clinical implementation of GT brachytherapy.

A national audit of facilities, human and material resources for the comprehensive management of diabetes in Ghana-A 2023 update.

INTRODUCTION: The human and material resources as well as the systems for managing diabetes in Africa are inadequate. This study or needs assessment, aimed at updating the human and material resources, identifying the gaps and unmet needs for comprehensive diabetes care in Ghana. METHODS: We conducted a national audit of 122 facilities in all 16 administrative regions of Ghana. Information obtained covered areas on personnel and multidisciplinary teams, access to medications, access to laboratory services, financing, screening services, management of diabetes complications, and availability/use of diabetes guidelines or protocols. Data was analysed using STATA version 16.1. P-values <0.05 were set as significant. RESULTS: Only 85(69.7%) out of the 122 surveyed facilities had a dedicated centre or service for diabetes care. Twenty-eight (23%) had trained diabetes doctors/specialists; and whilst most centres had ophthalmic nurses and dieticians, majority of them did not have trained diabetes educators (nurses), psychologists, ophthalmologists, podiatrists, and foot/vascular surgeons. Also, 13.9% had monofilaments, none could perform urine dipstick for microalbumin; 5 (4.1%) and just over 50% could perform laboratory microalbumin estimation and glycated haemoglobin, respectively. Access to and supply of human insulins was better than analogue insulin in most centres. Nearly 100% of the institutions surveyed had access to metformin and sulphonylurea with good to excellent supply in most cases, whilst access to Sodium Glucose Transporter-2 inhibitors and Glucagon-like peptide-1 analogues were low, and moderate for Dipeptidyl peptidase-4 inhibitors and thiazolidinediones. Majority of the health facilities (95.1%) offered NHIS as payment mechanism for clients, whilst 68.0% and 30.3% of the patients paid for services using out-of-pocket and private insurance respectively. Fifteen facilities (12.3%) had Diabetes Support Groups in their locality and catchment areas. CONCLUSION: An urgent multisectoral collaboration, including prioritisation of resources at the facility level, to promote and achieve acceptable comprehensive diabetes care is required.

Retinopathy of prematurity screening: prevalence and risk factors of ophthalmic complications in non-treated preterm infants.

INTRODUCTION: Retinopathy of prematurity (ROP) is a vision-threatening disease of premature infants. Practice guidelines recommend that all infants screened for ROP receive follow-up eye examinations to screen for ophthalmic complications.1 The purpose of this study was to identify risk factors for the development of strabismus, amblyopia, high refractive error, and cataracts among ROP-screened, non-treated infants. METHODS: Retrospective single-centre study of ROP-screened, non-treated premature infants with ophthalmic follow-up. Clinical variables were screened for association with ocular findings at follow-up. Multivariable logistic regression was used to determine the risk factors associated with ocular findings. RESULTS: 309 patients were seen for follow-up at 0.97 (0.69) [mean (SD)] years after neonatal intensive care unit (NICU) discharge. Strabismus was predicted by occipitofrontal circumference (OFC) z-score at NICU discharge (OR 0.61; 95% CI [0.42, 0.88]; p = 0.008), intraventricular haemorrhage (IVH) grade III or IV (OR 3.18; 95% CI [1.18, 8.54]; p = 0.02), and exclusive formula feeding at NICU discharge (OR 2.20; 95% CI [1.07, 4.53]; p = 0.03). Significant predictors of amblyopia were OFC z-score at discharge (OR 0.55; 95% CI [0.31, 0.96]; p = 0.03) and necrotising enterocolitis (NEC) (OR 6.94; 95% CI [1.38, 35.00]; p = 0.02). NEC was a significant risk factor for high refractive error (OR 7.27; 95% CI [1.39, 37.94]; p = 0.02). CONCLUSIONS: Among premature infants screened but not treated for ROP, severe IVH, NEC, low OFC z-score, and exclusive formula feeding at NICU discharge were risk factors for ocular morbidity. These findings affirm the value of ophthalmic follow-up for all ROP-screened infants, particularly those with the identified risk factors.

GammaTile® (GT) as a brachytherapy platform for rapidly proliferating glioblastomas: from case series to clinical trials.

PURPOSE: Radiation plays a central role in glioblastoma treatment. Logistics related to coordinating clinic visits, radiation planning, and surgical recovery necessitate delay in radiation delivery from the time of diagnosis. Unimpeded tumor growth occurs during this period, and is associated with poor clinical outcome. Here we provide a pilot experience of GammaTile ® (GT), a collagen tile-embedded Cesium-131 (131Cs) brachytherapy platform for such aggressive tumors. METHODS: We prospectively followed seven consecutive patients (2019-2023) with newly diagnosed (n = 3) or recurrent (n = 4) isocitrate dehydrogenase wild-type glioblastoma that grew > 100% in volume during the 30 days between the time of initial diagnosis/surgery and the radiation planning MRI. These patients underwent re-resection followed by GT placement. RESULTS: There were no surgical complications. One patient developed right hemiparesis prior to re-resection/GT placement and was discharged to rehabilitation, all others were discharged home-with a median hospital stay of 2 days (range: 1-5 days). There was no 30-day mortality and one 30-day readmission (hydrocephalus, requiring ventriculoperitoneal shunting (14%)). With a median follow-up of 347 days (11.6 months), median progression free survival of ≥ 320 days (10.6 months) was achieved for both newly and recurrent glioblastoma patients. The median overall survival (mOS) was 304 and 347 days (10 and 11.5 mo) for recurrent and newly diagnosed glioblastoma patients, respectively. CONCLUSION: Our pilot experience suggests that GT offers favorable local control and safety profile for patients afflicted with rapidly proliferating glioblastomas and lay the foundation for future clinical trial design.

Case report: ocular manifestations of a gain-of-function mutation in CLCN6, a newly diagnosed disease.

BACKGROUND: In 2020, a new disease was reported by Polovitskaya et al., caused by a monoallelic, gain-of-function mutation in CLCN6, encoding the ClC-6 Cl-/H±exchanger. METHODS: Here, we report the ophthalmic findings of one of the first three patients with this disease (the proband) and review the findings in the other two patients in the literature. RESULTS: The CLCN6 gene is part of the voltage-dependent chloride channel protein family. It functions as either a chloride channel aiding in cell-volume regulation and acidification of intracellular organelles or as an antiporter, which are membrane proteins involved in the transport of molecules across a phospholipid membrane. This particular gene is found in late endosomes. Ion transport across endosome membranes is essential for endosomal function. The proband carried a de novo c.1658A>G (p.Tyr553Cys) mutation in CLCN6. The patient reported herein has a notable optic nerve appearance. The nerve initially appeared elevated. Over time, the optic nerve elevation appearance decreased, associated with progressive vision loss with a visual acuity of 20/470 at last follow-up. CONCLUSION: While Clcn6-/- mice have been found to have a mild neuronal lysosomal storage phenotype, the three reported children with a de novo c.1658A>G (p.Tyr553Cys) variant displayed significant developmental delay and neurodegeneration.

S-adenosylmethionine and nicotinamide riboside therapy in Arts syndrome: A case report and literature review.

Phospho-ribosyl-pyrophosphate synthetase 1 (PRPS1) deficiency is secondary to loss of function variants in PRPS1. This enzyme generates phospho-ribosyl-pyrophosphate (PRPP), which is utilized in the synthesis of purines, nicotinamide adenine dinucleotide (NAD), and NAD phosphate (NADP), among other metabolic pathways. Arts syndrome, or severe PRPS1 deficiency, is an X-linked condition characterized by congenital sensorineural hearing loss, optic atrophy, developmental delays, ataxia, hypotonia, and recurrent infections that can cause progressive clinical decline, often resulting in death before 5 years of age. Supplementation of the purine and NAD pathways outside of PRPP-dependent reactions is a logical approach and has been reported in a handful of patients, two with S-adenosylmethionine (SAMe) and one with SAMe and nicotinamide riboside (NR). We present the clinical course of a fourth Arts syndrome patient who was started on therapy and review previously reported patients. All patients had stability or improvement of symptoms, suggesting that SAMe and NR can be a treatment option in Arts syndrome, though further studies are warranted.

Comparison of peripheral leukocyte parameters in patients receiving conventionally and hypofractionated radiotherapy schemes for the treatment of newly diagnosed glioblastoma.

Introduction: Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown. Methods: To determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment. Results: This study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy. Discussion: Understanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.

The effect of governance structures on optimal control of two-patch epidemic models.

Infectious diseases continue to pose a significant threat to the health of humans globally. While the spread of pathogens transcends geographical boundaries, the management of infectious diseases typically occurs within distinct spatial units, determined by geopolitical boundaries. The allocation of management resources within and across regions (the "governance structure") can affect epidemiological outcomes considerably, and policy-makers are often confronted with a choice between applying control measures uniformly or differentially across regions. Here, we investigate the extent to which uniform and non-uniform governance structures affect the costs of an infectious disease outbreak in two-patch systems using an optimal control framework. A uniform policy implements control measures with the same time varying rate functions across both patches, while these measures are allowed to differ between the patches in a non-uniform policy. We compare results from two systems of differential equations representing transmission of cholera and Ebola, respectively, to understand the interplay between transmission mode, governance structure and the optimal control of outbreaks. In our case studies, the governance structure has a meaningful impact on the allocation of resources and burden of cases, although the difference in total costs is minimal. Understanding how governance structure affects both the optimal control functions and epidemiological outcomes is crucial for the effective management of infectious diseases going forward.

Chiasmal Compression by the Third Ventricle in Obstructive Hydrocephalus: Case Report and Review of the Literature.

The authors review the phenomenon of third ventricular dilation causing chiasmal compression and vision loss, emphasize the need for further study given continued poor outcomes, and, in a patient case, illustrate the value of obtaining magnetic resonance imaging and nerve and macular optical coherence tomography in a patient with an unclear mechanism of vision loss. [J Pediatr Ophthalmol Strabismus. 2023;60(5):e49-e54.].

Birth prevalence and characteristics of congenital corneal opacities.

PURPOSE/AIM: To report the birth prevalence and natural history of congenital corneal opacities among a population-based cohort of children. MATERIALS AND METHODS: The medical records of patients <5 years diagnosed with a congenital onset corneal opacity while residing in Olmsted County, Minnesota, from January 1, 1977, through December 31, 2016, were retrospectively reviewed. RESULTS: Fourteen patients were diagnosed with a congenital corneal opacity during the 40-year study period for a birth prevalence of 1 in 5188 live births. The mean age at diagnosis was 7.5 months (range 0-48 months) and 9 (64.3%) were males. Four patients had congenital glaucoma, 4 had limbal dermoids, 2 had sclerocornea, and 1 patient each had Descemet's tear from birth trauma, herpes simplex virus type 1 keratitis, corneal leukoma, and an undiagnosed scar. Six (42.8%) patients required treatment for their underlying corneal opacity including the four patients with congenital glaucoma. The other 8 (57.1%) patients had a clear central axis. Four (28.6%) of 14 patients required amblyopia therapy, and 4 (28.6%) developed strabismus. Four (28.6%) patients had associated systemic conditions. During a mean follow up of 5.4 years (range 1.3-27.0 years), the median best corrected visual acuity (BCVA) was logmar 0.16 (20/25) (range 20/20-hand motion) with one patient with unilateral BCVA less than 20/60 and one patient with bilateral BCVA less than 20/60. CONCLUSIONS: In this 40-year cohort, congenital corneal opacities were relatively rare and the result of a variety of disorders. Although amblyopia and strabismus occurred commonly, most patients had good visual outcomes.

A Comprehensive Report of Intrinsically Disordered Regions in Inherited Retinal Diseases.

BACKGROUND/PURPOSE: A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated. METHODS: IRD genes from RetNet were included in this study. Publicly available data on the genome aggregation database (gnomAD) were used to analyze the number of total and pathogenic missense variants. Metapredict, an accurate and high-performance predictor that reproduces consensus disorder scores, was used to calculate disorder. MAIN OUTCOME MEASURES: The main outcome measures were percent disorder, percent pathogenicity, number of total missense variants, and percent total missense variation. RESULTS: We included 287 RetNet genes with relevant data available from gnomAD. Mean percent disorder was 26.3% ± 26.0%, mean percent pathogenicity was 5.2% ± 11.0%, mean number of total missense variants was 424.4 ± 450.0, and mean percent total missense was 50.0% ± 13.4%. The percent disorder followed a bimodal distribution with the highest number of occurrences in the 0 to 10th disorder decile. The five outlier proteins in the first disorder decile with a higher-than-expected number of total missense variation were identified (HMCN1, ADGRV, USH2A, DYNC2H1, LAMA1, and SLC38A8). When excluded, % total missense was significantly associated with percent disorder (R = 0.238 and p = 0.0240). CONCLUSIONS: This novel study examining all genes implicated in IRDs found that the majority genes had a disorder in the 0 to 10th decile and were relatively intolerant to missense variation. This may have future utility when interpreting variants of undetermined significance and missense variants.

Clinical characteristics and severity of diabetic ketoacidosis: A cross-sectional study from a tertiary hospital in Ghana.

OBJECTIVES: Diabetic ketoacidosis (DKA) is a common, severe and often fatal complication of diabetes. This study aimed to investigate the clinical characteristics and precipitants of DKA, as well as factors associated with DKA severity in Ghanaian patients. METHODS: Cross-sectional study of the medical records of all 70 adult patients >18 years managed for DKA in the adult emergency room of Korle-Bu Teaching Hospital in Ghana from March 2019 to July 2019. DKA diagnosis was based on hyperglycaemia >11.0 mmol/L, ketonuria (more than 2+) plus acidaemia of (pH < 7.3) or bicarbonate (HCO3 - ) <15.0 mmol/L. However, when serum bicarbonate and pH were not available, clinical signs of acidosis, for example, Kussmaul breathing aided in the diagnosis. DKA severity was assessed based on the Joint British Diabetes Societies (JBDS) guidelines of factors suggestive of severe DKA. Multivariable logistic regression was used to determine the factors associated with DKA severity. Odds ratio and 95% confidence interval for factors associated with DKA severity were determined. RESULTS: The mean (±standard deviation) age, diabetes duration and blood sugar at admission were 44.06 (±16.23) years, 7.19 (±6.04) years and 26.37 (±6.70) mmol/L, respectively. Females comprised 51.4% of the study population. The most common presenting symptoms were generalised weakness (30.0%) and fever (14.3%). The major precipitants were infection (70.0%) and non-compliance (22.9%). Overall, 71.4% of participants had features suggestive of severe DKA. In a multivariable regression model, Type 2 diabetes was associated with over fourfold decreased odds of severe DKA (OR 0.23, 95% CI [0.07-0.76], p = 0.016). Patient education on prevention of DKA was documented for only 18.6% of patients before being discharged. CONCLUSION: In this study, more than 70% of the study participants had features suggestive of severe DKA, with infection being the most common precipitant of DKA. 51.4% of patients had Type 2 diabetes which was associated with a statistically lower risk of severe DKA. Female sex tended to be positively associated with DKA severity. In a setting where the venous/arterial pH and bicarbonate levels may be inaccessible and/or unaffordable, using clinical features as found in the JBDS guidelines may help categorise patients and escalate care when needed. Indeed it may be useful to validate the use of the JBDS criteria for use in such settings.

Characterization of vision in pediatric retinoblastoma survivors beyond visual acuity.

BACKGROUND: Retinoblastoma (RB) and its associated treatments can significantly impact visual acuity. However, little is known regarding other measures of vision, such as contrast sensitivity or saccades. The aim of this study was to describe contrast sensitivity and saccades in children treated for retinoblastoma. METHODS: This cross-sectional study included children aged 5-17 years who had completed treatment for RB. Visual acuity, saccades via fixation analysis, and contrast sensitivity by Cardiff contrast sensitivity were assessed, and multivariable linear regression was performed. RESULTS: Eleven children were enrolled (mean age, 10.7 ± 3.9 years). Treatment included enucleation (8 children [73%]) and chemotherapy (10 [91%]). Of the 11, one participant was unable to complete testing of saccades, and another was unable to complete contrast sensitivity testing. Decreased saccade parameters (velocity, latency, or accuracy) and impaired contrast sensitivity were observed in all 10 participants who underwent visual testing. Multivariable analysis revealed that worse logMAR visual acuity (B, -4.54 [-6.8, -2.2]; P = 0.004) and bilateral disease (B, -3.9 [-6.4, -1.4]; P = 0.009) were associated with worse contrast sensitivity. Germline disease was associated with decreased vertical saccade accuracy (P = 0.02). CONCLUSIONS: Decreased contrast sensitivity and impaired saccades were universally observed in this cohort of RB survivors. Comprehensive visual evaluation should be considered for all RB survivors to provide optimal rehabilitative services for these patients.

GammaTile® (GT) as a brachytherapy platform for rapidly growing brain metastasis.

Background: A subset of brain metastasis (BM) shows rapid recurrence post-initial resection or aggressive tumor growth between interval scans. Here we provide a pilot experience in the treatment of these BM with GammaTile® (GT), a collagen tile-embedded Cesium 131 (131Cs) brachytherapy platform. Methods: We identified ten consecutive patients (2019-2023) with BM that showed either (1) symptomatic recurrence while awaiting post-resection radiosurgery or (2) enlarged by >25% of tumor volume on serial imaging and underwent surgical resection followed by GT placement. Procedural complication, 30-day readmission, local control, and overall survival were assessed. Results: For this cohort of ten BM patients, 3 patients suffered tumor progression while awaiting radiosurgery and 7 showed >25% tumor growth prior to surgery and GT placement. There were no procedural complications or 30-day mortality. All patients were discharged home, with a median hospital stay of 2 days (range: 1-9 days). 4/10 patients experienced symptomatic improvement while the remaining patients showed stable neurologic conditions. With a median follow-up of 186 days (6.2 months, range: 69-452 days), no local recurrence was detected. The median overall survival (mOS) for the newly diagnosed BM was 265 days from the time of GT placement. No patients suffered from adverse radiation effects. Conclusion: Our pilot experience suggests that GT offers favorable local control and safety profile in patients suffering from brain metastases that exhibit aggressive growth patterns and support the future investigation of this treatment paradigm.

Eye-related quality of life and activities of daily living in pediatric retinoblastoma patients: A single-center, non-controlled, cross-sectional analysis.

INTRODUCTION: Childhood retinoblastoma (RB) survivors are known to experience long-term morbidity; however, eye-related quality of life (QoL), which may significantly impact activities of daily living (ADL), has not been extensively studied in this population. The purpose of this cross-sectional study was to assess QoL and ADL morbidity among school-age RB survivors. METHODS: The Pediatric Eye Questionnaire (PedEyeQ) and Roll Evaluation Activities of Life (REAL) were administered to childhood RB survivors between ages 5 and 17 followed at St. Louis Children's Hospital. Visual outcomes and demographic predictors of ADL and QoL were examined. RESULTS: Total 23 patients (mean age 9.6 years) consented for participation in this study. All children experienced at least one domain on the PedEyeQ ≤ 80%. Subjects and parents marked functional vision to be the most impacted domain with a median score of 82.5 and 83.4, respectively. Only 10.5% of participants scored above 75% on the ADL percentile rank. On multivariable analysis, decreased visual acuity (VA) was associated with worse "Child Functional" (odds ratio [OR] -59.2, p = .004) and "Parent Worry Function" (OR -66.5, p = .03) metrics. Decreased contrast sensitivity was associated with worse "Parent Impact" (OR 21.0, p = .02) and "Parent Worry Function" (OR 3.70, p = .04) metrics. Longer saccade horizontal latency was associated with a worse "Parent Worry Function" metric (OR 43.0, p = .009). On multivariable analysis, no variable was significantly associated with ADL. CONCLUSION: RB survivors have impaired QoL and ADL. Screening for such difficulties should strongly be considered for all RB patients. Additional studies may help predict morbidity based on visual metrics and demographic data.

Visual Autism.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors. It affects approximately 2.2% of children. Both genetic and environmental risk factors have been identified for ASD. Visual comorbidities are relatively common among children with ASD. Between 20 and 44% of ASD children have visually significant refractive error, on-third have strabismus, and one-fifth have amblyopia. In addition, ASD is 30 times more common in children with congenital blindness. It is unknown whether the association of ASD with visual morbidity is causal, comorbid, or contributing. Structural and functional abnormalities have been identified in MRIs of ASD children, and ASD children have been noted to have aberrant eye tracking. ASD children with visually significant refractive errors and poor spectacle compliance (present in 30% of ASD children) offer the opportunity for investigation into how improved visual acuity influences ASD behaviors. In this review, we focus on what is known of the visual system, refractive surgery, and ASD.

Comparing Gene Panels for Non-Retinal Indications: A Systematic Review.

IMPORTANCE: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD). OBJECTIVE: To describe gene panel testing options for inherited eye disease phenotypes and their differences. This review is important for making diagnostic decisions. EVIDENCE REVIEW: A licensed, certified genetic counselor (RP) used Concert Genetics and the search terms optic atrophy, corneal dystrophy, cataract, glaucoma, anterior segment dysgenesis, microphthalmia/anophthalmia, and nystagmus to identify available testing options performed by CLIA-certified commercial genetic testing laboratories. Other co-authors were surveyed with respect to genetic panels used for the indications of interest. Ophthalmic panels were then compared using Concert Genetics in addition to their own websites. FINDINGS: Panels from each clinical category were included and summarized. This comparison highlighted the differences and similarities between panels so that clinicians can make informed decisions. CONCLUSIONS: Access to genetic testing is increasing. The diagnostic yield of genetic testing is increasing. Each panel is different, so phenotyping or characterizing clinical characteristics that may help predict a specific genotype, as well as pre-test hypotheses regarding a genotype, should shape the choice of panels.

Trachoma, the world's leading infectious cause of blindness: The remaining gap in care and access to basic handwashing facilities.

PURPOSE: Trachoma, the world's leading infectious cause of blindness, has been targeted by the WHO for elimination through the SAFE strategy: surgery, antibiotics, facial cleanliness, and environmental improvement. Although significant progress has been made, there remains a gap in care. This project studied the association of geographical distribution of the remaining need for trachoma intervention and its association with access to basic handwashing facilities at home, as an indicator of water/sanitation infrastructure. We hypothesized that poor water sanitation would correspond to areas where trachoma intervention is still required. DESIGN: Retrospective analysis using the WHO Global Health Observatory. Spatial, correlation, and simple and multivariable regression analyses were used. METHODS: Using data from the WHO Global Health Observatory, a total of 194 countries were analyzed. Two choropleth maps were created, with inset maps focused on the South Pacific region, where the top 5 countries with the greatest population proportion requiring trachoma intervention are located. RESULTS: Correlations and the simple regression model of total population with access to handwashing facilities as the only risk factor were insignificant. However, the multivariable regression models with access to handwashing facilities (total, urban, and rural) and population density as risk factors for trachoma intervention were significant. CONCLUSION: Poor water/sanitation infrastructure correlates with trachoma burden. Therefore, water/sanitation infrastructure improvement is a worthwhile target in the efforts toward trachoma elimination, but further research on the association between these important public health indicators is warranted.