Predicting the onset of myopia in children by age, sex, and ethnicity: Results from the CLEERE Study.

SIGNIFICANCE: Clinicians and researchers would benefit from being able to predict the onset of myopia for an individual child. This report provides a model for calculating the probability of myopia onset, year-by-year and cumulatively, based on results from the largest, most ethnically diverse study of myopia onset in the United States. PURPOSE: This study aimed to model the probability of the onset of myopia in previously nonmyopic school-aged children. METHODS: Children aged 6 years to less than 14 years of age at baseline participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study who were nonmyopic and less hyperopic than +3.00 D (spherical equivalent) were followed up for 1 to 7 years through eighth grade. Annual measurements included cycloplegic autorefraction, keratometry, ultrasound axial dimensions, and parental report of children's near work and time spent in outdoor and/or sports activities. The onset of myopia was defined as the first visit with at least -0.75 D of myopia in each principal meridian. The predictive model was built using discrete time survival analysis and evaluated with C statistics. RESULTS: The model of the probability of the onset of myopia included cycloplegic spherical equivalent refractive error, the horizontal/vertical component of astigmatism (J0), age, sex, and race/ethnicity. Onset of myopia was more likely with lower amounts of hyperopia and less positive/more negative values of J0. Younger Asian American females had the highest eventual probability of onset, whereas older White males had the lowest. Model performance increased with older baseline age, with C statistics ranging from 0.83 at 6 years of age to 0.92 at 13 years. CONCLUSIONS: The probability of the onset of myopia can be estimated for children in the major racial/ethnic groups within the United States on a year-by-year and cumulative basis up to age 14 years based on a simple set of refractive error and demographic variables.

Normal joint range of motion in children with Down syndrome.

Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective of this study was to establish normative joint ROM values, using a standardized measurement approach, for upper and lower joints of healthy children of both genders with DS. This study evaluated joint ROM in healthy males and females with DS who had no previous musculoskeletal pathology. Younger males have more ROM than females at the same age and both genders lose ROM with age but continue to have increased ROM in the ankles compared to children without DS. This study establishes optimal estimates of joint ROM in children with DS, and this information should be helpful to clinicians when assessment requires evaluation of joint ROM to know if evaluation falls within the normal ROM. This reference should be helpful to track joint disease progression over time or as part of a musculoskeletal screen for abnormal joint ROM in children with DS.

History matters: Thermal environment before but not during wasp attack determines the efficiency of symbiont-mediated protection.

The outcome of natural enemy attack in insects is commonly impacted by the presence of defensive microbial symbionts residing within the host. The thermal environment is a factor known to affect symbiont-mediated traits in insects. Lower temperatures, for instance, have been shown to reduce Spiroplasma-mediated protection in Drosophila. Our understanding of protective symbiosis requires a deeper understanding of environment-symbiont-protection links. Here, we dissect the effect of the thermal environment on Spiroplasma-mediated protection against Leptopilina boulardi in Drosophila melanogaster by examining the effect of temperature before, during and after wasp attack on fly survival and wasp success. We observed that the developmental temperature of the mothers of attacked larvae, but not the temperature of the attacked larvae themselves during or after wasp attack, strongly determines the protective influence of Spiroplasma. Cooler maternal environments were associated with weaker Spiroplasma protection of their progeny. The effect of developmental temperature on Spiroplasma-mediated protection is probably mediated by a reduction in Spiroplasma titre. These results indicate that historical thermal environment is a stronger determinant of protection than current environment. Furthermore, protection is a character with transgenerational nongenetic variation probably to produce complex short-term responses to selection. In addition, the cool sensitivity of the Spiroplasma-Drosophila symbioses contrasts with the more common failure of symbioses at elevated temperatures, indicating a need to understand the mechanistic basis of low temperature sensitivity on this symbiosis.

Quality of life after wearing multifocal contact lenses for myopia control for 2 weeks in the BLINK Study.

PURPOSE: To validate Pediatric Refractive Error Profile 2 (PREP2) subscales that can be used to evaluate contact lens wearers and compare vision-specific quality of life measurements between children wearing multifocal and single vision contact lenses for 2 weeks. METHODS: Two hundred and ninety-four myopic children aged 7-11 years (inclusive) were enrolled in the 3-year, double-masked Bifocal Lenses In Nearsighted Kids (BLINK) Study. Participants completed the PREP2 survey after having worn contact lenses for 2 weeks. The Vision, Symptoms, Activities and Overall PREP2 subscales were used to compare participants' subjective assessment while wearing +1.50 or +2.50 D add multifocal or single vision contact lenses. Rasch analysis was used to validate each subscale and to compare participants' subjective assessment of contact lens wear. RESULTS: Item fit to the Rasch model was good for all scales, with no individual items having infit mean square statistics outside the recommended range (0.7-1.3). Response category function was acceptable for all subscales, with ordered category thresholds. Measurement precision, assessed by the Rasch person reliability statistic, was less than ideal (≥0.8) for three of the subscales, but met the minimum acceptable standard of 0.5. Scores for the Vision subscale differed by treatment assignment (p = 0.03), indicating that participants with the highest add power reported statistically worse quality of vision, although the difference was only 3.9 units on a scale of 1-100. Girls reported fewer symptoms than boys (p = 0.006), but there were no other differences between boys and girls. CONCLUSIONS: Rasch analysis demonstrates that the PREP2 survey is a valid instrument for assessing refractive error-specific quality of life. These results suggest that vision-related quality of life is not meaningfully affected by 2 weeks of soft multifocal contact lens wear for myopia control.

Vergence/accommodative therapy for symptomatic convergence insufficiency in children: Time course of improvements in convergence function.

PURPOSE: To evaluate the time course of improvements in clinical convergence measures for children with symptomatic convergence insufficiency treated with office-based vergence/accommodative therapy. METHODS: We evaluated convergence measures from 205, 9- to 14-year-old children with symptomatic convergence insufficiency randomised to office-based vergence/accommodative therapy in the Convergence Insufficiency Treatment Trial - Attention and Reading Trial (CITT-ART). Near-point of convergence (NPC) and near-positive fusional vergence (PFV) were measured at baseline and after 4, 8, 12 and 16 weeks of therapy; mean change in NPC and PFV between these time points were compared using repeated measures analysis of variance. Rates of change in NPC and PFV from: (1) baseline to 4 weeks and (2) 4-16 weeks were calculated. For each time point, the proportion of participants to first meet the normal criterion for NPC (<6 cm), PFV blur (break if no blur; >15Δ and >2 times the exodeviation) and convergence composite (NPC and PFV both normal) were calculated. RESULTS: The greatest change in NPC and PFV (7.6 cm and 12.7 Δ) and the fastest rate of improvement in NPC and PFV (1.9 cm/week and 3.2 Δ/week, respectively) were both found during the first 4 weeks of therapy, with both slowing over the subsequent 12 weeks. After 12 weeks of therapy, the NPC, PFV and convergence composite were normal in 93.2%, 91.7% and 87.8% of participants, respectively, and normalised with another 4 weeks of therapy in 4.4%, 2.0% and 4.4% of participants, respectively. CONCLUSION: Although the greatest improvements in NPC and PFV occurred in the first 4 weeks of therapy, most participants had weekly improvements over the subsequent 12 weeks of treatment. While most children with convergence insufficiency obtained normal convergence following 12 weeks of therapy, an additional 4 weeks of vergence/accommodative therapy may be beneficial for some participants.

The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis.

Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.

Plastic orbital foreign body: the rise of plastic and its unintended consequences.

Intraorbital foreign bodies (IOrFBs) are a significant cause of ocular morbidity. Although plastic IOrFBs are rare, the increasing use of plastic and polymer composites in motor vehicles will increase their prevalence. Although challenging to identify, plastic IOrFBs have unique radiographic characteristics. The authors describe a case of an 18-year-old man with a history of a motor vehicle accident and a left upper eyelid laceration. In retrospect, imaging suggested a plastic IOrFB, which was initially overlooked. A follow-up examination demonstrated persistent left upper lid ptosis with an underlying mass. Further work-up revealed a retained IOrFB, which was removed via anterior orbitotomy. Scanning electron microscopy of the material was consistent with a plastic polymer. This case demonstrates the importance of maintaining a high suspicion for IOrFBs in the correct clinical context, the need for increased awareness of plastic and polymer composite IOrFBs, and the use of diagnostic imaging for identification.

Hypotension during propofol sedation for colonoscopy: a retrospective exploratory analysis and meta-analysis.

BACKGROUND: Intraoperative and postoperative hypotension occur commonly and are associated with organ injury and poor outcomes. Changes in arterial blood pressure (BP) during procedural sedation are not well described. METHODS: Individual patient data from five trials of propofol sedation for colonoscopy and a clinical database were pooled and explored with logistic and linear regression. A literature search and focused meta-analysis compared the incidence of hypotension with propofol and alternative forms of procedural sedation. Hypotensive episodes were characterised by the original authors' definitions (typically systolic BP <90 mm Hg). RESULTS: In pooled individual patient data (n=939), 36% of procedures were associated with episodes of hypotension. Longer periods of propofol sedation and larger propofol doses were associated with longer-lasting and more-profound hypotension. Amongst 380 patients for whom individual BP measurements were available, 107 (28%) experienced systolic BP <90 mm Hg for >5 min, and in 89 (23%) the episodes exceeded 10 min. Meta-analysis of 18 RCTs identified an increased risk ratio for the development of hypotension in procedures where propofol was used compared with the use of etomidate (two studies; n=260; risk ratio [RR] 2.0 [95% confidence interval: 1.37-2.92]; P=0.0003), remimazolam (one study; n=384; RR 2.15 [1.61-2.87]; P=0.0001), midazolam (14 studies; n=2218; RR 1.46 [1.18-1.79]; P=0.0004), or all benzodiazepines (15 studies; n=2602; 1.67 [1.41-1.98]; P<0.00001). Hypotension was less likely with propofol than with dexmedetomidine (one study; n=60; RR 0.24 [0.09-0.62]; P=0.003). CONCLUSIONS: Hypotension is common during propofol sedation for colonoscopy and of a magnitude and duration associated with harm in surgical patients.

Effect of Combining 0.01% Atropine with Soft Multifocal Contact Lenses on Myopia Progression in Children.

SIGNIFICANCE: Combining 0.01% atropine with soft multifocal contact lenses (SMCLs) failed to demonstrate better myopia control than SMCLs alone. PURPOSE: The Bifocal & Atropine in Myopia (BAM) Study investigated whether combining 0.01% atropine and SMCLs with +2.50-D add power leads to greater slowing of myopia progression and axial elongation than SMCLs alone. METHODS: Participants of the BAM Study wore SMCLs with +2.50-D add power daily and administered 0.01% atropine eye drops nightly (n = 46). The BAM subjects (bifocal-atropine) were age-matched to 46 participants in the Bifocal Lenses in Nearsighted Kids Study who wore SMCLs with +2.50-D add power (bifocal) and 46 Bifocal Lenses in Nearsighted Kids participants who wore single-vision contact lenses (single vision). The primary outcome was the 3-year change in spherical equivalent refractive error determined by cycloplegic autorefraction, and the 3-year change in axial elongation was also evaluated. RESULTS: Of the total 138 subjects, the mean ± standard deviation age was 10.1 ± 1.2 years, and the mean ± standard deviation spherical equivalent was -2.28 ± 0.89 D. The 3-year adjusted mean myopia progression was -0.52 D for bifocal-atropine, -0.55 D for bifocal, and -1.09 D for single vision. The difference in myopia progression was 0.03 D (95% confidence interval [CI], -0.14 to 0.21 D) for bifocal-atropine versus bifocal and 0.57 D (95% CI, 0.38 to 0.77 D) for bifocal-atropine versus single vision. The 3-year adjusted axial elongation was 0.31 mm for bifocal-atropine, 0.39 mm for bifocal, and 0.68 mm for single vision. The difference in axial elongation was -0.08 mm (95% CI, -0.16 to 0.002 mm) for bifocal-atropine versus bifocal and -0.37 mm (95% CI, -0.46 to -0.28 mm) for bifocal-atropine versus single vision. CONCLUSIONS: Adding 0.01% atropine to SMCLs with +2.50-D add power failed to demonstrate better myopia control than SMCLs alone.

Ocular and Nonocular Adverse Events during 3 Years of Soft Contact Lens Wear in Children.

SIGNIFICANCE: Children are being fitted at younger ages with soft contact lenses for myopia control. This 3-year investigation of adverse events related to contact lens wear in 7- to 11-year-old participants helps optometrists understand what to expect when fitting children with soft contact lenses. PURPOSE: The purpose of this article is to report the frequency and type of ocular and nonocular adverse events related to soft contact lens wear in children. METHODS: Seven- to 11-year-old children wore soft contact lenses for 3 years. Adverse events were defined by a slit-lamp examination finding of grade 3 or worse; parental report of a clinically meaningful change (determined by the examiner) in eyes, vision, or health; or a clinically meaningful response (determined by examiner) to a symptom checklist. Adverse events were categorized and reported by examiners and finalized by the Executive Committee. The presence or absence of an infiltrate and a list of diagnoses was determined at the conclusion of the study. RESULTS: The 294 participants wore their contact lenses 73.0 ± 26.5 hours per week, and 220 (74.8%) encountered at least 1 adverse event. Of the 432 adverse events, 75.2% were ocular, and 24.8% were nonocular. Contact lens wear was probably or definitely related to 60.6% of the ocular and 2.8% of the nonocular adverse events. None of the ocular adverse events were serious or severe or caused permanent contact lens discontinuation. The corneal infiltrate incidence was 185 cases per 10,000 patient-years of wear (95% confidence interval, 110 to 294). The incidence of moderate ocular adverse events that were definitely or probably related to contact lens wear was 405 cases per 10,000 patient-years of wear (95% confidence interval, 286 to 557). CONCLUSIONS: The adverse events experienced by 7- to 11-year-old myopic children rarely required meaningful treatment and never led to permanent discontinuation of contact lens wear or loss of best-corrected vision.

Does coexisting accommodative dysfunction impact clinical convergence measures, symptoms and treatment success for symptomatic convergence insufficiency in children?

PURPOSE: To determine whether coexisting accommodative dysfunction in children with symptomatic convergence insufficiency (CI) impacts presenting clinical convergence measures, symptoms and treatment success for CI. METHODS: Secondary data analyses of monocular accommodative amplitude (AA; push-up method), monocular accommodative facility (AF; ±2.00 D lens flippers) and symptoms (CI Symptom Survey [CISS]) in children with symptomatic CI from the Convergence Insufficiency Treatment Trial (N = 218) and CITT-Attention and Reading Trial (N = 302) were conducted. Decreased AA was defined as more than 2D below the minimum expected amplitude for age (15 - » age); those with AA < 5 D were excluded. Decreased AF was defined as <6 cycles per minute. Mean near point of convergence (NPC), near positive fusional vergence (PFV) and symptoms (CISS) were compared between those with and without accommodative dysfunction using analysis of variance and independent samples t-testing. Logistic regression was used to compare the effect of baseline accommodative function on treatment success [defined using a composite of improvements in: (1) clinical convergence measures and symptoms (NPC, PFV and CISS scores) or (2) solely convergence measures (NPC and PFV)]. RESULTS: Accommodative dysfunction was common in children with symptomatic CI (55% had decreased AA; 34% had decreased AF). NPC was significantly worse in those with decreased AA (mean difference = 6.1 cm; p < 0.001). Mean baseline CISS scores were slightly worse in children with coexisting accommodative dysfunction (decreased AA or AF) (30.2 points) than those with normal accommodation (26.9 points) (mean difference = 3.3 points; p < 0.001). Neither baseline accommodative function (p ≥ 0.12 for all) nor interaction of baseline accommodative function and treatment (p ≥ 0.50) were related to treatment success based on the two composite outcomes. CONCLUSIONS: A coexisting accommodative dysfunction in children with symptomatic CI is associated with worse NPC, but it does not impact the severity of symptoms in a clinically meaningful way. Concurrent accommodative dysfunction does not impact treatment response for CI.

Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression.

Glioblastoma is the most aggressive brain tumour with short survival, partly due to resistance to conventional therapy. Glioma stem cells (GSC) are likely to be involved in treatment resistance, by releasing extracellular vesicles (EVs) containing specific molecular cargoes. Here, we studied the EVs secreted by glioma stem cells (GSC-EVs) and their effects on radiation resistance and glioma progression. EVs were isolated from 3 GSCs by serial centrifugation. NanoSight measurement, cryo-electron microscopy and live imaging were used to study the EVs size, morphology and uptake, respectively. The non-GSC glioma cell lines LN229 and U118 were utilised as a recipient cell model. Wound healing assays were performed to detect cell migration. Colony formation, cell viability and invadopodium assays were conducted to detect cell survival of irradiated recipient cells and cell invasion post GSC-EV treatment. NanoString miRNA global profiling was used to select for the GSC-EVs' specific miRNAs. All three GSC cell lines secreted different amounts of EVs, and all expressed consistent levels of CD9 but different level of Alix, TSG101 and CD81. EVs were taken up by both LN229 and U118 recipient cells. In the presence of GSC-EVs, these recipient cells survived radiation exposure and initiated colony formation. After GSC-EVs exposure, LN229 and U118 cells exhibited an invasive phenotype, as indicated by an increase in cell migration. We also identified 25 highly expressed miRNAs in the GSC-EVs examined, and 8 of these miRNAs can target PTEN. It is likely that GSC-EVs and their specific miRNAs induced the phenotypic changes in the recipient cells due to the activation of the PTEN/Akt pathway. This study demonstrated that GSC-EVs have the potential to induce radiation resistance and modulate the tumour microenvironment to promote glioma progression. Future therapeutic studies should be designed to interfere with these GSC-EVs and their specific miRNAs.

Thermal sensitivity of the Spiroplasma-Drosophila hydei protective symbiosis: The best of climes, the worst of climes.

The outcome of natural enemy attack in insects is commonly influenced by the presence of protective symbionts in the host. The degree to which protection functions in natural populations, however, will depend on the robustness of the phenotype and symbiosis to variation in the abiotic environment. We studied the impact of a key environmental parameter-temperature-on the efficacy of the protective effect of the symbiont Spiroplasma on its host Drosophila hydei, against attack by the parasitoid wasp Leptopilina heterotoma. In addition, we investigated the thermal sensitivity of the symbiont's vertical transmission, which may be a key determinant of the ability of the symbiont to persist. We found that vertical transmission was more robust than previously considered, with Spiroplasma being maintained at 25°C, at 18°C and with 18/15°C diurnal cycles, with rates of segregational loss only increasing at 15°C. Protection against wasp attack was ablated before symbiont transmission was lost, with the symbiont failing to rescue the fly host at 18°C. We conclude that the presence of a protective symbiosis in natural populations cannot be simply inferred from the presence of a symbiont whose protective capacity has been tested under narrow controlled conditions. More broadly, we argue that the thermal environment is likely to represent an important determinant of the evolutionary ecology of defensive symbioses in natural environments, potentially driving seasonal, latitudinal and altitudinal variation in symbiont frequency.

Circulating tumor DNA for malignant peripheral nerve sheath tumors in neurofibromatosis type 1.

PURPOSE: The leading cause of early death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). The principles of management include early diagnosis, surgical clearance and close monitoring for tumor recurrence. Current methods for diagnosis, detection of residual disease and monitoring tumor burden are inadequate, as clinical and radiological features are non-specific for malignancy in patients with multiple tumors and lack the sensitivity to identify early evidence of malignant transformation or tumor recurrence. Circulating tumor DNA (ctDNA) is a promising tool in cancer management and has the potential to improve the care of patients with NF1. In the following article we summarise the current understanding of the genomic landscape of MPNST, report on the previous literature of ctDNA in MPNST and outline the potential clinical applications for ctDNA in NF1 associated MPNST. Finally, we describe our prospective cohort study protocol investigating the utility of using ctDNA as an early diagnostic tool for MPNSTs in NF1 patients.

Association between Vision Impairment and Physical Quality of Life Assessed Using National Surveillance Data.

SIGNIFICANCE: Physically unhealthy days assessments in national health surveillance datasets represent a useful metric for quantifying quality-of-life differences in those with and without vision impairment. Disproportionately poorer physical health in the visually impaired population provides further rationale for the inclusion of vision care in multidisciplinary approaches to chronic disease management. PURPOSE: This study aimed to assess the association between vision impairment and health-related quality of life using data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System. METHODS: Data from each of the 50 states were extracted from the 2017 Behavioral Risk Factor Surveillance System data set. Self-report of difficulty seeing was used to categorize visually impaired versus nonvisually impaired populations. Self-report number of physically unhealthy days in the previous 30 days was used to quantify quality of life. The number of unhealthy days was calculated for the visually impaired and nonvisually impaired cohorts for each state. The ratio of the number of physically unhealthy days in the visually impaired versus nonvisually impaired population was calculated for each state and for different age cohorts. RESULTS: Mean numbers of physically unhealthy days among persons with and without severe vision impairment across all states were 10.63 and 3.68 days, respectively, and demonstrated considerable geographic variability. Mean ratios of physically unhealthy healthy days in the visually impaired versus the nonvisually impaired population were 2.91 in the 18- to 39-year-old cohort, 2.87 in the 40- to 64-year-old cohort, and 2.16 in the ≥65-year-old cohort. CONCLUSIONS: National surveillance data demonstrate a greater number of physically unhealthy days in the visually impaired population, indicating a need to improve our understanding of causes that lead to reduced physical health among those with vision impairment. Additional research is needed to better understand how individuals perceive vision as part of their overall health.

Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years.

SIGNIFICANCE: This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction. PURPOSE: This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children. METHODS: Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves. RESULTS: Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors. CONCLUSIONS: Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.

A randomised clinical trial of multifocal contact lenses and contact lens discomfort.

PURPOSE: To determine how multifocal contact lenses affect contact lens discomfort. METHODS: This randomised, participant-masked, crossover clinical trial fitted 84 uncomfortable soft contact lens wearers (30-40 years old) with single vision and multifocal contact lenses. Contact lens discomfort was assessed using the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8). RESULTS: There was no difference between multifocal and single vision survey scores (p = 0.08). There was an interaction between lens type and age group (p = 0.05). CLDEQ-8 scores with the single vision lens were less symptomatic than multifocal scores in participants <35 years old (p = 0.01). Single vision and multifocal scores for the older age group were not different. Subjectively, those in the <35 year-old age group preferred the single vision lens for intermediate (p = 0.02), distance (p = 0.003), and overall vision (p = 0.002). In the ≥35 year-old age group, no lens was significantly preferred for vision. CONCLUSIONS: Participants in the younger age group had more favourable wearing experiences with the single vision lens compared to the multifocal lens. The older age group, however, had similar wearing experiences with both lens types. While younger contact lens wearers may prefer the wearing experience with single vision lenses, some uncomfortable contact lens wearers approaching 40 years old may benefit from wearing a multifocal contact lens sooner in life than is typically practised.

Effectiveness of vergence/accommodative therapy for accommodative dysfunction in children with convergence insufficiency.

PURPOSE: To determine the effectiveness of office-based vergence/accommodative therapy for improving accommodative amplitude and accommodative facility in children with symptomatic convergence insufficiency and accommodative dysfunction. METHODS: We report changes in accommodative function following therapy among participants in the Convergence Insufficiency Treatment Trial - Attention and Reading Trial with decreased accommodative amplitude (115 participants in vergence/accommodative therapy; 65 in placebo therapy) or decreased accommodative facility (71 participants in vergence/accommodative therapy; 37 in placebo therapy) at baseline. The primary analysis compared mean change in amplitude and facility between the vergence/accommodative and placebo therapy groups using analyses of variance models after 4, 8, 12 and 16 weeks of treatment. The proportions of participants with normal amplitude and facility at each time point were calculated. The average rate of change in amplitude and facility from baseline to week 4, and from weeks 4 to 16, were determined in the vergence/accommodative therapy group. RESULTS: From baseline to 16 weeks, the mean improvement in amplitude was 8.6 dioptres (D) and 5.2 D in the vergence/accommodative and placebo therapy groups, respectively (mean difference = 3.5 D, 95% confidence interval (CI): 1.5 to 5.5 D; p = 0.01). The mean improvement in facility was 13.5 cycles per minute (cpm) and 7.6 cpm in the vergence/accommodative and placebo therapy groups, respectively (mean difference = 5.8 cpm, 95% CI: 3.8 to 7.9 cpm; p < 0.0001). Significantly greater proportions of participants treated with vergence/accommodative therapy achieved a normal amplitude (69% vs. 32%, difference = 37%, 95% CI: 22 to 51%; p < 0.0001) and facility (85% vs. 49%, difference = 36%, 95% CI: 18 to 55%; p < 0.0001) than those who received placebo therapy. In the vergence/accommodative therapy group, amplitude increased at an average rate of 1.5 D per week during the first 4 weeks (p < 0.0001), then slowed to 0.2 D per week (p = 0.002) from weeks 4 to 16. Similarly, facility increased at an average rate of 1.5 cpm per week during the first 4 weeks (p < 0.0001), then slowed to 0.6 cpm per week from weeks 4 to 16 (p < 0.0001). CONCLUSION: Office-based vergence/accommodative therapy is effective for improving accommodative function in children with symptomatic convergence insufficiency and coexisting accommodative dysfunction.

A literature-based treatment algorithm for low-grade neuroendocrine liver metastases.

BACKGROUND: The optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM. METHODS: A treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments. RESULTS: Applying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p < 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics. CONCLUSION: This literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.

Symbiont-mediated fly survival is independent of defensive symbiont genotype in the Drosophila melanogaster-Spiroplasma-wasp interaction.

When a parasite attacks an insect, the outcome is commonly modulated by the presence of defensive heritable symbionts residing within the insect host. Previous studies noted markedly different strengths of Spiroplasma-mediated fly survival following attack by the same strain of wasp. One difference between the two studies was the strain of Spiroplasma used. We therefore performed a laboratory experiment to assess whether Spiroplasma-mediated protection depends upon the strain of Spiroplasma. We perform this analysis using the two strains of male-killing Spiroplasma used previously, and examined response to challenge by two strains of Leptopilina boulardi and two strains of Leptopilina heterotoma wasp. We found no evidence Spiroplasma strain affected fly survival following wasp attack. In contrast, analysis of the overall level of protection, including the fecundity of survivors of wasp attack, did indicate the two Spiroplasma strains tested varied in protective efficiency against three of the four wasp strains tested. These data highlight the sensitivity of symbiont-mediated protection phenotypes to laboratory conditions, and the importance of common garden comparison. Our results also indicate that Spiroplasma strains can vary in protective capacity in Drosophila, but these differences may exist in the relative performance of survivors of wasp attack, rather than in survival of attack per se.