Safety and efficacy of 0.01% and 0.1% low-dose atropine eye drop regimens for reduction of myopia progression in Danish children: a randomized clinical trial examining one-year effect and safety.

BACKGROUND: To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children. METHODS: Investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months followed by 0.01% for six months (loading dose group, Number (N) = 33), 0.01% for twelve months (0.01% group, N = 32) or vehicle for twelve months (placebo, N = 32). Primary outcomes were axial length and spherical equivalent refraction. Secondary outcomes included adverse events and reactions, choroidal thickness and ocular biometry. Outcomes were measured at baseline and three-month intervals. Data was analyzed with linear-mixed model analysis according to intention-to-treat. RESULTS: Mean axial elongation was 0.10 mm less (95% confidence interval (CI): 0.17; 0.02, adjusted-p = 0.06) in the 0.1% loading dose and 0.07 mm less (95% CI: 0.15; 0.00, adjusted-p = 0.16) in the 0.01% group at twelve months compared to placebo. Mean spherical equivalent refraction progression was 0.24 D (95% CI: 0.05; 0.42) less in the loading dose and 0.19 D (95% CI: 0.00; 0.38) less in the 0.01% groups at twelve months, compared to placebo (adjusted-p = 0.06 and 0.14, respectively). A total of 108 adverse events were reported during the initial six-month loading dose period, primarily in the loading dose group, and 14 were reported in the six months following dose switching, all deemed mild except two serious adverse events, unrelated to the intervention. CONCLUSIONS: Low-dose atropine eye drops are safe over twelve months in otherwise healthy children. There may be a modest but clinically relevant reduction in myopia progression in Danish children after twelve months treatment, but the effect was statistically non-significant after multiple comparisons adjustment. After dose-switching at six months the loading dose group approached the 0.01% group, potentially indicating an early "rebound-effect". TRIAL REGISTRATION: this study was registered in the European Clinical Trials Database (EudraCT, number: 2018-001286-16) 05/11/2018 and first posted at www. CLINICALTRIALS: gov (NCT03911271) 11/04/2019, prior to initiation.

Periocular basal cell carcinoma results and surgical outcome during a 5-year period in a larger Danish population.

BACKGROUND: To report tumour pathology, surgical procedure, complication rates and overall outcome of periocular basal cell carcinoma (BCC) in the Department of Ophthalmology at Sygehus Lillebaelt, Southern Denmark Region over a 5-year period. METHODS: Medical records for all patients who underwent surgery for periocular BCC between January 2016 and December 2020 were reviewed. All tumours were excised with a 3 mm margin beyond the clinically apparent delimitation of the tumour and analysed by frozen section histological examination. Paraffin sections were subsequently examined for a final histopathological diagnosis. Patient age, gender, date of resection, former cancer history, referring unit and follow-up time were recorded. Furthermore, histological subtypes identified from biopsy and resection, lesion location, lesion diameter, free margin after the first operation, lacrimal punctum involvement, reconstructive techniques and complications were also recorded. RESULTS: A total of 242 surgical excisions from 237 patients were recorded. The mean age was 69.7 ± 12.6 with women significantly predominant compared to men (1.8:1, p < 0.0001, binomial test). The mean tumour diameter was 4.29 mm (range 0.5-20 mm). The most common location and histological subtype was the lower eyelid and nodular BCC respectively (64.9% and 74.0% of cases). In 17.4% of the patients, the initial resection margin on the frozen section histology was not free of tumour cells and the risk was significantly greater for BCC subtypes considered aggressive in terms of growth pattern (morphea form, infiltrative and micronodular features) as compared to non-aggressive BCC subtypes (nodular and superficial) (p = 0.002, X2). In 239 (98.8%) of the patients, the BCC was found to be radically removed after final histopathological examination. The sensitivity of identification of aggressive subtypes of periocular BCC in biopsies was 47.7%. No recurrences were found during the 5-year period. CONCLUSION: This study demonstrated a tendency towards more women than men being diagnosed with periocular BCC. The initial biopsy performed for all patients underestimated the aggressiveness of BCC in almost half of the cases while aggressive BCC subtypes were more likely to need further resection after frozen section compared to non-aggressive subtypes.

Life-Cycle Costing of Food Waste Management in Denmark: Importance of Indirect Effects.

Prevention has been suggested as the preferred food waste management solution compared to alternatives such as conversion to animal fodder or to energy. In this study we used societal life-cycle costing, as a welfare economic assessment, and environmental life-cycle costing, as a financial assessment combined with life-cycle assessment, to evaluate food waste management. Both life-cycle costing assessments included direct and indirect effects. The latter are related to income effects, accounting for the marginal consumption induced when alternative scenarios lead to different household expenses, and the land-use-changes effect, associated with food production. The results highlighted that prevention, while providing the highest welfare gains as more services/goods could be consumed with the same income, could also incur the highest environmental impacts if the monetary savings from unpurchased food commodities were spent on goods/services with a more environmentally damaging production than that of the (prevented) food. This was not the case when savings were used, e.g., for health care, education, and insurances. This study demonstrates that income effects, although uncertain, should be included whenever alternative scenarios incur different financial costs. Furthermore, it highlights that food prevention measures should not only demote the purchase of unconsumed food but also promote a low-impact use of the savings generated.

A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models.

Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding associated with hemophilia A. To reduce the treatment burden, recombinant FVIII with a longer half-life was developed without changing the protein structure. FVIII-polyethylene glycol (PEG) conjugates were prepared using an enzymatic process coupling PEG (ranging from 10 to 80 kDa) selectively to a unique O-linked glycan in the FVIII B-domain. Binding to von Willebrand factor (VWF) was maintained for all conjugates. Upon cleavage by thrombin, the B-domain and the associated PEG were released, generating activated FVIII (FVIIIa) with the same primary structure and specific activity as native FVIIIa. In both FVIII- and VWF-deficient mice, the half-life was found to increase with the size of PEG. In vivo potency and efficacy of FVIII conjugated with a 40-kDa PEG (N8-GP) and unmodified FVIII were not different. N8-GP had a longer duration of effect in FVIII-deficient mouse models, approximately a twofold prolonged half-life in mice, rabbits, and cynomolgus monkeys; however, the prolongation was less pronounced in rats. Binding capacity of N8-GP on human monocyte-derived dendritic cells was reduced compared with unmodified FVIII, resulting in several-fold reduced cellular uptake. In conclusion, N8-GP has the potential to offer efficacious prevention and treatment of bleeds in hemophilia A at reduced dosing frequency.

Vision-related quality of life in children: Cross-cultural adaptation and test-retest reliability of the Danish version of the paediatric refractive error profile 2.

PURPOSE: To translate and cross-culturally adapt PREP2 into Danish and to investigate the face validity and reliability of Danish PREP2 through cognitive interviewing, Rasch and reliability analyses. METHODS: The Danish PREP2 was translated using a standardized procedure and then pretested following the Three-Steps-Interviews (TSTI) process. A total of 15 myopic children aged 7-14 wearing either orthokeratology lenses (ortho-k) or single-vision spectacles (SVS) were included in pretesting comprising cognitive interviews and Rasch analysis. Data from cognitive interviewing was analysed thematically according to Collins. Rasch analysis was used to pretest the psychometric properties in terms of person- and item-fit statistics. Reliability was assessed via test-retest using Intra-class correlation coefficient (ICC) in the CONTROL study population, which consisted of 60 Danish children aged 7-14 years wearing either ortho-k or SVS. RESULTS: Fifteen children participated in pilot studies comprising of cognitive interviewing and Rasch analysis and 44 out of 60 CONTROL children participated in test-retest reliability analysis. The translation process resulted in a Danish version of PREP2 corroborating the original. Pretesting highlighted issues in the contextualization of items and in marking responses. Thus, we introduced a digital format with help texts. Cognitive interviewing identified issues in the following Collins' themes: comprehension (understanding of concepts), judgement (ambiguity of items) and response (selecting answers). Rasch analysis indicated that help texts were useful for clarifying context. The ICC was 0.77 (95% CI: 0.66-0.85). CONCLUSIONS: The cross-cultural adaptation of PREP2 was satisfactory and issues were identified and corrected through pretesting. The test-retest reliability showed substantial consistency. The instrument could be validated in a more generalizable setting in future studies. TRIAL REGISTRATION: NCT03246464 (CONTROL study).

Two-Year Results of 0.01% Atropine Eye Drops and 0.1% Loading Dose for Myopia Progression Reduction in Danish Children: A Placebo-Controlled, Randomized Clinical Trial.

We investigated the two-year safety and efficacy of 0.1% loading dose and 0.01% low-dose atropine eye drops in Danish children for reduction in myopia progression in an investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months and then 0.01% for eighteen months (loading dose group, N = 33), 0.01% for two years (0.01% group, N = 32) or placebo for two years (placebo, N = 32). Axial length (AL) and spherical equivalent refraction (SER) were primary outcomes. Secondary outcomes included adverse events and reactions, choroidal thickness, and other ocular biometrical measures. Outcomes were measured from baseline and at six-month intervals. Individual eyes nested by participant ID were analyzed with linear-mixed model analysis. Data were analyzed with intention-to-treat. Mean AL was 0.08 mm less (95% confidence interval (CI): -0.01; 0.17, p-value = 0.08) in the 0.1% loading dose and 0.10 mm less (95% CI: 0.01; 0.19, p-value = 0.02) in the 0.01% group after two years of treatment compared to placebo. Mean SER progression was 0.12 D (95% CI: -0.10; 0.33) less in the loading dose and 0.26 D (95% CI: 0.04; 0.48) less in the 0.01% groups after two years of treatment compared to placebo (p-value = 0.30 and 0.02, respectively). In total, 17 adverse events were reported in the second-year follow-up, and all were rated as mild. Adjusting for iris color did not affect treatment effect estimates. Intra-ocular pressure increased over two years comparably between all groups but remained within normal limits. Two-year treatment with 0.01% low-dose atropine eye drops is a safe and moderately efficacious intervention in Danish children for reducing myopia progression.

The Macular Choroidal Thickness in Danish Children with Myopia After Two-Year Low-Dose Atropine and One-Year Wash-Out: A Placebo-Controlled, Randomized Clinical Trial.

INTRODUCTION: Our aim in this work was to investigate the macular choroidal thickness (ChT) changes in 6-12-year-old Danish children with myopia during 2 years of low-dose atropine treatment and 1-year wash-out vs. placebo in an investigator-initiated, placebo-controlled, double-blind randomized clinical trial. METHODS: Ninety-seven participants were randomized to either 0.01% for 2 years, 0.1% loading dose for 6 months followed by 0.01% for 18 months, or placebo, then a 1-year wash-out. The primary outcome was ChT in the sub-foveal and inner and outer superior, nasal, inferior, and temporal sectors. The secondary outcome was axial length (AL). Outcomes were measured at baseline and 6, 12, 24, and 36 months. One-way analysis of variance was used to detect baseline ChT differences between AL-stratified groups (< 24 mm, 24-25 mm, or > 25 mm). To determine the longitudinal changes in ChT and its effect on AL, all eyes were included in linear mixed modeling with individual eyes nested in the study ID as a random effect. RESULTS: Longer eyes had significantly thinner ChT in all choroidal sectors (adj-P < 0.01) at baseline. There was no statistically significant change in any ChT sector after 3 years in the placebo group. Sub-foveal and nasal ChT in the 0.1% loading dose and 0.01% group were not significantly different from placebo after 2-year treatment. In the placebo group, a 1-mm increase in AL was significantly associated with a 47-µm thinner nasal ChT after 3 years (95% confidence interval (CI): - 55; - 38, adj-P < 0.001). A 10-µm thicker nasal choroid at baseline was associated with 0.13 mm (95% CI: 0.009; 0.017, adj-P < 0.001) less 3-year axial elongation. CONCLUSIONS: The ChT in Danish children with myopia remained stable over the 3-year follow-up. A thinner choroid at myopia onset might predispose to increased axial elongation. Treatment with 0.01% atropine did not change the ChT. We speculate that low-dose atropine does not primarily reduce myopia progression via a choroidal mechanism. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03911271.

Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide.

Current management of hemophilia B entails multiple weekly infusions of factor IX (FIX) to prevent bleeding episodes. In an attempt to make a longer acting recombinant FIX (rFIX), we have explored a new releasable protraction concept using the native N-glycans in the activation peptide as sites for attachment of polyethylene glycol (PEG). Release of the activation peptide by physiologic activators converted glycoPEGylated rFIX (N9-GP) to native rFIXa and proceeded with normal kinetics for FXIa, while the K(m) for activation by FVIIa-tissue factor (TF) was increased by 2-fold. Consistent with minimal perturbation of rFIX by the attached PEG, N9-GP retained 73%-100% specific activity in plasma and whole-blood-based assays and showed efficacy comparable with rFIX in stopping acute bleeds in hemophilia B mice. In animal models N9-GP exhibited up to 2-fold increased in vivo recovery and a markedly prolonged half-life in mini-pig (76 hours) and hemophilia B dog (113 hours) compared with rFIX (16 hours). The extended circulation time of N9-GP was reflected in prolonged correction of coagulation parameters in hemophilia B dog and duration of effect in hemophilia B mice. Collectively, these results suggest that N9-GP has the potential to offer efficacious prophylactic and acute treatment of hemophilia B patients at a reduced dosing frequency.

External costs of atmospheric lead emissions from a waste-to-energy plant: a follow-up assessment of indirect exposure via topsoil ingestion.

In this study the Impact Pathway Approach (IPA) was used to calculate the external costs associated with indirect exposure, via topsoil ingestion, to atmospheric emissions of lead (Pb) from a waste-to-energy plant in Denmark. Three metal-specific models were combined to quantify the atmospheric dispersion of lead, its deposition and accumulation in topsoil, and the increase in blood lead concentration for children resulting from lead intake via topsoil ingestion. The neurotoxic impact of lead on children was estimated using a lead-specific concentration-response function that measures impaired cognitive development in terms of IQ points lost per each incremental µg/dl of lead in blood. Since IQ loss during childhood can be associated with a percent decrease in expected lifetime earnings, the monetary value of such an impact can be quantified and the external costs per kg of lead emitted from the plant were then calculated. The costs of indirect exposure calculated over a time horizon of 100 years, for the sub-population of children of 0-3 years, and discounted at 3%, were in the range of 15-30 €/kg. Despite the continued accumulation of lead in topsoil resulting in increasing future indirect exposure, the results indicate that costs associated with this exposure pathway are of the same order of magnitude as costs associated with direct exposure via inhalation, calculated at 45-91 €/kg. Moreover, when the monetary value of future impacts is discounted to the present, the differences between the two exposure pathways are diminished. Finally, setting a short time horizon reduces the uncertainties but excludes part of the costs of indirect exposure from the assessment.

Peripheral refraction, relative peripheral refraction, and axial growth: 18-month data from the randomised study-Clinical study Of Near-sightedness; TReatment with Orthokeratology Lenses (CONTROL study).

PURPOSE: To investigate changes in peripheral and relative peripheral refraction (RPR) during orthokeratology lens (OKL) use in children, and predictors for myopia progression in a randomized controlled trial. METHODS: Refraction and axial length (AL) were measured at baseline, 6, 12, and 18 months for children aged 6-12 years, with myopia of 0.5 to 4.75 dioptres (D) spherical component randomized to either OKL or single-vision spectacles (SVS) at baseline. Cycloplegic spherical equivalent refractive error (SEQ) was measured on-axis and eccentric at 10°, 20°, and 30° during nasal and temporal gaze in the horizontal plane with Shin-Nippon Nvision-K 5001. RPR was computed as SEQ(eccentricity) minus SEQ(on axis) . AL was measured with Lenstar LS900. RESULTS: Twenty-one and 28 subjects from the OKL and SVS groups, respectively were available for analysis. OKL wear induced significant myopic RPR at all eccentricities (p ≤ 0.004) whereas peripheral refraction only changed in two out of six eccentric measuring points. Baseline peripheral refraction SEQ at all eccentricities, baseline on-axis SEQ, and baseline RPR at 30° nasal eccentricity were positively correlated to treatment efficacy defined as change in AL. CONCLUSION: We found no correlations between change in RPR and treatment efficacy defined as change in AL. Interestingly, our results suggest that the central emmetropisation that occurs during OKL-use accounts for most of the optical changes and to a lesser extent the mid-peripheral plus-zone of the lens.

Low-Dose Atropine Induces Changes in Ocular Biometrics in Myopic Children: Exploring Temporal Changes by Linear Mixed Models and Contribution to Treatment Effect by Mediation Analyses.

This study aimed to investigate changes in non-cycloplegic ocular biometrics during the initial six months of treatment with a 0.1% atropine loading dose and 0.01% atropine compared with a placebo and analyze their contribution to the treatment effect on cycloplegic spherical equivalent (SE) progression. The study was based on a randomized, double-masked, placebo-controlled, multicenter trial evaluating a 0.1% atropine six-month loading dose and 0.01% atropine in reducing myopic progression in Danish children. The treatment phase was 24 months, and the washout phase was 12 months. Parameters measured included changes in axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and choroidal thickness (ChT), while cycloplegic SE and lens power were calculated. Longitudinal changes and contributions to treatment effects were analyzed using constrained linear mixed models and mediation analyses, respectively. After six months, AL was 0.13 mm shorter (95% confidence interval [CI], -0.18 to -0.07 [adjusted p < 0.001]) and 0.06 mm shorter (95% CI, -0.11 to -0.01 [adjusted p = 0.060]) with a 0.1% atropine loading dose and 0.01% atropine, respectively, compared to the placebo group. Similar concentration-dependent changes were found with ACD, LT, VCD, ChT, and cycloplegic SE. Although the treatment effects trended toward concentration-dependent responses, only the treatment effect mediated by AL at three months differed significantly between 0.01% atropine and a 0.1% atropine loading dose (adjusted p = 0.023). Several ocular biometrics, including AL, ACD, and LT, changed dose-dependently during low-dose atropine treatment. Moreover, the treatment effect of atropine on SE progression was mediated by a subset of ocular biometrics, mainly AL, with trends toward concentration dependency and distributional shifts over time.

Reproducibility of Mesopic and Photopic Pupil Sizes in Myopic Children Using a Dedicated Pupillometer with Human-Assisted or Automated Reading.

This study aimed to investigate the reproducibility of pupil size measurements over time and between reading methods when comparing human-assisted reading to automated reading. Pupillary data were analyzed on a subset of myopic children enrolled in a multicenter randomized clinical trial on myopia control with low-dose atropine. Pupil size measurements were obtained prior to randomization at two time points (screening and baseline visits) using a dedicated pupillometer under mesopic and photopic conditions. A customized algorithm was built to perform automated readings, allowing comparisons between human-assisted and automated readings. Reproducibility analyses followed the principles of Bland and Altman and included the calculation of the mean difference between measurements and limits of agreement (LOA). We included 43 children. Mean (standard deviation) age was 9.8 (1.7) years and 25 (58%) children were girls. Using human-assisted readings, reproducibility over time showed mesopic mean difference of 0.02 mm with LOA from -0.87 mm to 0.91 mm, whereas photopic mean difference was -0.01 mm with LOA from -0.25 mm to 0.23 mm. Reproducibility between human-assisted and automated readings was also higher under photopic conditions, with mean difference of 0.03 mm and LOA from -0.03 mm to 0.10 mm at screening and mean difference of 0.03 mm and LOA from -0.06 mm to 0.12 mm at baseline. Using a dedicated pupillometer, we found that examinations performed under photopic conditions demonstrated higher reproducibility over time and between reading methods. We speculate whether mesopic measurements are sufficiently reproducible to be monitored over time. Furthermore, photopic measurements may be of greater relevance when evaluating the side effects of atropine treatment, such as photophobia.

Myopia Control with Low-Dose Atropine in European Children: Six-Month Results from a Randomized, Double-Masked, Placebo-Controlled, Multicenter Study.

The effect and safety of low-dose atropine in myopia control have not been studied in randomized, placebo-controlled trials outside Asia. We investigated the efficacy and safety of 0.1% atropine loading dose and 0.01% atropine compared with a placebo in a European population. Investigator-initiated, randomized, double-masked, placebo-controlled, equal-allocation, multicenter study comparing 0.1% atropine loading dose (six months) followed by 0.01% atropine (18 months), 0.01% atropine (24 months), and placebo (24 months). Participants were monitored for a 12-months washout period. Outcome measures were axial length (AL), cycloplegic spherical equivalent (SE), photopic and mesopic pupil size, accommodation amplitude, visual acuity, intraocular pressure (IOP), and adverse reactions and events. We randomized 97 participants (mean [standard deviation] age, 9.4 [1.7] years; 55 girls (57%) and 42 boys (43%)). After six months, AL was 0.13 mm shorter (95% confidence interval [CI], -0.18 to -0.07 [adjusted p < 0.001]) with 0.1% atropine loading dose and 0.06 mm shorter (95% CI, -0.11 to -0.01 [adjusted p = 0.06]) with 0.01% atropine than in the placebo group. We observed similar dose-dependent changes in SE, pupil size, accommodation amplitude, and adverse reactions. No significant differences in visual acuity or IOP were found between groups, and no serious adverse reactions were reported. We found a dose-dependent effect of low-dose atropine in European children without adverse reactions requiring photochromatic or progressive spectacles. Our results are comparable to those observed in East Asia, indicating that results on myopia control with low-dose atropine are generalizable across populations with different racial backgrounds.

Myopia in children and adolescents.

The prevalence of myopia is estimated to be 2.6 billion people worldwide and the percentage of individuals with sight-threatening high myopia (≤ -6 diopters) is increasing. Myopia is primarily caused by excessive axial elongation of the eyeball, and treatment modalities attempt to reduce this progression. While increased outdoor time is known to delay myopia onset, new pharmacological and optical interventions aim to reduce myopia progression. This review finds that these promising interventions are expected to significantly decrease the future prevalence of sight-threatening high myopia.

Control of myopia using orthokeratology lenses in Scandinavian children aged 6 to 12 years. Eighteen-month data from the Danish Randomized Study: Clinical study Of Near-sightedness; TReatment with Orthokeratology Lenses (CONTROL study).

PURPOSE: To investigate the efficacy of myopia control defined by axial elongation and safety of orthokeratology lenses (OKL) in a Scandinavian (Danish) population. METHODS: Sixty Danish children aged 6-12 years with myopia ranging from 0.5 to 4.75 dioptres (D) spherical component and refractive astigmatism ≤2.5 D in both eyes were randomly assigned to either OKL or single-vision spectacles (SVS). Study duration was 18 months. Outcome measures were axial length (AL) measured with Lenstar LS900 (Haag-Streit, Koeniz, Switzerland) and adverse events graded with Efron Grading Scale for Contact Lens Complications. RESULTS: Nineteen participants completed the 18-month follow-up in the OKL group and 28 in the SVS group. The average AL elongation in the OKL group was 0.24 mm smaller as compared to the SVS group (95% confidence interval 0.12-0.36, mixed model adjusted for baseline sex, age and AL). There were no fast progressors (>0.75 D/year) in the OKL group during the follow-up period in contrast to 22% in the SVS group. No treatment-requiring or vision-threatening adverse events were observed. CONCLUSION: Orthokeratology lenses reduced AL elongation in myopic Scandinavian children by 59%, with no treatment-requiring or vision-threatening adverse events. The results align with outcomes of previous clinical trials.

Achieving Optimal Correction for Young Myopic Children: A Concept Study.

The purpose of this article is to explore alternative ways of achieving optimal correction for myopic children who cannot cooperate to subjective manifest refraction (SR). The study included myopic children aged 9-12 years who underwent non-cycloplegic SR and autorefraction with and without cycloplegia using the Shin-Nippon Nvision-K 5001 autorefractor (AR) as well as non-cycloplegic autorefraction using the Topcon KR-800S AR. There were 21 children (mean age, 10.62 years) included. The spherical equivalent refractive error of SR was not significantly different from that of non-cycloplegic AR measurements, but it was significantly different from that of cycloplegic Shin-Nippon Nvision-K 5001 measurements (p < 0.001). Compared with SR, cycloplegic Shin-Nippon Nvision-K 5001 measured a less myopic refractive error (median: -2.44 D vs. -2.88 D, p < 0.001). For both ARs, the axis measurements and astigmatic dioptre values between SR and autorefraction were not significantly different. Compared with non-cycloplegic SR, cycloplegic measurements showed a lesser degree of myopic refractive error. There was no significant difference between SR and non-cycloplegic autorefraction. Therefore, the Topcon KR-800S and the Shin-Nippon Nvision-K 5001 ARs may be useful for prescribing glasses in myopic children who cannot cooperate during SR. However, caution should be taken with cylinders <0.75 D because the agreement in axis between SR and AR measurement is poor. Therefore, in such cases, we suggest to add half the cylinder to the spherical component.

Repeatability and inter-observer variation of choroidal thickness measurements using swept-source optical coherence tomography in myopic danish children aged 6-14 years.

PURPOSE: To estimate repeatability and inter-observer variation of choroidal thickness measurements in myopic Danish children aged 7-14 years using swept-source optical coherence tomography (SS-OCT). METHODS: Thirty-nine children were enrolled. Optical correction was single-vision spectacles (SVS) or orthokeratology lenses (OKL). Three repeated 7 × 7 mm 3-dimensional SS-OCT macula scans and three repeated 9 mm SS-OCT line scans were collected for each child using a DRI OCT Triton. Choroidal thickness was measured using three different methods: line scan method 1 (LM1), line scan method 2 (LM2) and 3D macula scan method (3DM). Segmentation was adjusted if needed. Coefficients of repeatability (CR) and limits of agreement (LoA) were calculated. RESULTS: The CRs ranged from 13.4 to 23.9 µm, 14.5 to 26.2 µm and 5.2 to 10.7 µm for LM1, LM2 and 3DM, respectively. The LoA ranged from -22.9 to +31.5 µm, -23.3 to +32.2 µm and -10.2 to +12.4 µm for LM1, LM2 and 3DM, respectively. Segmentation was adjusted in most scans (63%-92%). Mean choroidal thickness ranged from 142.2 ± 47.2 to 253.8 ± 60.9 µm and 190.1 ± 64.0 to 299.0 ± 55.8 µm for the SVS and OKL groups, respectively, measured by 3DM. CONCLUSION: The 3DM was the most repeatable method in this paediatric population. It yielded a CR of 10.7 µm, confidence interval 2.4 µm, which makes the minimal detectable difference between two measurements 13.1 µm. Most inter-observer variation could be explained by the intramethod variation. Segmentation adjustment on 3D macula scans did not increase CR on a group level.

Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration.

PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26 previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow-up was performed at 1 week, 6 weeks, 3 months, and 6 months. RESULTS: Mean multifocal electroretinography P1 amplitudes were significantly improved at 1 week in the central zone and after 3 and 6 months, improvement was seen in all 6 concentric rings corresponding to +/-25 degrees of the central visual field. Full-field electroretinography results indicated a decrease in cone photoreceptor function at 3 months, which was normalized at 6 months compared with baseline. Furthermore, 2 of 3 of the combined rod-cone responses showed signs of decreased retinal function at 6 months. CONCLUSION: Our results indicate passing signs of an altered retinal cone photoreceptor function assessed by full-field electroretinography. The results do not show any conclusive signs of global retinal toxicity after 6 months. Multifocal electroretinography results show improved photoreceptor function with no sign of focal toxicity in the central retina.

Variations in keratometric values (K-value) after administration of three different eye drops - effects on the intraocular lens calculations in relation to cataract surgery.

PURPOSE: To investigate the variance in keratometric (K) values after administration of different eye drops (three tested), and the effects on intraocular lens (IOL) power calculations in relation to standard cataract surgery. METHODS: A prospective intervention study (pilot study) on 38 participants (22 women, 16 men, 58-88 years) undergoing 57 cataract surgeries. Three keratometries on each eye were performed: a baseline ('standard') keratometry about 9 weeks preoperatively, and two on the operation day; a 'dry'-measurement before interventions and a 'wet'-measurement after applying one of three eye drops (saline, Systane Ultra® , or Systane Complete® ). All standard cataract operations were uneventful. Variabilities in K-values, spherical equivalents (SEQs) for IOL power calculations (Barrett TK Universal II) and subjective manifest refractions (SRs) 6 weeks postoperatively were compared between groups. RESULTS: The 'wet' K-values had a similar variability to those of the 'standard' and 'dry' K-values (p > 0.05, anova on ranks). The mean paired differences in K-measurements between groups ranged within a small interval from -0.0107 to 0.0096 mm. After comparing the SEQ predictions with SR-measurements, the most precise IOL calculation was achieved after administration of a saline eye drop, but the precision was not statistically improved compared to the other drop modalities. CONCLUSION: The variability in K-values was not significantly changed by administration of any of the different eye drops tested, suggesting that artificial eye drops do not impact the keratometry or IOL power prediction.

Rectal evacuation and antegrade colonic luminal transport by sacral anterior root stimulation in pigs.

PURPOSE: Electrical sacral anterior root stimulation with a selective anodal block may relieve difficulties with bowel evacuation by selective colorectal activation and anal sphincter suppression. This study compares rectal evacuation induced by anodal block with that induced by unselective stimulation. METHODS: The sacral anterior roots were stimulated with cuff electrodes in seven chloralose-anesthetized minipigs. Anodal block and unselective stimulation were applied in random order and compared by anorectal manometry and by the obtained colorectal evacuation. Evacuation was quantified scintigraphically after retrograde radioactive paste installation. RESULTS: Unselective stimulation evoked sphincter activation which obstructed rectal evacuation during the 30-second stimulation period, after which poststimulation evacuation occurred (mean, 13%; P < 0.05). Anodal block reduced the anal canal pressure by median 83% compared with unselective stimulation. With unrestrained evacuation, a different evacuation pattern (mean, 18%; P < 0.05) occurred within the first ten seconds of the stimulation period and evacuated volume was higher (P = 0.08). Colonic evacuation reached a mean of 17% with unselective stimulation and 11% with anodal block. CONCLUSION: Anodal block and unselective sacral root stimulation induce rectal evacuation and colonic luminal transport in pigs. However, anodal block may improve stimulation-induced defecation by enabling a near-physiologic defecation pattern.