Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial.

BACKGROUND: Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. METHODS: EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3-8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. FINDINGS: Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. INTERPRETATION: The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. FUNDING: Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation.

Correlation of visual field deficits and q-ball high-resolution fiber tractography of the optic radiation for adjacently located intracerebral lesions: preliminary results from a single-center prospective study.

Visual field deficits (VFDs) are common in patients with temporal and occipital lobe lesions. Diffusion tensor fiber tractography (DTI-FT) is widely used for surgery planning to reduce VFDs. Q-ball high-resolution fiber tractography (QBI-HRFT) improves upon DTI. This study aims to evaluate the effectiveness of DTI-FT and QBI-HRFT for surgery planning near the optic radiation (OR) as well as the correlation between VFDs, the nearest distance from the lesion to the OR fiber bundle (nD-LOR), and the lesion volume (LV). This ongoing prospective clinical trial collects clinical and imaging data of patients with lesions in deterrent areas. The present subanalysis included eight patients with gliomas near the OR. Probabilistic HRFT based on QBI-FT and conventional DTI-FT were performed for OR reconstruction based on a standard diffusion-weighted magnetic resonance imaging sequence in clinical use. Quantitative analysis was used to evaluate the lesion volume (LV) and nD-LOR. VFDs were determined based on standardized automated perimetry. We included eight patients (mean age 51.7 years [standard deviation (SD) 9.5]) with lesions near the OR. Among them, five, two, and one patients had temporodorsal, occipital, and temporal lesions, respectively. Four patients had normal vision preoperatively, while four patients had preexisting VFD. QBI-FT analysis indicated that patients with VFD exhibited a significantly smaller median nD-LOR (mean, -4.5; range -7.0; -2.3) than patients without VFD (mean, 7.4; range -4.3; 27.2) (p = 0.050). There was a trend towards a correlation between tumor volume and nD-LOR when QBI-FT was used (rs = -0.6; p = 0.056). A meticulous classification of the spatial relationship between the lesions and OR according to DTI-FT and QBI-FT was performed. The results indicated that the most prevalent orientations were the FT bundles located laterally and intrinsically in relation to the tumor. Compared with conventional DTI-FT, QBI-FT suggests reliable and more accurate results when correlated to preoperative VFDs and might be preferred for preoperative planning and intraoperative use of nearby lesions, particularly for those with larger volumes. A detailed analysis of localization, surgical approach together with QBI-FT and DTI-FT could reduce postoperative morbidity regarding VFDs. The display of HRFT techniques intraoperatively within the navigation system should be pursued for this issue.

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

Yokoyama procedure for esotropia associated with high myopia: real-world data from a large-scale multicentre analysis.

PURPOSE: High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far. METHODS: We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models. RESULTS: We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia. CONCLUSION: Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large-scale real-world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.

The Swinging Flashlight Test - Flawed Execution and Interpretation in Ophthalmological Routine. / Der Swinging-Flashlight-Test ­ mangelhafte Durchführung und Interpretation in der augenärztlichen Routine.

BACKGROUND: The swinging flashlight test is a standard diagnostic procedure to detect relative afferent pupillary defects. The advantages of the test lie within its objectivity and minimal effort. However, its value depends on its correct execution and interpretation. This questionnaire-based survey investigates whether this is given among German speaking ophthalmologists. METHODS: A multiple-choice questionnaire with 14 questions on the use of the swinging flashlight test was designed. It was presented to German speaking ophthalmology specialists (primary data) and orthoptists (secondary data) on specialist conferences or by telephone interviews. RESULTS: 249 ophthalmologists and 76 orthoptists participated in the survey. Only 2% of ophthalmologists answered all 14 questions correctly. On average 66% (range 29 - 100%) of the questions were answered correctly by the ophthalmologists. The question with the lowest result had a rate of 19%, the question with the highest result was correctly answered by 95%. The orthoptists achieved similar results. CONCLUSION: The rate of correct answers appears disturbingly low. The swinging flashlight test being a basic tool and an obligatory test in a number of guidelines should rather be performed nearly error-free. In light of the high error rates, misdiagnoses and treatment errors must be feared. Better training seems necessary.

Current Recommendations on Optic Neuritis. / Aktuelle Empfehlungen zur Optikusneuritis.

BACKGROUND: Optic neuritis is a special challenge to the ophthalmologist. It is a relatively frequent condition but difficult to seize morphologically. It has neurological implications and is subject matter of recent trials. METHODS: Selective literature search including the authors' professional experience. RESULTS: Practical aids for the ophthalmological management of optic neuritis are derived from the best available evidence and the recent literature is discussed. CONCLUSIONS: The present paper provides evidence-based recommendations for a safe handling of optic neuritis as well as information on current issues.

Consideration of eyeball length and prismatic side-effects of spectacle lenses in strabismus surgery-a randomised, double-blind interventional study.

PURPOSE: Potential sources of error in dosage planning in strabismus surgery are (a) prismatic side-effects of spectacle lenses when measuring the preoperative angle with the alternating prism cover test and (b) a potential influence of eye ball axial length on dose response. As both errors take effect in opposite directions, many strabismus surgeons set aside their consideration. This study investigates whether considering both factors for dosage planning yields better operative results. METHODS: In this prospective, randomised, double-blind, interventional pilot study, we included patients scheduled for purely horizontal strabismus surgery and determined each patient's surgical dose (total amount of recession/plication) either with (study group) or without (control) consideration of the two factors. The deviation of the resulting angle from the target angle 3 months postoperatively was the primary endpoint. RESULTS: One hundred one patients were included, 51 of which in the intervention group and 50 in the control group. The primary endpoint showed a median deviation from the target of 3.0° in the intervention group and 4.8° in the control group. We observed a group difference of 1.8° in favour of the intervention group (p = 0.053). Subgroup analysis showed a difference between groups of 2.2° for esotropic patients and of 5.1° for patients with hyperopia > + 2 D. CONCLUSION: Taking prismatic side-effects of spectacle lenses and eye ball length into account when calculating strabismus surgery doses showed a trend towards more accurate results. Esotropic patients and patients with hyperopia > + 2 D seemed to benefit most. TRIAL REGISTRATION: International Clinical Trials Registry Platform: DRKS00011121.

Visual evoked potential-based acuity assessment: overestimation in amblyopia.

BACKGROUND/AIMS: When visual acuity (VA) is assessed with spatially repetitive stimuli (e.g., gratings) in amblyopes, VA can be markedly overestimated. We evaluated to what extent this also applies to VEP-based objective acuity assessment, which typically uses gratings or checkerboards. METHODS: Seventeen subjects with amblyopia (anisometropic and strabismic) participated in the study; decimal VA range of their amblyopic eye covered 0.03-1.0 (1.5-0.0 logMAR). Using the Freiburg Acuity VEP (FrAVEP) method, checkerboard stimuli with six check sizes covering 0.02°-0.4° were presented in brief-onset mode (40 ms on, 93 ms off) at 7.5 Hz. All VEPs were recorded with a Laplacian montage. Fourier analysis yielded the amplitude and significance at the stimulus frequency. Psychophysical VA was assessed with the Landolt-C-based automated Freiburg Visual Acuity Test (FrACT). RESULTS: Test-retest limits of agreement for both FrACT and FrAVEP were ±0.20 logMAR. In all but two dominant eyes and high-acuity amblyopic eyes (VA<0.3 logMAR), FrACT and FrAVEP agreed within the expected limits of ±0.3 logMAR. However, the VEP-based acuity procedure overestimated single Landolt-C acuity by more than 0.3 logMAR in 9 of 17 (53%) of the amblyopic eyes, up to 1 logMAR. While all subjects had a psychophysical acuity difference>0.2 logMAR between the dominant and amblyopic eye, only three of them showed such difference with the FrAVEP. CONCLUSION: Both measurements of visual acuity with the VEP and FrACT were highly reproducible. However, as expected, in amblyopia, acuity can be markedly overestimated using the VEP. We attribute this to the use of repetitive stimulus patterns (checkerboards), which also lead to overestimation in psychophysical measures. The VEP-based objective assessment never underestimated visual acuity, but needs to be interpreted with appropriate caution in amblyopia.