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.

Eye Movements But Not Vision Drive the Development of Palisade Endings.

Purpose: To test whether visual experience and/or eye movements drive the postnatal development of palisade endings in extraocular muscles. Methods: In three newborn cats, the right eye was covered until 30 days from postnatal (P) day 7 (before opening their eyes), and in three cats both eyes were covered until 45 days, also from P7. To block eye movements, another seven cats received a retrobulbar injection of botulinum neurotoxin A (BoNT-A) into the left orbit at birth and survived for 45 days (three cats) and 95 days (four cats). The distal third of the rectus muscles containing the palisade endings was used for whole-mount preparation and triple-fluorescence labeling with anti-neurofilament along with (1) anti-synaptophysin and phalloidin or (2) anti-growth associated protein 43 (GAP43) and phalloidin. Immunolabeled specimens were analyzed in the confocal laser scanning microscope. Results: After unilateral and bilateral dark rearing, palisade endings were qualitatively and quantitatively equal to those from age-matched controls. After BoNT-A induced eye immobilization for 45 or 95 days, palisade endings were absent in the superior rectus and lateral rectus muscles and only present in the inferior rectus and medial rectus muscle. These BoNT-A-treated palisade endings were rudimentary and reduced in number, and the expression of the neuronal developmental protein GAP43 was significantly reduced. Conclusions: This study demonstrates that eye immobilization, but not visual deprivation, affects palisade ending development. Palisade endings develop in the first month of life, and the present findings indicate that, during this time window, palisade endings are prone to oculomotor perturbations.

Cone-Beam Computed Tomography (CBCT) dacryocystography for imaging of the nasolacrimal duct system.

PURPOSE: To evaluate the usefulness and safety of cone-beam computed tomography (CBCT) dacryocystography in detecting lesions, identifying coexisting soft-tissue changes and determining treatment options in patients with epiphora. PATIENTS AND METHODS: Unilateral digital subtraction dacryocystography and CBCT dacryocystography were carried out on 45 patients. Stenoses and occlusions were identified and coexisting changes such as septal deviation and dacryoliths were noted. The diameter of the bony lacrimal duct of affected and unaffected side was measured and related to the clinically evident epiphora. An attempt was made to base the subsequent therapeutic planning on the CBCT dacryocystographic findings. Additionally, the radiation dose levels for CBCT dacryocystography in comparison to those of multislice computed tomography (MSCT) were evaluated in a standardized head-neck Rando-Alderson phantom. RESULTS: Nasolacrimal duct obstructions were present in 37/45 patients, 18 with a stenosis and 19 with an occlusion in parts of the lacrimal outflow system. The minimal bony diameter of the side with epiphora was significantly decreased compared to the unaffected side. Coexisting soft-tissue changes did not correlate significantly with the clinical sign of epiphora. Eight patients showed no underlying reason for the epiphora and were treated conservatively. A total of eleven patients received interventional therapy for their stenosis and 23 patients had to be treated surgically. A further three patients received medical treatment for infection, before surgery and interventional therapy, respectively, were carried out. Dose levels for CBCT imaging remained far below those of MSCT. CONCLUSION: CBCT dacryocystography is a safe and time-efficient modality for assessing the nasolacrimal duct system in patients with epiphora. CBCT dacryocystography provides detailed images of the nasolacrimal drainage system, surrounding soft tissue, and bony structures in one diagnostic tour. It allows clear measurement of the bony nasolacrimal duct and displays information beyond that of the drainage lumen, improving the planning of therapeutic interventional and surgical procedures.