Abstract: Background and Objective Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic neuritis and focused on conversions to multiple sclerosis (MS). Methods The TONE trial randomized 108 patients with acute optic neuritis but without previously known MS to either 33,000 IU EPO or placebo in conjunction with 1,000 mg methylprednisolone daily for 3 days. After reaching the primary end point at 6 months, we conducted an open-label follow-up 2 years after randomization. Results The follow-up was attended by 83 of 103 initially analyzed patients (81%). There were no previously unreported adverse events. The adjusted treatment difference of peripapillary retinal nerve fiber layer atrophy in relation to the fellow eye at baseline was 1.27 μm (95% CI −6.45 to 8.98, p = 0.74). The adjusted treatment difference in low-contrast letter acuity was 2.87 on the 2.5% Sloan chart score (95% CI −7.92 to 13.65). Vision-related quality of life was similar in both treatment arms (National Eye Institute Visual Functioning Questionnaire median score [IQR]: 94.0 [88.0 to 96.9] in the EPO and 93.4 [89.5 to 97.4] in the placebo group). The rate of multiple sclerosis-free survival was 38% in the placebo and 53% in the EPO group (hazard ratio: 1.67, 95% CI 0.96 to 2.88, p = 0.068). Discussion In line with the results at 6 months, we found neither structural nor functional benefits in the visual system of patients with optic neuritis as a clinically isolated syndrome, 2 years after EPO administration. Although there were fewer early conversions to MS in the EPO group, the difference across the 2-year window was not statistically significant. Classification of Evidence This study provides Class II evidence that for patients with acute optic neuritis, EPO as an adjunct to methylprednisolone is well tolerated and does not improve long-term visual outcomes. Trial Registration Information The trial was preregistered before commencement at clinicaltrials.gov (NCT01962571)

Abstract: Objective: To describe vascular changes in different stages of Stargardt disease (STGD) via double swept-source optical coherence tomography angiography. Methods and analysis: Prospective, cross-sectional case-control study. Twenty-three patients (45 eyes) with ABCA4 mutations graded according to the Fishman STGD classification and 23 controls (23 eyes) were included. Two independent investigators quantified the foveal avascular zone (FAZ) in the superficial and deep capillary plexus (SCP/DCP) and the areas presenting rarefied flow and complete vascular atrophy in the outer retina to choriocapillaris (ORCC) and choriocapillaris (CC) slab. Results: The mean age at first diagnosis of STGD was 24.0 years (range 9-50) and 37.9 years (range 18-74) at the time of examination. Eleven patients were assigned to the Fishman STGD classification stage (S) 1, three to S2, eight to S3 and one to S4. The FAZ in SCP and DCP was increased in all stages compared with controls (p0.01). Areas with rarefied flow signal and vascular atrophy were detected in the ORCC and the CC layer and grew with increasing stage of disease (p0.01). The duration of disease correlated with the extent of the enlarged FAZ in the SCP/DCP and with the area of reduced flow in the ORCC and CC layer (p

Abstract: 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

Abstract: Purpose: Idiopathic intracranial hypertension (IIH) leads to optic nerve head swelling and optic atrophy if left untreated. We wanted to assess an easy to perform volumetric algorithm to detect and quantify papilledema in comparison to retinal nerve fiber layer (RNFL) analysis using optical coherence tomography (OCT). Methods: Participants with and without IIH underwent visual acuity testing at different contrast levels and static perimetry. Spectralis-OCT measurements comprised standardimaging of the peripapillary RNFL and macular ganglion cell layer (GCL). The optic nerve head volume (ONHV) was determined using the standard segmentation software and the 3.45 mm early treatment diabetic retinopathy study (ETDRS) grid, necessitatingmanual correctionwithin Bruch membrane opening. Three neuro-ophthalmologists graded fundus images according to the Frisen scale. A mixed linear model (MLM) was used to determine differences between study groups. Sensitivity and specificity was evaluated using the area under the receiver-operating characteristic (ROC). Results: Twenty-one patients with IIH had an increased ONHV of 6.46 } 2.36 mm3 as compared to 25 controls with 3.20 } 0.25 mm3 (P 0.001). The ONHV cutoff distinguishing IIH from controls was 3.97 mm3 (i.e. no patient with IIH had an ONHV below and no healthy individual above this value). The area under the curve (AUC) for ONHV was 0.99 and for the RNFL at 3.5 mm 0.90. The Frisen scale grading correlated higher with the ONHV (r = 0.90) than with the RNFL thickness (r = 0.68). ONHV measurements were highly reproducible in both groups (coefficient of variation 0.01%).

Abstract: Hintergrund Die endokrine Orbitopathie ist die häufigste extrathyreoidale Manifestation des Morbus Basedow und tritt bei schätzungsweise 25-50 % der betroffenen Patienten auf. Krankheitsbedingt kommt es zu einer entzündlichen Schwellung der Orbitaweichteile. Die Behandlung erfolgt meist konservativ. Bei schweren Fällen mit beeinträchtigendem Exophthalmus oder akuter, steroidrefraktärer Visusbedrohung kann eine chirurgische Orbitadekompression die Beschwerden der Patienten lindern oder das Sehvermögen erhalten. Ein wesentlicher Aspekt der Versorgungsqualität besteht in der Vermeidung postoperativer Doppelbilder. Ziel der Arbeit Erfahrungs- und Ergebnisbericht von 100 chirurgischen Orbitadekompressionen bei 62 Patienten an einem interdisziplinären Orbitazentrum. Patienten mit Kompression der Orbitaspitze wurden mittels pterionaler Dekompression behandelt. Patienten ohne Hinweise auf Orbitaspitzenbeteiligung wurden mittels tiefer lateraler Wandresektion oder pterionaler Dekompression behandelt. Methodik Retrospektive Datenanalyse. Ergebnisse Die mittlere Exophthalmusreduktion betrug 2,9 mm. Augen mit visusbedrohendem Schweregrad gewannen im Mittel 2,2 Zeilen an Sehschärfe, der Visus bei rehabilitativer Indikation blieb stabil. Die Komplikationsrate betrug 4 %. Neue Doppelbilder wurden nach 2 Eingriffen beobachtet. Bei einem Patienten kam es zu einer Visusminderung von 0,8 auf 0,1. In 9 Fällen führte die Operation zu einem vollständigen Rückgang zuvor beklagter Doppelbilder. Diskussion Visusgewinn, Exophthalmusreduktion und Komplikationsrate sind in diesem Kollektiv vergleichbar mit zuvor publizierten Arbeiten. Diese Studie bestätigt die Rolle der Orbitadekompression bei visusbedrohender und schwer beeinträchtigender endokriner Orbitopathie