Deep Learning to Discriminate Arteritic From Nonarteritic Ischemic Optic Neuropathy on Color Images.

Importance: Prompt and accurate diagnosis of arteritic anterior ischemic optic neuropathy (AAION) from giant cell arteritis and other systemic vasculitis can contribute to preventing irreversible vision loss from these conditions. Its clinical distinction from nonarteritic anterior ischemic optic neuropathy (NAION) can be challenging, especially when systemic symptoms are lacking or laboratory markers of the disease are not reliable. Objective: To develop, train, and test a deep learning system (DLS) to discriminate AAION from NAION on color fundus images during the acute phase. Design, Setting, and Participants: This was an international study including color fundus images of 961 eyes of 802 patients with confirmed AAION and NAION. Training was performed using images from 21 expert neuro-ophthalmology centers in 16 countries, while external testing was performed in a cohort from 5 expert neuro-ophthalmology centers in the US and Europe. Data for training and external testing were collected from August 2018 to January 2023. A mix of deidentified images of 2 fields of view (optic disc centered and macula centered) were used. For training and internal validation, images were from 16 fundus camera models with fields of 30° to 55°. For external testing, images were from 5 fundus cameras with fields of 30° to 50°. Data were analyzed from January 2023 to January 2024. Main Outcomes and Measures: The performance of the DLS was measured using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: In the training and validation sets, 374 (54.9%) of patients were female, 301 (44.2%) were male, and 6 (0.9%) were of unknown sex; the median (range) age was 66 (23-96) years. When tested on the external dataset including 121 patients (35 [28.9%] female, 44 [36.4%] male, and 42 [34.7%] of unknown sex; median [range] age, 69 [37-89] years), the DLS achieved an AUC of 0.97 (95% CI, 0.95-0.99), a sensitivity of 91.1% (95% CI, 85.2-96.9), a specificity of 93.4% (95% CI, 91.1-98.2), and an accuracy of 92.6% (95% CI, 90.5-96.6). The accuracy of the 2 experts for classification of the same dataset was 74.3% (95% CI, 66.7-81.9) and 81.6% (95% CI, 74.8-88.4), respectively. Conclusions and Relevance: A DLS showing disease-specific averaged class-activation maps had greater than 90% accuracy at discriminating between acute AAION from NAION on color fundus images, at the eye level, without any clinical or biomarker information. A DLS that identifies AAION could improve clinical decision-making, potentially reducing the risk of misdiagnosis and improving patient outcomes.

Multifocal Optics for Myopia Control.

The rising prevalence of myopia among children and adolescents necessitates effective interventions to mitigate long-term risks, such as retinal detachment and macular degeneration. Traditional approaches like undercorrection with single-vision lenses have proven ineffective. Recent research underscores the significance of peripheral vision in managing myopia progression. While hyperopic defocus in the peripheral retina may encourage axial elongation, multifocal lenses designed to induce peripheral myopic defocus can potentially curb this elongation. Randomized controlled trials (RCTs) have demonstrated that spectacle lenses with peripheral modifications, such as highly aspherical lenslets (HAL) or defocus incorporated multiple segments (DIMS), reduce myopia progression and axial elongation over 2 years. Similarly, multifocal contact lenses, especially those with high-add power (+ 2.50 D), have shown comparable reductions over 3 years. Safety is a critical consideration in myopia control. Multifocal spectacle lenses with peripheral plus designs are generally well tolerated, with only transient side effects, like dizziness and blurred vision. Soft multifocal contact lenses also exhibit a favorable safety profile, with low rates of serious adverse events. Thorough monitoring and reporting in these studies are essential to provide assurance about the safety of these interventions for children. Future research should aim to include more diverse populations in order to ensure the generalizability of findings across various demographic groups. Additionally, real-world data would offer valuable insights into the performance of these treatments in everyday scenarios. Observational studies, less influenced by industry sponsorship, could further validate these findings. Lastly, the clinical significance of the observed effects should be critically assessed to confirm that the reported benefits lead to meaningful reductions in myopia progression.

Heterophoria in multiple sclerosis patients: a proof of principle cross-sectional study.

Objectives: The pathophysiology of multiple sclerosis (MS) involves inflammatory neurodegeneration in the brainstem, cerebellum, and retina. The clinical relevance of oculomotor involvement in MS, however, remains uncertain. Methods: In this cross-sectional study, we evaluated heterophoria as a (sub)clinical tool in 54 MS patients and 55 age-matched healthy controls (HCs). We quantified heterophoria in prism diopters for distance and near range with orthoptic examination. Our primary outcome was high degrees of horizontal heterophoria (HDHH) defined as measurements beyond ±2 standard deviations from the mean prism diopter of heterophoria of our HCs. Results: More than one-third (37%, n=20/54) of MS patients but only 11% (n=6/55) of HCs were classified as HDHH [distance, MS=9% (n=5/54) versus HC=6% (n=3/55); near, MS=19% (n=10/54) versus HC=5% (n=3/55)]. Our MS patients presented more combined vertical and horizontal deviations at near range [MS 19% (n=10/54) versus for HC 7% (n=4/55)]. We observed the combination of HDHH both at distance and at near testing in 9% (n=5/54) of MS patients but not at all in HCs (n=0/55). Discussion: Despite the high prevalence of heterophoria, HDHH may be an additional (sub)clinical tool of subclinical involvement in MS. Thus, orthoptic examination may be an additional tool to improve MS diagnostic procedures.

A Deep Learning Approach for Accurate Discrimination Between Optic Disc Drusen and Papilledema on Fundus Photographs.

BACKGROUND: Optic disc drusen (ODD) represent an important differential diagnosis of papilledema caused by intracranial hypertension, but their distinction may be difficult in clinical practice. The aim of this study was to train, validate, and test a dedicated deep learning system (DLS) for binary classification of ODD vs papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs collected in a large international multiethnic population. METHODS: This retrospective study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External testing was performed on an independent data set (221 patients), including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study. RESULTS: The DLS could accurately distinguish between all ODD and papilledema (all severities included): area under the receiver operating characteristic curve (AUC) 0.97 (95% confidence interval [CI], 0.96-0.98), accuracy 90.5% (95% CI, 88.0%-92.9%), sensitivity 86.0% (95% CI, 82.1%-90.1%), and specificity 94.9% (95% CI, 92.3%-97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90-0.96), accuracy 84.2% (95% CI, 80.2%-88.6%), sensitivity 78.4% (95% CI, 72.2%-84.7%), and specificity 91.3% (95% CI, 87.0%-96.4%). CONCLUSIONS: A dedicated DLS can accurately distinguish between ODD and papilledema caused by intracranial hypertension, even when considering buried ODD vs mild-to-moderate papilledema.

Ophthalmological research in Germany: suggestions by an international expert panel.

PURPOSE: To evaluate the research performance in ophthalmology in Germany based on the findings of the recent research map of the German Ophthalmological Society (DOG) and to suggest strategies for future improvements on a national level both to DOG as well as to politics. The focus is on preclinical and translational clinical research. METHODS: International expert panel evaluation and discussion organized by the Task Force Research of the German Ophthalmological Society (DOG). RESULTS: The international view on the German ophthalmological research landscape was generally positive. The value for money relationship was judged as very good. As Germany is facing an aging society and vision impairment will create an ever-increasing socioeconomic burden, the reviewers suggested several lines of future activities: an increased activity of securing intellectual property, more lay audience lobbying, intensified collaboration and critical mass building between "lighthouses" of ophthalmic research in Germany, as well as the establishment of a German national eye institute equivalent. CONCLUSION: The ophthalmological research performance in Germany was rated to be very good by an international expert panel. Nonetheless significant improvements were requested in the fields of translation (clinical trials, IP), synergy between specialized institutions and governmental funding for a German center for eye research.

[Ophthalmological research in Germany: evaluation by an international expert panel]. / Ophthalmologische Forschung in Deutschland: Evaluation durch ein internationales Expertengremium.

PURPOSE: To evaluate the research performance in ophthalmology in Germany based on the findings of the recent research map of the German Ophthalmological Society ( DOG) and to suggest strategies for future improvements on a national level both to DOG as well as to politics. The focus is on preclinical and translational clinical research. METHODS: International expert panel evaluation and discussion organized by the Task Force Research of the German Ophthalmological Society (DOG). RESULTS: The international view on the German ophthalmological research landscape was generally positive. The value for money relationship was judged as very good. As Germany is facing an aging society and vision impairment will create an ever-increasing socioeconomic burden, the reviewers suggested several lines of future activities: an increased activity of securing intellectual property, more lay audience lobbying, intensified collaboration and critical mass building between "lighthouses" of ophthalmic research in Germany, as well as the establishment of a German national eye institute equivalent. CONCLUSION: The ophthalmological research performance in Germany was rated to be very good by an international expert panel. Nonetheless significant improvements were requested in the fields of translation (clinical trials, IP), synergy between specialized institutions and governmental funding for a German center for eye research.

Retinopathy of prematurity in Germany over 13 years: incidences, treatment preferences and effects of national guideline changes.

OBJECTIVE: Retinopathy of prematurity (ROP) is a leading yet avoidable cause of childhood blindness. Screening for ROP is highly effective in preventing blindness secondary to ROP. We provide epidemiological data on ROP screening and treatment in Germany since 2010 and evaluate the effects of recently adopted as well as potential future screening guideline adaptations. METHODS: Data sets of the German Quality Assurance Procedure in Neonatology, the ROP screening programme of two German university hospitals, and the German section of the EU-ROP Registry were analysed. RESULTS: Over the 13-year period from 2010 to 2022, 141 550 infants received ROP screening in Germany. Mean annual incidences of ROP were 3.5% (±0.2%) in premature infants and 19.6% (±2.3%) in screened infants. Of screened infants, 2.0% (±0.3%) received treatment for ROP. Treatment preferences shifted from laser coagulation (46.2% in 2015) to anti-vascular endothelial growth factor therapy (83.7% in 2022). A revision of national screening criteria in 2020 with a reduction of the gestational age limit from <32 to <31 weeks resulted in a decrease of the annual number of infants requiring screening by 25.8% (p<0.001). Infants with a birth weight ≥1500 g accounted for 35.2% of the screening population but only for 0.4% of ROP stage 3-5 cases. CONCLUSIONS: Collection of epidemiological data on ROP in national and international registries enables the continuous surveillance and adaptation of ROP screening and treatment criteria. In Germany, infants with a birth weight ≥1500 g have a very low risk of developing treatment-requiring ROP, supporting an upper birth weight limit for ROP screening.

Disease Course of Clinically Isolated Optic Neuritis.

BACKGROUND AND OBJECTIVES: Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of visual pathway neuroprotection trials. METHODS: This is a secondary analysis of longitudinal data from the TONE trial, which included 103 patients from 12 German academic tertiary centers with acute unilateral optic neuritis as a clinically isolated syndrome and baseline high-contrast visual acuity <0.5 decimal. Patients were randomized to 1,000 mg methylprednisolone i.v./d plus either erythropoietin (33,000 IU/d) or placebo (saline solution) for 3 days. They were followed up at standardized intervals with a battery of tests including high-contrast visual acuity, low-contrast letter acuity, contrast sensitivity, visual fields, visual evoked potentials, and retinal optical coherence tomography. At 6 months, participants answered a standardized questionnaire on vision-related quality of life (NEI-VFQ 25). We describe the disease course with mixed-effects piecewise linear models and calculate structure-function correlations using Pearson r. Because erythropoietin had no effect on the visual system, we use pooled (treatment-agnostic) data. RESULTS: Patients experienced initial rapid and then decelerating improvements of visual function with thinning of inner and thickening of outer retinal layers. At 6 months, visual parameters were positively correlated with inner and negatively correlated with outer retinal thickness changes. Peripapillary retinal nerve fiber layer thinning predominantly occurred in sectors without previous swelling. At 6 months, macular ganglion cell and inner plexiform layer thinning was weakly correlated with the P100 peak time (r = -0.11) and moderately correlated with the amplitude of visual evoked potentials (r = 0.35). Only functional outcomes were at least moderately correlated with vision-related quality of life. DISCUSSION: The longitudinal data from this large study cohort may serve as a reference for the clinical course of acute optic neuritis. The pattern of correlation between visual evoked potentials and inner retinal thinning may argue that the latter is mostly due to ganglion cell loss, rather than dysfunction. Visual pathway neuroprotection trials with functional outcomes are needed to confirm that candidate drugs will benefit patients' vision-related quality of life. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov, NCT01962571.

Clinical value of neuroimaging indicators of intracranial hypertension in patients with cerebral venous thrombosis.

PURPOSE: Intracranial hypertension (IH) frequently complicates cerebral venous thrombosis (CVT). Distinct neuroimaging findings are associated with IH, yet their discriminative power, reversibility and factors favoring normalization in prospective CVT patients are unknown. We determined test performance measures of neuroimaging signs in acute CVT patients, their longitudinal change under anticoagulation, association with IH at baseline and with recanalization at follow-up. METHODS: We included 26 consecutive acute CVT patients and 26 healthy controls. Patients were classified as having IH based on CSF pressure > 25 cmH2O and/or papilledema on ophthalmological examination or ocular MRI. We assessed optic nerve sheath diameter (ONSD), optic nerve tortuousity, bulbar flattening, lateral and IVth ventricle size, pituitary configuration at baseline and follow-up, and their association with IH and venous recanalization. RESULTS: 46% of CVT patients had IH. ONSD enlargement > 5.8 mm, optic nerve tortuousity and pituitary grade ≥ III had highest sensitivity, ocular bulb flattening and pituitary grade ≥ III highest specificity for IH. Only ONSD reliably discriminated IH at baseline. Recanalization was significantly associated with regressive ONSD and pituitary grade. Other neuroimaging signs tended to regress with recanalization. After treatment, 184.9 ± 44.7 days after diagnosis, bulbar flattening resolved, whereas compared with controls ONSD enlargement (p < 0.001) and partially empty sella (p = 0.017), among other indicators, persisted. CONCLUSION: ONSD and pituitary grading have a high diagnostic value in diagnosing and monitoring CVT-associated IH. Given their limited sensitivity during early CVT and potentially persistent alterations following IH, neuroimaging indicators can neither replace CSF pressure measurement in diagnosing IH, nor determine the duration of anticoagulation.

Visual Pathway Outcomes Based on Sample Size in Clinical Neuroprotection Research.

This cohort study calculates clinical trial sample sizes powered by visual pathway outcomes of acute optic neuritis in neuroprotection research.

The Freiburg Acuity Test in Preschool Children: Testability, Test-Retest Variability, and Comparison With LEA Symbols.

Purpose: To determine the testability, performance, and test-retest variability (TRV) of visual acuity (VA) assessment using the Freiburg Visual Acuity Test (FrACT) compared to the LEA Symbols Test (LEA) in preschool children. Methods: In 134 preschool children aged 3.0 to 6.8 years, monocular VA of each eye was measured twice with a four-orientation Landolt C version of the FrACT and once with the LEA. FrACT runs were preceded by a binocular run for explanatory purposes. Test order alternated between subjects. Optotypes were presented on a computer monitor (FrACT) or on cards (LEA) at a distance of 3 m. Results: Overall, 68% completed the FrACT (91/134 children) and 88% completed the LEA (118/134 children). Testability depended on age: FrACT, 19% (<4 years) and 87% (≥4 years); LEA, 70% (<4 years) and 95% (≥4 years). Mean ± SD VA difference between tests was 0.11 ± 0.19 logarithm of the minimum angle of resolution [logMAR], with LEA reporting better acuity. The difference depended on age (0.27 ± 0.23 logMAR [<4 years], 0.09 ± 0.18 logMAR [≥4 years], P < 0.001) and on test sequence (higher age dependence of FrACT VAs for LEA first, P < 0.001). The 95% limits of agreement for the FrACT TRV were ±0.298 logMAR. Conclusions: The examiner-independent FrACT, using international reference Landolt C optotypes, can be used to assess VA in preschool children aged ≥4 years, with reliability comparable to other pediatric VA tests. Translational Relevance: Use of the automated FrACT for VA assessment in preschool children may benefit objectivity and validity as it is a computerized test and employs the international reference Landolt C optotype.

ZEISS PLEX Elite 9000 Widefield Optical Coherence Tomography Angiography as Screening Method for Early Detection of Retinal Hemangioblastomas in von Hippel-Lindau Disease.

Purpose: To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting. Methods: We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods. The underlying causes for the lack of detection were investigated. Results: In 91 eyes (48 patients), 67 RHs were observed (mean, 0.74 ± 1.59 RH per eye). FA was performed in eight eyes. Ophthalmoscopy overlooked 25 of the 35 RHs detected by wOCTA (71.4%) due to the background color of the choroid (n = 5), small tumor size (n = 13), masking by a bright fundus reflex (n = 2), and masking by surrounding retinal scars (n = 5). However, wOCTA missed 29 RHs due to peripheral location (43.3%). The overall detection rates were up to 37% on the basis of ophthalmoscopy alone, up to 52% for wOCTA, and 89% for FA. Within the retinal area covered by wOCTA, the detection rates were up to 46.7% for ophthalmoscopy alone, up to 92.1% for wOCTA, and 73.3% for FA. Conclusions: The overall low detection rate of RHs using wOCTA is almost exclusively caused by its inability to visualize the entire peripheral retina. Therefore, in unclear cases, FA is necessary after ophthalmoscopy. Translational Relevance: Within the imageable retinal area, wOCTA shows a high detection rate of RHs and therefore may be suitable to improve screening for RHs in VHLD.

Interrelation Between Cerebrospinal Fluid Pressure, Intracranial Morphology and Venous Hemodynamics Studied by 4D Flow MRI.

PURPOSE: To quantify the effects of CSF pressure alterations on intracranial venous morphology and hemodynamics in idiopathic intracranial hypertension (IIH) and spontaneous intracranial hypotension (SIH) and assess reversibility when the underlying cause is resolved. METHODS: We prospectively examined venous volume, intracranial venous blood flow and velocity, including optic nerve sheath diameter (ONSD) as a noninvasive surrogate of CSF pressure changes in 11 patients with IIH, 11 age-matched and sex-matched healthy controls and 9 SIH patients, before and after neurosurgical closure of spinal dural leaks. We applied multiparametric MRI including 4D flow MRI, time-of-flight (TOF) and T2-weighted half-Fourier acquisition single-shot turbo-spin echo (HASTE). RESULTS: Sinus volume overlapped between groups at baseline but decreased after treatment of intracranial hypotension (p = 0.067) along with a significant increase of ONSD (p = 0.003). Blood flow in the middle and dorsal superior sagittal sinus was remarkably lower in patients with higher CSF pressure (i.e., IIH versus controls and SIH after CSF leak closure) but blood flow velocity was comparable cross-sectionally between groups and longitudinally in SIH. CONCLUSION: We were able to demonstrate the interaction of CSF pressure, venous volumetry, venous hemodynamics and ONSD using multiparametric brain MRI. Closure of CSF leaks in SIH patients resulted in symptoms suggestive of increased intracranial pressure and caused a subsequent decrease of intracranial venous volume and of blood flow within the superior sagittal sinus while ONSD increased. In contrast, blood flow parameters from 4D flow MRI did not discriminate IIH, SIH and controls as hemodynamics at baseline overlapped at most vessel cross-sections.

Treated Cases of Retinopathy of Prematurity in Germany: 10-Year Data from the Retina.net Retinopathy of Prematurity Registry.

PURPOSE: To analyze changes in demographic parameters and retreatment patterns over a 10-year period in a clinical routine setting of infants with retinopathy of prematurity (ROP) requiring treatment documented in the German Retina.net ROP registry. DESIGN: Multicenter, noninterventional, observational registry study recruiting patients treated for ROP. SUBJECTS: A total of 692 eyes of 353 infants treated for ROP were documented in the Retina.net ROP registry over a 10-year period between 2011 and 2020. These cases cover about 15% of all infants treated for ROP in Germany. METHODS: The Retina.net ROP registry was established in 2012 to jointly collect information on infants treated for ROP. The database collects information on demographic parameters (gestational age [GA], birth weight, neonatal comorbidities) as well as treatment parameters (type of treatment, weight and age at treatment, and stage of ROP). A total of 19 centers contributed to the analysis. This is the 10-year analysis of data from 2011 to 2020, in which we focus on changes over time regarding the respective parameters. MAIN OUTCOME MEASURES: Changes over time in demographic parameters and treatment patterns for ROP in Germany. RESULTS: The overall incidence of treatment requiring ROP was 3.5% of all infants screened for ROP at participating centers. Gestational age, weight at birth, and weight at treatment remained stable over the 10-year period, whereas postmenstrual and postnatal age at treatment increased moderately but statistically significantly over the years. The most prevalent ROP severity stage at treatment was stage 3+ in zone II (76.6% of all treated eyes). Treatment patterns changed considerably from predominantly laser treatments in 2011 (75% of all treated eyes) to predominantly ranibizumab treatments in 2020 (60.9% of all treated eyes). The overall retreatment rate was 15.6%. Retreatment rates differed between initial treatment modalities (14.1% after laser coagulation, 12% after bevacizumab and 24.5% after ranibizumab). Treatment-associated systemic or ophthalmic complications were rare. CONCLUSIONS: This data analysis represents one of the largest documented cohorts of infants treated for ROP. The data on demographic parameters and treatment patterns provide useful information for further improvement of ROP management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Computer-Assisted Visual Training in Children and Adolescents with Developmental Visual Disorders.

BACKGROUND: In this systematic review, we address the question whether children and adolescents with developmental visual disorders benefit from computer-assisted visual training. METHODS: Systematic literature searches were carried out in three bibliographic databases (initial search in October 2021) and trial registries. Included were randomized controlled trials that evaluated the efficacy of computer-assisted visual training in children and adolescents with developmental visual disorders in comparison to no training, sham training, or conservative treatment. RESULTS: The inclusion criteria were met by 17 trials (with a total of 1323 children and adolescents) focusing on binocular or monocular computer-assisted visual training for the treatment of amblyopia. In these trials, visual training was carried out for 2 to 24 weeks, either as "stand alone" therapy or in addition to occlusion therapy. Six trials showed a statistically significant difference in favor of the visual training for the outcome "best corrected visual acuity of the amblyopic eye." However, this difference was small and mostly below the threshold of clinical relevance of -0.05 logMAR (equivalent to an improvement of 0.5 lines on the eye chart, or 2.5 letters per line). Only few data were available for the outcomes "binocular vision" and "adverse events"; the differences between the groups were similarly small. CONCLUSION: The currently available data do not permit any firm conclusions regarding the efficacy of visual training in children and adolescents with amblyopia. Moreover, treatment adherence was often insufficient and the treatment durations in the trials was relatively short. No results from randomized trials have yet been published with respect to other developmental visual disorders (refractive errors, strabismus).

[Conjunctival tumors in children : Histopathological diagnoses in 262 cases]. / Bindehauttumoren bei Kindern : Histopathologische Diagnosen in 262 Fällen.

BACKGROUND: The spectrum of conjunctival tumors in children and adolescents significantly differs from that of adults. OBJECTIVE: The aim of this study was to show the distribution of histopathological diagnoses of pediatric conjunctival tumors. MATERIAL AND METHODS: Retrospective case series including all conjunctival tumors of children and adolescents under 18 years of age examined histologically over a period of 25 years (1990-2015) at the Eye Center in Freiburg, Germany. RESULTS: Among the 262 conjunctival specimens, the most common diagnoses were conjunctival nevi (148, [56%]), most often with junctional activity (106/148, [72%]), pyogenic granulomas (26, [10%]), and dermolipomas (18, [7%]). In one case a malignant tumor (conjunctival melanoma) was detected (1, < 1%). CONCLUSION: The results suggest that pediatric conjunctival tumors are benign in most cases. Most of them were of melanocytic origin, with a junctional conjunctival nevus being the most common diagnosis.

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.

Treatment With Erythropoietin for Patients With Optic Neuritis: Long-term Follow-up.

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).

[Glaucoma in infancy and childhood]. / Glaukom im Säuglings- und Kindesalter.

Glaucoma in infancy and childhood is a rare disease. An immediate diagnosis and treatment are absolutely necessary to prevent blindness of affected children. Childhood glaucoma is characterized by a heterogeneous phenotype: besides primary congenital glaucoma, secondary types often exist and the individualized treatment requires an experienced interdisciplinary team. The pathogenesis is not always discernible and genetic alterations sometimes cause the disease. A surgical procedure is usually necessary to lower the intraocular pressure. Refractive and orthoptic care are equally important to avoid amblyopia. This article gives an overview of childhood glaucoma and outlines the most important diagnostic and therapeutic aspects.