Association of sleep traits with myopia in children and adolescents: A meta-analysis and Mendelian randomization study.

PURPOSE: The association between sleep and myopia in children and adolescents has been reported, yet it remains controversial and inconclusive. This study aimed to investigate the influence of different sleep traits on the risk of myopia using meta-analytical and Mendelian randomization (MR) techniques. METHODS: The literature search was performed in August 31, 2023 based on PubMed, Embase, Web of Science, and Cochrane library. The meta-analysis of observational studies reporting the relationship between sleep and myopia was conducted. MR analyses were carried out to assess the causal impact of genetic pre-disposition for sleep traits on myopia. RESULTS: The results of the meta-analysis indicated a significant association between the risk of myopia and both short sleep duration [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.08-1.42, P = 0.003] and long sleep duration (OR = 0.75, 95% CI = 0.66-0.86, P < 0.001). MR analyses revealed no significant causal associations of genetically determined sleep traits with myopia, including chronotype, sleep duration, short sleep duration and long sleep duration (all P > 0.05). CONCLUSIONS: No evidence was found to support a causal relationship between sleep traits and myopia. While sleep may not independently predict the risk of myopia, the potential impact of sleep on the occurrence and development of myopia cannot be disregarded.

Applications of artificial intelligence-enabled robots and chatbots in ophthalmology: recent advances and future trends.

PURPOSE OF REVIEW: Recent advances in artificial intelligence (AI), robotics, and chatbots have brought these technologies to the forefront of medicine, particularly ophthalmology. These technologies have been applied in diagnosis, prognosis, surgical operations, and patient-specific care in ophthalmology. It is thus both timely and pertinent to assess the existing landscape, recent advances, and trajectory of trends of AI, AI-enabled robots, and chatbots in ophthalmology. RECENT FINDINGS: Some recent developments have integrated AI enabled robotics with diagnosis, and surgical procedures in ophthalmology. More recently, large language models (LLMs) like ChatGPT have shown promise in augmenting research capabilities and diagnosing ophthalmic diseases. These developments may portend a new era of doctor-patient-machine collaboration. SUMMARY: Ophthalmology is undergoing a revolutionary change in research, clinical practice, and surgical interventions. Ophthalmic AI-enabled robotics and chatbot technologies based on LLMs are converging to create a new era of digital ophthalmology. Collectively, these developments portend a future in which conventional ophthalmic knowledge will be seamlessly integrated with AI to improve the patient experience and enhance therapeutic outcomes.

Chord mu and chord alpha as postoperative predictors in multifocal intraocular lens implantation.

PURPOSE: With the aging population, the prevalence of presbyopia and the popularity of multifocal intraocular lenses is also growing worldwide. Unfortunately, in some cases, they are still associated with postoperative visual disturbances. Recent literature started to evaluate angle kappa- and angle alpha-derived metrics of chord mu and chord alpha as possible predictive values for visual outcomes after multifocal intraocular lens implantation but the published results are inconsistent between studies. Thus, this article aims to review the role of chord mu and chord alpha as postoperative predictors after multifocal intraocular lens implantation and lay the foundation for further research. METHODS: Relevant articles were identified using the following keywords: "presbyopia," "multifocal intraocular lens," "angle kappa," "angle alpha," "Chord mu," and "Chord alpha" up to June 2022. An attempt was made to present the majority of publications that addressed the topic. CONCLUSIONS: Chord mu and chord alpha have a predictive role on the outcomes after multifocal intraocular lens implantation but to a different extent. Cataract surgeons should take them into consideration and avoid implanting a multifocal intraocular lens for patients with speculated critical values of chord mu and alpha above 0.5-0.6 mm, depending on the device used for measurement and the multifocal intraocular lens implanted. Currently, chord alpha seems to be a more stable, more widely applicable, and reliable determinant in predicting postoperative outcomes and in patient selection prior to multifocal intraocular lens implantation when compared to chord mu. To draw conclusions on the topic, a controlled study is needed.

Subthreshold laser treatment in retinal diseases: a mini review.

PURPOSE: To summarize the mechanism and the clinical applications of subthreshold laser (STL) in retinal practice. Subthreshold or "non-destructive" laser includes all types of laser treatments that produce minimal or no damage to the tissues and no visible signs after application. METHODS: A descriptive review of articles from literature databases (PubMed, Medline, Embase, Cochrane, Web of Science) published before August 2023, which discuss current STL treatments of retinal diseases. RESULTS: This review provides evidence for STL as a treatment option for central serous chorioretinopathy, diabetic retinopathy, age-related macular degeneration, macular edema due to retinal vein occlusion, and other maculopathies. In most published reports, STL has shown a therapeutic effect without damage to the underlying tissue. CONCLUSION: Subthreshold laser treatment has shown safety and efficacy in the management of some retinal and macular diseases. Stimulation of the retinal pigment epithelium without destroying adjacent neuroretina has been shown to be sufficient in inducing retinal repair in many clinical cases. Recent research and clinical studies continue to explore the mechanisms and improving therapeutic benefits of this technology as well as extend the range of retinal disorders treatable by this modality.

Fragility and Tendency to Crystallization for Structurally Related Compounds.

The present study was designed to investigate the physical stability of three organic materials with similar chemical structures. The examined compounds revealed completely different crystallization tendencies in their supercooled liquid states and were classified into three distinct classes based on their tendency to crystallize. (S)-4-Benzyl-2-oxazolidinone easily crystallizes during cooling from the melt; (S)-4-Benzylthiazolidine-2-thione does not crystallize during cooling from the melt, but crystallizes easily during subsequent reheating above Tg; and (S)-4-Benzyloxazolidine-2-thione does not crystallize either during cooling from the melt or during reheating. Such different tendencies to crystallize are observed despite the very similar chemical structures of the compounds, which only differ in oxide or sulfur atoms in one of their rings. We also studied the isothermal crystallization kinetics of the materials that were shown to transform into a crystalline state. Molecular dynamics and thermal properties were thoroughly investigated using broadband dielectric spectroscopy, as well as conventional and temperature-modulated differential scanning calorimetry in the wide temperature range. It was found that all three glass formers have the same dynamic fragility (m = 93), calculated directly from dielectric structural relaxation times. This result verifies that dynamic fragility is not related to the tendency to crystallize. In addition, thermodynamic fragility predictions were also made using calorimetric data. It was found that the thermodynamic fragility evaluated based on the width of the glass transition, observed in the temperature dependence of heat capacity, correlates best with the tendency to crystallize.

Management of inflammation after the cataract surgery.

PURPOSE OF REVIEW: To review most recent studies and clinical trials regarding pathogenesis, treatment, and prevention of inflammation after the cataract surgery. RECENT FINDINGS: FLACS gave opportunity to evaluate inflammatory cytokines in the aqueous humour right after the laser procedure, which led to acknowledging the inflammation pathogenesis during the phacoemulsification. Although there is still a lack of evidence, which would prove the long-term benefit of NSAIDs, they are indicated and effective when risk factors for PCME are present. PREMED studies showed that combination of NSAID and steroids after the surgery for healthy subjects is cost-effective. The triamcinolone injection together with topical steroids and NSAIDs for diabetic patients after the cataract surgery was the most cost-effective in preventing PCME according to the PREMED. Dropless cataract surgery is another emerging topic: dexamethasone implants and suspensions look promising as we await more clinical trials with drug-loaded IOLs. SUMMARY: Inflammation after the cataract surgery can be prevented, and these methods are one of the most essential topics with growing phacoemulsification rate. Topical NSAIDs are cost-effective not only for patients with risk factors for PCME but also for healthy subjects. New dropless techniques are being successfully introduced in the clinical practice.

Topical Review: Studies on Management of Myopia Progression from 2019 to 2021.

SIGNIFICANCE: Myopia is a common eye condition that increases the risk of sight-threatening complications. Each additional diopter increases the chance of complications. The purpose of this review was to make an overview of myopia control treatment options for children with myopia progression.In this nonsystematic review, we searched PubMed and Cochrane databases for English-language studies published from 2019 to September 2021. Emphasis was given to selection of randomized controlled trials. Nineteen randomized controlled trials and two retrospective studies were included. Topical atropine and orthokeratology remain the most used treatments, whereas lenses with novel designs are emerging treatments. Overall myopia progression in the treatment groups for low-dose atropine and orthokeratology was lower than in the control groups, and their efficacy was reported in several randomized controlled trials and confirmed by various systematic reviews and meta-analysis. The findings of myopia progression and axial elongation for the MiSight, defocus incorporated multiple segment spectacle lens, highly aspherical lenslets, and diffusion optics technology spectacle lens were comparable. Public health interventions to optimize environmental influences may also be important strategies to control myopia. Optimal choice of management of myopia depends on treatment availability, acceptability to child and parents, and specific patient features such as age, baseline myopia, and lifestyle. Eye care providers need to understand the advantages and disadvantages of each therapy to best counsel parents of children with myopia.

Diagnostic Accuracy of Automated Diabetic Retinopathy Image Assessment Softwares: IDx-DR and Medios Artificial Intelligence.

INTRODUCTION: Numerous studies have demonstrated the use of artificial intelligence (AI) for early detection of referable diabetic retinopathy (RDR). A direct comparison of these multiple automated diabetic retinopathy (DR) image assessment softwares (ARIAs) is, however, challenging. We retrospectively compared the performance of two modern ARIAs, IDx-DR and Medios AI. METHODS: In this retrospective-comparative study, retinal images with sufficient image quality were run on both ARIAs. They were captured in 811 consecutive patients with diabetes visiting diabetic clinics in Poland. For each patient, four non-mydriatic images, 45° field of view, i.e., two sets of one optic disc and one macula-centered image using Topcon NW400 were captured. Images were manually graded for severity of DR as no DR, any DR (mild non-proliferative diabetic retinopathy [NPDR] or more severe disease), RDR (moderate NPDR or more severe disease and/or clinically significant diabetic macular edema [CSDME]), or sight-threatening DR (severe NPDR or more severe disease and/or CSDME) by certified graders. The ARIA output was compared to manual consensus image grading (reference standard). RESULTS: On 807 patients, based on consensus grading, there was no evidence of DR in 543 patients (67%). Any DR was seen in 264 (33%) patients, of which 174 (22%) were RDR and 41 (5%) were sight-threatening DR. The sensitivity of detecting RDR against reference standard grading was 95% (95% CI: 91, 98%) and the specificity was 80% (95% CI: 77, 83%) for Medios AI. They were 99% (95% CI: 96, 100%) and 68% (95% CI: 64, 72%) for IDx-DR, respectively. CONCLUSION: Both the ARIAs achieved satisfactory accuracy, with few false negatives. Although false-positive results generate additional costs and workload, missed cases raise the most concern whenever automated screening is debated.

Glass Transition and Related Phenomena.

Despite recent advances in the study of complex systems, which were recognized by the Nobel Prize in Physics in 2021, glass transition and the physicochemical phenomena that occur in the supercooled liquid and glassy states have remained shrouded, at least partially, in mystery for various material groups [...].

The Role of Genetic Polymorphisms in Diabetic Retinopathy: Narrative Review.

Diabetic retinopathy (DR) is renowned as a leading cause of visual loss in working-age populations with its etiopathology influenced by the disturbance of biochemical metabolic pathways and genetic factors, including gene polymorphism. Metabolic pathways considered to have an impact on the development of the disease, as well as genes and polymorphisms that can affect the gene expression, modify the quantity and quality of the encoded product (protein), and significantly alter the metabolic pathway and its control, and thus cause changes in the functioning of metabolic pathways. In this article, the screening of chromosomes and the most important genes involved in the etiology of diabetic retinopathy is presented. The common databases with manuscripts published from January 2000 to June 2023 have been taken into consideration and chosen. This article indicates the role of specific genes in the development of diabetic retinopathy, as well as polymorphic changes within the indicated genes that may have an impact on exacerbating the symptoms of the disease. The collected data will allow for a broader look at the disease and help to select candidate genes that can become markers of the disease.

Low-concentration povidone-iodine for the prevention of intraocular infections in ophthalmic surgery.

PURPOSE OF REVIEW: Endophthamitis following intraocular surgery is rare using current antiseptic techniques, such as single application of 5% povidone-iodine to the ocular surface and adjuvant topical or intracameral antibiotics. Challenges remain, however, including increased multidrug-resistant bacterial endophthalmitis, increased fungal endophthalmitis, and the low but nonzero endophthalmitis rate attributable to the typical bacteria that colonize the ocular surface. RECENT FINDINGS: Povidone-iodine has a wide spectrum of activity, including activity against novel pathogens, such as SARS-CoV-2. Povidone-iodine alternatives, such as hypochlorous acid can have significantly less efficacy in vitro against endophthalmitis isolates. Repetitive application of dilute povidone-iodine has an excellent safety profile and strong evidence base for efficacy. SUMMARY: Povidone-iodine is widely available, inexpensive, and commonly used by ophthalmologists. The repetitive application of dilute povidone-iodine is a well studied, well tolerated, and efficacious way to transiently sterilize the ocular surface during intraocular surgery. Additional benefits include activity against multidrug-resistant bacteria, fungi, and lack of inducible resistance.

Density Scaling of Translational and Rotational Molecular Dynamics in a Simple Ellipsoidal Model near the Glass Transition.

In this paper, we show that a simple anisotropic model of supercooled liquid properly reflects some density scaling properties observed for experimental data, contrary to many previous results obtained from isotropic models. We employ a well-known Gay-Berne model earlier parametrized to achieve a supercooling and glass transition at zero pressure to find the point of glass transition and explore volumetric and dynamic properties in the supercooled liquid state at elevated pressure. We focus on dynamic scaling properties of the anisotropic model of supercooled liquid to gain a better insight into the grounds for the density scaling idea that bears hallmarks of universality, as follows from plenty of experimental data collected near the glass transition for different dynamic quantities. As a result, the most appropriate values of the scaling exponent γ are established as invariants for a given anisotropy aspect ratio to successfully scale both the translational and rotational relaxation times considered as single variable functions of densityγ/temperature. These scaling exponent values are determined based on the density scaling criterion and differ from those obtained in other ways, such as the virial-potential energy correlation and the equation of state derived from the effective short-range intermolecular potential, which is qualitatively in accordance with the results yielded from experimental data analyses. Our findings strongly suggest that there is a deep need to employ anisotropic models in the study of glass transition and supercooled liquids instead of the isotropic ones very commonly exploited in molecular dynamics simulations of supercooled liquids over the last decades.

Study of Thermal Properties, Molecular Dynamics, and Physical Stability of Etoricoxib Mixtures with Octaacetylmaltose near the Glass Transition.

In this paper, we thoroughly investigated the physical stability of the anti-inflammatory drug etoricoxib, which has been reported earlier to be resistant to recrystallization in its glassy and supercooled states at ambient pressure. Our unique application of the standard refractometry technique showed that the supercooled liquid of the drug was able to recrystallize during isothermal experiments in atmospheric conditions. This enabled us to determine the crystallization onset timescale and nucleation energy barrier of etoricoxib for the first time. As the physical instability of etoricoxib requires working out an efficient method for improving the drug's resistance to recrystallization to maintain its amorphous form utility in potential pharmaceutical applications, we focused on finding a solution to this problem, and successfully achieved this purpose by preparing binary mixtures of etoricoxib with octaacetylmaltose. Our detailed thermal, refractometry, and molecular dynamics studies of the binary compositions near the glass transition revealed a peculiar behavior of the glass transition temperatures when changing the acetylated disaccharide concentration in the mixtures. Consequently, the anti-plasticization effect on the enhancement of physical stability could be excluded, and a key role for specific interactions in the improved resistance to recrystallization was expected. Invoking our previous results obtained for etoricoxib, the chemically similar drug celecoxib, and octaacetylmaltose, we formulated a hypothesis about the molecular mechanisms that may cause an impediment to crystal nuclei formation in the amorphous mixtures of etoricoxib with octaacetylmaltose. The most plausible scenario may rely on the formation of hydrogen-bonded heterodimers of the drug and excipient molecules, and the related drop in the population of the etoricoxib homodimers, which disables the nucleation. Nevertheless, this hypothesis requires further investigation. Additionally, we tested some widely discussed correlations between molecular mobility and crystallization properties, which turned out to be only partially satisfied for the examined mixtures. Our findings constitute not only a warning against manufacturing the amorphous form of pure etoricoxib, but also evidence for a promising outcome for the pharmaceutical application of the amorphous compositions with octaacetylmaltose.

Tear Biomarkers in Alzheimer's and Parkinson's Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review).

Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015-2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.

EARLY DESCRIPTIONS OF VITREOUS SURGERY.

BACKGROUND: Vitreoretinal surgical techniques have evolved during the last decades because of the development and evolution of pars plana vitrectomy. The introduction of modern vitrectomy is credited to Robert Machemer (1933-2009). The aim of this review is to characterize the early developments of vitreous removal. METHODS: We used the PubMed web platform to search the terms: complications of cataract surgery, vitrectomy, vitreous body, vitreous humor, vitreous humour, vitreous tap, and vitreous transplantation. Other publications were also considered as a potential source of information when referenced in relevant articles. RESULTS: The first description of vitreous removal for treatment of eye disorders dates the 17th century; it was conducted by a Dutch surgeon Anton Nuck (1650-1692) in a case of hydrophthalmia. In English literature, the first description of vitrectomy is attributed to the American surgeon John Collins Warren (1778-1856). This method was implemented in the spontaneous dislocation of the crystalline lens. As the fibrillar structure of the vitreous once destroyed could not be regenerated, the researchers aimed to restore the chemical composition of the vitreous. For several decades, vitreous transplantation was performed for the treatment of vitreous hemorrhages and retinal detachment. CONCLUSION: Although the achievements of vitreoretinal surgery preceding Machemer's inventions are uncommonly reported, they have contributed to the concept and understanding of the treatment modalities.

Can a Set of Questions after Routine Cataract Surgery Predict Unexpected Findings and Avoid an Unnecessary Follow-Up Visit?

Background and Objectives: to evaluate whether a set of questions after a routine cataract surgery can predict unexpected findings and avoid an unnecessary follow-up visit. Materials and Methods: single-center, prospective, cohort study included 177 routine cataract surgery cases of two experienced surgeons between November 2019 and December 2020. Inclusion criteria included unremarkable postoperative day one follow-up examination. A set of seven questions regarding complaints with positive or negative answers was presented at the second follow-up visit (PV2)-one week (mean 8.34 ± 1.73 days) after the surgery. The outcome measures were the incidence of unexpected management changes (UMCs) at the PV2 visit (change or addition from a prescribed postoperative drop plan, extra procedures, an urgent referral to an ophthalmologist) and UMCs associations with the answers to a question set. Results: 81.4% of patients had no complaints about postoperative ocular status and answered with negative answers, 18.6% reported one or more complaint (positive answer): dissatisfaction with postoperative visual acuity (6.2%, 11 cases), eye pain (4.0%, 7 cases), increase in floaters after the surgery (4.0%, 7 cases), red eye (4.0%, 7 cases) and others. The prevalence of UMCs at PV2 was 1.7% (3 cases), of which 0.6% (1 case) was the prolonged antibiotic prescription due to conjunctivitis, 0.6% (1 case) was the addition of IOP lowering medication and 0.6% (1 case) was additional medication due to uveitis management. None of the complaints (positive answers) at PV2 were associated with the incidence of UMCs (p > 0.05). Conclusions: there were no associations of UMCs determined with positive answers to the questions. The prediction of UMCs incidence based on the positive answers was not obtained. Thus, we cannot exclude the necessity of a postoperative week one follow-up visit.

Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose.

In this paper, we explore the strategy increasingly used to improve the bioavailability of poorly water-soluble crystalline drugs by formulating their amorphous solid dispersions. We focus on the potential application of a low molecular weight excipient octaacetyl-maltose (acMAL) to prepare physically stable amorphous solid dispersions with ibuprofen (IBU) aimed at enhancing water solubility of the drug compared to that of its crystalline counterpart. We thoroughly investigate global and local molecular dynamics, thermal properties, and physical stability of the IBU+acMAL binary systems by using broadband dielectric spectroscopy and differential scanning calorimetry as well as test their water solubility and dissolution rate. The obtained results are extensively discussed by analyzing several factors considered to affect the physical stability of amorphous systems, including those related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and the number of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latter by density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendations give a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions.

Methods for achieving adequate pupil size in cataract surgery.

PURPOSE OF REVIEW: Cataract surgery is the most common surgical procedure performed worldwide. Small pupils have been an eternal challenge for cataract surgeons; insufficient pupil dilation is associated with increased complication rates, including capsule rupture, vitreous loss, iris trauma or postoperative inflammation. The aim of the current review is to present the methods for pupil dilation and the risk factors for a small pupil in a cataract patient. RECENT FINDINGS: Risk factors for intraoperative small pupil include diabetes, intraoperative floppy iris syndrome, pseudoexfoliation syndrome, receiving glaucoma medications, having undergone previous ocular surgery and iris sphincter sclerosis from aging. There is a wide range of options to manage the small pupil, including pharmacological treatment, mechanical stretching, dilation with iris hooks or pupil expanders. We recommend a stepwise approach for intraoperative pupil dilation, from pharmacological mydriasis to pupil expanders. SUMMARY: The current article discusses risk factors for a small pupil and the methods for pupil dilation in a cataract patient. Every cataract surgeon needs to be ready to cope with a small pupil, both manifesting preoperatively and intraoperatively.

Multifocal intraocular lenses and retinal diseases.

PURPOSE: Multifocal intraocular lenses (MIOLs) are often discouraged in patients with or at risk of retinal disorders (including diabetic retinopathy, age-related macular degeneration, and epiretinal membranes), as MIOLs are believed to reduce contrast sensitivity (CS). Concerns with MIOLs have also been raised in individuals with visual field defects, fixation instability or eccentric preferred retinal locations. The aim of this study is to review the influence of MIOL on quality of vision in patients with retinal diseases. METHODS: We reviewed the PubMed and Web of Science databases to identify relevant studies using the following keywords: multifocal intraocular lens, cataract surgery, cataract extraction, lens exchange, diabetic retinopathy, age-related macular degeneration, and contrast sensitivity. RESULTS: Studies evaluating CS in MIOLs present conflicting results: MIOLs either did not influence CS or resulted in worse performance under low-illuminance conditions and higher spatial frequencies when compared to monofocal IOLs. Nevertheless, MIOLs preserved CS levels within the age-matched normal range. Two studies reported that patients with concurrent retinal diseases receiving a MIOL, both unilaterally and bilaterally, reported a significant improvement in visual-related outcomes. Individuals with a monofocal IOL in one eye and a MIOL in the fellow eye reported greater subjective satisfaction with the MIOL. CONCLUSION: We were unable to find evidence suggesting that patients with retinal diseases should be advised against MIOLs. Nevertheless, more research is needed to address the aforementioned concerns and to optimize the use of MIOLs in eyes with retinal disease.

Off-label use of bevacizumab for wet age-related macular degeneration in Europe.

PURPOSE: To analyse current off-label use of bevacizumab for wet age-related macular degeneration (AMD) in Europe. METHODS: The study was conducted as a combined survey and literature review. It included the 22 most populous countries in Europe. In each country, ophthalmologists with particular knowledge about off-label treatment responded to a questionnaire. RESULTS: Answers were obtained from twenty European countries. The off-label use of bevacizumab for wet AMD greatly differed between nations; the bevacizumab proportion varied from non-existent (0%) to very high (97%). There were also large disparities within single countries (e.g. 0-80%), which were attributable to differences in regional decision-making. Both governmental institutions and national ophthalmological societies expressed highly diverging opinions on the use of off-label treatment. Intravitreal administration of bevacizumab had been a matter of legal dispute in several countries. The question about responsibility for off-label therapy mainly remained unanswered. CONCLUSIONS: There was a highly varying utilization of bevacizumab between European countries. Despite an intention of a consistent approach to medical regulations, Europe has not yet reached a professional or political consensus on the ophthalmic off-label use of bevacizumab.