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Strabismus Exotropia with/without vertical deviation was observed to be the most common form of strabismus in Asian patients with chronic progressive external ophthalmoplegia (CPEO) by Kim et al. Swept-source optical coherence tomography angiography imaging is useful to show microvascular anomalies in children with a history of retinopathy of prematurity according to Rezar-Dreindl et al. Prevalence of CBS was 20.1% for glaucoma patients treated in vision rehabilitation clinics. [Extracted from the article]

According to the dictionary of the Royal Academy of the Spanish Language, numismatics is the discipline that studies coins and medals, mainly ancient ones. In other places, this definition includes the study and collection of paper money or banknotes. The information we can obtain from coins with a minimum study of the aspects that appear on them is surprising. In relation to vision and ophthalmology, they show us important figures in the field, ocular symbology, they tell us about mythology and religion and curious stories that we would hardly have known without looking at the coins. Finally, we will talk about an important 19th century Valencian ophthalmologist, Rafael Cervera y Royo, and the collection of ancient coins that bears his name. This work is not intended to be an exhaustive description of all the coins and medals that speak of vision, but rather a sample of the valuable information that numismatics contributes to our speciality and to stimulate the public's curiosity about this fascinating science. [ABSTRACT FROM AUTHOR]

Writing for peer‐reviewed publication is an important part of the careers of many clinicians and researchers. Writing a paper and getting it published is hard work, even after the hard work that led to the publishable results. The presentation will focus on tips and tricks about how to make this process easier through an organized step by step algorithm to guide the writer from the first paragraph to the last in a clear and effective way. [ABSTRACT FROM AUTHOR]

Purpose: To study the osmoprotective and bioprotective effect of trehalose 3% during desiccation conditions. Methods: Normal human conjunctival epithelial cells (IOBA‐NHC) were exposed to: 1) culture media DMEM‐F12 (Control); 2) Carboxymethylcellulose 0.5% + glycerin 0.9% + PEG 400 0.25% (Vehicle); 3) Vehicle + trehalose 3% (Trehalose). Cultures were treated for 1 h and then exposed to desiccating conditions (25°C and 36–38% relative humidity). Metabolic activity by MTT assay and cell viability by Triptan Blue assay was evaluated. To evaluate water retention capacity, a gravimetric test was carried out by soaking a filter paper with 5 ml of each solution under evaluation and recording its weight over time. The data were analysed by analysis of variance (ANOVA) with a post hoc Tukey multiple comparisons test. Results:MTT assay: During the first 30 min under desiccating conditions there were no differences between groups (Control: 0.586 ± 0.012; Vehicle: 0.575 ± 0.278; Trehalose: 0.523 ± 0.035). After 45 min of exposure metabolic activity sharply decreased in control group (0.111 ± 0.007) and vehicle group (0.107 ± 0.027), while trehalose group maintained metabolic activity values (0.560 ± 0.008; p < 0.001). Triptan Blue assay: The cell viability of the trehalose group was maintained throughout the time (10 min: 62.7 ± 2.5; 15 min: 58.7 ± 8.1; 20 min: 62.3 ± 10.8; 30 min:41.7 ± 8.5%) and was statistically superior to the control and vehicle groups at all evaluated times (p < 0.01). Water retention capacity: Water content of papers soaked with control and vehicle solution was almost completely evaporated (less than 20% of water retention) at 10 min on desiccating conditions, while trehalose group show a significant delay of water evaporation of 5 and 7 min regarding the vehicle and control group, respectively. Conclusions: The addition of trehalose 3% prolonged cell viability and extended water retention time in conditions of high environmental dryness. This study confirms the bioprotective and osmoprotective role of trehalose evaluated in previous investigations and provides scientific evidence of its properties, representing an additional benefit in the treatment of dry eye. [ABSTRACT FROM AUTHOR]

The authors reflect on the intrinsic quality of the scientific content in a scientific paper. They state that how the scientific material is presented will determine the attention it receives from the readers. An overview of the general characteristics of a scientific material such as the title, keywords, and abstracts is offered. The authors suggest several advice such as having a good and descriptive title and the importance of selecting keywords.

Purpose: Based on the hypothesis that silicone oil (SO) with a higher refractive index than water induces unexpected vignetting effects during surgeries, we aimed to investigate the relationship between the volume of SO and light intensity using a surgical microscope. Methods: Using a light‐sensitive paper and model eye filled with varying volumes (0%, 50%, 62.5%, 75%, 87.5% and 100%) of SO, the light intensity of intraocular lens (IOL) with various refractive powers (0, 10 and 20 dioptres) illuminated by a surgical microscope was measured. Results: Light exposure density with 1.0% coaxial and oblique light was approximately 22‐fold higher than that with 0.1% coaxial and oblique light. Further, it was approximately 34‐fold higher in eyes with +20 D IOL than in those with no IOL. The density in eyes with 75% SO was the highest among all groups followed by that with 0% SO. Light exposure densities in the eyes with 75% and 0% SO were significantly higher than those with other volumes of SO. In SO‐filled eyes, a microscope set with only an oblique light and a filter successfully reduced light exposure. Conclusion: Silicone oil‐related vision loss (SORVL) during SO removal surgeries might be due to increased light exposure on the macular retina caused by the SO‐associated vignetting effect. SORVL could be prevented by placing a filter in the microscope during SO removal surgeries. [ABSTRACT FROM AUTHOR]

Purpose: To explore the trends in worldwide ophthalmic research production over a 21‐year period in relation to journals, contributing countries and dominating topics with special focus on the Nordic region. Methods: Articles published between 2000 and 2020 in 20 top‐ranked ophthalmology journals were included. Number of articles and impact points were measured per country for each year. The most frequently occurring keywords were calculated worldwide and for the top five contributing countries and the Nordic countries. Trends were explored using linear regression. Results: The analysis included 65 220 articles. Linear regression showed an increase with 56 articles per year (β = 56.3, R2 = 0.72, p‐value < 0.01). The United States published the most articles, comprising 35% of the worldwide total, followed by the United Kingdom (9%) and Japan (7%). Population‐adjusted productivity revealed that Iceland was the most prolific country with 10 articles per million inhabitants/year. Singapore was second and Denmark third with corresponding numbers of nine and seven. Analysing regional trends, Asia had the largest increase in yearly number of articles (β = 29.1, R2 = 0.89, p‐value < 0.01). The strongest positive trend was observed in China (β = 15.7, R2 = 0.94, p‐value < 0.01). The Nordic countries contributed with 3.6% of worldwide ophthalmological papers. Among these, Denmark was the only country with a significant positive trend in impact points per million inhabitants per year (β = 0.6, R2 = 0.54, p‐value < 0.01). The most frequently occurring eye disease within the whole time frame was myopia (5.8%) followed by macular degeneration (5.4%) and glaucoma (5.3%). Linear regression showed a significant increase in the proportion of articles about diabetic retinopathy (β = 0.2%, R2 = 0.88, p‐value < 0.01) a significant decrease in the proportion in articles about cataract (β = −0.1%, R2 = 0.70, p‐value < 0.01) and myopia (β = −0.1%, R2 = 0.67, p‐value < 0.01). Conclusions: The worldwide ophthalmic research productivity has maintained a growing trend from 2000 to 2020. While North America and Europe are the major contributors, the scientific activity in Asia and especially China is growing impressively. With the current progress, Asia is forecast to outweigh Europe in 2025 and North America in 2033. Diabetic retinopathy was the most common eye disease in ophthalmologic papers in 2020, and also the topic with the strongest positive trend during 2000–2020. [ABSTRACT FROM AUTHOR]

ENGLISH SUMMARY: Corneal blindness is a leading cause of visual impairment worldwide. The most common treatment is to replace the diseased cornea by standard corneal transplantation. In eyes at high risk of graft failure, the Boston keratoprosthesis type 1 (KPro) can be used to restore vision and is currently the most frequently used artificial cornea in the world. However, glaucoma is a well‐known complication of KPro surgery and is the most important threat to vision in KPro‐implanted eyes (paper I). This chronic disease is influenced by elevated intraocular pressure (IOP) and damages the optic nerve, leading to progressive vision loss. In KPro patients, glaucoma is highly prevalent and extremely challenging to manage, yet its exact cause remains unknown. The overall purpose of this PhD Thesis (Geoffrion, 2021) was to better understand the mechanisms and how to improve management of glaucoma after KPro implantation. The approaches used in this thesis included investigating one of the largest KPro patient cohorts in North America, with a total of 157 operated patients at that time, as well as studying KPro surgery and outcomes in mice. The first objective was to identify risk factors for glaucoma development and progression after KPro implantation (paper II). Multivariate logistic regression revealed that high preoperative IOP signals a higher risk for both glaucoma development and progression. Stromal and endothelial corneal disorders were less associated with glaucoma progression, while autoimmune and ocular surface diseases precipitated glaucoma development. Second, there is no objective evidence that indicates the best order for glaucoma surgeries and KPro implantation. By comparing medical and surgical management in KPro eyes with either preexisting or de novo glaucoma (paper III), we showed that glaucoma surgery may be performed before or at the time of KPro in eyes with preexisting glaucoma to limit progression without increasing complications. In eyes with de novo glaucoma, glaucoma surgery did not increase complications compared with medications. Third, among glaucoma surgery interventions, the two most frequently implanted glaucoma drainage devices were compared in KPro patients (paper IV). Compared with the Ahmed glaucoma valve, the Baerveldt glaucoma implant was associated with lower failure rates, without increased postoperative complications. Fourth, even with aggressive management, many KPro patients suffer from progressive optic nerve damage, sometimes despite normal IOP. Inflammatory cytokines play an important role in glaucomatous optic neuropathy, but their role in KPro‐associated glaucoma is still unknown. By analysing tear fluid of KPro patients by multiplex bead immunoassay (paper V), we identified that cytokines TNF‐a, IL‐1b, FGF‐basic and IFN‐g were elevated in KPro patients with glaucoma compared to those without. These cytokines correlated with optic nerve excavation and IOP. For the first time in humans, these results concorded with the elevations of TNF‐a and IL‐1b documented in the mouse KPro model. Ocular surface inflammation may thus reflect the inflammatory processes that perpetuate glaucoma damage years after KPro surgery. Fifth, we determined that miniaturized mouse KPro implantation requires extensive practice to be used as a reproducible model of glaucoma post‐KPro (paper VI). KPro animal models with larger eyes and a full‐thickness, 360‐degree corneal excision should be prioritized to best validate human outcomes. In conclusion, glaucoma in KPro eyes is a long‐lasting and multifactorial process. Most probable mechanisms combine IOP‐independent inflammation mediated by TNF‐a and IL‐1b that prolong glaucoma damage, together with post‐surgical angle closure elevating the IOP. Altogether, our results inform glaucoma risk profiling of transplant recipients, improvement of surgical management of KPro patients with glaucoma and development of targeted treatments to minimize glaucomatous damage after KPro. Ultimately, this work has the potential to preserve the vision of thousands of patients who undergo KPro surgery every year worldwide and to provide insight for the role of inflammation in other diseases involving neuronal damage. RÉSUMÉ (FRENCH SUMMARY) La cécité cornéenne est l'une des causes les plus importantes de déficience visuelle dans le monde. Le traitement usuel est de remplacer la cornée malade par une greffe de cornée traditionnelle. Dans les yeux à haut risque d'échec de greffe, la kératoprothèse de Boston de type 1 (KPro) peut rétablir la vision et est la cornée artificielle la plus utilisée au monde. Cependant, le glaucome est une complication importante de la KPro (papier I). Cette maladie chronique est influencée par une pression intraoculaire (PIO) élevée et endommage le nerf optique, menant à une perte de vision. Chez les patients avec KPro, le glaucome est fréquent et difficile à contrôler, mais sa cause exacte demeure inconnue. L'objectif principal de cette thèse est de découvrir les mécanismes et d'optimiser la prise en charge du glaucome après l'implantation de la KPro. Pour ce faire, nous avons investigué l'une des plus grandes cohortes de patients KPro en Amérique du Nord avec un total de 157 patients, ainsi qu'un groupe de souris ayant reçu une implantation de kératoprothèse. Le premier but était d'identifier les facteurs de risque pour le développement et la progression du glaucome après la KPro (papier II). Par régression logistique multivariée, nous avons démontré qu'une PIO préopératoire élevée mène à un plus grand risque de développement et de progression du glaucome. Les maladies cornéennes stromales ou endothéliales sont moins associées à une progression, alors que les maladies autoimmunes ou de la surface oculaire précipitent le développement du glaucome. Deuxièmement, il n'existe aucune donnée objective pour indiquer le meilleur ordre des chirurgies de glaucome et de KPro. En comparant les traitements médicaux et chirurgicaux des yeux KPro avec glaucome (papier III), nous avons démontré que les chirurgies de glaucome peuvent limiter la progression en étant effectuées avant ou pendant l'implantation de KPro dans les yeux avec glaucome préexistant, sans augmenter les complications. Dans le glaucome de novo, les chirurgies de glaucome n'augmentent pas les complications en comparaison aux médicaments. Troisièmement, les deux implants de glaucome les plus communs ont été étudiés chez les patients KPro (papier IV). Comparé à la valve Ahmed, l'implant Baerveldt est associé à des taux d'échec plus bas, sans augmentation des complications. Quatrièmement, même avec une prise en charge agressive, plusieurs patients KPro souffrent de glaucome qui progresse, parfois sans PIO élevée. Les cytokines inflammatoires jouent un rôle dans la pathophysiologie du glaucome, mais leur rôle dans le glaucome associé à la KPro est inconnu. En analysant les larmes de patients KPro (papier V), nous avons identifié que les cytokines TNF‐a, IL‐1b, FGF‐basic et IFN‐g sont élevées chez les patients KPro avec glaucome comparé à ceux sans glaucome. Ces cytokines corrèlent avec l'excavation du nerf optique et la PIO. Pour la première fois chez les humains, ces résultats concordent avec les niveaux élevés de TNF‐a et IL‐1b documentés dans le modèle murin de KPro. L'inflammation de la surface oculaire pourrait donc refléter les processus inflammatoires qui perpétuent le dommage glaucomateux. Cinquièmement, nous avons déterminé que l'implantation de la KPro miniature chez la souris requiert beaucoup de pratique pour être utilisé comme modèle de glaucome post‐KPro (papier VI). Des modèles animaux avec des yeux plus larges et une excision cornéenne de pleine épaisseur sur 360 degrés devraient être priorisés pour valider les résultats chez l'humain. En conclusion, le glaucome associé à la KPro est un processus multifactoriel qui persiste à long terme. Les mécanismes probables combinent l'inflammation médiée par TNF‐a et IL‐1b et une fermeture de l'angle qui augmente la PIO. Nos résultats contribuent à établir les facteurs de risque de glaucome pour les receveurs de KPro, à améliorer leur prise en charge et à développer des thérapies ciblées. Ce travail a le potentiel de préserver la vision de milliers de patients recevant une KPro chaque année dans le monde et d'aider à mieux comprendre le rôle de l'inflammation dans d'autres maladies avec atteinte neuronale. [ABSTRACT FROM AUTHOR]

Summary: Dansk Resumé (Danish summary): Aldersrelateret makuladegeneration (AMD) er den hyppigste årsag til uopretteligt synstab og blindhed i højindkomstlande. Det er en progredierende nethindesygdom som gradvist fører til ødelæggelse af de celler som er ansvarlige for vores centralsyn. De tidlige stadier er ofte asymptomatiske, imens senstadie AMD, som opdeles i to former, neovaskulær AMD (nAMD) og geografisk atrofi (GA), begge udviser gradvist synstab, dog generelt med forskellig hastighed. Tidlig AMD er karakteriseret ved tilstedeværelsen af druser og pigmentforandringer i nethinden mens nAMD og GA udviser henholdsvis karnydannelse i og atrofi af nethinden. Ætiologien er multifaktoriel og udover alder omfatter patogenesen miljø‐ og genetiske risikofaktorer. Forskning har specielt fokuseret på lokale forandringer i øjet hvor man har fundet at inflammation spiller en betydelig rolle for udviklingen af sygdommen, men flere studier tyder også på at systemiske forandringer og specielt systemisk inflammation spiller en væsentlig rolle i patogenesen. De Philadelphia‐negative myeloproliferative neoplasier (MPNs) er en gruppe af hæmatologiske kræftsygdomme med en erhvervet genetisk defekt i den tidlige pluripotente stamcelle som medfører en overproduktion af en eller flere af blodets modne celler. Sygdommene er fundet at udvikle sig i et biologisk kontinuum fra tidligt cancerstadie, essentiel trombocytose (ET) over polycytæmi vera (PV) og endelig til det sene myelofibrose stadie (PMF). Symptomer hos disse patienter skyldes især den ændrede sammensætning af blodet, hyperviskositet, kompromitteret mikrocirkulation og nedsat vævsgennemblødning. Den øgede morbiditet og mortalitet beror i høj grad på tromboembolier, blødninger og leukemisk transformation. En række mutationer som driver MPN sygdommene er identificeret, bl.a. JAK2V617F‐mutationen som medfører en deregulering JAK/STAT signalvejen, der bl.a. har betydning for cellers vækst og overlevelse. Et tidligere stort registerstudie har vist at patienter med MPNs har en øget risiko for neovaskulær AMD og et pilotstudie har vist øget forekomst af intermediær AMD. Dette ønsker vi at undersøge nærmere i et større studie i dette Ph.d.‐ projekt. Flere studier har også vist at kronisk inflammation spiller en vigtig rolle for både initiering og udvikling af den maligne celleklon hos MPNs og herfra er en "Human Inflammationsmodel" blevet udviklet. Siden er MPN sygdommene blevet anvendt som "model sygdomme" for en tilsvarende inflammationsmodel for udvikling af Alzheimers sygdom. I dette Ph.d.‐projekt vil vi tilsvarende forsøge at undersøge systemisk inflammation i forhold til forekomst af druser. Det vil vi gøre ved at sammenligne systemiske immunologiske markører som tidligere er undersøgt hos patienter med AMD og sammenligne med MPN. Specielt er vi interesseret i systemiske immunologiske forskelle på patienter med MPN og druser (MPNd) og MPN med normale nethinder (MPNn). Denne afhandling består af to overordnede studier. I Studie I, undersøgte vi forekomsten af retinale forandringer associeret med AMD hos 200 patienter med MPN (artikel I). Studie II, omhandlede immunologiske ligheder ved AMD og MPN, og var opdelt i yderligere tre delstudier hvor vi undersøgte hhv. systemiske markører for inflammation, aldring og angiogenese (artikel II, III og IV). Vi undersøgte markørerne i fire typer af patienter: nAMD, intermediær AMD (iAMD), MPNd og MPNn. Undersøgelsen af forskelle mellem MPNd og MPNn, vil gøre det muligt at identificere forandringer i immunsystemet som kunne være relevante for AMD‐patogenesen. Vi vil endvidere sammenholde resultaterne for patienter med MPN med patienter som har iAMD og nAMD. I studie I (Artikel I) fandt vi at patienter med MPN har en signifikant højere prævalens af store druser og AMD tidligere i livet sammenlignet med estimater fra tre store befolkningsundersøgelser. Vi fandt også at forekomst af druser var associeret med højere neutrofil‐lymfocyt ratio, hvilket indikerer et højere niveau af kronisk inflammation i patienterne med druser sammenlignet med dem uden druser. I studie II (Artikel II, III og IV) fandt vi flere immunologiske forskelle mellem patienter med MPNd og MPNn. Da vi undersøgte markører for inflammation, fandt vi en højere grad af systemisk inflammation i MPNd end MPNn. Dette blev vist ved en højere inflammationsscore (udregnet på baggrund af niveauer af pro‐inflammatoriske markører), en højere neutrofil‐lymfocyt ratio, samt indikationer på et dereguleret komplementsystem. Ved undersøgelse af aldringsmarkører fandt vi tegn på accelereret immunaldring hos MPNd i forhold til MPNn, hvilket kommer til udtryk ved en større procentdel af "effector memory T celler". Endelig fandt vi en væsentlig lavere ekspression af CXCR3 på T celler og monocytter hos patienter med nAMD sammenlignet med iAMD, MPNd og MPNn. Dette er i overensstemmelse med tidligere studier hvor CXCR3 ekspression er fundet lavere end hos raske kontroller. Derudover fandt vi en faldende CXCR3 ekspression på monocytter over det biologiske MPN‐kontinuum. Disse studier indikerer en involvering af CXCR3 i både nAMD og PMF, begge sygdomsstadier som er karakteriseret ved angiogenese og fibrose. Ud fra resultaterne af denne afhandling kan vi konkludere at forekomsten af druser og AMD hos MPN er øget i forhold til baggrundsbefolkningen. Endvidere viser vores resultater at systemisk inflammation muligvis spiller en væsentlig større rolle i udviklingen af AMD end tidligere antaget. Vi foreslår derfor en AMD‐model (Figur 18) hvor inflammation kan initiere og accelerere den normale aldersafhængige akkumulation af affaldsstoffer i nethinden, som senere udvikler sig til druser, medførende øget lokal inflammation og med tiden tidlig og intermediær AMD. Dette resulterer i den øgede risiko for udvikling til de invaliderende senstadier af AMD. English summary: Age‐related macular degeneration (AMD) is the most common cause of irreversible vision loss and blindness in high‐income countries. It is a progressive retinal disease leading to damage of the cells responsible for central vision. The early stages of the disease are often asymptomatic, while late‐stage AMD, which is divided into two entities, neovascular AMD and geographic atrophy (GA), both show vision loss, though generally with different progression rates. Drusen and pigmentary abnormalities in the retina characterise early AMD, while nAMD and GA show angiogenesis in and atrophy of the retina, respectively. The aetiology is multifactorial and, in addition to ageing, which is the most significant risk factor for developing AMD, environmental‐ and genetic risk factors are implicated in the pathogenesis. Research has focused on local changes in the eye where inflammation has been found to play an essential role, but studies also point to systemic alterations and especially systemic inflammation to be involved in the pathogenesis. The Philadelphia‐negative myeloproliferative neoplasms (MPN) are a group of haematological cancers with an acquired genetic defect of the pluripotent haematopoietic stem cell, characterised by excess haematopoiesis of the myeloid cell lineage. The diseases have been found to evolve in a biological continuum from early cancer state, essential thrombocythemia, over polycythaemia vera (PV), to the advanced myelofibrosis stage (PMF). The symptoms in these patients are often a result of the changes in the blood composition, hyperviscosity, microvascular disturbances, and reduced tissue perfusion. The major causes of morbidity and mortality are thromboembolic‐ and haemorrhagic events, and leukemic transformation. A group of mutations that drive the MPNs has been identified, e.g., the JAK2V617F mutation, which results in deregulation of the JAK/STAT signal transduction pathway important, for instance, in cell differentiation and survival. A previous large register study has shown that patients with MPNs have an increased risk of neovascular AMD, and a pilot study has shown an increased prevalence of intermediate AMD. We wish to study this further in a larger scale study. Several studies have also shown that systemic inflammation plays an essential role in both the initiation and progression of the malignant cell clone in MPNs. From this knowledge, a "Human inflammation model" has been developed. Since then, the MPNs has been used as model diseases for a similar inflammation model for the development of Alzheimer's disease. In this PhD project, we would like to investigate systemic inflammation in relation to drusen presence. We will do this by comparing systemic immunological markers previously investigated in patients with AMD and compare with MPN. We are primarily interested in systemic immunological differences between patients with MPN and drusen (MPNd) and MPN with normal retinas (MPNn). This thesis consists of two main studies. Study I investigated the prevalence of retinal changes associated with AMD and the prevalence of different AMD stages in 200 patients with MPN (paper I). Study II examined immunological similarities between AMD and MPNs. This study was divided into three substudies exploring systemic markers of inflammation, ageing and angiogenesis, respectively. This was done in four types of patients: nAMD, intermediate AMD (iAMD), MPNd and MPNn. Investigating, differences between MPNd and MPNn, will make it possible to identify changes in the immune system, relevant for AMD pathogenesis. Additionally, we will compare patients with MPNs with patients with iAMD and nAMD. In study I (Paper I), we found that patients with MPNs have a significantly higher prevalence of large drusen and consequently AMD from an earlier age compared to the estimates from three large population‐based studies. We also found that drusen prevalence was associated with a higher neutrophil‐to‐lymphocyte ratio indicating a higher level of chronic low‐grade inflammation in patients with drusen compared to those without drusen. In study II (papers II, III and IV), we found immunological differences between patients with MPNd and MPNn. When we investigated markers of inflammation, we found a higher level of systemic inflammation in MPNd than MPNn. This was indicated by a higher inflammation score (based on levels of pro‐inflammatory markers), a higher neutrophil‐to‐lymphocyte ratio, and indications of a deregulated complement system. When examining markers of ageing, we found signs of accelerated immune ageing in MPNd compared to MPNn, shown by more senescent effector memory T cells. Finally, when exploring a marker of angiogenesis, we found a lower CXCR3 expression on monocytes and T cells in nAMD compared to iAMD, MPNd and MPNn, in line with previous studies of nAMD compared to healthy controls. Further, we found decreasing CXCR3 expression over the MPN biological continuum. These studies indicate CXCR3 involvement in both nAMD and PMF, two disease stages characterised by angiogenesis and fibrosis. From the results of this PhD project, we can conclude that the prevalence of drusen and AMD is increased in patients with MPN compared to the general population. Further, our results show that systemic inflammation may play a far more essential role in AMD pathogenesis than previously anticipated. We, therefore, propose an AMD model (Figure 18) where inflammation can initiate and accelerate the normal age‐dependent accumulation of debris in the retina, which later evolve into drusen, resulting in increased local inflammation, and over time early‐ and intermediate AMD. This results in the increased risk of developing the late debilitating stages of AMD. [ABSTRACT FROM AUTHOR]

This is my personal memories concerning the Nordic periodical Acta Ophthalmologica in the period 1970-88. Poul Brændstrup was scientific secretary for Acta 1950-70 and chief editor 1970-75. His many important scientific works and enormous work for Acta is described, but also personal topics are mentioned. Acta meetings in the Danish Ophthalmol Society (DOS) and in the Nordic ophtalmol. Congresses are discussed. A referee-system is established from 1976, but with political contra scientific motives. Only a few papers arrived to Acta. A catastrophe in 1978 is mentioned. The new secretary Ingelise Truberg did an enormous work for the next ten years. Erik Jørgensen (1928-90) was our printer, and from 1975 our idealistic publisher after Munksgaard. The economy became better and the number of papers of high quality increased. The relationship to the new Nordic periodical Oftalmolog was discussed in 1982. [ABSTRACT FROM AUTHOR]

Surgical approaches for rhegmatogenous retinal detachment (RRD) have evolved rapidly in the past century. This has resulted in an increase in the anatomical success rate from zero per cent in the beginning of the 1900s to now almost 100 per cent. Rhegmatogenous retinal detachment is regarded as an acute eye disease that needs immediate treatment. With the increasing number of cataract surgeries and an increased elderly population, the numbers of RRD occurrences are increasing. The aim of this thesis is to create knowledge on how treatment and care of RRD patients can be optimized. In the first paper, data on the incidence of RRD in Denmark are presented based on data from a nation register the National Patient Registry ( NPR). It was discovered that the incidence of RRD in Denmark is similar to previous reported numbers and that the incidence has been increasing due to increasing numbers of cataract surgeries and an increased elderly population. Using data from the NPR, we estimated that the risk of a RRD occurring on the fellow eye is 100 times larger than on the first eye and that middle aged men have the highest risk. Having an increase in the incidence of RRD we need to ensure that the patients are also treated in the most optimal way. To ensure this, an indicator is needed to monitor the quality at the different centres. This indicator presented in the second paper is based in the occurrence of redetachment. We define a detachment to be caused by poor surgery if the retina detaches within one year after initial surgery with pneumatic retinopexy, scleral buckling and VTX with gas, and one and a half years after surgery with VTX with oil. Also lack of oil removal within the first year is a failed operation. It is widely accepted that RRD is an acute disease but when should surgery be performed to attain the most optimal result? In the third paper, we evaluated the progression of posterior RRD with an optical coherence tomography to make an objective assessment of the movement. We found that the risk of a macula on RRD progressing to affect the fovea is small if the patient is postured appropriately. We found that the movement of the RRD is dynamic but the detachments will ultimately approach the fovea. Having an opportunity to postpone surgery without risking the outcome for the patient allows a more optimal surgery. The results of this thesis can be used by all health care systems to establish optimal conditions in the treatment of RRD. [ABSTRACT FROM AUTHOR]

Abstract not provided [ABSTRACT FROM AUTHOR]

Purpose: The management of blepharitis continues to challenge clinicians due to the poorly understood aetiology of the condition. We recently identified the family of intracellular plakin proteins as essential driving forces underlying anterior blepharitis. A large‐scale protein analysis was used to study if a topical dexamethasone/tobramycin solution could be used to reverse the expression of plakin proteins. Methods: Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) were collected with Schirmer filtration paper. A subgroup of the patients (n = 10) received treatment with a dexamethasone/tobramycin 1 + 3 mg/mL ophthalmic suspension (Tobradex®) for 3 weeks and collection of tear film samples was repeated. The samples were analysed with label‐free quantification nano liquid chromatography–tandem mass spectrometry requiring quantification in at least 70% of the samples in each group. Proteins were considered differentially expressed if p < 0.05. Results: Following Tobradex® intervention, 27 proteins were upregulated while 61 proteins were downregulated. Regulated proteins after Tobradex® treatment were involved in intermediate filament cytoskeleton organization including downregulation of the plakin proteins envoplakin, epiplakin and periplakin. Plectin, a protein of the plakin family, remained unchanged after Tobradex® therapy. Tobradex® treatment resulted in the regulation of proteins involved in translation including a cluster of downregulated ribosomal proteins. Tobradex® intervention was associated with the regulation of proteins involved in fructose metabolism and glycolytic processes including fructose‐1.6‐bisphosphatase 1, fructose‐bisphosphate aldolases A and B, pyruvate kinase PKM and transketolase. Ig lambda chain V‐I region, prominin‐1, and protein Niban were upregulated after Tobradex® treatment. Conclusions: Tobradex treatment reversed the expression of plakin proteins in anterior blepharitis. Topical solutions which inhibit the expression of plakin proteins may have the potential to restore the ocular surface integrity in anterior blepharitis and should be explored further. [ABSTRACT FROM AUTHOR]

Background and Purpose: Late secondary glaucoma is an often‐severe complication after acute events like anterior segment surgery, trauma and infection. TNF‐α is a major mediator that is rapidly upregulated, diffusing also to the retina and causes apoptosis of the ganglion cells and degeneration of their optic nerve axons (mediating steps to glaucomatous damage). Anti‐TNF‐α antibodies are in animals very effective in protecting the retinal cells and the optic nerve—and might therefore be useful prophylactically against secondary glaucoma in future such patients. Here we evaluate (1) toxicity and (2) efficacy of two TNF‐α inhibitors (adalimumab and infliximab), in rabbits by subconjunctival administration. Methods: For drug toxicity, animals with normal, unburned corneas were injected with adalimumab (0.4, 4, or 40 mg), or infliximab (1, 10, or 100 mg). For drug efficacy, other animals were subjected to alkali burn before such injection, or steroids (for control). The rabbits were evaluated clinically with slit lamp and photography, electroretinography, optical coherence tomography, and intraocular pressure manometry. A sub‐set of eyes were stained ex vivo after 3 days for retinal cell apoptosis (TUNEL). In other experiments the optic nerves were evaluated by paraphenylenediamine staining after 50 or 90 days. Loss of retinal cells and optic nerve degeneration were quantified. Results: Subconjunctival administration of 0.4 mg or 4.0 mg adalimumab were well tolerated, whereas 40.0 mg was toxic to the retina. 1, 10, or 100 mg infliximab were also well tolerated. Analysis of the optic nerve axons after 50 days confirmed the safety of 4.0 mg adalimumab and of 100 mg infliximab. For efficacy, 4.0 mg adalimumab subconjunctivally in 0.08 mL provided practically full protection against retinal cell apoptosis 3 days following alkali burn, and infliximab 100 mg only slightly less. At 90 days following burn injury, control optic nerves showed about 50% axon loss as compared to 8% in the adalimumab treatment group. Conclusions: Subconjunctival injection of 4.0 mg adalimumab in rabbits shows no eye toxicity and provides excellent neuroprotection, both short (3 days) and long‐term (90 days). Our total. accumulated data from several of our studies, combined with the present paper, suggest that corneal injuries, including surgery, might benefit from routine administration of anti‐TNF‐α biologics to reduce inflammation and future secondary glaucoma. [ABSTRACT FROM AUTHOR]

The intraoperative optical coherence tomography (iOCT) is recently introduced in Descemet membrane endothelial keratoplasty (DMEK) surgery, which aims to increase clinical performance and surgery safety. However, the acquisition of this modality is a substantial investment. The objective of this paper is to report on the cost‐effectiveness of an iOCT‐protocol in DMEK surgery with the Advanced Visualization in Corneal Surgery Evaluation (ADVISE) trial. This cost‐effectiveness analysis uses data 6 months postoperatively from the multicentre prospective randomized clinical ADVISE trial. Sixty‐five patients were randomized to usual care (n = 33) or the iOCT‐protocol (n = 32). Quality‐Adjusted Life Years (EQ‐5D‐5L), Vision‐related Quality of Life (NEI‐VFQ‐25) and self‐administered resources questionnaires were administered. Main outcome is the incremental cost‐effectiveness ratio (ICER) and sensitivity analyses. The iOCT protocol reports no statistical difference in ICER. For the usual care group compared with the iOCT protocol, respectively, the mean societal costs are €5027 compared with €4920 (Δ€107). The sensitivity analyses report the highest variability on time variables. This economic evaluation learned that there is no added value in quality of life or cost‐effectiveness in using the iOCT protocol in DMEK surgery. The variability of cost variables depends on the characteristics of an eye clinic. The added value of iOCT could gain incrementally by increasing surgical efficiency, and aiding in surgical decision‐making. [ABSTRACT FROM AUTHOR]

Purpose: The macular ganglion cell layer (mGCL) is a strong potential biomarker of axonal degeneration in multiple sclerosis (MS). For this reason, this study aims to develop a computer‐aided method to facilitate diagnosis and prognosis in MS. Methods: This paper combines a cross‐sectional study of 72 MS patients and 30 healthy control subjects for diagnosis and a 10‐year longitudinal study of the same MS patients for the prediction of disability progression, during which the mGCL was measured using optical coherence tomography (OCT). Deep neural networks were used as an automatic classifier. Results: For MS diagnosis, greatest accuracy (90.3%) was achieved using 17 features as inputs. The neural network architecture comprised the input layer, two hidden layers and the output layer with softmax activation. For the prediction of disability progression 8 years later, accuracy of 81.9% was achieved with a neural network comprising two hidden layers and 400 epochs. Conclusion: We present evidence that by applying deep learning techniques to clinical and mGCL thickness data it is possible to identify MS and predict the course of the disease. This approach potentially constitutes a non‐invasive, low‐cost, easy‐to‐implement and effective method. [ABSTRACT FROM AUTHOR]

The incidence of type 1 diabetes is rising all over the world. Furthermore, the increased life-expectancy of type 1 diabetic patients is likely to cause a higher number of diabetes-related micro- and macrovascular complications in the years to come. In order to examine the level of long-term complications in type 1 diabetes as well as potential markers of micro- and macroangiopathy, a population-based cohort of Danish type 1 diabetic patients was examined in order to achieve the following aims: In Paper I it was a major finding that, despite a mean age of only 38.3 years at baseline, 44.7% of the patients died during the 25-year follow-up. Patients who had proliferative retinopathy as well as proteinuria at the baseline examination had a significantly higher mortality. For these, the 10-year survival was only 22.2%. As demonstrated in Paper II, blindness is an important issue in type 1 diabetes. The 25-year cumulative incidence of blindness was 7.5%. Glycaemic regulation and maculopathy at baseline were both identified as risk factors of blindness. Finally, mortality was higher in patients who went blind during the follow-up. Cataract surgery is quite common in type 1 diabetes. In Paper III a 25-year cumulative incidence of 20.8% was found. Adjusted for mortality, this was even higher (29.4%). As compared to patients without diabetes, cataract surgery takes place approximately 20 years earlier in type 1 diabetic patients. Age and maculopathy at baseline were both identified as predictors of cataract surgery. In Paper IV it was demonstrated that patients with retinal arteriolar narrowing were 2.17 and 3.17 times more likely to have nephropathy and macrovascular disease, respectively. This was an important finding that suggests that retinal fundus photos may be used in order to predict the risk of non-ophthalmological complications in type 1 diabetes. Retinal fractal analysis is another way to evaluate the vascular system of the retina. In Paper V we found associations between retinal fractal and microvascular - but not macrovascular - disease. For instance, patients with lower fractal dimensions were more likely to have proliferative retinopathy (OR 1.45, 95% CI 1.04-2.03) and neuropathy (OR 1.42, 95% CI 1.01-2.01). NT-proBNP is likely to be a future predictor of diabetes-related complications. In Paper VI higher levels of NT-proBNP were related to nephropathy (OR 5.03, 95% CI 1.77-14.25), neuropathy (OR 4.08, 95% CI 1.52-10.97) and macrovascular disease (OR 5.84, 95% CI 1.65-20.74). These associations should be confirmed in future prospective studies. As opposed to NT-proBNP, osteoprotegerin is less likely to be a predictor of either micro- or macrovascular disease in type 1 diabetes. As demonstrated in Paper VII, even though association between higher levels of OPG and nephropathy were found in an age- and sex-adjusted model (OR 2.54, 95% CI 1.09-5.90), this was no longer statistically significant when other factors were taken into account. Overall, it was demonstrated that various complications such as mortality, blindness and cataract surgery were high in type 1 diabetes. Furthermore, retinal arteriolar narrowing, decreased retinal fractals and plasma NT-proBNP were associated with various micro- and macrovascular complications. If confirmed by prospective studies, these modalities may be used in order to identify patients at risk of diabetes-related complications. This could, ultimately, lead to decreased mortality and morbidity in type 1 diabetic patients. [ABSTRACT FROM AUTHOR]

Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE® and Cochrane databases were searched for all studies examining the effects of standard, trans-epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (±1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness. [ABSTRACT FROM AUTHOR]

Purpose: This paper is a scoping review of research on multiple sclerosis (MS)‐associated uveitis to determine its epidemiology, pathophysiology, clinical features and treatment. Methods: A comprehensive search of the medical databases MEDLINE (PubMed), EMBASE, Web of Science and Cochrane was carried out on 25 November 2019, to identify papers published between 1980 and 2019 that focus on patients with MS‐associated uveitis. Results: Based on large cohort studies (n ≥ 1000), the prevalence of uveitis in patients with MS is estimated to be 0.53–1.34% (mean = 0.83%), and MS is diagnosed in 0.52–3.20% (mean = 1.30%) of patients with uveitis. The condition is most frequent among middle‐aged women. Patients usually complain of floaters and/or blurred vision, with bilateral intermediate uveitis (with retinal vasculitis) as the most frequent ophthalmological finding. Both MS and intermediate uveitis are associated with HLA‐DRB1*15:01 and IL‐2RA gene polymorphism rs2104286 A > G, suggesting a common genetic background. T cells, and possibly B cells, play an important role in both autoimmune disorders. Multiple sclerosis (MS)‐related uveitis is classically treated as non‐infectious uveitis, with corticosteroids as the first treatment step. Other treatments include immunosuppressants, cryotherapy, laser photocoagulation and vitrectomy. These treatment options have a limited, if any, effect on the course of MS and can be complicated by side‐effects. As treatment strategies for MS have increased in the last decade, it would be interesting to evaluate the efficacy of these new treatments during the course of uveitis. Moreover, the correlation between retinal periphlebitis and MS could be established more accurately with the recently developed techniques of wide‐field fluorescein angiography in a large cohort of MS patients. Conclusion: MS‐associated uveitis is a rare, highly discussed pathology about which much is still unknown. Large epidemiological studies and extrapolation of new MS treatments to this condition are warranted. [ABSTRACT FROM AUTHOR]

During early summer 2019, the Netherlands experienced an outbreak of the exotic oak processionary caterpillar. The vast number of caterpillars, which live in large nests on oak trees before they turn into moths, possess thousands of small, barbed hairs (setae) that are disseminated with the wind. The hairs cause a range of primarily dermatologic problems. However, Dutch ophthalmologists started reporting patients with ophthalmologic complaints caused by the penetrating hairs of the oak processionary caterpillar. This paper focuses on the ophthalmologic complications caused by the caterpillar hairs. We collected a series of four cases with reports ranging from a corneal erosion with hairs lodged into the cornea, to a sterile endophthalmitis in which hairs were found in the vitreous. A literature review for similar cases was performed using the PubMed and Embase database. Together with the Dutch Ophthalmic Society (Nederlands Oogheelkundig Gezelschap, NOG), a national survey was issued to determine the scale of this new problem. This showed that oak processionary caterpillar related complaints are primarily limited to the south of the Netherlands. Suggested ophthalmic treatment guidelines are presented. With the next summer at the doorstep, and limited preventative measures against the caterpillar hairs, we expect a new wave of ophthalmologic complaints coming year as well. [ABSTRACT FROM AUTHOR]

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first‐choice treatment for primary open‐angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes. [ABSTRACT FROM AUTHOR]

The Year 2023 is particularly important for Acta Ophthalmologica journal. It is an anniversary year, as Acta Ophthalmologica celebrates its 100th anniversary. The journal was founded by Konrad Kristian Karl (K.K.K) Lundsgaard in 1923. The goal was to present the clinical and experimental achievements of the ophthalmological communities of the Nordic countries. With the passage of time and increasing interest from scientific communities in other countries, it has become one of the most visible ophthalmology journals in the world. Acta Ophthalmologica publishes a wide variety of high‐quality ophthalmological papers. Here, we present the activities of Acta Ophthalmologica over the past 100 years. [ABSTRACT FROM AUTHOR]

Optic disc drusen (ODD) are calcium‐containing deposits in the optic nerve head, capable of causing visual field defects and sudden visual loss. The underlying pathophysiology remains inadequately understood and treatment options are missing. In this paper, we systematically reviewed prevalence studies of ODD in non‐selected populations to provide an overview of its prevalence, conducted meta‐analyses to determine modality‐specific prevalence estimates and performed a forecasting study to estimate current and future global population number of individuals with ODD. We searched 11 literature databases on 25 October 2022 for prevalence studies of ODD in non‐selected populations. Eight eligible studies provided data from a total of 27 463 individuals. Prevalence estimates were stratified according to diagnostic modalities: ophthalmoscopy 0.37% (95% CI: 0.10–0.95%), fundus photography 0.12% (95% CI: 0.03–0.24%), spectral domain optical coherence tomography with enhanced depth imaging 2.21% (95% CI: 1.25–3.42%) and histopathology 1.82% (95% CI: 1.32–2.38%). Using histopathology‐based summary prevalence estimate, we forecast 145 million individuals with ODD currently, a number expected to increase further due to world population growth. These numbers underscore the importance of including ODD in health education and highlight the necessity of continuing research in ODD. [ABSTRACT FROM AUTHOR]

The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on the association between nutrition and antioxidant, vitamin, and mineral supplements and the development or progression of age‐related macular degeneration (AMD). The Cochrane Database of Systematic Reviews, Cochrane register CENTRAL, MEDLINE and Embase were searched and studies published between January 2015 and May 2021 were included. The certainty of evidence was assessed according to the GRADE methodology. The main outcome measures were development of AMD, progression of AMD, and side effects. We included 7 systematic reviews, 7 RCTs, and 13 NRS. A high consumption of specific nutrients, i.e. β‐carotene, lutein and zeaxanthin, copper, folate, magnesium, vitamin A, niacin, vitamin B6, vitamin C, docosahexaenoic acid, and eicosapentaenoic acid, was associated with a lower risk of progression of early to late AMD (high certainty of evidence). Use of antioxidant supplements and adherence to a Mediterranean diet, characterized by a high consumption of vegetables, whole grains, and nuts and a low consumption of red meat, were associated with a decreased risk of progression of early to late AMD (moderate certainty of evidence). A high consumption of alcohol was associated with a higher risk of developing AMD (moderate certainty of evidence). Supplementary vitamin C, vitamin E, or β‐carotene were not associated with the development of AMD, and supplementary omega‐3 fatty acids were not associated with progression to late AMD (high certainty of evidence). Research in the last 35 years included in our overview supports that a high intake of specific nutrients, the use of antioxidant supplements and adherence to a Mediterranean diet decrease the risk of progression of early to late AMD. [ABSTRACT FROM AUTHOR]

Systematic reviews (SRs) and meta‐analyses (MAs) are of great importance for basing clinical decisions. However, misleading interpretations may result when informed decisions rest on biased review papers with methodological issues. To evaluate which treatment is optimal, an overview was made of SRs and MAs to establish the quality and certainty of meta‐evidence published on the efficacy of laser‐based refractive surgery techniques for treating myopia in adults. A search was made in five databases and was updated using Really Simple Syndication (RSS) feed appliances up to April 2021; SRs with or without MAs were included. Methodological quality was appraised using the AMSTAR‐2 tool. The best available reviews were summarized using the GRADE approach. The corrected covered area (CCA) was used to determine the degree of over‐representation of publications. The risk of bias of the primary studies was disclosed visually. Thirty‐six studies published between 2003 and 2021 were included. Twenty SRs (56%) were conducted in China. The most studied comparisons were SMILE versus FS‐LASIK (19%) and FS‐LASIK versus MM‐LASIK (11%). Of the 251 overlapping index publications, 165 were unique (CCA = 0.015%), representing a negligible risk of skewed reporting. The AMSTAR‐2 tool showed most SRs to have critically low or low quality. Nine reviews presented moderate quality. The GRADE approach of the 41 a priori outcomes evidenced critically low and low certainty of evidence. Only the spherical equivalent refraction changes at 12 months between LASEK and PRK showed moderate certainty of evidence, favouring PRK (mean difference 0.06, 95%CI [−0.02 to 0.14], I2 = 0%; p ≥ 0.05). Index trials among less biased reviews are prone to selection, performance and reporting bias. The appraised techniques exhibit comparable results in terms of efficacy. There is moderate certainty of evidence in favour of the use of PRK over LASEK in terms of the spherical equivalent refraction error changes at 1 year of follow‐up. Most appraised SRs presented methodological flaws in critical domains, resulting in a low to critically low certainty of evidence after GRADE appraisal. Therefore, investigators need to study and compare the different laser‐based refractive techniques to provide better evidence‐based medicine. Further well‐designed, high‐quality clinical trials and SRs are needed to reappraise the current findings. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To highlight the variations in published definitions of hypotony and their impact on reported clinical outcomes. To propose a revised definition, focusing on clinically significant hypotony (CH). Methods: Literature review of hypotony definitions published between January 2010 and December 2015 was carried out. Numerical definitions for hypotony, its onset, duration and associated clinical signs were recorded. Each definition was applied to surgical outcomes data collected prospectively from a cohort of 300 glaucoma patients treated at a single centre. The sensitivity and specificity of each definition in identifying CH [defined as low intraocular pressure (IOP) with signs of maculopathy hypotony and choroidal detachment] were calculated. Results: A total of 128 eligible papers were identified, and 14 different definitions for hypotony were extracted. In 53 (41.4%), hypotony was not defined. In the remaining 75 (58.6%), the numerical definitions varied between 4 and 8 mmHg, and of these, 24 (32%) included the onset and duration of hypotony as part of the definition. Definition‐dependent hypotony rates within the cohort varied between 1% and 59.3%. No statistical differences were found between the groups based on corneal thickness or axial length. Clinically significant hypotony (CH) was identified in 37 (12.3%), with large differences in the sensitivity and specificity among published definition. Conclusion: Variations in defining postoperative hypotony can have a large impact on the reported success and failure rates among studies. There is a need for a more robust universal definition, focusing on clinically important signs, to allow better comparison between different treatment modalities. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Circulating anti-retinal antibodies in response to anti-angiogenic therapy in exudative age-related macular degeneration." in the December 2014 issue is presented.

This paper describes a holistic, yet simple and comprehensible, ecosystem model to deal with multiple and complex challenges in eyecare. It aims at producing the best possible wellbeing and eyesight with the available resources. When targeting to improve the real‐world cost‐effectiveness, what gets done in everyday practice needs be measured routinely, efficiently and unselectively. Collection of all real‐world data of all patients will enable evaluation and comparison of eyecare systems and departments between themselves nationally and internationally. The concept advocates a strategy to optimize real‐life effectiveness, sustainability and outcomes of the service delivery in ophthalmology. The model consists of three components: (1) resource‐governing principles (i.e., to deal with increasing demand and limited resources), (2) real‐world monitoring (i.e., to collect structured real‐world data utilizing automation and visualization of clinical parameters, health‐related quality of life and costs), and (3) digital innovation strategy (i.e., to evaluate and benchmark real‐world outcomes and cost‐effectiveness). The core value and strength of the model lies in the consensus and collaboration of all Finnish university eye clinics to collect and evaluate the uniformly structured real‐world outcomes data. In addition to ophthalmology, the approach is adaptable to any medical discipline to efficiently generate real‐world insights and resilience in health systems. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to present a new surgical technique to remove vitreous cortex remnants. Methods: Non‐consecutive retrospective interventional case series. Results: When the posterior vitreous is split, its outermost layer may remain attached to the retina, developing vitreoschisis‐induced vitreous cortex remnants (VCR). Their role in macular pathology etiopathogenesis has been well documented; however, recently, it has been proposed that VCR also play a crucial role in proliferative vitreoretinopathy and consequent retinal redetachment. The prevalence of VCR is underestimated because triamcinolone acetonide is not routinely used for vitreous staining. Vitreous cortex remnants (VCR) removal is challenging, and several surgical techniques have been proposed. However, they require sclerotomy enlargement, material that may not be readily available, and manual fashioning. Alternatively, a diamond‐dusted membrane scraper (DDMS), already widely used in macular pathology treatment, can follow the contour of the retina, as it is a silicone tube, and remove VCR with its abrasive tip. A DDMS may also be introduced in the vitreous cavity through a standard trocar. Finally, the use of a DDMS provides predictable feedback, making the learning curve short. In this case series, 34 eyes affected by primary rhegmatogenous retinal detachment were enrolled. The retinal redetachment rate was 2.9% at six months of follow‐up, below the average literature value of 21%. No adverse events were reported. Conclusion: A DDMS can be suitable for use in VCR removal, although further studies are warranted to understand the indications and extent of this surgical technique for improving the management of rhegmatogenous retinal detachment. [ABSTRACT FROM AUTHOR]

Danish Ophthalmological Society (DOS) strongly supports prolonged and individualized screening intervals and urge all interested parties involved in DR screening in Denmark to support and follow the existing guidelines. In a recent paper by Byberg et al. (2020), the authors recommend longer screening intervals for diabetic retinopathy (DR), allegedly longer than the ones recommended by the Danish Ophthalmological Society (DOS). [Extracted from the article]

Corneal blindness is a leading cause of visual impairment worldwide. The most common treatment is to replace the diseased cornea with standard corneal transplantation. In eyes at high risk of graft failure, the Boston keratoprosthesis type 1 (KPro) can be used to restore vision and is currently the most frequently used artificial cornea in the world. However, glaucoma is a well‐known complication of KPro surgery and is the most important threat to vision in KPro‐implanted eyes. This chronic disease is influenced by elevated intraocular pressure (IOP) and damages the optic nerve, leading to progressive vision loss. In KPro patients, glaucoma is highly prevalent and extremely challenging to manage, yet its exact cause remains unknown. [ABSTRACT FROM AUTHOR]

The incidence of type 1 diabetes is increasing in Denmark as well as the rest of the world. Due to diabetes-related micro- and macrovascular complications, the morbidity and the mortality is higher among type 1 diabetic patients. The aim of this thesis was to examine a population-based cohort of 727 type 1 diabetic patients from Fyn County, Denmark, with an onset of diabetes before 1 July 1973 in order to: (1) Evaluate the all-cause mortality rates and the influence of sex, duration of diabetes and calendar year of diagnosis in a 33-year follow-up ( Paper I). (2) Examine glycaemic regulation, lipids and renal dysfunction as risk factors for all-cause mortality, cardiovascular mortality and IHD ( Paper II). (3) Estimate the prevalence of DR as well as the 25-year incidence of PDR and associated risk factors in long-time surviving patients ( Paper III). (4) To compare the grading of DR between ETDRS seven standard field 30° stereoscopic colour films and nine field 45° monoscopic digital colour images in long-term surviving patients ( Paper IV). In the years 1973–2006 an overall MR of 22.3 per 1000 person-years was found. Furthermore a relative mortality of 3.4 was found as compared to the general population in Denmark. The relative mortality was especially high for patients aged 30–39 (SMR 9.8). There was a tendency towards a better survival for patients diagnosed after 1964. This was especially seen for men. Diabetes was the most common cause of death for those who died in the group. In 1993–1996 blood samples were drawn and glycaemic regulation, lipids and renal markers were subsequently used as predictors of all-cause mortality, cardiovascular mortality and ischaemic heart disease. Glycaemic regulation, dyslipidaemia and creatinine were all significantly associated with all three endpoints. Furthermore, variations in glycaemic control were also identified as a risk factor for overall mortality. Two hundred and one patients were examined for diabetic retinopathy in 1981–1982 and 2007–2008. At follow-up, 97.0% had DR and 42.9% of all patients without PDR at baseline developed this during the follow-up period. Patients who had had a poor glycaemic regulation as well as those who had NPDR at baseline were more likely to develop PDR than the remaining patients. On the other hand, other risk factors such as high blood pressure and proteinuria did not predict PDR. In the comparative study between ETDRS seven standard field 30° stereoscopic colour films and nine field 45° monoscopic digital colour images, 43 eyes of 43 patients were examined in 2008. A poor correlation was found between the two methods: only 29.3% were graded alike. In the remaining, the level of DR was graded higher in the digital photos. Among these, PDR was detected in three eyes using digital photos but remained undetected on all films. This suggests that digital photos with wide fields are the best way to detect DR in long-term type 1 diabetic patients. Overall, it is concluded that mortality is still higher among type 1 diabetic patients. This depends, among other things, on glycaemic regulation, lipid status and, partly, renal dysfunction. Diabetic retinopathy is almost universal in long-term type 1 diabetic patients, and almost half of all patients will develop PDR in 25 years. Nine field digital photos provide the best grading of retinopathy in long-term type 1 diabetic patients. [ABSTRACT FROM AUTHOR]

In the context of the COVID‐19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID‐19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS‐CoV‐2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow‐up of the ophthalmic diseases. With this update (5th) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Despite the growing importance of real‐world evidence (RWE) for guiding clinical decisions in retinal disease, there is currently no widely used guidance available for assessing the quality and relevance of RWE studies in ophthalmology. This paper summarizes the development of a user‐friendly tool that facilitates assessment of the quality of available RWE for neovascular age‐related macular degeneration (nAMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). A literature search was conducted to identify tools developed to assess the quality of RWE, in order to identify the most appropriate framework on which to base this tool. The Good Research for Comparative Effectiveness (GRACE) guidelines was chosen for this purpose as it is designed to assess the quality of observational studies and has been extensively validated, including demonstration of strong sensitivity and specificity. The GRACE guidelines were adapted to develop a straightforward tabular tool that allows simple assessment and comparison of the quality of published evidence in retinal disease for researchers and physicians alike, and includes guidance on treatment details, outcome measures, study population, and controlling for bias. The newly developed tool provides a simple method to support assessment of the strength of evidence and certainty of conclusions drawn from RWE in retinal disease, to ensure clinical decision‐making is influenced by the highest quality evidence. [ABSTRACT FROM AUTHOR]

The main purpose of this thesis was to examine whether the Danish National Patient Registry (NPR) could be used to monitor and assess the quality of cataract surgery in Denmark by studying the risks of two serious postoperative complications following cataract surgery - retinal detachment (RD) and postoperative endophthalmitis (PE). The thesis consists of four retrospective studies. In the first study (paper I), we used data from the NPR in the calendar period 2000-2010 to investigate the risk of pseudophakic retinal detachment (PRD) using the fellow non-operated eyes of the patients as reference. The study showed that over a 10-year study period, the risk of PRD was increased by a factor of 4.2 irrespective of sex and age. The risk of PRD was highest in the first part of the postoperative period and then gradually decreased but remained statistically significantly higher than the risk of RD in non-operated fellow eyes up to 10 years after cataract surgery. The epidemiology of RD in the non-operated fellow eyes was different from the epidemiology of RD in the background population as young men had the highest risk of RD in the non-operated fellow eyes. This means that the absolute risk of PRD was highest for young men because they had a higher risk of RD before they underwent cataract surgery. In the second study (paper II), we used data from the NPR and reviewed patient charts to assess the risk of PE after cataract surgery performed in public eye departments and private hospitals/clinics in the study period 2002-2010. The overall risk of PE among the seven public eye departments was 0.36 per 1000 registered cataract operations, and the PE risk among the departments was homogeneous. The overall risk of PE among the 28 private hospitals/clinics was 0.73 per 1000 registered cataract operations, and the risk among the private hospitals/clinics was heterogeneous. Most private hospitals/clinics had a risk of PEthat was lower than or similar to the risk ofPEafter registered cataract surgery in public eye departments, but six private hospitals/clinics had a statistically significantly higher risk of PE compared to the public eye departments. We used PE as a proxy measure of the registration of cataract surgery and found that 98% of the cataract operations performed in public eye departments were registered in theNPRwhile only 38% of the cataract operations performed in private hospitals/ clinics were registered in the NPR. In general, the coding of the PE cases was not uniform and the lack of registration by the private hospitals/clinics meant that the NPR could not be used to monitor the true risk of PE. NPR data were also used in the third study (paper III) to examine whether patients who had surgical intervention for PE following cataract surgery with either a pars plana vitrectomy (PPV) or a vitreous tap (VT) had a higher risk of subsequent surgical complications. There was no statistically significant difference in the overall risk of complications among the two groups, but the risk of surgery for vitreous opacities was statistically significantly higher for patients who underwent a VT. A surgical complication occurred in 27.3% of the patients and 9.9% of the patients developed more than one surgical complication. Ninety-seven per cent of the primary surgical complications occurred within the first 5 months. The risk of surgical complications in this study was similar to or higher than the risk of complications in the landmarkEndophthalmitisVitrectomyStudy from the early 1990s. In the fourth study (paper IV), we used data from all three Danish cataract registries to describe the epidemiology of cataract operations performed in public hospitals and private hospitals/clinics in the study period 2004-2012. Again, PE was used as a proxy measure of the registration of cataract surgery. There were several noticeable differences in the epidemiology of the cataract operations performed in public hospitals and private hospitals/clinics. Patients who had cataract surgery in public hospitals had a statistically significantly higher mortality compared to patients who had cataract surgery in private hospitals/ clinics during the entire period. The decrease in the mean age at first eye cataract surgery in private hospitals/clinics was statistically significantly greater compared to public hospitals during the study period. There was a statistically significantly shorter median time interval between first and second eye cataract surgery at private hospitals/clinics compared to public hospitals during the entire study period. The study showed that only 54% of the cataract operations performed in private hospitals/clinics that led to PE were registered. The lack of registration of cataract surgery is the main reason why the NPR has limitations when used as a tool to monitor and assess the quality of cataract surgery in Denmark. [ABSTRACT FROM AUTHOR]

On a global scale, myopia is one of the most common causes of visual impairment. Given the increasing prevalence of myopia, it is vital to understand the pathogenesis and to identify potential interventions. Some studies have described physical activity as a potential correlation for myopia. The objective of this study was to make a systematic review regarding the correlation between physical activity and myopia. A total of 263 papers were identified in a systematic database search of PubMed/Medline and Embase. Five steps of screening removed studies of a low evidence quality and animal studies. Studies included had refractive error and physical activity (as measured by questionnaires, accelerometers and cycle ergometers) as separate, well-defined outcomes. Nine studies (six cross-sectional, two cohorts and one case-control study) with a total of 17 634 subjects were included. Six studies demonstrated a reverse association between physical activity and myopia. Three studies supported this, but also attributed the results to time spent outdoors and not physical activity per se. One cross-sectional study found no relation. We could not identify trends among the papers regarding the type of studies, population sizes, ethnicity or age of study subjects. A consistent relationship between more physical activity and less myopia was observed. No evidence of physical activity as an independent risk factor for myopia was seen. Evidence suggests that time outdoors remain the most important factor. Future studies should include objective measurements of physical activity to determine a potential independent effect. Distinction between physical activity and outdoor exposure remains important. [ABSTRACT FROM AUTHOR]

Peer review is designed to evaluate the validity, quality and often the originality of articles for publication. Its aim is to provide the integrity of science by filtering out invalid or poor‐quality submissions. Moreover, the process of peer review adds value to the article by helping to improve that work. 90% of researchers feel that peer review improves the quality of their published paper. Peer reviewing is a critical, and constructive evaluation of submission, particularly including analysis of the paper structure and presentation, methodology strength and clarity; and originality of the study. There are some benefits related with reviewing. It makes a person better writer and better author of future scientific pieces. It helps to think critically about own research and become a better researcher. It is often a sign and proof of the reputation within the field. High‐quality reviews are noticed and appreciated by the editors, who often will invite reviewer to be more involved in editorial work, as an author of editorials or editorial board member. Very often journals invite new editorial members only with some previous history of reviewing for the journal. Reviewers also have often access to emerging ideas and trends much earlier than others. [ABSTRACT FROM AUTHOR]

. This thesis addresses several aspects of glaucoma diagnostics from both a clinical and a screening perspective. New instruments for diagnosing glaucoma have been developed over the past years, but little information is available regarding their performance as screening methods and their usefulness in ordinary clinical practice. Purpose of the research underlying this thesis: The objectives of this research were as follows: to compare the accuracy of results of analysis of the optic nerve head (ONH) achieved by computerized imaging using the Heidelberg Retina Tomograph (HRT) and by subjective assessment performed by physicians with different degrees of experience of glaucoma (paper III); to evaluate the effect of a continuous medical education (CME) lecture on subjective assessment of the ONH for diagnosis of glaucoma (paper II); to investigate subjective assessment of perimetric test results by physicians with varying knowledge of glaucoma with a trained artificial neural network (ANN) and to compare the certainty of the classifications (paper IV); and to compare the diagnostic performance of time-domain Stratus optical coherence tomography (OCT) with that of spectral-domain Cirrus OCT (paper I), frequency doubling technology (FDT) screening perimetry and scanning laser polarimetry with the GDx variable corneal compensator (VCC) in a random population-based sample and in patients with glaucoma of varying disease severity. Methods and results: In evaluation of the ONH, use of the HRT statistical tools, Moorfields regression analysis (MRA) and the Glaucoma Probability Score (GPS) was compared with subjective assessment performed by 45 physicians. Optic nerve head images and photographs from 138 healthy and 97 glaucoma subjects were included. The sensitivity of MRA was higher (87-94%) than that of the average physician (62-82%), considerably greater than that of ophthalmologists with subspecialties other than glaucoma (53-77%) and non-significantly better than that of glaucoma experts (72-88%). Sensitivity achieved by GPS (79-93%) was also greater than that of the average physician. MRA correctly classified all eyes with advanced glaucomatous visual field defects, a result that was not achieved by GPS or even by the glaucoma experts. In eyes with small discs, MRA sensitivity (88%) was comparable with that of glaucoma experts (85%) and much better than that of GPS (50%). Also, the group comprising all physicians provided specificity (75-92%) similar to that of both MRA (69 - 86%) and GPS (72-94%) (Andersson et al. 2011a). A 1-hr CME lecture on ONH assessment led to a significant improvement in sensitivity (from 70% to 80%) and a significant decrease in uncertain assessments (from 22% to 13%), whereas specificity remained unchanged (68%) (Andersson et al. 2011b). A rise in sensitivity was seen in all subgroups of physicians, including glaucoma experts. Thirty physicians assessing standard automated perimetry (SAP) test results as Humphrey Field Analyzer single-field analysis printouts with full StatPac information from 99 patients with glaucoma and 66 healthy subjects were compared with a trained ANN regarding diagnostic performance. ANN reached significantly higher sensitivity (93%) than the average physician (83%), whereas specificity was similar for these two groups (91% and 90%, respectively). Diagnostic accuracy was similar among the different groups of physicians and seemingly rather independent of experience. Sensitivity ranged from 82% in the subgroup of other subspecialists to 87% in the glaucoma expert group, and specificity ranged from 88% among general ophthalmologists to 91% for glaucoma experts. The ANN attained certainty of classification that was in parity with that provided by the glaucoma experts and did not make any completely incorrect classifications of the visual fields (i.e. erroneous classifications were in the borderline zone) (Andersson et al. 2012). From a population-based randomly selected sample ( n = 308) of older subjects (aged ≥50 years) living in southern Sweden, 170 subjects underwent a comprehensive examination that included Stratus OCT, Cirrus OCT, an FDT screening programme and the GDx VCC. The same test protocol was applied to 138 randomized clinical patients with different stages of glaucoma. In the population-based sample, both Stratus and Cirrus OCT showed high diagnostic accuracy with area under the receiver-operating curve (aROC) values close to 1.0 (Bengtsson et al. 2012). Both OCT instruments correctly classified all of the clinical glaucoma patients with advanced disease. FDT screening showed high sensitivity (91%) but erroneously gave normal test results for some eyes with advanced disease. GDx VCC had lower sensitivity (73-92%) and also led to a large proportion of examinations with an atypical retardation pattern that is known to affect the diagnostic efficiency of this instrument. Conclusions: The HRT MRA performed better than most physicians and was consistent with the glaucoma experts. These results suggest that MRA can be a valuable tool for diagnosing glaucoma in ordinary practice, particularly when only a few glaucoma experts are available. Even though MRA provided 100% sensitivity in eyes with advanced glaucoma, it probably does not offer sufficient specificity to make it suitable as a screening method. Continuing medical education on ONH analysis had a small, but positive effect on diagnostic accuracy for glaucoma. An ANN trained to classify visual fields seemed to perform at least as well as most of the participating physicians, whose performances were remarkably similar regardless of their level of experience. This indicates that available tools for interpreting SAP findings are helpful in assessments of visual field test results. However, SAP is associated with learning effects (Heijl et al. 1989) that may entail low specificity for untrained subjects, and hence, it is not an ideal screening method for glaucoma. By comparison, the screening test of FDT is rapid and easy, but it is probably less suitable for screening purpose, because some eyes with advanced glaucoma were missed in this investigation. GDx VCC images for a relatively large number of eyes could not be analysed and is thus not appropriate for screening. The OCT instruments offer both high sensitivity and high specificity, and all eyes with advanced disease were correctly classified as glaucomatous in this evaluation. However, these instruments are still expensive and require special operator skills. Additional development to obtain OCT instrument that is more compact, easier to use and less expensive might render such tomography suitable as a screening tool for glaucoma. [ABSTRACT FROM AUTHOR]

The table of contents for the 2008 issue of "Acta Ophthalmologica" is presented.