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Achtergrond: Coronavirus disease 19 (COVID-19) veroorzaakt naast een lagere luchtweginfectie ook een multisystemische aantasting waarbij zeldzaam ook oculaire complicaties optreden. Meest frequent is conjunctivitis maar ook in het posterieur segment zijn manifestaties beschreven. Doel: Deze literatuurstudie poogt een overzicht te bieden van het groeiend aantal artikels over de impact en manifestaties van COVID-19 op de retina en choroïdea. Methode: Het is een review van de huidige literatuur waarbij aan de hand van een systematische zoektocht tussen December 2021 en December 2022 in de PubMed databank gezocht werd naar meta analyses, cross sectionele studies, case control studies, case series en case reports over de impact van COVID-19 op de retina en choroïdea. Resultaten: 39 artikels werden geïncludeerd voor een kwalitatieve synthese. COVID-19 kan de retina en de choroïdea aantasten met voornamelijk een spectrum van microvasculopathie gaande van cotton wool spots, retinale bloedingen, vasculaire dilatatie en tortuositeit tot occlusieve retinopathie. Daarnaast kan COVID-19 leiden tot multipele inflammatoire manifestaties in het posterieur segment zoals neuro-retinitis en posterior uveïtis waarbij een overactieve immuunrespons, autoimmuniteit en genetische predispositie een rol spelen. Bij ernstige COVID-19 kan de immunosupressieve behandeling voorbeschikken tot opportunistische infecties zoals endogene endoftalmitis. Naast de temporale relatie hebben vele patiënten geen oftalmologische voorgeschiedenis of comorbiditeit wat de correlatie met COVID-19 versterkt. Conclusie: Voor oftalmologen is het belangrijk om zich bewust te zijn van deze oculaire manifestaties van COVID-19. Verder onderzoek aan de hand van prospectieve studies is nodig om een sterker causaal verband aan te tonen en meer inzicht te verkrijgen in pathogenese, preventie en mogelijke behandelingsopties.

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Current advanced non-invasive retinal imaging instruments permit to detect and measure accurately small focal changes of the retina in patients[PSt1] . These findings can help in determining the cause of unexplained visual symptoms and visual loss. For example, the macula of patients with vitreomacular traction may show only subtle changes detectable by ophthalmoscopy. However, optical coherence tomography (OCT) images allow a precise classification supporting treatment decision and prognosis.1 Additional improvements in OCT technology have permitted to obtain an axial resolution of approximately 3 to 5 µm.2,3 This high resolution allows excellent tomographic visualization of the retinal architecture and helps to indicate pathologic changes in the microstructure of the retina, especially the photoreceptor layer.Despite the high axial resolution, the relatively low transverse resolution remains a constraint in OCT imaging.^ Generally, the transverse resolution of OCT is approximately 20 µm, which exceeds the cone [PSt2] mosaic spacing of 5 to 10 µm. The main reasons [PSt3] inducing this limitation are the ocular optical aberrations and the saccadic eye movements. 4,5Adaptive optics (AO) systems are designed to overcome these optical limitations[PSt4] . An AO system consists of a wavefront sensor to measure ocular aberrations and a deformable mirror to compensate for these aberrations. Correcting the ocular aberrations with the AO system yields a transverse resolution of less than 2 µm, which is required to visualize individual cone photoreceptors [PSt5] in the living retina.6,7 This enables accurate detection and measurement of small anatomical lesions. In contrast to OCT imaging, the limitation of the AO system is its low axial resolution.^ It is larger than 100 µm in conjunction with conventional flood-illumination fundus photography.6Because Fourier-domain [PSt6] (FD) OCT provides a high axial resolution enabling visualization of retinal lamination, and the AO system delivers a high transverse resolution allowing direct visualization of the cone photoreceptor mosaic5,8, we think it is valuable to study the [PSt7] retinal architecture in parallel using both instruments.Recently, the advent of ocriplasmin (JetreaÒ) introduced pharmacological vitreolysis as a new treatment modality for diseases of the vitreomacular interface (VMI)9. This has created the need to obtain data on the incidence of these pathologies in the adult population. Although OCT allows accurate diagnosis and classification of diseases of the VMI1,10 , little is known about the epidemiology.^ An epidemiological study examining a group of almost 500 visitors using OCT at the ‘Dag van de Wetenschap’ on November 24th 2013 was organized.Adaptive Optics can visualize individual retinal cones and analysis of the obtained images allows determination of cone density. In addition, spatial distribution of cones can be described by determining spacing and packing arrangement[PSt8] (number of nearest neighbours). Obtaining normative data of these parameters is crucial for further analysis in diseased retina. Healthy volunteers will be examined with a flood-illumination Adaptive Optics camera (rtx 1TM, Imagine Eyes[JJ9] , France). Limited data on cone density, spacing and packing are available. Although some authors report data in SLO-Adaptive Optics systems11,12,13,14, and Lombardo’s group15 report data in a flood-illumination camera, quantitative analysis in different age groups have not been reported using a flood-illumination camera.^ Since there is no standardized analyzing method available, we designed a novel technique [PSt10] that we value as also useful for comparison purposes in diseased retinas.General hypothesis and specific aims of the projectThe first project includes an epidemiological study on the incidence of diseases of the vitreomacular interface in the adult population. This study was organized on November 24th 2013 with a total of almost 500 visitors. OCT data recorded from these healthy volunteers will allow to determine the incidence of VMI abnormalities and to create a normative database with data obtained from this study population.The second project targets a description of the cone photoreceptor density, spacing and packing arrangement in 2[PSt11] different age groups of healthy volunteers. This will allow the creation of a normative database, useful for referencing purposes in a wide variety of retinal pathologies.^ Adaptive optics is a novel technology that has been used to address a range of basic science questions and has been able to detect even minor changes in the cone mosaic in eyes that appeared healthy by standard clinical tests.16 Early detection of modest structural changes at the cellular level can be beneficial for patients by shortening the diagnostic lag time of treatment effects and selection of optimal patients to test emerging treatments.17In addition to this project, patients with various retinal pathologies affecting the outer retina will be examined with AO as to determine and measure morphological changes in the pathologic retina and subsequently these data will be compared to the obtained normative data.MethodologyThe data capturing of the epidemiological study on the incidence of vitreomacular diseases in an adult population has taken place on the 24th of November 2013 during the ‘Dag van de Wetenschap’.^ After an information session on the increased interest of the vitreomacular interface due to the advent of a new pharmaceutical treatment modality, visitors were given the opportunity to have an OCT scan taken of the macular area from both eyes after signing the informed consent form. Five similar OCT machines (Cirrus 5000 HD OCT, Carl Zeiss Meditec, Germany) were operated by experienced technicians of the department of Ophthalmology UZ Leuven. Residents in training from the same department provided information on the results of the examination and took a short history (general and ophthalmologic history), as well as the objective refraction of both eyes. Visitors were given a print of their OCT scans along with some relevant explanation.This study was approved by the Ethics Committee of the UZLeuven (study S55784). The obtained OCT scans will be viewed and interpreted by Dr J. Jacob and Prof Dr P. Stalmans.^ If required to build a normative database, additional OCT imaging from healthy subjects may be necessary, which in that case will be performed in an additional clinical study.[PSt12]The second project [PSt13] consists of Adaptive Optics images on healthy adult subjects of different ages. Subjects without ocular history will be recruited among the hospital staff of the Department of Ophthalmology at Hôpital Lariboisière (AP-HP), Paris. Comprehensive information will be provided and an informed consent will be obtained. For[JJ14] a better interpretation of Adaptive Optics images other measurements and multimodal imaging of the retinal fundus will also take place: measurement of visual acuity, refractometry, axial length, OCT and fundus photography (Spectralis, Heidelberg engineering, Germany). Adaptive optics images will be obtained using a commercially available flood-illumination camera (rtx1TM, Imagine Eyes, France).^ Multiple images will be obtained on the horizontal axis and the vertical axis at different eccentricities focused on the photoreceptor layer. Treatment of the images and analysis of density, spacing and packing arrangement will be effected with the use of following software: AO-CK, AO-detect, i2k, GIMP and Powerpoint. Single-frame AO images will be stitched into a montage, and superimposed on a standard clinical fundus photograph, showing the cone mosaic at high resolution and the corresponding area within the wide field image. To[JJ15] better understand changes, AO imaging of patients with various retinal pathologies will be performed similarly.Acquisition, treatment and analysis of the images will be performed by Dr J. Jacob, Prof Dr R. Tadayoni and Prof Dr A. Gaudric.This[JJ16] institutional clinical study was registered in clinicaltrials.gov (NCT01546181) and the procedures conformed to the tenets of the Declaration of Helsinki.^ Approval of the Ethics Committee of the Saint-Antoine hospital (AP-HP, Paris, France) was obtained.Milestones and timing of the PhD-projectPart-time PhD projectOur six-year project can be divided in 7 work packages (WP):WP 1: analysis of OCT data obtained during ‘dag van de wetenschap’WP 2: recruitment of patients for AO and acquisition of imagesWP 3: reporting results of OCT data from ‘dag van de wetenschap’, possibly designing an additional clinical trial for data collection in healthy subjectsWP 4: treatment of AO images and counting procedureWP 5: preparation of progress reportWP 6: reporting results AO imagesWP 7: writing PhD manuscriptConclusionRecent advances in retinal imaging instruments are able to provide noninvasive in vivo images of the retina with unprecedented resolution.^ Ultra-high resolution OCT with its high axial resolution allowing visualization of retinal lamination and Adaptive Optics with its high transverse resolution allowing direct visualization of the cone mosaic, are complementary in imaging the retinal architecture. These techniques enable detection of subtle structural changes in the retina in eyes that appear healthy by standard clinical tests. Data obtained from a population of healthy eyes are fundamental in determining the density, distribution, and appearance of normal retinal tissue, more specifically photoreceptor cells in vivo. This will allow determination of the normal physiological range in retinal cellular structure, which permits comparison with the diseased retina, even in an early stage. Earlier detection of structural changes at the cellular level of the retina could improve the understanding of physiopathology, accelerate the assessment of treatment effects, hence may allow better selection

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Background Diabetic retinopathy (DR) is a leading cause of preventable blindness in the active population worldwide, and the incidence continues to increase. Hyperglycemia, hypertension and dyslipidemia are considered the most important risk factors in the pathogenesis of DR and are the main focus of current treatment modalities. Recent publications suggest other risk factors may play a role in the onset and progression of DR. Until today, controversy remains concerning their importance as literature is still scarce. This report aims to give an overview of the available evidence concerning all risk factors that can cause the development or worsening of retinopathy in diabetic patients. Ultimately, the goal is for it to serve as a base for clinical guidelines for the prevention and treatment of diabetic retinopathy. Methods A literature search was conducted using PubMed database and Cochrane Library. Studies published from September 1993 until October 2020 in the English language were considered for review. Duplicates were removed and after screening based on title and abstract, 467 articles were selected. Subsequently, 93 articles were eligible for further review. A total of 59 articles met the inclusion criteria and were included and submitted for reading and analysis. Results Hyperglycemia has shown to be the strongest predictive factor in both the onset and progression of diabetic retinopathy. Opinions on the role of hypertension and dyslipidemia are not always consistent, although both blood pressure and lipid control have shown to be beneficial in the prevention of diabetic microvascular complications. Previous cataract surgery would increase DR onset rates, but it has no significant effect on the development of PDR nor DME. Up till now, it is still unclear whether nephropathy is a cause or a consequence of DR. Finally, with the currently available data, it remains impossible to draw conclusions concerning the effect of pregnancy, obesity, metabolic syndrome and bariatric surgery, hypothyroidism, smoking and alcohol intake on DR onset and progression, as literature on these topics is scarce. Conclusion This literature review confirmed previous statements on the importance of blood glucose, blood pressure and lipid profile control. Other risk factors have been studied lately, suggesting the possibility of new treatment focuses for the future. However, data is still limited and the results remain controversial. More research needs to be done in order to optimize current treatment options in the prevention and control of DR onset and progression.

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Achtergrond: Diabetische retinopathie (DR) is wereldwijd de belangrijkste oorzaak van slechtziendheid bij de beroepsactieve bevolking (20-74 jaar). De slechtziendheid binnen deze groep is doorgaans het gevolg van diabetisch maculair oedeem (DME). Echter, ondanks anti-VEGF-A therapie blijft er momenteel een aanzienlijke behoefte aan meer doeltreffende en langer werkende therapieën voor DME. Daarnaast is een adequate screening noodzakelijk aangezien een vroegtijdige behandeling visus sparend is. Doel: Een update geven omtrent de nieuwe moleculen/geneesmiddelen in ontwikkeling ter behandeling van DME en omtrent de vernieuwing in de screening naar DR. Methoden: Er werd gezocht via PubMed en in de databanken van Cochrane en EMBASE. Via officiële persberichten, presentaties betreffende deze topics en www.clinicaltrials.gov kon bijkomende informatie worden ingewonnen over de lopende en geplande studies. Resultaten: Brolucizumab, abicipar pegol, conbercept, RG7716, ALG1001 en CLS-TA bezitten momenteel de meeste potentie om de behandeling van DME naar een hoger niveau te tillen. Met de komst van ‘Automated Retinal Image Analysis’ (ARIA), gekenmerkt door een hoge sensitiviteit (87-95%) en een lage specificiteit (49,6-68,8%), kan een verlaagde werklast en bijhorende kostenreductie bekomen worden. Het ‘IDx-DR device’ kreeg als eerste de toestemming om als autonoom screeningsapparaat te worden gebruikt. Conclusie: Tal van moleculen in ontwikkeling staan klaar om de behandeling van DME te optimaliseren. Daarnaast kan ARIA een prominente rol spelen binnen de screening naar DR.

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ABSTRACT Background: Autoimmune retinopathies (AIR) are a group of disorders that are characterized by autoantibodies targeting crucial retinal proteins, leading to vision loss. Diagnosis relies on visual symptoms, identification of autoantibodies and electrophysiological changes. However, diagnosis remains challenging due to the rare nature of AIR and the lack of disease-specific features during testing. Objectives: Our objective was to identify the characteristics of full-field electroretinography (ffERG) in cancer-associated (CAR), melanoma-associated (MAR) and non-paraneoplastic autoimmune retinopathy (npAIR). Methods: A systematic search in PubMed yielded 94 case reports and case series describing ffERG findings in 322 patients with CAR, MAR or npAIR. We analyzed individual parameter distribution per ffERG protocol, wave amplitudes of different ffERG protocols and ffERG response symmetry between eyes, for the three AIR groups. Results: We provided evidence that CAR and npAIR subjects display a wide range of ffERG profiles, though simultaneous scotopic and photopic dysfunction were frequent, ranging from reduced to extinguished responses. On the contrary, the findings of MAR patients were much more homogenous. An electronegative rod-cone combined ERG pattern was dominant in MAR patients and indicate an impaired ON-bipolar cell function. Asymmetrical ERG findings were found in some patients with AIR, as expected. Symmetry was most notable in the MAR group. Conclusion: This systematic review indicates different ffERG profiles for the three subgroups of autoimmune retinopathy. CAR and npAIR share varying degrees of severity and features. These joint features could possibly be explained by the presence of overlapping candidate antiretinal antibodies that have been associated with both CAR and npAIR. Whereas with MAR, a specific electronegative combined response can be expected together with positive anti-ON bipolar antibodies. Antibody testing and electroretinography are complementary and should not be held back when a patient presents itself with sudden vision loss and unremarkable findings with other ophthalmological tests.