LASER FLARE PHOTOMETRY IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: An Evaluation of 2,487 Cases.

PURPOSE: Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD). METHODS: The authors measured laser flare values of all 3,048 prescreened patients excluding those with comorbidities. A mixed regression analysis evaluated the strength of the influencing factors like age, sex, lens status, and presence and extent of RRD on laser flare. RESULTS: Rhegmatogenous retinal detachment was more frequent in men (65.8%) than in women (34.2%, P < 0.001) and in right (52%) than in left eyes (48%, P = 0.045). Phakic RRD affected less quadrants and was less likely to be associated with macula-off status than pseudophakic RRD (48.4% vs. 58.0% macula off, 23% vs. 31% ≥3 quadrants, P < 0.001). Laser flare of affected eyes was significantly higher compared with fellow eyes (12.6 ± 15.2 vs. 8.3 ± 7.4 pc/ms, P < 0.001). The factors age, sex, lens status, presence of RRD, and the number of quadrants affected were independent influencing factors on laser flare. R 2 was 0.145 for phakic and 0.094 for pseudophakic eyes. CONCLUSION: The results indicate that there may be more factors affecting laser flare than previously assumed. This might limit flare as predictive value for PVR and retinal redetachment.

[Age-related macular degeneration - Part 1: Pathophysiology, classification and diagnostic]. / Altersbedingte Makuladegeneration.

Age-related macular degeneration (AMD) continues to be the most common hereditary disease among older people in the western world. In addition to the clinical examination, multimodal imaging with fluorescein angiography, optical coherence tomography, fundus autofluorescence and fundus photography are crucial for the correct diagnosis and classification. This is particularly important with regard to risk assessment for the development of a late form of the disease. Since the introduction of intravitreal therapy against vascular endothelial growth factor (VEGF), the treatment options for neovascular AMD have increased significantly and the prognosis for patients in terms of maintaining their vision has improved. The hope is to develop stronger and longer-lasting drugs and also to obtain approval for drugs to treat geographic atrophy. It is therefore of great importance to be able to make a quick and correct diagnosis for patients. In this paper we want to present an overview of the pathophysiology, classification and diagnosis of AMD.

Is Exudative Neovascular AMD a Chronic Disease? Analysis of Long-term Progression under Anti-VEGF Therapy. / Ist die exsudative neovaskuläre AMD eine chronische Erkrankung? Analyse von Langzeitverläufen unter einer Anti-VEGF-Therapie.

BACKGROUND: Anti-VEGF therapy is the standard treatment for exudative neovascular age-related macular degeneration (nAMD) caused by the development of macular neovascularisation (MNV) with associated fluid exudation. The therapeutic strategies (T&E or PRN) assumed a scarring transformation of the MNV and exit strategies and were formulated accordingly. The present study investigates this hypothesis as a real-life long-term analysis. PATIENTS: 150 eyes of 97 patients were continuously followed up over a mean period of 5.1 years (1 - 14 years) after initiation of anti-VEGF therapy between 2009 - 2017 until 2022. Treatment was based on the PRN regimen analogous to the IVAN study with ranibizumab, aflibercept or bevacizumab. The length and intensity of therapy were evaluated. RESULTS: Of these 150 eyes, 119 (79.3%) required ongoing anti-VEGF therapy, while in 18 eyes (12.0%) therapy could be discontinued due to stabilisation of the situation. In 13 eyes (8.7%), therapy was discontinued due to deterioration in visual acuity to < 0.05. With ongoing therapy, therapy was often protracted, with an indication for therapy at the last documented doctor's visit, while stabilisation was often achieved within the first 2 years of treatment. The treatment intensity increased to 7.7 - 8.0 injections/year, especially after 2013, with the introduction of OCT-based treatment criteria. Most eyes (74.8%) with ongoing therapy required 6 - 9 injections/year even in the last three years of treatment. CONCLUSION: The fact that in the present study there is a long-term and intensive need for therapy in the majority of patients (approx. 80%) with exudative nAMD, supports the assessment that nAMD should be regarded as a chronic disease. Therefore, a proactive treatment strategy with consistent therapy at any sign of lesion activity might be recommended. Particularly in view of the risk of irreversible loss of vision, long term adherence of patients is also crucial for the best possible long term therapeutic outcome.

See clearer: survey on the subjective and objective information levels as well as perception and information transfer using virtual reality headsets in patients with diabetic macular edema receiving anti-VEGF treatment.

PURPOSE: The purpose of this study is to investigate the use of a VR Headset in routine clinical practice as an additional source of information for patients with diabetic macular edema (DME) and their companions. METHODS: Survey including 121 patients with DME, 22 companions, and 14 healthcare professionals from 8 ophthalmology centers in Germany. Patients' and their companions' health literacy was assessed by questionnaires including knowledge statements before and after watching a VR-based 3-D educational video. HCPs' perspectives on the usability of a VR Headset were also assessed. RESULTS: Patients' mean age was 63.4 ± 12.2 years, 64.5% were men, and 76% (92/121) had previous anti-VEGF (VEGF, vascular endothelial growth factor) injections. After using the VR Headset, over 85% of patients and companions felt better informed about DME and its treatment. Patients' mean (± SD) number of correct answers to knowledge statements increased from 13.2 ± 3.7 before to 15.5 ± 2.3 after using the VR Headset. Over 95% of patients and companions rated content and ease of understanding of the video as "very good" or "good." Most patients and all companions considered the use of a VR Headset as a positive experience, most wishing to obtain information via VR Headset in the future. Most physicians and all medical assistants rated the effect of the VR Headset on patient satisfaction as positive and suggested further VR modules. CONCLUSION: After using the VR Headset, patients with DME and their companions demonstrated knowledge gains that may be meaningful individually and contribute to better adherence. This may offer an additional opportunity for knowledge transfer.

[Pachychoroid Disease]. / Pachychoroidale Erkrankungen.

Pachychoroid spectrum disorders include uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularisation, focal choroidal excavation and peripapillary pachychoroid syndrome. They are characterized by a thickened and hyperpermeable choroid and thinning of the choriocapillaris. The disorders are being diagnosed with increasing frequency and differentiation due to the advancement of multimodality imaging. Current understanding of the development, course, possible complications and treatment of these diseases is growing rapidly, but not all mechanisms have yet been elucidated. A correct diagnosis is important, especially the differentiation between the presence of active neovascularisation or a purely exudative stage, in order to initiate a therapy. It is also not yet clear why patients have a thickened choroid and why some of these patients develop pathological changes such as subretinal fluid, RPE changes or neovascularisation.

[Less Frequent Vascular Disorders of the Retina - Part 1]. / Seltene vaskuläre Erkrankungen der Netzhaut ­ Teil 1.

This review provides an overview of retinal vascular disorders that are less frequent in Germany and Europe compared to diabetic retinopathy and retinal venous or arterial occlusive disorders. The knowledge of these disorders is important for the differential diagnosis of retinal vascular disorders as well as potentially associated systemic disorders. In the current part one epidemiology, pathophysiology, clinical presentation, and therapy are discussed for hypertensive retinochoroidopathy, ocular ischemic syndrome, retinal alterations in sickle cell disease, Eales disease, radiation retinopathy, peripheral exudative hemorrhagic chorioretinopathy, and retinal disorders associated with pregnancy.

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Optical coherence tomography angiography (OCT-A) in retinitis pigmentosa and macular dystrophy patients: a retrospective study.

PURPOSE: To evaluate macular vascular abnormalities in patients with macular dystrophies (MD) and retinitis pigmentosa (RP) through application of optical coherence tomography angiography (OCT-A). METHODS: In this retrospective study, patients with MD and RP were examined by OCT-A and compared to healthy individuals. OCT-A images were analyzed regarding the diameter and surface area of the foveal avascular zone (FAZ) as well as flow (FL) in different retinal layers (superficial vascular complex (SVC), intermediate capillary complex (ICP), deep capillary complex (DCP), choriocapillaris (CC), and choroid (CD)). RESULTS: Twenty-one patients with MD, 21 patients with RP without macular edema (RPnE), 8 patients with RP with edema (RPwE), and 41 healthy individuals were enrolled. The group of MD and RPnE patients showed none or only minor changes in FAZ. In RPwE patients, the FAZ was significantly smaller in vertical and horizontal measurements and surface area in SVC, whereas it was markedly enlarged in ICP. FL was significantly reduced compared to healthy individuals by an average of 13.2% in CD, 14.2% in CC, and 8.4% in DCP in all patient groups. In ICP, the reduction was 9.2% for RPnE and 12.7% for RPwE patients. The SVC showed reduced FL in the MD (8.1%) and RPnE (10.3%) group. CONCLUSIONS: OCT-A is a valuable tool to examine retinal vascular abnormalities in patients with MD and RP. OCT-A revealed a reduced flow in various retinal layers in MD, RPnE, and RPwE. Alterations of the FAZ were less distinct in these groups which add to the variation reported previously.

Clinically applicable deep learning-based decision aids for treatment of neovascular AMD.

PURPOSE: Anti-vascular endothelial growth factor (Anti-VEGF) therapy is currently seen as the standard for treatment of neovascular AMD (nAMD). However, while treatments are highly effective, decisions for initial treatment and retreatment are often challenging for non-retina specialists. The purpose of this study is to develop convolutional neural networks (CNN) that can differentiate treatment indicated presentations of nAMD for referral to treatment centre based solely on SD-OCT. This provides the basis for developing an applicable medical decision support system subsequently. METHODS: SD-OCT volumes of a consecutive real-life cohort of 1503 nAMD patients were analysed and two experiments were carried out. To differentiate between no treatment class vs. initial treatment nAMD class and stabilised nAMD vs. active nAMD, two novel CNNs, based on SD-OCT volume scans, were developed and tested for robustness and performance. In a step towards explainable artificial intelligence (AI), saliency maps of the SD-OCT volume scans of 24 initial indication decisions with a predicted probability of > 97.5% were analysed (score 0-2 in respect to staining intensity). An AI benchmark against retina specialists was performed. RESULTS: At the first experiment, the area under curve (AUC) of the receiver-operating characteristic (ROC) for the differentiation of patients for the initial analysis was 0.927 (standard deviation (SD): 0.018), for the second experiment (retreatment analysis) 0.865 (SD: 0.027). The results were robust to downsampling (» of the original resolution) and cross-validation (tenfold). In addition, there was a high correlation between the AI analysis and expert opinion in a sample of 102 cases for differentiation of patients needing treatment (κ = 0.824). On saliency maps, the relevant structures for individual initial indication decisions were the retina/vitreous interface, subretinal space, intraretinal cysts, subretinal pigment epithelium space, and the choroid. CONCLUSION: The developed AI algorithms can define and differentiate presentations of AMD, which should be referred for treatment or retreatment with anti-VEGF therapy. This may support non-retina specialists to interpret SD-OCT on expert opinion level. The individual decision of the algorithm can be supervised by saliency maps.

Impact of the COVID 19 Pandemic on Treatment of nAMD via a Portal-Based Collaboration. / Auswirkung der COVID-19-Pandemie auf die Therapie der nAMD in einer portalbasierten Kooperation.

BACKGROUND: Under the influence of the COVID 19 pandemic and the lockdown in Germany, there were significantly fewer consultations in almost all medical disciplines. Especially given the need for consistent treatment and follow-up of nAMD patients, this can have far-reaching consequences for visual function, especially in elderly patients. METHODS: In a retrospective analysis of nAMD patients, the number of visits (IVI or follow-up), OCTs or IVIs performed and the mean worst visual acuity for the period before and after the first COVID 19-associated lockdown were compared in a portal-based collaboration of 50 eye care practices. Patients were treated according to the pro re nata (PRN) regimen that included intravitreal injection of VEGF inhibitors based on activity criteria in the OCT follow-up. RESULTS: A total of 34,660 visits from 55 months were included in the analysis. Before lockdown (16 March 2020), an average of 81.8% ± 2.1% of patients were regularly checked or treated (every 4 to 5 weeks). With the onset of lockdown, the proportion of patients receiving optimum treatment dropped to 64.0%. Initially, the proportion of OCT follow-ups decreased from 48.4% to 30.9% and, with a delay, the proportion of injections decreased from 57.5% to 45.8%. This was also reflected in the number of OCT follow-ups: 15.5 before, 11.4 during and 17.2 after lockdown (p < 0.001). In 29% of cases, an individual worsening of visual acuity by more than 0.1 logMAR after the end of the lockdown compared to before the lockdown could be observed. On average, mean visual acuity decreased significantly by 0.054 logMAR (p < 10-11). This significant impairment was not reversed again during the remaining observation period, although the number of visits, OCT examinations and IVIs in the following 12 months were at the pre-lockdown level. CONCLUSIONS: The pandemic-related lockdown resulted in unintended treatment breaks in nAMD patients receiving IVI therapy. The decrease in visits as well as in IVIs caused a loss of visual function in the observed cohort. The consistent treatment regimen of nAMD patients was resumed shortly after the lockdown with an immediate normalization of the number of OCT examinations and IVIs. However, a permanent loss of visual function was observed, and this did not improve within a year after the lockdown. This finding highlights the importance of better case management, leading to improved patient adherence in the event of further waves of COVID or other pandemics.

Quantification of Early and Intermediate Age-related Macular Degeneration Using OCT "en face" Presentation. / Quantifizierung der frühen und intermediären altersabhängigen Makuladegeneration mittels OCT-"en-face"-Darstellung.

BACKGROUND: Early and intermediate age-related macular degeneration (AMD) results in drusen deposits under the retinal pigment epithelium (RPE). These early stages of AMD exhibit different risks of progressing to late AMD. To date, early AMD has been classified and quantified by fundus photography. This does not appear to be sensitive enough for clinical trials studying the impact on drusen. SD-OCT with two-dimensional rendering of the segmented slices analysed allows for en face imaging of the drusen. The present trial studied the potential of quantifying early and intermediate AMD by en-face optical coherence tomography (OCT). MATERIAL AND METHODS: Thirty-one eyes of 29 patients in different stages of early and intermediate AMD were studied. To this end, fundus photographs (Kowa VX-10i, Kowa, Tokyo, Japan) and en-face OCT images (RTVue XR Avanti, Optovue, Inc., Fremont, CA, USA) were taken. First, different segmentation levels (6 µm underneath the RPE, on the RPE, 6 µm and 9 µm above the RPE) and different layer thicknesses (5 µm, 10 µm, 20 µm and 30 µm) were analysed to determine the best segmentation for visualising drusen. Drusen were marked manually and their number and surface area calculated. This analysis was then compared with the standardised drusen analyses on fundus photography. Additional changes in early and intermediate AMD such as pigment epithelial detachments (PEDs) and subretinal drusenoid deposits (SDD) as well as small atrophies were also documented and compared. OUTCOMES: The best segmentation for delineating the drusen on the en-face OCT images was found to be a segmentation 6 µm underneath the RPE with a slice thickness of 20 µm. Comparison of drusen quantification on en-face OCT images with the standardised drusen analysis on fundus photography revealed particularly good similarity. Other changes in early and intermediate AMD, such as PEDs, SDD and small atrophies, were easier to assess on the en-face OCT images. CONCLUSIONS: The analysis and quantification of drusen from en-face OCT images with 20 µm segmentation at 6 µm underneath the RPE allows differentiated quantification of various drusen characteristics. Moreover, other changes in early and intermediate AMD can also be analysed. In future observational and clinical trials, this could help quantify drusen.

Correlation of retinal alterations with vascular structure of macular neovascularisation in swept-source optical coherence tomography angiography in age-related macular degeneration.

PURPOSE: The aim of this study was to find out whether the vascular architecture of untreated macular neovascularisations (MNV) in neovascular age-related macular degeneration (nAMD) as visualised with optic coherence tomography angiography (OCTA) is associated with functional and known morphological alterations of the retina in optic coherence tomography (SD-OCT). METHODS: The study design was retrospective with consecutive patient inclusion. In 107 patients with newly diagnosed nAMD, MNV were detected by means of OCTA and automated quantitative vascular analysis was performed. The MNV characteristics measured were area, flow density, total vascular length (sumL), density of vascular nodes (numN), fractal dimension (FD) and average vascular width (avgW). These parameters were assessed for associations with vision (BCVA), central retinal thickness (CRT), fluid distribution, the elevation of any pigment epithelial detachment (PED), the occurrence of subretinal haemorrhage and atrophy. RESULTS: BCVA was significantly worse with greater MNV area and sumL. Fluid distribution differed significantly in relation to area (p < 0.005), sumL (p < 0.005) and FD (p = 0.001). Greater PED height was significantly associated with higher numN (p < 0.05) and lower avgW (p < 0.05). Atrophy was present significantly more often in MNV with larger area (p < 0.05), higher sumL (p < 0.05) and higher flow density (p = 0.002). None of the MNV parameters had a significant association with CRT or the occurrence of haemorrhage. CONCLUSION: OCTA is not restricted to evaluation of secondary changes but offers the opportunity to analyse the vascular structure of MNV in detail. Differences in vascular morphology are associated with certain secondary changes in retinal morphology. There are thus grounds for optimism that further research may identify and classify OCTA-based markers to permit more individualised treatment of nAMD.

[Are There Different Phenotypes in Geographic Atrophy of AMD? - Pilot Study on Differentiation Using Multimodal Imaging]. / Gibt es unterschiedliche Phänotypen bei der geografischen Atrophie der AMD? ­ Pilotstudie zur Differenzierung mittels multimodaler Bildgebung.

BACKGROUND: Geographic atrophy (GA) in patients with age-related macular degeneration (AMD) involves a loss of photoreceptors (PR), retinal pigment epithelium (RPE) and choriocapillaris (CC). For treatment decisions, it is crucial to discern which of these layers the damage originates, subsequently spreading to the others. It has long been thought that the RPE, with its accumulation of lipofuscin, is the site of primary damage in the development of GA. However, histological studies have shown that in some patients, the PR are affected first, followed by secondary damage to the RPE and CC, and in others regression of the CC is the first manifestation. The aim of this study was to use multimodal imaging to determine the extent of the damage at the levels of the PR, RPE and CC, to characterise the individual phenotypic variations of GA and to investigate the corresponding functional impairment. PATIENTS AND METHODS: Twenty eyes of 20 patients (mean age 78 years; 14 female, 6 male) with the clinical diagnosis of GA were examined by means of fundus autofluorescence (FAF) to evaluate the damage to the RPE, en face SD-OCT at the level of the PR to characterise the area of cell loss in this layer and OCT angiography (OCT-A, AngioVue, Optovue; 50 µm CC-segmentation with localization below the RPE) to assess regression of the CC. The affected area of each layer was measured. Best-corrected visual acuity (BCVA) test and fundus correlated automated 10° microperimetry (MAIA Microperimetry, CENTERVUE; 4-2 strategy, 68 stimuli) were performed in all patients. The results of these examinations were evaluated and correlated. RESULTS: All eyes showed a different extent of the areas of atrophy in the PR, RPE and CC. The layer with the largest area of atrophy was the RPE in 13 eyes (65%), the PR in 3 eyes (15%) and the CC in 4 eyes (20%). While the visual loss depended entirely on the presence of foveal sparing, microperimetry revealed a correlation between the extent of detectable functional deficit and the largest atrophic area. CONCLUSIONS: Multimodal imaging with FAF, en face OCT, OCT-A and a correlation with microperimetry enables a clinical phenotypic differentiation in GA as well as a more precise characterisation of the associated functional impairment. This confirms clinically the histologically demonstrated diversity of the damaged structure (PR, RPE or CC) in patients with GA. However, the variations identified in this pilot study must be confirmed in Reading Center-based larger cohorts. The approach described here may lead to differentiated consideration of the anatomical and functional aspects of the disease and turn out to be helpful in patient selection as well as in identifying and monitoring future therapeutic approaches.

[Analysis of the "Portal" Care Model - Examination of the Outcome Quality of IVOM Therapy with Regard to Latency Periods in Exudative AMD]. / Analyse des Versorgungsmodells "Portal" ­ Untersuchung der Ergebnisqualität der IVOM-Therapie im Hinblick auf Latenzzeiten bei exsudativer AMD.

BACKGROUND: For many maculopathies, the management of intravitreal injection (IVOM) presents a logistical challenge. To ensure contemporary and timely treatment, patients have to organise their rides to the surgery, and the clinic has to provide enough short term resources. The objective of this study is an evaluation of the IVOM therapy for patients with exudative AMD according to four quality indicators a) latency time within the treatment and monitoring cycle, b) the treatment and monitoring frequency, c) the adherence and d) the medical outcome. MATERIALS AND METHODS: For more than seven years, patients with exudative AMD have been treated by many ophthalmologists using a networked portal system. Therefore, conservative doctors and surgical eye centres exchange treatment-relevant data. In total there are documented 2283 eyes of 1850 patients. We evaluate these electronic medical records retrospectively according to the mentioned quality indicators. RESULTS: This evaluation results in a latency time from OCT monitoring and the start of a new IVOM series of 8.1 working days. Within the first two treatment years, we achieve 10.5 injections and 8.2 monitoring visits in average. After two years, 72.9% of the cases were still in treatment or monitoring. We observed stabilisation of mean visual accuracy of about 0.05 logMAR. CONCLUSIONS: To improve the visual acuity, it is essential to achieve consistent therapy over a long period of time, especially in the case of treatment-relevant exudative AMD. The evaluation of our treatment system demonstrated that the PRN-scheme can be implemented by a cooperatively organised IVOM therapy. It is possible to achieve rapid retreatment and good adherence over many treatment years. For treatment-relevant exudative AMD it is essential for the improvement of the visual accuracy to implement consistent therapy over a long period of time. The evaluation of our treatment system demonstrates that the PRN scheme can be implemented in a cooperatively organised IVOM therapy. It is possible to achieve rapid retreatment and good patients' adherence over many treatment years.

Systematic review: non-adherence and non-persistence in intravitreal treatment.

PURPOSE: Intravitreal injection of VEGF inhibitors has become the standard of care for different macular diseases within the last years resulting in improved visual outcomes. Under real-life conditions, however, the necessity for frequent retreatments and reexaminations poses a burden for patients and treatment centers. Non-adherence and non-persistence to intravitreal treatment may lead to inferior clinical outcomes, and knowledge of contributing factors is crucial to improve adherence. This systematic review analyzes current literature for potential factors involved in non-adherence and non-persistence. METHODS: A systematic search was conducted in PubMed and Embase including three different aspects of intravitreal injection therapy: (1) diseases with intravitreal injections as treatment, (2) intravitreal injection, and (3) aspects of therapy adherence or therapy persistence. Data from identified quantitative studies were further extracted and grouped according to WHO criteria (condition, socio-economy, therapy, patient, and health system). The methodological quality of identified studies was graded. Identified qualitative studies (i.e., interviews) were descriptively analyzed and their findings narratively reported. RESULTS: Twenty-four publications were included. In 16 of those publications, a quantitative data analysis was conducted, analyzing factors associated with non-adherence. Worse visual acuity at baseline and unfavorable development of visual acuity, higher age, and greater distance to the treatment center were associated with non-adherence, while there was inconsistent evidence for an association of comorbidity. In qualitative studies, high follow-up/treatment burden, fear and anxiety, disappointed patient expectations, and lack of motivation to continue treatment were reported as reasons for non-persistence. CONCLUSIONS: Knowledge of potential barriers in IVT treatment may improve adherence and potentially clinical results. Improvements can be achieved particularly in the healthcare complex (organizational improvements) and the "patient" complex by establishing realistic expectations. Recurrent education of the patient may be necessary.

[OCT Angiography]. / OCT-Angiografie.

OCTA expands the spectrum of multimodal retinal imaging as a non-invasive procedure. Subtraction analysis of two temporally dense and identical B-scan images only show changes corresponding to the flow in the blood vessels. Freely selectable segmentation visualization of different layers of the retina, RPE, choriocapillars and choroid. By means of manufacturer-specific quantification options and 3-D representation changes in findings under a therapy can be well represented. At present, OCTA is still bound to a corresponding B-scan. The OCTA is currently not a substitute for the conventional FAG, as it can give no indication of permeability disorders and fluid movements over time and the image is still very limited. These limitations will soon disappear as a result of rapid technological development and provide the OCTA with a permanent place in the multimodal imaging of the retina. With further development, new biomarkers for therapy and re-treatment may be safely defined for some diseases.

[The Management of Vitreous Opacities]. / Das Management von Glaskörpertrübungen.

The management of symptomatic vitreous opacities is often complicated in daily practice. The technically significantly improved surgical possibilities lead to an increased number of surgical interventions. The Nd:YAG laser vitreolysis is increasingly becoming a therapeutic option. Unfortunately, there are no comparative randomized studies on vitrectomy, Nd:YAG laser vitreolysis and a wait-and-see approach to spontaneous progress. This article gives an overview of this problem.

[Uveitis Masquerade Syndrome: Typical Symptoms and Presentations]. / Uveitis-Masquerade-Syndrome: Leitsymptome und Krankheitsbilder.

The uveitis masquerade syndrome (UMS) describes a series of malignant diseases that mimic inflammatory conditions without belonging to the group of immune-mediated uveitis entities. The correct diagnosis is often difficult to establish, despite a detailed ophthalmological and general medical history using all imaging modalities and interdisciplinary cooperation. In the case of recurrent inflammation, it is very important to consider an UMS, since any delay in proving the underlying diagnosis and initiating the appropriate therapy may be associated with the risk of systemic spread and consecutive deterioration of the prognosis. Often, after all conservative options have been exhausted, the only remaining option to confirm the correct diagnosis might be an intraocular biopsy. The present work focuses on the leading symptoms, differential diagnoses and clinical signs of UMS.

Analysis of the Vascular Morphology of the Fibrotic Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography. / Analyse der Gefäßmorphologie der fibrosierten choroidalen Neovaskularisation bei neovaskulärer altersabhängiger Makuladegeneration mittels optischer Kohärenztomografie-Angiografie.

PURPOSE: Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA). METHODS: In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruch's membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images. RESULTS: Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006). CONCLUSION: In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.

NEGATIVE EFFECTS OF VITAL DYES AFTER UNEVENTFUL VITREOMACULAR SURGERY.

PURPOSE: Vital dyes have become a clinical standard during chromovitrectomy but toxicity remains an issue. We compared the clinical outcome of one supposedly toxic vital dye (AV 17 with 5% mannitol) with a standard vital dye (MBB Dual) and performed a power analysis for future comparative studies. METHODS: Retrospective analysis of 270 eyes after chromovitrectomy with internal limiting membrane peeling because of macular holes. Primary endpoint was loss in BCVA >2 lines and photoreceptor atrophy as seen on optical coherence tomography examination. RESULTS: In 173 eyes, staining of the epiretinal membrane and extracellular matrix was performed using MBB (Group A), and in 97 using AV 17-M (Group B). The mean BCVA was not significantly different after more than 3 months and also not in the early postoperative period after surgery between Group A and Group B. The number of patients suffering from a decline in BCVA of two lines and more was not significantly higher in patients of Group B. There was not a significantly higher percentage of patients with an inner segment/outer segment defect. CONCLUSION: Our rather homogeneous study showed no significant difference between both dyes. Thousand five hundred patients would need to be examined to find a significant difference in future studies.