[Vitreomacular traction: diagnostics, natural course, treatment decision and guideline recommendations]. / Vitreomakuläre Traktion: Diagnostik, natürlicher Verlauf, Therapieentscheidung und Leitlinienempfehlungen.

Vitreomacular traction is a tractive foveolar adhesion of the posterior vitreous limiting membrane, resulting in pathological structural alterations of the vitreomacular interface. This must be differentiated from physiological vitreomacular adhesion, which exhibits a completely preserved foveolar depression. Symptoms depend on the severity of the macular changes and typically include reduced visual acuity, reading problems and metamorphopsia. High-resolution spectral domain optical coherence tomography (SDOCT) imaging enables classification of the sometimes only subtle morphological changes. If pronounced vitreomacular traction is accompanied by epiretinal gliosis and alterations to the outer retina, it is referred to as a vitreomacular traction syndrome. Vitreomacular traction has a high probability of spontaneous resolution within 12 months. Therefore, treatment should only be carried out in cases of undue suffering of the patient and with symptoms during bilateral vision and a lack of spontaneous resolution. In addition to pars plana vitrectomy, alternative treatment options, such as intravitreal injection of ocriplasmin and pneumatic vitreolysis are discussed for vitreomacular traction with an associated macular hole; however, ocriplasmin is no longer available in Germany. The best anatomical results in comparative investigations were achieved by vitrectomy. Pneumatic vitreolysis is controversially discussed due to the increased risk of retinal tears. In one of the current S1 guidelines of the German ophthalmological societies evidence-based recommendations for the diagnostics and treatment of vitreomacular traction are summarized.

Diabetic Retinopathy - a Common Disease. / Volkskrankheit diabetische Retinopathie.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and one of the leading causes of visual impairment in working age individuals in the western world. The treatment of DR depends on its severity, so it is of great importance to detect patients as early as possible, in order to initiate early treatment and preserve vision. Despite currently insufficient screening participation, patients with diabetes already visit ophthalmological practices and clinics above average. Their medical care, including DR diagnostics and treatment has been making up an increasing proportion of ophthalmic activity for years. Since the prevalence of diabetes is increasing dramatically worldwide and a further increase is also predicted for Germany, the challenge for ophthalmologists is likely to grow considerably. As the same time, the diagnostic possibilities for differentiating DR and the therapeutic measures, especially with IVOM therapy, are becoming more and more complex, which increases the time burden in everyday clinical practice. The hope to avoid healthcare deficits and to further improve screening rates and visual acuity prognosis in patients with DR is based, among other things, on camera-assisted screening supported by artificial intelligence. Better diabetes management to reduce the prevalence of DR, as well as longer-acting drugs to treat DR, could also improve the care and help reduce the burden on ophthalmology practices.

[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.

The Architecture of Macular Neovascularizations Predicts Treatment Responses to Anti-VEGF Therapy in Neovascular AMD.

Introduction: Anti-VEGF therapy is an effective option for improving and stabilizing the vision in neovascular age-related macular degeneration (nAMD). However, the response to treatment is markedly heterogeneous. The aim of this study was therefore to analyze the vascular characteristics of type 1,2, and 3 macular neovascularizations (MNV) in order to identify biomarkers that predict treatment response, especially with regard to changes in intraretinal and subretinal fluid. Materials and Methods: Overall, 90 treatment-naive eyes with nAMD confirmed by optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA) were included in this retrospective study. The MNV detected by OCTA were subjected to quantitative vascular analysis by binarization and skeletonization of the vessel using ImageJ. We determined their area, total vascular length (sumL), fractal dimension (FD), flow density, number of vascular nodes (numN), and average vascular diameter (avgW). The results were correlated with the treatment response to the initial three injections of anti-VEGF and the changes in intraretinal (IRF) and subretinal fluid (SRF) and the occurrence of pigment epithelial detachements (PED). Results: All patients found to have no subretinal or intraretinal fluid following the initial three injections of anti-VEGF showed a significantly smaller MNV area (p < 0.001), a lower sumL (p < 0.0005), and lesser FD (p < 0.005) before treatment than those who still exhibited signs of activity. These parameters also showed a significant influence in the separate analysis of persistent SRF (p < 0.005) and a persistent PED (p < 0.05), whereas we could not detect any influence on changes in IRF. The vascular parameters avgW, numN, and flow density showed no significant influence on SRF/IRF or PED changes. Conclusions: The size, the total vessel length, and the fractal dimension of MNV at baseline are predictors for the treatment response to anti-VEGF therapy. Therefore, particularly regarding the development of new classes of drugs, these parameters could yield new insights into treatment response.

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.

Single-Cell Protein and Transcriptional Characterization of Epiretinal Membranes From Patients With Proliferative Vitreoretinopathy.

Purpose: Proliferative vitreoretinopathy (PVR) remains an unresolved clinical challenge and can lead to frequent revision surgery and blindness vision loss. The aim of this study was to characterize the microenvironment of epiretinal PVR tissue, in order to shed more light on the complex pathophysiology and to unravel new treatment options. Methods: A total of 44 tissue samples were analyzed in this study, including 19 epiretinal PVRs, 13 epiretinal membranes (ERMs) from patients with macular pucker, as well as 12 internal limiting membranes (ILMs). The cellular and molecular microenvironment was assessed by cell type deconvolution analysis (xCell), RNA sequencing data and single-cell imaging mass cytometry. Candidate drugs for PVR treatment were identified in silico via a transcriptome-based drug-repurposing approach. Results: RNA sequencing of tissue samples demonstrated distinct transcriptional profiles of PVR, ERM, and ILM samples. Differential gene expression analysis revealed 3194 upregulated genes in PVR compared with ILM, including FN1 and SPARC, which contribute to biological processes, such as extracellular matrix (ECM) organization. The xCell and IMC analyses showed that PVR membranes were composed of macrophages, retinal pigment epithelium, and α-SMA-positive myofibroblasts, the latter predominantly characterized by the co-expression of immune cell signature markers. Finally, 13 drugs were identified as potential therapeutics for PVR, including aminocaproic acid and various topoisomerase-2A inhibitors. Conclusions: Epiretinal PVR membranes exhibit a unique and complex transcriptional and cellular profile dominated by immune cells and myofibroblasts, as well as a variety of ECM components. Our findings provide new insights into the pathophysiology of PVR and suggest potential targeted therapeutic options.

Vascular Analysis of Type 1, 2, and 3 Macular Neovascularization in Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Angiography Shows New Insights into Differences of Pathologic Vasculature and May Lead to a More Personalized Understanding.

Background: The clinical appearance of macular neovascularization (MNV) in age-related macular degeneration (nAMD) varies widely, but so far, this has had no relevance in terms of therapeutic approaches or prognosis. Therefore, our purpose was to investigate if and which differences exist in the vascular architecture of MNV and to quantify them. Methods: In 90 patients with newly diagnosed nAMD, MNV was identified by means of optical coherence tomography angiography (OCTA), and automated quantitative vascular analysis was carried out. The analyzed vascular parameters were area, flow, fractal dimension (FD), total vascular length (sumL), number of vascular nodes (numN), flow, and average vessel caliber (avgW). The current classification of MNVs divides them according to their localization into type 1 (grown from the choroid below the RPE), type 2 (grown from the choroid through RPE), and type 3 (grown from the retina toward the RPE). We compared the analyzed vascular parameters of each of the three MNV types. Kruskal−Wallis test was applied, Dunn test was performed for post hoc analysis, and for pairwise comparison, p-values were adjusted using Bonferroni comparison. Results: Regarding the MNV area, there was no significant difference between types 1 and 2, but type 3 was significantly smaller than types 1 and 2 (p < 0.00001). For FD, types 1 and 2 did not differ significantly, but again, type 3 was lower than type 1 and 2 (p < 0.00001). The numN were significantly higher in types 1 and 3 than in 2 (p < 0.005), but not between types 1 and 3. No significant differences were found between MNV types for flow. As for sumL, types 1 and 2 did not differ significantly, but type 3 was significantly lower than types 1 and 2 (p < 0.00001). For avgW, there was no significant difference between types 1 and 2 or between types 2 and 3, but type 3 was significantly larger than type 1 (p < 0.05). Conclusions OCTA yields detailed information on the vascular morphology of MNV in patients with nAMD and is able to show differences among types 1, 2, and 3. Especially comparing types 1 and 2 with type 3 reveals significant differences in area, FD, sumL, and numN. One explanation could be the similar pathogenesis of types 1 and 2 with their origin in the choroid and their growth towards the retinal pigment epithelium (RPE), whereas type 3 originates in the deep capillary plexus. Between types 1 and 2, however, only the numN differ significantly, which could be due to the fact that type 1 spreads horizontally below the RPE and, thus, display more vascular branching, while type 2 grows more vertically through the RPE and under the neurosensory retina. Detailed information about the pathologic vasculature is important for proper monitoring of the disease and to assess the efficacy of medication, especially with regard to new substances. This should be taken into consideration in future studies.

Axial Stretching of Vessels in the Retinal Vascular Plexus With 3D OCT-Angiography.

PURPOSE: The purpose of this study is to describe and quantify the nonpathological axial stretching in the retinal vascular plexus in three-dimensional (3D) optical coherence tomography angiography (OCTA) images. METHODS: The 3D vascular network underneath the inner limiting membrane of OCTA volumes was labeled as ground truth (GT) data. To analyze the cross-section area of the vessels the width and depth of the vessels in the GT data were computed and an elliptical quotient was proposed to quantify the axial stretching. RESULTS: A total of 21 3D OCTA volumes were labeled. It was found that the vessels in 3D OCTA images are stretched in the direction of the A-Scan by a factor of 2.46 ± 1.82 with a median of 2.24. Furthermore, a larger cross-section area leads to higher axial stretching. CONCLUSIONS: The elliptical shape of the cross-section area of the vessel does not match with the expected pathology of the vascular network in the human eye. Therefore a correction of the volume data before a 3D analysis is recommended. TRANSLATIONAL RELEVANCE: This work gives a systematic insight to the stretched shape of vessels in 3D OCTA images and is relevant for further clinical research analyzing the 3D vascular network.

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.

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.

In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy.

Background: Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR. Methods: A total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease. Results: The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR. Conclusion: This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach.

Incidence and phenotypical variation of outer retina-associated hyperreflectivity in macular telangiectasia type 2.

BACKGROUND: Macular telangiectasia type 2 (MacTel) is a neurodegenerative disease resulting in photoreceptor loss. Optical coherence tomography (OCT) reveals outer retina-associated hyperreflectivity (ORaH) as part of this process. The purpose of this study was to describe the incidence and phenotypical variation of ORaH. METHODS: Different parameters of ORaH were analysed: OCT characteristics (Spectralis SD-OCT), correlation with vascular changes (OCT angiography; OCTA 3×3 mm Optovue) and correlation with hyperpigmentation (autofluorescence/fundus images). ORaH was also evaluated regarding the grade of severity of photoreceptor loss (Disease Severity Scale). RESULTS: Of 220 eyes with MacTel type 2, 106 demonstrated ORaH. On OCT, the size, the extension into the inner retina and the contact with retinal pigment epithelium (RPE) of the ORaH were variable. On OCTA neovascularisation (NV) in the outer retina (OR) was present at the location of the ORaH in 97.6%. Increasing size of NV correlated with progressive photoreceptor loss. In 86.6% with NV, the flow signals were visible between the OR and the choriocapillaris. In 85.7%, the ORaH was associated with hyperpigmentation on autofluorescence and fundus colour images. CONCLUSIONS: The presence of ORaH is associated with increasing photoreceptor loss and disease severity. In these more advanced cases of the present study, a variable presentation of ORaH in respect to size and form was seen, but in most cases, ORaH was in contact to the RPE. Additionally, ORaH was associated with hyperpigmentation and OR NV on OCTA. These results are consistent with the concept of ORaH representing fibrovascular OR-NV with RPE proliferation after contact with the RPE.

[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.

[Differential diagnosis of papilledema and macular exudation-the exophytically growing juxtapapillary retinal capillary hemangioma]. / Differenzialdiagnose bei Papillenschwellung und makulärer Exsudation ­ das exophytisch wachsende juxtapapilläre retinale kapilläre Hämangiom.

In a 38-year-old female patient, who had been treated for acute visual impairment and suspected optic neuritis with no organic evidence in the right eye, an exophytically growing juxtapapillary retinal capillary hemangioma was found. The benign tumor is a rare but important differential diagnosis in cases of papilledema and macular exudation. The treatment is difficult; various therapeutic concepts are discussed.

[Influence of CNV vascular morphology in exudative age-related macular degeneration on development of visual acuity and need for anti-VEGF therapy after 1 year]. / Einfluss der CNV-Gefäßmorphologie bei exsudativer altersabhängiger Makuladegeneration auf die Visusentwicklung und den Anti-VEGF-Therapiebedarf nach 1 Jahr.

BACKGROUND: The aim of this pilot study was to investigate vascular morphological characteristics of choroidal neovascularization (CNV) at the time of the initial diagnosis of exudative age-related macular degeneration (nAMD), which enable a prognosis for the development of visual acuity and the necessity for treatment in the first year. METHODS: In 57 patients with the initial diagnosis of nAMD, CNV was detected by optical coherence tomography angiography (OCT-A) and an automated quantitative vessel analysis was performed with respect to area, total vessel length, flow value and average vessel caliber of the CNV. After 12 months patients were divided into 2 groups based on visual acuity (visual loss vs. visual gain) and necessity of anti-VEGF therapy (<7 intravitreal injections, IVOM vs. ≥7 IVOM). RESULTS: The mean CNV area was 0.95 mm2 ± 1.07 mm2 (group visual loss 1.56 mm2 ± 1.54 mm2; group visual gain 0.65 mm2 ± 0.53 mm2; p = 0.002/<7 IVOM 1.05 mm2 ± 1.40 mm2; ≥7 IVOM 0.98 mm2 ± 0.94 mm2, p = 0.60). The average total vessel length of the CNV was 9.84 mm ± 11.35 mm (visual loss 16.00 mm ± 16.58 mm; visual gain 6.74 mm ± 5.42 mm; p < 0.003/<7 IVOM 11.21 mm ± 15.10; ≥7 IVOM 9.90 mm ± 9.68 mm; p = 0.68). The mean flow value of the CNV was 0.40 ± 0.06 (visual loss 0.37 ± 0.04; visual gain 0.41 ± 0.07; p = 0.004/<7 IVOM 0.42 ± 0.08; ≥7 IVOM 0.38 ± 0.06; p = 0.02). The average vessel caliber was 28.86 µm ± 2.93 µm (visual loss 28.39 µm ± 2.97 mm; visual gain 29.32 µm ± 3.05 µm; p = 0.24/<7 IVOM 30.26 µm ± 3.49 µm; ≥7 IVOM 28.23 µm ± 2.25 µm; p = 0.02). CONCLUSION: The results show that a mathematical quantification of the CNV in nAMD is possible using OCT­A. This analysis confirmed again that the size of the CNV (area and total vessel length) is decisive for the prognosis of visual acuity. It also shows that a larger flow value as a sign of a well-differentiated CNV is associated with a better functional prognosis. The number of IVOMs required, however, depends primarily on the composition of the CNV (flow value and vascular caliber). More precise imaging and larger examination cohorts could possibly reveal further relevant biomarkers.

[Fibrovascular transformation of CNV in nAMD after long-term anti-VEGF therapy : Methodological evaluation of quantifying morphological changes]. / Die fibrovaskuläre Umwandlung der CNV bei nAMD unter lang andauernder Anti-VEGF-Therapie : Methodenevaluation zur Quantifizierung morphologischer Veränderungen.

BACKGROUND: Under long-term anti-VEGF therapy neovascular age-related macular degeneration (nAMD) may result in fibrovascular transformation of choroidal neovascularization (CNV). So far there is a lack of definitions on how a differentiated quantification of the associated morphological changes can best be carried out. This pilot study aimed to define the most appropriate imaging modalities. PATIENTS AND METHODS: In 56 eyes with fibrotic CNV after at least 2 years of anti-VEGF therapy and at least 12 intravitreal anti-VEGF injections, the following imaging modalities were investigated with respect to the delimitation of vascular and fibrous portions of CNV as well as associated atrophy of retinal pigment epithelium (RPE) and disruption of the ellipsoid zone (EZ): multicolor imaging (MC), fundus autofluorescence (FAF), fluorescein angiography (FA) and indocyanine green angiography (ICGA), spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). RESULTS: The vascular portion of fibrotic CNV was best visualized by OCTA, the fibrous portion by SD-OCT. The RPE atrophy was best delimitated by FAF, but differentiation was also possible by MC and ICGA. Disruption of the EZ could be delineated by SD-OCT b­scan. CONCLUSION: The use of MC is suitable for visualization of RPE atrophy and the fibrous portion of fibrotic CNV and FAF is suitable for differentiation of RPE atrophy. The SD-OCT can be used to quantify the fibrous portion of CNV; the EZ interruption is delimitable in the b­scan but not in the transverse structure-scan. The vascular part can best be detected by OCTA.

Quantitative Comparison of the Vascular Structure of Macular Neovascularizations Between Swept-Source and Spectral-Domain Optical Coherence Tomography Angiography.

PURPOSE: The aim of this study was to ascertain and quantify the differences between swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA) imaging of macular neovascularizations (MNV) in neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: SD-OCTA (RTVue Avanti) and SS-OCTA (PLEX® Elite 9000) were performed in 37 patients with MNV in nAMD. The MNV was delineated and the data were processed via ImageJ. The parameters MNV area, nodes per area, fractal dimension (FD), and flow density were analyzed using MatLab. RESULTS: There was close agreement between the two devices regarding MNV area (ICCc 0.977, ICCa 0.977, R2 0.977), but only slight agreement regarding nodes per area (ICCa 0.008, ICCc 0.548, R2 0.51), FD (ICCa 0.425, ICCc 0.846, R2 0.96), and flow density (ICCa 0.451, ICCc 0.656, R2 0.65). The difference between the two devices was insignificant for MNV area (type 1: p=0.328; type 2: p=0.426; type 3: p=0.615), but significant for nodes per area (type 1: p=0.002; type 2: p=0.00001; type 3: p=0.003), FD (type 1: p<0.00001; type 2: p<0.00001; type 3: p=0.015) and flow density (type 1: p=0.0004; type 2: p=0.004; type 3: p=0.052). CONCLUSION: MNV area is closely comparable between devices using SS-OCTA and SD-OCTA imaging. However, the two methods differ significantly in their precise assessment of the vascular morphology (FD, flow density, nodes per area). Therefore, results obtained using different devices are not comparable and should not be amalgamated in clinical trials.

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.

Morphologic analysis of macular neovascularizations by OCT angiography-Technical limitations in the comparison of 3×3mm and 6×6mm images.

BACKGROUND: The aim of this study was to ascertain whether there are relevant differences between the vascular morphology of macular neovascularizations (MNV) in 3×3mm and 6×6mm images, produced by optical coherence tomography angiography (OCTA). METHODS: MNV of 49 patients were automated quantitative analysed, measuring area, flow, the fractal dimension, average vessel length, vascular density, and average vessel caliber. These parameters were compared between the 3×3mm and the 6×6mm images. RESULTS: A strong linear association was found between the 3×3mm and the 6×6mm images. While area, flow, and FD of the MNV were very similar, the 3×3mm images showed significantly lower average total vessel length, greater vascular density, and lower average vessel caliber. CONCLUSION: In quantitative analysis of the morphologic parameters of MNV in 3×3mm and 6×6mm images, the structures are not directly equivalent in the two sizes of scan. The images must be evaluated on an individual basis.

[Hand, foot and mouth disease-associated maculopathy: a 2-year course]. / Hand-Fuß-Mund-Krankheit-assoziierte Makulopathie: ein 2­Jahres-Verlauf.

This article reports the case of a 35-year-old male patient with acute hand, foot and mouth disease and unilateral viral maculopathy of the right eye. In the course of 2 years an improvement of the subjective symptoms with a corresponding decrease of the findings in multimodal imaging could be observed. This case report demonstrates that acute maculopathy associated with hand, foot and mouth disease is a rare but relevant differential diagnosis with mostly good regression of symptoms and findings.