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.

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.

[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.

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.

Characteristics of type 1 and 2 CNV in exudative AMD in OCT-Angiography.

BACKGROUND: With FA and SD-OCT, different types of CNV in exudative AMD may be differentiated: type 1 CNV (within the sub-RPE space, typically corresponding to angiographically occult CNV), type 2 CNV (within the subretinal space, typically corresponding to angiographically classic CNV) and type 3 NV (intraretinal retinal angiomatous proliferation). OCT-angiography (OCT-A) is a new method to visualize vasculature based on flow characteristics. A correlation of type 1 and 2 CNV was performed. METHODS: Thirty-six eyes (17 type 1 CNV, 9 combined type 1 and 2 CNV, and 10 type 2 CNV) of 36 patients were examined by FA, SD-OCT and OCT-A. Standardized OCT-A segmentations were performed at the level of mid-choroid, choriocapillaris (CC), RPE and outer retina. On these images the size and demarcation of CNV lesions were classified: "not distinguishable", "minor" or "sharp" demarcation. Furthermore, the size of the different CNV subtypes was determined and compared. RESULTS: Both types of CNV were visible in OCT-A. They could be detected on the slabs "mid-choroid", "CC" and "RPE". While type 1 CNV showed most often a minor demarcation from the surrounding vasculature, type 2 CNV showed nearly always a sharp demarcation. In addition, type 2 CNV extended into the slab "outer retina" and were much smaller than type 1 CNV. CONCLUSIONS: Different types of CNV in exudative AMD can be visualized and differentiated with OCT-A. Type 1 CNV were larger with minor demarcation from the surrounding vasculature and were visible on the slab "mid-choroid", "CC" and "RPE". In contrast, type 2 CNV demonstrated a sharp demarcation from the surrounding vasculature reaching the slab "outer retina".

[Exudative AMD in OCT Angiography]. / Exsudative AMD in der OCT-Angiografie.

OCT angiography provides a combination of vascular and structural information. In contrast to conventional fluorescein angiography, there is no need for dye injection to give an image of choroidal neovascularisation. Although there is currently no classification of OCT angiography, different neovascular patterns can be observed, with criteria for activity. In the future, OCT angiography may help us to understand pathophysiological mechanisms and to develop therapeutic strategies.

[Changes in OCT Angiography of Type 2 CNV in Neovascular AMD during Anti-VEGF Treatment]. / OCT-angiografische Veränderungen von der Typ-2-CNV bei exsudativer AMD unter Anti-VEGF-Therapie.

Purpose OCT-A is a new method to visualise the 2D and 3D structures of neovascular complexes in exudative AMD. The aim of the present study was to characterise type 2 CNV in different 2D segmentations and in 3D imaging and to investigate changes during anti-VEGF treatment. Methods 12 patients with type 2 CNV in FA and SD-OCT were selected. OCT-A (Avanti, Optovue) was obtained initially and after the first three injections and thereafter, if "new activity" (increase in sub- or intraretinal fluid) occurred. The characteristics of the type 2 CNV were classified initially and during follow-up in different segmentations (outer retina, RPE, CC, choroidea), in respect to the size of the CNV, the flow area within the CNV and flow index (% of flow area within the total lesion). Results Comparison of the vessel characteristics before and after anti-VEGF treatment showed a significant reduction in the size of CNV at every level (p < 0.05). This was most significant at the RPE level (p < 0.005). After new activity, a significant increase in size was only recognised at the CC level (p < 0.05). Similarly, the most significant changes in the flow area were measured at the RPE level before and after treatment (p < 0.01) and at the CC level after new activity (p < 0.05). Demarcation from type 2 CNV of the bordering tissue was much better when activity occurred. Conclusions OCT-A provides a new opportunity for the assessment of vascular characteristics of type 2 CNV, and quantifies CNV size and vascularisation under anti-VEGF therapy. This may be used in further studies in combination with SD-OCT scans to describe characteristics of this type of CNV under treatment. OCT-A is an additional medical imaging procedure to SD-OCT and FA, but more experience is needed in distinguishing CNV in the active and non-active stages.

[OCT Angiography in Exudative AMD with Detachment of Vascularised Retinal Pigment Epithelium]. / OCT-Angiografie bei exsudativer AMD mit vaskularisierter Pigmentepithelabhebung.

Background The aim of the following extended case study was to analyse whether choroidal neovascularisation (CNV) in vascularised epithelial detachments (PED) in OCT angiography (OCT-A) can be better visualised in OCT-A than in the established angiographic methods during the course of anti-VEGF therapy and if possible used to quantify the CNV size and flow area. These findings were compared with other SD-OCT characteristics of the lesion (PED height, retinal thickness). Patients and Methods 8 patients with PED and associated CNV were diagnosed with multimodal imaging and additionally OCT angiography was performed. The CNV region in the B-scan of the OCT-A was detected with a fine segmentation setting (20 µm) parallel and just below the retinal pigment epithelium (RPE). The CNV area was manually marked, and the size of the CNV and the vessel section (flow area) were analysed with the evaluation tool of the device. This measurement was performed both initially and after anti-VEGF therapy (3 injections). At the same time, the visual acuity (logMAR) and the SD-OCT parameters of PED height and retinal thickness were determined before and after therapy and also statistically compared. Results Initially, the size of CNV in OCT-A showed a large phenotypic range of variation (0.33 - 1.35 mm2, mean 0.71 mm2). This decreased significantly under therapy (after therapy 0.44 - 0.84 mm2, mean 0.57 mm2, p = 0.02). The proportion of the vessels analysed within the CNV (flow area) varied as well (0.21 - 0.88 mm2, mean 0.45) and decreased under therapy (0.08 - 0.44 mm2 after therapy), mean 0.27 mm2, p = 0.07). The height of PED in SD-OCT was initially different (initially 274 - 1459 µm, mean 607 µm), but showed only small changes (132 - 1317 µm, mean 524 µm, p = 0.09) under therapy. This also applied to the mean retinal thickness (before therapy 315 µm, after therapy 294 µm, p = 0.5). Mean visual acuity also improved only slightly (p = 0.7) after therapy. from initially 0.51 to 0.45 logMAR. Conclusions The combination of SD-OCT and OCT-A offers significantly improved visualisation and quantification of CNV in a vascularised PED. With the help of OCT-A imaging, changes in the perfusion/size of the CNV can be quantified. Together with the retinal activity signs, this allows a second activity assessment of the CNV under anti-VEGF therapy. Due to its three-dimensional structure, especially for this subtype of the exudative AMD, it is of the utmost importance to develop three-dimensional imaging for both structural SD-OCT and the OCT-A.

[OCT Angiography of RPE Tears in Exudative AMD: Morpohological Analysis of the Choriocapillaris and the RPE]. / OCT-Angiografie bei RPE-Einrissen im Rahmen einer exsudativen AMD: morphologische Analysen der Choriokapillaris und des RPE.

Background Retinal pigment epithelium (RPE) tears are a typical complication of vascular pigment epithelium detachment in age-related macular degeneration (AMD). During proactive intense anti-VEGF therapy, stabilisation or improvement of function may occur. With the new method of OCT angiography (OCT-A), retinal vessels and flow density can be quantified. This pilot study investigates changes in the choriocapillars (CC) in areas with increasing FAF in OCT following an RPE-tear. Methods In six eyes with an RPE-tear, prospectively initially and every three months thereafter, multimodal imaging was performed, including fundus autofluorescence (FAF) (HRA2, Heidelberg Engineering, Heidelberg, Deutschland) and OCT-A (RTVue XR Avanti, SSDA-Modus, Angiovue, Optovue, Freemont, CA, USA). With interactive MATLAB-software (MATLAB, MathWorks, Natick, MA, USA), FAF and OCT were geometrically superimposed. With the help of the Fiji software (National Institutes of Health, Bethesda, MD, USA), areas with increasing FAF flow intensity in OCT-A with CC-segmentation were measured during an average follow-up period of 12 months. Results We measured a reduction in the RPE-free area - due to an increase in autofluorescence tissue - of an average of 2.94 mm2 (SD 2.1 mm2; 42.1% of initial RPE-free area) in the boundary area of RPE-tears. At the end of the different follow-ups, some patients exhibited lower flow density in areas of regenerated autofluorescence than the initial findings. On the other hand, in some follow-ups, the same or increased flow density was seen. Conclusion In this pilot study, OCT-A was tested to analyse the structure of CC in areas of regenerated FAF after RPE-tears. Using external image editing software, FAF and OCT-A were compared during the follow-up. Thus apparent initial regression of the CC in the area mentioned above could be observed. During the follow-up and development of autofluorescent SHT, CC also regenerates up to the level of the initial findings of CC.

[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.

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.

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.

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.

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.

[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.

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.

[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.