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.

Myopic macular pits: a case series with multimodal imaging.

OBJECTIVE: To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration. METHODS: A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG). RESULTS: Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients. CONCLUSION: Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera.

Longitudinal Assessment of Ellipsoid Zone Recovery Using En Face Optical Coherence Tomography After Retinal Detachment Repair.

PURPOSE: Suboptimal functional outcomes after rhegmatogenous retinal detachment (RRD) repair may be related to photoreceptor abnormalities, including alterations of the ellipsoid zone (EZ) that may not be apparent on cross-sectional optical coherence tomography (OCT). This study assessed EZ recovery using en face OCT after RRD repair and its association with visual acuity. DESIGN: Post hoc analysis of a randomized controlled trial. METHODS: Patients with macula-off RRD were monitored at 3, 6, 12, and 24 months postoperatively and annually thereafter. En face OCT of the EZ slab were analyzed. Hyporeflective areas were colocalized with EZ abnormalities on cross-sectional OCT B-scans and measured by 2 masked graders. Primary outcome was change in area of EZ hyporeflectivity from 3 to 24 months, and its association with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity recovery was also assessed. RESULTS: In total, 271 images of 61 patients were assessed. Mean area of hyporeflectivity significantly decreased from 3 to 24 months (-2.98 mm2; 95% CI, 1.82-4.13 mm2; P < .0001), with further reductions up to 4 years. Linear regression revealed an association between change in hyporeflective area and change in the ETDRS letter score from 3 to 24 months (ß = -0.31, P = .009, R2 = 14.8%) and between duration of macula-off and change in hyporeflective area from 3 to 24 months (ß = -0.37, P = .018, R2 = 13.7%). CONCLUSIONS: En face OCT provides a novel biomarker for visualizing and quantifying EZ recovery after RRD repair that is associated with ETDRS visual acuity recovery. A steady decline in the area of EZ hyporeflectivity was observed over many years with delayed recovery in patients with longer duration of macula-off.

Postoperative Photoreceptor Integrity Following Pneumatic Retinopexy vs Pars Plana Vitrectomy for Retinal Detachment Repair: A Post Hoc Optical Coherence Tomography Analysis From the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial.

IMPORTANCE: Pneumatic retinopexy (PnR) is associated with superior visual acuity and reduced vertical metamorphopsia compared with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). It is important to determine postoperative photoreceptor integrity with both surgical techniques. OBJECTIVE: To compare photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months postoperatively. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Primary RRDs with specific criteria were included. Data were analyzed between April and August 2020. INTERVENTION: Randomization to PnR vs PPV stratified by macular status. MAIN OUTCOMES AND MEASURES: Difference in proportion of patients with discontinuity of the ellipsoid zone (EZ) and external limiting membrane (ELM) between groups assessed independently by 2 masked graders at an external masked image reading center. RESULTS: A total of 150 participants completed the 12-month follow-up visit. A total of 145 patients (72 PPV and 73 PnR) had gradable spectral-domain optical coherence tomography at 12 months. Analysis of the central 3-mm (foveal) scans found that 24% (n = 17 of 72) vs 7% (n = 5 of 73) displayed EZ discontinuity (difference, 17%; odds ratio [OR], 4.204; 95% CI, 1.458-12.116; P = .005) and 20% (n = 14 of 71) vs 6% (n = 4 of 73) displayed ELM discontinuity (difference, 14%; OR, 4.237; 95% CI, 1.321-13.587; P = .01) in the PPV and PnR groups, respectively. Analysis of the 6-mm (foveal and nonfoveal) scans revealed that EZ and ELM discontinuity was greater in the PPV vs PnR groups (EZ, 32% [n = 23 of 72] vs 11% [n = 8 of 73]; difference, 21%; OR, 3.814; 95% CI, 1.573-9.249; P = .002; ELM, 32% [n = 23 of 71] vs 18% [n = 13 of 73]; difference, 14%; OR, 2.211; 95% CI, 1.015-4.819; P = .04). CONCLUSIONS AND RELEVANCE: Discontinuity of the EZ and ELM was more common at 12 months postoperatively following PPV vs PnR for RRD repair. The findings of this post hoc analysis suggest that less discontinuity of the EZ and ELM may provide an anatomic basis for the previously reported superior functional outcomes with PnR, although the analysis does not prove a cause-and-effect relationship. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01639209.

Pentosan Polysulfate Maculopathy: Prevalence, Spectrum of Disease, and Choroidal Imaging Analysis Based on Prospective Screening.

PURPOSE: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis. DESIGN: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed. RESULTS: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group. CONCLUSIONS: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.

Identification and Characterization of Epivascular Glia Using En Face Optical Coherence Tomography.

PURPOSE: The purpose of this study was to describe the clinical features of epivascular glia (EVG) using en face optical coherence tomography (OCT). DESIGN: Retrospective cross-sectional study. METHODS: Single-institution en face OCT images were reviewed. Eyes displaying EVG were captured with manual internal limiting membrane (ILM) segmentation and analyzed with customized segmentation . A random age- and sex-matched control group was selected to determine relative epiretinal membrane (ERM) prevalence. RESULTS: Characteristic hyper-reflective ILM plaques with dendrite-like radiations were identified using en face OCT and displayed vascular predilection. A total of 161 eyes with EVG (the EVG group) and 2,315 eyes without EVG (control group) were identified from a total cohort of 1,298 patients (or 2,476 eyes). The prevalence of EVG was 161 of 2,476 eyes (6.5%) and 119 of 1,298 patients (9.2%) in the cohort. Mean age was 79.3 ± 10.7 years old in the EVG group and 55.9 ± 24.6 years old in the control group (P <.001). An advanced posterior vitreous detachment (PVD) stage was more common in the EVG group (grade 3: 41.7%; grade 4: 48.6%) than in the control group (grade 3: 18.5%; grade 4: 26.9%; P <.001). Contractile ERM was present in 71 of 161 eyes (44.1%) with EVG compared to 30 of 161 eyes (18.6%) in a random age- and sex-matched control cohort without EVG (P <.001). CONCLUSIONS: EVG previously described with histopathology and scanning electron microscopy can be identified using en face OCT. In this study, these lesions were associated with older age, pseudophakia, and advanced PVD, supporting the role of Müller cell activation through ILM breaks triggered by PVD, a pathogenic mechanism proposed by previous studies.

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.

Non-neovascular age-related macular degeneration with subretinal fluid.

PURPOSE: To evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes. METHODS: This retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes. RESULTS: Forty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy. CONCLUSION: Non-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

Relationship Between Nerve Fiber Layer Hemorrhages and Outcomes in Central Retinal Vein Occlusion.

Purpose: To evaluate the depth and pattern of retinal hemorrhage in acute central retinal vein occlusion (CRVO) and to correlate these with visual and anatomic outcomes. Methods: Retinal hemorrhages were evaluated with color fundus photography and fluorescein angiography at baseline and follow-up. Snellen visual acuity (VA), central foveal thickness (CFT), extent of retinal ischemia, and development of neovascularization were analyzed. Results: 108 eyes from 108 patients were evaluated. Mean age was 63.6 ± 16.1 years with a predilection for the right eye (73.1%). Average follow-up was 17.2 ± 19.2 months. Mean VA at baseline was 20/126 and 20/80 at final follow-up. Baseline (P = 0.005) and final VA (P = 0.02) in eyes with perivascular nerve fiber layer (NFL) hemorrhages were significantly worse than in eyes with deep hemorrhages alone. Baseline CFT was greater in the group with perivascular hemorrhages (826 ± 394 µm) compared to the group with deep hemorrhages alone (455 ± 273 µm, P < 0.001). The 10 disc areas of retinal ischemia was more common in patients with perivascular (80.0%) and peripapillary (31.3%) versus deep hemorrhages alone (16.1%, P < 0.001). Neovascularization of the iris was more common, although this differrence was not significant, in the groups with peripapillary (14.3%) and perivascular (2.0%) NFL versus deep hemorrhages alone (0.0%). Conclusions: NFL retinal hemorrhages at baseline correlate with more severe forms of CRVO, with greater macular edema, poorer visual outcomes, and greater risk of ischemia and neovascularization. This may be related to the organization of the retinal capillary plexus. The depth and pattern of distribution of retinal hemorrhages in CRVO may provide an easily identifiable early biomarker of CRVO prognosis.

Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.

OBJECTIVE: To describe the prevalence and spectrum of multimodal imaging findings of pentosan polysulfate sodium (PPS)-associated maculopathy and to recommend dosage-related screening guidelines. DESIGN: Cross-sectional study. METHODS: Patients previously or currently treated with PPS at University of California, Los Angeles, were randomly ascertained and prospectively screened for PPS-associated maculopathy with multimodal retinal imaging. Daily and cumulative dosages of PPS exposure were calculated for each patient. Images were studied to identify the characteristic findings of toxicity. The prevalence of PPS-associated maculopathy and screening guidelines were determined. RESULTS: The prevalence of PPS-associated maculopathy in this cohort was 20% (10/50 patients). Both average duration of PPS therapy and average cumulative dosage were significantly lower in the unaffected (6.3 ± 6.6 years, 691.7 ± 706.6 g) versus the affected groups (20.3 ± 6.6 years, 3375.4 ± 1650.0 g, p < 0.001). Near-infrared reflectance (NIR) illustrated characteristic punctate retinal pigment epithelium (RPE) macular lesions early. Fundus autofluorescence (FAF) showed speckled autofluorescence in the posterior pole with peripapillary extension. Co-localization with optical coherence tomography (OCT) displayed focal RPE thickening and, in more severe cases, RPE atrophy in the macula and even the periphery. CONCLUSIONS: A prevalence of 20% in this study cohort suggests a significant risk of macular toxicity for PPS-treated patients. Characteristic alterations are best detected with FAF and NIR. More significant PPS exposure was associated with more severe atrophy. We recommend an initial baseline eye examination to include OCT and, most importantly, NIR and FAF with annual retinal imaging thereafter especially with cumulative dosages approaching 500 g. Patients exposed to greater than 1500 g of PPS are at significant risk of retinal toxicity.

Volumetric Analysis of Vascularized Serous Pigment Epithelial Detachment Progression in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography.

Purpose: To analyze the evolution of type 1 neovascularization associated with vascularized serous pigment epithelial detachment (vsPED) using three-dimensional, volumetric, en face optical coherence tomography angiography (OCTA). Methods: This was a retrospective case series from four tertiary medical centers. OCTA images were analyzed at baseline and at the 3-, 6-, 12-, 18-, and 24-month follow-up visit when available. Visual acuity, number of injections, PED maximal height and PED area and volume, and choroidal neovascularization (CNV) flow area and progression were determined at each visit. Qualitative and quantitative analysis of CNV progression (including CNV/PED flow area) and final PED morphology was performed to determine anatomic outcomes. Results: Twenty-four eyes in 22 patients were studied. Median follow-up was 20 months. Across all eyes, maximum PED height decreased from 395.5 to 369.5 µm while CNV/PED flow ratio increased from 27.3% to 40.2%. Median visual acuity was unchanged at 20/40. Final PED outcomes included filled fibrovascular versus persistent vsPED. Filled vsPEDs decreased in PED height and volume and displayed a multilayered morphology in contrast to persistent vsPEDs. Fibrovascular PEDs received on average seven less injections as compared to persistent vsPEDs. Conclusions: Three-dimensional, volumetric, en face OCTA analysis of vsPED progression illustrated two anatomic outcomes: filled, typically multilayered fibrovascular PED versus persistent vsPED. The filled multilayered PED displayed a reduction in PED height and volume, greater CNV/PED flow ratio, and fewer anti-VEGF injections versus the persistent vsPED and may represent a more stable anatomic outcome while the persistent vsPED may indicate a more unstable morphology.

Progression of vascular changes in macular telangiectasia type 2: comparison between SD-OCT and OCT angiography.

PURPOSE: To investigate the different appearances of vascular changes in macular telangiectasia type 2 (MacTel) and to describe their possible progression, the vascular patterns in different retinal layers were analyzed with optical coherence tomography angiography (OCT-A) and the findings were correlated with a spectral-domain OCT (SD-OCT) disease severity scale based on the extent of ellipsoid zone (EZ) loss. METHODS: Participants from the MacTel Study Group in Muenster and a healthy cohort were investigated with OCT-A using RTVue XR Avanti. After segmentation of the superficial capillary network, the deep capillary network, and the outer retina (OR), flow density was analyzed using Optovue software. Then, the images were exported using the software Fiji (National Institute of Mental Health, Bethesda, MD, USA) and analyzed with the automated MATLAB program (Mathworks, Version R2014b). Four parameters (total vessel length, number of vessel branches, number of vessel segments, and fractal dimension) were examined on the vascular skeletons (temporal, foveal, nasal, and total fields of the ETDRS grid). In addition, linear and area measurements of EZ loss were performed on SD-OCT volume scans. Progression characteristics and correlation between linear and area measurements were analyzed using linear mixed effects models. RESULTS: Twenty eyes of healthy probands (20 OCT-A and 20 SD-OCT scans) and 122 eyes of 61 MacTel patients were included. In order to classify the severity of the disease, MacTel eyes were assigned to a SD-OCT "disease severity scale" (grade 1 = no EZ loss; grade 2 = EZ loss temporal to the fovea; grade 3 = EZ loss including the fovea and the region nasal to the fovea). Flow density and total vessel length showed only limited differences between healthy eyes and different grades of MacTel, but particularly the numbers of branches and vessel segments, as well as the fractal dimension values, demonstrated significant and progressive reduction in the superficial and deep capillary networks of the temporal, nasal, and total ETDRS fields. Moreover, the outer retina showed a progressive presence of hyperreflective material in SD-OCT grades 2 and 3 eyes with associated vascular patterns in the OR on OCT-A. CONCLUSIONS: In SD-OCT, the severity of MacTel is characterized by progressive EZ loss, which may be used as a simple clinical "disease severity scale". In addition, OCT-A enables visualization and quantification of vascular patterns with mathematical methods. The morphological progression of the disease correlated significantly with progressive vascular changes, especially in respect of the numbers of branches and vessel segments as well as fractal dimension. This suggests that the severity of neurodegenerative and neurovascular changes develops in parallel and that the analysis and quantification of the vascular changes in the superficial and deep capillary networks may become an additional parameter for future treatment trials. Moreover, the significant association between hyperreflective material progressively visible on SD-OCT in the OR, which most often contains vessels in OCT-A, and advancing SD-OCT severity grades, as well as vascular changes in OCT-A, supports the concept of retinal neovascularization in the OR in patients with advanced MacTel.

Progression characteristics of ellipsoid zone loss in macular telangiectasia type 2.

PURPOSE: To investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity. METHODS: Participants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models. RESULTS: A total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p < 0.001) and could predict it. The location of the EZ break had a significant impact on visual acuity. CONCLUSION: Ellipsoid zone (EZ) loss in MacTel has a non-linear progression characteristic, and its rate depends on area size at baseline, which must be taken into account at sample selection in clinical trials. Our results show a good correlation of linear and area measures of EZ loss and a segregation of best-corrected visual acuity by EZ location, which may help routine clinical practice.

Optical coherence tomography angiography of types 1 and 2 choroidal neovascularization in age-related macular degeneration during anti-VEGF therapy: evaluation of a new quantitative method.

PURPOSE: The aim of this pilot study was to test whether mathematical parameters of the vascular morphology of choroidal neovascularization (CNV) can be used as biomarkers and to investigate how these parameters change during anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Treatment-naive CNV in exudative age-related macular degeneration (AMD) was diagnosed in 28 patients. OCT-angiography (OCT-A) (Avanti/FA Optovue) performed before and after anti-VEGF therapy. The OCT-A data sets were exported to an external image processing program and vessel skeletonization was accomplished by means of edge detection. Based on this technique the total vessel length, the number of segments and the fractal dimension (FD) of the CNV were calculated before and after therapy. The results were compared with other clinical parameters such as VA and central retinal thickness (RT). RESULTS: The total vessel length of the CNV was significantly reduced by anti-VEGF-therapy (mean value 652 pixels vs. 397 pixels; p < 0.0001), as well as the number of individual vessel segments of the CNV (mean value 117 vs. 76; p < 0.0001). The FD of the CNV also decreased significant reduction during therapy (mean 1.23 vs. 1.16, p < 0.0001). The changes in these parameters during treatment corresponded with an increase in VA and a reduction in RT. CONCLUSION: This pilot study demonstrates that the vascular pattern of CNV in AMD can be visualized and described using mathematical parameters of OCT-A. The changes during therapy correlate significantly with established "activity" parameters of CNV, so changes in these parameters (especially FD) may represent additional CNV "activity" biomarkers.

[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 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.

[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.