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.

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

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

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

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

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

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

NEGATIVE EFFECTS OF VITAL DYES AFTER UNEVENTFUL VITREOMACULAR SURGERY.

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

RANIBIZUMAB IN PIGMENT EPITHELIAL TEARS SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Prospective Study.

PURPOSE: To assess efficacy of intravitreal ranibizumab in retinal pigment epithelium tears secondary to neovascular age-related macular degeneration. METHODS: The Ranibizumab In Pigment epithelial tears secondary to age-related macular degeneration (RIP) study is a prospective, single-arm, multicenter, investigator-initiated trial. Twenty four eyes of 24 patients with a retinal pigment epithelium tear secondary to age-related macular degeneration received monthly intravitreal injection of 0.5mg ranibizumab for 12 months, together with monthly assessments of morphologic and functional efficacy parameters. Primary outcome measure was mean best-corrected visual acuity at final visit compared with baseline. RESULTS: Mean best-corrected visual acuity remained stable over the 12-month study period with 50.3 Early Treatment of Diabetic Retinopathy Study letters (±18.7; Snellen equivalent 20/100) at baseline and 52.9 letters (±19.7; Snellen equivalent 20/100) at final visit (P = 0.39). One eye (4%) experienced a vision loss of ≥15 letters, and 2 eyes (8%) gained ≥15 letters. Mean central retinal thickness decreased from 571 µm (±185 µm) to 436 µm (±171 µm; P = 0.0001). Vision-related quality of life was stable with a mean VFQ-25 score of 79.0 (±10.8) at baseline and 74.3 (±13.9) at final visit (P = 0.12). CONCLUSION: In retinal pigment epithelium tears secondary to age-related macular degeneration, monthly intravitreal ranibizumab therapy results in stabilization of visual acuity over 12 months.

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 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.

RETINAL PIGMENT EPITHELIAL TEAR AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION: Clinical Course and Long-Term Prognosis.

BACKGROUND: To document the long-term outcome in cases of retinal pigment epithelial (RPE) tears after treatment of vascularized pigment epithelial detachments with anti-vascular endothelial growth factor therapy. METHODS: A retrospective analysis of the long-term outcome of a consecutive series of eyes with RPE tear developed during anti-vascular endothelial growth factor therapy for pigment epithelial detachment associated with choroidal neovascularization or retinal angiomatous proliferation (vascularized pigment epithelial detachment) was performed. Best-corrected visual acuity (BCVA), spectral domain optical coherence tomography, and autofluorescence images and also fluorescein angiograms were analyzed to determine the functional and morphologic development over time. RESULTS: The long-term outcome of 22 eyes (21 patients, 13 women and 8 men; 65-85 years; mean: 76 years) with RPE tear was performed with minimal follow-up of 3 years (range: 3-5 years, mean: 44 months) and re-treatment with different therapeutic strategies. The eyes were differentiated in 2 groups according to the course of BCVA after the first 2 years of follow-up: Group 1 (11 eyes) demonstrated a stabilized or improved BCVA after 2 years and Group 2 (11 eyes) demonstrated a decrease in BCVA after 2 years. The initial BCVA between both groups was comparable. Also the mean initial size of the RPE tear was the same between the 2 groups, the area of the RPE tear decreased continuously during follow-up in Group 1, whereas this was the case in Group 2 only at the beginning of treatment with a further increase of the size of the RPE tear with longer follow-up. This corresponded with a different morphologic development between the two groups. In Group 1, increasing recovery of autofluorescence at the RPE-free area was visible beginning from the outer border, whereas in Group 2, further growth of the neovascular complex in the area of the RPE tear was observed resulting in larger fibrovascular scars. In addition, in both groups, the development of hyperreflective tissue was seen on spectral domain optical coherence tomography in the RPE-free area. The major therapeutic difference between the 2 groups was a significantly larger number of injections especially during the first year in Group 1. CONCLUSION: The development of RPE tear after anti-vascular endothelial growth factor therapy for vascularized pigment epithelial detachment in exudative age-related macular degeneration does not necessarily result in large disciform scars and functional loss, but multiple injections seem to be beneficial especially in the first year. With this strategy, RPE tears seem to be covered by autofluorescent and hyperreflective tissue and a regrowth of the neovascular complex can be prohibited. As a result, photoreceptor cells regain their metabolic support with functional recovery.

ASSOCIATION BETWEEN CHANGES IN MACULAR VASCULATURE IN OPTICAL COHERENCE TOMOGRAPHY- AND FLUORESCEIN- ANGIOGRAPHY AND DISTRIBUTION OF MACULAR PIGMENT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: We investigate the association between morphologic findings in optical coherence tomography angiography (OCTA) as a new method offering the visualization of deeper layers of retinal vasculature and fluorescein angiography (FA) and macular pigment imaging and in Type 2 macular telangiectasia. METHODS: Fourty-two eyes of 21 patients with macular telangiectasia (38-68 years, 14 female) were examined by FA and OCTA and 24 eyes additionally with dual-wavelength autofluorescence. Early and late FA, macular pigment density images, and (after segmentation of retinal vasculature into superficial and deep capillary network and outer) OCTA images were graded into standardized categories. Agreement between the methods was evaluated statistically. RESULTS: In OCTA, a reduction of density of superficial capillaries, dilated vessels in the deep capillary network, anastomoses toward the superficial capillary network, and "new" vessels in the outer retina layers can be detected. The described anatomical features, especially in the deep capillary plexus and outer retina corresponded well with changes in FA. Classes of macular pigment distribution correlated most with classes of changes in OCTA superficial capillary plexus. CONCLUSION: Progressive changes in macular telangiectasia apparent in FA and macular pigment imaging are most obvious in the deep capillary network and outer retina in OCTA. Optical coherence tomography angiography offers a noninvasive technology to analyze vascular changes in the retina and choroid of patients with macular telangiectasia.

Long-term visual course after anti-VEGF therapy for exudative AMD in clinical practice evaluation of the German reinjection scheme.

BACKGROUND: In phase III trials, the therapeutic efficacy of anti-VEGF therapy with ranibizumab (Lucentis) in patients with choroidal neovascularization due to AMD was demonstrated in a 24-month period with monthly injections. Other studies and models suggested that flexible reinjection regimens can provide similar visual results. The aim of the present study was to evaluate the flexible, predominantly visual acuity-driven ranibizumab retreatment regimen in clinical practice in Germany. PATIENTS AND METHODS: Best-corrected visual acuity (VA, logMAR) and central retinal thickness (CRT) were recorded initially and every 4-6 weeks during follow-up (mean follow-up 75.5 weeks) from 152 eyes. All eyes were treated initially 3 times with ranibizumab at 4-weekly intervals, and retreated with another three injections if visual acuity decreased and/or CRT increased (>100 µm), and/or if new angiographic leakage and/or new retinal hemorrhages developed. Visual acuity development was analyzed in the whole group. A quartile analysis was also performed, and visual course was correlated with CRT. In all groups, numbers and times of reinjections within the first year were registered and analyzed. RESULTS: An increase in mean VA of 0.14 (SD 0.22) logMAR could be observed after 3 months, but during follow-up from months 3 to 12 the mean visual acuity decreased again by 0.14 (SD 0.24) logMAR, and was similar to the initial VA despite several reinjections (mean five injections). Stratification of patients according to the visual effect after 3 months (quartile analysis) demonstrated a differentiation of the visual course. Quartile 1, with the largest increase in VA after 3 months and reduction of the retinal edema, lost this positive effect during follow-up (100% of eyes received further injections). In contrast, quartile 2, with a minor increase, and quartile 3 demonstrated a stabilized response during follow-up (80% reinjections), while quartile 4 demonstrated a further loss in VA despite reinjections initially and during follow-up (60% reinjections). CONCLUSIONS: The flexible, predominantly visual acuity-driven ranibizumab retreatment regimen employed in clinical practice in Germany generally resulted in a loss of initially gained VA during 12 months of follow-up. Subgroup analysis showed that this negative effect was especially present in patients with relatively bad VA at treatment entry as well as the highest visual gain. Because this result demonstratse that a visual acuity-related retreatment regimen can not preserve the initial positive treatment effects with ranibizumab in exudative AMD, a revision of this schematic retreatment regimen used in Germany and adaptation to more sensitive retreatment parameters is recommended.

[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.

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.

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.

Intravitreal and orbital floor triamcinolone acetonide injections in noninfectious uveitis: a comparative study.

PURPOSE: To compare the effect of orbital floor (OFTA) or intravitreal (IVTA) administration of triamcinolone acetonide on visual acuity and chronic cystoid macular edema (CME) in patients with uveitis. METHODS: Retrospective study of patients suffering from chronic noninfectious uveitis in whom CME (n = 97) did not respond to systemic corticosteroids and/or immunosuppression combined with acetazolamide. Patients received a single injection of either IVTA (n = 48, group 1) or OFTA (n = 49, group 2). Best-corrected visual acuity, macular edema (fluorescein angiography), uveitis activity, ocular hypertension, and cataract formation were analyzed over the course of 1 year. RESULTS: Improvement in visual acuity (> or = 2 lines, LogMAR) was noted in 50% (IVTA) and 34% (OFTA) after 3 months (p = 0.23), and in 18% (IVTA) and 20% (OFTA) after 12 months. CME improved in 100% (IVTA) and 76% (OFTA) of the eyes within the first month postoperatively (p = 0.36). Macular edema was reduced in 100% (group 1) and 20% (group 2) after 3 months (p < 0.01). At 1 year, cataract progression was noted in 68% (IVTA) and 27% (OFTA) (p < 0.01). Increased intraocular pressure (>21 mm Hg) was detected in 21% (IVTA) and 0% (OFTA) at 4 weeks (p < 0.01) after injection. CONCLUSION: Uveitic CME and visual acuity not responding to systemic immunosuppression and acetazolamide may improve after an IVTA and OFTA injection. The effect is mostly transient. While the IVTA injections were more effective for improving CME, ocular hypertension and cataracts developed more often.

Changes in the OCT angiographic appearance of type 1 and type 2 CNV in exudative AMD during anti-VEGF treatment.

OBJECTIVE: Optical coherence tomography angiography (OCT-A) enables detailed visualisation of the vascular structure of choroidal neovascularisation (CNV). The aim of this study was to determine whether mathematically ascertained OCT-A vascular parameters of type 1 and type 2 CNV in exudative age-related macular degeneration (AMD) change during antivascular endothelial growth factor (anti-VEGF) treatment. The OCT-A vascular parameters were also compared with previously obtained activity parameters (fluid distribution on spectral domain OCT (SD-OCT)) to establish whether they could potentially be used as further 'activity parameters' for assessment of anti-VEGF treatment. METHODS AND ANALYSIS: We evaluated 27 eyes of 27 patients (mean follow-up 9.8 months) with type 1, type 2 or mixed CNV who had received anti-VEGF treatment (IVAN scheme). The parameters analysed were area (aCNV), total length of all vessels (tlCNV), overall number of vascular segments (nsCNV) and fractal dimension (FD) of the CNV. The changes in each of these parameters were correlated with the central foveal thickness (CFT). RESULTS: Regression and renewed perfusion of the CNV corresponded with the decrease or increase, respectively, of macular fluid distribution on SD-OCT. The increase and decrease of CFT during anti-VEGF treatment were highly significantly correlated with changes in FD (p<0.00001), aCNV (p<0.00001), tlCNV (p<0.00001) and nsCNV (p<0.00001). CONCLUSION: OCT-A enables detailed analysis of AMD with regard to FD, aCNV, tlCNV and nsCNV. As the changes in these parameters correlate closely with changes on SD-OCT, they can be used as new activity parameters, alongside fluid distribution, for assessment of treatment effect and as parameters of stabilisation or the need for repeated treatment.

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.