Choroidal Neovascularization In Eyes Research Articles

Влияние осевой миопии на течение неоваскулярной формы возрастной макулярной дегенерации на фоне анти-VEGF-терапии

Purpose. To determine the effect of increased axial length of the eyes on the course of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD) during anti-VEGF therapy. Material and methods. The study included 29 people (34 eyes) with neovascular AMD occurring against the background of axial myopia, in comparison with control eyes. The length of the anterior-posterior axis (APA) was 25.42 (24.25; 27.55) mm. The influence of axial myopia on degenerative changes in the fundus such as myopic maculopathy and posterior staphyloma (PS) was analyzed. The type of CNV, parameters of the neovascular complex and retina, retinal microcirculation in the foveal area before treatment and at the end of the observation period, and correlations were assessed using optical coherence tomography (OCT) and OCT angiography (OCTA). Treatment was with intravitreal anti-VEGF. The follow-up period was 28.80 (15.18; 44.10) months. The number of intravitreal injections (IVI) was 7.75 (5.70; 9.85). Results. «Mild» categories of myopic maculopathy were detected by ophthalmoscopy – mosaic fundus (K1) in 20.60% and diffuse chorioretinal atrophy (K2) in 17.60% of cases. PS in eyes with CNV and fellow eyes was detected in 17.50 and 21.00% of eyes, respectively, types were identified exclusively without involvement of the macular area. CNV types 1 and 2 were detected in equal proportions – in 43.48 and 56.52% of eyes, respectively. Visual functions and OCT parameters of the retina and CNV reached the maximum positive values after 2 loading injections of anti-VEGF. A significant positive dynamics of retinal microcirculation in the foveal zone was established by the end of the observation period against the background of a decrease in exudative changes in the retina. Correlation analysis showed a direct relationship between the number of injections and the extent of CNV before treatment (rφ=0.743; p=0.009) and the height of the neuroepithelium above the CNV before treatment (r φ=0.378; p=0.027). Conclusion. The presence of axial myopia in patients with neovascular AMD contributes to the appearance of minimal degenerative changes in the posterior pole of the eyes, which has a positive effect on visual function and CNV during antiVEGF therapy. Key words: choroidal neovascularization, neovascular age-related macular degeneration, axial myopia, optical coherence tomography angiography, anti-VEGF therapy

ANATOMICAL AND FUNCTIONAL OUTCOMES OF BEVACIZUMAB TREATMENT IN PEDIATRIC AUTOSOMAL RECESSIVE BESTROPHINOPATHY.

The purpose of this study was to report functional and anatomical outcomes of anti-VEGF treatment in eyes with autosomal recessive bestrophinopathy (ARB) presenting in the first decade of life. The study included case series of four eyes from two siblings with compound heterozygous mutations in the BEST1 gene who were treated with eight monthly intravitreal bevacizumab injections. Response to treatment was analyzed using color fundus photography, fundus autofluorescence, optical coherence tomography, OCT angiography, and microperimetry. Patient 1 (male, age 9 years) had visual acuity of 20/20 in the right eye and 20/50 in the left eye. Patient 2 (female, age 10 years) had visual acuity of 20/25 in the right eye and 20/20 in the left eye. All eyes had multifocal subretinal deposition of lipofuscin and subretinal fluid, and three eyes had choroidal neovascularization (CNV). Lipofuscin material reabsorbed in 2 of 4 eyes, the CNV regressed in 3 of 3 eyes, a bacillary detachment resolved in 1 of 1 eye, but the subretinal fluid did not change. Functional improvement in visual acuity was noted, but MP showed scattered areas of reduced retinal sensitivity. No ocular or systemic side effects were detected. Anti-VEGF treatment of choroidal neovascularization in eyes with ARB resulted in anatomical changes that were only clinically significant in the eye with decreased visual acuity. The hyporeflective subretinal material remained unchanged suggesting a nonexudative cause. These findings provide new insights into the management of ARB, especially in pediatric subjects with CNV.

ARTIFICIAL INTELLIGENCE'S ROLE IN DIFFERENTIATING THE ORIGIN FOR SUBRETINAL BLEEDING IN PATHOLOGIC MYOPIA.

To identify salient imaging features to support human-based differential diagnosis between subretinal hemorrhage (SH) due to choroidal neovascularization (CNV) onset and SH without CNV (simple bleeding [SB]) in pathologic myopia eyes using a machine learning (ML)-based step-wise approach. Four different methods for feature extraction were applied: GradCAM visualization, reverse engineering, image processing, and human graders' measurements. GradCAM was performed on a deep learning model derived from Inception-ResNet-v2 trained with OCT B-scan images. Reverse engineering consisted of merging U-Net architecture with a deconvolutional network. Image processing consisted of the application of a local adaptive threshold. Available OCT B-scan images were divided in two groups: the first group was classified by graders before knowing the results of feature extraction and the second (different images) was classified after familiarization with the results of feature extraction. Forty-seven and 37 eyes were included in the CNV group and the simple bleeding group, respectively. Choroidal neovascularization eyes showed higher baseline central macular thickness ( P = 0.036). Image processing evidenced in CNV eyes an inhomogeneity of the subretinal material and an interruption of the Bruch membrane at the margins of the SH area. Graders' classification performance improved from an accuracy of 76.9% without guidance to 83.3% with the guidance of the three methods ( P =0.02). Deep learning accuracy in the task was 86.0%. Artificial intelligence helps identifying imaging biomarkers suggestive of CNV in the context of SH in myopia, improving human ability to perform differential diagnosis on unprocessed baseline OCT B-scan images. Deep learning can accurately distinguish between the two causes of SH.

LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS.

To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.

Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells

The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1β and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1β as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy.

Outer nuclear layer recovery as a predictor of visual prognosis in type 1 choroidal neovascularization of neovascular age-related macular degeneration

To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.

TLR9 agonist suppresses choroidal neovascularization by restricting endothelial cell motility via ERK/c-Jun pathway.

Choroidal neovascularization (CNV) is the feature of neovascular age-related macular degeneration (AMD). It has been demonstrated that inflammation plays a key role in the development of CNV. Here we aim to investigate how TLR9 agonist (CpG-ODN), one of the key regulators of inflammatory responses, suppresses CNV in vivo. The cell viability was assessed by MTT and EdU test after CpG-ODN treatment. Endothelial cells gap assay, tube formation assay and transwell assay were practiced to observe how CpG-ODN affected the endothelial cells functions. The choroidal explants and laser-induced CNV model were built to investigate how CpG-ODN suppressed angiogenesis. The ERK and c-Jun expression were evaluated to assess if CpG-ODN affected cell proliferation. Flow cytometry and qPCR was practiced to observe how CpG-ODN regulated cell proliferation. Our data showed that CpG-ODN not only reduced CNV area in vivo, but also decreased the RPE damage. CpG-ODN inhibited endothelial cells from migration and forming tubes, while the effect was not toxic. EdU test and MTT test suggested that CpG-ODN inhibited endothelial cells proliferation. CpG-ODN significantly increased protein expression of phosphorylated c-Jun but reduced phosphorylated ERK in HUVECs, which was confirmed in ERK transfected 293T cells. JNK inhibitor abolished the suppression of endothelial cells migration and tube formation by CpG-ODN. The findings were also in agreement with the observation in CpG-ODN treated CNV eyes in vivo. The flow cytometry and qPCR data revealed that the suppression of cell motility by CpG-ODN was achieved by arresting endothelial cells cell cycle at G0/G1 phase. Our study demonstrated that CpG-ODN suppressed endothelial cell motility by restricting the cell cycle progression at G0/G1 phase, the effect of which was achieved by interacting with ERK/c-Jun pathways.

OCT Angiography Fractal Analysis of Choroidal Neovessels Secondary to Central Serous Chorioretinopathy, in a Caucasian Cohort.

Central serous chorioretinopathy (CSCR) can be complicated by different types of choroidal neovascularization (CNV). The purpose of this study was to investigate the incidence and quantitative optical coherence tomography angiography (OCT-A) features of CSCR-related CNVs. Methods: This was a retrospective multicenter study including 102 eyes of 102 Caucasian patients with acute or complex CSCR. All patients underwent a comprehensive ophthalmological examination. Quantitative OCT-A parameters, including vascular perfusion density (VPD), fractal dimension (FD), and lacunarity (LAC), were measured in CNV eyes. Results: Forty eyes (39.2%) had acute CSCR, whereas the remaining sixty-two (60.8%) had complex CSCR. CNV was observed in 37 (36.27%) eyes, all of which had the complex form. CNVs were classified as type 1 CNV in 11/37 (29.73%) cases and as polypoidal choroidal vasculopathy (PCV) in the remaining 26/37 (70.27%). Overall, the mean VPD, FD, and LAC of CSCR-related CNVs were 0.52 ± 0.20%, 1.44 ± 0.12, and 2.40 ± 1.1, respectively. No significant difference between type 1 CNV and PCV was found. Conclusion: Complex CSCR is often complicated by type 1 CNV and PCV with similar neovascular architecture and branching complexity, a finding supporting the idea that they might be different stages of the same neovascular process. Future OCT-A fractal analysis-based studies that also include other relevant parameters, such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions.

Clinical findings in eyes with BEST1-related retinopathy complicated by choroidal neovascularization.

To determine the characteristics of eyes diagnosed with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB) complicated by choroidal neovascularization (CNV). This was a retrospective, multicenter observational case series. Fourteen genetically confirmed BVMD patients and 9 ARB patients who had been examined in 2 ophthalmological institutions in Japan were studied. The findings in a series of ophthalmic examinations including B-scan optical coherence tomography (OCT) and OCT angiography (OCTA) were reviewed. CNV was identified in 5 eyes (17.9%) of BVMD patients and in 2 eyes (11.1%) of ARB patients. Three of 5 eyes with BVMD were classified as being at the vitelliruptive stage and 2 eyes at the atrophic stage. The CNV in 2 BVMD eyes were diagnosed as exudative because of acute visual acuity reduction, retinal hemorrhage, and intraretinal fluid, while the CNV in 3 BVMD eyes and 2 ARB eyes were diagnosed as non-exudative. The visual acuity of the two eyes with exudative CNV did not improve despite anti-VEGF treatments. None of the eyes with non-exudative CNV had a reduction of their visual acuity for at least 4years. All of the CNV were located within hyperreflective materials which were detected in 16 eyes (57.1%) of the BVMD eyes and in 7 eyes (38.9%) of the ARB eyes. CNV is a relatively common complication in BEST1-related retinopathy in Asian population as well. The prognosis of eyes with exudative CNV is not always good, and OCTA can detect CNV in eyes possessing hyperreflective materials.

Choroidal Neovascularization Screening on OCT-Angiography Choriocapillaris Images by Convolutional Neural Networks

Choroidal Neovascularization (CNV) is the advanced stage of Age-related Macular Degeneration (AMD), which is the leading cause of irreversible visual loss for elder people in developed countries. Optical Coherence Tomography Angiography (OCTA) is a recent non-invasive imaging technique widely used nowadays in diagnosis and follow-up of CNV. In this study, an automatic screening of CNV based on deep learning is performed using OCTA choriocapillaris images. CNV eyes (advanced wet AMD) are diagnosed among healthy eyes (no AMD) and eyes with drusen (intermediate AMD). An OCTA dataset of 1396 images is used to train and evaluate the model. A pre-trained convolutional neural network (CNN) is fine-tuned and validated on 80% of the dataset while the remaining 20% is used independently for predictions. The model can accurately detect CNV on the test set with an accuracy of 89.74%, precision of 0.96 and 0.99 area under the curve of the receiver operating characteristic. A good overall classification accuracy of 88.46% is obtained on a balanced test set. Detailed analysis of misclassified images shows that they are also considered ambiguous images for expert clinicians. This novel CNN-based application is truly a breakthrough to assist clinicians in the challenging task of screening for neovascular complications.

Clinical course after the onset of choroidal neovascularization in eyes with central serous chorioretinopathy.

Chronic central serous chorioretinopathy (CSC) can be complicated with choroidal neovascularization (CNV); however, the timing of its occurrence and its clinical significance are not well understood. This study aimed to observe the time of choroidal neovascularization detection after CSC diagnosis and determine whether clinical features and prognosis differed in patients with chronic CSC or age-related retinal degeneration.In this retrospective study, medical records of CSC patients complicated with CNV who visited Seoul St. Mary's hospital of Korea between October 2009 and December 2020 were reviewed. The presence of CNV was determined using fluorescein, indocyanine green, or optical coherent tomography angiography (OCTA). Based on the patients’ medical records, we observed the change of clinical pattern, best-corrected visual acuity (BCVA) and central macular thickness (CMT) at CNV detection and at 6 months, 1 year, 3 years, and 5 years following CNV detection.Thirty eyes of 30 patients (male: female ratio of 13:17) were enrolled. Mean age at diagnosis of CSC was 54.0 ± 8.5 years (mean ± standard deviation). On average, CNV was detected 1.65 ± 2.30 years after the diagnosis of CSC. The mean CMT was significantly decreased at 6 months, 1 year, and 3 years after choroidal neovascularization detection (P < .001, P < .001, P = .001 respectively). BCVA tend to improve after CNV detection, but there was no statistical significance at 6 months, 1 year, 3 years, and 5 years (all with P > .05). There were no clinical findings suggesting age-related macular degeneration such as intraretinal, subretinal hemorrhage or drusen in any of the case during follow-up. None of the subjects had severe visual acuity loss of 1.0 logarithm of the minimum angle of resolution (logMAR) (20/200 Snellen equivalent) or greater. Among the subjects, 6 patients (20%) did not require any treatment during observation, while 24 other patients required anti-vascular endothelial growth factor (anti-VEGF) or photodynamic therapy. At the last visit, 22 patients (73.3%) remained stable for more than 6 months, without subretinal fluid recurrence.Choroidal neovascularization was detected earlier than previously reported. There was no rapid deterioration of visual acuity or clinical features even after CNV detection.

The role of optical coherence tomography angiography in diagnosis of central serous chorioretinopathy

Purpose To detect the findings of optical coherence tomography angiography (OCTA) in eyes with central serous chorioretinopathy (CSCR), in comparison with conventional multimodal imaging. Patients and methods In the current case series, 80 eyes of 80 patients were diagnosed to have CSCR, and they underwent spectral domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and OCTA. OCTA images are performed at two main depth intervals: automatically segmented outer retina and automatically segmented choriocapillaris. Results In 40 of 80 eyes, OCTA images showed detached retina adjacent to the leakage point, compared with 40 of 80 eyes using FA, and 80 of 80 eyes using SD-OCT. In 44 of 80 eyes, irregular flow patterns were observed on OCTA images through the choriocapillaris. OCTA images could not identify leakage points in any of the included eyes, compared with 68 of 80 eyes on FA, and 56 of 80 eyes on SD-OCT. In 12 of 80 eyes, abnormal vessels (associated choroidal neovascularization) were observed on OCTA images, compared with eight of 80 eyes in SD-OCT and four of 80 eyes in FA. Conclusion OCTA images of the superficial and deep retinal plexus, outer retina, and choriocapillaris did not reveal altered flow patterns directly associated with the leakage point in acute CSCR. However, OCTA was able to visualize altered choroidal flow in some of the included eyes and was the best between all other modalities in detection of choroidal neovascularization in eyes with chronic CSCR.

Detection and clinical course of choroidal neovascularization in central serous chorioretinopathy

PurposeThe objective of this study was to observe the detection of choroidal neovascularization (CNV) after central serous chorioretinopathy (CSC) diagnosis and to determine whether clinical features and prognosis differ in CNV eyes from chronic CSC after CNV detection.MethodsThe medical records of 30 eyes of 30 patients with CSC were retrospectively analyzed in this study. The presence of CNV was diagnosed using fluorescein angiography (FA), indocyanine green angiography (ICGA), or optical coherent tomography angiography (OCTA). The time of initial symptom diagnosis and the period from the diagnosis of CSC to the detection of CNV were estimated based on the medical records. We observed the clinical change pattern by measuring the best‐corrected visual acuity (BCVA), central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) for one year since the detection of CNV.ResultsThe average period until CNV detection was 24.18 ± 29.43 months (mean ± standard deviation) from the initial symptom initiation and 20.10 ± 28.49 months from the first diagnosis of CSC. The CMT significantly decreased in patients with CSC in the one‐year follow‐up after CNV detection (p = 0.01), but no statistically significant changes were found in BCVA and SFCT.ConclusionsIn CSC patients, CNV detection was observed earlier than previously reported, and after CNV detection, there was no rapid deterioration of visual acuity or clinical features.

Multimodal imaging and electroretinography highlights the role of VEGF in the laser-induced subretinal fibrosis of monkey

Age-related macular degeneration (AMD) is a leading cause of blindness. Laser-induced nonhuman primate choroidal neovascularization (CNV) is a widely used animal model of neovascular AMD. Subretinal fibrosis (SFb) is the major limiting factor of effective anti-VEGF therapy for neovascular AMD, yet SFb has never been systematically analyzed in the primate CNV model and if VEGF directly affect SFb is unknown. We recruited a large cohort of rhesus macaques to study the occurrence, multimodal imaging and electroretinography (ERG) features, and related cytokines of SFb. Here we show that among 33 rhesus macaques, 88% CNV eyes developed SFb. Spectral domain optical coherence tomography (SD-OCT) identified four types of subretinal hyper-reflective material (SHRM) of SFb in primate. Multimodal imaging is reliable for monitoring SFb and matches the histological results well. Reduced amplitude of oscillatory potentials correlates with the thinning of inner retina layers and is a possible SFb indicator. Iba1+ microglia/macrophage cells infiltrated in the fibrotic lesions, and aqueous cytokine analysis identified four fibrosis-related factors (GM-CSF, IL-10, TGFβ2 and VEGF). Unexpectedly, we found sustained expression of VEGF may be an important inducer of SFb, and anti-VEGF therapy actually partially suppresses SFb. Taken together, our data suggest the laser-induced primate SFb model, coupled with multimodal imaging and ERG recording, is a useful system to dissect the pathogenesis and explore the rationale of treatment for SFb; and combined therapy with anti-VEGF and anti-fibrosis agents is necessary for AMD treatment.

PSS22 Intravitreal Therapies Pattern of Use in Italy: A Real-World Evidence Study on Maculopathies

To investigate drug utilization and prescribing practices regarding intravitreal therapies for neovascular age-related macular degeneration (wAMD), retinal vein occlusions (RVO), diabetic macular edema (DME) and choroidal neovascularization (CNV) treatment, providing real-world evidence regarding their patterns of use, in the Italian clinical context. A study, based on data from pharmacy databases, was conducted in 6 Italian hospitals. Treatment-naïve wAMD, RVO, DME, and CNV patients’ eyes, who received an intravitreal injection from 01/01/2016 to 06/31/2017, were eligible for inclusion, and a 24-month follow-up was assumed. Information about the number of injections received and administered drugs were considered, for whom frequencies and descriptive statistics were assessed. 5,527 eyes were diagnosed for a maculopathy requiring intravitreal therapy. 33% received treatment up to 24 months. Focusing on wAMD, considering a single-year treatment (N=3,260;64%), eyes received on average 3.39±0.04(range:1-12), 3.54±0.06(range:1-8) and 3 injections with ranibizumab, aflibercept and pegaptanib respectively. Considering a two-year treatment (N=1,798;36%), wAMD eyes received on average 8.00±0.10(range:2-18) and 8.11±0.10(range:2-14) ranibizumab or aflibercept injections. Out of 1,210 DME eyes, 71% received a single-year treatment, with 3.02±0.02(range:1-8), 3.60±0.13(range:1-8), 1.43±0.05(range:1-5) ranibizumab, aflibercept and dexamethasone respectively. Within a 24-month timeframe (N=348; 29%), 8.05±0.23(range:1-17) ranibizumab, 8.12±0.24(range:3-14) aflibercept and 4.59±0.17(range:2-11) dexamethasone injections were administered. 560 RVO eyes received treatment within a 12-month period, with 3.31±0.11(range: 1-10), 3.24±0.15(range:1-9), 1.47±0.06(range:1-7) or 1.67±0.33(range:1-2) ranibizumab, aflibercept, dexamethasone or triamcinolone injections. Considering a two-year treatment (N=197), 8.67±0.29(range:3-15) ranibizumab, 8.51±0.27(range:2-15) aflibercept or 3.92±0.21(range:2-6) injections were performed. CNV eyes (N=300) were treated with ranibizumab and aflibercept drugs receiving 2.08±0.08(range:1-8) and 1.83±0.40(range:1-3) injections respectively considering a single-year treatment (N=244 eyes). 56 eyes treated for a 24-month time horizon, were administered with 5.52±0.36(range:1-6) ranibizumab injections. The study highlights differences between clinical practice and prescribing information, in terms of intravitreal injections frequency, suggesting the need to further analyze and describe reasons and related organizational factors and potential problems.

Clinical Course of Treated Choroidal Neovascularization in Eyes with Pre-existing Geographic Atrophy: Case Series and Reappraisal of the Literature

ABSTRACT Purpose: To report the clinical course of choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (VEGF) treatment in eyes with pre-existing geographic atrophy (GA). Material and Methods: Multicenter retrospective series. Electronic medical records, clinical notes, and multimodal retinal imaging of patients attending four tertiary referring centers with a diagnosis of unilateral CNV in the context of a pre-existing diagnosis of GA were included. GA was assessed on multimodal retinal imaging including spectral-domain optical coherence tomography (SD-OCT) scan with simultaneous near-infrared (NIR) reflectance imaging (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany) which was acquired at baseline and every follow-up visit. GA area was measured in treated eyes and fellow eyes using NIR. Results: Fifty-four eyes from 27 patients (23 females, mean age 80.89 ± 7.5) were included. The mean number of injections in the treated eyes was 5.52 ± 1.9 by month 12. From baseline to month 12, stabilization of best-corrected visual acuity (BCVA) and a significant decrease (P = .002) of central macular thickness (CMT) in the treated eyes were observed; there was a slight worsening of BCVA (−2 ETDRS letters) and a non-significant change (P = .4) of CMT in the fellow eyes. GA significantly increased in both treated and untreated eyes (P < .001 and P < .001, respectively) with a similar absolute increase (+2.68 mm2 and +2.59 mm2, respectively) and growth rate (0.4 and 0.34, respectively). Conclusions: In our study anti-VEGF treatment for CNV in eyes with pre-existing GA was effective in terms of decrease of exudative changes and stabilization of VA by month 12. A similar growth rate of GA between treated and untreated eyes does not support a causal relationship between anti-VEGF treatment and GA progression in this subset of patients. Further studies with a longer follow-up are mandatory to confirm these results.

Clinical and angiographic characterization of choroidal neovascularization in diabetic retinopathy.

To report the clinical and angiographic characteristics of choroidal neovascularization in patients with diabetic retinopathy. Patients of type 2 diabetes mellitus with presence of choroidal neovascularization in at least one eye were retrospectively analyzed. The study eyes were divided into three groups based on presence (active or scarred) or absence of choroidal neovascularization (fellow eyes). Imaging characteristics of active choroidal neovascularization were recorded using optical coherence tomography, fluorescein, and indocyanine angiography. Central macular thickness, subfoveal choroidal thickness, and large choroidal vessel layer thickness were compared at baseline and final visit. Our study reports the prevalence rate of choroidal neovascularization in eyes with diabetic retinopathy (0.27%; 36 out of 13,382 eyes). A total of 64 eyes of 32 patients (age, mean ± standard deviation: 68.5 ± 9.3 years) with baseline visual acuity of 0.69 ± 0.69 logarithm of minimum angle of resolution (Snellen equivalent 20/100) were included. Nonproliferative diabetic retinopathy (57 eyes) comprised the majority followed by proliferative diabetic retinopathy (7 eyes). Eyes with choroidal neovascularization (36, 56.25%) included both active (25) and scarred (11) choroidal neovascularization, with bilateral choroidal neovascularization in 4 patients. Type 1 choroidal neovascularization was the most common subtype of choroidal neovascularization on optical coherence tomography. Common etiologies for active choroidal neovascularization included age-related macular degeneration (3; 12%), myopia (1; 4%), and inflammatory choroidal neovascularization secondary to chorioretinitis (1; 4%). In the remaining 20 eyes, choroidal neovascularization formation was primarily due to diabetic choroidopathy. The prevalence of choroidal neovascularization in eyes with diabetic retinopathy is very low, with a lower prevalence of age-related macular degeneration. Diabetic choroidopathy plays a significant role in formation of choroidal neovascularization in eyes with diabetic retinopathy.

A new rat model of treatment-naive quiescent choroidal neovascularization induced by human VEGF165 overexpression.

ABSTRACTVascular endothelial growth factor (VEGF) is a crucial stimulator for choroidal neovascularization (CNV). Our aim was to develop a reproducible and valid treatment-naive quiescent CNV (i.e. without signs of exudation and with normal visual acuity) rat model by subretinal injection of an adeno-associated virus (AAV)-VEGFA165 vector. The CNV development was longitudinally followed up in vivo by scanning laser ophthalmoscopy/optical coherence tomography, fluorescein and Indocyanine Green angiographies and ex vivo by electron microscopy (EM) and immunohistochemistry. In total, 57 eyes were analysed. In vivo, a quiescent CNV was observed in 93% of the eyes 6 weeks post-transduction. In EM, CNV vessels with few fenestrations, multi-layered basement membranes and bifurcation of endothelial cells were observed sharing the human CNV features. Human VEGF overexpression, multi-layered retinal pigment epithelium (RPE) (RPE65) and macrophages/activated microglia (Iba1) were also detected. In addition, 19 CNV eyes were treated for up to 3 weeks with bevacizumab. The retinal and CNV lesion thickness decreased significantly in bevacizumab-treated CNV eyes compared with untreated CNV eyes 1 week after the treatment. In conclusion, our experimental CNV resembles those seen in patients suffering from treatment-naive quiescent CNV in wet age-related macular degeneration (AMD), and responds to short-term treatment with bevacizumab. Our new model can, therefore, be used to test the long-term effect of new drugs targeting CNV under precisely-defined conditions.

Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials

To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials. Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N= 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n= 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n= 32). Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics. Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA). At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were-13.88 (1.40) and-7.64 (1.20) in Proxima A,-9.49 (1.29) and-7.57 (1.26) in Proxima B fellow eye CNV cohort, and-11.48 (3.39) and-8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively. The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

Short-time effect of intravitreal injections on retinal vascular oxygenation and vessel diameter in patients with diabetic macular oedema or neovascular age-related macular degeneration.

PurposeTo investigate the short‐time effect of intravitreal injections (IVI) of the vascular endothelial growth factor inhibitors ranibizumab and aflibercept on retinal arterial and venous oxygen saturation (SO2a and SO2v), arteriovenous oxygen saturation difference (AVD) and vessel diameter (VDa and VDv) in patients with diabetic macular oedema (DME) and patients with choroidal neovascularization (CNV) due to age‐related macular degeneration.MethodsUncontrolled prospective observational study in 100 eyes. Retinal vessel oxygen saturation and diameters were assessed using a retinal oximeter before and minutes after IVI of ranibizumab or aflibercept.Results40 eyes with CNV and 34 eyes with DME were included in the analysis. At baseline, SO2a and SO2v were significantly higher in DME (p = 0.043 and p = 0.009, respectively). After IVI, SO2a significantly decreased in CNV and DME eyes by 2.6% (p = 0.016) and 4.6% (p = 0.002) and SO2v decreased by 14.0% (p = 0.004) and 12.4% (p = 0.017), respectively. However, a significant increase in AVD was only found in CNV (15.7%, p = 0.001). VDa decreased significantly only in DME by 5.7% (p = 0.010). No medication‐specific disease effect was found and vice versa.ConclusionsThe observed changes can be interpreted as signs of increased metabolic demand during the physiological stress after an IVI. The abnormal arterial constriction and the abolished increase in AVD seen only in eyes with DME indicate an impairment of vascular autoregulation and oxygen distribution and a reduced neuroretinal metabolism in the diabetic retina with a significant impact on inner retinal oxygen consumption shortly after IVI.