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Background As intravitreal anti-VEGF injections became the mainstay of treatment for many retinal diseases, the cause of a secondary sustained elevated intraocular pressure is still unclear. The aim of our study was to study the clearance of Aflibercept from the anterior chamber angle, in a rat model, to test if an aggregation exists. Methods Choroidal neovascular lesions (CNV) were induced in the right eye of 12 brown Norway rats, using indirect laser ophthalmoscope. Intravitreal Aflibercept injection (0.12 mg/3 µl) was performed 3 days after CNV induction. Rats were euthanized at predetermine time intervals of 3, 6, 24 and 48 h post injection, with immediate enucleation for histological analysis with H&E and immunofluorescence staining. Aflibercept molecules were stained with red fluorescence thanks to the formation of the immune complex Aflibercept-Rabbit anti human IgG-Anti rabbit antibodies-Cy3. Results Immediately after the injection, a strong fluorescence signal was detected, indicating the presence of Aflibercept in the iridocorneal angle. At 3- and 6-h interval a strong signal of Aflibercept was still seen. Six hours post injection, the signal was highly concentrated in Schlemm’s canal. In the 2 eyes harvested 24 h post Aflibercept injection, red fluorescence signal intensity was decreased in one eye, occupying mainly intra scleral venous plexuses, and absent in the other eye. At 48 h there was no fluorescence signal, confirming complete clearance of Aflibercept. Conclusions In our rat model, a complete clearance of Aflibercept from the anterior chamber angle, was seen 48 h after the injection. This finding refutes the theory of possible connection between IOP elevation and mechanical obstruction. Evacuation time of Aflibercept through the angle is of the same magnitude as that of Bevacizumab in the same rat model.

Lymphatic-venous malformations (LVMs) are development defects that result in abnormal connections between the lymphatic and venous systems. The authors describe a 7-weeks-old female infant who presented with a right orbital LVM extending to the ipsilateral cheek and subconjunctiva of the right eye, intracranial developmental venous anomalies in the right cerebellum, and a significant right eye intraocular retinal vascular malformation. Since orbital LVM is usually diagnosed in infancy or childhood, pediatric ophthalmologists should actively look for intraocular vascular malformations as such findings can poorly affect a patient’s vision.

Purpose: To study choriocapillaris (CC) flow in eyes with Type 3 neovascularization (NV) and age-related macular degeneration, using optical coherence tomography angiography analysis. Methods: In this multicenter, retrospective, observational study, we collected data from 21 patients with unilateral Type 3 NV and age-related macular degeneration, based on clinical examination, structural optical coherence tomography, and fluorescein angiography when available. An additional group of 20 nonneovascular age-related macular degeneration eyes with unilateral Type 1 or Type 2 NV due to age-related macular degeneration was included for comparison. En face optical coherence tomography angiography imaging (3 · 3 mm scans) with quantitative microvascular analysis of the CC was performed. Main outcome measures were: 1) the percent nonperfused choriocapillaris area; and 2) the average CC signal void size. Results: We included 21 patients with unilateral Type 3 NV (15 female, 71.5%) and 20 patients with unilateral Type 1 or 2 NV (9 female, 45.0% P = 0.118). Mean ± SD age was 82.1 ± 7.4 years in the unilateral Type 3 patients and 78.3 ± 8.1 in unilateral Type 1/2 NV subjects (P = 0.392). The percent nonperfused choriocapillaris area was 56.3 ± 8.1% in eyes with Type 3 NV and 51.9 ± 4.3% in the fellow eyes (P = 0.016). The average signal void size was also increased in those eyes with Type 3 NV (939.9 ± 680.9 mm 2 ), compared with the fellow eyes (616.3 ± 304.2 mm 2 , P = 0.039). The number of signal voids was reduced in the Type 3 NV eyes (604.5 ± 282.9 vs. 747.3 ± 195.8, P = 0.046). The subfoveal choroidal thickness was 135.9 ± 54.2 mm in eyes with Type 3 NV and 167.2 ± 65.4 mm in the fellow eyes (P = 0.003). In addition, the fellow eyes of patients with unilateral Type 3 NV displayed more significant CC flow abnormalities versus the fellow eyes with unilateral Type 1/2 NV (percent nonperfused choriocapillaris area = 51.9 ± 4.3% vs. 46.0 ± 2.1%, respectively, P, 0.0001; and average signal void size 616.3 ± 304.2 mm 2 versus 351.4 ± 65.5 mm 2 , respectively, P, 0.0001; and number of signal voids 747.3 ± 195.8 vs. 998.5 ± 147.3, respectively, P, 0.0001). Conclusion: Eyes with unilateral Type 3 NV illustrated increased CC nonperfusion versus fellow nonneovascular eyes. These results suggest that choroidal ischemia may play an important role in the development of Type 3 NV.

Purpose To describe the preclinical and very early stages of type 3 neovascularization using multimodal retinal imaging to expand our understanding of the pathogenesis of this disorder and potentially to prevent late treatment. Design Retrospective cohort study. Participants Patients diagnosed with treatment-naive type 3 neovascularization in the setting of age-related macular degeneration were identified at 4 retina referral centers. Inclusion criteria were: patients older than 55 years with at least 1 OCT and OCT angiography (OCTA) examination before the onset of clinically active type 3 neovascularization (i.e., preclinical stage). Methods Patients underwent a complete ophthalmologic examination including at least OCT and OCTA at the baseline and preclinical stage examinations, and dye angiographies when available. Demographics and clinical findings were analyzed. Main Outcome Measures Description of multimodal imaging features of nascent type 3 neovascularization. Results Fifteen eyes (15 patients; mean age, 83 ± 9 years) were included. At the baseline, mean BCVA was 0.32 ± 0.17 logarithm of the minimum angle of resolution and central macular thickness was 313 ± 50 μm. Preclinical (i.e., prebaseline) structural OCT illustrated the presence of intraretinal hyperreflective foci (HRF) at the site of type 3 neovascularization development in all patients. These foci were characterized by hyperfluorescence on dye angiography and by detectable flow on OCTA, identified with either the avascular slab (20%) or with both the deep retinal capillary plexus (DCP) and avascular slabs (80%). Typically, HRF with detectable flow on OCTA were characterized by the absence of intraretinal exudation (or very mild microcystic changes) until the lesion progressed from the DCP into the retinal pigment epithelium (RPE) and sub-RPE space. Of note, in 1 patient we observed the complete resolution of HRF despite the presence of OCTA flow and dye angiography hyperfluorescence detected at the preclinical stage examination. Conclusions Hyperreflective foci on structural OCT may represent early intraretinal neovascularization originating from the DCP, namely nascent type 3 neovascularization; these lesions can progress to active type 3 neovascularization or more rarely may regress without functional impairment. An advanced multimodal imaging approach is useful in detecting nascent type 3 lesions, which should be followed up carefully and treated as soon as possible if flow progresses to the RPE and sub-RPE space to prevent progression to late stages.

Objective. To describe an unusual cluster of multiple evanescent white dot syndrome (MEWDS) encountered within a 3-month period. Methods. This retrospective observation study is comprised of seven patients who presented with MEWDS in a 3-month period in central Israel. Data were collected from patients’ medical records on clinical, multimodal imaging, and viral serology findings. Results. Six women and one man of mean age 31.5 ± 7.2 years. Three reported a precedent viral infection. All had unilateral decreased vision. Funduscopy revealed foveal granularity. Main Imaging Findings. Hyperfluorescent spots on blue autofluorescence (BAF), hypofluorescent spots on indocyanine green angiography, dark lesions on infrared photos, and ellipsoid zone irregularities on spectral domain optical coherence tomography (SD-OCT). Resolution of the spots on BAF correlated with anatomic (SD-OCT) and visual recovery. OCT angiography performed following the convalescence stage demonstrated intact retinal and choroidal flow. Serologic findings were inconclusive. Conclusion. We report a unique cluster of MEWDS patients presented in a short period of time. SD-OCT findings of ellipsoid zone disruption in combination with other multimodal imaging modalities are outlined meticulously. Recognizing these imaging features along with high index of clinical suspicion is important for the diagnosis of MEWDS. Serologic testing might be considered in future patients.