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PurposeThe purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA).MethodsOptical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments.ResultsTwenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003).ConclusionsThe areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

IMPORTANCE Zika virus (ZIKV) can cause severe changes in the retina and choroid that may result in marked visual impairment in infants with congenital Zika syndrome (CZS), the term created for a variety of anomalies associated with intrauterine ZIKV infection.OBJECTIVE To evaluate the affected retinal layers in infants with CZS and associated retinal abnormalities using optical coherence tomography (OCT). DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional, consecutive case series included 8 infants (age range, 3.0-5.1 months) with CZS. Optical coherence tomographic images were obtained in the affected eyes of 7 infants with CZS who had undergone previous ophthalmologic examinations on March 17, 2016, and in 1 infant on January 1, 2016. An IgM antibody-capture enzyme-linked immunosorbent assay for ZIKV was performed on the cerebrospinal fluid samples of 7 of the 8 infants (88%), and other congenital infections were ruled out. MAIN OUTCOMES AND MEASURESObservation of retinal and choroidal findings in the OCT images.RESULTS Among the 8 infants included in the study (3 male; 5 female; mean [SD] age at examination, 4.1 [0.7] months), 7 who underwent cerebrospinal fluid analysis for ZIKV had positive findings for IgM antibodies. Eleven of the 16 eyes (69%) of the 8 infants had retinal alterations and OCT imaging was performed in 9 (82%) of them. Optical coherence tomography was also performed in 1 unaffected eye. The main OCT findings in the affected eyes included discontinuation of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium in 9 eyes (100%), retinal thinning in 8 eyes (89%), choroidal thinning in 7 eyes (78%), and colobomatouslike excavation involving the neurosensory retina, retinal pigment epithelium, and choroid in 4 eyes (44%).CONCLUSIONS AND RELEVANCE Zika virus can cause severe damage to the retina, including the internal and external layers, and the choroid. The colobomatouslike finding seen in the OCT images relate to the excavated chorioretinal scar observed clinically.

PurposeTo compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm.MethodsPatients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 μm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well.ResultsTwenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test).ConclusionsThe automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

In the last few years, monoclonal antibodies have revolutionized the treatment of retinal neovascular diseases. More recently, a different class of drugs, fusion proteins, has provided an alternative treatment strategy with pharmacological differences. In addition to commercially available aflibercept, two other drugs, ziv-aflibercept and conbercept, have been studied in antiangiogenic treatment of ocular diseases. In this scenario, a critical review of the currently available data regarding fusion proteins in ophthalmic diseases may be a timely and important contribution. Aflibercept, previously known as VEGF Trap Eye, is a fusion protein of VEGF receptors 1 and 2 and a treatment for several retinal diseases related to angiogenesis. It has firmly joined ranibizumab and bevacizumab as an important therapeutic option in the management of neovascular AMD-, DME- and RVO-associated macular edema. Ziv-aflibercept, a systemic chemotherapeutic agent approved for the treatment of metastatic colorectal cancer, has recently drawn attention because of its potential for intravitreal administration, since it was not associated with ERG-related signs of toxicity in an experimental study and in human case reports. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity for VEGF and a long half-life in vitreous. It has been studied in a phase three clinical trial and has shown efficacy and safety. This review discusses three fusion proteins that have been studied in ophthalmology, aflibercept, ziv-aflibercept and conbercept, with emphasis on their clinical application for the treatment of retinal diseases.

Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema.

IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.