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Background To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). Methods In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit’s eyes following injection. Results Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p Conclusion A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.

Nonexudative choroidal neovascularization (CNV) is a new phenomenon that has only recently been described in the literature with the advent of optical coherence tomography angiography (OCTA) imaging. The authors present a 1-year longitudinal follow-up of a nonexudative CNV lesion secondary to age-related macular degeneration. This report describes the appearance of the lesion on two commercially available spectral-domain OCTA devices and one prototype swept-source OCTA device. Management of these cases is still debatable. Watchful waiting with regular follow-up using serial OCTA to monitor disease progression has been valuable in this case., National Institutes of Health (U.S.) (Grant R01-EY011309), United States. Air Force Office of Scientific Research (Grant FA9550-15-1-0473), United States. Air Force Office of Scientific Research (Grant FA9550-12-1-0499)

Purpose To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. Design Comparative analysis of diagnostic instruments. Methods Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of, National Institutes of Health (U.S.) (R01-EY011289-28), National Institutes of Health (U.S.) (R44-EY022864-03), National Institutes of Health (U.S.) (R01-CA075289-17), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), United States. Air Force Office of Scientific Research (FA9550-12-1-0499)

PURPOSE: To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). DESIGN: A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. PARTICIPANTS: Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. MAIN OUTCOME MEASURES: A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. RESULTS: Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. CONCLUSIONS: Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images., Macula Vision Research Foundation, National Institutes of Health (U.S.) (NIH R01-EY011289-29A), National Institutes of Health (U.S.) (R44-EY022864), National Institutes of Health (U.S.) (R01-CA075289-16), United States. Air Force. Office of Scientific Research (AFOSR FA9550-15-1-0473), United States. Air Force. Office of Scientific Research (FA9550-12-1-0499), Praevium Research Inc., Massachusetts Lions Clubs, Samsung (Firm) (Scholarship)

Purpose: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). Methods: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. Results: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. Conclusion: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials., National Institutes of Health (U.S.) (Grants NIH R01-EY011289-29A, R44-EY022864, R01-CA075289-16, FA9550-15-1-0473 and FA9550-12-1-0499)

To describe the appearance of a scleral-derived feeder vessel in a highly myopic eye with secondary choroidal neovascularization (CNV) as visualized on both en face high-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype, and a commercially available spectral-domain (SD) OCTA, with the corresponding en face and cross-sectional structural OCT images. In this case report, a 60-year-old white male presented with high myopia and secondary CNV in the right eye, previously treated with anti-vascular endothelial growth factor, and was imaged on both SD-OCT and SS-OCT. The neovascular complex could be visualized on both devices. Structural en face SS-OCT images demonstrated a large choroidal-scleral feeder vessel that was not visualized with SD-OCT. The authors concluded that structural en face SS-OCT better visualizes scleral feeder vessel compared to SD-OCT due to the longer wavelength (∼1,050 nm) with increased choroidal penetration and decreased sensitivity roll-off in the SS-OCT system. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:960–964.]

Background To investigate the choroidal thickness in older patients with central serous chorioretinopathy (CSCR) compared to age-matched normal subjects. Methods Fifteen patients (30 eyes) with CSCR, all aged ≥60 years, and 21 age-matched normal subjects (21 eyes) underwent high-definition raster scanning using SD-OCT. Both eyes from CSCR patients were included in the analysis. The eyes in patients with CSCR were divided into two groups: active CSCR (17 eyes) if there was foveal-involving subretinal fluid and inactive contralateral eye group (13 eyes). Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroidal–scleral junction at 500 µm intervals up to 2500 µm temporal and nasal to the fovea (11 locations). Results The mean age of the patients with CSCR was 68.87 ± 6.83 years (mean ± standard deviation). Reliable measurements of choroidal thickness were obtainable in 70.6 % of eyes examined. The choroid was statistically significantly thicker in eyes with both active CSCR (P 0.05). Conclusion Choroid in older patients with active CSCR was thicker than the choroid in age-matched normal eyes. It is important to consider CSCR as a differential diagnosis of serous retinal detachment in elderly patients with thickened choroid and to consider SD-OCT as an imaging modality by which to evaluate the choroidal thickness.

Purpose: To investigate the appearance of choriocapillaris (CC) flow under drusen by comparing long-wavelength (1050 nm) swept-source optical coherence tomography (SS-OCT) angiography with shorter-wavelength (840 nm) spectral-domain (SD) OCT angiography. Methods: Patients with drusen imaged on both devices on the same day were selected and graded. Ambiguous OCT angiography (OCTA) signal loss was defined as low OCTA signal on the en face OCTA CC image that also had low OCT signal in the corresponding area on the en face OCT CC image and OCT B-scans. Unambiguous OCTA signal loss was defined as low OCTA signal on the en face OCTA CC image that did not have low OCT signal in the corresponding area on the en face OCT CC image and OCT B-scans. False-positive flow impairment on SS-OCTA was defined as ambiguous OCTA signal loss on SS-OCTA but no OCTA signal loss on SD-OCTA. False-positive flow impairment on SD-OCTA was defined as ambiguous OCTA signal loss on SD-OCTA but no OCTA signal loss on SS-OCTA. Results: Nine eyes from seven patients were enrolled, 23 drusen were analyzed. On 840-nm SD-OCTA, 17 drusen (73.9%) exhibited OCTA signal loss. Fourteen (82.4%) were classified as ambiguous, and three (17.6%) were classified as unambiguous; 10 (58.8%) were classified as having false-positive flow impairment. On 1050-nm SS-OCTA, seven drusen (30.4%) exhibited OCTA signal loss and were classified as unambiguous; none were classified as having false-positive flow impairment. Conclusions: Results showed that 1050-nm SS-OCTA appears less prone to producing areas of false-positive flow impairment under drusen., Macula Vision Research Foundation, National Institutes of Health (U.S.) (NIH R01-EY011289-30), National Institutes of Health (U.S.) (R44-EY022864-03), National Institutes of Health (U.S.) (R01-CA075289-19), United States. Air Force Office of Scientific Research (AFOSR FA9550-15-1-0473), United States. Air Force Office of Scientific Research (AFA9550-12-1-0499), Champalimaud Foundation, Massachusetts Lions Club, Birdshot Uveitis Society/Fight for Sight (24BU151), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil. Ministry of Education

Purpose: To evaluate the perifoveolar retinal capillary network at different depths and to quantify the foveal avascular zone (FAZ) in eyes with retinal vein occlusion (RVO) compared with their fellow eyes and healthy controls using spectral-domain optical coherence tomography angiography (SD-OCTA). Methods: We prospectively recruited 23 patients with RVO including 15 eyes with central RVO (CRVO) and 8 eyes with branch RVO (BRVO), their fellow eyes, and 8 age-matched healthy controls (8 eyes) for imaging on prototype OCTA software within RTVue-XR Avanti. The 3 × 3 mm and 6 × 6 mm en face angiograms of superficial and deep retinal capillary plexuses were segmented. Perifoveolar retinal capillary network was analyzed and FAZ was quantified. Results: Decrease in vascular perfusion at the deep plexus was observed in all eyes with CRVO (8/8, 100%) and BRVO (6/6, 100%) without cystoid macular edema, and in 8 of 15 (53%) and 2 of 8 (25%) of the fellow eyes, respectively. Vascular tortuosity was observed in 13 of 15 (87%) CRVO and 5 of 8 (63%) BRVO eyes. Collaterals were seen in 10 of 15 (67%) CRVO and 5 of 8 (63%) BRVO eyes. Mean FAZ area was larger in eyes with RVO than their fellow eyes (1.13 ± 0.25 mm[superscript 2] versus 0.58 ± 0.28 mm[superscript 2]; P = 0.007) and controls (1.13 ± 0.25 mm[superscript 2] versus 0.30 ± 0.09 mm[superscript 2]; P < 0.0001), and in fellow eyes of RVO patients when compared to controls (0.58 ± 0.28 mm[superscript 2] versus 0.30 ± 0.09 mm[superscript 2]; P = 0.01). Conclusions: Spectral-domain OCTA reveals abnormalities at different levels of perifoveolar retinal capillary network and is able to quantify the FAZ in RVO. Longitudinal studies may be considered to evaluate the clinical utility of OCTA in RVO and other retinal vascular diseases., Massachusetts Lions Eye Research Fund, Inc., Brazil. Ministry of Education

Purpose. To compare fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) images of foveal avascular zone (FAZ) in patients with diabetic retinopathy (DR) with and without diabetic macular ischemia (DMI).Methods. The Wilcoxon signed-rank test was used to compare area measurements andpvalues of 2) and “small” (inferior to 0.32 mm2) groups. Quantitative analyses of the FAZ were performed using custom software.Results. Thirty-four eyes from 34 diabetic patients were enrolled. Subjects with DMI presented a mean area on FA and OCTA of 0.68 ± 0.53 mm2and 0.58 ± 0.35 mm2, respectively (p=0.1374). Patients without DMI presented a mean area on FA and OCTA of 0.19 ± 0.67 mm2and 0.20 ± 0.79 mm2, respectively (p=0.9594). The ICC for the FAZ measurements between the 2 observers on FA and OCTA was 0.96 and 0.92, respectively.Conclusion. OCTA represents a novel technique for the diagnosis of DMI and it may become an alternative to FA for this purpose.

Purpose: To use a novel optical coherence tomography angiography (OCTA) algorithm termed variable interscan time analysis (VISTA) to evaluate relative blood flow speeds in polypoidal choroidal vasculopathy (PCV). Methods: Prospective cross-sectional study enrolling patients with confirmed diagnosis of PCV. OCTA of the retina and choroid was obtained with a prototype swept-source OCT system. The acquired OCT volumes were centered on the branching vascular network (BVN) and polyps as determined by indocyanine-green angiography (ICGA). The relative blood flow speeds were characterized on VISTAOCTA. Results: Seven eyes from seven patients were evaluated. Swept-source OCTA enabled detailed enface visualization of the BVN and polyps in six eyes. VISTA-OCTA revealed variable blood flow speeds in different PCV lesion components of the same eye, with faster flow in the periphery of polyps and slower flow in the center of each polyp, as well as relatively slow flow in BVN when compared with retinal vessels. BVNs demonstrated relatively faster blood flow speeds in the larger trunk vessels and relatively slower speeds in the smaller vessels. Conclusions: Swept-source OCTA identifies polyps in most, but not all, PCV lesions. This limitation that may be related to relatively slow blood flow within the polyp, which may be below the OCTA’s sensitivity. VISTA-OCTA showed heterogeneous blood flow speeds within the polyps, which may indicate turbulent flow in the polyps. Translational Relevance: These results bring relevant insights into disease mechanisms that can account for the variable course of PCV, and can be relevant for diagnosis and management of patients with PCV. Keywords: OCTA; optical coherence tomography angiography; PCV; polypoidal choroidal vasculopathy; variable interscan time analysis, National Institutes of Health (U.S.) (Grant R01-EY011289-29A), National Institutes of Health (U.S.) (Grant R44- EY022864), National Institutes of Health (U.S.) (Grant R01-CA075289-16), Air Force Office of Scientific Research (Grant FA9550-15-1-0473), Air Force Office of Scientific Research (Grant FA9550-12-1-0499)

Purpose: To utilize optical coherence tomography (OCT) and OCT angiography (OCTA) to describe alterations in the retinal and choriocapillaris vasculature following remote laser photocoagulation. Lesions are classified on the basis of choriocapillaris alteration as evaluated on en face OCTA. Methods: This was a retrospective, cross-sectional study analyzing 28 laser photocoagulation scars from 8 patients treated for diabetic macular edema. All eyes were analyzed using a combination of OCTA, en face and cross-sectional OCT, and fundus photography. Two masked readers scored images for alterations at the level of the retinal pigment epithelium (RPE), choroid, and choriocapillaris. Laser photocoagulation lesions were classified as deep if choriocapillaris alteration was present on OCTA; lesions were classified as superficial if no choriocapillaris alteration was present on OCTA. Results: Optical coherence tomography angiography was found to be useful for evaluation of choriocapillaris alteration underlying regions of laser scarring. Of the 28 analyzed laser scars, 13 were classified as superficial and 15 were classified as deep. Conclusions: Optical coherence tomography angiography can be used to visualize choriocapillaris alterations associated with focal laser photocoagulation treatment., Massachusetts Lions Eye Research Fund, Inc., Macular Vision Research Foundation