To establish a normative database for vascular density (VD) and foveal avascular zone (FAZ) at the superficial (SCP) and deep capillary plexus (DCP) in healthy subjects with optical coherence ...tomography (OCT) angiography.
The study was a retrospective chart review of healthy patients who had undergone OCT angiography imaging. A 3- × 3-mm area, centered on the fovea, was scanned for all the study eyes. The automated segmentation allowed separate analysis of the SCP, the DCP, and a comprehensive C-scan including both vascular layers. On the obtained images, VD and FAZ measurements were computed. Interobserver reproducibility and intraobserver repeatability were also assessed.
A total of 135 eyes of 70 subjects (51% male) were analyzed. The mean age was 48.3 ± 17.5. We divided patients into group 1, from 20 to 39 years of age; group 2, from 40 to 59 years; and group 3, age 60 years or older. At the level of the SCP, mean VD and mean FAZ ± SD were, respectively, 52.58 ± 3.22% and 0.28 ± 0.1 mm2. At the level of the DCP, mean VD and mean FAZ were 57.87 ± 2.82% and 0.37 ± 0.12 mm2, respectively. The mean VD was significantly higher (P < 0.05) in DCP compared with SCP in all Early Treatment Diabetic Retinopathy Study (ETDRS) sectors and in all age groups. Vascular density was higher in women than in men after 60 years (P < 0.01). After adjustment on the signal strength index (SSI), the mean VD remained directly correlated with the age range and sex. The mean FAZ area was lower in group 3 (P < 0.05). Interobserver reproducibility was 0.78 to 0.99 in SCP and 0.67 to 0.92 in DCP, and intraobserver repeatability was 0.64 to 0.93 in SCP and 0.63 to 0.87 in DCP.
Our study has provided, for the first time, age-related VD mapping data using OCT angiography in healthy subjects. The prototype software used in this study may help to improve the concept of VD grading with high inter- and intraexaminer repeatability and interexaminer reproducibility.
Cryptococcus neoformans is a facultative intracellular pathogen and its interaction with macrophages is a key event determining the outcome of infection. Urease is a major virulence factor in C. ...neoformans but its role during macrophage interaction has not been characterized. Consequently, we analyzed the effect of urease on fungal-macrophage interaction using wild-type, urease-deficient and urease-complemented strains of C. neoformans. The frequency of non-lytic exocytosis events was reduced in the absence of urease. Urease-positive C. neoformans manifested reduced and delayed intracellular replication with fewer macrophages displaying phagolysosomal membrane permeabilization. The production of urease was associated with increased phagolysosomal pH, which in turn reduced growth of urease-positive C. neoformans inside macrophages. Interestingly, the ure1 mutant strain grew slower in fungal growth medium which was buffered to neutral pH (pH 7.4). Mice inoculated with macrophages carrying urease-deficient C. neoformans had lower fungal burden in the brain than mice infected with macrophages carrying wild-type strain. In contrast, the absence of urease did not affect survival of yeast when interacting with amoebae. Because of the inability of the urease deletion mutant to grow on urea as a sole nitrogen source, we hypothesize urease plays a nutritional role involved in nitrogen acquisition in the environment. Taken together, our data demonstrate that urease affects fitness within the mammalian phagosome, promoting non-lytic exocytosis while delaying intracellular replication and thus reducing phagolysosomal membrane damage, events that could facilitate cryptococcal dissemination when transported inside macrophages. This system provides an example where an enzyme involved in nutrient acquisition modulates virulence during mammalian infection.
To describe the qualitative and quantitative changes in choroidal neovascularization (CNV) flow pattern after anti-vascular endothelial growth factor therapy, by optical coherence tomography ...angiography (OCTA).
Consecutive patients with neovascular age-related macular degeneration underwent multimodal imaging, including OCTA at initial examination and at last visit. High-flow networks in the choriocapillaris segmentation of OCTA were qualitatively and quantitatively analyzed at baseline and at follow-up, to characterize vascular flow changes after anti-vascular endothelial growth factor treatment and to correlate these changes with final exudation signs on spectral domain optical coherence tomography.
Seventeen eyes were included. Mean follow-up was of 11.7 ± 3.3 months. Baseline images showed six medusa pattern (35.3%), four seafan pattern (23.5%), and seven indistinct network patterns (41.2%). Mean CNV area at baseline was 1.58 ± 1.72 mm. Final OCTA images revealed a decrease in CNV total area of 21.6%. In 6/17 eyes, the baseline neovascular pattern was unchanged; these cases were associated with exudation at the final spectral domain optical coherence tomography examination (P = 0.034) and a decrease in CNV area of 34.1%. Conversely, in 11/17 eyes (64.7%), the initial pattern had changed to a pruned vascular tree pattern, with variable exudative status on spectral domain optical coherence tomography at the final visit and a decrease in total CNV area of 0.07%.
The vascular flow remodeling induced by recurrent anti-vascular endothelial growth factor treatment can be assessed by OCTA. Optical coherence tomography angiography may help to accurately evaluate treatment response and to recognize patterns usually associated with recurrent exudative activity.
To evaluate the size of type 1 choroidal neovascularization (CNV) in neovascular AMD by optical coherence tomography angiography (OCTA) and to compare with indocyanine green angiography (ICGA).
...Patients diagnosed type 1 CNV underwent multimodal imaging by fluorescein angiography (FA), ICGA, spectral-domain (SD)-OCT, and OCTA. Lesion size was measured both on OCTA at the choriocapillaris level with "select area" and "vessel area" functions, incorporated in AngioVue software and on ICGA at intermediate and late phases, by two masked independent readers.
Nineteen eyes of 17 patients (mean age 80.6 ± 8.36) were included in the analysis. Mean visual acuity was 0.2 logMAR. All OCTA revealed a high flow neovascular network in the choriocapillaris segmentation. On OCTA, interclass correlation between readers 1 and 2 was 0.96 (95% confidence interval CI 0.94-0.99) for select area and 0.97 (95% CI 0.96-0.99) for vessel area. The difference between lesion size in OCTA versus ICGA was detected in all eyes and it was statistically significant for both readers (P < 0.05).
Optical coherence tomography angiography provides both quantitative and qualitative information on type 1 CNV and appears as a new reproducible way to evaluate CNV area and vessels area. Type 1 CNV lesion size in the choriocapillaris segmentation of OCTA and ICGA intermediate and late phases revealed that the OCTA size is significantly smaller than the ICGA size. This supports the idea that OCTA could be considered for evaluation of the neovascular lesion and for evaluation of therapeutic responses.
To characterize the macular lesions in multifocal choroiditis using multimodal imaging (MMI) and to evaluate optical coherence tomography angiography (OCTA) in distinguishing neovascular from ...inflammatory lesions.
Retrospective review of medical records of consecutive patients diagnosed with multifocal choroiditis and macular involvement, between September 2014 and May 2016, were included. All patients underwent standard examination and MMI, including fundus color photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography. They also underwent OCTA examination. Multimodal imaging and OCTA characteristics of inflammatory lesions and choroidal neovascularization (CNV) were compared.
Eighteen eyes of 13 patients (11 females) were analyzed. The mean age was 42.9 ± 13.4 years. The lesions were first categorized as active or inactive CNV and active or inactive inflammatory lesions through conventional MMI. Using OCTA, an abnormal blood flow was observed in all active CNV (9/9) and most inactive CNV (5/6), but also in 2 of 14 lesions previously classified as active inflammatory lesions. On the contrary, no case of inactive inflammatory lesions showed abnormal blood flow. Therefore, the use of OCTA allowed a diagnosis of CNV that was not made through conventional MMI in 14% of cases of active inflammatory lesions.
The combined findings of conventional imaging and OCTA demonstrate distinctive features of inflammatory lesions and CNV in multifocal choroiditis, allowing an appropriate management of these sight-threatening lesions. However, OCTA alone did not distinguish between active and inactive CNVs and should be integrated into an MMI approach.
To assess the variations induced by exercise in retinal vascular density (VD), foveal avascular zone (FAZ) area, and fractal dimension (FD) at the superficial (SCP) and deep (DCP) capillary plexa in ...healthy subjects by means of optical coherence tomography angiography (OCT-A).
Consecutive healthy subjects were prospectively included into two groups, ranging in age from 18 to 29 years for group 1 and from 30 to 40 years for group 2. Data from 3 × 3-mm OCT-A acquisition centered on the macula at SCP and DCP (VD, FAZ area, and FD), heart rate, and systolic-diastolic blood pressure were collected before and after a 20-minute standardized physical exercise on a stationary bicycle.
Both eyes of 32 healthy volunteers were prospectively included (15 in group 1 and 17 in group 2). Mean age was 27 ± 7 years. In the overall analysis and for each group, a decrease of VD at the level of SCP and an increase of FD at the level of DCP were significant after exercise. A significant correlation was found between these modifications of retinal vascularization and the increase of systolic blood pressure induced by exercise. All cardiovascular parameters increased significantly with exercise. No significant difference was found between the two groups, and no incident was reported.
A significant correlation was established between systemic cardiovascular modifications (reflected by systolic blood pressure) and local retinal vascularization changes at SCP during exercise. A rest period might be recommended before OCT-A data acquisition, as modifications of cardiovascular parameters could distort retinal vascular data.
To report the imaging features of subretinal fibrosis secondary to exudative age-related macular degeneration (AMD) on optical coherence tomography angiography.
All consecutive patients diagnosed ...with subretinal fibrosis complicating exudative AMD were imaged by color retinal photographs or multicolor imaging, fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography. Eyes with active exudative features observed during the last 6 months were compared with those without any sign of exudation >6 months.
Forty-nine eyes of 47 consecutive patients were included. A blood flow inside the fibrotic scar could be detected in 46 of 49 cases (93.8%). Three patterns of vascular networks could be distinguished, that were described as pruned vascular tree (26 of 49 eyes; 53.1%), tangled network (14 of 49; 28.6%), and/or vascular loop (25 of 49; 51.0%). Furthermore, 2 types of hyporeflective structures, large flow void, and/or dark halo were observed in 63% and in 65% of eyes, respectively. The observed patterns did not differ between eyes with active or inactive lesions.
Optical coherence tomography angiography of subretinal fibrosis showed almost constantly a perfused, abnormal vascular network and collateral architectural changes in the outer retina and the choriocapillaris layer. These features were associated with both active and inactive fibrotic choroidal neovessels.
To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment associated with dry ...age-related macular degeneration.
Twenty eyes with large soft drusen and/or drusenoid pigment epithelial detachment age-related macular degeneration were included and treated using the LumiThera Valeda Light Delivery System. All patients underwent two treatments per week for 5 weeks. Outcome measures included best-corrected visual acuity, microperimetry-scotopic testing, drusen volume, central drusen thickness, and quality of life score at baseline and month 6 (M6) follow-up. Data of best-corrected visual acuity, drusen volume, and central drusen thickness were also recorded at week 5 (W5).
Best-corrected visual acuity significantly improved at M6 with a mean score gain of 5.5 letters ( P = 0.007). Retinal sensitivity decreased by 0.1 dB ( P = 0.17). The mean fixation stability increased by 0.45% ( P = 0.72). Drusen volume decreased by 0.11 mm 3 ( P = 0.03). Central drusen thickness was reduced by a mean of 17.05 µ m ( P = 0.01). Geographic atrophy area increased by 0.06 mm 2 ( P = 0.01) over a 6-month follow-up, and quality of life score increased by 3,07 points on average ( P = 0.05). One patient presented a drusenoid pigment epithelial detachment rupture at M6 after PBM treatment.
The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and drusenoid pigment epithelial detachment age-related macular degeneration and may potentially slow the natural course of the disease.
To report the prevalence and treatment outcomes of eyes with sub-retinal pigment epithelium (sub-RPE) multilaminar hyperreflectivity at the onset/clinical detection of Type 3 macular ...neovascularization (MNV) secondary to exudative age-related macular degeneration.
Retrospective analysis of consecutive patients diagnosed with Type 3 MNV secondary to age-related macular degeneration was performed. Eyes presenting with sub-RPE multilaminar hyperreflectivity on structural optical coherence tomography at the onset of Type 3 MNV were included in this study. An age-, sex-, and stage-matched control group was composed of eyes affected by Type 3 MNV without sub-RPE multilaminar hyperreflectivity. Prevalence and treatment outcomes after anti-vascular endothelial growth factor injections at 1-year follow-up were analyzed in both groups.
Nineteen treatment-naïve eyes of 19 patients (8 men/11 women, mean age 83 ± 8 years old) presenting with sub-RPE multilaminar hyperreflectivity before or at the onset/clinical detection of Type 3 MNV were included from a cohort of 162 eyes with treatment-naïve Type 3 MNV. This accounts for an estimated prevalence of 11.7% (5.8-15.2, 95% confidence intervals). No significant differences were disclosed between cases studied and the control group (143 eyes of 143 patients) in age, sex, best-corrected visual acuity at baseline, and number of injections. Best-corrected visual acuity did not improve during the 1-year follow-up in patients showing sub-RPE multilaminar hyperreflectivity (P = 0.45), whereas best-corrected visual acuity significantly increased in the control group (P < 0.001). The presence of sub-RPE multilaminar hyperreflectivity in the context of Type 3 MNV was significantly associated with regressive calcific drusen (P < 0.001) and multiple Type 3 lesions/eye (P < 0.001).
The detection of multilaminar hyperreflectivity at the onset/clinical detection of Type 3 MNV suggests that chronic exudation (i.e., the "onion-sign") in the sub-RPE space (i.e., focal sub-RPE neovascularization) may precede the onset/clinical detection of Type 3 MNV. Sub-retinal pigment epithelium multilaminar hyperreflectivity at the onset of Type 3 MNV may be an important predictor of poor visual outcome in these eyes.
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