MACULAR MICROVASCULAR NETWORKS IN HEALTHY PEDIATRIC SUBJECTS.

PURPOSE: To report optical coherence tomography angiography (OCTA) values in healthy pediatric eyes and to identify factors that may modify these values. METHODS: In this prospective observational cross-sectional study, macular OCTA images were acquired from healthy pediatric patients. Main outcome measures were 1) foveal avascular zone (FAZ) area at the level of the superficial retinal capillary plexus (SCP); 2) SCP and deep retinal capillary plexus (DCP) perfusion density (based on the area of vessels); 3) SCP and DCP vessel density (based on a map with vessels of 1-pixel width); and 4) CC perfusion density. Multiple regression analysis was performed to assess the effect of age, sex, ethnicity, refraction, and foveal macular thickness (FMT) on OCTA parameters. RESULTS: Seventy-seven eyes from 52 subjects (23 male and 29 female) were included in analysis. Mean age was 11.1 ± 3.3 years (range = 5.0-17.0 years). Twenty-nine (55.8%) subjects were white, 14 (27.0%) Hispanic, 8 (15.4%) Asian, and 1 (1.8%) African-American. Mean refraction was -0.1 ± 2.4 diopters (D) (range = -5.75 to +9.0 D). Mean FMT was 248.6 ± 18.6 µm. Larger FAZ area was significantly associated with older age (P = 0.014). Furthermore, larger FAZ area was associated with reduced FMT (P < 0.0001). Male sex was associated only with increased SCP perfusion density (P = 0.042). Increased CC perfusion density was associated with younger age (P = 0.022). CONCLUSION: We report data for pediatric OCTA parameters in healthy subjects. Several variables influence the density of macular microvascular networks, and these factors should be considered in the OCTA study of pediatric eye disorders.

BIOMARKERS OF NEOVASCULAR ACTIVITY IN AGE-RELATED MACULAR DEGENERATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the qualitative and quantitative features of choroidal neovascular (NV) membranes in age-related macular degeneration using optical coherence tomography angiography in patients with active and quiescent NV lesions before and after treatment with anti-vascular endothelial growth factor. METHODS: Macular optical coherence tomography angiography images were obtained using RTVue XR Avanti with AngioVue. Morphologic features and quantitative measurements of the NV lesion were analyzed using en face projection images. The NV lesion was subdivided into inner segment and outer fringe for further fractal dimension analysis. RESULTS: In a series of 31 eyes, 11 eyes with active NV lesions at baseline and after consecutive follow-up after treatment with anti-vascular endothelial growth factor therapy and 20 eyes with quiescent NV lesions were included in this study. Morphologically, all the quiescent NV lesions versus 63.6% of the active NV lesions demonstrated a prominent central vessel and active leasions demonstrated a greater rate of small vessels branching (82%) and peripheral arcades (82%) than quiescent lesions (30% and 40% respectively) and this was statistically significant. The lesion area and vessel density was not statistically significantly different after treatment or versus quiescent lesions although the latter lesions were reduced in area. Lesion pattern complexity measured by the fractal dimension was statistically significantly lower in the inner part of the lesion after treatment and statistically significantly lower in the total lesion of the quiescent NV compared with the active NV. CONCLUSION: Optical coherence tomography angiography is a new, noninvasive imaging modality that can be used to perform qualitative and quantitative analyses of NV lesions. In the future, OCT angiography may provide biomarkers of activity and guide the evaluation and treatment and monitoring of neovascularization in age-related macular degeneration.

Quantitative Analysis of Three Distinct Retinal Capillary Plexuses in Healthy Eyes Using Optical Coherence Tomography Angiography.

Purpose: To identify and quantify the three distinct retinal capillary plexuses and the foveal avascular zone (FAZ) in healthy subjects according to age using optical coherence tomography angiography (OCTA) with novel projection artifact removal (PAR) software and improved segmentation. Methods: All eyes in this cross-sectional study underwent OCTA imaging using RTVue XR Avanti with novel PAR AngioVue software. OCTA scans were analyzed and the three main parafoveal retinal capillary plexuses were segmented and vessel density and FAZ area were calculated. Results: A total of 152 normal eyes from 95 subjects (39 males, 56 females, mean age 42 ± 25 years) were included. The mean vessel density was 15.48 ± 2.04 mm-1 in the superficial retinal capillary plexus (SCP), 15.28 ± 1.82 mm-1 in the intermediate retinal capillary plexus (ICP), and 16.33 ± 2.32 mm-1 in the deep retinal capillary plexus (DCP) for 3 × 3-mm OCTA images. Analysis of 3 × 3-mm scans yielded a mean FAZ area of 0.270 ± 0.101 mm2. The average reduction in vessel density per year of age with 3 × 3-mm OCTA scans was 0.04 mm-1 (0.22%) in the SCP, 0.05 mm-1 (0.27%) in the ICP, and 0.06 mm-1 (0.30%) in the DCP. The average increase in FAZ area per year of age was 0.0015 mm2 (0.72%). Conclusions: Novel PAR software may provide improved visualization of all three major parafoveal retinal capillary plexuses including the ICP. Using this technology, SCP, ICP, and DCP vessel density decreased with increasing age while FAZ area increased with age.

Quantitative OCT Angiography of the Retinal Microvasculature and the Choriocapillaris in Myopic Eyes.

Purpose: To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using quantitative optical coherence tomography angiography (OCTA) analysis. Methods: Macular OCTA images of 3 × 3 mm were obtained using the RTVue-XR Avanti with AngioVue. Quantitative measurements of the retinal capillary microvascular layers and the CC were analyzed using en face projection images. Vessel density and fractal dimension of the superficial and deep retinal capillary plexus, and area and density of flow reduction in the CC were analyzed, quantified, and compared with an age-matched control group. Results: Fifty eyes with myopia and 34 age-matched healthy eyes were included in this study. The vessel density and the vessel branching complexity using fractal dimension of the retinal capillary microvasculature were significantly lower in myopic eyes (P < 0.001 and P = 0.001). The total number of flow voids in the CC was lower (108.93 vs. 138.63, P = 0.001) but the total and average flow void area was significantly higher (total area 3.715 ± 0.257 vs. 3.596 ± 0.194 mm2, P = 0.026; average area 0.044 ± 0.029 vs. 0.028 ± 0.010 mm2, P = 0.002) compared with the healthy control group. Average choroidal thickness was lower in the myopic group versus the normal control cohort (123.538 ± 73.477 vs. 246.97 ± 41.745 µm, P < 0.05) and significantly reduced in eyes with lacquer cracks (LC) compared with myopic eyes without LC formation (P = 0.003). There was no correlation between choroidal thickness and quantitative parameters of the CC in the myopic eyes. Conclusions: The density of the retinal capillary microvasculature is reduced and the area of flow deficit in the CC is increased in eyes with greater myopia. The relevance of microvascular alterations in the setting of myopia warrants further study.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEA IN CHILDREN BORN PRETERM.

PURPOSE: To compare the foveal avascular zone (FAZ) area measured by optical coherence tomography angiography in children who had been born preterm with age-matched controls. METHODS: In this cross-sectional observational comparative case series, 43 eyes of 26 children (28 eyes of 15 former preterm infants and 15 eyes of 11 former term infants) between the ages of 4 and 12 years old were included. Optical coherence tomography angiography with a scan size of 3 × 3 was performed for all eyes. Foveal avascular zone area was measured using the Optovue RTVue AVANTI instrument (Optovue Inc, Fremont, CA) software. Inner and outer retinal thicknesses were measured with the instrument caliper. RESULTS: A distinct FAZ was absent in 12 eyes (42.8%) of children with a history of preterm birth, however, it was present in all (100%) control eyes. The FAZ area was significantly correlated with gestational age (r = 0.82, P < 0.001) and birth weight (r = 0.80, P < 0.001). The gestational age was less than 29 weeks and birth weight was less than 1,480 grams in eyes with no distinct FAZ. Mean central foveal vessel density in the superficial capillary plexus was 41.8 ± 4.4% in the preterm group and 32.8 ± 5.8% in the control group (P < 0.001). In all eyes, a significant negative correlation was found between the central foveal vessel density and gestational age (r = -0.63, P = 0.001) and birth weight (r = -0.59, P = 0.002). On spectral domain optical coherence tomography examination, the foveal depression was absent and the inner retinal layers were preserved in all eyes with absent FAZ. In all eyes, a significant negative correlation was found between the inner retinal thickness and gestational age (r = -0.68, P < 0.001) and birth weight (r = -0.61, P = 0.001). Ten eyes of 6 preterm children had a history of laser therapy for retinopathy of prematurity. A distinct FAZ was absent in six eyes (60%) with retinopathy of prematurity with history of laser therapy, and six eyes (33.3%) with preterm birth without laser therapy. Eyes with history of laser therapy had a statistically significantly higher inner retinal thickness and central foveal vessel density and smaller FAZ compared with the eyes with preterm birth without laser therapy (P < 0.001, P = 0.04 and P = 0.03, respectively). CONCLUSION: Optical coherence tomography angiography is a novel modality for noninvasive visualization of the retinal vasculature in pediatric patients and expands our knowledge of foveal abnormalities in retinopathy of prematurity. A small or absent FAZ seems to be a distinct sign of prematurity.

Optical Coherence Tomography Angiography Analysis of the Foveal Avascular Zone and Macular Vessel Density After Anti-VEGF Therapy in Eyes With Diabetic Macular Edema and Retinal Vein Occlusion.

Purpose: To evaluate the changes in foveal avascular zone (FAZ) area and the retinal capillary density after a single intravitreal anti-VEGF injection for macular edema secondary to diabetic retinopathy or retinal vein occlusion. Methods: In this prospective noncomparative case series, 18 eyes of 15 patients with diabetic macular edema (13 eyes) or macular edema secondary to central retinal vein occlusion (5 eyes) were included. Optical coherence tomography angiography (OCTA) images were obtained, and retinal capillary vessel density and FAZ area were measured in the foveal and parafoveal regions at the level of the superficial (SCP) and deep retinal capillary plexus (DCP) before and at the first visit after intravitreal injection. Results: The mean interval between baseline and follow up OCTA was 32.5 ± 9.4 (range, 21-50) days. Foveal and parafoveal vessel density in the SCP and DCP were not significantly different before and after intravitreal injection (all P > 0.1), nor was FAZ area (P = 0.48 and P = 0.42, respectively). No significant difference was found between eyes with diabetic macular edema and those with retinal vein occlusion with respect to the mean change of vessel density and FAZ area (all P > 0.05). Conclusions: In this pilot study, retinal capillary density and FAZ area remained statistically unchanged in the short-term after a single intravitreal injection of an anti-VEGF agent.

Optical Coherence Tomography Angiography Reveals Choriocapillaris Flow Reduction in Placoid Chorioretinitis.

PURPOSE: To elucidate the origin of disease in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and related placoid disorders, and to determine the principle tissue level of involvement: retinal pigment epithelium (RPE) versus choriocapillaris (CC). To determine the prevalence, extent, and persistence of choroidal flow reduction in placoid chorioretinitis using en face optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN: Multicenter, prospective case series. PARTICIPANTS: Patients with a clinical diagnosis of APMPPE, persistent placoid maculopathy (PPM), or relentless placoid chorioretinitis (RPC). METHODS: Morphologic evaluation of en face structural OCT and OCTA images with customized segmentation through the deep capillary plexus, outer nuclear layer, inner segment ellipsoid band, choriocapillaris, and outer choroid. MAIN OUTCOME MEASURES: Segmented images were graded by 3 masked readers with regard to reduction of flow and signal attenuation, and intergrader agreement was determined by mean unweighted kappa analysis. RESULTS: In this study, 24 eyes of 15 patients with APMPPE, PPM, or RPC were recruited and 60% of patients were male (N = 9) and the mean age was 33.6 years (range, 19-73 years). Of the 24 eyes, 96% (23/24) were graded as definite (18/24, 75%) or questionable (5/24, 21%) flow reduction within the choriocapillaris on OCTA, and 58% (14/24) were graded as definite decreased flow within the outer choroid. Mean weighted kappa analysis among readers was 0.655 for OCTA of the choriocapillaris and 0.684 for OCTA of the outer choroid. Areas of choriocapillaris flow deficit correlated closely with ischemic lesions seen with fluorescein angiography and indocyanine green angiography but were more extensive with OCTA and significantly improved with treatment or nontreatment follow-up. Corresponding zones of outer retinal disruption also were identified and colocalized with the areas of choriocapillaris flow reduction seen with OCTA. CONCLUSIONS: Optical coherence tomography angiography indicates that the inner choroid is the primary site of disease pathogenesis in APMPPE and related placoid disorders with secondary photoreceptor disruption. Optical coherence tomography angiography may be used to enhance diagnosis of placoid disorders and to monitor the progression of choriocapillaris ischemia and its response to therapy.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AND DEEP RETINAL CAPILLARY PLEXUS INFARCTION SECONDARY TO REPERFUSED CENTRAL RETINAL ARTERY OCCLUSION.

PURPOSE: To report a case of reperfused central retinal artery occlusion causing a globular pattern of paracentral acute middle maculopathy with en face optical coherence tomography (OCT). METHODS: Retrospective case report. Widefield fluorescein angiography, en face OCT, and OCT-angiography were performed. Retinal capillary plexus vessel density (mm) was measured using OCT-angiography analysis and was defined as total vessel length (mm) per area (mm). RESULTS: A 76-year-old female presented with decreased vision in the left eye for 1 day. Widefield fluorescein angiography revealed delayed venous filling in the early phase and selective arterial staining in the late phase. Spectral domain OCT demonstrated paracentral acute middle maculopathy. Optical coherence tomography-angiography showed an ischemic deep retinal capillary plexus that colocalized with a globular shaped hyper-reflective pattern identified with structural en face OCT. Quantitative vessel density analysis comparing the fellow eye to the affected eye at presentation demonstrated 43% reduction in the superficial capillary plexus vessel density and 33% reduction of the deep capillary plexus in the affected eye. At 2 months follow-up, the reduction of superficial capillary plexus vessel density improved to 33%, whereas the deep capillary plexus vessel density reduced further to 35% compared with the fellow eye. CONCLUSION: The authors report a case of reperfused central retinal artery occlusion leading to a globular shaped paracentral acute middle maculopathy lesion with en face OCT. Quantitative OCT-angiography vessel density analysis in the chronic phase revealed disproportionate reduction of deep capillary plexus vessel density. The globular pattern of paracentral acute middle maculopathy with en face OCT can be an important clue to the diagnosis of central retinal artery occlusion.

OUTER RETINAL FOLDS FOLLOWING PARS PLANA VITRECTOMY WITH MEMBRANE PEEL.

PURPOSE: To report a case of outer retinal folds following pars plana vitrectomy with epiretinal membrane peel. METHODS: Retrospective case report. Spectral-domain and en face optical coherence tomography findings are described. RESULTS: A 54-year-old man presented with distorted vision 1 month following pars plana vitrectomy with epiretinal membrane peel and subsequent cataract extraction. Optical coherence tomography of the affected eye revealed ripple-type and taco-type outer retinal folds. En face optical coherence tomography illustrated a curvilinear characteristic pattern of the folds that spontaneously resolved with follow-up. CONCLUSION: The authors report a case of outer retinal folds developing in a patient following pars plana vitrectomy with membrane peel. En face optical coherence tomography findings of outer retinal folds may enhance diagnosis.

Retinal Capillary Density and Foveal Avascular Zone Area Are Age-Dependent: Quantitative Analysis Using Optical Coherence Tomography Angiography.

PURPOSE: The purpose of this study was to quantify retinal capillary density and the foveal avascular zone (FAZ) area in normal subjects according to age, using optical coherence tomography angiography (OCTA). METHODS: All eyes in this cross-sectional study underwent OCTA using RTVue XR Avanti with AngioVue. OCTA scans were analyzed and processed, and vessel density and FAZ dimensions were calculated. RESULTS: A total of 113 normal eyes from 70 subjects were included (30 males, 40 females; mean 48 ± 20 years of age). The mean vessel density and FAZ dimensions were significantly smaller in the superficial retinal capillary plexus (SCP) than in the deep retinal capillary plexus (DCP), using quantitative OCTA analysis (all P< 0.0001). With 3 × 3-mm scans, the mean vessel density was 13.431 ± 1.758 mm-1 in the SCP, 18.812 ± 1.796 mm-1 in the DCP, and 5.913 ± 1.308 mm-1 and 10.447 ± 1.262 mm-1 with 6 × 6-mm scans in the SCP and DCP, respectively. Mean FAZ areas were 0.289 ± 0.108 mm2 at the SCP and 0.614 ± 0.200 mm2 at the DCP. Age was a predictor of SCP and DCP vessel density and FAZ area in the SCP. Vessel density decreased 0.0393 mm-1 (0.26%) per year in the SCP and 0.0574 mm-1 (0.27%) per year in the DCP. FAZ areas increased 0.0014 mm2 (0.63%) and 0.0011 mm2 (0.20%) per year in the SCP and DCP, respectively. CONCLUSIONS: SCP and DCP vessel density decreased with increasing age, while FAZ area increased with age. Normal age-matched measurements provide important standardized values that may facilitate management of retinal vascular disorders.

Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration.

Age-related macular degeneration continues to be the leading cause of severe central vision loss in older adults of European descent. Optical coherence tomography angiography (OCT-A) enables more accurate identification of type 1 neovascularization in age-related macular degeneration than traditional fluorescein and indocyanine green angiographies. In addition, OCT-A facilitates the morphological classification of type 1 lesions, including features characteristic of early, mature, and fibrotic lesions. Vessel complex analysis, including lesion area and capillary density quantification, can also be readily measured and monitored over time. Performing this analysis following anti-vascular endothelial growth factor therapy may lead to a better understanding of the efficacies and responses to such treatments. Although some limitations currently exist, OCT-A is a promising imaging modality that could prove to have profound implications if incorporated into regular clinical practice.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TYPE 3 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize the vascular structure of Type 3 neovascularization secondary to age-related macular degeneration using optical coherence tomography angiography. METHODS: Optical coherence tomography angiography cube scans (3 mm × 3 mm) were acquired in 29 eyes of 24 patients with Type 3 lesions secondary to age-related macular degeneration using the RTVue XR Avanti with AngioVue, Split-spectrum amplitude-decorrelation, and motion correction technology. Automated layer segmentation boundaries were adjusted to best visualize the neovascular complex on en face projection images. RESULTS: A distinct neovascular complex could be identified in 10 (34%) eyes, all of which were active on optical coherence tomography imaging. In all 10 eyes, the neovascular complex appeared as a small tuft of bright, high-flow tiny vessels with curvilinear morphology located in the outer retinal layers with a feeder vessel communicating with the inner retinal circulation (i.e., deep retinal capillary plexus). The mean (SD) size of the neovascular complex measured 0.07 (± 0.07) mm. CONCLUSION: With optical coherence tomography angiography, it is possible to identify small intraretinal neovascular complexes communicating with the deep retinal capillary plexus in eyes with Type 3 neovascularization secondary to age-related macular degeneration. Qualitative and quantitative analyses of Type 3 neovascular complexes can be performed using optical coherence tomography angiography.

Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration.

PURPOSE: To analyze type 1 neovascular membranes in age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography, to correlate morphologic characteristics with imaging and clinical criteria, and to analyze structural features of type 1 neovascularization sequentially after anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Prospective interventional case series. METHODS: Macular OCT angiography images were acquired using the RTVue XR Avanti with AngioVue. Distinct morphologic patterns and quantifiable features of the neovascular membranes were studied on en face projection images at baseline and follow-up. RESULTS: Thirty-three eyes of 25 patients were included. In 75% of the eyes, a highly organized vascular complex could be identified. A large main central vessel trunk/feeder vessel could be seen in 72% of these eyes, with vessels radiating in a branching pattern either in all directions from the center of the lesion ("medusa" pattern), or from one side of the lesion ("seafan" pattern). Of the 18 eyes with follow-up OCT angiography, the lesion area and vessel density remained unchanged, even after anti-vascular endothelial growth factor (VEGF) therapy, indicating a more mature longstanding neovascular complex resistant to anti-VEGF therapy. CONCLUSIONS: OCT angiography provides a unique opportunity to study the morphology of occult type 1 neovascular membranes in AMD and allows precise structural and vascular assessment noninvasively. We identified a large mature neovascular complex in approximately 75% of eyes, typically consisting of a feeder vessel and large branching vessels resistant to anti-VEGF therapy. OCT angiography may better guide evaluation and treatment of neovascular AMD, and may contribute to the development of improved therapies.