Nicholas A. Iafe

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) mm2. 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.

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.

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 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 of Type 2 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 A29 BIRDSHOT CHORIORETINOPATHY COMPLICATED BY RETINAL NEOVASCULARIZATION

Purpose: To describe the quantitative optical coherence tomography angiography analysis of the superficial and deep retinal capillary plexus in a case of A29 birdshot chorioretinopathy (BCR) complicated by retinal neovascularization. Methods: Multimodal retinal imaging, including optical coherence tomography angiography with quantitated vessel density analysis of the superficial and deep retinal capillary plexus, was performed in a case of A29 BCR. Capillary density (mm−1) was defined as the total vessel length (mm) per area (mm2). Results: A 39-year-old healthy white man presented with vitreous hemorrhage and retinal neovascularization at baseline. Clinical presentation was consistent with BCR and human leukocyte antigen testing confirmed A29 positivity. Optical coherence tomography angiography was performed 6 years after the diagnosis and revealed capillary density reduction in the superficial and especially in the deep retinal capillary plexus. Quantitative vessel density analysis was compared with the mean capillary density of 11 age-matched normal eyes and demonstrated 6% and 18% reduction of the superficial plexus in the right and left eyes of our patient, respectively. For the deep plexus, a reduction of 25% and 32% was found in the right and left eyes, respectively. Conclusion: In this patient with BCR, capillary density reduction was most marked at the deep retinal capillary plexus level and may explain the development of retinal neovascularization in this case. Quantitative optical coherence tomography angiography may be a useful tool to study and to monitor retinal microvascular changes in patients with BCR and should be further explored as a biomarker of therapeutic response.

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.

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.

BIOMARKERS OF NEOVASCULAR ACTIVITY IN AGE-RELATED MACULAR DEGENERATION USING OCT 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.

Central Retinal Vein Occlusion and Paracentral Acute Middle Maculopathy Diagnosed With En Face Optical Coherence Tomography.

A 21-year-old healthy female presented with acute-onset vision loss in the left eye. Multimodal imaging, including fundus photography and fluorescein angiography, was unremarkable. En face optical coherence tomography (OCT) demonstrated paracentral acute middle maculopathy (PAMM) lesions in a perivenular fern-like pattern leading to the diagnosis of central retinal vein occlusion (CRVO). En face OCT can be an important modality to identify the distribution of abnormalities of the middle retina such as PAMM. The distribution of PAMM lesions in the posterior pole will be a critical element in the determination of the etiologic disorder. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:862-864.].