Lawrence Geyman

Acircularity index and axis ratio of the foveal avascular zone in diabetic eyes and healthy controls measured by optical coherence tomography angiography

&NA; Given the complexity of the current system used to stage diabetic retinopathy (DR) and the risks and limitations associated with intravenous fluorescein angiography (IVFA), noninvasive quantification of DR severity is desirable. We examined the utility of acircularity index and axis ratio of the foveal avascular zone (FAZ), metrics that can noninvasively quantify the severity of diabetic retinopathy without the need for axial length to correct for individual retinal magnification. A retrospective review was performed of type 2 diabetics and age‐matched controls imaged with optical coherence tomography angiography (OCTA). Diabetic eyes were divided into three groups according to clinical features: No clinically observable diabetic retinopathy (NoDR), nonproliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). OCTAs of the superficial and deep vascular layers centered at the fovea were superimposed to form a full vascular layer on which the FAZ was manually traced. Acircularity index and axis ratio were calculated for each FAZ. Significant differences in acircularity index were observed between all groups except for controls vs. NoDR. Similar results were found for axis ratio, although there was no significant difference observed between NPDR and PDR. We demonstrate that acircularity index and axis ratio can be used to help noninvasively stage DR using OCTA, and show promise as methods to monitor disease progression and detect response to treatment. HighlightsAcircularity index and axis ratio can quantify FAZ abnormalities in diabetics.They do not require axial length measurement.They can be used to noninvasively stage severity of diabetic retinopathy using OCTA.These metrics show promise as methods to monitor disease over time.

Imaging Foveal Microvasculature: Optical Coherence Tomography Angiography Versus Adaptive Optics Scanning Light Ophthalmoscope Fluorescein Angiography.

Purpose To compare the use of optical coherence tomography angiography (OCTA) and adaptive optics scanning light ophthalmoscope fluorescein angiography (AOSLO FA) for characterizing the foveal microvasculature in healthy and vasculopathic eyes. Methods Four healthy controls and 11 vasculopathic patients (4 diabetic retinopathy, 4 retinal vein occlusion, and 3 sickle cell retinopathy) were imaged with OCTA and AOSLO FA. Foveal perfusion maps were semiautomatically skeletonized for quantitative analysis, which included foveal avascular zone (FAZ) metrics (area, perimeter, acircularity index) and vessel density in three concentric annular regions of interest. On each set of OCTA and AOSLO FA images, matching vessel segments were used for lumen diameter measurement. Qualitative image comparisons were performed by visual identification of microaneurysms, vessel loops, leakage, and vessel segments. Results Adaptive optics scanning light ophthalmoscope FA and OCTA showed no statistically significant differences in FAZ perimeter, acircularity index, and vessel densities. Foveal avascular zone area, however, showed a small but statistically significant difference of 1.8% (P = 0.004). Lumen diameter was significantly larger on OCTA (mean difference 5.7 μm, P < 0.001). Microaneurysms, fine structure of vessel loops, leakage, and some vessel segments were visible on AOSLO FA but not OCTA, while blood vessels obscured by leakage were visible only on OCTA. Conclusions Optical coherence tomography angiography is comparable to AOSLO FA at imaging the foveal microvasculature except for differences in FAZ area, lumen diameter, and some qualitative features. These results, together with its ease of use, short acquisition time, and avoidance of potentially phototoxic blue light, support OCTA as a tool for monitoring ocular pathology and detecting early disease.

Peripapillary perfused capillary density in primary open-angle glaucoma across disease stage: an optical coherence tomography angiography study

Aims To assess peripapillary perfused capillary density (PCD) in primary open-angle glaucoma (POAG) across stage of disease. Methods In this observational, cross-sectional study, 60 eyes with varying stages of POAG and 24 control eyes were imaged on a spectral domain optical coherence tomography angiography system (AngioVue, Optovue, Fremont, California, USA) generating images centred on the optic nerve head. Major blood vessels were removed using custom automated software. PCD was calculated as a percentage as the ratio of pixels associated with perfused capillaries to the total number of pixels in the corresponding region-of-interest (ROI). Analysis of covariance was used to compare PCD among the subject groups and control for possible covariates. Area under the receiver operating characteristic curve (AROC) and sensitivity at 95% specificity were calculated to assess the capability of PCD to distinguish mild glaucoma from control. The Pearsons product-moment correlation coefficient was used to assess correlations between PCD and circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and visual field mean deviation (MD). Results PCD demonstrated a progressive stepwise decrease from control eyes throughout worsening POAG stage at all ROIs. PCD demonstrated AROC and sensitivity values comparable to cpRNFLT and visual field parameters and exhibited significant correlations with cpRNFLT and MD at all corresponding ROIs. Conclusions PCD displayed significant correlations with morphological and functional indices and exhibited diagnostic capabilities comparable to currently employed clinical variables. Our preliminary results suggest that PCD analysis may prove to be a useful tool in monitoring POAG across stage and identifying early POAG.

Visualization of Radial Peripapillary Capillaries Using Optical Coherence Tomography Angiography: The Effect of Image Averaging

Objectives To assess the effect of image registration and averaging on the visualization and quantification of the radial peripapillary capillary (RPC) network on optical coherence tomography angiography (OCTA). Methods Twenty-two healthy controls were imaged with a commercial OCTA system (AngioVue, Optovue, Inc.). Ten 10x10° scans of the optic disc were obtained, and the most superficial layer (50-μm slab extending from the inner limiting membrane) was extracted for analysis. Rigid registration was achieved using ImageJ, and averaging of each 2 to 10 frames was performed in five ~2x2° regions of interest (ROI) located 1° from the optic disc margin. The ROI were automatically skeletonized. Signal-to-noise ratio (SNR), number of endpoints and mean capillary length from the skeleton, capillary density, and mean intercapillary distance (ICD) were measured for the reference and each averaged ROI. Repeated measures analysis of variance was used to assess statistical significance. Three patients with primary open angle glaucoma were also imaged to compare RPC density to controls. Results Qualitatively, vessels appeared smoother and closer to histologic descriptions with increasing number of averaged frames. Quantitatively, number of endpoints decreased by 51%, and SNR, mean capillary length, capillary density, and ICD increased by 44%, 91%, 11%, and 4.5% from single frame to 10-frame averaged, respectively. The 10-frame averaged images from the glaucomatous eyes revealed decreased density correlating to visual field defects and retinal nerve fiber layer thinning. Conclusions OCTA image registration and averaging is a viable and accessible method to enhance the visualization of RPCs, with significant improvements in image quality and RPC quantitative parameters. With this technique, we will be able to non-invasively and reliably study RPC involvement in diseases such as glaucoma.

Pattern of peripapillary capillary density loss in ischemic optic neuropathy compared to that in primary open-angle glaucoma

Purpose Both non-arteritic anterior ischemic optic neuropathy (NAION) and primary open-angle glaucoma (POAG) damage retinal ganglion cell axons, which are perfused by the radial peripapillary capillaries. To evaluate the pattern of ischemia, we compared peripapillary capillary density (PCD) in NAION eyes to POAG eyes matched for visual field mean deviation and retinal nerve fiber layer thickness. Methods 31 chronic NAION (>6 months after the acute event) and unaffected fellow eyes (31 subjects), 42 moderate and severe POAG eyes (27 subjects), and 77 control eyes (46 healthy subjects) were imaged with a commercial optical coherence tomography angiography system (AngioVue, Avanti RTVue-XR, Optovue, CA) at two academic institutions. Two concentric circles of diameters 1.95mm (inner) and 3.45mm (outer) were manually placed on images centered on the optic nerve head, producing an annular region-of-interest. Image analysis with major vessel removal was performed using a custom program. Whole-image, whole-annulus, and sectoral PCDs were measured. Results Whole-image and whole-annulus PCDs in NAION and moderate and severe POAG eyes were significantly decreased compared to unaffected fellow eyes and control eyes (all P<0.001). Superior and temporal PCD values were affected more than other sectors in both NAION and POAG groups compared to control group. Whole-image and whole-annulus PCDs were not statistically different between NAION and POAG eyes (both P = 0.99). However, of all peripapillary sectors, the inferior sector PCD value was less affected in POAG eyes compared to NAION eyes (P = 0.001). Univariate analysis results also revealed a significant positive correlation between superior and inferior PCDs and corresponding RNFL thicknesses. The inferior sector correlation was greater in POAG than NAION eyes. Conclusion While the whole PCD values were not different in chronic NAION and POAG, the greater correlation of inferior PCD with corresponding RNFL sectors in POAG compared to NAION suggests greater susceptibility of the inferior radial peripapillary capillary in the pathogenesis of POAG.

A method for age-matched OCT angiography deviation mapping in the assessment of disease- related changes to the radial peripapillary capillaries

Purpose To present a method for age-matched deviation mapping in the assessment of disease-related changes to the radial peripapillary capillaries (RPCs). Methods We reviewed 4.5x4.5mm en face peripapillary OCT-A scans of 133 healthy control eyes (133 subjects, mean 41.5 yrs, range 11–82 yrs) and 4 eyes with distinct retinal pathologies, obtained using spectral-domain optical coherence tomography angiography. Statistical analysis was performed to evaluate the impact of age on RPC perfusion densities. RPC density group mean and standard deviation maps were generated for each decade of life. Deviation maps were created for the diseased eyes based on these maps. Large peripapillary vessel (LPV; noncapillary vessel) perfusion density was also studied for impact of age. Results Average healthy RPC density was 42.5±1.47%. ANOVA and pairwise Tukey-Kramer tests showed that RPC density in the ≥60yr group was significantly lower compared to RPC density in all younger decades of life (p<0.01). Average healthy LPV density was 21.5±3.07%. Linear regression models indicated that LPV density decreased with age, however ANOVA and pairwise Tukey-Kramer tests did not reach statistical significance. Deviation mapping enabled us to quantitatively and visually elucidate the significance of RPC density changes in disease. Conclusions It is important to consider changes that occur with aging when analyzing RPC and LPV density changes in disease. RPC density, coupled with age-matched deviation mapping techniques, represents a potentially clinically useful method in detecting changes to peripapillary perfusion in disease.

Risk Factors for Multiple Epinephrine Doses in Food-Triggered Anaphylaxis in Children

BACKGROUND Food-related anaphylactic reactions may require treatment with more than 1 dose of epinephrine. Current guidelines advise patients at risk of anaphylaxis to carry 2 epinephrine autoinjectors. OBJECTIVE The objective of this study was to determine risk factors of multiple-dose epinephrine treatment in pediatric food-related anaphylaxis. METHODS Parents of children with physician-confirmed diagnosis of food allergy were administered a standardized questionnaire at the time of their clinic visit. These patients were then followed-up prospectively by phone. RESULTS Six hundred forty-two subjects had allergic reactions. Twenty-six percent of patients reported at least 1 reaction treated with epinephrine, for a total of 221 reactions. Among reactions treated with epinephrine, 24 reactions (11%) received 2 or more doses of epinephrine. The most common triggers were milk (30%) and peanut (18%). Milk-triggered allergic reactions (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.2-8.4) and treatment with oxygen (OR 5.0, 95% CI 2.0-12.4) were significant risk factors for requiring multiple doses of epinephrine to treat an allergic reaction. CONCLUSION This study demonstrates that treatment of anaphylaxis may require more than 1 epinephrine injection. Reactions triggered by milk or requiring treatment with oxygen are at higher risk for needing more than 1 dose of epinephrine. Families of food-allergic children should be counseled on the importance of carrying 2 epinephrine auto-injectors.

Qualitative and quantitative evaluation of acute angle-closure mechanisms

BackgroundTo evaluate ocular biometric parameters in different subtypes of acute angle closure and compared to fellow eyes of AAC and PACS eyes.MethodsThis is a retrospective chart review study. A total of 167 eyes (96 patients) consisting of 71 AAC eyes, 71 fellow eyes of AAC, and 25 PACS eyes were recruited. All patients underwent ocular examination and biometry. The mechanism of AAC was confirmed by ultrasound biomicroscopy. We then subdivided AAC eyes into four subgroups: crowded-angle (CR), lens subluxation (LS) pupillary block (PB), and plateau iris syndrome (PL). Outcome variables included anterior chamber depth (ACD), lens thickness (LT), vitreal length (VL), axial length (AL), lens position and relative lens position (LP and RLP, respectively), and lens axial length factor (LAF).ResultsAmong the three groups, ACD was shallower in AAC eyes than fellow eyes of AAC and PACS eyes (p < 0.01 for both) and AAC eyes demonstrated a lesser LP and RLP. The LT, VL, AL, and LAF were not significantly different among the three groups. Among the four subgroups, LS displayed the most shallow ACD (p = 0.01). The lens position in PL was greater than in CR and LS (p < 0.05 and <0.01, respectively).ConclusionsAAC eyes had a more anterior lens position than fellow eyes and PACS eyes, though lens thickness did not differ among the groups. As such, an anterior lens position may offer more sensitive prognostication regarding future development of AAC compared to lens thickness.