Search

PurposeTo compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects.DesignRandomized, single center, crossover clinical trial.MethodsEligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment.ResultsOne eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P=0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P=.04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all).ConclusionsTopical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD.

To evaluate the correlation between structural parameters and visual acuity (VA) in advanced glaucoma.Prospective, cross-sectional study.A total of 238 eyes from 238 patients (82 were men and mean ± SD age was 59.9 ± 13.8 years) from a tertiary center were divided into an advanced (mean deviation of 24-2 visual field tests from -12.01 to -20.0 dB) and severe (-20 dB) glaucoma group. Structural parameters were obtained by RTVue (Optovue Inc) optical coherence tomography and angiography. Pearson correlation, partial correlation adjusted for age and axial length, and receiver operating characteristic curves to detect decreased VA (20/25) were performed.In the advanced glaucoma group (133 eyes), superficial (Pearson correlation coefficient, r = -0.46, P.001; partial correlation coefficient, r' = -0.30, P.001) and deep macular vessel densities (VDs) (r = -0.47, P.001; r' = -0.30, P.001) showed highest correlation with VA. The area under the receiver operating characteristic curves of the superficial parafoveal/macular VDs were 0.816 (95% CI, 0.735-0.897) and 0.808 (95% CI, 0.725-0.891), respectively. In the severe glaucoma group (105 eyes), deep nasal grid VD (r = -0.31, P = 0.002; r' = -0.35, P.001) showed highest correlation with VA. Deep macular VD showed better correlation with VA than other structural parameters. The area under the receiver operating characteristic curves of deep macular VD and deep nasal grid VD were 0.740 (95% CI, 0.632-0.849) and 0.748 (95% CI, 0.640-0.857), respectively.Macular VD showed better correlation with VA in advanced glaucoma. Deep macular VD, especially nasal grid, may be a promising structural parameter in severe glaucoma.

PurposeTo compare convolutional neural network (CNN) analysis of en face vessel density images to gradient boosting classifier (GBC) analysis of instrument-provided, feature-based optical coherence tomography angiography (OCTA) vessel density measurements and OCT retinal nerve fiber layer (RNFL) thickness measurements for classifying healthy and glaucomatous eyes.DesignComparison of diagnostic approaches.MethodsA total of 130 eyes of 80 healthy individuals and 275 eyes of 185 glaucoma patients with optic nerve head (ONH) OCTA and OCT imaging were included. Classification performance of a VGG16 CNN trained and tested on entire en face 4.5×4.5-mm radial peripapillary capillary OCTA ONH images was compared to the performance of separate GBC models trained and tested on standard OCTA and OCT measurements. Five-fold cross-validation was used to test predictions for CNNs and GBCs. Areas under the precision recall curves (AUPRC) were calculated to control for training/test set size imbalance and were compared.ResultsAdjusted AUPRCs for GBC models were 0.89 (95% CI=0.82, 0.92) for whole image vessel density GBC, 0.89 (0.83, 0.92) for whole image capillary density GBC, 0.91 (0.88, 0.93) for combined whole image vessel and whole image capillary density GBC, and 0.93 (0.91, 095) for RNFL thickness GBC. The adjusted AUPRC using CNN analysis of en face vessel density images was 0.97 (0.95, 0.99) resulting in significantly improved classification compared to GBC OCTA-based results and GBC OCT-based results (P ≤ 0.01 for all comparisons).ConclusionDeep learning en face image analysis improves on feature-based GBC models for classifying healthy and glaucoma eyes.

PURPOSE: To evaluate the occurrence of retinal micro-vasculopathy in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developed coronavirus disease (COVID-19). DESIGN: Systematic review and meta-analysis. METHODS: The Pubmed and Embase databases were comprehensively searched to identify studies that reported retina vascular changes in eyes with COVID-19. Two independent reviewers selected papers and extracted data for analysis. Data of interest were extracted and analysed in RevMan Web versions 3.3. Quality of evidence was assessed using the National institute of health (NIH) quality assessment tool of case-control study. RESULTS: Thirty one studies reporting on 1373 subjects (972 COVID-19 and 401 controls) were included. Only case control studies were included in the pooled analysis. There was a significantly higher likelihood of retinal micro-vasculopathy in subjects with COVID-19 compared to controls. (odds ratio [95% confidence interval], 8.86 [2.54-27.53], p

Purpose To present select cases of paracentral acute middle maculopathy (PAMM) demonstrating progressive vascular occlusion and the ischemic cascade, and illustrate scenarios in which therapeutic intervention may be considered. Design Perspective. Methods Review and interpretation of selected literature, with perspective on the evaluation and management of patients with PAMM lesions. Multimodal imaging, including cross sectional and en face optical coherence tomography (OCT), of three illustrative cases of PAMM are presented, with progressive vascular occlusion and evidence of the ischemic cascade noted in two of the cases. Results All three cases showed evidence of PAMM at baseline, including perivenular PAMM in two of the cases. Progression from a mild central retinal vein occlusion (CRVO) to a more severe CRVO was noted in the first case, while the second case progressed from an incomplete to complete central retinal artery occlusion. In the third case, there was resolution of PAMM lesions associated with partial CRAO after the patient was started on aspirin. Conclusions Perivenular PAMM can be the only presenting sign of retinal vascular occlusion. In such cases it is important to differentiate between partial CRVO and incomplete CRAO as the underlying cause. This Perspective provides guidance on making this important distinction, which plays a critical role in directing the nature and urgency of the systemic work up. In patients with PAMM caused by partial retinal arterial occlusion, a benign empirical approach such as low-dose aspirin (81 mg) may be reasonable to reduce the likelihood of subsequent vision loss from progression to complete arterial occlusion. A clinical trial, however, is necessary to support such a strategy.

PURPOSE: To investigate hemiretinal asymmetry in radial peripapillary capillary vessel area density (VAD) of healthy, glaucoma suspect, and glaucoma eyes of varying severity and its diagnostic utility for glaucoma. DESIGN: Population-based, cross-sectional study. METHODS: 6×6-mm optic disc scans were collected on optical coherence tomography angiography (OCTA) to obtain VAD and on OCT to measure circumpapillary retinal nerve fiber layer (RNFL) thickness. Hemiretinal difference in VAD (hdVAD) was defined as the absolute difference between superior and inferior hemiretinal VAD. Age-adjusted multivariable linear regression of hdVAD on glaucoma severity was performed. Area under curves (AUCs) were calculated from predicted probabilities generated by multiple logistic regression of glaucoma severity on age-adjusted single and combined parameters. RESULTS: 1043 eyes of 1043 participants (587 healthy, 270 suspect, 67 mild, 54 moderate, 65 severe glaucoma) were included. After age adjustment, mean hdVAD was similar between healthy and suspect (P = 0.225), higher in mild versus suspect (P < 0.001), higher in moderate versus mild (P = 0.018), but lower in severe versus moderate (P = 0.001). AUCs of hdVAD were highest for discriminating mild (0.685) and moderate (0.681) glaucoma from healthy. Combining hdVAD and global RNFL (gRNFL) yielded the highest AUCs of all parameters for mild (0.817) and any POAG (0.859) and resulted in significantly better diagnostic accuracy than either hdVAD or gRNFL alone (P < 0.05 for all comparisons). CONCLUSIONS: hdVAD is higher in early glaucoma and may help with early detection when damage is focal, but its diagnostic ability appears less robust in advanced glaucoma when damage is diffuse.

The purpose of this study was to investigate the association between the vertical position of the central retinal vessel (CRV) within the optic nerve head (ONH) and the site of visual field defects (VFDs) in glaucoma.Cross-sectional study.The vertical position of the CRV was identified in 134 glaucoma eyes and 61 normal eyes at the point at which CRV exited the lamina cribrosa (LC) onto the ONH surface, by using spectral-domain optical coherence tomography (exit position). The position was also identified at the entry point into the LC from the retrolaminar ONH region (entry position), which was little influenced by glaucomatous LC deformation, therefore close to the original position before the glaucoma development. Positions were compared among glaucoma eyes with different sites of VFDs, and between glaucoma and normal eyes.In glaucoma eyes, the entry position of the CRV was in the superior ONH region in 63.0% of eyes with superior VFDs and in the inferior ONH region in 97.8% of eyes with inferior VFDs (P.0001). The exit position exhibited a similar percentage. The vertical CRV positions were not significantly different between glaucoma and normal eyes, both at the entry and exit positions.Eyes with CRVs in the superior ONH region were significantly more likely to form VFDs in the superior hemifields and vice versa. The vertical position of the CRV was little altered by the development of glaucoma. The original position of the CRV before the development of glaucoma may influence regional susceptibility to glaucomatous stress and may be useful in predicting initial sites of VFDs.

To assess the effect of changing anterior eye refractive power with contact lenses on the transverse magnification of en face images and associated vascular indices from optical coherence tomographic angiography (OCT-A).Prospective crossover study.Spherical soft contact lenses (-6 diopter [D] to +6 D in 2 D steps) were used to induce anterior eye refractive power changes in 11 healthy young adults and 3 × 3-mm macular scans were captured using OCT-A (Zeiss AngioPlex, software version 11.0; Cirrus HD-OCT 5000, Carl Zeiss Meditec Inc). Image transverse magnification was predicted based on refraction and biometry measurements and compared with empirical changes in the en face images measured with image analysis. Linear regression analysis was performed to assess the relationship between induced refractive ametropia and foveal avascular zone (FAZ) area, perimeter, circularity, and vessel density and perfusion density.The predicted transverse magnification was linearly related to induced refractive ametropia and to the empirical transverse magnification changes (average slope: 1.02, 95% CI: 0.90-1.34). All the OCT-A indices showed linear relationships with induced refractive ametropia (P.05) with the 12 D tested range altering the indices by 7% to 12%. After correcting for transverse magnification, all OCT-A indices except FAZ area were linearly related to induced refractive ametropia (P.05) and were reduced to 1% to 9%.This study is the first to show that induced refractive ametropia can affect OCT-A image magnification and indices. These changes are clinically important and need to be considered along with biometry effects when interpreting OCT-A indices. Transverse magnification changes can affect the ability of OCT-A to precisely measure linear dimensions of blood vessels.

Purpose We compared the ability of ophthalmologists to identify neovascularization (NV) in patients with proliferative diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA). Design Retrospective study comparing diagnostic instruments. Methods Eyes with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy and a high suspicion of NV based on clinical examination were imaged using SS-OCTA and FA at the same visit. Two separate grading sets consisting of scrambled, anonymized SS-OCTA and FA images were created. The ground truth for presence of NV was established by consensus of 2 graders with OCTA experience who did not participate in the subsequent assessment of NV in this study. The 2 anonymized image sets were graded for presence or absence of NV by 12 other graders that included 2 residents, 6 vitreoretinal fellows, and 4 vitreoretinal attending physicians. The percentage of correct grading of NV using SS-OCTA and FA was assessed for each grader and across grader training levels. Results Forty-seven eyes from 24 patients were included in this study. Overall, the mean percentage of correct NV grading was 87.8% using SS-OCTA with B-scans and 86.2% using FA (P = .92). Assessing each grader individually, there was no statistically significant asymmetry in correct grading using SS-OCTA and FA. Conclusions Ophthalmologists across training levels were able to identify diabetic NV with equal accuracy using SS-OCTA and FA. Based on these results, SS-OCTA may be an appropriate standalone modality for diagnosing diabetic NV.

To assess choroidal structural parameters in symptomatic Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitively healthy control subjects.Prospective cross-sectional study.This study took place in an outpatient neurological disorders clinic. Participants included 67 patients (112 eyes) with AD, 74 patients (143 eyes) with MCI, and 137 (248 eyes) control subjects. Subjects with diabetes, glaucoma, or retinal pathology were excluded. High-definition enhanced depth imaging foveal scans were obtained using Zeiss Cirrus HD-5000 AngioPlex. Subfoveal choroidal thickness (SFCT) was measured by 2 masked graders with a third adjudicator. Total choroidal area (TCA), luminal area (LA), and the choroidal vascularity index (CVI) were calculated after image binarization. Association of choroidal parameters with AD, MCI, or control subjects was assessed using multivariable generalized estimating equations, adjusted for age, sex, and visual acuity.After adjustment for age, sex, and visual acuity, TCA was significantly greater in patients with AD (ß = 2.73; p = .001) and MCI (ß = 4.38; p.001) compared with control subjects. LA was significantly greater in patients with AD (ß = 1.68; p = .001) and MCI (ß = 2.69; p.001) compared with control subjects, and CVI was significantly lower in patients with MCI (ß = -0.58; p = .002) compared with control subjects. SFCT was similar among patients with AD and MCI and control subjects on multivariable analysis (p.05).TCA, LA, and CVI may differ between patients with AD, MCI, and healthy cognition, whereas SFCT may not differ among these groups. TCA, LA, and CVI deserve further study in subjects on the Alzheimer continuum.

Purpose To evaluate the mononuclear cells in the subretinal exudate in Coats' disease. Design Retrospective case series. Methods Five enucleated globes and 1 cytology sample from a patient with Coats' disease and 1 case of chronic retinal detachment following repair of an open globe injury were examined immunohistochemically to identify intraretinal and subretinal exudative cells. The 2 biomarkers were RPE65 for retinal pigment epithelium and CD163 for histiocytes, each tagged with different chromogens, yellow for pigment epithelium and purple for CD163-positive (CD163+) monocytes/histiocytes. Expression levels were sought from both biomarkers together and singly. A color shift to red in the cells' chromogenic reaction indicated the simultaneous presence of the 2 biomarkers. Results Most of the mononuclear cells in Coats' disease samples were CD163+ (purple), and a minority were RPE65+ (yellow). An intermediate number of cells were RPE65+/CD163+ (orange-red). The eye with a chronic retinal detachment had an equal distribution of CD163+ and RPE65+/CD163+ cells. Conclusions RPE has several well-delineated phenotypes and functions. In normal visual physiology, the pigment epithelium supports photoreceptors and participates in their renewal by phagocytosis of the tips of the photoreceptors. The expression of CD163, a feature of hematopoietically derived monocytes, together with RPE65 in the retinal pigment epithelium, supports differentiation toward histiocytes. Yellow staining of detached pigment epithelial cells were rare. The presence of histiocytoid pigment epithelium at the Bruch membrane probably also has implications for macular degeneration.

Purpose To identify characteristics of patients with early open-angle glaucoma exhibiting greater macular perfusion density (PD) loss compared with macular ganglion cell layer (GCL) thickness loss. Design Cross-sectional study. Methods Optical coherence tomography (OCT) imaging of the optic nerve head and macula was conducted in patients and healthy control subjects. Minimum rim width, retinal nerve fiber layer and GCL thickness, and PD from OCT angiography were derived. Only high-quality images were included. For direct comparison, raw PD and GCL thickness values in patients were converted to relative age-corrected loss values based on data from controls. Demographic and ocular variables related to greater PD loss compared with GCL thickness loss were identified with multivariate logistic regression. Results Data from 89 patients (median mean deviation with the 24-2 and 10-2 tests, Humphrey Field Analyzer: −1.96 dB and −1.49 dB, respectively) and 54 controls were analyzed. Sixty-three (71%) patients had relatively more GCL thickness loss, whereas 26 (29%) had relatively more PD loss. More PD loss was associated with lower OCT and OCT-angiography signal strength (odds ratio [95% confidence interval], 0.64 [0.40, 0.96] and 0.60 [0.38, 0.86], per dB, respectively), thicker retinal nerve fiber layer thickness (1.08 [1.01, 1.16] per μm), and female sex (6.57 [1.25, 48.79]). Conclusion Less than one-third of patients with early glaucoma had more loss of perfusion compared with conventional structural loss in the macula. Even within a range of high-quality images, lower signal strength may be at least partially responsible for apparent perfusion loss.

To evaluate the foveal development in preterm children with optical coherence tomography and OCT angiography.Retrospective cohort study.This study included children aged 6-8 years who were born prematurely and who did not receive retinopathy treatment. They were evaluated between September 2018 and July 2019, categorized according to gestational age (GA) (group I: GA ≤30 weeks; group II: GA between 31 and 34 weeks), and compared with full-term children (group III). Central foveal thickness (CFT), inner retinal thickness (IRT), outer retinal thickness (ORT), subfoveal choroidal thickness (CT), temporal and nasal CT, foveal avascular zone (FAZ) diameter, and vessel densities of superficial (SCP-VD) and deep capillary plexuses (DCP-VD) of the foveal and parafoveal areas were examined in detail.The study included 126 eyes of 63 patients (group I: 40 eyes; group II: 46 eyes; and group III: 40 eyes). In group I, CFT, IRT, ORT, foveal SCP-VD, and foveal DCP-VD were significantly greater than those in the other groups, and temporal CT and FAZ diameter were significantly lower (P.05). GA showed a significant negative correlation with CFT, IRT, ORT, foveal SCP-VD, and foveal DCP-VD and a significant positive correlation with subfoveal CT, temporal and nasal CT, and FAZ diameter (P.05).The morphological and vascular foveal structures in early school-age children who were born premature were different from those of full-term children. These differences were correlated with GA and more pronounced in those with GA of ≤30 weeks.

To quantify the macular microvasculature in healthy children of various ages by using optical coherence tomography angiography (OCTA).Prospective cross-sectional study.A total of 333 normal children from 4 to 16 years old were included. OCTA was performed on a 3- × 3-mm area centered on the macular region. Vascular density, perfusion density, fovea avascular zone (FAZ) area, FAZ perimeter, and FAZ acircularity index (AI) were measured and adjusted for axial length. Differences were compared among various ages.Among the different age groups, both macular vascular density and perfusion density increased with age (P.0001 and P = .0028, respectively). After adjustments were made for the spherical equivalent (SE) and axial length, macular vascular density was significantly associated with age (r = 0.183; P = .001) No factors were significantly correlated with the perfusion density after adjustment for the age, SE, or axial length. The FAZ area and FAZ perimeter did not change among groups of different ages. Nevertheless, the AI of FAZ in the 4.00-6.99-year-old group was smaller to that of the 13.00-15.99-year-old group (P = .03). Younger children had significantly higher rates of nonconsecutive vessels branched toward the macular center (P = .0002) and vascular loops contributing to irregular shapes of FAZ (P = .024).Macular vascular density and perfusion density continuously increase with age in children. Despite the fact that FAZ area and perimeter did not change, the microstructure of FAZ pruned and tended to form a smooth and regular avascular area during development.

Purpose To identify optical coherence tomography angiography (OCTA) derived vessel metrics of the macula and optic nerve head (ONH) that predict diabetic retinopathy (DR) disease progression. Design Secondary analysis of clinical trial data Methods This was a sub-analysis of prospectively collected data from 73 subjects that participated in the TIME-2b Study (Aerpio Pharmaceuticals), a multi-center clinical trial for patients with moderate to severe DR treated with AKB-9778 and followed over a 12-month period. Eligible subjects were tested every 3 months with color fundus photography, spectral domain OCT and slit-lamp biomicroscopy. OCTA of the macula and ONH was obtained for a subset of patients enrolled at participating sites. En-face, full-depth retinal projections centered at the macula were analyzed for multiple metrics including foveal avascular zone (FAZ) area and perimeter, non-perfusion area, vessel density (VD) and presence of intraretinal microvascular abnormalities (IRMA). VD of the radial peripapillary capillaries was evaluated in four quadrants surrounding the optic disc for ONH images. Progression was defined as a ≥ 2-step increase in DR severity scale score or development of diabetic macular edema. Results Over a follow-up period of 12 months, 15 of 73 (20.5%) subjects progressed. At pre-treatment baseline, larger FAZ area, presence of IRMA, and reduced peripapillary VD in the superior temporal and inferior temporal regions were significantly associated with increased odds of progression. Conclusions FAZ area and temporal peripapillary VD are predictors of DR progression. OCTA metrics may improve progression risk assessment in DR when compared to established risk factors alone.

PURPOSE: To determine the key optical coherence tomography (OCT) and OCT angiography (OCTA) parameters that correlate with visual field loss in optic disc drusen (ODD). DESIGN: Retrospective cross-sectional study. METHODS: SETTING: Single academic center. PATIENT OR STUDY POPULATION: 17 patients with ODD (29 eyes) and 35 age-matched controls (53 eyes) INTERVENTION OR OBSERVATION PROCEDURES: Static perimetry, OCT and OCTA imaging of optic disc and macula. MAIN OUTCOME MEASURES: static perimetry, OCT, and OCTA measurements. RESULTS: We investigated the relationship between static perimetry and 14 OCT/OCTA measurements in patients with ODD vs. age-matched controls and found 5 key measurements that most correlated with visual field loss included: peripapillary retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC), peripapillary vessel area density (VAD), macular vessel diameter (VD) and flux. Hierarchical clustering of these 5 measurements vs. all clinical characteristics revealed 3 distinct clusters. ODD and control eyes with no visual field loss (mean deviation (MD) > −2.0 dB) had high RNFL, GCC, and low macular VD and flux. ODD eyes with mild visual field loss (MD −2.0 to −5.0 dB) had high RNFL, GCC, and increased macular VD and flux. ODD eyes with moderate/severe visual field loss (MD < −5.0 dB) had decreased RNFL, GCC, peripapillary VAD, and increased macular VD and flux. CONCLUSIONS: OCT and OCTA provided objective measurements that can help predict visual field loss in ODD. Our data suggest that increased macular flow may be an early biomarker of visual field loss in ODD, while decreased peripapillary vessel density and RNFL thickness are late biomarkers of visual field loss in ODD.

Purpose To compare gradient-boosting classifier (GBC) analysis of optical coherence tomography angiography (OCTA)-measured vessel density (VD) and OCT-measured tissue thickness to standard OCTA VD and OCT thickness parameters for classifying healthy eyes and eyes with early to moderate glaucoma. Design Comparison of diagnostic tools. Methods A total of 180 healthy eyes and 193 glaucomatous eyes with OCTA and OCT imaging of the macula and optic nerve head (ONH) were studied. Four GBCs were evaluated that combined 1) all macula VD and thickness measurements (Macula GBC), 2) all ONH VD and thickness measurements (ONH GBC), 3) all VD measurements from the macula and ONH (vessel density GBC), and 4) all thickness measurements from the macula and ONH (thickness GBC). ROC curve (AUROC) analyses compared the diagnostic accuracy of GBCs to that of standard instrument-provided parameters. A fifth GBC that combined all parameters (full GBC) also was investigated. Results GBCs had better diagnostic accuracy than standard OCTA and OCT parameters with AUROCs ranging from 0.90 to 0.93 and 0.64 to 0.91, respectively. The full GBC (AUROC = 0.93) performed significantly better than the ONH GBC (AUROC = 0.91; P = .036) and the vessel density GBC (AUROC = 0.90; P = .010). All other GBCs performed similarly. The mean relative influence of each parameter included in the full GBC identified a combination of macular thickness and ONH VD measurements as the greatest contributors. Conclusions GBCs that combine OCTA and OCT macula and ONH measurements can improve diagnostic accuracy for glaucoma detection compared to most but not all instrument provided parameters.

This study was performed to investigate the association between changes in retinal layer thickness and perfusion status in the extramacular areas of eyes with diabetic retinopathy.Retrospective cross-sectional study.The medical records of 70 eyes from 55 patients with diabetes were reviewed. The status of retinal perfusion in extramacular areas was evaluated using swept-source optical coherence tomography angiography. Retinal layer thickness was measured in nonperfused areas (NPA) larger than 2 optic disc areas, areas of sparse capillaries (SC), and perfused areas (PA-DR) in eyes with diabetic retinopathy. Retinal layer thickness was also measured in perfused areas in eyes without diabetic retinopathy (PA-NDR), and the thicknesses were then compared. In addition, swept-source optical coherence tomography angiography images and retinal thickness maps were compared to investigate the distribution of retinal thickness changes and spatial relationships to areas of retinal perfusion.The inner retinal thickness in NPA was significantly thinner than the inner retinal thicknesses in SC, PA-DR, and PA-NDR (all P.001), and the inner retinal thickness in PA-NDR and SC was significantly thinner than that in PA-DR (P = .006 and .031, respectively). In a distribution analysis of the extramacular areas, NPA spatially overlapped with areas of severe retinal thinning in all locations. Local thickening with smooth shapes and gentle borders overlapped with areas of capillary abnormalities. Neovascularization was present at sites of local thickening with irregular shapes and unnatural clear borders.Changes in retinal layer thickness were associated with perfusion status, suggesting that retinal thickness maps can reflect perfusion status.

To compare different scan protocols of wide-field swept-source optical coherence tomography angiography (SS-OCTA) for the detection of diabetic retinopathy (DR) lesions.Comparison of diagnostic approaches.A prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to July 2019. Proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), and diabetic patients without DR were included. All patients were imaged using SS-OCTA using the following scan protocol: 3- × 3-mm Angio centered on the fovea; 6- × 6-mm Angio centered on the fovea and the optic disc; 15- × 9-mm Montage; and 12- × 12-mm Angio centered on the fovea and the optic disc. Images were independently evaluated by 2 graders for the presence or absence of DR lesions including microaneurysms, intraretinal microvascular abnormalities, neovascularization, nonperfusion areas, venous looping, and hard exudates. All statistical analyses were performed using commercial software.A total of 176 eyes in 119 participants were included in the study. The detection rate of neovascularization on 6- × 6-mm Angio centered on the fovea was approximately one-half that on 15- × 9-mm Montage (P.05) imaging. Combining 6- × 6-mm Angio imaging centered on the fovea and the optic disc could increase the rate to approximately two-thirds (P.05). The 12- × 12-mm Angio imaging centered on the combination of fovea and optic disc had detection rates comparable to those of 15- × 9-mm Montage imaging for all DR lesions (P.05). For microaneurysms, 6- × 6-mm Angio had better performance than 15- × 9-mm Montage (P.05).Wide-field SS-OCTA images were useful in detecting DR lesions. The 12- × 12-mm Angio imaging centered on the fovea and on the optic disc may be an optimal balance between speed and efficacy for evaluation of DR in clinical practice.

Purpose To investigate whether ophthalmologic findings in children with fetal alcohol spectrum disorders (FASD) persist into young adulthood. Design Prospective cohort study. Methods Thirty children (13 female) adopted from eastern Europe to Sweden in the 1990s and diagnosed with FASD by a multidisciplinary team at the median age of 7.9 years were followed up by the same team 13-18 years later. Visual acuity (VA), refraction, stereoacuity, strabismus, ocular media, and fundus were investigated. Results Median VA in right/left eye (OD/OS) was 20/32/20/32 (0.2/0.2 logMAR) in childhood and 20/22/20/20 (0.05/0.0 logMAR) in adulthood. Median (range) refraction OD/OS was +0.88/+1.25 (-8.75 to +4.75/−9.38 to +5.25) spherical equivalent diopter (D) in childhood and −0.25/−0.25 (−12 to +2.75/−13.25 to +2.63) in adulthood. Astigmatism (≥1 D) was the most common refractive error, in 13 (40%) and 14 (47%) subjects, respectively. Defective stereoacuity (>60 arc second) was noted in 20 subjects (67%) in childhood and 22 (73%) in adulthood. Heterotropia occurred in 12 subjects (40%) in childhood and 13 (43%) in adulthood. Increased tortuosity of the retinal vessels was found in 8 (27%) subjects in childhood vs 11 (37%) in adulthood. Optic nerve hypoplasia was recorded in 3 children and in 4 young adults. Conclusions Ophthalmologic findings such as refractive errors, strabismus, and fundus abnormalities are frequent in children with FASD and persist into early adulthood. The facial features characteristic of FAS diminish with age, making a dysmorphology evaluation in adulthood less reliable. An ophthalmologic examination is an important part of the evaluation of FASD in childhood as well as in young adulthood.

Purpose Widefield swept source optical coherence tomography angiography (WF SS-OCTA) imaging was compared with ultra-widefield (UWF) fluorescein angiography (FA) imaging to better understand changes in retinal nonperfusion before and after panretinal photocoagulation (PRP) in treatment-naive eyes with proliferative diabetic retinopathy (PDR). Design Prospective, observational, consecutive case series. Methods Participants with treatment-naive PDR were imaged using the SS-OCTA 12- × 12-mm scan pattern at baseline and at 1 week, 1 month, and 3 months after PRP. UWF FA was obtained at baseline and 3 months after PRP. Selected eyes were imaged using 5 SS-OCTA 12- × 12-mm scans to create a posterior pole montage, and 5 eyes also underwent SS-OCTA imaging at 6 months and 1 year. Areas of retinal nonperfusion (RNP) were drawn independently by 2 masked graders, and analysis of variance (ANOVA) tests were used to compare areas of RNP over time. Main outcome measurements consisted of areas and boundaries of RNP visualized using WF SS-OCTA and UWF FA. Results From January 2018 through January 2019, WF SS-OCTA was performed on 20 eyes with treatment-naive PDR from 15 patients. Areas of RNP identified on UWF FA images co-localized with RNP areas visualized on WF SS-OCTA images. There were no statistically significant changes in RNP area on WF SS-OCTA images through 3 months after PRP. Even eyes that were severely ischemic at baseline had no significant changes in RNP area 1 year after PRP. Conclusions RNP in PDR can be identified at baseline and imaged serially after PRP using WF SS-OCTA. Retinal perfusion in PDR does not change significantly after PRP. The ability of WF SS-OCTA to longitudinally evaluate RNP areas provides additional justification for adopting WF SS-OCTA as the sole imaging modality for clinical management of PDR.

PurposeAlthough the choroid contributes to the pathogenesis of age-related macular degeneration (AMD), the role of retinal perfusion is unclear. We sought to compare retinal vascular measurements between eyes with nonexudative and exudative AMD using optical coherence tomography angiography (OCT-A).DesignRetrospective, cross-sectional study.MethodsOCT-A images were analyzed from 310 eyes of 182 patients (mean age ± standard deviation [SD], 78.8 ± 8.8 years) with nonexudative (54.2%) and exudative (45.8%) AMD to measure retinal vessel density (VD) from the superficial capillary plexus in the foveal, parafoveal, and full macular regions and foveal avascular zone (FAZ) area, perimeter, and circularity. Multivariate regressions were used to compare nonexudative and exudative AMD eyes and the impact of anti-vascular endothelial growth factor (anti-VEGF) treatments or geographic atrophy (GA).ResultsIn eyes with AMD, VD decreases with age in the foveal (β=-0.211, P < .001), parafoveal (β=-0.305, P < .001), and full macular regions (β=-0.295, P < .001). Eyes with exudative AMD demonstrated lower VD, especially in the parafoveal (29.8% ± 6.3% vs 33.0% ± 5.7%, P < .001) and full regions (27.9% ± 6.2% vs 31.2% ± 5.5%, P < .001) compared with nonexudative AMD. There were no differences in FAZ area, perimeter, or circularity between the 2 groups (P= .503-.907). In eyes with exudative AMD, previous anti-VEGF treatments did not impact retinal vascular measurements (P= .324-.986). Nonexudative AMD severity and presence of central GA also impacted retinal VD and FAZ morphology.ConclusionsRetinal VD is decreased in eyes with exudative AMD compared with nonexudative AMD but is unaffected by anti-VEGF treatments, suggesting a retinal vascular contribution to the pathogenesis of AMD.

To determine the predictive value of the microcirculation of the optic nerve head by swept-source optical coherence tomography angiography for identifying individuals with high risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development.Prospective observational cohort study.A total of 946 patients (1879 eyes) with type 2 diabetes mellitus were recruited who had no DR or mild nonproliferative DR at baseline, and no DME. All subjects underwent 3 × 3 mm swept-source optical coherence tomography angiography centered on the optic nerve head to generate angiograms in 4 layers: radial peripapillary plexus, superficial retinal capillary plexus (SCP), deep retinal capillary plexus, and choriocapillaris (CC). The CC flow deficit percentage (CC FD%), vessel density (VD), and perfusion density (PD) were quantified.During the 3 consecutive years of follow-up, 312 eyes (16.60%) experienced DR progression and 115 eyes (6.12%) developed DME. The DR progression was related to a lower VD of the SCP (relative risk per standard deviation decrease, 95% confidence interval): 1.30, 1.14-1.48; P.001), a lower PD of the SCP (1.41, 1.24-1.60; P.001), a lower VD of the radial peripapillary plexus (1.23, 1.08-1.40; P = .002), and an elevated CC FD% (1.62, 1.40-1.88; P.001). The DME occurrence was associated with a lower VD of SCP (1.35, 1.09-1.66; P = .005), a lower PD of SCP (1.29, 1.05-1.59; P = .016), and a higher CC FD% (1.29, 1.03-1.61; P.001). The CC FD% significantly improved the predictive power, with the increase of the C-statistic for DR progression and DME occurrence by 3.83% (P = .002) and 5.24% (P.001), respectively.This study provides the first longitudinal evidence suggesting that peripapillary CC FD% can improve the prediction of DR progression and DME development beyond traditional risk factors.

To assess whether the 3-dimensional (3D) structural configuration of the central retinal vessel trunk and its branches (CRVTB) could be used as a diagnostic marker for glaucoma.Retrospective, deep-learning approach diagnosis study.We trained a deep learning network to automatically segment the CRVTB from the B-scans of the optical coherence tomography (OCT) volume of the optic nerve head. Subsequently, 2 different approaches were used for glaucoma diagnosis using the structural configuration of the CRVTB as extracted from the OCT volumes. In the first approach, we aimed to provide a diagnosis using only 3D convolutional neural networks and the 3D structure of the CRVTB. For the second approach, we projected the 3D structure of the CRVTB orthographically onto sagittal, frontal, and transverse planes to obtain 3 two-dimensional (2D) images, and then a 2D convolutional neural network was used for diagnosis. The segmentation accuracy was evaluated using the Dice coefficient, whereas the diagnostic accuracy was assessed using the area under the receiver operating characteristic curves (AUCs). The diagnostic performance of the CRVTB was also compared with that of retinal nerve fiber layer (RNFL) thickness (calculated in the same cohorts).Our segmentation network was able to efficiently segment retinal blood vessels from OCT scans. On a test set, we achieved a Dice coefficient of 0.81 ± 0.07. The 3D and 2D diagnostic networks were able to differentiate glaucoma from nonglaucoma subjects with accuracies of 82.7% and 83.3%, respectively. The corresponding AUCs for the CRVTB were 0.89 and 0.90, higher than those obtained with RNFL thickness alone (AUCs ranging from 0.74 to 0.80).Our work demonstrated that the diagnostic power of the CRVTB is superior to that of a gold-standard glaucoma parameter, that is, RNFL thickness. Our work also suggested that the major retinal blood vessels form a "skeleton"-the configuration of which may be representative of major optic nerve head structural changes as typically observed with the development and progression of glaucoma.

PURPOSE: This study investigated changes in retinal vessel density in macular and papillary regions in post-SARS-CoV-2 pneumonia patients by means of optical coherence tomography angiography (OCTA). DESIGN: Prospective, observational, cohort study. METHODS: Forty eyes of 40 patients (mean age: 49.7 ± 12.6 years old) post-SARS-CoV-2 infection and 40 healthy subjects were enrolled in this study. COVID-19 patients had to be fully recovered from COVID-19 pneumonia and were evaluated 6 months after COVID-19 infection. The primary outcome resulted from OCTA studies of the following vascular structures: vessel density (VD) in the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and radial peripapillary capillaries (RPC) compared to those of controls. Structural spectral domain (SD)-OCT parameters were also evaluated: ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). RESULTS: The patients showed a significant reduction in VD of the SCP in whole images and in the DCP in all sectors compared to those in healthy subjects (P

Purpose To examine retinal vasculometry associations with different glaucomas in older British people. Design Cross-sectional study. Methods A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined. Results A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (−3.2 μm; 95% confidence interval [CI] −4.4 μm, −1.9 μm) and venules (−2.7 μm; 95% CI −4.9 μm, −0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (−0.2 mm2; 95% CI −0.3 mm2, −0.1 mm2) and NTG (−0.2 mm2; 95% CI −0.3 mm2, −0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (−3.9%; 95% CI −7.7%, −0.1% and −4.8%; 95% CI −7.4%, −2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses. Conclusions Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma., Highlights • Retinal vessel measurements, including (as a first report) vessel tortuosity and area, were associated with high-tension glaucoma and other glaucoma-related outcomes. • Novel analyses showing that within-person-between-eye glaucoma diagnoses, intraocular pressure, and retinal vasculometry were uncorrelated provides further evidence that systemic microvascular changes may cause glaucoma.

PURPOSE: To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: Study participants underwent macular 3×3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500 μm GA rim regions, and non-GA regions to similar macular locations in control eyes. RESULTS: Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8±2.4% vs. 60.8±3.1%, P

To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA).Cross-sectional study.Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared.While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P.001). FD for the entire retina was negatively associated with global nonperfusion area (R = -0.44; P.001), and this relationship was also present within the 3 concentric retinal zones (posterior: R = -0.31, P = .016; midperiphery: R = -0.35, P = .007; and far periphery: R = -0.31, P = .015).Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.

To compare the severity of macular vascular changes in children with sickle cell disease (SCD) vs age- and race-matched controls.Cross-sectional study.Children (18 years old) with HbSS and HbS variant (HbSC and HbS thalassemia) genotypes, and their age- and race-matched controls, were recruited between January 2017 and December 2018. All subjects underwent optical coherence tomography angiography (OCTA) scans centered on the fovea and temporal macula. Retinal thickness, superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), and foveal avascular zone (FAZ) size were measured and compared between HbSS and HbS variant vs controls.Thirty-four HbSS, 34 HbS variant (Goldberg staging 0-3 for SCD eyes), and 24 control eyes (total 48 children, aged 5-17 years) were included. Total VD (3-mm ETDRS circle) was lower in HbS variant eyes than in controls for both the SCP (42.9% vs 47.7%, P = .02) and DCP (47.4% vs 52.6%, P = .01). In HbSS eyes, VD was lower in the DCP (47.7%, P = .008) but not in the SCP (45.5%, P = .5), compared to controls. A higher proportion of HbSS (n = 18, 55%) than HbS variant eyes (n = 9, 26%) had pathologic areas of retinal thinning associated with SCP and DCP flow loss (P = .03). However, retinal thickness measurements and FAZ size did not differ between either HbSS or HbS variant group vs controls.Children with SCD have similar retinal thickness but less dense vasculature on OCTA compared to age and race-matched controls, suggesting that microvascular insult may precede structural thinning.

Purpose The pathophysiology of nonarteritic anterior ischemic optic neuropathy (NAION) is not completely understood. Studies of the retinal vasculature phenotype in patients with NAION could help us to understand vascular abnormalities associated with the disease. Design Retrospective case series with matched control subjects. Methods Study population: 57 patients with NAION and 57 control subjects matched to NAION patients for sex, age, systemic hypertension, diabetes, and obstructive sleep apnea syndrome between September 2007 and July 2017. Main Outcome Measures All patients and control subjects underwent a complete ocular examination and 45° funduscopic color photographs. The widths of the 6 largest arteries in zone B (between 0.5 and 1 optic disc diameter from the optic disc), summarized by the central retinal artery equivalent (CRAE), the widths of the 6 largest veins in zone B, summarized by the central retinal vein equivalent (CRVE), the arteriole to venule ratio, tortuosity, and fractal dimension were measured on the 2 groups using Vessel Assessment and Measurement Platform for Images of the Retina, a software tool for efficient semiautomatic quantification of the retinal vasculature morphology in fundus camera images. The Wilcoxon signed-rank test and MacNemar χ2 test for paired sample and generalized estimating equations for modeling the Vessel Assessment and Measurement Platform for Images of the Retina parameters as dependent variables were used. Results CRVE and fractal dimension (D0a) were significantly higher in the NAION group when compared with the control group, whereas the arteriole to venule ratio and vascular tortuosity were significantly lower. Compared with control subjects, acute NAION yielded an increased CRAE value (174 ± 33 vs 160 ± 13 μm) while resolution NAION yielded a decreased CRAE value (152 ± 12 vs 156 ± 33 μm). Acute NAION yielded an increased CRVE value (244 ± 35 vs 210 ± 21 μm) while resolution NAION yielded an unchanged CRVE value. We found no difference between groups for age, refraction, optic disc diameter, CRAE, or fractal dimension. Conclusions Retinal vascular parameters were different in our sample between NAION and control patients, especially at the acute stage of the disease. Our results suggest a normalization of the same parameters at the resolution stage.

To study the structural and angiographic optical coherence tomography (OCT) data of the macula from controls, patients with diabetes, and patients with glaucoma to evaluate neurovascular and structural relationships.This was a retrospective study of 89 eyes from 49 patients in a community-based retinal referral practice with diabetes, glaucoma, and normal controls. The patients were evaluated with OCT to include retinal nerve fiber layer (RNFL) thickness measurement and ganglion cell layer (GCL) volume determination. The vascular density of the radial peripapillary capillary network and the vascular plexuses in the macula were evaluated with OCT angiography. The main outcome measures were the data obtained per disease state and the interrelationships the data displayed.The mean GCL volumes were significantly lower than the control group in both the diabetic (P = .016) and glaucoma (P.001) groups. The difference between the diabetic and glaucoma groups was not significant (P = .052). The mean global vascular density was greater in the control group than the diabetic group (P = .002) and the glaucoma group (P.001). The mean RNFL thicknesses were lowest in the glaucoma group. Both the diabetic and glaucoma groups had significantly lower radial peripapillary network and deep vascular plexus density values compared to controls.Although there are important differences in disease pathogenesis between diabetes and glaucoma, they share certain similarities in the structural and angiographic abnormalities eventually produced. This suggests that, in addition to canonical pathways of disease, a component of both could represent neurodegenerative disease, offering the possibility for the development of new treatments. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

PURPOSE: To determine the relationship between systemic factors and radial peripapillary capillary (RPC) vessel density (VD) in healthy African American (AA) participants of the African American Eye Disease Study. DESIGN: A population-based, cross-sectional study. METHODS: 4135 eyes from 2127 AA participants aged 40 years and older in Inglewood, California, were imaged for 6×6mm optic disc scans on a spectral-domain optical coherence tomography angiography (OCTA) device. Of these, 1029 eyes from 1029 participants who met the inclusion and exclusion criteria were analyzed, including only one eye per participant. Custom software was used to quantify RPC VD. Multivariate linear regression was used to identify systemic factors associated with RPC VD with a significance level set at 0.05. The contribution of each variable to the final model was estimated with the magnitude of standardized regression coefficients (SRC). The fit of the final model was measured by the R(2). RESULTS: Average RPC VD was 0.346±0.045. Controlling for signal strength, the systemic variables in the final multivariate model associated with reduced RPC VD were older age (β=−0.0123 per decade; SRC=−0.2733; p=

PURPOSE: To detect plexus-specific peripapillary retinal perfusion defects in glaucoma using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: One eye each of 45 perimetric glaucoma participants and 37 age-matched normal participants were scanned using 4.5-mm OCTA scans centered on the disc. The PR-OCTA algorithm removed flow projection artifacts in OCT angiograms. Five en face OCTA slabs were analyzed: nerve fiber layer plexus (NFLP), ganglion cell layer plexus (GCLP), superficial vascular complex (SVC = NFLP + GCLP), deep vascular complex (DVC), and all plexuses combined. Peripapillary retinal capillary density (CD) and vessel density (VD) were calculated using a reflectance-compensated algorithm. RESULTS: Focal capillary dropout could be visualized more clearly in the NFLP than the other slabs. The NFLP, SVC and all-plexus CD in the glaucoma group were significantly lower (P

To investigate whether abnormal glucose metabolism in diabetes mellitus (DM) affects the retinal microcirculation of children with well-controlled type 1 DM and to compare these results with those obtained from healthy children.Cross-sectional prospective study.This study enrolled 60 patients with DM without clinically detectable diabetic retinopathy (DR) and 57 age-matched control subjects. Optical coherence tomography angiography (OCT-A) was performed using AngioVue (Avanti, Optivue). Foveal avascular zone (FAZ) area, nonflow area, superficial and deep vessel densities, FAZ perimeter, acircularity index of FAZ (AI; the ratio of the perimeter of FAZ and the perimeter of a circle with equal area), and foveal density (FD-300; vessel density in 300 μm around FAZ) were analyzed. Correlations between the investigated OCT-A parameters with DM duration and glycated hemoglobin (HbA1c) levels were evaluated among patients with type 1 DM.Differences in the mean values for FAZ perimeter, AI, and FD-300 were statistically significant between DM group and control group (P.001, P = .001, and P = .009, respectively). There were also statistically significant differences between the groups for vessel densities of deep superior hemi-parafovea, deep temporal parafovea, and deep superior parafoveal zones (P = .008, P = .015, and P = .005, respectively). There were no significant correlations between DM duration and HbA1c levels with the investigated OCT-A parameters.Diabetic eyes without clinically detectable DR exhibited alterations in FD-300, AI, perimeter, and vessel density of parafoveal capillaries in deep capillary plexus preceding the enlargement of FAZ; therefore, these new parameters might be sensitive imaging biomarkers to define early DR.

To investigate the morphological changes of posterior vitreous in highly myopic (HM) eyes of patients 50 years of age and older.Retrospective, observational case series.Ultra-widefield swept-source OCT (UWF-OCT) examinations were performed on 768 eyes of 448 HM patients (50-89 years of age) and 54 eyes of 52 non-HM subjects with scan widths of 23 mm and depths of 5 mm. HM was defined as an axial length longer than 26.5 mm. The area and morphology of the posterior vitreous detachments (PVDs) and adhesions onto retinal vessels were examined for in 167 HM eyes and in 11 non-HM eyes in which the vitreal images were clear.Paramacular PVD, perifoveal PVD, peripapillary PVD, and complete PVD were found in 9%, 47%, 41%, and 3% of the 167 HM eyes, respectively, and in 37%, 45%, 18%, and 0% of the 11 non-HM eyes, respectively. In eyes with vitreofoveal adhesions, the PVDs were more commonly asymmetrical relative to the fovea in the HM eyes than in the non-HM eyes (94% vs. 44%, respectively; P.001). The area of the PVD corresponded with the area where the sclera protruded posteriorly. A thickened vitreous was observed to adhere to the retinal vessels at multiple points and was accompanied by paravascular abnormalities including lamellar holes in HM eyes. A total of 54 of the 167 HM eyes had macular retinoschisis, and the eyes commonly had vitreal traction on retinal vessels compared to HM eyes without macular retinoschisis (P = .031).PVD progressed asymmetrically and were associated with scleral curvature in HM eyes. Vitreous traction spanning a wide distance may lead to myopic traction maculopathy.

Purpose To define the retinal and choroidal imaging findings of carotid cavernous fistula (CCF) including central foveal thickness, subfoveal choroidal thickness, choroidal vascularity index (CVI) parameters, and tortuosity indexes (TIs) as compared to a control group (CG). Design Cross-sectional study. Materials and Methods The spectral domain enhanced-depth imaging optical coherence tomography images of 19 eyes of 19 consecutive patients with angiographically proven CCF and 19 eyes of 19 age- and sex-matched healthy control subjects were included. The patient group was divided according to CCF venous drainage pattern as anterior (A-CCF: draining into ophthalmic veins) and posterior (P-CCF: not draining into ophthalmic veins). The clinically affected eyes of the patient group, ipsilateral to the fistula, were included in the analysis. Results There were 15 A-CCFs (78.9%) and 4 P-CCFs (21.1%). The mean SFCT of the A-CCF group (395.21 ± 111.69 μm) was significantly higher than those of the P-CCF (246.84 ± 94.12 μm) and CG groups (280.79 ± 111.36 μm) (P = .039 and P = .006, respectively). The mean CVI of the A-CCF group was significantly higher than that of the CG (68.97 ± 4.81 and 65.66 ± 3.37, respectively, P = .033). The A-CCF group had significantly higher inferior, superior, and total venous TI than the CG group (P = .001, P = .001, and P Conclusion In this first study investigating the CVI and TI in CCF patients, we demonstrated that SFCT, CVI, and TI could potentially be used to aid in the diagnosis of A-CCF.

Purpose This study evaluated the macular microvascular changes in eyes with proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP). Design Using optical coherence tomographic angiography (OCTA), we prospectively studied 10 eyes of 10 subjects with high-risk PDR immediately before, at 1 month, and at 3-6 months following PRP, using a 3- × 3-mm OCTA scan at each visit. Methods The following parameters were calculated for the superficial (SCP), middle (MCP), and deep capillary plexuses (DCP): parafoveal vessel density (VD), adjusted flow index (AFI), and percent area of nonperfusion (PAN). Parafoveal SCP vessel-length density (VLD) was also evaluated. We performed univariate and multivariable statistics, adjusting for age and signal strength. To model the hemodynamic effect of PRP, we also present a mathematical model based on electrical circuits. Results We found no significant difference for the vascular density parameters following PRP, except for decreased density at the MCP at the latest timepoint in the adjusted multivariable model. PAN, a metric of nonperfusion adjusted for noise, and AFI, a surrogate metric of blood flow, showed significant increases at all capillary levels in the adjusted model. Our mathematical model explained how PRP would increase macular blood flow. Conclusions Using OCTA, we found an overall increase in the flow metrics of all capillary layers in the macula following PRP, unrelated to macular edema or thickening, in line with the mathematical model. Our results suggest an overall redistribution of blood flow to the posterior pole following PRP, adding a new dimension to our understanding of the complex biologic effects of PRP in PDR. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Binarization is a critical technique in optical coherence tomography angiography (OCTA) image analysis, but there is no consistency in the method used in published OCTA studies. This study assessed whether differences in OCTA binarization and brightness and contrast adjustments affect quantification measurements.Prospective cross-sectional validity study.This was a single-center study examining 21 eyes of 11 healthy individuals. All eyes were imaged using a swept-source OCTA (Zeiss), and quantitative measurements resulting from five binarization thresholding and five brightness/contrast adjustment methods were compared. All measurements were calculated for the superficial plexus and choriocapillaris (CC), as well as unaveraged and averaged en face OCTA images.There were statistically significant differences between measurements from different binarization thresholding methods (P0.0001), as well as measurements from different histogram adjustments (P 0.0001). The binarization thresholds yielded different measurements when combined with variable brightness/contrast adjustments. The method of analysis also affected the directionality of trends in imaging measurements between unaveraged and averaged CC images.The method of OCTA image binarization thresholding and histogram adjustment significantly alters quantitative measurements and the directionality of trends. Results obtained from different OCTA binarization methods should be seen as valid only for that given method. This has significant consequences for clinical trials using OCTA measurements as outcome measurements. A consensus is needed across the research community for a consistent method for OCTA image quantification and greater attention paid to fully describing methods in published studies.

PURPOSE:To evaluate the association between optical coherence tomography angiography (OCTA) macular and circumpapillary vessel density and visual field mean deviation (MD) in advanced primary open angle glaucoma. DESIGN:Cross-sectional study. METHODS:Macula (superficial layer) and optic nerve head (ONH) with capillary density (CD) and without vessel density (VD) automated removal of large vessels OCTA of 34 eyes (34 patients, MD < -10 dB) were investigated as macula whole image VD (wiVD), parafoveal VD (pfVD), ONH wiVD, wiCD, circumpapillary VD, and cpCD. Spectral domain OCT circumpapillary retinal nerve fiber layer, macular ganglion cell complex, and ganglion cell inner plexiform layer were also analyzed. RESULTS:Macular and ONH VD decreased significantly with worsening MD. Each 1-dB decrease in MD was associated with a reduction of 0.43% and 0.46% for macular wiVD and pfVD with R2 of 0.28 and 0.27, respectively (all P < .01). The association between MD and VD was strongest for measures of ONH with large vessels removed, wiCD, and cpCD, followed by wiVD and circumpapillary VD with R2 of 0.26, 0.22, 0.17, 0.14, and a VD reduction of 0.43%, 0.51%, 0.33%, and 0.40%, respectively (all P < .02). There was a reduction of 1.19μm in Avanti parafoveal ganglion cell complex, 1.13μm in Spectralis ganglion cell inner plexiform layer, and 1.01μm in Spectralis circumpapillary retinal nerve fiber layer, with R2 of 0.19 (P= .006), 0.23 (P= .002), and 0.24 (P= .002), respectively. CONCLUSIONS:ONH and macula OCTA VD and thickness are associated with the severity of visual field damage in advanced primary open angle glaucoma.

To investigate the topographic relationship among focal lamina cribrosa (LC) defect, microvasculature dropout (MvD) and border tissue morphology in open angle glaucoma (OAG) eyes using spectral-domain (SD) optical coherence tomography (OCT) and OCT angiography.Cross-sectional study.One hundred twenty-six OAG eyes and 97 normal eyes were included. The maximum externally oblique border tissue (EOBT) length was measured by using enhanced depth imaging SD-OCT as well as focal LC defect size. Circumferential MvD width and height ratio were measured using OCT angiography.Significant correlations were found among the locations of focal LC defect, MvD and maximum EOBT length. The mean absolute locational difference was 29.1° (95% CI, -47.6 to 105.7) between focal LC defect and MvD, 10.0° (95% CI, -79.4 to 99.4) between focal LC defect and maximum EOBT length, and 10.6° (95% CI, -71.1 to 92.3) between MvD and maximum EOBT length. In multivariate logistic regression analysis, a worse VF defect was significantly associated with the presence of focal LC defects and MvDs (P.002; P = .002, respectively). MvD circumferential width was associated with glaucoma severity (R = -0.66, P.001), whereas focal LC defect size and MvD height ratio were associated with maximum EOBT length (R = 0.48, P.001; R = 0.65, P.001, respectively) and AL (R = 0.53, P.001; R = 0.52, P.001, respectively).There was a topographical correlation among the locations of focal LC defect, MvD and maximum border length. In addition, the presence of focal LC defect and MvD were also strongly associated with glaucoma severity. Thus, it is thought that focal LC defect and MvD may be biomarkers that reflect glaucoma severity especially at the location of maximum border tissue elongation.

To evaluate the association between optical coherence tomography angiography (OCT-A)-derived parapapillary deep-layer microvasculature dropout and glaucomatous visual field (VF) progression.Retrospective, cohort study.A total of 138 eyes of 138 patients with primary open-angle glaucoma (mean follow-up, 5.5 years) and with ≥5 VFs prior to OCT-A imaging were included. VF progression was defined as either a Guided Progression Analysis-based "likely progression" event or a significant VF index (VFI) slope. Microvasculature dropout was defined as parapapillary deep-layer microvasculature dropout based on a qualitative analysis of OCT-A. Prevalence of dropout was compared between eyes with and without VF progression.Fifty-five eyes (39.9%) demonstrated VF progression. A higher proportion of eyes with dropout progressed than those without dropout (50/84 eyes [59.5%] vs 5/54 eyes [9.3%]; P.001). In multivariable logistic regression analysis, mean and standard deviation intraocular pressure, optic disc hemorrhage, focal lamina cribrosa defect, and dropout were significantly associated with prior VF progression (P.05). The VFI progression rate was significantly faster in eyes with dropout than in those without dropout (-2.23% ± 3.22%/year vs -0.05% ± 1.24%/year, respectively; P.001), and the location of dropout and VF progression were spatially correlated.Eyes with parapapillary deep-layer microvasculature dropout detected by OCT-A had a significantly higher rate of VF progression than eyes without dropout. These findings implicate dropout as a structural parameter suggestive of past glaucomatous VF progression. Further prospective longitudinal studies are needed to elucidate the role of deep-layer microvasculature damage in the pathogenesis of glaucoma.