Evaluation of retinal vessel quantity within individual retinal structural layers using optical coherence tomography angiography.

PURPOSE: To evaluate retinal vessel quantity within various retinal structural layers using optical coherence tomography angiography (OCTA). METHODS: In this IRB-approved study, 22 normal eyes (from 22 subjects) were imaged using the Spectralis OCT2, with a 15 × 15 degree OCTA scan centered on fovea and two additional 15 × 5 degree OCTA scans, displaced temporally and nasally by 15 degrees along the fovea-Bruch's membrane opening (BMO) axis. Following projection artifact removal (PAR), vessel quantity (i.e., amount of flow signal) within each retinal nuclear and plexiform layer was assessed across the scan and was plotted as a vessel quantity profile over this fovea-BMO axis. Vessel quantity was correlated against the retinal layer thickness at the corresponding locations using the Spearman correlation. RESULTS: For the nerve fiber layer (NFL), the vessel quantity was highest nasally and declined towards the fovea and was near zero temporal to the fovea with or without PAR. For all other retinal layers, the retinal vessel quantities were greatest in the parafoveal retina, peaking approximately 5 degrees from the foveal center. Before PAR, the parafoveal vessel quantity was highest in the inner plexiform layer (IPL). Following PAR, the vessel quantity in the IPL decreased but was relatively unchanged in the other layers. The vessel quantity correlated moderately well with retinal layer thickness (r = 0.432 to 0.511; P < 0.05 among the various layers). CONCLUSIONS: Retinal vessel quantity varies significantly among the various structural layers, with significant regional variability. Projection artifact can significantly impact retinal vessel quantity in the deeper layers, but the effect appears to be most pronounced in the IPL.

Choriocapillaris flow impairment predicts the development and enlargement of drusen.

PURPOSE: To evaluate the choriocapillaris flow in regions of enlarged or new incident drusen in patients with early and intermediate age-related macular degeneration (AMD). METHODS: We retrospectively reviewed and analyzed structural optical coherence tomography (OCT) and OCT angiography (OCTA) images of consecutive patients with early or intermediate AMD evaluated at the Doheny-UCLA Eye Centers between 2015 and 2018. All patients were imaged using a Cirrus OCT, and only one eye was included in the study. To be eligible for this analysis, patients were required to have a 3 × 3-mm OCTA scan acquired during the first visit (considered as baseline) and a fovea-centered 512 × 128 macular cube (6 × 6 mm) acquired at both the baseline visit and after a minimum of 1 year follow-up. The drusen maps generated from the macular cubes were used to generate a drusen area (DA) measurement and compute the difference between baseline and follow-up (ΔDA). After registering the structural OCTs to the baseline choriocapillaris (CC) OCTA, we analyzed and compared the baseline flow deficits (FD) within drusen-free region (FDDF), regions into which drusen enlarged or expanded at follow-up (FDEN), and regions in which new incident drusen (FDND) appeared at follow-up. RESULTS: Forty-six patients were eligible for the analysis and had a mean follow-up of 1.47 years. Twelve eyes of 12 subjects had a ΔDA < 0.1 mm2. In these eyes, only the FDDF was calculated (40.37 ± 2.29%) and it was not significantly different from the FDDF of eyes with ΔDA ≥ 0.1 mm2 (40.25 ± 4.37%, p = 0.849). When comparing the different regions within the eyes with ΔDA ≥ 0.1 mm2, there was no significant difference between FDED and FDND (43.61 ± 4.36% and 44.16 ± 2.38%, p = 528), but both were significantly higher than FDDF (p = 0.001 and p < 0.001, respectively). CONCLUSIONS: Significant CC flow impairment is present under regions of intact retinal pigment epithelium (RPE) where existing drusen will enlarge into or new drusen will appear within 2 years. These findings suggest that location of drusen may not be stochastic but may be driven by regional deficits in the choriocapillaris.

MACULAR MICROVASCULAR NETWORKS IN HEALTHY PEDIATRIC SUBJECTS.

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

Assessment of Corneal Changes Associated with Topical Antiglaucoma Therapy Using in vivo Confocal Microscopy.

PURPOSE: Ocular surface disease (OSD) is highly prevalent in eyes treated with chronic, topical antiglaucoma (A/G) therapy. The purpose of this study was to utilize in vivo confocal microscopy (IVCM) to evaluate the corneal morphology, including characteristics of corneal epithelial cells, presence of epithelial dendritic cells (DCs), and characteristics of subbasal nerve plexus, of eyes under topical A/G therapy versus normal eyes. METHODS: Central corneal images were prospectively captured from 30 eyes of 16 patients under topical A/G therapy (>6 months) and 20 normal control eyes, using IVCM (HRT 3 RCM, Heidelberg, Germany). Demographic data were collected, as well as information on the types and duration of A/G therapy. In addition, OSD index (OSDI) score, tear film breakup time, Schirmer 1 test results, density of epithelial wing cells (WCs) and basal cells (BCs), subbasal nerve features (density, tortuosity, and reflectivity), and presence of DCs were all assessed and recorded by trained Doheny Image Reading Center graders. RESULTS: IVCM findings of 30 glaucomatous eyes and 20 normal control eyes were analyzed. The mean OSDI score was 8.72 in controls and 32.06 in patients under A/G therapy (p = 0.002). Nerve fiber density, nerve fiber reflectivity, and BC density were all decreased in the A/G group (1,789.07 ± 785.70 µm/frame, 2.79 ± 0.83, 6,457.67 ± 692.55 cells/mm2, respectively) as compared to controls (2,815.981 ± 563.77 µm/frame, 3.52 ± 0.50, 7,854.13 ± 1,073.69 cells/mm2, respectively) (p < 0.05), whereas the decrease in WC density was statistically nonsignificant (p = 0.5). Nerve tortuosity and DC density were both significantly greater in the A/G eyes (3.00 ± 0.57, 71.24 ± 61.74 cells/mm2, respectively) compared to controls (2.10 ± 0.42, 34.08 ± 11.70 cells/mm2, respectively) (p < 0.05). Tear film breakup time and Schirmer 1 test results were significantly lower in the A/G group as compared to controls (p < 0.001). CONCLUSIONS: Using IVCM, our study identified significant microstructural alterations in the corneas of eyes treated with topical A/G therapy. In addition, our study also revealed that glaucoma patients treated with topical A/G therapy report significantly higher OSDI scores compared to controls. Thus, IVCM may be a useful tool in providing structural parameters to correlate with the functional OSDI assessments in the evaluation of ocular surface toxicity associated with topical A/G therapy.

Analysis of ocular inflammation in anterior chamber-involving uveitis using swept-source anterior segment OCT.

PURPOSE: To evaluate the utility of swept-source (SS) optical coherence tomography (OCT) to objectively analyze the degree of anterior chamber (AC) inflammation. METHODS: Thirty-eight eyes of 32 patients with uveitis and 20 control eyes were enrolled. SS OCT B-scans were obtained, and the number of cells in the B-scans was counted using two methods: (1) manual grading by Point Picker plug-in of Image J ( http://bigwww.epfl.ch/thevenaz/pointpicker/ ) and (2) automated grading by the Image J Particle Analysis algorithm ( http://imagej.net/Particle_Analysis ). The automated and manual AC cell counts were correlated with the Standardization of Uveitis Nomenclature score. RESULTS: The average numbers of AC inflammatory cells counted by the automated method were 8 ± 4.0, 18 ± 3.0, 42 ± 14.0, 81 ± 32.0, 117 ± 57.0, and 275 ± 67.0 cells/mm2 for grades 0, 0.5 + , 1 + , 2 + , 3 + , and 4 + , respectively. For the same clinical categories, the average manual cell counts were 6 ± 4.0, 18 ± 3.0, 34 ± 14.0, 72 ± 32.0, 92 ± 43.0, and 168 ± 65.0 cells/mm2, respectively. Zero cells were detected in the AC of healthy eyes. The automated and manual methods were highly correlated (R = 0.98, p < 0.001) and showed good correlation with the clinical grading (R = 0.88, p < 0.001). A mean AC particle size of 117.4 ± 108.8 µm was obtained by the automated method. CONCLUSIONS: Quantification of the AC cells imaged by SS AS-OCT shows good correlation with categorical clinical severity assessments in uveitis eyes. This approach may provide a more objective method for monitoring uveitis and response to uveitis therapy.

Role of in vivo confocal microscopy in the diagnosis of infectious keratitis.

PURPOSE: To investigate the utility of in vivo confocal microscopy (IVCM) in the diagnosis of infectious keratitis (IK). METHODS: Retrospective chart review of 46 patients with a final diagnosis of IK were included in the study. All patients received IVCM corneal imaging using the Heidelberg Retinal Tomography III system. All available scans were randomized and analyzed in a masked fashion. Sensitivity and specificity of IVCM in diagnosing bacterial keratitis (BK), Acanthamoeba keratitis (AK), fungal keratitis (FK), and HSV viral keratitis (VK) were assessed. RESULTS: The pooled sensitivity and specificity of IVCM in identifying atypical IK (AK and FK cases combined) were 85.3% (95% CI 68.2-94.5%) and 100% (95% CI 74.7-100%), respectively. The sensitivity and specificity of IVCM in identifying BK were 66.7% (95% CI 35.4-88.7%) and 89.2% (95% CI 73.4-96.5%), respectively. The sensitivity and specificity of IVCM in identifying VK were 100% (95% CI 46.3-100%) and 93.2% (95% CI 80.3-98.2%). Additionally, IVCM was able to make the correct diagnosis in 8 out of the 11 atypical keratitis cases misdiagnosed clinically. In the AK subgroup, IVCM was more accurate than clinical assessment (16 vs. 11). In the FK subgroup, IVCM were as accurate as clinical assessment, but did correct one misdiagnosed cases by identfying fungal hyphae. CONCLUSION: IVCM is an non-invasive imaging modality that can rapidly and accurately diagnose IK even for experienced corneal specialists. In complex cases of polymicrobial infection, IVCM may guide the correct clinical diagnosis and initiation of the appropriate treatment.

Evaluation of the corneal epithelium in non-Sjögren's and Sjögren's dry eyes: an in vivo confocal microscopy study using HRT III RCM.

BACKGROUND: The corneal epithelium is directly affected in dry eye syndrome. Thus, we attempted to describe the morphological features and evaluate the cellular density within the corneal epithelial layers in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE) by in vivo confocal microscopy (IVCM). METHODS: Central cornea was prospectively imaged by IVCM in 68 clinically diagnosed aqueous tear-deficient dry eyes and 10 healthy age-matched control eyes. Morphological characteristics of corneal epithelial layers and cellular densities were evaluated by four trained graders from the Doheny Eye Institute. RESULTS: Corneal epithelium in dry eyes presents morphological changes such as areas of enlarged and irregular shaped cells. In comparison with controls, the density of superficial epithelial cells was decreased in both the NSDE (P < 0.05) and SSDE groups (P < 0.01); the density of the outer layer of wing cells was smaller but not significantly different in NSDE (P > 0.05), but was lower in the SSDE group (P < 0.01); the density of the inner layer of wing cells was decreased in both the NSDE (P < 0.05) and SSDE groups (P < 0.01) and the density of basal epithelial cells was lower in both the NSDE (P < 0.01) and SSDE groups (P = 0.01). For all cell counts, the interclass correlation coefficient showed good agreement between graders (ICC =0.75 to 0.93). CONCLUSIONS: IVCM represents a reliable technique for examining the corneal epithelial microstructural changes associated with dry eyes, as well as for objectively and reproducibly quantifying cell densities within all corneal epithelial layers.

Comparison of Noncontact Specular and Confocal Microscopy for Evaluation of Corneal Endothelium.

PURPOSE: To compare endothelial cell analysis obtained by noncontact specular and confocal microscopy, using the Konan NSP-9900 and Nidek ConfoScan4 systems, respectively. METHODS: Three groups including 70 healthy eyes, 49 eyes with Fuchs endothelial corneal dystrophy (FECD), and 78 eyes with glaucoma were examined with both the Konan NSP-9900 specular microscope and the Nidek ConfocScan4 confocal microscope. Certified graders at the Doheny Image Reading Center compared corneal endothelial images from both instruments side by side to assess image quality. Endothelial cell density (ECD) measurements were calculated and compared using three different modalities: (1) each instrument's fully automated analysis; (2) each instrument's semiautomatic analysis with grader input; and (3) manual grading methods by certified grader. RESULTS: All normal eyes yielded gradable endothelial images, and most but not all glaucomatous eyes yielded images with high enough image quality to allow grading. In addition, in corneas with severe FECD, poor image quality precluded ECD grading by specular microscopy in 20 eyes (40.8%) but in only 4 (8.2%) confocal images from the same eyes. For the gradable images, the ECD values obtained using the manual grading method from either device were comparable with no statistically significant difference (P>0.05) between specular and confocal devices. Machine-generated ECD values were significantly different from manual results, measuring greater in all cases with specular microscopy. Machine-generated ECD values from confocal microscopy also differed significantly from manual determinations, but not in a consistent direction. Semiautomatic methods for both instruments obtained clinically acceptable ECD values. CONCLUSIONS: Automatic machine-generated ECD measurements differed significantly from manual assessments of corneal endothelium by both specular and confocal microscopy, suggesting that automated results should be used with caution. But ECD values derived manually were comparable between the two devices in both normal and glaucomatous eyes, suggesting that manually graded images from the two instruments can be used interchangeably for reliable ECD measurements. Because of a higher proportion of gradable images, confocal microscopy may be superior to specular microscopy for ECD measurements in FECD.

Validity of a new comprehensive pterygia grading scale for use in clinical research and clinical trial.

PURPOSE: To determine the reliability and agreement of a new comprehensive pterygium grading scale for use in clinical research and clinical trials. METHODS: Thirty eyes with pterygia were enrolled in this study. Primary gaze position and lateral gaze position images were taken of each eye with a modified single-lens reflex camera system. Our grading scale includes five parameters: two hyperemia parameters of pterygia on two different gaze position images and three size parameters, quantifying length, width, and area of the cornea encroachment of pterygium, using ImageJ software. All images were graded on the five parameters by two masked, certified reading center graders. Two graders independently graded all the images to determine inter-grader reliability. One grader regraded the images after 3 days to determine intra-grader reliability. Intraclass correlation coefficient (ICC) and inter-rater agreement statistic (κ) calculations were performed. RESULTS: The intra-grader reliability for hyperemia grading was high on both primary and lateral gazing positions (κ value is 0.93 and 0.96). The inter-grader reliability for hyperemia grading was also good (κ value is 0.85 and 0.87). The mean value of width, length, and area of the cornea encroachment of pterygium was 4.31 ± 2.04 mm, 2.08 ± 1.43 mm, and 7.84 ± 7.62 mm2, respectively. The intra-grader agreement on width, length, and area were excellent, with ICCs of 0.98 (95% CI 0.96-0.99), 0.99 (95% CI 0.98-1.0), and 0.97 (95% CI 0.94-0.99), respectively. The inter-grader agreement on width, length, and area were also excellent, with ICCs of 0.96 (95% CI 0.90-0.98), 0.99 (95% CI 0.98-0.99), and 0.99 (95% CI 0.97-0.99), respectively. CONCLUSIONS: There was excellent intra- and inter-observer reproducibility with the new comprehensive grading scale. This scale could lead to the development of standardized grading assessments and quantification of pterygia that would be valid in clinical research and clinical trials.

Choroidal Imaging with Swept-Source Optical Coherence Tomography in Patients with Birdshot Chorioretinopathy: Choroidal Reflectivity and Thickness.

PURPOSE: To characterize choroidal thickness and choroidal reflectivity in the eyes of patients with birdshot chorioretinopathy (BSCR). DESIGN: Cross-sectional observational study. PARTICIPANTS: Two hundred twenty BSCR patients and 59 healthy controls. METHODS: Patients with BSCR and healthy controls underwent imaging of the macula in both eyes with a swept-source optical coherence tomography device (DRI-OCT1 Atlantis; Topcon). Images were exported from the device, and analysis was performed by 2 graders in the Doheny Image Reading Center using Image J software. The choroidal thickness at the foveal center was measured. In addition, the inner and outer boundaries of the choroid and retinal pigment epithelium (RPE) as well as the inner retinal surface all were segmented to allow the brightness and reflectivity of the pixels in the choroid, RPE band, and overlying vitreous to be quantified. An adjusted or normalized choroidal reflectivity, with the RPE as the bright reference standard and the vitreous as the dark reference standard, was computed using the formula: normalized choroidal reflectivity = (choroidal reflectivity-vitreous reflectivity)/RPE reflectivity. MAIN OUTCOME MEASURES: Choroidal reflectivity and choroidal thickness. RESULTS: Three hundred eighty-six eyes in the BSCR group and 59 eyes in the control group were included in this analysis. Higher choroidal reflectivity and lower choroidal thickness were documented in inactive BSCR patients compared with active BSCR and controls (P < 0.01). Active BSCR patients showed lower choroidal thickness compared with controls (P < 0.01). There was a negative correlation between choroidal reflectivity and choroidal thickness (r = -0.793; P < 0.001). On multiple regression analysis, choroidal thickness, age, and disease duration (all P < 0.01) all were significant predictors of choroidal reflectivity. CONCLUSIONS: Choroidal reflectivity and choroidal thickness changes are evident in active and inactive BSCR patients. Novel choroidal parameters such as choroidal reflectivity may warrant further study in the setting of BSCR.

Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study.

PURPOSE: To evaluate corneal innervation and inflammatory cell infiltration using in vivo confocal microscopy (IVCM) and to correlate these findings with subjective symptoms of dry eye, as measured by the Ocular Surface Disease Index (OSDI) in patients with non-Sjögren's (NSDE) and Sjögren's syndrome dry eyes (SSDE). METHODS: Central corneal images were prospectively captured from 10 age-matched healthy control eyes, 24 eyes with clinically diagnosed NSDE and 44 eyes with clinically diagnosed SSDE, using IVCM (HRT III RCM). Density, tortuosity and reflectivity of corneal nerves, presence of inflammatory dendritic cells (DCs) and OSDI scores were evaluated. RESULTS: Images obtained by IVCM from 78 eyes were analyzed. The density of nerve fibers was 1562 ± 996 µm/frame in the SSDE group, 2150 ± 1015 µm/frame in the NSDE group and 2725 ± 687 µm/frame in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of nerve fibers was decreased in the SSDE (P < 0.001) and the NSDE groups (P = 0.06), with increased nerve tortuosity and decreased reflectivity in both groups (both P < 0.05). The density of DCs was 71.65 ± 72.54 cells/mm2 in the SSDE group, 40.33 ± 31.63 cells/mm2 in the NSDE group and 27.53 ± 5.58 cells/mm2 in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of DCs was increased in the SSDE (P < 0.001) and the NSDE groups (P = 0.07). Significant correlations were found between the nerve density and DC density (r = -0.57, P < 0.001), between the nerve density and OSDI scores (r = -0.91, P < 0.001) and between the nerve reflectivity and OSDI scores (r = -0.75, P < 0.001). CONCLUSIONS: The corneas of eyes affected with NSDE and SSDE are characterized by alterations in corneal innervation and infiltration of inflammatory DCs. Corneal nerve density and reflectivity are correlated with severity of subjective dry eye symptoms, as measured by OSDI score.

Corneal features in ocular graft-versus-host disease by in vivo confocal microscopy.

PURPOSE: The purpose of our study was to determine the morphological features of the corneal epithelial layers, sub-basal nerve plexus and anterior stroma in patients with ocular graft-versus-host disease (oGVHD) compared to non-GVHD dry eyes and normal controls, using in vivo confocal microscopy (IVCM). METHODS: IVCM was used to capture central cornea images from eight volunteers with normal healthy eyes, ten patients with non-GVHD dry eye syndrome (DES) and 15 patients with clinically diagnosed oGVHD, in a cross-sectional study. Morphological changes of the corneal epithelial layers and anterior stroma, characteristics of corneal nerves and presence of dendritic cells (DCs) were then evaluated. RESULTS: IVCM images obtained from 66 eyes were analyzed. The density of superficial epithelial cells was 636.07 ± 101.05 cells/mm2 in the oGVHD group, 827 ± 99.62 cells/mm2 in the DES group and 1277.2 ± 121.42 cells/mm2 in the control group (P < 0.001). The density of wing cells was 4499.79 ± 976.36 cells/mm2 in the oGVHD group, 4662.85 ± 319.72 cells/mm2 in DES group and 6556.38 ± 503.99 cells/mm2 in the control group (p < 0.001). The density of basal cells was 7850.93 ± 723.51 cells/mm2 in the oGVHD group, 8570 ± 913.32 cells/mm2 in DES group and 9759.8 ± 251.99 cells/mm2 in the control group (p < 0.01). The density of nerve fibers was 11.22 ± 5.46 mm/mm2 in the oGVHD group, 14.50 ± 4.27 mm/mm2 in DES group and 19.56 ± 4.75 mm/mm2 in the control group (p < 0.01). The DC density was 67.88 ± 71.82 cells/mm2 in the oGVHD group, 40.06 ± 31.95 cells/mm2 in the DES group and 29.45 ± 8.1 cells/mm2 in the control group (P > 0.05). Visible networks of activated keratocytes were seen in the anterior stroma of eyes with oGVHD and DES, but not in normal controls. CONCLUSIONS: IVCM revealed distinct microstructural changes in the corneas of patients with oGVHD and DES, similar between the two groups. Our findings suggest implications for use of IVCM to evaluate and monitor patients with dry eyes associated or not with GVHD.

Relationship Between Choriocapillaris Flow and Scotopic Microperimetry in Early and Intermediate Age-related Macular Degeneration.

PURPOSE: To evaluate the correlation between choriocapillaris (CC) flow alterations and scotopic macular sensitivity (sMS) in patients with early and intermediate age-related macular degeneration (AMD). DESIGN: Prospective cross-sectional study. METHODS: We acquired 2 3 × 3 mm and 2 6 × 6 mm swept-source optical coherence tomography angiography (OCTA) images of 1 eye of consecutive early or intermediate AMD patients at the Doheny UCLA Eye Centers. After 30 minutes of dark adaptation, the same eye underwent scotopic microperimetry with an 18-degree-wide grid (52 stimuli) centered on the fovea. The 2 en face CC angiograms obtained from each scan pattern were compensated for signal loss and averaged. The main outcome measures were correlation between percentages of flow deficits (FD3mm and FD6mm) and sMS in the central 10° (MS10) and the overall pattern (MS18). RESULTS: Thirty eyes of 30 patients were enrolled, with 14 (46.7%) having subretinal drusenoid deposits (SDD). In the averaged OCTA scans, the FD3mm was 12.56% ± 2.41% while the FD6mm was 9.33% ± 1.84%. The mean MS10 and MS18 were 13.84 ± 5.89 dB and 14.64 ± 5.21 dB, respectively. For the MS10, the multivariate regression analysis showed a significant association only with FD3mm (ß: -0.628, P < .001) while the MS18 was significantly correlated with both SDD (ß: -0.32, P = .047) and FD6mm (ß: -0.473, P = .005). CONCLUSIONS: Our study reports a significant correlation between the CC flow impairment and the sMS in eyes with early or intermediate AMD. If replicated in future longitudinal studies, the choriocapillaris FD may prove to be a useful parameter for evaluating the functional status and prognosis of these eyes.

Comparison and Correlation of Retinal Sensitivity Between Microperimetry and Standard Automated Perimetry in Low-tension Glaucoma.

PRéCIS:: Our study demonstrated that in low-tension glaucoma (LTG) patients, Microperimeter-3 (MP-3)-derived and Humphrey Field Analyzer (HFA)-derived retinal sensitivities were similar and strongly correlated, allowing the respective data to be interrelated. PURPOSE: To compare and correlate retinal sensitivities obtained by Nidek MP-3 with those obtained from the HFA in eyes with LTG. MATERIALS AND METHODS: In this prospective comparative study, 45 eyes of 24 LTG patients underwent retinal sensitivity assessments using the MP-3 (Nidek Technologies) and the HFA (Carl Zeiss Meditec) at the UCLA-Doheny Eye Center. Global and pointwise retinal sensitivity measurements were compared and correlated between the 2 devices. RESULTS: No statistically significant differences (P=0.85) were noted between the mean retinal sensitivities determined by each device (MP-3: 26.33±4.31 dB; range, 13.05 to 31.60 vs. HFA: 26.42±3.98 dB; range, 17.17 to 30.96), and a strong correlation (r=0.66, P<0.001) was noted for retinal sensitivity measurements. In addition, moderate to strong correlations were observed between the mean retinal sensitivity derived by MP-3 versus HFA-derived mean deviation (r=0.57, P<0.001), as well as, the pattern standard deviation (r=0.67, P<0.001). The intraclass correlation coefficient was excellent (ICC=0.80, 95% confidence interval, 0.63-0.89), while the Bland-Altman analysis showed good agreement between the 2 devices with respect to retinal sensitivity. CONCLUSION: Retinal sensitivity measurements obtained by the MP-3 microperimetry instrument and the standard automated HFA perimeter were similar and highly correlated in patients with LTG. Given the potential benefits of microperimetry technology such as auto-eye-tracking and potentially more precise structure-function correlations, the use of microperimetry to monitor visual function in glaucoma management warrants further consideration.

Reduction of Acanthamoeba Cyst Density Associated With Treatment Detected by In Vivo Confocal Microscopy in Acanthamoeba Keratitis.

PURPOSE: Acanthamoeba keratitis (AK) is a severe vision-threatening ocular infection that is frequently a diagnostic challenge. Treatment course is lengthy and often not fully effective. Contact lens wear has been recognized as the prime risk factor for AK. In vivo confocal microscopy (IVCM) is a noninvasive imaging modality that allows direct visualization of potential causative pathogens in real time with an established utility in the diagnosis of AK. In this study, we aim to assess the utility of IVCM in monitoring disease progression in contact lens wearers with culture-confirmed keratitis. METHODS: Fourteen eyes from 11 patients with culture-confirmed AK were included in this retrospective study. IVCM was performed during the patient's initial visit and all follow-up visits. All available confocal sequences were reviewed and graded in a masked fashion. Density of Acanthamoeba cyst infiltration and changes in the cyst density as a percentage of baseline cyst density measured at each patient's initial visit were calculated. A univariate regression analysis was performed to assess the association between treatment and changes in cyst density per month of treatment. RESULTS: Acanthamoeba cysts were identified by IVCM in all of these culture-confirmed cases of keratitis. Mean cyst density in the central cornea at presentation was 99 ± 64.9 cells per square millimeter (range, 38-255/mm). Cyst density in our study population significantly decreased by approximately 5.3% with each month of antiamebic treatment (P = 0.001; R = 0.41). CONCLUSIONS: Reduction in Acanthamoeba cyst density with treatment can be monitored by IVCM, which in turn can be used clinically in prognostication and disease monitoring of AK.

Evaluation of Corneal Epithelial Thickness Imaged by High Definition Optical Coherence Tomography in Healthy Eyes.

PURPOSE: To evaluate corneal epithelial thickness (CET) and corneal thickness (CT) in healthy eyes using spectral domain optical coherence tomography. METHODS: Thirty-six healthy eyes were imaged using the Cirrus high-definition (HD)-optical coherence tomography device. The average CET and CT were assessed using Cirrus Review Software within predefined concentric corneal ring-shaped zones. Specific regions of CET (superior, inferior, temporal, nasal, superonasal, inferotemporal, superotemporal, and inferonasal) were also assessed. The difference between zones was compared between males and females. RESULTS: The average CET was 48.3, 47.1, 46.1, and 45.8 µm in the 4 concentric zones (0-2, 2-5, 5-7, and 7-9 mm), respectively (P < 0.001). The average CT was 533.5, 550.8, and 579.4 µm in the 3 zones (0-2, 2-5, and 5-7 mm), respectively (P < 0.001). There was no statistically significant correlation between CET and CT in any of the measured zones. Males had thicker corneas than did females in each of the 3 CT zones (P < 0.05), but CET did not differ significantly. The CET superonasal-inferotemporal in 2.0 to 5.0 mm and CET superotemporal-inferonasal in 5.0- to 7.0-mm zones were significantly thinner in males than in females (-1.15 vs. 0.9 µm, -3.5 vs. -1.9 µm), respectively (P < 0.05). CONCLUSIONS: Optical coherence tomography-based analysis of CET reveals that it is thinner in the periphery, whereas the total corneal thickness is greater. Although total CT seems to be influenced by sex, CET is not. Regional and sex-based variations in CT may need to be considered when assessing corneal and epithelial alterations in the setting of disease.

Quantitative Analysis of Retinal and Choroidal Vascular Parameters in Patients With Low Tension Glaucoma.

PRéCIS:: By using OCT-A, we observed a reduction of the superficial macular, peripapillary, and optic nerve, as well as the choriocapillaris in eyes with low tension glaucoma, compared with normal controls. PURPOSE: The purpose of this study was to investigate macular and optic disc vascular parameters in patients with low tension glaucoma (LTG) using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, images were prospectively acquired from both eyes of 26 patients with clinically diagnosed LTG and 22 age-matched volunteers with normal healthy eyes using the Zeiss swept-source (SS) OCTA (Plex Elite 9000, Carl Zeiss Meditec). Perfusion density (PD) and vessel length density (VLD) within a 5 mm diameter circle centered over the macula and optic nerve head were analyzed. RESULTS: The final analysis cohort included 49 eyes with LTG and 40 healthy control eyes. Mean age was 60±10 years in the LTG group and 60±17 years in the control group. The LTG group had a statistically significant reduction in PD of the choriocapillaris (CC) compared with normal controls (71.74±8.37% vs. 80.48±3.84%; P<0.001). There was no statistically significant difference in PD between the LTG and control groups for the superficial vascular plexus (SVP), deep capillary plexus (DCP) or the optic nerve head and peripapillary area (ONH+PP) (P>0.05). The LTG group did show statistically significant reductions in VLD compared with normal controls for the SVP (2083.64±153.76 mm/mm vs. 2154.63±144.18 mm/mm; P=0.03) and ONH + PP (1813.76±271.69 mm/mm vs. 1950.23±169.33 mm/mm; P=0.03), whereas the DCP VD was similar between the 2 groups (P>0.05). CONCLUSIONS: Eyes with low tension glaucoma seems to show a lower CC perfusion density, as well as a lower SVP and ONH+PP vessel length density compared to normal eyes.

Correlation between Guttata Severity and Thickness of Descemet's Membrane and the Central Cornea.

Purpose: To characterize and correlate guttata severity, Descemet's membrane thickness (DMT), central cornea thickness (CCT) in corneas with guttae using specular microscopy and spectral-domain optical coherence tomography (SD-OCT) and test the Doheny Image Reading Center (DIRC) specular microscopy-based corneal guttata severity scale. Methods: Forty-nine eyes of 49 patients with guttata and 36 eyes of age-matched of 36 normal controls were enrolled in the study. Three images of the central cornea and four of the peripheral cornea (inferior, superior, nasal and temporal) of each eye were taken using the Konan NSP-9900 specular microscope. A volume scan of the central cornea cross-section was collected on each eye using the Heidelberg Spectralis SD-OCT. The density of endothelial guttata based on specular images was graded on a 0-4 scale, and the Descemet's membrane thickness (DMT) and central corneal thickness (CCT) were manually measured by two trained graders. Results: The DIRC corneal guttata severity scale showed good reproducibility of all corneal endothelial images (weighted Kappa = 0.87). Mean DMT was 16.1 ± 2.4 µm in controls and 25.5 ± 10.9 µm in corneas with guttata (P < 0.001). Mean CCT was 552 ± 26 µm in controls and 603 ± 55 µm in corneas with guttata (P < 0.001). Guttata severity was significantly correlated with both DMT (r = 0.743, P < 0.001) and CCT (r = 0.569, P < 0.001). Age was moderately correlated with DMT (r = 0.472, P = 0.003) and mildly correlated with guttata severity (r = 0.285, P = 0.031), but was not correlated with CCT (r = 0.058, P = 0.681). Guttatta grade 3 corneas displayed an increase in DMT and guttata grade 4 was associated with a significant increase in CCT. Conclusions: The DMT and CCT are increased in corneas with guttata. The higher density of guttae is correlated with increased thickness. Specular microscopy combined with SD-OCT can be used as a good approach to assess the severity of FECD.

Distinct Retinal Capillary Plexuses in Normal Eyes as Observed in Optical Coherence Tomography Angiography Axial Profile Analysis.

Optical coherence tomography angiography (OCTA) allows the retinal microvasculature to be visualized at various retinal depths. Previous studies introduced OCTA axial profile analysis and showed regional variations in the number and location of axially distinct vascular retinal plexuses. OCTA acquisition and processing approaches, however, vary in terms of their resulting transverse and axial resolutions, and especially the latter could potentially influence the profile analysis results. Our study imaged normal eyes using the Spectralis OCT2 with a full-spectrum, probabilistic OCTA algorithm, that, in marked contrast to split-spectrum approaches, preserves the original high OCT axial resolution also within the resulting OCTA signal. En face OCTA images are generally created by averaging flow signals over a finite axial depth window. However, we assessed regional OCTA signal profiles at each depth position at full axial resolution. All regions had two sharp vessel density peaks near the inner and outer boundaries of the inner nuclear layer, indicating separate intermediate and deep capillary plexuses. The superficial vascular plexus (SVP) separated into two distinct peaks within the ganglion cell layer in the parafoveal zone. The nasal, superior, and inferior perifovea had a deeper SVP peak that was shifted anteriorly compared to the parafoveal zone. Axial vascular density analysis with high-resolution, full spectrum OCTA thus allows healthy retinal vasculature to be precisely reconstructed and may be useful for clinically assessing retinal pathology.