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Purpose To identify baseline risk factors for macular atrophy (MA) development in HARBOR via a longitudinal assessment of monthly spectral-domain (SD)-OCT scans. Previous analyses of MA in HARBOR examined data from color fundus photography (CFP) and fluorescein angiography (FA). Design Retrospective, post hoc analysis of SD-OCT images from HARBOR ( ClinicalTrials.gov identifier, NCT00891735 ), a phase 3, multicenter, prospective, randomized, double-blind, active treatment–controlled clinical trial. Participants Patients (N = 1097) with subfoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD) treated with intravitreal ranibizumab 0.5 mg monthly (n = 275), 0.5 mg pro re nata (PRN) after 3 loading doses (n = 275), 2.0 mg monthly (n = 274), or 2.0 mg PRN (n = 273). Methods Evaluable SD-OCT macular cube scans from patients with 24 months of follow-up (N = 941) were examined monthly from baseline to month 24 by masked reading center–trained graders. Atrophy diagnosis criteria were consistent with those proposed by the Classification of Atrophy Meetings (CAM) group: hypertransmission of light into the choroid, loss of retinal pigment epithelium, and loss of outer retinal layers. Multivariable proportional hazards regression was performed for time to atrophy development. Main Outcome Measures Risk factors for MA as determined by time to MA development over 24 months of treatment. Results Baseline risk factors for MA were confirmed from prior analyses that used CFP and FA data: absence of subretinal fluid, presence of intraretinal cysts, presence of Type 3 neovascularization, and presence of atrophy in the fellow eye. This analysis of SD-OCT data identified new baseline risk factors for MA: higher central drusen volume, lower choroidal thickness, presence of nascent atrophy, presence of reticular pseudodrusen, and increased central foveal thickness. Ranibizumab treatment regimen and dose level were not found to be risk factors for MA development. Conclusions In this analysis of a major nAMD trial using CAM atrophy criteria, new baseline risk factors for MA development were identified using an SD-OCT dataset. Risk factors for MA development identified by prior analyses were confirmed. Monthly treatment with ranibizumab 0.5 mg was not found to be a risk factor for MA development over 24 months.

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

Purpose Previous studies of macular atrophy (MA) in HARBOR analyzed color fundus photography and fluorescein angiography image data. This study performed a longitudinal assessment of monthly spectral-domain (SD) OCT scans to determine MA prevalence, incidence, and progression in HARBOR. Design Post hoc analysis of SD OCT images from HARBOR ( ClincalTrials.gov identifier, NCT00891735 ), a phase 3 multicenter, prospective, randomized, double-blind, active treatment–controlled clinical trial. Participants Patients (n = 1097) with subfoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg monthly (n = 275), 0.5 mg pro re nata (PRN) after 3 loading doses (n = 275), 2.0 mg monthly (n = 274), or 2.0 mg PRN (n = 273). Methods Evaluable SD OCT macular cube scans from patients with 24 months of follow-up (N = 941) were examined by masked reading center–trained graders monthly from baseline to month 24. Atrophy diagnosis criteria were consistent with those proposed by the Classification of Atrophy Meetings (CAM) group: hypertransmission of light into the choroid, retinal pigment epithelium loss, and loss of outer retinal layers. Macular atrophy was considered Definite if all 3 criteria were met and Questionable if 2 were met. Study arms were compared for time to MA detection (log-rank test) and enlargement rates (time × arm interaction test). Main Outcome Measures Prevalence, incidence, and enlargement rates of MA. Results At baseline, imbalance in MA rates across ranibizumab arms was evident (0.5 mg monthly, 19.1%; 0.5 mg PRN, 16.1%; 2.0 mg monthly, 10.1%; 2.0 mg PRN, 10.5%). At month 24, new MA development rates in eyes without baseline MA were similar between ranibizumab doses (0.5 mg, 25.9%; 2.0 mg, 25.4%) and treatment regimens (monthly, 26.4%; PRN, 25.0%). No significant differences in enlargement rate of new atrophy area (P = 0.479, square-root transformed) or time to detection of new MA (P = 0.997) were evident among study arms. Conclusions In this analysis of a major nAMD trial using CAM atrophy criteria, no differences were observed in incidence or progression rates of new MA among study arms, ranibizumab doses, or treatment regimens. Monthly versus PRN treatment did not influence MA incidence or progression.

Purpose The purpose of this study was to investigate the choroidal luminal and interstitial stromal alterations using choroidal vascularity index (CVI) among different cohorts of dry age-related macular degeneration (dAMD) compared to healthy subjects. Methods Four distinct cohorts were collected: three different cohorts of patients with dAMD (i.e. drusen, reticular pseudodrusen [RPD], and geographic atrophy [GA]) and an age-matched cohort of healthy subjects (controls). CVI (the ratio between the luminal choroidal area [LCA] and the total choroidal area [TCA]) was calculated in the subfoveal 1000 µm area. Results One hundred twenty eyes (from 120 patients) were included (30 eyes in each cohort). The mean age was 76.6 ± 7.1 years. No statistical differences were disclosed in terms of age, axial length, and central macular thickness among study groups. TCA showed a different distribution among the four cohorts (P = 0.003), mainly due to the LCA changes (P = 0.001). Interestingly, CVI showed a different distribution among the four cohorts (P < 0.001). RPD showed a lower CVI in comparison to controls (P = 0.040), whereas GA showed a lower CVI in comparison to drusen, RPD, and controls (P = 0.001, P = 0.046, and P < 0.001, respectively). Conclusions Different cohorts of dAMD are characterized by different impairments of the choroidal vascular and stromal components, reflecting different degrees of AMD severity. Translational Relevance CVI provides insights for better understanding the pathogenesis of AMD.

To investigate the choroidal vascularity index (CVI) in patients affected by leptochoroid.Three distinct age-matched cohorts were collected: patients with reticular pseudodrusen (RPD) secondary to age-related macular degeneration, patients with high-myopia, and healthy controls. CVI was calculated in the subfoveal 6000 μm diameter area.54 eyes (54 patients) were included (18 eyes in each cohort). No statistical differences were disclosed in terms of age between controls, RPD patients (p = 0.062), and myopic patients (p = 0.070). Total choroidal area showed a different distribution among the 3 cohorts (p 0.001), due to the reduction of luminal and stromal choroidal area in both RPD and myopic groups in comparison to controls (p 0.001). Interestingly, CVI showed a different distribution between the 3 cohorts (p 0.001). In detail, RPD group showed no changes in CVI in comparison to controls (p = 1.000), whereas the myopic group showed a higher CVI in comparison to both RPD group and controls (p 0.001 in both analyses).Different changes of the choroidal vascular and stromal components characterize the leptochoroid secondary to RPD eyes and high-myopic eyes. The relative greater impairment of the vascular area in RPD eyes in comparison to myopic eyes could be at the basis of the lower development of RPD in patients with high myopia.

Preterm children have an increased risk of impaired vision from retinopathy, strabismus, and high refractive error. The aim of this study was to investigate the relationship between foveal parameters generated by optical coherence tomography angiography and visual function in preterm children.Eighty eyes (32 eyes of former preterm infants and 48 age-matched full-term control eyes) were analyzed. Subjects underwent complete eye examinations including best-corrected visual acuity and retinal imaging with the Optovue XR Avanti optical coherence tomography angiography device. Foveal morphologic parameters including foveal depth, central foveal thickness, inner retinal area, and outer retinal area were measured on a central horizontal B-scan. Foveal vasculature parameters including foveal avascular zone, superficial capillary plexus-vessel density, and deep capillary plexus-vessel density were measured on optical coherence tomography angiography.The best-corrected visual acuity was significantly affected in preterm children compared with controls (P0.0001). The central foveal thickness (P0.0001), inner retinal area (P = 0.01), and outer retinal area (P = 0.03) were significantly increased in preterm compared with control eyes. Foveal depth (P0.001) and foveal avascular zone (P0.001) were significantly decreased in preterm compared with control eyes. The superficial capillary plexus-vessel density (P = 0.01) and deep capillary plexus-vessel density (P = 0.003) at the fovea (1 mm) were significantly increased in preterm compared with control eyes. The best-corrected visual acuity was negatively correlated with foveal depth (r = -0.42, P = 0.001) and foveal avascular zone (r = -0.53, P0.001), and positively correlated with central foveal thickness (r = 0.32, P = 0.01) and inner retinal area (r = 0.32, P = 0.01), indicating that worse visual acuity was associated with a smaller foveal avascular zone, shallower foveal depth, increased central foveal thickness, and larger inner retinal area.Foveal morphology and vasculature changes in preterm children were associated with impaired visual function. Further longitudinal studies are required to evaluate these changes over time.

Purpose To quantify inner and outer retinal layer thicknesses and understand their relevance to visual function among young adults born extremely preterm (EP). Design Prospective observational study with 19 years of follow-up. Participants A total of 354 eyes (226 eyes of former EP infants and 128 age-matched full-term control eyes) from 177 young adults were evaluated. Among EP participants, 50% of eyes (112/226) were not previously diagnosed with neonatal retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require treatment in the neonatal period, and 13% of eyes (30) had neonatal cryotherapy or laser ablation for ROP. Methods Subjects underwent eye examinations including best-corrected visual acuity (BCVA) and Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) macular spectral-domain (SD) OCT imaging. Retinal layers were auto-segmented and thickness profiles were computed at the fovea by the instrument software. Main Outcome Measures Correlation between retinal sublayer thickness and BCVA. Results Compared with control eyes, the inner and outer retinal layers of EP eyes were significantly thicker and BCVA was significantly reduced. Retinal layer thicknesses and BCVA were similar for untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had increased inner and outer retinal layer thickness and decreased vision. Inner retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, P Conclusions Extremely premature birth influences maturation of the fovea and visual outcomes into early adult life. Increased ganglion cell layer thickness was associated with worse BCVA. Eyes requiring neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

Purpose: To compare foveal avascular zone density (FAZ) in the superficial (SCP) and deep (DCP) capillary plexus and vessel density (VD) in the macula in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept.Methods: Patients with DME were imaged at baseline, and 30 days after the 1st, 2nd and 3rd intravitreal aflibercept injection. Images were analyzed for the FAZ area in the SCP and DCP in each visit and VD.Results: Twenty eyes were enrolled. FAZ was 0.304 ± 0.131 mm2 in the SCP and 0.738 ± 0.5836 mm2 in the DCP at baseline. SCP FAZ was not significantly different whereas, FAZ in the DCP decreased (p = .035) after treatment. VD in the center was 20.62 ± 4.31 at baseline and decreased by 8% (p = .002). Parafoveal VD remained unchanged with treatment.Conclusion: DCP ischemia may improve after aflibercept treatment. Central macular vessel density was found to decrease post-treatment, but the clinical relevance needs further investigation.

Purpose To assess the reproducibility of confocal white-light color fundus photography (C-CFP) for the measurement of retinal pigment epithelial atrophy in comparison with confocal blue-light fundus autofluorescence (FAF) imaging and flash color fundus photography (F-CFP). Methods In this prospective study, eyes with age-related macular degeneration associated with evidence of retinal pigment epithelial atrophy were imaged by C-CFP, F-CFP, and FAF. Intergrader reproducibility of each modality was assessed by comparison of manual measurements by two expert graders. Results The mean areas of atrophy measured by the 2 graders were 6.67 ± 6.39, 6.35 ± 6.13, and 6.07 ± 5.48 mm for FAF, C-CFP, and F-CFP, respectively. The mean differences between the 2 graders in measuring the atrophic areas were 0.52, 0.69, and 1.62 mm for the three modalities. The intraclass correlation coefficient between the 2 graders for each modality was 0.998, 0.990, and 0.961, respectively. Conclusion Measurements of atrophy from C-CFP were similar to those obtained by FAF and F-CFP. The grading reproducibility for C-CFP, however, was better than that for F-CFP and approached the level of FAF imaging. The use of C-CFP as a tool for quantitatively monitoring atrophic age-related macular degeneration lesions warrants further study, particularly in the context of clinical trials.

Purpose To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design Multicenter, international, prospective cohort study. Methods Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Prog ression of Star gardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

Purpose To study the macular microvascular networks in patients affected by chronic Leber hereditary optic neuropathy (LHON) using optical coherence tomography angiography (OCTA), and to quantify these changes in different macular sectors. Design Prospective cross-sectional study. Methods Patients with a clinical and molecularly confirmed diagnosis of LHON (affected patients in the chronic stage) were enrolled from the neuro-ophthalmology clinic at the Doheny-UCLA. Patients and controls underwent a complete ophthalmologic evaluation, including imaging with OCTA. Results Twenty-nine eyes from 15 LHON patients (14 male) and 20 eyes from 20 healthy subjects (13 male) were included in the analysis. Mean age was 32.0 ± 14.2 years (range 16-49 years) in the LHON group and 34.2 ± 10.1 years (range 23-48 years) in the control group (P = .552). In the parafoveal region, the vessel length density was lower in LHON patients, at both the SCP (9.1% ± 0.5% and 9.3% ± 0.4%, P = .041) and DCP (9.4% ± 0.5% and 9.8% ± 0.3%, P = .008) levels. In the sectorial analysis, vascular changes remained significant only in the parafoveal nasal and inferior regions. Univariate linear regression analysis demonstrated that the strongest associations with visual acuity were with parafoveal SCP perfusion density (R2 = .276, P = .045) and parafoveal SCP vessel length density (R2 = .277, P = .044). Conclusions LHON eyes have SCP and DCP changes that are mainly confined to the nasal and inferior parafoveal sectors that correspond to the papillomacular bundle. Furthermore, visual loss is associated with the SCP flow impairment, but not with the OCT-detectable structural damage.

Purpose To investigate the effect of multiple enface image averaging on image quality of the optical coherence tomography angiography (OCTA). Methods Twenty-one normal volunteers were enrolled in this study. For each subject, one eye was imaged with 3 × 3 mm scan protocol, and another eye was imaged with the 6 × 6 mm scan protocol centred on the fovea using the ZEISS Angioplex™ spectral-domain OCTA device. Eyes were repeatedly imaged to obtain nine OCTA cube scan sets, and nine superficial capillary plexus (SCP) and deep capillary plexus (DCP) were individually averaged after registration. Results Eighteen eyes with a 3 × 3 mm scan field and 14 eyes with a 6 × 6 mm scan field were studied. Averaged images showed more continuous vessels and less background noise in both the SCP and the DCP as the number of frames used for averaging increased, with both 3 × 3 and 6 × 6 mm scan protocols. The intensity histogram of the vessels dramatically changed after averaging. Contrast-to-noise ratio (CNR) and subjectively assessed image quality scores also increased as the number of frames used for averaging increased in all image types. However, the additional benefit in quality diminished when averaging more than five frames. Averaging only three frames achieved significant improvement in CNR and the score assigned by certified grades. Conclusion Use of multiple image averaging in OCTA enface images was found to be both objectively and subjectively effective for enhancing image quality. These findings may of value for developing optimal OCTA imaging protocols for future studies.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. In this study, we compare the performance of retinal fundus images and genetic-information-based machine learning models for the prediction of late AMD. Using data from the Age-related Eye Disease Study, we built machine learning models with various combinations of genetic, socio-demographic/clinical, and retinal image data to predict late AMD using its severity and category in a single visit, in 2, 5, and 10 years. We compared their performance in sensitivity, specificity, accuracy, and unweighted kappa. The 2-year model based on retinal image and socio-demographic (S-D) parameters achieved a sensitivity of 91.34%, specificity of 84.49% while the same for genetic and S-D-parameters-based model was 79.79% and 66.84%. For the 5-year model, the retinal image and S-D-parameters-based model also outperformed the genetic and S-D parameters-based model. The two 10-year models achieved similar sensitivities of 74.24% and 75.79%, respectively, but the retinal image and S-D-parameters-based model was otherwise superior. The retinal-image-based models were not further improved by adding genetic data. Retinal imaging and S-D data can build an excellent machine learning predictor of developing late AMD over 2–5 years, the retinal imaging model appears to be the preferred prognostic tool for efficient patient management.

BackgroundTo compare and correlate the retinal sensitivity measurements obtained with Nidek Microperimetry-3 (MP-3) and the CenterVue Macular Integrity Assessment (MAIA) microperimeters among healthy subjects.MethodsIn this prospective comparative study, 31 eyes of 23 subjects underwent complete ophthalmological examination including retinal sensitivity assessments using two microperimeters, the MP-3 (Nidek Technologies) and the MAIA (CenterVue). The mean retinal sensitivity (dB) and its corresponding luminance (asb) and contrast (log units) were analysed between the two instruments. The interdevice reproducibility and level of agreement between the sensitivity values of the devices were assessed.ResultsThe mean retinal sensitivity (dB) measured by the MP-3 (25.02±1.06 dB, range: 20.90–26.70) was significantly (pConclusionRetinal sensitivity measures higher, but luminance and contrast sensitivity measure lower for MAIA-generated values compared with the MP-3. The relationships, however, appeared fairly consistent, and application of a standard correction factor allowed the data to be inter-related, at least for normal eyes.

Purpose To evaluate retinal vascular status during pregnancy by using optical coherence tomography angiography (OCTA). Methods Women in their third trimester of pregnancy and nonpregnant age-matched women were recruited for this prospective, case-control study. Subjects were imaged with OCTA. Main outcome measures were foveal avascular zone parameters, perfusion density (PD) percentage in the superficial retinal capillary plexus (SCP), PD percentage in the deep retinal capillary plexus (DCP), SCP vessel length density (VLD), DCP-VLD, and choriocapillaris (CC) flow voids (i.e., flow deficits in the CC). Results Nineteen eyes of 10 pregnant subjects and 44 eyes of 27 nonpregnant control women were included. Mean ages were 36 ± 7 and 35 ± 8 years (SD), respectively (P value = 0.78). Mean gestational age of pregnant women was 33 weeks (range = 29-39, SD = 3). There was a significant reduction in the SCP-PD in the entire scan and in the nasal Early Treatment Diabetic Retinopathy Study subfield (47.9 vs. 49.7, P = 0.04 and 49.3 vs. 51.6, P = 0.03, respectively) in the pregnant cohort versus controls. There was a significant increase in the DCP-PD in the parafoveal region and in the temporal and inferior Early Treatment Diabetic Retinopathy Study subfields (58.0 vs. 55.9, P = 0.03; 57.9 vs. 55.5, P = 0.02; 58.0 vs. 55.9, P = 0.05, respectively) in the pregnant cohort. There was no significant difference in foveal avascular zone parameters, SCP-VLD, DCP-VLD, or CC flow voids between the two populations. Conclusions This study detected retinal vasculature changes in the third trimester of pregnancy. Mean SCP-PD was significantly decreased and mean DCP-PD was significantly increased without a difference in VLD.

To report optical coherence tomography angiography (OCTA) values in healthy pediatric eyes and to identify factors that may modify these values.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.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 (P0.0001). 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).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.

Background/AimsTo investigate the presence of short-wave fluorophores within regions of age-related macular degeneration (AMD)-associated macular atrophy (MA) area.MethodsThis is a prospective, observational, cross-sectional case series. 25 eyes (18 patients) with late AMD and clinically identified MA were enrolled. Eyes were imaged using a confocal light-emitting diode blue-light fundus autofluorescence (FAF) device (EIDON, CenterVue, Padua, Italy) with 450 nm excitation wavelength and the capability for ‘colour’ FAF imaging, including both the individual red and green components of the emission spectrum. To produce images with a high contrast for isolating the green component, the red component was subtracted from the total FAF image. The main outcome measure was the presence of green emission fluorescence component (GEFC) within the MA area. Volume spectral domain optical coherence tomography (SD-OCT) scans were obtained through the macula and the OCT was correlated with the MA lesions identified on the FAF images, including regions of increased GEFC.ResultsOf the investigated eyes, 11 out of 25 (44.0 %) showed the absence of GEFC in the MA area, whereas 14 eyes (56.0%) were characterised by GEFC within the MA area. The presence and distribution of GEFC in the MA area correlated with the presence of hyper-reflective material over Bruch’s membrane on the corresponding SD-OCT scans.ConclusionShort-wave fluorophores, which contribute to the GEFC, are present in the MA area and appear to correspond to residual debris or drusenoid material. Short-wavelength fluorophores revealed by colour FAF imaging may warrant further study.

Purpose To investigate the choriocapillaris in children with amblyopia, using optical coherence tomography angiography (OCT-A). Methods Patients with amblyopia and age-matched controls were prospectively imaged using OCT-A. On OCT-A, the choriocapillaris measures 30 μm starting 31 μm posterior to the retinal pigment epithelium. The section of choriocapillaris under superficial retinal vessels was excluded from analysis to avoid shadowing or projection artifacts. The main outcome measure was choriocapillaris vessel density. Secondary outcome measures were foveal macular thickness and parafoveal macular thickness. Results A total of 20 eyes of 16 patients with amblyopia and 25 eyes of 25 controls were included. Mean age of amblyopic subjects was 7.6 ± 3.6 years; of controls, 9.3 ± 2.2 years ( P = 0.10). Mean refractive error of subjects was 4.3 ± 6.2 D; of controls, 0.0 ± 1.6 D ( P = 0.004). Mean choriocapillaris vessel density was 74.8 ± 5.8 in the amblyopic group and 71.1 ± 3.6 in the control group, which was significant even after adjusting for age and refractive error ( P = 0.012). There was no difference between groups in foveal macular thickness or parafoveal macular thickness; however, outer parafoveal macular thickness (the inner boundary of the inner nuclear layer to the retinal pigment epithelium outer boundary) was significantly greater in amblyopic eyes than in control eyes, even after adjusting for age and refractive error (203 ± 11 μm and 189 ± 12 μm, resp. [ P = 0.014]). Conclusions In our study cohort, amblyopic eyes were found to have increased choriocapillaris vessel density as well as a greater outer parafoveal macular thickness, which may be due to alterations in outer retinal maturation.

Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging.To investigate multiple en face image averaging on OCTA images of the choriocapillaris.Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016.All participants underwent OCTA imaging of the macula covering a 3 × 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images.Vessel caliber measurement.Seventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) µm (range, 9.6-40.2 µm). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P .001), smaller average size of the flow voids (911 [95% CI, 301-1521] µm2 vs 1364 [95% CI, 645-2083] µm2, P .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0%-67.8%], P .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images.Multiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers.

Purpose The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Methods Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. Results A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Conclusion Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration.

Importance The repeatability and reproducibility of quantitative metrics from optical coherence tomographic angiography (OCTA) must be assessed before these data can be confidently interpreted in clinical research and practice. Objective To evaluate the repeatability and reproducibility of OCTA-derived retinal vascular quantitative metrics. Design, Setting and Participants In this cross-sectional study, 21 healthy volunteers (42 eyes) and 22 patients with retinal disease (22 eyes), including 14 with age-related macular degeneration, 3 with epiretinal membrane, 2 with diabetic retinopathy, 2 with myopic macular degeneration, and 1 with retinal vein occlusion, were enrolled. Participants were recruited from September 1 through November 31, 2016. Each eye underwent 3 repeated scans with 3 instruments for a total of 9 acquisitions. Eyes were randomly assigned to scanning with a 3 × 3-mm or 6 × 6-mm pattern. Eyes were excluded from subsequent analysis if any acquisition had a signal strength of less than 7. Repeatability (defined as the agreement in measurements within a device) and reproducibility (defined as the agreement between devices of the same type) were assessed by intraclass correlation coefficient (ICC) and coefficient of variation. Exposures All eyes underwent scanning using 3 separate devices. Main Outcomes and Measures Vessel length density (VLD) and perfusion density (PD) of the superficial retinal vasculature. Results A total of 21 healthy volunteers (8 men and 13 women; mean [SD] age, 36 [6] years) and 22 patients with retinal disease (15 men and 7 women; mean [SD] age, 79 [9] years) underwent evaluation. Of these, 40 of 42 normal eyes and 15 of 22 eyes with retinal disease met signal strength criteria and were included in this analysis. The ICC among the 3 consecutive scans ranged from 0.82 to 0.98 for VLD and from 0.83 to 0.95 for PD. The coefficient of variation (CV) ranged from 2.2% to 5.9% for VLD and from 2.4% to 5.9% for PD. For reproducibility, the ICC ranged from 0.62 to 0.95 and the CV was less than 6% in all groups. The agreement was highest for the 3 × 3-mm pattern in the inner ring (ICC range, 0.92 [95% CI, 0.85-0.96] to 0.96 [95% CI, 0.93-0.98]) and 6 × 6-mm pattern in the outer ring (ICC range, 0.93 [95% CI, 0.86-0.97] to 0.96 [95% CI, 0.92-0.98]). Conclusions and Relevance Vessel length density and PD of the superficial retinal vasculature can be obtained from OCTA images with high levels of repeatability and reproducibility but can vary with scan pattern and location.

BACKGROUND AND OBJECTIVE: To compare macular thickness measurement algorithms of two different spectral-domain optical coherence tomography (SD-OCT) devices in eyes affected by dry age-related macular degeneration (AMD). PATIENTS AND METHODS: Patients with dry AMD and healthy volunteers from the retina clinic of the Doheny Eye Center – UCLA were imaged using two different SD-OCT devices: the RS-3000 Advance (Nidek, Padova, Italy) and the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). All patients had been previously diagnosed with drusen or geographic atrophy due to AMD. The commercial instrument software was used to generate the macular retinal thickness measurements, and measurements were compared between devices. RESULTS: Eighty-five diseased eyes from 49 patients and 16 healthy control eyes from eight normal volunteers were included in this study. The macular thickness measurements generated by the two instruments in eyes with AMD differed significantly in mean retinal thickness in the foveal center subfield (257.34 μm ± 51.72 μm using the Nidek OCT vs. 238.20 μm ± 51.89 μm using the Cirrus OCT; P < .001). The mean difference in macular thickness between the two devices was 19.14 μm ± 5.84 μm for diseased eyes and 17.06 μm ± 5.28 μm in normal control eyes, and this was not statistically different between the two groups ( P > .05). The macular thickness measurements in diseased eyes, as evaluated by the two different instruments, however, showed excellent correlation (r = 0.99; P < .001), with an intraclass correlation coefficient of 0.99 (95% confidence interval, 0.98–0.99). Post hoc evaluation of cases with larger differences also showed differences in foveal center selection and variabilities in boundary selection with specific pathology. CONCLUSION: Macular thickness measurements provided by the Nidek and Cirrus OCT instruments in eyes with dry AMD are highly correlated but show a consistent difference, which may allow the use of a standard correction factor to be applied to better interrelate measurements between the devices. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:410–415.]

To investigate the impact of multiple en face image averaging on quantitative measurements of the retinal microvasculature using optical coherence tomography angiography (OCTA).Prospective, observational, cross-sectional case series.Twenty-one healthy individuals with normal eyes.Macular OCTA images were acquired from all participants using the Zeiss Cirrus 5000 with Angioplex OCTA software (Carl Zeiss Meditec, Dublin, CA). Nine OCTA cube scans per eye were obtained and 9 superficial retinal layer (SRL) and deep retinal layer (DRL) en face OCTA image slabs were averaged individually after registration. Quantitative parameters from the retinal microvasculature were measured on binarized and skeletonized OCTA images and compared with single OCTA images without averaging.Vessel density (VD), vessel length density (VLD), vessel diameter index (VDI), and fractal dimension (FD).Participants with artifact or poor image quality were excluded, leaving 18 eyes for the analysis. After averaging, qualitatively there was apparent reduction in background noise, and fragmented vessels in the images before averaging became continuous with smoother walls and showed sharper contrast in both the SRL and DRL. Binarized and skeletonized derivates of these averaged images also showed fewer line fragments and dots in nonvascular areas and more continuous vessel images than those of images without averaging. In both SRL and DRL, VD (P = 0.0010 and P = 0.0003, respectively), VLD (P0.0001 for both), and FD (P0.0001 for both) significantly decreased and VDI significantly increased after averaging (P0.0001 for both).Averaging of multiple en face OCTA images improves image quality and also significantly impacts quantitative measurements. Reducing noise that could be misinterpreted as flow and annealing discontinuous vessel segments seem to be major mechanisms by which averaging may be of benefit.

Purpose To investigate the level of inaccuracy of retinal thickness measurements in tilted and axially stretched optical coherence tomography (OCT) images. Methods A consecutive series of 50 eyes of 50 patients with age-related macular degeneration were included in this study, and Cirrus HD-OCT images through the foveal center were used for the analysis. The foveal thickness was measured in three ways: (1) parallel to the orientation of the A-scan (Tx), (2) perpendicular to the retinal pigment epithelium (RPE) surface in the instrument-displayed aspect ratio image (Ty), and (3) thickness measured perpendicular to the RPE surface in a native aspect ratio image (Tz). Mathematical modeling was performed to estimate the measurement error. Results The measurement error was larger in tilted images with a greater angle of tilt. In the simulation, with axial stretching by a factor of 2, Ty/Tz ratio was > 1.05 at a tilt angle between 13° to 18° and 72° to 77°, > 1.10 at a tilt angle between 19° to 31° and 59° to 71°, and > 1.20 at an angle ranging from 32° to 58°. Of note with even more axial stretching, the Ty/Tz ratio is even larger. Tx/Tz ratio was smaller than the Ty/Tz ratio at angles ranging from 0° to 54°. The actual patient data showed good agreement with the simulation. The Ty/Tz ratio was greater than 1.05 (5% error) at angles ranging from 13° to 18° and 72° to 77°, greater than 1.10 (10% error) angles ranging from 19° to 31° and 59° to 71°, and greater than 1.20 (20% error) angles ranging from 32° to 58° in the images axially stretched by a factor of 2 (b/a = 2), which is typical of most OCT instrument displays. Conclusions Retinal thickness measurements obtained perpendicular to the RPE surface were overestimated when using tilted and axially stretched OCT images. Translational relevance If accurate measurements are to be obtained, images with a native aspect ratio similar to microscopy must be used.

To develop a simple, clinically practical, optical coherence tomography (OCT)-based scoring system for early age-related macular degeneration (AMD) to prognosticate risk for progression to late AMD. We retrospectively reviewed OCT images (512 × 128 macular cube, Cirrus) from 138 patients diagnosed of early AMD in at least one eye and follow-up of at least 12 months. For patients with early AMD in both eyes, only the right eye was chosen as the study eye for longitudinal assessment. Scans were graded on four SD-OCT criteria associated with disease progression in previous studies: drusen volume within a central 3-mm circle ≥0.03 mm3, intraretinal hyperreflective foci (HRF), hyporeflective foci (hRF) within a drusenoid lesion (DL), and subretinal drusenoid deposits (SDD). Each criterion was assigned one point. For risk assessment of the study eye, the baseline status of the fellow eye was also considered, and thus these four features were also assessed in the fellow eye. The number of risk factors were summed for both eyes, yielding a total score (TS) of 0 to 8 for each patient. A fellow eye with evident choroidal neovascularization (CNV) or atrophy automatically received 4 points. Scores were then grouped into four categories to facilitate comparative analysis: I. (TS of 0, 1, 2), II. (TS of 3, 4), III. (TS of 5, 6) and IV. (TS of 7, 8). Correlation of baseline category assignment with progression to late AMD (defined as the presence of atrophy or CNV on OCT) by the last follow-up visit was evaluated with logistic regression analysis. The rate of progression to late AMD was 39.9% (55/138). Progression rates by category (I to IV) were 0, 14.3, 47.5, and 73.3%, respectively. Logistic regression analysis showed risk of progression to late AMD was 3.0 times (95% CI: 1.2–7.9) higher for an eye assigned to category IV than for an eye in category III and 16.4 (95% CI: 4.7–58.8) times higher than for an eye in category II. A simple scoring system relevant to prognosis for early AMD, and practical for use in a busy clinic, can be developed using SD-OCT criteria alone.

Purpose Keratoconus is a degenerating disease of the eye which causes an irregularly shaped cornea leading to impairment of vision.The role of proteases in keratoconus has been a topic of substantial discussion and speculation over many years.This study was designed to examine the levels and activity of proteases in the tear film of people with keratoconus. Methods A case-controlled study was performed studying the tear proteome of keratoconus patients(K) and controls(N).Basal tears were collected using a capillary tube.Total protein(TP)in tears was estimated using BCA assay;the levels of lactoferrin(Lf),secretory immunoglobin A(sIgA) and serum albumin were measured using specific ELISAs.Levels and activity of tear proteases were studied using Raybiotech® Antibody Array and EnzChek® Assay Kits respectively. Results There was a two-fold (p=0.0001) decrease in TP levels between K(3.86+1.62 mg/ml) and N(7.00+1.58 mg/ml). Levels of Lf(0.67+0.28 vs. 1.13+0.29 mg/ml) and sIgA(0.78+0.36 vs. 1.70+0.66 mg/ml) were also significantly(p=0.0001) reduced in K. The expression levels of matrix metalloproteinases(MMP)-1,-2,-3,-7,-13,interleukins(IL)-1α,-3,-4,-5,-6,-8,-10 and tumour necrosis factor(TNF)-α,-β were significantly(p=0.01)altered between K and N. Tear proteolysis(gelatinase/collagenase)was expressed as Fluorescence Intensity(FI).The activity of gelatinases(87.54+33.57 vs. 45.79+24.60 FI,p=0.0002)and collagenases(6.11+3.18 vs. 3.56+2.03 FI,p=0.03)were significantly increased in K. Conclusion The tears of people with keratoconus expressed high levels of proteases, increased proteolysis and a profoundly altered protein profile, which might change with the severity of the disease.These findings may lead the way to understanding or monitoring disease progression.