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PURPOSE: Epidemiologically, men have a higher incidence, severity, and progression of diabetic retinopathy (DR) than women. We investigated microvascular differences between men and women with diabetes on optical coherence tomography angiography (OCTA). METHODS: Three × 3 mm OCTA macula scans of non-diabetic and patients with diabetes were obtained. Vascular parameters included parafoveal vessel density (VD), vessel length density (VLD), and flow index (FI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) as well as foveal avascular zone (FAZ) area and perimeter. Multivariable linear regression was used for statistical analysis. RESULTS: There were 1809 patients with diabetes and 217 non-diabetic participants that were included in this study. Diabetic individuals included those with no DR (n = 1356), mild non-proliferative DR (NPDR; n = 286), moderate NPDR (n = 126), and severe NPDR/proliferative DR (PDR; n = 41). Male sex was significantly associated with smaller FAZ area/perimeter and lower DCP VLD in both non-diabetic subjects and patients with diabetes. Male sex in the diabetic group was additionally associated with lower SCP VD/VLD and DCP VD. Addition of an interaction between male sex and diabetes status in the interaction analysis showed that being male and diabetic conferred increased reduction in DCP VD and VLD compared to sex-based changes in non-diabetics. Larger FAZ perimeter, lower SCP VD/VLD, and lower DCP VLD were associated with poorer visual acuity in diabetics. CONCLUSIONS: On OCTA, male patients with diabetes may have more severe microvascular disease especially in the DCP compared to women. TRANSLATIONAL EVIDENCE: Sex-based alterations in diabetic microvascular disease has the potential to influence future basic and clinical studies as well as the implementation of OCTA disease markers.

PurposeTo investigate any associations between cigarette smoking and retinal microvascular changes in diabetic patients without visible retinopathy.DesignRetrospective, cross-sectional study.Participants1099 eyes from 1099 diabetic patients with no clinical evidence of diabetic retinopathy (DR) were included in this study.MethodsDiabetic patients underwent optical coherence tomography angiography (OCTA) scanning at Zuckerberg San Francisco General Hospital and Trauma Center between April 2018 and September 2019. Patient demographic and clinical information was collected. Standard bivariate statistics and multivariate linear regression were performed.Main outcome measuresOCTA parameters included metrics related to the foveal avascular zone (FAZ; area, perimeter, circularity), perfusion density (PD; full, center, inner), and vessel length density (VLD; full, center, inner).ResultsThe study population included 750 non-smokers and 349 smokers. FAZ perimeter was the only OCTA parameter that was significantly different between the two groups on uncontrolled analysis (P = 0.033). Multivariate regression analyses revealed significant associations between lower VLD full (β = -0.31, P = 0.048), lower VLD inner (β = -0.35, P = 0.046) and a history of smoking. No significant associations between cigarette smoking and either FAZ or PD were detected.ConclusionsOur results suggest that smoking is likely associated with deleterious changes in the retinal microvasculature of patients with a history of diabetes and no visible DR. Based on these findings, diabetic patients with a history of smoking may benefit from higher prioritization in terms of ophthalmic screening.

Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45-65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities (p = 0.029 and p = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 (p = 0.025) and day 90 (p = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.

PurposeTo 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.DesignComparison of diagnostic tools.MethodsA 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.ResultsGBCs 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.ConclusionsGBCs 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.

PURPOSE: To characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred thirty-nine eyes (23 healthy eyes, 36 preperimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for preperimetric glaucoma eyes, and 2.6 years for POAG eyes. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the same 3×3-mm2 GCC scan slab were evaluated. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors were evaluated. MAIN OUTCOME MEASURES: The rates of GCC thinning and macular vessel density loss. RESULTS: Significant rates of GCC thinning and macular vessel density decrease were detectable in all diagnostic groups (all P < 0.05). In healthy eyes and preperimetric glaucoma eyes, the normalized rates of GCC thinning and macular vessel density decrease were comparable (all P > 0.1). In contrast, the normalized rate (mean, 95% confidence interval) of macular vessel density decrease in the POAG eyes (-7.12 [-8.36, -5.88]%/year) was significantly faster than GCC thinning (-2.13 [-3.35, -0.90]%/year; P < 0.001). In the POAG group, more than two thirds of the eyes showed faster macular vessel density decrease than GCC thinning; faster macular vessel density decrease rate was associated significantly with worse glaucoma severity (P = 0.037). The association between GCC thinning rate and glaucoma severity was not significant (P = 0.586). Intraocular pressure during follow-up significantly affected the rate of GCC thinning in all groups (all P < 0.05) but showed no association with the rate of macular vessel density decrease. CONCLUSIONS: Both GCC thinning and macular vessel density decrease were detectable over time in all diagnostic groups. In POAG eyes, macular vessel density decrease was faster than GCC thinning and was associated with severity of disease. Macular vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

PurposeTo investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline.DesignLongitudinal cohort study.ParticipantsA total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected.MethodsOCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity.Main outcome measuresMagnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time.ResultsThe median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding.ConclusionsCorrelations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

BackgroundTo assess the functional and structural outcomes of macular buckling using a silicone sponge-titanium exoplant for the treatment of foveoschisis (FS) and full-thickness macular holes (FTMHs) in highly myopic eyes.MethodsForty-nine consecutive patients with high myopia who underwent macular buckling for the treatment of FS and FTMHs were included. The outcomes measured included the anatomical success rate with FS resolution, retinal reattachment, MH closure, best corrected visual acuity (BCVA), axial length (AL) and complications of surgery. Moreover, the correlations between the BCVA at year three and series of factors, including age, duration of symptoms, baseline BCVA, AL, surgical type, preoperative macular status and severity of myopic maculopathy, were analysed.ResultsThis study involved 28 patients (28 eyes) with FS and 21 patients (21 eyes) with FTMHs with macular detachment. Retinal reattachment was achieved in 100% of cases, while MH closure was achieved in 76.19% of cases. The BCVA significantly improved one year after macular buckling in the FS cases and two years after macular buckling in the FTMH cases, and it remained stable throughout the rest of the follow-up period. The mean AL decreased by 2.09 mm postoperatively. No major perioperative complications were observed, although one patient needed to explant the buckling device due to intolerable diplopia.ConclusionMacular buckling with a silicone sponge-titanium exoplant may represent a safe and effective surgical option for the treatment of FS and FTMH in highly myopic eyes. Macular buckling showed a high closure rate and virtually no tendency to recur.

PurposeTo determine whether quantitative OCT angiography (OCTA) parameters can be used to distinguish among eyes at various stages of diabetic retinopathy (DR) in an urban safety-net hospital population.DesignProspective cross-sectional study.ParticipantsThree hundred twenty-nine eyes from 329 patients were included in this study: 90 nondiabetic patients, 170 diabetic patients without DR, 57 diabetic patients with mild to moderate nonproliferative DR (NPDR), and 12 diabetic patients with severe NPDR to proliferative DR.MethodsPatients underwent OCTA imaging and ultra-widefield fundus photography at Zuckerberg San Francisco General Hospital and Trauma Center between April and October 2018. For participants with diabetes, imaging was classified according to DR severity by a telemedicine reading center. Eight OCTA parameters were analyzed. Perfusion density and vessel length density (VD) were examined from both the superficial capillary plexus (SCP) and deep capillary plexus. The other 4 parameters were examined only from the SCP. Total extrafoveal avascular area (tEAA) was based on the area of absent capillary vessels. Foveal avascular zone (FAZ)-related metrics consisted of FAZ area, FAZ circularity index, and FAZ acircularity index.Main outcome measuresArea under the receiver operating characteristic curve (AUC) for OCTA parameters to distinguish among groups according to DR severity.ResultsAll OCTA parameters demonstrated a significant relationship with DR severity (P < 0.05). No significant difference was found when comparing nondiabetic participants versus diabetic participants without retinopathy. The FAZ area was the only metric that demonstrated a significant difference between genders: mean of 0.29±0.12 mm2 in men and 0.34±0.13 mm2 in women (P < 0.001). Receiver operating characteristic curve analyses showed that tEAA had the highest AUC when comparing various stages of the disease.ConclusionsIn this urban, public hospital population, quantification of retinal vascular findings with OCTA imaging was a useful means of distinguishing patients according to DR severity. Because these results were similar to those of other tertiary referral centers, it would be reasonable to perform further DR-related OCTA studies in this population and expect generalizable results.

PRéCIS:: There is diagnostic information in the outer region of optical coherence tomography angiography (OCT-A) macula scans not available in the inner region, and this information is especially useful in the early stages of glaucoma.PurposeThe aim of this study was to evaluate the diagnostic accuracy of 3×3 and 6×6 mm macula OCT-A scans for classifying healthy, mild glaucoma, and moderate to severe glaucoma eyes.MethodsParticipants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality 3×3 and 6×6 mm OCT-A images of the macula acquired on the same day were included in this cross-sectional study. The area under the receiver operating characteristic (AUC) curves were calculated to assess the diagnostic accuracy of vessel density (VD) of both scan sizes for differentiating between 3 diagnostic groups.ResultsTwo hundred seventy-nine eyes (89 healthy, 127 with mild glaucoma, and 63 with moderate to severe glaucoma) from 190 subjects were included in this study. The VD of the outer area of the 6×6 mm scan size had higher diagnostic accuracy compared with the VD of the inner area of the 3×3 mm scan when differentiating between healthy and mild glaucoma (3×3 mm AUC=0.71 and 6×6 mm AUC=0.79, P=0.032). The VD of the outer area of the 6×6 mm scans had only similar diagnostic accuracy compared with the inner area of the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes (AUC=0.90 for 3×3 mm and 0.92 for 6×6 mm, P=0.279). The VD of the inner area of the 6×6 mm scan size had similar diagnostic accuracy to the corresponding area of the 3×3 mm scan in both diagnostic categories.ConclusionThe diagnostic accuracy of VD using the 6×6 mm macula OCT-A scan was better than the 3×3 mm scan when differentiating between healthy and mild glaucoma eyes, and similar to the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes.

PurposeTo investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity.MethodsParticipants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models.ResultsA total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p

PurposeTo review central structure-function (SF) relationships in glaucoma; to compare contributions of within-session and between-session variability to total variability of macular optical coherence tomography (OCT) thickness measurements; and to test the hypothesis that longitudinal within-eye variability of central SF relationships is smaller than between-individual variability.MethodsWe reviewed the pertinent literature on central SF relationships in glaucoma. Thirty-eight eyes (20 normal or glaucoma subjects) had ×3 macular images per session over 3 sessions, and superpixels thickness measurements for ganglion cell layer (GCL), ganglion cell/inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full macular thickness (FMT) were exported. Linear mixed models were used for estimating contributions of between- and within-session variability to total thickness variability. One hundred twenty eyes with ≥3 10° visual fields (VFs)/OCT images were enrolled for the longitudinal study. We investigated within-eye longitudinal SF relationships (GCIPL thickness vs VF total deviations) with a change-point regression model and compared within-eye to between-individual variabilities with components-of-variance models.ResultsIn the cross-sectional study, the between-session component contributed 8%, 11%, 11%, and 36% of total variability for GCL, GCIPL, GCC, and FMT, respectively. In the longitudinal study, between-individual variability explained 78%, 77%, and 67% of total SF variability at 3.4°, 5.6°, and 6.8° eccentricities, respectively (P < .05). SF relationships remained stable over time within individual eyes.ConclusionsWithin-session variability accounts for most of macular thickness variability over time. Longitudinal within-eye SF variability is smaller than between-individual variability. Study of within-eye SF relationships could help clinicians better understand SF linking in glaucoma and help refine progression algorithms. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

PurposeTo assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer.MethodsThis was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader.ResultsSixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05).ConclusionOptical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.

PurposeTo 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.DesignCross-sectional study.MethodsMacula (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.ResultsMacular 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 1.19 μm in Avanti parafoveal ganglion cell complex, 1.13 μm in Spectralis ganglion cell inner plexiform layer, and 1.01 μm in Spectralis circumpapillary retinal nerve fiber layer, with R2 of 0.19 (P = .006), 0.23 (P = .002), and 0.24 (P = .002), respectively.ConclusionsONH and macula OCTA VD and thickness are associated with the severity of visual field damage in advanced primary open angle glaucoma.

PurposeTo characterize and compare the ganglion cell complex (GCC) thickness and macula vessel density in preperimetric and early primary open-angle glaucoma (POAG) eyes.DesignCross-sectional study.MethodsFifty-seven healthy, 68 preperimetric, and 162 early POAG eyes enrolled in the Diagnostic Innovations in Glaucoma Study. Optical coherence tomography angiography (OCT-A)-based superficial macula vessel density and OCT-based GCC thickness were evaluated simultaneously. Percent loss from normal of GCC thickness and macula vessel density was compared. Area under the receiver operating characteristic curve was used to describe the diagnostic utility.ResultsBoth GCC thickness and vessel density were significantly lower in preperimetric and early POAG eyes compared to healthy eyes. Compared to the preperimetric POAG group, the early POAG group showed larger GCC thickness percent loss (whole image 4.72% vs 9.86%; all P < .01) but similar vessel density percent loss (whole image 4.97% vs 6.93%; all P > .05). In preperimetric POAG, GCC thickness and vessel density percent losses were similar (all P > .1). In contrast, in early POAG, GCC thickness percent loss was larger than that of vessel density (all P ≤ .001). To discriminate preperimetric or early glaucoma eyes from healthy eyes, GCC thickness and macula vessel density showed similar diagnostic accuracy (all P > .05).ConclusionsBoth GCC thinning and macula vessel density dropout were detectable in preperimetric and early POAG eyes. GCC loss was greater than macula vessel density loss in early perimetric POAG. However, OCT-A and OCT measurements showed similar efficiency to detect early glaucoma.

PurposeTo evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non-proliferative diabetic retinopathy.MethodsPatients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm "Angio Retina" scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated.ResultsForty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29).Conclusion3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.

Age-related macular degeneration (AMD) - the leading cause of vision loss in the elderly - share many risks factors as atherosclerosis, which exhibits loss of vascular compliance resulting from aging and oxidative stress. Here, we attempt to explore choroidal and retinal vascular compliance in patients with AMD by evaluating dynamic vascular changes using live ocular imaging following treatment with oral sildenafil citrate, a phosphodiesterase type 5 (PDE5) inhibitor and potent vasodilator. Enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A) were performed on 46 eyes of 23 subjects, including 15 patients with non-exudative AMD in one eye and exudative AMD in the fellow eye, and 8 age-matched control subjects. Choroidal thickness, choroidal vascularity, and retinal vessel density were measured across the central macula at 1 and 3 hours after a 100 mg oral dose of sildenafil citrate. Baseline choroidal thickness was 172.1 ± 60.0 μm in non-exudative AMD eyes, 196.4 ± 89.8 μm in exudative AMD eyes, and 207.4 ± 77.7 μm in control eyes, with no difference between the 3 groups (P = 0.116). After sildenafil, choroidal thickness increased by 6.0% to 9.0% at 1 and 3 hours in all groups (P = 0.001-0.014). Eyes from older subjects were associated with choroidal thinning at baseline (P = 0.005) and showed less choroidal expansion at 1 hour and 3 hours after sildenafil (P = 0.001) regardless of AMD status (P = 0.666). The choroidal thickening appeared to be primarily attributed to expansion of the stroma rather than luminal component. Retinal vascular density remained unchanged after sildenafil in all 3 groups (P = 0.281-0.587). Together, our studies suggest that vascular response of the choroid to sildenafil decreases with age, but is not affected by the presence of non-exudative or exudative AMD, providing insight into changes in vessel compliance in aging and AMD.

PurposeGeographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis.MethodsNineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation. Retinal layer volumes in the central 3-mm and surrounding 6-mm diameter were measured. Linear mixed models were used for statistics.ResultsThe GCL volume in the central 3 mm of the macula is less (P = 0.003), and the retinal nerve fiber layer volume is more (P = 0.02) in patients with GA when compared with controls. Ganglion cell layer volume positively correlated with outer nuclear layer volume (P = 0.020).ConclusionThe patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.

PurposeTo describe the earliest features of ABCA4-associated retinopathy.DesignCase series.ParticipantsChildren with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.MethodsThe retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.Main outcome measuresVisual acuity, OCT, FAF, electroretinography, and AOSLO results.ResultsEight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.ConclusionsIn childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.

PurposeThe purpose of this study was to investigate the diurnal variation in peripapillary and macular vessel density (VD) measurements using optical coherence tomographic angiography (OCT-A) and its correlation to intraocular pressure (IOP) changes in glaucoma patients.MethodsProspective, observational cross-sectional study including 37 patients (74 eyes; age, 63.8±12.9 y) with open-angle glaucoma. OCT-A imaging and IOP measurements were performed at 08:00, 11:00, 14:00, and 16:00 timepoints on a single day. At each timepoint, 2 scan protocols were used to generate 3-dimensional en face OCT angiograms: 4.5×4.5-mm scan centered on the optic nerve head and 6×6-mm scan centered on the fovea. For each scan mode, the "radial peripapillary capillary" segment, composed of the vasculature of the retinal nerve fiber layer and ganglion cell layer, was calculated. Two trained readers reviewed OCT-A image quality. Only scans with signal strength intensity (SSI) higher than 46 and without image artifacts interfering with measurements were included. Variation in VD measurements assessed using analysis of variance (ANOVA) and the association between VD and IOP changes assessed using linear mixed modeling methods.ResultsThe optic nerve head and peripapillary VD measurements at 14:00 and 16:00 timepoints were greater than the measurements at 08:00 and 11:00 timepoints. The 14:00 and 16:00 VD measurements were statistically significantly greater (P

PurposeTo evaluate strength of associations between optical coherence tomography (OCT)-angiography vessel density (VD) measurements in the macula and peripapillary region of the optic nerve head (ONH) with standard structural OCT thickness measures.Materials and methodsThis cross-sectional study included 333 eyes of 219 primary open-angle glaucoma patients, 41 glaucoma suspects, and 73 healthy participants from the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality OCT angiography images. The strength of associations between microvasculature measures in the ONH retinal nerve fiber layer (RNFL) and superficial macula layer was assessed using linear regression models. Associations between ONH and macula VD, and circumpapillary (cp) RNFL thickness and macular ganglion cell complex (mGCC) measures were also evaluated.ResultsThe strength (r) of associations among VD and thickness measures of ONH and macula ranged from 14.1% to 69.4%; all were statistically significant (P

PurposeTo compare the visualization of the epiretinal membrane (ERM) using multicolor imaging (MCI) (Heidelberg Engineering, Carlsbad, CA) and conventional white light flood color fundus photography (FP) (Topcon).MethodsThe paired images of patients with ERM who underwent same-day MCI and FP examinations were reviewed. Visibility of the ERM was graded using a scale (0: not visible, 1: barely visible, and 2: clearly visible) by masked readers, and surface folds were counted to quantify the membrane visibility for each method. Images from individual color channels in MCI (green, blue, and infrared) were also graded using the same method to further investigate MCI images.ResultsForty-eight eyes of 42 patients were included. The average ERM visibility score was 1.8 ± 0.37 for MCI and 1.01 ± 0.63 for FP (P < 0.001). The number of the surface folds detected per quadrant was signifi8cantly higher in MCI than that in FP (6.79 ± 3.32 vs. 2.85 ± 2.81, P < 0.001). The ERM was graded with similar scores on the two modalities in 43.8% of the eyes; in 56.2%, the ERM was better visualized on MCI than that on FP. Conventional FP failed to detect ERM in 11.4% of eyes when the mean central retinal thickness was

PURPOSE:Pigment in the midretina is a characteristic sign in Type 2 idiopathic macular telangiectasia (MacTel) and is considered to characterize the late stage of the disease. Our aim was to investigate its incidence, and relationship with risk factors for MacTel, including outer retinal vascularization and subretinal neovascular proliferation (SRNV). METHODS:Pigment extent was measured in fundus autofluorescence images of 150 eyes of 75 MacTel probands, using the Region Finder tool of Heidelberg Eye Explorer. A linear mixed model was used to analyze the dynamics of pigment and its associations with other features of the phenotype. The relative incidence of pigment and of outer retinal outer retinal vascularization and SRNV was analyzed within the full MacTel Study cohort (1,244 probands). RESULTS:Mean pigment area at baseline was 0.157 mm (range = 0-1.295 mm, SD = 0.228 mm, n = 101). Progression demonstrated a nonlinear pattern (P < 0.001) at an overall rate of 0.0177 mm/year and was associated with the initial plaque size and with SRNV. There was a strong correlation between fellow eyes (P ≤ 0.0001). In approximately 25% of all SRNV cases, SRNV may coincide with or precede pigment. CONCLUSION:Our data may be useful for refining the current system for staging disease severity in MacTel.

PurposeTo determine if different types of retinal fluid in the central macula affect the reproducibility of choroidal thickness (CT) measurements on enhanced depth imaging optical coherence tomography (EDI-OCT).DesignRetrospective reliability analysis.MethodsEDI-OCT images were obtained and the choroidal-scleral junction was analyzed through semiautomated segmentation. CT was measured at the fovea and averaged across the central 3-mm horizontal segment. Demographic data, central macular thickness, and type of fluid present were recorded. Intragrader and intergrader repeatability were assessed using the intraclass correlation coefficient (ICC) and coefficient of repeatability (CR).ResultsOf 124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had neovascular age-related macular degeneration, and 32 (25.8%) had other causes of fluid. Intergrader ICC (CR) was 0.95 (74.1 μm) and 0.96 (63.9 μm) for subfoveal and average CT, respectively. CR was similar across various causes of retinal fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal pigment epithelial fluid. CR also worsened with increasing choroidal thickness, but was not affected by retinal thickness. Intragrader repeatability was generally greater than intergrader values, and followed the same trend.ConclusionsThe presence of macular fluid reduces CT measurement reproducibility, particularly in eyes with subretinal fluid and greater choroidal thickness. A difference of 74.1 μm in subfoveal CT or 63.9 μm in average CT may be necessary to detect true clinical change in eyes with macular fluid.

PurposeTo characterize the rate of macula vessel density loss in primary open-angle glaucoma (POAG), glaucoma-suspect, and healthy eyes.DesignLongitudinal, observational cohort from the Diagnostic Innovations in Glaucoma Study.MethodsOne hundred eyes (32 POAG, 30 glaucoma-suspect, and 38 healthy) followed for at least 1 year with optical coherence tomography angiography (OCT-A) imaging on at least 2 visits were included. Vessel density was calculated in the macula superficial layer. The rate of change was compared across diagnostic groups using a multivariate linear mixed-effects model.ResultsBaseline macula vessel density was highest in healthy eyes, followed by glaucoma-suspect and POAG eyes (P < .01). The rate of vessel density loss was significantly different from zero in the POAG, but not in the glaucoma-suspect or healthy eyes. The mean rate of change in macula whole en face vessel density was significantly faster in glaucoma eyes (-2.23%/y) than in glaucoma-suspect (0.87%/y, P = .001) or healthy eyes (0.29%/y, P = .004). Conversely, the rate of change in ganglion cell complex (GCC) thickness was not significantly different from zero in any diagnostic group, and no significant differences in the rate of GCC change among diagnostic groups were found.ConclusionsWith a mean follow-up of less than 14 months, eyes with POAG had significantly faster loss of macula vessel density than either glaucoma-suspect or healthy eyes. Serial OCT-A measurements also detected glaucomatous change in macula vessel density in eyes without evidence of change in GCC thickness.

PurposeOptical coherence tomography angiography (OCT-A) is a noninvasive technology that allows visualization of retinal blood vessels. It is important to determine reproducibility of measurements as low precision can impair its diagnostic capabilities. The purpose of this study is to determine intravisit and intervisit reproducibility of optic nerve head (ONH) and macular vessel density measurements with OCT-A.Patients and methodsFifteen healthy volunteers and 14 glaucoma patients completed 2 OCT-A (AngioVue; Optovue Inc.) scanning sessions on each of 2 separate days to assess intravisit and intervisit reproducibility. A series of ONH and macula scans were acquired at each session. Vessel density (%), the proportion of vessel area over the total measurement area was calculated. Reproducibility was summarized using coefficients of variation (CV) and intraclass correlation coefficients calculated from variance component models.ResultsIn healthy eyes, the CV of intravisit and intervisit global vessel density measures ranged from 1.8% to 3.2% in ONH scans and 2.5% to 9.0% in macular scans. In glaucoma eyes, the CV of intravisit and intervisit global vessel density measures ranged from 2.3% to 4.1% in ONH scans and 3.2% to 7.9% in macular scans. CVs were lower for global than sectorial measures. Global OCT-A ONH intraclass correlation measurements for the retinal nerve fiber layer in healthy eyes were lower (range: 0.65 to 0.85) than in glaucoma eyes (range: 0.89 to 0.94). Scan size did not make large differences in measurement CVs.ConclusionsReproducibility of OCT-A ONH and macula vessel density measurements is good. Moreover, glaucoma patients have sparser vessel density with poorer reproducibility than healthy subjects.

PurposeTo describe a novel macular phenotype that is associated with normal visual function.DesignRetrospective, observational case series.ParticipantsThirty-six affected individuals from 23 unrelated families.MethodsThis was a retrospective study of patients who had a characteristic macular phenotype. Subjects underwent a full ocular examination, electrophysiologic studies, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence imaging. Genomic analyses were performed using haplotype sharing analysis and whole-exome sequencing.Main outcome measuresVisual acuity, retinal features, electroretinography, and whole-exome sequencing.ResultsTwenty-six of 36 subjects were female. The median age of subjects at presentation was 15 years (range, 5-59 years). The majority of subjects were asymptomatic and presented after a routine eye examination (22/36 subjects) or after screening because of a positive family history (13/36 subjects) or by another ophthalmologist (1/36 subjects). Of the 3 symptomatic subjects, 2 had reduced visual acuity secondary to nonorganic visual loss and bilateral ametropic amblyopia with strabismus. Visual acuity was 0.18 logarithm of the minimum angle of resolution (logMAR) or better in 30 of 33 subjects. Color vision was normal in all subjects tested, except for the subject with nonorganic visual loss. All subjects had bilateral symmetric multiple yellow dots at the macula. In the majority of subjects, these were evenly distributed throughout the fovea, but in 9 subjects they were concentrated in the nasal parafoveal area. The dots were hyperautofluorescent on fundus autofluorescence imaging. The OCT imaging was generally normal, but in 6 subjects subtle irregularities at the inner segment ellipsoid band were seen. Electrophysiologic studies identified normal macular function in 17 of 19 subjects and normal full-field retinal function in all subjects. Whole-exome analysis across 3 unrelated families found no pathogenic variants in known macular dystrophy genes. Haplotype sharing analysis in 1 family excluded linkage with the North Carolina macular dystrophy (MCDR1) locus.ConclusionsA new retinal phenotype is described, which is characterized by bilateral multiple early-onset yellow dots at the macula. Visual function is normal, and the condition is nonprogressive. In familial cases, the phenotype seems to be inherited in an autosomal dominant manner, but a causative gene is yet to be ascertained.

PurposeTo compare hemifield differences in the vessel density of the peripapillary and macula in open-angle glaucoma eyes with visual field (VF) defect confined to one hemifield using optical coherence tomography angiography (OCT-A).DesignCross-sectional study.ParticipantsA total of 58 eyes of 58 patients with glaucoma with VF loss confined to a single hemifield and 28 healthy eyes.MethodsRetinal vasculature information was summarized as circumpapillary vessel density (cpVD) and perifoveal vessel density (pfVD). Circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thickness were calculated using spectral domain optical coherence tomography (SD OCT). Paired and unpaired t tests were used to evaluate differences between the perimetrically affected and intact hemiretinae and healthy hemiretinae. Linear regression analyses were performed to evaluate the associations between VF measures with vascular and structural measurements.Main outcome measuresTotal and hemispheric cpVD, pfVD, cpRNFL, mGCC, and mean sensitivity (MS).ResultsMean cpVD and pfVD in the intact hemiretinae of glaucoma eyes (59.0% and 51.1%, respectively) were higher than in the affected hemiretinae (54.7% and 48.3%, respectively; P < 0.001) but lower than in healthy eyes (62.4% and 53.8%, respectively; P < 0.001). Similar results were noted with cpRNFL and mGCC thickness measurements (P < 0.05 for both). The strongest associations between MS in the affected hemifields were found for cpVD (r = 0.707), followed by pfVD (r = 0.615), cpRNFL (r = 0.496), and mGCC (r = 0.482) in the corresponding hemiretinae (P < 0.001 for all). Moreover, the correlations in the intact hemifields between MS with cpVD and pfVD were higher (r = 0.450 and 0.403) than the correlations between MS and cpRNFL and mGCC thickness measurements (r = 0.340 and 0.290; P values

PurposeTo compare the diagnostic abilities of vessel density measurements of the optic nerve head (ONH), peripapillary and macular regions on optical coherence tomography (OCT) angiography in eyes with primary open angle glaucoma (POAG) with that of the ONH rim area, peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (GCC) thickness measurements.MethodsIn a cross sectional study, 78 eyes of 50 control subjects and 117 eyes of 67 POAG patients underwent vessel density and structural measurements with spectral domain OCT. POAG was diagnosed based on the masked evaluation of optic disc stereo photographs. Area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities of vessel densities in ONH, peripapillary and macular regions were compared with rim area, RNFL and GCC thickness.ResultsThe AUC (sensitivity at 95% specificity) of average vessel densities within the ONH, peripapillary and macular region were 0.77 (31%), 0.85 (56%) and 0.70 (18%) respectively. The same of ONH rim area, average RNFL and GCC thickness were 0.94 (83%), 0.95 (72%) and 0.93 (62%) respectively. AUCs of vessel densities were significantly lower (p

PurposeWe tested the hypothesis that the macular ganglion cell layer (GCL) thickness demonstrates a stronger structure-function (SF) relationship and extends the useful range of macular measurements compared with combined macular inner layer or full thickness.MethodsNinety-eight glaucomatous eyes and eight normal eyes with macular spectral domain optical coherence tomography (SD-OCT) volume scans and 10-2 visual fields were enrolled. Inner plexiform layer (IPL), GCL, macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full thickness (FT) measurements were calculated for 8 × 8 arrays of 3° superpixels. Main outcome measures were local structure-function relationships between macular superpixels and corresponding sensitivities on 10-2 fields after adjusting for ganglion cell displacement, dynamic range of measurements, and the change point (total deviation value where macular parameters reached measurement floor).ResultsMedian (interquartile range [IQR]) mean deviation was -7.2 (-11.6 to -3.2) dB in glaucoma eyes. Strength of SF relationships was highest for GCIPL, GCL, GCC, and IPL (ρ = 0.635, 0.627, 0.621, and 0.577, respectively; P ≤ 0.046 for comparisons against GCIPL). Highest SF correlations coincided with the peak of GCL thickness, where the dynamic range was widest for FT (81.1 μm), followed by GCC (65.7 μm), GCIPL (54.9 μm), GCL (35.2 μm), mRNFL (27.5 μm), and IPL (20.9 μm). Change points were similar for all macular parameters (-7.8 to -8.9 dB).ConclusionsGCIPL, GCL, and GCC demonstrated comparable SF relationships while FT, GCC, and GCIPL had the widest dynamic range. Measurement of GCL did not extend the range of useful structural measurements. Measuring GCL does not provide any advantage for detection of progression with current SD-OCT technology.

PurposeWe examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma.MethodsA cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression.ResultsThere was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R(2) = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R(2) = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R(2) = 0.350, P < 0.001) and SAP MD (R(2) = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness.ConclusionsObjective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma.

PurposeTo investigate macular ganglion cell-inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs.Methods112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.Result47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P

PurposeTo evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements.MethodsThe study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes.ResultsMean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements.ConclusionAssessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection.

PurposeOptical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting.MethodsAt entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods.ResultsThe average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm-derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation-derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods.ConclusionsSpectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.).

PurposeTo investigate the relationship between macular ganglion cell-inner plexiform layer (mGCIPL) thickness and estimated macular retinal ganglion cell (RGC) counts in glaucoma.DesignObservational cohort study.ParticipantsCross-sectional study of 77 healthy, 154 glaucoma suspect, and 159 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study.MethodsAll eyes underwent 24-2 standard automated perimetry (SAP) and optic nerve and macular imaging using high-definition optical coherence tomography (OCT). The total number of RGCs was estimated using a previously described model that uses SAP and OCT circumpapillary retinal nerve fiber layer (cpRNFL) measurements. The number of macular RGCs was estimated from the temporal cpRNFL and SAP test points within the central 10°.Main outcome measuresThe correlation between mGCIPL thickness and estimates of macular RGC counts.ResultsThe average estimated macular RGC count in glaucomatous eyes was 306 010 ± 109 449 cells, which was significantly lower than the estimate of 520 678 ± 106 843 cells in healthy eyes (P < 0.001). Glaucomatous eyes had 41% fewer estimated macular RGCs than healthy eyes and suspects had 21% fewer estimated macular RGCs. There was strong correlation between estimated macular RGC counts and mGCIPL thickness (R(2) = 0.67; P < 0.001). Macular RGC counts performed better than average mGCIPL thickness in discriminating healthy and glaucomatous eyes with receiver operating characteristic curve areas of 0.873 and 0.775, respectively (P = 0.015).ConclusionsThe strong association between estimated macular RGC counts and mGCIPL thickness and the better diagnostic performance of the macular RGC counts compared with mGCIPL thickness provides further evidence that estimates of RGC number from cpRNFL thickness and SAP sensitivity can be used to assess neural losses in glaucoma.

PurposeOptical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting.MethodsAt entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods.ResultsThe average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm-derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation-derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods.ConclusionsSpectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.).

PurposeFixation stability is known to be poor for people with macular disease and has been suggested as a contributing factor for the poor visual performance of these individuals. In this study, we examined the characteristics of the different components of fixational eye movements and determined the component that plays a major role in limiting fixation stability in people with macular disease.MethodsSixteen observers with macular disease and 14 older adults with normal vision (control observers) monocularly fixated a small cross presented using a Rodenstock scanning laser ophthalmoscope, for trials of 30 seconds. The retinal image and the position of the cross on the retina were recorded digitally. Eye movements were extracted from the recorded videos at a sampling rate of 540 Hz using a cross-correlation technique. A velocity criterion of 8°/s was used to differentiate between slow drifts and microsaccades.ResultsObservers with macular disease demonstrated higher fixation instability, larger amplitudes of slow drifts and microsaccades, and lower drift velocities, when compared with older adults with normal vision. The velocity and the rate of microsaccades were comparable between the two groups of observers. Multiple linear regression analysis showed that the amplitude of microsaccades, and to a smaller extent, the amplitude of slow drifts, play a major role in limiting fixation stability.ConclusionsFixation stability in people with macular disease is primarily limited by the amplitude of microsaccades, implying that rehabilitative strategies targeted at reducing the amplitude of microsaccades should improve fixation stability, and may lead to improved visual functions.

PurposeTo compare laser photocoagulation plans for diabetic macular edema (DME) using fluorescein angiography (FA) versus optical coherence tomography (OCT) thickness map superimposed on the retina.MethodsFourteen eyes with DME undergoing navigated laser photocoagulation with navigated photocoagulator had FA taken using the same instrument. Optical coherence tomography central retinal thickness map was imported to the photocoagulator and with same magnification aligned onto the retina. Three retina specialists placed laser spot marks separately on FA and OCT image in a masked fashion. The spots placed by each physician were compared between FA and OCT and among physicians. The area of dye leakage on FA and increased central retinal thickness on OCT of the same eye were also compared.ResultsThe average number of spots using FA and OCT template was 36.64 and 40.61, respectively (P = 0.0201). The average area of dye leakage was 7.45 mm, whereas the average area of increased central retinal thickness on OCT of the same eye was 10.92 mm (P = 0.013).ConclusionThere is variability in the treatment planning for macular photocoagulation with a tendency to place more spots when guided by OCT than by FA. Integration of OCT map aligned to the retina may have an impact on treatment plan once such information is available.

BACKGROUND: Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis. METHODS: The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as "reduced" or "not reduced" for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed "abnormal" if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation. RESULTS: The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning. CONCLUSION: RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS. Copyright © 2013 North American Neuro-Ophthalmology Society.

PurposeTo evaluate serially long-term macular morphologic changes after successful macula-involving rhegmatogenous retinal detachment repair and correlate changes with macular function.MethodsRepeat Fourier domain optical coherence tomography (FD OCT) imaging and microperimetry (MP-1) testing of 8 of the initial cohort of 17 eyes studied 5 years earlier.ResultsThe mean follow-up after rhegmatogenous retinal detachment repair was 3.4 months (range, 1-8.5 months) for the first FD OCT and 5 years (range, 3.75-5.75 years) for the follow-up FD OCT. The final postoperative best-corrected visual acuity mean was 20/201 (range, 20/20 to counting fingers). Six eyes with final best-corrected visual acuity >20/40 had an intact external limiting membrane and progressive resolution of photoreceptor inner segment-outer segment junction disruption and/or subretinal fluid on serial FD OCT, which correlated with improvement in macular function on MP-1. Two eyes with poor or worsening best-corrected visual acuity on follow-up had persistent or worsening inner segment-outer segment disruption on serial FD OCT. External limiting membrane was intact in one eye and persistently disrupted in the other.ConclusionMacular function may progressively improve or worsen long-term after successful rhegmatogenous retinal detachment repair. Progressive resolution of subretinal fluid and/or inner segment-outer segment disruption on FD OCT correlated with improvement in macular function, whereas worsening or persistent inner segment-outer segment disruption correlates with worsening or persistently poor visual outcome.

PurposeTwo methods were used to study the stages of macular telangiectasia (MACTEL): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids.MethodsAmong 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT.ResultsStage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea.ConclusionsPD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel.

ObjectiveTo determine whether fingolimod, an oral sphingosine-1-phosphate receptor modulator approved for treatment of multiple sclerosis (MS), generally leads to increased retinal tissue volume.MethodsIn this longitudinal observational study, we compared changes in macular volume on spectral-domain optical coherence tomography (OCT) between consecutive patients with MS who initiated fingolimod and a matched reference cohort of patients with MS never exposed to the drug. The primary reference cohort was matched based on time interval between OCT examinations. A secondary reference cohort was matched based on age and disease duration. Change in macular volume within each group was analyzed using the paired t test. Change in macular volume between groups was examined using multiple linear regression.ResultsMacular volume increased by a mean of 0.025 mm3 (95% confidence interval [CI] +0.017 to +0.033, p < 0.001) in the 30 patients with MS who initiated fingolimod over a mean follow-up time of 5 months (SD 3). Macular volume did not significantly change over a mean follow-up time of 6 months (SD 4) in a comparison group of 30 patients with MS never treated with fingolimod (mean change of -0.003 mm3, 95% CI -0.009 to +0.004, p = 0.47). Overall, 74% of eyes in the fingolimod-treated group exhibited an increase in macular volume vs. 37% of eyes in the comparison group.ConclusionInitiation of fingolimod in MS is associated with a modest, relatively rapid increase in macular volume.

PurposeTo determine the macular morphologic features that correlate best with visual outcome in eyes with surgically closed idiopathic macular hole.MethodsTransversal observational case series of 24 eyes (22 subjects) imaged postoperatively using high-resolution Fourier domain optical coherence tomography (FD-OCT). Total and inner macular volume for central 3 mm area, central foveal thickness, and size of foveal inner segment-outer segment junction abnormality were correlated with best-corrected visual acuity. Microperimetry (MP-1) test was performed in a subset of 18 eyes.ResultsMean postoperative best-corrected visual acuity was 20/36 (range, 20/25-20/70). Postoperative follow-up mean was 32.97 ± 24.68 months (range, 5-96 months). Eighteen eyes underwent internal limiting membrane (ILM) peeling. Among FD-OCT parameters, logarithm of the minimum angle of resolution best-corrected visual acuity and mean total microperimetry-1 sensitivity correlated best with inner macular volume in all eyes and ILM-peeled eyes (P < 0.05). Macular surface irregularities were noted in 12 eyes (66.7%) with ILM peeling but in none of the non-ILM-peeled eyes (P = 0.02). No significant correlation was found between microperimetry-1 sensitivity and other FD-OCT parameters.ConclusionBecause inner macular volume strongly correlated with visual outcome in eyes with surgically closed macular hole, the possible effect of ILM peeling on visual outcome needs to be further investigated.

PurposeTo investigate how objects (flankers) placed on either side of a target affect reaching and grasping behavior in visually impaired (VI) subjects due to macular disorders compared with age-matched normals.MethodsSubjects reached out to grasp a cylindrical target placed on its own and when it had two identical objects (flankers) placed either half or one target diameter away on each side of the target. A motion analysis system (Vicon 460) recorded and reconstructed the 3-dimemsional (3D) hand and finger movements. Kinematic data for transport and grasping mechanisms were measured.ResultsIn subjects with VI, crowding effected the overall movement duration, time after maximum velocity, and maximum grip aperture. Maximum effect was shown when the flankers were placed close to the target (high-level crowding) with a decreased effect shown for flankers placed farther away (medium-level crowding). Compared with normals, subjects with VI generally took longer to initiate the hand movement and to complete the movement. Time after maximum velocity and time after maximum grip aperture were also longer in subjects with VI. No interaction effects were found for any of the indices for the different levels of crowding in the two visual groups.ConclusionsReaching and grasping behavior is compromised in subjects with VI due to macular disorders compared with normals, and crowding affected performance for both normal subjects and those with VI. Flankers placed half an object diameter away showed greater deterioration than those placed further away.

PurposeThe purpose of this study is to evaluate the macular morphological changes associated with idiopathic epiretinal membrane (iERM) using high-resolution Fourier-domain optical coherence tomography (FD-OCT), as they correlate with visual acuity and microperimetry (MP-1).MethodsIn all, 24 eyes (19 subjects) with iERM were imaged prospectively using FD-OCT with axial resolution of 4.5 μm and transverse resolution of 10 to 15 μm. MP-1 and Stratus OCT were carried out in a subset of eyes.ResultsThe mean log of the minimum angle of resolution best-corrected visual acuity (BCVA) was 0.18±0.16 (range: -0.08 to 0.48, Snellen equivalent 20/15(-1) to 20/60). ERM was visualized in all 24 eyes with FD-OCT and in 17 eyes (85%) of 20 eyes imaged with Stratus OCT. Although BCVA correlated with macular thickening in the central 1 mm sub-field of the Stratus ETDRS (P=0.0005) and macular volume (central 3 mm area) on FD-OCT (P

ObjectiveTo evaluate the morphologic changes in the macula of subjects with repaired macula-off retinal detachment (RD) using high-resolution Fourier-domain optical coherence tomography (FD OCT) and to perform functional correlation in a subset of patients using microperimetry (MP-1).DesignProspective observational case series.ParticipantsSeventeen eyes from 17 subjects who had undergone anatomically successful repair for macula-off, rhegmatogenous RD at least 3 months earlier and without visually significant maculopathy on funduscopy.MethodsFD OCT with axial and transverse resolution of 4.5 mum and 10 to 15 mum, respectively, was used to obtain rapid serial B-scans of the macula, which were compared with that from Stratus OCT. The FD OCT B-scans were used to create a 3-dimensional volume, from which en face C-scans were created. Among 11 patients, MP-1 was performed to correlate morphologic changes with visual function.Main outcome measuresStratus OCT scans, FD OCT scans, and MP-1 data.ResultsStratus OCT and FD OCT images of the macula were obtained 3 to 30 months (mean 7 months) postoperatively in all eyes. Although Stratus OCT revealed photoreceptor disruption in 2 eyes (12%), FD OCT showed photoreceptor disruption in 13 eyes (76%). This difference was statistically significant (P

PurposeTo introduce and examine the utility of a retinal imaging technique using high-speed optical coherence tomography (OCT) for creating a more complete retinal structural map to aid in the evaluation of patients with macular pathology.DesignProspective observational case series.ParticipantsFive patients with a variety of macular pathologies.MethodsPatients were imaged with a Fourier-domain high-speed high-resolution OCT system built at our institution. A sweeping serial OCT B-scan of the macula was acquired to create a detailed retinal structural map. The data were then used to make individual clinical observations.ResultsRapid serial OCT B-scans produced detailed macular maps for all 5 patients. Diagnoses of imaged patients included macular hole, lamellar macular hole, regressed macular hole or macular microhole, choroidal neovascular membrane (CNV) from age-related macular degeneration, and CNV from presumed ocular histoplasmosis syndrome. Reconstructed B-scans and C-scans are shown for selected patients to illustrate the additional perspectives gained by obtaining a detailed retinal map.ConclusionsRapid serial Fourier-domain OCT B-scanning can be used to create a detailed retinal structural map. This technique provides additional information that can be missed on single OCT images and provides an accurate way to image large or complex lesions, and allows B-scan and C-scan reconstructions to be made that provide additional perspectives into retinal structures that may be missed using traditional imaging methods.

PurposeTo evaluate the donor retina of a patient with X-linked cone-rod dystrophy caused by an RPGR exon ORF15 mutation.DesignHistopathologic study of the retina.MethodsThe eye of a 69-year-old man was fixed at 1.6 hours postmortem and processed for histopathology and immunocytochemistry.ResultsGrossly, the macula was atrophic with a bull's-eye appearance. The remaining retina showed postmortem edema but no intraretinal pigment. Microscopically, the macular retinal pigment epithelium was absent focally and had pigmentary changes elsewhere. Cones and rods were absent from the perifovea and reduced with shortened outer segments elsewhere in the macula. In the remainder of the retina, cones but not rods were reduced and all photoreceptor outer segments were shortened.ConclusionsThe abnormalities in both cone and rod photoreceptors confirm the importance of RPGR in both cell types but leaves unresolved how various exon ORF15 mutations lead to different clinical phenotypes.

Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective or modify photoreceptor degeneration in concentric retinitis pigmentosa.