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Purpose The purpose of this study was to assess the associations between baseline choriocapillaris (CC) flow deficits and geographic atrophy (GA) progression. Methods In this prospective cohort study, patients with GA underwent 3 × 3-mm macular spectral-domain optical coherence tomographic angiography (OCTA) at baseline and follow-up visits. Annual GA enlargement rate was defined as change of square root of GA area in 12 months. Shadow areas due to iris, media opacity, retinal vessels, and drusen were excluded. CC vessel density (CC-VD) in non-GA areas was measured using a validated machine-learning-based algorithm. Low perfusion area (LPA) was defined as capillary density below the 0.1 percentile threshold of the same location of 40 normal healthy control eye. Focal perfusion loss (FPL) was defined as percentage of CC loss within LPA compared with normal controls. Results Ten patients with GA were enrolled and followed for 26 months on average. At baseline, the mean GA area was 0.84 ± 0.70 mm2. The mean CC-VD was 44.5 ± 15.2%, the mean LPA was 4.29 ± 2.6 mm2, and the mean FPL was 50.4 ± 28.2%. The annual GA enlargement rate was significantly associated with baseline CC-VD (r = −0.816, P = 0.004), LPA (r = 0.809, P = 0.005), and FPL (r = 0.800, P = 0.005), but not with age (r = 0.008, P = 0.98) and GA area (r = −0.362, P = 0.30). Conclusions Baseline CC flow deficits were significantly associated with a faster GA enlargement over the course of 1 year, suggesting the choriocapillaris perfusion outside of a GA area may play a role in GA progression.

Purpose Reduction in inner retinal oxygen delivery (DO2) can cause retinal hypoxia and impair inner retinal oxygen metabolism (MO2), leading to vision loss. The purpose of the current study was to establish measurements of DO2 and MO2 in healthy subjects and test the hypothesis that DO2 and MO2 are reduced in sickle cell retinopathy (SCR) subjects. Methods Dual wavelength retinal oximetry and Doppler optical coherence tomography were performed in 12 healthy control and 12 SCR subjects. Images were analyzed to measure retinal arterial and venous oxygen content (O2A and O2V), venous diameter (DV), and total retinal blood flow (TRBF). Retinal arteriovenous oxygen content difference (O2AV), DO2, MO2, and oxygen extraction fraction (OEF) were calculated according to the following equations: O2AV = O2A - O2V; DO2 = TRBF * O2A; MO2 = TRBF * O2AV; OEF = MO2/DO2. Results Retinal DV and TRBF were higher in the SCR group as compared to the control group, whereas, O2A, O2V, and O2AV were lower in SCR group as compared to the control group. DO2, MO2, and OEF were not significantly different between control and SCR groups. MO2 and DO2 were linearly related, such that higher MO2 was associated with higher DO2. There was an inverse relationship between TRBF and OEF, such that lower TRBF was associated with higher OEF. Conclusions Increased blood flow compensated for decreased oxygen content, thereby maintaining DO2, MO2, and OEF at predominately lower stages of SCR. Quantitative assessment of these parameters has the potential to advance knowledge and improve diagnostic evaluation of retinal ischemic conditions.

Purpose The purpose of this study was to evaluate an automated algorithm for detecting avascular area (AA) in optical coherence tomography angiograms (OCTAs) separated into three individual plexuses using a projection-resolved technique. Methods A 3 × 3 mm macular OCTA was obtained in 13 healthy and 13 mild nonproliferative diabetic retinopathy (NPDR) participants. A projection-resolved algorithm segmented OCTA into three vascular plexuses: superficial, intermediate, and deep. An automated algorithm detected AA in each of the three plexuses that were segmented and in the combined inner-retinal angiograms. We assessed the diagnostic accuracy of extrafoveal and total AA using segmented and combined angiograms, the agreement between automated and manual detection of AA, and the within-visit repeatability. Results The sum of extrafoveal AA from the segmented angiograms was larger in the NPDR group by 0.17 mm2 (P < 0.001) and detected NPDR with 94.6% sensitivity (area under the receiver operating characteristic curve [AROC] = 0.99). In the combined inner-retinal angiograms, the extrafoveal AA was larger in the NPDR group by 0.01 mm2 (P = 0.168) and detected NPDR with 26.9% sensitivity (AROC = 0.62). The total AA, inclusive of the foveal avascular zone, in the segmented and combined angiograms, detected NPDR with 23.1% and 7.7% sensitivity, respectively. The agreement between the manual and automated detection of AA had a Jaccard index of >0.8. The pooled SDs of AA were small compared with the difference in mean for control and NPDR groups. Conclusions An algorithm to detect AA in OCTA separated into three individual plexuses using a projection-resolved algorithm accurately distinguishes mild NPDR from control eyes. Automatically detected AA agrees with manual delineation and is highly repeatable.

Purpose To compensate for reflectance variation when quantifying vessel density by optical coherence tomography angiography (OCTA). Methods Healthy participants received 6×6-mm macular and 4.5×4.5-mm optic nerve head (ONH) angiography scans on a 70-kHz spectral-domain optical coherence tomography system. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute the OCTA signal. Mean reflectance projection and maximum decorrelation projection were used to create en face OCT and OCTA images. Background OCTA noise in static tissue was evaluated in the foveal avascular zone (FAZ). Vessel density was calculated from en face retinal OCTA that was binarized according to a decorrelation threshold. Results The average retinal decorrelation noise in the FAZ was linearly related to the average logarithmic-scale OCT reflectance signal. Based on this relationship, a reflectance-adjusted decorrelation threshold equation was developed to filter out 97.5% of background OCTA noise. A fixed threshold was also used for comparison. The superficial vascular complex vessel density in the macula and ONH were significantly correlated with reflectance signal strength index (SSI) using the fixed threshold. This correlation was removed by using the reflectance-adjusted threshold. Reflectance compensation reduced population variation in 25 healthy eyes from 8.5% to 4.8% (coefficient of variation) in the macula and from 6.7% to 5.4% in the peripapillary region. Within-visit repeatability also improved from 4.4% to 1.8% in the macula and from 3% to 1.7% in the peripapillary region. Conclusions Compensating for reflectance variation resulted in more reliable vessel density quantification in OCTA.

Author(s): Tang, Maolong; Li, Yan; Chamberlain, Winston; Louie, Derek J; Schallhorn, Julie M; Huang, David | Abstract: PurposeTo differentiate between keratoconus and contact lens-related corneal warpage by combining focal change patterns in anterior corneal topography, pachymetry, and epithelial thickness maps.MethodsPachymetry and epithelial thickness maps of normal, keratoconus, and warpage, and forme fruste keratoconus (FFK) eyes were obtained from a Fourier-domain optical coherence tomography (OCT). Epithelial pattern standard deviation (PSD) was calculated and combined with two novel indices, the Warpage Index and the Anterior Ectasia Index, to differentiate between normal, keratoconus, and warpage eyes. The values of the three parameters were compared between groups.ResultsThe study included 22 normal, 31 keratoconic, 11 warpage, and 8 FFK eyes. The epithelial PSD was normal (l 0.041) for 100% normal eyes and abnormal (g 0.041) for 100% of keratoconic eyes, 81.8% of warpage eyes, and 87.5% of FFK eyes. The Anterior Ectasia Index of normal eyes (1.66 ± 0.74) was significantly lower than that for the keratoconus eyes (17.5 ± 7.17), the warpage eyes (2.98 ± 1.69), and the FFK eyes (6.95 ± 5.86). The Warpage Index was positive in all warpage eyes and negative for all keratoconic and FFK eyes except three wearing rigid gas-permeable contact lens.ConclusionsThe epithelial PSD can distinguish normal from keratoconus or warpage, but does not distinguish between these two conditions. The Anterior Ectasia Index is abnormal in keratoconus but not warpage. The Warpage Index is positive for warpage and negative for keratoconus, except in cases where keratoconus and warpage coexist. Together, the three parameters are strong tripartite discriminators of normal, keratoconus, and warpage.

Purpose To evaluate the accuracy of the optical coherence tomography–based (OCT formula) and Barrett True K (True K) intraocular lens (IOL) calculation formulas in eyes with previous radial keratotomy (RK). Methods In 95 eyes of 65 patients, using the actual refraction following cataract surgery as target refraction, the predicted IOL power for each method was calculated. The IOL prediction error (PE) was obtained by subtracting the predicted IOL power from the implanted IOL power. The arithmetic IOL PE and median refractive PE were calculated and compared. Results All formulas except the True K produced hyperopic IOL PEs at 1 month, which decreased at ≥4 months (all P < 0.05). For the double-K Holladay 1, OCT formula, True K, and average of these three formulas (Average), the median absolute refractive PEs were, respectively, 0.78 diopters (D), 0.74 D, 0.60 D, and 0.59 D at 1 month; 0.69 D, 0.77 D, 0.77 D, and 0.61 D at 2 to 3 months; and 0.34 D, 0.65 D, 0.69 D, and 0.46 D at ≥4 months. The Average produced significantly smaller refractive PE than did the double-K Holladay 1 at 1 month (P < 0.05). There were no significant differences in refractive PEs among formulas at 4 months. Conclusions The OCT formula and True K were comparable to the double-K Holladay 1 method on the ASCRS (American Society of Cataract and Refractive Surgery) calculator. The Average IOL power on the ASCRS calculator may be considered when selecting the IOL power. Further improvements in the accuracy of IOL power calculation in RK eyes are desirable.

Optical coherence tomography angiography (OCTA) is a noninvasive approach that can visualize blood vessels down to the capillary level. With the advent of high-speed OCT and efficient algorithms, practical OCTA of ocular circulation is now available to ophthalmologists. Clinical investigations that used OCTA have increased exponentially in the past few years. This review will cover the history of OCTA and survey its most important clinical applications. The salient problems in the interpretation and analysis of OCTA are described, and recent advances are highlighted.

Purpose To investigate the relationship between retinal perfusion and retinal thickness in the peripapillary and macular areas of healthy subjects. Methods Using spectral-domain optic coherence tomography and split-spectrum amplitude decorrelation angiography (SSADA) algorithm, retinal perfusion and retinal thicknesses in the macular and peripapillary areas were measured in healthy volunteers, and correlations among these variables were analyzed. Results Overall, 64 subjects (121 eyes) including 28 males and 36 females with a mean ± SD age of 38 ± 13 years participated. Linear mixed-models showed that vessel area density was significantly correlated with the inner retinal thickness (from the inner limiting membrane to the outer border of the inner nucleus layer; P < 0.05), but not with the thickness of the full retina (P > 0.05) in the parafoveal area. The area of the foveal capillary-free zone was negatively correlated with the inner and full foveal thicknesses (all P < 0.001). In the peripapillary area, the vessel area density was positively correlated with the thickness of the retinal nerve fiber layer (P < 0.001). Conclusions In healthy subjects, retinal perfusion in small vessels was closely correlated with the thickness of the inner retinal layers in both the macular and peripapillary areas.

The complexity in structure and function of retinal tissue makes it one of the most metabolically active locations in the body.1 The retina must maintain a high oxygen concentration that remains stable despite changes in hemodynamics and atmospheric partial pressures.2–6 Retinal blood vessels are unique in that they can regulate vascular tone, and therefore blood flow, without the presence of an autonomic nerve supply.7 This autoregulation is essential to preserving the function of retinal tissue.8 Uncontrolled hyperfusion during the early stages of diabetic retinopathy suggests that deficits in the autoregulatory response have an important role in pathogenesis.9–11 Quantification of retinal blood flow change due to autoregulation may thus be useful in a clinical setting. Several techniques have been implemented to investigate blood flow in the healthy eye. Blue field entopic phenomenon12,13 and scanning laser Doppler flowmetry14 have both been successfully implemented to investigate retinal blood flow variation. These methods have shown that in order to maintain relatively constant retinal oxygen levels, retinal blood velocity decreases with an increase in arterial oxygen partial pressure (hyperoxia). Other techniques using laser Doppler velocimetry15 and Doppler optical coherence tomography (OCT)16 have been able to measure decreases in retinal blood vessel diameter and blood flow during hyperoxia. Optical coherence tomography is well established in clinical ophthalmology for structural imaging and evaluation of diseases.17 The recent development of OCT angiography has allowed for the mapping of ocular circulation down to the capillary level. We have developed an efficient OCT angiography algorithm called “split-spectrum amplitude-decorrelation angiography” (SSADA)18–20 that greatly reduces the scan time and improves the signal-to-noise ratio of flow detection, making it possible to obtain high-quality angiograms with a commercial OCT retinal scanner. Optical coherence tomography angiography has great potential for quantifying microvascular change as a response to physiologic changes. The purpose of this study was to investigate the change of the peripapillary retinal blood flow in healthy eyes before and after hyperoxia.

The retinal vascular system, especially the part that perfuses the macular area, is essential to normal visual function.1 Numerous factors (e.g., pathology, trauma) can cause severe and irreversible visual damage to the macula.1,2 Ophthalmologists have used a variety of different methods to observe the vasculature in the macular area, including fundus camera3 and fundus fluorescein angiography (FFA).4 While these methods provide important clinical information, their use in clinical settings is limited by their invasive nature or low resolution. Moreover, the monitoring of early and subtle changes in the macular capillary system in clinical settings has proven challenging. Thus, an effective and noninvasive method for monitoring macular perfusion would provide not only a means for early detection of changes related to various pathologies, leading in turn to early interventions, but also a more thorough understanding of the pathophysiology of macular vascular disease. Recently, development of a new technique known as split-spectrum amplitude-decorrelation angiography (SSADA) has promised new insights for understanding ocular perfusion. The technique, based on optical coherence tomography (OCT), is able to rapidly and accurately quantify retinal and disc blood flow in a noninvasive manner.5,6 Previous research has demonstrated that OCT angiography (angio-OCT) with SSADA offers results with high intravisit repeatability and intervisit reproducibility.7,8 However, an understanding of the status in normal eyes is necessary before its application in clinical settings. Moreover, some previous studies have found that the thicknesses of the retinal nerve fiber layer (RNFL), the macula, and the choroid vary with both age and sex.9–13 Thus, we here report on macular perfusion in normal volunteer subjects to explore the potential effects of age and sex on macular retinal functions.

To analyze the relationship among macular ganglion cell complex (GCC) thickness, peripapillary nerve fiber layer (NFL) thickness, and visual field (VF) defects in patients with glaucoma.A Fourier-domain optical coherence tomography (FD-OCT) system was used to map the macula and peripapillary regions of the retina in 56 eyes of 38 patients with perimetric glaucoma. The macular GCC and peripapillary NFL thicknesses were mapped and standard automated perimetry (SAP) was performed. Loss of GCC and NFL were correlated with the VF map on both a point-by-point and regional basis.Correlation between GCC thickness and peripapillary NFL thickness produced a detailed correspondence map that demonstrates the arcuate course of the NFL in the macula. Corresponding regions within the GCC, NFL, and VF maps demonstrate significant correlation, once parafoveal retinal ganglion cell (RGC) displacement is taken into account.There are significant point-specific and regional correlations between GCC loss, NFL loss, and deficits on SAP. Using these different data sources together may improve our understanding of glaucomatous damage and aid in the management of patients with glaucoma.

To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma.Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale.Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03).There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

The development of noninvasive methods such as magnetic resonance angiography1 and functional magnetic resonance imaging (MRI)2 to measure cerebral hemodynamics has greatly enhanced the study of neurologic diseases and functional neuroanatomy. Such methods would also be very helpful in the eye because the leading causes of blindness in the industrialized world—diabetic retinopathy, macular degeneration, and glaucoma—are all related to abnormal retinal3,4 or optic nerve blood flow.5 Unfortunately, MRI resolution is too coarse for quantitative imaging of retinal blood vessels, which have a very fine caliber. Although several techniques are being used for retinal blood flow evaluation, they all have serious limitations. Ultrasound color Doppler imaging has sufficient resolution to measure only the larger retrobulbar vessels.6 It can measure blood velocity but not vessel diameter; therefore, volumetric blood flow cannot be determined. Several types of laser Doppler techniques are able to measure flow in individual retinal vessels7–9 or capillary beds.10 Although it is possible to measure total retinal blood flow by adding measurements from individual vessels, this requires many measurements over a long session.8 These specialized instruments are generally available only in major research centers because they are expensive. Fluorescein and indocyanine green angiographies are widely used to visualize retinal and choroidal circulations. However, they do not provide quantitative measurements of blood flow and require the intravenous injection of dyes that have potential side effects.11 Optical coherence tomography (OCT)12 is commonly used in the diagnosis and management of retinal diseases.13–16 It has the requisite resolution to image retinal blood vessels.17 Because it is a coherent detection technique, OCT can detect the Doppler frequency shift of back-scattered light, which provides information on blood flow velocity.18,19 With the development of high-speed Fourier-domain OCT,20–22 it has become possible to capture the pulsatile dynamics of blood flow.23,24 Using Doppler Fourier-domain OCT, we developed a double circular scanning pattern (Fig. 1) that measures flow in all the blood vessels around the optic nerve head four to six times per second.25 Total retinal blood flow could be calculated with the data sampled within 2 seconds. We have demonstrated that flow measurements in normal subjects26 and in a patients with diabetic retinopathy27 can be reproducibly obtained. In this study, we used this new technique in a systematic investigation of blood flow abnormalities in retinal and optic nerve diseases. Figure 1. (a) Fundus photograph showing the double circular pattern of the OCT beam scanning retinal blood vessels emerging from the optic disc. (b) The relative position of a blood vessel in the two OCT cross-sections is used to calculate the Doppler angle θ ...

PURPOSE. To evaluate the reproducibility of anterior chamber (AC) angle measurements obtained using anterior segment optical coherence tomography (AS-OCT). METHODS. Patients with suspected glaucoma and those with glaucoma, ocular hypertension, or anatomically narrow angles were recruited from the glaucoma service at the National University Hospital, Singapore. All subjects underwent imaging of the nasal, temporal, and inferior AC angles with an AS-OCT prototype under standardized dark and light conditions. For short-term reproducibility analysis, a single observer acquired two sets of images followed by a third set of images acquired by a second observer. The interval between sessions was 10 minutes. For long-term reproducibility analysis, a single observer acquired two sets of images at least 24 hours apart. Images were measured using custom software to determine the AC depth (ACD), angle opening distance at 500 m (AOD500), angle recess area at 500 m (ARA500), and trabecular–iris space area at 500 m (TISA500). The intraclass correlation coefficient (ICC) was calculated as a measure of intraobserver and interobserver reproducibility. RESULTS. Twenty eyes of 20 patients were analyzed for shortterm reproducibility, and 23 eyes of 23 patients were analyzed for long-term reproducibility. AC depth measurement demonstrated excellent reproducibility (ICC 0.93–1.00) in both dark and light conditions. For the nasal and temporal quadrants, all AC angle parameters demonstrated good to excellent shortterm (ICC 0.67– 0.90) and long-term (ICC 0.56 – 0.93) reproducibility in both dark and light conditions. In the inferior quadrant, reproducibility was lower in all categories of analysis and varied from poor to good (ICC 0.31– 0.73). CONCLUSIONS. AS-OCT allows quantitative assessment of the AC angle. The reproducibility of AC angle measurements was good to excellent for the nasal and temporal quadrants. The lower reproducibility of measurements in the inferior quadrant may be unique to this prototype due to difficulty in acquiring high-quality images of the inferior angle. Further assessment of the commercially available AS-OCT is needed to clarify this finding. (Invest Ophthalmol Vis Sci. 2007;48:3683–3688) DOI: 10.1167/iovs.06-1120