Response of Retinal Blood Flow to Systemic Hyperoxia as Measured with Dual-Beam Bidirectional Doppler Fourier-Domain Optical Coherence Tomography

Purpose

There is a long-standing interest in the study of retinal blood flow in humans. In the recent years techniques have been established to measure retinal perfusion based on optical coherence tomography (OCT). In the present study we used a technique called dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT) to characterize the effects of 100% oxygen breathing on retinal blood flow. These data were compared to data obtained with a laser Doppler velocimeter (LDV).

Methods

10 healthy subjects were studied on 2 study days. On one study day the effect of 100% oxygen breathing on retinal blood velocities was studied using dual-beam bidirectional Doppler FD-OCT. On the second study day the effect of 100% oxygen breathing on retinal blood velocities was assessed by laser Doppler velocimetry (LDV). Retinal vessel diameters were measured on both study days using a commercially available Dynamic Vessel Analyzer. Retinal blood flow was calculated based on retinal vessel diameters and red blood cell velocity.

Results

As expected, breathing of pure oxygen induced a pronounced reduction in retinal vessel diameters, retinal blood velocities and retinal blood flow on both study days (p<0.001). Blood velocity data correlated well between the two methods applied under both baseline as well as under hyperoxic conditions (r = 0.98 and r = 0.75, respectively). Data as obtained with OCT were, however, slightly higher.

Conclusion

A good correlation was found between red blood cell velocity as measured with dual-beam bidirectional Doppler FD-OCT and red blood cell velocity assessed by the laser Doppler method. Dual-beam bidirectional Doppler FD-OCT is a promising approach for studying retinal blood velocities in vivo.     

Circumpapillary Course of Retinal Pigment Epithelium Can Be Fit to Sine Wave and Amplitude of Sine Wave Is Significantly Correlated with Ovality Ratio of Optic Disc

The purpose of this study was to develop a method of quantifying the degree of optic disc tilt in normal eyes. This was a prospective, observational cross sectional study of 126 right eyes of 126 healthy volunteers. The optic disc tilt was determined from the circular peripapillary optical coherence tomographic (OCT) scan images. The course of the retinal pigment epithelium (RPE) layer in the peripapillary cross sectional scan images was fit to a sine wave curve, and the amplitude of the sine curve was used to reflect the degree of the optic disc tilt in the optical axis. The repeatability of the amplitude determinations was calculated. The correlation between the amplitude and the ovality ratio of the optic disc was determined. The correlation between the amplitude and the body height was also calculated. The mean amplitudewas 36.6 ± 17.5 pixels, which was significantly and inversely correlated with the ovality ratio of the optic disc (R = -0.59, P<0.001). The intra-rater and inter-rater correlation coefficients of the amplitude were significant high (P<0.001, both). The amplitude was significantly and inversely correlated with the body height (R = -0.38, P<0.001), but not with the axial length. In conclusion, a sine wave function can be used to describe the course of the RPE in the circumpapillary OCT images. The results indicate that the amplitude of the sine wave can be used to represent the degree of optic disc tilt. Thus, the sine wave analyses can be used as a quantifiable and repeatable method to determine the optic disc tilt.     

Retinal pulse wave velocity measurement using spectral‐domain optical coherence tomography

The human eyes provide a natural window for noninvasive measurement of the pulse wave velocity (PWV) of small arteries. By measuring the retinal PWV, the stiffness of small arteries can be assessed, which may better detect early vascular diseases. Therefore, retinal PWV measurement has attracted increasing attention. In this study, a jump‐scanning method was proposed for noninvasive measurement of retinal PWV using spectral‐domain optical coherence tomography (SD‐OCT). The jump‐scanning method uses the phase‐resolved Doppler OCT to obtain the pulse shapes. To realize PWV measurement, the jump‐scanning method extracts the transit time of the pulse wave from an original OCT scanning site to another through a transient jump. The measured retinal arterial PWV of a young human subject with normal blood pressure was in the order of 20 to 30 mm/s, which was consistent with previous studies. As a comparison, PWV of 50 mm/s was measured for a young human subject with prehypertension, which was in accordance with the finding of strong association between retinal PWV and blood pressure. In summary, it is believed the proposed jump‐scanning method could benefit the research and diagnosis of vascular diseases through the window of human eyes.      

Parafoveal Retinal Vascular Response to Pattern Visual Stimulation Assessed with OCT Angiography

We used optical coherence tomography (OCT) angiography with a high-speed swept-source OCT system to investigate retinal blood flow changes induced by visual stimulation with a reversing checkerboard pattern. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to quantify blood flow as measured with parafoveal flow index (PFI), which is proportional to the density of blood vessels and the velocity of blood flow in the parafoveal region of the macula. PFI measurements were taken in 15 second intervals during a 4 minute period consisting of 1 minute of baseline, 2 minutes with an 8 Hz reversing checkerboard pattern stimulation, and 1 minute without stimulation. PFI measurements increased 6.1±4.7% (p = .001) during the first minute of stimulation, with the most significant increase in PFI occurring 30 seconds into stimulation (p<0.001). These results suggest that pattern stimulation induces a change to retinal blood flow that can be reliably measured with OCT angiography.     

Profile and Determinants of Retinal Optical Intensity in Normal Eyes with Spectral Domain Optical Coherence Tomography

Purpose

To investigate the profile and determinants of retinal optical intensity in normal subjects using 3D spectral domain optical coherence tomography (SD OCT).

Methods

A total of 231 eyes from 231 healthy subjects ranging in age from 18 to 80 years were included and underwent a 3D OCT scan. Forty-four eyes were randomly chosen to be scanned by two operators for reproducibility analysis. Distribution of optical intensity of each layer and regions specified by the Early Treatment of Diabetic Retinopathy Study (ETDRS) were investigated by analyzing the OCT raw data with our automatic graph-based algorithm. Univariate and multivariate analyses were performed between retinal optical intensity and sex, age, height, weight, spherical equivalent (SE), axial length, image quality, disc area and rim/disc area ratio (R/D area ratio).

Results

For optical intensity measurements, the intraclass correlation coefficient of each layer ranged from 0.815 to 0.941, indicating good reproducibility. Optical intensity was lowest in the central area of retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and photoreceptor layer, except for the retinal pigment epithelium (RPE). Optical intensity was positively correlated with image quality in all retinal layers (0.553<β<0.851, p<0.01), and negatively correlated with age in most retinal layers (-0.362<β<-0.179, p<0.01), except for the RPE (β = 0.456, p<0.01), outer nuclear layer and photoreceptor layer (p>0.05). There was no relationship between retinal optical intensity and sex, height, weight, SE, axial length, disc area and R/D area ratio.

Conclusions

There was a specific pattern of distribution of retinal optical intensity in different regions. The optical intensity was affected by image quality and age. Image quality can be used as a reference for normalization. The effect of age needs to be taken into consideration when using OCT for diagnosis.     

A Simple Sign for Recognizing Off–Axis OCT Measurement Beam Placement in the Context of Multicentre Studies

Purpose

Optical coherence tomography (OCT) allows quantification of the thickness of the retinal nerve fibre layer (RNFL) thickness, a potential biomarker for neurodegeneration. The estimated annual RNFL loss in multiple sclerosis amounts to 2 μm using time domain OCT. The recognition of measurement artifacts exceeding this limit is relevant for the successful use of OCT as a secondary outcome measure in clinical trials.

Methods

Prospective study design. An exploratory pilot study (ring and volume scans) followed by a cohort study (1,980 OCT ring scans). The OCT measurement beam was placed off–axis to the left, right, top and bottom of the subjects pupil and RNFL thickness of these scans were compared to the centrally placed reference scans.

Results

Off–axis placement of the OCT measurement beam resulted in significant artifacts in RNFL thickness measurements (95%CI 9μm, maximal size of error 42μm). Off–axis placement gave characteristic patterns of the OCT live images which are not necessarily saved for review. Off–axis placement also causes regional inhomogeneity of reflectivity in the outer nuclear (ONL) and outer plexiform layers (OPL) which remains visible on scans saved for review.

Conclusion

Off–axis beam placement introduces measurement artifacts at a magnitude which may mask recognition of RNFL loss due to neurodegeneration in multiple sclerosis. The resulting pattern in the OCT live image can only be recognised by the technician capturing the scans. Once the averaged scans have been aligned this pattern is lost. Retrospective identification of this artifact is however possible by presence of regional inhomogeneity of ONL/OPL reflectivity. This simple and robust sign may be considered for quality control criteria in the setting of multicentre OCT studies. The practical advice of this study is to keep the OCT image in the acquisition window horizontally aligned whenever possible.     

Optic Disc Hemorrhage Is Related to Various Hemodynamic Findings by Disc Angiography

Background

To investigate the hemodynamic characteristics of glaucoma eyes with disc hemorrhage (DH) by disc fluorescein angiography, and its relationship with glaucomatous changes of the optic disc and surrounding retinal nerve fiber layer (RNFL).

Methods

This study included 35 glaucoma eyes with DH who were followed up at least 5 years and had DH at presentation. Eyes were classified as eyes with DH at the border of localized RNFL defects and eyes with DH not related to localized RNFL defects. Prevalence of DH and location of the proximal border were recorded from disc photographs. Fluorescein angiography was performed 3 months after detecting the DH. Arm-retina time, arteriovenous transit time, disc filling time, choroidal filling time, and venous filling time were measured as retinal circulation parameters. The presence of disc filling defects and disc leaks were evaluated.

Results

There were 19 (54.3%) eyes with DH accompanying localized RNFL defects. The arm-retina time was prolonged in eyes with DH not related to RNFL defects (P = 0.044) and the arteriovenous transit time was prolonged in eyes with DH accompanying RNFL defects (P = 0.029). Among eyes with DH accompanying RNFL defects, 11 (57.9%) had vessel filling defects or delayed filling indicating blood flow stasis at the cup margin proximal to where DH occurred. Eyes with DH not related to RNFL defects did not show vessel filling defects or delayed filling.

Conclusions and Relevance

Eyes with DH related to RNFL defects showed prolonged arteriovenous transit time and had frequent vessel filling defects or delayed filling indicating blood flow stasis and thrombus formation at the site DH occurred. These findings suggest that vascular and hemodynamic changes due to glaucomatous structural changes cause DH in relation to localized RNFL defects.     

Phase unwrapping for Doppler spectral domain optical coherence tomography flow measurement

Doppler optical coherence tomography (OCT) offers additional flow velocity information, which extends the application of OCT. Phase wrapping is the inherent problem that limits measureable range of Doppler OCT. We propose a phase unwrapping method which is suitable for correcting phase in Doppler OCT images. Points (pixels) in flow region are divided into groups according to the radial distance. Points in the same group are supposed to have close velocity. Phase unwrapping algorithm begins at the boundary layer group and is performed sequentially toward the center. Using the proposed criterion, points in a group are separated into two categories, signal points and noise points. Wrapping rounds are determined for signal points phase unwrapping. Mean value of the corrected signal points replaces the noise points for noise reduction. The method is validated with capillary tube flow phantom and in vivo blood flow.     

Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Purpose

To investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia.

Methods

A total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure β-peripapillary atrophy (PPA) lengths with and without Bruch''s membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well.

Results

LC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P<0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P<0.001), and larger vertical/horizontal tilt angles (vertical, P<0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P<0.001) and vertical tilt angle (P<0.001) were identified as significant.

Conclusions

The presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.     

Correlation of Retinal Nerve Fibre Layer Thickness and Spontaneous Retinal Venous Pulsations in Glaucoma and Normal Controls

Purpose

To study the relationship between amplitude of spontaneous retinal venous pulsatility (SRVP) and retinal nerve fibre layer (RNFL) thickness in glaucomatous eyes, and to determine if this parameter may be a potential marker for glaucoma severity.

Method

85 subjects including 50 glaucoma (21 males, 67±10 yrs) and 35 normals (16 males, 62±11 yrs) were studied. SRVP amplitude was measured using the Dynamic Vessel Analyser (DVA, Imedos, Germany) at four regions of the retina simultaneously within one disc diameter from the optic disc—temporal-superior (TS), nasal-superior (NS), temporal-inferior (TI) and nasal-inferior (NI)). This was followed by RNFL thickness measurement using spectral domain optical coherence tomography (Spectralis OCT). The correlation between SRVP amplitude and corresponding sectoral RNFL thickness was assessed by means of non-linear regression (i.e. logarithmic). Linear regression was also applied and slopes were compared using analysis of covariance (ANCOVA).

Results

Greater SRVP amplitude was associated with thicker RNFL. Global SRVP amplitude was significantly lower in glaucoma eyes compared with normals (p<0.0001). The correlation coefficient of the linear regression between RNFL and SRVP at TS, NS, TI and NI quadrants in the glaucoma group were r = 0.5, 0.5, 0.48, 0.62. Mean SRVP amplitude and RNFL thickness for TS, NS, TI and NI quadrants were 4.3±1.5, 3.5±1.3, 4.7±1.6, 3.1±1 μm and 96±30, 75±22, 89±35 and 88±30 μm, respectively. The ANCOVA test showed that the slope of linear regression between the four quadrants was not significant (p>0.05). Since the slopes are not significantly different, it is possible to calculate one slope for all the data. The pooled slope equals 10.8 (i.e. RNFL = 10.8SRVP+41).

Conclusion

While SRVP was present and measurable in all individuals, the amplitude of SRVP is reduced in glaucoma with increasing RNFL loss. Our findings suggest the degree of SRVP may be an additional marker for glaucoma severity. Further studies are needed to determine the mechanism of reduction in SRVP, and whether changes can predict increased risk of progression.     

Astrocyte invasion and vasculogenesis in the developing ferret retina

We studied the time course of astrocyte invasion and blood vessel formation in the developing ferret retina using glial fibrillary acidic protein (GFAP)-immunohistochemistry for astrocytes and isolectin B4 histochemistry for blood vessels. As in other mammals, strongly GFAP positive astrocytes invade the ferret retina from the optic nerve. At birth, strongly GFAP positive astrocytes have reached about 22% of the distance between optic disc and outer retinal edge whereas weakly GFAP positive processes already extend to the edge of the retina. At postnatal days P30–P37 about 82% of the distance between optic disc and outer retinal edge and in the adult 88% of this distance is covered with strongly labelled astrocytes. Superficial blood vessels form from the optic disc. They reach up to about 24% of the retinal radius at birth and grow radially across the retina during further development. At P30–P37, the whole retina is covered with superficial blood vessels. The deep vascular layer forms later (around P30) through sprouting from superficial vessels. The radial pattern of astrocyte and vessel growth from the optic disc is not affected by the formation of the area centralis and visual streak.     

Reproducibility of In-Vivo OCT Measured Three-Dimensional Human Lamina Cribrosa Microarchitecture

Purpose

To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT).

Methods

Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS−) OCT in a 3.5×3.5×3.64 mm (400×400×896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans.

Results

The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects.

Conclusion

The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC.     

Repeatability Using Automatic Tracing with Canon OCT- HS100 and Zeiss Cirrus HD-OCT 5000

Background

Optical coherence tomography (OCT), can be used in clinical practice to provide high resolution cross-sectional images of the retina, optic disc and macula structure. These measurements can be useful for early detection, diagnosis, monitoring and treatment guidance for retinal diseases. Therefore, repeatability of measurements in OCT is of great importance.

Methods

Macula and optic disc parameters from the right eye of 30 healthy subjects were obtained twice with the Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. Repeatability was evaluated by use of the coefficient of repeatability (CR) and the coefficient of repeatability as a percentage of the mean (CR%), and the obtained measurements were compared between the instruments.

Results

CR% of optic disc parameters ranged between 0.90 and 22.22% and 0.00 and 16.00% with the Canon and Zeiss OCT respectively. For macular parameters CR% ranged between 0.62 and 2.81% and 0.99 and 1.81% with the Canon and Zeiss OCT respectively. No statistical difference could be found when comparing the CR of all macular and disc measurements between the instruments. Compared to our previously published data repeatability has significantly improved with the inclusion of automatic tracking systems with both the Canon and Zeiss OCT.

Conclusion

Automatic tracking function improves repeatability in both Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. However, measurements generated by the two instruments are still not interchangeable.     

Optic Disc Change during Childhood Myopic Shift: Comparison between Eyes with an Enlarged Cup-To-Disc Ratio and Childhood Glaucoma Compared to Normal Myopic Eyes

BackgroundProgressive disc tilting and the development or enlargement of peripapillary atrophy (PPA) are observed during a myopic shift in children. This could be related to the changes around the optic nerve head during eyeball elongation. If the biomechanical properties at or around the optic nerve head are changed after exposure to elevated intraocular pressure (IOP) in glaucoma eyes, different response of the disc tilting and PPA changes could take place during eyeball elongation by myopic shift. On the basis of this background, the aim of this study was to compare the morphological changes in the optic disc induced by a myopic shift during childhood between normal control eyes, eyes from disc suspects with an enlarged cup-to-disc ratio (CDR), and eyes with childhood glaucoma.MethodsTotal of 82 eyes from 82 subjects younger than 14 years of age were included in the study. Serial disc photographs were classified into one of two groups: eyes with an optic nerve head (ONH) or peripapillary atrophy (PPA) change or without an ONH/PPA change. Using ImageJ software, the outlines of the optic disc and PPA were plotted, and the vertical disc diameter (VDD), horizontal disc diameter (HDD), and maximum PPA width (PPW) were measured. The changes in the ratios of these parameters and the relationships between the degree of myopic shift or the ONH/PPA change were analyzed.ResultsTwenty-five eyes with normal optic disc appearance, 36 eyes with enlarged cup-to-disc ratio, and 21 eyes of glaucoma patients were analyzed. The initial intraocular pressure (IOP) at diagnosis was significantly different among the groups (P<0.001). The degree of myopic shift during follow-up period was not significantly different among the groups (P=0.612). However, the changes in the HDD/VDD and PPW/VDD ratios were significantly greater in the disc suspect group and significantly smaller in the glaucoma group. Among the 42 eyes with an ONH/PPA change, 16 (38.1%) were from the normal control group, 24 (57.1%) were from the disc suspect group, and 2 (4.8%) were from the glaucoma group (P < 0.001).

Conclusions and Relevance

The optic disc change during childhood myopic shift was different in eyes with various conditions. Eyes of childhood glaucoma showed less change in the disc morphology during myopic shift compared to eyes with normal disc or enlarged cup-to-disc ratio.     

Comparison of the Deep Optic Nerve Head Structure between Normal-Tension Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy

PurposeTo compare the deep optic nerve head (ONH) structure between normal-tension glaucoma (NTG) and nonarteritic anterior ischemic optic neuropathy (NAION) and also in healthy subjects as a control using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT).MethodsThis prospective cross-sectional study included 21 NAION patients who had been diagnosed as NAION at least 6 months prior to study entry, and 42 NTG patients and 42 healthy controls who were matched with NAION patients in terms of age, intraocular pressure (IOP), and optic disc area. The retinal nerve fiber layer (RNFL) thickness in the affected sector was also matched between NAION and NTG patients. The ONH was imaged using SD-OCT with the EDI technique. The anterior lamina cribrosa surface depth (LCD) and average prelaminar tissue (PT) thickness were measured in a sector of interest in each eye and compared among the three groups.ResultsIn the sector-matched comparison, LCD was largest in NTG patients, followed by NAION patients, while PT was thinner in NTG patients than in NAION patients (all P < 0.001). NAION patients had a comparable LCD and a thinner PT relative to normal controls (P = 0.170 and < 0.001, respectively).ConclusionThe deep ONH configuration is strikingly different between NTG and NAION. The differing features provide comparative insight into the pathophysiology of the two diseases, and may be useful for differential diagnosis.     

Biometry of Anterior Segment of Human Eye on Both Horizontal and Vertical Meridians during Accommodation Imaged with Extended Scan Depth Optical Coherence Tomography

Purpose

To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation.

Methods

Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR).

Results

There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation.

Conclusion

The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation.     

The OSCAR-IB consensus criteria for retinal OCT quality assessment

Background

Retinal optical coherence tomography (OCT) is an imaging biomarker for neurodegeneration in multiple sclerosis (MS). In order to become validated as an outcome measure in multicenter studies, reliable quality control (QC) criteria with high inter-rater agreement are required.

Methods/Principal Findings

A prospective multicentre study on developing consensus QC criteria for retinal OCT in MS: (1) a literature review on OCT QC criteria; (2) application of these QC criteria to a training set of 101 retinal OCT scans from patients with MS; (3) kappa statistics for inter-rater agreement; (4) identification reasons for inter-rater disagreement; (5) development of new consensus QC criteria; (6) testing of the new QC criteria on the training set and (7) prospective validation on a new set of 159 OCT scans from patients with MS. The inter-rater agreement for acceptable scans among OCT readers (n = 3) was moderate (kappa 0·45) based on the non-validated QC criteria which were entirely based on the ophthalmological literature. A new set of QC criteria was developed based on recognition of: (O) obvious problems, (S) poor signal strength, (C) centration of scan, (A) algorithm failure, (R) retinal pathology other than MS related, (I) illumination and (B) beam placement. Adhering to these OSCAR-IB QC criteria increased the inter-rater agreement to kappa from moderate to substantial (0.61 training set and 0.61 prospective validation).

Conclusions

This study presents the first validated consensus QC criteria for retinal OCT reading in MS. The high inter-rater agreement suggests the OSCAR-IB QC criteria to be considered in the context of multicentre studies and trials in MS.     

Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma,as Measured with Swept Source Optical Coherence Tomography

PurposeTo investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon).MethodsThis retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 μm), centered on the circular Bruch’s membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24–2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman''s rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela’s method.ResultsWe found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT (P < 0.001) and 0.46 (P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 μm, PPG: 248 ± 13 μm, OAG: 233 ± 20 μm). Multiple regression analysis showed that MD (β = 0.29, P = 0.013), vertical C/D ratio (β = -0.25, P = 0.020) and tissue MBR (β = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 μm) than the non-GE patients (243.6 ± 19.5 μm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 (P < 0.001) in the GE patients and 0.39 (P = 0.013) in the non-GE patients.ConclusionCupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.     

High-resolution imaging of the retinal nerve fiber layer in normal eyes using adaptive optics scanning laser ophthalmoscopy

Purpose

To conduct high-resolution imaging of the retinal nerve fiber layer (RNFL) in normal eyes using adaptive optics scanning laser ophthalmoscopy (AO-SLO).

Methods

AO-SLO images were obtained in 20 normal eyes at multiple locations in the posterior polar area and a circular path with a 3–4-mm diameter around the optic disc. For each eye, images focused on the RNFL were recorded and a montage of AO-SLO images was created.

Results

AO-SLO images for all eyes showed many hyperreflective bundles in the RNFL. Hyperreflective bundles above or below the fovea were seen in an arch from the temporal periphery on either side of a horizontal dividing line to the optic disc. The dark lines among the hyperreflective bundles were narrower around the optic disc compared with those in the temporal raphe. The hyperreflective bundles corresponded with the direction of the striations on SLO red-free images. The resolution and contrast of the bundles were much higher in AO-SLO images than in red-free fundus photography or SLO red-free images. The mean hyperreflective bundle width around the optic disc had a double-humped shape; the bundles at the temporal and nasal sides of the optic disc were narrower than those above and below the optic disc (P<0.001). RNFL thickness obtained by optical coherence tomography correlated with the hyperreflective bundle widths on AO-SLO (P<0.001)

Conclusions

AO-SLO revealed hyperreflective bundles and dark lines in the RNFL, believed to be retinal nerve fiber bundles and Müller cell septa. The widths of the nerve fiber bundles appear to be proportional to the RNFL thickness at equivalent distances from the optic disc.     

Imaging of retinal ganglion cells in glaucoma: pitfalls and challenges

Imaging has gained a key role in modern glaucoma management. Traditionally, interest was directed toward the appearance of the optic nerve head and the retinal nerve fiber layer. With the improvement of the resolution of optical coherence tomography, the ganglion cell complex has also become routinely accessible in the clinic. Further advances have been made in understanding the structure-function relationship in glaucoma. Nevertheless, direct imaging of the retinal ganglion cells in glaucoma would be advantageous. With the currently used techniques, this goal cannot be achieved, because the transversal resolution is limited by aberrations of the eye. The use of adaptive optics has significantly improved transversal resolution, and the imaging of several cell types including cones and astrocytes has become possible. Imaging of retinal ganglion cells, however, still remains a problem, because of the transparency of these cells. However, the visualization of retinal ganglion cells and their dendrites has been achieved in animal models. Furthermore, attempts have been made to visualize the apoptosis of retinal ganglion cells in vivo. Implementation of these techniques in clinical practice will probably improve glaucoma care and facilitate the development of neuroprotective strategies.