Adaptive Optics Scanning Laser Ophthalmoscopy Images Research Articles

Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy

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.

Characterization of In Vivo Retinal Lesions of Diabetic Retinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy.

Purpose To characterize hallmark diabetic retinopathy (DR) lesions utilizing adaptive optics scanning laser ophthalmoscopy (AOSLO) and to compare AOSLO findings with those on standard imaging techniques. Methods Cross-sectional study including 35 eyes of 34 study participants. AOSLO confocal and multiply scattered light (MSL) imaging were performed in eyes with DR. Color fundus photographs (CF), infrared images of the macula (Spectralis, Heidelberg), and Spectralis spectral domain optical coherence tomography SDOCT B-scans of each lesion were obtained and registered to corresponding AOSLO images. Main Outcome Measures Individual lesion characterization by AOSLO imaging. AOSLO appearance was compared with CF and SDOCT imaging. Results Characterized lesions encompassed 52 microaneurysms (MA), 20 intraretinal microvascular abnormalities (IRMA), 7 neovascularization (NV), 11 hard exudates (HE), 5 dot/blot hemorrhages (HEM), 4 cotton wool spots (CWS), and 14 intraretinal cysts. AOSLO allowed assessment of perfusion in vascular lesions and enabled the identification of vascular lesions that could not be visualized on CF or SDOCT. Conclusions AOSLO imaging provides detailed, noninvasive in vivo visualization of DR lesions enhancing the assessment of morphological characteristics. These unique AOSLO attributes may enable new insights into the pathological changes of DR in response to disease onset, development, regression, and response to therapy.

CHARACTERIZING PHOTORECEPTOR CHANGES IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY USING ADAPTIVE OPTICS.

To characterize lesions of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) by multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO). We included patients with APMPPE at different stages of evolution of the placoid lesions. Color fundus photography, spectral domain optical coherence tomography, infrared reflectance, fundus autofluorescence, and AOSLO images were obtained and registered to correlate microstructural changes. Eight eyes of four patients (two women) were included and analyzed by multimodal imaging. Photoreceptor reflectivity within APMPPE lesions was more heterogeneous than in adjacent healthy areas. Hyperpigmentation on color fundus photography appeared hyperreflective on infrared reflectance and on AOSLO. Irregularity of the interdigitation zone and the photoreceptor inner and outer segment junctions (IS/OS) on spectral domain optical coherence tomography was associated with photoreceptor hyporeflectivity on AOSLO. Interruption of the interdigitation zone or IS/OS was associated with loss of photoreceptor reflectivity on AOSLO. Irregularities in the reflectivity of the photoreceptor mosaic are visible on AOSLO even in inactive APMPPE lesions, where the photoreceptor bands on spectral domain optical coherence tomography have recovered. Adaptive optics scanning laser ophthalmoscopy combined with multimodal imaging has the potential to enhance our understanding of photoreceptor involvement in APMPPE.

High-resolution Imaging in Male Germ Cell–Associated Kinase (MAK)-related Retinal Degeneration

To describe the characteristics of MAK-related retinal degeneration using optical coherence tomography angiography (OCTA) and adaptive optics scanning laser ophthalmoscopy (AOSLO). Cross-sectional study. Six patients with rod-cone degeneration and disease-causing mutations in MAK were evaluated with visual acuity, spectral-domain OCT, confocal AOSLO, and OCTA. Foveal avascular zone (FAZ) area, vessel densities, and perfusion densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the central macula in all 6 patients were compared with 5 normal subjects. Cone spacing was measured in 4 patients from AOSLO images and compared with 37 normal subjects. Patients ranged from 25 to 81 years of age (mean, 52 years). Visual acuity varied from 20/13 to 20/40+2, except in 1 patient with cystoid macular edema whose vision was 20/60- and 20/70+1. The SCP (P= .012) and DCP (P= .013) vessel density and perfusion density (P=.015 and .013, respectively) were significantly lower in patients compared to normal subjects in the parafoveal region 1.0-3.0mm from the fovea, but were similar to normal subjects within 1.0mm of the fovea. The FAZ area was not significantly different from normal (all P ≥ .24). Cone spacing was normal at almost all locations in 2 patients with early disease and increased in 2 patients with advanced disease. Although retinal vascular densities are reduced and cone spacing is increased in advanced disease, central foveal structure is maintained until late stages of disease, which may contribute to preservation of foveal vision in eyes with MAK-related retinal degeneration.

In Vivo Adaptive Optics Ophthalmoscopy Correlated with Histopathologic Results in Cancer-Associated Retinopathy

To demonstrate the validity of adaptive optics scanning laser ophthalmoscopy (AOSLO) imaging of the retina in human disease based on clinicopathologic correlation in a patient with cancer-associated retinopathy (CAR). Case report. Sixty-four-year-old man with CAR. Fundus photography, electroretinography, visual field testing, fundus autofluorescent imaging, spectral-domain OCT scans, AOSLO, and histopathologic analysis were performed. Comparison of AOSLO with histopathologic results. Changes in photoreceptor morphologic features were correlated highly between AOSLO and histopathologic results. We present a unique case where a patient with a rare and fatal disease, CAR, underwent AOSLO imaging during the course of the disease, and then shortly thereafter, postmortem histopathologic analysis of the eyes was carried out. This is the first report of use of AOSLO to elucidate further the retinal changes that occur in CAR and the first study to demonstrate correlation of AOSLO with histopathologic results in any human disease.

Imaging of Retinal Vascular Layers: Adaptive Optics Scanning Laser Ophthalmoscopy Versus Optical Coherence Tomography Angiography.

PurposeRetinal vascular networks are observed as a layered structure residing in a nerve fiber layer and an inner nuclear layer of the retina. This study aimed to evaluate reflectance confocal adaptive optics scanning laser ophthalmoscopy (AO-SLO) for imaging of the layered retinal vascular networks.MethodsThis study included 16 eyes of 16 healthy cases. On the fovea, 2.8- and 3.0 mm2-areas were imaged using a prototype AO-SLO and optical coherence tomography angiography (OCTA), respectively. AO-SLO images focused on the nerve fiber and photoreceptor layers were recorded in the area. Two different vessel images (capillary networks in the superficial layer and in all layers) were generated to examine if the deep capillary network could be distinguished. We compared AO-SLO with OCTA in imaging of the layered retinal vascular networks.ResultsSufficient images of capillary networks for analysis could be generated when the motion contrast was enhanced with AO-SLO movies in seven cases (43.8%). The deep capillary network could be distinguished in the merged image. Vascular depiction performance in AO-SLO was significantly better than in OCTA at both 0.5- and 1.0-mm areas from the fovea (P < 0.05).ConclusionsRetinal vascular imaging using AO-SLO might be a useful adjunct to OCTA as a supportive method to evaluate the retina in healthy patients and patients with disease.Translational RelevanceIn cases requiring accurate and detailed retinal vasculature observation, AO-SLO might be useful for evaluating retinal vascular lesions as a supportive imaging method of OCTA.

Outcomes in Autoimmune Retinopathy Patients Treated With Rituximab

To evaluate clinical and ancillary testing, including adaptive optics, outcomes in autoimmune retinopathy (AIR) patients treated with rituximab. Retrospective, interventional case series. patients: Sixteen AIR patients treated with rituximab. All patients were treated with a loading and maintenance dose schedule of intravenous rituximab. Visual acuity (VA), electroretinography (ERG), and spectral-domain optical coherence tomography (SDOCT) and visual field (VF) results were recorded. A subset of patients was also imaged using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Rates of VA change before vs after rituximab initiation were compared with mixed-model linear regression. The rate of visual decline was significantly less after rituximab initiation compared with the rate of visual decline prior to rituximab initiation (P= .005). Seventy-seven percent of eyes had stable or improved VA 6months after rituximab initiation. Amplitudes and implicit times on ERG, mean deviation on VF, central subfield mean thickness, and total macular volume did not decrease to a significant degree over the rituximab treatment period. Six eyes had serial AO-SLO imaging. Cone densities did not change significantly over the treatment period. VA was stable or improved in a majority of AIR patients while they were being treated with rituximab. OCT and ERG parameters, as well as AO-SLO cone densities, were stable during treatment. Studies with additional patients and longer follow-up periods are needed to further explore the utility of rituximab in the management of AIR.

Dysflective cones: Visual function and cone reflectivity in long-term follow-up of acute bilateral foveolitis

PurposeConfocal adaptive optics scanning laser ophthalmoscope (AOSLO) images provide a sensitive measure of cone structure. However, the relationship between structural findings of diminished cone reflectivity and visual function is unclear. We used fundus-referenced testing to evaluate visual function in regions of apparent cone loss identified using confocal AOSLO images. MethodsA patient diagnosed with acute bilateral foveolitis had spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista, CA, USA]) images indicating focal loss of the inner segment-outer segment junction band with an intact, but hyper-reflective, external limiting membrane. Five years after symptom onset, visual acuity had improved from 20/80 to 20/25, but the retinal appearance remained unchanged compared to 3 months after symptoms began. We performed structural assessments using SD-OCT, directional OCT (non-standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom-built system). We also administered fundus-referenced functional tests in the region of apparent cone loss, including analysis of preferred retinal locus (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype system). To determine AOSLO-corrected visual acuity, the scanning laser was modulated with a tumbling E consistent with 20/30 visual acuity. Visual sensitivity was assessed in and around the lesion using TSLO microperimetry. Complete eye examination, including standard measures of best-corrected visual acuity, visual field tests, color fundus photos, and fundus auto-fluorescence were also performed. ResultsDespite a lack of visible cone profiles in the foveal lesion, fundus-referenced vision testing demonstrated visual function within the lesion consistent with cone function. The PRL was within the lesion of apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but measurable: for trials in which the stimulus remained completely within the lesion, the subject got 48% correct, compared to 78% correct when the stimulus was outside the lesion. TSLO microperimetry revealed reduced, but detectible, sensitivity thresholds within the lesion. Conclusions and importanceFundus-referenced visual testing proved useful to identify functional cones despite apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD-OCT appear to be sensitive for the detection of abnormal or absent photoreceptors, changes in photoreceptors that are identified with these imaging tools do not correlate completely with visual function in every patient. Fundus-referenced vision testing is a useful tool to indicate the presence of cones that may be amenable to recovery or response to experimental therapies despite not being visible on confocal AOSLO or SD-OCT images.

Adaptive Optics Reveals Photoreceptor Abnormalities in Diabetic Macular Ischemia.

Diabetic macular ischemia (DMI) is a phenotype of diabetic retinopathy (DR) associated with chronic hypoxia of retinal tissue. The goal of this prospective observational study was to report evidence of photoreceptor abnormalities using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with DR in the setting of deep capillary plexus (DCP) non-perfusion. Eleven eyes from 11 patients (6 women, age 31–68), diagnosed with DR without macular edema, underwent optical coherence tomography angiography (OCTA) and AOSLO imaging. One patient without OCTA imaging underwent fluorescein angiography to characterize the enlargement of the foveal avascular zone. The parameters studied included photoreceptor heterogeneity packing index (HPi) on AOSLO, as well as DCP non-perfusion and vessel density on OCTA. Using AOSLO, OCTA and spectral domain (SD)-OCT, we observed that photoreceptor abnormalities on AOSLO and SD-OCT were found in eyes with non-perfusion of the DCP on OCTA. All eight eyes with DCP non-flow on OCTA showed photoreceptor abnormalities on AOSLO. Six of the eight eyes also had outer retinal abnormalities on SD-OCT. Three eyes with DR and robust capillary perfusion of the DCP had normal photoreceptors on SD-OCT and AOSLO. Compared to eyes with DR without DCP non-flow, the eight eyes with DCP non-flow had significantly lower HPi (P = 0.013) and parafoveal DCP vessel density (P = 0.016). We found a significant correlation between cone HPi and parafoveal DCP vessel density (r = 0.681, P = 0.030). Using a novel approach with AOSLO and OCTA, this study shows an association between capillary non-perfusion of the DCP and abnormalities in the photoreceptor layer in eyes with DR. This observation is important in confirming the significant contribution of the DCP to oxygen requirements of photoreceptors in DMI, while highlighting the ability of AOSLO to detect subtle photoreceptor changes not always visible on SD-OCT.

Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema.

PurposeTo determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME).MethodsParticipants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated.ResultsFifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04).ConclusionsAlthough absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM.

Detection of airbag impact-induced cone photoreceptor damage by adaptive optics scanning laser ophthalmoscopy: a case report

BackgroundThe purpose of this study was to report a case of traumatic maculopathy with para-central visual field defects following an impact by airbag deployment using adaptive optics scanning laser ophthalmoscopy (AO-SLO).Case presentationA 51-year-old man was involved in a motor vehicular accident and his left eye was struck by the deployed airbag, resulting in a para-central scotoma. The patient underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with prototype AO-SLO systems (Canon Inc.) at 14 and 22 months after the injury. Images focused on the photoreceptor layer were recorded in the foveal area, and a montage of AO-SLO images was created. On AO-SLO, focal dark areas could be observed in the left eye at 14 months after the injury. The analysis showed that the cone mosaic (cone density, 16503/mm2; ratio of hexagonal Voronoi domain, 36.3 %; average nearest-neighbor distance (NND)/expected NND, 0.606) was disordered compared with the normal area of the same eye (cone density, 24821/mm2; ratio of hexagonal Voronoi domain, 44.1 %; average NND/expected NND, 0.739). The cone defect area corresponded to the area of the scotoma. A second AO-SLO was performed on the patient at 22 months after the injury and although there were still areas with reduced cone reflectivity, partial improvement of cone mosaic was detected by AO-SLO at this time point.ConclusionPartial recovery of damaged cone photoreceptors following closed globe blunt ocular trauma can be documented using AO-SLO longitudinal tracking.

Eye-tracking technology for real-time monitoring of transverse chromatic aberration.

Objective measurements of transverse chromatic aberration (TCA) between two or more wavelengths with an adaptive optics scanning laser ophthalmoscope (AOSLO) are very accurate, but frequent measurements are impractical in many experimental settings. Here, we demonstrate a pupil tracker that can accurately measure relative changes in TCA that are caused by small shifts in the pupil relative to the AOSLO imaging beam. Corrections for TCA caused by these shifts improve the measurement of TCA as a function of eccentricity, revealing a strong linear relationship. We propose that pupil tracking be integrated into AOSLO systems, where robust and unobtrusive control of TCA is required.

Comparison of retinal vessel measurements using adaptive optics scanning laser ophthalmoscopy and optical coherence tomography.

We compared adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT) vessel caliber measurements. AOSLO videos were acquired from 28 volunteers with healthy eyes. Artery measurements were made 0.5-1 disc diameters away from the optic disc margin. Individual segmented retinal arterial caliber was measured in synchronization with cardiac pulsation and averaged to obtain final horizontal retinal arterial caliber (ACH) and horizontal retinal arterial lumen (ALH). All OCT images were obtained with the Spectralis OCT, a spectral-domain OCT system. Vertical retinal arterial caliber (ACV) and vertical retinal arterial lumen (ALV) were measured on the same artery measured with AOSLO. Measurements made with the two imaging systems were compared. Average ACH, measured with AOSLO, was 123.4±11.2 and average ALH was 101.8±10.2µm. Average ACV, measured with OCT, was 125.5±11.4 and average ALV was 99.1±10.6µm. Both arterial caliber (r=0.767, p<0.0001) and arterial lumen (r=0.81, p<0.0001) measurements were significantly correlated between imaging modalities. Additionally, ACH and ACV were not significantly different (p=0.16). However, ALH measurements were significantly higher than ALV measurements (p=0.03). Vessel measurements made with AOSLO and OCT were well correlated. Moreover, plasma is visible and distinguishable from the retinal vessel wall in AOSLO images but not in OCT images. Therefore, AOSLO may measure vessel width more precisely than OCT.

Evaluation of Photoreceptors in Bietti Crystalline Dystrophy with CYP4V2 Mutations Using Adaptive Optics Scanning Laser Ophthalmoscopy

To evaluate photoreceptors in Bietti crystalline dystrophy patients with CYP4V2 mutations using high-resolution images of the macula obtained with adaptive optics scanning laser ophthalmoscopy (AO-SLO). Prospective observational case series with comparison to healthy controls. Seven eyes of 7 Bietti crystalline dystrophy patients with CYP4V2 mutations and 12 normal eyes of 12 age- and axial length-matched healthy volunteers were studied. All participants underwent ophthalmologic examinations and AO-SLO assessments. All patients underwent spectral-domain optical coherence tomography, fundus autofluorescence, Humphrey field analysis, and electroretinography. AO-SLO images were analyzed 0.5 mm and 1.0 mm from the center of the fovea in the superior, inferior, nasal, and temporal quadrants. Mean ± standard deviation cone density (cells/mm(2)) 0.5 mm from the center of the fovea was 17,209 ± 2276 in patients and 20 493 ± 2758 in controls, which was statistically different (P = .001); however, mean cone density 1.0 mm from the center of the fovea was 15 685 ± 2302 in patients and 15 705 ± 1848 in controls, which was not statistically different (P = .20). There was no correlation between cone density and mean deviation measured using a Humphrey field analysis or visual acuity in patients. In Bietti crystalline dystrophy patients with CYP4V2 mutations, cone density remained for visual dysfunction by evaluation using high-resolution AO-SLO. These findings support the theory that disorder of the retinal pigment epithelium and the photoreceptors in the patients are the primary and secondary pathologic changes, respectively. This is consistent with results from previous basic studies.

Repeatability of Cone Spacing Measures in Eyes With Inherited Retinal Degenerations.

To determine short-term variability of adaptive optics scanning laser ophthalmoscopy (AOSLO)-derived cone spacing measures in eyes with inherited retinal degenerations (IRD) and in normal eyes. Twenty IRD patients and 10 visually normal subjects underwent AOSLO imaging at two visits separated by no more than 1 month (NCT00254605). Cone spacing was measured in multiple macular regions in each image by three independent graders. Variability of cone spacing measures between visits, between graders, and between eyes was determined and correlated with standard clinical measures. Cone spacing was measured in 2905 regions. Interobserver agreement was high both in normal eyes and eyes with IRD (mean intraclass correlation coefficient [ICC] = 0.838 for normal and 0.892 for eyes with IRD). Cone spacing measures were closely correlated between visits (ICC > 0.869 for both study groups). Mean relative intervisit spacing difference (absolute difference in measures divided by the mean at each region) was 4.0% for normal eyes and 4.9% for eyes with IRD. Cone spacing measures from fellow eyes of the same subject showed strong agreement for all subjects (ICC > 0.85 for both study groups). Adaptive optics scanning laser ophthalmoscopy-derived macular cone spacing measures were correlated between observers, visits, and fellow eyes of the same subject in normal eyes and in eyes with IRD. This information may help establish the role of cone spacing measures derived from images of the cone mosaic obtained with AOSLO as a sensitive biomarker for longitudinal tracking of photoreceptor loss during disease progression and in response to treatment. (ClinicalTrials.gov number, NCT00254605.).

High-speed adaptive optics for imaging of the living human eye.

The discovery of high frequency temporal fluctuation of human ocular wave aberration dictates the necessity of high speed adaptive optics (AO) correction for high resolution retinal imaging. We present a high speed AO system for an experimental adaptive optics scanning laser ophthalmoscope (AOSLO). We developed a custom high speed Shack-Hartmann wavefront sensor and maximized the wavefront detection speed based upon a trade-off among the wavefront spatial sampling density, the dynamic range, and the measurement sensitivity. We examined the temporal dynamic property of the ocular wavefront under the AOSLO imaging condition and improved the dual-thread AO control strategy. The high speed AO can be operated with a closed-loop frequency up to 110 Hz. Experiment results demonstrated that the high speed AO system can provide improved compensation for the wave aberration up to 30 Hz in the living human eye.

Active eye-tracking for an adaptive optics scanning laser ophthalmoscope.

We demonstrate a system that combines a tracking scanning laser ophthalmoscope (TSLO) and an adaptive optics scanning laser ophthalmoscope (AOSLO) system resulting in both optical (hardware) and digital (software) eye-tracking capabilities. The hybrid system employs the TSLO for active eye-tracking at a rate up to 960 Hz for real-time stabilization of the AOSLO system. AOSLO videos with active eye-tracking signals showed, at most, an amplitude of motion of 0.20 arcminutes for horizontal motion and 0.14 arcminutes for vertical motion. Subsequent real-time digital stabilization limited residual motion to an average of only 0.06 arcminutes (a 95% reduction). By correcting for high amplitude, low frequency drifts of the eye, the active TSLO eye-tracking system enabled the AOSLO system to capture high-resolution retinal images over a larger range of motion than previously possible with just the AOSLO imaging system alone.

The Association Between the Foveal Avascular Zone and Retinal Thickness

To investigate the association between the size and shape of the foveal avascular zone and retinal thickness in healthy subjects. In vivo imaging of the foveal microvasculature was performed on 32 subjects by using an adaptive optics scanning laser ophthalmoscope (AOSLO). Motion contrast maps of the AOSLO images were used to generate a montage revealing the foveal capillary network. Foveal avascular zone (FAZ) diameters along the horizontal (FAZH) and vertical (FAZV) meridians were measured on the montages. An asymmetry index (AI) of the FAZ was then computed as the ratio of the FAZH to FAZV. Retinal thickness was investigated by using spectral-domain optical coherence tomography (SDOCT). Inner retinal layer (INLFAZ) thickness and outer nuclear layer (ONLFAZ) thickness were measured at the edges of the FAZ on the horizontal and vertical SDOCT scans on the same eye. The foveal capillary network was readily visualized in all subjects. As expected there was individual variation in the size and shape of the FAZ. Along the horizontal and vertical meridians, the mean±SD (μm) of the FAZ diameter was 607±217 and 574±155, respectively. The INLFAZ thickness was 68±9 and 66±9, and the ONLFAZ thickness was 103±13 and 105±11, respectively. The mean±SD of the AI was 1.03±0.27. The difference between FAZH and FAZV decreases with increasing FAZ area (P=0.004). Mean ONLFAZ was negatively correlated with FAZ effective diameter (P<0.0001). No significant correlation was found between mean INLFAZ and FAZ effective diameter (P=0.16). Despite large individual variations in size and shape of the FAZ, the INLFAZ has a relatively constant thickness at the margins of the FAZ, suggesting the presence of retinal capillaries is needed to sustain an INLFAZ thickness greater than 60 μm. A smaller FAZ area is associated with a vertically elongated FAZ.

Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy.

Adaptive optics scanning laser ophthalmoscopy (AO-SLO) is a noninvasive technique that allows for the direct monitoring of erythrocyte aggregates in retinal capillaries. We analyzed the retinal hemorheologic characteristics in normal subjects, diabetic patients without diabetic retinopathy (NDR), and diabetic patients with nonproliferative diabetic retinopathy (NPDR), using spatiotemporal (ST) blood flow images to visualize blood corpuscle trajectory. AO-SLO images of the parafoveal capillary network were acquired for three groups: 20 healthy volunteers, 17 diabetic patients with NDR (8 type 1 and 9 type 2 patients), and 10 diabetic patients with NPDR (4 type 1 and 6 type 2). The erythrocyte aggregate velocity assigned to a relative cardiac cycle and the elongation rate of the erythrocyte aggregate were calculated. Careful observation revealed that flow velocity fluctuations were found with higher frequency in diabetic patients than in normal subjects. The total average velocities were 1.26 ± 0.22 mm/s in the normal group, 1.31 ± 0.21 mm/s in the NDR group, and 1.63 ± 0.35 mm/s in the NPDR group. The average velocities of the NPDR group were higher than those in the normal (P = 0.001) and NDR (P = 0.009) groups. The average elongation rates of the 3 groups were 0.67 ± 0.20, 0.39 ± 0.19, and 0.33 ± 0.11, respectively. Elongation rate differed significantly between the normal and NDR (P = 0.003) groups as well as the normal and NPDR (P = 0.001) groups. AO-SLO can be used to detect retinal hemorheologic changes in the early stages of diabetic retinopathy.

Progress on Developing Adaptive Optics-Optical Coherence Tomography for In Vivo Retinal Imaging: Monitoring and Correction of Eye Motion Artifacts.

Recent progress in retinal image acquisition techniques, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), combined with improved performance of adaptive optics (AO) instrumentation, has resulted in improvement in the quality of in vivo images of cellular structures in the human retina. Here, we present a short review of progress on developing AO-OCT instruments. Despite significant progress in imaging speed and resolution, eye movements present during acquisition of a retinal image with OCT introduce motion artifacts into the image, complicating analysis and registration. This effect is especially pronounced in high-resolution datasets acquired with AO-OCT instruments. Several retinal tracking systems have been introduced to correct retinal motion during data acquisition. We present a method for correcting motion artifacts in AO-OCT volume data after acquisition using simultaneously captured adaptive optics-scanning laser ophthalmoscope (AO-SLO) images. We extract transverse eye motion data from the AO-SLO images, assign a motion adjustment vector to each AO-OCT A-scan, and re-sample from the scattered data back onto a regular grid. The corrected volume data improve the accuracy of quantitative analyses of microscopic structures.