Zoran Popovic

Noninvasive imaging of human foveal capillary network using dual-conjugate adaptive optics.

PURPOSE To demonstrate noninvasive imaging of human foveal capillary networks with a high-resolution, wide-field, dual-conjugate adaptive optics (DCAO) imaging instrument. METHODS The foveal capillary networks of five healthy subjects with no previous history of ocular or neurologic disease or surgery were imaged with a novel high-resolution, wide-field DCAO instrument. The foveal avascular zone (FAZ) in each image was defined using a manual procedure. An automated algorithm based on publicly available and custom-written software was used to identify vessels and extract morphologic FAZ and vessel parameters. Capillary densities were calculated in two annular regions of interest (ROIs) outside the FAZ (500 μm and 750 μm outer radius from the foveal center) and in the superior, inferior, temporal, and nasal quadrants within the two ROIs. RESULTS Mean FAZ area was 0.302 ± 0.100 mm(2), and mean capillary density (length/area) in the inner ROI was 38.0 ± 4.0 mm(-1) and 36.4 ± 4.0 mm(-1) in the outer ROI. The difference in ROI capillary density was not significant. There was no significant difference in quadrant capillary density within the two ROIs or between quadrants irrespective of ROI. CONCLUSIONS The authors have demonstrated a technique for noninvasive imaging and semiautomated detection and analysis of foveal capillaries. In comparison with other studies, their method yielded lower capillary densities than histology but similar results to the current clinical gold standard, fluorescein angiography. The increased field of view of the DCAO instrument opens up new possibilities for high-resolution noninvasive clinical imaging of foveal capillaries.

Resolution, separation of retinal ganglion cells, and cortical magnification in humans.

We present direct comparisons of resolution thresholds and quantitative estimates of retinal ganglion cell separation in humans with reported functional magnetic resonance imaging estimates of the human linear cortical magnification factor. Measurements of resolution thresholds (MAR), retinal ganglion cell (GC) densities, and linear cortical magnification factor (M) values were taken from the literature. Our objective was to analyse the apparent overrepresentation of human central vision in the visual cortex and to determine whether the cause of this is an effect of the uneven distribution of GC in the retina and/or that central GC have more devoted cortical area per cell. The reserved amount of cortical distance per retinal unit, i.e. the product of M on the one hand and effective GC separation, MAR, and GC receptive field separation on the other, indicates an overrepresentation of the fovea and immediately surrounding retina in the human striate cortex due to an increase in devoted cortical distance per central GC or resolution unit. This cannot be explained by lateral displacement of foveal ganglion cells nor by peripheral scaling, but rather by an additional magnification in the retino-cortical pathway.

Dual-conjugate adaptive optics for wide-field high-resolution retinal imaging

We present analysis and preliminary laboratory testing of a real-time dual-conjugate adaptive optics (DCAO) instrument for ophthalmology that will enable wide-field high resolution imaging of the retina in vivo. The setup comprises five retinal guide stars (GS) and two deformable mirrors (DM), one conjugate to the pupil and one conjugate to a plane close to the retina. The DCAO instrument has a closed-loop wavefront sensing wavelength of 834 nm and an imaging wavelength of 575 nm. It incorporates an array of collimator lenses to spatially filter the light from all guide stars using one adjustable iris, and images the Hartmann patterns of multiple reference sources on a single detector. Zemax simulations were performed at 834 nm and 575 nm with the Navarro 99 and the Liou- Brennan eye models. Two correction alternatives were evaluated; conventional single conjugate AO (SCAO, using one GS and a pupil DM) and DCAO (using multiple GS and two DM). Zemax simulations at 575 nm based on the Navarro 99 eye model show that the diameter of the corrected field of view for diffraction-limited imaging (Strehl >or= 0.8) increases from 1.5 deg with SCAO to 6.5 deg using DCAO. The increase for the less stringent condition of a wavefront error of 1 rad or less (Strehl >or= 0.37) is from 3 deg with SCAO to approximately 7.4 deg using DCAO. Corresponding results for the Liou-Brennan eye model are 3.1 deg (SCAO) and 8.2 deg (DCAO) for Strehl >or= 0.8, and 4.8 deg (SCAO) and 9.6 deg (DCAO) for Strehl >or= 0.37. Potential gain in corrected field of view with DCAO is confirmed both by laboratory experiments on a model eye and by preliminary in vivo imaging of a human eye.

The decline in visual acuity in elderly people with healthy eyes or eyes with early age-related maculopathy in two Scandinavian population samples.

Purpose:  This study aimed to analyse the decline in visual acuity (VA) during normal ageing in two Scandinavian population samples of subjects aged ≥ 70 years and to study the age‐specific decline in VA in eyes with early age‐related maculopathy (ARM).

The relation between resolution measurements and numbers of retinal ganglion cells in the same human subjects

Limiting factors of resolution have previously only been investigated by using resolution data and retinal ganglion cell spacing data from different individuals. We report on our unique opportunity to study the intra-individual relationship in three human subjects between retinal ganglion cell separations and resolution thresholds, measured with high-pass resolution perimetry. Our data show that resolution is directly proportional to half the midget population, in accordance with the hypothesis that a dichotomous midget ON/OFF population mediates resolution.

Resolution visual fields in children surgically treated for bilateral congenital cataract

PURPOSE To evaluate visual acuity (best corrected visual acuity) and peripheral sensitivity, measured by high-pass resolution (HRP) visual fields, in children surgically treated for congenital cataract. METHODS Acuity and peripheral sensitivity were recorded from 16 children, aged 10 to 15 years, either surgically treated for bilateral dense cataract before the age of 4.6 months (n = 10) or surgically treated for bilateral partial cataract at ages 4 to 139 months (n = 6). Data from 22 healthy children, mean age 11 years, served as control. RESULTS The children with cataract had significantly (P < 0.0001) lower decimal acuity in their better eye (median, 0.55; range, 0.1-1.3) than did the control subjects (median, 1.2; range, 1.0-1.6). Five children were visually impaired according to the World Health Organizations definition (i.e., acuity in the better eye <0.3). The children with previous dense bilateral cataract showed significantly lower peripheral sensitivity than did the control subjects (P = 0.004). Significant correlations were observed between acuity and visual field parameters. CONCLUSIONS Dense cataract, even when surgically treated before the age of 4.6 months, causes persistent impairment of spatial vision, both in the fovea and the visual field. The effect on the visual field is less pronounced than that on visual acuity. This finding has to be taken into account when evaluating visual field results in, for example, the diagnosis of glaucoma, a frequent complication after cataract surgery in early infancy.

Arrested Foveal Development in Preterm Eyes: Thickening of the Outer Nuclear Layer and Structural Redistribution Within the Fovea

Purpose The aim of this study was to define landmarks to better characterize foveal microstructure in normal subjects and in preterms with or without signs of immaturity, and to report on thickness changes of outer foveal layers following analysis of optical coherence tomography (OCT) B-scan images. Methods Selected eyes from eight young adults with a history of prematurity (24-33 weeks of gestation) and five controls were imaged using conventional and directional OCT. Retinal layer thickness analysis was performed at selected temporal eccentricities defined by the individual distance between two landmarks for each case, the foveal center and the foveal rim. Results The use of a foveal center and foveal rim landmark transformation enabled comparisons of interindividual B-scans at corresponding landmark positions in both controls and preterms. We found a 20% shorter foveal center to foveal rim distance in preterms with an immature fovea than in controls. Reflectometric and manual segmentation measurements showed increased thickness of inner retinal layers and photoreceptor cell body and outer plexiform layers centrally, but no observable change of photoreceptor inner and outer segment thickness. Conclusions Our landmark-based analysis of OCT images using reflectometry and manual segmentation provides complementary findings in comparisons of normal and immature foveal structures. We show a central thickness increase in the outer nuclear layer, outer plexiform layer, and postreceptor layers in preterms with signs of arrested foveal development. We found no indication of abnormal photoreceptor inner or outer segment development in preterms.

Dual Conjugate Adaptive Optics Prototype for Wide Field High Resolution Retinal Imaging

Retinal imaging is limited due to optical aberrations caused by imperfections in the optical media of the eye. Consequently, diffraction limited retinal imaging can be achieved if optical aberrations in the eye are measured and corrected. Information about retinal pathology and structure on a cellular level is thus not available in a clinical setting but only from histological studies of excised retinal tissue. In addition to limitations such as tissue shrinkage and distortion, the main limitation of histological preparations is that longitudinal studies of disease progression and/or results of medical treatment are not possible. Adaptive optics (AO) is the science, technology and art of capturing diffraction-limited images in adverse circumstances that would normally lead to strongly degraded image quality and loss of resolution. In non-military applications, it was first proposed and implemented in astronomy. AO technology has since been applied in many disciplines, including vision science, where retinal features down to a few microns can be resolved by correcting the aberrations of ocular optics. As the focus of this chapter is on AO retinal imaging, we will focus our description to this particular field.