C.–Y. Liu

Functional slit lamp biomicroscopy for imaging bulbar conjunctival microvasculature in contact lens wearers

PURPOSE To develop, test and validate functional slit lamp biomicroscopy (FSLB) for generating non-invasive bulbar conjunctival microvascular perfusion maps (nMPMs) and assessing morphometry and hemodynamics. METHODS FSLB was adapted from a traditional slit-lamp microscope by attaching a digital camera to image the bulbar conjunctiva to create nMPMs and measure venular blood flow hemodynamics. High definition images with a large field of view were obtained on the temporal bulbar conjunctiva for creating nMPMs. A high imaging rate of 60 frames per second and an ~210× high magnification were achieved using the camera inherited high speed setting and Movie Crop Function, for imaging hemodynamics. Custom software was developed to segment bulbar conjunctival nMPMs for further fractal analysis and quantitatively measure blood vessel diameter, blood flow velocity and flow rate. Six human subjects were imaged before and after 6h of wearing contact lenses. Monofractal and multifractal analyses were performed to quantify fractality of the nMPMs. RESULTS The mean bulbar conjunctival vessel diameter was 18.8 ± 2.7 μm at baseline and increased to 19.6 ± 2.4 μm after 6h of lens wear (P=0.020). The blood flow velocity was increased from 0.60 ± 0.12 mm/s to 0.88 ± 0.21 mm/s (P=0.001). The blood flow rate was also increased from 129.8 ± 59.9 pl/s to 207.2 ± 81.3 pl/s (P=0.001). Bulbar conjunctival nMPMs showed the intricate details of the bulbar conjunctival microvascular network. At baseline, fractal dimension was 1.63 ± 0.05 and 1.71 ± 0.03 analyzed by monofractal and multifractal analyses, respectively. Significant increases in fractal dimensions were found after 6h of lens wear (P<0.05). CONCLUSIONS Microvascular networks fractality, morphometry and hemodynamics of the human bulbar conjunctiva can be measured easily and reliably using FSLB. The alternations of the fractal dimensions, morphometry and hemodynamics during contact lens wear may indicate ocular microvascular responses to contact lens wear.

Impaired retinal microcirculation in multiple sclerosis

Background: The transparent ocular structure enables quantitative analysis of microvasculature of retina, a neuronal tissue affected by multiple sclerosis (MS). Objective: The aim of this study was to determine whether the retinal blood flow velocity and flow volume at the macula are impaired in patients with relapsing remitting multiple sclerosis (RRMS). Methods: A total of 17 RRMS patients and 17 age- and gender-matched healthy subjects were assessed. A retinal function imager was used to measure the blood flow velocity of retinal arterioles and venules and to calculate the total perifoveal blood flow volume. Results: The blood flow velocities of the retinal arterioles (3.34 ± 0.89 mm/s) and venules (2.61 ± 0.6 mm/s) were significantly lower in MS patients than normal subjects (arteriole: 4.10 ± 0.87 mm/s; venule: 3.22 ± 0.65 mm/s, both p = 0.01). In addition, the total perifoveal blood flow volume in arterioles (3.74 ± 1.64 nL/s) and venules (3.81 ± 1.60 nL/s) were significantly lower in MS patients than in normal subjects (arteriole: 4.87 ± 1.41 nL/s, p = 0.02; venule: 4.71 ± 1.64 nL/s, p = 0.04). Conclusion: The impaired retinal microcirculation in RRMS patients indicates microvascular dysfunction in MS.

The measurement repeatability using different partition methods of intraretinal tomographic thickness maps in healthy human subjects

Purpose To determine the repeatability and profiles with different partition methods in intraretinal thickness layers in healthy human subjects, using optical coherence tomography (OCT). Methods A custom-built ultrahigh-resolution OCT was used to acquire three-dimensional volume of the macula in 20 healthy subjects. The dataset was acquired twice using the macular cube 512×128 protocol in an area of 6×6 mm2 centered on the fovea. Commercially available segmentation software (Orion™) was used to segment the dataset into thickness maps of six intraretinal layers. The coefficient of repeatability and intraclass coefficient of correlation (ICC) were analyzed using hemispheric zoning and sectors defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). Results All datasets were successfully segmented to create six thickness maps of individual intraretinal layers. Coefficients of repeatabilities of these layers in hemispheric zones ranged from 0.9 to 6.6 µm, with an average of 3.6 µm (standard deviation [SD] 1.4), which was not significantly different compared to ETDRS sectors (P>0.05). ICCs of these layers in hemispheric zones ranged from 0.68 to 0.99, with an average of 0.91 (SD 0.07). There were no significant differences in ICCs between two zoning methods (P>0.05). Significant variations of tomographic intraretinal thicknesses were found between the inner and outer annuli and among the quadrantal sectors within the inner and outer annuli (P<0.05). Significant variations of the quadrantal sectors including both inner and outer annuli were evident in intraretinal layers (P<0.05) except for the outer plexiform layer. Conclusion The measurement repeatabilities of tomographic thicknesses of intraretinal layers are comparable using both hemispheric and ETDRS partitions in volumetric data combined with the commercially available segmentation software. In keeping with known, normal anatomical variation, significant differences in tomographic thickness in various intraretinal layers were apparent in both hemispheric and ETDRS sectors.

Slitlamp Photography and Videography With High Magnifications.

Purpose: To demonstrate the use of the slitlamp photography and videography with extremely high magnifications for visualizing structures of the anterior segment of the eye. Methods: A Canon 60D digital camera with Movie Crop Function was adapted into a Nikon FS-2 slitlamp to capture still images and video clips of the structures of the anterior segment of the eye. Images obtained using the slitlamp were tested for spatial resolution. The cornea of human eyes was imaged with the slitlamp, and the structures were compared with the pictures captured using the ultra-high-resolution optical coherence tomography (UHR-OCT). The central thickness of the corneal epithelium and total cornea was obtained using the slitlamp, and the results were compared with the thickness obtained using UHR-OCT. Results: High-quality ocular images and higher spatial resolutions were obtained using the slitlamp with extremely high magnifications and Movie Crop Function, rather than the traditional slitlamp. The structures and characteristics of the cornea, such as the normal epithelium, abnormal epithelium of corneal intraepithelial neoplasia, laser in situ keratomileusis interface, and contact lenses, were clearly visualized using this device. These features were confirmed by comparing the obtained images with those acquired using UHR-OCT. Moreover, the tear film debris on the ocular surface and the corneal nerve in the anterior corneal stroma were also visualized. The thicknesses of the corneal epithelium and total cornea were similar to that measured using UHR-OCT (P<0.05). Conclusions: We demonstrated that the slitlamp photography and videography with extremely high magnifications allow better visualization of the anterior segment structures of the eye, especially of the epithelium, when compared with the traditional slitlamp.

The relationship between high-order aberration and anterior ocular biometry during accommodation in young healthy adults

Purpose This study investigated the anterior ocular anatomic origin of high-order aberration (HOA) components using optical coherence tomography and a Shack-Hartmann wavefront sensor. Methods A customized system was built to simultaneously capture images of ocular wavefront aberrations and anterior ocular biometry. Relaxed, 2-diopter (D) and 4-D accommodative states were repeatedly measured in 30 young subjects. Custom software was used to correct optical distortions and measure biometric parameters from the images. Results The anterior ocular biometry changed during 2-D accommodation, in which central lens thickness, ciliary muscle thicknesses at 1 mm posterior to the scleral spur (CMT1), and the maximum value of ciliary muscle thickness increased significantly, whereas anterior chamber depth, CMT3, radius of anterior lens surface curvature (RAL), and radius of posterior lens surface curvature (RPL) decreased significantly. The changes in the anterior ocular parameters during 4-D accommodation were similar to those for the 2-D accommodation. \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm Z}_4^0\)\end{document} decreased significantly during 2-D accommodation, and \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm{Z}}_3^{ - 1}\)\end{document}, \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm{Z}}_3^1\)\end{document}, \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm{Z}}_4^0\)\end{document}, and \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm{Z}}_6^0\)\end{document} shifted to negative values during 4-D accommodation. The change in \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm{Z}}_4^0\)\end{document} negatively correlated with those in CMT1, and the negative change in \begin{document}\newcommand{\bialpha}{\boldsymbol{\alpha}}\newcommand{\bibeta}{\boldsymbol{\beta}}\newcommand{\bigamma}{\boldsymbol{\gamma}}\newcommand{\bidelta}{\boldsymbol{\delta}}\newcommand{\bivarepsilon}{\boldsymbol{\varepsilon}}\newcommand{\bizeta}{\boldsymbol{\zeta}}\newcommand{\bieta}{\boldsymbol{\eta}}\newcommand{\bitheta}{\boldsymbol{\theta}}\newcommand{\biiota}{\boldsymbol{\iota}}\newcommand{\bikappa}{\boldsymbol{\kappa}}\newcommand{\bilambda}{\boldsymbol{\lambda}}\newcommand{\bimu}{\boldsymbol{\mu}}\newcommand{\binu}{\boldsymbol{\nu}}\newcommand{\bixi}{\boldsymbol{\xi}}\newcommand{\biomicron}{\boldsymbol{\micron}}\newcommand{\bipi}{\boldsymbol{\pi}}\newcommand{\birho}{\boldsymbol{\rho}}\newcommand{\bisigma}{\boldsymbol{\sigma}}\newcommand{\bitau}{\boldsymbol{\tau}}\newcommand{\biupsilon}{\boldsymbol{\upsilon}}\newcommand{\biphi}{\boldsymbol{\phi}}\newcommand{\bichi}{\boldsymbol{\chi}}\newcommand{\bipsi}{\boldsymbol{\psi}}\newcommand{\biomega}{\boldsymbol{\omega}}\({\rm{Z}}_3^1\)\end{document} correlated with changes in RAL and CMT1. Conclusions HOA components altered during step-controlled accommodative stimuli. Ciliary muscle first contracted during stepwise accommodation, which may directly contribute to the reduction of spherical aberration (SA). The lens morphology was then altered, and the change in anterior lens surface curvature was related to the variation of coma.