Pablo Pérez-Merino

Dynamic OCT measurement of corneal deformation by an air puff in normal and cross-linked corneas

A new technique is presented for the non-invasive imaging of the dynamic response of the cornea to an air puff inducing a deformation. A spectral OCT instrument combined with an air tonometer in a non-collinear configuration was used to image the corneal deformation over full corneal cross-sections, as well as to obtain high speed measurements of the temporal evolution of the corneal apex. The entire deformation process can be dynamically visualized. A quantitative analysis allows direct extraction of several deformation parameters, such as amplitude, diameter and volume of the maximum deformation, as well as duration and speed of the increasing deformation period and the recovery period. The potential of the technique is demonstrated on porcine corneas in vitro under constant IOP for several conditions (untreated, after riboflavin instillation and under cross-linking with ultraviolet light), as well as on human corneas in vivo. The new technique has proved very sensitive to detect differences in the deformation parameters across conditions. We have confirmed non-invasively that Riboflavin and UV-cross-linking induce changes in the corneal biomechanical properties. Those differences appear to be the result of changes in constituent properties of the cornea, and not a consequence of changes in corneal thickness, geometry or IOP. These measurements are a first step for the estimation of the biomechanical properties of corneal tissue, at an individual level and in vivo, to improve diagnosis and prognosis of diseases and treatments involving changes in the biomechanical properties of the cornea.

Corneal topography from spectral optical coherence tomography (sOCT)

We present a method to obtain accurate corneal topography from a spectral optical coherence tomography (sOCT) system. The method includes calibration of the device, compensation of the fan (or field) distortion introduced by the scanning architecture, and image processing analysis for volumetric data extraction, segmentation and fitting. We present examples of three-dimensional (3-D) surface topography measurements on spherical and aspheric lenses, as well as on 10 human corneas in vivo. Results of sOCT surface topography (with and without fan-distortion correction) were compared with non-contact profilometry (taken as reference) on a spherical lens, and with non-contact profilometry and state-of-the art commercial corneal topography instruments on aspheric lenses and on subjects. Corneal elevation maps from all instruments were fitted by quadric surfaces (as well as by tenth-order Zernike polynomials) using custom routines. We found that the discrepancy in the estimated radius of curvature from nominal values in artificial corneas decreased from 4.6% (without fan distortion correction) to 1.6% (after fan distortion correction), and the difference in the asphericity decreased from 130% to 5%. In human corneas, the estimated corneal radius of curvature was not statistically significantly different across instruments. However, a Bland-Altman analysis showed consistent differences in the estimated asphericity and corneal shape between sOCT topographies without fan distortion correction and the rest of the measurements.

Multiphoton microscopy of ex vivo corneas after collagen cross-linking.

PURPOSE To investigate changes in the morphology of the corneal stroma after collagen cross-linking (CXL) treatment in bovine and porcine eyes using a nonlinear microscope providing both two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) corneal images. METHODS Freshly enucleated eyes were imaged using a tomographic nonlinear imaging method that was highly suitable to track temporal changes in corneal structures. CXL (riboflavin instillation plus UV irradiation) was applied on the enucleated eyes using similar protocols as in the clinic. A set of eyes without treatment were measured to be used as control. RESULTS In control corneas, SHG images showed a regular distribution of lamellae across the stroma that appeared stable for at least 6 hours postmortem. CXL changed the collagen distribution pattern showing some abnormal structures. TPEF revealed a large reduction in corneal thickness in CXL corneas immediately after treatment. The changes in the distribution of collagen bundles appeared also in corneas treated with riboflavin only, but not followed by UV irradiation. SHG tomography also revealed a partial recovery of the corneal thickness with time. CONCLUSIONS Nonlinear microscopy (in both tomographic and regular XY imaging configurations) was used to study spatial and temporal changes in the cornea during and after CXL on intact ocular globes. SHG imaging showed changes in the morphology of anterior corneal stroma after CXL. Regular collagen patterns turned into random distributed structures with thicker bundles at some localized areas. This might be a consequence of the corneal thickness decrease as a result of riboflavin-dextran instillation.

In vivo human crystalline lens topography

Custom high-resolution high-speed anterior segment spectral domain optical coherence tomography (OCT) was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo. The system was provided with custom algorithms for denoising and segmentation of the images, as well as for fan (scanning) and optical (refraction) distortion correction, to provide fully quantitative images of the anterior and posterior crystalline lens surfaces. The method was tested on an artificial eye with known surfaces geometry and on a human lens in vitro, and demonstrated on three human lenses in vivo. Not correcting for distortion overestimated the anterior lens radius by 25% and the posterior lens radius by more than 65%. In vivo lens surfaces were fitted by biconicoids and Zernike polynomials after distortion correction. The anterior lens radii of curvature ranged from 10.27 to 14.14 mm, and the posterior lens radii of curvature ranged from 6.12 to 7.54 mm. Surface asphericities ranged from −0.04 to −1.96. The lens surfaces were well fitted by quadrics (with variation smaller than 2%, for 5-mm pupils), with low amounts of high order terms. Surface lens astigmatism was significant, with the anterior lens typically showing horizontal astigmatism (Z22 ranging from −11 to −1 µm) and the posterior lens showing vertical astigmatism (Z22 ranging from 6 to 10 µm).

Full OCT anterior segment biometry: an application in cataract surgery.

In vivo three-dimensional (3-D) anterior segment biometry before and after cataract surgery was analyzed by using custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT). The system was provided with custom algorithms for denoising, segmentation, full distortion correction (fan and optical) and merging of the anterior segment volumes (cornea, iris, and crystalline lens or IOL), to provide fully quantitative data of the anterior segment of the eye. The method was tested on an in vitro artificial eye with known surfaces geometry at different orientations and demonstrated on an aging cataract patient in vivo. Biometric parameters CCT, ACD/ILP, CLT/ILT Tilt and decentration are retrieved with a very high degree of accuracy. IOL was placed 400 μm behind the natural crystalline lens, The IOL was aligned with a similar orientation of the natural lens (2.47 deg superiorly), but slightly lower amounts (0.77 deg superiorly). The IOL was decentered superiorly (0.39 mm) and nasally (0.26 mm).

In vivo chromatic aberration in eyes implanted with intraocular lenses

PURPOSE To measure in vivo and objectively the monochromatic aberrations at different wavelengths, and the chromatic difference of focus between green and infrared wavelengths in eyes implanted with two models of intraocular lenses (IOL). METHODS EIGHTEEN EYES PARTICIPATED IN THIS STUDY: nine implanted with Tecnis ZB99 1-Piece acrylic IOL and nine implanted with AcrySof SN60WF IOL. A custom-developed laser ray tracing (LRT) aberrometer was used to measure the optical aberrations, at 532 nm and 785 nm wavelengths. The monochromatic wave aberrations were described using a fifth-order Zernike polynomial expansion. The chromatic difference of focus was estimated as the difference between the equivalent spherical errors corresponding to each wavelength. RESULTS Wave aberration measurements were highly reproducible. Except for the defocus term, no significant differences in high order aberrations (HOA) were found between wavelengths. The average chromatic difference of focus was 0.46 ± 0.15 diopters (D) in the Tecnis group, and 0.75 ± 0.12 D in the AcrySof group, and the difference was statistically significant (P < 0.05). Chromatic difference of focus in the AcrySof group was not statistically significantly different from the Longitudinal chromatic aberration (LCA) previously reported in a phakic population (0.78 ± 0.16 D). The impact of LCA on retinal image quality (measured in terms of Strehl ratio) was drastically reduced when considering HOA and astigmatism in comparison with a diffraction-limited eye, yielding the differences in retinal image quality between Tecnis and AcrySof IOLs not significant. CONCLUSIONS LRT aberrometry at different wavelengths is a reproducible technique to evaluate the chromatic difference of focus objectively in eyes implanted with IOLs. Replacement of the crystalline lens by the IOL did not increase chromatic difference of focus above that of phakic eyes in any of the groups. The AcrySof group showed chromatic difference of focus values very similar to physiological values in young eyes.

Aberrometry in patients implanted with accommodative intraocular lenses.

PURPOSE To evaluate the objective accommodative response, change of aberrations, and depth of focus in eyes implanted with the Crystalens accommodative intraocular lens (IOL) at different accommodative demands. DESIGN Prospective, observational study. METHODS Eleven cataract patients (22 eyes) who underwent implantation of a Crystalens accommodative IOL, and control groups of 9 normal subjects (17 eyes) and 17 pseudophakic patients (17 eyes) implanted with monofocal IOLs were evaluated. A custom-developed laser ray tracing aberrometer was used to measure the optical aberrations. The monochromatic wave aberrations were described using a sixth-order Zernike polynomial expansion. Measurements were obtained under dilated and natural viewing conditions (for accommodative efforts ranging from 0 to 2.5 diopters [D]). The accommodative response was obtained by analyzing changes in paraxial defocus (associated to changes in defocus) and by evaluating the differences in the effective defocus (associated with defocus, spherical aberrations, and pupil diameter) with the accommodative demand. Depth of focus was estimated from through-focus objective optical quality. RESULTS Wave aberration measurements were highly reproducible. Vertical trefoil (Z3(-3)) was the predominant higher-order aberration in the Crystalens group and significantly higher (P < .0001) than in the young group, but similar to the monofocal IOL group. The coma root mean square also was higher (P < .005) in the Crystalens group than in the young group. On average, the defocus term (Z2(0)), astigmatism, or higher-order aberrations did not change systematically with accommodative demand in Crystalens eyes. As found for paraxial defocus, the effective defocus in Crystalens eyes did not show significant differences between conditions: 0.34 ± 0.48 D (far), 0.32 ± 0.50 D (intermediate), and 0.34 ± 0.44 D (near). Depth of focus was statistically significantly higher in the Crystalens eyes than in the control groups. CONCLUSIONS The accommodative response of eyes implanted with the Crystalens accommodative IOLs, measured objectively using laser ray tracing aberrometry, was lower than 0.4 D in all eyes. Several subjects showed changes in astigmatism, spherical aberration, trefoil, and coma with accommodation, which must arise from geometrical and alignment changes in the lens with accommodative demand. Pseudoaccommodation from increased depth of focus may contribute to near vision functionality in Crystalens-implanted patients.

Static and dynamic crystalline lens accommodation evaluated using quantitative 3-D OCT

Custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT) provided with automatic quantification and distortion correction algorithms was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo in four subjects, for accommodative demands between 0 to 6 D in 1 D steps. Anterior and posterior lens radii of curvature decreased with accommodative demand at rates of 0.73 and 0.20 mm/D, resulting in an increase of the estimated optical power of the eye of 0.62 D per diopter of accommodative demand. Dynamic fluctuations in crystalline lens radii of curvature, anterior chamber depth and lens thickness were also estimated from dynamic 2-D OCT images (14 Hz), acquired during 5-s of steady fixation, for different accommodative demands. Estimates of the eye power from dynamical geometrical measurements revealed an increase of the fluctuations of the accommodative response from 0.07 D to 0.47 D between 0 and 6 D (0.044 D per D of accommodative demand). A sensitivity analysis showed that the fluctuations of accommodation were driven by dynamic changes in the lens surfaces, particularly in the posterior lens surface.

Ocular and optical coherence tomography-based corneal aberrometry in keratoconic eyes treated by intracorneal ring segments.

PURPOSE To analyze corneal and total aberrations using custom-developed anterior segment spectral optical coherence tomography (OCT) and laser ray tracing in keratoconic eyes implanted with intracorneal ring segments (ICRS). DESIGN Evaluation of technology. Prospective study. Case series. METHODS Nineteen keratoconic eyes were measured before and after ICRS surgery. Anterior and posterior corneal topographic and pachymetric maps were obtained pre- and postoperatively from 3-dimensional OCT images of the anterior segment, following automatic image analysis and distortion correction. The pupil center coordinates were used as reference for estimation of corneal aberrations. Corneal aberrations were estimated by computational ray tracing on the anterior and posterior corneal surfaces. Total aberrations were measured using a custom-developed laser ray tracing aberrometer. Corneal and total aberrations were compared in 8 eyes pre- and postoperatively for 4-mm pupils. RESULTS Total and corneal aberrations were highly correlated. Average root mean square of corneal and total high-order aberrations (HOAs) were 0.78 ± 0.35 μm and 0.57 ± 0.39 μm preoperatively, and 0.88 ± 0.36 μm and 0.53 ± 0.24 μm postoperatively (4-mm pupils). The anterior corneal surface aberrations were partially compensated by the posterior corneal surface aberrations (by 8.3% preoperatively and 4.1% postoperatively). Astigmatism was 2.03 ± 1.11 μm preoperatively and 1.60 ± 0.94 μm postoperatively. The dominant HOA aberrations both pre- and postoperatively were vertical coma (Z3(-1)), vertical trefoil (Z3(-3)), and secondary astigmatism (Z4(4)). ICRS decreased corneal astigmatism by 27% and corneal coma by 5%, but on average, the overall amount of HOA did not decrease significantly with ICRS treatment. CONCLUSIONS OCT is a reproducible technique to evaluate corneal aberrations. OCT-based corneal aberrations and ocular aberrations show a high correspondence in keratoconic patients before and after ICRS implantation. ICRS produced a decrease in astigmatism, but on average did not produce a consistent decrease of HOAs.

Quantitative OCT-Based Longitudinal Evaluation of Intracorneal Ring Segment Implantation in Keratoconus

PURPOSE To characterize the geometrical properties of keratoconic corneas upon intracorneal ring segments (ICRS) implantation, using custom-developed optical coherence tomography (OCT). METHODS Ten keratoconic corneas were measured pre- and post-ICRS surgery (7, 30, and 90 days). Corneal topographic and pachymetric maps were obtained from three-dimensional (3D) images acquired with OCT, provided with custom algorithms for image analysis, distortion correction, and quantification. The 3D positioning of the ICRS was also estimated longitudinally, relative to the pupil center and iris plane. RESULTS Preoperatively, the average corneal radii of curvature were 7.02 ± 0.54 mm (anterior) and 5.40 ± 0.77 mm (posterior), and the minimum corneal thickness was 384 ± 60 μm. At 90 days, the average corneal radii of curvature were 7.26 ± 0.53 mm (anterior) and 5.44 ± 0.71 mm (posterior), and the minimum corneal thickness was 396 ± 46 μm. ICRS implantation produced a significant decrease of corneal power (by 1.71 ± 1.83 diopters [D] at 90 days). Corneal irregularities (defined by high order Zernike terms of the corneal elevation maps) and the corneal thickness distribution decreased in some patients and increased in others. The 3D ICRS depth matched the planned ICRS depth well (within 23.93 ± 23.49 μm). On average, ICRS showed an overall tilt of -6.8 ± 2.6° (temporal) and -2.1 ± 0.8° (superior) at 7 days. CONCLUSIONS Spectral OCT (sOCT) provided with distortion correction and analysis tools, is an excellent instrument for evaluating the changes produced by ICRS in keratoconic corneas, and for analyzing the 3D ICRS position during the follow up. ICRS produced flattening on the anterior corneal surface, although the benefit for corneal surface regularization varied across patients.