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Imaging techniques to measure ocular structure and optical properties

Prof. Susana Marcos
Picture Susana Marcos

Quantitative imaging is essential to measure the structural properties of the ocular components. Surface shapes, refractive index (gradient, in case of the crystalline lens), and the alignment and tuning of the cornea and crystalline lens of the eye determine their optical properties. Techniques implemented at the Visual Optics and Biophotonics  include laser ray tracing techniques for the measurement of ocular aberrations in normal eyes and patients; a laser ray tracing system and reconstruction algorithms of the gradient index distribution in the crystalline lens, a Hartmann-Shack, wavefront sensor to measure ocular aberrations in animal models, a Purkinje imaging system to measure in vivo the radii of curvature of the anterior and posterior lens surfaces, and tilt and decentration of the crystalline and intraocular lenses, a Scheimpflug anterior segment imaging system, with optical and geometrical distortion correction algorithms; anterior segment optical coherence tomography systems (for cornea and crystalline lens); and an adaptive-optics system (with a wavefront sensor and a magnetic deformable mirror for the measurement and real time correction of ocular aberrations), with a channel to perform psychophysical measurements; a structured illumination microscope for the acquisition of sectioned images of the cornea in vitro, also provided with a fluorescence channel (which allows visualization of ocular pathogens –acanthomeba and fungi- marked with fluorescent probes) ...

Experimental models in vitro (a plastic model for corneal refractive laser ablation; physical model eye for the evaluation of intraocular lenses; in vitro porcine model for corneal biomechanics and corneal microscopy evaluation; a rabbit model of ocular infection) and animal models in vivo (form-deprivation myopia model in chicks; refractive surgery model in chick; a wild-type mouse model and models for myopia, accommodation and presbyopia in primates) allow us to test conditions prior to human eye measurements and make predictions of performance. Customized computer eye models, with individual biometric, structural and alignment data produce excellent predictions of the ocular aberrations measured experimentally on pseudophakic eyes.

Understanding basic mechanisms in the eye

Aberrations and ocular biometry in myopia

We have investigate the basic mechanisms of myopia development. In particular, we have tested the hypothesis that ocular aberrations are a cause (or consequence) of myopia and the optical and structural changes that occur during myopia development. The animal models allow longitudinal measurements in short periods, the manipulation of visual experience and cause-effect relationships in myopia development. In particular, by means of occlusion with diffusers, we have achieved ocular elongation and high myopia (up to 18 D) in a chick model eye. We have shown that the retinal image quality increases during ocular development, both in the normal and the contralateral myopic eye. Alternatively, a refractive surgery treatment does not achieve to alter axial elongation, nor to induce changes in keratometry, although high order aberrations increase. These results are consistent with a passive tuning of the ocular components, non-visually guided, and are indicative that aberrations are not a cause but a consequence of myopia development.

Accomodation and presbyopia.

Presbyopia affects 100% of the population older than 45 years. It is critical to know the dynamics of the crystalline lens to understand its aging process. We have used a primate model for accommodation and presbyopia (Rhesus monkeys) for the dynamic characterization in vivo of the geometrical changes in the crystalline lens during stimulated accommodation, in collaboration with Prof. Adrian Glasser (University of Houston). In addition, we have measured the changes of the crystalline lens during static accommodation in humans (through Purkinje and Scheimpflug imaging), in collaboration with Profs. Van der Heijde and Dubbleman (de Vrije Universtiy, Amsterdam), Figure 1 A. More recently, we have been able to image the accommodating crystalline lens dynamically, for the first time in the literature using Optical Coherence Tomography, in collaboration.

The accommodation dynamics (increased accommodative lag and fluctuations, Fig. 1B) is affected in myopes, although it is not well understood whether it is a result of myopia or rather precedes myopia development.  We investigated the effect of manipulating aberrations on accommodation dynamics, using both adaptive optics and retinal image simulations to modify visual experience, and found that lag decreased under corrected optics and increased when coma or positive spherical aberration were added.

Relationship between optical and visual quality

The visual impact of ocular aberrations on visual performance is one of the most critical questions in visual optics today. We investigate the effect of aberrations on vision using adaptive optics.  We have found that correction of high order aberrations improves visual acuity significantly at most luminances and both contrast polarities (Fig. 3C). Only for bright targets on black backgrounds correcting aberrations did not produced better acuity. We have found that the improvement in visual acuity was well correlated with the improvement in optical quality. We also found that correcting aberrations increases dramatically the subjective impression of sharpness in images, and improves slightly visual performance of some real-life visual tasks (i.e. recognition of familiar faces), but not all (i.e. facial expression recognition). We have also explored the neural adaptation to astigmatism and asymmetric high order aberrations and found strong meridional after-effects after adaptation to asymmetrically blurred targets, suggesting that previous experience to aberrations may have an impact on the visual response. 

Figure 1

Evaluating and improving refractive/presbyopic correction alternatives

Refractive surgery: Optimization of ablation algorithms, corneal biomechanics and collagen cross-linking. Our laboratory has pioneered the demonstration that spherical aberration is induced by laser refractive surgery and the identification of its causes. We have studied the effect of laser efficiency losses on corneal asphericity, in plastic (PMMA and Filofocon A) model eyes, and we have proposed a method to optimize the laser ablation profiles by estimating a correction factor of those losses. We also investigate optimized ablation profiles and their impact on corneal shape and corneal aberrations (Fig. 2A). While we have shown that a large part of the increased aberrations after refractive surgery can be explained from physical laws, it is expected that corneal biomechanics still plays a role in the optical outcomes. Post-operative changes in the posterior corneal surface (usually associated to biomechanics) are minor (and only significant one day after surgery, Fig.2B). We investigate the corneal biomechanical properties by measuring corneal deformation as a function of intraocular pressure, in an inflation in vitro intact porcine eye model. Some procedures (such as corneal collagen cross-linking) aim at altering the stiffness of the cornea. The inflation model allowed us to estimate the changes in corneal biomechanical properties after this procedure, in comparison to untreated control eyes. These results will contribute to increase predictability and outcomes of refractive procedures.

Intraocular lenses: In vivo evaluation and new designs. We have assessed corneal and total aberrations, as well as IOL tilt and decentration in patients implanted with aspheric IOL designs. Customized pseudophakic eye models (Fig. 2C) allow to identify the relative contribution of different factors to surgical outcomes. We have found that corneal aberrations (and incision) play a significant role in optical degradation, while the effect of misalignments is relatively minor. The aspheric design produces a compensation of both spherical aberration and coma.

Contact lenses: Presbyopic corrections. An alternative to the correction of presbyopia are multifocal corrections, aiming at expanding depth-of-focus Our measurements of optical and visual function through-focus with multifocal refractive soft contact lenses show that in most cases the conformity of the lens to the cornea, and the impact of the natural aberrations of the eye prevent these lenses from providing effective multifocality.

Figure 2

Susana Marcos

The focus of Prof. Susana Marcos research is the development of non-invasive techniques to evaluate the optical and structural properties of the eye, and their application in the advancement in the understanding of biological mechanisms of the visual system (i.e. myopia development, accommodation and presbyopia), the early diagnosis of ocular conditions and the evaluation and optimization of ocular surgery and treatments (i.e. refractive surgery, cataract surgery, collagen cross-linking, contact lenses).

CV of Prof. Susana Marcos [pdf]