Alterations in Lens Free Water Distribution Are Associated with Shape Deformation in Accommodation.

Objective: To investigate whether a redistribution of water within the crystalline lens is associated with the shape deformation that occurs during accommodation. Design: Observational, cross sectional study. Subjects: Eleven young adults without presbyopia (aged 18-39 years) and 9 middle-aged adults with presbyopia (aged 40-55 years). Methods: Magnetic resonance imaging (MRI) scans of the lens were acquired on a 3 Tesla clinical MRI scanner, without and with the presentation of a 3 Diopter accommodative stimulus. The MRIs were postprocessed using established methods to extract the geometric dimensions and spatial maps of water distribution of the lens. Main Outcome Measures: Accommodative changes in the full 3-dimensional description of lens shape, the lens total-water distribution profile, and the lens free-water distribution profile. Results: Viewing of an accommodative stimulus by young subjects elicited an elastic shape deformation of the lens consistent with accommodation that was associated with an elevated, smoother free-water distribution, primarily in the anterior region of the lens. In contrast, viewing of an accommodative stimulus by presbyopic subjects produced an atypical shape deformation of the lens that was instead associated with a lowered free-water distribution, primarily in the anterior region of the lens. No discernible changes to the lens total-water distribution were observed in response to the accommodative stimulus in either subject cohort. Conclusions: The present study suggests that protein-mediated alterations in the free-water distribution of the anterior region of the lens influence the shape deformation in accommodation, presenting pharmacological modulation of free-water distribution as an attractive novel approach for treating presbyopia. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Age-Dependent Changes in Total and Free Water Content of In Vivo Human Lenses Measured by Magnetic Resonance Imaging.

Purpose: To use magnetic resonance imaging (MRI) to measure age-dependent changes in total and free water in human lenses in vivo. Methods: Sixty-four healthy adults aged 18 to 86 years were recruited, fitted with a 32-channel head receiver coil, and placed in a 3 Tesla clinical MR scanner. Scans of the crystalline lens were obtained using a volumetric interpolated breath-hold examination sequence with dual flip angles, which were corrected for field inhomogeneity post-acquisition using a B1-map obtained using a turbo-FLASH sequence. The spatial distribution and content of corrected total (ρlens) and free (T1) water along the lens optical axis were extracted using custom-written code. Results: Lens total water distribution and content did not change with age (all P > 0.05). In contrast to total water, a gradient in free water content that was highest in the periphery relative to the center was present in lenses across all ages. However, this initially parabolic free water gradient gradually developed an enhanced central plateau, as indicated by increasing profile shape parameter values (anterior: 0.067/y, P = 0.004; posterior: 0.050/y, P = 0.020) and central free water content (1.932 ms/y, P = 0.022) with age. Conclusions: MRI can obtain repeatable total and free water measurements of in vivo human lenses. The observation that the lens steady-state free, but not total, water gradient is abolished with age raises the possibility that alterations in protein-water interactions are an underlying cause of the degradation in lens optics and overall vision observed with aging.

Using the Lens Paradox to Optimize an In Vivo MRI-Based Optical Model of the Aging Human Crystalline Lens.

Purpose: To optimize our in vivo magnetic resonance imaging (MRI)-based optical model of the human crystalline lens, developed with a small group of young adults, for a larger cohort spanning a wider age range. Methods: Subjective refraction and ocular biometry were measured in 57 healthy adults ages 18 to 86 years who were then scanned using 3T clinical magnetic resonance imaging (MRI) to obtain lens gradient of refractive index (GRIN) and geometry measurements. These parameters were combined with ocular biometric measurements to construct individualized Zemax eye models from which ocular refractive errors and lens powers were determined. Models were optimized by adding an age-dependent factor to the transverse relaxation time (T2)-refractive index (n) calibration to match model-calculated refractive errors with subjective refractions. Results: In our subject cohort, subjective refraction shifted toward hyperopia by 0.029 diopter/year as the lens grew larger and developed flatter GRINs with advancing age. Without model optimization, lens powers did not reproduce this clinically observed decrease, the so-called lens paradox, instead increasing by 0.055 diopter/year. However, modifying the T2-n calibration by including an age-dependent factor reproduced the decrease in lens power associated with the lens paradox. Conclusions: After accounting for age-related changes in lens physiology in the T2-n calibration, our model was capable of accurately measuring in vivo lens power across a wide age range. This study highlights the need for a better understanding of how age-dependent changes to the GRIN impact the refractive properties of the lens. Translational Relevance: MRI is applied clinically to calculate the effect of age-related refractive index changes in the lens paradox.

Development of an in vivo magnetic resonance imaging and computer modelling platform to investigate the physiological optics of the crystalline lens.

We have developed and validated in vivo magnetic resonance imaging (MRI) protocols to extract parameters (T2 and geometry) of the human lens that, combined with biometric measures of the eye and optical modelling, enable us to investigate the relative contributions made by the gradient of refractive index (GRIN) and the shape of the lens to the refractive properties of each subject tested. Seven young and healthy participants (mean age: 25.6 ± 3.6 years) underwent an ophthalmic examination, and two sessions of MRI scans using a 3 T clinical magnet. Our MRI protocols for studying lens physiological optics and geometrical measurements were repeatable and reliable, using both 1D (95% confidence interval (CI) for mean differences for exponents = [-2.1, 2.6]) and 2D analysis (anterior T2 CI for differences [-6.4, 8.1] ms; posterior T2 CI for differences [-6.4, 8.3] ms). The lens thickness measured from MRI showed good correlation with that measured with clinical 'gold standard' LenStar (mean differences = [-0.18, 0.2] mm). The predicted refractive errors from ZEMAX had reasonable agreements with participants' clinic records (mean differences = [-1.7, 1.2] D). Quantitative measurements of lens geometry and GRIN with our MRI technique showed high inter-day repeatability. Our clinical MRI technique also provides reliable measures of lens geometry that are comparable to optical biometry. Finally, our ZEMAX optical models produced accurate refractive error and lens power estimations.

Orientation Tuning and Contrast Dependence of Continuous Flash Suppression in Amblyopia and Normal Vision.

Purpose: Suppression in amblyopia may be an unequal form of normal interocular suppression or a distinct pathophysiology. To explore this issue, we examined the orientation tuning and contrast dependence of continuous flash suppression (CFS) in adults with amblyopia and visually normal controls. Methods: Nine patients (mean age, 26.9 ± SD 4.7 years) and 11 controls (mean age, 24.8 ± SD 5.3 years) participated. In the CFS paradigm, spatially one-dimensional noise refreshing at 10 Hz was displayed in one eye to induce suppression of the other eye, and suppression strength was measured by using a grating contrast increment detection task. In experiment 1, noise contrast was fixed and the orientation difference between the noise and the grating was varied. In experiment 2, noise and grating orientations were identical and noise contrast was varied. Results: Suppression patterns varied in both groups. In experiment 1, controls showed consistently orientation-tuned CFS (mean half-height bandwidth, 35.8° ± SD 21.5°) with near-equal strength between eyes. Five of nine patients with amblyopia exhibited orientation-independent CFS. Eight patients had markedly unequal suppression between eyes. Experiment 2 found that increasing the noise contrast to the amblyopic eye may produce suppression of the fellow eye, but suppression remained unequal between eyes. Conclusions: Our data revealed that orientation specificity in CFS was very broad or absent in some patients with amblyopia, which could not be predicted by clinical measures. Suppression was unbalanced across the entire contrast range for most patients. This suggests that abnormal early visual experience disrupts the development of interocular suppression mechanisms.