Age dependence of the average refractive index of the isolated human crystalline lens.

We measured the average group refractive index (RI) of 120 isolated lenses from 120 human donors (age: 0.03 to 61 years). The average group RI was calculated from a measurement of the optical thickness of the lens using optical coherence tomography and the apparent window shift of the test chamber caused by the lens. The estimated measurement uncertainty was ±0.004. The group RI at 880 nm was converted to phase RI at 589 nm using the dispersion equation of water and protein. From 2 to 61 years, the mean value of the RI was 1.415 ± 0.002 (group index at 880 nm) and 1.406 ± 0.002 (phase index at 589 nm) independent of age (p = 0.774). Two lenses from donors of age 0.33 and 3 months had significantly lower RI (group index: 1.405 and 1.403; phase index: 1.396 and 1.394). From age 2 to 61, the average lens RI is constant with age within the measurement uncertainty (±0.004).

Dynamic refraction and anterior segment OCT biometry during accommodation.

Accommodation is the process by which the eye changes focus. These changes are the result of changes to the shape of the crystalline lens. Few prior studies have quantified the relation between lens shape and ocular accommodation, primarily at discrete static accommodation states. We present an instrument that enables measurements of the relation between changes in lens shape and changes in optical power continuously during accommodation. The system combines an autorefractor to measure ocular power, a visual fixation target to stimulate accommodation, and an optical coherence tomography (OCT) system to image the anterior segment and measure ocular distances. Measurements of ocular dimensions and refraction acquired dynamically on three human subjects are presented. The individual accommodative responses are analyzed to correlate the ocular power changes with changes in ocular dimensions.

Peripheral defocus of monofocal intraocular lenses.

PURPOSE: To quantify the angular dependence of monofocal intraocular lens (IOL) power. SETTING: Ophthalmic Biophysics Laboratory, Kallam Anji Reddy campus, L V Prasad Eye Institute, Hyderabad, India. DESIGN: Laboratory study. METHODS: Experiments were performed on IOLs from 2 different manufacturers (APPALENS 207, Appasamy Associates and SN60WF, Alcon Laboratories, Inc.). IOL powers ranged from 17 to 25 diopters (D). The IOLs were mounted in a fluid-filled chamber, and the on-axis and off-axis powers were measured using a laser ray tracing system over the central 3 mm zone with delivery angles ranging from -30 to +30 degrees in 5-degree increments. The position of the best focus was calculated for each IOL at each angle. The angular dependence of IOL power was compared with theoretical predictions. RESULTS: Peripheral defocus increased significantly with increasing incidence angle and power. The peripheral defocus at ±30 degrees increased from 5.8 to 8.5 D when the power increased from 17.5 to 24.5 D for APPALENS 207 and from 4.9 to 7.4 D when the power increased from 17 to 25 D for SN60WF. The mean difference between the measured and theoretical tangential power at ±30 degrees was 0.50 ± 0.16 D for the APPALENS 207 and -0.40 ± 0.10 D for the SN60WF, independent of IOL power. CONCLUSIONS: IOLs introduce a significant amount of peripheral defocus which varies significantly with IOL power and design. Given that peripheral defocus is related to lens power, replacement of the crystalline lens (approximately 24 D) with an IOL will produce a significant difference in peripheral defocus profile after surgery.

Lens Thickness Microfluctuations in Young and Prepresbyopic Adults During Steady-State Accommodation.

Purpose: To determine whether lens mechanical dynamics change with age and with accommodative demands. Methods: Lens thickness microfluctuations were measured using a high-speed custom-built spectral domain optical coherence tomography system in five young adults (20 to 25 years old) at 0 diopters (D), 2 D, 4 D, and maximum accommodative demand and in five prepresbyopes (38 to 45 years old) under relaxed and maximal accommodation. For each state, the measurements were repeated four times during the same session. Images of the central 2-mm zone of the lens comprising 170 A-lines/frame were acquired for 10 seconds, and axial lens thickness change was measured. Lens thickness microfluctuations (µm²/Hz) were assessed by integrating the power spectrum of lens thickness microfluctuations between 0 and 4 Hz. Results: The amplitude of lens microfluctuations was higher in the accommodated states than in the relaxed state in both age groups. Lens microfluctuations were higher in young adult participants than in prepresbyopes, with a significant difference in relaxed and maximally accommodated states (P = 0.04 and P = 0.04). In the young participants, the amplitude of microfluctuations reached a plateau at maximum accommodation. Conclusions: Lens mechanical dynamics are both age and accommodation dependent. The decrease in lens thickness microfluctuations with age is consistent with an age-related increase in lens stiffness or decrease of the ciliary muscle displacement. The lens does not contribute to the high-frequency component of ocular dioptric microfluctuations.

Objective Quantification and Topographic Dioptric Demand of Near-Work.

Purpose: The assessment of myopigenic environmental risk factors such as near-work relies on subjective data. Although diaries and questionnaires on near-work show correlation to some degree, it remains unknown how they may correspond to ground truth. This is an important consideration because valid estimates of near-work have great utility for understanding the mechanisms by which dioptric demand drives excessive eye-growth, which is not yet entirely understood. To this end, we assessed a novel eye-tracking system to quantify near-work. Method: We compared subjective entries from diaries to objective data on accommodative demand acquired with a three-dimensional eye-tracker in 20 participants. Each test involved approximately one-hour exposure to ecological near-work environments. Furthermore, topographical dioptric demand maps were computed in retinal coordinates. Results: Our study suggests a frequent mismatch between objectively and subjectively labeled data of near-work tasks (concordance 74.6%). Objective and subjective estimates of dioptric demand showed a moderate correlation and were not significantly different (R2 = 0.59, P = .35). Instead, accommodative demand with an agreement between objective and subjective near-work labels showed a high correlation and were significantly different (R2 = 0.79, P = .016). The accumulated topographical dioptric demand of ecological near-work environments did not present myopigenic defocus stimuli to the retina periphery. Thus extreme close-up near-work presented peripheral defocus stimuli that have been proposed to curb excessive eye growth. Conclusions: The proposed objective measurement method may provide improvements over subjective methods for estimating near-work parameters. Translational Relevance: The topographic dioptric demand maps highlight a possible conflict of causal mechanisms of the two myopia models: "excessive near-work" and "peripheral optical defocus."

Paraxial equivalent of the gradient-index lens of the human eye.

The lens of the eye has a refractive index gradient that changes as the lens grows throughout life. These changes play a key role in the optics of the eye. Yet, the lens is generally simulated using a homogeneous model with an equivalent index that does not accurately represent the gradient. We present an analytical paraxial model of the gradient lens of the eye that gives the direct relation between refractive index distribution and paraxial characteristics. The model accurately simulates the changes in lens power with age and accommodation. It predicts that a decrease in equivalent index with age is associated with a flattening of the axial refractive index profile and that changes in lens power with accommodation are due primarily to changes in the axial variation of the iso-indicial curvature, consistent with Gullstrand's intracapsular theory of accommodation. The iso-indicial curvature gradient causes a shift of the principal planes compared to the homogeneous equivalent model. This shift introduces a clinically significant error in eye models that implement a homogenous lens. Our gradient lens model can be used in eye models to better predict the optics of the eye and the changes with age and accommodation.

Estimating 3D spatiotemporal point of regard: a device evaluation.

This paper presents and evaluates a system and method that record spatiotemporal scene information and location of the center of visual attention, i.e., spatiotemporal point of regard (PoR) in ecological environments. A primary research application of the proposed system and method is for enhancing current 2D visual attention models. Current eye-tracking approaches collapse a scene's depth structures to a 2D image, omitting visual cues that trigger important functions of the human visual system (e.g., accommodation and vergence). We combined head-mounted eye-tracking with a miniature time-of-flight camera to produce a system that could be used to estimate the spatiotemporal location of the PoR-the point of highest visual attention-within 3D scene layouts. Maintaining calibration accuracy is a primary challenge for gaze mapping; hence, we measured accuracy repeatedly by matching the PoR to fixated targets arranged within a range of working distances in depth. Accuracy was estimated as the deviation from estimated PoR relative to known locations of scene targets. We found that estimates of 3D PoR had an overall accuracy of approximately 2° omnidirectional mean average error (OMAE) with variation over a 1 h recording maintained within 3.6° OMAE. This method can be used to determine accommodation and vergence cues of the human visual system continuously within habitual environments, including everyday applications (e.g., use of hand-held devices).

Predictability of pseudophakic refraction using patient-customized paraxial eye models.

PURPOSE: To determine whether patient-customized paraxial eye models that do not rely on exact ray tracing and do not consider aberrations can accurately predict pseudophakic refraction. SETTING: Bascom Palmer Eye Institute, Miami, Florida. DESIGN: Prospective study. METHODS: Cataract surgery patients with and without a history of refractive surgery were included. Manifest refraction, corneal biometry, and extended-depth optical coherence tomography (OCT) imaging were performed at least 1 month postoperatively. Corneal and OCT biometry were used to create paraxial eye models. The pseudophakic refraction simulated using the eye model was compared with measured refraction to calculate prediction error. RESULTS: 49 eyes of 33 patients were analyzed, of which 12 eyes from 9 patients had previous refractive surgery. In eyes without a history of refractive surgery, the mean prediction error was 0.08 ± 0.33 diopters (D), ranging from -0.56 to 0.79 D, and the mean absolute error was 0.27 ± 0.21 D. 31 eyes were within ±0.5 D, and 36 eyes were within ±0.75 D. In eyes with previous refractive surgery, the mean prediction error was -0.44 ± 0.58 D, ranging from -1.42 to 0.32 D, and the mean absolute error was 0.56 ± 0.46 D. 7 of 12 eyes were within ±0.5 D, 8 within ±0.75 D, and 10 within ±1 D. All eyes were within ±1.5 D. CONCLUSIONS: Accurate calculation of refraction in postcataract surgery patients can be performed using paraxial optics. Measurement uncertainties in ocular biometry are a primary source of residual prediction error.

The role of retinotopic cues in deciphering the direction and magnitude of monocular dynamic ocular accommodation: A review.

Accommodative responses of humans operate seamlessly to ensure clear vision of targets at different viewing distances, up until the onset of presbyopia. To achieve this, the visual system must correctly decipher the polarity and magnitude of retinal defocus in real-time, and often under very challenging viewing conditions. The past seven decades of research in this area has identified several retinotopic cues that may potentially provide the desired odd- and even-error information to the visual system for solving these challenges. These studies have used a variety of technology, experimental paradigms and outcome measures to determine the putative contribution of a given cue, or set of cues, in solving this problem. A variety of results, some offering consensus and others conflicting, have been observed in these studies. The present review distils this large volume of literature into specific, take-away points for the early reader of this topic, acknowledging that the problem is non-trivial and far from being solved. The review also reveals that many of these studies may not have used appropriate/sensitive methodology or outcome measures to tease apart the relative contribution of a cue in solving the direction and magnitude challenge. The review concludes with the proposal that, since a multitude of cues may be used by the visual system for solving these problems, future studies could employ a Bayesian statistical cue-combination approach to address this problem. Such approaches have yielded very meaningful insights in other areas of human decision-making involving multiple inter- and intra-modal combination of cues.

Combined anterior segment OCT and wavefront-based autorefractor using a shared beam.

We have combined an anterior segment (AS) optical coherence tomography (OCT) system and a wavefront-based aberrometer with an approach that senses ocular wavefront aberrations using the OCT beam. Temporal interlacing of the OCT and aberrometer channels allows for OCT images and refractive error measurements to be acquired continuously and in real-time. The system measures refractive error with accuracy and precision comparable to that of clinical autorefractors. The proposed approach provides a compact modular design that is suitable for integrating OCT and wavefront-based autorefraction within the optical head of the ophthalmic surgical microscope for guiding cataract surgery or table-top devices for simultaneous autorefraction and ocular biometry.

In vivo measurement of the attenuation coefficient of the sclera and ciliary muscle.

We acquired 1325 nm OCT images of the sclera and ciliary muscle of human subjects. The attenuation coefficients of the sclera and ciliary muscle were determined from a curve fit of the average intensity profile of about 100 A-lines in a region of interest after correction for the effect of beam geometry, using a single scattering model. The average scleral attenuation coefficient was 4.13 ± 1.42 mm-1 with an age-related decrease that was near the threshold for statistical significance (p = 0.053). The average ciliary muscle attenuation coefficient was 1.72 ± 0.88 mm-1, but this value may be an underestimation due to contributions from multiple scattering. Overall, the results suggest that inter-individual variations in scleral attenuation contribute to variability in the quality of transscleral OCT images of the ciliary muscle and the outcome of transscleral laser therapies.

Relationship of the cornea and globe dimensions to the changes in adult human crystalline lens diameter, thickness and power with age.

It is well known that human crystalline lens shape, dimensions and optical properties change throughout life and influence whole eye refraction. However, it is not clear if lens properties are associated with other ocular parameters. The purpose of the present study was to investigate the relationship of corneal and external globe dimensions with adult lens diameter (LD), lens thickness (LT) and lens power (LP) in order to determine if external factors influence lens properties. Postmortem human eyes (n = 66, age = 20-78 years) were obtained from the Ramayamma International Eye Bank, Hyderabad, India. Globe antero-posterior length (GAPL) and mean (average of horizontal and vertical) diameters of cornea (MCD) and globe (MGD) were measured using digital calipers. Eyes were dissected to produce ocular structures that contain the lens maintained in its accommodating framework, including intact zonules, ciliary body and sections of sclera. Specimens were mounted in a mechanical lens stretching system. LD, LT and LP were measured using high magnification retro-illumination photography, slit illumination photography and Scheiner principle-based optical system respectively in the unstretched (accommodated) state. Relationships between external globe and corneal dimensions and LD, LT or LP were assessed by multiple regression analysis. Age (0.012 ± 0.003 mm/year; p<0.001) and GAPL (0.185 ± 0.045 mm/mm; p<0.001) were significant (p<0.0001) predictors of LD. After adjusting for age-related increases, LD appears to be positively correlated with GAPL. Age (0.010 ± 0.004 mm/year; p = 0.009) and GAPL (-0.143 ± 0.060 mm/mm; p = 0.02) were significant (p = 0.001) predictors of LT. After adjusting for the age-related increase, LT appears to be negatively correlated with GAPL. Only age was a significant predictor of LP (-0.26 ± 0.04 D/year; p<0.001). The results suggest that, apart from aging, lens diameter and thickness are dependent on the anteroposterior length of the eye globe. Lens power is not influenced by globe dimensions.

Lifetime Corneal Edema Load Model.

Purpose: To highlight the potential benefits for long-term use of silicone hydrogels daily disposable (DD) contact lenses, particularly with patients who are noncompliant, sleeping or napping while wearing their lenses, or those who have higher oxygen demands and wear this modality for decades. Methods: Published data for corneal swelling with lenses and no lens wear were used to develop a nonlinear least squares model. The edema load experienced with a range of oxygen transmissibilities (Dk/t) and wear compliance (sleep and napping) was determined. A mixed-effects linear regression model was used to compare the edema load for high and average corneal swellers. Results: The edema load generated demonstrates that a high Dk/t silicone hydrogel lens results in edema levels close to that with no lens wear. In comparison, hydrogels with a Dk/t of 27 (× 10-9 [cm mL{O2}][s mL mm Hg]), worn on a daily wear schedule will result in 1.5 times more edema and up to two times more if the patient is noncompliant over each decade of wear. High swellers after four decades of wear will have an edema load 10 to 17 times greater than average swellers depending on Dk/t and their degree of noncompliance with the daily wear modality. Conclusions: Prescribing silicone hydrogel DD lenses, particularly with higher DK/t, may help to maintain the long-term ocular health of patients, when they wear their lenses fulltime for many decades. Translational Relevance: Illustrates the importance of Dk/t for any CL wear modality where patients nap or sleep in lenses or have high oxygen needs.

Age-Dependence of the Peripheral Defocus of the Isolated Human Crystalline Lens.

Purpose: To characterize the peripheral defocus of isolated human crystalline lenses and its age dependence. Methods: Data were acquired on 116 isolated lenses from 99 human eyes (age range, 0.03-61 years; postmortem time, 40.1 ± 21.4 hours). Lenses were placed in a custom-built combined laser ray tracing and optical coherence tomography system that measures the slopes of rays refracted through the lens for on-axis and off-axis incidence angles. Ray slopes were measured by recording spot patterns as a function of axial position with an imaging sensor mounted on a positioning stage below the tissue chamber. Delivery angles ranged from -30° to +30° in 5° increments using a 6 mm × 6 mm raster scan with 0.5-mm spacing. Lens power at each angle was calculated by finding the axial position that minimizes the root-mean-square size of the spot pattern formed by the 49 central rays, corresponding to a 3-mm zone on-axis. The age dependence of the on-axis and off-axis optical power and the relative peripheral defocus (difference between off-axis and on-axis power) of lenses were quantified. Results: At all angles, lens power decreased significantly with age. Lens power increased with increasing delivery angle for all lenses, corresponding to a shift toward myopic peripheral defocus. There was a statistically significant decrease in the lens peripheral defocus with age. Conclusions: The isolated human lens power increases with increasing field angle. The lens relative peripheral defocus decreases with age, which may contribute to the age-related changes of ocular peripheral defocus during refractive development.

Morphometric analysis of in vitro human crystalline lenses using digital shadow photogrammetry.

There is a great need for accurate biometric data on human lenses. To meet this, a compact tabletop optical comparator, the minishadowgraph, was built for measuring isolated eye lens shape and dimensions while the lens was fully immersed in supporting medium. The instrument was based around a specially designed cell and an illumination system which permitted image recording in both sagittal and equatorial (coronal) directions. Data were acquired with a digital camera and analyzed using a specially written MATLAB program as well as by manual measurements in image analysis software. The possible effect of lens orientation and gravity on the dimensions was examined by measuring dimensions with anterior or posterior surfaces up and by measuring lenses with calipers after removal from the minishadowgraph cell. Dimensions, curvatures and shape factors were obtained for 134 fully accommodated lenses ranging in age from birth to 88 years postnatal. Of these, 41 were from donors aged under 20 years, ages which are generally of limited availability. Thickness and diameter showed the same age-related trends described in previous studies but, for the lenses measured in air, age-dependent differences were observed in thickness (-5 to 0%) and diameter (+5 to 0%), consistent with gravitational sag. Anterior and posterior radii of curvature of the central 3 or 6 mm, depending on lens diameter, increase with age, with the anterior increase greater than the posterior. The anterior surface shape of the neonatal lens is that of a prolate ellipse and the posterior, an oblate ellipse. Both surfaces become hyperbolic after age 20. The data presented here on dimensions, shape and sagging will be of great value in assessing age-related changes in the optical and mechanical performance of the lens. In particular, the comprehensive data set from donors aged under 20 years provides a unique and valuable insight to the changes in size and shape during the early dynamic growth period of the lens.

Computational Model of Sclerotic Scatter.

PURPOSE: A clinical examination technique to detect pathology within the anterior eye is known as "sclerotic scatter" (SS). Its propagation pathway has not been thoroughly investigated. Although conventionally theorized to occur by "total internal reflection" (TIR) within the cornea, existing data suggest that this may be an incomplete explanation. METHODS: An anterior eye model representative of a human eye has been constructed using nonsequential ray tracing (OpticStudio 18.1). Three generations of the model were constructed to support the analyses of the pathway of light in SS. A design of experiment methodology involving the key parameters was used to determine the slit-lamp setup for optimum clinical visualization. RESULTS: Most of the light directed into the temporal limbus in SS is lost (52%) into the sclera or reemitted back to the clinician. Only 0.006% of light that transits the central cornea undergoes TIR off the anterior cornea and more significantly 0.000125% off the posterior cornea. The optimal slit-lamp setup parameters to maximize the clinician's visualization are also summarized. CONCLUSIONS: The propagation of light within SS primarily does not occur by TIR off the posterior cornea but rather the direct transcameral propagation of light. SS also represents an inefficient usage of light, with approximately half of the light creating a potential glare source for clinicians. We have formulated a recommended set of parameters for the slit-lamp setup to maximize clinical visualization. We also describe the transcameral pathways involved in SS that create a corneal "backlighting" effect. Almost a century after Graves original description, the optics of this phenomenon are described here.

The risk of vision loss in contact lens wear and following LASIK.

PURPOSE: To compare the risk of vision loss following contemporary laser-assisted in situ keratomileusis (LASIK) with different types and modality of use of contact lenses. METHODS: Data from a previously published study were used to derive the incidence of vision loss (≥ 2 line loss of best corrected spectacle acuity) following microbial keratitis for different contact lens types and wearing modality, stratified by duration of lens wear. A literature search on vision loss following LASIK was performed between 2003 and 2019. The prevalence of vision loss at six months post-surgery was captured from clinical trials published after 2003. A proportion meta-analysis was applied to derive the prevalence of vision loss following LASIK. A least-squares fitting of cumulative vision loss (P, /10 000 wearers) over time (t, years) using an exponential model estimated the years of contact lens wear to which the risk of vision loss with LASIK was equivalent. RESULTS: Vision loss following LASIK occurred in 66 (95% confidence interval [CI] 34-108) per 10 000 wearers. As a conservative estimate based on the lower confidence interval of the estimated equivalent years of contact lens wear, daily wear contact lenses and extended overnight silicone wear hydrogel contact lens need to be worn for 103 (95% [CI] 103-391) and 25 (95% [CI] 25-79) years respectively, to equal the rate of vision loss equivalent to a one-off LASIK procedure. CONCLUSIONS: The risk of vision loss to the individual is low with either contact lens wear or refractive surgery. Contact lens wear does not pose a higher risk of vision loss than LASIK surgery for the most common wear modalities.

In vivo measurement of the human crystalline lens equivalent refractive index using extended-depth OCT.

The lens equivalent refractive index (RI) is commonly used in calculations of crystalline lens power. However, accurate determination of the equivalent RI in vivo is challenging due to the need of multiple measurements with different ocular biometry devices. A custom extended-depth Spectral Domain-OCT system was utilized to provide measurements of corneal and lens surface curvatures and all intraocular distances required for determination of the lens equivalent RI. Ocular biometry and refraction were input into a computational model eye from which the equivalent RI was calculated. Results derived from human subjects of a wide age range show a decrease in RI with age and demonstrate the capability of in vivo measurements of the equivalent RI with extended-depth OCT.

System for on- and off-axis volumetric OCT imaging and ray tracing aberrometry of the crystalline lens.

We present a new in vitro instrument for measuring shape and wavefront aberrations of the primate crystalline lens, both on- and off-axis, while simulating accommodation with a motorized lens stretching system. The instrument merges spectral domain optical coherence tomography (SD-OCT) imaging and ray tracing aberrometry using an approach that senses wavefront aberrations of the lens with the OCT probing beam. Accuracy and repeatability of aberration measurements were quantified. Preliminary experiments on two human and four cynomolgus monkey lenses demonstrate the ability of the system to measure the lens shape, spherical aberration and peripheral defocus, and their changes during simulated accommodation.