Contribution of genetic and environmental effects on lens thickness: the Guangzhou Twin Eye study.

PURPOSE:

This study investigated the heritability of lens thickness (LT) and relative lens thickness (LT/axial length, rLT) measured by Lenstar among Chinese children and adolescents in the Guangzhou Twin Eye study.

METHODS:

Twins aged 8 to 22 years were enrolled from the Guangzhou Twin Registry. A series of LT and axial length (AL) measurements using the Lenstar were taken for each twin. Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling, after adjustment for age and sex with the Mx program.

RESULTS:

Seven hundred sixty-eight twin pairs (482 monozygotic [MZ] and 286 dizygotic [DZ] twins) were available for data analysis. The mean (standard deviation) LT and rLT were 3.45 (0.18) mm and 0.142 (0.01), respectively. The intraclass correlation coefficients (ICCs) for LT were 0.90 for the MZ and 0.39 for the DZ twins; and those for rLT were 0.90 for the MZ and 0.40 for the DZ twins, respectively. The best-fitting model yielded 89.5% (95% CI: 87.8%-91.0%) of additive genetic effects and 10.5% (95% CI: 9.0%-12.2%) of unique environmental effects for LT, and 89.3% (95% CI: 89.2%-89.3%) of additive genetic effects and 10.7% (95% CI: 10.7%-11.4%) of unique environmental effects for rLT.

CONCLUSIONS:

This study confirms that the LT in young healthy subjects may be mainly affected by additive genetic factors. High heritability remains even when the data are corrected for the influence of AL with the use of rLT.

MRI study of the changes in crystalline lens shape with accommodation and ageing in humans

Magnetic Resonance Imaging was used to study changes in the crystalline lens and ciliary body with accommodation and aging. Monocular images were obtained in 15 young (19-29 years) and 15 older (60-70 years) emmetropes when viewing at far (6m) and at individual near points (14.5 to 20.9 cm) in the younger group. With accommodation, lens thickness increased (mean±95% CI: 0.33±0.06mm) by a similar magnitude to the decrease in anterior chamber depth (0.31±0.07mm) and equatorial diameter (0.32±0.04mm) with a decrease in the radius of curvature of the posterior lens surface (0.58±0.30mm). Anterior lens surface shape could not be determined due to the overlapping region with the iris. Ciliary ring diameter decreased (0.44±0.17mm) with no decrease in circumlental space or forward ciliary body movement. With aging, lens thickness increased (mean±95% CI: 0.97±0.24mm) similar in magnitude to the sum of the decrease in anterior chamber depth (0.45±0.21mm) and increase in anterior segment depth (0.52±0.23mm). Equatorial lens diameter increased (0.28±0.23mm) with no change in the posterior lens surface radius of curvature. Ciliary ring diameter decreased (0.57±0.41mm) with reduced circumlental space (0.43±0.15mm) and no forward ciliary body movement. Accommodative changes support the Helmholtz theory of accommodation including an increase in posterior lens surface curvature. Certain aspects of aging changes mimic accommodation.

Comparing methods to estimate the human lens power

Purpose: To compare accuracies of different methods for calculating human lens power when lens thickness is not available. Methods: Lens power was calculated by four methods. Three methods were used with previously published biometry and refraction data of 184 emmetropic and myopic eyes of 184 subjects (age range [18, 63] years, spherical equivalent range [–12.38, +0.75] D). These three methods consist of the Bennett method, which uses lens thickness, our modification of the Stenström method and the Bennett¬Rabbetts method, both of which do not require knowledge of lens thickness. These methods include c constants, which represent distances from lens surfaces to principal planes. Lens powers calculated with these methods were compared with those calculated using phakometry data available for a subgroup of 66 emmetropic eyes (66 subjects). Results: Lens powers obtained from the Bennett method corresponded well with those obtained by phakometry for emmetropic eyes, although individual differences up to 3.5D occurred. Lens powers obtained from the modified¬Stenström and Bennett¬Rabbetts methods deviated significantly from those obtained with either the Bennett method or phakometry. Customizing the c constants improved this agreement, but applying these constants to the entire group gave mean lens power differences of 0.71 ± 0.56D compared with the Bennett method. By further optimizing the c constants, the agreement with the Bennett method was within ± 1D for 95% of the eyes. Conclusion: With appropriate constants, the modified¬Stenström and Bennett¬Rabbetts methods provide a good approximation of the Bennett lens power in emmetropic and myopic eyes.

Gradients of refractive index in the crystalline lens and transient changes in refraction among patients with diabetes

Transient hyperopic refractive shifts occur on a timescale of weeks in some patients after initiation of therapy for hyperglycemia, and are usually followed by recovery to the original refraction. Possible lenticular origin of these changes is considered in terms of a paraxial gradient index model. Assuming that the lens thickness and curvatures remain unchanged, as observed in practice, it appears possible to account for initial hyperopic refractive shifts of up to a few diopters by reduction in refractive index near the lens center and alteration in the rate of change between center and surface, so that most of the index change occurs closer to the lens surface. Restoration of the original refraction depends on further change in the refractive index distribution with more gradual changes in refractive index from the lens center to its surface. Modeling limitations are discussed.

Methods to estimate the size and shape of the unaccommodated crystalline lens in vivo

Purpose. The purpose of this article was to present methods capable of estimating the size and shape of the human eye lens without resorting to phakometry or magnetic resonance imaging (MRI). Methods. Previously published biometry and phakometry data of 66 emmetropic eyes of 66 subjects (age range [18, 63] years, spherical equivalent range [−0.75, +0.75] D) were used to define multiple linear regressions for the radii of curvature and thickness of the lens, from which the lens refractive index could be derived. MRI biometry was also available for a subset of 30 subjects, from which regressions could be determined for the vertex radii of curvature, conic constants, equatorial diameter, volume, and surface area. All regressions were compared with the phakometry and MRI data; the radii of curvature regressions were also compared with a method proposed by Bennett and Royston et al. Results. The regressions were in good agreement with the original measurements. This was especially the case for the regressions of lens thickness, volume, and surface area, which each had an R2 > 0.6. The regression for the posterior radius of curvature had an R2 < 0.2, making this regression unreliable. For all other regressions we found 0.25 < R2 < 0.6. The Bennett-Royston method also produced a good estimation of the radii of curvature, provided its parameters were adjusted appropriately. Conclusions. The regressions presented in this article offer a valuable alternative in case no measured lens biometry values are available; however care must be taken for possible outliers.

Age-dependence of the average and equivalent refractive indices of the crystalline lens

Lens average and equivalent refractive indices are required for purposes such as lens thickness estimation and optical modeling. We modeled the refractive index gradient as a power function of the normalized distance from lens center. Average index along the lens axis was estimated by integration. Equivalent index was estimated by raytracing through a model eye to establish ocular refraction, and then backward raytracing to determine the constant refractive index yielding the same refraction. Assuming center and edge indices remained constant with age, at 1.415 and 1.37 respectively, average axial refractive index increased (1.408 to 1.411) and equivalent index decreased (1.425 to 1.420) with age increase from 20 to 70 years. These values agree well with experimental estimates based on different techniques, although the latter show considerable scatter. The simple model of index gradient gives reasonable estimates of average and equivalent lens indices, although refinements in modeling and measurements are required.

The effect of topical adrenergic and anticholinergic agents on the choroidal thickness of young healthy adults

The human choroid is capable of rapidly changing its thickness in response to a variety of stimuli. However little is known about the role of the autonomic nervous system in the regulation of the thickness of the choroid. Therefore, we investigated the effect of topical parasympatholytic and sympathomimetic agents upon the choroidal thickness and ocular biometrics of young healthy adult subjects. Fourteen subjects (mean age 27.9 ± 4 years) participated in this randomized, single-masked, placebo-controlled study. Each subject had measurements of choroidal thickness (ChT) and ocular biometrics of their right eye taken before, and then 30 and 60 min following the administration of topical pharmacological agents. Three different drugs: 2% homatropine hydrobromide, 2.5% phenylephrine hydrochloride and a placebo (0.3% hydroxypropyl methylcellulose) were tested in all subjects; each on different days (at the same time of the day) in randomized order. Participants were masked to the pharmacological agent being used at each testing session. The instillation of 2% homatropine resulted in a small but significant increase in subfoveal ChT at 30 and 60 min after drug instillation (mean change 7 ± 3 μm and 14 ± 2 μm respectively; both p < 0.0001). The parafoveal choroid also exhibited a similar magnitude, significant increase in thickness with time after 2% homatropine (p < 0.001), with a mean change of 7 ± 0.3 μm and 13 ± 1 μm (in the region located 0.5 mm from the fovea center), 6 ± 1 μm and 12.5 ± 1 μm (1 mm from the fovea center) and 6 ± 2 μm and 12 ± 2 μm (1.5 mm from the fovea center) after 30 and 60 min respectively. Axial length decreased significantly 60 min after homatropine (p < 0.01). There were also significant changes in lens thickness (LT) and anterior chamber depth (ACD) (p < 0.05) associated with homatropine instillation. No significant changes in choroidal thickness, or ocular biometrics were found after 2.5% phenylephrine or placebo at any examination points (p > 0.05). In human subjects, significant increases in subfoveal and parafoveal choroidal thickness occurred after administration of 2% homatropine and this implies an involvement of the parasympathetic system in the control of choroidal thickness in humans.

Lens shape and refractive index distribution in type 1 diabetes

Purpose: To compare lens dimensions and refractive index distributions in type 1 diabetes and age-matched control groups. Methods: There were 17 participants with type 1 diabetes, consisting of two subgroups (7 young [23 ± 4 years] and 10 older [54 ± 4 years] participants), with 23 controls (13 young, 24 ± 4 years; 10 older, 55 ± 4 years). For each participant, one eye was tested with relaxed accommodation. A 3T clinical magnetic resonance imaging scanner was used to image the eye, employing a multiple spin echo (MSE) sequence to determine lens dimensions and refractive index profiles along the equatorial and axial directions. Results: The diabetes group had significantly smaller lens equatorial diameters and larger lens axial thicknesses than the control group (diameter mean ± 95% confidence interval [CI]: diabetes group 8.65 ± 0.26 mm, control group 9.42 ± 0.18 mm; axial thickness: diabetes group 4.33 ± 0.30 mm, control group 3.80 ± 0.14 mm). These differences were also significant within each age group. The older group had significantly greater axial thickness than the young group (older group 4.35 ± 0.26 mm, young group 3.70 ± 0.25 mm). Center refractive indices of diabetes and control groups were not significantly different. There were some statistically significant differences between the refractive index fitting parameters of young and older groups, but not between diabetes and control groups of the same age. Conclusions: Smaller lens diameters occurred in the diabetes groups than in the age-matched control groups. Differences in refractive index distribution between persons with and without diabetes are too small to have important effects on instruments measuring axial thickness.

Perfect imaging of three object points with only two analytic lens surfaces in two dimensions

In this work, a new two-dimensional analytic optics design method is presented that enables the coupling of three ray sets with two lens profiles. This method is particularly promising for optical systems designed for wide field of view and with clearly separated optical surfaces. However, this coupling can only be achieved if different ray sets will use different portions of the second lens profile. Based on a very basic example of a single thick lens, the Simultaneous Multiple Surfaces design method in two dimensions (SMS2D) will help to provide a better understanding of the practical implications on the design process by an increased lens thickness and a wider field of view. Fermat?s principle is used to deduce a set of functional differential equations fully describing the entire optical system. The transformation of these functional differential equations into an algebraic linear system of equations allows the successive calculation of the Taylor series coefficients up to an arbitrary order. The evaluation of the solution space reveals the wide range of possible lens configurations covered by this analytic design method. Ray tracing analysis for calculated 20th order Taylor polynomials demonstrate excellent performance and the versatility of this new analytical optics design concept.

Accuracy of cornea and lens biometry using anterior segment optical coherence tomography

We assess the accuracy of the Visante anterior segment optical coherence tomographer (AS-OCT) and present improved formulas for measurement of surface curvature and axial separation. Measurements are made in physical model eyes. Accuracy is compared for measurements of corneal thickness (d1) and anterior chamber depth (d2) using-built-in AS-OCT software versus the improved scheme. The improved scheme enables measurements of lens thickness (d 3) and surface curvature, in the form of conic sections specified by vertex radii and conic constants. These parameters are converted to surface coordinates for error analysis. The built-in AS-OCT software typically overestimates (mean±standard deviation(SD)]d1 by +62±4 μm and d2 by +4±88μm. The improved scheme reduces d1 (-0.4±4 μm) and d2 (0±49 μm) errors while also reducing d3 errors from +218±90 (uncorrected) to +14±123 μm (corrected). Surface x coordinate errors gradually increase toward the periphery. Considering the central 6-mm zone of each surface, the x coordinate errors for anterior and posterior corneal surfaces reached +3±10 and 0±23 μm, respectively, with the improved scheme. Those of the anterior and posterior lens surfaces reached +2±22 and +11±71 μm, respectively. Our improved scheme reduced AS-OCT errors and could, therefore, enhance pre- and postoperative assessments of keratorefractive or cataract surgery, including measurement of accommodating intraocular lenses. © 2007 Society of Photo-Optical Instrumentation Engineers.

Axial length charges during accommodation in myopes and emmetropes

Purpose: To investigate the influence of accommodation upon axial length (and a comprehensive range of ocular biometric parameters), in populations of young adult myopic and emmetropic subjects. Methods: Forty young adult subjects had ocular biometry measured utilizing a non-contact optical biometer (Lenstar LS 900) based upon the principle of optical low coherence reflectometry, under three different accommodation demands (0 D, 3 D and 6 D). Subjects were classified as emmetropes (n=19) or myopes (n=21) based upon their spherical equivalent refraction (mean emmetropic refraction -0.05 ± 0.27DS and mean myopic refraction -1.82 ± 0.84 DS). Results: Axial length changed significantly with accommodation, with a mean increase of 11.9 ± 12.3 µm and 24.1 ± 22.7 µm for the 3 D and 6 D accommodation stimuli respectively. A significant axial elongation associated with accommodation was still evident even following correction of the axial length data for potential error due to lens thickness change. The mean ‘corrected’ increase in axial length was 5.2 ± 11.2 µm, and 7.4 ± 18.9 µm for the 3 D and 6 D stimuli respectively. There was no significant difference between the myopic and emmetropic populations in terms of the magnitude of change in axial length with accommodation, regardless of whether the data were corrected or not. A number of other ocular biometric parameters, such as anterior chamber depth, lens thickness and vitreous chamber depth also exhibited significant change with accommodation. The myopic and emmetropic populations also exhibited no significant difference in the magnitude of change in these parameters with accommodation. Conclusions: The eye undergoes a significant axial elongation associated with a brief period of accommodation, and the magnitude of this change in eye length increases for larger accommodation demands, however there is no significant difference in the magnitude of eye elongation in myopic and emmetropic subjects.

Axial elongation associated with biomechanical factors during near work

Purpose: To investigate the changes occurring in the axial length, choroidal thickness and anterior biometrics of the eye during a 10 minute near task performed in downward gaze. Methods: Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure ocular biometrics in downward gaze, an optical biometer was inclined on a custom built, height and tilt adjustable table. Baseline measures were collected after each subject performed a distance primary gaze control task for 10 mins, to provide wash-out period for prior visual tasks before each of three different accommodation/gaze conditions. These other three conditions included a near task (2.5 D) in primary gaze, and a near (2.5 D) and a far (0 D) accommodative task in downward gaze (25°), all for 10 mins duration. Immediately after, and then 5 and 10 mins from the commencement of each trial, measurements of ocular biometrics (e.g. anterior biometrics, axial length, choroidal thickness and retinal thickness) were obtained. Results: Axial length increased with accommodation and was significantly greater for downward gaze with accommodation (mean change ± SD 23 ± 13 µm at 10 mins) compared to primary gaze with accommodation (mean change 8 ± 15 µm at 10 mins) (p < 0.05). A small amount of choroidal thinning was also found during accommodation that was statistically significant in downward gaze (13 ± 14 µm at 10 mins, p < 0.05). Accommodation in downward gaze also caused greater changes in anterior chamber depth and lens thickness compared to accommodation in primary gaze. Conclusion: Axial length, choroidal thickness and anterior eye biometrics change significantly during accommodation in downward gaze as a function of time. These changes appear to be due to the combined influence of biomechanical factors (i.e. extraocular muscle forces, ciliary muscle contraction) associated with near tasks in downward gaze.

Changes in ocular biometrics and refraction during near work in downward gaze over time

PURPOSE To investigate changes in the characteristics of the corneal optics, total optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 min. METHODS Ten emmetropes (mean - 0.14 ± 0.24 DS) and 10 myopes (mean - 2.26 ± 1.42 DS) aged from 18 to 30 years were recruited. To measure ocular biometrics and corneal topography in downward gaze, an optical biometer (Lenstar LS900) and a rotating Scheimpflug camera (Pentacam HR) were inclined on a custom built, height and tilt adjustable table. The total optics of the eye were measured in downward gaze with binocular fixation using a modified Shack-Hartmann wavefront sensor. Initially, subjects performed a distance viewing task at primary gaze for 10 min to provide a "wash-out" period for prior visual tasks. A distance task (watching video at 6 m) in downward gaze (25°) and a near task (watching video on a portable LCD screen with 2.5 D accommodation demand) in primary gaze and 25°downward gaze were then carried out, each for 10 min in a randomized order. During measurements, in dichoptic view, a Maltese cross was fixated with the right (untested) eye and the instrument’s fixation target was fixated with the subject’s tested left eye. Immediately after (0 min), 5 and 10 min from the commencement of each trial, measurements of ocular parameters were acquired in downward gaze. RESULTS Axial length exhibited a significant increase with downward gaze and accommodation over time (p<0.05). The greatest axial elongation was observed in downward gaze with 2.5 D accommodation after 10 min (mean change from baseline 23±3 µm). Downward gaze also caused greater changes in anterior chamber depth (ACD) and lens thickness (LT) with accommodation (ACD mean change -163±12µm at 10 min; LT mean change 173±17 µm at 10 min) compared to primary gaze with accommodation (ACD mean change -138±12µm at 10 min; LT mean change 131±15 µm at 10 min). Both corneal power and total ocular power changed by a small but significant amount with downward gaze (p<0.05), resulting in a myopic shift (~0.10 D) in the spherical power of the eye compared with primary gaze. CONCLUSION The axial length, anterior biometrics and ocular refraction change significantly with accommodation in downward gaze as a function of time. These findings provide new insights into the optical and bio-mechanical changes of the eye during typical near tasks.

Optics of the human eye in diabetes

This study compared optics of eyes in people with diabetes with those age-balanced controls. Relative to the control group, the diabetes group demonstrated greater lens thickness, more curved lens shapes, smaller lens diameters, higher light scatter, greater lens yellowing, and poorer focusing ability. While the optics of the people with diabetes made them appear as older eyes than those of people of the same age without diabetes, the differences did not increase significantly with age. It was concluded that age-related changes in eyes of people with diabetes need not be accelerated if the diabetes is well controlled.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

BACKGROUND Tilted disc syndrome (TDS) is associated with characteristic ocular findings. The purpose of this study was to evaluate the ocular, refractive, and biometric characteristics in patients with TDS. METHODS This case-control study included 41 eyes of 25 patients who had established TDS and 40 eyes of 20 healthy control subjects. All participants underwent a complete ocular examination, including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry, keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. RESULTS There were no significant differences in spherical equivalent (P = 0.13) and total astigmatism (P = 0.37) between groups. However, mean best spectacle-corrected visual acuity (Log Mar) was significantly worse in TDS patients (P = 0.003). The lenticular astigmatism was greater in the syndrome group, whereas the corneal component was greater in controls (P = 0.059 and P = 0.028, respectively). The measured biometric features were the same in both groups, except for the lens thickness and lens-axial length factor, which were greater in the TDS group (P = 0.007 and P = 0.055, respectively). CONCLUSIONS Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lenses were characteristic findings in patients with TDS.