Melissa D. Bailey

Ciliary Body Thickness and Refractive Error in Children

PURPOSE To determine whether ciliary body thickness (CBT) is related to refractive error in school-age children. METHODS Fifty-three children, 8 to 15 years of age, were recruited. CBT was measured from anterior segment OCT images (Visante; Carl Zeiss Meditec, Inc., Dublin, CA) at 1 (CBT1), 2 (CBT2) and 3 (CBT3) mm posterior to the scleral spur. Cycloplegic refractive error was measured with an autorefractor, and axial length was measured with an optical biometer. Multilevel regression models determined the relationship between CBT measurements and refractive error or axial length. A Bland-Altman analysis was used to assess the between-visit repeatability of the ciliary body measurements. RESULTS The between-visits coefficients of repeatability for CBT1, -2, and -3 were 148.04, 165.68, and 110.90, respectively. Thicker measurements at CBT2 (r = -0.29, P = 0.03) and CBT3 (r = -0.38, P = 0.005) were associated with increasingly myopic refractive errors (multilevel model: P < 0.001). Thicker measurements at CBT2 (r = 0.40, P = 0.003) and CBT3 (r = 0.51, P < 0.001) were associated with longer axial lengths (multilevel model: P < 0.001). CONCLUSIONS Thicker ciliary body measurements were associated with myopia and a longer axial length. Future studies should determine whether this relationship is also present in animal models of myopia and determine the temporal relationship between thickening of the ciliary muscle and the onset of myopia.

Vitamin D Receptor (VDR) and Group-Specific Component (GC, Vitamin D–Binding Protein) Polymorphisms in Myopia

PURPOSE Epidemiologic evidence indicates that time outdoors reduces the risk of myopia, suggesting a possible role for vitamin D. This case-control study was conducted to determine whether single-nucleotide polymorphisms (SNPs) within VDR at 12q13.11 and GC at 4q12-13 are associated with myopia. METHODS The primary analysis was conducted on 81 white adult control subjects between 18 and 50 years of age with a spherical equivalent refractive error between +0.50 and +2.00 D in both eyes and less than 1.50 D of astigmatism. Affected myopic subjects were 289 unrelated white adults at least 18 years of age with at least -0.75 D myopia in both principal meridians of both eyes. RESULTS One SNP within VDR was significantly associated with myopia in the multivariate analysis of the primary sample (rs2853559: odds ratio = 1.99, P = 0.003). In a subsample of less severely myopic white subjects between -0.75 and -4.00 D, three SNPs within VDR were significantly associated in a multivariate model after adjustment for multiple comparisons (rs2239182: odds ratio = 2.17, P = 0.007; rs3819545: odds ratio = 2.34, P = 0.003; rs2853559: odds ratio = 2.14, P = 0.0035), accounting for 12% of model variance over age alone. CONCLUSIONS Polymorphisms within VDR appear to be associated with low to moderate amounts of myopia in white subjects. Future studies should determine whether this finding can be replicated and should explore the biological significance of these variations with respect to myopia.

Estimation of pupil size by digital photography

Purpose: To evaluate a digital photography method of pupil size estimation over a broad range of illumination conditions and to compare this method with common clinical techniques. Setting: College of Optometry, Ohio State University, Columbus, Ohio, USA. Methods: Two examiners measured the pupil diameter in 45 right eyes at 3 illumination levels: <0.63 lux (dark), 5 lux (dim), and 1000 lux (bright). Estimation by infrared video recording, the reference standard, was compared with measurements by digital photography, ruler, semicircular templates, and the Colvard pupillometer. Masked graders measured pupil size from infrared video recordings and digital photographs. Results: The repeatability of the measurement method determined by the mean intraclass correlation coefficients was highest for video recording across conditions (0.86–0.97), followed by digital photography (0.76–0.94), Colvard pupillometry (0.63–0.82), ruler (0.71–0.85), and templates (0.70–0.83). An analysis of variance showed a significant difference in pupil size by method (P<.001). All methods except digital photography estimated smaller pupil sizes under dark and dim illumination than infrared video measurements (all P<.01). Under bright illumination, the ruler measurements were significantly smaller (–0.15 mm) and the Colvard pupillometer measurements were greater (+0.30 mm) than the reference (P<.01). The 95% limits of agreement (LoA) between examiners were smallest for video measurements at all light levels. The remaining measures ranked from best to worst by 95% LoA were digital photography, Colvard pupillometry, ruler, and templates. Conclusions: Estimation of pupil size by digital photography was more repeatable and accurate than estimates by common clinical techniques over a wide range of illumination. Although not as quick as other methods, digital photography is relatively inexpensive, permits lasting documentation, and allows independent grading suitable for clinical research purposes.

Measuring Changes in Ciliary Muscle Thickness with Accommodation in Young Adults

Purpose. To develop a measurement protocol for changes in the shape and size of the ciliary muscle with accommodation using the Zeiss Visante™ anterior segment optical coherence tomography (AS-OCT) and to determine the test-retest repeatability of these measurements. Methods. Subjects were 25 adults aged 23 to 28 years. The ciliary muscle was imaged at two visits with the Visante™ while accommodative response was monitored during imaging using the PowerRefractor. Ciliary muscle thickness (CMT) was measured at 1 mm (CMT1), 2 mm (CMT2), and 3 mm (CMT3) posterior to the scleral spur and at the point of maximal thickness (CMTMAX). Thickness was measured at these locations while subjects viewed a target at distance and at a 4.00 D accommodative stimulus. Outcome measures were the change in thickness between distance and the 4.00 D stimulus and the change in thickness per diopter of accommodative response (PowerRefractor). Finally, the repeatability measurements between visit 1 and visit 2 were determined with a Bland-Altman analysis. Results. The statistically significant modeled changes in CMT were as follows: CMTMAX = 69.2 &mgr;m (4.00 D stimulus) and 18.1 &mgr;m (per diopter of accommodation); CMT1 = 45.2 &mgr;m (4.00 D stimulus) and 12.3 &mgr;m (per diopter of accommodation); and CMT3 = −45.9 &mgr;m (4.00 D stimulus) and −12.0 &mgr;m (per diopter of accommodation); p < 0.0001 for all. Conclusions. The combination of the Visante™ and the PowerRefractor is a feasible tool for measuring thickening of ciliary muscle at more anterior locations and thinning at more posterior locations during accommodation. We noted a wide range of accommodative responses during the time of image capture in this study indicating that the most accurate estimates of the change in ciliary muscle dimensions with accommodation may be obtained by using accommodative response rather than stimulus values and by using measurements taken simultaneously with image capture.

Repeatability of autorefraction and axial length measurements after laser in situ keratomileusis

Purpose: To assess the repeatability and agreement of refractive error measurements and the repeatability of axial length (AL) measurements in patients after laser in situ keratomileusis (LASIK). Setting: The Ohio State University College of Optometry, Columbus, Ohio, USA. Methods: Subjective refraction, autorefraction measurements with the Grand Seiko and Humphrey autorefractors, and AL measurements with the IOLMaster were completed for 40 previously myopic LASIK patients under noncycloplegic and cycloplegic conditions on 2 separate occasions. Results: The mean difference between visits for axial length measurements was 0.008 mm ± 0.04 (SD). The between visits repeatability for all refractive error measurements were <0.75 diopter (D). The mean difference between the subjective refraction and the Humphrey autorefractor for spherical equivalent was statistically significant under noncycloplegic conditions (–0.90 D, P<.0001) and cycloplegic conditions (–2.05 D, P<.0001). The mean difference between subjective refraction and Grand Seiko autorefraction measurements was not significant under noncycloplegic conditions (+0.05 D, 95% limits of agreement [LoA] = −0.99, 1.09; P = .52) conditions but was statistically significant, but not clinically relevant, under cycloplegic conditions (+0.17 D, 95% LoA = −0.73, 1.07; P = .03). Conclusions: Refractive error measurements after LASIK using the Grand Seiko autorefractor are reliable and agree well with subjective refraction measurements.

Accommodative fluctuations, lens tension, and ciliary body thickness in children.

Purpose. To investigate the relationship among microfluctuations in accommodation, resting tension on the crystalline lens, ciliary body thickness, and refractive error in children. Methods. Subjects were 49 children, aged 8 to 15 years. Subjects wore habitual correction over their left eye and an infrared filter over the right eye during accommodative measurements. Monocular accommodation was measured continuously for two, 30-second periods using a PowerRef I at a sampling rate of 25 Hz while subjects viewed a high-contrast target at 0.25 m. The high (1.0 to 2.3 Hz) and low- (0 to 0.6 Hz) frequency components of the power spectrum from a fast Fourier transform of the accommodative response were used in analysis. Resting tension on the crystalline lens was assessed by measuring the amplitude of the oscillations of the crystalline lens after a rightward 20° saccadic eye movement. Ciliary body thickness was measured 2 mm posterior to the scleral spur from images obtained with a Zeiss Visante optical coherence tomography (OCT). Cycloplegic spherical equivalent refractive error was obtained with the Grand Seiko autorefractor. Results. The mean ± SD spherical equivalent refractive error was −1.00 D ± 2.25 (range, −6.00 D to +3.44 D). Greater power in the log of the high-frequency component of accommodative microfluctuations was associated with thinner ciliary bodies (p = 0.03) and lower ages (p = 0.0004). More hyperopic refractive errors with greater power in the high-frequency component (p = 0.0005) and the low-frequency component (p = 0.02). No statistically significant relationship was found for the low-frequency component or root mean square of accommodative microfluctuations and refractive error. Conclusions. High-frequency microfluctuations of accommodation appear to be suppressed with thicker ciliary bodies. These variations in accommodation need to be observed in a longitudinal study to better assess the functional significance of their relationship to ciliary body size and refractive error.

The Effect of Phenylephrine on the Ciliary Muscle and Accommodation

Purpose. To objectively measure changes in the human ciliary muscle dimensions in vivo after instillation of topical phenylephrine, a mydriatic and vasodilating agent. Methods. A cross-sectional study of 25 healthy young adults was conducted. Measurements of pupil size, accommodation, and ciliary muscle thickness were made both before and 30 min after instillation of 1% proparacaine and 2.5% phenylephrine. Accommodation was measured in three ways: subjectively using a push-up technique and Royal Air Force (RAF) rule, and objectively using both the Grand Seiko autorefractor and PowerRefractor. Images of the temporal ciliary muscle were acquired using the Visante Anterior Segment Optical Coherence Tomographer (OCT). Ciliary muscle images were objectively analyzed using a computer-based segmentation technique. Results. Amplitude of accommodation using the push-up test was reduced by about 1 D with phenylephrine (p < 0.001). Phenylephrine did not change the accommodative response to a 4 D Badal target as measured by either autorefraction or photorefraction (p > 0.30). There was statistically significant thickening of the anterior region and thinning of the posterior region of the ciliary muscle with accommodation (p < 0.001, all locations). Phenylephrine did not affect either baseline ciliary muscle thickness or the accommodative contraction of the muscle (p > 0.09). Conclusions. Low-dose phenylephrine does not affect ciliary muscle dimensions, ciliary muscle contractility, or accommodative response to a 4 D near target.

Semiautomatic extraction algorithm for images of the ciliary muscle.

Purpose. To develop and evaluate a semiautomatic algorithm for segmentation and morphological assessment of the dimensions of the ciliary muscle in Visante Anterior Segment Optical Coherence Tomography images. Methods. Geometric distortions in Visante images analyzed as binary files were assessed by imaging an optical flat and human donor tissue. The appropriate pixel/mm conversion factor to use for air (n = 1) was estimated by imaging calibration spheres. A semiautomatic algorithm was developed to extract the dimensions of the ciliary muscle from Visante images. Measurements were also made manually using Visante software calipers. Interclass correlation coefficients and Bland-Altman analyses were used to compare the methods. A multilevel model was fitted to estimate the variance of algorithm measurements that was due to differences within- and between-examiners in scleral spur selection vs. biological variability. Results. The optical flat and the human donor tissue were imaged and appeared without geometric distortions in binary file format. Bland-Altman analyses revealed that caliper measurements tended to underestimate ciliary muscle thickness at 3 mm posterior to the scleral spur in subjects with the thickest ciliary muscles (t = 3.6, p < 0.001). The percent variance due to within- or between-examiner differences in scleral spur selection was found to be small (6%) when compared with the variance because of biological difference across subjects (80%). Using the mean of measurements from three images, achieved an estimated interclass correlation coefficient of 0.85. Conclusions. The semiautomatic algorithm successfully segmented the ciliary muscle for further measurement. Using the algorithm to follow the scleral curvature to locate more posterior measurements is critical to avoid underestimating thickness measurements. This semiautomatic algorithm will allow for repeatable, efficient, and masked ciliary muscle measurements in large datasets.

Validation of optical coherence tomography-based crystalline lens thickness measurements in children.

Purpose. To evaluate the validity and repeatability of crystalline lens thickness measurements obtained by anterior segment optical coherence tomography (OCT). Methods. Forty-seven normal children (mean age, 11.06 ± 2.30 yr) had their crystalline lens thickness measured with the Visante anterior segment OCT (Carl Zeiss Meditec, Dublin, CA) and with conventional corneal touch A-scan ultransonography (ultrasound) (Humphrey 820). The subjects’ right corneas were anesthetized, and their right eyes were cyclopleged. Five ultrasound measurements were recorded per eye, and three Visante OCT measurements were recorded per eye. Thirty-eight subjects had measurements at a second visit where three additional Visante OCT measurements were recorded. Results. The mean of the differences between the Visante OCT and ultrasound was −0.045 mm (p = 0.017) with 95% limits of agreement from −0.29 to 0.20 mm, indicating that the measurement of crystalline lens thickness was slightly thinner with the Visante OCT. When validity was assessed using only Visante OCT images that contained the corneal reflex, the mean of the differences was 0.019 mm (p = 0.11) with 95% limits of agreement from −0.091 to 0.13 mm. For the repeatability of the Visante OCT, the mean of the differences between visit one and visit two was −0.008 mm (p = 0.25) with 95% limits of agreement from −0.088 to 0.072 mm. Repeatability improved when reassessed using only images that contain the corneal reflex; the mean of the differences was −0.0001 mm (p = 0.97) with 95% limits of agreement from −0.030 to 0.030 mm. Conclusion. The Visante OCT is a non-contact instrument that is simple to use, and it provides valid crystalline lens thickness measurements with excellent repeatability. Validity and repeatability are optimized when the Visante OCT images contain the corneal reflex and a consistent corneal index refraction is applied to the entire image.

Region-Specific Relationships Between Refractive Error and Ciliary Muscle Thickness in Children

PURPOSE To determine if there is a relationship between refractive error and ciliary muscle thickness in different muscle regions. METHODS An anterior segment optical coherence tomographer was used to measure cycloplegic ciliary muscle thicknesses at 1 mm (CMT1), 2 mm (CMT2), and 3 mm (CMT3) posterior to the scleral spur; maximum (CMTMAX) thickness was also assessed. An autorefractor was used to determine cycloplegic spherical equivalent refractive error (SPHEQ). Apical ciliary muscle fibers were obtained by subtracting corresponding CMT2 values from CMT1 and CMTMAX. Multilevel regression models were used to determine the relationship between ciliary muscle thickness in various regions of the muscle and refractive error. RESULTS Subjects included 269 children with a mean age of 8.71 ± 1.51 years and a mean refractive error of +0.41 ± 1.29 diopters. In linear models with ciliary muscle thicknesses and SPHEQ, SPHEQ was significantly associated only with CMT2 (β = -11.34, P = 0.0008) and CMT 3 (β = -6.97, P = 0.007). When corresponding values of CMT2 were subtracted from CMT1 and CMTMAX, apical fibers at CMT1 (β = 14.75, P < 0.0001) and CMTMAX (β = 18.16, P < 0.0001) had a significant relationship with SPHEQ. CONCLUSIONS These data indicated that in children the posterior ciliary muscle fibers are thicker in myopia (CMT2 and CMT3), but paradoxically, the apical ciliary muscle fibers are thicker in hyperopia (CMTMAX and CMT1). This may be the first evidence that hyperopia is associated with a thicker apical ciliary muscle region.