Gregor F. Schmid

In Vivo Human Choroidal Thickness Measurements: Evidence for Diurnal Fluctuations

PURPOSE The authors applied partial coherence interferometry (PCI) to estimate the thickness of the human choroid in vivo and to learn whether it fluctuates during the day. METHODS By applying signal processing techniques to existing PCI tracings of human ocular axial length measurements, a signal modeling algorithm was developed and validated to determine the position and variability of a postretinal peak that, by analogy to animal studies, likely corresponds to the choroidal/scleral interface. The algorithm then was applied to diurnal axial eye length datasets. RESULTS The postretinal peak was identified in 28% of subjects in the development and validation datasets, with mean subfoveal choroidal thicknesses of 307 and 293 microm, respectively. Twenty-eight of 40 diurnal PCI datasets had at least two time points with identifiable postretinal peaks, yielding a mean choroidal thickness of 426 microm and a mean high-low difference in choroidal thickness of 59.5 +/- 24.2 microm (range, 25.9-103 microm). The diurnal choroidal thickness fluctuation was larger than twice the SE of measurement (24.5 microm) in 16 of these 28 datasets. Axial length and choroidal thickness tended to fluctuate in antiphase. CONCLUSIONS Signal processing techniques provide choroidal thickness estimates in many, but not all, PCI datasets of axial eye measurements. Based on eyes with identifiable postretinal peaks at more than one time in a day, choroidal thickness varied over the day. Because of the established role of the choroid in retinal function and its possible role in regulating eye growth, further development and refinement of clinical methods to measure its thickness are warranted.

Validation of laser Doppler interferometric measurements in vivo of axial eye length and thickness of fundus layers in chicks.

Purpose. Laser Doppler interferometry (LDI) permits the measurement of intraocular distances to a precision of better than 20 microm. The signal complex from the posterior segment of the eye consists of four peaks in the chick, an animal frequently used in ocular development studies. The present study sought to identify anatomical landmarks corresponding to these LDI peaks. Methods. Distances obtained with LDI at the posterior pole were compared to axial length components measured with three independent methods: vernier calipers, tissue sections and high frequency A-scan ultrasound. Results. LDI reflections appear to originate from the retinal inner limiting membrane, Bruchs membrane and the inner and outer scleral surfaces. Conclusions. The non-invasive and highly precise nature of LDI measurements enables repetitive and accurate assessment of intraocular distances. Such measurements should prove particularly useful for the assessment of short-term cyclic variations in intraocular distances as well as post-natal eye growth.

Induction of axial eye elongation and myopic refractive shift in one-year-old chickens

Depriving the eyes of neonatal animals of form vision induces axial eye elongation and ipsilateral myopia. We studied one-year-old chickens, an age at which full body growth has been attained, to learn if form deprivation myopia can develop at a later stage. We found that ocular reactivity to visual form deprivation continues in one-year-old chickens; but both the growth stimulation and the myopic shift in refraction are attenuated compared with newly hatched birds. Neurochemical changes in visually deprived eyes of one-year-old chickens parallel those in newly hatched chicks: ipsilateral decreases in retinal dopamine and in the activity of ciliary ganglion and uveal choline acetyltransferase. These findings strengthen the relevance of the form deprivation model to more common human myopia and suggest a common eye growth control mechanism at both ages.

Exaggerated eye growth in IRBP-deficient mice in early development

PURPOSE Because interphotoreceptor retinoid-binding protein (IRBP) is expressed before being needed in its presumptive role in the visual cycle, we tested whether it controls eye growth during development. METHODS The eyes of congenic IRBP knockout (KO) and C57BL/6J wild-type (WT) mice ranging in age from postnatal day (P)2 to P440 were compared by histology, laser micrometry, cycloplegic photorefractions, and partial coherence interferometry. RESULTS The size and weight of IRBP KO mouse eyes were greater than those of the WT mouse, even before eye-opening. Excessive ocular enlargement started between P7 and P10, with KO retinal arc lengths becoming greater compared with WT from P10 through P30 (18%; P < 0.01). The outer nuclear layer (ONL) of KO retinas became 20% thinner between P12 to P25, and progressed to 38% thinner at P30. At P30, there were 30% fewer cones per vertical section in KO than in WT retinas. Bromodeoxyuridine (BrdU) labeling indicated the same number of retinal cells were born in KO and WT mice. A spike in apoptosis was observed in KO outer nuclear layer at P25. These changes in size were accompanied by a large decrease in hyperopic refractive error, which reached -4.56 ± 0.70 diopters (D) versus +9.98 ± 0.993 D (mean ± SD) in WT, by postnatal day 60 (P60). CONCLUSIONS; In addition to its role in the visual cycle, IRBP is needed for normal eye development. How IRBP mediates ocular development is unknown.

Axial and peripheral eye length measured with optical low coherence reflectometry

An optical low-coherence reflectometer (OLCR device) is described that allows the precise and noncontact measurement of eye length. The device measures eye length both on-axis and off-axis, thus enabling the determination of eye shape, an ocular parameter thought to be important in the development of refractive error. It is essential for several applications in ophthalmology and vision science. This improved OLCR device operates using a single-beam interferometer with a beam deflection mechanism that allows the precise measurement of eye length along the visual axis and within 15 deg horizontally and vertically from the fovea. The validity of this instrument and its revised software is evaluated by measuring the reproducibility of axial length results in an adult eye and an artificial eye, and by correlating axial eye length measured in a group of ten adult eyes with axial eye length obtained with A-scan ultrasound in the same eyes. The precision obtained with adult subjects is compared with that obtained with children.

Association between retinal steepness and central myopic shift in children.

Purpose. Retinal steepness at the posterior pole was shown to be associated with peripheral refraction, and there exists strong evidence that peripheral refraction influences central refractive development. The purpose of this study was to investigate whether retinal steepness is associated with central myopic shift in children. Methods. Central refraction was measured in OD of 140 children aged 7 to 11 years as central sphere equivalent refraction (CSER) and central sphere refraction at baseline and after ∼30 months. For the estimation of retinal steepness, relative peripheral eye length (RPEL) was determined in OD by measuring length axially with a custom-made optical low coherence interferometer and subtracting it from eye length measured peripherally at 20° in the nasal, inferior, temporal, and superior fields. Association between baseline RPEL at the various locations and shift in central refraction was evaluated with a Structural Equation Modeling analysis. Results. CSER at baseline measured +0.05 ± 0.54 diopters (D) (mean ± SD). Shift in CSER, as standardized over a 30-month interval to account for individual differences in the follow-up period, was −0.21 ± 0.56 D. A weak, but significant, correlation was observed between baseline RPEL in the temporal retina and myopic shift in CSER (r = 0.207, p = 0.049), steeper retinas displaying greater myopic shifts. Myopic shift was correlated with axial elongation but not correlated with baseline refraction. Analyses were performed for both CSER and central sphere refraction with near-identical results. RPEL did not change significantly. Conclusions. The significant correlation between temporal RPEL and central myopic shift, with the latter being independent of baseline refraction, supports the hypothesis that eye shape at the posterior pole is one of the factors influencing visually guided axial eye growth, possibly through associated peripheral defocus. Its predictive value for refractive development and limitation to the temporal retina require further investigation.

Assessment of Axial Length Measurements in Mouse Eyes

Purpose. To compare measurements of murine ocular axial lengths (ALs) made with 780 nm partial coherence interferometry (PCI) and 1310 nm spectral domain-optical coherence tomography (SD-OCT). Methods. AL was measured at postnatal day (P) 58 in C57BL/6J mice. Repeated AL measurements were taken using a custom-made 780 nm PCI and a commercial 1310 nm SD-OCT. Intra- and interuser variability was assessed along the central optical axis and 2-degree off-axes angles with the SD-OCT. Data were collected and analyzed using Cronbach alpha (&agr;), Bland-Altman coefficient of repeatability, agreement plots, and intraclass correlation coefficients (ICC). Results. AL measurements agreed well between the two instruments (3.262 ± 0.042 mm for PCI; 3.264 ± 0.047 mm for SD-OCT; n = 20 eyes). The ICC for PCI compared with SD-OCT was 0.92, confirming high agreement between the two instruments. Intrauser ICC for the PCI and SD-OCT were 0.814 and 0.995, respectively. Similarly, interuser ICC for PCI and SD-OCT were 0.970 and 0.943, respectively. Using SD-OCT, a 2-degree misalignment of the eye along the horizontal meridian produced mean differences in AL of −0.002 ± 0.017 mm relative to the centrally aligned images, whereas similar misalignment along the vertical meridian created 0.005 ± 0.018 mm differences in AL measurements. Conclusions. AL measurements from the 780 nm PCI and 1310 nm SD-OCT correlate well. Multiple statistical indices indicate that both instruments have good precision and agreement for measuring murine ocular AL in vivo. Although the vertical meridian had the greater variability in AL in the small mouse eye; 2-degree off-axes differences were within the SD of centrally aligned AL.

Measurement by laser Doppler interferometry of intraocular distances in humans and chicks with a precision of better than ±20 μm

A laser Doppler interferometer was built for the precise measurement of intraocular optical distances in humans and chicks. A technique using Purkinje images was developed to position the chicks eye reproducibly. A computer algorithm for the objective analysis of the interference signal and determination of the optical distances is presented. The precision of this noncontact interferometric method for measuring the cornea-retina distance is better than ±20 µm.

Measurement of eye length and eye shape by optical low coherence reflectometry

Background: The precise and rapid measurement ofeye length and eye shape isessential for investigating eye growth regulation andmyopia. For this purpose, we developedan optical low coherence reflectometer (OLCR) andpresent preliminary measurements.Methods: The OLCR includes a super luminescentdiode (wavelength: 845 nm,coherence length: ∼30 μm) and rotatingglass cube to produce longitudinal scansat a velocity of 0.42 m/s and a repetition rateof ∼13 scans/s. Heterodyne detection oflight reflected from the anterior cornea andthe posterior retina permits to measure axial eyelength and eye shape (off-axis eye length).Each measurement consists of five consecutivescans. Reproducibility and precision weredetermined in one volunteer by measuring axialeye length five consecutive times, each timerepositioning the eye. Eye shapes weredetermined in right eyes of four volunteers bymeasuring eye length every 3.3° from10° nasally to 10° temporally.Results: Axial eye length measured repeatedlyin one volunteer did not differ between orwithin the measurements (one-factor ANOVA). Theaverage standard deviation was11 μm. Eye shapes (a) varied substantiallyamong subjects and (b) differed considerablyfrom the corresponding shapes of sphericalmodel eyes with identical axial eye lengths.Conclusion: The newly developed OLCRpermits the precise and rapid measurement ofeye length and eye shape. Such measurements,especially in children, may provide importantinformation about mechanisms of eye growthregulation and the development of myopia.

Corneal surface area: an index of anterior segment growth.

Corneal surface area and perimeter were assessed as novel indices to monitor anterior segment growth, using chicks reared under different photoperiods. We obtained central and mid‐peripheral corneal curvatures using photokeratometry. Anatomical tracings of the anterior corneal surface also were made from freeze‐dried non‐fixed preparations of the anterior segments of the same eyes. Using either photokeratometry or anatomical data, the profile of the anterior corneal surface was fit to a general equation for conical sections; corneal surface area was estimated from surfaces of revolution. Optical techniques modeled the chick cornea as a circle or as an ellipse closely resembling a circle. The anatomical technique, in contrast, modeled the chick corneal profile as a hyperbola. Potential explanations of this discrepancy are discussed. Regardless of which model is evaluated, the corneal surface area and perimeter of two‐week‐old chicks are affected by the photoperiod of rearing. Corneal surface area in particular proved more sensitive than conventional measurements in identifying anterior segment effects of rearing under different photoperiods. Analysis of corneal area may prove useful in evaluating the mechanisms governing anterior segment growth.