The relationship between refractive and biometric changes during Edinger–Westphal stimulated accommodation in rhesus monkeys

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Abstract

Experiments were undertaken to understand the relationship between dynamic accommodative refractive and biometric (lens thickness (LT), anterior chamber depth (ACD) and anterior segment length (ASL=ACD+LT)) changes during Edinger–Westphal stimulated accommodation in rhesus monkeys. Experiments were conducted on three rhesus monkeys (aged 11·5, 4·75 and 4·75 years) which had undergone prior, bilateral, complete iridectomies and implantation of a stimulating electrode in the Edinger–Westphal (EW) nucleus. Accommodative refractive responses were first measured dynamically with video-based infrared photorefraction and then ocular biometric responses were measured dynamically with continuous ultrasound biometry (CUB) during EW stimulation. The same stimulus amplitudes were used for the refractive and biometric measurements to allow them to be compared. Main sequence relationships (ratio of peak velocity to amplitude) were calculated. Dynamic accommodative refractive changes are linearly correlated with the biometric changes and accommodative biometric changes in ACD, ASL and LT show systematic linear correlations with increasing accommodative amplitudes. The relationships are relatively similar for the eyes of the different monkeys. Dynamic analysis showed that main sequence relationships for both biometry and refraction are linear. Although accommodative refractive changes in the eye occur primarily due to changes in lens surface curvature, the refractive changes are well correlated with A-scan measured accommodative biometric changes. Accommodative changes in ACD, LT and ASL are all well correlated over the full extent of the accommodative response.

Introduction

In primates, the accommodative refractive change of the eye is brought about by a change in the crystalline lens surface curvatures (Cramer, 1853, Helmholtz von, 1909, Young, 1801). When accommodation occurs, lens equatorial diameter decreases (Glasser and Kaufman, 1999, Storey and Rabie, 1987, Strenk et al., 1999, Wilson, 1997), the lens anterior and posterior surface curvatures steepen (Brown, 1973, Garner and Yap, 1997, Koretz et al., 1984, Koretz et al., 1987), anterior chamber depth decreases, lens axial thickness increases (Beers and Van der Heijde, 1996, Koretz et al., 1987, Storey and Rabie, 1983) and the posterior lens surface generally moves posteriorly (Beauchamp and Mitchell, 1985, Brown, 1973, Drexler et al., 1997). The accommodative change in shape of the young lens is brought about by the force the capsule exerts on the lens (Fincham, 1925, Fincham, 1937, Glasser et al., 2001, Glasser and Campbell, 1998, Glasser and Campbell, 1999). The accommodative change in optical power of the eye is primarily due to an increase in lens surface curvatures. There is also a lesser contribution to the optical change in power of the eye from the axial changes in optical distances due to the increase in lens thickness, the decrease in anterior chamber depth and the decrease in vitreous chamber depth. The accommodative increase in lens surface curvatures is biomechanically coupled to the increase in lens thickness. To understand more fully how the lens produces accommodative optical changes, it is of interest to precisely quantify the accommodative axial biometric changes as a function of the accommodative dioptric change.

Axial biometric accommodative changes that can be measured with A-scan ultrasonography are lens thickness (LT) and associated changes in anterior chamber depth (ACD) and vitreous chamber depth (VCD) (Beauchamp and Mitchell, 1985, Koretz et al., 1997, Storey and Rabie, 1983). Anterior segment length (ASL=ACD+LT) can also be determined as an indication of the extent of movement of the posterior lens surface. A-scan ultrasonography has been used to measure static changes in ocular biometry with accommodation in monkeys using both Edinger–Westphal (EW) and pharmacological stimulated accommodation (Koretz et al., 1987). Partial coherence interferometry (Drexler et al., 1997) and Scheimpflug photography (Brown, 1973, Dubbelman et al., 2003, Koretz et al., 1984, Koretz et al., 1987, Koretz et al., 1997) have also been used to measure static biometric changes during accommodation in humans.

Van der Heijde and colleagues developed and used continuous high-resolution A-scan ultrasound biometry to measure and analyse dynamic accommodative biometric changes in human eyes (Beers and Van der Heijde, 1994a, Beers and Van der Heijde, 1996, Beers and Van der Heijde, 1994b, de Vries et al., 1987, Van der Heijde et al., 1996, Van der Heijde and Weber, 1989). The transducer of the continuous ultrasound biometer (CUB) was attached to the eye with negative vacuum pressure (Beers and Van der Heijde, 1994b). This provides stable, reliable biometry recorded during accommodation at a rate of 100 Hz, uncontaminated by convergent eye movements. The subjects viewed a far and near accommodative stimulus with the contralateral eye while lying supine.

Efforts to relate the biometric changes to the refractive changes are challenging because the biometry instrument generally covers the eye being measured so it has not so far been possible to simultaneously measure the accommodative biometric and refractive changes in the same eye (Beers and Van der Heijde, 1996, Drexler et al., 1997, Dubbelman et al., 2003). Therefore, accommodative biometric changes have typically been compared with stimulus dioptric demand rather than actual accommodative dioptric response amplitudes. The actual accommodative response generally lags behind the stimulus demand, so a comparison with stimulus demands provide an inaccurate representation of the biometry changes per diopter of accommodation. The lag of accommodation increases with increasing stimulus amplitude and varies in extent for different individuals (Gwiazda et al., 1993, Kasthurirangan et al., 2003). Biometric changes could be compared with the true dioptric changes in human subjects by, for example, presenting the subject with a fixed amplitude stimulus and first objectively measuring the accommodative refractive change and subsequently measuring the accommodative biometric change, or by measuring the refractive change in one eye and simultaneously measuring the biometric change in the contralateral eye. However, variability in the latency of the visual stimulus driven accommodative responses from one stimulus presentation to the next, fluctuations in the accommodative response, intraocular differences and convergence introduce complexities.

Accommodative biometric and objectively measured optical refractive changes have been compared in rhesus monkeys (Koretz et al., 1987). The relationship between the biometric and refractive changes was described using averaged data from several different methods in which static refractive and biometric measurements were made only at several discrete accommodative states. It is of interest to characterize the dynamic relationship between the refractive and biometric changes in individual monkeys to determine if this relationship changes with the amplitude of the response, is different between different monkeys or different eyes, or changes systematically with increasing age.

The goal of this study was to understand dynamic biometric changes during accommodation and how they relate to dynamic refractive changes. In a previous preliminary study it was established that refraction and biometry could be correlated using EW stimulated accommodation in rhesus monkeys (Vilupuru and Glasser, 2003). However, the low resolution A-scan ultrasound used in that study precluded accurate comparisons for low amplitude responses or for the small changes that occur in ASL, for example. In this current study, a higher resolution, high dynamic acquisition frequency A-scan ultrasound instrument has been used that provides sufficient resolution to allow small changes to be measured with improved resolution and accuracy.

EW stimulated accommodation in anesthetized rhesus monkeys allows rigorous and reliable control of the amplitude and duration of dynamic accommodative response (Ostrin and Glasser, 2004, Vilupuru and Glasser, 2002). The EW nucleus provides parasympathetic innervation to the ciliary muscles of the eye via the ciliary ganglion. A controlled stimulus current can be presented repeatedly to the EW nucleus to reliably elicit accommodative responses of the same amplitude and duration while first refraction and then subsequently biometry can be recorded dynamically. This study was undertaken to characterize the dynamic accommodative biometric and optical relationships in normal adolescent rhesus monkeys to better understand how the lens undergoes accommodative changes.

Section snippets

Materials and methods

All experiments conformed to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and were in accordance with institutionally approved animal protocols. Experiments were performed on both eyes each of three rhesus monkeys (Macaca mulatta) #4, #38, #70, aged 11·5, 4·75 and 4·75 years, respectively. Each monkey had previously had a stimulating electrode surgically implanted in the EW nucleus of the brain (Crawford et al., 1989, Glasser and Kaufman, 1999, Vilupuru and

Dynamic refractive measurements

Video-based infrared photorefraction (Schaeffel et al., 1993) was used to measure dynamic refractive changes during EW stimulated accommodation at 30 Hz. Three, 4-sec long stimuli were delivered at each current amplitude to elicit accommodation and the refractive responses were recorded to video tape for later off-line analysis. The stimulus onset, duration and termination were also recorded to the video tape with a text overlay. The three individual responses were averaged and fit with

Dynamic biometric measurements

A CUB developed by Dr Van der Heijde (Beers and Van der Heijde, 1994b) was used to measure dynamic changes in ocular biometry in each eye of each monkey. The same stimulus current amplitudes used for the dynamic refractive measurements were used for the dynamic biometric measurements. The CUB has a 10 MHz transducer, is able to detect a movement of ±2 μm and records ocular biometry data to a computer via the RS232 port at a frequency of 100 Hz (Beers and Van der Heijde, 1994b).

A 1 cm long rubber

Function fitting

Functions were fitted to the accommodative and disaccommodative biometric and refractive phases of the responses as described previously (Vilupuru and Glasser, 2002). For the 30 Hz refraction measurements, based on visual inspection of the responses, the accommodative response was considered to begin two video frames (∼66 msec) after the stimulus onset (to remove the latency between stimulus onset and the start of the response), and to continue until the stimulus terminated. The disaccommodative

Results

The three individual accommodative refractive and biometric responses averaged for each stimulus amplitude were virtually superimposable. Three individual traces each for refractive and lens thickness measurements for two stimulus amplitudes are shown in Fig. 1a and b. Examples of accommodative refractive changes (Fig. 1c), measured first and biometric (Fig. 1d–f) response measured subsequently from the left eye of monkey #4 at the same eight stimulus current amplitudes are shown. Dynamic

Discussion

Besides the prior preliminary study (Vilupuru and Glasser, 2003), dynamically recorded biometric and refractive accommodative responses have not been compared. Prior experiments in humans compared static biometric changes to accommodative stimulus demands rather than accommodative responses (Drexler et al., 1997). A replot of the data from Fig. 5a from that study (Drexler et al., 1997; with permission from the authors) is compared with a similar plot from two monkey eyes from the current study (

Biometric and refractive changes: dynamic comparison

Relatively systematic relationships exists between changes in LT, ACD, ASL and refraction. The data indicates that, on average, lens thickness increases by 0·063 mm D−1, ACD decreases by 0·046 mm D−1 and ASL increases by 0·017 mm D−1. This implies that about 72% of the increase in LT occurs as an anterior movement of anterior pole of the lens and 28% due to a posterior movement of posterior lens pole (Fig. 5). Prior data from rhesus monkeys and humans shows that about 75% of the increase in lens

Biometric changes

Lens accommodative axial changes can be understood by comparing ACD and ASL with LT (Fig. 3, Fig. 5b and c). Because ACD and LT are measured simultaneously with the CUB in the same accommodative response, the variability is relatively low. The biometric accommodative relationships in the eye follow relatively linear paths for increasing accommodative amplitudes. Data from all six eyes shows that lens biometric changes are relatively consistent between different eyes of different monkeys with

Main sequence relationships

Main sequence relationships have been established for EW stimulated accommodative and disaccommodative phases of LT and refractive changes. Main sequence relationships for refraction and biometry are similar for accommodation (Fig. 4a and c) and are also similar for disaccommodation (Fig. 4b and d), although the relationships between accommodation and disaccommodation differ. The refractive changes are a consequence of the lens biometric changes, therefore the first order dynamics of the

Acknowledgements

Thanks to thank Dr Rob Van der Heijde for providing the CUB, to Drs Wolfgang Drexler and Oliver Findl and their coauthors for allowing us to use their prior published data, to Chris Kuether for technical assistance and to Siddharth Poonja for programming. This study was funded in part by a grant from Pharmacia and NIH grant #1 RO1 EY 014651-01 to AG.

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