Iridocorneal angle measurements in mammalian species: normative data by optical coherence tomography.

Objective Gonioscopy provides limited quantitative information to compare the iridocorneal anatomy across different species. In addition, the anatomic relationships by histologic examination are altered during processing. As a result, the comparative anatomy of the iridocorneal angle across several mammalian species was evaluated by Optical Coherence Tomography (OCT). Methods Cats, beagle dogs, minipigs, owl monkeys, cynomolgus monkeys, and rhesus monkeys (n = 6 or 7 per species) were evaluated. Imaging was performed using the OCT. The anterior chamber angle (ACA), angle opening distance (AOD), and the angle recess area (ARA) were evaluated. Results AC angle: cat (63 ± 6°) > owl monkey (54 ± 4°) > beagle dog (42 ± 4°) > minipig (40 ± 3°) > rhesus monkey (36 ± 1°) > cynomolgus monkey (34 ± 2°). AOD: cat (3.3 ± 0.5 mm) > owl monkey (2.05 ± 0.2 mm) > beagle dog (1.08 ± 0.1 mm) > rhesus monkey (0.92 ± 0.06 mm) > minipig (0.64 ± 0.04 mm) > cynomolgus monkey (0.43 ± 0.03 mm). ARA: cat (3.5 ± 0.1 mm(2) ) > owl monkey (1.41 ± 0.2 mm(2) ) > dog (0.88 ± 0.1 mm(2) ) > rhesus monkey (0.62 ± 0.06 mm(2) ) > minipig (0.21 ± 0.05 mm(2) ) > cynomolgus monkey (0.15 ± 0.01 mm(2) ). Conclusions This study benchmarks the normative iridocorneal angle measurements across different mammalian species by OCT. These data can be useful to compare iridocorneal angle measurements in disease states as OCT evolves as a common diagnostic tool in veterinary ophthalmic research and practice.

Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina cribrosa.

The lamina cribrosa has been postulated from in vitro studies as an early site of damage in glaucoma. Prior in vivo measures of laminar morphology have been confounded by ocular aberrations. In this study the lamina cribrosa was imaged after correcting for ocular aberrations using the adaptive optics scanning laser ophthalmoscope (AOSLO) in normal and glaucomatous eyes of rhesus monkeys. All measured laminar morphological parameters showed increased magnitudes in glaucomatous eyes relative to fellow control eyes, indicating altered structure. The AOSLO provides high-quality images of the lamina cribrosa and may have potential as a tool for early identification of glaucoma.

The relationship between nerve fiber layer and perimetry measurements.

PURPOSE: Losses of retinal ganglion cells (RGCs) in glaucoma are the cause of visual field defects and thinning of the retinal nerve fiber layer (RNFL), but methods of correlating these events have not been developed. The present study was conducted to investigate the relationship between standard automated perimetry (SAP) measures of RGCs and optical coherence tomography (OCT) measures of the ganglion cell axons entering the optic nerve from corresponding visual field locations. METHODS: SAP and OCT data from normal monkeys were used to develop methods for estimating neuron counts and mapping SAP visual field locations onto the optic nerve head (ONH). The procedures developed for normal eyes were applied to monkeys with experimental glaucoma. RESULTS: The number of neurons derived from SAP and OCT data for normal eyes were in close agreement. The estimates of the number of RGCs in retinal areas of the Humphrey Field Analyzer 24-2 (Carl Zeiss Meditec, Inc., Dublin, CA) visual field and the axons entering the ONH were both approximately 1.5 million. The neural losses derived from subjective and objective measurements in monkeys with early experimental glaucoma correlated highly, with a mean +/- SD difference of 0.6% +/- 22% between the two estimates in control eyes and 3% +/- 24% in laser-treated eyes. CONCLUSIONS: SAP measures of visual field defects and OCT measures of RNFL defects are correlated measures of glaucomatous neuropathy. The normal intersubject variability and the dynamic ranges of the measurements suggest that RNFL thickness may be a more sensitive measurement for early stages and perimetry a better measure for moderate to advanced stages of glaucoma.

Accommodative lens refilling in rhesus monkeys.

PURPOSE: Accommodation can be restored to presbyopic human eyes by refilling the capsular bag with a soft polymer. This study was conducted to test whether accommodation, measurable as changes in optical refraction, can be restored with a newly developed refilling polymer in a rhesus monkey model. A specific intra- and postoperative treatment protocol was used to minimize postoperative inflammation and to delay capsular opacification. METHODS: Nine adolescent rhesus monkeys underwent refilling of the lens capsular bag with a polymer. In the first four monkeys (group A) the surgical procedure was followed by two weekly subconjunctival injections of corticosteroids. In a second group of five monkeys (group B) a treatment intended to delay the development of capsular opacification was applied during the surgery, and, in the postoperative period, eye drops and two subconjunctival injections of corticosteroids were applied. Accommodation was stimulated with carbachol iontophoresis or pilocarpine and was measured with a Hartinger refractometer at regular times during a follow-up period of 37 weeks in five monkeys. In one monkey, lens thickness changes were measured with A-scan ultrasound. RESULTS: In group A, refraction measurement was possible in one monkey. In the three other animals in group A, postoperative inflammation and capsular opacification prevented refraction measurements. In group B, the maximum accommodative amplitude of the surgically treated eyes was 6.3 D. In three monkeys the accommodative amplitude decreased to almost 0 D after 37 weeks. In the two other monkeys, the accommodative amplitude remained stable at +/-4 D during the follow-up period. In group B, capsular opacification developed in the postoperative period, but refraction measurements could still be performed during the whole follow-up period of 37 weeks. CONCLUSIONS: A certain level of accommodation can be restored after lens refilling in adolescent rhesus monkeys. During the follow-up period refraction measurements were possible in all five monkeys that underwent the treatment designed to prevent inflammation and capsular opacification.

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

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.

Dynamics of accommodative fatigue in rhesus monkeys and humans.

Changes in accommodative dynamics with repeated accommodation were studied in three anesthetized rhesus monkeys and two conscious humans. Maximum accommodation was centrally stimulated via the Edinger-Westphal nucleus in monkeys with a 4 s on, 4 s off paradigm (4 x 4) for 17 min, 4 x 1.5 for 27 min and 2 x 1 for 16 min. Humans accommodated repeatedly to visual targets (5 x 5; 5D and 2 x 2; 6D) for 30 min. In all cases, accommodation was sustained throughout. The anesthetized monkeys showed inter-individual variability in the extent of changes in accommodative dynamics over time while no systematic changes were detected in the human accommodative responses. Little accommodative fatigue was found compared to previous studies which have reported a complete loss of accommodation after 5 min of repeated stimulation in monkeys.

A population study on changes in wave aberrations with accommodation.

Wave aberrations were measured with a Shack-Hartmann wavefront sensor (SHWS) in the right eye of a large young adult population when accommodative demands of 0, 3, and 6 D were presented to the tested eye through a Badal system. Three SHWS images were recorded at each accommodative demand and wave aberrations were computed over a 5-mm pupil (through 6th order Zernike polynomials). The accommodative response was calculated from the Zernike defocus over the central 3-mm diameter zone. Among all individual Zernike terms, spherical aberration showed the greatest change with accommodation. The change of spherical aberration was always negative, and was proportional to the change in accommodative response. Coma and astigmatism also changed with accommodation, but the direction of the change was variable. Despite the large inter-subject variability, the population average of the root mean square for all aberrations (excluding defocus) remained constant for accommodative levels up to 3.0 D. Even though aberrations change with accommodation, the magnitude of the aberration change remains less than the magnitude of the uncorrected aberrations, even at high accommodative levels. Therefore, a typical eye will benefit over the entire accommodative range (0-6 D) if aberrations are corrected for distance viewing.

Spatially variant changes in lens power during ocular accommodation in a rhesus monkey eye.

This study investigated the changes in ocular aberrations that occur over the entire lens equatorial diameter during accommodation in iridectomized rhesus monkey eyes to understand the nature of accommodative lenticular deformation. Accommodation was centrally stimulated to a range of different response amplitudes (0 D to approximately 11 D), and ocular aberrations were measured with a Shack-Hartmann wavefront sensor in both eyes of one previously iridectomized 10-year-old rhesus monkey. At the highest amplitude in the two eyes, aberrations were analyzed over entrance pupil diameters ranging from 3 to 8 mm in steps of 1 mm. Root mean square error of the total measured aberrations, excluding defocus, increased systematically with increasing accommodation from about 1 to 3.5 microns. Spherical aberration became systematically more negative, and vertical coma increased significantly in magnitude with accommodation. There was a strong accommodative change in power near the center of the lens and little change in power at the periphery. At the highest accommodative state, decreasing the analyzed entrance pupil diameter from 8 to 3 mm considerably reduced the wavefront error. The greater increase in optical power near the central region of the lens, combined with an accommodative pupillary miosis, would serve to maximize accommodative refractive change while maintaining acceptable image quality.

Amplitude dependent accommodative dynamics in humans.

Dynamics of accommodation (far-to-near focus) and disaccommodation (near-to-far focus) are described as a function of response amplitude. Accommodative responses to step stimuli of various amplitudes presented in real space were measured in eight 20-30 year old subjects. Responses were fitted with exponential functions to determine amplitude, time constant and peak velocity. Despite the intersubject variability, the results show that time constants of accommodation and peak velocity of disaccommodation increase with amplitude in all subjects. The dynamics of accommodation and disaccommodation are dependent on amplitude, but have different properties in each case.

Dynamic accommodative changes in rhesus monkey eyes assessed with A-scan ultrasound biometry.

PURPOSE: Prior studies in humans measured time constants of biometric accommodative changes as a function of amplitude, and prior studies in monkeys used slit lamp videography to analyze dynamic lenticular accommodative movements. Neither of these studies related biometric changes to refractive changes. We wished to develop and test methodology to begin to test the hypothesis that ocular biometric changes are well correlated with accommodative refractive changes in rhesus monkeys. METHODS: Methodology is described to dynamically measure biometric accommodative changes with A-scan ultrasonography. Lens thickness, anterior chamber depth, and anterior segment length (anterior chamber depth plus lens thickness) were measured dynamically during Edinger-Westphal-stimulated accommodation in two eyes of one rhesus monkey. In addition, dynamic accommodative refractive changes were measured with infrared photorefraction. Functions were fit to the accommodative and disaccommodative responses to obtain time constants. Derivatives of these functions allow peak velocities to be determined for each amplitude. Dynamic changes in lens thickness and anterior chamber depth measured with A-scan biometry were compared with dynamic measures of accommodation using infrared photorefraction. RESULTS: Lens thickness and anterior segment length increase and anterior chamber depth decreases during accommodation. The biometric changes are well correlated with the accommodative optical changes. Peak velocities of accommodative changes in lens thickness and anterior chamber depth increase with amplitude and peak velocities for disaccommodation were higher than those for accommodation. CONCLUSIONS: Dynamic A-scan provides a method for dynamic analysis of the accommodative biometric changes during Edinger-Westphal-stimulated accommodation in monkeys, although the measurement resolution of this approach is limited.

Dynamic accommodation in rhesus monkeys.

The dynamics of Edinger-Westphal (EW) stimulated accommodation were studied in two young rhesus monkeys to understand the relationships between accommodative amplitude and rates of accommodation and disaccommodation. Accommodative responses were recorded with infrared photorefraction at five different amplitudes spanning the full EW stimulated accommodative range available to each eye. Combined exponential and polynomial functions were fit to the accommodation and disaccommodation responses. Derivatives of these functions provided the maximum rates of accommodation and disaccommodation as well as time constants for each amplitude. Maximum rates of EW stimulated accommodation and disaccommodation were found to increase linearly with amplitudes from 0.58 to 17.41 D in the two monkeys. The results suggests that the rate of EW stimulated accommodation is dictated by the amplitude. We conclude that if dynamic accommodative responses are to be compared in monkeys of different ages it is necessary to compare responses for the same accommodative amplitudes in order to draw conclusions about age related changes.