Assessment of the oculomotor response in human factor environments

The need to measure the response of the oculomotor system, such as ocular accommodation, accurately and in real-world environments is essential. New instruments have been developed over the past 50 years to measure eye focus including the extensively utilised and well validated Canon R-1, but in general these have had limitations such as a closed field-of-view, a poor temporal resolution and the need for extensive instrumentation bulk preventing naturalistic performance of environmental tasks. The use of photoretinoscopy and more specifically the PowerRefractor was examined in this regard due to its remote nature, binocular measurement of accommodation, eye movement and pupil size and its open field-of-view. The accuracy of the PowerRefractor to measure refractive error was on averaging similar, but more variable than subjective refraction and previously validated instrumentation. The PowerRefractor was found to be tolerant to eye movements away from the visual axis, but could not function with small pupil sizes in brighter illumination. The PowerRefractor underestimated the lead of accommodation and overestimated the slope of the accommodation stimulus response curve. The PowerRefractor and the SRW-5000 were used to measure the oculomotor responses in a variety of real-world environment: spectacles compared to single vision contract lenses; the use of multifocal contact lenses by pre-presbyopes (relevant to studies on myopia retardation); and ‘accommodating’ intraocular lenses. Due to the accuracy concerns with the PowerRefractor, a purpose-built photoretinoscope was designed to measure the oculomotor response to a monocular head-mounted display. In conclusion, this thesis has shown the ability of photoretinoscopy to quantify changes in the oculomotor system. However there are some major limitations to the PowerRefractor, such as the need for individual calibration for accurate measures of accommodation and vergence, and the relatively large pupil size necessary for measurement.

Analysis of the intraocular pressure pulse

This thesis was concerned with investigating methods of improving the IOP pulse’s potential as a measure of clinical utility. There were three principal sections to the work. 1. Optimisation of measurement and analysis of the IOP pulse. A literature review, covering the years 1960 – 2002 and other relevant scientific publications, provided a knowledge base on the IOP pulse. Initial studies investigated suitable instrumentation and measurement techniques. Fourier transformation was identified as a promising method of analysing the IOP pulse and this technique was developed. 2. Investigation of ocular and systemic variables that affect IOP pulse measurements In order to recognise clinically important changes in IOP pulse measurement, studies were performed to identify influencing factors. Fourier analysis was tested against traditional parameters in order to assess its ability to detect differences in IOP pulse. In addition, it had been speculated that the waveform components of the IOP pulse contained vascular characteristic analogous to those components found in arterial pulse waves. Validation studies to test this hypothesis were attempted. 3. The nature of the intraocular pressure pulse in health and disease and its relation to systemic cardiovascular variables. Fourier analysis and traditional parameters were applied to the IOP pulse measurements taken on diseased and healthy eyes. Only the derived parameter, pulsatile ocular blood flow (POBF) detected differences in diseased groups. The use of an ocular pressure-volume relationship may have improved the POBF measure’s variance in comparison to the measurement of the pulse’s amplitude or Fourier components. Finally, the importance of the driving force of pulsatile blood flow, the arterial pressure pulse, is highlighted. A method of combining the measurements of pulsatile blood flow and pulsatile blood pressure to create a measure of ocular vascular impedance is described along with its advantages for future studies.

An analysis of progressive addition spectacles lens design by the use of interferometry

Progressive addition spectacle lenses (PALs) have now become the method of choice for many presbyopic individuals to alleviate the visual problems of middle-age. Such lenses are difficult to assess and characterise because of their lack of discrete geographical locators of their key features. A review of the literature (mostly patents) describing the different designs of these lenses indicates the range of approaches to solving the visual problem of presbyopia. However, very little is published about the comparative optical performance of these lenses. A method is described here based on interferometry for the assessment of PALs, with a comparison of measurements made on an automatic focimeter. The relative merits of these techniques are discussed. Although the measurements are comparable, it is considered that the interferometry method is more readily automated, and would be ultimately capable of producing a more rapid result.

Some clinical aspects of the eye in extended contact lens wear

The limbal vascular response to extended contact lens wear was examined in a group comparative study initially intended to last eighteen months. After six months all patients wearing contact lenses had presented with micro-epithelial cysts. This unanticipated occurrence of the micro-epithelial-cysts necessitated termination of the study, and limited the quantity of data collected. However, sufficient results were available to allow a limited description of •the vascular response to this form of contact lens wear. Interpretations of the date collected ore discussed in relation to suggested vasostimulating factors in the cornea. The micro-epithelial cysts observed after extended wear were classified and their rate of recovery recorded. A further clinical study was undertaken to observe cysts in both contact lens - and non contact lens-wearing eyes. Cysts were observed in every category of patient, although the characteristic patterns varied. These observations of micro-epithelial cysts are discussed with respect to the aetiopathogeneses of corneal epithelial cystic disorders. Subsequently, attempts were made to induce cysts in rabbit corneae by extended contact lens wear. Clinical observations revealed cyst-like appearances. Histological sections did not contain cysts but did exhibit signs characteristic •of cystic disorders of the corneal epithelium. In general, the results from the study indicate that extended wear is subjectively acceptable to contact lens wearers. However, the objective findings of significant vascular changes, micro-epithelial cysts and cases of acute red eye response cast considerable doubt on the recommendation of extended wear contact lenses for purely cosmetic applications.

Physical and psychophysical analysis of progressive addition lens embodiments

The extent to which the surface parameters of Progressive Addition Lenses (PALs) affect successful patient tolerance was investigated. Several optico-physical evaluation techniques were employed, including a newly constructed surface reflection device which was shown to be of value for assessing semi-finished PAL blanks. Detailed physical analysis was undertaken using a computer-controlled focimeter and from these data, iso-cylindrical and mean spherical plots were produced for each PAL studied. Base curve power was shown to have little impact upon the distribution of PAL astigmatism. A power increase in reading addition primarily caused a lengthening and narrowing of the lens progression channel. Empirical measurements also indicated a marginal steepening of the progression power gradient with an increase in reading addition power. A sample of the PAL wearing population were studied using patient records and questionnaire analysis (90% were returned). This subjective analysis revealed the reading portion to be the most troublesome lens zone and showed that patients with high astigmatism (> 2.00D) adapt more readily to PALs than those with spherical or low cylindrical (2.00D) corrections. The psychophysical features of PALs were then investigated. Both grafting visual acuity (VA) and contrast sensitivity (CS) were shown to be reduced with an increase in eccentricity from the central umbilical line. Two sample populations (N= 20) of successful and unsuccessful PAL wearers were assessed for differences in their visual performance and their adaptation to optically induced distortion. The possibility of dispensing errors being the cause of poor patient tolerance amongst the unsuccessful wearer group was investigated and discounted. The contrast sensitivity of the successful group was significantly greater than that of the unsuccessful group. No differences in adaptation to or detection of curvature distortion were evinced between these presbyopic groups.

Accommodation and intraocular pressure

The relationship between accommodation and intraocular pressure (lOP) has not been addressed as a research question for over 20 years, when measurement of both of these parameters was less advanced than today. Hence the central aim of this thesis was to evaluate the effects of accommodation on lOP. The instrument of choice throughout this thesis was the Pulsair EasyEye non-contact tonometer (NCT) due principally to its slim-line design which allowed the measurement of lOP in one eye and simultaneous stimulation of accommodation in the other eye. A second reason for using the Pulsair EasyEye NCT was that through collaboration with the manufacturers (Keeler, UK) the instrument's operational technology was made accessible. Hence, the principle components underpinning non-contact lOP measures of 0.1mmHg resolution (an order of magnitude greater than other methods) were made available. The relationship between the pressure-output and corneal response has been termed the pressure-response relationship, aspects of which have been shown to be related to ocular biometric parameters. Further, analysis of the components of the pressure-response relationship together with high-speed photography of the cornea during tonometry has enhanced our understanding of the derivation of an lOP measure with the Pulsair EasyEye NCT. The NCT samples the corneal response to the pressure pulse over a 19 ms cycle photoelectronically, but computes the subject's lOP using the data collected in the first 2.34 ms. The relatively instantaneous nature of the lOP measurement renders the measures susceptible to variations in the steady-state lOP caused by the respiratory and cardiac cycles. As such, the variance associated with these cycles was minimised by synchronising the lOP measures with the cardiac trace and maintaining a constant pace respiratory cycle at 15 breathes/minute. It is apparent that synchronising the lOP measures with the peak, middle or trough of the cardiac trace significantly reduced the spread of consecutive measures. Of the 3 locations investigated, synchronisation with the middle location demonstrated the least variance (coeflicient of variation = 9.1%) and a strong correlation (r = 0.90, p = <0.001) with lOP values obtained with Goldmann contact tonometry (n = 50). Accordingly lOP measures synchronised with the middle location of the cardiac cycle were taken in the RE while the LE fixated low (L; zero D), intermediate (I; 1.50 D) and high (H; 4 D) accommodation targets, Quasi-continuous measures of accommodation responses were obtained during the lOP measurement period using the portable infrared Grand Seiko FR-5000 autorefractor. The lOP reduced between L and I accommodative levels by approximately 0.61 mmHg (p <0.00 I). No significant reduction in IOP between L and H accommodation levels was elicited (p = 0.65) (n = 40). The relationship between accommodation and lOP was characterised by substantial inter-subject variations. Myopes demonstrated a tendency to show a reduction in IOP with accommodation which was significant only with I accommodation levels when measured with the NCT (r = 0.50, p = 0.01). However, the relationship between myopia and lOP change with accommodation reached significance for both I (r = 0.61, p= 0.003) and H (r = 0.531, p= 0.0 1) accommodation levels when measured with the Ocular blood Flow Analyser (OBFA). Investigation of the effects of accommodation on the parameters measured by the OBFA demonstrated that with H accommodation levels the pulse amplitude (PA) and pulse rate (PR) responses differed between myopes and emmetropes (PA: p = 0.03; PR: p = 0.004). As thc axial length increased there was a tendency for the pulsatile ocular blood flow (POBF) to reduce with accommodation, which was significant only with H accommodation levels (r = 0.38, p = 0.02). It is proposed that emmetropes arc able to regulate the POBF responses to changes in ocular perfusion pressure caused by changes in lOP with I (r = 0.77, p <0.001) and H (r = 0.73, p = 0.001) accommodation levels. However, thc relationship between lOP and POBF changes in the myopes was not correlated for both I (r = 0.33, p = 0.20) and H (r = 0.05, p = 0.85) accommodation levels. The thesis presents new data on the relationships between accommodation, lOP and parameters of the OBFA,: and provides evidence for possible lOP and choroidal blood flow regulatory mechanisms. Further the data highlight possible deficits in the vascular regulation of the myopic eye during accommodation, which may play a putative role in the aetiology of myopia development.

Another angle on contact lens surface analysis

Purpose: Dynamic contact angle (DCA) methods have advantages over other contact angle methodologies, not least that they can provide more than single contact angle values. Here we illustrate the use of DCA analysis to provide “fingerprint” characterisation of contact lens surfaces, and the way that different materials change in the early stages of wear. Method: The DCA method involves attaching to a microbalance weighted strips cut from a lens. The strips are then cyclically inserted into and removed from an aqueous solution. Conventionally, readings of force taken from linear portions of the resultant dipping curves are translated into advancing (CAa) and receding contact (CAr) angles. Additionally, analysis of the force versus immersion profile provides a “fingerprint” characterisation of the state of the lens surface. Results: CAa and CAr values from DCA traces provide a useful means of differentiating gross differences in hydrophilicity and molecular mobility of surfaces under particular immersion and emersion conditions, such as dipping rate and dwell times. Typical values for etafilcon A (CAa:63.1; CAr:37) and balafilcon B (CAa:118.4; CAr:36.4) illustrate this. Surface modifications induced in lens manufacture are observed to produce not only changes in these value, which may be small, but also changes in the DCA “fingerprint” (slope, undulations, length of plateau). Interestingly, similar changes are induced in the first few hours of lens wear with some lens-patient combinations. Conclusions: Although single parameter contact angles are useful for material characterisation, information of potential clinical interest can be obtained from more detailed analysis of DCA traces.

Tear analysis and lens-tear interactions:part II. Ocular lipids-nature and fate of meibomian gland phospholipids

Purpose: Published data indicate that the polar lipid content of human meibomian gland secretions (MGS) could be anything between 0.5% and 13% of the total lipid. The tear film phospholipid composition has not been studied in great detail and it has been understood that the relative proportions of lipids in MGS would be maintained in the tear film. The purpose of this work was to determine the concentration of phospholipids in the human tear film. Methods: Liquid chromatography mass spectrometry (LCMS) and thin layer chromatography (TLC) were used to determine the concentration of phospholipid in the tear film. Additionally, an Amplex Red phosphatidylcholine-specific phospholipase C (PLC) assay kit was used for determination of the activity of PLC in the tear film. Results: Phospholipids were not detected in any of the tested human tear samples with the low limit of detection being 1.3 µg/mL for TLC and 4 µg/mL for liquid chromatography mass spectrometry. TLC indicated that diacylglycerol (DAG) may be present in the tear film. PLC was in the tear film with an activity determined at approximately 15 mU/mL, equivalent to the removal of head groups from phosphatidylcholine at a rate of approximately 15 µM/min. Conclusions: This work shows that phospholipid was not detected in any of the tested human tear samples (above the lower limits of detection as described) and suggests the presence of DAG in the tear film. DAG is known to be at low concentrations in MGS. These observations indicate that PLC may play a role in modulating the tear film phospholipid concentration.