Ocular biometric correlates of early-and late-onset myopia

Myopia is a refractive condition and develops because either the optical power of the eye is abnormally great or the eye is abnormally long, the optical consequences being that the focal length of the eye is too short for the physical length of the eye. The increase in axial length has been shown to match closely the dioptric error of the eye, in that a lmm increase in axial length usually generates 2 to 3D of myopia. The most common form of myopia is early-onset myopia (EO M) which occurs between 6 to 14 years of age. The second most common form of myopia is late-onset myopia (LOM) which emerges in late teens or early twenties, at a time when the eye should have ceased growing. The prevalence of LOM is increasing and research has indicated a link with excessive and sustained nearwork. The aim of this thesis was to examine the ocular biometric correlates associated with LOM and EOM development and progression. Biometric data was recorded on SO subjects, aged 16 to 26 years. The group was divided into 26 emmetropic subjects and 24 myopic subjects. Keratometry, corneal topography, ultrasonography, lens shape, central and peripheral refractive error, ocular blood flow and assessment of accommodation were measured on three occasions during an ISmonth to 2-year longitudinal study. Retinal contours were derived using a specially derived computer program. The thesis shows that myopia progression is related to an increase in vitreous chamber depth, a finding which supports previous work. The myopes exhibited hyperopic relative peripheral refractive error (PRE) and the emmetropes exhibited myopic relative PRE. Myopes demonstrated a prolate retinal shape and the retina became more prolate with myopia progression. The results show that a longitudinal, rather than equatorial, increase in the posterior segment is the principal structural correlate of myopia. Retinal shape, relative PRE and the ratio of axial length to corneal curvature have been indicated, in this thesis, as predictive factors for myopia onset and development. Data from this thesis demonstrates that myopia progression in the LOM group is the result of an increase in anterior segment power, owing to an increase in lens thickness, in conjunction with posterior segment elongation. Myopia progression in the EOM group is the product of a long posterior segment, which over-compensates for a weak anterior segment power. The weak anterior segment power in the EOM group is related to a combination of crystalline lens thinning and surface flattening. The results presented in this thesis confirm that posterior segment elongation is the main structural correlate in both EOM and LOM progression. The techniques and computer programs employed in the thesis are reproducible and robust providing a valuable framework for further myopia research and assessment of predictive factors.

Ocular biometric investigation of anisometropia

The thesis aims to define further the biometric correlates in anisometropic eyes in order to provide a structural foundation for propositions concerning the development of ametropia.Biometric data are presented for 40 anisometropes and 40 isometropic controls drawn from Caucasian and Chinese populations.The principal finding was that the main structural correlate of myopia is an increase in axial rather than equatorial dimensions of the posterior globe. This finding has not been previously reported for in vivo work on humans. The computational method described in the thesis is a more accessible method for determination of eye shape than current imaging techniques such as magnetic resonance imaging or laser Doppler interferometry (LDI). Retinal contours derived from LDI and computation were shown to be closely matched. Corneal topography revealed no differences in corneal characteristics in anisometropic eyes, which supports the finding that anisometropia arises from differences in vitreous chamber depth.The corollary to axial expansion in myopia, that is retinal stretch in central regions of the posterior pole, was investigated by measurement of disc-to-fovea distances (DFD) using a scanning laser ophthalmoscope. DFD was found to increase with increased myopia, which demonstrates the primary contribution made by posterior central regions of the globe to axial expansion.The ocular pulse volume and choroidal blood flow, measured with the Ocular Blood Flow Tonograph, were found to be reduced in myopia; the reductions were found to be significantly correlated with vitreous chamber depth. The thesis includes preliminary data on whether the relationship arises from the influx of a blood bolus into eyes of different posterior volumes or represents actual differences in choroidal blood flow.The results presented in this thesis show the utility of computed retinal contour and demonstrate that the structural correlate of myopia is axial rather than equatorial expansion of the vitreous chamber. The technique is suitable for large population studies and its relative simplicity makes it feasible for longitudinal studies on the development of ametropia in, for example, children.

A study of the effects of orally administered female hormones on the volume and composition of lacrimal fluid related to the toleration of corneal contact lenses

This study was designed to evaluate the effects of certain orally active contraceptive steroids on the eye, related to the tolerance of a corneal contact lens. An oestrogen, ethinyloestradiol BP. 0.05 mg, a progestogen, norethisterone acetate BP. 2.50 mg and a control tablet (vitamin C, 50 mg) were utilised. The effect of these preparations on corneal curvature, lacrimal fluid volume and protein composition and directly on corneal lens tolerance was monitored in a group of 23 volunteer patients. The progestogen was found to produce a significant (P≥ 0.05) decrease in tear volume as measured by a 3 minute Schirmer test. A smaller volume reduction was observed with ethinyloestradiol. A normal cornea appears unaffected, within the measurement limits available, by the use of either hormone. However, in the presence of a corneal lens, oestrogen was found to induce substantial corneal steepening, indicative of tissue oedema, during the initial 2-3 weeks of medication. Progestogen occasionally produced a similar effect, which could recur with either hormone shortly after the end of the treatment period. A new method of acrylamide gel electrophoresis was developed for examination of the protein concentration and composition of lacrimal fluid. This allowed much greater resolution of microquantities of unconcentrated fluid than anything previously reported. Quantitation by densitometry has permitted the recording of medication and lens-induced changes in the protein pattern. Tear albumin has been shown to differ from serum albumin and to consist of up to 3 subfractions, 7 further protein fractions may also be resolved. The concentration and probable origin of these proteins have been established and the overall effects of hormone administration described. Individual idiosyncratic responses are also discussed. The study has established tbenature of some effects of contraceptive steroids on the anterior eye, and the probable reasons for resultant corneal lens intolerance.

Ocular changes and other factors relating to two forms of contact lenses:a comparative study

The work utilising a new material for contact lenses has fallen into three parts: Physioloeical considerations: Since the cornea is devoid of blood vessels, its oxygen is derived from the atmosphere. Early hydrophilic gel contact lenses interrupted the flow of oxygen and corneal insult resulted. Three techniques of fenestration were tried to overcome this problem. High speed drilling with 0.1 mm diameter twist drills. was found to be mechanically successful, but under clinical conditions mucous blockage of the fenestrations occurred. An investigation was made into the amount of oxygen arriving at the corneal interface; related to gel lens thickness. The results indicated an improvement in corneal oxygen as lens thickness was reduced. The mechanism is thought to be a form of mechanical pump. A series of clinical studies con:firmed the experimental work; the use of thin lenses removing the symptoms of corneal hypoxia. Design: The parameters of lens back curvature. lens thickness and lens diameter have been isolated and related to three criteria of vision (a) Visual acuity. (b) Visual stability and (c) Induced astigmatism. From the results achieved a revised and basically successful design of lens has been developed. Comparative study: The developed form of lens was compared with traditional lenses in a controlled survey. Twelve factors were assessed over a twenty week period of wear using a total of eighty four patients. The results of this study indicate that whilst the expected changes were noted with the traditional lens wearers, gel lens wearers showed no discernible change in any of the factors measured. ldth the exception of' one parameter. In addition to a description of' the completed l'iork. further investigations are ·sug~ested l'lhich. it is hoped. l'iould further improve the optical performance of gel lenses.

Biomechanical aspects of the anterior segment in human myopia

The thesis investigates the relationship between the biomechanical properties of the anterior human sclera and cornea in vivo using Schiotz tonometry (ST), rebound tonometry (RBT, iCare) and the Ocular Response Analyser (ORA, Reichert). Significant differences in properties were found to occur between scleral quadrants. Structural correlates for the differences were examined using Partial Coherent Interferometry (IOLMaster, Zeiss), Optical Coherent tomography (Visante OCT), rotating Scheimpflug photography (Pentacam, Oculus) and 3-D Magnetic Resonance Imaging (MRI). Subject groups were employed that allowed investigation of variation pertaining to ethnicity and refractive error. One hundred thirty-five young adult subjects were drawn from three ethnic groups: British-White (BW), British-South-Asian (BSA) and Hong-Kong-Chinese (HKC) comprising non-myopes and myopes. Principal observations: ST demonstrated significant regional variation in scleral resistance a) with lowest levels at quadrant superior-temporal and highest at inferior-nasal; b) with distance from the limbus, anterior locations showing greater resistance. Variations in resistance using RBT were similar to those found with ST; however the predominantly myopic HKC group had a greater overall mean resistance when compared to the BW-BSA group. OCT-derived scleral thickness measurements indicated the sclera to be thinner superiorly than inferiorly. Thickness varied with distance from the corneolimbal junction, with a decline from 1 to 2 mm followed by a successive increase from 3 to 7 mm. ORA data varied with ethnicity and refractive status; whilst axial length (AL) was associated with corneal biometrics for BW-BSA individuals it was associated with IOP in the HKC individuals. Complex interrelationships were found between ORA Additional-Waveform-Parameters and biometric data provided by the Pentacam. OCT indicated ciliary muscle thickness to be greater in myopia and more directly linked to posterior ocular volume (from MRI) than AL. Temporal surface areas (SAs, from MRI) were significantly smaller than nasal SAs in myopic eyes; globe bulbosity (from MRI) was constant across quadrants.

Shape of the posterior vitreous chamber in human emmetropia and myopia

PURPOSE - To compare posterior vitreous chamber shape in myopia to that in emmetropia. METHODS - Both eyes of 55 adult subjects were studied, 27 with emmetropia (MSE =-0.55; <+0.75D; mean +0.09 ±0.36D) and 28 with myopia (MSE -5.87 ±2.31D). Cycloplegic refraction was measured with a Shin Nippon autorefractor and anterior chamber depth and axial length with a Zeiss IOLMaster. Posterior vitreous chamber shapes were determined from T2-weighted MRI (3-Tesla) using procedures previously reported by our laboratory. 3-D surface model coordinates were assigned to nasal, temporal, superior and inferior quadrants and plotted in 2-D to illustrate the composite shape of respective quadrants posterior to the second nodal point. Spherical analogues of chamber shape were constructed to compare relative sphericity between refractive groups and quadrants. RESULTS - Differences in shape occurred in the region posterior to points of maximum globe width and were thus in general accord with an equatorial model of myopic expansion. Shape in emmetropia is categorised distinctly as that of an oblate ellipse and in myopia as an oblate ellipse of significantly less degree such that it approximates to a sphere. There was concordance between shape and retinotopic projection of respective quadrants into right, left, superior and inferior visual fields. CONCLUSIONS - The transition in shape from oblate ellipse to sphere with axial elongation supports the hypothesis that myopia may be a consequence of equatorial restriction associated with biomechanical anomalies of the ciliary apparatus. The synchronisation of quadrant shapes with retinotopic projection suggests that binocular growth is coordinated by processes that operate beyond the optic chiasm.

In vivo measurement of regional variation in anterior scleral resistance to Schiotz indentation

Purpose: Recent studies indicate that ocular and scleral rigidity is pertinent to our understanding of glaucoma, age related macular degeneration and the development and pathogenesis of myopia. The principal method of measuring ocular rigidity is by extrapolation of data from corneal indentation tonometry (Ko) using Friedenwald’s transformation algorithms. Using scleral indentation (Schiotz tonometry) we assess whether regional variations in resistance to indentation occur in vivo across the human anterior globe directly, with reference to the deflection of Schiotz scale readings. Methods: Data were collected from both eyes of 26 normal young adult subjects with a range of refractive error (mean spherical equivalent ± S.D. of -1.77 D ± 3.28 D, range -10.56 to +4.38 D). Schiotz tonometry (5.5 g & 7.5 g) was performed on the cornea and four scleral quadrants; supero-temporal (ST) and -nasal (SN), infero-temporal (IT) and -nasal (IN) approximately 8 mm posterior to the limbus. Results: Values of Ko (mm3)-1 were consistent with those previously reported (mean 0.0101 ± 0.0082, range 0.0019–0.0304). In regards to the sclera, significant differences (p < 0.001) were found across quadrants with indentation readings for both loads between means for the cornea and ST; ST and SN; ST and IT, ST and IN. Mean (±S.D.) scale readings for 5.5 g were: cornea 5.93 ± 1.14, ST 8.05 ± 1.58, IT 7.03 ± 1.86, SN 6.25 ± 1.10, IN 6.02 ± 1.49; and 7.5 g: cornea 9.26 ± 1.27, ST 11.56 ± 1.65, IT 10.31 ± 1.74, SN 9.91 ± 1.20, IN 9.50 ± 1.56. Conclusions: Significant regional variation was found in the resistance of the anterior sclera to indentation produced by the Schiotz tonometer.

Theoretical and empirical evaluation of phakic and pseudophakic accomodation

The binding theme of this thesis is the examination of both phakic and pseudophakic accommodation by means of theoretical modelling and the application of a new biometric measuring technique. Anterior Segment Optical Coherence Tomography (AS-OCT) was used to assess phakic accommodative changes in 30 young subjects (19.4 2.0 years; range, 18 to 25 years). A new method of assessing curvature change with this technique was employed with limited success. Changes in axial accommodative spacing, however, proved to be very similar to those of the Scheimpflug-based data. A unique biphasic trend in the position of the posterior crystalline lens surface during accommodation was discovered, which has not been alluded to in the literature. All axial changes with accommodation were statistically significant (p < 0.01) with the exception of corneal thickness (p = 0.81). A two-year follow-up study was undertaken for a cohort of subjects previously implanted with a new accommodating intraocular lens (AIOL) (Lenstec Tetraflex KH3500). All measures of best corrected distance visual acuity (BCDVA; +0.04 0.24 logMAR), distance corrected near visual acuity (DCNVA; +0.61 0.17 logMAR) and contrast sensitivity (+1.35 0.21 log units) were good. The subjective accommodation response quantified with the push-up technique (1.53 0.64 D) and defocus curves (0.77 0.29 D) was greater than the objective stimulus response (0.21 0.19 D). AS-OCT measures with accommodation stimulus revealed a small mean posterior movement of the AIOLs (0.02 0.03 mm for a 4.0 D stimulus); this is contrary to proposed mechanism of the anterior focus-shift principle.

Myopia control with orthokeratology contact lenses in Spain (MCOS):refractive and biometric changes

PURPOSE. To compare axial length growth between white children with myopia wearing orthokeratology contact lenses (OK) and distance single-vision spectacles (SV) over a 2-year period. METHODS. Subjects 6 to 12 years of age with myopia -0.75 to -4.00 diopters of sphere (DS) and astigmatism ≤1.00 diopters of cylinder (DC) were prospectively allocated OK or SV correction. Measurements of axial length (Zeiss IOLMaster), corneal topography, and cycloplegic refraction were taken at 6-month intervals. RESULTS. Thirty-one children were fitted with OK and 30 with SV. Following 24 months, axial length increased significantly over time for both the OK group (0.47 mm) and SV group (0.69 mm; P < 0.001), with a significant interaction between time and group (P = 0.05) reflecting a greater increase in the SV group. Significant differences in refraction were found over time, between groups and for the interaction between time and group for spherical (all P < 0.001) but not cylindrical components of refraction (all P > 0.05). Significantly greater corneal flattening was evident in the OK group for the flatter and steeper corneal powers and for corneal shape factor (all P ≤0.05). CONCLUSIONS. Orthokeratology contact lens wear reduces axial elongation in comparison to distance single-vision spectacles in children. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Ocular biometric correlates of ciliary muscle thickness in human myopia

Purpose - Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. Methods - Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18–40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) =-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. Results - MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. Conclusions - Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.

The relationship between measurement method and corneal structure on apparent intraocular pressure in glaucoma and ocular hypertension

Purpose: To analyse the relationship between measured intraocular pressure (IOP) and central corneal thickness (CCT), corneal hysteresis (CH) and corneal resistance factor (CRF) in ocular hypertension (OHT), primary open-angle (POAG) and normal tension glaucoma (NTG) eyes using multiple tonometry devices. Methods: Right eyes of patients diagnosed with OHT (n=47), normal tension glaucoma (n=17) and POAG (n=50) were assessed, IOP was measured in random order with four devices: Goldmann applanation tonometry (GAT); Pascal(R) dynamic contour tonometer (DCT); Reichert(R) ocular response analyser (ORA); and Tono-Pen(R) XL. CCT was then measured using a hand-held ultrasonic pachymeter. CH and CRF were derived from the air pressure to corneal reflectance relationship of the ORA data. Results: Compared to the GAT, the Tonopen and ORA Goldmann equivalent (IOPg) and corneal compensated (IOPcc) measured higher IOP readings (F=19.351, p<0.001), particularly in NTG (F=12.604, p<0.001). DCT was closest to Goldmann IOP and had the lowest variance. CCT was significantly different (F=8.305, p<0.001) between the 3 conditions as was CH (F=6.854, p=0.002) and CRF (F=19.653, p<0.001). IOPcc measures were not affected by CCT. The DCT was generally not affected by corneal biomechanical factors. Conclusion: This study suggests that as the true pressure of the eye cannot be determined non-invasively, measurements from any tonometer should be interpreted with care, particularly when alterations in the corneal tissue are suspected.