Investigation of chromatic function in the normal and abnormal eye

This study examined the use of non-standard parameters to investigate the visual field, with particular reference to the detection of glaucomatous visual field loss. Evaluation of the new perimetric strategy for threshold estimation - FASTPAC, demonstrated a reduction in the examination time of normals compared to the standard strategy. Despite an increased within-test variability the FASTPAC strategy produced a similar mean sensitivity to the standard strategy, reducing the effects of patient fatigue. The new technique of Blue-Yellow perimetry was compared to White-White perimetry for the detection of glaucomatous field loss in OHT and POAG. Using a database of normal subjects, confidence limits for normality were constructed to account for the increased between-subject variability with increase in age and eccentricity and for the greater variability of the Blue-Yellow field compared to the White-White field. Effects of individual ocular media absorption had little effect on Blue-Yellow field variability. Total and pattern probability analysis revealed five of 27 OHTs to exhibit Blue-Yellow focal abnormalities; two of these patients subsequently developed White-White loss. Twelve of the 24 POAGs revealed wider and/or deeper Blue-Yellow loss compared with the White-White field. Blue-Yellow perimetry showed good sensitivity and specificity characteristics, however, lack of perimetric experience and the presence of cataract influenced the Blue-Yellow visual field and may confound the interpretation of Blue-Yellow visual field loss. Visual field indices demonstrated a moderate relationship to the structural parameters of the optic nerve head using scanning laser tomography. No abnormalities in Blue-Yellow or Red-Green colour CS was apparent for the OHT patients. A greater vulnerability of the SWS pathway in glaucoma was demonstrated using Blue-Yellow perimetry however predicting which patients may benefit from B-Y perimetric examination is difficult. Furthermore, cataract and the extent of the field loss may limit the extent to which the integrity of the SWS channels can be selectively examined.

Effect of disability glare on visual performance

The object of the study was to investigate, establish and quantify the relationship between contrast sensitivity, intraocular light scatter and glare. The aim was to establish the effects on vision, in an effort to provide a more comprehensive understanding of the visual world of subjects prone to increased light scatter in the eye. Disability glare refers to the reduction in visual performance produced by a glare source. The reduction in visual performance can be explained by intraocular scattered light producing a veiling luminance which is superimposed upon the retinal image. This veiling luminance lowers contrast thus sensitivity to the stimulus declines. The effect of glare of luminance and colour contrast sensitivity for young and elderly subjects was examined. For both age groups, disability glare was greatest for the red-green stimulus and least for the blue-yellow. The precise effect of a glare source on colour discrimination depends upon the interaction between the chromaticity of the glare source and that of the stimulus. The effect of a long wavelength pass (red) and a short wavelength pass filter (blue) on disability glare was examined. Disability glare was not significantly different with the red and blue filters, even in the presence of wavelength dependent scatter. An equation was derived which allowed an intrinsic Light Scatter Factor (LSF) to be determined for any given glare angle (Paulsson and Sjöstrand, 1980). Corrections to the formula to account for factors such as pupil size changes are unnecessary. The results confirm the suitability of measuring the LSF using contrast threshold with and without glare, provided that appropriate methods are used. Using this formula an investigation into the amount of wavelength dependent scatter indicated that wavelength dependent scatter in normal young, elderly or cataractous eyes is of little or no significance. Finally, it seemed desirable to investigate the effect ultraviolet (UV) radiation has on intraocular light scatter and subsequently visual performance. Overall the results indicated that the presence or absence of UV radiation has relatively little effect on visual function for the young, elderly or cataract patient.

Rotational and centration stability of an aspheric intraocular lens with a simulated toric design

Purpose: To assess the stability of the Akreos AO intraocular lens (IOL) platform with a simulated toric design using objective image analysis. Setting: Six hospital eye clinics across Europe. Methods: After implantation in 1 eye of patients, IOLs with orientation marks were imaged at 1 to 2 days, 7 to 14 days, 30 to 60 days, and 120 to 180 days. The axis of rotation and IOL centration were objectively assessed using validated image analysis. Results: The study enrolled 107 patients with a mean age of 69.9 years ± 7.7 (SD). The image quality was sufficient for IOL rotation analysis in 91% of eyes. The mean rotation between the first day postoperatively and 120 to 180 days was 1.93 ± 2.33 degrees, with 96% of IOLs rotating fewer than 5 degrees and 99% rotating fewer than 10 degrees. There was no significant rotation between visits and no clear bias in the direction of rotation. In 71% of eyes, the dilation and image quality was sufficient for image analysis of centration. The mean change in centration between 1 day and 120 to 180 days was 0.21 ± 0.11 mm, with all IOLs decentering less than 0.5 mm. There was no significant decentration between visits and no clear bias in the direction of the decentration. Conclusion: Objective analysis of digital retroillumination images taken at different postoperative periods shows the aspheric IOL platform was stable in the eye and is therefore suitable for the application of a toric surface to correct corneal astigmatism.

Characterization of tissue transglutaminase 2 in macrophage function

Apoptosis is a highly regulated process that removes damaged or unwanted cells in vivo and defective clearance of apoptotic cells by macrophages has significant immunological implications. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in cell proliferation, differentiation, carcinogenesis, programmed death, and aging. TG2 as a guanosine triphosphate (GTP)-binding or GTP- hydrolyzing protein for mediating signal transduction and as a cell cycle regulator emphasized the importance of this enzyme in aging process. The ubiquitous presence of TG2 compared to the other organ-specific TGases has attracted special attention as a cellular aging device. TG2 activity and expression are known to increase in aging humans suggesting possible involvement in several age-related processes such as decrease in vascular compliance and increased stiffening of conduit arteries, cataract formation, Alzheimer's disease and senescent epidermal keratinocytes. Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function. THP-1 cell derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors resulted in significant inhibition of interaction. Macrophage cell surface TG2 and, in particular, its cell surface cross linking activity was found to be crucial in apoptotic cell clearance. Syndecan-4 association with TG2 implies possible cooperation of these proteins and knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance.

Tablet App halometer for the assessment of dysphotopsia

Purpose To assess the validity and repeatability of the Aston Halometer. Setting University clinic, United Kingdom. Design Prospective, repeated-measures experimental study. Methods The halometer comprises a bright light-emitting-diode (LED) glare source in the center of an iPad4. Letters subtending 0.21° (∼0.3 logMAR) were moved centrifugally from the LED in 0.05 degree steps in 8 orientations separated by 45 degrees for each of 4 contrast levels (1000, 500, 100, and 25 Weber contrast units [Cw]) in random order. Bangerter occlusion foils were inserted in front of the right eye to simulate monocular glare conditions in 20 subjects (mean age 27.7 ± 3.1 years). Subjects were positioned 2 meters from the screen in a dark room with the iPad controlled from an iPhone via Bluetooth operated by the researcher. The C-Quant straylight meter was also used with each of the foils to measure the level of straylight over the retina. Halometry and straylight repeatability was assessed at a second visit. Results Halo size increased with the different occlusion foils and target contrasts (F = 29.564, P <.001) as expected and in a pattern similar to straylight measures (F = 80.655, P <0.001). Lower contrast letters showed better sensitivity but larger glare-obscured areas, resulting in ceiling effects caused by the screen's field-of-view, with 500 Cw being the best compromise. Intraobserver and interobserver repeatability of the Aston Halometer was good (500Cw: 0.84 to 0.93 and 0.53 to 0.73) and similar to the straylight meter. Conclusion The halometer provides a sensitive, repeatable way of quantifying a patient-recognized form of disability glare in multiple orientations to add objectivity to subjectively reported discomfort glare.

The SECURE study:long-term safety of Ranibizumab 0.5 mg in neovascular age-related macular degeneration

Objective - To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Design - Twenty-four–month, open-label, multicenter, phase IV extension study. Participants - Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Methods - Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Main Outcome Measures - Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Results - Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. Conclusions - The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

Visual outcomes and subjective experience after bilateral implantation of a new diffractive trifocal intraocular lens

Purpose - To assess clinical outcomes and subjective experience after bilateral implantation of a diffractive trifocal intraocular lens (IOL). Setting - Midland Eye Institute, Solihull, United Kingdom. Design - Cohort study. Methods - Patients had bilateral implantation of Finevision trifocal IOLs. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and manifest refraction were measured 2 months postoperatively. Defocus curves were assessed under photopic and mesopic conditions over a range of +1.50 to -4.00 diopters (D) in 0.50 D steps. Contrast sensitivity function was assessed under photopic conditions. Halometry was used to measure the angular size of monocular and binocular photopic scotomas arising from a glare source. Patient satisfaction with uncorrected near vision was assessed using the Near Activity Visual Questionnaire (NAVQ). Results - The mean monocular CDVA was 0.08 logMAR ± 0.08 (SD) and the mean binocular CDVA, 0.06 ± 0.08 logMAR. Defocus curve testing showed an extended range of clear vision from +1.00 to -2.50 D defocus, with a significant difference in acuity between photopic conditions and mesopic conditions at -1.50 D defocus only. Photopic contrast sensitivity was significantly better binocularly than monocularly at all spatial frequencies. Halometry showed a glare scotoma of a mean size similar to that in previous studies of multifocal and accommodating IOLs; there were no subjective complaints of dysphotopsia. The mean NAVQ Rasch score for satisfaction with near vision was 15.9 ± 10.7 logits. Conclusions - The trifocal IOL implanted binocularly produced good distance visual acuity and near and intermediate visual function. Patients were very satisfied with their uncorrected near vision.

Design and validity of a miniaturized open-field aberrometer

PURPOSE: To validate a new miniaturised, open-field wavefront device which has been developed with the capacity to be attached to an ophthalmic surgical microscope or slit-lamp. SETTING: Solihull Hospital and Aston University, Birmingham, UK DESIGN: Comparative non-interventional study. METHODS: The dynamic range of the Aston Aberrometer was assessed using a calibrated model eye. The validity of the Aston Aberrometer was compared to a conventional desk mounted Shack-Hartmann aberrometer (Topcon KR1W) by measuring the refractive error and higher order aberrations of 75 dilated eyes with both instruments in random order. The Aston Aberrometer measurements were repeated five times to assess intra-session repeatability. Data was converted to vector form for analysis. RESULTS: The Aston Aberrometer had a large dynamic range of at least +21.0 D to -25.0 D. It gave similar measurements to a conventional aberrometer for mean spherical equivalent (mean difference ± 95% confidence interval: 0.02 ± 0.49D; correlation: r=0.995, p<0.001), astigmatic components (J0: 0.02 ± 0.15D; r=0.977, p<0.001; J45: 0.03 ± 0.28; r=0.666, p<0.001) and higher order aberrations RMS (0.02 ± 0.20D; r=0.620, p<0.001). Intraclass correlation coefficient assessments of intra-sessional repeatability for the Aston Aberrometer were excellent (spherical equivalent =1.000, p<0.001; astigmatic components J0 =0.998, p<0.001, J45=0.980, p<0.01; higher order aberrations RMS =0.961, p<0.001). CONCLUSIONS: The Aston Aberrometer gives valid and repeatable measures of refractive error and higher order aberrations over a large range. As it is able to measure continuously, it can provide direct feedback to surgeons during intraocular lens implantations and corneal surgery as to the optical status of the visual system.

Requirement for and optimisation of premium intraocular lenses

Premium intraocular lenses (IOLs) aim to surgically correct astigmatism and presbyopia following cataract extraction, optimising vision and eliminating the need for cataract surgery in later years. It is usual to fully correct astigmatism and to provide visual correction for distance and near when prescribing spectacles and contact lenses, however for correction with the lens implanted during cataract surgery, patients are required to purchase the premium IOLs and pay surgery fees outside the National Health Service in the UK. The benefit of using toric IOLs was thus demonstrated, both in standard visual tests and real-world situations. Orientation of toric IOLs during implantation is critical and the benefit of using conjunctival blood vessels for alignment was shown. The issue of centration of IOLs relative to the pupil was also investigated, showing changes with the amount of dilation and repeat dilation evaluation, which must be considered during surgery to optimize the visual performance of premium IOLs. Presbyopia is a global issue, of growing importance as life expectancy increases, with no real long-term cure. Despite enhanced lifestyles, changes in diet and improved medical care, presbyopia still presents in modern life as a significant visual impairment. The onset of presbyopia was found to vary with risk factors including alcohol consumption, smoking, UV exposure and even weight as well as age. A new technique to make measurement of accommodation more objective and robust was explored, although needs for further design modifications were identified. Due to dysphotopsia and lack of intermediate vision through most multifocal IOL designs, the development of a trifocal IOL was shown to minimize these aspects. The current thesis, therefore, emphasises the challenges of premium IOL surgery and need for refinement for optimum visual outcome in addition to outlining how premium IOLs may provide long-term and successful correction of astigmatism and presbyopia.

Evaluation of modern intraocular lenses

Accommodating Intraocular Lenses (IOLs), multifocal IOLs (MIOLs) and toric IOLs are designed to provide a greater level of spectacle independency post cataract surgery. All of these IOLs are reliant on the accurate calculation of intraocular lens power determined through reliable ocular biometry. A standardised defocus area metric and reading performance index metric were devised for the evaluation of the range of focus and the reading ability of subjects implanted with presbyopic correcting IOLs. The range of clear vision after implantation of an MIOL is extended by a second focal point; however, this results in the prevalence of dysphotopsia. A bespoke halometer was designed and validated to assess this photopic phenomenon. There is a lack of standardisation in the methods used for determining IOL orientation and thus rotation. A repeatable, objective method was developed to allow the accurate assessment of IOL rotation, which was used to determine the rotational and positional stability of a closed loop haptic IOL. A new commercially available biometry device was validated for use with subjects prior to cataract surgery. The optical low coherence reflectometry instrument proved to be a valid method for assessing ocular biometry and covered a wider range of ocular parameters in comparison with previous instruments. The advantages of MIOLs were shown to include an extended range of clear vision translating into greater reading ability. However, an increased prevalence of dysphotopsia was shown with a bespoke halometer, which was dependent on the MIOL optic design. Implantation of a single optic accommodating IOL did not improve reading ability but achieved high subjective ratings of near vision. The closed-loop haptic IOL displayed excellent rotational stability in the late period but relatively poor rotational stability in the early period post implantation. The orientation error was compounded by the high frequency of positional misalignment leading to an extensive overall misalignment of the IOL. This thesis demonstrates the functionality of new IOL lens designs and the importance of standardised testing methods, thus providing a greater understanding of the consequences of implanting these IOLs. Consequently, the findings of the thesis will influence future designs of IOLs and testing methods.

Astigmatism and vision:should all astigmatism always be corrected?

As technology and medical devices improve, there is much interest in when and how astigmatism should be corrected with refractive surgery. Astigmatism can be corrected by most forms of refractive surgery, such as using excimer lasers algorithms to ablate the cornea to compensate for the magnitude of refractive error in different meridians. Correction of astigmatism at the time of cataract surgery is well developed and can be achieved through incision placement, relaxing incisions and toric intraocular lens (IOL) implantation. This was less of an issue in the past when there was a lower expectation to be spectacle independent after cataract surgery, in which case the residual refractive error, including astigmatism, could be compensated for with spectacle lenses. The issue of whether presurgical astigmatism should be corrected can be considered separately depending on whether a patient has residual accommodation, and the type of refractive surgery under consideration. We have previously reported on the visual impact of full correction of astigmatism, rather than just correcting the mean spherical equivalent. Correction of astigmatism as low as 1.00 dioptres significantly improves objective and subjective measures of functional vision in prepresbyopes at distance and near.

Corneal pachymetry in normal and keratoconic eyes:Orbscan II versus ultrasound

Purpose: To compare corneal thickness measurements using Orbscan II (OII) and ultrasonic (US) pachymetry in normal and in keratoconic eyes. Setting: Eye Department, Heartlands and Solihull NHS Trust, Birmingham, United Kingdom. Methods: Central corneal thickness (CCT) was measured by means of OII and US pachymetry in 1 eye of 72 normal subjects and 36 keratoconus patients. The apical corneal thickness (ACT) in keratoconus patients was also evaluated using each method. The mean of the difference, standard deviation (SD), and 95% limits of agreement (LoA = mean ± 2 SD), with and without applying the default linear correction factor (LCF), were determined for each sample. The Student t test was used to identify significant differences between methods, and the correlation between methods was determined using the Pearson bivariate correlation. Bland-Altman analysis was performed to confirm that the results of the 2 instruments were clinically comparable. Results: In normal eyes, the mean difference (± 95% LoA) in CCT was 1.04 μm ± 68.52 (SD) (P>.05; r = 0.71) when the LCF was used and 46.73 ± 75.40 μm (P = .0001; r = 0.71) without the LCF. In keratoconus patients, the mean difference (± 95% LoA) in CCT between methods was 42.46 ± 66.56 μm (P<.0001: r = 0.85) with the LCF, and 2.51 ± 73.00 μm (P>.05: r = 0.85) without the LCF. The mean difference (± 95% LoA) in ACT for this group was 49.24 ± 60.88 μm (P<.0001: r = 0.89) with the LCF and 12.71 ± 68.14 μm (P = .0077; r = 0.89) when the LCF was not used. Conclusions: This study suggests that OII and US pachymetry provide similar readings for CCT in normal subjects when an LCF is used. In keratoconus patients, OII provides a valid clinical tool for the noninvasive assessment of CCT when the LCF is not applied. © 2004 ASCRS and ESCRS.

Poly(methyl methacrylate) model study of optical surface quality after excimer laser photorefractive keratectomy

Purpose: To evaluate lenses produced by excimer laser ablation of poly(methyl methacrylate) (PMMA) plates. Setting: University research laboratory. Methods: Two Nidek EC-5000 scanning-slit excimer laser systems were used to ablate plane-parallel plates of PMMA. The ablated lenses were examined by focimetry, interferometry, and mechanical surface profiling. Results: The spherical optical powers of the lenses matched the expected values, but the cylindrical powers were generally lower than intended. Interferometry revealed marked irregularity in the surface of negative corrections, which often had a positive “island” at their center. Positive corrections were generally smoother. These findings were supported by the results of mechanical profiling. Contrast sensitivity measurements carried out when observing through ablated lenses whose power had been neutralized with a suitable spectacle lens of opposite sign confirmed that the surface irregularities of the ablated lenses markedly reduced contrast sensitivity over a range of spatial frequencies. Conclusion: Improvements in beam delivery systems seem desirable.

Refracting the pseudophakic patient

Pseudophakic patients are frequently encountered in optometric practice, often the result of cataract extraction but also presbyopia correction. Given advances in technology and surgery, the demand for intraocular lenses for correcting a variety of refractive requirements has increased owing to an ageing population. Based on the patient’s needs, either fixed focus, toric, accommodating or multifocal intraocular lenses (IOLs) may be implanted. During optometric examination, attention should be drawn to a history of IOLs and the potential complications they may cause in order to manage them effectively, particularly where sight is threatened. Although objective and subjective refraction does not differ greatly between phakic and pseudophakic patients, care should be taken to set the patient up correctly and the reflex during retinoscopy observed for posterior sub-capsular opacification. Additional tests such as reading speed, and glare and contrast sensitivity are necessary to determine the outcome of IOL surgery and detect potential problems associated with multifocal and accommodating IOLs. Based upon the results of these tests, refraction, and type of IOL, contact lens or spectacle correction may be required to meet the visual demands of the patient.

Exploring the optimum step size for defocus curves

Purpose: To evaluate the effect of reducing the number of visual acuity measurements made in a defocus curve on the quality of data quantified. Setting: Midland Eye, Solihull, United Kingdom. Design: Evaluation of a technique. Methods: Defocus curves were constructed by measuring visual acuity on a distance logMAR letter chart, randomizing the test letters between lens presentations. The lens powers evaluated ranged between +1.50 diopters (D) and -5.00 D in 0.50 D steps, which were also presented in a randomized order. Defocus curves were measured binocularly with the Tecnis diffractive, Rezoom refractive, Lentis rotationally asymmetric segmented (+3.00 D addition [add]), and Finevision trifocal multifocal intraocular lenses (IOLs) implanted bilaterally, and also for the diffractive IOL and refractive or rotationally asymmetric segmented (+3.00 D and +1.50 D adds) multifocal IOLs implanted contralaterally. Relative and absolute range of clear-focus metrics and area metrics were calculated for curves fitted using 0.50 D, 1.00 D, and 1.50 D steps and a near add-specific profile (ie, distance, half the near add, and the full near-add powers). Results: A significant difference in simulated results was found in at least 1 of the relative or absolute range of clear-focus or area metrics for each of the multifocal designs examined when the defocus-curve step size was increased (P<.05). Conclusion: Faster methods of capturing defocus curves from multifocal IOL designs appear to distort the metric results and are therefore not valid. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2013 ASCRS and ESCRS.