M.Phil. (Optometry) / The primary aim of this research was to investigate whether the Icare® rebound tonometer may be used in place of the Goldmann tonometer to obtain accurate and reliable intraocular pressure measurements on a sample of the general population seeking eye care, in a South African context. Due to the portability of the Icare®, lack of dependency on other instrumentation and power source, together with the ease of use with minimal training, and without the use of topical anaesthetic favourable results of the instrument may lead to its widespread use. This could aid in earlier diagnosis of glaucoma where intraocular pressure remains the only modifiable risk factor. In the South African context, where a high prevalence of undiagnosed primary open angle glaucoma has been found, access and accuracy of intraocular pressure measurement could save and extend functional vision in this country. Patients presenting at the Department of Optometry for routine eye examinations were selected utilizing convenience sampling. The right and left eyes of 113 patients were assessed using both the Icare® TA01i and the Goldman applanation tonometer by independent examiners for each method, all readings of intraocular pressure with the Goldman being taken by the same experienced examiner. The age of the patients ranged from 20 to 89 years with a mean age 50.29 ±20.97 years. Using the Oculus Pachycam® when it became available, central corneal thickness was obtained on 71 patients (142 eyes). Analysis of data using descriptive statistics from SPSS (Statistical Programs for the Social Sciences) was performed in addition to the Bland-Altman method of comparative analysis for sets of data of corrected and uncorrected measurements between the instruments...

Background : Frequency Doubling Perimetry ( FDP ) is a recently developed form of perimetry, which may be more sensitive for detecting visual field loss from glaucoma than conventional Achromatic Automated Perimetry ( AAP ). This thesis was undertaken to study aspects of FDP for the detection of early glaucoma. Method : FDP was compared with other forms of perimetry at one point in time using one dataset ( n = 83 ) and longitudinally over a four - year period with another dataset ( n = 62 ). Several aspects were studied : ( 1 ) the ability of FDP to detect visual field loss earlier than AAP, ( 2 ) its ability to detect early functional abnormality in the presence of mild glaucomatous structural abnormality ( 3 ) visual field topography compared with other perimetry and ( 4 ) its ability to predict future field loss when only the nasal quadrants were considered. Results : When subjects at risk of glaucoma with initial visual field loss on FDP were followed over a three - year period, a significant proportion developed field loss with AAP, whilst those without initial FDP loss did not. FDP detected cases of early glaucomatous optic disc damage, which had not been detected using AAP ; however, there was still a proportion of those with abnormal optic discs which remained normal on FDP. FDP field topography was hill - shaped with the most sensitive point centrally ; however, it was considerably flatter and more sensitive than AAP. Finally, if FDP field loss was only considered significant when it occurred within the nasal step location of the visual field, then this may improve the accuracy of glaucoma diagnosis. Conclusion : This thesis has demonstrated that FDP is not only more sensitive than AAP in the detection of glaucomatous optic disc damage, but it is able to predict future field loss on AAP. FDP may therefore be useful in the early detection and management of glaucoma. / Thesis (Ph.D.)--School of Medicine, 2006.

Background: As a multifactorial disease glaucoma may be associated with pressure-dependent and -independent factors. Ocular hypertension (OHT) may develop into primary open angle glaucoma (POAG) for many patients. We compared groups with OHT and POAG for pressure-dependent and -independent risk factors. A high prevalence of any factor(s) could indicate a contribution to progression from OHT to POAG. Method: A sample of patients with POAG (n 438) and with OHT (n 301) were selected from those attending a tertiary referral private glaucoma practice, and data were collected regarding age and intraocular pressure at the time of diagnosis, gender, family history of glaucoma, systemic hypertension, diabetes, Raynaud's phenomenon, migraine and myopia. Results: After multivariate analysis, older age at time of diagnosis (P<0.001), myopia (odds ratio (O.R) 1.5, 95percent confidence interval (C.I)1.0-2.2; P 0.05), a family history of glaucoma (O.R 1.6, 95 percent C.I 1.1-2.3; P 0.01) and a high intraocular pressure (P 0.002) were associated with POAG. No other significant differences were found between the two groups. Conclusion: Patients who have OHT may be at higher risk of developing POAG if they also have myopia, a family history of glaucoma or are of older age.

Thesis (Ph.D.)--Texas Christian University, 2007. / Title from dissertation title page (viewed Apr. 25, 2007). Includes abstract. Includes bibliographical references.

Glaucoma is defined as a progressive optic neuropathy, characterized by loss of visual function and often associated with high intra-ocular pressure. Testing the patients' visual function with Standard Automated Perimetry (SAP) is currently the clinical standard for detecting glaucomatous visual field loss. A new test algorithm using the Frequency Doubling illusion has been introduced on the Matrix perimeter (Humphrey Matrix; Carl Zeiss Meditech, Dublin CA) that measures the central 10° using a 2°x 2° square flickering stimulus. This stimulus has the theoretical advantage of being both a large target, with good repeatability, and being perceptually selective, by preferentially stimulating the magnocellular projecting ganglion cells. <br /><br /> The purpose of this thesis was to determine the within-technique, between-visits repeatability and the within-visit, between-technique comparison of several techniques available to measure the central 10° visual field in patients with late stage glaucoma. In particular, to examine test-retest variability and compare sensitivity threshold values, visual field indices, and total and pattern deviation probability maps among the following techniques: Full Threshold SAP 10-2 size III (SAP III), Full Threshold SAP size V (SAP V), SITA SAP 10-2 size III (SS III), and Matrix 10-2 2° stimulus (M2). <br /><br /> Forty nine patients with advanced glaucomatous visual field defects attended 3 visits. During each visit, 1 eye was examined with each of the 4 techniques mentioned above. Data from the first visit was discarded to eliminate bias that may occur from the learning effect. Coefficient of Repeatability values of SAP III, SAP V, SS III, and M2 were calculated to be 10. 33, 9. 00, 9. 90, and 12. 04%dB respectively, relative to the average difference in threshold estimates between visits. M2 had the most uniform test-retest characteristics across the full range of sensitivities; however the 90% confidence interval was the widest of all techniques in the normal to near normal range (24 to 38dB). M2 showed the greatest defects in both total and pattern deviation probability plots. Threshold estimates of SAP III and SS III were shown to be similar and slightly more variable than SAP V. M2 showed greater defects than SAP III in both total and pattern deviation probability plots. Compared to SAP III and SS, M2 estimated sensitivity as less severe. Estimates of 20 dB and above on M2 were estimated at approximately 30 dB with SAP V. In the moderate to abnormal sensitivity range, Matrix estimated points to be shallower than that estimated by SAP V. <br /><br /> This thesis showed that test-retest variability of the SAP techniques decreased with increasing sensitivity whereas; variability was constant throughout the dynamic range for M2 and smaller in the moderate to severe range. However M2 was worst in the normal to near-normal sensitivity range. This suggests that M2, compared to all SAP techniques, will be disadvantaged for the detection of early visual field loss but better positioned to repeatably detect and follow moderate to severe loss in the central 10° of patients with late stage glaucoma.

Glaucoma is defined as a progressive optic neuropathy, characterized by loss of visual function and often associated with high intra-ocular pressure. Testing the patients' visual function with Standard Automated Perimetry (SAP) is currently the clinical standard for detecting glaucomatous visual field loss. A new test algorithm using the Frequency Doubling illusion has been introduced on the Matrix perimeter (Humphrey Matrix; Carl Zeiss Meditech, Dublin CA) that measures the central 10° using a 2°x 2° square flickering stimulus. This stimulus has the theoretical advantage of being both a large target, with good repeatability, and being perceptually selective, by preferentially stimulating the magnocellular projecting ganglion cells. <br /><br /> The purpose of this thesis was to determine the within-technique, between-visits repeatability and the within-visit, between-technique comparison of several techniques available to measure the central 10° visual field in patients with late stage glaucoma. In particular, to examine test-retest variability and compare sensitivity threshold values, visual field indices, and total and pattern deviation probability maps among the following techniques: Full Threshold SAP 10-2 size III (SAP III), Full Threshold SAP size V (SAP V), SITA SAP 10-2 size III (SS III), and Matrix 10-2 2° stimulus (M2). <br /><br /> Forty nine patients with advanced glaucomatous visual field defects attended 3 visits. During each visit, 1 eye was examined with each of the 4 techniques mentioned above. Data from the first visit was discarded to eliminate bias that may occur from the learning effect. Coefficient of Repeatability values of SAP III, SAP V, SS III, and M2 were calculated to be 10. 33, 9. 00, 9. 90, and 12. 04%dB respectively, relative to the average difference in threshold estimates between visits. M2 had the most uniform test-retest characteristics across the full range of sensitivities; however the 90% confidence interval was the widest of all techniques in the normal to near normal range (24 to 38dB). M2 showed the greatest defects in both total and pattern deviation probability plots. Threshold estimates of SAP III and SS III were shown to be similar and slightly more variable than SAP V. M2 showed greater defects than SAP III in both total and pattern deviation probability plots. Compared to SAP III and SS, M2 estimated sensitivity as less severe. Estimates of 20 dB and above on M2 were estimated at approximately 30 dB with SAP V. In the moderate to abnormal sensitivity range, Matrix estimated points to be shallower than that estimated by SAP V. <br /><br /> This thesis showed that test-retest variability of the SAP techniques decreased with increasing sensitivity whereas; variability was constant throughout the dynamic range for M2 and smaller in the moderate to severe range. However M2 was worst in the normal to near-normal sensitivity range. This suggests that M2, compared to all SAP techniques, will be disadvantaged for the detection of early visual field loss but better positioned to repeatably detect and follow moderate to severe loss in the central 10° of patients with late stage glaucoma.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Glaucoma is the leading cause of irreversible blindness worldwide with the most prevalent form, primary open-angle glaucoma (POAG), accounting for the vast majority of glaucoma cases. The main risk-factor for POAG is an elevated intraocular pressure (IOP), and is due to an increased resistance to aqueous humor outflow in the conventional outflow pathway at the juxtacanalicular region of the trabecular meshwork (TM) and the inner wall of Schlemm’s canal (SC). Reducing elevated IOP is the most effective method to prevent further loss of vision in glaucoma; therefore, it is important to understand how outflow resistance is regulated in the conventional outflow pathway in order to find effective methods to reduce ocular hypertension. Sphingosine-1-phosphate (S1P) is an endogenous lipid that reduces outflow facility in porcine eyes, thereby increasing resistance. S1P plays a major role in affecting cell migration, endothelial permeability, and junctional formation, processes that are intimately linked and regulated by cytoskeletal dynamics. Due to S1P’s known effect of decreasing endothelial permeability in vascular endothelial cells, the overall hypothesis of this dissertation is that the S1P-induced decrease in outflow facility occurs through a mechanism that involves S1P receptor activation in SC cells. The results from the studies within this dissertation demonstrate the expression of the S1P₁₋₃ receptor subtypes in SC and TM cells and a decrease of outflow facility by S1P in perfused human eyes. Additionally, S1P promotes F-actin formation and myosin light chain (MLC) phosphorylation at the SC cell cortex. The S1P-promoted MLC phosphorylation in both SC and TM cells, in addition to the S1P-induced decrease of outflow facility in porcine and human eyes, were blocked by the S1P₂ antagonist JTE-013. Results from these studies demonstrate S1P to actively regulate actomyosin dynamics in the cells of the outflow pathway through the S1P₂ receptor. S1P₂ also mediates the S1P-induced increase in outflow resistance. Therefore, S1P₂ is a novel pharmacological target in the conventional outflow pathway to reduce elevated IOP in glaucoma patients.

Purpose: To determine the association of plasma and aqueous humor selenium with glaucoma; and to determine those factors influencing biological levels of selenium in patients with glaucoma and cataractMethods: 47 primary open angle glaucoma (POAG) cases and 54 controls were recruited from surgery patients at the University Physician's Ophthalmology Clinic in Tucson, Arizona. Aqueous humor and plasma selenium concentration was determined by high performance liquid chromatography ion channel plasma-mass spectrometry (HPLC ICP-MS). Potential confounders were assessed via questionnaire. Outcome measures included the odds of glaucoma in relation to plasma selenium and aqueous humor selenium. Factors driving plasma and aqueous humor selenium in the study population were determined via linear regression.Results: After adjustment for risk factors and multiple outcomes, the odds of glaucoma in the highest tertile of plasma selenium (OR = 13.51; p=.03) and the middle tertile of aqueous humor selenium (OR = 0.05; p=0.02) were significantly associated with glaucoma. Selenium concentration in plasma and aqueous humor was primarily driven by metabolic factors (cancer, DMII, and ARMD).Conclusions: Although a causal pathway cannot be inferred from the analysis, it may be prudent to explore these relations in a larger sample in varying areas of geographic selenium distribution. Such information could be helpful in examining a larger study population and comparing biological data. Evaluating a subject's selenium levels over time and in relation to glaucoma onset could also lend pertinent informationDriving forces behind selenium concentrations in this population are mainly metabolic in nature. Selenium levels fluctuate in most tissue as it is metabolized by the body. Selenium supplementation is a significant predictor but this effect is small and may be transient as supplementation only temporarily increases selenium pools. It is interesting to note that sex is a significant predictor of aqueous humor selenium but not of plasma selenium. In this model, female sex predicts a decrease in the selenium within the aqueous humor. This point should be explored in future studies that are powered to discern possibly subtle differences that sex plays in relation to selenium concentrations in plasma and aqueous humor and its possible role in glaucoma.

Background: As a multifactorial disease glaucoma may be associated with pressure-dependent and -independent factors. Ocular hypertension (OHT) may develop into primary open angle glaucoma (POAG) for many patients. We compared groups with OHT and POAG for pressure-dependent and -independent risk factors. A high prevalence of any factor(s) could indicate a contribution to progression from OHT to POAG. Method: A sample of patients with POAG (n 438) and with OHT (n 301) were selected from those attending a tertiary referral private glaucoma practice, and data were collected regarding age and intraocular pressure at the time of diagnosis, gender, family history of glaucoma, systemic hypertension, diabetes, Raynaud's phenomenon, migraine and myopia. Results: After multivariate analysis, older age at time of diagnosis (P<0.001), myopia (odds ratio (O.R) 1.5, 95percent confidence interval (C.I)1.0-2.2; P 0.05), a family history of glaucoma (O.R 1.6, 95 percent C.I 1.1-2.3; P 0.01) and a high intraocular pressure (P 0.002) were associated with POAG. No other significant differences were found between the two groups. Conclusion: Patients who have OHT may be at higher risk of developing POAG if they also have myopia, a family history of glaucoma or are of older age.