Cellular responses to changes in pressure are implicated in numerous disease processes. In glaucoma apoptosis of retinal ganglion cells (RGCs) is associated with elevated intra-ocular pressure (IOP), however the exact cellular basis of this link remains unclear. This research aimed to examine the direct response of neuronal cells to elevated hydrostatic pressure in terms of apoptosis. We developed an in vitro model consisting of a pressure chamber to adjust ambient hydrostatic pressure, a source of neuronal cells and methods to measure apoptosis in these cells. The neural cells examined were primary retinal cultures, four neuronal cell lines (B35, PC12, C17, NT2), and the RGC-5 cell line. Pressure conditions selected were within physiological limits; 100 mmHg above atmospheric pressure (as seen clinically in severe acute glaucoma) and extended in RGC-5 neurons to 30 mmHg (chronic glaucoma) and 15 mmHg (normal IOP). Apoptosis was detected by cell morphology and specific immunochemical markers: TUNEL and Annexin V. Caspase-3 activation, a known pathway of apoptosis, was also investigated in RGC-5 neurons. These fluorescent markers were detected and quantified by automated Laser Scanning Cytometry. Negative controls were treated identically except for the application of pressure, while positive controls were generated by treatment with a known apoptotic stimulus. The results showed that neurons responded to elevated hydrostatic pressure directly and that an apoptotic process was induced. There was a greater level of apoptosis in pressurised cells compared to the negative controls. This apoptotic effect at high pressures was seen in primary rat retinal cultures and in both undifferentiated (B35, C17, NT2, RGC-5) and differentiated (PC12, RGC-5) neuronal cell lines. RGC-5 neurons showed a graded response, proportionate to the level of pressure elevation, representative of the severity of analogous clinical settings (acute, chronic glaucoma & normal). RGC-5 neurons also showed increased activation of Capsase-3. Thus this pathway may play a role in pressure induced apoptosis. Our findings indicate that pressure alone may act as a stimulus for apoptosis in neuronal cells. We suggest the possibility of novel mechanisms of pressure related mechanotransduction and cell death, relevant to the pathogenesis of glaucoma.

Objective: To examine the changes of visual field and retinal nerve fiber layer (RNFL) measurements and the risk of glaucoma progression before and after taking off intraocular pressure (IOP) lowering medication in Chinese patients with ocular hypertension. Design: Prospective study. Participants: 106 ocular hypertension patients (4 were excluded because there was no 1 year follow up examination). Method: All patients underwent visual field testing by Humphrey Field Analyser and Retinal Nerve Fiber Layer (RNFL) thickness measurement by a spectral-domain optical coherence tomography. Eyes without glaucomatous visual field defect and had an IOP ?30mmHg were instructed to stop taking IOP lowering medication and measurements of IOP, visual field and RNFL measurements were taken. Changes in the visual field mean deviation, average, superior and inferior RNFL thickness and the risk of developing glaucoma between the baseline and follow-up examinations were compared between the groups with and without stopping IOP lowering medications. Logistic regression was used to analyze the association between corneal hysteresis, ocular pulse amplitude and the onset of glaucoma. Results: There were 73 patients with IOP lowering medications taken off and 29 with continued medications. No significant differences were found in the changes of visual field mean deviation, average RNFL thickness and the risk of glaucoma progression (P=0.92, P=0.81, P=0.35, respectively) between the groups. Ocular pulse amplitude was a significant predictor of glaucoma development by functional (-0.61, P=0.047) and structural criteria (-0.74, P=0.024). Conclusion: There were no functional and structural changes in patients with ocular hypertension after stopping IOP lowering medications in one year. Low ocular pulse amplitude could be a predictive factor for the conversion from ocular hypertension to glaucoma. Clinicians should not prescribe IOP-lowering medication simply base on high IOP. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Diss. (sammanfattning) Umeå : Univ., 2006. / Härtill 5 uppsatser.

Man, Xiaofei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 138-162). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

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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...

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.

Purpose: We evaluate solutions for an applanating surface modification to the Goldmann tonometer prism, which substantially negates the errors due to patient variability in biomechanics. Methods: A modified Goldmann or correcting applanation tonometry surface (CATS) prism is presented which was optimized to minimize the intraocular pressure (lOP) error due to corneal thickness, stiffness, curvature, and tear film. Mathematical modeling with finite element analysis (FEA) and manometric lOP referenced cadaver eyes were used to optimize and validate the design. Results: Mathematical modeling of the optimized CATS prism indicates an approximate 50% reduction in each of the corneal biomechanical and tear film errors. Manometric lOP referenced pressure in cadaveric eyes demonstrates substantial equivalence to GAT in nominal eyes with the CATS prism as predicted by modeling theory. Conclusion: A CATS modified Goldmann prism is theoretically able to significantly improve the accuracy of lOP measurement without changing Goldmann measurement technique or interpretation. Clinical validation is needed but the analysis indicates a reduction in CCT error alone to less than +/- 2 mm Hg using the CATS prism in 100% of a standard population compared to only 54% less than +/- 2 mm Hg error with the present Goldmann prism. Translational Relevance: This article presents an easily adopted novel approach and critical design parameters to improve the accuracy of a Goldmann applanating tonometer.

Purpose: To compare the effect of topical prednisolone acetate 1% (PA) used after routine cataract surgery to the effect of difluprednate 0.05% (DFBA) used for the same indication on intraocular pressure (IOP). Methods: An electronic query was created to gather information from all cataract surgeries between January 2010 and January 2015 within the electronic health record database at Barnet Dulaney Perkins, a multicenter, multiphysician private practice in Phoenix, Arizona. Information collected included age, sex, diabetes status, glaucoma history, medication regimen (use of PA or DFBA), and IOP before surgery, 5-10 days postoperatively (TP1) and 3-6 weeks postoperatively (TP2). Postoperative IOP measurements were compared to baseline IOP measurement in each patient. Results: Regardless of steroid used, all patients in this study experienced an increase in IOP within TP1 and returned to baseline IOP (+/- 2.0 mmHg) by TP2. Patients who received DFBA showed a statistically significant increase in IOP at TP1 compared to those on PA (P<0.001) with the mean IOP an average 0.60 mmHg higher (95% CI = 0.3, 0.9). The odds ratio of a clinically significantly increased IOP at TP1 (defined as overall IOP >= 21 mmHg and an increase of >= 10 mmHg) in DFBA-treated patients was 1.84 (95% CI = 1.4, 2.6). In patients treated with PA, 3% reached a significantly increased IOP, compared to 4.4% of patients in the DFBA group (P<0.05). Risk factors for increased IOP were identified, and include advanced age (>75) (P<0.005) and a history of glaucoma (P<0.001). Conclusion: In postoperative cataract patients, use of DFBA increased the risk of a clinically significant IOP increase.