Genistein stimulates the viability and prevents myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-ß.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma leading to blindness. The search for ways to prevent/treat this entity is one of the main challenges of today's ophthalmology. One of such solution seems to be biologically active substances of natural origin, such as genistein (GEN), which can affect the function of isolated trabecular meshwork by the inhibition of protein tyrosine kinase. However, the role of GEN in viability as well as myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-ß is unknown. Using human trabecular meshwork cells (HTMCs) we investigated the effect of genistein on cell viability and myofibroblastic transformation stimulated by TGF-ß1 and TGF-ß2. Using Real-Time PCR, western blot and immunofluorescence we determined the effect on the expression changes of αSMA, TIMP1, collagen 1 and 3 at mRNA and protein level. We found that genistein increases the viability of HTMCs (1, 2, 3 µg/ml; P < 0.05 and 4, 5, 10, 15, 20 µg/ml; P < 0.01). Moreover, we found that addition of 10, 15 and 20 µg/ml is able to prevent myofibroblastic transformation of HTMCs by decreasing αSMA, TIMP1, collagen 1 and 3 mRNA and protein expression (P < 0.01). Based on the obtained results, we can conclude that genistein is a potential factor that can prevent the myofibroblastic transformation of HTMCs accompanying glaucoma. Describing GEN influence on myofibroblastic transformation processes in HTMC allows us to conclude that it can be considered a potential therapeutic agent or a substance supporting treatment in patients with glaucoma.

Continuous 24-hour measurement of intraocular pressure in millimeters of mercury (mmHg) using a novel contact lens sensor: Comparison with pneumatonometry.

PURPOSE: To address the unmet need of continuous IOP monitoring, a Pressure-Measuring Contact Lens (PMCL) was developed to measure IOP in millimeters of mercury (mmHg) continuously over 24 hours. The present study assessed the reliability of the novel PMCL. METHODS: In this prospective open-label clinical study, healthy and open-angle glaucoma (OAG) subjects were fitted with the PMCL, and pneumatonometry was performed on study eyes (in absence of the PMCL) and on fellow eyes before, during, and after provocative tests. The primary outcome measures were (1) mean IOP difference between same-eye measurements, and (2) percentage of timepoints at which IOP measured by the PMCL was within 5 mmHg of that measured by pneumatonometry in the fellow eye. RESULTS: Eight subjects were analysed (4 healthy, 4 OAG). The average difference in successive IOP measurements made by pneumatonometry and with the PMCL was 2.0±4.3mmHg at placement-time, and 6.5±15.2mmHg at removal time. During water drinking test, a significant increase in IOP was detected both by PMCL in the study eye (2.4±2.5mmHg, p = 0.03) and by pneumatonometry in the fellow eye (1.9±1.9mmHg, p = 0.02). Over the 24-hour recording, 88.0% of IOP variations measured by the PMCL were within 5mmHg of that measured with the pneumatonometer in the fellow eye. A transient corneal erosion of severe intensity was observed following removal of the PMCL on one single eye, and may have affected measurement accuracy in that eye. CONCLUSIONS: This study is a proof-of-concept for this novel PMCL, and its results are encouraging, with a fair accuracy in IOP values measurement and good sensitivity to subtle IOP variations.

First-in-human continuous 24-hour measurement of intraocular pressure and ocular pulsation using a novel contact lens sensor.

BACKGROUND/AIMS: This study assessed the feasibility of a novel contact lens device for intraocular pressure (IOP) and ocular pulse amplitude (OPA) continuous measurements over 24 hours. METHODS: This prospective, open-label, single-centre, non-randomised study included glaucoma and healthy subjects. IOP and OPA values acquired by the pressure-measuring contact lens (PMCL) device in one patient's eye at the beginning of the measurement were compared with tonometry values (Goldman applanation tonometry (GAT) and dynamic contour tonometry (DCT)) in the same eye just before PMCL placement. Furthermore, IOP and OPA values measured with PMCL on the study eye during a water drinking test (WDT) were compared with DCT values in the fellow eye. Comparisons were performed using t-tests with 95% Confidence Intervals. RESULTS: Twenty-four-hour IOP and OPA curves were obtained for eight subjects. The mean IOP difference between PMCL and tonometry on the same eye was within ±5 mm Hg in 75% (GAT) and 87.5% (DCT) of subjects. IOP variations due to WDT were detected by PMCL and DCT, showing an average increase of 2.43 and 1.85 mm Hg, respectively. Differences between PMCL and DCT for IOP variations in fellow eyes were within ±5 mm Hg for 97.2% of time points. The difference between OPA in fellow eyes was within ±5 mm Hg for 85.5% of the time points. CONCLUSIONS: This first-in-human study is a proof-of-concept for 24-hour continuous measurements of IOP and OPA with the PMCL. This device is non-invasive and has good comparability with standard tonometry.

Use of Machine Learning on Contact Lens Sensor-Derived Parameters for the Diagnosis of Primary Open-angle Glaucoma.

PURPOSE: To test the hypothesis that contact lens sensor (CLS)-based 24-hour profiles of ocular volume changes contain information complementary to intraocular pressure (IOP) to discriminate between primary open-angle glaucoma (POAG) and healthy (H) eyes. DESIGN: Development and evaluation of a diagnostic test with machine learning. METHODS: Subjects: From 435 subjects (193 healthy and 242 POAG), 136 POAG and 136 age-matched healthy subjects were selected. Subjects with contraindications for CLS wear were excluded. PROCEDURE: This is a pooled analysis of data from 24 prospective clinical studies and a registry. All subjects underwent 24-hour CLS recording on 1 eye. Statistical and physiological CLS parameters were derived from the signal recorded. CLS parameters frequently associated with the presence of POAG were identified using a random forest modeling approach. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (ROC AUC) for feature sets including CLS parameters and Start IOP, as well as a feature set with CLS parameters and Start IOP combined. RESULTS: The CLS parameters feature set discriminated POAG from H eyes with mean ROC AUCs of 0.611, confidence interval (CI) 0.493-0.722. Larger values of a given CLS parameter were in general associated with a diagnosis of POAG. The Start IOP feature set discriminated between POAG and H eyes with a mean ROC AUC of 0.681, CI 0.603-0.765. The combined feature set was the best indicator of POAG with an ROC AUC of 0.759, CI 0.654-0.855. This ROC AUC was statistically higher than for CLS parameters or Start IOP feature sets alone (both P < .0001). CONCLUSIONS: CLS recordings contain information complementary to IOP that enable discrimination between H and POAG. The feature set combining CLS parameters and Start IOP provide a better indication of the presence of POAG than each of the feature sets separately. As such, the CLS may be a new biomarker for POAG.

[Central corneal thickness measurement in normal tension glaucoma]. / Centralna grubosc rogówki w jaskrze normalnego cisnienia.

PURPOSE: To evaluate corneal thickness in eyes with normal tension glaucoma. MATERIAL AND METHODS: CCT (measured by specular microscope Topcon SP2000P) was evaluated in 70 eyes of 39 patients with diagnosed NTG, 35 women and 4 men in age 31-78 years (mean 68 years). RESULTS: Mean central corneal thickness measured by the specular microscope (between 11 and 1), was 523.7 microm in range 465-575 microm. Impact of CCT on results of Goldman aplanation tonometry was detected in 55.7% of NTG eyes--overestimated in 20% and underestimated in 35% of them. Corrected maximal IOP > 21 mmHg, was found in 14% of NTG eyes. CONCLUSIONS: Central corneal thickness measurement should be part of routine ophthalmological examination in glaucomatous patients (especially in NTG), being helpful in choice of optimal therapeutic strategy.

[Glaucoma and ocular ischemic syndrome--case report]. / Jaskra a oczny zespól niedokrwienny--opis przypadku.

PURPOSE: Ocular ischemic syndrome (OIS) is often poorly diagnosed and treated as primary open angle glaucoma or later on, as neovascular glaucoma. We present a 54 year old male, treated topical since 23 years for glaucoma and sent to our clinic for trabeculectomy because of rapid worsening of vision on right eye with bilateral total excavation of optic disc. MATERIAL AND METHODS: Observational case report. RESULTS: Because of typical signs of IOS (iris neovascularization, mid-peripheral dot and blot hemorrhages in both eyes, narrowed arterioles in right eye, following examinations were performed: Doppler ultrasonography of carotid arteries, digital subtractional angiography of the carotid vessels and magnetic resonance angiography. The examinations showed occlusion of the right common carotid artery and with 80% stenosis of the left common carotid artery, occlusion of abdominal aorta. After phacoemulsification with implantation of intraocular lens because of rapid intumescence cataract in the right eye, and endarterectomy of left external carotid artery, the neovascularization of the iris regressed in both eyes. CONCLUSION: In case of iris neovascularization or mid-peripheral hemorrhages the Doppler sonography of carotid arteries should be performed. Quick cooperation between ophthalmologist, radiologist and vascular surgeon following endarterectomy seems to stop progressing changes of ocular ischemic syndrome.

[Cataract in persons over 90 years old]. / Zacma u osób powyzej 90. roku zycia.

PURPOSE: To evaluate effect of age over 90-ty on cataract surgery course, perioperative period and final corrected visual acuity. MATERIAL AND METHODS: A case series of 34 patients aged over 90 years (39 eyes) undergoing cataract extraction between 1993 - 2000 was studied. Detailed ophthalmological examination (best corrected visual acuity, tonometry, retinometry, anterior and posterior segment exmination, ultrasonography scan A and B), before and after operations was performed. Analyzed data was widen by internal physical examination. RESULTS: ECCE with posterior intraocular lens (IOL) in 38 eyes, and anterior IOL in 1 case (intraopertive posterior lens capsule rupture) implantation was performed. Postoperative course without complications in 35 eyes (89,7%), complications in 4 eyes (10,3%): keratopathy (2), exudative membrane (2). Improvement in visual acuity (defined as at least 2 lines in Snellen tables) was noted in 35 eyes (89,7%). Visual acuity over 0,3 was achieved in 23 eyes (58,9%), over 0,5 in 20 eyes (51,3%). Ocular comorbids: age related macular degeneration 7 eyes (17,9%), glaucomatous atrophy of optic nerve 5 eyes (12,8%), no diabetic retinopathy was diagnosed. CONCLUSIONS: 1. Advance in years is not a contradiction for cataract extraction. 2. Cataract surgery improved visual acuity: to far in 89,7%, to near in 71,8% - comparing with preopertive status. 3. Restoration of visual function, especially in persons with severe visual acuity reduction, has good impact on psychological status of patients. 4. Accurate perioperative care protects patients from serious systemic complications.