The management of glaucoma and intraocular hypertension: current approaches and recent advances

Noecker, Robert J.

doi:10.2147/tcrm.2006.2.2.193

Cited by 46 publications

(27 citation statements)

References 111 publications

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“…Finally, elevated intraocular pressure is one of several risk factors involved in the progression of glaucoma [157]. Using an animal model of ocular hypertension in which macrophages were systematically eliminated by treatment with clodronate liposomes, Huang et al [153] showed that inhibition of the JAK/STAT pathway was detrimental to retinal ganglion survival in vivo following acute experimentally-induced intraocular pressure elevation, but this response did not occur in the normal eye.…”

Section: The Visual Systemmentioning

confidence: 99%

Targeting JAK/STAT Signaling Pathway in Inflammatory Diseases

Malemud¹,

Pearlman²

2009

CST

116

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In immune-mediated chronic inflammation the balance between pro-inflammatory and anti-inflammatory cytokines is skewed so that elevated levels of circulating pro-inflammatory cytokines of the interleukin (IL), interferon (IFN) protein families and TNF-is favored. Several of the pro-inflammatory IL-family cytokines, including most prominently, IL-6, IL-12, IL-17, IL-23, as well as IFN-, activate the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway where phosphorylated (i.e. activated) STAT proteins become potent transcription factors for specific STAT-target genes. Moreover, 'cross-talk' between JAK/STAT signaling, SAP/MAPK and the phosphatidyl inositide-3-kinase (PI3K) pathway has been demonstrated. Thus, activation of the SAP/MAPK and PI3K pathways by JAK/STAT can initiate pleiotypic cellular responses that regulate cellular proliferation, survival, development and apoptosis. Further, inflammatory responses typically seen in rheumatoid arthritis, irritable bowel disease, chronic heart failure and diseases of the eye appear to accelerate when the JAK/STAT pathway itself becomes dysregulated. Of note, the outcomes of several human clinical trials demonstrated efficacy in reducing some objective markers of chronic inflammation by inhibiting IL-6-mediated signaling. In addition, evidence from one of these trials showed that suppression of IL-6 signaling also dampened STAT phosphorylation. This result suggested that the targeting of JAK/STAT signaling with small molecule inhibitors may also suppress chronic inflammatory responses.

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Section: The Visual Systemmentioning

confidence: 99%

Targeting JAK/STAT Signaling Pathway in Inflammatory Diseases

Malemud¹,

Pearlman²

2009

CST

116

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“…2 Glaucoma, a neurodegenerative disease of the retinal ganglion cells, is the second leading cause of blindness worldwide. 3 In the United States, 4 million people have glaucoma and 130 000 are legally blind from the disease. 3 In the Australian Blue Mountains Eye study of adults 49 years of age and older, the prevalence of open-angle glaucoma was 3% and OHT was found in 3.7% of participants.…”

Section: Introductionmentioning

confidence: 99%

“…3 In the United States, 4 million people have glaucoma and 130 000 are legally blind from the disease. 3 In the Australian Blue Mountains Eye study of adults 49 years of age and older, the prevalence of open-angle glaucoma was 3% and OHT was found in 3.7% of participants. 1 Control of IOP is important in patients with glaucoma: 4 a decrease of 1 mm Hg may lead to a 10% reduction in the risk of progressive nerve damage.…”

Section: Introductionmentioning

confidence: 99%

Potential effects of systematic errors in intraocular pressure measurements on screening for ocular hypertension

Turner

Graham

Avolio

et al. 2013

Eye

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Aim Raised intraocular pressure (IOP) increases the risk of glaucoma. Eye-care professionals measure IOP to screen for ocular hypertension (OHT) (IOP421 mm Hg) and to monitor glaucoma treatment. Tonometers commonly develop significant systematic measurement errors within months of calibration, and may not be verified often enough. There is no published evidence indicating how accurate tonometers should be. We analysed IOP measurements from a population study to estimate the sensitivity of detection of OHT to systematic errors in IOP measurements. Methods We analysed IOP data from 3654 participants in the Blue Mountains Eye Study, Australia. An inverse cumulative distribution indicating the proportion of individuals with highest IOP421 mm Hg was calculated. A second-order polynomial was fitted to the distribution and used to calculate over-and under-detection of OHT that would be caused by systematic measurement errors between À 4 and þ 4 mm Hg. We calculated changes in the apparent prevalence of OHT caused by systematic errors in IOP. Results A tonometer that consistently under-or over-reads by 1 mm Hg will miss 34% of individuals with OHT, or yield 58% more positive screening tests, respectively. Tonometers with systematic errors of À 4 and þ 4 mm Hg would miss 76% of individuals with OHT and would over-detect OHT by a factor of seven. Over-and under-detection of OHT are not strongly affected by cutoff IOP. Conclusion We conclude that tonometers should be maintained and verified at intervals short enough to control systematic errors in IOP measurements to substantially less than 1 mm Hg.

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“…2 Although several factors such as genetic predisposition, weakness of the optic nerve, severe myopia and thinness of the cornea have been identified to increase the risk of developing glaucoma, 3 one of the main risk factors is still considered to be elevated intra-ocular pressure (IOP). Therefore the available therapies for open angle glaucoma aim to lower the IOP in the anterior chamber of the eye by using various pharmaceuticals, laser trabeculoplasty or trabeculectomy.…”

Section: Introductionmentioning

confidence: 99%

Tracking ophthalmic drugs in the eye using confocal fluorescence microscopy

Buttenschön

Girkin

Daly

2012

Advanced Biomedical and Clinical Diagnostic Systems X

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We report on the development of a non-invasive instrument based on scanning confocal microscopy for tracking inherently fluorescent drugs and measuring spatial features in the anterior chamber of the eye. The new instrument incorporates all features of the initial instrument 1 with the addition of fluorescence detection from within the anterior chamber of the eye. We have measured the diffusion of Fluorescein with high time resolution within a cuvette, an artificial eye and ex vivo porcine eyes. Results are be presented that demonstrate the capability of the instrument to accurately measure the concentration and the location of the fluorescent drug over a given period of time along the optical axis of the eye with an axial resolution of under 200 μm and temporal resolution of < 1s. We show that the instrument has high sensitivity and can measure concentrations of < 1µM/L of compounds having a quantum yield as low as 0.01 with high specificity for the compound of interest over competing background signals. The role of the instrument in assessing the efficiency of any inherently fluorescent ophthalmic drug as well as monitoring other medication that might produce fluorescent compounds in the eye will be discussed. We furthermore believe that the instrument might also be capable of monitoring certain bodily processes which have an impact on the compounds present in the eye.

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The management of glaucoma and intraocular hypertension: current approaches and recent advances

Cited by 46 publications

References 111 publications

Targeting JAK/STAT Signaling Pathway in Inflammatory Diseases

Targeting JAK/STAT Signaling Pathway in Inflammatory Diseases

Potential effects of systematic errors in intraocular pressure measurements on screening for ocular hypertension

Tracking ophthalmic drugs in the eye using confocal fluorescence microscopy

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