Posterior Capsule Opacification: A Cell Biological Perspective

Wormstone, I. Michael

doi:10.1006/exer.2001.1153

Cited by 211 publications

(44 citation statements)

References 50 publications

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“…The new synthetic IOL is placed on the posterior capsule, which acts as a scaffold or structure to support the new lens. 131 Lens epithelial cells (LECs) are the cause of PCO and can affect vision in two ways. Pearl-type PCO is caused by LECs from the anterior chamber migrating to the lens over the axis of vision, proliferating and then becoming cloudy as collagen is laid down and lens fibre regeneration occurs.…”

Section: Overview Of Posterior Capsule Opacificationmentioning

confidence: 99%

“…Both processes cause vision to degenerate, light becomes scattered and patients suffer from glare from lights at night and reduction in visual acuity (VA). [131][132][133] PCO or 'secondary cataract' is the most common complication of cataract surgery; 134 incidence is reported to be 12%, 21% and 28% at 1, 3 and 5 years respectively. 135 …”

Section: Overview Of Posterior Capsule Opacificationmentioning

confidence: 99%

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Using clinical practice variations as a method for commissioners and clinicians to identify and prioritise opportunities for disinvestment in health care: a cross-sectional study, systematic reviews and qualitative study

Hollingworth

Rooshenas

Busby

et al. 2015

Health Services and Delivery Research

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BackgroundNHS expenditure has stagnated since the economic crisis of 2007, resulting in financial pressures. One response is for policy-makers to regulate use of existing health-care technologies and disinvest from inefficiently used health technologies. A key challenge to disinvestment is to identify existing health technologies with uncertain cost-effectiveness.ObjectivesWe aimed to explore if geographical variation in procedure rates is a marker of clinical uncertainty and might be used by local commissioners to identify procedures that are potential candidates for disinvestment. We also explore obstacles and solutions to local commissioners achieving disinvestment, and patient and clinician perspectives on regulating access to procedures.MethodsWe used Hospital Episode Statistics to measure geographical variation in procedure rates from 2007/8 to 2011/12. Expected procedure numbers for each primary care trust (PCT) were calculated adjusting for proxies of need. Random effects Poisson regression quantified the residual inter-PCT procedure rate variability. We benchmarked local procedure rates in two PCTs against national rates. We conducted rapid systematic reviews of two high-use procedures selected by the PCTs [carpal tunnel release (CTR) and laser capsulotomy], searching bibliographical databases to identify systematic reviews and randomised controlled trials (RCTs). We conducted non-participant overt observations of commissioning meetings and semistructured interviews with stakeholders about disinvestment in general and with clinicians and patients about one disinvestment case study. Transcripts were analysed thematically using constant comparison methods derived from grounded theory.ResultsThere was large inter-PCT variability in procedure rates for many common NHS procedures. Variation in procedure rates was highest where the diffusion or discontinuance was rapidly evolving and where substitute procedures were available, suggesting that variation is a proxy for clinical uncertainty about appropriate use. In both PCTs we identified procedures where high local use might represent an opportunity for disinvestment. However, there were barriers to achieving disinvestment in both procedure case studies. RCTs comparing CTR with conservative care indicated that surgery was clinically effective and cost-effective on average but provided limited evidence on patient subgroups to inform commissioning criteria and achieve savings. We found no RCTs of laser capsulotomy. The apparently high rate of capsulotomy was probably due to the coding inaccuracy; some savings might be achieved by greater use of outpatient procedures. Commissioning meetings were dominated by new funding requests. Benchmarking did not appear to be routinely carried out because of capacity issues and concerns about data reliability. Perceived barriers to disinvestment included lack of collaboration, central support and tools for disinvestment. Clinicians felt threshold criteria had little impact on their practice and that prior approval systems would not be cost-effective. Most patients were unaware of rationing.ConclusionsPolicy-makers could use geographical variation as a starting point to identify procedures where health technology reassessment or RCTs might be needed to inform policy. Commissioners can use benchmarking to identify procedures with high local use, possibly indicating overtreatment. However, coding inconsistency and limited evidence are major barriers to achieving disinvestment through benchmarking. Increased central support for commissioners to tackle disinvestment is needed, including tools, accurate data and relevant evidence. Early engagement with patients and clinicians is essential for successful local disinvestment.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

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Section: Overview Of Posterior Capsule Opacificationmentioning

confidence: 99%

Section: Overview Of Posterior Capsule Opacificationmentioning

confidence: 99%

Using clinical practice variations as a method for commissioners and clinicians to identify and prioritise opportunities for disinvestment in health care: a cross-sectional study, systematic reviews and qualitative study

Hollingworth

Rooshenas

Busby

et al. 2015

Health Services and Delivery Research

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“…Due to fibrotic modifications to the lens epithelial cells and consequent matrix alterations, the posterior capsule exhibits light scattering structures that reduce visual quality (d); this condition is known as posterior capsule opacification. First published in Eldred et al [3] with permission from the Royal Society and Wormstone [2] with permission from Experimental Eye Research…”

Section: Inflammationmentioning

confidence: 98%

“…The lens epithelium is a critical component in the maintenance of the normal healthy lens; however, fibrotic modifications can occur that are disruptive to visual quality [1][2][3]. Fibrosis affects many tissues and has been described as "a pathological condition in which tissue structure is disrupted by production of excessive extracellular matrix (ECM)" [4,5].…”

Section: Fibrosis and The Lensmentioning

confidence: 99%

Fibrotic Modifications of the Lens Epithelium

Wormstone

Eldred

Dawes

2014

Lens Epithelium and Posterior Capsular Opacification

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Maintaining lens integrity is a lifetime ambition of the lens. However, if this integrity is breached through an altered ocular environment or physical disruption, such as cataract surgery, then fibrotic modifications to the lens can occur that are ultimately detrimental to vision. Fibrotic changes involve hyperproliferation, transdifferentiation from an epithelial to a myofibroblast phenotype, matrix deposition and matrix contraction. Fibrotic conditions of the lens include anterior subcapsular cataract and posterior capsule opacification, which affect millions. In this chapter we will discuss the regulatory mechanisms that facilitate fibrotic events, which will involve the intimate relationship between growth factors (especially transforming growth factor beta-TGF-β), signal transduction pathways and the extracellular matrix.

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“…TGF-b2 has been identified recently as a critical regulator of many pathological growth conditions in the lens [11,12]. The three mammalian TGF-b isoforms, TGF-b1, TGF-b2, and TGF-b3, encoded by three distinct genes, are structurally nearly identical (nine conserved cysteine residues, 76-80% amino acid homology), and synthesized by a wide variety of cell types, including platelets, macrophages, fibroblasts, and tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen peroxide-induced cellular apoptosis is mediated by TGF-β2 signaling pathway in cultured human lens epithelial cells

Cao

et al. 2009

Int Ophthalmol

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The objective of this study was to investigate the signaling characteristics of transforming growth factor-beta2 (TGF-beta2) and the Smads (Caenorhabditis elegans, Sma; Drosophila mothers against dpp, Mad) signal pathway of cellular apoptosis induced by hydrogen peroxide with human lens epithelial cells (HLECs). HLECs were starved for 24 h before exposure to 0.1 mumol/ml of hydrogen peroxide in the presence and in the absence of 0.01 mug/ml of AF-302-NA, a monoclonal anti-TGF-beta2 neutralization antibody. Non-stimulated cells served as controls. Cell apoptosis was examined by in situ immunocytochemistry using terminal deoxynucleotidyl transferase dUTP-mediated biotin nick end labeling (TUNEL) and by flow cytometry (FCM) using Annexin V-FITC apoptosis detection. Gene expression was assessed using the reverse transcription-polymerase chain reaction (RT-PCR). Smad-4 localization was observed by immunocytochemistry. Hydrogen peroxide induced the accumulation of Smad-4 in the nucleus of HLECs, and upregulated the expression of TGF-beta receptors (TbetaRs) mRNA in HLECs, as well as upregulated the expression of the apoptotic gene bax, which leads HLECs to apoptosis. AF-302-NA decreased cellular apoptosis induced by hydrogen peroxide in HLECs and inhibited the translocation of Smad-4 from the cytoplasm to the cell nucleus. Moreover, AF-302-NA upregulated the expression of TbetaRs mRNA and downregulated the expression of bax mRNA in HLECs incubated with hydrogen peroxide. Our study demonstrated that the TGF-beta2 signal pathway participated in the apoptotic signal transfer and might be an initiator of cellular apoptosis of HLECs after incubation with hydrogen peroxide. Interruption of the TGF-beta2 signal pathway could partially protect HLECs from apoptosis induced by incubation with hydrogen peroxide.

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Posterior Capsule Opacification: A Cell Biological Perspective

Cited by 211 publications

References 50 publications

Using clinical practice variations as a method for commissioners and clinicians to identify and prioritise opportunities for disinvestment in health care: a cross-sectional study, systematic reviews and qualitative study

Using clinical practice variations as a method for commissioners and clinicians to identify and prioritise opportunities for disinvestment in health care: a cross-sectional study, systematic reviews and qualitative study

Fibrotic Modifications of the Lens Epithelium

Hydrogen peroxide-induced cellular apoptosis is mediated by TGF-β2 signaling pathway in cultured human lens epithelial cells

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