Overview
Cataract affects tens of millions of people. It leads to blurred vision as the lens in the eye clouds over (cataract). It can be treated with surgery to remove the cataract and replace it with a clear artificial lens. But some cells from the original lens will always remain. In time, these cells can grow across the back of the artificial lens, making vision hazy again, usually about two years after surgery. This is known as ‘posterior capsule opacification’ or PCO. It’s the most common complication of cataract surgery. PCO can be delayed with different artificial lens designs, but this hasn’t completely solved the problem.
There is evidence that keeping the artificial lens out of contact with the layer of tissue (called the capsular bag) that surrounds it can prevent PCO. This is done by keeping the bag open after surgery so that fluid in the eye (aqueous humour) can flow in and out of the bag. It changes the way lens cells behave.
However we don’t know exactly how the change helps prevent PCO. So this projects aim is to learn more about how an ‘open bag’ affects lens cells. This could lead to new designs for future artificial lenses that can reduce PCO and mean better vision for patients.
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Publications
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Eldred JA, McDonald M, Wilkes HS, Spalton DJ, Wormstone IM. Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target. Scientific Reports. 2016 Apr 14;6:24453.
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Wormstone IM, Eldred JA. Experimental models for posterior capsule opacification research. Exp Eye Res. 2016 Jan;142:2–12.
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Eldred JA, Spalton DJ, Wormstone IM. An in vitro evaluation of the Anew Zephyr open-bag IOL in the prevention of posterior capsule opacification using a human capsular bag model. Invest Ophthalmol Vis Sci. 2014 Nov;55(11):7057–64.
- Spalton DJ, Russell SL, Evans-Gowing R, Eldred JA, Wormstone IM. Effect of total lens epithelial cell destruction on intraocular lens fixation in the human capsular bag. J Cataract Refract Surg. 2014 Feb;40(2):306–12
- Wormstone IM, Eldred JA, Dawes LJ. Fibrotic Modifications of the Lens Epithelium. In: Saika S, Werner L, Lovicu FJ, editors. Lens Epithelium and Posterior Capsular Opacification. Springer Japan; 2014. p. 143–58
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Research update
In this project the research team looked at whether there is a critical number of cells left behind after surgery to remove the natural lens, in order for PCO to develop. They found that even a very small number can trigger it, and the fewer cells left, the slower PCO is to develop. However they also found that getting rid of all of the remaining cells has an impact on the artificial lens, which in turn might affect the patient’s vision. This is something that artificial lens manufacturers will need to consider in future designs.
The team has also found more evidence to support the idea that keeping the capsular bag open can delay PCO by diluting the signals from growth factors that encourage the lens cells to grow and spread. They’ve found that vascular endothelial growth factor (VEGF) plays an important role in cell growth and survival, so it could be a good target for developing anti-VEGF drugs to work together with new lens designs.
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Scientific summary
To identify the biological basis of open bag strategies for the prevention of posterior capsule opacification
At cataract surgery an intraocular lens (IOL) is placed in the capsular bag. Within 3-4 weeks this shrinks and fibroses around the IOL. Clinical studies show that IOLs with a square edge profile and complete contact between the IOL and the anterior capsule are currently the best way to prevent PCO. This has been challenged by recent clinical and experimental observations. Studies in rabbits suggest that if the capsular bag is kept open with separation of contact between the anterior and posterior capsule by an ‘open bag device’ PCO is dramatically reduced. The hypothesis is that circulation of aqueous through the bag alters LEC behaviour, possibly by washing out growth factors from the bag, but a scientific basis for this is lacking.
In this project the research team investigates the effect of open bag strategies on LEC behaviour to further understanding of the physiological mechanisms regulating LEC migration, proliferation and transformation. To assess open-bag devices the team is employing several versions of the human post mortem capsular bag models, with which they have extensive experience, and that reflect changes seen clinically and in post-mortem tissue. On-going cellular changes to the capsular bag are being observed using phase and modified dark-field microscopy.
Cellular organisation and structure at end-point will be assessed using immunolabelling and fluorescence microscopy. Growth factor levels in culture medium and in the lens capsule will be determined using suspended bead protein array. This project will establish the advantages of open bag devices over conventional IOLs and influence the future design of IOLs