Scarring and contraction in and around the eye are very important causes of visual morbidity, and play a part in the failure
of treatment for most major blinding diseases today. Examples include lens capsule contraction, proliferative vitreoretinopathy,
macular scarring, corneal scarring, glaucoma surgery, and eyelid and orbital contraction following disease.
The theme also includes diseases such as severe retinopathy of prematurity, for which there are no effective treatments and which
result in a lifetime of blindness. Many researchers and groups at Moorfields and the UCL Institue of Ophthalmology work on virtually
all of these conditions. Appropriate delivery and formulation systems will be developed through this theme.
We are focussing on developing new surgical techniques to improve surgery based on basic laboratory understanding of
biological responses; the role of growth factors and their effect on ocular scarring; the cellular and molecular basis of cell motility
(spontaneous movement) and scarring; and ocular stem cells – basic biology and therapeutic use including prevention of
scarring, tissue reconstruction and regeneration.
Why scarring is important
Our focus is the efficient development of new
clinical treatments to control scarring (fibrosis)
after surgery and disease. The causes of fibrosis are
complex and contribute to many human diseases,
including every major blinding disease. There is a
large unmet need for anti-scarring therapies that
can be used for disease treatment and to manage
healing after surgery. Preventing scarring also helps
the body to regenerate, and encourages stem cells
to restore the eye.
Improving anti-scarring treatments
Administration of anti-cancer agents directly into the eye after
glaucoma filtration surgery to control fibrosis, and therefore manage healing,
is currently the best clinical treatment available. There are many side effects
because repeat injections of high doses that are naturally and rapidly cleared in
some regions of the eye (eg the conjunctiva) are nevertheless toxic locally and
systemically.
To address toxicity, we have discovered that repeat
injections of a drug called metalloprotease inhibitor
(MMPI) have a markedly beneficial effect on scarring
reduction without the toxicity of anti-cancer agents.
New methods of drug delivery
To address tissue-specific pharmacokinetics
(what the body actually does to the drug, as
opposed to what the drug does to the body),
we have developed a novel, small, resorbable
tissue tablet to release MMPI locally at the fibrotic
site. Our results support a clear pathway to develop
the MMPI tablet to treat post-surgical fibrosis that
has a very good chance of success. If post-surgical
scarring can be controlled and the surgery is
successful long term, we have shown in large
trials that it is possible to halt the progression
of glaucoma.
We have also developed a prolonged dosage
form of an antibody, a protein-based medicine.
Antibodies are usually administered as injections,
but we have developed a tablet form, whereby a
single tablet can be placed at the site of surgery,
and remain biologically active over an extended
period of time. A recent study has shown this new
antibody tissue tablet to be more efficacious than
any treatment now used clinically.
Since glaucoma is the second leading cause of
blindness worldwide, the development of these
new medicines will allow simplification during
surgery and in post-surgical procedures. This will
potentially allow glaucoma filtration surgery to
be conducted more widely to halt progression
of glaucoma in a greater number of patients.