Eyeblog November 2015

There have been plenty more fascinating articles for us this month.  We include further developments in the treatment of cataracts with simple eye drops.  Could this mean that surgery becomes a thing or the past or will this simply prove an excellent alternative for those that surgery is not an option?  And we are happy to hear that NICE have approved the use of ciclosporin for the treatment of severe keratitis. This will provide clinicians greater access to an excellent treatment options for those patients in whom lubricants have failed.

Please contact me with any questions you might have.

Rachel

Eye drops for cataracts a step closer with newly identified compound[i]

Researchers at the University of California-San Francisco (UCSF) recently published their findings in the journal Science.

Around 30% of the UK population aged 65 or older has a cataract in one or both eyes, with the incidence increasing exponentially with age[ii]

In the early stages, cataracts may be improved with magnifying lenses, new glasses, anti-glare sunglasses or brighter lighting. However, if such treatments fail, surgery is currently the only option.

Surgery for cataracts involves removing the cloudy lens and replacing it with an artificial one. However, Gestwicki and colleagues note that - although highly successful - cataract surgery is costly, and many people with cataracts in developing countries often go untreated as a result.

But in this latest study, the team demonstrates the possibility of a cheaper, more practical alternative to treating cataracts: eye drops containing a chemical that dissolves crystallins - proteins that clump together and cloud the lens.

Crystallins are arranged in the lens in a certain way that allows light to pass through it, enabling us to see. As we get older, however, these proteins can clump together, preventing light from being able to pass through the lens.

For their study, the team used a process called high-throughput differential scanning fluorimetry (HT-DSF) - a method in which proteins give off light when their melting point is reached - to apply heat to both healthy crystallins and their amyloid forms, while also applying various chemical compounds.

The researchers began testing 2,450 compounds, gradually narrowing them down to 12 that helped reduce the melting point of crystallin amyloids to the normal range. The 12 compounds identified were part of a class of chemicals called sterols.

The team identified one - referred to as "compound 29" - that they believed could be added to eye drops to help dissolve amyloid crystallins.

Gestwicki and colleagues then tested compound 29 on crystallin amyloids in a laboratory dish. They found the compound not only prevented clumps from forming, but it also successfully dissolved the clumps that had already formed.

Next, the researchers added compound 29 to eye drops and tested them in mice that possessed mutations that predisposed them to cataracts.

The team used a slit-lamp test to measure lens transparency in the mice and found the eye drops partially restored transparency to the lenses of mice with cataracts. What is more, on applying the eye drops to mice that developed age-related cataracts and cataract-affected human lens tissue that had been removed through surgery, they saw similar results.

The team stresses that the slit-lamp test does measure visual awareness, and as such, clinical trials are needed to determine whether compound 29 can improve vision in humans with cataracts.

The compound has already been licensed, and study co-leader Leah N. Makley, is in the process of formulating the compound so it is ready for human use.

If compound 29 is found to be a success, it may not only lead to new treatments for cataracts; it could also open the door to new treatments for other conditions involving amyloid proteins, such as Alzheimer's disease.

NICE recommends the use of IKERVIS® in England for the treatment of severe keratitis in adult patients with dry eye disease[iii]

NICE issues positive Final Appraisal Determination (FAD) recommending the use of Santen's IKERVIS® (ciclosporin 1 mg/mL eye drops emulsion in single-dose containers) for the treatment of severe keratitis in adult patients with dry eye disease, which has not improved despite treatment with tear substitutes.

IKERVIS® is the first and only topical ciclosporin preparation licensed for the treatment of severe keratitis in patients with dry eye disease in the UK. Approximately 700,000 adults in Europe suffer from the severe form of dry eye disease. Symptoms of dry eye disease include burning, itching and dryness, gritty sensation and photophobia.  Severe keratitis is an inflammation of the cornea, which can result from dry eye disease.

Patients may present with signs of serious ocular surface damage but their symptoms may not correlate to the clinical signs, making diagnosis difficult. However, inflammation if left untreated can lead to further complications, permanent corneal damage and even loss of sight.

Professor Figueiredo, Professor of Ophthalmology at Newcastle's Royal Victoria Infirmary and Newcastle University, said, "NICE's positive appraisal of Ikervis means that UK patients with severe keratitis and dry eye disease will have access for the first time to a licensed product with the potential to have a significant positive impact. Patients with this particularly unpleasant and disabling condition have a seriously impaired quality of life, and patients often have been unable to access licensed treatment that they need. Ophthalmologists now have a new and licensed treatment option that could make a real difference to our patients"

Ciclosporin works by reducing inflammation in dry eye disease.  However, until the launch of IKERVIS®, there has been no topical preparation of ciclosporin licensed in the UK.  With this recommendation from NICE, IKERVIS® provides an important new option for the treatment of patients in England who have not responded to tear substitutes.

The NICE decision was based on data from the SANSIKA trial. This was a double-masked multicentre, randomised, vehicle-controlled six month pivotal phase III trial with a six month open label treatment safety follow up period, which evaluated the efficacy and safety of IKERVIS®, administered once daily in adult patients with severe dry eye disease. Key evidence from SANSIKA showed that IKERVIS® with once-daily dosing, reduces ocular surface inflammation and reduces corneal damage, and is consistent with an improvement in patients' disease severity.

Mr Craig Wallace, General Manager for Santen UK and Ireland said, "This recommendation by the globally renowned NICE institute underscores what an important medicine Ikervis® is for patients with severe dry eye diseases. This is a very proud moment for Santen."



[i] H Whiteman, “Eye drops for cataracts a step closer with newly identified compound”, 6th November 2015, Medical News Today. Retrieved from http://www.medicalnewstoday.com/articles/302121.php. Last accessed on 9th November 2015

[ii] Royal College of Ophthalmology, Cataract Surgery Guidelines, 2010

[iii] “NICE recommends the use of IKERVIS® in England for the treatment of severe keratitis in adult patients with dry eye disease”, 6th November 2015, Medical News Today. Retrieved from http://www.medicalnewstoday.com/releases/302214.php . Lat accessed on 9th November 2015.