|Posted on April 11, 2021 at 11:05 PM|
|Posted on March 17, 2021 at 7:30 PM|
Two Australian ophthalmologists are repurposing a common cholesterol-lowering drug into a topical ocular therapy for dry eye and blepharitis, which was given to a patient as part of an initial trial who went 90 seconds without blinking.
Dr Kenneth Ooi and Professor Stephanie Watson, from the University of Sydney’s Save Sight Institute, have completed a pilot study of their therapy called Atorvastatin, which they believe has the potential to treat both evaporative and aqueous deficient forms of the disease.
Unlike other therapies on the market, the formulation has multiple mechanisms of action and, if successful, could fill a distinct gap in a global market estimated to be worth up to $7.7 billion within the next five years. However, the research will need to overcome funding hurdles to reach the next phase of development.
The tear film stabiliser has been repurposed from oral statins, which have well known cholesterol-lowering and immunomodulatory properties. Pfizer’s Lipitor is the gold standard statin and continues to generate roughly $2 billion per year in sales, despite its patent expiring eight years ago.
Ooi and Watson’s use of statins as a topical ocular therapy for dry eye and blepharitis is novel. It is non-steroidal with no steroid-like related side effects.
According to Ooi, the Australian market is reflective of much of the western world, with treatment choices largely limited to LFA-1 inhibitor lifitegrast (Xiidra) and variants of cyclosporine (such as Restasis, Cequa and more recently Ikervis). There are also many over-the-counter therapies, some of which are wetting agents that don’t address the underlying mechanisms of dry eye. These have a place for minor dry eye but there remains an unmet need for cost-effective, side effect-free treatments for moderate to severe forms of the disease.
“Atorvastatin is multi-modal in its mechanism of action compared to a number of competitors on the market or in the pipeline which have only one or predominantly one mechanism of action,” Ooi said.
In a recent pilot study of 10 patients with blepharitis and dry eye, which often co-exist, Ooi recorded positive results with reduced corneal fluorescein staining and conjunctival redness, improved tear break-up times (TBUT) and normalised Schirmer’s wetting. There was improved blepharitis, as well as dry eye symptom scores.
“One patient in particular was able to keep her eyes open after treatment (without blinking) for 90 seconds. Her initial TBUT was four seconds and her Schirmer’s wetting, initially at 7mm, stabilised to 15mm after one month of treatment,” he said.
“No local or systemic adverse effects were recorded and patients favourably rated acceptability and ease of use of topical statin therapy.”
Ooi now has his sights set on obtaining further clinical data to optimise the dosing frequency. They are looking to offer the opportunity to the pharmaceutical industry and venture capitalists locally and overseas to fund the work.
He hoped Atorvastatin may one day be used to treat evaporative dry eye, as well as the aqueous deficient form, including post-cataract and refractive surgery dry eye, post-intravitreal injection dry eye and Sjogren’s syndrome, as well as allergic dry eye and ocular pain.
The work stems from Ooi’s research into statins as a potential oral steroid- sparing agent for uveitis at the Institute of Ophthalmology, University College London.
“Knowing that inflammation is associated with dry eye and that research indicates there may be an excess of free cholesterol in the lipid layer in meibomian gland dysfunction contributing to evaporative dry eye, statins came to me as being potentially ideally placed as repurposed novel tear film stabilisers,” he said.
They have secured patents for topical statins as a novel tear film stabiliser in Australia, Japan and Europe, and are filing in the US. There is the potential for novel spin-off patent generation as well.
|Posted on March 17, 2021 at 7:25 PM|
Patients suffering from dry eye disease symptoms have a lower quality of life compared to those without symptoms, a new study reports. The findings showed that patients with the condition reported negative effects on visual function, their ability to carry out daily activities and their work productivity.
Dry eye disease is a common condition and a frequent reason for patients to seek medical care. It can affect people of any age but is most prevalent in women and in older people. Symptoms include irritation and redness in the eyes, blurred vision, and a sensation of grittiness or a foreign body in the eye. It has been reported that up to a third of adults over 65 years old have the condition, although the actual number is likely to be higher as there is no established diagnostic test and people with mild symptoms are less likely to report them to their doctor.
Treatment often involves prescriptions of artificial tears, ocular lubricants and astringents, which come at a cost to the NHS; in 2014, 6.4 million items were prescribed at a cost of over £27 million.
This new study, led by the University of Southampton, set out to explore how dry eye disease affects the lives of adults in the UK through an online survey of one thousand patients with the condition and further one thousand without. Participants undertook a questionnaire from the National Eye Institute about their visual function and a EuroQol questionnaire on health-related quality of life. Those who declared that they experienced dry eye disease also answered further questions to assess the severity of their symptoms.
The results, published in the journal BMJ Open, showed that a higher proportion of participants with dry eye disease had problems with mobility and experienced more difficulties in their day-to-day activities than patients without the condition. The surveys also revealed they were more likely to suffer from anxiety and depression.
Those with the most severe symptoms we more likely to experience a negative impact on their social and emotional functioning as well work productivity, including missing more time from work as a result of their symptoms.
Dr Parwez Hossain, Associate Professor in Ophthalmology at the University of Southampton, led the study. He said: "This study provided some very useful information on the burden that dry eye disease places on patients. As well as confirming the impact on work and social lives we also discovered showed that the extent of the effects are consistent with the severity of symptoms. We also found that participants with dry eye disease symptoms were a lot more likely to suffer from other comorbidities, twice as many suffered from arthritis, hearing loss or irritable bowel disease compared to the cohort without symptoms.
"Whilst we cannot draw causal associations through this study, the presence of dry eye disease does appear to impact on an individual's health and vision related quality of life."
Although both groups reported similar levels of digital screen use and reading, the cohort with symptoms reported more exposure to environmental factors such as air conditioning, forced heating or air pollution. The research team believe that these factors could either contribute to dry eye disease, or be noticed more by sufferers.
Reference: Hossain P, Siffel C, Joseph C, et al. Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey. BMJ Open. 2021;11(3):e039209. doi: 10.1136/bmjopen-2020-039209
|Posted on March 17, 2021 at 7:20 PM|
Whether they are tears of pain or tears of joy, the truth about tears is that these tiny, salty droplets are essential for the nutrition, lubrication, and protection of our eyes.
But the precise biological mechanism behind how tears accomplish these feats was hazy. Part of the problem is there are few good ways to study crying in the lab, but a new study might offer a pathway to greater clarity. In a new paper published this week in the journal Cell Stem Cell, scientists describe how they grew cultured cell analogs of human tear glands in the lab, known as organoids, and, perhaps more incredibly, how they managed to make these tear glands cry.
WHY IT MATTERS — Aside from the visual poetry of having artificial lacrimal glands bawling away in a petri dish in a lab, the fact is this may represent a watershed moment in treating dry-eye disease.
Hans Clevers is group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research in the Netherlands and lead author on the new study. He tells Inverse that the organoids open new avenues for treatment previously denied people who experience chronic dry eyes. An estimated 5 percent of the population experience dry eyes.
“The biggest promise is the fact that we are now in a position to start thinking about treatment of dry eyes with cells,” Clevers tells Inverse.
“And I guess the nicest takeaway for the non-scientists is the fact that you can actually grow tear glands in a dish and make them cry,” he adds.
The lab-grown organoids, which are essentially a collection of human stem cells cultured in a dish and coaxed into taking on certain traits analogous with actual human cells, could potentially parlay into a totally new treatment themselves. Essentially, it may be possible to one day transplant organoid-based replacement glands into a human eye: something the research community has been working towards for years.