Dry Eye Disease

Dry eye disease (DED), or more formally known as Keratoconjunctivitis sicca (KCS) or keratitis sicca, is an inflammatory eye disease characterised by eye dryness on the surface of the eye. It is the most common eye disease by far, affecting 5-6% of the population in general, and it becomes more common with age, with a third of elderly people suffering from DED. It is usually a chronic problem and it can be debilitating in severe cases.


Symptoms and cause

DED is characterised by eye dryness and is associated with one or more of the following symptoms:

  • Pain
  • Itching
  • Redness
  • Blurring of vision
  • Grittiness (may be likened to a feeling of a foreign body or sand in the eye)
  • Light sensitivity

Most sufferers have mild-to-moderate symptoms and can gain adequate symptomatic relief from topical lubricants (eye drops). However, when severe, the disease can have a significant impact on a person’s quality of life as their vision may be notably blurred or they may struggle to keep their eyes open. Over time, the lack of appropriate lubrication can also result in increased wear on the surface of the eye, leading to longer term changes and other complications which in some rare instances can result in a loss of vision.

The exact cause of DED remains unclear but it is known to be an inflammatory disease and tear abnormality commonly results in the symptoms of DED. The eye depends on tears to provide constant moisture and lubrication to maintain vision and comfort. Tears also contain a range of other important molecules, including certain growth factors and vitamin A which play important roles in the maintenance of a healthy ocular surface (epithelial layer).

Reduced tear production, which is common post-menopause and with aging, or abnormal spreading of tears, due to certain problems with the eyes or eyelids, can also lead to DED. It is also known that about half of contact lens wearers suffer from dry eyes while several classes of drugs increase the risk of DED. It can also be caused by heat or chemical burns, or sometime by certain viruses.

Prevalence and diagnosis

The exact prevalence of DED is unknown due to a lack of consistent definition of the disease over the years and until recently, the lack of a simple conclusive diagnostic test. However, it is generally estimated to affect 5-6% of adults, with women more commonly affected than men. It increases with age, with more than 15% of the population over the age of 65 suffering from dry eye, although some estimates are as high as one third.

DES can usually be diagnosed on the basis of the symptoms alone although specific tests are also available.

Treatment and unmet needs

The use of ‘artificial tears’ eye drops can provide temporary relief when used every few hours to provide additional lubrication and rehydration to the eye. It is the mainstay of DED treatment and a large proportion of sufferers with mild to moderate disease simply self-medicate with such products obtained over-the-counter. However, doctors may also look to manage the underlying inflammation, particularly in more severe cases, using mild topical steroids or with topical immunosuppressants. While generally effective in the short-term, they are not suited to long-term therapy due to safety and tolerability issues. In severe cases, eye specialists may look to a range of other treatment options to improve the lubrication of the eye.

Although many patients self-medicate, creating a global market for artificial tears which exceeds half a billion dollars each year, a large number of patients still seek medical help, creating a considerable healthcare burden.  As currently available treatments have limited efficacy, particularly over the long-term, provide only symptomatic improvement and or are associated with side-effects that include burning and stinging, there remains a major unmet medical need for more effective treatments for DES.

Our approach

TopiVert’s NSKIs promise to deliver long-term efficacy, improving both signs and symptoms of dry eye disease by effectively treating the underlying inflammation. TOP1630, the Company’s lead NSKI for ophthalmology, has demonstrated an excellent activity profile in in vitro and in vivo pre-clinical inflammatory models where it was shown to be potent and have a fast onset of action. When administered as eye drops, TOP1630 is taken up and retained by target inflammatory cells in the cornea but has minimal systemic absorption, making it an ideal topical eye therapy. TOP1630 recently demonstrated proof of concept in a Phase 1/2a study in patients with DED in the US. 

  • TOP1630 improved multiple symptom and sign endpoints in both environmental and controlled challenge settings
  • TOP1630 demonstrated excellent safety and placebo-like tolerability and comfort profiles