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Keratoconus: Know Your Cone

Keratoconus is a worldwide problem, affecting around one in 400 to one in 2,000 people. It can lead to a host of visual problems, all the way from simple discomfort to blindness. The precise etiology of keratoconus has long been a mystery, though it’s known to be a multifactorial problem. Because its onset is poorly understood, methods of prevention and targeted treatments have been difficult to develop. 

However, a potential biomarker may shed light on the development of keratoconus. Dr. Jesper Hjortdal discussed such a biomarker in a recent talk at the 37th World Ophthalmology Congress  (WOC2020 Virtual®). 

Prolactin-Inducible Protein and Keratoconus

Keratoconus: Know Your Cone
Unfortunately, the type of cone in keratoconus isn’t sweet or desirable. 

The biomarker indicated by Dr. Hjortdal is prolactin-inducible protein (PIP), which he and a team first identified in 2014. PIP is known to be regulated by sex hormones. It’s found in lacrimal fluid, saliva, tears, sweat, breast milk and other human secretions. Upregulated PIP has been indicated as a potential cause of breast cancer

Dr. Hjortdal’s research indicates that keratoconus patients have notably downregulated PIP levels compared to healthy subjects. In Dr. Hjortdal’s work, keratoconus patients displayed significantly lower levels of PIP in tears, saliva and plasma. PIP is known to play a role in the cornea, but its exact function is still a bit of a mystery.

According to Dr. Hjortdal, “If PIP were to be used as a keratoconus biomarker and/or a therapeutic target, this would be a paradigm shift in keratoconus research, and a huge step towards eliminating keratoconus and all the vision threats that come with it.” 

He noted that targeting PIP directly or indirectly may lead to effective treatments both in the early and advanced stages of keratoconus. Measuring PIP levels may also prove a useful diagnostic supplement test, and may even be more useful for diagnosis than tomography. Interestingly, PIP levels were unaffected by the severity of keratoconus.

Keratoconus Associations

Keratoconus: Know Your Cone
Keratoconus appears to be bundled with other conditions.

Keratoconus often begins during adolescence, when sex hormones change rapidly in individuals. This link may raise eyebrows when one recalls that PIP levels are regulated by sex hormones. More research needs to be done into the connection, but it’s an interesting start. 

Oddly enough, keratoconus is associated with a wide range of other conditions. For example, keratoconus patients had:

  • Twice the average rate of asthma
  • Three times the average rate of allergic rhinitis
  • Seven times the average rate of atopic dermatitis
  • A 69% higher rate of depression

There appears to be no significant link between diabetes and keratoconus or breast cancer and keratoconus, despite the latter’s association with PIP. 

Some social factors are also associated with keratoconus. For example, in Dr. Hjortdal’s work, 67% of keratoconus patients were male. In a further head-scratcher, non-Europeans had three times the chance of developing keratoconus as Europeans did. What’s more, people living in small towns had a lower chance of developing keratoconus as those living in the Danish capital of Copenhagen. Further, single people had a 27% higher chance of developing keratoconus than those in a relationship, though income appeared to have no effect. 

Where to Go From Here?

Keratoconus: Know Your Cone
There are still plenty more steps to take to get to the top.

From the outside, it certainly looks like there are some puzzle pieces to match up. The link between sex hormones, PIP and keratoconus provide one major part of the equation. The social aspect provides some interesting leads as well, but to draw any conclusions yet would be … well, jumping to conclusions. In the meantime, having a potential biomarker for keratoconus can lead to further steps for valuable treatments for the disease. 

Knowing that lower PIP levels are related to keratoconus, for example, could lead to treatments that upregulate PIP. But knowing that upregulated PIP levels are associated with breast cancer, for example, means that caution is advisable. 

Whatever the case, a valuable step in science of any variety is just that. Baby steps are as important as giant leaps. Here’s to hoping there will be more of them. 

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