Glaucoma is one of the leading causes of preventable vision loss and the second leading cause of blindness in the world.1 Many treatment options exist to manage its progression; for example, topical medications are one of the longstanding, first-line therapies for these patients.
However, beyond the usual focus on eye pressure, we're discovering how the health of the ocular surface is a key player in the well-being of those managing their glaucoma.
This article looks to shed some light on the link between ocular surface disease (OSD) and glaucoma and how it affects comfort, mental health, and the treatment compliance of our patients.
How glaucoma impacts the ocular surface
As mentioned previously, glaucoma affects tens of millions of people worldwide, and it’s estimated nearly 10 to 15% of patients suffer from OSD. The connection between these two disorders is quite significant, as it’s estimated that 49 to 59% of glaucoma patients using topical treatment have concurrent ocular surface disease.1
OSD becomes more prevalent and severe as the number of anti-glaucomatous medications increases and as the duration of the treatment extends.2 Some smaller studies have elucidated the glaucoma-OSD link by showing that nearly 50% of ocular hypertensives will require at least two topical medications within 5 years of their diagnosis.1
The role of topical glaucoma medications in OSD
This increased association is thought to be due to the extended and repeated exposure to the medication(s) itself as well as its preservatives. Eye drop preservatives aim to reduce the risk of bacterial contamination of the medication and can also aid in drug penetration.
The most common preservative used in glaucoma management drops is benzalkonium chloride (BAK). BAK can increase ocular surface inflammation, damage corneal and conjunctival tissue, and cause a decrease in goblet cell density.3
Likewise, patients who use topical glaucoma medications have been found to have more conjunctival keratinization and increased inflammatory cells of their ocular surface than those who have not been using these treatments. The pathways of ocular surface stress are all well explained in the article by Li et al., but will be briefly summarized here.
Beta-blockers
Beta-blockers are normally dosed once to twice a day and can reduce the intraocular pressure (IOP) by around 20%. These drops work to decrease aqueous humor production by binding to ocular beta receptors.
These receptors can also be found in the lacrimal glands, and blocking them can result in reduced tear production. It’s also been suggested that these drops have a negative impact on the activity of limbal stem cells and can result in delayed corneal wound healing.3
Alpha-antagonists
Alpha-agonists aim to decrease aqueous production while increasing outflow by the uveoscleral pathway. They’re typically dosed twice a day and reduce IOP by roughly 20%.
Medications in this category are known to pose a risk of follicular or allergic conjunctivitis in about 1 in 3 patients.3
Carbonic anhydrase inhibitors
Carbonic anhydrase inhibitors (CAIs) can be dosed two times per day to reduce the production of aqueous humor and, in turn, the IOP by about 20%. These drops are thought to have a low pH level that contributes to their ocular surface damage.
This typically remains superficial, similar to how acids denature and break down epithelial cells without significant penetration.
Prostaglandin analogs
Prostaglandin analogs are conveniently dosed once a day to increase the uveoscleral outflow of aqueous humor and decrease IOP by about 30%. These drops have been linked to meibomian gland dysfunction (MGD), though some of their effects on the ocular surface remain uncertain at this time.
Rho-kinase inhibitors
Rho-kinase inhibitors are usually prescribed once per day and increase the outflow of aqueous humor via the trabecular meshwork, thereby reducing the IOP to a slight degree (~5mmHg).3
It’s been demonstrated these cause conjunctival hyperemia, but it’s worth noting these are some of the more recently released topical options, and they will require more testing better to understand their long-term effects on the ocular surface.
Diminished glaucoma patient compliance due to side effects
Given the plethora of side effects, compliance suffers. One study reported only 50% of patients were still using their prescribed medication after 6 months, and an even lower 37% remained compliant after 3 years.4
Considering that we know glaucoma requires monitoring and treatment well beyond this timeline, it’s up to us to determine the reasons for this dropout and do our best to minimize it. To do so, we may need to look at other therapy options or surgical procedures to manage their glaucoma, minimize treatment complexity or the number of drops instilled, and treat concurrent OSD.
It’s been suggested that anxiety, depression, and other mental health changes can have connections with ocular surface disease as well.5 Meaning, people with more severe objective findings may experience more of these psychological complications, and they also may not self-report their symptoms to the extent one would hope or expect.
Assessing glaucoma patients for OSD
As you can see, there’s a variety of negative impacts these drops can have on the ocular surface. Therefore, it’s important for providers to address these signs and symptoms early and effectively, especially before beginning topical therapy.
This will set the stage to improve patient comfort and glaucoma treatment compliance, thereby slowing and/or preventing progression.
Integrating OSD diagnostic tests into eye exams
When it comes to assessing the eye for OSD, you don’t know if you don’t look and ask. It’s worth mentioning that an ocular surface assessment can be quite thorough and take a not-insignificant amount of time, so take that into consideration when scheduling these appointments and consider creating a separate encounter to focus solely on the ocular surface.
Questionnaires can be very helpful in establishing what and how a patient is feeling with the comfort of their eyes. This can provide a reference point in the future to compare how they may feel their condition is being managed. Properly utilize tests and vital dyes at your disposal to evaluate the ocular surface and tear chemistry carefully.
Checking for OSD during eye exams
When examining the ocular surface, I like to work my way out to in, starting with the eyelids. A few findings that are worth looking for here can include meibomian gland quantity and quality, telangiectasia, hyperkeratinization of the lid margin, eyelid notching or scalloped margins, lid wiper epitheliopathy, staining of the line of Marx, lid laxity, and incomplete blinks.
Next, let’s move on to the conjunctiva with all of its creases and folds. Take your time looking for hyperemia, chemosis, conjunctivochalasis, papillae or follicles under both the lower and upper lids (get out those cotton swabs), and conjunctival staining.
Lastly, it’s time to focus on the tear film and cornea. Carefully observing the cornea for surface staining, noting its location and pattern, measuring tear break-up time, measuring the height of the tear meniscus, and assessing the tear film osmolarity can be important factors to consider.
Some of these OSD signs and symptoms can have ties to toxicity-related findings, especially for alpha-agonist medications. These may include redness and injection of the conjunctiva, conjunctival chemosis, itch and irritation of the eyes and surrounding tissue, periorbital edema, telangiectasia, and MGD.
Managing OSD linked with glaucoma
When recommending OSD management options for someone with glaucoma, there are many pathways at our disposal. Preservative-free artificial tears can be utilized during the day to alleviate discomfort.
Options such as Optase, iVizia, Blink, and other solutions that include sodium hyaluronate can be especially beneficial for their prolonged effect and viscoelasticity. According to iVizia’s reference material, their ingredients of povidone, hyaluronic acid, and trehalose have demonstrated protection of the ocular surface and goblet cells.
Additionally, omega-3 supplements can also be helpful in reducing inflammation that occurs with prolonged topical glaucoma medications. Likewise, topical immunomodulation options such as cyclosporine drops can help combat the ocular surface inflammation and irritation that occurs in these patients.
If meibomian gland dysfunction is present, or lid pathology exists, one should also address those findings. This may include the use of moist-heat compresses and lid hygiene practices.
Minimizing the medication burden on glaucoma patients
It’s worth bringing up again the toll that comes from managing so many medications, drops, and the burden that builds from this. Ocular surface management options that reduce, or simply do not add, to that load can be especially helpful to a patient.
Therapies such as varenicline solution nasal spray, thermal pulsation of the meibomian glands, radiofrequency treatments, intense pulsed light (IPL) sessions, or other non-drop options are worth considering.
These can free up time for the patient during the day, reduce the number of drops they’re juggling, and provide effective, long-lasting relief for their signs and symptoms
Alternative glaucoma treatments to topical therapies
Newer treatment options for glaucoma are rapidly arising and becoming more accepted. These would reduce the need for topical glaucoma management for some patient groups. By removing frequently dosed, chronic topical medications, we improve our patients' ocular surface as we’re now dealing with one, two, or even three fewer variables.
Sometimes this transition is easier said than done, and their signs and symptoms may continue to need management. However, these drops bear their own mental and psychological burden, and we can alleviate that with these options.
Some options in this new category include selective laser trabeculoplasty (SLT), minimally or micro-invasive glaucoma surgeries (MIGS), and various new injectable implants and punctal plugs. Again, some of these therapies are relatively new but are gaining traction quickly and moving to providers' preferred first-line treatment for certain patients.
The Laser in Glaucoma and Ocular Hypertension (LiGHT) study demonstrated a lower side-effect profile and improved quality of life with SLT compared to long-term topical management.3
Conclusions
Glaucoma is more than a disease of the posterior segment. If we end our exam there, we’ve missed a few key components of managing their glaucoma including the ocular surface integrity, compliance, and how quality of life can be improved.
Navigating the crossroads of OSD and glaucoma requires careful attention, the prioritizing of the ocular surface, and a proactive approach to the evolving treatment options available.
