Acknowledgments
I would like to thank Sunita Radhakrishnan, Robert Honkanen, and Sarah Weissbart for their valuable input on this topic. Thank you to Samuel Gurevich for helping in editing and being an endless source of support.
Introduction
Glaucoma is an optic neuropathy that most commonly presents clinically with loss of peripheral visual field. 60 million people are estimated to have glaucoma worldwide making it the second most common cause of blindness. , The burden of this visually devastating disease is only expected to increase amid the rapid growth of the aging population, with an estimated 112 million people affected by the year 2040. Glaucomatous visual loss is incurable but its progression can be mitigated with proper intraocular pressure (IOP) control which is the only modifiable risk factor proven to prevent the progression of glaucoma. Current first-line therapy for treatment of this devastating disorder consists of daily drop regimens and/or laser trabeculoplasty. Surgical intervention is traditionally reserved for more advanced or poorly controlled disease although this has changed somewhat in the last several years with the increasing popularity of minimally invasive glaucoma surgery or MIGS as it has been coined.
Although dry eye syndrome (DES) is not generally a blinding disorder, it is incredibly common and has significant morbidity, particularly in the elderly population. Ocular surface disease has an estimated prevalence of approximately 19% in those over the age of 75 and often presents with symptoms of discomfort and blurred vision. Glaucoma and dry eye are two of the most prevalent issues facing ophthalmology patients and they often present together to form a “perfect storm” of trouble. Both glaucoma and dry eye increase with age so it is expected that many patients carry both diagnoses and patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. This is at least in part due to the use of preservative agents such as benzalkonium chloride (BAK) in glaucoma drugs which have a toxic effect on the corneal epithelium. Dry eye is associated with both a decrease in quality of life and a concurrent decrease in compliance with glaucoma topical therapy.
It is helpful to approach glaucoma patients from the perspective of identifying those at high risk for treatment failure because of ocular surface symptoms and target our regimen to optimizing the ocular surface. Likewise, we need to approach our patients presenting for dry eye evaluations that have concurrent glaucoma by optimizing the ocular surface without compromising treatment to optimal IOP to prevent vision loss. We have a significant knowledge gap still to overcome in terms of understanding the interaction of these two disorders. For example, when do the risks of undertaking more invasive glaucoma treatments outweigh the risks of glaucoma progression due to poor compliance? The current thinking on treatment of glaucoma is to increase compliance with therapy as much as possible by making treatment regimens tolerable. We can do this by decreasing the number of drops per day, decreasing the amount of preservative in glaucoma drops, and increasing our use of targeted laser and surgical treatments for glaucoma to decrease the number of drops needed. In addition, we can use our current understanding of dry eye to target treatments that improve the ocular surface so that our glaucoma treatments are better tolerated.
Dry Eye in the Glaucoma Patient
Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film. We see this clinically as tear film instability, ocular surface inflammation, and through our patients’ complaints of ocular symptoms. Glaucoma drops find many “victims” in the tear film including goblet cells, epithelial cells, limbal stem cells, and even the corneal nerves and the eyelids and orbit can be affected. Glaucoma specialists frequently overlook or accept that their treatments aimed at preventing glaucomatous vision loss can cause issues with the ocular surface. Rather than becoming singularly focused on control of IOP above all costs, patient care demands that we try to understand the tear film better. The most recent DEWS II report classifies dry eye into the categories of aqueous deficient, evaporative, and mixed. In the aqueous deficient type, the lipid portion of the tear film is decreased or lacking. This includes Sjögren’s syndrome and lacrimal deficiency or obstructions. The evaporative type can be further divided into intrinsic or extrinsic subtypes. Allergies to glaucoma drops and damage caused by topical drop preservatives fall under the category of extrinsic evaporative dry eye. Meibomian gland deficiency is also a very common sequelae of topical glaucoma medication use. This can be seen clinically as inspissated Meibomian glands with capping and increased telangiectasias at the lid margins.
Preservatives in our medications are understood to be one of the culprits in DES. , Allergic, toxic, and inflammatory mechanisms, as well as type IV allergy can all be involved. In addition to preservative-free glaucoma medications, alternatives to BAK have been used in some commercially available drugs and have shown some decrease in toxicity. In addition, there is some evidence that the active ingredients of both beta clockers and prostaglandins can contribute to DES. Even glaucoma surgery can likewise influence the ocular surface by contributing to limbal stem cell deficiency through limbal-based surgery, cautery, application of antimetabolites, and by bleb formation which changes the contour of the ocular surface making it more difficult for smooth distribution of tears. ,
To make the dry eye diagnosis we have several tools at our disposal. A thorough history is very important. We can quantify patient symptoms more precisely by using questionnaires such as the Ocular Surface Disease Index, Standardized Patient Evaluation of Eye Dryness questionnaire, or Dry Eye Questionnaire 5. , Objectively, tear production is commonly measured with Schirmer’s test or by measuring tear meniscus height. We also quantify tear film stability and ocular surface integrity with fluorescein, rose bengal, or lissamine green dyes. Several commercial devices are available to quickly assess for tear osmolarity and matrix metalloprotein (MMP-0) which have been correlated to ocular surface disease. While these qualitative measures of dry eye can be useful, it is known that the objective severity and the degree of patient complaints do not always correlate. Glaucoma specialists should have a high interest in dry eye as the prevalence of DES in glaucoma population is 40%–60% as compared to the prevalence in the general population of 10%–30%. It has been shown that the number of glaucoma medication and dosing frequency are directly correlated to the prevalence of dry eye and that glaucoma-related dry eye is directly correlated to quality of life. In addition, studies have shown that surgical outcomes for glaucoma procedures may be adversely affected by preexisting ocular inflammation due to glaucoma medications. Many advocate for glaucoma medication holidays and/or pretreatment with topical corticosteroids prior to glaucoma surgery.
There are many options when it comes to treating dry eye. Lubrication is the mainstay of ocular surface treatment, but we need to consider advocating for preservative-free artificial tears and using lubricants of increased viscosity when possible. This is particularly important for our glaucoma patients who are often already getting a dose of preservative in their glaucoma medications. In addition, use of pro-tear film agents such as cyclosporine and lifitegrast, serum tears, and limited use of topical corticosteroids is helpful. , Heat and massage of Meibomian glands can be particularly useful in those with a blepharitis component. More specialized treatments such as in office thermal pulsation treatments and intense light therapy can be considered as well. There has been increased use of scleral contact lenses and PROSE lenses; however, these may limit uptake of glaucoma topical medications and also can cause issues in the setting of previous trabeculectomy or glaucoma drainage device surgery. With all these treatments available, we need to approach the treatment of dry eye in the glaucoma patient in a systematic way that incorporates both appropriate use of dry eye–specific therapies and also tailoring glaucoma therapy to limit ocular surface toxicities.
How to Treat Glaucoma in the Dry Eye Patient
Now that we have discussed how to diagnose and treat dry eye in the glaucoma patient, we will shift our focus toward how to treat glaucoma in our patients with dry eye issues. When both dry eye and glaucoma exist in the same patient, our attention is usually focused on the more vision threatening disease of glaucoma. Dry eye on the other hand tends to be more symptomatic so should not be ignored. Start by finding common ground with your patient. Make a conscious effort to look for dry eye signs and listen to patient symptoms. Studies have shown that most patients tend to tolerate one to two glaucoma medications without too much difficulty. Those patients who have issues tolerating even one topical medication should be offered laser trabeculoplasty early on.
Laser Treatment
Selective laser trabeculoplasty has several advantages. It has good efficacy, eliminates side effects related to topical treatment if used as a first-line approach, and has no adherence issues. Selective laser trabeculoplasty was first introduced in 1995 and received US FDA approval in 2001. It functions by reducing IOP by increasing aqueous outflow through the trabecular meshwork. Recently, a randomized controlled trial (LiGHT), comparing topical medication to selective laser trabeculoplasty as initial treatment, has reaffirmed findings of previous trials showing that laser is an efficacious first-line treatment for primary open angle glaucoma. In the LiGHT trial the majority of patients were drop free at 36 months in this treatment naïve group with no sight-threatening complications. While these studies have not shown specific improvement in health-related quality of life indicators, a decrease in eyelid erythema and conjunctival hyperemia was present in the laser group as opposed to the topical medication group. Laser trabeculoplasty is also not feasible in all types and stages of glaucoma. Finally, although rare, there are potential side effects to laser including inflammation, immediate postlaser elevated IOP, uveitis, and keratitis after laser that in rare cases could necessitate additional intervention.
Medical Therapy
While one might expect the evidence for selective laser trabeculoplasty to promote its use as primary treatment, many patients are still hesitant to have laser as first-line therapy. Another approach would be to try to eliminate or reduce the BAK load on glaucoma patients. We can do this through use of preservative-free medications, BAK-free medications (those with an alternative preservative), and use of fixed combination drugs that reduces the total number of drops per day. Also, we can reduce frequency of medication administration such as use of beta-blocker once per day instead of twice per day, or CAI or alpha agonist twice per day instead of three times per day. Preservative-free medications that are currently available in the United States include tafluprost, timolol, and dorzolamide-timolol fixed combination. It is also possible to obtain glaucoma medications from compounding pharmacies which can prepare a variety of fixed combination and preservative-free compounded medications. All these medication alternatives, while appealing, are often more expensive and/or more difficult to obtain. In addition to topical medications for glaucoma, recently approved in the United States is a sustained release medication therapy which can be administered intraocularly for continuous release over a period of months. This form of delivery could eliminate the need for topical therapy in some patients. It is not clear how well accepted this treatment may be to patients. In addition, the treatment is currently only approved for one-time dosing which means patients may have to restart topical therapy once the effect of the treatment wears off.
Surgical Therapy
When surgical treatment is deemed necessary, we have several things to consider in our treatment paradigm. With the advent of MIGS, the choices for surgical glaucoma treatment have increased drastically and their use in the glaucoma treatment is increasing. As stated previously, the true definition of MIGS is a matter of debate but it is generally agreed that these are glaucoma surgeries that have a more favorable risk profile than traditional trabeculectomy or glaucoma drainage device surgery. They have lower rates of hypotony, lower risk of both early and late infections, and lower risk of vision loss. , In addition, they are generally conjunctival sparing and so preserve the naïve conjunctiva for possible trabeculectomy surgery in the future.
Trabecular bypass MIGS are only approved in the United States for use in combination with cataract surgery and are best suited for controlled mild to moderate glaucoma. Studies comparing cataract surgery with or without a trabecular bypass stent utilize both pressure lowering and decreased need to topical glaucoma medications as endpoints. In the pivotal trial for one type of trabecular bypass system, glaucoma patients had a 7 mmHg average decrease in unmedicated IOP from baseline at 2 years follow-up and control patients with cataract surgery alone had a 5.4 mmHg decrease. In addition, a greater number of patients treated with trabecular bypass were medication free with and IOP ≤18 at 2 years when compared to patients who had cataract surgery alone. Other MIGS include goniotomy which can be done from an ab interno approach via different techniques including Trabectome (MicroSurgical Technology, Redmond WA), Kahook Dual Blade (New World Medical, Rancho Cucamonga CA), Omni (Sight Sciences, Menlo Park CA), or threading a catheter or suture through Schlemm’s canal internally often termed Gonioscopy-Assisted Transluminal Trabeculotomy. All these techniques have been shown to reduce IOP in glaucoma patients done either in conjunction with cataract surgery or as stand-alone procedures.
Some would include cyclodestructive procedures in the MIGS category as they do not disrupt the conjunctiva. These can be performed via endocyclophotocoagulation (ECP), micropulse (mCPC), and transscleral routes (tsCPC). , Gel stents are another category of MIGS that shunt fluid from the anterior chamber to the subconjunctival space. These are like traditional trabeculectomy in that they shunt fluid to the subconjunctival space. However, they have a lower rate of hypotony because of the flow restriction of the stent. These surgeries do utilize the conjunctiva and often use antimetabolites with its inherent risks but the bleb created is usually small and in the superonasal quadrant, still preserving the superotemporal conjunctival for potential more traditional glaucoma surgery if needed in the future. All three of the latter procedures discussed here, goniotomy, cyclodestruction, and gel stents, can be done with or without concurrent cataract surgery. There are also data to support use of these three procedures in more uncontrolled and/or advanced glaucomas as stand-alone procedures without cataract surgery.
In the treatment spectrum of glaucoma surgery surrounding the MIGS space, there continues to be utility in cataract surgery alone as an IOP lowering technique. Cataract surgery alone as an IOP lowering procedure is supported by multiple studies showing a sustained decrease in IOP after cataract without any adjunct glaucoma procedure. The amount and duration of IOP reduction varies greatly by type of glaucoma, preoperative IOP, and length of time after surgery. In the pivotal trial of ab interno trabecular microbypass system, the control group of cataract surgery alone had a >20% reduction in preoperative medication washout IOP in 62% of patients (compared to 76% of patients in the group receiving the trabecular bypass) sustained to 24 months. There are multiple theories for why this may be the case. The cataract in many cases may have a phacomorphic component of angle closure. Secondly cataract surgery may partially clear the trabecular meshwork of microdebris and increase flow. It is important to remember that patients with uncontrolled, advanced, and/or medication resistant glaucoma are unlikely to get a significant pressure reduction from cataract surgery alone or cataract surgery with trabecular stent. These patients likely have a large degree of blockage or nonfunctionality of the trabecular meshwork and downstream drainage pathways.
When considering cataract surgery in severe dry patients, remember that those with dry eye may be more likely to have neuropathic pain with cataract surgery and may be more likely to have keratopathy specifically related to topical nonsteroidal antiinflammatory (NSAID) use. We can preempt these issues by aggressively treating the dry eye prior to surgery with increased use of preservative-free lubricants. Starting treatment with steroidal antiinflammatories 1–2 weeks prior to surgery can be useful if we do not cause a steroid response in the IOP. To avoid keratopathy, it may be necessary to either use topical NSAIDs that are dosed fewer times per day and/or follow patients more frequently in the postoperative period to catch potential issues and intervene by either stopping the NSAID and/or using lubricant gel or ointments.
On the other end of the treatment spectrum, we have traditional glaucoma procedures including trabeculectomy and glaucoma drainage device surgery. These techniques have an excellent probability of success in terms of lowering IOP and decreasing dependence on topical glaucoma drops but can have significant postoperative complications such as hypotony, early- and late-onset infections, diplopia, erosions, and corneal decompensation. As such, it should not be discounted, particularly in our glaucoma patients with severe dry eye. Trabeculectomy with use of antifibrotic agent remains one of the most effective procedures with a high chance of the patient needing few or no glaucoma drops postoperatively. Those dry eye patients who require two or more drops and have more advanced damage (and who may have already had more conservative laser trabeculoplasty) are likely to be on fewer glaucoma medications for the first 2 years of follow-up after trabeculectomy but do average one or more medications after 3 years. Glaucoma drainage device surgery patients consistently average of 1.3–1.4 glaucoma drops at all time points through 5 years after surgery.
Conclusion
In summary, glaucoma and dry eye often coexist. Treatment of both is important as untreated dry eye can adversely impact adherence to glaucoma treatment. We must individualize treatment based on severity of both the glaucoma and severity of the dry eye understanding that the two disorders are intricately linked.
References
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
