How is Glaucoma Treated?

Johnson Laboratory at the Johns Hopkins Wilmer Eye Institute

How is Glaucoma Treated?

While there are no treatments available that can restore vision after it has been lost to glaucoma, there are fortunately many effective therapies that do slow or stop the worsening of glaucoma over time.  All of these treatments are aimed at reducing the eye pressure (intraocular pressure or IOP), which is the most important risk factor for glaucoma.  Whether a patient is diagnosed with glaucoma occurring at abnormally high IOP (often quoted as >21mmHg) or “normal” IOP, reducing the IOP with therapy is the only intervention proven to slow down the rate of further worsening. As one can see below, there are numerous treatment options available for glaucoma, and each option has its own risks and benefits.  Decisions about which treatment may be best for individual patients should be made in consultation with their treating eye doctor.

Eye Drops

The most common treatment for glaucoma is the use of eye drops that lower the IOP.  While many patients may only need to take one eye drop to lower their IOP to a safe level, there are actually many different classes of medication that can be used to accomplish this and some patients require multiple eye drops.

The most important thing to understand about glaucoma eye drops is that they only work if patients remember to and can correctly administer them into the eye.  Taking medications as directed is called “adherence to therapy” and numerous studies have shown that one of the leading reasons why glaucoma patients experience worsening of their disease is because of poor adherence to therapy.  Patients with glaucoma who take drops for their disease must remember to put them in the eye every single day at the times of day recommended by their doctor, and patients should understand that glaucoma eye drops are typically a lifelong treatment (unless they have a laser procedure or surgery to reduce the eye pressure in another way).  For patients who find it challenging to remember to take eye drops, we will often recommend that they set a timer on their phone to remind them, or consider downloading a reminder app on this phone, such as EyeDropAlarm (https://www.eyedropalarm.com/).

Eyedrop technique
© Harry A Quigley, used with permission

Prostaglandin analogues (PGAs) include latanoprost (Xalatan), travoprost (Travatan), bimatoprost (Lumigan) and tafluprost (Zioptan). PGAs typically are provided with a teal-colored cap and lower eye pressure by increasing the drainage of fluid out of the eye. These medications are typically prescribed first-line because they have the strongest ability to lower eye pressure, only need to be taken once per day, and have essentially no side effects outside of the eye.  However, in a subset of patients they can cause eye redness, eyelash growth, changes to color of the eye lids, orbital fat atrophy (which makes the eyeballs move slightly backwards into the eye socket), and changes to color of the iris. 

 

Beta adrenergic antagonists (beta blockers or BBs) are typically the second-line drugs used to treat glaucoma.  There are many BBs on the market, including timolol, levobunolol, betimol, and carteolol, and they typically have a yellow cap (or sometimes a light blue cap if coming in a low concentration). BBs work by slowing down how fast the eye produces internal fluid. They can be taken once in the morning or twice per day (morning and evening).  BBs can contribute to dry eye in some patients, and caution should be used in patients who have slow heart rate or breathing problems (like asthma or COPD) as they can exacerbate these issues.

 

Carbonic anhydrase inhibitors (CAI) eye drops include dorzolamide and brinzolamide, though there are also pill forms of CAIs that include acetazolamide and methazolamide.  CAIs work by slowing down how fast the eye produces internal fluid and the eye drop formulations come with an orange cap. The eye drop form of CAIs can contribute to dry eye, whereas the pill forms of CAIs are associated with many side effects which often mean that patients will be unable to take them over the long term.  These include feelings of nausea, fatigue, or malaise; tingling in the hands and feet; a metallic taste to carbonated beverages; changes in the blood electrolytes including potassium; increased risk of kidney stones; and very rarely, aplastic anemia (a condition where the bone marrow cannot produce blood cells).  CAIs are taken twice per day.

 

Alpha adrenergic agonists (AAs) include brimonidine (Alphagan) and apraclonidine and are typically supplied with a purple cap.  AAs work by both slowing down how fast the eye produces internal fluid and increasing how fast the eye drains that fluid.  The primary side of effect of AAs is their relatively high rate of allergy, which can cause eye redness, itching, and irritation.  AAs are taken twice (and rarely three times) per day.

 

Rho kinase inhibitors are a relatively new class of glaucoma medication, and the only drop in its class is netarsudil (Rhopressa). This drop works by increasing the outflow of fluid from the eye and is supplied with a white cap.  Though this drop is powerful and can lower the IOP as much as PGAs, it has a relatively high risk of causing eye redness, irritation, and periodic bleeding on the surface of the eye (called “subconjunctival hemorrhage”, which looks concerning with patients see this in the mirror, but is actually harmless to the eye). It can also cause deposits to form within the cornea (called verticillata) but these do not tend to affect a patient’s vision.  Rho kinase inhibitors are taken once per day.

 

There are also several combination eye drops available, which are nice because they can save patients the hassle of having to put two different drops in their eyes. The BB timolol is available in combination with the CAI dorzolamide (called Cosopt) or in combination with the AA brimonidine (called Combigan) and both are supplied with dark blue caps and taken twice per day. The CAI brinzolamide is available in combination with the AA brimonidine (called Simbrinza) and is supplied with a bright green cap and taken twice per day. The PGA latanoprost is available in combination with the rho kinase inhibitor netarsudil (called Rocklatan) and is supplied with a white cap and taken once per day. In addition, there is a relatively new combination drop called Vyzulta, which contains a version of latanoprost that splits into two molecules once inside the eye – the latanoprost lowers eye pressure through its typical mechanism whereas nitric oxide is also released to lower eye pressure though further promoting the drainage of fluid from the eye. Vyzulta is supplied with a teal colored cap and is taken once per day.

 

Example of the small hole created in an iris by laser peripheral iridotomy. © Dr. Harry A Quigley. Used with permission

Lasers

Believe it or not, there are actually several different kinds of lasers that are used to treat eye diseases, and they work in all different ways.  While you may have friends or family who have had laser treatment on their eyes, this does not necessarily mean they had a procedure to treat glaucoma.  Many people have eye laser surgery done for other reasons.  LASIK or PRK uses lasers to change the shape of the cornea to make patients less dependent on glasses.  YAG capsulotomy is a laser procedure used to remove a cloudy membrane that can sometimes form after cataract surgery, to improve the vision.  Retinal laser photocoagulation (focal laser or pan-retinal laser photocoagulation [PRP]) is used to treat diseases of the retina.  That said, there are three different types of laser procedures that are highly relevant to patients with glaucoma.

Laser Peripheral Iridotomy (LPI)

LPI is used for the treatment of a specific type of glaucoma – angle closure glaucoma.  This subtype of glaucoma exists when there is a blockage that prevents internal eye fluid from getting from its place of production (behind the iris) to its place of drainage (the anterior chamber angle in front of the iris).  This can occur because there is contact between the lens of the eye and the iris tissue at the pupil (primary angle closure, due to the anatomy of small eyes of patients which are usually far-sighted) or due to scar tissue formation between the pupillary iris and the lens (as seen in uveitic glaucoma or neovascular glaucoma). 

When a blockage of fluid at the pupil occurs, the internal fluid of the eye cannot reach the drainage tissue of the eye and this causes the IOP to become high.  To fix this problem, eye doctors can create a new pathway for fluid to get from behind to in front of the iris.  This involves using a laser to create a small hole in the periphery of the iris, and is termed LPI.  LPI is an office-based procedure (it does not need to be done in an operating room) that is performed with anesthetic eye drops and takes only about 1-2 minutes to perform.  During the procedure, the patient will place their head in a slit lamp microscope (just as they would for an eye examination) and a contact lens is placed on the surface of the eye.  The eye doctor then delivers light energy to the iris which results in the formation of a small hole.  The procedure is typically not painful, though there may be a very short sensation of pressure or a feeling like a mild pinch in the eye. 

The left image shows a schematic of the normal flow of fluid inside the eye. Aqueous humor is produced by the ciliary body (next to the lens) and flows through the pupil to get into the anterior chamber where it is drained. The middle images shows blockage of fluid flow in an eye with angle closure. Contact between the iris and lens prevents fluid from flowing through the pupil, which leads to a build up in pressure behind the iris, pushing it forward and closing the anterior chamber angle. The right panel shows the flow of fluid in an angle closure eye after an LPI has been performed. Fluid can now get to the front of the eye through a small hole created in the peripheral iris. © Harry A Quigley, adapted and used with permission.

Side effects of LPI are mild and rare.  Sometimes the procedure can result in a small amount of bleeding in the eye (called “hyphema”, but this self-resolves quickly.  LPI can cause some mild inflammation in the eye, but this is treated with a short course of topical steroid eye drops after the procedure.  About 5-10% of patients will sometimes report glare after the procedure.

Laser Trabeculoplasty (LTP)

LTP is a procedure that uses light energy in the form of a laser to stimulate the cells within the drainage tissue of the eye (the trabecular meshwork) to remodel the drain and increase the rate at which the eye drains internal fluid.  There are two different types of laser that can be used to perform LTP. The older form uses an argon or diode laser, and is termed argon laser trabeculoplasty (ALT) though this has been largely supplanted by a newer laser that is called selective laser trabeculoplasty (SLT).  For many years, LTP was used as a second-line treatment for glaucoma after patients failed therapy with eye drops.  However, a landmark clinical trial called the LiGHT Study (published in 2019) has shown that LTP works just as well as eye drops when used a first-line therapy in newly diagnosed glaucoma patients, and its adoption has increased dramatically since that paper was published.  As such, patients with open angle glaucoma are typically offered their choice of eye drops or LTP as first line pressure lowering therapy.

LTP is an office-based procedure that requires about 5 minutes per eye to perform.  Similar to an LPI, LTP is performed with the patient’s head positioned at a slit lamp microscope and a contact lens is placed on the surface of the eye.  A laser is then used to deliver light energy to the trabecular meshwork in approximately 80-120 pulses around the periphery of the eye.  This procedure tends to be very comfortable, with most patients reporting no feeling of the laser or just a mild tingling sensation inside the eye. 

LTP is very safe with most side effects by mild and short lived.  LTP can cause mild inflammation and many patients are prescribed an anti-inflammatory eye drop to take for a week after the procedure.  Rarely, the procedure can cause the eye pressure to go up for a short period of time immediately after, which may necessitate temporarily taking glaucoma eye drops.  There have been extremely rare reports in the literature of SLT causing a chance in the shape of the cornea, which can cause a shift in the glasses prescription.  When LTP works, it can be a great alternative to eye drops. However, only about 2/3 of patients respond well to the laser, whereas the other 1/3 of patients may experience to IOP reduction from the treatment.  In this case, the patient may need to take eye drops.

Laser cyclophotocoagulation (CPC)

 

CPC is a laser-based procedure that uses light energy to treat, shrink, and cause atrophy to the tissue inside the eye that is responsible for producing internal fluid (called the ciliary body).  If you think of an eye with high pressure like a bathtub that is overflowing because of a slow drain, then CPC is akin to turning down the faucet.

There are two main ways to perform CPC.  Transscleral CPC involves placing a laser on the outside surface of the eye so that light energy is transmitted through the wall of the eye and taken up by the ciliary body.  There are two main forms of transscleral CPC – continuous CPC has been around for decades and is very effective in lowering IOP but can cause significant inflammation in the eye, swelling of the retina, and sometimes blurring of vision.  For this reason, it has typically been reserved for patients who already have poor vision from glaucoma or other causes.  Micropulse CPC is a newer technology that breaks the laser energy up into tiny pulses.  Research suggests that micropulse CPC has less risk of side effects than continuous CPC, though it is also less effective in reducing the IOP.  Both procedures are typically performed in an operating room because they can be uncomfortable, and patients are more comfortable when they are given anesthesia for the procedure, which lasts less than 5 minutes.  Because there are no incisions into the eyeball, the risk of infection with this procedure is incredibly low.

Endocyclophotocoagulation (ECP) is similar to transscleral CPC in that it uses light energy to cause atrophy to the ciliary body.  However, ECP is done using a tiny probe that has a camera embedded in it.  The probe is inserted into the eye through an incision in the cornea, and the camera allows the surgeon to visualize the tissue to which the laser energy is being applied.  This procedure can only be done in patients after they have had cataract surgery, and is sometimes combined with cataract surgery as a single procedure.  It has a similar risk/benefit provide as transscleral CPC, but is typically less effective than continuous transscleral CPC.  ECP is also performed in an operating room but takes a bit longer to perform – approximately 10 minutes.

Incisional Glaucoma Surgery

For patients in whom eye drops and/or LPT fail to adequately reduce the eye pressure, or for those that do not want to take eye drops, incisional glaucoma surgery can be a treatment option.  There are many different types of glaucoma surgery that can be performed, and they are typically performed in an operating room. The factors that determine whether an individual patients may qualify for a particular type of surgery are complicated, and any patient considering glaucoma surgeon should have a detailed discussion with their surgeon about their particular case.

Schematic of a trabeculectomy. © Dr. Harry A Quigley. Used with permission

Trabeculectomy

Trabeculectomy (sometimes called a “trab” for short) is an incisional procedure that creates a new way for fluid to leave the eye, which reduces the IOP.  It works by rearranging the tissues on the top of the eye to create a flap in the wall of the eye.  Underneath this flap, a hole in the wall of the eye is created, which lets fluid out.  Of course, if the surgery were left like that, then fluid would leave the eye in an uncontrolled manner which result in an IOP of zero and poor vision.  Therefore, surgeons who perform trabeculectomy tie the flap down to the wall of the eye using stitches, with a goal of making the flap just tight enough to enable a trickle of fluid to leave the eye, resulting in an eye pressure of 8-12mmHg.  Once this is accomplished the tissue that covers the outside of the eye (called the conjunctiva) is placed over the flap so that the fluid that drains out of the eye is constrained within a blister of fluid (called a “bleb”) on the top of the eye.  The fluid in the bleb is then resorbed back into the blood vessels around the eye.  The bleb lives on the top of the eye underneath the eye lid and most patients will not feel or see the bleb unless the lift up the eye lid.

The post-operative care period is incredibly important following a trabeculectomy, and following up with your glaucoma surgeon is very important.  Steroid eye drops are typically prescribed at high frequency (as much as every two hours during the day) to prevent the eye from forming scar tissue that can close down the trabeculectomy drainage site.  Our research has shown that patients who take their post-operative steroid eye drops as instructed are more likely to have successful surgery than those who do not.  In addition, over the course of the first 1-6 weeks after surgery, the doctor may be able to open up the flap to allow greater drainage of fluid in trabeculectomies that are draining too slowly.  This is performed using a laser in the clinic to melt the stitches that are holding flap closed and is called “laser suture lysis”.  This procedure takes less than a minute to perform and is typically painless for the patient.

Studies have shown that 75% of patients who undergo trabeculectomy experience successful long-term reduction of their eye pressure for at least 5 years.  But there are some risks of this procedure that patients should be aware of.  In some cases (perhaps 5-10% of the time) the eye pressure after trabeculectomy can be too low.  Frequently this problem resolves on its own, though it can cause blurry vision while the eye pressure is low.  More rarely a second surgery needs to be performed to tighten up the trabeculectomy flap and increase the eye pressure.  The most worrisome complication of surgery is an infection – since the surgeon is creating a new pathway for fluid to leave the eye, in theory bacteria could use that pathway to enter and infect the eye if the bleb breaks down or leaks.  The risk of infection after trabeculectomy is about 1/1000 per year, but there is a small lifetime risk of infection after this procedure.  For this reason, patients who have had a trabeculectomy and experience sudden change in vision, eye pain, eye redness, or purulent discharge should contact their surgeon immediately.  We also recommend that patients who have had trabeculectomy do not wear contact lenses and do not swim in bodies of water that can have bacteria, such as lakes, streams, and oceans, especially without goggles that cover the face. Other rare complications of trabeculectomy include double vision and droopy eyelid, though these can be addressed with other procedures.

Glaucoma Tube Shunt Implantation

A glaucoma tube shunt functions based on the same principles as a trabeculectomy – it reduces eye pressure by creating a new pathway for internal eye fluid to be drained into the eye socket.  However, a glaucoma tube shunt implants a physical device into the eye, which is composed of a small silicone tube connected to a plate or reservoir.  The plate is sewn to the wall of the eye, the tube is inserted into the front of the eye, and the tube and plate are covered up with conjunctiva.  Similar to a trabeculectomy, this allows internal fluid of the eye to drain into a pool underneath the conjunctival where it is resorbed into the blood vessels around the eye.  Tube shunts can be placed in the superotemporal (top, ear-side) or inferonasal (bottom, nose-side) portion of the eye and are usually hidden by the eyelids.

The left two panels show a schematic of a tube shunt implanted into an eye. The right panel shows an example of a tube shunt in the anterior chamber of an eye, in front of the brown iris. © Dr. Harry A Quigley, used with permission.

There are to main types of tube shunts.  Ahmed tube shunts have valves that are mean to close to prevent the eye pressure from going too low.  Because of this valve, they are able to function as soon as they are implanted to lower the eye pressure.  Valveless glaucoma tubes (Baerveldt and Clearpath shunts) do not have an intrinsic way of restricting the flow of fluid out of the eye and so they need to be temporarily tied shut to prevent the eye pressure from going too low immediately after surgery.  These types of tubes are usually tied off with stitches that dissolve over the course of about 6 weeks, which means that the IOP will not drop fully until that time point after surgery, and patients may need to take eye drops until that happens.

Studies have shown that tube shunts and trabeculectomies have pretty similar success rates in lowering the eye pressure, through trabeculectomies may work slightly better and have slightly higher risks of complications.  Similarly, valveless tube shunts, on average, work slightly better to lower the eye pressure than Ahmed tube shunts, though valveless tube shunt also have slightly higher risks of complications.  The potential complications of tube shunts are similar to trabeculectomy and include hypotony (eye pressure that is too low and causes blurred vision), infection, double vision, and droopy eye lid.  In addition, there is some risk that, over the long term, a silicone tube inside the eye could cause damage to the cornea.  For this reason, some surgeons may choose to implant the tube behind the iris or into the vitreous cavity, if the anatomy of the eye of a particular patient enables the surgeon to do so.

Microinvasive glaucoma surgery (MIGS)

MIGS encompasses an entire range of relatively new glaucoma surgeries.  While most MIGS are capable of lowering the eye pressure in select patients, they tend to have a lower ability to reduce the IOP than trabeculectomy and tube shunts do.  That said, they also tend to have a significantly reduced risk of complications including infection.

Trabecular bypass surgeries work by either removing strips of tissues from the drain of the eye, or by inserting stents through that tissue in order to give the internal eye fluid greater ability to be drained from the eye.  Strips of trabecular meshwork tissue can be removed though a procedure called goniotomy, which can be performed with instruments such as a Kahook dual blade, a bent 25g needle, an Omni device, or a prolene suture (in a procedure called gonioscopy assisted transluminal trabeculotomy or GATT).  Small metal stents can also be placed through the trabecular meshwork and into Schlemm’s canal to provide the internal eye fluid better access to the drainage pathways of the eye. The two stents that are approved for use in the US are the Hydrus Microstent and the iStent.

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