Prostaglandin Analogs Medication for Glaucoma

A relative newcomer to medical glaucoma treatments. This class has only been FDA approved for a little over two decades.

How this class of glaucoma medication works:

Although the prostaglandin analog class works at the ciliary body like many other IOP lowering medications, it has a unique, and very effective, mechanism of action. It does not decrease production of aqueous fluid. Instead it increases the flow of fluid out of the eye through what is termed the uveoscleral outflow pathway. This pathway is usually a minor pathway like a side street next to a freeway. However, just as during rush hour Waze will often recommend taking a side street, when the trabecular meshwork is congested this accessory outflow pathway becomes more important. Prostaglandin analogs are like adding a few lanes to freeway-adjacent side streets.

Exactly how the prostaglandin analogs increase flow through the uveoscleral pathway, however, is not know. There is some evidence that this class of medication relaxes the ciliary muscle^[1]. Other evidence suggests that it remodels the connective tissue within the ciliary muscle essentially making it more permeable (“leaky”)^[2].

How well does this class of glaucoma medication work?

Really, really well for most people^[3]. Studies have shown it to lower IOP as much as^[4] or even more than^[5] timolol 0.5%. However, unlike timolol which has little IOP-lowering benefit at night, the prostaglandin analogs work around-the-clock^[6].

Commonly prescribed:

• Xalatan^® (latanoprost) – first in class to be approved
• Lumigan^® (bimatoprost)
• Travatan-Z^® (travoprost)
• Zioptan^® (tafluprost)

Cap color:

Teal

Note about Preservative-Free options:

Most prescription eye drops have a preservative which keeps bacteria from growing in the bottle. However, the most commonly used preservative, Benzalkonium chloride (BAK), can worsen dry eye and may even be toxic to the trabecular meshwork over time. Given that the trabecular meshwork is already not functioning well in most forms of glaucoma, I generally prefer to prescribe preservative-free versions of glaucoma eye drops when available and affordable.

Travatan-Z^® (travoprost) does not have BAK in the bottle. Instead, it is formulated with SofZia™ which effectively prevents bacterial growth in the bottle but is inactivated when exposed to the tear film^[7]. As such, it appears to be as far more gentle to the ocular surface than BAK^[8].

Zioptan^® (tafluprost) is truly preservative-free. As such, this is my preferred brand of prostaglandin analog for those who have adequate insurance coverage.

How it is taken:

One every evening. One advantage of this class of medications is that it appears to be very forgiving in that if a dose is missed, the IOP-lowering effect may continue for 12-24 more hours. Oddly, however, this class of medications works less well when dosed twice a day^[9]. So, if you are prescribed this medication and forget to put it in your eye at night, it’s ok to use it anytime the next day, but don’t double up in an attempt to “make up” for the missed dose.

Note on Fixed Combinations: The prostaglandin analogs appear to further reduce IOP when added to all other FDA-approved IOP-lowering agents. However, no fixed-combination agents are currently available in the USA.

Cost?

All over the place^[10]. Generic latanoprost is covered by most (if not all) insurances. Indeed, if you have an insurance that does not cover generic latanoprost then you should really look for a different insurance with the next “open enrollment”.

Branded prostaglandin analogs can range from a small copay to hundreds of dollars per bottle (which is generally a month’s supply).

If you are prescribed this medication and it is not covered by your insurance or even with insurance coverage it’s quite expensive then I recommend you search out a good cash price through the website “GoodRx”. I frequently recommend this site to my patients and have been surprised at how much they can often save on certain classes of medications despite not using their insurance.

When might these be prescribed?

These are often the first medication prescribed for those with glaucoma.

Side effects:

Local:

• Cosmetic effects
  • • Conjunctival hyperemia (red eyes)^[11]
  • • Eyelash growth^[12]
  • • Pigmentation of the iris and skin around the eye^[13]
  • Loss of connective tissue around the eye
• Irritation of the eye
• Blurred vision (usually temporary)
• May worsen already existing inflammation in the eye^[14]

Systemic (rare):

• Night-time (“nocturnal”) headache
• Backache
• Chest pain
• Muscle aches
• “Cold” symptoms

Interactions with other medications:

• The prostaglandin analogs appear to further reduce IOP when added to all other FDA-approved IOP-lowering agents.

How to minimize side effects:

• Use a tissue to remove excess drop volume and limit contact with eyelid skin
• Use an eye drop applicator such as the Simply Touch (available on Amazon.com)

Summary:

This unique class of IOP lowering medications is one of the most effective available, works primarily via a mechanism not shared by other classes, and is available in a preserved generic form as well as a branded preservative-free formulation. As for side effects, it even has a few desirable ones. It’s no wonder it is one of the world’s most commonly prescribed glaucoma treatments.

References:

[1] Poyer JF, Millar C, Kaufman PL. Prostaglandin F2 alpha effects on isolated rhesus monkey ciliary muscle. Invest Ophthalmol Vis Sci.1995;36(12):2461–2465.

[2] Sagara T, Gaton DD, Lindsey JD, et al. Topical prostaglandin F2 alpha treatment reduces collagen types I, III, and IV in the monkey uveoscleral outflow pathway. Arch Ophthalmol. 1999;117(6):794–801

[3] Camras CB, Hedman K. Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma. J Glaucoma. 2003;12(6):466–469.

[4] Watson P, Stjernschantz J. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension. The Latanoprost Study Group. Ophthalmology. 1996;103(1):126–137.

[5] Goldberg I, Cunha-Vaz J, Jakobsen JE, et al. Comparison of topical travoprost eye drops given once daily and timolol 0.5% given twice daily inpatients with open-angle glaucoma or ocular hypertension. J Glaucoma. 2001;10(5):414–422.

[6] Racz P, Ruzsonyi MR, Nagy ZT, et al. Around-the-clock intraocular pressure reduction with once-daily application of latanoprost by itself or in combination with timolol. Arch Ophthalmol. 1996;114(3):268–273.

[7] Kahook MY, Travoprost Z. Ophthalmic solution: clinical safety and efficacy. Expert Rev. Ophthalmol.2(3),363–368 (2007).

[8] Kahook MY, Noecker RJ. Comparison of corneal and conjunctival changes after dosing of Travoprost preserved with sofZia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears. Cornea. 27(3),339–343 (2008).

[9] Watson P, Stjernschantz J. A six-month, randomized, double-masked study comparing latanoprost with timolol in open-angle glaucoma and ocular hypertension. The Latanoprost Study Group. Ophthalmology. 1996;103(1):126–137.

[10] Priluck AZ, Havens SJ. Variation in Prostaglandin Analog Prices Paid for Through Medicare Part D. Journal of Glaucoma. 28(1):e17-e20, January 2019.

[11] Feldman RM. Conjunctival hyperemia and the use of topical prostaglandins in glaucoma and ocular hypertension. J Ocul Pharmacol Ther. 2003;19(1):23–3.

[12] Johnstone MA, Albert DM. Prostaglandin-induced hair growth. Surv Ophthalmol. 2002;47(suppl 1):S185–S202.

[13] Kook MS, Lee K. Increased eyelid pigmentation associated with use of latanoprost. Am J Ophthalmol. 2000;129(6):804–806.

[15] Warwar RE, Bullock JD, Ballal D. Cystoid macular edema and anterior uveitis associated with latanoprost use. Experience and incidence in a retrospective review of 94 patients. Ophthalmology. 1998;105(2):263–268.

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