What are the side effects and contraindications of prostaglandin analogs (e.g. latanoprost, bimatoprost, travoprost) in patients with open-angle glaucoma, particularly those with a history of uveitis, macular edema, herpetic keratitis, asthma, or chronic obstructive pulmonary disease (COPD)?

Prostaglandin Analogs for Glaucoma: Side Effects and Contraindications

Prostaglandin analogs (latanoprost, bimatoprost, travoprost, tafluprost) are first-line therapy for open-angle glaucoma due to superior IOP-lowering efficacy and once-daily dosing, but must be avoided or used with extreme caution in patients with active uveitis, macular edema (particularly in pseudophakic/aphakic patients), and history of herpetic keratitis. 1, 2

Common Ocular Side Effects

Hyperemia and Surface Changes

• Conjunctival hyperemia occurs in approximately 30% of patients and is the most common side effect, though typically mild and rarely requiring discontinuation (less than 1% discontinuation rate) 3, 4
• Bimatoprost causes more hyperemia than latanoprost or travoprost 5, 6
• Punctate epithelial keratopathy, dry eye, excessive tearing, and foreign body sensation occur in 5-15% of patients 3

Pigmentary Changes (Unique to Prostaglandin Analogs)

• Iris hyperpigmentation develops in 12-18% of Caucasian patients over 1-2 years of use, with higher rates in Asian populations 7
• This pigmentation is permanent and does not reverse after discontinuation 7
• Increased pigmentation of eyelids (periorbital darkening) occurs commonly 3, 5
• Eyelash changes (increased length, thickness, pigmentation, and number) develop in the majority of patients after 6 months of use 3, 7
• Latanoprost causes the most significant eyelash growth and iris discoloration compared to other prostaglandin analogs 8

Vision-Related Effects

• Blurred vision, burning and stinging occur in 5-15% of patients 3
• Eye pain, lid discomfort, lid edema, and photophobia occur in 1-4% of patients 3

Serious Ocular Complications (Rare but Vision-Threatening)

Intraocular Inflammation

• Anterior uveitis/iritis can occur or be exacerbated by prostaglandin analogs due to their pro-inflammatory mode of action 3, 4
• Reactivation of herpes keratitis has been reported postmarketing 3, 7

Macular Edema

• Cystoid macular edema (CME) is a recognized complication, particularly in pseudophakic and aphakic patients 3, 4, 7
• Close follow-up is necessary in these high-risk patients 4

Other Rare Serious Events

• Extremely rare reports include retinal artery embolus, retinal detachment, and vitreous hemorrhage from diabetic retinopathy 3
• Corneal edema and erosions have been reported postmarketing 3

Systemic Side Effects

Respiratory Effects

• Asthma exacerbation and dyspnea have been reported postmarketing 3
• Prostaglandin analogs have near absence of systemic side effects compared to beta-blockers, making them preferable in patients with COPD or asthma 5, 4

Other Systemic Effects

• Upper respiratory tract infection/cold/flu occurs at approximately 4% 3
• Chest pain/angina pectoris, muscle/joint/back pain occur at 1-2% 3
• Headache, dizziness, and rash/allergic skin reaction are uncommon 3
• Toxic epidermal necrolysis has been reported (extremely rare) 3

Absolute and Relative Contraindications

Absolute Contraindications

• Active or recurrent intraocular inflammation (uveitis/iritis) - prostaglandin analogs have a pro-inflammatory mechanism that can worsen inflammation 4
• Active herpetic keratitis - risk of reactivation 3, 7

Relative Contraindications Requiring Caution

• Cystoid macular edema (current or history), especially in pseudophakic/aphakic patients - requires close monitoring 3, 4, 7
• History of herpetic eye disease - even when inactive, use with caution due to reactivation risk 3, 7
• Pregnancy - FDA Category C (latanoprost) 1

Conditions Where Prostaglandin Analogs Are PREFERRED Over Alternatives

• Asthma and COPD - prostaglandin analogs are safer than beta-blockers (timolol) which can cause bronchospasm 1, 5
• Cardiovascular disease - prostaglandin analogs lack the cardiac effects of beta-blockers 5, 4
• No contraindication exists for rho kinase inhibitors (netarsudil) 1

Clinical Pitfalls and Monitoring

Key Monitoring Points

• Examine iris pigmentation at baseline and document with photography, as changes are permanent 7
• In pseudophakic/aphakic patients, monitor closely for macular edema development 4, 7
• Patients with history of uveitis require careful evaluation before initiating therapy 4
• Conjunctival hyperemia may reduce efficacy and duration of future trabeculectomy 4

Tolerability Differences Between Agents

• Travoprost (polyquad formulation) has superior Ocular Surface Disease Index scores compared to bimatoprost, latanoprost, and tafluprost 8
• Latanoprost appears least tolerated based on quality of life measures despite similar efficacy 8
• Benzalkonium chloride (BAK) preservative concentration varies: bimatoprost 0.3 mg/mL, latanoprost 0.2 mg/mL, with BAK-free options (tafluprost) available 8