Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension

Abstract

Prostaglandin analogs (PGA) are powerful topical ocular hypotensive agents available for the treatment of elevated intraocular pressure (IOP). Latanoprost 0.005% and travoprost 0.004% are prodrugs and analogs of prostaglandin F2α. Bimatoprost 0.03% is regarded as a prostamide, and debate continues as to whether it is a prodrug. The free acids of all 3 PGAs reduce IOP by enhancing uveoscleral and trabecular outflow via direct effects on ciliary muscle relaxation and remodeling of extracellular matrix. The vast majority of clinical trials demonstrate IOP-lowering superiority of latanoprost, bimatoprost and travoprost compared with timolol 0.5%, brimonidine 0.2%, or dorzolamide 2% monotherapy. Bimatoprost appears to be more efficacious in IOPlowering compared with latanoprost, with weighted mean difference in IOP reduction documented in one meta-analysis of 2.59% to 5.60% from 1-to 6-months study duration. PGAs reduce IOP further when used as adjunctive therapy. Fixed combinations of latanoprost, bimatoprost or travoprost formulated with timolol 0.5% and administered once daily are superior to monotherapy of its constituent parts. PGA have near absence of systemic side effects, although do have other commonly encountered ocular adverse effects. The adverse effects of PGA, and also those found more frequently with bimatoprost use include ocular hyperemia, eyelash growth, and peri-ocular pigmentary changes. Iris pigmentary change is unique to PGA treatment. Once daily administration and near absence of systemic side effects enhances tolerance and compliance. PGAs are often prescribed as first-line treatment for ocular hypertension and open-angle glaucoma.

Periorbital muscle atrophy associated with topical bimatoprost therapy

“…Topical bimatoprost is highly efficacious and superior to many other anti-glaucoma eye drops. 2 , 3 However, it commonly causes side effects such as ocular hyperemia, periocular and iris pigmentary changes, although these are mostly reversible with cessation of use. 4 Periorbital lipodystrophy resulting in periorbital hollowing, eyelid retraction, and enophthalmos from chronic use of bimatoprost has also been well-documented.…”

Hirsutism following the use of bimatoprost eyedrops for glaucoma

“…The systemic exposure from ocular dosing with prostaglandin analogues including bimatoprost is low. [ 2 ] It has been seen that after one drop of bimatoprost 0.03% in each eye (9 μg of drug), the maximum plasma concentration of bimatoprost was approximately 10 -10 M (Lumigan product info, Allergan). The levels peaked within 10 minutes of dosing and became undetectable within 1.5 h. The values of the mean maximum blood concentration and area under the curve were similar (0.08 ng/mL and 0.09 ng/h/mL respectively on days 7 and 14).…”

“…[ 1 ] The free acids of all prostaglandin analogues (PGAs) reduce intraocular pressure (IOP) by their effects on ciliary muscle relaxation and remodeling of extracellular matrix thereby enhancing uveoscleral and trabecular outflow. [ 2 ] Conjunctival hyperemia, hypertrichosis of the lashes, periocular hyperpigmentation and iris pigmentation are well known ocular side effects of prostaglandin analogues. Anecdotal reports of cystoid macular edema, iris cysts, anterior uveitis and herpes simplex have been noted in patients on PGF2α drugs.…”

“…Anecdotal reports of cystoid macular edema, iris cysts, anterior uveitis and herpes simplex have been noted in patients on PGF2α drugs. [ 2 ] There have been reports of periorbital fat atrophy and deepening of the superior sulcus following their use. [ 3 ] Bimatoprost and other prostaglandin analogues can increase thickness and length of lashes, produce additional lash rows and can convert vellus to terminal hairs in canthal areas and in regions adjacent to lash rows.…”

Allergic Contact Dermatitis Caused by Topical Eye Drops Containing Latanoprost

“…Prostaglandin analogues are increasingly used as the first choice of drug for an open angle glaucoma 1 . They are known to be highly effective and have little systemic side effects.…”