Difluprednate

Table of contents

• What is difluprednate?
• How does difluprednate work?
• Which conditions is difluprednate used or studied for?
• How is difluprednate given?
• What do the clinical trials show?
• What side effects are known?

What is difluprednate?

Difluprednate is a corticosteroid medicine used in ophthalmology to reduce inflammation and pain in the eye. It was first approved in the United States in 2008 and is available as a prescription eye drop.^[3] The product information describes it as difluprednate ophthalmic emulsion 0.05% for topical ophthalmic use.^[3] In the EU clinical trial registry, difluprednate is listed as an auxiliary medicine in one authorised trial, meaning it plays a supporting role rather than being the main treatment under investigation.^[1]

How does difluprednate work?

Difluprednate belongs to the corticosteroid class of medicines. Corticosteroids work by reducing inflammation in the body. In the eye, difluprednate helps control swelling, redness, and pain caused by surgery or by inflammatory conditions such as uveitis.^[3] The prescribing information notes that prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, which is why the medicine is used under medical supervision.^[3]

Which conditions is difluprednate used or studied for?

• Inflammation and pain after ocular surgery — Difluprednate is indicated for treating inflammation and pain associated with eye surgery, such as cataract surgery.^[3]
• Endogenous anterior uveitis — This is an inflammatory condition affecting the front part of the inside of the eye. Difluprednate is indicated for its treatment.^[3]
• Macular neovascularization secondary to age-related macular degeneration (nAMD) — Difluprednate is not the main treatment here but is used as an auxiliary medicine in a Phase 3 trial investigating a gene therapy called 4D-150 for this condition.^[1]

How is difluprednate given?

Difluprednate is given as an ophthalmic emulsion (an eye drop) at a strength of 0.05%, applied topically to the eye.^[3] In the EU trial registry, its route of administration is recorded as topical use.^[1] The product information describes the dosing schedule for inflammation and pain after ocular surgery as one drop into the conjunctival sac of the affected eye four times daily beginning 24 hours after surgery, continuing through the first two weeks, then two times daily for a week, followed by a taper based on the response. For endogenous anterior uveitis, the product information describes one drop four times daily for 14 days, followed by tapering as clinically indicated.^[3]

What do the clinical trials show?

In the EU clinical trial registry, difluprednate appears in one trial as an auxiliary medicine. The trial is a Phase 3, randomised, double-masked, active-controlled study called 4FRONT-2, which is investigating a single intravitreal injection of an investigational gene therapy called 4D-150 in adults with macular neovascularization secondary to age-related macular degeneration (nAMD).^[1]

The trial is currently authorised and plans to enrol 480 participants.^[1] The main comparison is between a single intravitreal injection of 4D-150 and aflibercept (Eylea) 2 mg given by intravitreal injection every 8 weeks.^[1] The primary outcome is the mean change from baseline in best corrected visual acuity (BCVA), measured using the ETDRS letter score at Week 52.^[1] The trial aims to show that a single injection of 4D-150 is not inferior to aflibercept given every 8 weeks in terms of this visual acuity measure.^[1]

Difluprednate is not the main treatment being tested in this trial. It is listed as an auxiliary medicine, which means it is used to support the trial treatment — for example, to manage inflammation related to the intravitreal injection procedure.^[1]

What side effects are known?

The prescribing information highlights that prolonged use of corticosteroids such as difluprednate may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision.^[3] Difluprednate is contraindicated in most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures.^[3] A systematic review and meta-analysis comparing difluprednate with prednisolone acetate after cataract surgery, which included six randomised controlled trials with 883 patients, assessed corneal oedema and intraocular pressure as safety outcomes and graded the evidence quality as moderate for these measures.^[2] A Phase 3 study comparing difluprednate 0.05% with prednisolone acetate 1% for endogenous anterior uveitis was conducted as a multicentre, randomised trial.^[4]