Anti-inflammatories, Steroids

Define Inflammation

A protective physiological response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult.

What can stimulate inflammation?

• Infection

• Mechanical/Trauma

• Toxic (foreign substance)

• Immunologic/Hypersensitive

  • Exogenous substances: allergies

  • Endogenous substances: autoimmune conditions

What is the goal of inflammation?

To get as many WBC and other immune system components from the bloodstream into the tissues at the site of the inflammatory stimulus.

What is the physiological sequence of the inflammatory response?

1. Vasodilation to increase blood flow to site of origin

2. Increase vascular permeability to allow WBC to enter tissue

3. Chemotaxis to signal WBC where to go

What are the signs and symptoms from inflammatory response?

1. Rubor: redness from increased blood flow

2. Tumor: increase vascular perm leading to swelling

3. Calor: heat from increased blood flow

4. Dolar: pain from swelling causing increase in pressure → stimulates pain nerves

What are the major clinical consequences of an aggressive or chronic ocular inflammatory response?

• Neovascularization:chronic inflammation stimulates angiogenic factors (e.g., VEGF), leading to abnormal vessel growth.

• Tissue necrosis: prolonged inflammatory damage causes cellular death and structural breakdown.

• Scar formation: fibroblast activation → fibrosis → permanent structural and functional impairment.

What does the cyclo-oxygenase pathway produce?

• Thromboxane A2 to help platelets aggregate

• PGE2, PGF2, PGD2

• Prostacyclin (PGI2)

What does the lipoxygenase pathway produce?

Leukotrienes and related compounds.

What part of the arachidonic acid cascade is inhibited by corticosteriods?

Phosphoipase A2 making arachidonic acid from phospholipids.

What is the MOA of steriods?

1. Bind receptor, pass through cell membrane

2. Bind cytoplasmic receptor

3. Enter nucleus to alter protein synthesis, creating lipocortin-1 which inhibits Phospholipase A2

4. Limits formation of arachidonic acid, which is the precursor to prostaglandins and leukotrienes

What are the effects of inhibiting arachidonic acid (e.g., using steroids)?

Inhibition of arachidonic acid prevents formation of prostaglandins & leukotrienes → reduces the 4 classic signs of inflammation:

• ↓ Vasodilation → reduces redness (mainly mediated by PGD₂).

• ↓ Vascular permeability → decreases swelling/edema (from PGD₂ & leukotrienes).

• ↓ Chemotaxis & inflammatory cell recruitment → reduces tissue swelling and cellular infiltration (leukotriene‑mediated).

• ↓ Pain → reduces nociceptor sensitization from PGE₂.

• ↓ circulating WBC’s and lymphocyte proliferation

• Inhibit lymphocyte cell mediated responce

• Inhibit cytokine sythesis

• Inhibit migration of neutrophils

• Inhibit fibroblast proliferation

• Inhibit fibrin deposition

• Inhibit collagen deposition

What are the ocular SE of steroids?

1. Increase IOP/ Spike in IOP. 7-8% will increase IOP when given steroids for 2+ weeks

2. Posterior Subcapsular cataracts: depens on route of admin; highest risk via intra-ocular injections, then oral admin

3. Increased risk of infection

4. Decreased healing/delayed wound healing

What are the contraindications for topical ocular steroid use?

• Presence or suspicion of infection, especially of ocular dendritic keratits

• Unsure of diagnosis

• Concurrent contact lens wear (must wear glasses when using topical steroids)

• Epithelial Defects* Dependent on size and cause of defect. May need to use antibioc for prophylaxis if risk of infection

• Glaucoma: More likely if have FHx of glaucoma, but can use for short durations (less than 10 days)

Are there systemic SE of topical ocular steroid use?

No,

How is anti-inflammatory efficacy determined?

• Ocular absorption

• Receptor affinity

• Rate of metabolization: ketone-based vs ester-based steroids

How do the “–ates” (acetates, prednates, propionates, etabonates) behave in terms of corneal absorption?

• Highly lipophilic → greatest hydrophobicity.

• Result: Highest tissue absorption + best corneal penetrance of all steroid formulations.

• Example: Prednisolone acetate penetrates far better than prednisolone sodium phosphate.

How well do alcohol‑based ophthalmic steroid formulations penetrate the cornea?

• Intermediate corneal penetration (between acetates and phosphates).

• Balanced hydrophilic/lipophilic properties → moderate tissue absorption.

What is the corneal absorption profile of sodium phosphate steroid formulations?

• Hydrophilic (water‑soluble) formulations.

• Lowest corneal/tissue penetrance among steroid types.

• Best used for more superficial inflammation (e.g., conjunctival).

What is Pred Forte and what is its general characteristics?

• 1.0% prednisolone acetate suspension

• Considered gold standard due to highest efficacy from combo of

  • great absorption,

  • high receptor affinity, and

  • ketone based steroid

How do the generics compare to Pred Forte?

They are outperformed/not as efficacious as Pred Forte.

What is Pred Forte used for?

• PDA approved to tx ocular inflammation

• Common uses:

  • Uveitis

  • Keratitis

  • Post-op inflam

  • Moderate-severe ocular surface inflam

What risk does pred forte have?

Highest risk of increasing IOP d/t its efficacy.

What is Pred Mild?

• 0.12% prednisolone acetate suspension

• Rarely used

• FDA approved to treat ocular inflam

• No generic available in this conc

What is 1.0 prednisolone NaPh and what are its indications?

• Generic solution

• FDA indications: Tx ocular inflammation

• Uses: external diseases of ocular surface:

  • Pingueculitis

  • Allergic conjunctivitis

  • Episcleritis

What is Durezol and what are its general characteristics?

• An emulsion of 0.05% difluprednate, generic is a suspension (shake)

• Equal efficacy to Pred Forte with 50% less dosing pattern

• FDA indicated for: Uveitis, post-op inflam and pain

• Dosing for post-op: QID x14 days, then taper accordingly

What is Byqlovi and what are its general characteristics?

• 0.05% clobetasol propionate suspension (Shake)

• FDA indicated for: post-op inflam and pain after ocular surgery

• Uses active pharmaceutical nanoparticle technology (APNT) to enhance ocular absorption

• Dosage: BID x 2wks following surgery

What is Loteprednol and what are its unique characteristics?

• ONLY ester-based steroid → rapidly metabolized

• Nearly equal efficacy to pred forte

• Less likely to induce IOP spike

• Patent expired so many diff names, brand name: Lotemax

What are the indications, concentration, and preservative of Lotemax suspension?

• 0.5% loteprednol etabonate ophthalmic suspension.

• Open indication for any ocular inflammation.

• Preserved with BAK 0.01%.

What are the indications, concentration, and preservative of Lotemax gel?

• 0.5% loteprednol etabonate

• Only indicated for use following ocular surgery

• Preserved with BAK 0.003%.

• Dosage: QID x2weeks, then taper accordingly

What are the indications, concentration, and preservative of Lotemax SM gel?

• 0.38% loteprednol etabonate

• Only indicated for use following ocular surgery

• Preserved with BAK 0.003%.

• Dosage: TID x2weeks, then taper accordingly

What are the indications, concentration, and preservative of Lotemax Ointment?

• 0.5% loteprednol etabonate

• Only indicated for use following ocular surgery

• No preservatives

• Dosage: QID x2weeks, then taper accordingly

What is Alrex?

Another brand name for loteprednol etabonate. It is a suspension. Only FDA indicated for allergic conjunctivitis.

What is Inveltys and how does its formulation enhance ocular penetration?

• Inveltys = 1.0% loteprednol etabonate ophthalmic suspension.

• Uses AMPPLIFY nanotechnology with mucus‑penetrating particles (MPP).

• AMPPLIFY and MPP improves corneal and intraocular absorption

What is the FDA indication and dosing regimen for Inveltys?

• FDA indicated for post-op ocular inflammation and pain.

• Dosing: 1 drop BID for 2 weeks.

What is Eysuvis and how does its formulation enhance ocular penetration?

• Eysuvis = 0.25% loteprednol etabonate ophthalmic suspension.

• Uses AMPPLIFY nanotechnology with mucus‑penetrating particles (MPP).

• AMPPLIFY and MPP improves corneal and intraocular absorption

What is the FDA indication and dosing regimen for Eysuvis ?

• FDA indicated for short term tx of signs and symptoms of dry eye.

• Dosing: 1 gt QID x up to 2wk

What are the common uses of Loteprednol?

Based on formulation:

• Dry eye (short-term use as a diagnostic agent or management of flare ups)

• Inflammatory Keratitis (DOC for Thygeson’s SPK)

• Post-op inflammation (particularly refractive surgery)

• Episcleritis (particularly nodular)

• Allergic conjunctivitis

• DOC for GPC and VKC

• Any inflammatory condition requiring long, protracted steroid therapy due to its safety profile

What is Maxidex and what is it used for?

• 0.1% dexamethasone alcohol suspension

• FDA indicated for ocular inflammation

• Also available in generic

What is FML and what are its uses?

• 0.1% fluorometholone alcohol suspension

• Available in generic

• FDA indicated for ocular inflammation:

  • Episcleritis

  • Superficial inflammation

• Generic is often preferred on insurance formularies

What is FML Forte and what are its uses?

• A 0.25% fluorometholone alcohol

• FDA indicated for ocular inflammation

• Rarely used, no generic available

What is Flarex and its uses?

• 0.1% fluorometholone acetate suspension

• FDA indicated for ocular inflammation

• Rarely used, no generic available

• Possible benefit in Tx protracted or recalcitrant Thygeson’s Keratits

Rank the relative efficacy of the topical ophthalmic steroids

1. Pred Forte and Durezol

2. Lotemax/Inveltys

3. Maxidex

4. Alrex/Eysuvis

5. FML/Flarex

Mnemonic: “Powerful Drops Leave Many Angry Flames”

Rank the relative IOP spike of the topical ophthalmic steroids

1. Maxidex

2. Durezol and Pred Forte

3. Lotemax/Inveltys

4. Alrex/Eysuvis

5. FML/Flarex

Mnemonic: “My Doctor Prescribes Less Agressive Formulations”

What are the guidlines for dosing topical ophthalmic steriods?

• Dosage and length of course of Tx is determined by severity of presentation

• If condition warrants steroid Tx, initial dose usally no less than QID

• For mild to moderate inflam, common dosage is QID x7 days

• Initial dosage for significant cases of uveitis is commonly Q1h with pred forte or Q2h with Durezol

When are topical ophthalmic steriods tapered?

• Necessary if high dosage or long duration of Tx

• Need to taper if dose > QID or if > 10-14 days

• Only start taper when improvement is seen on follow up at current dose

How do you taper topical ophthalmic steroids?

Reduce dosage frequency by < 50% of previous usage. Pts need proper monitoring to determine taper schedule and to rule out IOP spike.

When would you pulse topical steroids?

For non-uveitic conditions with more severe symptoms.

Why would you pulse dosing?

To rapidly reach peak drug conc in the target tissue to have early impact on significant symptoms.

Do topical ophthalmic steroids cause systemic side effects, and what is the general risk of ocular side effects with short‑term use?

• Systemic side effects are extremely rare with topical ophthalmic formulations.

• Short‑term ocular use rarely causes IOP elevation or posterior subcapsular cataract (PSC).

• Because risks are low short‑term, clinicians may treat aggressively early to shorten duration of therapy.

What baseline evaluation and monitoring are recommended when prescribing topical steroids?

• Measure baseline IOP before starting therapy.

• Monitor IOP at every follow‑up visit, especially in steroid responders.

• Taper when appropriate to avoid rebound inflammation.

What administration and handling instructions are important for topical steroid suspensions?

• Suspensions must be shaken well to ensure correct dosing.

• Ensure patient can physically shake the bottle (elderly may need alternatives like gels/ointments).

• No Refills! Discard after use.

What is Dextenza?

0.4 mg dexamethasone intracanalicular insert that provides sustained release for 30 days. It disintegrates and is flushed thru nasolacrimal system. Has improved compliance vs ~70 drops in 30 days.

What is Dextenza used for?

FDA approved for: inflammation and pain following ophthalmic surgery and allergic conjunctivitis.

Does Dextenza risk increasing IOP?

only 3-6% of pts experience increased IOP.

What would 0.1% triamcinolone cream be used for?

For short term use for acute dermatitis of periocular adnexa (Dermatological). Not for ocular surface.

How efficacious is triamcinolone cream and what are its risks?

• 10 times efficacy of OTC 1% hydrocortisone

• High dose or chronic/excessive use of steroids on skin can lead to thinning and/or de-pigmentation of skin.

  • Educate Pt to not use chronically

What are some systemic steroids that optometrists use and what are thier indications?

• Oral formulations: Prednisone and Medrol (methylprednisolone)

• Ocular Indications:

  • Graves Ophthalmopathy

  • Orbital Pseudotumor

  • Retinal Vasculitis

  • Uveitis

  • Myasthenia Gravis

  • Giant Cell arteritis

  • Allergic inflammation of the conjunctiva, lids, and adnexa

    • (Only indication allowed for ODs in OH)

What are some potential causes for allergic inflammation of the conj, lids, and adnexa.

• Contact dermatitis

• Severe allergic conjunctivitis/blepharitis

• Poison ivy

• Bee stings

What systemic steroid can Ohio optometrists prescribe, and to which patients?

• Ohio ODs may prescribe oral methylprednisolone only.

• Adults ≥18 years old only (not permitted in minors).

• Must relate to treatment of an ocular condition within OD scope.

What are the restrictions on quantity and refills when Ohio ODs prescribe oral steroids?

• Prescription cannot exceed a single course of therapy.

• No refills allowed.

What are the concerns/SE of chronic, long-term systemic steroid use?

• Muscle wasting and altererd fat distribution → Cushing’s syndrome

• Suppress adreno-pituitary axis → Adrenal insufficiency → malaise, myalgia, muscle atrophy, hypotension, increased risk of infection, decreased wound healing

• Osteroporosis

• Steroid psychosis

• Thinning and depigmentation of the skin

What are the concerns/SE of systemic steroids for short-term use?

• Peptic ulcers

• Increase blood glucose (gluconeogenesis)

• Pregnancy

What steroids are available for periocular and intraocular injections?

• Kenalog (triamcinolone)

• Xipere (Triamcinolone)

• Dexycu (9% dexamethasone)

Where is Kenalog (traimcinolone) injected into and what for?

• Intralesional injection for chalazion

• SubTenon’s injection for posterior uveitis

• Intravitreal injection for diabetic macular edema (DME) or macular edema secondary to vein occlusion, or temporal arteritis

Where is Xipere (triamcinolone) injected into and what for?

• Suprachoroidal space (SCS) for macular edema associated with uveitis

  • SCS gives higher absorption into retinal tissue than intravitreal injection

Where is Dexycu (9% dexamethasone) injected into and what for?

• Intracameral injection for cataract post-op inflammation

What are some intraocular steroid implants?

• Ozurdex (0.7mg Dexamethasone implant)

• Yutiq (0.18 mg fluocinolone implant)

• Retisert (0.59mg fluocinolone implant)

• Iluvien (0.19mg fluocinolone implant)

What is Ozurdex used for?

• Slow sustained rug release for 6 months

• FDA approved for:

  • Macular edema 2^o to CRVO or BRVO

  • Non-infectious posterior uveitis

  • Tx of Diabetic Macular Edema (DME)

What is Yutiq used for?

FDA approved for chronic non-infectious uveitis.

What is Retisert used for?

• FDA approved for chronic non-infectious uveitis

• Slow, sustained drug release for 30 months

• 77% of pts need IOP lowering therapy, 37% requiring trab surgery to reach target IOP

• All phakic eyes develop cataracts, requiring surgery

What is Iluvien used for?

• FDA approved for Tx of DME

• Slow, sustained drug release for 36 months

• 34% have IOP spike > 10 mmHg

• 20% have IOP spike > 30 mmHg

• 80% develop cataracts requiring surgery within 18 months

Are intraocular steriod implants inside or outside the scope of practice in OH?

Currently outside.