Unlike certain glaucoma or dry eye medications, which are indicated for a specific ocular condition, steroids and non-steroidal anti-inflammatory drugs (NSAIDs) can have an array of clinical applications to treat a myriad of inflammatory ocular conditions. Familiarity with the ophthalmic steroid and NSAID portfolio, and understanding how they may be used depending on clinical presentations, will make your clinical decision-making much easier.
Ophthalmic steroid use
Let’s begin by reviewing four potential uses for ophthalmic steroids: uveitis, bacterial corneal ulcers, conjunctivitis, and dry eye disease (DED).
Uveitis
Defined as inflammation of the uvea (the iris, ciliary body, and choroid), most cases (48 to 70%) of uveitis are idiopathic.1 However, trauma, underlying systemic inflammation, previous intraocular surgery, neoplastic processes, or infection may be causative.1 Presentation can be categorized as either anterior, intermediate, posterior, or panuveitis.
1) Anterior—inflammation present in the anterior chamber
- Symptoms: Red, painful eye that is most often unilateral, photosensitive, and has circumlimbal flush with possible decreased vision
- Signs: Anterior chamber cell and/or flare, posterior synechiae, keratic precipitates (KPs), hypopyon, Busacca/Koeppe iris nodules, and high/low intraocular pressure (IOP) measurements
- Systemic causes: HLA-B27-associated entities, inflammatory bowel disease, sarcoidosis, Lyme disease, juvenile idiopathic arthritis, Behcet’s disease, tubulointerstitial nephritis and uveitis (TINU), varicella-zoster virus (VZV), and herpes simplex virus (HSV)
2) Intermediate—inflammation present in the vitreous cavity
- Symptoms: Increased floaters and worsening vision
- Signs: Cell and haze in vitreous, vitreous snowballs, vitreous snow banking at pars plana, and cystoid macular edema (CME)
- Systemic causes: Multiple sclerosis (MS), sarcoidosis, TINU, VZV, and Lyme disease
3) Posterior—inflammation present in the choroid and/or retina
- Symptoms: Worsening vision, visual field loss, and photopsia
- Signs: Retinal whitening, vascular sheathing, chorioretinal lesions, and candle wax drippings (periphlebitis)
- Systemic causes: Leukemia, systemic lupus erythematosus (SLE), Vogt-Koyanagi-Harada (VKH) syndrome, Behcet’s disease, MS, Lyme Disease, Candida Albicans, Cytomegalovirus (CMV), human immunodeficiency virus (HIV), syphilis, and VZV
4) Panuveitis—inflammation affecting all parts of the uvea
- Symptoms: Red, painful eye, severely decreased vision, and floaters
- Signs: Anterior chamber cell/flare, vitreous cell/haze, retinal whitening, chorioretinal lesions, ischemia, macular edema, optic nerve atrophy
- Systemic causes: Fungal infections, syphilis, tuberculosis, Behcet’s disease, malignant melanomas, leukemia, lymphoma, toxoplasmosis, sympathetic ophthalmia, and Lyme disease
Using ophthalmic steroids to treat uveitis
Infectious etiologies account for approximately 20% of cases and may include viruses, bacteria, fungi, or parasites/worms. On the other hand, anterior uveitis is the most common presentation and may be treated topically with steroids and cycloplegics in most patients.
Pred Forte (prednisolone acetate 1%) and Durezol (difluprednate 0.05%) are the most appropriate ophthalmic drugs, as usage is on-label. Dosing will depend on the severity of the presentation. For mild cases, an initial dosage of every 4 hours (Q4H) or QID is common.
For moderate to severe cases, a loading dose of every 1 to 2 hours for the first day or two of treatment is often beneficial. Tapering should be performed as resolution is observed, and close monitoring is integral. This includes measuring IOP on the initial visit, at each follow-up, and between 2 to 4 weeks post-diagnosis. Additionally, a uveitis workup should be considered, including blood work, and should be tailored based on case presentation, particularly in bilateral, granulomatous, or recurrent cases.
Intermediate, posterior, and panuveitis require systemic steroids, blood work, and extensive monitoring, as well as treatment of the underlying condition causing the inflammation. Referral to a general ophthalmologist or uveitis specialist is common in these cases.
Download the Ophthalmic Topical Steroids and NSAIDs Cheat Sheet
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Ophthalmic Topical Steroids and NSAIDs Cheat Sheet
Use this cheat sheet for quick reference on ophthalmic steroids and NSAIDS.
Bacterial corneal ulcers
The most common form of corneal ulcer, bacterial ulcers, are often related to poor contact lens hygiene and may present peripherally or centrally on the cornea.2 The top three bacterial pathogens for corneal ulcers are Staphylococcus aureus, coagulase-negative staphylococcus, and Pseudomonas aeruginosa.2
Treatment for peripheral ulcers, first and most importantly, includes a topical antibiotic, typically a fluoroquinolone, with close monitoring.3 Topical steroids are often used in clinical practice to treat the associated keratitis, mild iritis, and prevent scarring only after a positive response to the topical antibiotic has been established, and infection is controlled.3 For dense sub-epithelial infiltrates, consider increasing the initial dosage short-term.3
“Steroid dosage is commonly started at QID, with tapering dependent upon resolution.”
There has been suspicion that steroids can decrease the effectiveness of the topical antibiotic; however, animal studies have not shown this to be accurate. Again, here is a reminder to check IOP when there is corneal re-epithelialization or when deemed medically necessary, based on case presentation (prior to complete resolution of the condition).
It’s important to note that the use of topical steroids has been viewed as controversial over the years, and studies are overall inconclusive regarding how beneficial administration may be. The Steroids for Corneal Ulcers Trial (SCUT I) did show that outcome was not negatively affected by the use of steroids for the study population as a whole, and in certain cases, steroid dosage improved outcomes.
Central ulcers are at high-risk for permanent vision loss and often require consultation by a cornea specialist.
Conjunctivitis
Conjunctivitis is defined as inflammation or infection of the conjunctiva and is the leading cause of eye redness and discharge.4 This condition may be infectious in nature, with viral conjunctivitis being the most common form, then followed by bacterial.4 Non-infectious conjunctivitis may stem from allergy or toxin-induced etiology.
Treatment for conjunctivitis depends heavily on the cause:
- Bacterial conjunctivitis should be treated with a topical antibiotic and allergic conjunctivitis with a topical antihistamine or mast-cell stabilizer (or combination).
- Viral infections will eventually resolve over time, though palliative therapy with artificial tears and cold compresses helps with patient comfort.4
- Adenoviral conjunctivitis, if caught early, responds well to in-office administration of betadine 5% therapy.
Steroid treatment in conjunctivitis cases is considered off-label but is utilized frequently clinically to reduce inflammation and provide comfort for the patient. Steroid use has also been beneficial in reducing the chances of scarring in severe cases.5
Dexamethasone may be used and has been studied extensively for ocular inflammation. Additionally, Pred Forte, Lotemax Gel (loteprednol etabonate 0.5%), Eysuvis (loteprednol etabonate 0.25%), and Lotemax SM (loteprednol etabonate 0.38%) may be used off-label when appropriate.5
“Like other conditions discussed, dosage is variable, but QID is a good starting point.”
Both dexamethasone and loteprednol are available in a combination with tobramycin, which can be useful if a bacterial component is suspected.5 These drugs should be used short-term with Q4-6H dosing recommended. Once again, it is important to check IOP at the initial visit and between 2 to 4 weeks post-diagnosis.
Dry eye disease
It is important to remember that dry eye disease is a complex and layered condition that could certainly warrant its own extensive article. However, it has been shown to be associated with abnormalities in the pre-corneal tear film that lead to subsequent inflammation in the entire ocular surface.6 This strong link to an inflammatory response drives the use of steroids in the treatment of dry eye disease.
“Several clinical studies have shown the effectiveness of topical steroids in DED management.”
Both 1% solution of non-preserved methylprednisolone and loteprednol etabonate 0.5% have been studied at QID dosing and have shown clinically significant improvement in patients’ signs and symptoms.6 Loteprednol etabonate and fluorometholone are often preferred in clinical practice due to their lower risk of IOP increase.6 Currently, Eysuvis is the only on-label steroid indicated to treat the signs and symptoms of dry eye, including those who might suffer from dry eye flares.
Steroids should not be used in cases where herpes simplex virus epithelial keratitis is suspected. Also, patients should be monitored for negative side effects, including prolonged infection and IOP spikes in the short term, as well as cataract or glaucoma development with long-term use.
Commonly used topical NSAIDs
Now we’ll evaluate some uses of topical NSAIDs in primary eye care. NSAIDs are used much less frequently by primary care optometrists than by ophthalmologists due to the role and indication of these medications in postoperative management.
“However, there are conditions outside of postoperative care that NSAIDs are useful in managing off-label.”
The most frequent of these is ocular pain. Topical NSAIDs are effective at breaking the pain feedback loop that is associated with superficial ocular insult, which can result from corneal abrasion, corneal foreign bodies, chemical keratitis, and recurrent corneal erosion.7
NSAIDs are widely utilized to treat and prevent postoperative macular edema due to its inflammatory nature. Research has shown that inflammation is present in macular edema associated with exudative age-related macular degeneration (AMD) as well as diabetic macular edema.8 Therefore, NSAIDs have shown to be beneficial as preventative or supplemental treatments for these patients.8
One other condition in which topical NSAIDs are showing promise is central serous chorioretinopathy (CSCR or CSR). A study published in 2019 demonstrated that treatment with topical bromfenac or topical nepafenac led to a faster and more significant reduction in subretinal fluid volume over a period of a few weeks when compared to untreated eyes.9
Recommended dosage in each of the above situations depends on which drug is selected.
A note on the cheat sheet
You will notice that the steroid table does not have a dosage column. This is because the recommended dosage will change dramatically depending on the patient’s presentation and diagnosis, as discussed above. Just remember to taper if you’re using a steroid for more than a few days!
