Optometrists are well-equipped to treat patients with anterior uveitis, but the condition’s clinical presentations and potential for underlying systemic associations can present various challenges for the eye care professional. The inflammation resulting from the disease can be tough to control and sometimes requires systemic nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressants. Treatment regimens with topical steroids often require frequent dosing — and poor compliance with dosing schedules can lead to poor patient outcomes. Patients may also delay or avoid prescribed blood work visits.
But patients aren’t the only individuals who make anterior uveitis management a challenge for clinicians. When laboratory testing is needed, false positives and negatives can cloud the clinical picture. The process of getting the results sent back to the office can be a challenge as well.
Despite these challenges, optometrists are poised to play a vital role in the care of patients with uveitis. The condition frequently does not require surgery, and most states allow optometrists to completely manage the disease. Only a small portion of patients with uveitis require intravitreal injections, implants, or systemic immunotherapy. A shortage of uveitis specialists and a disinterest among ophthalmologists in managing uveitis creates an opportunity for optometrists to showcase their clinical skills in providing uveitis management.
Uveitis Causes and Clinical Characteristics
Uveitis, or iridocyclitis, is the inflammation of the uveal tissue of the eye, which manifests when there is a disruption of the blood barrier in these tissues leading to a leakage of inflammatory cells. This disruption is usually caused by injury, autoimmune disease, or infection. Uveitis can be caused by both systemic and local ocular disease and can be characterized by location, type of inflammation, and chronicity. Anterior uveitis is the most common form of uveitis encountered in the clinical setting, comprising 80% of cases.1 The condition involves inflammation of the iris and ciliary body. Uveitis can also be described as being either granulomatous or non granulomatous, according to the presence of granulomatous nodules on the iris for the former, or mutton fat keratic precipitate on the corneal endothelium for the latter. The length of time a patient has uveitis is also used to categorize the disease. Uveitis lasting 3 months or less is referred to as acute, while chronic uveitis describes a disease duration longer than 3 months.2
HLA-B27 Anterior Uveitis
While anterior uveitis is often caused by ocular and systemic disease, it is idiopathic in 50% of cases. However, research shows that human leukocyte antigen (HLA)-B27, which is associated with uveitis, can account for 40-70% of cases in various patient populations.3 The HLA molecule is a major histocompatibility protein found on the surface of leukocytes that plays a role in immune system regulation. Specifically, HLA-B27 has a strong association with anterior uveitis. A 2012 study revealed that the HLA-B27 antigen was found to be the most common etiology of anterior uveitis.4 While the tertiary care center setting and the influence of geographic location may have affected etiology in this investigation, the data is consistent with other examples in the literature that show HLA-B27 to be the most prevalent known factor associated with anterior uveitis. This is important, as uveitis can be the presenting sign of a systemic disease.
HLA-B27 and Spondyloarthritis
HLA-B27 anterior uveitis is associated with a group of seronegative spondyloarthropathies, which include ankylosing spondylitis (AS), inflammatory bowel disease (IBD), psoriatic arthritis, reactive arthritis, and undifferentiated spondylitis, but a patient can have HLA-B27 acute anterior uveitis without systemic disease. AS is the most common of the spondyloarthropathies to be associated with uveitis.4 Approximately, 90% of patients with AS are HLA-B27 positive, and approximately 25% develop uveitis.5,6 The disease is characterized by an axial arthropathy affecting the lower spine and sacroiliac joints.
IBD includes Crohn disease and ulcerative colitis and uveitis is not a common extra-intestinal manifestation of IBD.7 However, when patients with IBD demonstrate uveitis, it tends to be chronic, bilateral, and have a higher probability of involving the posterior segment than other HLA-B27 uveitides.3
Psoriatic arthritis affects the phalangeal joints and has dermatologic and nail involvement. The likelihood of uveitis increases when psoriasis is accompanied by arthritis.5 About one-fifth of patients affected by psoriatic arthritis develop uveitis.5
Reactive arthritis, formerly known as Reiter’s syndrome, is accompanied by a triad of clinical manifestations, which include urethritis, arthritis, and conjunctivitis with uveitis. This condition is more common in men and boys and occurs after an enteric or chlamydial infection. Approximately 75% to 90% of individuals with reactive arthritis are HLA-B27 positive and about 25% of patients with a HLA-B27 seronegative spondyloarthropathy develop anterior uveitis.6,8 These data highlight the need for optometrists to understand systemic health when evaluating patients with uveitis.
Other Systemic Causes
Other systemic causes of anterior uveitis are sarcoidosis, syphilis, and Behcet disease — all of which are likely to result in posterior uveitis and panuveitis. Juvenile idiopathic arthritis and tubulointerstitial nephritis are potential causes of anterior uveitis in pediatric patients. Ocular diseases, including herpes simplex and zoster, uveitic-glaucoma-hyphema (UGH) syndrome, Fuchs heterochromic iridocyclitis, and Posner-Schlossman syndrome can cause uveitis. Clinicians must also be mindful that certain medications, such as bisphosphonates and immune checkpoint inhibitors, are known to cause uveitis.
Diagnosing and Treating Anterior Uveitis
Laboratory testing is warranted in patients with recurrent or bilateral uveitis, as these conditions signal a higher likelihood of systemic disease. Patients experiencing unilateral uveitis for the first time with concurrent systemic complaints may also benefit from a laboratory workup. Once a clinician decides that laboratory testing is necessary, they must establish a balance between ordering every laboratory test available and piecemealing tests together. Extensive testing that is unlikely to be associated with anterior uveitis increases the odds of a false positive. Contrarily, ordering 1 or 2 tests at a time delays a potential diagnosis and wastes time for the patient. Patients with anterior uveitis and no specific systemic complaints may benefit from HLA-B27, sarcoidosis (ACE), and syphilis (RPR/FTA-ABS) testing as a baseline. These tests must be tailored to the patient and ordered following a thorough review of demographics and systemic health.
Topical Corticosteroid Treatment
Topical corticosteroids are the mainstay for treatment of anterior uveitis. Stronger steroids are needed to suppress the inflammation and prevent rebounding. Difluprednate and prednisolone acetate are the ideal medications for management. Uveitis is frequently undertreated, but rarely overtreated. Difluprednate, dosed 1 drop every 2 hours, or prednisolone acetate, dosed every hour, are sometimes needed with moderate to severe anterior uveitis. A taper is necessary to prevent rebound inflammation and should be instituted slowly. A safe clinical protocol may involve reducing the daily treatment by 1 dose for a 1-week period, reducing it by another dose for a second week, and continuing the pattern until the patient has been weaned off of the medication. Tapering by more than half, such as going from every 2 hours to twice per day dosing increases the risk of rebound inflammation.2 Clinicians must be vigilant to monitor for a spike in intraocular pressure (IOP) if the patient is a steroid responder. When IOP increase occurs, it is usually after about 1 week of therapy.9 Immediately discontinuing steroid treatment is not necessary, but an aqueous suppressant may be added while the clinician tapers the steroid dose. Sometimes oral steroids are needed for recalcitrant uveitis. There is no set dosage, but the clinician must consider the patient’s size and medical history. Prescribing 3 to 4 doses of prednisone per day for a daily total of 40 to 60 mg is common. Again, a slow taper is recommended when discontinuing the medication.
Medications Frequently Used During Comanagement
Oral NSAIDs are not the first line of treatment, but they may be prescribed when oral steroids are contraindicated. Contraindications, such as uncontrolled diabetes, may warrant treatment with immunosuppressants as the next step. These may be oral, injectable, or infusion treatments. Comanagement with rheumatologists or ophthalmologists specializing in uveitis would likely be necessary, as they would be the individuals prescribing these medications. Subtenon, intravitreal, and steroid eluting implants are also viable treatment options, but they come with the risk of elevated IOP.10 Cycloplegics are a useful adjuvant to steroids due to their ability to stabilize the blood aqueous barrier, prevent or break synechiae, and alleviate photophobia. Cyclopentolate, homatropine, or atropine are all commercially available treatment options — each with its own benefits and challenges. Cyclopentolate has a shorter duration of action and must be dosed multiple times per day. This can be cumbersome, particularly if the patient is already frequently instilling steroid drops. Homatropine is effective, but availability is an ongoing issue. Many clinicians opt for atropine due the longevity of its treatment effect. Instilling 1 drop in-office can provide patients with symptomatic relief for several days. In addition to cycloplegia, a dilated fundus exam should be performed to rule out any posterior inflammation.
Optometry’s scope of practice may vary by state, but optometrists can diagnose anterior uveitis, provide symptomatic relief, and prevent vision loss in their patients. Clinicians who understand the challenges associated with this condition, prescribe the appropriate treatments, and devise comanagement strategies can confidently manage anterior uveitis, demonstrate their credibility as medical professionals, and improve quality of life in their patients.
- Uy HS, Christen WG, Foster CS. HLA-B27-associated uveitis and cystoid macular edema. Ocul Immunol Inflamm. 2001;9(3):177-183. doi:10.1076/ocii.18.104.22.16863
- Gerstenblith AT, Rabinowitz MP. The Wills Eye manual: office and emergency room diagnosis and treatment of eye disease. Fourth edition. Lippincott Williams & Wilkins; 2012.
- Waheed, N. HLA-B27 Associated Uveitis. Massachusetts Eye Research and Surgery Institute, Harvard Medical School Case Report. Published November 1999. Accessed January 20, 2023. https://uveitis.org/wp-content/uploads/2017/05/hla_b27_related_uveitis.pdf
- Barisani-Asenbauer T, Maca SM, Mejdoubi L, Emminger W, Machold K, Auer H. Uveitis—a rare disease often associated with systemic diseases and infections—a systematic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57. doi:10.1186/1750-1172-7-57
- Kaiser PK, Friedman NJ. The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. Fourth edition. Saunders; 2014.
- Onofrey BE. Ocular therapeutics handbook: a clinical manual. Third edition. Lippincott, Williams & Wilkins; 2011
- Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol. 2011;7(4)235-241.
- Wakefield D, Chang JH, Amjadi S, Maconochie Z, El-Asrar AA, McCluskey P. What is new HLA-B27 acute anterior uveitis? Ocul Immunol Inflamm. 2011;19(2):139-144. doi:10.3109/09273948.2010.542269
- Fiorelli VMB, Bhat P, Foster CS. Nonsteroidal anti-inflammatory therapy and recurrent acute anterior uveitis. Ocul Immunol Inflamm. 2010;18(2):116-120. doi:10.3109/09273941003587558
- Bodh SA, Kumar V, Raina UK, Ghosh B, Thakar M. Inflammatory Glaucoma. Oman J Ophthalmol. 2011;4(1):3-9. doi:10.4103/0974-620X.77655