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Early Immunosuppressive Therapy Linked to Better Outcomes for RA-Associated Peripheral Ulcerative Keratitis


Patients who received early immunosuppressive therapy for their rheumatoid arthritis (RA)–associated peripheral ulcerative keratitis experienced earlier inflammatory control, fewer recurrences, and better visual outcomes.

Individuals with rheumatoid arthritis (RA)–associated peripheral ulcerative keratitis (PUK) were more likely to achieve earlier inflammatory control if they received early immunosuppressive therapy (IMT), according to a small study published in British Journal of Ophthalmology.

PUK is a rare inflammatory disease affecting the peripheral cornea, with nearly half of all patients having an associated rheumatic disease and 34% of patients having RA-associated PUK.

The single-center, retrospective, comparative cohort study found that individuals who received early IMT also experienced fewer PUK recurrences and had better visual outcomes, compared with patients who did not receive early IMT.

To come to this finding, the study authors analyzed 52 eyes among 36 patients with RA-associated PUK. Most (80.6%) were women, the mean (SD) age was 55.9 (11.4) years, and mean follow-up time was 41.2 (53.3) months.

Patients were divided into 2 groups based on whether they were exposed to early IMT, defined as receiving therapy within the first 4 weeks from PUK onset. Of 52 eyes, 37 (71.2%) received early IMT and 15 (28.8%) did not. Outcomes included PUK recurrence, inflammatory control, and development of ocular complications such as corneal scarring and perforation, cataract formation or progression, and permanent visual loss.

Of the 36 patients, 11 had RA associated with secondary Sjögren syndrome (SS), an immune system condition that often accompanies immune conditions such as RA and lupus. Bilateral involvement was observed in 16 patients, and 19 eyes among 13 patients were receiving IMT at PUK onset.

The authors noted that 24 patients had already received a RA diagnosis by the time of PUK onset, while 12 patients received the diagnosis after PUK onset. Additionally, many of the included patients were women of low socioeconomic status who were attending a public tertiary eye care clinic. This led the authors to believe health care disparities among the Mexican-mestizo population included in the study may be linked to these delayed diagnoses and, therefore, advanced RA disease activity.

“Such factors have been linked to late referral to rheumatologists, delayed diagnosis, delayed disease-modifying antirheumatic drug or IMT initiation, and higher disease activity scores in early RA,” the authors said. “It is widely recognised that initiating IMT within 12 weeks from symptom onset represents the best therapeutic window of opportunity to achieve remission and prevent further RA progression.”

Data showed that early IMT was a protective factor against PUK recurrence (HR, 0.345; 95% CI, 0.126-0.946; P = .039).

However, delayed RA diagnosis after PUK onset (HR, 4.93; 95% CI, 1.75-13.85; P = .002) and slower control of inflammation, defined as taking 2 months or longer (HR, 8.37; 95% CI, 1.88-37.16; P = .005), were risk factors for PUK recurrence.

Risk factors for visual loss included:

  • delayed IMT (OR, 7.75; 95% CI, 2.00-29.99; P = .003)
  • unknown diagnosis of RA at first visit (OR, 4.14; 95% CI, 1.15-14.91; P = .030)
  • at least 1 PUK recurrence (OR, 6.42; 95% CI, 1.71-24.07; P = .006)

According to a survival analysis, eyes exposed to early IMT had a lower risk of PUK recurrence (P =.039).

As the authors noted, there are currently no guidelines on how long systemic corticosteroids and IMT need to be maintained to avoid inflammation recurrence in general.

They also noted that while this was a small retrospective study, the findings reflect the need for early diagnosis and treatment of RA and RA-associated PUK.

“Patients with PUK must undergo a hasty diagnostic workup to discard infection and initiate prompt and aggressive IMT,” the authors noted. “Close collaboration between ophthalmologists and rheumatologists is required to adequately establish, titrate and manage drug-induced complications of IMT.”


Ruiz-Lozano RE, Ramos-Davila EM, Garza-Garza LA, Gutierrez-Juarez K, Hernandez-Camarena JC, Rodriguez-Garcia A. Rheumatoid arthritis-associated peripheral ulcerative keratitis outcomes after early immunosuppressive therapy. Br J Ophthalmol. Published online April 13, 2022. doi:10.1136/bjophthalmol-2022-321132

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