In 2018, a 43-year-old Chinese woman complained about a 14-day history of progressing pain and redness in her right eye. She had no ocular disease and medical history. There was no evidence of inflammatory arthritis or other symptoms of connective tissue disease. The best-corrected visual acuity was 20/40 in the right eye and 20/20 in the left eye. A crescent-shaped marginal corneal ulcer was noted from the 9 to 3 o'clock position on the right eye ( Figure 1A ). The cornea of the left eye was normal. There was no other evidence of posterior segment involvement in both eyes. Bacterial and fungal cultures were negative in corneal scrapings. The results of serum immunological examination were as follows: RF, 104 IU/ml (normal range, 0-20 IU/mL); anti-CCP antibody, 65.29 U/mL (normal range, 0-17 U/mL); anti-nuclear antibody (ANA), 1:100 (normal range, 1:100); anti-mutated citrullinated vimentin (anti-MCV), 303.6 U/mL (normal range, 0-20 U/ml). Antibodies against the glomerular basement membrane were negative. In addition, c-ANCA, anti-protease 3, and HLA-B27 were negative. Related laboratory results and minimum/maximum values are in  Supplementary Table 1 . The primary diagnosis was PUK in the right eye and its association with autoimmune disease was highly suspected. Treatment with topical tacrolimus and tobramycin dexamethasone eye drops was initiated but was found to be ineffective after a three-day observation. Slit-lamp examination showed a newly emerged conjunctival congestion and peripheral ulcerative keratitis was observed in the left eye ( Figure 1B ). In addition to the eye drops of topical tacrolimus and tobramycin dexamethasone in both eyes, intravenous cyclophosphamide (200 mg, once every 2 weeks) and methylprednisolone (40 mg/day) were also given immediately.
However, the corneal ulcers were not well controlled and rapidly developed into nearly 360-degree ulcers in both eyes within one week. Nodular episcleritis appeared in the right eye ( Figures 1C, D ). The conjunctival biopsy of the right eye revealed vascular proliferation, telangiectasis, perivascular lymphocytes and plasma cells infiltration ( Figure 2A ). At the same time, the patient received a further systemic examination. No obvious abnormality was found in joint X-rays on both hands and wrists ( Figure 2B ). Chest CT showed multiple nodules in the inferior lobes of both lungs ( Figure 2C ). The laboratory results showed no apparent abnormality in antiphospholipid antibody, interferon detection, mixed lymphocyte culture, tuberculosis testing, thyroid function, renal function, and an ultrasonic cardiogram. Infliximab (3 mg/kg for three starter doses at 0, 2, and 6 weeks respectively, and the same dose every 8 weeks after the three starter doses) and an increased dose of 60 mg/day oral prednisolone following pulsed methylprednisolone (1,000 mg/day for 3 consecutive days per week) twice were administered. The oral prednisolone was continued at a stable dose for four weeks and then gradually tapered by 5 mg every ten days. At the 2-month follow-up visit, corneal ulcers almost healed up in both eyes ( Figures 3A, B ).
However, PUK recurrence in both eyes was observed two years later, half a year after she stopped using Infliximab due to the impact of the COVID-19 pandemic in 2019. Slit-lamp examination showed that the superior two-thirds of the cornea was covered by neovascularization and necrotic tissue in the right eye, and corneal ulceration was observed throughout the cornea except for the central cornea in the left eye ( Figures 3C, D ). No new symptoms and abnormal results were found in systemic examination and serum immunological examination, respectively. Infliximab (5 mg/kg every 4 weeks) and an increased dose of 60 mg/day of oral prednisolone were administered again besides the topical eye drops. At the 2-month follow-up visit, the patient's ocular condition remained stable. Her visual acuity was hand movements in the right eye and 20/400 in the left eye. She was suffered from the loss of vision and under great pressure of huge medical fees.  Figure 4  was showcasing a timeline with relevant data from the episode of care.