A 56-year-old man going wild fishing nearly every day complained of a blurred vision and an inferior visual field defect in the right eye for one day. At presentation, he denied any systemic symptoms, but mentioned an insect-bite-like skin induration in his left leg two or three days prior to his visual symptom onset. His past medical history was remarkable. Ophthalmic examination in the medical record of local hospital showed a visual acuity of 20/20, no conjunctival injection, clear cornea, quiet anterior chamber, normal pupil size and light reflex, and swollen optic disc in the right eye, and normal left eye. He was diagnosed as ON in the right eye, immediately admitted to the local hospital, and treated with intravenous injection of dexamethasone 10 mg once per day for seven days.
However, his right eye vision progressively deteriorated to 20/50 during steroid therapy. Hence, the patient refused further steroid therapy. Unfortunately, 3 days after the cease of steroid therapy, he suffered from a high fever of 39 C and painful subcutaneous masses in the left groin. He then came to other hospitals for consultation, where physical examination revealed an eschar on the lateral skin of his left leg, and enlarged lymph nodes in the left groin which was confirmed by B-type ultrasound. His white blood cell count was 10.5 x 10 cells/L with neutrophils 88.3% (higher), lymphocytes 6.8% (lower), monocytes 4.6%, basophil 0.3%, and eosinophils 0%, red blood cell count 4.76 x 10 cells/L, platelet 118 x 10 cells/L. Activated partial thromboplastin time was 28 seconds (normal), thrombin time 18 seconds (normal), prothrombin time 10.4 seconds (normal), fibrinogen 2.13 g/L (normal), and D-Dimer 0.52 mg/L (normal). Erythrocyte sedimentation rate was 3 mm/hour (normal), C reactive protein was 12 mg/L (higher). Serum IgM was 3.333 g/L(higher), whereas serum IgG, IgA, Complement C3 and C4 were all within normal limits. Serum tests for pathogens including treponema pallidum, mycobacterium tuberculosis, herpes simplex virus, varicella-zoster virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, HIV, Dengue virus, novel bunyavirus, and toxoplasma gondii, as well as antinuclear antibodies, and antineutrophil cytoplasmic antibodies, were all negative. CBA revealed a triple negative test result for serum AQP-4 Ab, MOG-Ab, and GFAP-Ab. Serum test for Orientia tsutsugamushi by mNGS was positive. He was then diagnosed as scrub typhus and ON, and treated with doxycycline 100 mg twice per day, and omadacycline 300 mg per day for 6 days. His fever and diffuse shin rash which appeared on the day of antibiotic therapy rapidly resolved after treatment. However, his vision in the right eye continuously deteriorated to hand motion.
The patient was then referred to our neuro-ophthalmology clinic for further consultation. At presentation, physical examination confirmed the skin eschar on the left leg (Figure 1A), and B-type ultrasound revealed enlarged lymph nodes in both groins (Figure 1B). Ophthalmic examination revealed his right eye had a visual acuity of light perception, clear cornea, quiet anterior chamber, dilated pupils of 6 mm with sluggish light reflex, clear lens, and swollen optic disc (Figure 2A), and his left eye was normal (Figure 2B). Intraocular pressure was normal in both eyes. Further serum tests showed anticardiolipin IgM antibody of 154.4 GPL/ml (higher), beta-2-glycoprotein-I IgM antibody of 112.3 SMU/ml (higher), and C reactive protein 1.1 mg/L (normal). TBA revealed granular intracytoplasmic and circular perinuclear immunofluorescence staining in Purkinje cells (Figure 3, arrow) of monkey cerebellum tissues when they were incubated with the serum samples (diluted as 1:100) of the patient. Orbital MRI showed normal optic nerves with no enhancement (Figures 4A, B).
His diagnosis of unilateral ON secondary to scrub typhus was confirmed, and sequential intravenous methylprednisolone 500 mg per day for 3 days, 240 mg per day for 3 days, and 120 mg per day for 3 days, tapered by oral prednisone, together with doxycycline 100 mg twice per day, were prescribed. His serum titers of anticardiolipin IgM and beta-2-glycoprotein-I IgM antibodies decreased to 88.6 GPL/ml and 66.0 SMU/ml respectively one week later. Another one month later (11 weeks after the onset of ON), his right eye vision was gradually improved to 20/80, ophthalmic examination showed a pale optic disc (Figure 2C), and visual field test showed a tunnel field (Figure 2D) in the right eye. Repeated serum test revealed a further decrease in titers of anticardiolipin IgM and beta-2-glycoprotein-I IgM antibodies to 25.5 GPL/ml and 26.5 SMU/ml, respectively. The patient was followed up by telephone five months after the onset of ON, and he reported a stable visual acuity in the right eye, though steroid and doxycycline therapy already ceased.