A 49-year-old female patient was referred to our clinic, complaining of a bilateral floating black shadow for approximately 4 months. There was no history of fever, backache, weight loss, hearing loss, mouth ulcers, skin lesions, or any other associated systemic illness. The patient's sister-in-law had tuberculosis 10 years previously. The patient had not received a Bacillus Calmette-Guerin vaccine and had been diagnosed with capillary occlusion in another ophthalmology clinic.
The best corrected visual acuity (VA) was 20/20 in both eyes. Anterior segment examination was within normal limits in both eyes. The intraocular pressure (IOP) was 11.7 mmHg in the right eye and 11.6 mmHg in the left eye. A color fundus photograph (CFP) and ultra-wide fundus photograph (UWFP) of both eyes showed dotted and segmental perivascular grayish-white deposits involving major vessels in the posterior pole and midperiphery with vitreous opacity (Figures 1A,B,D,E, 2A, 3A). Fundus autofluorescence (FAF) showed dotted and segmental hypoautofluorescence around vessels corresponding to the deposits on the CFP (Figures 1C,F). Optical coherence tomography (OCT) showed hump-like elevated hyperreflective deposits (HRDs) in the interface of the retinal vessels and vitreous cavity (VC), and several clusters of hyperreflective materials (HRMs) in the VC (Figures 2A, 3A). Fundus fluorescence angiography (FFA) showed dotted perivascular hypofluorescence in the posterior pole and midperiphery throughout all the phases in both eyes. In addition, early FFA of both eyes showed some hyperfluorescent dots in the midperiphery, which leaked in the late phase. Hyperfluorescence of the optic disc was also noted in both eyes on late FFA (Figures 4A-D). Indocyanine green angiography (ICGA) served to exhibit clear shapes and the sites of these deposits, which had a hypofluorescent appearance (Figures 4E-H). The imaging findings of PDs are summarized in Supplementary Table S1.
The patient was investigated through a complete work-up, including complete blood count, a renal and liver function test, infectious diseases tests (syphilis, hepatitis B and C, and human immunodeficiency virus), serum angiotensin-converting enzyme, Mycobacterium tuberculosis-IFN-gamma release assay (TB-IGRA), erythrocyte sedimentation rate, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, and antinuclear antibody, which were within normal limits except for a positive TB-IGRA of 301.9 pg./mL (normally not more than 14 pg./mL). Toxoplasmosis IgG and IgM were within normal limits. The viral analysis of the aqueous humor, including cytomegalovirus (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), revealed no positive results. Serum antibody of human T cell lymphotropic virus type 1 (HTLV-I) was supplementally conducted with no positive result. Purified protein derivative of tuberculin was performed in the local clinic and revealed that the local redness and induration was 15 mm in diameter and without necrosis and blisters. Computed tomography (CT) of the thorax showed well-defined nodules in the right upper lobe and the right middle lobe and nodular calcified lesions with lengths of approximately 5.5 mm in the posterior segment of the right upper lobe and nodular calcified lesions in the right hilum of the lung (Supplementary Figure S1) (the laboratory results are shown in Supplementary Table S2).
After consultation in the respiratory department, owing to TB infection, systemic anti-tubercular treatment was initiated with 600 mg of isoniazid, 300 mg of rifampicin, 1,500 mg of pyrazinamide, and 250 mg of levofloxacin along with oral prednisolone at 50 mg a day (the body weight of the patient was 76.8 kg). At the 1-month follow-up, a fundus examination of both eyes showed that the floaters in the VC were still present. However, the shrinkage of the HRDs was noted by OCT in both eyes (Figures 2B, 3B).
At the 6-month follow-up, the steroid was gradually tapered and remained at 7.5 mg. Fundus examination of the right eye showed both perivascular grayish-white deposits and the black floaters in the VC had disappeared. In addition, the HRDs of the right eye resolved and no hyperreflective materials were found in the VC with OCT (Figure 2C). However, in the left eye, the grayish-white deposits seemed to occur much more in the nasal periphery on the UWFP and the size of the HRDs became smaller than before and even disappeared at some sites. The black floats in the VC were much larger than before (Figure 3C). On FFA, the fluorescence leakage and staining of vessels could be noted in the periphery of both eyes. Additionally, a hot optic disc was observed in the late phase for both eyes. Furthermore, the hypofluorescence of PDs and vitreous opacity could be found in the left eye (Supplementary Figure S2).
At the 10-month follow-up, the patient complained of a decreased VA in the left eye. The systemic anti-tubercular treatment was accordingly changed to a dual anti-tubercular plan with the guidance of the respiratory department. Owing to the long-term use of systematic steroids and unilaterally decreased VA, 0.5 mL of 40 mg/mL triamcinolone acetonide (TA) sterile suspension (Kenacort-A, Jida Pharmac, Kunming, China) mixed with 0.5 mL of 2% lidocaine was slowly injected 1.5 cm into the orbit along the orbital margin of the lower eyelid. TA was administered in the presence of no blood in the pumpback after insertion to the left eye.
At the 11-month follow-up, the patient said that the symptoms in the left eye were relieved with the improvement of VA, suggesting the effectiveness of regional steroids. However, the regional steroids of TA might just work for approximately 2 to 3 weeks. So, methotrexate (MTX) was initiated as a steroid-sparing therapy in a weekly dose of 7.5 mg after an evaluation of liver and renal function. Another retrobulbar injection of TA was administered for supplementary anti-inflammatory therapy because MTX takes 6 to 8 weeks to have an effect. We enjoined the patient's steroid tapering to 5 mg per day beyond 6 weeks after adding MTX.
At the 13-month follow-up, the right eye remained stationary when the patient took MTX for 2 months. By contrast, the grayish-white deposits of the left eye increased and the vitreous floaters were not improved (Figure 3D). MTX was increased to 10 mg per week. Then, 0.7 mg of dexamethasone intravitreal implant (Ozurdex, Allergan, Irvine, CA, United States) was injected for the left eye, given the previously effective response of regional steroids. In addition, the patient showed normal intraocular pressure (IOP) after regional steroids and a dexamethasone implant. Notably, 3 months after the intravitreal dexamethasone implant (IVDI) for the left eye, the deposits disappeared on the UWFP, and the HRDs were resolved correspondingly (Figure 3E).
At the 20-month follow-up, fundus examinations of both eyes showed restoration and a quiet condition. FFA and ICGA were performed again. The early FFA showed mottled hyperfluorescence in the posterior pole and periphery. The late FFA revealed mild leakage of the deep capillaries. The late ICGA showed hyperfluorescence corresponding to the hyperfluorescence on the FFA (Supplementary Figure S3). Owing to the mild leakage of the left eye, we recommended another IVDI for the patient.
At the 25-month follow-up, FFA showed the leakage level of the left eye had been relieved. There was only capillary leakage in the posterior pole and midperiphery (Supplementary Figure S4). MTX was maintained for 14 months with regular liver and renal function monitoring. OCT showed no macular abnormalities, except for the epiretinal membrane. The patient showed no secondary complications and there was a clear improvement in the previous symptoms at the last follow-up. The changes in VA and IOP are depicted as line graphs in Supplementary Figure S5.