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Objective To investigate optical coherence tomography (OCT) characteristics of tuberculous serpiginous-like choroiditis (Tb-SLC) and serpiginous choroiditis (SC) and to perform OCT to differentiate between these conditions. Methods This retrospective, case-control study examined consecutively enrolled patients with active Tb-SLC or SC. Patients underwent comprehensive ocular examinations and imaging (OCT, color fundus photography, autofluorescence imaging, fluorescein angiography, and indocyanine green angiography). Findings were examined and compared between eyes with SC and Tb-SLC. Results Nine patients with active Tb-SLC (14 eyes) and 8 with active SC (12 eyes) were included. The following OCT findings were observed significantly more often in the Tb-SLC group than in the SC group: vitreal hyper-reflective spots [5 Tb-SLC eyes (36%), no SC eyes; P = 0.02], intraretinal edema [11 Tb-SLC eyes (79%), 3 SC eyes (25%); P = 0.01], sub-retinal pigment epithelium (RPE) drusenoid deposits [11 Tb-SLC eyes (79%), 2 SC eyes (17%); P < 0.01], and choroidal granulomas [8 Tb-SLC eyes (57%), 2 SC eyes (17%); P = 0.03]. A hyporeflective, wedge-shaped band was observed more often in the SC group [5 Tb-SLC eyes (36%), 9 SC eyes (75%); P = 0.045] than in the Tb-SLC group. The incidence of other OCT signs did not differ between the groups and included outer nuclear layer hyper-reflection, outer retinal tabulation, and choriocapillaris point-like hyper-reflection. Conclusion Vitreal hyper-reflective spots, intraretinal fluid, sub-RPE drusenoid deposits, and choroidal granulomas on OCT images may indicate Tb-SLC. Additionally, a hyporeflective, wedge-shaped band may indicate SC. Therefore, OCT is likely helpful in differentiating between Tb-SLC and SC.