Of 120 smear-positive cases of fungal keratitis enrolled in the trial, 101 had positive growth on culture (84%). Forty-four were identified as Fusarium species (44%): 21 were randomised to natamycin (48%) and 23 to voriconazole (52%). Nineteen isolates were identified as Aspergillus species, two of which were mixed infections, so 17 (17%) were included in this analysis (11 (58%) A flavus, 5 (26%) A fumigatus and 1 (5%) A terreus); 10 were randomised to natamycin (59%) and 7 to voriconazole (41%). At baseline, median infiltrate/scar size in Fusarium cases was 3.2 mm (IQR 2.2–5.1) in the natamycin arm and 3.7 mm (IQR 2.7–4.3) in the voriconazole arm (p=0.68). Median infiltrate/scar size in Aspergillus cases was 4.1 mm (IQR 3.4–6.0) in the natamycin arm, and 4.4 mm (IQR 2.1–5.5) in the voriconazole arm (p=0.44). The majority of patients in each arm in both Fusarium and Aspergillus cases had an infiltrate depth of >0–33% at baseline (for Fusarium, 11 of 21, 52%, in the natamycin arm, and 16 of 23, 70%, in the voriconazole arm, p = 0.60; for Aspergillus, 6 of 10, 60%, in the natamycin arm, and 4 of 7, 57% in the voriconazole arm, p = 1.00).
In Fusarium cases, there was no difference in 3-month BSCVA with voriconazole versus natamycin (0.11 logMAR, 95% CI −0.24 to 0.46, p = 0.54). Voriconazole was associated with an increase in perforation in Fusarium cases (OR 33.4, 95% CI 1.16 to 962.9, p = 0.041, ). Of seven perforations total in Fusarium cases, six were in the voriconazole arm and one in the natamycin arm. Six TPKs were performed, all of which were in cases that had perforated, five in the voriconazole arm and one in the natamycin arm. In Aspergillus cases, there was no difference in 3-month BSCVA with voriconazole versus natamycin (−0.21 logMAR, 95% CI −0.71 to 0.29, p = 0.38) or perforation (OR 0.09, 95% CI 0.0002 to 40.6, p = 0.44, ). Of four perforations, three were in the natamycin arm and one was in the voriconazole arm. Of these, there were two TPKs in the natamycin arm, and one in the voriconazole arm. There was one additional TPK in a case in the natamycin arm that had not perforated. There was no difference in perforation between the cases randomised to rescraping or no rescraping in either the Fusarium species or Aspergillus species subgroups.
Perforation in Fusarium and Aspergillus keratitis patients