The patient received a 2-day course of intravenous vancomycin and ceftriaxone, oral prednisolone, and Kefzol eye drops. The hypopyon was completely resolved within 3 days from onset. No Gram staining or cultures were performed, but the mild course and response to steroids suggest that sterile endophthalmitis had occurred. Based on this severe ocular inflammation, the maximum tolerated dose was determined to be 1.0 mg. A second stage of the study that was planned to evaluate repeat doses of MP0112 was not initiated because ocular inflammation was observed and was attributed

RAD001 to impurities in the investigative product. AEs noted by the investigator to be related to the procedure were reported in 3 of 32 (9%) patients (conjunctival hemorrhage, vitreous detachment and hypertension, each occurring in 1 patient). Antidrug antibodies were detected in the serum of 8 patients. No further characterization of these was performed. The mean and median CRTs at baseline were 352 μm and 334 μm, respectively (standard deviation, 107.8 μm; range, 191–790) (Table 1). Generally, the higher-dose cohorts experienced a greater decrease in CRT during the 4-week study period (Figure 2). Patients who received 1.0 and 2.0 mg of MP0112 showed the greatest median reductions at week 4 of −95 μm and −111 μm, respectively, compared with

7 μm, −12 μm, and −62 μm in patients who received 0.04 mg, 0.15 mg, and this website 0.4 mg, respectively. The overall change in CRT across the dosing cohorts is shown in Figure 2. The initial reduction in CRT observed at week 1 was maintained and further reduced at week 4 in the higher-dose cohorts. Patients receiving 1.0 mg showed median reductions in CRT of −51 μm and −95 μm at weeks 1 and 4, respectively. The median reduction at week 1 in patients receiving 2.0 mg was −6.5 μm. This compared with a median reduction of −111 μm at week 4. In contrast, the CRT of lower-dose cohorts increased or stabilized after an initial decline (Figure 2, center). Patients who received 0.04 mg or 0.15 mg MP0112

had median changes of −33 μm and 7 μm (week 1) or −11 μm and −12 μm (week 4), respectively. The VA remained stable (defined as loss of <15 letters compared with baseline) TCL and did not vary from baseline in all dosing cohorts across the study period. Up to 100% of patients experienced either no loss in VA or a gain from baseline in letters on the ETDRS charts at each time point (94%, 97%, 94%, 91%, 91%, and 100% of patients at weeks 1, 2, 4, 8, 12, and 16, respectively). Of 32 patients, 4 (12.5%) experienced reversible loss of ≥15 letters secondary to inflammation at various time points. At initial screening, FA showed that patients had both mean and median leakage areas of 11.5 mm2 (±5.1; range, 1.6–20.8) across dose cohorts. At week 4, the mean and median leakage areas had decreased to 2.4 mm2 and 0 mm2, respectively (±3.8; range, 0–14.3) (Figure 3). FA also demonstrated a mean decrease in lesion size from 11.1 mm2 (median, 10.