The efficacy of topical citrate after alkali injury is dependent on the period of time it is administered.

The neutrophilic response in the alkali-injured rabbit cornea can be separated into two peaks: the first from 12-24 hr and the second at 21 days. In the experiments detailed here, alkali-injured rabbit eyes were treated for 0-7 days (early peak), 6-35 days (late peak), or 0-35 days (both peaks) with 6.5% or 10% topical citrate. Clinical evaluation of these eyes showed that treatment with 10% citrate (0-35 days) significantly reduced the incidence and severity of corneal ulceration from the control level. When 10% citrate was administered to block the early neutrophilic peak, the incidence of corneal ulceration was also significantly reduced (33.3% from 72.2%). The average ulcer depth increased gradually, reaching an intermediate level well below the control group by day 35. In contrast, 10% citrate treatment of the late peak had no significant effect on the incidence of ulceration; however, these ulcers were less severe than those in the control. When 6.5% topical citrate (0-35 days) was used, there was a significant reduction in the severity but not the incidence of ulceration. In addition, the beneficial effects obtained from separate treatment of the early and late PMN peaks were mostly lost. These experiments suggest that both the early and late peak of the PMN response after alkali injury are important to the development of corneal ulcers. We hypothesize that the early use of 10% citrate diminishes the initial peak of PMNs, interfering with the release of self-perpetuating inflammatory mediators, thereby decreasing the later accumulation of PMNs that cause ulceration.