Untoward effects of high dose methylprednisolone therapy on blood-retinal barrier closure, retinal hole repair, and long-term scarring

Thirty-seven New Zealand Red rabbits were either dosed with methylprednisolone sodium succinate (MP, n=18) about 20 min before laser irradiation, or they were left untreated (n=19). Dosing with MP was tapered at 30, 30, 20, 20, and 10 mg/kg/day for five consecutive days. Retinas were irradiated with a multi-line argon laser to produce retinal injuries (grid of 16 lesions/eye) near hemorrhaging levels (285 mW/10msec, 290 μm retinal spot size). A variety of funduscopic and histologic assessments were made for hemorrhagic and non-hemorrhagic lesions from 10 min to 6 mo after injury. Fluorescein angiography showed that non-hemorrhagic control lesions stopped leaking at 3d post injury, but MP-treated lesions leaked for 2-4 days longer. After MP treatment, funduscopic lesion areas were similar to controls during the first 24 h then became smaller by 1 mo. After 1 mo, MP-treated lesions increased in area while controls became reduced. Histologic analysis showed no effect on reduction of neutrophils (PMN) in MP-treated lesions over controls at 3 hr. At 24 hr, retinal PMN values in hemorrhagic lesions of the MP group were elevated (p<0.05) while monocyte/macrophage counts were reduced (p<0.05) compared to control. At 4d, MP impeded replacement of lost retinal tissue, and contributed to retinal hole development at 1 mo followed by extensive enhancement of chorio-retinal scarring at 6 mo. In severe laser-induced retinal trauma, the immunosuppressive effects of high dose MP therapy contributed to a variety of untoward wound healing outcomes, thereby suggesting caution in its use to treat similar injuries in humans