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Cintia S. De Paiva, Fang Bian, Eugene Volpe, Li De-Quan, Stephen C Pflugfelder; Anti-inflammatory therapy preserves corneal clarity in alkali burned corneas associated with dry eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4691.
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This study investigated the hypothesis that anti-inflammatory therapy preserves corneal clarity, speeds wound closure and decreases neutrophil infiltration in a concomitant dry eye and corneal alkali burn murine model.
C57BL/6 mice were subjected to unilateral alkali ocular burn with 1N NaOH (OB) without or with concomitant desiccating stress (DS) for 2 or 5 days (D). A separate group of mice that received both OB and DS were topically treated either with 2µL Dexamethasone (Dex, 0.1%), 2uL of Doxycycline (Doxy, 0.025%) or vehicle (balanced salt solution, BSS) QID. Corneal clarity was graded daily using a 4 point scale. Presence of wound closure was investigated using 0.1% sodium fluorescein and a survival curve was generated. Mice were euthanized after 2 or 5 days and eyes and adnexa were collected for histology. Neutrophils were counted in frozen sections stained with Ly6G antibody using image analysis software.
Corneas subjected to OB+DS had significantly lower total wound closure rate (40% closure at 5 days vs. 100% controls, P=0.01), greater corneal opacity score (3.12± 0.62 vs. 2.4±0.5, p<0.01) and greater neutrophil infiltration in corneal stroma compared to OB controls 5D post injury. OB+DS eyes treated with Doxy had 100% of wound closure at 3D post injury, and significant lower corneal opacity scores at days 4 and 5 compared to OB+DS eyes treated with vehicle at the same time points (2.00±0.78 and 2.38±0.65 vs.3.28±0.76 and 3.30±0.75, P<0.01 and P<0.01, respectively). Although eyes treated with Dex had just 50% total wound closure at 5D, corneas in this treatment group showed the lowest corneal opacity score as soon as 2D post-injury which kept improving until 5D (2.00.63; 1.83±0.75; 1.77±0.44; 1.66±0.78, P<0.01 at days 2,3,4 and 5 vs. BSS treated eyes). Treatment with topical Dex in the OB+DS group significantly decreased neutrophil infiltration in corneal stroma compared with BSS treated corneas at both 2 and 5 days post injury (31.519±19.2 and 24.6 ± 9.71 vs. 83 ±17 and 86.5± 9.2 Ly6G positive cells/40X field, respectively, P <0.01 for both).
Concomitant dry eye and alkali burn leads to delayed wound healing and increased corneal opacity and neutrophil infiltration. Early treatment with anti-inflammatory therapy is very efficacious in preserving corneal clarity and facilitating wound healing, while controlling migration of neutrophils.
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