Role of steroids in the treatment of bacterial keratitis

Palioura, Sotiria; Henry, Christopher R.; Amescua, Guillermo; Alfonso, Eduardo C.

doi:10.2147/opth.s80411

Cited by 20 publications

(10 citation statements)

References 58 publications

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“…In fact, although the use of corticosteroid in infectious keratitis remains controversial, 16 some authors believe that a judicious use of corticosteroids (combined with the appropriate antimicrobial) could improve the outcome of keratitis as it reduces damage caused by the host's inflammatory response, decreases corneal scarring, and inhibits neovascularization. 17,18 From a safety viewpoint, the use of corticosteroids is known to potentially delay corneal wound healing and exacerbate signs of ocular infection. In vitro , inhibition of corneal wound healing in dogs is only reported for prednisolone concentrations that are much higher (≥620 μg/mL) 19 than the ones reported herein.…”

Section: Discussionmentioning

confidence: 99%

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis

Sebbag

Yan

Smith

et al. 2019

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels. Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at selected times. Prednisone and prednisolone were quantified in tears by liquid chromatography-mass spectrometry. Results: Lacrimal prednisone and prednisolone concentrations ranged from 2 to 523 ng/mL and 5 to 191 ng/mL, respectively. Drug concentrations were overall greater in dogs receiving higher doses of prednisone, but were not correlated with tear flow rate. Eyes with conjunctivitis often had larger amounts of prednisone and prednisolone in tear fluid compared to control eyes (up to +64%), but differences were not statistically significant. Significantly greater, but clinically insignificant, levels of prednisolone were found in eyes with severe versus mild conjunctivitis for oral prednisone doses ≥1.0 mg/kg. Conclusions: Disruption of the blood–tear barrier with conjunctivitis did not significantly affect drug levels in tears. Based on drug PK in tears, oral prednisone is likely safe for the management of reflex uveitis and ocular surface diseases. However, further prospective trials using systemic corticotherapy in diseased animals are warranted to confirm findings from this preclinical study.

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Section: Discussionmentioning

confidence: 99%

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis

Sebbag

Yan

Smith

et al. 2019

Journal of Ocular Pharmacology and Therapeutics

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“…4–6 Clinical management of ocular infections is often challenging and requires close attention to controlling both the pathogen and host inflammation to preserve the visual axis. 7,8 Accordingly, it is important to consider the potential of vaccine- induced inflammatory responses during the initial stages of vaccine development when targeting pathogens that commonly affect the eye.…”

Section: Introductionmentioning

confidence: 99%

Vaccine-induced antibodies target sequestered viral antigens to prevent ocular HSV-1 pathogenesis, preserve vision, and preempt productive neuronal infection

et al. 2019

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The cornea is essential for vision yet highly sensitive to immune-mediated damage following infection. Generating vaccines that provide sterile immunity against ocular surface pathogens without evoking vision loss is therefore clinically challenging. Here, we tested a prophylactic live-attenuated vaccine against herpes simplex virus type 1 (HSV-1), a widespread human pathogen that can cause corneal blindness. Parenteral vaccination of mice resulted in sterile immunity to subsequent HSV-1 challenge in the cornea and suppressed productive infection of the nervous system. This protection was unmatched by a relevant glycoprotein subunit vaccine. Efficacy of the live-attenuated vaccine involved a T-dependent humoral immune response and complement C3 but not Fcγ-receptor 3 or interferon-α/β signaling. Proteomic analysis of viral proteins recognized by antiserum revealed an unexpected repertoire dominated by sequestered antigens rather than surface-exposed envelope glycoproteins. Ocular HSV-1 challenge in naive and subunit-vaccinated mice triggered vision loss and severe ocular pathologies including corneal opacification, scar formation, neovascularization, and sensation loss. However, corneal pathology was absent in mice receiving the live-attenuated vaccine concomitant with complete preservation of visual acuity. Collectively, this is the first comprehensive report of a prophylactic vaccine candidate that elicits resistance to ocular HSV-1 infection while fully preserving the cornea and visual acuity.

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“…The role of combination in therapy in the management of corneal ulceration has been less definitive. In the Steroids for Corneal Ulcers Trial (SCUT), the use of steroids in acute ulceration was examined (Palioura et al 2016). This study found an overall lack of benefit, but also a lack of harm in using steroids in conjunction with antibiotics for the treatment of bacterial corneal ulcers.…”

Section: Combined Use Of Anti-infectives and Anti-inflammatories In Smentioning

confidence: 99%

Anti-Infective and Anti-Inflammatory Pharmacotherapies

Rosenblatt

2017

Handbook of Experimental Pharmacology

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Ocular infection and inflammation are common and are associated with myriad ocular conditions ranging from mild disease to blinding conditions. There are numerous anti-invectives with spectra against inciting pathogens. Given the potential for ocular infections to rapidly progress initial broad spectrum therapy is usually required, with therapy tailored as microbiological identification and sensitivities become available. The emergence of antibiotic resistance has become a major health problem. Anti-inflammatory therapy can be institutes to prevent ocular symptoms and end-organ damage. A therapy should be selected which is potent enough to interrupt the inflammatory cascades in play, but which avoids potential side effects. Glucocorticoids, NSAIDs, and biological agents may be used singularly or in combination. New drug delivery devices may allow for better local treatment of chronic ocular inflammation.

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Role of steroids in the treatment of bacterial keratitis

Cited by 20 publications

References 58 publications

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis

Vaccine-induced antibodies target sequestered viral antigens to prevent ocular HSV-1 pathogenesis, preserve vision, and preempt productive neuronal infection

Anti-Infective and Anti-Inflammatory Pharmacotherapies

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