A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance

Pflugfelder, Stephen C.; Maskin, Steven L.; Anderson, Bruce D.; Chodosh, James; Holland, Edward J.; Paiva, Cintia S. de; Bartels, S P; Micuda, Teresa; Proskin, Howard M.; Vogel, Roger

doi:10.1016/j.ajo.2004.04.052

Cited by 206 publications

(149 citation statements)

References 14 publications

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“…109 Clinically, prolonged use of topical corticosteroids is plagued by frequent side effects, such as cataract induction and glaucoma, that limit their wide use in dry eye; 109 however, the introduction of "soft-steroids" that carry a markedly reduced risk of sightthreatening side effects has led to community acceptance of corticosteroid therapy on a limited basis. 110,111 Topical treatment with 0.1% dexamethasone for 2 weeks prior to a low-humidity exposure stress using specially designed goggles significantly decreased corneal and conjunctival staining, improved blink rate and decreased Human leukocyte antigen -D related (HLA-DR) RNA levels in conjunctiva of patients with aqueous deficient dry eye. 112 Significant improvement in signs and symptoms of dry eye were observed after 3 weeks of topical 0.1% fluorometholone therapy in dry eye patients subjected to a 2-hour challenge in a controlled adverse environment exposure, 113 which increases the concentrations of MMP-9 and other inflammatory markers in tears.…”

Section: Corticosteroidsmentioning

confidence: 99%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

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Dry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. Increased levels and activities of matrix metalloproteinases (MMPs), particularly MMP-9, have been detected in the tears and ocular surface epithelial and inflammatory cells in dry eye. MMPs have been found to participate in disruption of tight junctions in the apical cornea epithelium leading to their accelerated desquamation and barrier disruption. This review summarizes evidence showing the contribution of MMPs to dry eye pathogenesis and their roles as biomarkers and therapeutic targets. Keywords: matrix metalloproteinase, dry eye, keratitis sicca, cornea, barrier function, Sjögren syndrome Dry eye overviewDry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. It affects millions of people worldwide and is one of the most frequent conditions for which patients seek eye care.1 Aging and female sex are significant risk factors for dry eye which increases in prevalence around the fifth decade, with further increase every decade thereafter.2-13 Prevalence of dry eye varies from 2% to 50%, depending on the population studied and the diagnostic criteria for dry eye (symptom questionnaire vs. objective signs). [1][2][3]6,7,[9][10][11][14][15][16][17][18][19][20][21][22][23] There is scarce information about the natural history of dry eye, but there is a recognized disconnection between signs and symptoms; patients tend to be more symptomatic at early stages.24,25 Dry eye causes corneal irregularity [26][27][28] and decreases functional vision by altering contrast sensitivity [29][30][31] and, therefore, decreases quality of life with a significant burden on the individual as well as the society. 23,[32][33][34][35] A meta-analysis of 22 published studies showed increased odds ratio for depression and anxiety in patients with ocular Sjögren syndrome (SS). 36 There is increased evidence that dry eye is an inflammatory disease, and this review will focus on matrix metalloproteinases (MMPs) and their role in the pathogenesis of dry eye. Cornea barrier disruption is a feature of dry eyeAs the principal lens of the eye, the cornea has unique features to maintain its transparency and smooth surface that include a lack of blood vessels and a multilayered stratified, non-cornifying epithelium. The differentiated apical epithelial cells produce

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Section: Corticosteroidsmentioning

confidence: 99%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

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“…In murine models topical steroids protect the integrity of corneal epithelial tight junctions, prevent desquamation of epithelial cells, and decrease MMP-9 levels, thereby preserving barrier function (International Dry Eye Workshop (DEWS) Management and Therapy 2007). In humans, pulsed dosing of loteprednol 0.5% (an ester steroid) starting with use 4 times daily for 1 week, followed by a slow taper, has been shown to improve bulbar conjunctival hyperemia and central corneal fluorescein staining scores by over 25% (Pflugfelder et al 2004). Loteprednol and fluorometholone, a ketone steroid, have also been found to convey lower risk of elevated intraocular pressure when compared to other ketone steroid drops, prednisolone and dexamethasone.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

Narayanan

Kuppermann

2016

Handbook of Experimental Pharmacology

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“…[25] Although the overall safety of topical glucocorticoids in clinical trials in pSS and keratoconjunctivitis sicca was considered satisfactory, prolonged use of topical glucocorticoids in pSS patients is restricted by their ability to induce glaucoma, cataract, decreased wound healing, increased risk of secondary infections, and epithelial defects. [26][27][28][29] Therefore, topical glucocorticoids are only recommended for short-term use when treatment with artificial tears is insufficient, and rapid reduction of inflammation should be achieved.…”

Section: Topical Glucocorticoidsmentioning

confidence: 99%

Safety of treatments for primary Sjögren’s syndrome

Nimwegen

Moerman

Smitt

et al. 2016

Expert Opinion on Drug Safety

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Introduction: Primary Sjögren's syndrome (pSS) is a disabling auto-immune disease, affecting exocrine glands and several organs. Areas covered:In this review we analyze the safety of therapies used in pSS. Symptomatic treatment is widely applied due to the good supportive effect and good safety profile. Systemic stimulation of tears and saliva can be successful in pSS. However, cumbersome adverse events can influence the tolerability of this therapy. Evidence for the effectiveness of synthetic DMARDs therapies in pSS is limited, while there is a risk of adverse events. Several studies on biologic DMARD treatment of pSS patients have shown promising efficacy and safety results. Expert opinion: The safety of symptomatic treatment of pSS is very good. However, systemic therapy is necessary to achieve long-term relieve and prevention of organ-damage. Synthetic DMARDs have not shown much efficacy in earlier studies, and their benefits do not weigh up to the possible harms, while biologic DMARDs show promising results regarding efficacy and cause mostly mild adverse events. Many questions remain unanswered regarding safety of DMARDs in pSS. There is a need for well designed studies, in which safety should be evaluated in a uniform manner to be able to compare the results between studies.ARTICLE HISTORY

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A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance

Cited by 206 publications

References 14 publications

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

Safety of treatments for primary Sjögren’s syndrome

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