Efficacy of<scp>COX</scp>‐2 inhibitors in controlling inflammation and capsular opacification after phacoemulsification cataract removal

Brookshire, Heather L.; English, Robert V.; Nadelstein, Bradley; Weigt, Anne K.; Gift, Barrett W.; Gilger, Brian C.

doi:10.1111/vop.12159

Cited by 22 publications

(14 citation statements)

References 74 publications

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“…A standard, commercial NSAID was elected in the oral efficacy study for comparison. Oral carprofen, a selective cyclooxygenase (COX-2) inhibitor, plays an important role in veterinary ocular therapeutics to suppress prostaglandin-mediated anterior uveitis, as seen following intraocular surgery ( 37 , 38 , 40 ). Although COX-2 inhibitors are thought to have wider safety margins compared with COX-1 inhibitors, adverse side effects may still occur including nausea, diarrhea, gastrointestinal ulceration, nephrotoxicosis, platelet dysfunction, and idiosyncratic hepatotoxicosis ( 37 , 38 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation

Ganugula¹,

Arora²,

Lepiz

et al. 2020

Sci. Adv.

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Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)–coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GA2-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles (n = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) (n = 8) and untreated controls (n = 8). PLGA-GA2-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (<4 hours). This study highlights the potential of PLGA-GA2 nanoparticles for systemic drug delivery across ocular barriers.

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Section: Discussionmentioning

confidence: 99%

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation

Ganugula¹,

Arora²,

Lepiz

et al. 2020

Sci. Adv.

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“…Several prior studies have attempted to determine whether aggressive prevention of postsurgical inflammation can ameliorate PCO; however, the results are equivocal. 27 , 34 , 96 – 99 However, in each case, only a subset of the proinflammatory pathways active PCS have been targeted, so these studies do not definitively rule out the therapeutic potential of shutting down PCS inflammation in PCO prevention.…”

Section: Discussionmentioning

confidence: 99%

Lens Epithelial Cells Initiate an Inflammatory Response Following Cataract Surgery

Jiang

Shihan

Wang

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeLens epithelial cell (LEC) conversion to myofibroblast is responsible for fibrotic cataract surgery complications including posterior capsular opacification. While transforming growth factor beta (TGFβ) signaling is important, the mechanisms by which the TGFβ pathway is activated post cataract surgery (PCS) are not well understood.MethodsRNA-seq was performed on LECs obtained from a mouse cataract surgery model at the time of surgery and 24 hours later. Bioinformatic analysis was performed with iPathwayGuide. Expression dynamics were determined by immunofluorescence.ResultsThe LEC transcriptome is massively altered by 24 hours PCS. The differentially expressed genes included those important for lens biology, and fibrotic markers. However, the most dramatic changes were in the expression of genes regulating the innate immune response, with the top three altered genes exhibiting greater than 1000-fold upregulation. Immunolocalization revealed that CXCL1, S100a9, CSF3, COX-2, CCL2, LCN2, and HMOX1 protein levels upregulate in LECs between 1 hour and 6 hours PCS and peak at 24 hours PCS, while their levels sharply attenuate by 3 days PCS. This massive upregulation of known inflammatory mediators precedes the infiltration of neutrophils into the eye at 18 hours PCS, the upregulation of canonical TGFβ signaling at 48 hours PCS, and the infiltration of macrophages at 3 days PCS.ConclusionsThese data demonstrate that LECs produce proinflammatory cytokines immediately following lens injury that could drive postsurgical flare, and suggest that inflammation may be a major player in the onset of lens-associated fibrotic disease PCS.

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“…Previous work by Brookshire et al . demonstrated that POH was similar in dogs receiving either bromfenac alone or prednisolone acetate alone as postoperative anti‐inflammatory therapy after cataract surgery . The current study does not ascertain the role of corticosteroids in the generation of POH.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports within the veterinary literature have identified IOP elevations following their use in canines presumably as a result of an increase in outflow resistance and from the inhibition of endogenous PG synthesis . A recent canine study showed that there was no association between COX‐2 inhibitor administration and ocular hypertension following cataract surgery …”

Section: Introductionmentioning

confidence: 99%

Comparison of topically applied flurbiprofen or bromfenac ophthalmic solution on post‐operative ocular hypertension in canine patients following cataract surgery

English

Nadelstein

et al. 2016

Veterinary Ophthalmology

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Efficacy ofCOX‐2 inhibitors in controlling inflammation and capsular opacification after phacoemulsification cataract removal

Cited by 22 publications

References 74 publications

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation

Lens Epithelial Cells Initiate an Inflammatory Response Following Cataract Surgery

Comparison of topically applied flurbiprofen or bromfenac ophthalmic solution on post‐operative ocular hypertension in canine patients following cataract surgery

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