A randomised controlled trial of ranibizumab with and without ketorolac eyedrops for exudative age-related macular degeneration

Abstract

This pilot study is the first to prospectively investigate the efficacy and safety of a combination of 0.45% ketorolac eyedrops three times a day and intravitreal ranibizumab injections in patients with CNV, and suggests that topical ketorolac supplements the activity of intravitreal ranibizumab in reducing CMT in CNV.

The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective

“…Some of these issues evolve from the use of mono-factor therapies, such as anti-VEGF drugs, to address a multifactorial, multi-genetic disease, as is the case of nAMD. In order to improve effectiveness, combination of treatment with other proangiogenic inhibitors as blocking PDGF ( [183,184], clinicaltrials.gov/NCT01940900), steroids, e.g., triamcinolone [185], or AINEs, such as ketorolac [186], and integrin antagonists [187] has been suggested as adjuvants to anti-VEGF regiments. Collectively, these novel therapeutic approaches indicate the need to simultaneously address a multitude of nAMD-associated factors.…”

Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

“…COX-2 is the predominant isoform in the retinal pigment epithelium (RPE) [14] and is upregulated during inflammatory processes, pain, and fever, but it is also expressed under normal conditions in sites such as the brain and kidneys [15]. COX-2 has also been found in choroidal neovascularization (CNV) and in DR [4, 5, 7, 8, 16–19]. PGs act by upregulating a number of soluble mediators responsible for the expression of vascular endothelial growth factor (VEGF), which plays a key role in the CNV and in the DR [20–22].…”

“…Although the evidence coming from human clinical trials is less consistent than that arising from animal models, a favorable effect of additive topical NSAID therapy with regard to anti-VEGF for the control of exudative AMD has recently been reported in 3 prospective, randomized, and controlled clinical studies (Table 2) [4, 5, 7]. …”

“…Russo et al [7] demonstrated that topical ketorolac acts in conjunction with intravitreal anti-VEGF treatment; central macular thickness (CMT) is significantly lower (−37.1  μ m) after 6 months in patients receiving combination therapy, although there were no differences in either visual acuity or the number of injections between the 2 groups. Such results are partially in contrast with the findings of Gomi et al [5], in which the authors also reported a reduction in the frequency of ranibizumab injections over 6 months when topical bromfenac was used as an adjunctive treatment with ranibizumab.…”

Combination of ranibizumab and indomethacin for neovascular age-related macular degeneration: randomized controlled trial

“…In particular, free radicals and oxidized lipoproteins in the aging retina are major local triggers of parainflammation, which is the chronic status responsible for the initiation and progression of age-related chorioretinal damage. 5 , 6 Thus, inflammation itself plays an important role in the pathogenesis of CNV and administration of a topical nonsteroidal anti-inflammatory drug (NSAID) has been shown to supplement the effectiveness of anti-VEGF agents in reducing central retinal thickness (CRT) 7 , 8 and the rate of re-injection in CNV. 9 A recent assessment of the vitreous penetration of NSAIDs and their effects on prostaglandin E 2 (PGE 2 ) revealed a significant reduction in vitreous PGE 2 levels in response to indomethacin, bromfenac, and nepafenac.…”