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INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

Yang Y, Bailey C, Loewenstein A, Massin P - Retina (Philadelphia, Pa.) (2015)

Bottom Line: There is a relationship between visual gains and drug persistence in the intravitreal compartment.Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery.With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

View Article: PubMed Central - PubMed

Affiliation: *Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom; †University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom; ‡Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and §Department of Ophthalmology, Lariboisière Hospital, Paris, France.

ABSTRACT

Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema.

Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials.

Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans.

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Related in: MedlinePlus

Central macular thickness (A) and BCVA (B) after a single injection of triamcinolone or bevacizumab.38 *P < 0.05 and **P < 0.01 for within-group changes from baseline. Reproduced from Paccola L, et al. Br J Ophthalmol 2008;92:76–80, with permission from BMJ Publishing Group Ltd. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.
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Figure 7: Central macular thickness (A) and BCVA (B) after a single injection of triamcinolone or bevacizumab.38 *P < 0.05 and **P < 0.01 for within-group changes from baseline. Reproduced from Paccola L, et al. Br J Ophthalmol 2008;92:76–80, with permission from BMJ Publishing Group Ltd. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

Mentions: Intravitreal triamcinolone acetonide has been evaluated for the treatment of DME in numerous small and a few large clinical trials. The majority of data regarding the efficacy of IVTA in patients with DME suggests that efficacy is greatest 1 month after injection and that these effects are no longer significant at 6 months. A single injection of ITVA (4 mg/0.1 mL) or bevacizumab (1.5 mg/0.06 mL) was examined in patients with refractory DME, defined as having at least 1 previous macular laser photocoagulation treatment.38 The single intravitreal injection resulted in peak functional and anatomical improvement (best-corrected visual acuity [BCVA] and CMT) between Weeks 4 and 8, after which these parameters returned to baseline by Week 24 (Figure 7). Similarly, in a prospective controlled trial of IVTA for refractory diffuse DME, CMT decreased after injection and was significantly lower at Weeks 4 and 12; however, this was no longer significant at Week 24 because of recurrence of macular edema in 5 of 12 eyes.39


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

Yang Y, Bailey C, Loewenstein A, Massin P - Retina (Philadelphia, Pa.) (2015)

Central macular thickness (A) and BCVA (B) after a single injection of triamcinolone or bevacizumab.38 *P < 0.05 and **P < 0.01 for within-group changes from baseline. Reproduced from Paccola L, et al. Br J Ophthalmol 2008;92:76–80, with permission from BMJ Publishing Group Ltd. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697357&req=5

Figure 7: Central macular thickness (A) and BCVA (B) after a single injection of triamcinolone or bevacizumab.38 *P < 0.05 and **P < 0.01 for within-group changes from baseline. Reproduced from Paccola L, et al. Br J Ophthalmol 2008;92:76–80, with permission from BMJ Publishing Group Ltd. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.
Mentions: Intravitreal triamcinolone acetonide has been evaluated for the treatment of DME in numerous small and a few large clinical trials. The majority of data regarding the efficacy of IVTA in patients with DME suggests that efficacy is greatest 1 month after injection and that these effects are no longer significant at 6 months. A single injection of ITVA (4 mg/0.1 mL) or bevacizumab (1.5 mg/0.06 mL) was examined in patients with refractory DME, defined as having at least 1 previous macular laser photocoagulation treatment.38 The single intravitreal injection resulted in peak functional and anatomical improvement (best-corrected visual acuity [BCVA] and CMT) between Weeks 4 and 8, after which these parameters returned to baseline by Week 24 (Figure 7). Similarly, in a prospective controlled trial of IVTA for refractory diffuse DME, CMT decreased after injection and was significantly lower at Weeks 4 and 12; however, this was no longer significant at Week 24 because of recurrence of macular edema in 5 of 12 eyes.39

Bottom Line: There is a relationship between visual gains and drug persistence in the intravitreal compartment.Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery.With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

View Article: PubMed Central - PubMed

Affiliation: *Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom; †University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom; ‡Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and §Department of Ophthalmology, Lariboisière Hospital, Paris, France.

ABSTRACT

Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema.

Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials.

Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans.

Show MeSH
Related in: MedlinePlus