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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

Mean change in BCVA with a single treatment (sham control or FAc implant) in the FAME study among all patients with chronic DME (A) and patients with chronic DME who were pseudophakic at baseline (B) (data on file, Alimera Sciences).
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Figure 9: Mean change in BCVA with a single treatment (sham control or FAc implant) in the FAME study among all patients with chronic DME (A) and patients with chronic DME who were pseudophakic at baseline (B) (data on file, Alimera Sciences).

Mentions: In the FAME trials, which examined the safety and efficacy of ILUVIEN in patients with DME, the greatest treatment effect was seen in patients with chronic DME.17 To further examine efficacy in the context of the pharmacokinetic results, the mean change in BCVA was determined for patients with chronic DME who received only a single ILUVIEN implant during FAME. Figure 9A demonstrates that efficacy was maintained through Month 36 in these patients (data on file, Alimera Sciences). A majority of patients who were phakic at baseline (80%) required cataract surgery; however, those patients who underwent cataract surgery during the study still experienced a visual benefit. In patients who were pseudophakic at baseline (Figure 9B; data on file, Alimera Sciences), there was stability of visual acuity on follow-up, particularly in a subgroup of patients with chronic DME and pseudophakia at baseline. Overall, these data suggest that a sustained, low dose of steroid delivered to the eye can result in long-term efficacy.


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

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

Mean change in BCVA with a single treatment (sham control or FAc implant) in the FAME study among all patients with chronic DME (A) and patients with chronic DME who were pseudophakic at baseline (B) (data on file, Alimera Sciences).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Mean change in BCVA with a single treatment (sham control or FAc implant) in the FAME study among all patients with chronic DME (A) and patients with chronic DME who were pseudophakic at baseline (B) (data on file, Alimera Sciences).
Mentions: In the FAME trials, which examined the safety and efficacy of ILUVIEN in patients with DME, the greatest treatment effect was seen in patients with chronic DME.17 To further examine efficacy in the context of the pharmacokinetic results, the mean change in BCVA was determined for patients with chronic DME who received only a single ILUVIEN implant during FAME. Figure 9A demonstrates that efficacy was maintained through Month 36 in these patients (data on file, Alimera Sciences). A majority of patients who were phakic at baseline (80%) required cataract surgery; however, those patients who underwent cataract surgery during the study still experienced a visual benefit. In patients who were pseudophakic at baseline (Figure 9B; data on file, Alimera Sciences), there was stability of visual acuity on follow-up, particularly in a subgroup of patients with chronic DME and pseudophakia at baseline. Overall, these data suggest that a sustained, low dose of steroid delivered to the eye can result in long-term efficacy.

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