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M. H. Criswell, W.-Z. Hu, P. Yuan, K. G. Csaky, M. R. Robinson; Differences in the Intravitreal Dosage of Triamcinolone Acetonide Can Elicit Inhibition or Paradoxical Augmentation of Choroidal Neovascularization (CNV) in Rat. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3394.
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Intravitreally administered triamcinolone acetonide (TA) is used to treat various ocular conditions. Unfortunately, ideal concentration and volumetric dosing information remains sketchy. Since TA can evoke steroid-related complications, an appropriate therapeutic dosage range needs to be determined. This preclinical study evaluated the efficacy of different TA dosages to inhibit CNV development in a rat laser model.
Micronized (~4 µm) preservative-free TA (initial concentration: 160 mg/mL in hydroxypropyl methylcellulose) was diluted to designated dosage concentrations with sterile saline immediately before injection. After laser induction of CNV sites, 10 µL of TA suspension was injected intravitreally at dosage concentrations that ranged from 10 to 80 mg/mL. Control eyes received equivalent volumetric injections of normal saline solution. Eyes were examined and processed for histologic analysis at 28 days after lasing.
Optimal inhibition of CNV development corresponded to 40 and 50 mg/mL dosages. Lower concentrations (30 to 10 mg/mL) were progressively less effective in inhibiting CNV formation. At dosages from 50 to 80 mg/mL, abnormal retinal vessels, retinal angiomatous proliferations, and anastomoses were evident around lesion sites. At dosages from 60 to 80 mg/mL, fibrotic tissues occurred in some sites and augmented CNV development at others. Endophthalmitis occurred in one eye dosed at 80 mg/mL.
In rat, TA’s efficacy as a CNV inhibitor increased progressively up to a maximum dosage of 40 mg/mL (with an estimated depot-to-vitreous dosage concentration of ~6.2 mg/mL). Extrapolating this rat vitreous dosage concentration to the adult human eye would be roughly comparable to an administration of 25 mg of TA. Increasing dosage concentrations further evoked new and aggravated preexisting deleterious effects in pathologic eyes.
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