June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Suprachoroidal Microinjection Delivers Triamcinolone Acetonide to Therapeutically-Relevant Posterior Ocular Structures and Limits Exposure in the Anterior Segment
Author Affiliations & Notes
  • Henry Edelhauser
    Ophthalmology, Emory Univ Eye Center, Atlanta, GA
    Clearside Biomedical, Alpharetta, GA
  • Samirkumar Patel
    Clearside Biomedical, Alpharetta, GA
  • Carol Meschter
    Comparative Biosciences, Sunnyvale, CA
  • Robin Dean
    Comparative Biosciences, Sunnyvale, CA
  • Kendall Powell
    Tandem Labs, Durham, NC
  • Rozemarijn Verhoeven
    Clearside Biomedical, Alpharetta, GA
  • Footnotes
    Commercial Relationships Henry Edelhauser, Clearside Biomedical (P), Clearside Biomedical (I), Clearside Biomedical (C); Samirkumar Patel, Clearside Biomedical (E), Clearside Biomedical (I), Clearside Biomedical (P); Carol Meschter, None; Robin Dean, None; Kendall Powell, None; Rozemarijn Verhoeven, Clearside Biomedical (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5063. doi:
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      Henry Edelhauser, Samirkumar Patel, Carol Meschter, Robin Dean, Kendall Powell, Rozemarijn Verhoeven; Suprachoroidal Microinjection Delivers Triamcinolone Acetonide to Therapeutically-Relevant Posterior Ocular Structures and Limits Exposure in the Anterior Segment. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5063.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose: To evaluate the ocular and systemic PK of triamcinolone acetonide (TA) in the New Zealand White rabbit following intravitreal (IVT) injection or administration into the suprachoroidal space (SCS) using a Clearside Biomedical proprietary microneedle.

Methods: On Day 0, male rabbits (5/group) received a single bilateral administration of 4 mg TA (100 µL Triesence®) via SCS injection using a 33g 750µm microneedle or IVT injection using a standard 30g needle. Clinical observations, body weights, and intraocular pressure (IOP) were assessed up to 13 weeks post-dose. Plasma and ocular matrixes (aqueous humor (AH), lens, iris/ciliary body (ICB), vitreous humor (VH), sclera/choroid (SC), and retina) were sampled on Days 1, 14, 28, 56, and 91. Plasma (LLOQ 0.5 ng/mL) and ocular matrixes (LLOQ 2 - 15 ng/mL) were analyzed using LC-MS/MS, and resulting data were assessed for noncompartmental PK parameters.

Results: Preliminary data shows that there were no observed adverse effects related to treatment or method of administration. TA in plasma peaked on Day 1 at 4 ng/mL in both groups, and TA was quantifiable in all ocular matrixes through Day 91. Following SCS TA, TA was observed (in decreasing order) in SC>retina >VH>ICB>lens>AH. SCS TA Cmax and AUC (area under the concentration curve) was increased in SC (Cmax: 11-fold, AUC: 11-fold) compared with IVT TA. SCS and IVT TA retina Cmax and AUC were roughly equivalent, but SCS TA peaked more quickly (Day 1) compared with IVT TA (Day 14). Following IVT TA, TA was observed in VH>ICB>retina>lens>SC>AH. IVT TA Cmax and AUC was increased in AH (Cmax: 755-fold, AUC: 715-fold), lens (Cmax: 290-fold, AUC: 682-fold), ICB (Cmax: 24-fold, AUC: 44-fold) and VH (Cmax: 4-fold, AUC: 52-fold) compared with SCS TA.

Conclusions: Preliminary data suggest that both IVT and SCS TA were well tolerated in the albino rabbit and systemic exposure was minimal by either route. These data show that SCS TA is absorbed at much greater proportions into the clear/choroid and retina, while IVT TA distributes throughout the eye, indicating that SCS administration using a microneedle is a targeted approach for delivering TA to therapeutically-relevant ocular structures of posterior segment disease and limiting anterior segment exposure.

Keywords: 452 choroid • 487 corticosteroids • 561 injection  
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