TY - JOUR
T1 - Suprachoroidally injected pharmacological agents for the treatment of chorio-retinal diseases
T2 - a targeted approach
AU - Habot-Wilner, Zohar
AU - Noronha, Glenn
AU - Wykoff, Charles C.
N1 - Funding Information:
Surgical incision to enable suprachoroidal administration in humans has shown favourable efficacy for pharmacotherapies including bevacizumab and TA, along with reasonable safety, in small study populations (Table) (Rizzo et al.; Tetz et al.). The only treatment to have been evaluated in a substantive clinical development programme is CLS-TA, a proprietary, preservative free, terminally sterilized suspension formulation of TA administered into the SCS via microinjector. Exudative AMD (Tetz 2012) Subfoveal hard exudates secondary to central RVO, branch RVO or diffuse DMO (Rizzo 2012) Noninfectious uveitis (Goldstein 2016) Macular oedema in noninfectious uveitis (Yeh 2018a) Macular oedema in noninfectious uveitis (Yeh 2018b) Macular oedema in RVO (Campochiaro 2018) Macular oedema in RVO (Clearside Biomedical, Inc. 2018a) DMO (Wykoff 2018) DMO (Clearside Biomedical, Inc. 2018b) Dry AMD (Limoli 2014) Dry AMD (Limoli 2015) AMD = age-related macular degeneration, BCVA = best-corrected visual acuity, CST = central subfield thickness, DMO = diabetic macular oedema, ERG = electroretinogram, ETDRS = Early Treatment Diabetic Retinopathy Study, RVO = retinal vein occlusion, SCS = suprachoiroidal space, TA = triamcinolone acetonide. A prospective, phase 1/2 trial provided proof of concept for suprachoroidally injected CLS-TA in eyes of patients with noninfectious uveitis (Goldstein et al.). Subjects had noninfectious intermediate, posterior or panuveitis with either macular oedema [central subfield thickness (CST) ≥310 μm] or a vitreous haze score 1.5+ based on Standardization of Uveitis Nomenclature criteria (Jabs et al.). Nine patients received a single suprachoroidal injection of TA 4 mg in 100 μl approximately 4 mm posterior to the limbus. The most common adverse event was eye pain at or near the site of injection (six events).
Publisher Copyright:
© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
PY - 2019/8
Y1 - 2019/8
N2 - Delivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long-lasting control of elevated IOP, and as a mode of delivery for gene- or cell-based therapies for retinal disorders.
AB - Delivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long-lasting control of elevated IOP, and as a mode of delivery for gene- or cell-based therapies for retinal disorders.
KW - choroid
KW - macular edema
KW - macular oedema
KW - pharmacotherapy
KW - retina
KW - retinal vein occlusion
KW - suprachoroidal
KW - triamcinolone acetonide
KW - uveitis
UR - http://www.scopus.com/inward/record.url?scp=85060876092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060876092&partnerID=8YFLogxK
U2 - 10.1111/aos.14042
DO - 10.1111/aos.14042
M3 - Review article
C2 - 30702218
AN - SCOPUS:85060876092
SN - 1755-375X
VL - 97
SP - 460
EP - 472
JO - Acta Ophthalmologica
JF - Acta Ophthalmologica
IS - 5
ER -