Literature

Routes for Drug Delivery to the Retina: Topical, Transscleral, Suprachoroidal and Intravitreal Gas Phase Delivery
(2016) Nguyen, et al –

Review article on retinal drug delivery describing previous research in suprachoroidal drug delivery. (Routes for Drug Delivery to the Retina: Topical, Transscleral, Suprachoroidal and Intravitreal Gas Phase Delivery, Dev Ophthalmol. Basel, Karger, 2016, vol 55, pp 71–83)

Real-Time Monitoring of Suprachoroidal Space (SCS) Following SCS Injection Using Ultra-High Resolution Optical Coherence Tomography in Guinea Pig Eyes
(2016) Gu, et al –

Describes volume dependent expansion of the suprachoroidal space in guinea pig eyes. (Real-Time Monitoring of Suprachoroidal Space (SCS) Following SCS Injection Using Ultra-High Resolution Optical Coherence Tomography in Guinea Pig Eyes, Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3623-3634.)

The suprachoroidal pathway: a new drug delivery route to the back of the eye
(2015) Rai, et al –

Review article describing the suprachoroidal pathway as a route of posterior segment drug delivery (The suprachoroidal pathway: a new drug delivery route to the back of the eye, Drug Discovery Today Volume 20, Number 4 April 2015.)

Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles
(2015) Kim, et al –

Describes formulations to disperse or localize injections to the suprachoroidal space. Similar concepts to prior patent applications of Yamamoto et al. ), Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles, European Journal of Pharmaceutics and Biopharmaceutics 95 (2015) 398–406)

Efficacy and Safety Results in Non-infectious Uveitis Using a Single Suprachoroidal Injection of Triamcinolone Acetonide
(2015) Clearside

Reported on 8 patients with posterior uveitis. Treatment consisted of a single injection of triamcinolone to the suprachoroidal space. The average BCVA improvement was reported close to three lines at week 26. No patients demonstrated cataract progression or elevated IOP. (Ophthalmology Times Report, June 2015)

Light-Activated, In Situ Forming Gel for Sustained Suprachoroidal Delivery of Bevacizumab
(2013) Tyagi, et al –

Describes polymeric formulation for sustained release of bevacizumab in the suprachoroidal space. (Light activated, In situ Forming Gel for Sustained Suprachoroidal Delivery of Bevacizumab, Mol Pharm. 2013 August 5; 10(8): 2858–2867.)

Suprachoroidal Drug Delivery – A New Approach for the Treatment of Severe Macular Diseases
(2012) Augustin, et al –

Review article describing animal and clinical research in suprachoroidal drug delivery for the treatment of retinal disease. (Suprachoroidal Drug Delivery – A New Approach for the Treatment of Severe Macular Diseases, European Ophthalmic Review, 2012;6(1):25-7.)

Pharmacokinetics of Pars Plana Intravitreal Injections versus Microcannula Suprachoroidal Injections of Bevacizumab in a Porcine Model
(2012) Tyagi et al –

Suprachoroidal injection of sodium fluorescein in rats demonstrated high levels in the choroid and retina with lower levels in the vitreous as compared to intravitreal administration. (Comparison of Suprachoroidal Drug Delivery with Subconjunctival and Intravitreal Routes Using Noninvasive Fluorophotometry, Tyagi et al, Oct 2012, PLoS ONE 7(10): e48188.)

Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates.
(2012) Rizzo S

Reported on six patients (eyes) with retinal vein occlusion or diabetic macular edema with severe subfoveal hard exudates. Treatment consisted of a single dose of Avastin (4 mg) with triamcinolone (4 mg) administered by suprachoroidal catheterization. Mean follow up was 12 months; BCVA improved by 2+ lines in 4 eyes and remained stable in 2 eyes. At 1 to 2 months, the hard exudates had almost completely resolved in all eyes. There were no observed surgical or post-operative complications. (Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates, Rizzo S, Ebert FG, et al, Retina, 2012 Apr;32(4):776-84.)

Safety of Submacular Suprachoroidal Drug Administration via a Microcatheter: Retrospective Analysis of European Treatment Results
(2011) Tetz M, Rizzo S, Augustin A

Reported on 21 patients (eyes) with advanced, exudative AMD unresponsive to conventional therapy. Treatment consisted of a single dose of Avastin (4mg) with triamcinolone (4 mg) administered by suprachoroidal catheterization. Baseline mean BCVA was 0.98 LogMAR, at 1 month mean BCVA was 0.92 LogMAR and at 6 months mean BCVA was 0.93 LogMAR. Baseline mean CFT was 407.2 microns, at 1 month mean CFT was 333.3 microns, at 3 months mean CFT was 333.6 microns and at 6 months mean CFT was 384.8 microns. One patient demonstrated elevated IOP and two patients demonstrated cataract progression. (Safety of submacular suprachoroidal drug administration via a microcatheter: retrospective analysis of European treatment results, Tetz M, Rizzo S, Augustin AJ., Ophthalmologica. 2012;227(4):183-9.)

Suprachoroidal Bevacizumab Delivery for Neovascular AMD Treatment
(2011) Scharioth G, Raak P, Pavlidis F

Reported on a single case of a patient with wet AMD with poor responsiveness to anti-VEGF therapy. Treatment consisted of a single dose of Avastin administered by suprachoroidal catheterization. At four weeks post-operative, a reduction in retinal pigment epithelial detachment was observed. At eight weeks post-operative, a slight gain in BCVA to 0.16 and the resolution of subfoveal membrane was observed. No intraoperative or post-operative complications were observed. No recurrence was reported at six months. The authors report they have treated more than 25 eyes with the procedure.

(Suprachoroidal Bevacizumab Delivery for Neovascular AMD Treatment, Scharioth et al, Retinal Physician April 2011, 56-59.)

Pharmacokinetics of Pars Plana Intravitreal Injections versus Microcannula Suprachoroidal Injections of Bevacizumab in a Porcine Model
(2011) Olsen et al –

Suprachoroidal administration of bevacizumab in pigs demonstrated different distribution and kinetics. Intravitreal bevacizumab showed a slow decline in tissue levels over 30 to 60 days. Suprachoroidal bevacizumab showed rapid clearance with tissue levels not measurable at or beyond 7 days. (Pharmacokinetics of Pars Plana Intravitreal Injections versus Microcannula Suprachoroidal Injections of Bevacizumab in a Porcine Model, Olsen et al, IOVS Papers in Press. Published on March 29, 2011 as Manuscript iovs.10-6291.)

Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment
(2006) Olsen et al

Suprachoroidal administration of triamcinolone in pigs demonstrated sustained drug levels over 90 days. (Cannulation of the Suprachoroidal Space – Olsen, et al, Am J Ophthalmol 2006;142: 777–787.)

Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates

(2020) Glenn Yiu, Sook Hyun Chung, Iris N. Mollhoff, Jesse Yoo, Donna Taraborelli, Glenn Noronha –

A study on ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space.

AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression

(2019) Kun Ding et al –

Report on gene therapy delivery via suprachoroidal injection of AAV8 vectors.

The suprachoroidal space (SCS) as a route of administration to the posterior segment of the eye

(2018) Bryce Chiang, Jae Hwan Jung, Mark R. Prausnitz –

Review of the anatomy and physiology of the SCS; methods to access the SCS; kinetics of SCS drug delivery; strategies to target within the SCS; current and potential clinical indications; and the safety and efficacy of this approach in preclinical animal studies and clinical trials.

Update on ocular gene therapy and advances in treatment of inherited retinal diseases and exudative macular degeneration
(2016) Garoon RB and Stout JT –

Review article describing current ophthalmic gene therapy clinical trials. Describes administration methods and concerns regarding complications related to administration method. (Update on ocular gene therapy and advances in treatment of inherited retinal diseases and exudative macular degeneration, Curr Opin Ophthalmol 2016, 27:000–000).

Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2.
(2013) Testa, et al –

Article describing significant visual improvement after RPE65 gene therapy. The article describes issues regarding sub-retinal injections near the fovea. (Three Year Follow-Up after Unilateral Subretinal Delivery of Adeno-Associated Virus in Patients with Leber Congenital Amaurosis Type 2, Ophthalmology. 2013 June ; 120(6): 1283–1291.)

Suprachoroidal Electrotransfer: A Nonviral Gene Delivery Method to Transfect the Choroid and the Retina Without Detaching the Retina
(2012) Touchard et al –

Article describes novel method to transfect the choroid and retina through the suprachoroidal space. (Suprachoroidal Electrotransfer: A Nonviral Gene Delivery Method to Transfect the Choroid and the Retina Without Detaching the Retina, Molecular Therapy vol. 20 no. 8, 1559–1570 aug. 2012)

Ab-externo AAV-mediated gene delivery to the suprachoroidal space using a 250 micron flexible microcatheter

(2011) Peden et al –

Investigation of the safety and efficacy of delivering adeno-associated viral (AAV) vector to the suprachoroidal space using an ab externo approach that utilizes an illuminated microcatheter.

Surgical Approaches to Gene and Stem Cell Therapy for Retinal Disease

(2011) Stout JT and Francis PJ –

Article describes route of administration, including sub-retinal and suprachoroidal routes, for the emerging field of ophthalmic gene and cell therapy. (Surgical Approaches to Gene and Stem Cell Therapy for Retinal Disease, Human Gene Therapy 22:531– 535, May 2011)