Suprachoroidal space injection for the treatment of noninfectious uveitis

Macular edema—the swelling of the macula—is a common cause of vision loss due to a number of retinal conditions. The accumulation of fluid in the macula can lead to blurred vision and, if left untreated, to permanent vision loss. Noninfectious uveitis (NIU)—the inflammation of the uveal tract due to autoimmune disease or other noninfectious conditions—is a common cause of macular edema. Addressing the inflammation associated with NIU is essential for resolving macular edema and preserving or restoring visual function.

Corticosteroids are a mainstay of treatment for macular edema associated with NIU and can be administered systemically, topically (eye drops), or by injection into the eye. Systemic immunosuppressants, including antimetabolites and biologic agents, are also used for the treatment of NIU but may have variable or limited benefit in resolving macular edema. Systemic administration of corticosteroids is often associated with a variety of adverse effects, including increased blood sugar, high blood pressure, and mood swings, among others. While topical and intraocular administration of corticosteroids avoids systemic effects, these local approaches are associated with a risk of increased IOP, which can lead to steroid-induced glaucoma (SIG).

The increase in IOP following steroid administration is largely due to increased resistance to fluid outflow through the trabecular meshwork (TM),¹ the primary route of aqueous humor drainage from the eye.² Glucocorticoids have been shown to reversibly cross-link actin networks within TM cells, leading to a significant decrease in cell migration and proliferation.³ They also alter the balance between extracellular matrix (ECM) synthesis and degradation, as well as cellular interactions with ECM, which impacts TM properties and function.⁴ IOP, which when elevated leads to injury of retinal ganglion cells in the optic nerve head due to mechanical stress, is currently the most critical known factor and the only modifiable risk factor for glaucoma.⁵

Early intervention is essential to prevent permanent optic nerve damage and vision loss in patients with SIG. Typical interventions include discontinuing steroids, switching to lower-potency steroids, and initiation of a prostaglandin analog and a Rho kinase inhibitor. While this can help resolve SIG, it leaves the underlying macular edema untreated, which can also lead to permanent vision loss.⁶ The difficulty in balancing the anti-inflammatory effects of corticosteroids against their potential for significant adverse events presents challenges to the effective management of NIU.⁷

Suprachoroidal space injection for ocular diseases

Drug delivery to the suprachoroidal space (SCS) enables targeted administration between the sclera and the choroid. While these layers are typically in direct apposition, the injection of fluid between them opens the suprachoroidal space. Delivery to this space concentrates the drug in the back of the eye while minimizing off-target delivery to cells in the front of the eye. SCS is a route of administration that delivers targeted corticosteroid therapy. Medications administered via SCS injection are compartmentalized and concentrated in the posterior portion of the eye, with limited exposure to the TM in the anterior portion.⁸

SCS injection of a triamcinolone acetonide (TA) suspension for macular edema

A nuanced technique, SCS injection leverages the differential between the low-resistance system of the suprachoroidal space and the higher-resistance system of the sclera. A microinjector purpose-built for SCS injection (SCS Microinjector, Clearside Biomedical) simplifies administration via this route.

The SCS microinjector uses a 30-gauge needle (900 μm or 1100 μm, both included with the injector). The 1100-μm needle is used only if persistent resistance is felt with the 900-μm needle. The microneedle is driven by a proprietary manual piston and is designed to depress the conjunctiva and minimize medication reflux.⁸ As the microneedle is introduced into the correct plane, a loss of resistance is felt as the plunger is depressed, with manual feedback for the ophthalmologist during drug administration. Check the microneedle for perpendicularity, create a dimple on the injection site, and slowly inject the medication into the SCS once loss of resistance is felt. Consider utilizing subconjunctival anesthesia to reduce any pressure sensation as the medication is delivered.

SCS injection of Xipere (triamcinolone acetonide injectable suspension) 40 mg/mL, a widely used corticosteroid, has been shown to be effective in treating macular edema associated with noninfectious uveitis in 4 clinical trials, including PEACHTREE, a phase 3, randomized, sham-controlled trial.^9,10

The PEACHTREE study was conducted in 160 patients with macular edema associated with NIU and evaluated vision and IOP changes following SCS-TA 4 mg (0.1 mL) or a sham procedure at day 0 and day 12. Vision, as assessed by best-corrected visual acuity, was significantly improved in patients in the SCS-TA arm, with a mean increase of 10.8 letters (P < .001) compared with the sham arm. Changes in IOP were generally modest, and the most common treatment-emergent adverse events (AEs) related to IOP were considered mild or moderate. AEs included eye pain at the time of procedure (12.5% for SCS-TA, 4.7% for sham); corticosteroid-related IOP increase (11.5% SCS-TA, 15.6% sham; all IOP adverse events in the control group occurred after rescue with local corticosteroid administration); elevated IOP at time of procedure (8.3% SCS-TA vs 0% sham); and cataract (7.3% SCS-TA vs 6.3% sham).

The PEACHTREE data supported the US Food and Drug Administration approval of SCS-TA (Xipere) for the treatment of macular edema associated with NIU in 2021.¹⁰

Three-year postmarketing safety database analysis, which I presented earlier this year at the Hawaiian Eye & Retina 2026 conference, further supports the long-term safety of SCS-TA.¹¹ In this analysis, adverse experiences between October 2021 and October 2024 were tabulated using Medical Dictionary for Regulatory Activities preferred terms, reflecting AEs with SCS-TA in real-world settings. A total of 12,479 single-use vials of SCS-TA were distributed in the United States during the study period. Adverse drug experience reports included a total of 90 events, corresponding with an adverse experience incidence of 7 events per 1000 vials. These AEs included 13 events of eye pain (1 per 1000 vials) and 4 events of increased IOP (0.3 per 1000 vials). There were no reports of endophthalmitis, choroidal hemorrhage, or vitreous hemorrhage.

It should be noted that the AEs recorded during the study period were reported voluntarily, which could result in an underestimation of AE incidence. Additionally, reporting is descriptive and not designed to determine cause and effect, which can make it difficult to distinguish AEs resulting from SCS-TA from those due to unreported concomitant medications or other factors. Furthermore, AE incidence in this study was calculated based on the number of vials distributed rather than the number administered. Despite these limitations, the 3-year postmarketing database analysis results should give patients and clinicians confidence in the long-term safety of SCS-TA for the treatment of NIU.

Techniques for suprachoroidal drug delivery: Clinical experience and pearls

My clinical experience with SCS-TA in treating patients with NIU-related macular edema has been consistent with the significant improvements in visual acuity and reduction in macular edema reported in phase 3 clinical trials. Patients who develop mild elevations in IOP can be monitored to ensure a safe IOP at discharge, and I perform indirect ophthalmoscopy to ensure central retinal artery perfusion. I typically schedule follow-up visits at 3 to 4 weeks for patients undergoing their first SCS-TA injection or patients undergoing repeat injection who have a history of elevated IOP/steroid response or glaucoma. Patients without this history are typically seen for follow-up at 5 to 6 weeks (or longer).

Conclusion

Clinical evidence supports the safety and efficacy of SCS injection as a route of administration that enables targeted therapeutic delivery to the retina. The PEACHTREE and 3-year postmarketing data support the efficacy and long-term safety of SCS-TA in treating macular edema due to NIU. SCS injection is under investigation for the delivery of novel therapies for other vision-related diseases, including gene therapies or other therapies for which systemic administration is not appropriate. Devices used for SCS injection, such as the purpose-built microinjector used in the approved SCS-TA formulation, are important for facilitating the adoption of therapies administered by SCS injection. Pursuing training in SCS injection can help eye health professionals offer their patients targeted therapy for NIU-associated macular edema and, hopefully, additional indications in the future.

INDICATION

Xipere (triamcinolone acetonide injectable suspension) for suprachoroidal use is a corticosteroid indicated for the treatment of macular edema associated with uveitis.

Important Safety Information

Patients should be monitored following injection for elevated ocular pressure. See dosage and administration instructions in the full prescribing information.

• Xipere is contraindicated in patients with active or suspected ocular or periocular infections, including most viral diseases of the cornea and conjunctiva, such as active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.
• Xipere is contraindicated in patients with known hypersensitivity to triamcinolone acetonide or any other components of this product.
• Use of corticosteroids may produce cataracts, increased IOP, and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses, and should be used cautiously in patients with a history of ocular herpes simplex.
• Hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and hyperglycemia can occur following administration of a corticosteroid. Monitor patients for these conditions with chronic use.
• In controlled studies, the most common ocular adverse reactions were increased ocular pressure, nonacute (14%); eye pain, nonacute (12%); cataract (7%); increased IOP, acute (6%); vitreous detachment (5%); injection site pain (4%); conjunctival hemorrhage (4%); visual acuity reduced (4%); dry eye (3%); eye pain, acute (3%); photophobia (3%); and vitreous floaters (3%); and in 2% of patients, the following: uveitis, conjunctival hyperemia, punctate keratitis, conjunctival edema, meibomianitis, anterior capsule contraction, chalazion, eye irritation, eye pruritus, eyelid ptosis, photopsia, and vision blurred.
• The most common nonocular adverse event was headache (5%).
• Corticosteroids should be used during pregnancy or nursing only if the potential benefit justifies the potential risk to the fetus or nursing infant.

Click here for full prescribing information.

You are encouraged to report adverse effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

References

1. Feroze KB, Zeppieri M, Khazaeni L. Steroid-induced glaucoma. In: StatPearls. StatPearls Publishing; 2023. Accessed March 20, 2026. https://www.ncbi.nlm.nih.gov/books/NBK430903/

2. Buffault J, Labbé A, Hamard P, Brignole-Baudouin F, Baudouin C. The trabecular meshwork: structure, function and clinical implications: a review of the literature. J Fr Ophtalmol. 2020;43(7):e217-e230. doi:10.1016/j.jfo.2020.05.002

3. Clark AF, Wilson K, McCartney MD, Miggans ST, Kunkle M, Howe W. Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1994;35(1):281-294.

4. Keller KE, Peters DM. Pathogenesis of glaucoma: extracellular matrix dysfunction in the trabecular meshwork-a review. Clin Exp Ophthalmol. 2022;50(2):163-182. doi:10.1111/ceo.14027

5. Asrani SG, McGlumphy EJ, Al-Aswad LA, et al. The relationship between intraocular pressure and glaucoma: an evolving concept. Prog Retin Eye Res. 2024;103:101303. doi:10.1016/j.preteyeres.2024.101303

6. Rhee DJ. Managing steroid-induced glaucoma. Review of Ophthalmology. September 10, 2023. Accessed March 20, 2026. https://www.reviewofophthalmology.com/article/managing-steroidinduced-glaucoma

7. Kohli P, Tripathy K, Patel BC. Macular edema. In: StatPearls. StatPearls Publishing; 2024. Accessed March 20, 2026.https://www.ncbi.nlm.nih.gov/books/NBK576396/

8. Wu KY, Fujioka JK, Gholamian T, Zaharia M, Tran SD. Suprachoroidal injection: a novel approach for targeted drug delivery. Pharmaceuticals. 2023;16(9):1241. doi:10.3390/ph16091241

9. Yeh S, Khurana RN, Shah M, et al; PEACHTREE Study Investigators. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: phase 3 randomized trial. Ophthalmology. 2020;127(7):948-955. doi:10.1016/j.ophtha.2020.01.006

10. Xipere. Prescribing information. Bausch & Lomb; 2025. Accessed March 20, 2026. https://pi.bausch.com/globalassets/pdf/packageinserts/vision-care/xipere_prescribing_information.pdf

11. Yeh S. Safety of triamcinolone acetonide injectable suspension for suprachoroidal use in patients with uveitic macular edema: analysis of a postmarketing database. Presented at: Hawaiian Eye & Retina 2026; January 17-23, 2026; Big Island, HI.