Triamcinolone Acetonide Suspension Research Articles

Comparison of dual-plane micro-drop injection of botulinum toxin type A with two traditional methods for treating hypertrophic scars in the tension zone: A long-term clinical application study.

Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension. To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension. Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual-plane micro-drop injections, triamcinolone acetonide (TAC) suspension, and CO2 via fractional CO2 laser. Interventions were implemented in all three groups once a month for three consecutive sessions. After the final treatment, scarring was evaluated at 1, 3, 6, 12, and 24 months using the Patient and Observer Scar Assessment Scale (POSAS). The 3-month POSAS score for each scar indicator in the treatment groups was significantly lower than that in the preoperative groups (p < 0.001). The scar score in the TAC group decreased at 3 months and increased thereafter. For other groups, the scar score continually decreased at all time points according to the Patient Scar Assessment Scale. Based on the Observer Scar Assessment Scale, the scar score continuously decreased at all time points in the BTA group; in the TAC group, it decreased at 1 month and increased thereafter; and in the CO2 group, the scar score decreased at 3 months and subsequently stabilized. All three treatment methods were effective. However, the BTA group experienced a reduced risk of scar recurrence and maintained long-term treatment effects.

Safety and Efficacy of CLS-TA by Anatomic Location of Inflammation: Results from the Phase 3 PEACHTREE Clinical Trial

ABSTRACT Purpose To explore the efficacy of CLS-TA, a proprietary suprachoroidal injectable suspension of triamcinolone acetonide, in noninfectious uveitis (NIU) with macular edema (ME), categorized by anatomic subtype. Methods Patients diagnosed with ME associated with NIU of any etiology and anatomic subtype were eligible for the phase 3 PEACHTREE trial of CLS-TA. Post-hoc analyses were performed, stratified by discrete anatomic subtype of uveitis (anterior, intermediate, posterior, and panuveitis.) Results Across all anatomic subtypes at 24 weeks, patients receiving CLS-TA at baseline and week 12 demonstrated mean increases in BCVA ranging from +12.1 to +15.9 letters, mean central subfield thickness (CST) improvement ranging from −120.1 µm to −189.0 µm, and IOP changes ranging from +0.5 to +3.1 mmHg. Overall, reports of adverse events were similar among subtypes. Conclusions Irrespective of the uveitic anatomic subtype among patients treated for ME associated with NIU, a clinical benefit in participants treated with CLS-TA was demonstrated, with a comparable safety profile.

Glycerospanlastics: State-of-the-art two-in-one nano-vesicles for boosting ear drug delivery in otitis media treatment

The purpose of this research was to design innovative nanovesicles for ototopical conveyance of triamcinolone acetonide (TA) for otitis media (OM) treatment via incorporating glycerol into nanospanlastics to be termed “Glycerospanlastics”. The glycerospanlastics were formulated employing ethanol injection procedure, and central composite design (CCD) was harnessed for optimization of the vesicles. Various attributes of the nanovesicles, viz. particle size distribution, surface charge, TA entrapment efficiency, morphology as well as ex-vivo permeation across the tympanic membrane (TM) were characterized. In vivo implementation of the optimized glycerospanlastics loaded with TA was appraised in OM-induced rats via histopathological and biochemical measurements of the tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) levels in ear homogenates. The safety and tolerability of optimized TA glycerospanlastics was also investigated in non-OM induced animals. The results demonstrated that the optimized TA-glycerospanlastics were in a nanometer range (around 200 nm) with negative charges, high TA entrapment (>85%), good storage properties and better TM permeation relative to TA suspension. More importantly, TA-glycerospanlastics performed better than marketed drug suspension in OM treatment as manifested by restoration of histopathological alterations in TM and lowered values of IL-1β and TNF-α. Glycerospanlastics could be promising safe ototopical nanoplatforms for OM treatment and other middle ear disorders.

In Situ Formation of Injectable Gelatin Methacryloyl (GelMA) Hydrogels for Effective Intraocular Delivery of Triamcinolone Acetonide.

A novel drug delivery system designed for intraocular injection, gelatin methacryloyl (GelMA), has attracted much attention due to its sustained-release character and low cytotoxicity. We aimed to explore the sustained drug effect of GelMA hydrogels coupled with triamcinolone acetonide (TA) after injection into the vitreous cavity. The GelMA hydrogel formulations were characterized using scanning electron microscopy, swelling measurements, biodegradation, and release studies. The biological safety effect of GelMA on human retinal pigment epithelial cells and retinal conditions was verified by in vitro and in vivo experiments. The hydrogel exhibited a low swelling ratio, resistance to enzymatic degradation, and excellent biocompatibility. The swelling properties and in vitro biodegradation characteristics were related to the gel concentration. Rapid gel formation was observed after injection, and the in vitro release study confirmed that TA-hydrogels have slower and more prolonged release kinetics than TA suspensions. In vivo fundus imaging, optical coherence tomography measurements of retinal and choroid thickness, and immunohistochemistry did not reveal any apparent abnormalities of retinal or anterior chamber angle, and ERG indicated that the hydrogel had no impact on retinal function. The GelMA hydrogel implantable intraocular device exhibited an extended duration, in situ polymerization, and support cell viability, making it an attractive, safe, and well-controlled platform for treating the posterior segment diseases of the eye.

An ultralow-cost portable centrifuge from discarded materials for medical applications

Reliable centrifugation for medical applications has historically required access to expensive, bulky, and electricity-dependent commercial devices, which are generally unavailable in resource-poor settings. Although several portable, low-cost, non-electric centrifuges have been described, these solutions have predominately been designed for diagnostic applications requiring sedimentation of relatively small volumes. Moreover, construction of these devices frequently requires access to specialized materials and tools that are often unavailable in underserved areas. Herein, we describe the design, assembly, and experimental validation of the CentREUSE—an ultralow-cost, portable, discarded material-based, human-powered centrifuge for use in therapeutic applications. The CentREUSE demonstrated a mean centrifugal force of 10.5 relative centrifugal force (RCF) ± 1.3. Sedimentation of 1.0 mL triamcinolone acetonide suspension for intravitreal use after 3 min of CentREUSE centrifugation was comparable to that achieved after 12 h of gravity-mediated sedimentation (0.41 mL ± 0.04 vs. 0.38 mL ± 0.03, p = 0.14). Sediment compactness after 5 min and 10 min of CentREUSE centrifugation was similar to that observed after centrifugation with a commercial device for 5 min at 10 RCF (0.31 mL ± 0.02 vs. 0.32 mL ± 0.03, p = 0.20) and 50 RCF (0.20 mL ± 0.02 vs. 0.19 mL ± 0.01, p = 0.15), respectively. Templates and instructions for construction of the CentREUSE are included as part of this open-source publication.

Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina.

Purpose:To compare ocular pharmacokinetics (PK), systemic absorption, and injectability of triamcinolone acetonide (TA) suprachoroidal (SC) and intravitreal (IVT) suspensions.Methods:New Zealand White (NZW) rabbits received a bilateral injection of 4 mg TA injectable suspension, TRI (TRIESENCE ®; Alcon) through either microneedle-based SC or standard IVT injection. Another group of NZW rabbits received a bilateral SC injection (4 mg) of either TRI or a proprietary TA suspension for SC use, CLS-TA (Clearside Biomedical). Blood and ocular tissues were analyzed for TA over 3 months. Separately, injectability of TRI and CLS-TA through a proprietary SC delivery system (SCS Microinjector®; Clearside Biomedical) was compared using microinjector syringe-plunger glide force measurement.Results:Suprachoroidal delivery of TRI, compared with IVT-TRI, resulted in ∼12-fold higher exposure in the retinal pigment epithelium–choroid–sclera, and comparable exposure in the retina. Conversely, SC-TRI, compared to IVT-TRI, resulted in 460-, 34-, and 22-fold lower exposure in the lens, iris-ciliary body, and vitreous humor, and negligible exposure in the aqueous humor. SC injection of either CLS-TA or TRI resulted in comparable and sustained ocular TA levels. Plasma TA levels were generally undetectable in both studies. A significantly greater and more variable glide force was measured for TRI vs. CLS-TA.Conclusions:Suprachoroidal delivery of TA enabled high and durable TA levels targeted to the chorioretina with limited anterior segment exposure. SC delivery of either CLS-TA or TRI resulted in comparable ocular PK profiles with low systemic exposure; however, CLS-TA required lower and less variable glide force than TRI, potentiating more consistent, controlled administration.

Local retention efficacy of steroid-loaded PLGA microspheres in epidural injection

Long-term effects of epidural steroid injections for pain management require novel drug formulations that increase tissue retention time. Present study aimed to investigate the local retention of steroid-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in epidural injection using a rabbit model. Twenty rabbits were randomly assigned to a PLGA group (n = 10) and a triamcinolone acetonide (TA) group (n = 10). Each animal was injected with either TA-loaded PLGA microspheres or conventional TA suspension into the lumbar epidural space. The lumbar segments were then harvested from the sacrificed rabbits on day 1, week 1, 2, and 4 after the injection. On day 1, the residual steroid concentration (RSC) was lower in the PLGA group than in the TA group (5.03 ppm vs. 13.01 ppm). However, after a week, more steroids remained in the PLGA group (3.29 ppm vs. 0.58 ppm). After 2 weeks, fewer steroids remained in the PLGA group than in the TA group, although both contained less than 10% of the initial retention dose. This study shows that steroid-loaded PLGA tended to have higher steroid retention in tissue than the steroid itself at the first week after epidural injection. However, most of the steroids disappeared after 2 weeks in both groups.

Comparison of Suprachoroidal Injection of Triamcinolone Acetonide Versus Intravitreal Bevacizumab in Primary Diabetic Macular Odema

Objective: Present study aims to compare the efficacy of single dose triamcinolone acetonide suspension in suprachoroidal space and intravitreal bevacizumab in primary diabetic macular edema patients. Study design: Prospective observational study Study duration and settings: Study was conducted at department of ophthalmology, Eye Unit III, Mayo hospital Lahore (KEMU) from March 2020 to August 2020. Material and methods: The WHO calculator was used to estimate a sample size of 136 patients (66 patients in each group). Non-probability sequential sampling was used to identify patients.. Intravitreal bevacizumab injections (2.5 mg/0.1 mL) were given to patients in Group A, and triamcinolone acetonide was given to patients in Group B, all at random. After one and three months, patients were reassessed. Results: Total 135 patients were included in study. There were 71(52.2%) male and 65(47.8%) female. Mean age of patients was 41.1±6.9SD. BCVA improved 5 letters after 3 month was significantly high in TA group as compared to IVB (P=0.002). Moreover, CSF decreased at least 10% from baseline after one and three months was comparatively high in TA group (p=0.01 and p=0.04 respectively). Among all the patients in IVB group, 29.5% showed efficacy while in group TA, 37.5% showed efficacy (p=0.03) Conclusion: Triamcinolone acetonide is an efficient drug for management of diabetic macular edema. Triamcinolone had long standing effect as compared to intravitreal bevacizumab on structural and functional outcome of the patients with primary diabetic macular odema. Both interventions are associated with limited complications. Keywords: Triamcinolone acetonide, Diabetic macular edema, Intravitral bevacizumab

Suprachoroidal CLS-TA with and without Systemic Corticosteroid and/or Steroid-Sparing Therapy: A Post-Hoc Analysis of the Phase 3 PEACHTREE Clinical Trial

ABSTRACT Purpose To study the efficacy and safety of suprachoroidal CLS-TA (proprietary suspension of triamcinolone acetonide) in uveitic macular edema (UME) with and without concurrent systemic corticosteroid or steroid-sparing therapy (ST). Methods Post hoc analysis of the PEACHTREE phase 3 randomized trial. Results Among UME patients receiving no ST, at week 24, mean BCVA change was +15.6 letters in 68 CLS-TA patients versus +4.9 letters in 49 sham-control patients (p < .001), while mean CST change was −169.8 µm versus −10.3 µm, respectively (p < .001). Among patients receiving ST, at week 24, mean BCVA change was +9.4 letters in 28 CLS-TA patients versus −3.2 letters in 15 sham-control patients (p = .019), while mean CST change was −108.3 µm versus −43.5 µm, respectively (p = .190). No SAEs related to treatment were reported. Conclusions A clinically meaningful benefit of CLS-TA was noted in UME patients, regardless of concurrent ST usage. Abbreviation and Acronyms CST = central subfield thickness; BCVA = best corrected visual acuity; ME = macular edemaI; IVT = intravitreal; AE = adverse event; FA = fluocinolone acetonide; SD-OCT = spectral-domain optical coherence tomography; NIU = noninfectious uveitis; SAE = serious adverse event; TEAE = treatment emergent adverse event; ITT = intent to treat; CI = confidence interval

Impact of particle flocculation on the dissolution and bioavailability of injectable suspensions

Injectable suspensions occasionally exhibit variations in dissolution and bioavailability, which may impact the clinical outcome of the drug product. Here, variation in the injection method (i.e., applied shear) for triamcinolone acetonide (TA) injectable suspension (40 mg/mL) altered the flocculation state of the particles and subsequently their dissolution. Notably, TA suspensions contained primary particles of approximately 2 µm and secondary flocculates of tens of microns. The conversion between flocculated and deflocculated particles was rapid, reversible and highly shear dependent. As such, changing shear rates during laser diffraction (LD) measurement like stirring rate, sonication, and sample introduction method (micropipette vs 25-gauge needle) may result in variability in particle size distributions (PSD) that have the potential to alter drug dissolution. Furthermore, a non-sink, discriminatory in vitro release testing (IVRT) method was developed, which combined in-situ fiber optic UV with LD to simultaneously monitor the dissolution and changing PSD of the suspension. The simultaneously measured dissolution and PSD data showed that flocculated and deflocculated particles followed different dissolution pathways. Importantly, deflocculated particles dissolved up to six times faster than the flocculated particles. Similar shear-induced changes during injection could occur in a clinical setting and have implications for drug bioavailability.

Novel Suture Systems: High‐Dose Steroid Dissolving Microneedle for Relieving Atopic Dermatitis (Adv. Healthcare Mater. 7/2021)

In article number 2001691 by Hyungil Jung, Ohsang Kwon, and co-workers, triamcinolone acetonide (TA) suspension is introduced to encapsulate therapeutic dosage. The composition of the TA suspension is optimized, and TA-loaded dissolving microneedles are fabricated using the TA suspension. TA-loaded dissolving microneedles have physical properties to be inserted into the skin and have anti-inflammatory effects in vivo.

Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation.

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

High‐Dose Steroid Dissolving Microneedle for Relieving Atopic Dermatitis

Dissolving microneedles (DMN) supplemented with therapeutic molecules have been developed to enhance transdermal delivery efficiency of topically applied drugs in a minimally invasive manner. However, the dose of the drugs in DMN system is limited owing to the low solubility of drug. In fact, although triamcinolone acetonide (TA) is one of the most widely prescribed drugs for relieving atopic dermatitis (AD), its poor dissolving nature makes it difficult to design and fabricate DMN containing therapeutic dosage of TA. In this study, TA suspension is introduced to encapsulate therapeutic dosage of TA. Sonication and composition optimization of polymers is key to fabricate high dose TA-DMN to induce particle size reduction and dispersion stability of suspension, respectively. After confirming the physical performance of TA-DMN using the selected formulation in vitro, the anti-inflammatory effects of TA-DMN are evaluated in vivo using a mouse model affected with skin inflammation to mimic AD in humans. Herein, high-dose TA-DMN is presented as a candidate agent for relieving AD and, furthermore, for wide application in the treatment of skin inflammatory diseases in which high-dose steroid drugs are required.

Bilayer dissolving microneedle array containing 5-fluorouracil and triamcinolone with biphasic release profile for hypertrophic scar therapy

Hypertrophic scar (HS) is an undesirable skin abnormality following deep burns or operations. Although intralesional multi-injection with the suspension of triamcinolone acetonide (TA) and 5-fluorouracil (5-Fu) has exhibited great promise to HS treatment in clinical, the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy. Besides, the traditional injection with great pain is highly dependent on the skill of the experts, which results in poor compliance. Herein, a bilayer dissolving microneedle (BMN) containing TA and 5-Fu (TA-5-Fu-BMN) with biphasic release profile was designed for HS therapy. Equipped with several micro-scale needle tips, the BMN could be self-pressed into the HS with uniform drug distribution and less pain. Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property. Subsequently, the rabbit ear HS model was established to assess therapeutic efficacy. The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition. It was also found that the value of scar elevation index was ameliorated to a basal level, together with the downregulation of mRNA and protein expression of Collagen I (Col I) and transforming growth factor-β1 (TGF-β1) after application of TA-5-Fu-BMN. In conclusion, the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior.

Nanodelivery of triamcinolone acetonide with PLGA-chitosan nanoparticles for the treatment of ocular inflammation

Triamcinolone acetonide (TA) is widely indicated in the treatment of several ocular disorders, but the free drug suspension limits its clinical benefits and commercial compositions cause adverse ocular effects. In this study, TA was formulated in poly(d,l-lactide-co-glycolide) (PLGA)-chitosan (PLC) nanoparticles (NPs) for the treatment of ocular inflammatory diseases. TA-loaded PLC NPs exhibited excellent anti-inflammatory activity against human corneal epithelial (HCE) cells and significantly reduced the secretion of interleukin (IL)-6 in tumour necrosis factor (TNF)-α activated cells. In a rabbit model, TA-loaded PLC NPs did not show any typical clinical signs of eye inflammation and significantly alleviated inflammatory signs, compared with free TA suspension, at 24 h after a single dose. TA-loaded PLC NPs exhibited a greater aqueous humour transparency (%AHT), compared with that of normal saline (NS) or free TA suspension, indicating reduction in anterior chamber fogginess. Pharmacokinetic analysis of rabbit eyes revealed that TA-loaded PLC NPs peaked at 6 h. Substantial concentrations of TA were observed until 24 h, indicating the superiority of this PLC-based nanocarrier system. Overall, PLC-based NP formulations offer a new approach for the treatment of ocular inflammatory diseases.

Endoscopic Wedge Excisions with CO2 Laser for Subglottic Stenosis.

Endoscopic Wedge Excisions with CO2 Laser for Subglottic Stenosis.

Suprachoroidal CLS-TA plus Intravitreal Aflibercept for Diabetic Macular Edema: A Randomized, Double-Masked, Parallel-Design, Controlled Study

This study evaluated the potential safety, efficacy, and durability advantages of investigational triamcinolone acetonide suspension (CLS-TA; Clearside Biomedical, Alpharetta, GA) administered suprachoroidally in conjunction with intravitreal aflibercept compared with aflibercept monotherapy for treatment of diabetic macular edema (DME). TYBEE was a prospective, controlled, double-masked study. Patients were randomized 1:1 to CLS-TA and aflibercept (active) or aflibercept monotherapy (control), and assessed over 24 weeks. Treatment-naive DME patients with best-corrected visual acuity (BCVA) of 20 to 70 letters and central subfield retinal thickness (CST) of more than 300 μm. Patients in the active group (n= 36) received CLS-TA and aflibercept at baseline and week 12. Patients in the control group (n= 35) received aflibercept at baseline, week 4, week 8, and week 12. To mask both groups, sham suprachoroidal and intravitreal injections were utilized. All patients were eligible to receive aflibercept as needed at weeks 4, 8, 16, and 20 per prespecified criteria. Mean change in BCVA from baseline. Treatment differences were assessed with a 2-sided significance level of 0.10. Mean BCVA changes from baseline to week 24 were not statistically different in the active and control groups (intention-to-treat [ITT] population:+11.4 letters and+13.8 letters [P= 0.288]; per protocol [PP] population:+12.3 letters and+13.5 letters [P= 0.664]; respectively). Greater improvement in CST was seen in the active versus control group (ITT population: -212.1 μm and -178.6 μm [P= 0.089]; PP population: -226.5 μm and -176.1 μm [P= 0.035]; respectively). Compared with the control group, eyes in the active group received fewer treatments (scheduled plus as-needed treatments averaging 4.6 versus 2.6, respectively). No treatment-related serious adverse events were observed. Ocular adverse events were low for both arms. Cataract events, all assessed as unrelated to treatment, and events of elevated intraocular pressure trended higher in the active group. CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept for treatment of DME provides simliar visual benefit at 24 weeks' follow-up compared with aflibercept monotherapy, is well tolerated and shows modest anatomic benefit with potential to reduce treatment burden.

Treatment of keloids using 5-fluorouracil in combination with crystalline triamcinolone acetonide suspension: evaluating therapeutic effects by using non-invasive objective measures.

Intralesional 5-fluorouracil (5-FU) in combination with triamcinolone acetonide (TAC) has been recommended as a promising alternative for keloids not responding to silicone-based products, cryotherapy or intralesional corticosteroids alone. Although numerous studies support the efficacy of this regime, there is a lack of objective data. In this study, we evaluate the therapeutic effect of four courses of intralesional 5-FU in combination with TAC (3:1) utilizing 3D analysis (PRIMOS®pico ), ultrasound and scar scales such as the Patient and Observer Scar Assessment Scales (POSAS) and the Dermatology Life Quality Index (DLQI). Twenty-five patients with keloids were treated using 5-FU and TAC every 4weeks. Objective assessments were performed and the scar scales administered at baseline, as well as during consecutive visits at 1- and 12-month follow-up (FU). Routine laboratory tests were performed at baseline and at 1-month FU. 3D PRIMOS and ultrasound measurements revealed highly significant and stable reductions in height (baseline mean score: 4.0±1.7mm, 1-month FU mean score: 1.5±0.8mm, 12-month FU mean score: 1.8±0.9mm, P=<0.0001), volume (baseline mean score: 1,105±911.5 mm3 , 1-month FU mean score: 416.1±218.1mm3 , 12-month FU mean sore: 431.2±253.6mm3 , P=<0.0001, respectively) and penetration depth of keloids (relative reduction between baseline and 12-month FU of 74.4%, P=<0.0001). The POSAS and DLQI scales confirmed significant objective and subjective improvements in scar appearance in all categories. The life quality associated with keloid appearance improved from a 'moderate effect' to a 'small effect' throughout the course of the study. Results of this study confirm the efficacy and safety of the combination of 5-FU and TAC in keloids. Treatments were well tolerated and demonstrated stable results at 12-month FU.

Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial

Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME). Phase 3 masked, randomized trial. One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye. Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week12. The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week24. In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 μm versus 18 μm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively). Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder.

Suprachoroidal Injection of Triamcinolone- Review of a Novel Treatment for Macular Edema Caused by Noninfectious Uveitis.

Macular edema is the most frequent cause of visual deterioration in noninfectious uveitis. The treatment of noninfectious uveitis with associated macular edema commonly includes systemic or locally administered corticosteroids, with long-term use limited by significant side effects. The need for a treatment with an improved safety profile has driven the development of a novel ophthalmic therapy: a proprietary triamcinolone acetonide suspension (CLS-TA) administered in the suprachoroidal space (XIPERE™; Clearside Biomedical, Alpharetta, GA, USA). Suprachoroidal delivery of corticosteroids allows higher steroid concentration in the posterior segment and decreases the risk of other adverse ocular events. Recent results from the PEACHTREE trial (ClinicalTrials.gov Identifier: NCT02595398), a phase III trial with two suprachoroidal injections of CLS-TA at 0 and 12 weeks with follow up lasting 24 weeks, showed the significant improvement in visual acuity and reduction in central subfield thickness, all without increasing the risk of elevated intraocular pressure or accelerated cataract progression.