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PubMed2005

A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide.

Transscleral delivery of triamcinolone acetonide into the vitreous using sub-Tenon's injections may be a safer alternative to reduce the sight-threatening complications of direct intravitreal injections. However, sub-Tenon's injections have demonstrated low and poorly sustained vitreous drug levels in animal studies. To improve our understanding of the clearance mechanisms of corticosteroids, we evaluated vitreous drug levels following sub-Tenon's injection of triamcinolone acetonide in rabbits with selective elimination of conjunctival lymphatic/blood vessels and the choroid. Pigmented rabbits were given a sub-Tenon's injection of a preservative-free triamcinolone acetonide formulation of either a 10- or 20-mg dose in the superotemporal quadrant. The effect eliminating both conjunctival and choroidal clearance was evaluated by injecting the drug, followed by immediate euthanasia, effectively terminating both lymph and blood flow in the conjunctiva and choroid. To inhibit only the clearance from conjunctival lymphatics/blood vessels of a sub-Tenon's injection of triamcinolone acetonide, a group of rabbits had a 'conjunctival window' created by incising an 7 mmx7 mmx7 mm square through the conjunctiva to bare sclera in the superotemporal quadrant. To eliminate only the clearance of drug from the choroidal circulation, cryotherapy was performed in another group of rabbits creating a chorioretinal scar in the superotemporal quadrant. Following the sub-Tenon's drug injection, the eyes were enucleated in all groups after 3 hr and vitreous drug levels were measured with HPLC. In normal animals, a 10-mg sub-Tenon's injection showed no detectable vitreous drug levels; however, a 20-mg injection showed positive vitreous drug levels. This suggested that collectively, the transscleral clearance mechanisms inhibiting delivery into the vitreous may be saturated with a drug depot that has a higher release rate. A 10-mg sub-Tenon's drug depot was able to deliver drug into the vitreous when both the conjunctival and choroidal drug clearance was eliminated by euthanizing the animal immediately following the drug injection. In rabbits that had only a 'conjunctival window', selectively eliminating conjunctival drug clearance, vitreous drug levels were detected. However, in rabbits that had only cryotherapy, selectively eliminating choroidal drug clearance, vitreous drug levels were not detected suggesting that the conjunctival lymphatics/blood vessels may be an important barrier to the transscleral delivery of triamcinolone acetonide. Variability in the vitreous drug levels between rabbits in each group precluded statistical testing. In summary, the rabbit appeared to demonstrate saturable ocular barriers to transscleral delivery of triamcinolone acetonide into the vitreous following a sub-Tenon's injection. The results suggested that the conjunctival lymphatics/blood vessels may be an important barrier to the delivery of triamcinolone acetonide to the vitreous in this rabbit model. The barrier location and clearance abilities of the ocular tissues are important to consider when developing a successful transscleral drug delivery system. Animal models, retaining the dynamics of blood and lymph flow, may improve the basic understanding of the ocular barriers involved with transscleral drug transport and warrants further investigation.

Animals↗
PubMed2005

Adherence of triamcinolone acetonide to various intraocular lens materials.

PURPOSE: To determine the adherence of triamcinolone acetonide to various intraocular lens (IOL) materials. SETTING: Department of Ophthalmology, Dokuz Eylül University, Izmir, Turkey. METHODS: Four IOLs of 4 materials (single-piece poly(methyl methacrylate) [PMMA], 3-piece foldable silicone, 3-piece hydrophobic acrylic, and single-piece hydrophilic acrylic) were first immersed in triamcinolone acetonide (40 mg/mL) for 15 minutes and then bathed in a balanced salt solution for another 15 minutes. Afterward, each lens optic was examined under light microscopy and digital images were obtained with a digital color video camera. The percentage of optic area covered with triamcinolone acetonide was determined by image analysis. RESULTS: Mean triamcinolone coverage was 7.62% +/- 4.06% (SD) for PMMA IOLs (range 1.97% to 11.43%), 9.09% +/- 4.60% for silicone IOLs (range 4.70% to 15.32%), 8.75 +/- 7.20% for hydrophobic acrylic IOLs (range 1.31% to 16.86%), and 23.16 +/- 8.53% for hydrophilic acrylic IOLs (range 15.02% to 35.12%). Adherence of triamcinolone acetonide to hydrophilic acrylic lenses was statistically significant when compared with other IOL materials. CONCLUSION: Intraoperative triamcinolone injection may obscure visualization intraoperatively and postoperatively, especially in eyes with hydrophilic acrylic lenses, because triamcinolone acetonide seems to have a tendency to adhere to hydrophilic acrylic lenses in vitro.

Acrylates↗
PubMed2004

A single intraoperative sub-Tenon's capsule triamcinolone acetonide injection for the treatment of post-cataract surgery inflammation.

PURPOSE: To compare a single intraoperative sub-Tenon's capsule triamcinolone acetonide injection with steroid drops in the treatment of ocular inflammation after cataract surgery. DESIGN: Randomized, double-masked controlled trial. PARTICIPANTS: A total of 100 patients were randomized prospectively into 2 groups: 50 patients treated with 1% prednisolone eyedrops (control group A) and 50 patients treated with sub-Tenon's capsule triamcinolone (treatment group B). METHODS: All patients underwent phacoemulsification and intraocular posterior lens implantation. After surgery, patients were randomized to receive either (group B) an intraoperative 40 mg triamcinolone acetonide sub-Tenon's capsule injection or (group A) 1% prednisolone acetate eyedrops, according to the following schedule: 1 drop 4 times daily (week 1), 3 times daily (week 2), 2 times daily (week 3), once daily (week 4). To mask the study, group B received vehicle drops administered on a similar schedule, and group A received an intraoperative sub-Tenon's capsule injection of a 1 ml balanced salt solution. MAIN OUTCOME MEASURES: The main outcome measures included inflammation (cell, flare, ciliary flush), intraocular pressure, and lack of response. RESULTS: Triamcinolone was shown to have anti-inflammatory efficacy clinically equivalent to conventional 1% prednisolone eyedrops in reducing intraocular inflammation, as measured by clinical methods. Triamcinolone was found to be as safe as the prednisolone in terms of adverse effects, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. On the third, seventh, fourteenth, and twenty-eighth postoperative days, a significantly lower intraocular pressure (P<0.01) was noted in the triamcinolone group than in the prednisolone group. CONCLUSIONS: A single intraoperative 40-mg triamcinolone acetonide sub-Tenon's capsule injection demonstrated a clinically equivalent therapeutic response and ocular tolerance compared with 1% prednisolone drops in controlling postoperative inflammation after uncomplicated cataract surgery and merits further investigation.

Aged↗
PubMed2005

Comparison of intravitreal versus posterior sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema.

PURPOSE: To compare the safety and efficacy of intravitreal versus posterior Sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. DESIGN: Prospective, double-masked, randomized controlled trial. PARTICIPANTS: Twelve patients (24 eyes) with bilateral diffuse diabetic macular edema. INTERVENTION: One eye of each patient was randomly assigned to receive a single 4-mg triamcinolone acetonide intravitreal injection and the fellow eye to receive a 40-mg triamcinolone acetonide posterior Sub-Tenon's capsule injection. MAIN OUTCOME MEASURES: Changes in visual acuity and central macular thickness obtained using optical coherence tomography were measured during a 6-month follow-up. Potential treatment complications were monitored, including increases in intraocular pressure (IOP) and cataract progression. RESULTS: Both intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide resulted in significant but transient improvements in central macular thickness. The mean (+/-standard deviation [SD]) central macular thickness in eyes with intravitreal injection was significantly thinner than in the Sub-Tenon's capsule-injected eyes at 1 month (226.8+/-41.7 microm and 431.5+/-165.8 microm, respectively; P = 0.002) and 3 months (242.3 +/- 93.9 microm and 364.7+/-78.2 microm, respectively; P = 0.005) after triamcinolone acetonide injection. The mean visual acuity (logarithm of the minimum angle of resolution) in the intravitreally injected eyes was significantly better than in the Sub-Tenon's capsule-injected eyes at 3 months post injection (0.832+/-0.293 and 1.107+/-0.339, respectively; P = 0.004). Intraocular pressure did not show any significant difference between the 2 forms of triamcinolone acetonide delivery at any follow-up visit, and no eyes had IOPs >25 mmHg. CONCLUSIONS: The findings from our study neither advocate nor support the use of corticosteroids for the treatment of diabetic macular edema, but do imply that both intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide may be equally tolerated, with short-term performance clearly favoring the intravitreal (4 mg) more than the SBT capsule (40 mg) route for the anatomic and functional aspects of improvement tested in this investigation.

Adult↗
PubMed1984

Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque.

To test the effect of dose and time on fetal lung maturation by exogenous glucocorticosteroids, triamcinolone acetonide was given to time-mated pregnant rhesus macaques (Macaca mulatta). Triamcinolone acetonide (10 mg/kg or 1 mg/kg) was administered intramuscularly during the midpseudoglandular (63 to 65 days' gestational age) or midcanalicular phase (110 to 112 days' gestational age) of lung development. Fetectomies were performed at 90, 120, or 150 days' gestational age. Nontreated control fetuses and postnatal animals from 59 days' gestational age to 31 days' postnatal age were collected for study of normal developmental lung morphology in the rhesus monkey. Lungs from fetuses of 90 days' gestational age and older were fixed by tracheal infusion, and lungs from fetuses less than 90 days' gestational age were fixed by immersion and embedded for high-resolution light microscopy. Body weight, crown-rump length, and fixed lung volume were determined for all fetuses. Morphometric evaluation of the volume percent of parenchyma, the volume percent of air space and the mean linear intercept as an estimate of air space size was also done. Lungs from fetuses treated during the canalicular phase had thinner, longer, less cellular septa, larger air spaces, and increased numbers of alveolar divisions in terminal air spaces as compared to those of controls. Lungs of fetuses treated during the pseudoglandular phase also had some septa which were thinner, less cellular, and longer than those of controls and had a marked increase in air space size. However, most septa were greatly reduced in height and appeared fewer in number. Alveolar divisions were decreased. The volume percent of air space was larger in all treated groups. Fixed lung volume normalized to body size (body weight and crown-rump length) was greater than that for controls for the high-dose canalicular phase treatment group. The same parameter was lower than that of controls for the high-dose, pseudoglandular phase treatment group of 150 days' gestational age. Body weight and crown-rump length for all pseudoglandular phase triamcinolone acetonide-treated fetuses also tended to be lower than those of controls. We concluded that: (1) there is both a time-dependent and a dose-dependent effect on triamcinolone acetonide on fetal lung maturation in rhesus macaques, (2) triamcinolone acetonide accelerates maturation of the interstitial and epithelial component of the developing fetal rhesus lung independent of age, (3) triamcinolone acetonide accelerates alveolarization only at later treatment ages, and (4) triamcinolone acetonide induces retardation of growth of some of the lung septa and body growth only

Animals↗
PubMed1980

Cushing's syndrome: complication of triamcinolone injection for urethral strictures in children.

We report 2 cases of Cushing's syndrome following intralesional triamcinolone acetonide injections of urethral strictures in children. The pharmacology of triamcinolone and its 2 parenteral forms, triamcinolone acetonide and triamcinolone diacetate, is discussed. For children we recommend the short-acting triamcinolone diacetate at 4-week intervals with dosage adjusted to age. In adults either type of triamcinolone may be used but triamcinolone acetonide should be given at 6-week intervals.

Child↗
PubMed1998

Comparison of intramuscular triamcinolone and oral prednisone in the outpatient treatment of acute asthma: a randomized controlled trial.

STUDY OBJECTIVE: To determine whether a one-time dose of triamcinolone diacetate, 40 mg intramuscular (i.m.), given to adult patients treated in the emergency department for mild to moderate exacerbation of asthma would decrease the rate of relapse during the following week, compared with a nontapering course of oral prednisone, 40 mg/day over 5 days. METHODS: A randomized, double-blind, controlled clinical trial was conducted at two university-affiliated community teaching hospitals with a combined annual census of 97,000. Patients were eligible if they were between the ages of 18 and 50 years, had an initial peak expiratory flow rate of less than 350 L/minute, and were to be discharged from the ED taking steroids. Patients were randomly assigned to receive either triamcinolone (40 mg i.m.) and placebo tablets or a placebo injection and prednisone (40 mg/day orally for 5 days). Patients were instructed to use a beta-agonist metered-dose inhaler, to continue other routine medications, to complete symptom diary cards, and to return in 7 to 10 days for follow-up. The main outcome measure was relapse, which was defined as an unscheduled visit to a physician's office or ED for worsening or persistent symptoms within 7 days of the initial ED visit. RESULTS: A total of 168 patients were initially enrolled; 6 patients were withdrawn for protocol violations and 8 because they could not be contacted for follow-up. A total of 154 patients were available for outcome analysis, 78 in the triamcinolone group and 76 in the prednisone group. There were no differences between the two patient groups with regard to demographics, smoking history, weight, or symptom severity. Mean initial peak flows were 244+/-64 L/minute for the triamcinolone group and 245+/-83 L/minute for the prednisone group. Fifty percent of the study patients were current smokers. The relapse rates were 9.0% (7/78) in the triamcinolone group and 14.5% (11/76) in the prednisone group (P=.29). The absolute difference in relapse rates was 5.5% (95% confidence interval [CI], 4.6% to 15.6%). There was no difference in symptom frequency or severity between the two groups during the first 5 days of outpatient treatment. Analysis between the groups stratified for smoking showed no difference in relapse rate between smokers and nonsmokers. CONCLUSION: A single dose of triamcinolone diacetate, 40 mg i.m., produced a relapse rate similar to that of prednisone, 40 mg/day orally for 5 days, after ED treatment of mild to moderate exacerbations of asthma. Intramuscular triamcinolone would appear to be an attractive alternative when compliance with a daily oral regimen is of concern.

Acute Disease↗
PubMed2003

Effects of triamcinolone on quality of life in patients with persistent allergic rhinitis.

OBJECTIVE: To study the effects of triamcinolone acetonide on health-related quality of life (HRQL) in adult patients with allergic rhinitis. METHODS: This study was conducted in South Africa as a placebo-controlled, multicenter, randomized, double-blind study. Following a 7-day baseline run-in, patients were treated for 28 days with either triamcinolone or placebo. Interviewer-assisted quality-of-life assessments were conducted using the Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Total symptom scores, including nasal congestion, were measured using daily diary cards. RESULTS: A total of 337 patients were recruited and 253 patients completed the study per protocol, of which 55 had seasonal allergic rhinitis (SAR) and 198 had persistent allergic rhinitis (PAR). Improvements in the mean scores per area of the RQLQ were significantly better with triamcinolone compared with placebo for the entire study group for activities (P = .04 at visit 4) and sleep, nasal symptoms, emotional problems, and overall score (P = .002, P = .04, P = .03, and P = .04, respectively, at visit 3). When the patients with SAR were separated from the patients with PAR in the analysis, improvement with triamcinolone was better than placebo only in the PAR patients. The overall investigator and patient assessments of relief favored triamcinolone. CONCLUSIONS: Triamcinolone given for 4 weeks improves symptom scores and HRQL in patients with allergic rhinitis. The ability of triamcinolone to relieve nasal congestion symptoms in PAR patients was correlated with improvements in HRQL.

Adolescent↗
PubMed2001

Markers of allergic inflammation in peripheral blood of children with asthma after treatment with inhaled triamcinolone acetonide.

BACKGROUND: It is important to monitor inflammation regularly in asthma in addition to clinical symptoms, and there is a great need for noninvasive tests that could routinely be used in clinical practice. OBJECTIVE: Our hypothesis was that the improvement of clinical parameters, together with decreased airway responsiveness, could be correlated with changes in the levels of serum markers of inflammation after a 4-week treatment with triamcinolone. METHODS: In this double-blind, randomized, placebo-controlled trial, 48 children, aged 6 to 18 years, with mild to moderate atopic asthma, were randomly allocated to receive triamcinolone or matching placebo for 4 weeks. The following parameters were measured: the symptom score, forced expiratory volume in 1 second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20) for histamine and peripheral blood eosinophil count, serum levels of the inflammatory markers eosinophil cationic protein (ECP), soluble receptor of interleukin-2 (sIL-2R), interleukin-4, soluble intercellular adhesion molecule-1 before and after treatment. RESULTS: The clinical parameters significantly improved after treatment with triamcinolone; the mean value of FEV1 changed from 74% of predicted value before, to 90% of predicted after treatment (P < 0.001). PC20 for histamine after treatment with triamcinolone increased significantly from the mean value 2.5 mg/mL to 4.7 mg/mL (P < 0.001). Treatment with triamcinolone significantly (P < 0.05) decreased serum levels of all the measured inflammatory markers. The mean concentration of eosinophil blood count was 380 and 261 cells/mm3; ECP, 83 and 58 ng/mL; serum sIL-2R, 734 and 487 pg/mL; soluble intercellular adhesion molecule-1, 266 and 210 ng/mL, before and after treatment, respectively. The values of interleukin-4 were low and close to the sensitivity of the assay. A significant correlation was found between ECP and sIL-2R levels before and after treatment with triamcinolone. CONCLUSIONS: A significant decrease of all the measured serum parameters was observed after treatment with triamcinolone; however, no significant correlation was found among any of those parameters and clinical markers of disease severity (such as FEV1 or PC20H).

Administration, Inhalation↗
PubMed1998

A controlled trial of twice daily triamcinolone oral inhaler in patients with mild-to-moderate asthma.

BACKGROUND: National and international guidelines recommend inhaled anti-inflammatory medications for patients with all but the mildest forms of asthma. Patients may also be more compliant with twice daily dosing. OBJECTIVE: To evaluate the efficacy and safety of triamcinolone acetonide (triamcinolone acetonide), 400 microg bid, in mild-to-moderate asthma patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled study with a 7- to 21-day baseline and 6-week treatment period. Adult mild-to-moderate asthma patients poorly controlled by beta2-agonists alone were randomized to receive placebo (48) or triamcinolone acetonide (53). Patients recorded daytime and nighttime asthma symptoms, albuterol use, and morning and evening peak expiratory flow (PEF) rates on diary cards. Clinic spirometry measures included FEV1, FEF25-75%, FVC, FEV1/FVC, and PEF. RESULTS: Triamcinolone acetonide treatment resulted in improvement from baseline of 17% for FEV1 (P < .0001); 44% for albuterol use (P = .0009); 9% for FVC (P = .0185); 19% for PEF (P = .0011); 42% for FEF25-75% (P < .0001); 8% for FEV1/FVC (P = .0016); 36% for daytime, 39% for nighttime, and 38% for total asthma symptoms (P < or = .0001); and 12% for morning, and 10% for evening PEF (P < or = .001). These changes were highly significant when compared with placebo (P < or = .0185). Significant improvement for all variables was demonstrated within 1 to 2 weeks of active treatment, and maintained for most variables over the 6-week treatment phase. Both treatments were well tolerated. Respiratory adverse events occurred more frequently with placebo; pharyngitis was reported more frequently with triamcinolone acetonide. CONCLUSIONS: Triamcinolone acetonide, administered twice daily, can effectively and safely treat patients with milder forms of asthma. In these patients, triamcinolone acetonide improves asthma symptoms and decreases the need for as-needed beta2-agonists.

Administration, Inhalation↗
PubMed1997

Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis is a common and distressing illness for which treatment is often inadequate. There is a clinical need for safe and effective therapeutic options, including preseasonal treatment, to manage many of these patients. OBJECTIVE: The goal of this study was to evaluate the clinical effects of preseasonal administration of triamcinolone acetonide nasal aerosol in the management of this illness. METHODS: This multicenter, double-blind, placebo-controlled, randomized, parallel group study involved otherwise healthy subjects with a 2-year consecutive history of ragweed-induced seasonal allergic rhinitis. Patients were asymptomatic when randomized to receive 220 micrograms triamcinolone acetonide or placebo nasal aerosol (n = 56 each) once daily for 6 weeks, beginning at least 1 week before significant ragweed pollen was airborne. RESULTS: Triamcinolone acetonide was significantly (P < .001) more effective than placebo in preventing nasal symptoms as determined by mean placebo-adjusted nasal index scores. Patients in the triamcinolone acetonide group had significantly (P < or = .0004) lower scores in the severity of individual nasal symptoms and the overall mean nasal index score. Severity of ocular symptoms was reduced more in the triamcinolone acetonide than in the placebo group (not significant). Physicians' and patients' global evaluations of efficacy favored triamcinolone acetonide, with statistically significant between-group differences in moderate or complete prevention of rhinitis symptoms. The incidence of adverse effects was similar in the two groups, with the most common being headache and increased rhinitis. CONCLUSIONS: This study demonstrates that preseasonal administration of triamcinolone acetonide nasal aerosol is safe and effective for managing seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1996

Efficacy and safety of triamcinolone acetonide aqueous nasal spray in patients with seasonal allergic rhinitis.

BACKGROUND: In order to accommodate increasing patient preferences a new aqueous formulation of triamcinolone acetonide nasal spray was developed for the relief of symptoms associated with seasonal and perennial allergic rhinitis. OBJECTIVE: This multicenter, randomized, double-blind study was designed to compare the efficacy and safety of once-daily triamcinolone acetonide aqueous nasal spray (220 micrograms/day) with placebo in relieving the symptoms of seasonal allergic rhinitis due to ragweed. METHODS: One hundred forty patients received either a once daily 220-microgram dose of triamcinolone acetonide aqueous nasal spray or placebo for 2 weeks. Patients evaluated the severity of seasonal allergic rhinitis symptoms daily for 2 weeks according to a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Physician and patient global evaluations of overall treatment effectiveness were assessed at the end of the treatment period. RESULTS: Patients receiving triamcinolone acetonide aqueous nasal spray, 220 micrograms/day, had significantly (P < .05) greater improvements in all rhinitis symptoms at weeks 1 and 2 and overall for the 2-week treatment period compared with the placebo group. A significant (P = .006) improvement in the nasal index occurred as early as 12 hours after the first dose of triamcinolone acetonide aqueous nasal spray. Both patients and physicians reported a greater overall improvement in symptoms for the triamcinolone acetonide aqueous nasal spray group. There were no differences between the two treatment groups in the incidence of adverse events. CONCLUSIONS: This study confirmed that a 220-microgram dose of triamcinolone acetonide aqueous nasal spray, administered once daily for 2 weeks, is well tolerated and reduces effectively the severity of symptoms of seasonal allergic rhinitis due to ragweed.

Administration, Intranasal↗
PubMed2000

Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) results from a progressive decline in lung function, which is thought to be the consequence of airway inflammation. We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline. METHODS: We enrolled 1116 persons with COPD whose forced expiratory volume in one second (FEV1) was 30 to 90 percent of the predicted value in a 10-center, placebo-controlled, randomized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily. The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator. The secondary outcome measures included respiratory symptoms, use of health care services, and airway reactivity. In a substudy of 412 participants, we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment. RESULTS: The mean duration of follow-up was 40 months. The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group (44.2+/-2.9 vs. 47.0+/-3.0 ml per year, P= 0.50). Members of the triamcinolone group had fewer respiratory symptoms during the course of the study (21.1 per 100 person-years vs. 28.2 per 100 person-years, P=0.005) and had fewer visits to a physician because of a respiratory illness (1.2 per 100 person-years vs. 2.1 per 100 person-years, P=0.03). Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months (P=0.02 for both comparisons). After three years, the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group (P < or = 0.007). CONCLUSIONS: Inhaled triamcinolone does not slow the rate of decline in lung function in people with COPD, but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems. These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density.

Administration, Inhalation↗
PubMed2004

Intravitreal concentration and clearance of triamcinolone acetonide in nonvitrectomized human eyes.

PURPOSE: To determine the intravitreal concentration and clearance of triamcinolone acetonide at various intervals after intravitreal injection into nonvitrectomized eyes. METHODS: Six participants were administered 4 mg (0.1 cc) of triamcinolone acetonide ophthalmic suspension. All six eyes underwent therapeutic pars plana vitrectomy with membranectomy at various post injection intervals ranging from 1.25 to 5 months from the intravitreal injection. Undiluted specimens of vitreous overlying the macula and of aqueous humor were submitted for analysis. Vitreous and aqueous humor concentrations of triamcinolone were measured by high performance liquid chromatography. RESULTS: Four eyes demonstrated detectable intravitreal concentrations of triamcinolone acetonide between 1.25 and 2.75 months after a single injection. Two eyes had an undetectable level of triamcinolone in both the vitreous and aqueous at 3 and 5 months post single injection. CONCLUSIONS: The intravitreal concentration of triamcinolone acetonide is detectable up to 2.75 months post a single 4 mg injection in nonvitrectomized eyes. A reinjection interval of 3 months may be needed to achieve sustained measurable levels of triamcinolone in nonvitrectomized patients.

Aged↗
PubMed2005

The glucocorticoid triamcinolone acetonide inhibits osmotic swelling of retinal glial cells via stimulation of endogenous adenosine signaling.

The glucocorticoid triamcinolone acetonide is clinically used for the treatment of macular edema. However, the edema-resolving mechanisms of triamcinolone are incompletely understood. Since cell swelling is a central cause of cytotoxic edema in the brain and retina, we determined the effects of triamcinolone acetonide on the swelling of retinal ganglion and Müller glial cells in acutely isolated retinas from rats and guinea pigs in situ. Triamcinolone acetonide (100 microM) had no effect on the swelling of ganglion cells that was evoked in isolated whole mounts of the guinea pig retina by acute application of glutamate (1 mM) or high K+ (50 mM). However, triamcinolone reversed the osmotic swelling of Müller glial cells in retinas of the rat that was observed under various experimental conditions: in retinas isolated at 3 days after transient retinal ischemia, in retinas of eyes with lipopolysaccharide-induced ocular inflammation, and in control retinas in the presence of Ba2+ (1 mM), H2O2 (200 microM), arachidonic acid (10 microM), or prostaglandin E2 (30 nM). The inhibiting effect of triamcinolone on osmotic glial cell swelling was mediated by stimulation of transporter-mediated release of endogenous adenosine and subsequent A1 receptor activation, resulting in an elevation of the intracellular cAMP level and activation of the protein kinase A, and, finally, in an opening of extrusion pathways for K+ and Cl- ions. The inhibitory effect on the cytotoxic swelling of glial cells may contribute to the fast edema-resolving effect of vitreal triamcinolone observed in human patients.

Adenosine↗
PubMed2005

Effect of triamcinolone acetonide on proliferation of retinal endothelial cells in vitro and in vivo.

AIM: To assess the effect of crystalline triamcinolone acetonide on retinal endothelial cell proliferation in vivo and in vitro. METHODS: For in vitro analysis, a sprouting assay was employed. Bovine retinal endothelial cells were stimulated with basic fibroblast growth factor (bFGF) and incubated with different concentrations of triamcinolone acetonide (0.05 mg/ml to 8 mg/ml). For in vivo analysis, a retinopathy of prematurity (ROP) model was used. 16 C57BL/J6 mice were exposed to 75% oxygen from postnatal day 7 to day 12. On day 12, triamcinolone acetonide was intravitreally injected into one eye ("study eye") and isotonic saline into the contralateral eye ("control eye"). On day 17, the mice were sacrificed and the eyes removed for quantitative analysis of preretinal neovascularisation. Four non-exposed mice served as negative control. RESULTS: The sprouting assay demonstrated a dose dependent inhibition of bovine retinal endothelial cell proliferation from 0.05 mg triamcinolone acetonide/ml (no inhibition) to 3 mg triamcinolone acetonide/ml (complete inhibition). Dosages of more than 2 mg/ml resulted in cytotoxic changes of endothelial cells. The ROP model demonstrated a significantly lower neovascular cell count of 58% in the study group compared to the control group (6.35 (SD 2.1) cells per histological section versus 14.9 (SD 5.3) cells; p<0.005). CONCLUSIONS: Triamcinolone acetonide inhibits bFGF induced proliferation of retinal endothelial cells in vivo and in vitro. These findings contribute to understanding the mode of action and effects of triamcinolone acetonide on retinal neovascularisation.

Animals↗
PubMed2005

Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema.

AIM: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. METHODS: The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3-12 months). Main outcome measures were visual acuity and intraocular pressure. RESULTS: Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). CONCLUSIONS: In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used.

Aged↗
PubMed2005

Comparison of different techniques for purification of triamcinolone acetonide suspension for intravitreal use.

BACKGROUND: Intravitreal triamcinolone has increasingly been used for the treatment of oedematous and neovascular diseases and purification of triamcinolone suspension may be important in order to avoid the potential toxic effects of the vehicle. The aim was to evaluate different techniques used to reduce the solvent agent benzyl alcohol (9.9 mg/ml) from a commercially prepared triamcinolone acetonide suspension. METHODS: Different techniques were used to reduce the solvent agent benzyl alcohol: filter techniques using 0.22 mum or 5 mum pore size, and non-filter techniques using sedimentation or centrifugation. Quantification of triamcinolone acetonide and benzyl alcohol was performed by high pressure liquid chromatography (HPLC). RESULTS: Benzyl alcohol concentration was decreased significantly in all the techniques used compared with the original commercial suspension (p<0.05), with no significant differences among them. The reduction was approximately one tenth of its original concentration. However, triamcinolone acetonide concentration differed significantly depending on the method used. Centrifugation method showed no differences versus the original commercial solution; sedimentation technique reduced the expected dose only 25%; the filter technique using a 5 mum pore size membrane reduced the expected dose to one fourth, while the filter technique using a 0.22 mum pore size membrane reduced the expected dose to 45%. CONCLUSIONS: All the different techniques employed effectively reduced the concentration of benzyl alcohol. However, the final concentration of triamcinolone was much lower than expected using the filter techniques. The pore size membrane inversely influenced the final concentration, with part of the triamcinolone crystals probably being entrapped in the filter. Centrifugation is recommended as the best way of administering the drug.

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