Intravitreal triamcinolone acetonide for serous retinal pigment epithelial detachments in exudative age-related macular degeneration

BACKGROUND: Due to the high risk of RPE tears PDT is usually not performed in eyes with serous RPE detachments (sRPED). For this reason this subform of exudative AMD was so far untreatable. PATIENTS AND METHODS: We report on a prospective uncontrolled observational case series. 20 eyes of 20 patients with subfoveal sRPED demonstrated by OCT were treated between June 2005 and April 2006 with intravitreal triamcinolone acetonide (IVTA). In 15 cases there was a primary sRPED, in 5 cases it had developed after one or more sessions of photodynamic therapy with Visudyne. RESULTS: There was a trend for better average visual acuity in the group with primary sRPED from 0.73 logMAR (0.19 Snellen equivalent) at baseline (n = 15) to 0.68 logMAR (0.21 Snellen) after one month (n = 15) (p = 0.19) and to 0.60 logMAR (0.25 Snellen) after three months (n = 14) (p = 0.41). The maximal height of sRPED decreased to an average of 35.3 % after one month (n = 15) and increased again to 56.9 % after 3 months (n = 14). One patient was lost to follow-up. In the group of eyes with sRPED after PDT, one eye developed an RPE tear with severe vision loss two weeks after IVTA. In the remaining four eyes average visual acuity improved from 0.90 logMAR (0.13 Snellen) at baseline to 0.73 logMAR (0.19 Snellen) after one month and to 0.80 logMAR (0.16 Snellen) after 3 months. Complete resolution of sRPED was observed in 8/20 eyes (4/5 eyes with sRPED after PDT and 4/15 eyes with primary sRPED). CONCLUSIONS: IVTA seems to be a therapeutic option in otherwise untreatable eyes with sRPED.

Comparison between intravitreal and orbital floor triamcinolone acetonide after phacoemulsification in patients with endogenous uveitis

PURPOSE: To compare the effect of intravitreal and orbital floor triamcinolone acetonide (TA) on macular edema, visual outcome, and course of postoperative inflammation after cataract surgery in uveitis patients. DESIGN: Prospective, randomized clinical trial. METHODS: Monocenter study (40 patients) with chronic endogenous uveitis who underwent phacoemulsification with intraocular lens implantation with either 4 mg intravitreal TA (n = 20) or 40 mg orbital floor TA (n = 20). The primary outcome was influence on cystoid macular edema (CME). Secondary outcome measures were best-corrected visual acuity (BCVA), anterior chamber cell grade, laser flare photometry, giant cell deposition, posterior capsule opacification (PCO), and intraocular pressure. RESULTS: Mean central foveal thickness decreased in the intravitreal TA group and increased in the orbital floor TA group (P < .001 at one and three months). CME improved in 50% of patients after intravitreal TA, whereas it was unchanged after orbital floor TA (difference between the groups at three months, P = .049). Mean BCVA (logarithm of the minimal angle of resolution) improved postoperatively (P < .001) from 0.76 and 0.74 to 0.22 and 0.23 in the intravitreal TA and orbital floor TA group, respectively. Anterior chamber cell count at one month was lower in the intravitreal TA than in the orbital floor TA group (P = .02). Laser flare photometry values and giant cell numbers were slightly higher after orbital floor TA than after intravitreal TA. The groups did not differ with respect to PCO rate and ocular hypertension. CONCLUSIONS: The CME improvement and anti-inflammatory effect after intravitreal TA was better than after orbital floor TA injection in cataract surgery in uveitis patients.

Effects of sodium hyaluronate and triamcinolone acetonide on proteoglycan metabolism in equine articular chondrocytes treated with interleukin-1

The objective of this study is to determine if the effects of a high molecular weight sodium hyaluronate (HA) alone or in combination with triamcinolone acetate (TA) can mitigate chondrocyte proteoglycan catabolism caused by interleukin-1 (IL-1) administration. Chondrocytes were collected from fetlock joints of ten horses euthanized for reasons unrelated to joint disease. Chondrocyte pellets were treated with media (negative control); media containing IL-1 only (positive control); or media containing IL-1 with HA only (0.5 or 2.0 mg/mL), TA only (0.06 or 0.6 mg/mL), or HA (0.5 or 2.0 mg/mL) and TA (0.06 or 0.6 mg/mL) in combination. Chondrocyte pellets were assayed for newly synthesized GAG, total GAG content, total DNA content, and mRNA levels of collagen type II, aggrecan, and COX-2. The high concentration of HA (2.0 mg/mL) increased GAG synthesis while the high concentration of TA (0.6 mg/mL) decreased loss of GAG into the media. Both the high concentration of HA and TA increased the total GAG content within the pellet. There was no change in pellet DNA content with either treatment. TA reduced COX-2 mRNA levels as well as aggrecan and collagen type II expression. Treatment with HA had no effect on mRNA levels of COX-2, aggrecan or collagen type II. These results indicate that the high concentration of HA or TA alone or in combination will mitigate effects of IL-1 administration on proteoglycan catabolism of equine articular chondrocytes.

Screening and Quantitative Confirmatory Method for the Analysis of Glucocorticoids in Bovine Milk Using Liquid Chromatography-Tandem Mass Spectrometry

An LC/MS/MS method was developed and validated for the simultaneous identification, confirmation, and quantification of 12 glucocorticoids in bovine milk. The method was validated in accordance with the criteria defined in Commission Decision 2002/657/EC. The developed method can detect and confirm the presence of dexamethasone, betamethasone, prednisolone, flumethasone, 6 alpha-methylprednisolone, fluorometholone, triamcinolone acetonide, prednisone, cortisone, hydrocortisone, clobetasol propionate, and clobetasol butyrate in bovine milk. Milk samples are extracted with acetonitrile; sodium chloride is subsequently added to aid partition of the milk and acetonitrile mixture. The acetonitrile extract is then subjected to liquid-liquid purification by the addition of hexane. The purified extract is evaporated to dryness and reconstituted in a water acetonitrile mixture, and determination is carried out by LC/MS/MS. The method permits analysis of up to 30 samples in 1 day.

Treatments for macular oedema following central retinal vein occlusion: systematic review

Objectives: To review systematically the randomised controlled trial (RCT) evidence for treatment of macular oedema due to central retinal vein occlusion (CRVO).

Data sources: MEDLINE, EMBASE, CDSR, DARE, HTA, NHSEED, CENTRAL and meeting abstracts (January 2005 to March 2013).

Study eligibility criteria, participants and interventions: RCTs with at least 12 months of follow-up assessing pharmacological treatments for CRVO were included with no language restrictions.

Study appraisal and synthesis methods: 2 authors screened titles and abstracts and conducted data extracted and Cochrane risk of bias assessment. Meta-analysis was not possible due to lack of comparable studies.

Results: 8 studies (35 articles, 1714 eyes) were included, assessing aflibercept (n=2), triamcinolone (n=2), bevacizumab (n=1), pegaptanib (n=1), dexamethasone (n=1) and ranibizumab (n=1). In general, bevacizumab, ranibizumab, aflibercept and triamcinolone resulted in clinically significant increases in the proportion of participants with an improvement in visual acuity of ≥15 letters, with 40–60% gaining ≥15 letters on active drugs, compared to 12–28% with sham. Results for pegaptanib and dexamethasone were mixed. Steroids were associated with cataract formation and increased intraocular pressure. No overall increase in adverse events was found with bevacizumab, ranibizumab, aflibercept or pegaptanib compared with control. Quality of life was poorly reported. All studies had a low or unclear risk of bias.

Limitations: All studies evaluated a relatively short primary follow-up (1 year or less). Most had an unmasked extension phase. There was no head-to-head evidence. The majority of participants included had non-ischaemic CRVO.

Conclusions and implications of key findings: Bevacizumab, ranibizumab, aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO. Long-term data on effectiveness and safety are needed. Head-to-head trials and research to identify ‘responders’ is needed to help clinicians make the right choices for their patients. Research aimed to improve sight in people with ischaemic CRVO is required.

Drug treatment of macular oedema secondary to central retinal vein occlusion: a network meta-analysis

Objective
To indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network meta-analysis (NMA).

Design
NMA.

Data sources
The following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science.

Eligibility criteria for selecting studies
Only randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions.

Results
Seven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections.

Conclusions
We found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by clinicians because it might require fewer injections.

Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.

Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action.

Production of pH-responsive microparticles by spray drying: investigation of experimental parameter effects on morphological and release properties

During spray drying, emphasis is placed on process optimisation to generate favourable particle morphological and flow properties. The effect of the initial feed solution composition on the drug release from the prepared microparticles is rarely considered. We investigated the effects of solvent composition, feed solution concentration and drug-loading on sodium salicylate, hydrocortisone and triamcinolone release from spray dried Eudragit L100 microparticles. Eudragit L100 is a pH-responsive polymer whose dissolution threshold is pH 6 so dissolution testing of the prepared microparticles at pH 5 and 1.2 illustrated non-polymer controlled burst release. Increasing the water content of the initial ethanolic feed solution significantly reduced hydrocortisone burst release at pH 5, as did reducing the feed solution concentration. These findings caution that changes in feed solution concentration or solvent composition not only affect particles’ morphological characteristics but can also negatively alter their drug release properties. This work also illustrate that drug-free microparticles can have different morphological properties to drug-loaded microparticles. Therefore, process optimisation needs to be carried out using drug-loaded systems. Depending on the physicochemical properties of the encapsulated API, drug-loading can affect the polymer solubility in the initial feed solution with consequent impact on microparticles morphological and release properties.

Subconjunctival Delivery of Antibiotics in a Controlled-Release System A Novel Anti-infective Prophylaxis Approach for Cataract Surgery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chitosan-pectin multiparticulate systems associated with enteric polymers for colonic drug delivery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Exposição de fibroblastos de pterígios recidivados e da cápsula de Tenon normal à triancinolona

Purpose: To evaluate the proliferation rate of recurrent pterygium and normal Tenon's capsule fibroblasts after exposure to triamcinolone.Methods: Explants of recurrent pterygia and normal Tenon's capsule of the same carrier were cultured. The fibroblasts were cultured and subcultured until the third passage and subsequently exposed to triamcinolone. The cell proliferation rate was evaluated 3, 6, 12 and 18 days after the exposure.Results: Fibroblasts exposed to triamcinolone had significantly lower proliferation rate (P < 0.05) compared to those not exposed, when the evaluation was performed 3, 6 and 12 days later. In the 18th day after exposure, there was a return in the proliferation rate, with statistical significance, only in the pterigyum fibroblasts.Conclusion: Both the fibroblasts from normal Tenon's capsule as from recurrent pterygia showed significantly lower proliferation rate after exposure to triamcinolone. After 18 days from the exposition, pterygium fibroblasts recovered the proliferation. The results suggested the triamcinolone might be useful as adjuvant in pterygium treatment.

Granuloma facial: A proposito de dois casos

Granuloma faciale is a benign and rare disease restricted to the skin. Its etiopathogenesis is not related to systemic granulomatous and eosinophilic diseases. Two adult patients with reddish-brown lesions on the facial are reported. Among the treatments used, the more consistent results were observed with intralesional triamcinolona (Case 1) and with CO2 Laser (Case 2), with clear advantage of the laser therapy. The histopathology and the therapeutic options are discussed.