Objetivo: Avaliar a eficiência da Triancinolona Acetonida como agente modulador da resposta inflamatória e cicatricial em coelhos submetidos a cirurgia de músculo extra-ocular. Método: Foi realizado estudo prospectivo, mascarado, em dois estádios. No primeiro estádio, dez coelhos foram submetidos a retrocesso do músculo reto superior em ambos os olhos. Aplicouse, em um deles, 0,15 cc de Triancinolona Acetonida (40mg/cc) nos tecidos circunjacentes ao local de reinserção muscular e, como controle, 0,15cc de solução de cloreto de sódio a 0,9% no local equivalente no olho contra-lateral. Quinze dias após, cinco coelhos foram submetidos a exenteração das órbitas e os restantes dos animais tiveram o mesmo procedimento realizado após trinta dias. O material do sítio de reinserção muscular foi avaliado por meio de análise histopatológica qualitativa e quantitativa (morfometria). No segundo estádio, com incrementação da agressão cirúrgica, dezesseis coelhos foram submetidos aos mesmos procedimentos com exenteração das órbitas após quinze dias, e posterior análise histopatológica dos tecidos. Resultados: Houve efeito inibitório sobre a intensidade da resposta inflamatória nos olhos tratados em comparação com os olhos controle. Conclusão: Nas condições de realização do presente estudo o uso per-operatório da triancinolona acetonida foi efetivo no controle da resposta inflamatória em olhos de coelhos submetidos a cirurgia de músculo extra-ocular. / Purpose: To evaluate the efficiency of triamcinolone acetonide (TRI) in limiting the postoperative inflammatory response and scarring following strabismus surgery. Methods: A prospective, two-stage, masked, controlled trial was conducted. In the first stage, the inflammatory response at the extraocular reattachment site was analyzed following superior rectus recession in ten rabbits. One eye had 0,15 cc of triamcinolone acetonide (40mg/cc) applied around the new insertion site and, similarly, 0,15 cc of isotonic saline solution (0,9%) was applied to the fellow eye following the same procedure, thus serving as a control. Fifteen days later, orbital exenteration was performed in five rabbits and the remaining five were exenterated thirty days later. The reattachment site tissues were submitted to qualitative and quantitative histological examinations. In the second stage 16 rabbits were submitted to amplified surgical trauma, after which the aforementioned steps were also carried out. Granuloma total area at the extraocular muscle reattachment sites of control and treated eyes were compared. Results: There was an inhibitory effect of TRI on the inflammatory response of treated eyes as compared to control eyes. Conclusions: TRI was effective in controlling the postoperative inflammatory response in rabbit eyes submitted to traumatic recession of the superior rectus muscle.

INTRODUÇÃO: O tratamento padrão estabelecido pelo Early Treatment Diabetic Retinopathy Study (ETDRS) para retinopatia diabética proliferativa (RDP), com ou sem edema macular clinicamente significativo (EMCS), é a panfotocoagulação com laser. Essa forma de tratamento reduz o risco de perda visual, mas não proporciona ganho de visão. O objetivo deste estudo é avaliar os efeitos do acetonido de triancinolona associado à panfotocoagulação na RDP. MÉTODOS: Realizou-se um ensaio clínico randomizado, prospectivo e aberto com portadores de RDP bilateral e simétrica, submetidos à panfotocoagulação com laser em ambos os olhos. Portadores de EMCS foram tratados com fotocoagulação focal na região macular no primeiro episódio da panfotocoagulação. A injeção intravítrea de acetonido de triancinolona (4 mg/0,1 ml) foi administrada aleatoriamente em um dos olhos (grupo estudo), após último episódio da laserterapia, e o contralateral foi adotado para comparação (grupo controle), sendo seguidos por 6 meses. Os parâmetros adotados para avaliar os efeitos terapêuticos foram: acuidade visual com melhor correção óptica (tabela do ETDRS), medidas de espessura central e de volume macular por meio da tomografia de coerência óptica e taxa de sangramento (hemorragia pré-retiniana ou vítrea). As potenciais complicações da droga foram avaliadas durante o seguimento (pressão intra-ocular, catarata, endoftalmite e pseudo-endoftalmite). RESULTADOS: Foram incluídos 28 (vinte e oito) indivíduos com diabetes melito tipo 2. Quanto ao EMCS, 22 olhos apresentaram no grupo estudo e 23, no grupo controle (p= 0,317). A média de idade foi de 61,36 ± 5,77 anos, com predominância do sexo ferminino (57,1%). A maioria era portadora de hipertensão arterial sistêmica (82,1%) e usuária de insulina (75,0%). Não houve diferença significante nas médias de número de disparos da panfotocoagulação e da fotocoagulação na região macular entre os grupos. Quanto à acuidade visual, o grupo estudo apresentou pior acuidade antes do tratamento em relação ao grupo controle (p= 0,040), não havendo diferença significativa na primeira semana do tratamento. Durante o seguimento, o grupo estudo evoluiu com melhora na acuidade visual no primeiro (p< 0,001), no terceiro (p< 0,001) e no sexto meses (p< 0,001) em relação ao controle. Em relação às medidas de espessura central e de volume macular, os grupos não apresentaram diferença significativa antes do tratamento, no entanto, o grupo estudo apresentou medidas significativamente menores na primeira semana, no primeiro, no terceiro e no sexto meses em relação ao controle. Quanto à taxa de sangramento, 9 olhos (32,1%) do grupo controle evoluíram com sangramento e nenhum do grupo estudo (p< 0,001). Os grupos apresentaram diferença na pressão intra-ocular apenas na primeira semana do tratamento, quando as medidas do grupo estudo foram maiores que as do controle (p< 0,05). Nenhum dos olhos apresentou catarata com indicação cirúrgica, endoftalmite ou pseudo-endoftalmite. CONCLUSÃO: Os resultados deste estudo sugerem que a injeção intravítrea de triancinolona é um procedimento seguro e pode melhorar o prognóstico funcional e estrutural da mácula em olhos com RDP submetidos a panfotocoagulação com laser. / INTRODUCTION: The gold standard treatment for proliferative diabetic retinopahty (PDR) with and without clinically significant macular edema (CSME), as stablished by the Early Treatment Diabetic Retinopathy Study (ETDRS), is panretinal photocoagulation (PRP). This treatment lowers the rate of severe vision loss, but does not increase vision. The aim of this study is to evaluate the efficacy and safety of triamcinolone acetonide associated to PRP for the management of PDR. METHOD: This is a prospective, randomized clinical trial for patients with bilateral and symmetrical PDR who had undergone PRP in both eyes. Patients who had CSME were treated with macular focal photocoagulation on the first episode of the PRP. Intravitreal injection of triamcinolone acetonide (4 mg/0.1 ml) was given to the study eye after the last episode of PRP and the fellow eye was used as control. Follow up was 6 months long. Best-corrected visual acuity (BCVA) using ETDRS charts, central macular thickness and macular volume as measured by the optical coherence tomography software, and the amount of bleeding (both preretinal and vitreous) were the parameters chosen to analyse outcome. Side effects of triamcinolone acetonide such as intraocular pressure, cataracts and severe inflammation, were also followed during the study. RESULTS: Twenty eight diabetes type 2 patients were included. Twenty two study eyes and 23 fellow eyes (controls) presented with CSME (p= 0.317). Mean age was 61.36 ± 5.77 years, with 57.1% females. Many patients had hypertension (82.1%) and used insulin (75.0%). There was no significant difference on the number of spots used for PRP or macular photocoagulation in between the groups. The study eyes had lower BCVA on baseline than the control eyes (p= 0.040). One week after the treatment, there was no difference on BCVA between the study and control eyes. During the follow up, the study group increased their BCVA on the first (p< 0.001), third (p< 0.001) and sixth month (p< 0.001) compared to control. Even thought there was no significant difference on central macular thickness and macular volume between groups on baseline, the study eyes had significant lower measurements on the first week and first, third and sixth months in comparison to controls. Nine control eyes (32.1%) had hemorrhages and none study eyes (p< 0.001). Injected eyes had higher intraocular pressure than controls on the first week of treatment (p< 0.05). None of the eyes developed cataracts that needed surgery, endophthalmits or severe inflammation. CONCLUSION: This study suggests intravitreal injection of triamcinolone is a safe procedure that increases funcional and anatomical prognosis of the macula in PDR eyes that underwent PRP.

INTRODUÇÃO: O tratamento padrão estabelecido pelo Early Treatment Diabetic Retinopathy Study (ETDRS) para retinopatia diabética proliferativa (RDP), com ou sem edema macular clinicamente significativo (EMCS), é a panfotocoagulação com laser. Essa forma de tratamento reduz o risco de perda visual, mas não proporciona ganho de visão. O objetivo deste estudo é avaliar os efeitos do acetonido de triancinolona associado à panfotocoagulação na RDP. MÉTODOS: Realizou-se um ensaio clínico randomizado, prospectivo e aberto com portadores de RDP bilateral e simétrica, submetidos à panfotocoagulação com laser em ambos os olhos. Portadores de EMCS foram tratados com fotocoagulação focal na região macular no primeiro episódio da panfotocoagulação. A injeção intravítrea de acetonido de triancinolona (4 mg/0,1 ml) foi administrada aleatoriamente em um dos olhos (grupo estudo), após último episódio da laserterapia, e o contralateral foi adotado para comparação (grupo controle), sendo seguidos por 6 meses. Os parâmetros adotados para avaliar os efeitos terapêuticos foram: acuidade visual com melhor correção óptica (tabela do ETDRS), medidas de espessura central e de volume macular por meio da tomografia de coerência óptica e taxa de sangramento (hemorragia pré-retiniana ou vítrea). As potenciais complicações da droga foram avaliadas durante o seguimento (pressão intra-ocular, catarata, endoftalmite e pseudo-endoftalmite). RESULTADOS: Foram incluídos 28 (vinte e oito) indivíduos com diabetes melito tipo 2. Quanto ao EMCS, 22 olhos apresentaram no grupo estudo e 23, no grupo controle (p= 0,317). A média de idade foi de 61,36 ± 5,77 anos, com predominância do sexo ferminino (57,1%). A maioria era portadora de hipertensão arterial sistêmica (82,1%) e usuária de insulina (75,0%). Não houve diferença significante nas médias de número de disparos da panfotocoagulação e da fotocoagulação na região macular entre os grupos. Quanto à acuidade visual, o grupo estudo apresentou pior acuidade antes do tratamento em relação ao grupo controle (p= 0,040), não havendo diferença significativa na primeira semana do tratamento. Durante o seguimento, o grupo estudo evoluiu com melhora na acuidade visual no primeiro (p< 0,001), no terceiro (p< 0,001) e no sexto meses (p< 0,001) em relação ao controle. Em relação às medidas de espessura central e de volume macular, os grupos não apresentaram diferença significativa antes do tratamento, no entanto, o grupo estudo apresentou medidas significativamente menores na primeira semana, no primeiro, no terceiro e no sexto meses em relação ao controle. Quanto à taxa de sangramento, 9 olhos (32,1%) do grupo controle evoluíram com sangramento e nenhum do grupo estudo (p< 0,001). Os grupos apresentaram diferença na pressão intra-ocular apenas na primeira semana do tratamento, quando as medidas do grupo estudo foram maiores que as do controle (p< 0,05). Nenhum dos olhos apresentou catarata com indicação cirúrgica, endoftalmite ou pseudo-endoftalmite. CONCLUSÃO: Os resultados deste estudo sugerem que a injeção intravítrea de triancinolona é um procedimento seguro e pode melhorar o prognóstico funcional e estrutural da mácula em olhos com RDP submetidos a panfotocoagulação com laser. / INTRODUCTION: The gold standard treatment for proliferative diabetic retinopahty (PDR) with and without clinically significant macular edema (CSME), as stablished by the Early Treatment Diabetic Retinopathy Study (ETDRS), is panretinal photocoagulation (PRP). This treatment lowers the rate of severe vision loss, but does not increase vision. The aim of this study is to evaluate the efficacy and safety of triamcinolone acetonide associated to PRP for the management of PDR. METHOD: This is a prospective, randomized clinical trial for patients with bilateral and symmetrical PDR who had undergone PRP in both eyes. Patients who had CSME were treated with macular focal photocoagulation on the first episode of the PRP. Intravitreal injection of triamcinolone acetonide (4 mg/0.1 ml) was given to the study eye after the last episode of PRP and the fellow eye was used as control. Follow up was 6 months long. Best-corrected visual acuity (BCVA) using ETDRS charts, central macular thickness and macular volume as measured by the optical coherence tomography software, and the amount of bleeding (both preretinal and vitreous) were the parameters chosen to analyse outcome. Side effects of triamcinolone acetonide such as intraocular pressure, cataracts and severe inflammation, were also followed during the study. RESULTS: Twenty eight diabetes type 2 patients were included. Twenty two study eyes and 23 fellow eyes (controls) presented with CSME (p= 0.317). Mean age was 61.36 ± 5.77 years, with 57.1% females. Many patients had hypertension (82.1%) and used insulin (75.0%). There was no significant difference on the number of spots used for PRP or macular photocoagulation in between the groups. The study eyes had lower BCVA on baseline than the control eyes (p= 0.040). One week after the treatment, there was no difference on BCVA between the study and control eyes. During the follow up, the study group increased their BCVA on the first (p< 0.001), third (p< 0.001) and sixth month (p< 0.001) compared to control. Even thought there was no significant difference on central macular thickness and macular volume between groups on baseline, the study eyes had significant lower measurements on the first week and first, third and sixth months in comparison to controls. Nine control eyes (32.1%) had hemorrhages and none study eyes (p< 0.001). Injected eyes had higher intraocular pressure than controls on the first week of treatment (p< 0.05). None of the eyes developed cataracts that needed surgery, endophthalmits or severe inflammation. CONCLUSION: This study suggests intravitreal injection of triamcinolone is a safe procedure that increases funcional and anatomical prognosis of the macula in PDR eyes that underwent PRP.

Glucocorticoids (GCs) have been widely used as a therapeutic agent for diverse inflammatory ocular diseases. However, a high percentage of patients undergoing this treatment develop high intraocular pressure (IOP), which if left unsupervised may lead to glaucoma. It is believed that the IOP elevation in response to GC treatment has a genetic determinant. In order to test this hypothesis, we analyzed in 52 patients the presence of single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene (GR), the principal mediator of GCs uptake by the cells. We studied six GR SNPs previously reported to be associated with sensitivity and resistance to GCs: GluArg22/23GluLys (codon 22-23), Asn363Ser (codon 363), IVS2+646C>G (intron 2/BclI), IVS3-46G>C (intron 3), IVS4-16G>T (intron 4), Asn766Asn (Codon 766). Nevertheless, the results of this preliminary study did not show any specific correlation between SNPs in the GR gene and IOP elevation. Therefore, we proceeded to perform a whole genome SNP screen with the DNA samples of these patients to search for possible target genes responsible for the elevated IOP after GC treatment. As a result, we identified forty-eight SNPs in thirty-three genes that correlate with the high IOP response. The gene showing the strongest association is a poorly known G-protein coupled receptor. In addition, four SNPs hit a single transporter gene. Other candidate genes identified are a translation elongation factor, an F-box protein, an oxysterol binding protein, and a solute carrier family gene. These results support our hypothesis that IOP elevation following GC treatment is a genetically determined response. GCs are a common treatment for innumerable medical conditions; we believe that a genetic association between GC treatment and its physiological response may be important for improving treatment management and drug development for retinal diseases as well as for other medical ailments. However, further studies need to be performed to analyze in depth the association between the candidate genes identified in this study and the steroid response.

Η Ακετονική Τριαμσινολόνη είναι ένα συνθετικό γλυκοκορτικοειδές το οποίο έχει ευρέως χρησιμοποιηθεί στη θεραπεία ενός αριθμού φλεγμονωδών και αγγειακών / εξιδρωματικών παθήσεων του οφθαλμού, χορηγούμενη υπό μορφή ένεσης παραβόλβια, υποτενόνια ή ενδοϋαλοειδικά. Δυστυχώς έχει περιορισμένο χρόνο ημιζωής με συνέπεια να είναι συχνά αναγκαίες επανειλημμένες ενέσεις για να επιτευχθεί παρατεταμένη δράση. Αυτό αυξάνει τη συχνότητα των επιπλοκών, οι οποίες σχετίζονται τόσο με το ίδιο το φάρμακο όσο και με την οδό χορήγησης. Σκοπός της μελέτης: Η παρασκευή σκληρικών συστημάτων ελεγχόμενης αποδέσμευσης Ακετονικής Τριαμσινολόνης βασιζόμενα στο βιοδιασπόμενο πολυμερές Πόλυ[γαλακτικό] (PLA) και η αξιολόγηση των in vitro/ex vivo χαρακτηριστικών τους σε σχέση με τη δυνητική χρήση τους για παρατεταμένη διασκληρική χορήγηση ΤΑ. Υλικό και Μέθοδος: Μικροσφαίρες PLA που περιείχαν ΤΑ παρασκευάστηκαν με τη μέθοδο του απλού και του διπλού γαλακτώματος. Εξετάστηκαν η μορφολογία τους, το μέγεθός τους, η επίδραση της αρχικής ποσότητας ΤΑ και της μεθόδου παρασκευής στη φόρτιση των μικροσφαιρών καθώς και η in vitro αποδέσμευση ΤΑ από αυτές. Παρασκευάστηκαν δισκία αποτελούμενα από μικροσφαίρες καθαρού PLA και ΤΑ (με αναλογία βάρους 1:1, 2:1 και 4:1 αντίστοιχα) και εξετάστηκε η in vitro καμπύλη αποδέσμευσης ΤΑ από αυτά. Αξιολογήθηκε η καμπύλη διασκληρικής διάχυσης in vitro τοποθετώντας ένα δισκίο αναλογίας PLA:TA=1:1 σε ένα δοχείο δότη και μετρώντας τη συγκέντρωση ΤΑ σε δοχείο δέκτη. To δοχείο δότης και το δοχείο δέκτης διαχωρίζονταν διαμέσου ενός τμήματος σκληρού χιτώνα κουνελιού. Σε δύο πτωματικούς οφθαλμούς κουνελιών τοποθετήθηκε επισκληρικά ένα δισκίο 1:1 PLA-ΤΑ και καλύφθηκε με ένα σκληρικό μόσχευμα. Η συγκέντρωση της ΤΑ στο υδατοειδές υγρό και στο υαλοειδές μετρήθηκε 5, 10 και 20 ημέρες μετά από την ένθεση. Aποτελέσματα: Η μέση διάμετρος των μικροσφαιρών ήταν 2 μm. H μέθοδος του διπλού γαλακτώματος καθώς και η αύξηση της αρχικής ποσότητας του φαρμάκου οδήγησε στην αύξηση της τιμής φόρτισης και ενκαψακίωσης των μικροσφαιρών. Παρατηρήθηκε παρατεταμένη για αρκετές μέρες αποδέσμευση ΤΑ από τις μικροσφαίρες, με το ρυθμό αποδέσμευσης να εξαρτάται από την περιεκτικότητά τους σε ΤΑ. H ΤΑ αποδεσμευόμενη από δισκία PLA-TA παρουσίασε παρατεταμένη αποδέσμευση, με το ρυθμό της να εξαρτάται από το λόγο PLA:TA. H TA μπόρεσε να διαπεράσει το σκληρό χιτώνα με περίπου 21% του φαρμάκου στο δοχείο δότη να έχει διαχυθεί διαμέσου του σκληρού χιτώνα μετά από 45 ημέρες. Μετά από σκληρική χορήγηση η ΤΑ εμφάνισε συγκεντρώσεις στο υδατοειδές υγρό και στο υαλοειδές σε πτωματικούς οφθαλμούς. Συμπεράσματα: Οι μικροσφαίρες και τα δισκία PLA-TA που αναπτύχθηκαν σε αυτήν τη μελέτη παρουσιάζουν παρατεταμένη και ελεγχόμενη αποδέσμευση ΤΑ, έχουν τα πλεονεκτήματα της καθιερωμένης βιοαποικοδομησιμότητας και βιοσυμβατότητας του πολυμερούς PLA, παρέχουν ευελιξία ως προς το ρυθμό αποδέσμευσης και τη συνολική δόση ΤA και παρουσιάζουν ευκολία στους χειρουργικούς χειρισμούς. Αυτά τα συστήματα φαίνεται να είναι υποσχόμενα για την ελεγχόμενη διασκληρική χορήγηση ΤΑ και δικαιολογείται η περαιτέρω μελέτη τους. / Triamcinolone Acetonide (TA) is a synthetic glucocorticoid, which has been widely used to treat a number of inflammatory and vascular and/or exudative diseases of the eye, administered via a peribulbar, sub-tenon or intravitreal injection. Unfortunately, it has a limited half-life and thus repeated injections are often required to establish a prolonged effect. This increases the rate of complications, which are related to the drug itself as well as to the administration route. Study Purpose: To develop scleral controlled-release-systems of Τriamcinolone Αcetonide based on biodegradable Poly[lactide] (PLA) and evaluate their in vitro/ex vivo properties with regard to their possible application for the prolonged transscleral delivery of TA. Materials and Methods: PLA microspheres containing TA were prepared by a single or double emulsification-solvent evaporation method. Morphology, size, effect of drug input and method of microsphere preparation on drug loading, and in vitro TA release of the microspheres were investigated. Tablets consisting of blank PLA-microspheres and TA (weight ratios of 1:1, 2:1, and 4:1, respectively) were developed and their release profile οf TA in vitro was evaluated. The in vitro transscleral diffusion profile was evaluated by placing a PLA-TA (1:1) tablet in a donor chamber and measuring the TA concentration in a receptor chamber. Donor and receptor chambers were separated by rabbit sclera. Two cadaver rabbit eyes received a 1:1 PLA-TA tablet episclerally, which was covered by a scleral patch. TA aqueous humor and vitreous concentrations were measured 5, 10, and 20 days post implantation. Results: Microsphere average diameter was 2 μm. The double emulsification method and increasing drug input led to an increase in microsphere drug loading and encapsulation. Sustained release of TA over several days from the microspheres in vitro was observed, with the rate of release being affected by their TA content. TA exhibited sustained release profile from the PLA-TA tablets, with the rate of release being affected by the PLA:TA ratio. TA could cross the sclera tissue in vitro, with approximately 21% of the initial drug in the donor compartment having diffused through the sclera in 45 days. Following scleral administration of the PLA-TA tablets, TA accumulated in the vitreous and aqueous humor of cadaver eyes. Conclusions: The PLA-TA microspheres and tablets developed in this study provide a sustained and controlled release of TA, provide the advantages of established biodegradability and biocompatibility of the PLA polymer, demonstrate flexibility concerning their TA release rate and total TA dosage and are easy to surgically manipulate. These systems appear promising for the controlled transscleral delivery of TA and justify further investigation.

Made available in DSpace on 2015-07-22T20:50:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Objetivo: Comparar efetividade e tolerância, a médio prazo, entre lavagem articular associada à infiltração intra-articular (IIA) com hexacetonide de triancinolona (HT) versus a IIA isolada de HT em pacientes com osteoartrite (OA) primária de joelhos. Material e Métodos: Foi realizado um estudo controlado, randomizado, duplo-cego com 60 pacientes que apresentavam OA primária de joelhos com dor em pelo menos um dos joelhos e índice de Kellgren Lawrence (KL) II e III divididos em dois grupos de intervenção: Grupo LA/HT: submetidos à LA com SF 0,9% (1000ml), finalizada pela introdução de HT 60 mg; Grupo HT: submetidos apenas à simulação de LA finalizada pela IIA de HT 60 mg. Os pacientes foram avaliados durante 12 semanas em cinco tempos de avaliação (T0, T1, T4, T8 e T12 semanas) por um avaliador “cego” através dos seguintes instrumentos de avaliação: escala visual analógica (EVA) para dor em repouso e ao movimento, goniometria, índice de WOMAC, questionário funcional de Lequesne, tempo de caminhada de 50 pés, porcentagem subjetiva de melhora, escala visual analógica de melhora (EVAM), segundo o paciente e segundo o avaliador, necessidade de anti-inflamatórios e analgésicos, número e tipo de efeitos colaterais locais. Foi realizada subanálise estatística na amostra segundo a classificação radiológica (KL II e KL III). Foi considerada uma significância estatística de 5%. Resultados: A média de idade foi de 63,7 (±8,59) anos, média de tempo de doença de 5,69 (±5,01) anos, proporção KL II/III de 33/27, sendo 88,3% de mulheres e 48,3.% de brancos. Apesar de ambos os grupos melhorarem estatisticamente na avaliação intragrupo, exceto para consumo de anti-inflamatório e EVAM, segundo o paciente, não houve diferença estatística na avaliação intergrupo para todas as variáveis estudadas no período de 12 semanas. De acordo com a subanálise realizada, observou-se, nos pacientes KL II, diferença estatística significante a favor do grupo HT para a variável flexão articular (p=0,03) no T4. Para os pacientes KL III, observou-se diferença estatística significante a favor do grupo LA/HT para as variáveis Lequesne (p=0,021) e WOMAC dor (p=0,01), assim como para a variável EVAM, segundo paciente (p=0,028) e avaliador (p=0,034) no T8. Conclusão: A combinação de LA à IIA com HT se mostrou mais efetiva a médio prazo que a IIA isolada com HT para o tratamento da OA primária de joelhos em pacientes KL III. Não houve diferença estatística quanto a tolerância destas duas intervenções. / Objective: Compare the medium-term effectiveness and tolerance intraarticular injection (IAI) with triamcinolone hexacetonide (TH) associated to joint lavage versus IAI with TH alone in patients with primary osteoarthritis (OA) of the knee. Methods: A randomized, double-blind, controlled study was carried out on 60 patients with primary OA of the knee, with pain in at least one of the knees and Grades II and III on the Kellgren-Lawrence index (KL II and III). Patients were randomized into two intervention groups: JL/TH Group – patients submitted to joint lavage with 0.9% saline solution (1000 ml) followed by a 60-mg injection of TH (3 ml); and TH Group – patients submitted to simulated joint lavage (sham) followed by a 60-mg injection of TH (3 ml). Patients were followed up for 12 weeks by a blinded observer using: visual analogue scale (VAS) for pain at rest and on movement; range of movement; Womac index; Lequesne’s questionnaire; timed 50-foot walk; subjective perception of improvement; Likert scale (0-5) for improvement assessment; the need for non-hormonal anti-inflammatory medication and analgesics; the local side effects. Results: Average age was 63.7 (± 8.59) years; mean duration of disease was 5.69 (± 5.01) years; the KL II/III proportion was 33/27; 88.3% were women and 48.3% were Caucasian. Although both groups demonstrated statistically significant improvement in the intra-group evaluation (except for Likert improvement scale according to the patient and the use of anti-inflammatory drugs), there were no statistically significant differences in the inter-group analysis for any of the variables studied over the 12-week period. In the KL II and III sub-analysis, there was a statistically significant difference regarding joint flexion among patients classified as KL II, favoring the TH group (p=0.03). For the KL III patients there were statistically significant differences favoring the JL/TH group regarding Lequesne score (p=0.021), WOMAC-pain score (p=0.01) and Likert improvement scale according to the patient (p=0.028) and the physician (p=0.034) at eight weeks. Conclusion: The combination of joint lavage and IAI with TH was more effective than IAI with TH alone in the treatment of primary OA of the knee in KL 3 patients. / TEDE / BV UNIFESP: Teses e dissertações

Introdução: Os corticosteroides intra-articulares (IA) são amplamente utilizados no tratamento da osteoartrite (OA) de joelho, porém é desconhecido qual dentre estes agentes é o mais eficaz. Objetivo: O objetivo do presente estudo foi comparar a eficácia das infiltrações IA de triancinolona hexacetonida (TH) e de acetato de metilprednisolona (AM) na OA de joelho. Pacientes e Métodos: Pacientes com OA sintomática de joelho, graus II ou III de Kellgren-Lawrence, foram randomizados para receber uma única infiltração IA com 40mg de TH ou AM. As avaliações clínicas foram realizadas nas semanas 4, 12 e 24. O desfecho primário do estudo foi a melhora da dor do joelho pelo paciente por escala visual analógica (EVA) da visita basal à semana 4. Os desfechos secundários incluíram a avaliação global da doença pelo paciente e pelo médico, o questionário de osteoartrite Western Ontario and McMaster Universities (WOMAC), o índice de Lequesne e o critério de resposta Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI). Na análise estatística, foram empregadas equações de estimativa generalizada, com estatística de Wald para contrastes do tipo 3 e ajustes de Tukey-Kramer para comparações múltiplas. Resultados: Cem pacientes foram incluídos na população com intenção de tratar, 50 em cada braço do estudo. Uma melhora significativa na dor pela EVA foi observada na semana 4 para ambos os grupos (P < 0,0001), não havendo diferença entre eles (P=0,352). Esta melhora foi sustentada até a semana 24. Uma melhora significativa em relação à avaliação basal foi observada na avaliação global da doença pelo paciente e pelo médico, no questionário WOMAC e no índice de Lequesne, não havendo diferença entre os grupos. A melhora nos desfechos secundários de avaliação foi sustentada durante o estudo, exceto para a avaliação global da doença pelo paciente. O critério de resposta OMERACT-OARSI foi alcançado por 74% e 72% dos pacientes dos grupos TH e AM, respectivamente. Conclusão: TH e AM são igualmente eficazes na OA de joelho, e a melhora na dor e na função física pode ser sustentada por até 24 semanas / Introduction: Intra-articular (IA) corticosteroid injections are broadly used in the treatment of knee osteoarthritis (OA), but it is unknown which of these agents is the most effective. Objective: The aim of the present study was to compare the efficacy of triamcinolone hexacetonide (TH) and methylprednisolone acetate (MA) IA injections in knee OA. Patients and Methods: Patients with symptomatic knee OA, Kellgren-Lawrence grades II or III, were randomized to receive a single IA injection with 40mg of TH or MA. Evaluations were performed at 4, 12 and 24 weeks. The primary outcome of the study was to evaluate the improvement in the patient\'s knee pain by visual analogue scale (VAS) from baseline to week 4. Secondary outcomes included the global assessment of the disease by the patient and the physician, the Western Ontario and McMaster Universities osteoarthritis questionnaire (WOMAC), the Lequesne index and the Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of response. Generalized estimating equations with Wald statistics for type 3 contrasts and Tukey-Kramer multiple comparison adjustment were employed in statistical analysis. Results: The intention-to-treat population included one hundred patients; 50 in each study arm. A significant improvement in pain by VAS was observed at week 4 for both groups (P<0.0001), with no difference between them (P=0.352). This improvement was sustained up to week 24. A significant improvement from the baseline was observed for the patients\' and the physicians\' global assessments, WOMAC questionnaire, and Lequesne index, with no differences between the groups. Improvements in the secondary outcomes were sustained during the study, except for the patients\' global assessment of disease. OMERACT-OARSI criteria of response was achieved by 74% and 72% of patients in the TH and the MA groups, respectively. Conclusion: TH and MA are equally effective in knee OA and improvement in pain and physical function can be sustained for up to 24 week

Submitted by Mariana De Almeida Lourenço (maalmeida1@terra.com.br) on 2019-01-29T12:04:26Z No. of bitstreams: 1 TESE_Mariana_Almeida_FINAL.pdf: 3376155 bytes, checksum: 3ab5bd7934378b17e0fc5c3b3bdc4cb9 (MD5) / Rejected by Adriana Aparecida Puerta null (dripuerta@rc.unesp.br), reason: Prezada Mariana, O documento enviado para a coleção Campus Unesp Rio Claro foi recusado pelo(s) seguinte(s) motivo(s): - Ficha catalográfica: Note que abaixo do quadrado conta o Instituto errado. Está Biblioteca da Faculdade de Ciências Farmacêuticas, Araraquara. Necessário refazer no site e corrigir o campus. Agradecemos a compreensão e aguardamos o envio do novo arquivo. Atenciosamente, Biblioteca Campus Rio Claro Repositório Institucional UNESP https://repositorio.unesp.br on 2019-01-29T18:30:27Z (GMT) / Submitted by Mariana De Almeida Lourenço (maalmeida1@terra.com.br) on 2019-01-30T11:47:23Z No. of bitstreams: 1 TESE_Mariana_Almeida_Lourenco.pdf: 3376137 bytes, checksum: b295dd19c611a8e8c01700329ec22a7f (MD5) / Approved for entry into archive by Adriana Aparecida Puerta null (dripuerta@rc.unesp.br) on 2019-01-30T12:50:36Z (GMT) No. of bitstreams: 1 lourenço_ma_dr_rcla.pdf: 3179228 bytes, checksum: 9affa4b46e866d3534005db21feb3961 (MD5) / Made available in DSpace on 2019-01-30T12:50:36Z (GMT). No. of bitstreams: 1 lourenço_ma_dr_rcla.pdf: 3179228 bytes, checksum: 9affa4b46e866d3534005db21feb3961 (MD5) Previous issue date: 2018-12-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A articulação do joelho é frequentemente acometida por sinovite em pacientes com artrite reumatoide (AR). Esse processo inflamatório provoca um reflexo de inibição muscular artrogênica e consequente diminuição de força nos extensores de joelho, além de dor, edema e prejuízos funcionais. A infiltração intra-articular (IIA) com hexacetonide de triancinolona (HT) tem se mostrado eficaz no controle do acometimento articular em pacientes com AR. O objetivo geral do presente estudo foi analisar os efeitos da infiltração intra-articular em mulheres com AR de HT ou solução salina em parâmetros como força muscular de extensores de joelho, dor, edema, funcionalidade e amplitude de movimento. Vinte e uma mulheres com AR foram randomizadas aleatoriamente para receber 3ml de HT (GI) ou de solução salina (GC) no joelho, com avaliações feitas em 4 momentos: imediatamente antes a IIA, após 2, 6 e 12 semanas. Foram aplicados questionários para funcionalidade (WOMAC, Lequesne, HAQ), escala visual analógica para dor ao repouso e ao movimento, circumetria, teste de força de extensores de joelho, biofotogrametria para amplitude de movimento e os testes físicos Timed Up And Go (TUG) e Teste de Sentar e Levantar. Na análise estatística foi realizado teste de normalidade de Shapiro-Wilk, Teste de Levene para homogeneidade dos grupos, análise de variância (ANOVA) mista com medidas repetidas para comparação intra e inter grupos, correlação de Pearson e regressão linear com significância de P< 0,05. Foi observado diminuição da dor ao repouso e ao movimento, redução do edema e melhora da funcionalidade no grupo que recebeu o medicamento, porém não houve diferença significativa entre os grupos com relação à força muscular e amplitude de movimento. O presente estudo mostrou que, embora não haja diferença na força muscular e amplitude de movimento, a eficácia da IIA com HT em joelho parece ser superior na melhora da dor, edema e funcionalidade quando comparada a solução salina em mulheres com AR. / The knee joint is often affected by synovitis in rheumatoid arthritis (RA) patients. This inflammatory process causes a reflex of arthrogenic muscle inhibition and consequent decrease of strength in the knee extensors, pain, swelling and functional impairment. Intra-articular infiltration (IIA) with triamcinolone hexacetonide (HT) has been shown to be effective in controlling joint involvement in RA patients. The general objective of the present study was to analyze the effects of intraarticular infiltration in RA women´s knee with HT or saline solution in parameters such as knee extensors muscle strength, pain, swelling, functionality and range of motion. Twenty-one RA women were randomly assigned to receive 3ml of TH (GI) or saline solution (GC) in the knee, with assessments made in 4 moments: immediately before the IIA, after 2, 6 and 12 weeks. Functional questionnaires (WOMAC, Lequesne, HAQ), visual analogue scale for pain, circummetry, knee extensor strength test, biophotogrammetry for range of motion and the physical test Timed Up And Go (TUG). Statistical analysis was performed using the Shapiro-Wilk normality test, Levene test for homogeneity of groups, mixed analysis of variance (ANOVA) with repeated measures for intra and inter group comparison, Pearson's correlation and linear regression with significance of P <0,05. Decreased pain at rest and movement, reduction of swelling and improvement of functionality in the group receiving the medication were observed, but there was no significant difference between the groups in relation to muscle strength and range of motion. The present study showed that, although there is no difference in muscle strength and range of motion, the effectiveness of IIA with HT in knee appears to be superior in improving joint inflammation and functionality when compared to saline solution in RA women.

Introdução: Os corticosteroides intra-articulares (IA) são amplamente utilizados no tratamento da osteoartrite (OA) de joelho, porém é desconhecido qual dentre estes agentes é o mais eficaz. Objetivo: O objetivo do presente estudo foi comparar a eficácia das infiltrações IA de triancinolona hexacetonida (TH) e de acetato de metilprednisolona (AM) na OA de joelho. Pacientes e Métodos: Pacientes com OA sintomática de joelho, graus II ou III de Kellgren-Lawrence, foram randomizados para receber uma única infiltração IA com 40mg de TH ou AM. As avaliações clínicas foram realizadas nas semanas 4, 12 e 24. O desfecho primário do estudo foi a melhora da dor do joelho pelo paciente por escala visual analógica (EVA) da visita basal à semana 4. Os desfechos secundários incluíram a avaliação global da doença pelo paciente e pelo médico, o questionário de osteoartrite Western Ontario and McMaster Universities (WOMAC), o índice de Lequesne e o critério de resposta Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI). Na análise estatística, foram empregadas equações de estimativa generalizada, com estatística de Wald para contrastes do tipo 3 e ajustes de Tukey-Kramer para comparações múltiplas. Resultados: Cem pacientes foram incluídos na população com intenção de tratar, 50 em cada braço do estudo. Uma melhora significativa na dor pela EVA foi observada na semana 4 para ambos os grupos (P < 0,0001), não havendo diferença entre eles (P=0,352). Esta melhora foi sustentada até a semana 24. Uma melhora significativa em relação à avaliação basal foi observada na avaliação global da doença pelo paciente e pelo médico, no questionário WOMAC e no índice de Lequesne, não havendo diferença entre os grupos. A melhora nos desfechos secundários de avaliação foi sustentada durante o estudo, exceto para a avaliação global da doença pelo paciente. O critério de resposta OMERACT-OARSI foi alcançado por 74% e 72% dos pacientes dos grupos TH e AM, respectivamente. Conclusão: TH e AM são igualmente eficazes na OA de joelho, e a melhora na dor e na função física pode ser sustentada por até 24 semanas / Introduction: Intra-articular (IA) corticosteroid injections are broadly used in the treatment of knee osteoarthritis (OA), but it is unknown which of these agents is the most effective. Objective: The aim of the present study was to compare the efficacy of triamcinolone hexacetonide (TH) and methylprednisolone acetate (MA) IA injections in knee OA. Patients and Methods: Patients with symptomatic knee OA, Kellgren-Lawrence grades II or III, were randomized to receive a single IA injection with 40mg of TH or MA. Evaluations were performed at 4, 12 and 24 weeks. The primary outcome of the study was to evaluate the improvement in the patient\'s knee pain by visual analogue scale (VAS) from baseline to week 4. Secondary outcomes included the global assessment of the disease by the patient and the physician, the Western Ontario and McMaster Universities osteoarthritis questionnaire (WOMAC), the Lequesne index and the Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of response. Generalized estimating equations with Wald statistics for type 3 contrasts and Tukey-Kramer multiple comparison adjustment were employed in statistical analysis. Results: The intention-to-treat population included one hundred patients; 50 in each study arm. A significant improvement in pain by VAS was observed at week 4 for both groups (P<0.0001), with no difference between them (P=0.352). This improvement was sustained up to week 24. A significant improvement from the baseline was observed for the patients\' and the physicians\' global assessments, WOMAC questionnaire, and Lequesne index, with no differences between the groups. Improvements in the secondary outcomes were sustained during the study, except for the patients\' global assessment of disease. OMERACT-OARSI criteria of response was achieved by 74% and 72% of patients in the TH and the MA groups, respectively. Conclusion: TH and MA are equally effective in knee OA and improvement in pain and physical function can be sustained for up to 24 week

<p>Intra-articular glucocorticoid injection therapy is frequently used to relieve symptoms of arthritis, but there is considerable variation in injection routines among physicians. One issue of debate concerns the importance of synovial fluid aspiration during the injection procedure. In the present randomised controlled study of patients with rheumatoid arthritis (RA), a significantly reduced risk for arthritis relapse was observed when arthrocentesis was included in the intra-articular injection procedure of the knee. </p><p>Furthermore, there is no consensus about the post-injection regimes. Previous studies have shown beneficial effects of post-injection rest of the knee, but also injection routines for other joints often include such recommendations. The present randomised controlled trial showed that 48-hour rest in elastic orthosis after intra-articular injection in the wrist did not improve the outcome. Thus, the effect of post-injection rest varies between different joints. </p><p>The improved treatment result of post-injection rest of the knee is supposed to be caused by retarded steroid resorption from the joint. In order examine the metabolic effects in cartilage, bone and the hypothalamic-piuitary-adrenal (HPA)-axis, resting and mobile RA patients were studied after intra-articular knee injections. Serum levels of the injected glucocorticoid, triamcinolone hexacetonide (THA), were analysed, as well as cartilage oligomeric matrix protein (COMP) as a marker of cartilage turnover, osteocalcin for bone formation and deoxypyridinoline for bone resorption. The HPA-axis was assessed using serum levels of cortisol and adrenocorticotropine hormone. The result showed a short term and reversible suppression of the HPA-axis and bone formation, whereas bone resorption was unaffected. No differences between mobile and resting patients were observed. In both groups reduction of COMP levels were seen, but these were significantly more pronounced in resting patients, suggesting a cartilage-protective effect. The THA levels increased similarly in both groups, indicating that rest did not affect glucocorticoid resorption. </p><p>Consequently, another explanation for the beneficial effects of postinjection rest of knee synovitis should be considered. In the present material the incidence of infectious complications of intra-articular treatment was less than 1/12,000 injections. </p><p>The findings in this thesis can be applied in the clinical practice and should be considered when new guidelines for intra-articular glucocorticoid therapy are created.</p>