Eficacia y seguridad del implante intravítreo de dexametasona de liberación prolongada sostenida para el tratamiento de pacientes adultos con edema macular secundario a oclusión venosa retiniana con disminución de la agudeza visual y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab / Efficacy and safety of intravitreal sustained-release dexamethasone implant for the treatment of adult patients with macular edema secondary to retinal vein occlusion with decreased visual acuity and/or increased or maintained macular thickness despite the use of three injections of bevacizumab

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N' 111-IETSI-ESSALUD-2021 se ha elaborado el presente dictamen. el cual expone la evaluación de la eficacia y seguridad del implante intravítreo de dexametasona de liberación prolongada sostenida para el tratamiento de pacientes adultos con edema macular secundario a oclusión venosa retiniana con disminución de la agudeza visual y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. Así. la médica Fiorella Norabuena Mautino. especialista en oftalmología del Servicio de Retina, a través del Comité Farmacoterapéutico del Hospital Nacional Edgardo Rebagliati Martins y siguiendo la Directiva N' 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de autorización de uso del producto farmacéutico dexametasona (implante intravítreo) no incluido en el Petitorio Farmacológico de EsSalud. ASPECTOS GENERALES: La oclusión venosa retiniana (OVR), una obstrucción parcial o completa del sistema venoso retinal, es considerada la segunda causa más común de trastorno vascular de la retina (Cugati et al., 2006; PAAO, 2019), y es una causa importante de pérdida de la visión en adultos a nivel mundial (Rogers et al., 2010: Song et al., 2019). En el 2015, se estimó que la prevalencia global de la OVR en personas de entre 30 y 89 años fue de 0.77 % (Song et al., 2019). Los dos tipos más comunes de OVR, son la oclusión de la rama venosa de la retina (ORVR), que ocurre en la vena retinal distal y ocasiona hemorragia en un vaso pequeño de la retina; y la oclusión de la vena central de la retina (OVCR), que ocurre en la vena retinal proximal y ocasiona hemorragia en toda la retina (Han & Ahmad, 2021). En un estudio realizado con datos de Europa, Asia, Australia y Estados Unidos se reporta que la prevalencia ajustada por edad y sexo de la ORVR es de 3.77 por 1000 personas, y de la OVCR es de 0.65 por 1000 personas. METODOLOGÍA: Se realizó una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad del uso de IIDLPS en el tratamiento de pacientes adultos con EM secundario a ORVR u OVCR con disminución de la AV y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library, LILACS y The Web of Science. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas. evaluaciones de tecnologías sanitarias y guías de práctica clínica. tales como The National Institute for Health and Care Excellence (NICE). RESULTADOS: De la búsqueda bibliográfica, se incluyó una GPC elaborada por The Royal College of Ophthalmologists (RCO) (The Royal College of Ophthalmologists. 2022). y tres estudios retrospectivos que evaluaron el cambio de bevacizumab a IIDLPS (Chiquet et al.. 2016: Lee et al.. 2017: Sharareh et al., 2013). Además se incluyeron dos GPC que fueron sugeridas por los especialistas de EsSalud, elaboradas por The European Society of Retina Specialists (EURETINA) (Schmidt-Erfurth et al., 2019) y la Sociedad Española de Retina y Vítreo (SERV) (SERV, 2015). No se identificaron RS con MA ni ETS que respondan a la pregunta PICO del presente dictamen. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de implante intravitreo de dexametasona de liberación prolongada sostenida (IIDLPS) para el tratamiento de pacientes adultos con edema macular (EM) secundario a oclusión de la vena central de la retina (OVCR) u oclusión de la rama venosa de la retina (ORVR) con disminución de la AV y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud. según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de 1 año a partir de la fecha de publicación. La continuación de dicha aprobación está sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

Influencia del tratamiento intravítreo en la presión intraocular en pacientes con glaucoma y degeneración macular / Influence of Intravitreal Treatment on Intraocular Pressure in Patients with Glaucoma and Macular Degeneration

En los últimos años, la aparición de los fármacos antiangiogénicos ha revolucionado el tratamiento de numerosas enfermedades de la retina, su asociación con la hipertensión ocular tras las inyecciones ha sido objeto de estudio en numerosas ocasiones. Se presenta un caso clínico de una paciente con glaucoma y degeneración macular asociada a la edad con la que se estudió la relación entre la administración de antiangiogénicos intravítreos y la elevación de la presión intraocular, a corto y largo plazo. La administración de fármacos antiangiogénicos es en la actualidad el procedimiento oftalmológico más empleado en las consultas de todo el mundo. La administración de intravítreas se ha asociado a la producción de un pico hipertensivo transitorio en el momento agudo y a la elevación de la presión intraocular a largo plazo. Un estrecho intervalo entre inyecciones ( 7 al año), pacientes con cámara estrecha, fáquicos y con diagnóstico previo de glaucoma son los principales factores de riesgo para el desarrollo de una elevación sostenida de presión intraocular tras el tratamiento intravítreo con antiangiogénicos. Identificar a los pacientes con alto riesgo de desarrollar hipertensión ocular tras el uso de inyecciones intravítreas y adoptar medidas que reduzcan dicho riesgo, como la administración de hipotensores tópicos antes de la inyección, es fundamental para mejorar su salud visual. Se presenta el caso de una paciente de 78 años de edad con diagnóstico de glaucoma primario de ángulo abierto de cinco años de evolución en ambos ojos(AU)

In recent years, the emergence of antiangiogenic drugs has revolutionized the treatment of numerous retinal diseases, their association with ocular hypertension after injections has been the subject of study on numerous occasions. We present a clinical case of a patient with glaucoma and age-related macular degeneration in which the relationship between the administration of intravitreal antiangiogenic drugs and the elevation of intraocular pressure, in the short and long term, was studied. The prescribing of antiangiogenic drugs is currently the most widely used ophthalmologic procedure in practices worldwide. Intravitreal administration has been associated with the production of a transitory hypertensive peak in the acute setting and long-term elevation of intraocular pressure. A narrow interval between injections ( 7 per year), patients with narrow chamber, phakic and with a previous diagnosis of glaucoma are the main risk factors for the development of sustained intraocular pressure elevation after intravitreal treatment with antiangiogenics. Identifying patients at high risk of developing ocular hypertension after intravitreal injections and adopting measures to reduce this risk, such as the administration of topical hypotensives before the injection, is essential to improve their eyesight health. The case of a 78-year-old female patient with a diagnosis of primary open-angle glaucoma of five years of evolution in both eyes is presented(AU)

Protocolo assistencial de injeções intravítreas do HCPA: edema macular diabético / HCPA's patient care protocol for intravitreal injections: diabetic macular edema

RESUMO: O edema macular diabético é uma das principais causas de baixa visual no mundo e a indicação mais frequente de injeções intravítreas no Hospital de Clínicas de Porto Alegre. O tratamento com injeção intra-vítrea de medicamentos anti-vascular endothelial growth factor, incluindo o bevacizumaberevolucionou o desfecho visual destes pacientes às custas de múltiplas aplicações mensais. Assim como em outros centros, discrepâncias entre condutas da equipe assistencial e dificuldades logísticas acabam comprometendo a efetividade do tratamento. Portanto, desenvolvemos um protocolo de tratamento para a doença embasado na literatura, estabelecendo critérios de inclusão, exclusão, regime de tratamento e seguimento do paciente. Com isto, esperamos otimizar a efetividade e assistência do paciente com edema macular diabético.

ABSTRACT: Diabetic macular edema is one of the leading causes of visual impairment worldwide and the most common indication for intravitreal injections at the Hospital de Clínicas de Porto Alegre. Treatment with intravitreal injection of anti-vascular endothelial growth factor drugs, including bevacizumab, has revolutionized patient outcome at the expense of multiple monthly injections. As in other hospitals, discrepancies in health team conduct and logistical difficulties compromise treatment effectiveness. Therefore, we developed a literature-based treatment protocol for diabetic macular edema, in which we established criteria for patient inclusion and exclusion, treatment regimen, and patient follow-up. We expect the treatment protocol to optimize patient care effectiveness in diabetic macular edema.

Manejo da coroidite interna punctata complicada por membrana neovascular sub-retiniana / Management of punctate inner choroidopathy complicated by subretinal neovascular membrane

RESUMO Este trabalho visou evidenciar a importância da detecção precoce da coroidite interna punctata e destacar sua fisiopatologia inflamatória e possíveis diagnósticos diferenciais dentro das white dot syndromes. O destaque foi dado principalmente à coroidite multifocal e à panuveíte, ao se demonstrar sua epidemiologia peculiar em mulheres jovens, caracterizar sua apresentação clínica típica na fundoscopia e explorar as vantagens e as desvantagens de realizar os exames complementares que fazem parte da análise multimodal útil para o diagnóstico (especialmente a angiografia fluoresceínica, a tomografia de coerência óptica e a indocianina verde). Descreve-se o caso de uma mulher de 28 anos diagnosticada com coroidite interna punctata com membrana neovascular coroidal em olho direito. O tratamento foi realizado com injeção intravítrea de aflibercepte e corticoterapia sistêmica 1mg/kg ao dia. Este relato é importante por permitir debater o manejo da coroidite interna punctata durante a gestação e a decisão de realizar o tratamento mediante uma diversidade de opções terapêuticas.

ABSTRACT This work aimed to demonstrate the importance of early detection of punctate inner choroidopathy, highlighting the pathophysiology of inflammation and the differential diagnoses among white dot syndromes. Special attention was given to multifocal choroiditis and panuveitis, by demonstrating the peculiar epidemiology in young women, characterizing the typical clinical presentation in ophthalmoscopy, and exploring the advantages and disadvantages of performing the complementary examinations, which are part of the multimodal analysis useful for diagnosis (particularly fluorescein angiography, optical coherence tomography, and indocyanine green). We report the case of a 28-year-old female, diagnosed as punctate inner choroidopathy with choroidal [N.T. no título aparece subretinal = subrretiniana] neovascular membrane in the right eye. She was treated with intravitreal injection of aflibercept and systemic corticosteroid 1 mg/kg/day. This case report is important for addressing the management of punctate inner choroidopathy during pregnancy, and the decision to carry out treatment considering diverse therapeutic options.

Cystoid macular edema secondary to intraocular lens sub-luxation and iris perforation by iol haptic / Edema macular cistóide secundário a subluxação de lente intraocular e perfuração da íris por haptico da lente

Abstract We present a case of 50-years-old, man with vision loss, dysmorphopsia and micropsy in the right eye with for 6 months. Ocular history included uncomplicated cataract surgery 10 years before. Best corrected visual acuity was 20/100 in the right eye and 20/20 in the left eye. Anterior segment OD demonstrated intra-ocular lens (IOL) haptic in the anterior chamber with iris perforation. Fundus examination revealed cystoid macular edema in right eye. Surgical approach with reposition of the IOL and triamcinolone acetonide intravitreal injection were performed with visual and tomographical improvement.

Resumo Apresentamos o caso de um homem de 50 anos, com queixa de perda de visão, dismorfopsia e micropsia em olho direito (OD) há 6 meses. A história ocular incluiu cirurgia de catarata sem complicações 10 anos antes. A melhor acuidade visual corrigida foi 20/100 em OD e 20/20 em olho esquerdo. O segment anterior do OD demonstrou háptica da lente intraocular (LIO) na câmara anterior com perfuração da íris. A fundoscopia revelou edema macular cistoide em OD. A abordagem cirúrgica com reposição da LIO e injeção intravítrea de triancinolona acetonida foi realizada com melhora visual e tomográfica.

Release of silicone oil and the off-label use of syringes in ophthalmology.

BACKGROUND/AIMS: To assess silicone oil (SO) release by different brands of syringes used for intravitreal injection under different handling conditions. METHODS: Eight syringes were analysed: from the USA, Terumo 0.5 mL, Becton-Dickinson (BD) Tuberculin 1 mL, BD Luer-lok 1 mL, BD Ultra-Fine 0.3 mL and Exel Insulin 0.3 mL; from Germany, Braun Omnifix-F 1 mL and Braun Injekt-F 1 mL and from Spain, BD Plastipak 1 mL. The impact of air, priming the plunger, agitation by flicking and fluid temperature on SO release were assessed by light microscopy. Fourier transform infrared spectroscopy (FTIR) was performed to identify the molecular compound in each syringe. RESULTS: Five hundred and sixty syringes were analysed. Terumo 0.5 mL and BD Ultra-Fine 0.3 mL released more SO than all others. BD Luer-lok 1 mL, BD Plastipak and Braun Omnifix-F 1 mL released little SO; BD Tuberculin 1 mL, Exel 0.3 mL and Braun Injekt-F 1 mL released the least SO. Priming the syringe and different temperatures did not significantly affect SO release. Agitation by flicking caused a significantly higher proportion of samples to have SO droplets and an increased number of oil droplets. Air had an additive effect on the release of oil in the agitation groups. FTIR identified polysiloxane in all syringes but Injekt-F. CONCLUSION: Syringes commonly used for intravitreal injections frequently release SO droplets, especially when agitated by flicking. To avoid unnecessary ocular risks, syringes should not be agitated before intravitreal injection. It is desirable that syringes be manufactured specifically for ophthalmic use.

Intravitreal injection of peptides PnPa11 and PnPa13, derivatives of Phoneutria nigriventer spider venom, prevents retinal damage

PnPa11 and PnPa13 are synthetic peptides derived from Phoneutria nigriventer spider venom, which display antinociceptive and neuroprotective properties. In this work, we evaluated the safety of intravitreal use and the neuroprotective effect of these peptides. Methods: The cytotoxicity and the antiangiogenic activity of these peptides were evaluated by the sulforhodamine-B method and chicken chorioallantoic membrane (CAM) assay, respectively. The in vivo safety was analyzed in Wistar rats that were intravitreally injected with different doses (0.50; 1.25; 2.50; 3.75 and 5.00 µg/mL) of these peptides (right eye, n = 6). The retinal function was assessed by electroretinography exams (ERG), intraocular pressure (IOP), and histological analyzes. In order to investigate the neuroprotective effect, Wistar rats received intravitreal injections (right eye, n = 6) of peptides at 1.25 µg/mL and then were exposed to blue LED light. In addition, the visual function and the retinal microstructure were verified. Results: Cytotoxicity analyses demonstrated that the peptides did not present any toxicity over ARPE-19 (adult retinal pigmented epithelial) cell line and the antiangiogenic study highlighted that the peptides promoted the reduction of blood vessels. The intravitreal injection did not cause major changes, neither induced any irreversible damage. In the retinal degeneration assay, the ERG records demonstrated that the prior treatment with PnPa11 and PnPa13 protected the retina from damage. Morphological analyses confirmed the ERG findings. Immunoblotting analyses revealed that PnPa11 increased Erk1/2, NR2A, and NR2B retinal expression after the light stress model, but did not cause Akt1 activation, while PnPa13 prevented Erk1/2 and Akt1 dephosphorylation. Conclusions: The intraocular administration of these peptides was well tolerated and presented protective activity against retinal degeneration, suggesting the potential use of these peptides as neuroprotectors in the ophthalmological field.(AU)

Optical biometry-based axial length alterations after intravitreal dexamethasone implant / Alterações do comprimento axial com base na biometria óptica após o implante de dexametasona intravítrea

ABSTRACT Purpose: To investigate changes in axial length after intravitreal dexamethasone implantation in patients with macular edema. Methods: We performed a prospective comparative study of 46 patients with unilateral macular edema, due to diabetic retinopathy, retinal vein occlusion, and non-infectious uveitis, who underwent dexamethasone implantation. The fellow eyes of the patients were considered the control group. The central macular thickness was measured by spectral-domain optical coherence tomography, and axial length was measured by IOLMaster 700 optical coherence biometry. We compared axial length and central macular thickness values within the groups. Results: In the study group, the baseline central macular thickness was 460.19 ± 128.64 mm, significantly decreasing to 324.00 ± 79.84 mm after dexamethasone implantation (p=0.000). No significant change in central macular thickness measurements was seen in the control group (p=0.244). In the study group, the baseline axial length was 23.16 ± 0.68 mm, significantly increasing to 23.22 ± 0.65 mm after dexamethasone implantation (p=0.039). However, the control group exhibited no significant change in axial length (p=0.123). Conclusions: In addition to significantly reducing central macular thickness measurements, intravitreal dexamethasone implantation also significantly changes optical biometry-based axial length measurements.

RESUMO Objetivo: Investigar alterações no comprimento axial após implante de dexametasona intravítrea em pacientes com edema macular. Métodos: Foi realizado um estudo prospectivo e comparativo de 46 pacientes com edema macular unilateral, devido à retinopatia diabética, oclusão da veia retiniana e uveíte não infecciosa, que foram submetidos ao implante de dexametasona. Os olhos contralateral de cada paciente foram considerados o grupo controle. A espessura macular central foi medida por tomografia de coerência óptica de domínio espectral, e o comprimento axial foi medido por meio de biometria de coerência óptica de domínio espectral e o comprimento axial foi medido pela biometria de coerência óptica com IOLMaster 700. Comparamos o comprimento axial e os valores da espessura macular central dentro dos grupos. Resultados: No grupo de estudo, a espessura macular basal foi de 460,19 ± 128,64 mm, diminuindo significativamente para 324,00 ± 79,84 mm após o implante de dexametasona (p=0,000). Nenhuma mudança significativa nas medidas da espessura macular central foi observada no grupo controle (p=0,244). No grupo de estudo, o comprimento axial basal foi de 23,16 ± 0,68 mm, aumentando significativamente para 23,22 ± 0,65 mm após o implante de dexametasona (p=0,039). No entanto, o grupo controle não apresentou alteração significativa no comprimento axial (p=0,123). Conclusões: Além de reduzir significativamente as medidas da espessura macular central, o implante de dexametasona intravítrea também altera significativamente as medidas de comprimento axial baseadas na biometria óptica.

Intravitreal and posterior subtenon triamcinolone acetonide for severe acute posterior multifocal placoid pigment epitheliopathy / Triancinolona intravítrea e sub-tenoniana para epiteliopatia pigmentar placóide multifocal posterior aguda grave

ABSTRACT A 21-year-old man presented with visual acuity of 20/200 in both eyes. The fundus picture, fluorescein angiography, and optical coherence tomography revealed severe bilateral acute posterior multifocal placoid pigment epitheliopathy and serous macular detachments. We treated the patient with triamcinolone acetonide, an intravitreal injection (4 mg/0.1 mL) in one eye and a posterior subtenon injection (40 mg/1 mL) in the other eye. Within 2 weeks the visual acuity was 20/80 in both eyes. At the 8-week follow-up visit his vision was 20/63 bilaterally. One year later the vision remained 20/63 in both eyes. In this patient, the triamcinolone acetonide injections, whether administered intravitreally or via the posterior subtenon route, achieved similar anatomic and functional recovery results.

RESUMO Um homem de 21 anos apresentou acuidade visual de 20/200 em ambos os olhos. O quadro de fundo de olho, angiofluoresceinografia e a tomografia de coerência óptica revelaram epiteliopatia pigmentar placóide multifocal posterior aguda e descolamento macular seroso. Tratamos o paciente com triancinolona acetonida, uma injeção intravítrea (4 mg/0,1 ml) em um olho e uma injeção subtenoniana posterior (40 mg/1 ml) no outro olho. Após 2 semanas, a acuidade visual foi de 20/80 em ambos os olhos. Na visita de acompanhamento de 8 semanas, sua visão foi de 20/63 bilateralmente. Um ano depois, a visão permaneceu 20/63 em ambos os olhos. Neste paciente, as injeções de triancinolona, administradas por via intravítrea ou por via subtenoniana posterior, obtiveram resultados semelhantes na recuperação anatômica e funcional.

Intravitreal and posterior subtenon triamcinolone acetonide for severe acute posterior multifocal placoid pigment epitheliopathy.

A 21-year-old man presented with visual acuity of 20/200 in both eyes. The fundus picture, fluorescein angiography, and optical coherence tomography revealed severe bilateral acute posterior multifocal placoid pigment epitheliopathy and serous macular detachments. We treated the patient with triamcinolone acetonide, an intravitreal injection (4 mg/0.1 mL) in one eye and a posterior subtenon injection (40 mg/1 mL) in the other eye. Within 2 weeks the visual acuity was 20/80 in both eyes. At the 8-week follow-up visit his vision was 20/63 bilaterally. One year later the vision remained 20/63 in both eyes. In this patient, the triamcinolone acetonide injections, whether administered intravitreally or via the posterior subtenon route, achieved similar anatomic and functional recovery results.

Optical biometry-based axial length alterations after intravitreal dexamethasone implant.

PURPOSE: To investigate changes in axial length after intravitreal dexamethasone implantation in patients with macular edema. METHODS: We performed a prospective comparative study of 46 patients with unilateral macular edema, due to diabetic retinopathy, retinal vein occlusion, and non-infectious uveitis, who underwent dexamethasone implantation. The fellow eyes of the patients were considered the control group. The central macular thickness was measured by spectral-domain optical coherence tomography, and axial length was measured by IOLMaster 700 optical coherence biometry. We compared axial length and central macular thickness values within the groups. RESULTS: In the study group, the baseline central macular thickness was 460.19 ± 128.64 mm, significantly decreasing to 324.00 ± 79.84 mm after dexamethasone implantation (p=0.000). No significant change in central macular thickness measurements was seen in the control group (p=0.244). In the study group, the baseline axial length was 23.16 ± 0.68 mm, significantly increasing to 23.22 ± 0.65 mm after dexamethasone implantation (p=0.039). However, the control group exhibited no significant change in axial length (p=0.123). CONCLUSIONS: In addition to significantly reducing central macular thickness measurements, intravitreal dexamethasone implantation also significantly changes optical biometry-based axial length measurements.

Effects of topical azithromycin, moxifloxacin, and povidone iodine on conjunctival bacterial flora in patients undergoing intravitreal injection / Os efeitos da azitromicina tópica, moxifloxacina e iodopovidona na flora bacteriana conjuntival em injeções intravítreas

ABSTRACT Purpose: To compare effects of 5% topical povidone iodine with prophylactic topical azithromycin and moxifloxacin on bacterial flora in patients undergoing intravitreal injection. Methods: A total of 132 patients were randomly assigned to receive treatment with azithromycin or moxifloxacin, or no treatment (control group). In total, 528 specimens were obtained at the time of admission, 4 days before intravitreal injection, 4 days after intravitreal injection, and 8 days after intravitreal injection. Samples were immediately sent to the microbiology laboratory for incubation. Results: The microorganism observed most frequently was coagulasenegative Staphylococcus (23.8%). When the results of samples obtained on Day 4 before injection were assessed, growth of coagulase-negative Staphylococcus was significantly lower in the moxifloxacin group, compared with controls (p=0.049). Acinetobacter baumannii continued to grow after administration of azithromycin (p=0.033). When the results of four days after intravitreal injection were evaluated, growth of coagulase-ne gative Staphylococcus was higher in controls, compared with patients who received azithromycin or moxifloxacin (p=0.004). Eradication rate was significantly higher in the moxifloxacin group than in the control group (p=0.001). Samples obtained on Day 8 after intravitreal injection showed similar levels of bacterial growth in all groups (p=0.217). Conclusion: Moxifloxacin was more effective than 5% povidone iodine in controlling the growth of conjunctival bacterial flora. Use of moxifloxacin in combination with 5% povidone iodine resulted in a synergistic effect.

RESUMO Objetivo: Comparar os efeitos de iodopovidona tópico a 5% com azitromicina e moxifloxacina profiláticas sobre a flora bacteriana em pacientes submetidos à injeção intravítrea. Métodos: Um total de 132 pacientes foram aleatoriamente designados para receber tratamento com azitromicina ou moxifloxacina ou nenhum tratamento (grupo controle). No total, 528 amostras foram obtidas no momento na admissão, 4 dias antes da injeção intravítrea, 4 dias após a injeção intravítrea e 8 dias após a injeção intravítrea. As amostras foram imediatamente enviadas para o laboratório de microbiologia para incubação. Resultados: O microorganismo mais frequentemente observado foi o Staphylococcus coagulase-negativo (23,8%). Quando os resultados das amostras obtidas no dia 4 antes da injeção foram avaliados, o crescimento do Staphylococcus coagulase-negativo foi significativamente menor no grupo mo xifloxacina, em comparação com os controles (p=0,049). Acinetobacter baumannii continuou a crescer após a administração de azitromicina (p=0,033). Quando os resultados de 4 dias após a injeção intravítrea foram avaliados, o crescimento do Staphylococcus coagulase-negativo foi maior no controle, em comparação com pacientes que receberam azitromicina ou moxifloxacina (p=0,004). A taxa de erradicação também foi significativamente maior no grupo moxifloxacina do que no grupo controle (p=0,001). As amostras obtidas no dia 8 após injeção intravítrea mostraram níveis semelhantes de crescimento bacteriano em todos os grupos (p=0,217). Conclusão: A moxifloxacina foi mais eficaz do que 5% de iodopovidona no controle do crescimento da flora bacteriana conjuntival. O uso de moxifloxacina em combinação com 5% de iodopovidona resultou em um efeito sinérgico.

Effects of topical azithromycin, moxifloxacin, and povidone iodine on conjunctival bacterial flora in patients undergoing intravitreal injection.

PURPOSE: To compare effects of 5% topical povidone iodine with prophylactic topical azithromycin and moxifloxacin on bacterial flora in patients undergoing intravitreal injection. METHODS: A total of 132 patients were randomly assigned to receive treatment with azithromycin or moxifloxacin, or no treatment (control group). In total, 528 specimens were obtained at the time of admission, 4 days before intravitreal injection, 4 days after intravitreal injection, and 8 days after intravitreal injection. Samples were immediately sent to the microbiology laboratory for incubation. RESULTS: The microorganism observed most frequently was coagulasenegative Staphylococcus (23.8%). When the results of samples obtained on Day 4 before injection were assessed, growth of coagulase-negative Staphylococcus was significantly lower in the moxifloxacin group, compared with controls (p=0.049). Acinetobacter baumannii continued to grow after administration of azithromycin (p=0.033). When the results of four days after intravitreal injection were evaluated, growth of coagulase-ne gative Staphylococcus was higher in controls, compared with patients who received azithromycin or moxifloxacin (p=0.004). Eradication rate was significantly higher in the moxifloxacin group than in the control group (p=0.001). Samples obtained on Day 8 after intravitreal injection showed similar levels of bacterial growth in all groups (p=0.217). CONCLUSION: Moxifloxacin was more effective than 5% povidone iodine in controlling the growth of conjunctival bacterial flora. Use of moxifloxacin in combination with 5% povidone iodine resulted in a synergistic effect.

What do Cochrane systematic reviews say about interventions for age-related macular degeneration?

BACKGROUND: Age-related macular degeneration (AMD) is the third largest cause of blindness worldwide, accounting for 8.7% of all cases. A considerable number of preventive or therapeutic interventions have been used for AMD. OBJECTIVE: This study presents a critical view of the interventions that have been assessed through Cochrane systematic reviews. DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: Review of Cochrane systematic reviews about interventions for AMD. RESULTS: The 18 systematic reviews included assessed the effects of surgical techniques, laser/photo/radiotherapy, intravitreal injections, systemic drugs and phytotherapy/vitamins/supplements. CONCLUSION: The Cochrane systematic reviews found evidence that use of bevacizumab, ranibizumab, pegaptanib, laser photocoagulation, photodynamic therapy and multivitamin compounds may present some benefits for treating AMD. There was insufficient evidence for supporting the use of macular translocation, submacular surgery, steroid implantation, radiotherapy, intravitreal aflibercept, interferon alfa, statins or omega-3 fatty acids for treating AMD; or the use of multivitamin antioxidant vitamins or mineral supplementation for preventing AMD. Future randomized controlled trials are imperative to reduce the uncertainty in several clinical questions regarding AMD.

Análise da variação da pressão intraocular após injeção intravítrea de ranibizumabe / Analysis of intraocular pressure variation after intravitreal injection of ranibizumab

Resumo Objetivo: O tratamento com anti-angiogêncios é uma das modalidades mais utilizadas em patologias relacionadas ao edema macular. A injeção intravítrea de um inibidor do VEGF-A tem alta efetividade, porém está relacionada com efeitos adversos, como o aumento da pressão intraocular. O objetivo deste estudo foi avaliar a variação da pressão intraocular (PIO) em pacientes que se submeteram a injeções intravítreas de ranibizumabe, a variação de acordo com facia e com história de injeções prévias. Métodos: Este foi um estudo um estu-do observacional transversal. Foram incluídos todos os pacientes submetidos a injeções intravítreas com diagnóstico de degeneração macular relacionada à idade exsudativa, oclusão de veia central da retina com edema macular, ou edema macular diabético. A pressão intraocular foi aferida antes da injeção, imediatamente após e 30 minutos após a injeção com tonômetro portátil. Resultados Foram realizadas 143 injeções intravítreas, restando para a análise 96 injeções realizadas em 55 participantes. A comparação entre a PIO antes e 30 minutos após a injeção intravítrea mostrou-se estatisticamente significativa com PIO final maior que a inicial (p<0,0001) em pacientes com edema macular diabético. Pacientes fácicos e afácicos não mostraram diferenças significativas com relação a variação da PIO. Quando analisados apenas os participantes que haviam recebido injeções prévias, não foi encontrado uma variação significativa. Conclusão: Concluímos neste estudo que existe uma diferença significativa entre a pressão intraocular antes e 30 minutos após a injeção intravítrea de ranibizumabe em pacientes com edema macular diabético, mos-trando que esse período de tempo não foi suficiente para a regressão da PIO ao valor pré-injeção. Não encontramos diferenças significativas entre outros grupos, comparação entre fácicos e afácicos, nem em pacientes que haviam recebido injeções prévias.

Abstract Objective: Treatment with anti-angiogenic drugs is one of the most widely used modalities of treatment of macular edema related conditions. Intravitreal injection of a VEGF-A inhibitor is highly effective, but is related to adverse effects such as increased intraocular pressure. The objective of this study was to evaluate intraocular pressure (IOP) variation in patients who underwent intravitreal injections of ranibizumab, variation according to phakic/aphakic and history of previous injections. Methods: This was a cross-sectional observational study. All patients submitted to intravitreal injections with diagnosis of exudative age-related macular degeneration, retinal central vein occlusion with macular ede-ma, or diabetic macular edema were included. The IOP was measured before the injection, immediately after and 30 minutes after the injection with a portable tonometer. Results: 143 intravitreal injections were performed, with 96 injec-tions performed in 55 participants. The comparison between IOP before and 30 minutes after intravitreal injection showed to be statistically significant with higher than initial IOP (p <0.0001) in patients with diabetic macular edema. Phakic and aphakic patients did not show significant differences regarding IOP variation. When only those participants who had received previous injections were analyzed, no significant variation was found. Conclusion: We conclude in this study that there is a significant difference between intraocular pressure before and 30 minutes after intravitreal injection of ranibizumab in patients with diabetic macular edema, showing that this period of time was not sufficient for regression of IOP at the pre-injection value . We did not find significant differences between other groups, comparing phakic and aphakic patients, nor in patients who had received previous injections.

Endoftalmitis posvitrectomía por Pseudomona aeruginosa / Post-vitrectomy endophthalmitis caused by Pseudomona aeruginosa

Se describe el caso de un paciente varón de 22 años, miope, sometido a vitrectomía pars plana 23 G en ojo único (valioso), por desprendimiento de retina regmatógeno. A las 24 horas presentó pérdida de visión, dolor, signos inflamatorios en globo y anejos oculares. Acudió al Servicio de Emergencias, donde se decidió su ingreso hospitalario para la toma de muestra y la aplicación de inyección intravítrea de vancomicina (1 mg/0,1 mL) y ceftazidima (2 mg/0,1 mL), con lo que mostró mejoría clínica. El estudio microbiológico reportó Pseudomona aeruginosa sensible a la ceftazidima y a la ciprofloxacina. La mejor visualización fundoscópica al quinto día posintravítrea permitió observar depósitos blanquecinos en la interfaz aceite de silicona-retina, y se decidió la extracción de aceite por incisiones mixtas 23 g y 20 g (infusión, endoiluminación y extracción respectivamente), lavado de cámara anterior, cámara vítrea, reposición de aceite de silicón y segunda dosis de ceftazidima, con evolución posoperatoria favorable. Se dio el alta una semana después, con la retina aplicada y una mejor visión corregida de 0,1(AU)

This is the report about a male 22 years-old myopic patient who underwent a pars plana 23 G vitrectomy in one eye (valuable) due to regmatogen retinal detachment. Twenty four hours after the surgery, he presented with vision loss, pain, eye bulb inflammation and ocular adnexa. He went to the emergency service where it was decided to admitted him to the hospital for sample taking and application of intravitreal injection of vancomycin (1 mg/0,1 mL) and ceftazidime (2 mg/0,1 mL) which brought about clinical improvement. The microbiological test reported the presence of ceftazidime and ciprofloxacine-susceptible Pseudomona aeruginosa. The fundus oculi performed five days after vitrectomy allowed observing whitish deports in the silicon oil/retina interface, so it was decided to remove the oil by making mixed incisions of 23 and 20 g (infusion, endoilumination and extraction, respectively), washing the anterior chamber, the vitreal chamber, returning the silicon oil and a second dosage of ceftazidime, all of which caused favorable postoperative progress. One week later, he was discharged from the hospital with replaced retina and better corrected vision of 0.1(AU)

Ocular safety of Intravitreal Clindamycin Hydrochloride Released by PLGA Implants.

BACKGROUND: Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels. METHODS: Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR. RESULTS: After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1ß, TNF-α, IL-6), VEGF, and iNOS at day 30. CONCLUSION: These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis.

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT.

PURPOSE: To evaluate choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT) imaging at baseline and 6 months after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). METHODS: A retrospective chart review was performed to identify patients with DME who underwent intravitreal injection of anti-VEGF (bevacizumab or ranibizumab) in a pro re nata (PRN) regimen. Subfoveal choroidal thickness was compared between values obtained at baseline and at 6-month follow-up visits. RESULTS: Thirty-nine eyes (15 females, 24 males) from 39 patients were enrolled (mean age, 62.43 ± 8.7 years; range, 44-79 years). Twenty-three and 16 eyes were treated with ranibizumab and bevacizumab respectively. The mean number of anti-VEGF injections was 2.28 ± 1.27 (range, 1-5). Mean nasal, subfoveal, and temporal choroidal thickness (CT) measurements at baseline were 234.10 ± 8.63 µm, 246.89 ± 8.94 µm, and 238.12 ± 8.20 µm, respectively, and those at 6 months post-treatment were 210.46 ± 8.00 µm, 215.66 ± 8.29 µm, and 212.43 ± 8.14 µm, respectively. Significant differences in CT were observed between baseline and the 6-month follow-up at all measured points (p=0.0327). CONCLUSIONS: Over a 6-month period, the use of intravitreal anti-VEGF was associated with significant thinning of the choroid in patients with DME. The clinical significance of a thinner choroid in DME is currently unknown; however, it may contribute to long-term adverse effects on choroidal and retinal function, representing an area requiring future investigation.

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT / Efeito de injeção intravítrea na espessura de coroide em pacientes com edema macular diabético utilizando OCT de domínio espectral

ABSTRACT Purpose: To evaluate choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT) imaging at baseline and 6 months after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). Methods: A retrospective chart review was performed to identify patients with DME who underwent intravitreal injection of anti-VEGF (bevacizumab or ranibizumab) in a pro re nata (PRN) regimen. Subfoveal choroidal thickness was compared between values obtained at baseline and at 6-month follow-up visits. Results: Thirty-nine eyes (15 females, 24 males) from 39 patients were enrolled (mean age, 62.43 ± 8.7 years; range, 44-79 years). Twenty-three and 16 eyes were treated with ranibizumab and bevacizumab respectively. The mean number of anti-VEGF injections was 2.28 ± 1.27 (range, 1-5). Mean nasal, subfoveal, and temporal choroidal thickness (CT) measurements at baseline were 234.10 ± 8.63 µm, 246.89 ± 8.94 µm, and 238.12 ± 8.20 µm, respectively, and those at 6 months post-treatment were 210.46 ± 8.00 µm, 215.66 ± 8.29 µm, and 212.43 ± 8.14 µm, respectively. Significant differences in CT were observed between baseline and the 6-month follow-up at all measured points (p=0.0327). Conclusions: Over a 6-month period, the use of intravitreal anti-VEGF was associated with significant thinning of the choroid in patients with DME. The clinical significance of a thinner choroid in DME is currently unknown; however, it may contribute to long-term adverse effects on choroidal and retinal function, representing an area requiring future investigation.

RESUMO Objetivos: Avaliar a espessura de coroide pré-tratamento e após 6 meses da injeção intravítrea de anti-fator de crescimento vascular endotelial (anti-VEGF) em pacientes com edema macular diabético (EMD), utilizando a tomografia de coerência óptica de domínio espectral (SD-OCT). Métodos: Análise retrospectiva, com revisão de prontuários, foi realizada para identificação de pacientes submetidos a tratamento com injeções intravítreas de anti-VEGF, no regime pro re nata, para tratamento de EMD. As medidas da espessura de coroide pré-tratamento foi comparada com as medidas após acompanhamento de 6 meses. Resultados: Trinta e nove olhos de 39 pacientes (15 femininos, 24 masculinos) foram incluídos, com idade média de 62,43 ± 8,7 anos (variando de 44-79 anos). Trinta e três olhos foram tratados com ranibizumab e 18 com bevacizumab. O número médio de injeções de anti-VEGF foi 2,28 ± 1,27 (variando de 1-5). A medida média pré-tratamento da espessura de coroide nasal, subfoveal e temporal foi 234,10 ± 8,63 µm, 246,89 ± 8,94 µm e 238,12± 8,20 µm, respectivamente. Após acompanhamento de 6 meses as medidas médias da espessura de coroide foram 210,46 ± 8,00 µm, 215,66 ± 8,29 µm e 212,43 ± 8,14 µm. A diferença entre as medidas médias pré e pós tratamento foi estatisticamente significante (p=0,0327) em todos os pontos medidos. Conclusão: Após um período de 6 meses, o uso de injeções intravítreas de anti-VEGF foi associado com diminuição significante da espessura de coroide nos pacientes com EMD. O significado clínico de uma coroide mais fina nos pacientes com EMD é desconhecido mas pode causar eventos adversos a longo prazo para função da coroide e retina, representando uma área para futura investigações.

Análisis de costo-efectividad de ranibizumab comparado con implante intravítreo de dexametasona, triamcinolona, aflibercept y bevacizumab, para pacientes el tratamiento de pacientes con edema macular secundario a oclusión de la vena central de la retina (OVCR) en Colombia / Ranibizumab cost-effectiveness analysis compared to intravitreal implantation of dexamethasone, triamcinolone, aflibercept and bevacizumab, for patients in the treatment of patients with macular edema secondary to central retinal vein occlusion (OVCR

Problema de investigación: Realizar el análisis de costo-efectividad del uso de ranibizumab comparado con aflibercept, implante intravítreo de dexametasona, triamcinolona y bevacizumab para pacientes con edema macular secundario a oclusión de la vena central de la retina en Colombia. Tipo de evaluación económica: Evaluación económica descriptiva de tipo costo-efectividad. Población objetivo: Población con la condición de degeneración macular relacionada a la edad mayor de 50 años en Colombia. Intervención y comparadores: I: Ranibizumab, C: aflibercept, implante intravítreo de dexametasona, triamcinolona y bevacizumab. Horizonte temporal: 24 años. Perspectiva: La del Sistema General de Seguridad Social en Salud (SGSSS). Tasa de descuento: Es de 5% tanto para los costos como para los desenlaces de efectividad. Estructura del modelo: Modelo de Markov de 6 estados con ciclos de 6 meses. Fuentes de datos de efectividad y seguridad: Ensayos clínicos y meta-análisis. Desenlaces y valoración: Años de vida ajustados por calidad (AVAC). Costos incluidos: Costos de medicamentos, Costos de procedimientos e insumos. Fuentes de datos de costos: Consulta a proveedores, SISMED, Manual tarifario ISS 2001. Resultados del caso base: El ranibizumab presenta una efectividad similar, expresada en AVAC, frente a los demás medicamentos antiangiogénicos (bevacizumab y aflibercept). Con respecto al aflibercept, el ranibizumab es una estrategia dominada. Por su parte, al compararlo con bevacizumab, no es una estrategia costo efectiva ya que su RICE supera el umbral de tres PIB per cápita. Análisis de sensibilidad: El ranibizumab es una estrategia dominada en cada uno de los escenarios planteados para las distintas tasas de descuento. El bevacizumab por su parte sigue presentando la mejor costo-efectividad en cada uno de los escenarios, ya que aunque su efectividad es similar, el costo asociado al tratamiento es menor que el de otras alternativas antiangiogénicas. \r\nConclusiones y discusión: Ranibizumab no es una alternativa costo-efectiva comparada con bevacizumab ni con aflibercept. El ranibizumab es costo-efectivo comparado con implante intravítreo de dexametasona y \r\npotencialmente costo-efectivo con triamcinolona.(AU)