[Translated article] Syringes for intraocular administration: A systematic review.

OBJECTIVE: The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous of some patients. This situation derives from the lack of approved syringes for intraocular use in the Spanish market. The aim of this work is to review the use of syringes for intraocular administration, as well as to search for alternatives that meet the legal requirements for these unmet needs. METHOD: A systematic review was performed following the PRISMA 2020 guidelines by searching PubMed with the descriptors: (silicone) AND (syringes) AND ((intraocular) OR (intravitreal)) and filtering all existing publications from January 2006 to December 2023, including all those articles dealing with silicone oil release in intravitreal injections and analysing the possible consequences. RESULTS: Sixty-eight results were found, 23 of which were excluded because they did not deal with the subject under study, leaving a total of 45 articles for the systematic review. These were classified according to the conclusions obtained in 4 groups: the adverse reactions produced by silicone; the administration technique; the physicochemical aspects of silicone release; and the characteristics of the medical device. After reviewing the current manufacturers and technical data sheets of commercialised syringes, the existing syringes for this use have been collected, finding 2 that will probably be commercialised in Spain at the beginning of 2024: Zero Residual™ 0.2 ml SiO-free and VitreJect® Ophthalmic. CONCLUSIONS: From the results obtained, it can be interpreted that the use of syringes and needles with silicone for intravitreal use is a concern for health professionals due to the implications and consequences that may arise in patients, the most important being adverse reactions, so it is necessary to have silicone-free syringes on the market that are specific for intraocular use. Safety and legality in the use of intraocular syringes and needles is essential to guarantee ocular integrity and patient health.

Syringes for intraocular administration: Systematic review. / Jeringas para administración intraocular: revisión sistemática.

OBJECTIVE: The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous of some patients. This situation derives from the lack of approved syringes for intraocular use in the Spanish market. The aim of this work is to review the use of syringes for intraocular administration, as well as to search for alternatives that meet the legal requirements for these unmet needs. METHOD: A systematic review was performed following the PRISMA 2020 Guidelines by searching PubMed with the descriptors: "silicone" AND "syringes" AND ("intraocular" OR "intravitreal") and filtering all existing publications from January 2006 to December 2023, including all those articles dealing with silicone oil release in intravitreal injections and analysing the possible consequences. RESULTS: Sixty-eight results were found, 23 of which were excluded because they did not deal with the subject under study, leaving a total of 45 articles for the systematic review. These were classified according to the conclusions obtained in 4 groups: the adverse reactions produced by silicone, the administration technique, the physicochemical aspects of silicone release, and the characteristics of the medical device. After reviewing the current manufacturers and technical data sheets of commercialized syringes, the existing syringes for this use have been collected, finding two that will probably be commercialized in Spain at the beginning of 2024: Zero Residual™ 0.2 ml SiO-free and VitreJect® Ophthalmic. CONCLUSIONS: From the results obtained, it can be interpreted that the use of syringes and needles with silicone for intravitreal use is a concern for health professionals due to the implications and consequences that may arise in patients, the most important being adverse reactions, so it is necessary to have silicone-free syringes on the market that are specific for intraocular use. Safety and legality in the use of intraocular syringes and needles is essential to guarantee ocular integrity and patient health.

Análisis coste-utilidad del modelo de unidad de terapia intravítrea (UTI) frente a la administración tradicional de terapia intravítrea / Cost-utility model of new intravítreous units vs. current patient journey model in Spain

Objetivo Comparar la efectividad y los costes de la implantación del Modelo de Unidad de Terapia Intravítrea (UTI), avalado por la Sociedad Española de Retina y Vítreo (SERV), Sociedad Española de Calidad Asistencial (SECA), Sociedad Española de Oftalmología (SEO) y Sociedad Española de Directivos Sanitarios (SEDISA) vs. el procedimiento habitual. Método Modelo de decisión analítico que compara una organización asistencial tipo UTI con cuatro escenarios de práctica habitual en España, en cuanto al resultado en la calidad de vida por pérdida de agudeza visual y la utilización de recursos. Se estimó la probabilidad, el coste y los años de vida ajustados por calidad (AVAC) para cada escenario planteado. Se realizó un análisis de sensibilidad univariante para cada uno de los parámetros empleados. Resultado Se observó que la implantación del modelo UTI mejora la calidad de vida de los pacientes y presenta un menor coste frente a la práctica habitual. Se produjo ahorro de costes y ganancia de AVAC. El análisis de sensibilidad mostró que el resultado no cambiaría de signo con la modificación de ninguna variable de partida. Conclusiones En las patologías oculares con indicación de tratamiento intravítreo, cualquier reducción en el tiempo que transcurre desde la sospecha diagnóstica hasta la primera inyección intravítrea disminuye la pérdida de agudeza visual. Así, actuar para acortar los tiempos sospecha-aguja es clave para mantener la visión funcional de los pacientes. La mejora de la eficiencia de los servicios de oftalmología que se organizan siguiendo el modelo UTI puede generar ahorros que varían entre los 175 € y 85 € por paciente atendido y año (AU)

Aim To compare the effectiveness and costs of the implementation of the intravitreal therapy unit model, endorsed by the SERV, SECA, SEO and SEDISA, compared to the usual procedure. Method Analytical decision model that compares an UTI-type healthcare organization with four usual practice scenarios in Spain, in terms of quality-of-life results due to loss of visual acuity and the use of resources. The probability, cost, and quality-adjusted life years (QALYs) were estimated for each scenario proposed. A univariate sensitivity analysis was performed for each of the parameters used in the model. Result The model showed that from any of the initial scenarios of the usual practice, transitioning to the UTI-type implementation improves the quality of life of patients and requires lower cost. UTI-type is dominant respect usual practice. The sensitivity analysis showed that the results would not change sign with the variation of any starting variable. Conclusions Shorten suspicion-needle times is key to maintaining functional vision in patients requiring intravitreal treatment. The UTI-type model seeks the efficiency of ophthalmology services and can produce savings that vary between €175 and €85 per patient attended per year (AU)

Transoperative intravitreal dexamethasone implantation in patients with proliferative vitreoretinopathy.

OBJECTIVE: To compare the anatomical results in patients with rhegmatogenous retinal detachment, at least grade B of proliferative vitreoretinopathy, and with a trans-surgical dexamethasone implant vs the control group. We also assessed the diminution of proliferative vitreoretinopathy and the final visual acuity (VA). METHOD: The patients were evaluated clinically and with optical coherence tomography for 10 months. Logistic regression analyses were performed to evaluate the effect of the dexamethasone implant on retinal detachment. Correlational analyses were explored depending on the variables' distribution, and an independent samples t-test was used to compare the VA in both groups. RESULTS: The study included 38 eyes of patients with proliferative vitreoretinopathy: 18 with the implant and 20 for the control group. The evaluation of the main objective showed significant differences (p < 0.05) in the anatomical success between the two groups (61.1% vs. 20%, treatment vs. control); odds ratio of 6.29; 95% confidence interval: 1.5- 26.8; p = 0.013; Nagelkerke's R2 = 0.225. The t-test showed a significant difference in the final VA of the patients (t = 2.047; df = 36; p = 0.048; Cohen's d = 0.66). CONCLUSIONS: Retinal redetachment was less frequent, and better VA was observed, in patients with the dexamethasone implant in comparison with the control group.

OBJETIVO: Comparar los resultados anatómicos en pacientes con desprendimiento de retina regmatógeno, vitreorretinopatía proliferativa a partir de grado B y aplicación de implante de dexametasona transquirúrgico frente a un grupo control. También se valoraron la disminución de la vitreorretinopatía proliferativa y la agudeza visual (AV) final. MÉTODO: Los pacientes se evaluaron clínicamente y con tomografía de coherencia óptica por 10 meses. Se realizaron análisis de regresión logística para evaluar el efecto del implante en el redesprendimiento de retina. Se exploraron análisis correlacionales dependiendo de la distribución de variables y se aplicó la prueba t de muestras independientes para comparar la AV en ambos grupos. RESULTADOS: Se incluyeron 38 ojos de pacientes con vitreorretinopatía proliferativa: 18 con el implante y 20 del grupo control. La evaluación del objetivo principal mostró diferencias significativas (p < 0.05) en el éxito anatómico entre ambos grupos (61.1% en los ojos con tratamiento frente a 20% en el grupo control); razón de momios de 6.29; intervalo de confianza del 95%: 1.5- 26.8; p = 0.013; R2 de Nagelkerke = 0.225. La prueba t mostró una diferencia significativa entre la AV final de los pacientes (t = 2.047; gl = 36; p = 0.048; d de Cohen = 0.66). CONCLUSIONES: Se observó menor redesprendimiento, así como mejor AV, en los pacientes con el implante de dexametasona en comparación con el grupo control.

Cost-utility model of new intravitreous units vs. current patient journey model in Spain.

AIM: To compare the effectiveness and costs of the implementation of the Intravitreal Therapy Unit Model, endorsed by the SERV, SECA, SEO and SEDISA, compared to the usual procedure. METHOD: Analytical decision model that compares an UTI-type healthcare organization with 4 usual practice scenarios in Spain, in terms of quality-of-life results due to loss of visual acuity and the use of resources. The probability, cost, and quality-adjusted life years (QALYs) were estimated for each scenario proposed. A univariate sensitivity analysis was performed for each of the parameters used in the model. RESULT: The model showed that from any of the initial scenarios of the usual practice, transitioning to the UTI-type implementation improves the quality of life of patients and requires lower cost. UTI-type is dominant respect usual practice. The sensitivity analysis showed that the results would not change sign with the variation of any starting variable. CONCLUSIONS: Shorten suspicion-needle times is key to maintaining functional vision in patients requiring intravitreal treatment. The UTI-type model seeks the efficiency of ophthalmology services and can produce savings that vary between Є175 and Є85 per patient attended per year.

Diagnóstico diferencial de las reacciones inflamatorias tras uso de medicación intravítrea en degeneración macular asociada a la edad: estéril vs. infeccioso / Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: Sterile vs. infectious

El interés por las complicaciones inflamatorias tras la inyección intravítrea de fármacos antiangiogénicos ha aumentado tras la comercialización de brolucizumab y el desarrollo de nuevas moléculas como el abicipar pegol. Dichos fármacos se asocian a una tasa de complicaciones inflamatorias mayor a los antiangiogénicos clásicos. En este contexto resulta clave el diferenciar procesos infecciosos y estériles para realizar un tratamiento efectivo y precoz. El solapamiento del cuadro clínico entre procesos infecciosos y estériles, la baja tasa de positividad en los cultivos y la heterogeneidad en la terminología son barreras para el correcto diagnóstico y reporte de las complicaciones inflamatorias tras la inyección de medicación antiangiogénica intravítrea. Los cuadros estériles comienzan de forma precoz tras la inyección, dentro de las primeras 48 h, o alrededor de 20 días después en los casos de vasculitis asociada a brolucizumab. Los procesos infecciosos comienzan como promedio en el tercer día tras la inyección, y hasta una semana después de la misma. La disminución grave de la agudeza visual, el dolor severo, la hiperemia severa, el hipopion y un mayor grado de inflamación intraocular deben orientar hacia procesos infecciosos. En los casos en que exista duda sobre la etiología de la inflamación, debe procederse a un control muy estrecho del paciente o al tratamiento antimicrobiano empírico junto con la toma de muestra para evitar complicaciones derivadas de una endoftalmitis infecciosa. Por el contrario, los fenómenos estériles deben ser tratados con observación en los casos más leves o corticoterapia adaptada a la gravedad de inflamación en los casos más graves (AU)

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or “tap and inject” antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation (AU)

Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: sterile vs. infectious.

The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48 h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or "tap and inject" antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation.

Staphylococcus hominis: a rare cause of endophthalmitis / Staphylococcus hominis: uma causa rara de endoftalmite

ABSTRACT Staphylococcus hominis (S. hominis) is a coagulase-negative Staphylococci and an infrequent cause of endophthalmitis. Due to its ability to produce biofilm, especially in diabetic patients, strains may acquire antibiotic resistance. We present two cases of S. hominis endophthalmitis, one with acute endophthalmitis after intravitreal bevacizumab injection and one with chronic endophthalmitis following undiagnosed penetrating ocular trauma. Although there are only four published S. hominis endophthalmitis cases in the literature, to the best of our knowledge, there has been no previously published case after intravitreal bevacizumab.

RESUMO Staphylococcus hominis (S. hominis) é um estafilococo coagulase-negativo e uma causa pouco frequente de endoftalmite. Devido à sua capacidade de produzir biofilme, especialmente em pacientes diabéticos, cepas dessa bactéria podem adquirir resistência a antibióticos. Este relato apresenta dois casos de endoftalmite por S. hominis: um de endoftalmite aguda após injeção intravítrea de bevacizumabe e outro de endoftalmite crônica após trauma ocular penetrante não diagnosticado. Embora existam apenas quatro casos de endoftalmite por S. hominis publicados na literatura, até onde sabemos não houve nenhum caso publicado anteriormente após bevacizumabe intravítreo.

Viscotrabeculotomy with anterior chamber irrigation versus Ahmed glaucoma valve implantation for silicone oil glaucoma in the pseudophakic eye / Viscotrabeculotomia com irrigação da câmara anterior versus implante de válvula de Ahmed para glaucoma por óleo de silicone em olho pseudofácico

ABSTRACT Purpose: To compare viscotrabeculotomy with anterior chamber irrigation to Ahmed glaucoma valve implantation for secondary glaucoma following silicone oil removal. Methods: A prospective study was conducted on 43 vitrectomized pseudophakic eyes with persistent glaucoma after silicone oil removal. Patients were randomized to either viscotrabeculotomy with anterior chamber irrigation or Ahmed glaucoma valve implantation. All patients were examined on day 1, week 1, and months 1, 3, 6, 9, 12, 18, and 24 postoperatively. Postoperative complications were noted. Success was defined as an intraocular pressure between 6 and 20 mmHg and with an intraocular pressure reduction of >30% compared with the preoperative intraocular pressure. Results: There were 22 eyes in the viscotrabeculotomy with anterior chamber irrigation and 21 eyes in the Ahmed glaucoma valve implantation group. The mean preoperative and postoperative intraocular pressure in the viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation groups were 35.5 ± 2.6 mmHg and 35.5 ± 2.4 mmHg and 16.9 ± 0.7 mmHg and 17.9 ± 0.9 mmHg respectively (p˂0.0001). There was a statistically significant intraocular pressure reduction at all follow-up time points compared to preoperative values (p˂0.0001) in both groups. The unqualified success rate in the viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation groups were 72.73% and 61.9%, respectively. A minimal self-limited hyphema was the most common complication. Conclusions: Both viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation are effective in lowering the intraocular pressure in glaucoma after silicone oil removal with viscotrabeculotomy with anterior chamber irrigation providing greater reduction, higher success rates, and minimal complications.

RESUMO Objetivo: Comparar a viscotrabeculotomia com irrigação da câmara anterior com o implante de válvula de glaucoma de Ahmed para glaucoma secundário após remoção de óleo de silicone. Métodos: Foi realizado um estudo prospectivo de 43 olhos pseudofácicos vitrectomizados com glaucoma persistente após a remoção de óleo de silicone. Os pacientes foram randomizados para viscotrabeculotomia com irrigação da câmara anterior ou implante de válvula de Ahmed. Todos os pacientes foram examinados no primeiro dia, na primeira semana e 1, 3, 6, 9, 12, 18 e 24 meses após a cirurgia. Observaram-se complicações pós-operatórias. O sucesso foi definido como uma pressão intraocular entre 6 e 20 mmHg e uma redução da pressão intraocular >30% em comparação com a pressão intraocular pré-operatória. Resultados: Foram designados 22 olhos para o grupo da viscotrabeculotomia com irrigação da câmara anterior e 21 olhos para o grupo do implante de válvula de Ahmed. A pressão intraocular média pré-operatória foi de 35,5 ± 2,6 mmHg para o grupo da viscotrabeculotomia com irrigação da câmara anterior e pós- e de 35,5 ± 2,4 mmHg no grupo do implante de válvula de Ahmed. e Os valores pós-ope­ratórios foram de 16,9 ± 0,7 mmHg e 17,9 ± 0,9 mmHg para esses mesmos grupos, respectivamente (p<0,0001). Ambos os grupos tiveram uma redução estatisticamente significativa da pressão intraocular em relação aos valores pré-operatórios (p<0,0001) em todos os momentos do acompanhamento. A taxa de sucesso não qualificado nos grupos da viscotrabeculotomia com irrigação da câmara anterior e do implante de válvula de Ahmed foi de 72,73% e 61,9%, respectivamente. A complicação mais comum foi o hifema, autolimitado e mínimo. Conclusões: Tanto a viscotrabeculotomia com irrigação da câmara anterior quanto o implante de válvula de Ahmed são eficazes na redução da pressão intraocular no glaucoma após injeção de óleo de silicone, mas a viscotrabeculotomia com irrigação em câmara anterior proporcionou maior redução da pressão intraocular e maiores taxas de sucesso, com complicações mínimas.

Visual outcomes and prognostic factors following 23G vitrectomy for vitreous hemorrhage in eyes with proliferative diabetic retinopathy / Desfechos visuais e fatores prognósticos após vitrectomia 23G para hemorragia vítrea em olhos com retinopatia diabética proliferativa

ABSTRACT Purpose: We aimed to evaluate the factors influencing the visual gain following pars plana vitrectomy for vitreous hemorrhage in patients with proliferative diabetic retinopathy. Methods: A retrospective study was conducted on 172 eyes of 143 consecutive patients with diabetes mellitus between January 2012 and January 2018. Demographic data, ophthalmological findings, surgery details, and visual outcomes were gathered after consulting the patients' records. The main outcome measured was the improvement of best corrected visual acuity and the secondary outcomes measured were rebleeding and complications. Results: Best corrected visual acuity improved in 103 eyes (59.88%), worsened in 45 eyes (26.16%), and remained unchanged in 24 eyes (13.95%). Type 2 diabetes mellitus was significantly associated with better final best corrected visual acuity (p=0.0244). Previous treatment by pan-retinal laser photocoagulation or intravitreal bevacizumab determined better final best corrected visual acuity, but not significantly (p>0.05). Preoperative rubeosis iridis and neovascular glaucoma did not influence the outcomes. The lack of fibrovascular proliferation requiring dissection was a significant factor for better final best corrected visual acuity (p=0.0006). Rebleeding occurred in 37.1% of the eyes and it was not influenced by the antiplatelet drugs (p>0.05). Postoperative neovascular glaucoma was a negative prognostic factor (p=0.0037). Conclusion: The final best corrected visual acuity was influenced positively by type 2 diabetes mellitus and the absence of preoperative extensive fibrovascular proliferation and negatively by postoperative neovascular glaucoma.

RESUMO Objetivo: Avaliar os fatores que influenciam o ganho visual após vitrectomia via pars plana para hemorragia vítrea em pacientes com retinopatia diabética proliferativa. Métodos: Foi realizado um estudo retrospectivo de 172 olhos de 143 pacientes consecutivos com diabetes mellitus entre janeiro de 2012 e janeiro de 2018. Dados demográficos, achados oftalmológicos, detalhes da cirurgia e resultados visuais foram coletados através de consulta aos prontuários dos pacientes. A principal medida de desfecho foi o aumento da melhor acuidade visual corrigida e as medidas de desfecho secundário foram a recidiva da hemorragia e a ocorrência de complicações. Resultados: A melhor acuidade visual corrigida aumentou em 103 olhos (59,88%), diminuiu em 45 olhos (26,16%) e permaneceu inalterada em 24 olhos (13,95%). O diabetes mellitus tipo 2 foi significativamente associado a maiores valores finais da melhor acuidade visual corrigida (p=0,0244). O tratamento prévio por fotocoagulação panretiniana com laser ou bevacizumabe intravítreo determinou maiores valores da melhor acuidade visual final corrigida, mas não significativamente (p>0,05). A presença de rubeose iridiana pré-operatória ou de glaucoma neovascular não influenciou os desfechos. A ausência de proliferação fibrovascular com necessidade de dissecção foi um fator significativo para maiores valores da melhor acuidade visual final corrigida (p=0,0006). Ocorreu recidiva da hemorragia em 37,1% dos olhos e não foi influenciada por fármacos antiplaquetários (p>0,05). O glaucoma neovascular pós-operatório foi um fator prognóstico negativo (p=0,0037). Conclusão: O resultado final da melhor acuidade visual corrigida foi influenciado positivamente pelo diabetes mellitus tipo 2 e pela ausência de proliferação fibrovascular extensa no pré-operatório, e negativamente pela ocorrência de glaucoma neovascular pós-operatório.

Quantitative assessment of silicone oil release with siliconized and silicone oil-free syringes by microflow imaging microscopy / Avaliação quantitativa da liberação de óleo de silicone por seringas siliconizadas e sem óleo de silicone usando microflow imaging microscopy

ABSTRACT Purpose: Since particles are released in syringes during intravitreal injections, we assessed them quantitatively after agitating syringes commonly used for intravitreal injections. Methods: With and without agitation, the SR 1-ml insulin, Becton-Dickinson Ultra-Fine 0.3-ml Short Needle with a half-unit scale, HSW Norm-Ject Tuberculin, and Becton-Di­ckinson 1-ml Luer Lok Tip were examined with buffer and bevacizumab, aflibercept, and ziv-aflibercept. Flow imaging microscopy was performed to assess the particle numbers, concentrations, morphology, and size distribution. Results: Using the Becton-Dickinson Ultra-Fine syringe, the average particle count after agitation was higher than in the no-agitation group. For particles greater than 10 and 25 µm, differences were observed using the SR syringe between the two studied conditions. There were no significant differences in the means for the other syringes. Without agitation, the SR syringe had the highest number of particles (2,417,361.7 ± 3,421,575.5) followed by the Becton-Dickinson Ultra-Fine with 812.530,9 ± 996.187,2. The Becton-Dickinson Luer Lok Tip and HSW Norm-Ject performed equally with 398,396.8 ± 484,239.2 and 416,016.4 ± 242,650.1 particles, respectively. Conclusions: Flicking syringes to eliminate air bubbles results in increased numbers of particles released during intravitreal injections into the human vitreous.

RESUMO Objetivo: Visto que partículas são liberadas nas seringas durante as injeções intravítreas (IVIs), estas foram avaliadas quantitativamente após a agitação das seringas mais comumente usadas para injeções intravítreas. Métodos: A seringa SR de 1 ml de insulina, a agulha curta Becton-Dickinson Ultra-Fine 0,3 ml com escala de meia unidade, HSW Norm-Ject Tuberculin e a Becton-Dickinson Luer Lok Tip de 1 ml foram estudadas com placedo e com bevacizumabe, aflibercept e ziv-aflibercept, com e sem agitação. MicroFlow Imaging Mi­croscopy foi realizada para avaliar o número de partículas, con­centração, morfologia e distribuição das mesmas por tamanho. Resultados: A contagem média de partículas após agitação foi maior do que no grupo sem agitação usando a seringa Becton-Di­ckinson Ultra-Fine. Diferenças foram observadas usando a seringa SR entre as duas condições estudadas para partículas maiores que 10 e 25 µm. Para as demais seringas, não foram observadas diferenças significativas nas médias. A seringa SR apresentou o maior número de partículas sem agitação (2.417.361,7 ± 3.421.575,5) seguida da Becton-Dickinson Ultra-Fine com 812.530,9 ± 996.187,2. A BD Luer Lok Tip e a HSW Norm-Ject se comportaram de forma semelhante com 398.396,8 ± 484.239,2 e 416.016,4 ± 242.650,1 partículas, respectivamente. Conclusões: Agitar seringas para remover bolhas de ar resulta em um maior número de partículas liberadas durante Becton-Dickinson no vítreo humano.

Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab / Avaliação da sensibilidade ao contraste em retinopatia diabética proliferativa de não alto risco tratada com panfotocoagulação retiniana com ou sem injeções intravítrea de ranibizumabe

ABSTRACT Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

RESUMO Objetivos: Avaliar a sensibilidade ao contraste em pacientes virgens de tratamento com retinopatia diabética proliferativa de não alto risco, submetidos a panfotocoagulação retiniana com injeções intravítreas de ranibizumabe versus pan­fotocoagulação isolada. Métodos: Sessenta olhos de 30 pa­cientes foram randomizados em dois grupos: um submetido a panfotocoagulação com injeções de ranibizumabe (grupo estudo), e o outro submetimedo a panfotocoagulação isolada (grupo controle). Todos olhos foram tratados em 3 sessões de laser, seguindo recomendação do Early Treatment Diabetic Retinopathy Study (ETDRS). Avaliação da sensibilidade ao contraste foi realizada sob condições fotópicas (85 cd/m2) com tabela Visual Contrast Test Sensitivity 6500, permitindo avaliação de cinco frequências espaciais medidas com redes senoidais: 1.5, 3.0, 6.0, 12.0 e 18.0 ciclos por grau de ângulo visual (cpd). Foram realizadas medidas dos limiares de sensibilidade ao contraste intra e entre grupos na visita inicial, no 1º, 3º, e 6º mês de seguimento. Resultados: Cinquenta e oito olhos, 28 do grupo estudo e 30 do grupo controle, atingiram o término do estudo. Análise comparativa da SC entre os grupos mostrou diferença estatisticamente significante, nas baixas frequências espaciais, no 1º mês em 1.5 cpd (p=0,001) e 3.0 cpd (p=0,04), no 3º mês em 1.5 cpd (p=0,016) e no 6º mês em 3.0 cpd (p=0,026) a favor do grupo estudo. Conclusão: O tratamento com panfotocoagulação associada a injeção de ranibizumabe parece causar menos danos a sensibilidade ao contraste quando comparada com panfotocoagulação isolada em olhos com retinopatia diabética proliferativa de não alto risco. Dessa forma, os resultados apresentados podem justificar a associação do ranibizumabe à panfotocoagulação nestes pacientes.

Brevibacterium casei endophthalmitis after intravitreal dexamethasone implant.

CLINICAL CASE: 49-year-old man with diabetic macular edema refractory to antiangiogenics, it is decided to perform therapy with intravitreal dexamethasone implant (Ozurdex; Allergan, California, United States of America). Seven days after treatment, he showed acute endophthalmitis suggestive signs. Despite the intravitreal injection of antibiotics, the patient got worse. Vitreous sampling was repeated for Gram and cultures, and vitrectomy was performed via pars plana. The culture suggested the development of Brevibacterium species. Through an additional test, the presence of Brevibacterium casei was confirmed. Despite the treatment adjusted by antibiogram, retinal ischemia and macular atrophy was evident. DISCUSSION: Brevibacterium casei is a Gram-positive bacterium, barely pathogenic, that mainly affects immunodepressed patients. Only two cases of endophthalmitis are described, one endogenous and the other one secondary to vegetal trauma. This is the first case of endophthalmitis, secondary to an ophthalmological procedure.

Fundus autofluorescence in the evaluation of diabetic macular edema treatment response.

INTRODUCTION: Fundus autofluorescence (FAF) has shown sensitivity in the detection of macular edema. OBJECTIVES: To evaluate indices formed with FAF and retinal anatomical-functional variables in patients with diabetic macular edema (DME) treated with ziv-aflibercept (ziv-AFL). METHODS: Twenty-nine eyes of 15 DME patients who received ziv-AFL intravitreal injections were included in the study. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT) and FAF were evaluated before treatment and at one and two months. OCT variables were central subfield thickness (CST), macular volume (MV) and macular cube average thickness (MCAT). FAF/BCVA, FAF/CS, FAF/CST, FAF/MV and AF/MCAT indices baseline values were obtained. Analysis was performed with Spearman's rank correlation coefficient and linear regression analysis. RESULTS: There was a significant correlation between baseline FAF/BCVA index and BCVA at second month (rs = - 0.78, p = 0.000), between baseline FAF/CS index and BCVA at second month (rs = -0.68, p = 0.0009) and between baseline FAF/CS index and MV at first month of follow-up (rs = 0.64, p = 0.002). CONCLUSIONS: In DME, composite indices with baseline FAF predict variables such as BCVA in the follow-up of patients receiving ziv-AFL.

INTRODUCCIÓN: La autofluorescencia retiniana (AF) ha mostrado sensibilidad en la detección del edema macular. OBJETIVOS: Evaluar índices formados con la AF y variables anatomofuncionales retinianas en pacientes con edema macular diabético (EMD) tratados con ziv-aflibercept (ziv-AFL). MÉTODOS: Fueron incluidos 29 ojos de 15 pacientes con EMD que recibieron inyecciones intravítreas de ziv-AFL. Se evaluó agudeza visual mejor corregida (AVMC), sensibilidad al contraste (SC), tomografía de coherencia óptica (TCO) y AF, antes del tratamiento, así como al primer y segundo mes de iniciado este. Las variables de la TCO fueron grosor foveal central (GFC), volumen macular (VM) y grosor promedio macular (GPM). Se obtuvieron los valores basales de AF/AVMC, AF/SC, AF/GFC, AF/VM y AF/GPM. Se realizó análisis con el coeficiente de correlación de rangos de Spearman y análisis de regresión lineal. RESULTADOS: Hubo una correlación significativa entre el índice AF/AVMC basal y la AVMC en el segundo mes (rs = −0.78, p = 0.000), entre el índice AF/SC basal y la AVMC en el segundo mes (rs = −0.68, p = 0.0009) y entre AF/SC basal y el VM en el primer mes de seguimiento (rs = 0.64, p = 0.002). CONCLUSIONES: En el EMD, los índices compuestos con AF basales predicen variables como AVMC en el seguimiento de pacientes que reciben ziv-AFL.

Endoftalmitis aguda por Brevibacterium casei tras implante intravítreo de dexametasona / Brevibacterium casei endophthalmitis after intravitreal dexamethasone implant

Caso clínico Hombre de 49años, con edema macular diabético refractario a antiangiogénicos, en el que se realizó terapia intravítrea con implante de dexametasona (Ozurdex; Allergan, California, Estados Unidos). Tras 7días presentó signos sugerentes de endoftalmitis aguda. Pese a la inyección intravítrea de antibióticos, el paciente empeoró. Se repitió la toma de muestras en vítreo para Gram y cultivos, y se realizó vitrectomía vía pars plana. El cultivo sugirió el desarrollo de Brevibacterium species. Mediante una prueba adicional, se confirmó la presencia de Brevibacterium casei. Pese al tratamiento ajustado por antibiograma, se evidenció isquemia retiniana y atrofia macular. Discusión Brevibacterium casei es una bacteria grampositiva, escasamente patógena, que afecta principalmente a inmunodeprimidos. Se han descrito solo dos casos de endoftalmitis, una endógena y otra secundaria a trauma vegetal. Este es el primer caso de endoftalmitis por Brevibacterium casei secundaria a procedimiento oftalmológico (AU)

Clinical case A 49-year-old man with diabetic macular edema refractory to antiangiogenics was treated with intravitreal dexamethasone implant (Ozurdex; Allergan, California, USA). Seven days after treatment, he showed acute endophthalmitis suggestive signs. Despite the intravitreal injection of antibiotics, the patient got worse. Vitreous sampling was repeated for Gram and cultures, and vitrectomy was performed via pars plana. The culture suggested the development of Brevibacterium species. Through an additional test, the presence of Brevibacterium casei was confirmed. Despite the treatment adjusted by antibiogram, retinal ischemia and macular atrophy was evident. Discusion Brevibacterium casei is a Gram-positive bacterium, barely pathogenic, that mainly affects immunodepressed patients. Only two cases of endophthalmitis are described, one endogenous and the other one secondary to vegetal trauma. This is the first case of Brevibacterium casei endophthalmitis, secondary to an ophthalmological procedure (AU)

Brevibacterium casei endophthalmitis after intravitreal dexamethasone implant. / Endoftalmitis aguda por Brevibacterium casei tras implante intravítreo de dexametasona.

CLINICAL CASE: A 49-year-old man with diabetic macular edema refractory to antiangiogenics was treated with intravitreal dexamethasone implant (Ozurdex; Allergan, California, USA). Seven days after treatment, he showed acute endophthalmitis suggestive signs. Despite the intravitreal injection of antibiotics, the patient got worse. Vitreous sampling was repeated for Gram and cultures, and vitrectomy was performed via pars plana. The culture suggested the development of Brevibacterium species. Through an additional test, the presence of Brevibacterium casei was confirmed. Despite the treatment adjusted by antibiogram, retinal ischemia and macular atrophy was evident. DISCUSION: Brevibacterium casei is a Gram-positive bacterium, barely pathogenic, that mainly affects immunodepressed patients. Only two cases of endophthalmitis are described, one endogenous and the other one secondary to vegetal trauma. This is the first case of Brevibacterium casei endophthalmitis, secondary to an ophthalmological procedure.

Effectiveness of treat-and-extend versus pro re nata regimens in the treatment of Neovascular Age Macular Degeneration: A Real World Comparison. / Efectividad de los regímenes tratar y extender vs. pro re nata para el tratamiento de degeneración macular neovascular vinculada a la edad: una comparación en un entorno real.

PURPOSE: Evaluate and compare the visual and morphological results of Pro re nata (PRN) and treat-and-extend (T&E) treatment regimens at 3 years in real world clinical practice. METHODS: Retrospective study of patients with neovascular age macular degeneration (AMD) treated with anti-VEGF with 3 years of continuous follow-up and no previous anti-VEGF treatment. Best corrected visual acuity (BCVA), central foveal thickness (CFT) and number of intravitreal injections outcomes were tested for statistical differences between the two groups at baseline and during follow-up. RESULTS: A total of 240 eyes were included in the study, 170 in the PRN group and 70 in the T&E group. At 12 months, mean BCVA (ETDRS letters) gain from baseline was at its highest point in the T&E group (+6.38±13.32; p=0.25). In the PRN group, BCVA peaked at 3 months and slowly decreased until end of follow-up. With both regimens, from baseline, CFT continued to decrease until the second year (PRN -138.81 [-846.7 to +162.77] and T&E -81 [-604 to +100] µm, p=0.06). After that, T&E group maintained this tendency, reaching the lowest CFT value at 36 months, whereas PRN group showed an increased in CFT values (PRN -104 [-807.7 to +297] µm and T&E -103 [-575 to +244], µm p=0.63). Patients treated with T&E regimen received a significantly higher number of injections (PRN 16.3±7.6 vs T&E 23.9 ±9.4, p<0.01). CONCLUSION: Our results demonstrated a trend towards for T&E to achieve higher marks in BCVA, peaking at 12 months, and lower CFT thickness at the end of three years. Despite the higher number of injections performed in the T&E group the mean BCVA reverts to baseline values at 3 years.

Análise das injeções intravítreas do Hospital do Servidor Público Estadual de São Paulo / Analysis of intravitreal injections at the State Public Servant Hospital of São Paulo

Resumo Objetivo: Analizar o perfil dos pacientes submetidos a Injeções Intravítreas (IVTs), as indicações e os custos do tratamento. Métodos: O estudo foi realizado através de protocolos próprios, aplicados por meio de análise de prontuários dos pacientes submetidos a IVTs no Hospital do Servidor Público Estadual de São Paulo no período de janeiro de 2017 a junho de 2018. Os dados obtidos foram submetidos a análise descritiva. Resultados: Os resultados encontrados demonstraram que 3181 injeções foram realizadas em 1421 olhos no período do estudo; não foi evidenciada nenhuma complicação durante os procedimentos; nenhum paciente evoluiu com endoftalmite durante o seguimento; a principal droga injetada foi o Bevacizumabe; a principal patologia tratada foi a Maculopatia Diabética; e o custo com estes procedimentos foi de pelo menos R$ 776.257,56. Somente 10% dos pacientes diabéticos possuíam a Hemoglobina Glicada inferior a 7%. Apenas 25% dos pacientes com Doença macular Relacionada a Idade tiveram melhora documentada de Acuidade Visual. Conclusão: Concluiu-se que as indicações de IVTs devem ser avaliadas quanto ao prognóstico visual para benefício dos servidores públicos do estado de São Paulo. Filas de espera de acordo com o prognóstico visual são uma opção a ser aventada. As informações geradas por este estudo poderão ser utilizadas para aprimorar o serviço através do desenvolvimento de protocolos terapêuticos, como também como ponto de partida para novas pesquisas e ações ligadas ao tema.

Abstract Objective: The objective of this work was to generate information about the profile of the patients submitted to Intravitreal Injections (IVIs) and also to evaluate the indications and costs of the procedure. Methods: The study was carried out with own protocols, applied through the analysis of medical records of patients submitted to IVIs at the State Public Servant Hospital of São Paulo from January 2017 to June 2018. Data were analyzed in the form of descriptive study. Results: The results showed that 3181 injections were performed in 1421 eyes in the study period; the main drug injected was Bevacizumab; the main pathology treated was Diabetic Maculopathy; and the cost with these procedures was at least R$ 776,257.56. Most diabetic patients did not have adequate glycemic control. Many patients with AMD had no documented improvement in Visual Acuity. Conclusion: It was concluded that deep analyzes about the indications of IVIs should be performed for the benefit of public servants of São Paulo. The information generated by this study can be used to improve the service through the development of therapeutic protocols, as well as serving as a starting point for new research and actions related to the topic.

Protocolo de injeções intravítreas do Hospital de Clínicas de Porto Alegre: uma revisão de condutas para uma assistência mais que qualificada / Hospital de Clínicas de Porto Alegre intravitreal injection protocol: a literature review to improve assistance

A injeção intravítrea é o procedimento oftalmológico mais realizado no mundo. Através dessa técnica é possível administrar medicamentos para o segmento posterior do olho, sendo a via de escolha para o tratamento da maioria das patologias coriorretinianas. O evento ocular adverso mais grave é a endoftalmite pós injeção. Diversas medidas foram sugeridas para diminuição do risco dessa complicação, com evidências variáveis. Tendo em vista o grande número de injeções realizado em nosso serviço de oftalmologia do Hospital de Clínicas de Porto Alegre (HCPA), realizamos uma revisão da literatura com o objetivo de definir as melhores práticas. Nós descrevemos a evidência disponível para os principais aspectos dos diferentes estágios do procedimento (pré injeção, peri injeção e pós injeção) e apresentamos nosso protocolo. A medida com maior evidência científica na profilaxia da endoftalmite é a aplicação de iodopovidona tópica pelo menos trinta segundos antes da injeção. (AU)

Intravitreal injection is the most widely performed ophthalmologic procedure in the world. This technique allows for delivering therapeutic substances to the posterior segment of the eye, being the route of choice for the treatment of most chorioretinal diseases. The most feared adverse event is post-injection endophthalmitis. Many measures have been described to lower the risk of this complication, with variable evidence. In view of the great number of injections performed at our ophthalmology practice at Hospital de Clínicas de Porto Alegre (HCPA), we searched the literature for available evidence on the best practice standards. We describe the available evidence for major aspects of the different stages of the procedure (pre-injection, peri-injection, and post-injection) and then introduce our protocol. The measure with most scientific evidence of efficacy in preventing endophthalmitis is topical povidone- iodine administration at least 30 seconds before the injection. (AU)

Intravitreal clindamycin as a therapeutic alternative in severe ocular toxoplasmosis. / Clindamicina intravítrea como alternativa terapéutica en la toxoplasmosis ocular severa.

Ocular toxoplasmosis is a disease than have severe consequences on the eyesight. The aim of this study article is to present a bilateral ocular toxoplasmosis in a sulfamide allergic patient with unilateral activation and her favourable progression with intravitreal Clindamycin and oral steroids treatment. Weekly intravitreal Clindamycin treatment is shown to be a suitable therapeutic alternative in cases of severe ocular toxoplasmosis and/or in patients with a contraindication to classical treatment. Intravitreal Clindamycin treatment is a safe alternative with favourable clinical results.