Prospective evaluation of the effectiveness of combined treatment of macular edema secondary to retinal vein occlusion with intravitreal bevacizumab and dexamethasone implants / Estudo intervencionista prospectivo para avaliar a eficácia da associação do bevacizumabe intravítreo ao implante de dexametasona para edema macular secundário à oclusão da veia retiniana

ABSTRACT Purpose: To evaluate the effectiveness of in­­­travitreal bevacizumab injections following a single dexamethasone implant in the treatment of macular edema secondary to branch and central retinal vein occlusion. Methods: This was a prospective interventional non-comparative study, 44 eyes of patients with naïve macular edema related to branch and central retinal vein occlusion were treated with a dexamethasone implant. Patients were followed-up at four-week intervals from the second to the sixth month. If persistent or recurrent macular edema occurred during this period, the patient was treated with intravitreal bevacizumab injections on an as-needed basis. The outcome measures were best-corrected visual acuity and central macular thickness changes. Results: The mean best-corrected visual acuity changed from 0.97 ± 0.33 LogMAR at baseline to 0.54 ± 0.40 at the six-month post-implant examination (p<0.00001). Improvement ≥3 Snellen lines were seen in 20 eyes (45.54%). The mean central macular thickness at baseline was 670.25 ± 209.9 microns. This had decreased to 317.43 ± 112.68 microns at the six-month follow-up (p<0.00001). The mean number of intravitreal bevacizumab injections received in the six months post-implant was 2.32. The mean time from dexamethasone implant to first anti-VEGF injection was 3.45 months. Conclusions: Intravitreal bevacizumab injections following a single dexamethasone implant were found to improve best-corrected visual acuity and central macular thickness in patients with macular edema due to branch and central retinal vein occlusion at six months, with few intravitreal injections required.

RESUMO Objetivo: Avaliar a eficácia da combinação de in­jeções intravítreas de bevacizumabe em olhos com edema macular secundário à oclusão de ramo e da veia central da retina após um único implante de dexametasona. Métodos: Foi realizado um estudo prospectivo intervencionista não comparativo com 44 olhos de pacientes com edema macular relacionado à oclusão de ramo e veia central da retina, sem tratamento prévio e tratados com um único implante de dexametasona, que foram acompanhados em intervalos de quatro semanas do segundo ao sexto mês. Se fosse constatado edema macular persistente ou recorrente durante esse período, os pacientes eram tratados com injeções intravítreas de bevacizumabe em um regime ajustado conforme a necessidade. Foram estudadas a melhor acuidade visual corrigida e alterações da espessura macular central. Resultados: A média da melhor acuidade visual corrigida mudou de 0,97 ± 0,33 LogMAR iniciais para 0,54 ± 0,40 no exame de 6 meses (p<0,00001). Vinte olhos (45,54%) melhoraram 3 linhas de Snellen ou mais. A média da espessura macular central inicial foi de 670,25 ± 209,9 μm e diminuiu para 317,43 ± 112,68 μm na visita de 6 meses (p<0,00001). O número médio de injeções intravítreas de bevacizumabe em 6 meses foi de 2,32 e o tempo médio entre o implante de dexametasona e a primeira injeção de anti-VEGF foi de 3,45 meses. Conclusão: Injeções intravítreas de bevacizumabe após um único implante de dexametasona podem proporcionar um aumento da melhor acuidade visual corrigida e diminuição da espessura macular central aos 6 meses em pacientes com edema macular devido à oclusão de ramo e da veia central da retina, com poucas injeções intravítreas.

Switch to aflibercept in the treatment of neovascular age-related macular degeneration: 30-month results / Mudança de tratamento para o aflibercepte no tratamento da Degeneração Macular neovascular Relacionada à Idade: resultados de 30 meses

ABSTRACT Purpose: This study was conducted to evaluate visual function and changes in the central macular thickness of patients with unresponsive neovascular age-related macular degeneration who were switched from ranibizumab (Lucentis®) to aflibercept (Eylea®) treatment at 30 months. Methods: This retrospective study examined patients with neovascular age-related macular degeneration who were switched to aflibercept after ≥6 previous intravitreal ranibizumab injections at 4- to 8-week intervals. All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections followed by a prore nata dosing regimen and after 30 months of treatment. Best corrected visual acuity, biomicroscopic examination, intraocular pressure, fundus examination, and central macular thickness were recorded at the start of treatment, before the transition to intravitreal aflibercept treatment, and at 6, 12, 18, 24, and 30 months of intravitreal aflibercept treatment. Results: A total of 33 eyes met the inclusion criteria. The median age of the patients was 73.57 ± 7.98 years, and 21 (61.8%) patients were males and 12 (35.3%) were females. Before the transition, the patients received a mean of 16.8 ± 8.8 ranibizumab injections (range 6-38).After the transition to intravitreal aflibercept treatment, the mean number of aflibercept injections was 9.09 ± 3.94. No significant differences were observed in best corrected visual acuity after the aflibercept switch in any of the months. The central macular thickness was significantly decreased at 6, 12, 18, and 30 months (p=0.01, p=0.03, p=0.05, p=0.05, p<0.001, respectively). Conclusion: Patients with neovascular age-related macular degeneration who were switched to intravitreal aflibercept treatment due to unresponsiveness to intravitreal ranibizumab exhibited a significant anatomic improvement in the retina, and although this state persisted, there was no significant functional gain.(AU)

RESUMO Objetivo: Avaliar, depois de 30 meses, a função visual e as alterações na espessura macular central de pacientes com degeneração macular relacionada à idade sem resposta terapêutica ao ranibizumabe (Lucentis®) que mudaram seu tratamento para o aflibercepte (Eylea®). Métodos: Realizou-se um estudo retrospectivo de pacientes com degeneração macular neovascular relacionada à idade que mudaram o tratamento para o aflibercepte após 6 ou mais injeções intravítreas de ranibizumabe a intervalos de 4-8 semanas. Todos os pacientes mudaram para o aflibercepte intravítreo (2,0 mg) e depois de 3 injeções consecutivas, seguidas de um regime de dosagem pro re nata, foram avaliados após 30 meses de tratamento. A melhor acuidade visual corrigida, o exame biomicroscópico, a pressão intraocular, a fundoscopia e a espessura macular central foram registrados no início do tratamento, antes da transição para o tratamento com aflibercepte intravítreo e aos 6, 12, 18, 24 e 30 meses de tratamento com o aflibercepte intravítreo. Resultados: Satisfizeram aos critérios de inclusão 33 olhos. A mediana da idade dos pacientes foi de 73,57 ± 7,98 anos. Dos pacientes, 21 (61,8%) eram homens e 12 (35,3%) eram mulheres. Antes da transição para o tratamento com o aflibercepte intravítreo, os pacientes receberam em média 16,8 ± 8,8 injeções de ranibizumabe (faixa 6-38).Depois da transição, o número médio de injeções de aflibercepte foi de 9,09 ± 3,94. Não houve diferenças significativas na melhor acuidade visual corrigida depois da mudança para o aflibercepte em qualquer das avaliações. Houve diminuição significativa da espessura macular central aos 6, 12, 18 e 30 meses (respectivamente, p=0,01, p=0,03, p=0,05, p=0,05 e p<0,001). Conclusão: Pacientes com degeneração macular neovascular relacionada à idade que mudaram seu tratamento para o aflibercepte intravítreo devido à falta de resposta ao ranibizumabe intravítreo, tiveram melhora anatômica significativa da retina; mas embora esse estado tenha persistido, não foi observado nenhum ganho funcional significativo.(AU)

ETDRS panretinal photocoagulation combined with intravitreal ranibizumab versus PASCAL panretinal photocoagulation with intravitreal ranibizumab versus intravitreal ranibizumab alone for the treatment of proliferative diabetic retinopathy / Panfotocoagulação retiniana a laser padrão ETDRS associado a injeção intravítrea de ranibizumabe versus panfotocoagulação retiniana a laser padrão PASCAL associado a injeção intravítrea de ranibizumabe versus somente injeção intravítrea de ranibizumabe para o tratamento da retinopatia diabética proliferativa

ABSTRACT Purpose: To compare visual acuity, macular thickness, and the area of active neovascularization based on fluorescein angiography outcomes associated with standard single-spot panretinal photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS) pattern combined with intravitreal ranibizumab injection versus multiple-spot full scatter (PASCAL) panretinal photocoagulation combined with intravitreal ranibizumab injection versus intravitreal injection alone in patients with proliferative diabetic retinopathy. Methods: Patients with proliferative diabetic retinopathy and no prior laser treatment were randomly assigned to receive three different types of treatment. Panretinal photocoagulation in the ETDRS group was administered in two sessions (weeks 0 and 2), and panretinal photocoagulation in the PASCAL group was administered in one session (week 0). Intravitreal injection of ranibizumab was administered at the end of the first laser session in both the ETDRS and PASCAL groups and at week 0 in the intravitreal injection group. Comprehensive ophthalmic evaluations were performed at baseline and every 4 weeks through week 48. Results: Thirty patients (n=40 eyes) completed the 48-week study period. After treatment, best-corrected visual acuity was significantly (p<0.05) improved at all follow-up visits in the group receiving intravitreal injection alone, at all but week 4 in the ETDRS group, and at all but weeks 4 and 8 for the PASCAL group. A significant decrease in central subfield macular thickness was observed in the PASCAL group at weeks 4, 8, and 48; only at week 48 in the intravitreal injection group; and never in the ETDRS group. There was no significant difference among the three treatment groups with respect to change from baseline to week 48 in best-corrected visual acuity, central subfield macular thickness, or fluorescein leakage from active neovascularization in best-corrected visual acuity, central subfield macular thickness, or fluorescein leakage from active neovascularization. Conclusions: Intravitreal injection alone or combined with single- or multiple-spot panretinal photocoagulation yielded similar outcomes with respect to mean change in best-corrected visual acuity, central subfield macular thickness, and fluorescein leakage from active neovascularization at up to one-year of follow-up. All subjects provided written informed consent to participate (NCT02005432 in clinicaltrials.gov).

RESUMO Objetivo: Comparar as medidas de acuidade visual, espessura macular central e área de neovasos ativos na an­giofluoresceinografia submetidos a panfotocoagulação retiniana padrão ETDRS associado a injeção intravítrea de ranibizumabe versus panfotocoagulação padrão PASCAL associado a injeção intravítrea de ranibizumabe versus somente injeção intravítrea de ranibizumabe em pacientes com retinopatia diabética pro­liferativa. Métodos: Pacientes com retinopatia diabética proliferativa e virgens de tratamento, randomicamente divididos nas três diferentes terapias retinianas. Panfotocoagulação no grupo ETDRS em 2 sessões (semanas 0 e 2) e no grupo PASCAL, na semana 0. Injeção intravítrea de ranibizumabe realizado ao fim da primeira sessão de laser em ambos os grupos: ETDRS e PASCAL, e na semana 0 no grupo injeção intravítrea de ranibizumabe. Avaliações oftalmológicas, tomografia de coerência óptica e angiofluoesceinografia realizados na visita basal e a cada 4 semanas por 48 semanas. Resultados: Trinta pacientes (n=40 olhos) completaram as 48 semanas de seguimento. Após o tratamento, a acuidade visual melhorou significantemente em todas a visitas no grupo injeção intravítrea de ranibizumabe (p<0,05); em todas exceto na semana 4 no grupo ETDRS, em todas exceto nas semanas 4 e 8 no grupo PASCAL. Redução significativa na espessura do subcampo central foi evidenciada no grupo PASCAL nas semanas 4, 8 e 48; somente na semana 48 no grupo injeção intravítrea de ranibizumabe, e em nenhuma visita no grupo ETDRS. Redução também na área de neovasos ativos em todas as visitas em todos os grupos. Não houve diferença significante entre os três grupos com relação a mudança media na medidas de acuidade visual, espessura macular central ou área de neovasos ativos da visita inicial para a semana 48. Conclusões: Somente IVB ou este associado a panfotocoagulação ETDRS ou PASCAL, apresentaram efeitos semelhantes em relação a medidas de acuidade visual, espessura do subcampo central e área de neovasos ativos no decorrer de 48 semanas de seguimento.

Treatment of Radiation Retinopathy with Intravitreal Injection of Ranibizumab (Lucentis®).

To report a treatment of radiation retinopathy in a patient exposed to ionizing radiation for a period of 2 years. A 26-year-old female patient with no comorbidities diagnosed with myelodysplasia confirmed by bone marrow biopsy. She presented a complaint of bilateral progressive visual acuity reduction. At the ophthalmologic examination, she presented alterations suggestive of radiation retinopathy as well as macular thickness to optical coherence tomography (OCT) of over 500 µm. The patient underwent intravitreal injection (0.05 mL) of ranibizumab (Lucentis®) monthly in both eyes and follow-up through visual acuity and OCT examination. She presented reduction of macular edema as well as a slight improvement of visual acuity. In this case, the treatment of radiation retinopathy with intravitreal injection of ranibizumab (Lucentis) was relatively useful, with a slight improvement of visual acuity, due to the regression of macular edema, not being curative.

The reactivation time in the treatment of AMD: a forgotten key parameter?

OBJECTIVE: Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). METHOD: Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). RESULTS: Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). CONCLUSION: There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.