Intravitreal bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary to age-related macular degeneration: case report series.

PURPOSE: To evaluate the feasibility of the combined use of bevacizumab (Avastin®) and combined with infliximab (Remicade®) in the treatment of naive choroidal neovascularization due to age-related macular degeneration eyes. METHODS: Intravitreal injections of bevacizumab combined with infliximab in 6 neovascular age-related macular degeneration eyes. All patients underwent complete ophthalmologic examination on the initial visit and at days 1, 30, 60, 90, 120, 150 and 180 following the first injection. Optical coherence tomography and fluorescein angiography were performed during at initial visit and monthly during the 6 months follow-up period. Electroretinography was performed before and 30 days after initial injection, in order to evaluate retinal toxicity induced by such treatment. RESULTS: Thirty days after the first injection, 5 eyes (83%) shown decrease in macular thickness. No change was seen in electroretinogram in any eyes compared to initially performed electroretinogram. All phakic eyes developed cataract. One patient developed vitritis and was submitted to medical treatment successfully. At the end of the 6 months follow-up period, 4 patients showed significant improvement in the exudative process of choroidal neovascularization. One eye had mild persistent submacular fluid without active choroidal neovascularization, and another eye had persistent amount of intraretinal fluid due to active choroidal neovascularization. CONCLUSION: The combined use of bevacizumab with infliximab in eyes with neovascular age-related macular degeneration was effective in reducing leakage and improving the macular thickness. However, it is not possible to assert that the results were related to synergic effects of the combination therapy. A controlled study with more cases is necessary to precisely define the complication rates; however the dosage and/or association of drugs studied in this research should not be recommended in clinical practice due to cataract as well as inflammatory reaction.

Intravitreal bevacizumab combined with infliximab in the treatment of choroidal neovascularization secondary to age-related macular degeneration: case report series / Administração intravítrea de bevacizumabe combinado com infliximabe no tratamento da neovascularização coroidiana secundária à degeneração macular relacionada à idade: relato de uma série de casos

PURPOSE: To evaluate the feasibility of the combined use of bevacizumab (Avastin®) and combined with infliximab (Remicade®) in the treatment of naive choroidal neovascularization due to age-related macular degeneration eyes. METHODS: Intravitreal injections of bevacizumab combined with infliximab in 6 neovascular age-related macular degeneration eyes. All patients underwent complete ophthalmologic examination on the initial visit and at days 1, 30, 60, 90, 120, 150 and 180 following the first injection. Optical coherence tomography and fluorescein angiography were performed during at initial visit and monthly during the 6 months follow-up period. Electroretinography was performed before and 30 days after initial injection, in order to evaluate retinal toxicity induced by such treatment. RESULTS: Thirty days after the first injection, 5 eyes (83%) shown decrease in macular thickness. No change was seen in electroretinogram in any eyes compared to initially performed electroretinogram. All phakic eyes developed cataract. One patient developed vitritis and was submitted to medical treatment successfully. At the end of the 6 months follow-up period, 4 patients showed significant improvement in the exudative process of choroidal neovascularization. One eye had mild persistent submacular fluid without active choroidal neovascularization, and another eye had persistent amount of intraretinal fluid due to active choroidal neovascularization. CONCLUSION: The combined use of bevacizumab with infliximab in eyes with neovascular age-related macular degeneration was effective in reducing leakage and improving the macular thickness. However, it is not possible to assert that the results were related to synergic effects of the combination therapy. A controlled study with more cases is necessary to precisely define the complication rates; however the dosage and/or association of drugs studied in this research should not be recommended in clinical practice due to cataract as well as inflammatory reaction.

OBJETIVO: Avaliar a viabilidade do uso combinado do bevacizumabe (Avastin®) e do infliximabe (Remicade®) no tratamento da degeneração macular relacionada à idade neovascular em pacientes sem tratamentos prévio. MÉTODOS: Foram realizadas injeções intravítreas de bevacizumabe combinado com infliximabe em 6 pacientes portadores de degeneração macular relacionada à idade neovascular. Todos foram submetidos ao exame oftalmológico completo, no primeiro dia de consulta, no dia seguinte a cada injeção e mensalmente até completar seis meses após a primeira injeção. Foram realizados tomografia de coerência óptica e angiografia fluoresceínica na primeira consulta e mensalmente, até completar 6 meses após o primeiro procedimento. Eletrorretinografia também foi realizada antes da injeção e 30 dias após, no intuito de avaliar toxidade retiniana. RESULTADOS: Ao final de 30 dias da primeira injeção, 5 (83%) pacientes apresentaram diminuição na espessura macular. Não foi visualizada alteração à eletrorretinografia em relação ao exame inicial em 100% os pacientes. Cinco pacientes (100% dos fácicos) desenvolveram catarata. Um paciente desenvolveu vitreíte e foi tratado com sucesso. Ao final dos 6 meses, 4 pacientes apresentaram melhora significativa da neovascularização de coroide, porém ainda com foco de neovascularização em atividade, um paciente apresentava discreta persistência de fluido submacular sem neovascularização ativa e 1 paciente persistia importante quantidade de fluido intrarretiniano com neovascularização em atividade. DISCUSSÃO: Avaliou-se o uso combinado do bevacizumabe com infliximabe em pacientes portadores de degeneração macular relacionada à idade neovascular e a associação mostrou-se eficaz na redução do vazamento da neovascularização de coroide e da espessura macular ao tomografia de coerência óptica. Não é possível, no entanto, afirmar se os resultados apresentam efeitos sinérgicos pela associação entre as duas drogas. Um estudo com maior número de casos é necessário para definir exatamente as taxas de catarata e vitreíte da associação entre as drogas, no entanto, ao menos na dosagem estudada no presente trabalho, a associação não deveria ser recomendada na prática clínica.

Intra-operative use of 5-Fluorouracil in pterygium surgery: a comparative study.

PURPOSE: Evaluate the efficacy and safety of intraoperative application of 5-Fluorourail in pterygium surgery and the recurrent pterigyum postoperative. MATERIALS AND METHODS: 240 eyes of 120 patients with bilateral primary pterygium were operated. One hundred twenty eyes had 5-FLU (25 mg/ml) applied intraoperatively on a sponge for five minutes. One hundred twenty contralateral eyes served as controls. RESULTS: After a follow-up of 90 days, 7 (5.83%) recurrences of the eyes which had 5-FLU applied intraoperatively were observed. In the control eyes, 25 (25.5%) recurrences were observed. Complications such as keratitis and lid edema were common in both groups. CONCLUSION: This study suggests that antifibroproliferative therapy with intraoperative sponge 5-FLU is effective and safe. Its use may be a useful adjunct in primary pterygium surgery.

Correlation between central subfield thickness, visual acuity and structural changes in diabetic macular edema.

PURPOSE: To correlate the central subfield thickness (CST) measured by Cirrus™ SD-OCT with best-corrected visual acuity (BCVA) and structural changes in diabetic macular edema (DME). METHODS: The transversal study evaluated 200 patients with non-proliferative diabetic retinopathy (NPDR) and selected 55 eyes with DME between January, 2010 and April, 2011. Spectral domain OCT was performed in patients with type 2 diabetes and DME. CST and BCVA were correlated with the edema morphology and the ELM (external limiting membrane) integrity. Statistical tests were applied to validate the results. RESULTS: There was no difference between genders in the NPDR classification. 47.3% of the patients showed moderate NPDR. The CST average for male was of 393.58 µm and 434.16 µm for female, with no statistically significant difference. The patients with continuous ELM showed lower CST average (368.73 µm) than those with disrupted ELM (521.43 µm). There was a strong correlation between the macular volume and CST (59.63%), but poor correlation between age and CST (2.9%). Also, there was a significant difference between the average CST and the type of macular edema. Patients with serous detachment showed higher CST average (488.71 µm) than those with cystoid macular edema (CME) and diffuse edema. Patients with severe NPDR showed higher CST average (491.45 µm), if compared to mild and moderate NPDR. Cystoid macular edema was the most common type of edema (49.1%) and showed the worse VA. Patients with disrupted ELM showed worse BCVA. Patients with higher CST showed worse BCVA. There was a significant difference between the CST average of the case group (407.6 ± 113,1 µm) and the control group (diabetic patients without DME: 252 ± 12.5 µm). There was also a significant difference in the BCVA variables and macular volume between case and control groups. CONCLUSION: The study suggests that the CST of diabetic patients with edema is higher than the control group, the increase in CST of diabetic patients with edema leads to worsening of BCVA and macular volume. Continuous ELM showed lower CST average, and the serous detachment showed higher CST average. Cirrus™ proved to be an important tool in the DME evaluation.

Correlation between central subfield thickness, visual acuity and structural changes in diabetic macular edema / Correlação entre a espessura do subcampo central, a acuidade visual e mudanças estruturais no edema macular diabético

PURPOSE: To correlate the central subfield thickness (CST) measured by CirrusTM SD-OCT with best-corrected visual acuity (BCVA) and structural changes in diabetic macular edema (DME). METHODS: The transversal study evaluated 200 patients with non-proliferative diabetic retinopathy (NPDR) and selected 55 eyes with DME between January, 2010 and April, 2011. Spectral domain OCT was performed in patients with type 2 diabetes and DME. CST and BCVA were correlated with the edema morphology and the ELM (external limiting membrane) integrity. Statistical tests were applied to validate the results. RESULTS: There was no difference between genders in the NPDR classification. 47.3% of the patients showed moderate NPDR. The CST average for male was of 393.58 µm and 434.16 µm for female, with no statistically significant difference. The patients with continuous ELM showed lower CST average (368.73 µm) than those with disrupted ELM (521.43 µm). There was a strong correlation between the macular volume and CST (59.63%), but poor correlation between age and CST (2.9%). Also, there was a significant difference between the average CST and the type of macular edema. Patients with serous detachment showed higher CST average (488.71 µm) than those with cystoid macular edema (CME) and diffuse edema. Patients with severe NPDR showed higher CST average (491.45 µm), if compared to mild and moderate NPDR. Cystoid macular edema was the most common type of edema (49.1%) and showed the worse VA. Patients with disrupted ELM showed worse BCVA. Patients with higher CST showed worse BCVA. There was a significant difference between the CST average of the case group (407.6 ± 113,1 µm) and the control group (diabetic patients without DME: 252 ± 12.5 µm). There was also a significant difference in the BCVA variables and macular volume between case and control groups. CONCLUSION: The study suggests that the CST of diabetic patients with edema is higher than the control group, the increase in CST of diabetic patients with edema leads to worsening of BCVA and macular volume. Continuous ELM showed lower CST average, and the serous detachment showed higher CST average. CirrusTM proved to be an important tool in the DME evaluation.

OBJETIVO: Correlacionar a espessura do subcampo central (ESCC) medida pelo CirrusTM SD-OCT com a acuidade visual (AV) e as mudanças estruturais no edema macular diabético (EMD). MÉTODOS: Um estudo transversal avaliou 200 pacientes com retinopatia diabética não proliferativa (RDNP) e selecionados 55 olhos com EMD entre janeiro de 2010 e abril de 2011. OCT spectral foi realizado em pacientes com diabetes tipo 2 e com edema macular diabético (EMD). A ESCC e a AV foram correlacionados com a morfologia do edema e a integridade da membrana limitante externa (MLE). Aplicaram-se testes estatísticos para validação dos resultados. RESULTADOS: Não houve diferença entre os sexos na classificação RDNP. 47,3% dos pacientes apresentou RDNP moderada. A média da ESCC no sexo masculino foi de 393,58 µm e no feminino de 434,16 µm, sem diferença estatística significativa. Pacientes com MLE íntegra apresentaram menor média da ESCC (368,73 µm) que aqueles com MLE descontínua (521,43 µm). Encontrou-se forte correlação entre o volume macular e a ESCC (59,63%), porém pequena correlação entre a idade e a ESCC (2,9%). Encontrou-se diferença significativa entre a média da ESCC e o tipo de edema macular, aqueles com descolamento seroso apresentaram maior média de ESCC (488,71 µm). Pacientes com RDNP grave apresentaram maior média da ESCC (491,45 µm), quando comparados à RDNP leve e moderada. O edema macular cistoide foi o tipo de edema mais frequente (49,1%) e apresentou pior AV. Pacientes com MLE íntegra apresentaram melhor AV. Pacientes com maior ESCC apresentaram pior AV. Houve diferença significativa entre a média da ESCC do grupo de casos (407,60 ± 113,05 µm) e controle (diabéticos sem edema macular: 252,0 ± 12,46 µm). Também houve diferença significativa nas variáveis AV e volume macular entre o grupo de casos e controle. CONCLUSÃO: O estudo sugere que a ESCC de diabéticos com edema é maior que o grupo controle; o aumento da ESCC de diabéticos com edema cursa com piora da AV e do volume macular. MLE contínua mostrou menor média da ESCC e o descolamento seroso mostrou maior média da ESCC. CirrusTM mostrou ser importante ferramenta na avaliação do EMD.

Comparing intravitreal triamcinolone acetonide and bevacizumab injections for the treatment of diabetic macular oedema: a randomized double-blind study.

PURPOSE: To compare the effect of a single intravitreal injection of triamcinolone acetonide and bevacizumab in reducing macular thickness, which was measured by optical coherence tomography (OCT) in patients with diabetic macular oedema (DMO). METHODS: The patients received a single intravitreal injection of 1.25 mg bevacizumab in one randomly selected eye and 4.0 mg triamcinolone acetonide in the contralateral eye. Central foveal thickness measurement (CFT) with OCT was taken at the initial visit and at the 4-week, 12-week and 24-week visits. RESULTS: Eleven patients (22 eyes) were enrolled and statistically analysed. CFT reduced in the eyes treated with triamcinolone and those treated with bevacizumab in weeks 4 and 12 (p < 0.05). At the 24-week follow-up, no significant difference was noted, relative to the initial visit. Comparing the two groups treated with different drugs, a statistically significant difference in CFT in weeks 4 and 12 was noted, with a more significant reduction in triamcinolone-treated eyes (p < 0.05). Regarding visual acuity (VA), patients treated with triamcinolone had improvement in VA at 4-week (p = 0.02) and 12-week follow-up (p = 0.01), while the group treated with bevacizumab had VA improvement at 4 -week follow-up (p = 0.02). Among the eyes treated with triamcinolone, intraocular pressure (IOP) measurement of more than 21 mmHg was found in three eyes (27.3%). CONCLUSIONS: Intravitreal triamcinolone proved to be more efficient in reducing DMO, providing longer lasting visual improvement, relative to bevacizumab. Eyes treated with triamcinolone had the highest percentage increase in IOP. Further studies are needed to corroborate these findings.

[A safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyes]. / Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos.

PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13% smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid.

Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos / A safety study of retinal toxicity after serial intravitreal injections of infliximab in rabbits eyes

OBJETIVO: Determinar os níveis de toxicidade de duas e três aplicações intravítreas de infliximabe na retina de coelhos albinos, por meio de exames clínicos oftalmológicos, eletrorretinográficos e histológicos. MÉTODOS: Foram utilizados doze coelhos albinos divididos em dois grupos. No primeiro grupo de 10 coelhos, cada olho recebeu duas (n=10 olhos) ou três injeções (n=10 olhos) intravítreas de 2 mg de infliximabe dissolvidos em 0,06 ml de solução salina, em intervalos mensais. Um segundo grupo de dois coelhos, que serviu como grupo controle (n=4 olhos), foram submetidos a duas e três aplicações intravítreas de BSS. Noventa dias após, os coelhos foram novamente submetidos a exame oftalmológico (biomicroscopia, oftalmoscopia e tonometria), eletrorretinográfico e, após enucleados, a exame histológico. RESULTADOS: O exame biomicroscópico e oftalmoscópico não revelou anormalidades retinianas nos olhos injetados com infliximabe e no grupo controle. Alteração histológica notada foi a presença de raros linfócitos e eosinófilos no vítreo posterior em quatro e em seis olhos submetidos a duas e três aplicações de infliximabe sem significado clínico. A única alteração clinicamente significante foi uma reação inflamatória severa com presença de exsudatos vítreos na interface vítreo retiniana e discreto edema de células ganglionares nos dois olhos de um único coelho, sem alterações no vítreo posterior. Os exames eletrorretinográficos mostraram amplitudes em média 12-13 por cento menores daquelas obtidas antes do tratamento, contudo não houve nenhuma diferença estatisticamente significante quando comparamos as amplitudes e a latencia entre os achados electrorretinográficos pré e pós-tratamento. CONCLUSÃO: Duas e três aplicações intravítreas de infliximabe em olhos de coelhos em intervalos mensais, na dosagem de 2 mg, não provocam alterações significantes após um seguimento de noventa dias, quer no exame histológico, na eletrorretinografia e na avaliação clínica oftalmológica. Conclui-se que doses seriadas de infliximabe por via intravítrea é um procedimento seguro. Estudos clínicos em humanos devem ser realizados para melhor avaliação da segurança do seu uso no tratamento de determinadas doenças que acometem a retina e a coroide.

PURPOSE: To determine retinal and choroid toxicity levels of two and three infliximab intravitreous injections in albino rabbits by means of electroretinographic, histological and ophthalmological clinical tests. METHODS: 12 albino rabbits were used in the study. Each eye was given two (n=10 eyes) or three (n=10 eyes) serial intravitreous 2 mg infliximab injections dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the study had begun, the rabbits underwent clinical and electroretinographic tests, and after being enucleated, the eyes were examined for histological changes. RESULTS: Slit-lamp biomicroscopy and fundoscopic examination did not reveal any significant retinal abnormalities in the eyes injected with infliximab and control eyes or in pre- and post-treated eyes. The histological change that was noted was the presence of rare lymphocytes and eosinophils in the posterior vitreous of some of the rabbits subjected to two or three injections, but it was not considered clinically significant. A severe inflammatory reaction with vitreous exudates and ganglion cell edema in a single rabbit was clinically significant. The electroretinographic tests showed amplitudes that were on the average 12-13 percent smaller than those obtained before the treatment, however, there were no statistically significant differences when comparing the amplitude or the implicit time between pre- and post-treatment electroretinographic findings. CONCLUSION: Two and three intravitreous 2 mg infliximab injections in rabbits at monthly intervals did not cause any changes after a 90-day follow-up, according to histological and electroretinographic tests and after clinical evaluation. Differently from prior studies that have investigated potential retinotoxicity effects after single administrations, this study investigated the possibility of retinotoxicity after multiple injections. Clinical studies in humans should be conducted to better evaluate the safety of this drug in the treatment of certain diseases affecting the retina and the choroid.