Effects of topical and subconjunctival use of bevacizumab on corneal neovascularization in rabbits' eyes / Efeitos do uso tópico e subconjuntival do bevacizumabe na neovascularização corneana de olhos de coelhos

ABSTRACT Purpose: To evaluate and compare the effects of topical application and subconjunctival injection of bevacizumab on corneal neovascularization (CNV) in rabbits' eyes after chemical burning of the cornea. Methods: The animals were randomly distributed into four groups of five animals. In one group, the drug was instilled, while in another, it was administered by subconjunctival injection. The two procedures using bevacizumab were compared with instillation and subconjunctival injection of saline solution (S). Neovascularization was evaluated according to the size of the invasion area of new blood vessels and through computerized analysis of this area. The data were analyzed using the Kruskal-Wallis test followed by Dunn's test for two-by-two comparison of the groups, to assess the external examination of CNV. Analysis of variance was used to assess the area of CNV. P<0.05 was considered statistically significant. Results: Assessing both the external examination and the invasion area of neovessels on the 5th and 10th days, there was a clear difference between the groups. The group to which saline solution had been applied showed higher scores for CNV, as well as increases in the invasion area of neovessels. Two-by-two comparison of groups revealed no significant differences. However, an analysis of the factors involved (injection vs. instillation and bevacizumab vs. saline solution) showed that injection did not differ from instillation, but that bevacizumab differed from saline solution. Conclusion: Bevacizumab showed an inhibitory effect on CNV in rabbits' eyes after chemical burning of the cornea. There was no difference between the topical or subconjunctival administration of bevacizumab in the inhibition of CNV.

RESUMO Objetivos: Avaliar e comparar o efeito do uso tópico e da injeção subconjuntival do bevacizumabe na neovascularização corneana de olhos de coelhos após queimadura química. Métodos: Os animais foram distribuídos de forma aleatória em quatro grupos de cinco animais. Em um grupo de coelhos a droga foi instilada, enquanto em outro foi aplicada injeção subconjuntival, sendo os dois procedimentos comparados com a instilação e injeção subconjuntival de soro fisiológico 0,9% (SF) e entre si. A neovascularização foi avaliada conforme o tamanho da área de invasão dos neovasos e com análise computadorizada da mesma. Na análise de dados aplicou-se o teste de Kruskal-Wallis seguido do teste de Dunn com p<0,05 para comparação dos grupos dois a dois na análise do exame externo da neovascularização corneana. Na análise da área de neovascularização corneana, aplicou-se o teste F de análise de variância. A significância estatística foi definida como valor de p<0.05. Resultados: A avaliação do exame externo e da área de invasão de neovasos, no 5º e 10º dia, mostrou nítida diferença entre os grupos. Com o uso de soro fisiológico houve maior graduação na escala de neovascularização corneana e também na área de invasão dos nevasos, o que demonstrou o efeito inibitório do bevacizumabe. Nas comparações dos grupos dois a dois não foram detectadas diferenças significativas, porém, ao analisar os fatores envolvidos (procedimentos: injeção ou instilação, e as drogas: bevacizumabe ou soro fisiológico), verificou-se que a injeção não diferiu da instilação, mas o bevacizumabe diferiu do soro fisiológico. Conclusão: O bevacizumabe apresentou efeito inibitório na neovascularização corneana de olhos de coelhos após queimadura química, tanto por via tópica como por via subconjuntival e não houve diferença entre a via tópica e a via subconjuntival de administração do bevacizumabe na inibição da neovascularização corneana.

Evolving strategies in the management of diabetic retinopathy

Diabetic retinopathy [DR], the most common long-term complication of diabetes mellitus, remains one of the leading causes of blindness worldwide. Tight glycemic and blood pressure control has been shown to significantly decrease the risk of development as well as the progression of retinopathy and represents the cornerstone of medical management of DR. The two most threatening complications of DR are diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]. Focal/grid photocoagulation and panretinal photocoagulation are standard treatments for both DME and PDR, respectively. Focal/grid photocoagulation is a better treatment than intravitreal triamcinolone acetonide in eyes with DME. Currently, most experts consider combination focal/grid laser therapy and pharmacotherapy with intravitreal antivascular endothelial growth factor agents in patients with center-involving DME. Combination therapy reduces the frequency of injections needed to control edema. Vitrectomy with removal of the posterior hyaloid seems to be effective in eyes with persistent diffuse DME, particularly in eyes with associated vitreomacular traction. Emerging therapies include fenofibrate, ruboxistaurin, renin-angiotensin system blockers, peroxisome proliferator-activated receptor gamma agonists, pharmacologic vitreolysis, and islet cell transplantation

Combined therapy for diabetic macular edema

Diabetic macular edema [DME] is the main cause of visual impairment in diabetic patients. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. The management of DME is complex and often multiple treatment approaches are needed. This review demonstrates the benefits of intravitreal triamcinolone, bevacizumab and ranibizumab as adjunctive therapy to macular laser treatment in DME. The published results indicate that intravitreal injections of these agents may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present. Therefore, pharmacotherapy could complement focal/grid laser photocoagulation in the management of DME. For this review, we performed a literature search and summarized recent findings regarding combined therapy for DME

Current concepts in intravitreal drug therapy for diabetic retinopathy

Diabetic retinopathy [DR] is a major cause of preventable blindness in the developed countries. Despite the advances in understanding and management of DR, it remains a challenging condition to manage. The standard of care for patients with DR include strict metabolic control of hyperglycemia, blood pressure control, normalization of serum lipids, prompt retinal laser photocoagulation and vitrectomy. For patients who respond poorly and who progressively lose vision in spite of the standard of care, intravitreal administration of steroids or/and anti-vascular endothelial growth factor [anti-VEGF] drugs appear to be a promising second-line of therapy. This review discusses the current concepts and the role of these novel therapeutic approaches in the management of DR

role of vascular endothelial growth factor and its inhibitors in diabetic macular edema: a review

Experimental and clinical evidence have shown the pivotal role of vascular endothelial growth factor [VEGF] in the etiology of diabetic macular edema [DME] as well as proliferative diabetic retinopathy as a permeability and angiogenesis factor. In the absence of an effective treatment to improve vision in most cases of DME, which is a very common cause of central vision impairment in adults, it is logical to investigate the efficacy of anti-VEGF therapy in DME. Short-term results showed that anti-VEGF drugs are effective and safe in the treatment of DME, especially the diffuse types. A major concern is the short duration of action of available ones and the lack of long-term, randomized clinical trails. These agents are a very good add to our armamentarium in the management of DME and should be used with care in selected cases for the time being. The future is promising for longer acting and more specific anti-VEGF agents that would increase efficacy and decrease possible side effects