Terapias actuales en la vascularización corneal / Current therapies in corneal vascularization

Una córnea transparente es esencial para una excelente visión; es por eso que es avascular. Pero existen condiciones que favorecen la invasión de neovasos al tejido corneal, como infecciones, inflamación, hipoxia, trauma, entre otras, que reducen la calidad visual y en algunos casos llegan hasta la pérdida de esta. La neovascularización corneal representa un problema importante de salud pública a nivel mundial. Se realizó una búsqueda automatizada con el objetivo de encontrar información actualizada sobre el tratamiento de la neovascularización corneal, para lo cual se utilizó la plataforma infomed. La información se resumió en el documento final. Sobre el tema, existe un progreso notable en el entendimiento de la patogénesis, el mejoramiento y la seguridad de los nuevos tratamientos. Los corticoesteroides y los agentes anti-VEGF (factor de crecimiento endotelial vascular) continúan siendo los medicamentos de primera línea, usados principalmente para evitar la formación de los nuevos vasos, no así para vasos maduros, donde la mejor opción son los procedimientos quirúrgicos o combinados. Se necesitan más estudios experimentales, y los ya existentes deben ser utilizados en ensayos clínicos para investigar sobre la dosis segura y los efectos secundarios, y así encontrar terapias radicales, más eficaces, que le den a los pacientes con neovascularización corneal la esperanza de una mejor calidad visual(AU)

A clear cornea is essential for excellent vision; that is why it is avascular. But there are conditions that favor the invasion of neovessels into the corneal tissue, such as infections, inflammation, hypoxia, trauma, among others, which reduce visual quality and in some cases even lose it. Corneal neovascularization represents a major public health problem worldwide. An automated search was carried out in order to find updated information on the treatment of corneal neovascularization, for which the infomed platform was used. The information was summarized in the final document. On the subject, there is notable progress in understanding the pathogenesis, improvement and safety of new treatments. Corticosteroids and anti-VEGF (vascular endothelial growth factor) agents continue to be the first-line drugs, used mainly to prevent the formation of new vessels, not for mature vessels, where the best option is surgical or combined procedures. More experimental studies are needed; and the existing ones should be used in clinical trials to investigate the safe dose and side effects, and thus find radical and more effective therapies that give patients with corneal neovascularization the hope of better visual quality(AU)

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.

Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization / Comparação do efeito da terapia anti-VEGF (bevacizumab) subconjuntival e tópica na neovascularização corneana experimental

Purpose: To compare the effects of bevacizumab applied either subconjunctivally or topically, in a rat model of corneal neovascularization induced by alkali burn. Methods: The right corneas of 24 Wistar-Albino rats were cauterized with silver nitrate sticks. The rats were divided randomly and equally into three groups: no treatment control (n=8), subconjunctival bevacizumab treatment (n=8), and topical bevacizumab treatment (n=8). Immediately following cauterization, the subconjunctival group was treated with a 0.05 ml (1.25 mg) bevacizumab subconjunctival injection. The topical group was treated with 10 mg/ml bevacizumab twice daily, and the control group received subconjunctival saline injections twice daily. The burn stimulus and neovascularization scores were evaluated using a technique previously described by Mahoney and Waterbury. Digital photographs were obtained before the eyes were enucleated and corneal sections were then analyzed by histopathology. Results: The mean burn stimulus score was 1.86 ± 0.6 and there was no statistical difference between the groups (p=0.730). The mean neovascularization scores in the subconjunctival and topical bevacizumab groups were statistically lower than the control group (p<0.05). The mean percentage area of corneal neovascularization was 82.5 ± 22.1 in the control group, 42.7 ± 15.0 in the subconjunctival group, and 55.8 ± 18.2 in the topical group. The differences between the control and treatment groups were statistically significant (p<0.05). Histopathology showed that the treatment groups presented less neovascularization, inflammation, and fibroblast activity than the control group (p<0.05). Conclusions: This study demonstrates that both subconjunctival and topical administrations of bevacizumab inhibit corneal neovascularization and decrease inflammation and fibroblast activity in a rat model of corneal neovascularization induced by alkali burn. .

Objetivo: Comparar o efeito de bevacizumab aplicado subconjuntival e topicamente em um modelo de neovascularização de córnea de ratos induzida por queimadura alcalina. Métodos: Córneas direitas de 24 ratos Wistar-Albino foram cauterizados por nitrato de prata. Os indivíduos foram divididos aleatoriamente e igualmente em três grupos: controle (n=8), o bevacizumab subconjuntival (n=8), o bevacizumab tópico (n=8). Imediatamente após a cauterização, 0,05 ml (1,25 mg) de bevacizumab foi injetado no grupo subconjuntival. Grupo tópico foi inculcado com 10 mg/ml de bevacizumab duas vezes por dia. O grupo controle recebeu solução salina normal, topicamente, duas vezes ao dia. A graduação do estímulo da queimadura e a graduação da neovascularização foram avaliados utilizando a técnica descrita por Mahoney e Waterbury. Fotografias digitais foram obtidas dos olhos serem enucleados. Seções da córnea foram analisadas por histopatologia. Resultados: A média da graduação do estímulo da queimadura foi de 1,86 ± 0,6 e não houve diferença estatisticamente entre os grupos (p=0,730). As médias das graduações da neovascularização no grupo bevacizumab subconjuntival e no grupo bevacizumab tópico foram estatisticamente menores do que o grupo controle (p<0,05). A percentagem média de área de neovascularização da córnea foi de 82,5 ± 22,1 no grupo controle, 42,7 ± 15,0 no grupo subconjuntival e 55,8 ± 18,2 no grupo tópico. As diferenças entre os grupos de tratamento e grupo de controlo foram estatisticamente significativos (p<0,05). A histopatologia mostrou que os grupos de tratamento apresentavam menos neovascularização, inflamação e atividade de fibroblastos do que o grupo controle (p<0,05). ...

Ranibizumab Injection for Corneal Neovascularization Refractory to Bevacizumab Treatment

Vascular endothelial growth factor inhibitor is an emerging therapeutic modality for various ocular diseases with neovascularization (NV). However, for corneal NV, controversy remains regarding whether bevacizumab or ranibizumab is superior. A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory corneal NV despite two previous subconjunctival and intrastromal bevacizumab injections, received two subconjunctival and intrastromal ranibizumab injections. Six months postoperatively, there was significant regression of the neovascular area and vessel caliber. Here, the authors report a case of improvement in corneal NV with subconjunctival and intrastromal ranibizumab injections, which was previously refractory to bevacizumab injection. The findings may suggest a new prospect in treating corneal NV.

Bevacizumab subconjuntival y su efectividad en la regresión de la neovascularización corneal evaluado mediante angiografía fluoresceínica de segmento anterior / Subconjunctival bevacizumab effectiveness in corneal neovascularization regression evaluated with anterior segment fluorescein angiography

Objetivo: evaluar objetivamente mediante el uso de angiografía de segmento anterior la reducción del grado de neovascularización corneal con la aplicación de bevacizumab subconjuntival. Diseño: serie de casos con intervención. Metodología: nueve ojos con neovascularización corneal estromal secundaria a diferentes condiciones se sometieron a la realización de angiografía fluoresceínica de segmento anterior; cuatro semanas después se aplicaron 3 dosis de bevacizumab subconjuntival limbar de 2,5 mg/0,1cc cada una sobre el cuadrante comprometido con un intervalo de un mes entre cada aplicación. Cuatro semanas después se realizó una nueva angiografía. Las fotos pre-aplicación y post aplicación fueron analizadas por 3 evaluadores. Se definió como mejoría si había una mejoría ≥30%, basado en una escala de mejoría de 0 a 10. Resultados: se encontró un alto rango de variabilidad en la regresión de la neovascularización corneal (entre 3% y 92%) con un promedio de mejoría del 41% y posibilidad de falla de 44,4% independientemente de su etiología. Se obtuvieron pobres resultados en presencia de cuerpos extraños en córnea (segmentos intraestromales o suturas corneales) con una mejoría entre 3% y 7%. Pacientes sin cuerpo extraño en córnea obtuvieron una mejoría promedio de la neovascuarización corneal del 70%. No hubo efectos secundarios sistémicos o locales. Conclusion: el uso del bevacizumab subconjuntival como terapia antiangiogénica es una alternativa con buena tasa de efectividad en pacientes con neovascularización corneal sin presencia de cuerpos extraños corneales.

Purpose: to assess corneal stromal neovascularization accurately and its improvement by using anterior segment fluorescein angiography imaging after subconjunctival bevacizumab injection. Design: interventional case series. Methodology: an anterior segment fluorescein angiography was performed in nine eyes with stromal neovascularization secondary to different etiologies. Patients underwent subconjunctival bevacizumab injections, each one receiving three injections containing 2,5mg/0,1ml bevacizumab each, at monthly intervals. Four weeks after the last injection was applied, a new anterior segment fluorescein angiography was done; pre and post-treatment angiographies were analyzed by three ophthalmologists. A favorable outcome was defined as an improvement of 30% in corneal neovascularization based on a previously established score from 0 to 10. Results: findings were variable, with corneal neovascularization improving between 3% and 92% (mean improvement 41%) for all eyes included, and a 44,4% chance of failure. Poor results were obtained from eyes that had some type of intracorneal foreign body such as intracorneal ring segments (ICRS) and corneal sutures with an improvement range from 3% to 7% whereas eyes with no foreign bodies had a mean reduction in corneal neovascularization of 70%. No side effects were reported. Conclusions: subconjunctival Bevacizumab use as antiangiogenic therapy is an alternative with a high success rate in patients without intracorneal foreign bodies, although it is clearly not as effective in patients with foreing body-induced neovascularization.

The Effect of Bevacizumab versus Ranibizumab in the Treatment of Corneal Neovascularization: A Preliminary Study

PURPOSE: To compare the short term effects of bevacizumab and ranibizumab injections on the regression of corneal neovascularization (NV). METHODS: Sixteen eyes of 16 patients with corneal NV were randomly assigned for an injection with 2.5 mg of bevacizumab (group 1, n = 8) or 1 mg of ranibizumab (group 2, n = 8) through subconjunctival and intrastromal routes. The patients were prospectively followed-up for one month after the injections. Corneal NV areas, as shown on corneal slit-lamp photographs stored in JPEG format, were calculated using Image J software before the injection, one week after the injection, and one month after the injection. The corneal NV areas were compared before and after the injections. RESULTS: Seven women and nine men, with an average age of 51 years, presented with corneal NV secondary to herpetic keratitis (7 cases), graft rejection (6), chemical burn (1), pemphigoid (1), and recurrent ulcer (1). In group I, the preoperative corneal NV area (8.75 +/- 4.33%) was significantly decreased to 5.62 +/- 3.86% one week after the injection and to 6.35 +/- 3.02% one month after the injection (p = 0.012, 0.012, respectively). The corneal NV area in group 2 also exhibited a significant change, from 7.37 +/- 4.33% to 6.72 +/- 4.16% one week after the injection (p = 0.012). However, no significant change was observed one month after the injection. The mean decrease in corneal NV area one month after injection in group 1 (28.4 +/- 9.01%) was significantly higher than in group 2 (4.51 +/- 11.64%, p = 0.001). CONCLUSIONS: Bevacizumab injection resulted in a more effective and stable regression of corneal NV compared to the ranibizumab injection. The potency and dose of these two drugs for the regression of corneal NV require further investigation.

Intrastromal injection of bevacizumab in patients with corneal neovascularization / Injeção intraestromal de bevacizumabe em pacientes com neovascularização corneana

Corneal neovascularization (NV) not only reduces visual acuity, but it also causes loss of the cornea's immune privilege, strongly contributing to a worse prognosis in penetrating keratoplasty. Several mediators participate in corneal angiogenesis, and the role of vascular endothelial growth factor (VEGF) has been extensively proven. Anti-VEGF agents have been shown to be effective in slowing the growth of corneal neovessels. Bevacizumab, an anti-VEGF agent, has been successfully used in the treatment of corneal neovascularization. In this paper, we report a series of patients who underwent intracorneal bevacizumab injections to treat corneal vascularization.

Além de causar redução da acuidade visual, a neovascularização corneana leva à perda do privilégio imunológico da córnea, contribuindo para um pior prognóstico em casos de ceratoplastia penetrante. Diversos mediadores participam da angiogênese corneana. O papel do fator de crescimento endothelial vascular (VEGF) já foi amplamente descrito. Agentes inibidores do VEGF são eficazes na redução do crescimento de neovasos corneanos. Bevacizumabe, um agente anti-VEGF, tem sido utilizado com sucesso no tratamento de neovascularização corneana. Neste artigo, relatamos uma série de pacientes que foram submetidos à injeção intraestromal de bevacizumabe para o tratamento de vascularização corneana.

Efficacy of subconjunctival bevacizumab injection in corneal neovascularisation.

Aim: To evaluate the therapeutic effect of subconjunctival Bevacizumabon corneal neovascularisation Design: A prospective randomized noncomparative study. Method: The charts of 10 consecutive patients with corneal neovascularisation who received single S.C. inj. of Bevacizumab (2.5mg/0.1ml) were reviewed. Digital photographs of the cornea were taken pre & post injection & then at 1 wk,3wk & 2months duration. Digital photographs of the cornea were analyzed to determine the length, density, extent, centricity of corneal neovascularisation and the area of cornea covered by neovascularisation as a percentage of the total corneal area. Results: Subconjunctival injection of Bevacizumab (Avastin) caused significant regression of corneal neovascularisation in 1 pt, partial regression in 6 pts and no effect in 3 pts as measured by length and surface area of neovascularisation. No significant ocular or systemic complications were found. Conclusion: Subconjunctival inj. of Bevacizumab is effective in regressing corneal neovascularisation.

The effect of subconjunctival bevacizumab on corneal neovascularization, inflammation and re-epithelization in a rabbit model

PURPOSE: To evaluate the use of subconjunctival bevacizumab on corneal neovascularization in an experimental rabbit model for its effect on vessel extension, inflammation, and corneal epithelialization. METHODS: In this prospective, randomized, blinded, experimental study, 20 rabbits were submitted to a chemical trauma with sodium hydroxide and subsequently divided into two groups. The experimental group received a subconjunctival injection of bevacizumab (0.15 m; 3.75 mg), and the control group received an injection of 0.15 ml saline solution. After 14 days, two blinded digital photograph analyses were conducted to evaluate the inflammation/diameter of the vessels according to pre-established criteria. A histopathological analysis of the cornea evaluated the state of the epithelium and the number of polymorphonuclear cells. RESULTS: A concordance analysis using Kappa's statistic showed a satisfactory level of agreement between the two blinded digital photography analyses. The neovascular vessel length was greater in the control group (p<0.01) than in the study group. However, the histopathological examination revealed no statistically significant differences between the groups in terms of the state of the epithelium and the number of polymorphonuclear cells. CONCLUSIONS: Subconjunctival bevacizumab inhibited neovascularization in the rabbit cornea. However, this drug was not effective at reducing inflammation. The drug did not induce persistent corneal epithelial defects.

Uso do bevacizumab (Avastin®) na síndrome KID: relato de caso / Use of bevacizumab (Avastin®) in KID syndrome: case report

A síndrome KID é uma displasia ectodérmica congênita rara, caracterizada pela associação de lesões hiperceratóticas de pele, surdez neurossensorial e ceratite. O comprometimento ocular ocorre em 95 por cento dos portadores da síndrome. Embora as manifestações dermatológicas tenham sido bastante estudadas, sabe-se pouco sobre o manejo e o prognóstico do acometimento oftalmológico. Até o momento, o tratamento ocular da síndrome KID inclui tratamento sintomático, não havendo na literatura drogas ou tratamento cirúrgico que possam modificar o curso e prognóstico da doença. Neste relato de caso, descrevemos os achados oftalmológicos de um portador de síndrome KID e o uso de bevacizumab (Avastin®) subconjuntival como sugestão para o tratamento da neovascularização corneana. Apesar da ausência de melhora e da raridade da doença, os autores acreditam que a utilização do bevacizumab subconjuntival possa ser útil para o tratamento da neovascularização corneana que se estabelece na síndrome KID e incentivam os pesquisadores a se aprofundar neste tema.

KID syndrome is a congenital ectodermal dysplasia characterized by the association of keratitis, hyperkeratotic skin lesions and neurosensorial hearing loss. Ocular involvement occurs in 95 percent of patients. Although KID syndrome cutaneous manifestations have been studied in-depth, the treatment and prognosis of ophthalmic impairment have not been described in detail. At present, the treatment of the ocular damage caused by the syndrome is symptomatic and there are no studies defining a treatment that could change the disease course. In this case, ophthalmologic findings of a patient with KID syndrome and the use of subconjunctival bevacizumab to treat corneal neovascularization are described. In spite of the absence of improvement in this patient and the few reports of this disease, aditional studies with bevacizumab to treat corneal deep neovascularization are suggested.

Factors Influencing the Prevalence of Amblyopia in Children with Anisometropia

PURPOSE: To evaluate factors that can influence the prevalence of amblyopia in children with anisometropia. METHODS: We retrospectively reviewed the records of 63 children 2 to 13 years of age who had anisometropic amblyopia with a difference in the refractive errors between the eyes of at least two diopters (D). The type of anisometropia (myopia, hyperopia, and astigmatism), degree of anisometropia (4 D), best corrected visual acuity (BCVA) of the amblyopic eye at the time of initial examination, BCVA differences between sound and amblyopic eyes, whether or not occlusion therapy was performed, compliance with occlusion therapy, and the patient's age when eyeglasses were first worn were investigated. RESULTS: There was an increase in the risk of amblyopia with increased magnitude of anisometropia (p=0.021). The prevalence of amblyopia was higher in the BCVA 4 lines between sound and amblyopic eyes (p=0.008 and p=0.045, respectively). There was no statistical relationship between the prevalence of amblyopia and the type of anisometropia or the age when eyeglasses were first worn. Poor compliance with occlusion therapy was less likely to achieve successful outcome (p=0.015). CONCLUSIONS: Eyes with poor initial visual acuities of 4 line difference in the BCVA between sound and amblyopic eyes at the initial visit may require active treatment.

The Effect of Bevacizumab on Corneal Neovascularization in Rabbits

PURPOSE: To determine the efficacy of topical application and subconjunctival injection of bevacizumab in the treatment of corneal neovascularization. METHODS: Corneal neovascularization was induced with a silk suture of the corneal stroma in 12 rabbits (24 eyes). One week after suturing, four rabbits were treated with topical bevacizumab at 5 mg/mL (group A) and another four rabbits were treated with topical bevacizumab 10 mg/mL (group B) in the right eyes twice a day for two weeks. A subconjunctival injection of bevacizumab 1.25 mg/mL was done in the right eyes of four rabbits (group C). All of the left eyes (12 eyes) were used as controls. The area of corneal neovascularization was measured after one and two weeks, and the concentration of vascular endothelial growth factor (VEGF) in corneal tissue was measured after two weeks. RESULTS: The neovascularized area was smaller in all treated groups than in the control group (p<0.001). Upon analysis of the neovascularized area, there was no significant difference between groups A and B. However, the mean neovascularized area of group B was significantly smaller than that of group C after two weeks of treatment (p=0.043). The histologic examination revealed fewer new corneal vessels in all treated groups than the control group. The concentration of VEGF was significantly lower in all treated groups compared to the control group (p<0.01), but no difference was shown between treated groups. CONCLUSIONS: Topical and subconjunctival bevacizumab application may be useful in the treatment of corneal neovascularization and further study is necessary.

The effects of the subconjunctival injection of bevacizumab (Avastin®) on angiogenesis in the rat cornea

The purpose of this study was to evaluate the effects of the use of the subconjunctival injection of bevacizumab (Avastin®) on angiogenesis in the rat cornea. Corneas of 20 Wistar male rats were cauterized with silver nitrate crystal. Animals were divided in four groups: control group (GC) that received subconjunctivally 0.02 ml of 0.9 percent saline solution on the day of the lesion; group GO that received subconjunctivally 0.02 ml of bevacizumab just after the lesion; group G3 that received bevacizumab on day 3 and group G5 that received bevacizumab on day 5 after lesion. Animals were euthanized on day 7. The newly formed vessels were quantified after China Ink perfusion and photographs were obtained and analyzed in a computerized system (Image Pro-Plus®). In the control group, neovascularization covered 53.56 percent ± 15.11 (mean ± SD) of the corneal surface, compared with 35.57 percent ± 18.80 (mean ± SD) in the G0 group, 30.60 percent±11.82 (mean±SD) in the G3 and 35.86 percent±0.07 (mean±SD) in the G5. The results showed an inhibition of angiogenesis when the control group was compared with all treated groups. These results suggest that subconjunctival injection of bevacizumab is able to inhibit corneal angiogenesis independently of the day of treatment.

O objetivo deste estudo foi avaliar os efeitos da aplicação subconjuntival de bevacizumab (Avastin®) na angiogênese corneal em ratos. Vinte ratos Wistar, machos, foram submetidos a cauterização química com cristal de nitrato de prata. Os animais foram divididos em 4 grupos: O grupo controle (GC), recebeu injeção de 0,02 ml de solução fisiológica pela via subconjuntival no momento da lesão. O grupo G0 recebeu 0,02 ml de bevacizumab (Avastin®) imediatamente depois da lesão. O grupo G3 recebeu 0,02 ml de bevacizumab no terceiro dia após a lesão.O grupo G5 recebeu 0,02 ml de bevacizumab no quinto dia após a lesão. Os animais foram eutanasiados 7 dias após a cauterização. Os vasos neoformados foram quantificados após preenchimento do leito vascular com Tinta da China e imagens foram obtidas e analisadas em sistema computadorizado (Image Pro-Plus®). No grupo controle a neovascularização ocupou 53,56 por cento ± 15,11 (média ± DP) da superfície corneal comparando a 35,57 por cento ± 18,80 no grupo G0, 30,60 por cento ± 11,82 (média ± DP) no G3 e 35,86 por cento ± 0,07 (média ± DP) no G5. Os resultados mostram uma inibição da angiogênese quando se compara GC com os grupos tratados. Os resultados sugerem que a injeção subconjuntival de Bevacizumab é capaz de inibir a angiogênese corneal independentemente do dia de aplicação.

Inhibition of corneal neovascularization by rapamycin

The purpose of this study was to determine whether rapamycin could inhibit corneal angiogenesis induced by basic fibroblast growth factor (bFGF). Using human dermal microvascular endothelial cells (HDMECs), we examined the effect of rapamycin on cell proliferation and migration, and the expression of vascular endothelial growth factor (VEGF). The rabbit's eye was implanted intrastromally into the superior cornea with pellet containing bFGF for the control group and pellet containing bFGF and rapamycin for the rapamycin group. Biomicrographically, corneal angiogenesis was evaluated for 10 days after pellet implantation. The neovascularized cornea also was examined histologically. bFGF induced corneal neovascularization was significantly reduced by treatment with rapamycin. Using in vitro model, rapamycin strongly inhibited bFGF induced proliferation, migration, and VEGF secretion of HDMECs. We could observe that the bFGF induced corneal angiogenesis was inhibited by rapamycin in a micropocket rabbit model. The score of neovascularization was significantly decreased in the rapamycin group than in the control group at 10 days after pellet implantation. Histologically, the cornea of rapamycin group also showed much less new vessels than that of control group. Collectively, rapamycin appears to inhibit bFGF induced angiogenesis in a rabbit corneal micropocket assay and may have therapeutic potential as an antiangiogenic agent.