Este estudo teve por objetivo avaliar a eficácia e a segurança da cirurgia de implante de Ahmed, associada à ressecção parcial da cápsula de Tenon e ao uso da mitomicina C, em portadores de glaucoma neovascular. A amostra foi constituída por 31 olhos de trinta pacientes portadores de glaucoma neovascular, secundário à retinopatia diabética proliferativa ou à oclusão da veia central da retina, com acuidade visual maior ou igual à percepção luminosa. Os olhos foram randomizados para formarem dois grupos: implante de Ahmed convencional, associado ao uso da mitomicina C (n=15), e implante de Ahmed de alta resistência, associado à ressecção parcial da cápsula de Tenon e ao uso da mitomicina C (n=16). Controlaram-se as variáveis procurando homogeneizar os grupos a fim de prevenir vieses nas avaliações dos desfechos. Definiram-se como sucesso cirúrgico simples os casos com pressões oculares maiores ou iguais a 5 mm Hg e menores ou iguais a 21 mm Hg. A média de idade foi de 58,06 anos ± 13,02 , sendo de 62,63 anos ± 10,23 no grupo com e de 53,20 anos ± 14,22 no grupo sem ressecção parcial da cápsula de Tenon (p = 0,109). Não houve diferença estatisticamente significativa entre os grupos com relação ao sexo (p = 0,722), olho operado (p = 1,0), causa do glaucoma neovascular (p = 1,0), existência de panfotocoagulação prévia (p = 1,0) e acuidade visual pré-operatória (p = 0,154). A pressão ocular média pré-operatória foi de 51,00 ± 10,05 mm Hg no grupo com ressecção parcial da cápsula de Tenon e de 51,20 ± 11,58 mm Hg no grupo sem ressecção da cápsula de Tenon (p = 0,889). Houve redução significativa da pressão ocular em ambos os grupos a partir do primeiro dia do pós-operatório. A pressão ocular média dos grupos com e sem ressecção parcial da cápsula de Tenon aos 24 meses de seguimento foi de, respectivamente, 17,00 ± 12,77 mm Hg e 19,78 ± 15,71 mm Hg (p = 0,820). O seguimento médio foi de 23,44 meses ± 9,63 no grupo com ressecção parcial da cápsula de Tenon e de 23,40 meses ± 9,62 no grupo sem ressecção parcial da cápsula de Tenon (p = 0,952). Registraram-se diferenças estatisticamente significativas entre as pressões médias nos grupos com e sem ressecção parcial da cápsula de Tenon apenas no primeiro dia, terceiro e sétimo meses do pós-operatório. Houve redução mais intensa da acuidade visual no grupo sem ressecção parcial da cápsula de Tenon do que no grupo com exérese da cápsula de Tenon (p = 0,023*). O sucesso simples foi de 62,5% (dez olhos) no grupo com e de 53,3% (oito olhos) no grupo sem ressecção parcial da cápsula de Tenon (p = 0,722). Não se verificaram bolhas transparentes, pálidas ou isquêmicas em fase alguma do pós-operatório, em ambos os grupos. As freqüências das complicações foram semelhantes em ambos os grupos, exceto por uma freqüência quase quatro vezes maior de exposição do implante no grupo com ressecção parcial da cápsula de Tenon. Em resumo, os índices de sucesso cirúrgico foram semelhantes entre os grupos com e sem ressecção parcial da cápsula de Tenon, após um seguimento médio de 23,42 meses. Houve redução significativa da acuidade visual nos dois grupos, a qual foi mais intensa naquele sem ressecção parcial da cápsula de Tenon. A exposição do implante de drenagem foi quase quatro vezes mais freqüente no grupo submetido à ressecção parcial da cápsula de Tenon / The objective of the study was to evaluate the safety and efficacy of Ahmed glaucoma valve implant surgery combined with partial Tenon\'s capsule resection and mitomycin C administration in neovascular glaucoma patients. Our sample comprised 31 eyes of 30 patients with neovascular glaucoma secondary to proliferative diabetic retinopathy or central retinal vein occlusion. The 30 patients all had visual acuity equal to or greater than their perception of light. The eyes were randomized into two groups: conventional Ahmed valve implant combined with mitomycin C administration (n = 15); and high-resistance Ahmed implant combined with partial Tenon\'s capsule resection and mitomycin C administration (n = 16). Variables were controlled in an attempt to homogenize the groups and thereby avoid any bias in the evaluation of the results. Simple surgical success was defined as ocular pressure equal to or greater than 5 mmHg but less than or equal to 21 mmHg. Median age was 58.06 ± 13.02 (53.20 ± 14.22 in the group not submitted to resection and 62.63 ± 10.23 in the group submitted to partial Tenon\'s capsule resection; p = 0.109). No statistically significant difference between the groups was found related to gender (p = 0.722), operated eye (p = 1.0), cause of neovascular glaucoma (p = 1.0), previous panphotocoagulation (p = 1.0), or preoperative visual acuity (p = 0.154). Mean preoperative ocular pressure was 51.20 ± 11.58 mmHg in the group not submitted to resection and 51 ± 10.05 mmHg in the group submitted to partial Tenon\'s capsule resection (p = 0.889). From the first preoperative day, there was a significant reduction in ocular pressure in both groups. At 24 months after surgery, mean ocular pressure of subjects not submitted and submitted to partial Tenon\'s capsule resection was 19.78 ± 15.71 mmHg and 17.00 ± 12.77 mmHg, respectively (p = 0.820). Mean length of the follow-up period was 23.40 ± 9.62 months in those not submitted to resection and 23.44 ± 9.63 months in the group submitted to partial Tenon\'s capsule resection (p = 0.952). Statistically significant differences in ocular pressure were found between the two groups only on postoperative day 1 and at 3 and 7 months after surgery. In the group not submitted to resection, there was a more marked reduction in visual acuity (p = 0.023*). Simple surgical success was achieved in 53.3% (8) of the eyes in the group not submitted to resection and in 62.5% (10) of the eyes in the group submitted to partial Tenon\'s capsule resection (p = 0.722). There were no pale or transparent blebs in either group during the postoperative phase. The incidence of complications was similar between the two groups, with the exception of the incidence of implant tube exposure, which was four times greater in the group submitted to partial Tenon\'s capsule resection. In conclusion, after a mean follow-up period of 23.42 months, the measures of surgical success were comparable between the two groups. There was significant reduction in visual acuity in both groups, more markedly in the group not submitted to resection. The implant drainage tube became exposed four times more frequently in the group submitted to partial Tenon\'s capsule resection

本研究採用結紮眼血管的方法誘發短暫性視網膜缺血，針對同缺血時間同存活時間化成年金黄地鼠中視網膜節細胞的存活和小型膠質細胞的激活。首先，我們的據顯示，和假缺血手術組相對應的存活時間比較，暫時性視網膜缺血10分鐘或30分鐘沒有導致視網膜節細胞的存活明顯下。暫時性視網膜缺血60分鐘再灌注後7天，視網膜節細胞的存活下至58%，14後為51%，28後為44%。暫時性視網膜缺血120分鐘之後再灌注7天，視網膜節細胞的存活急劇下，僅保22%，至14天，僅剩17%, 之後節細胞的死亡速減緩，至28天時，仍由18%存活。視網膜缺血10分鐘、30分鐘、60分鐘和120分鐘均引起大小型膠質細胞激活，激活在第七天達到頂峰，之後在14天和28天顯著並逐步下。相關性分析發現損傷後7天，視網膜節細胞的死亡和視網膜節細胞層中的小型膠質細胞存在緊密的相關性。 / 其次，我們首次證實缺血性預處僅有於提高視網膜節細胞對抗視網膜缺血/再灌注損傷，還對視神經斷後的視網膜節細胞同樣具有保護作用。結果顯示無是5分鐘還是10分鐘的缺血性預處，無是軸突橫斷術前1天還是前3天實施預處，都對視網膜節細胞有明顯的保護作用。在缺血性預處對抗神經橫斷損傷的實驗組, 的表達只表現在陽性細胞上的明顯優勢，但占全部存活細胞的百分比存在差；而缺血性預處對抗視網膜缺血再灌注損傷的實驗組，的陽性節細胞的無論還是存活百分比都存在差。在預處組和假處組的比較中， 的表達也只是陽性細胞上較多，占全部存活細胞的百分比存在差。在缺血性預處加視網膜缺血分鐘的實驗組中，我們測視網膜矢片中各層的厚。結果顯示，缺血性預處組中，視網膜的整體厚和節細胞層的厚都與正常組相當，而假處組中，這層的厚明顯減少。 / 進一步地，我們研究遠端缺血性後處對視網膜節細胞對抗視神經軸突橫斷術的保護作用。我們選用鉗夾右股動脈作為遠端缺血性後處的方法，鉗夾股動脈分鐘，之後放開，再鉗夾再放開，共個循環。結果顯示，軸突橫斷術后分鐘實施缺血性后處組，視網膜節細胞的存活較假處組明顯增加，包括術後天和天；軸突橫斷術后小時實施缺血性後處組，視網膜節細胞的存活只在術後天較假處組明顯較多，但在天的實驗組，者的差消失；軸突橫斷術小時實施缺血性後處組，視網膜節細胞的存活比假處組多。在缺血性後處的實驗中，視神經橫斷術后分鐘實施遠端缺血性後處的實驗組與假處組比較，的表達僅表現在陽性細胞上的明顯增加，而且占全部存活細胞的百分比也明顯增加。的表達與預處實驗組的結果相似，只存在上的優勢。 / 我们的實驗證明，缺血性預處在對抗視神經橫斷和視網膜缺血的損傷中，可以為節細胞提供有效的保護作用，遠端缺血性後處可以對抗視神經橫斷損傷提高節細胞的存活。陽性節細胞在三個同條件的實驗中，表現出同的結果，这可能暗示遠端缺血性後處對抗視神經橫斷術的損傷，節細胞的再生能較優，與遠端缺血性後處對抗視神經橫斷術的神經保護作用有一定關。的表達在三個實驗組中，處組與假處組比較，均只表現出陽性細胞上的優勢，占存活細胞的百分比就存在差，可能意味著與缺血性預處和後處的保護作用關係不大。 / Ligature of the ophthalmic vessels (LOV) was used as an animal model to study transient retinal ischemia/reperfusion in adult hamsters. Firstly, we quantified the loss of retinal ganglion cells (RGCs) and activation of microglia after10 min, 30 min, 60 min or 120 min retinal ischemia at 7, 14 and 28 days post-ischemia. The results showed that after 10-min or 30-min retinal ischemia, the number of RGCs had no significant decrease compared to sham LOV group at 7 days. In the retinal ischemia 60 min group, there were 58% of the RGCs population remained alive at 7 days, 51% at 14 days and 44% at 28 days post-ischemia, respectively. In the retinal ischemia 120 min group, the number of RGCs was reduced to 22% at 7 days and 17% at 14 days, but cell death slowed down from 14 to 28 days. Meanwhile, the number of microglia was increased sharply at 7 days and decreased gradually from 7 to 28 days. At the same time, it was found that the loss of RGCs and activation of microglia in the ganglion cell layer at 7 days post-insult existed strong positive correlation. / Secondly, the effects of ischemic preconditioning (IPC) were proved to promote RGCs survival after axotomy or retinal ischemia 120 min. It was presented firstly that a 5 or 10 min brief IPC which performed 1 or 3 days prior to axotomy enhanced the RGCs survival at 7 days and 14 days post-axotomy. The number of HSP27-positive RGCs was significantly higher in the IPC plus axotomy subgroup compared with the sham-operated subgroup, while the percentage of HSP27-positive RGCs did not show significant difference between subgroups. For the IPC plus retinal ischemia 60 min group, both the number and the percentage of HSP27-positive RGCs had no significant difference between IPC and sham-operated subgroups. The number of HSP70-positive RGCs exhibited significant difference but not the percentage in IPC plus axotomy or retinal ischemia 60 min experimental groups. The thicknesses of the whole retina and GCL were similar to the normal value in the IPC plus ischemia 60 min subgroup, while in the sham-operated subgroup, these two values decreased significantly. / Consequently, the effect of remote ischemic postconditioning (RIPostC) was also explored to promote RGCs survival after axotomy. Four cycles of 10 min occlusion and 10 min release of the right femoral artery were initiated on animals at 10 min, 6 h or 24 h after axotomy. In the10 min group, the effect of RIPostC on promoting RGCs survival was significant at both 7 and 14 days post-injury. In the 6 h group, the survival of RGCs was more in the RIPostC treatment subgroup at 7 days, while there was no significant difference at 14 days post-axotomy. In the 24 h group, RGC survival was not significantly different at 7 days post-axotomy. Both the number and the percentage of HSP27-positive RGCs were significantly higher in the RIPostC treatment subgroup. The results of the induction of HSP70 only showed a priority in absolute number of the HSP70-positive RGCs in the RIPostC treatment subgroup. / In summary, the effect of IPC has been proved that it could protect RGCs against axotomy and retinal ischemia/reperfusion injury, in addition, the application of RIPostC also protected RGCs from axotomy. The proportion of HSP27-positive RGCs increased significantly in the process of RIPostC against axotomy, which may clue that the ability of axonal regeneration is stronger which induced by the RIPostC intervention. The upregulation of HSP27 might play a role in the neuroprotection of the RIPostC against axotomy. The expression of HSP70 maybe plays a little role in the neuroprotection of the IPC and RIPostC. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liu, Xia. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 182-196). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.i / Abstract in Chinese --- p.iv / Acknowledgements --- p.vii / Table of Abbreviations --- p.viii / Table of Contents --- p.ix / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter Chapter 2 --- Changes of retinal ganglion cells and microglia after different types of injuries / Introduction --- p.38 / Materials and Methods --- p.43 / Results --- p.49 / Discussion --- p.57 / Figures and tables --- p.71 / Chapter Chapter 3 --- Ischemic preconditioning protect retinal ganglion cells against axotomy and retinal ischemia/reperfusion injury and expression of heat shock protein 27 and 70 / Introduction --- p.93 / Materials and Methods --- p.98 / Results --- p.103 / Discussion --- p.109 / Figures and tables --- p.116 / Chapter Chapter 4 --- Remote ischemic postconditioning protect retinal ganglion cells against axotomy and expression of heat shock protein 27 and 70 / Introduction --- p.143 / Materials and Methods --- p.147 / Results --- p.150 / Discussion --- p.154 / Figures and tables --- p.161 / Chapter Chapter 5 --- General Discussion --- p.175 / References --- p.182

Este estudo teve por objetivo avaliar a eficácia e a segurança da cirurgia de implante de Ahmed, associada à ressecção parcial da cápsula de Tenon e ao uso da mitomicina C, em portadores de glaucoma neovascular. A amostra foi constituída por 31 olhos de trinta pacientes portadores de glaucoma neovascular, secundário à retinopatia diabética proliferativa ou à oclusão da veia central da retina, com acuidade visual maior ou igual à percepção luminosa. Os olhos foram randomizados para formarem dois grupos: implante de Ahmed convencional, associado ao uso da mitomicina C (n=15), e implante de Ahmed de alta resistência, associado à ressecção parcial da cápsula de Tenon e ao uso da mitomicina C (n=16). Controlaram-se as variáveis procurando homogeneizar os grupos a fim de prevenir vieses nas avaliações dos desfechos. Definiram-se como sucesso cirúrgico simples os casos com pressões oculares maiores ou iguais a 5 mm Hg e menores ou iguais a 21 mm Hg. A média de idade foi de 58,06 anos ± 13,02 , sendo de 62,63 anos ± 10,23 no grupo com e de 53,20 anos ± 14,22 no grupo sem ressecção parcial da cápsula de Tenon (p = 0,109). Não houve diferença estatisticamente significativa entre os grupos com relação ao sexo (p = 0,722), olho operado (p = 1,0), causa do glaucoma neovascular (p = 1,0), existência de panfotocoagulação prévia (p = 1,0) e acuidade visual pré-operatória (p = 0,154). A pressão ocular média pré-operatória foi de 51,00 ± 10,05 mm Hg no grupo com ressecção parcial da cápsula de Tenon e de 51,20 ± 11,58 mm Hg no grupo sem ressecção da cápsula de Tenon (p = 0,889). Houve redução significativa da pressão ocular em ambos os grupos a partir do primeiro dia do pós-operatório. A pressão ocular média dos grupos com e sem ressecção parcial da cápsula de Tenon aos 24 meses de seguimento foi de, respectivamente, 17,00 ± 12,77 mm Hg e 19,78 ± 15,71 mm Hg (p = 0,820). O seguimento médio foi de 23,44 meses ± 9,63 no grupo com ressecção parcial da cápsula de Tenon e de 23,40 meses ± 9,62 no grupo sem ressecção parcial da cápsula de Tenon (p = 0,952). Registraram-se diferenças estatisticamente significativas entre as pressões médias nos grupos com e sem ressecção parcial da cápsula de Tenon apenas no primeiro dia, terceiro e sétimo meses do pós-operatório. Houve redução mais intensa da acuidade visual no grupo sem ressecção parcial da cápsula de Tenon do que no grupo com exérese da cápsula de Tenon (p = 0,023*). O sucesso simples foi de 62,5% (dez olhos) no grupo com e de 53,3% (oito olhos) no grupo sem ressecção parcial da cápsula de Tenon (p = 0,722). Não se verificaram bolhas transparentes, pálidas ou isquêmicas em fase alguma do pós-operatório, em ambos os grupos. As freqüências das complicações foram semelhantes em ambos os grupos, exceto por uma freqüência quase quatro vezes maior de exposição do implante no grupo com ressecção parcial da cápsula de Tenon. Em resumo, os índices de sucesso cirúrgico foram semelhantes entre os grupos com e sem ressecção parcial da cápsula de Tenon, após um seguimento médio de 23,42 meses. Houve redução significativa da acuidade visual nos dois grupos, a qual foi mais intensa naquele sem ressecção parcial da cápsula de Tenon. A exposição do implante de drenagem foi quase quatro vezes mais freqüente no grupo submetido à ressecção parcial da cápsula de Tenon / The objective of the study was to evaluate the safety and efficacy of Ahmed glaucoma valve implant surgery combined with partial Tenon\'s capsule resection and mitomycin C administration in neovascular glaucoma patients. Our sample comprised 31 eyes of 30 patients with neovascular glaucoma secondary to proliferative diabetic retinopathy or central retinal vein occlusion. The 30 patients all had visual acuity equal to or greater than their perception of light. The eyes were randomized into two groups: conventional Ahmed valve implant combined with mitomycin C administration (n = 15); and high-resistance Ahmed implant combined with partial Tenon\'s capsule resection and mitomycin C administration (n = 16). Variables were controlled in an attempt to homogenize the groups and thereby avoid any bias in the evaluation of the results. Simple surgical success was defined as ocular pressure equal to or greater than 5 mmHg but less than or equal to 21 mmHg. Median age was 58.06 ± 13.02 (53.20 ± 14.22 in the group not submitted to resection and 62.63 ± 10.23 in the group submitted to partial Tenon\'s capsule resection; p = 0.109). No statistically significant difference between the groups was found related to gender (p = 0.722), operated eye (p = 1.0), cause of neovascular glaucoma (p = 1.0), previous panphotocoagulation (p = 1.0), or preoperative visual acuity (p = 0.154). Mean preoperative ocular pressure was 51.20 ± 11.58 mmHg in the group not submitted to resection and 51 ± 10.05 mmHg in the group submitted to partial Tenon\'s capsule resection (p = 0.889). From the first preoperative day, there was a significant reduction in ocular pressure in both groups. At 24 months after surgery, mean ocular pressure of subjects not submitted and submitted to partial Tenon\'s capsule resection was 19.78 ± 15.71 mmHg and 17.00 ± 12.77 mmHg, respectively (p = 0.820). Mean length of the follow-up period was 23.40 ± 9.62 months in those not submitted to resection and 23.44 ± 9.63 months in the group submitted to partial Tenon\'s capsule resection (p = 0.952). Statistically significant differences in ocular pressure were found between the two groups only on postoperative day 1 and at 3 and 7 months after surgery. In the group not submitted to resection, there was a more marked reduction in visual acuity (p = 0.023*). Simple surgical success was achieved in 53.3% (8) of the eyes in the group not submitted to resection and in 62.5% (10) of the eyes in the group submitted to partial Tenon\'s capsule resection (p = 0.722). There were no pale or transparent blebs in either group during the postoperative phase. The incidence of complications was similar between the two groups, with the exception of the incidence of implant tube exposure, which was four times greater in the group submitted to partial Tenon\'s capsule resection. In conclusion, after a mean follow-up period of 23.42 months, the measures of surgical success were comparable between the two groups. There was significant reduction in visual acuity in both groups, more markedly in the group not submitted to resection. The implant drainage tube became exposed four times more frequently in the group submitted to partial Tenon\'s capsule resection