角膜溃疡穿孔临床分析
摘要
目的 探讨角膜溃疡穿孔的发病原因及相关的危险因素，不同临床治疗方法及其疗效评价。
方法 收集我院1993年1月——2003年6月角膜溃疡穿孔病例49例(49眼)，进行回顾性分析，分析角膜溃疡穿孔的病因及发生穿孔的相关危险因素，同时对不同病变所采用的不同治疗方法进行比较、评价各种治疗方法的疗效。
结果 49例患者中有16例经单纯药物治疗后角膜溃疡穿孔愈合，33例经药物联合手术治疗后角膜溃疡穿孔愈合。16例单纯药物治疗患者中，6例患者视力获得不同程度的提高，10例患者无明显改善或略下降；22例穿透性角膜移植患者中17例患者获得不同程度视力提高，5例无变化；2例板层角膜移植患者视力均无变化；3例结膜瓣掩盖术患者视力均无变化。24例角膜移植患者术后移植片18例透明，5例半透明，1例混浊。13例经单纯药物治疗和3例经结膜瓣掩盖术治疗患者遗留粘连性角膜白斑，3例经单纯药物治疗患者遗留单纯性角膜白斑。术后继发青光眼2例，均行青光眼减压术治愈。角膜移植患者术后有6例发生角膜移植排斥反应，均经药物治疗后好转。所有患者经6-12个月随访无溃疡复发者。
结论 病因方面就本组病例来看，感染性角膜溃疡并发穿孔的比例最大，考虑主要有以下原因：1. 角膜溃疡的发生绝大部分为外来感染性致病因子侵入角膜上皮细胞层所致。2. 角膜感染发生后，是否发生溃疡穿孔与许多因素相关，主要有以下两点：（1）角膜溃疡的治疗是否及时而且正确。（2）感染性致病因子的破坏力强弱。近年来随着抗生素特别是广谱抗生素的大量应用，导致耐药菌数量及种类大量增加。此外，绿脓杆菌毒力很强，在繁殖过程中产生一种蛋白溶解酶使角膜的胶原纤维被溶解，整个角膜可在很短时间内遭到严重破坏，2-3天角膜即可发生穿孔。近年来真菌性角膜溃疡在我国发病率逐年增加，它的临床表现多种多样，极易误诊。而且目前缺乏敏感有效的抗真菌药物，所以许多病例得不到有效及时的治疗。最后往往导致角膜穿孔的发生。病毒感染很常见，易于复发，较难完全治愈，且与全身身体状况有关，亦有穿孔危险。棘阿米巴角膜溃疡不常见，但其病程长、症状轻，易误诊，有穿孔危险。非感染性角膜溃疡原因很多，病情轻重各异，有发生角膜穿孔的危险。
临床表现与诊断方面应注意及早发现小的穿孔和穿孔倾向。穿孔面积较小时，房水流出速度很慢，前房略浅或基本正常，虹膜及晶状体维持原位，眼后节无明显异常，此时不易发现角膜穿孔，可用荧光素进行角膜染色，穿孔处荧光素可被缓
慢流出的房水冲走，即可诊断角膜溃疡穿孔。此时积极治疗有机会取得较疗效。如漏诊此类小穿孔导致穿孔面积扩大及并发症的发生，治疗则较为棘手且治疗效果较差。
病因的诊断是否明确关系到能否合理的选用敏感有效的药物进行治疗，对预后影响很大。感染性角膜溃疡穿孔的病因即病原体的明确诊断尤为重要。首先应根据病变的特点进行初步判定，然后应用相应的方法进行检测，对怀疑细菌感染者应进行细菌培养及药物敏感试验，对怀疑有真菌感染者应行角膜组织刮片检查。
治疗方面应强调及时、合理。
药物治疗是有效的方法，对于穿孔面积较小的病例效果较好。药物治疗主要包括以下几方面。（1）针对病因用药：对于感染性角膜溃疡穿孔，最重要的是针对病原体选用敏感有效的药物，尽可能防止穿孔的继续扩大，根据病情全身及眼局部应用，力求迅速控制感染。对无法确定致病菌者，应给予广谱抗生素治疗。对怀疑有真菌感染但无法确定者应给予抗真菌药物治疗。对非感染性角膜溃疡穿孔者，主要针对其病因用药，如蚕食性角膜溃疡穿孔应用免疫抑制剂等，但非感染性角膜溃疡一旦发生角膜穿孔，药物治疗短期内一般很难使穿孔愈合，多需手术治疗。（2）应用降眼压药：应用降眼压药物使眼内压力维持在较低水平，这样既可在一定程度上预防继发青光眼的发
生，又可减少眼内组织向穿孔处移动并嵌顿等并发症的发生，同时减轻眼内压力对角膜的作用、促进角膜愈合。对药物控制眼压效果不理想、有继发青光眼危险或已发生继发青光眼者应及时行青光眼减压术。（3）角膜营养剂治疗：角膜营养剂可促进角膜组织的生长，对提高角膜组织的抗病能力亦有一定的帮助。此外，应用自家血清点眼可促进角膜的愈合，因为自体血清可以起到非特异性脱敏的作用，同时可提供给角膜营养物质，支持角膜组织的生命过程，使其抵抗力增强，还可以提供感染区较高浓度的特异性抗体。
手术治疗方面重要的是根据病情及治疗条件的不同，选择合理的手术时机和方法。手术治疗的目的首先是恢复眼球的完整性，进而恢复眼内结构特别是眼前节结构的正常。手术治疗方法有结膜瓣掩盖术、羊膜移植术、角膜移植术等。（1）手术方法的选择：穿透性角膜移植术用完整健康的角膜代替病变的残缺的角膜，不但可以恢复眼球的完整性，还可以恢复角膜的透明性，达到清除病灶和恢复视力的双重作用，因此，如有角膜材料，穿透性角膜移植术无疑是最佳的治疗方法。板层角膜易于长时间保存，同时具有完整角膜的透明性，在无全层角膜材料的情况下用保存的板层角膜修补角膜穿孔处来恢复眼球的完整性是一种很有效的方法。结膜瓣
Objective: to study the etiology and related risk factors of cornea ulcer with perforation, different kind of clinical treatment and the evaluation of their prognosis.
Method: 49 cases of cornea ulcer perforation from January 1993 to June 2003 were collected and retrospective analysis performed. Mechanism and risky factors of different etiology was analyzed. Different ways of clinical treatment were compared and the prognosis evaluated.
Result: In 16 of the 49 cases, the ulcers were healed after simple drug therapy. In 33, the ulcers were healed after the combined therapy of drug and surgery. For 6 of the 16 cases of simple drug therapy, the vision acuity was increased and for the other 10, the vision acuity was not significantly improved or decreased a little. For 17 of the 22 cases of penetrative cornea transplantation, the vision acuity was increased and for the other 5 no
difference was observed. The vision acuity of 2 patients of lamellar cornea transplantation was not changed at all. The vision acuity of 2 patients of conjunctive flap was not changed at all. 18 transplants of the 24 cases of keratoplasty were transparent, 5 were semi-transparent, 1 was cloudy. Adherent leukoma of cornea was found in 13 of the cases of simple drug therapy and 3 cases of conjunctive flap. Simple leukoma of cornea were found in 3 cases of simple drug therapy. Glaucoma was developed for 2 cases after operation and glaucoma decompression was performed. Transplant rejection was developed in 6 patients after keratoplasy and the condition was improved after drug therapy. No recurrence of ulcer was found for all the cases afte 6-12 months of follow-up.
Conclusion: Of all the causes of the disease, infective cornea ulcer was the most ordinary, the reason of which is as follows: 1) the external invasion of infective factors was the most common reason for the ulcer of cornea; 2) the ongoing of perforation after the infection of cornea was related to many factors namely 2: (1) the cornea ulcer was treated correctly and duly; (2)
the damage caused by the infective factors is severe or not. Recently with the development of antibiotics, especially the wide application of wide-spectrum antibiotics, the number of drug resistant strains of bacteria increased a lot. Besides, pseudomonas aeruginosa was very virulent and they can produce a kind of proteinase, which can degrade the gelatin fibers of the cornea. The cornea will be destroyed in a very short period of time and perforation will occur in 2-3 days. Recently the incidence of fungal cornea ulcer increased annually in our country and it was always misdiagnosed because of it varied clinical symptoms. And usually this disease was not treated duly because of the lack of sensitive anti-fungal drugs. Perforation will ensue at last. Viral infections were very common and they were difficult to treat because they are ready to relapse. The occurrence of viral infection was not related with the health of the host and perforation always ensued. Amoebic cornea ulcer was not very common and because of its long course of disease and mild symptoms, it was always misdiagnosed and perforation always ensued. There were many reason for the occurrence
of non-infective cornea ulcers, the risk of cornea perforation depends upon the state of the illness.
Attention should be paid upon the early identification of small perforation and tendency of perforation. When the area of the perforation was small, the aqueous liquid effused slowly, the anterior chamber become a little shallow or normal. Iris and lens were kept at their original places. Perforation will not happen at this time. Cornea can be dyed with fluorescence, the fluorescence at the site of perforation will be washed out slowly and cornea ulcer with perforation can be diagnosed then. Better prognosis will be gained after active therapy. In case that these kind of small perforation was neglected and the area increased, the treatment will be very hard and the prognosis very poor.
Diagnosis of the cause of the disease will
方法 收集我院1993年1月——2003年6月角膜溃疡穿孔病例49例(49眼)，进行回顾性分析，分析角膜溃疡穿孔的病因及发生穿孔的相关危险因素，同时对不同病变所采用的不同治疗方法进行比较、评价各种治疗方法的疗效。
结果 49例患者中有16例经单纯药物治疗后角膜溃疡穿孔愈合，33例经药物联合手术治疗后角膜溃疡穿孔愈合。16例单纯药物治疗患者中，6例患者视力获得不同程度的提高，10例患者无明显改善或略下降；22例穿透性角膜移植患者中17例患者获得不同程度视力提高，5例无变化；2例板层角膜移植患者视力均无变化；3例结膜瓣掩盖术患者视力均无变化。24例角膜移植患者术后移植片18例透明，5例半透明，1例混浊。13例经单纯药物治疗和3例经结膜瓣掩盖术治疗患者遗留粘连性角膜白斑，3例经单纯药物治疗患者遗留单纯性角膜白斑。术后继发青光眼2例，均行青光眼减压术治愈。角膜移植患者术后有6例发生角膜移植排斥反应，均经药物治疗后好转。所有患者经6-12个月随访无溃疡复发者。
结论 病因方面就本组病例来看，感染性角膜溃疡并发穿孔的比例最大，考虑主要有以下原因：1. 角膜溃疡的发生绝大部分为外来感染性致病因子侵入角膜上皮细胞层所致。2. 角膜感染发生后，是否发生溃疡穿孔与许多因素相关，主要有以下两点：（1）角膜溃疡的治疗是否及时而且正确。（2）感染性致病因子的破坏力强弱。近年来随着抗生素特别是广谱抗生素的大量应用，导致耐药菌数量及种类大量增加。此外，绿脓杆菌毒力很强，在繁殖过程中产生一种蛋白溶解酶使角膜的胶原纤维被溶解，整个角膜可在很短时间内遭到严重破坏，2-3天角膜即可发生穿孔。近年来真菌性角膜溃疡在我国发病率逐年增加，它的临床表现多种多样，极易误诊。而且目前缺乏敏感有效的抗真菌药物，所以许多病例得不到有效及时的治疗。最后往往导致角膜穿孔的发生。病毒感染很常见，易于复发，较难完全治愈，且与全身身体状况有关，亦有穿孔危险。棘阿米巴角膜溃疡不常见，但其病程长、症状轻，易误诊，有穿孔危险。非感染性角膜溃疡原因很多，病情轻重各异，有发生角膜穿孔的危险。
临床表现与诊断方面应注意及早发现小的穿孔和穿孔倾向。穿孔面积较小时，房水流出速度很慢，前房略浅或基本正常，虹膜及晶状体维持原位，眼后节无明显异常，此时不易发现角膜穿孔，可用荧光素进行角膜染色，穿孔处荧光素可被缓
慢流出的房水冲走，即可诊断角膜溃疡穿孔。此时积极治疗有机会取得较疗效。如漏诊此类小穿孔导致穿孔面积扩大及并发症的发生，治疗则较为棘手且治疗效果较差。
病因的诊断是否明确关系到能否合理的选用敏感有效的药物进行治疗，对预后影响很大。感染性角膜溃疡穿孔的病因即病原体的明确诊断尤为重要。首先应根据病变的特点进行初步判定，然后应用相应的方法进行检测，对怀疑细菌感染者应进行细菌培养及药物敏感试验，对怀疑有真菌感染者应行角膜组织刮片检查。
治疗方面应强调及时、合理。
药物治疗是有效的方法，对于穿孔面积较小的病例效果较好。药物治疗主要包括以下几方面。（1）针对病因用药：对于感染性角膜溃疡穿孔，最重要的是针对病原体选用敏感有效的药物，尽可能防止穿孔的继续扩大，根据病情全身及眼局部应用，力求迅速控制感染。对无法确定致病菌者，应给予广谱抗生素治疗。对怀疑有真菌感染但无法确定者应给予抗真菌药物治疗。对非感染性角膜溃疡穿孔者，主要针对其病因用药，如蚕食性角膜溃疡穿孔应用免疫抑制剂等，但非感染性角膜溃疡一旦发生角膜穿孔，药物治疗短期内一般很难使穿孔愈合，多需手术治疗。（2）应用降眼压药：应用降眼压药物使眼内压力维持在较低水平，这样既可在一定程度上预防继发青光眼的发
生，又可减少眼内组织向穿孔处移动并嵌顿等并发症的发生，同时减轻眼内压力对角膜的作用、促进角膜愈合。对药物控制眼压效果不理想、有继发青光眼危险或已发生继发青光眼者应及时行青光眼减压术。（3）角膜营养剂治疗：角膜营养剂可促进角膜组织的生长，对提高角膜组织的抗病能力亦有一定的帮助。此外，应用自家血清点眼可促进角膜的愈合，因为自体血清可以起到非特异性脱敏的作用，同时可提供给角膜营养物质，支持角膜组织的生命过程，使其抵抗力增强，还可以提供感染区较高浓度的特异性抗体。
手术治疗方面重要的是根据病情及治疗条件的不同，选择合理的手术时机和方法。手术治疗的目的首先是恢复眼球的完整性，进而恢复眼内结构特别是眼前节结构的正常。手术治疗方法有结膜瓣掩盖术、羊膜移植术、角膜移植术等。（1）手术方法的选择：穿透性角膜移植术用完整健康的角膜代替病变的残缺的角膜，不但可以恢复眼球的完整性，还可以恢复角膜的透明性，达到清除病灶和恢复视力的双重作用，因此，如有角膜材料，穿透性角膜移植术无疑是最佳的治疗方法。板层角膜易于长时间保存，同时具有完整角膜的透明性，在无全层角膜材料的情况下用保存的板层角膜修补角膜穿孔处来恢复眼球的完整性是一种很有效的方法。结膜瓣
Objective: to study the etiology and related risk factors of cornea ulcer with perforation, different kind of clinical treatment and the evaluation of their prognosis.
Method: 49 cases of cornea ulcer perforation from January 1993 to June 2003 were collected and retrospective analysis performed. Mechanism and risky factors of different etiology was analyzed. Different ways of clinical treatment were compared and the prognosis evaluated.
Result: In 16 of the 49 cases, the ulcers were healed after simple drug therapy. In 33, the ulcers were healed after the combined therapy of drug and surgery. For 6 of the 16 cases of simple drug therapy, the vision acuity was increased and for the other 10, the vision acuity was not significantly improved or decreased a little. For 17 of the 22 cases of penetrative cornea transplantation, the vision acuity was increased and for the other 5 no
difference was observed. The vision acuity of 2 patients of lamellar cornea transplantation was not changed at all. The vision acuity of 2 patients of conjunctive flap was not changed at all. 18 transplants of the 24 cases of keratoplasty were transparent, 5 were semi-transparent, 1 was cloudy. Adherent leukoma of cornea was found in 13 of the cases of simple drug therapy and 3 cases of conjunctive flap. Simple leukoma of cornea were found in 3 cases of simple drug therapy. Glaucoma was developed for 2 cases after operation and glaucoma decompression was performed. Transplant rejection was developed in 6 patients after keratoplasy and the condition was improved after drug therapy. No recurrence of ulcer was found for all the cases afte 6-12 months of follow-up.
Conclusion: Of all the causes of the disease, infective cornea ulcer was the most ordinary, the reason of which is as follows: 1) the external invasion of infective factors was the most common reason for the ulcer of cornea; 2) the ongoing of perforation after the infection of cornea was related to many factors namely 2: (1) the cornea ulcer was treated correctly and duly; (2)
the damage caused by the infective factors is severe or not. Recently with the development of antibiotics, especially the wide application of wide-spectrum antibiotics, the number of drug resistant strains of bacteria increased a lot. Besides, pseudomonas aeruginosa was very virulent and they can produce a kind of proteinase, which can degrade the gelatin fibers of the cornea. The cornea will be destroyed in a very short period of time and perforation will occur in 2-3 days. Recently the incidence of fungal cornea ulcer increased annually in our country and it was always misdiagnosed because of it varied clinical symptoms. And usually this disease was not treated duly because of the lack of sensitive anti-fungal drugs. Perforation will ensue at last. Viral infections were very common and they were difficult to treat because they are ready to relapse. The occurrence of viral infection was not related with the health of the host and perforation always ensued. Amoebic cornea ulcer was not very common and because of its long course of disease and mild symptoms, it was always misdiagnosed and perforation always ensued. There were many reason for the occurrence
of non-infective cornea ulcers, the risk of cornea perforation depends upon the state of the illness.
Attention should be paid upon the early identification of small perforation and tendency of perforation. When the area of the perforation was small, the aqueous liquid effused slowly, the anterior chamber become a little shallow or normal. Iris and lens were kept at their original places. Perforation will not happen at this time. Cornea can be dyed with fluorescence, the fluorescence at the site of perforation will be washed out slowly and cornea ulcer with perforation can be diagnosed then. Better prognosis will be gained after active therapy. In case that these kind of small perforation was neglected and the area increased, the treatment will be very hard and the prognosis very poor.
Diagnosis of the cause of the disease will
引文
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Gong XM, Chen JQ, Feng CM. Penetrating keratoplasty in the treatment of corneal perforation [J] Zhonghua Yan Ke Za Zhi. 1994 Jan;30(1):8-10.
赵才 李桂芹 以虹膜为植床治疗周边部角膜穿孔缺损的板层角膜移植术 [J]眼外伤职业眼病杂志 2000；22（4）：364.
Bessant DA, Dart JK. Lamellar keratoplasty in the management of inflammatory corneal ulceration and perforation. [J]Eye. 1994;8 ( Pt 1):22-8.
Khodadoust A, Quinter AP. Microsurgical approach to the conjunctival flap. [J]Arch Ophthalmol. 2003 Aug;121(8):1189-93.
刘杰 崔葳 宋维俭 用新鲜羊膜移植治疗角膜穿孔 [J]中国实用眼科杂志2002；2；（8）： 631.
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