【作者】 王彬；

【导师】 谢立信；

【作者基本信息】 山东大学 ， 眼科学（专业学位）， 2019， 博士

【摘要】 在糖尿病患者中,角膜上皮的形态与结构异常、损伤后的修复愈合延迟,以及角膜神经形态异常、密度降低以及角膜知觉减退,角膜的抵抗力和修复能力下降;以上这些造成角膜上皮抵抗致病微生物的防御能力下降,易继发细菌和真菌等病原微生物的感染,导致感染性角膜病的发生。此外,糖尿病患者在白内障、玻璃体视网膜手术、角膜移植术后经常出现持续性的角膜上皮缺损,在此基础上极易造成角膜的继发感染。感染性角膜病是我国主要的致盲性眼病,也是可防治的致盲性角膜病,应该对其临床发病的相关危险因素进行更为细致的研究。让更多的医生和糖尿病患者了解和重视糖尿病性角膜病变以及糖尿病患者发生感染性角膜病的危险因素,将有助于预防感染性角膜病的发生。本研究通过回顾性分析,对T2DM和非糖尿病(non diabetes mellitus,NDM)患者的临床病例资料进行对比研究,旨在探讨T2DM患者发生感染性角膜病的危险因素,进而提出T2DM患者感染性角膜病预防及治疗的新策略。目的分析T2DM患者与NDM患者发生感染性角膜病的情况,比较二者感染性角膜病临床特征的异同,探讨T2DM患者发生感染性角膜病的危险因素。方法采用回顾性研究。将2001-2015年于山东省眼科研究所青岛眼科医院住院治疗的230例合并感染性角膜病的2型糖尿病患者及相同时间段内随机抽取的168例合并感染性角膜病的非糖尿病患者纳入本研究。其中,将2型糖尿病合并感染性角膜病患者设为实验组(糖尿病组),非糖尿病合并感染性角膜病患者设为对照组(非糖尿病组)。收集两组患者的一般资料(性别、年龄、职业、发病季节、是否吸烟、是否饮酒、有无诱因、病程)和住院资料(角膜感染的病原微生物、治疗方式及住院天数),并进行统计学分析。将一般资料比较有意义的指标纳入多因素Logistic回归分析,比较两组有无统计学差异。此外,将感染性角膜病分为单纯疱疹病毒性角膜炎(herpes simplex keratitis,HSK)、细菌性角膜炎(bacterial keratitis,BK)、真菌性角膜炎(fungal keratitis,FK)及棘阿米巴性角膜炎(acanthamoeba keratitis,AK),并进行统计学分析,比较糖尿病组与非糖尿病组间各种角膜感染的差别。结果糖尿病组中,男性146例(63.5%),女性84例(36.5%);非糖尿病组中,男性1 1 1例(66.1%),女性57例(33.9%)。两组患者性别、是否吸烟、是否饮酒及有无诱因的差异均无统计学意义(P>0.05)。糖尿病组的患者年龄大于非糖尿病组的患者年龄,差异有统计学意义(t=-2.352,P<0.05)。两组患者年龄段、职业、发病季节、病程长短的差异均有统计学意义(P<0.05)。糖尿病组病程大多≤3个月,非糖尿病组病程大多>3个月。糖尿病组患者平均住院13.15±9.51天,非糖尿病组患者平均住院10.67±6.23天,差异有统计学意义(P<0.05)。两组治疗方式的差异亦有统计学意义(P<0.05)。将一般资料分析有意义的指标代入多因素Logistic回归模型进行分析,发现患者年龄、发病季节与2型糖尿病患者感染性角膜病的发生有关。两组发生细菌性角膜炎及单纯疱疹病毒性角膜炎的差异有统计学意义(P<0.05),而发生真菌性角膜炎及棘阿米巴性角膜炎的差异无统计学意义(P>0.05)。结论高龄和夏冬季是2型糖尿病患者发生感染性角膜病的危险因素。与非糖尿病患者相比,2型糖尿病患者更容易发生细菌性角膜炎。对于高龄的2型糖尿病患者,尤其在夏冬季,应注意用眼卫生、避免眼部外伤,进而防止感染性角膜病的发生。2型糖尿病患者病程短,平均住院天数时间长。糖化血红蛋白Ale(glycosylated hemoglobin Ale,HbAlc)被作为诊断糖尿病的一个标准指标。HbAlc可以反映患者近8-12周的血糖控制情况,具有生物学变异性小、不易受血糖波动的影响、与是否使用胰岛素等因素无关等特点。短暂的血糖升高或降低不会造成HbAlc的增高和下降,故HbAlc可以比较全面地了解过去一段时间内的血糖控制水平。糖尿病性角膜病变的主要临床表现是容易出现角膜上皮的长期缺损,角膜的上皮保护屏障受到破坏,从而易于继发角膜感染。而2型糖尿病患者发生感染性角膜病时,其HbAlc和血糖水平如何?糖尿病患者及非糖尿病患者发生单纯疱疹病毒性角膜炎、细菌性角膜炎、真菌性角膜炎及棘阿米巴性角膜炎的具体治疗方式有何不同?本章节将重点对上述内容进行探讨。目的比较合并感染性角膜病的2型糖尿病和非糖尿病患者的HbAlc和血糖水平,探讨HbAlc和血糖水平对感染性角膜病的影响,分析2型糖尿病和非糖尿病患者感染性角膜病治疗方式的差异。方法采用回顾性研宄。将2001-2015年于山东省眼科研宄所青岛眼科医院住院治疗的230例合并感染性角膜病的2型糖尿病患者(糖尿病组)以及相同时间段内随机抽取的168例合并感染性角膜病的非糖尿病患者(非糖尿病组)纳入本研宄。收集两组患者的空腹血糖数据、收集糖尿病组患者三餐后两小时血糖值及HbAlc等数据。将患者的治疗方式分为药物治疗和手术治疗,手术治疗又分为角膜溃疡清创术、结膜瓣遮盖术、羊膜移植术、角膜溃疡清创术+结膜瓣遮盖术、角膜溃疡清创术+羊膜移植术、睑裂缝合术、羊膜移植术+睑裂缝合术、板层角膜移植术(lamellar keratoplasty,LKP)、穿透性角膜移植术(penetrating keratoplasty,PKP)、LKP+睑裂缝合术、PKP+结膜瓣遮盖术、PKP+睑裂缝合术、眼内容物剜除术以及眼球摘除术。结果糖尿病组中,患者空腹血糖平均值为8.2±3.5mmol/L,血糖波动范围6.0±1.8—10.3±3.4mmol/L;非糖尿病组中,患者空腹血糖5.3±0.5mmol/L,两组空腹血糖的差异有统计学意义(P<0.05)。糖尿病组中,三餐后两小时血糖平均值为12.2±6.7 mmol/L,血糖波动范围为6.7±3.1—17.8±4.3 mmol/L;糖尿病患者三餐后两小时平均血糖明显高于7.8 mmol/L,差异有统计学意义(P<0.05)。糖尿病患者HbAlc为9.U2.1%,明显高于6.5%,差异有统计学意义(P<0.05)。在糖尿病组的各种治疗方式中,细菌性角膜炎与单纯疱疹病毒性角膜炎以药物治疗居多,其所占比例分别为40.5%和45.5%;真菌性角膜炎以PKP治疗(38.5%)居多;2例棘阿米巴性角膜炎行眼内容物剜除术。在非糖尿病组的各种治疗方式中,细菌性角膜炎与单纯疱瘆病毒性角膜炎亦是以药物治疗居多,分别为42.2%和63.6%;真菌性角膜炎以药物治疗(32.6%)和角膜溃疡清创术治疗(30.2%)居多;3例棘阿米巴性角膜炎均接受药物治疗。两组患者中,糖尿病组有14例行眼内容物剜除术或眼球摘除术,而非糖尿病组中无一例行剜除眼内容物或摘除眼球。发生感染性角膜病的糖尿病患者大部分仅口服降糖药物(64.3%),血糖控制水平欠佳。结论2型糖尿病组发生感染性角膜病的患者空腹血糖、三餐后两小时血糖及HbAlc明显增高。两组中细菌性角膜炎与单纯疱疹病毒性角膜炎的治疗方式类似,均以药物治疗居多;而对于真菌性角膜炎,糖尿病组中以PKP治疗居多,非糖尿病组中以药物治疗和角膜溃疡清创术治疗居多。血糖控制水平欠佳、波动大可能对感染性角膜疾病治疗方式的选择有一定的影响。合并感染性角膜病的2型糖尿病患者需要更规范的控制血糖治疗。更多还原

【Abstract】 In diabetic patients,factors such as abnormal morphology and structure of the corneal epithelium,delayed healing after injury,abnormal corneal nerve morphology and decreased density,decreased corneal sensation,and decreased corneal resistance and repair ability cause a decline in the defensive ability of the corneal epithelium to resist pathogenic microorganisms,therefore it becomes easy for secondary infection caused by pathogenic microorganisms,such as bacteria and fungi to occur,leading to infectious keratopathy.In addition,diabetic patients often have persistent corneal epithelial defects after cataract surgery,vitreoretinal surgery,and corneal transplantation,which are likely to cause secondary infection of the cornea as well.Infectious keratopathy is the main blinding eye disease in China,and it is also a preventable blinding keratopathy.A more detailed study of the risk factors associated with clinical onset should be conducted as this will help more doctors and diabetic patients understand DK and recognize the risk factors for infectious keratopathy in diabetic patients,which in turn will aid the prevention of infectious keratopathy.This study was a retrospective analysis that compared the clinical data of patients with T2DM and non-diabetes mellitus(NDM),in order to investigate the risk factors of infectious keratopathy in T2DM patients.Furthermore,a new strategy for the prevention and treatment of infectious keratopathy in T2DM patients is proposed in the present study.Objective The purpose of this study was to analyse the incidence of infectious keratopathy in patients with T2DM and NDM,compare the clinical characteristics of infectious keratopathy in T2DM and NDM patients,and investigate the risk factors for infectious keratopathy in T2DM patients.Methods This was a retrospective study that included a total of 230 T2DM patients diagnosed with infectious keratopathy.They were selected from patients hospitalised at the Qingdao Eye Hospital in Shandong Eye Institute from 2001 to 2015,and 168NDM patients diagnosed with infectious keratopathy were randomly selected at the same time and included in the study.T2DM patients diagnosed with infectious keratopathy were categorized as the experimental group(diabetic group)whereas patients with NDM diagnosed with infectious keratopathy were categorized as the control group(non-diabetic group).General data including sex,age,occupation,season of onset,smoking and alcohol consumption habits,inducement disease duration,and hospitalisation data,including pathogenic microorganisms of corneal infection,treatments,and duration of hospitalization were collected,all collated data were then statistically analysed.The meaningful indicators of general data were included in the multivariate logistic regression analysis,and the difference between the two groups was compared.In addition,infectious keratopathies were divided into herpes simplex keratitis(HSK),bacterial keratitis(BK),fungal keratitis(FK)and acanthamoeba keratitis(AK),and statistical analysis was performed to compare the differences in various corneal infections between the diabetic and non-diabetic groups.Results The diabetic group consisted of 146(63.5%)males and 84(36.5%)females.The NDM group consisted of 111(66.1%)males and 57(33.9%)females.There was no significant difference in sex distribution,smoking,alcohol consumption habits and inducement between the two groups(P>0.05).The age of patients in the diabetic group was significantly higher than that of the patients in the non-diabetic group(t=-2.352,P<0.05).There were significant differences in age groups,occupation,season of onset,and disease duration between the two groups(P<0.05).For most of the patients in the diabetic group,the disease duration was<3 months whereas the disease duration was>3 months for most patients in the NDM group.The average duration of hospitalization for diabetic patients was 13.15±9.51 days whereas that of non-diabetic patients was 10.67±6.23 days,there was a significant difference between the two groups(P<0.05).There were significant differences in treatment between the two groups(P<0.05)as well.Meaningful indicators of general data analysis were substituted for a multivariate logistic regression model.Multivariate logistic regression analysis revealed that age and season of onset were related to the development of infectious keratopathy in the T2DM group.There were statistically significant differences in the incidences of BK and HSK between the two groups(P<0.05),but no statistically significant difference was found between the incidence of FK and that of AK(P>0.05).Conclusion Advanced age and the summer and winter seasons are identified as risk factors for infectious keratopathy in T2DM patients.Compared with non-diabetic patients,T2DM patients are more prone to BK.For T2DM patients of advanced age,attention should be paid to ocular hygiene and ocular trauma should be avoided,especially in summer and winter seasons,to prevent the occurrence of infectious keratopathy.T2DM patients have a short disease duration and a long average duration of hospitalization.Glycosylated hemoglobin Ale(HbAlc)is used as a criterion for the diagnosis of DM.HbAlc can reflect the patient’s blood glucose control level over a period of 8—12weeks.It has little biological variability,is not susceptible to blood glucose fluctuation,and is not influenced by the use of insulin and other factors.Short-term increase or decrease in blood glucose does not cause the increase or decrease of HbAlc,therefore,the HbAlc level of a diabetic patient can provide more comprehensive information on the glycaemic control level in the aforementioned period of time.The main clinical manifestation of DK is prone to long-term defects of the corneal epithelium,and the protective barrier of the corneal epithelium is destroyed,thus making the cornea vulnerable to secondary infection.This chapter focuses on examining the HbAlc and blood glucose levels in T2 DM patients who develop infectious keratopathy and determining the possible differences in the specific methods for the treatment of herpes simplex keratitis,bacterial keratitis,fungal keratitis,and acanthamoeba keratitis between diabetic and non-diabetic patients.Objective This study aimed to compare HbAlc and blood glucose levels in T2 DM and NDM patients with infectious keratopathy,to investigate the effects of HbAlc and blood glucose levels on infectious keratopathy,and to analyse the differences in the treatment of infectious keratopathy between T2 DM and NDM patients.Methods This was a retrospective study that included 230 T2 DM patients diagnosed with infectious keratopathy(diabetic group).They were selected from patients hospitalized at the Qingdao Eye Hospital in Shandong Eye Institute from 2001 to2015,168 NDM patients diagnosed with infectious keratopathy were randomly selected at the same time(non-diabetic group)and were included in the study as well.The fasting blood glucose records of the two groups were collected,the blood glucose value measured two hours after three meals,and the HbAlc data of the patients in the diabetic group were also collected.The treatment methods for the patients were divided into drug treatment and surgical treatment.Surgical treatment was divided into corneal ulcer debridement conjunctival flap covering,amniotic membrane transplantation,corneal ulcer debridement plus conjunctival flap covering,corneal ulcer debridement plus amniotic membrane transplantation,blepharoplasty,amniotic membrane transplantation plus blepharoplasty,lamellar keratoplasty(LKP),penetrating keratoplasty(PKP),LKP plus blepharoplasty,PKP plus conjunctival flap covering,PKP plus blepharoplasty,enucleation of eye contents and enucleation of the eyeball.Results In the diabetic group,the mean fasting blood glucose value was 8.2±3.5mmol/L,and the range of blood glucose fluctuation was 6.0± 1.8—10.3±3.4mmol/L.In the non-diabetic group,the mean fasting blood glucose value was 5.3±0.5 mmol/L.There was a significant difference in the fasting blood glucose values between the two groups(P<0.05).In the diabetic group,the mean blood glucose level measured two hours after three meals was 12.2±6.7 mmol/L,and the range of blood glucose fluctuation was 6.7±3.1—17.8±4.3 mmol/L,the average blood glucose level measured two hours after three meals in the diabetic patients was significantly higher than 7.8 mmol/L,there was significant difference(P<0.05).The mean HbAlc level of the diabetic patients was 9.1 ±2.1 %,which was significantly higher than 6.50/0,there was significant difference(P<0.05).Among the various treatment methods for patients in the diabetic group,bacterial keratitis and herpes simplex keratitis were mostly treated with drugs,the proportion of patients that were treated was 40.5% and45.5%.respectively.Fungal keratitis was mostly treated with PKP(38.5%).Enucleation of eye contents was performed for two cases of acanthamoeba keratitis.Regarding the various treatments performed for patients in the non-diabetic group,bacterial keratitis and herpes simplex keratitis were mostly treated with drugs,the proportion of patients that were treated was 42.2% and 63.6%,respectively.Drug treatment(32.6%)and corneal ulcer debridement(30.2%)were the most common treatments for fungal keratitis.Three cases of acanthamoeba keratitis were treated with drugs.Enucleation of eye contents or enucleation of the eyeball was performed for 14 patients in the diabetic group whereas none of the non-diabetic patients underwent enucleation of eye contents or enucleation of the eyeball.Most diabetic patients with infectious keratopathy only took oral hypoglycaemic drugs(64.3%),and their glycaemic control level was poor.Conclusion Fasting blood glucose,blood glucose measured two hours after three meals,and HbAIc levels were significantly increased in T2 DM patients with infectious keratopathy.In both groups,bacterial keratitis was treated similarly to herpes simplex keratitis,and most cases were treated with drugs.For fungal keratitis,PKP was the most common mode of treatment in the diabetic group whereas the non-diabetic patients were most commonly treated with drugs and comeal ulcer debridement.Poor glycaemic control levels and high fluctuations may have a certain impact on the choice of treatment methods for infectious keratopathy.T2DM patients with infectious keratopathy require more standardized glycaemic control therapy.更多还原