重视糖尿病眼部并发症的诊断和治疗

糖尿病是糖代谢紊乱导致的全身性慢性疾病,高血糖、高血脂和高血压是糖尿病患者的主要特征,长期的高血糖环境引起人体组织和器官的微血管和大血管相关并发症,是目前全球劳动力人口致残率和致死率较高的疾病之一.糖尿病已经成为发展中国家严重的公共卫生问题,而糖尿病患者眼部并发症发病风险增加,发病率也逐年升高,成为不容忽视的致盲眼病.常见的糖尿病眼部并发症包括糖尿病视网膜病变(DR)、糖尿病性视神经病变(DN)、青光眼、白内障、糖尿病眼表疾病等,治疗棘手,因此糖尿病眼部并发症的预防、早期诊断和及时治疗是眼科医师面临的主要挑战.眼科医师在临床工作中应对糖尿病患者及其眼部并发症给予足够的重视,实时跟踪国内外关于糖尿病眼部并发症诊疗指南的更新和研究现状,对相关疾病做到早期发现、合理管理和及时治疗,降低糖尿病眼部并发症的致盲率和经济负担.     

Study of ocular surface involvement in diabetic patients

INTRODUCTION: Diabetes mellitus leads to microvascular complications and altered basement membranes, which are partly responsible for ocular complications. Corneal nerve impairment is involved in ocular surface disease as well. We examined the possible relation between ocular surface signs and retinal or neuronal degenerative complications due to diabetes. PATIENTS AND METHODS: Diabetics and control subjects were compared for corneal sensitivity and tear function parameters such as the Schirmer test, tear film break-up time (BUT), and fluorescein and lissamine green stainings. The relation of the duration of the disease, the stage of retinopathy, metabolic control (HbA1c), and diabetic peripheral neuropathy with ocular surface disorders were noted. RESULTS: Twelve healthy patients were compared to 48 diabetics. The Schirmer test value, BUT, and fluorescein and lissamine green impregnations were significantly modified in diabetics compared to controls (p<0.0001), with no relation to the duration of the disease or metabolic control. The mean corneal sensitivity was significantly lower in diabetic patients (p<0.01), diabetics with peripheral neuropathy (p=0.00008), and diabetics with preproliferative retinopathy (p=0.0003). Tear function parameters were more frequently altered in patients presenting preproliferative retinopathy and peripheral neuropathy (p<0.001). CONCLUSIONS: Diabetes can lead to ocular surface impairments with qualitative and quantitative tear disorders, all of which seem to evolve in close relation with retinopathy and peripheral neuropathy. These lacrymal and corneoconjunctival abnormalities, even if not currently mentioned by diabetic patients, can result in severe neurotrophic complications.     

糖尿病相关干眼的研究进展

糖尿病在全世界发病率普遍增高,糖尿病可引起干眼、角膜病、糖尿病视网膜病变、青光眼、白内障、屈光异常改变等一系列眼部并发症,严重影响视力甚至失明。近些年糖尿病对眼表造成损害正逐渐引起临床医师关注,糖尿病相关干眼主要表现为角膜上皮反复剥脱、上皮再生延迟、角膜敏感性下降等,这主要与糖尿病条件下泪液异常、泪液渗透压升高、泪膜稳定性差、角膜神经退行性改变等异常有关。现将糖尿病相关干眼的主要临床特点结合泪液变化、角膜神经敏感性变化、血糖水平、病程、降糖药物等相关影响因素以及特殊诊断方法和治疗策略等方面的进展进行总结,为临床诊断和治疗提供理论依据。     

Neurotrophic keratopathy and diabetes mellitus

Diabetes mellitus is frequently associated with microvascular complications such as retinopathy, nephropathy, and peripheral neuropathy. Neurotrophic keratopathy occurs in response to a neuropathy of the ophthalmic division of the trigeminal nerve. Rarely has diabetic neurotrophic keratopathy been described. This paper discusses the ophthalmic histories of three patients who presented with diabetic neurotrophic keratopathy. In one patient the corneal ulceration was the sole presenting feature of his diabetes. We discuss the need for increased vigilance in the ophthalmic community for suspecting diabetes in patients with unexplained corneal epithelial disease.     

The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, with several underlying pathophysiological mechanisms, some of which are still uncertain. The cornea is an avascular tissue and sensitive to hyperglycemia, resulting in several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity, and tear film changes. The manifestation of DPN in the cornea is referred to as diabetic neurotrophic keratopathy (DNK). Recent studies have revealed that disturbed epithelial-neural-immune cell interactions are a major cause of DNK. The epithelium is supplied by a dense network of sensory nerve endings and dendritic cell processes, and it secretes growth/neurotrophic factors and cytokines to nourish these neighboring cells. In turn, sensory nerve endings release neuropeptides to suppress inflammation and promote epithelial wound healing, while resident immune cells provide neurotrophic and growth factors to support neuronal and epithelial cells, respectively. Diabetes greatly perturbs these interdependencies, resulting in suppressed epithelial proliferation, sensory neuropathy, and a decreased density of dendritic cells. Clinically, this results in a markedly delayed wound healing and impaired sensory nerve regeneration in response to insult and injury. Current treatments for DPN and DNK largely focus on managing the severe complications of the disease. Cell-based therapies hold promise for providing more effective treatment for diabetic keratopathy and corneal ulcers.     

几种糖尿病相关眼病的诊断治疗规范

糖尿病是全身糖代谢紊乱所导致的慢性炎症性疾病,目前仍然是全球严重的公共卫生问题.作为重要糖尿病靶器官损害之一,糖尿病眼部并发症是一组严重影响患者视觉质量乃至致盲的眼病.常见的糖尿病相关眼病包括糖尿病性视网膜病变、糖尿病性视神经病变、糖尿病性白内障、糖尿病相关眼表疾病、糖尿病性眼肌麻痹等,其规范化管理需要多学科密切合作....     

Dr. P. Siva Reddy Oration. Diabetic keratopathy

Diabetes mellitus, which affects millions of people all over the world, produces significant ocular morbidity. Corneal complications such as tear film dysfunction, elevated glucose in tears, different forms of epitheliopathy, neurotrophic ulcers, corneal edema, wrinkles in Descemet's membrane and decrease in corneal sensitivity have been reported. While a few reports described altered epithelial morphology as the possible basis for epithelial disease, all other clinical phenomena have been unexplained thus far. In this first-ever multifaceted approach to study the pathogenesis of diabetic keratopathy, striking abnormalities were observed in corneal nerves, corneal epithelium and corneal endothelium of diabetics. We have clearly demonstrated the existence of neuropathy in diabetic cornea, both in an animal model and in the humans, -- the first demonstration of such an abnormality. Our in vivo specular microscopic observations on epithelium confirmed in vitro observations in our study as well as of others while the analysis of endothelium provided the basis for the problems noticed in the diabetic cornea following intraocular surgical procedures. Our observations should help the clinician in the understanding of diabetic keratopathy and in developing better prophylactic and therapeutic strategy against some recalcitrant forms of corneal disease in this group of individuals.     

糖尿病与非视网膜眼部并发症相关性的研究进展

糖尿病是一种以持续高血糖为特征的慢性代谢性疾病,可引起全身大血管、微血管和神经系统的并发症。眼是受该病影响的主要器官之一。然而,糖尿病性眼病不仅包括糖尿病性视网膜病变,还包括非视网膜并发症。本文综述了与糖尿病相关的非视网膜眼部病变包括:角膜病变、干眼、青光眼、白内障、屈光不正、视神经病变、虹膜睫状体炎、星状玻璃体变性等,它们也可能导致视力丧失,在糖尿病患者中也应该引起重视。     

Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus

PURPOSE: To describe the ocular surface disorder in patients with diabetes. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Eighty-eight eyes of 50 noninsulin-dependent diabetes mellitus patients seen at the Department of Ophthalmology, Kobe University School of Medicine, from September 1998 through February 1999, and 40 eyes of 20 healthy control individuals were studied. INTERVENTION: All subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) analysis, and conjunctival impression cytologic analysis. MAIN OUTCOME MEASURES: Patients and control subjects were compared for corneal sensitivity, tear function parameters, goblet cell density, and squamous metaplasia grade. The relation of diabetic peripheral neuropathy, metabolic control, duration of disease, and status of retinopathy to the ocular surface disorder was also noted. RESULTS: The mean corneal sensitivity was significantly lower in diabetic patients, diabetic patients with peripheral neuropathy, and poorly controlled diabetes compared with control subjects (P < 0.001). The BUT and Schirmer test values were also significantly lower in the diabetic group, in patients with peripheral neuropathy and poor metabolic control. Impression cytologic analysis showed goblet cell loss and conjunctival squamous metaplasia, both of which again related to peripheral neuropathy, poor diabetic control, and decreased corneal sensitivity. The examined parameters did not relate to duration of disease or status of diabetic retinopathy. CONCLUSIONS: The ocular surface disease in diabetes is characterized by a disorder of tear quantity and quality, squamous metaplasia, and goblet cell loss, all of which seem to evolve in close proximity to the status of metabolic control and peripheral neuropathy.     

Changes of tear film and ocular surface in diabetes mellitus

This study was performed to investigate the changes of tear film and ocular surface in diabetic patients, as well as the ocular and systemic factors related to these changes. We assessed the scoring of keratoepitheliopathy, corneal sensitivity test, tear film break-up time (BUT), Schirmer test, and conjunctival impression cytology in 94 eyes of 47 patients with noninsulin-dependent diabetes mellitus and in 60 eyes of 30 normal subjects. The degree of keratoepitheliopathy was severe, and the corneal sensitivity, BUT, and tear secretion were significantly reduced in the diabetic patients. Conjunctival impression cytology showed a higher grade of conjunctival squamous metaplasia and lower goblet cell density in the diabetic patients. All parameters were related to the status of metabolic control, diabetic neuropathy, and stage of diabetic retinopathy. We think that diabetic patients with poor metabolic control, neuropathy, and advanced stage of retinopathy should be examined for tear film and ocular surface changes.     

Effects of diabetes on anterior ocular structure and function

Diabetes is a systemic disease that affects multiple organs including the entire eye. Although diabetic retinopathy is the main cause for vision loss in patients with diabetes, many anterior segment abnormalities have been described, including structural changes in the tear film, the conjunctiva, and the corneal epithelial and endothelial cells. Functional alterations in corneal wound healing, corneal sensitivity, and recovery from contact lens-induced edema also accompany diabetes, and this raises the issue of whether contact lens wear may be contraindicated in these patients. To address this issue, eye care providers must be able to recognize the effects of diabetes on the anterior ocular surface, understand the biochemical mechanism(s) believed to be responsible for these alterations, and determine the relevance of observed changes with respect to contact lens wear.     

糖尿病患者泪液及泪膜变化的研究进展

随着糖尿病在全球发病率的持续增加,由其引发的眼部并发症也日益受到关注.除了引起视网膜病变、白内障等常见的并发症外,糖尿病患者的眼表在结构及微环境方面也可能发生改变,进而影响泪液的成分、质量及泪膜的稳定性.本文就糖尿病患者眼表,泪液和泪膜的变化、相关检查方法以及影响因素的研究进展作一综述.     

谈羊膜移植在角膜和眼表疾病应用中的问题

由于羊膜具有抗炎、抗纤维化、抗新生血管生成、促进角膜修复的作用,羊膜已经成为治疗角膜和眼表疾病的理想材料.随着羊膜广泛应用于角膜和眼表疾病,在某种程度上改变了一些角膜及眼表疾病传统的治疗方式,但随之而来的临床问题也逐渐显露,主要体现在：适应证如何把握;手术如何进行个体化设计;如何观察术后并发症和术后规范用药等问题.在此,谈些个人的经验和看法,以期使羊膜移植手术能在临床治疗角膜和眼表疾病中发挥更好的作用.     

厄洛替尼在眼表的并发症：3个病例不同转归

目的 报道3例表皮生长因子受体抑制剂厄洛替尼眼表并发症患者的临床资料,并分析3个病例不同转归的原因。方法 病例系列报道。结果 病例1患者口服厄洛替尼近7年,眼部检查发现双眼角膜点状上皮脱落,未停用靶向药物而仅眼部用药后角膜上皮修复。病例2患者使用厄洛替尼2年余,单眼出现无菌性角膜溃疡伴角膜基质变薄,患眼接受多层羊膜移植同时停用厄洛替尼1周后,缺损的角膜上皮逐渐愈合。这2例患者全身除肺癌病史外,均无高血压、糖尿病及自身免疫性疾病等病史。病例3患者除了肺癌,还有明确的干燥综合征病史,在接受厄洛替尼治疗2年余后,眼表出现严重并发症,包括持续性角膜上皮缺损、角膜溶解和穿孔,并且进行了4次穿透性角膜移植术。停用厄洛替尼后眼表才逐渐趋于稳定。结论 在使用表皮生长因子受体抑制剂之前,需进行详细的眼部检查,排除眼表基础疾病,尤其是自身免疫性眼表疾病。同时,患者在使用此类药物期间需定期接受眼科随访,以避免眼表严重并发症的出现。     

糖尿病角膜上皮和泪膜改变的研究进展

随着糖尿病患者的日益增加，糖尿病患者的眼表疾病越来越受到人们的重视。研究发现，2型糖尿病患者泪膜功能发生改变，是干眼症的易患人群。糖尿病可导致眼表的改变．包括泪膜、角膜上皮和角膜神经的改变，与外周神经疾病、血糖控制不佳、眼底激光治疗等有关。糖尿病发生泪膜和角膜上皮改变的发病机制主要有蛋白质糖基化反应、醛糖还原酶通路、基质金属蛋白酶作用、蛋白激酶C通路、角膜神经递质异常等。眼科医师在对糖尿病患者进行常规检查时应考虑到眼表疾病的发生情况，并及时给予相应的治疗。     

A review of non-retinal ocular complications of diabetes mellitus

Significant attention is paid to the retinal complications of diabetes mellitus and their potentially devastating effects on vision. Diabetes mellitus, however, is a multisystem disease, and diabetic eye disease is an end-organ response to the effects of the condition on the human system. Each portion of the eye is susceptible to the harmful effects of diabetes. This article reviews diabetic effects on non-retinal ocular structures and provides references for those interested in pursuing further studies on diabetic eye disease.     

Cornea in diabetus mellitus

Diabetus mellitus is associated with numerous ocular complications. Diabetic keratopathy occurs in response to a neuropathy of the ophthalmic division of the trigeminal nerve, but also as a result of epithelial subclinical abnormalities, limbal vasculopathy and decrease in tear production. It comprises several symptomatic corneal conditions inducing superficial punctate keratopathy and persistent corneal epithelial erosions; the latter can progress to corneal ulceration and is often resistant to routine clinical management.     

Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease

PurposeTo describe the association between Sars-CoV-2 infection and small fiber neuropathy in the cornea identified by in vivo corneal confocal microscopy.MethodsTwenty-three patients who had overcome COVID-19 were recruited to this observational retrospective study. Forty-six uninfected volunteers were also recruited and studied as a control group. All subjects were examined under in vivo confocal microscopy to obtain images of corneal subbasal nerve fibers in order to study the presence of neuroma-like structures, axonal beadings and dendritic cells. The Ocular Surface Disease Index (OSDI) questionnaire and Schirmer tear test were used as indicators of Dry Eye Disease (DED) and ocular surface pathology.ResultsTwenty-one patients (91.31%) presented alterations of the corneal subbasal plexus and corneal tissue consistent with small fiber neuropathy. Images from healthy subjects did not indicate significant nerve fiber or corneal tissue damage. Eight patients reported increased sensations of ocular dryness after COVID-19 infection and had positive DED indicators. Beaded axons were found in 82.60% of cases, mainly in patients reporting ocular irritation symptoms. Neuroma-like images were found in 65.22% patients, more frequently in those with OSDI scores >13. Dendritic cells were found in 69.56% of patients and were more frequent in younger asymptomatic patients. The presence of morphological alterations in patients up to 10 months after recovering from Sars-CoV-2 infection points to the chronic nature of the neuropathy.ConclusionsSars-CoV-2 infection may be inducing small fiber neuropathy in the ocular surface, sharing symptomatology and morphological landmarks with DED and diabetic neuropathy.     

An integrated approach to diabetic retinopathy research

This review discusses the pathophysiology of diabetic retinopathy related to direct effects of loss of insulin receptor action and metabolic dysregulation on the retina. The resulting sensory neuropathy can be diagnosed by structural and functional tests in patients with mild nonproliferative diabetic retinopathy. Research teams can collaborate to integrate ocular and systemic factors that impair vision and to design strategies to maintain retinal function in persons with diabetes mellitus. Evolving concepts may lead to inclusion of tests of retinal function in the detection of diabetic retinopathy and neuroprotective strategies to preserve vision for persons with diabetes.     

Ocular surface diabetic disease: A neurogenic condition?

PurposeTo investigate clinical and inflammatory changes in the ocular surface of insulin-dependent type I diabetic patients.MethodsTwo hundred and nine eyes of 106 patients with diagnosis of type I diabetes were recruited in a prospective observational study. Ocular surface clinical assessment, corneal sensitivity and tear film stability tests were performed to evaluate ocular surface system function. Ocular Surface Disease Index (OSDI) questionnaire was administered to all enrolled subjects. Conjunctival impression cytology specimens were also collected to detect neuromediators and inflammatory molecules. Duration of disease, HbA1c levels and diabetic retinopathy stage were recorded.ResultsCorneal sensitivity assessed by Cochet-Bonnet esthesiometer was reduced in patients with more chronic disease, higher HbA1c levels and proliferative diabetic retinopathy. Tear break-up time (TBUT) was reduced in subjects with long-standing diabetes or with more severe retinopathy. OSDI questionnaire scores showed direct correlation with increased HbA1c values. Significant increase of NPY, STAT-5 and ICAM-1 was found in diabetic patients compared to healthy controls. A direct correlation between NPY concentration and ICAM-1 values in patients with type I diabetes was demonstrated.ConclusionsPatients with long-standing type I diabetes showed chronic inflammation of the ocular surface, due to neurogenic dysregulation of para-inflammatory homeostatic mechanisms. These patients with ocular surface system failure complained of ocular discomfort but had modest reduction of corneal sensitivity and no signs of neurotrophic keratopathy. Disease duration, increased HbA1c levels and severe diabetic retinopathy appear the most critical factors.