作者：蓝诚红 张铭志
作者单位：515041中国广东省汕头市,汕头大学·香港中文大学联合汕头国际眼科中心
【摘要】 葡萄膜炎是一组累及虹膜、睫状体、脉络膜或三者同时受累的炎症性病变。尽管目前对葡萄膜炎的诊断和治疗有了很大的进展，仍有35%～45%患者视力最终丧失。其病因和发病机制仍不太清楚，可能与环境及免疫遗传因素有关。很多研究显示人类组织相容性抗原基因多态性在葡萄膜炎的发病中起重要作用；近年来，非人类组织相容性抗原基因包括细胞因子和趋化因子基因亦被报道在葡萄膜炎的发病机制中起重要作用。本文对葡萄膜炎相关的细胞因子和趋化因子基因多态性的研究进展进行综述。
【关键词】 葡萄膜炎 基因多态性 细胞因子 趋化因子 Original article
Corneal ulceration and subsequent scarring is a leading cause of ocular morbidity and unilateral blindness in developing countries. Resnikoff et al estimated that corneal opacity was the cause of blindness in 45% of cases worldwide[1]. An estimate from the Malaysian National Eye Survey (1996) showed that the prevalence of corneal opacities causing visual impairment was 0.04% and blindness caused by corneal disease was 3.42%[2].
The knowledge of risk factors, clinical features, causative organisms and their antibiotic sensitivity is essential in successful treatment[3]. Prompt institution of the appropriate antibiotic therapy remains the cornerstone of treatment. This demands clinical suspicion of a microbial cause for keratitis, knowledge of the likely agents in a particular community, reliable microbiological investigations and the availability of effective antibiotics.
This study analyzes the cases admitted for management of corneal ulcers at UMMC over a 34 month period.
MATERIALS AND METHODS
This is a cross sectional analytical study of patients diagnosed with corneal ulcers. We recorded age, gender, ethnicity, presence of known risk factors, clinical features, microbiology results, outcome of the lesion and best corrected visual acuity after two months of follow up. This study was carried out from July 2003 to April 2006.
All patients admitted to UMMC with a diagnosis of corneal ulcer were included in this study. Corneal ulcer was diagnosed when there was disruption in the continuity of the corneal epithelium, with evidence of underlying stromal infiltration or inflammation. Patients without epithelial defects or corneal infiltrates were excluded.
Visual acuity was assessed using a standard metric Snellen chart on admission, followed by a complete slitlamp examination of the anterior segment and fundus. Site and size of the ulceration, as well as presence of hypopyon were recorded. After instillation of 5g/L propacaine hydrochloride, corneal scrapings were taken with the bevel of a sterile needle. The specimens were innoculated onto blood, chocolate and sabouraud agar plates. The material was also smeared on glass slides for Gram staining in all cases and also potassium hydroxide (KOH) preparation whenever fungal infection was suspected. They were then sent to the microbiology lab for microscopic examination and culture and sensitivity testing. Additional cultures were performed on contact lenses, their containers and their solutions when available.
All patients were aggressively treated with a broadspectrum empirical antibiotic therapy based on clinical suspicion of the causative organism. Choice of antibiotic was generally based on the appearance of the ulcer and any predisposing factors. Therapy was modified daily depending on the clinical response and culture and sensitivity results of corneal scraping.
This study included the subsequent outcome of the ulcers, whether complicated or otherwise. An ulcer was considered healed when there was reepithelialisation and notable resolution of the infiltrate. Patients with healed ulcers were further followedup in the eye clinic for the next two months. After this period, the residual scar and BCVA were noted.
Statistical Analysis Statistical analysis was done using Statistical Products and Services Solution (SPSS) 12.0. In this study, analyses were done using Chisquare and Pearson correlation tests. A level of significance of P<0.05 was used.
RESULTS
Demographic Characteristics A total of 87 eyes of 84 patients were included. One patient was admitted for bilateral corneal ulcers and another patient had three separate admissions for recurrence of herpetic keratitis. There were 46 female and 38 male patients. The ethnic distribution was 44(52%) Malays, 20 (24%) Chinese, 10 (12%) Indians and 10 (12%) foreign nationals including 6 Indonesians, 1 Burmese, 1 Vietnamese, 1 Bangladeshi and 1 Jordanian. In the three main local ethnic groups, more females were affected but in the group of foreigners all those affected were males.
Patients ages ranged from 9 to 87 years old (mean 34.8±19.2 years). The age group mode was 20 to 40 years. Gender difference was statistically significant (P<0.05) in contact lens wear (higher in females) and trauma (higher in males) but not in the ocular surface disease, previous surgery or glaucoma subgroups.
Risk Factors
Ocular risk factors The use of contact lenses was the most frequent ocular risk factor (47%). Ocular trauma or foreign body entry occurred in 25%, 24% had some form of ocular surface abnormality, 12% had a history of ocular surgery in the involved eye (either recent or in the past) and 9% had been diagnosed with glaucoma.
The majority of those with ocular trauma were bluecollar workers. Labourers (11 cases), factory workers (2 cases), grass cutters (2 cases), a gardener and a cook.
Of the ocular surface abnormalities, there were 6 eyes (7%) with bullous keratopathy; 5 of pseudophakic bullous keratopathy and 1 secondary to acute angle closure glaucoma. Chronic keratoconjunctivitis was seen in 5 cases (6%). There were 4 cases (5%) of herpetic keratitis, of which 3 were of the same patient who developed recurrence at different periods in time. Exposure keratopathy was seen in 3 eyes (3%); 1 patient had chronic progressive external ophthalmoplegia (CPEO) and had previous corrective surgery for ptosis, 1 patient was bedridden with spastic paralysis due to cerebrovascular accident (CVA) and the other one had thyroid eye disease (TED). 1 case was of dry eye due to StevenJohnson syndrome and 1 case of neurotrophic keratopathy was secondary to trigeminal nerve palsy in acoustic neuroma. Two patients each in the herpetic keratitis and chronic keratoconjunctivitis group were given topical steroids prior to presentation.
Table 1 Visual acuity during the course of this study
VAOn admissionOn discharge2 months after discharge>6/18203847<6/186/6017239<6/603/60412<3/601/60640<1/60PL36137NPL255Not available2317Total878787
Systemic risk factors Diabetes mellitus and hypertension were the most common systemic risk factors seen, with 7 (8%) and 8 cases (9%) respectively. There were 2 cases each of bronchial asthma, ischaemic heart disease, chronic osteomyelitis of the lower limbs and systemic lupus erythematosus (SLE). One of the cases who had chronic osteomyelitis was also an opium smoker. The other conditions with single occurrence were acoustic neuroma, autoimmune hepatitis, autoimmune haemolytic anaemia (AIHA), chronic obstructive airway disease, CVA, CPEO, pregnancy, psychiatric disorder, TED, StevenJohnson syndrome and glucose 6phosphate dehydrogenase deficiency (G6PD). The cases with SLE, autoimmune hepatitis and AIHA were on systemic steroids at the time of admission into this study.
Clinical Features
Visual acuity Visual acuity on admission (Table 1) was between <1/60 to perception of light in the majority (41%) of eyes. 2 eyes had no perception to light (NPL) for many years before presentation, 1 due to rubeotic glaucoma and the other due to a penetrating injury. We could not assess visual acuity in 2 patients, 1 with a psychiatric disorder and the other with spastic paralysis due to a CVA. On discharge, visual acuity was >6/60 in 61 eyes (70%). Eventually, the visual acuity at 2 months after discharge was >6/18 in 47 eyes (54%). However, there was also a considerable number of patients who defaulted followup at two months after discharge, 17 cases (20%). 2 eyes developed intractable endophthalmitis and one eye perforated, requiring eviscerations and enucleation respectively.
Thirtyfive eyes (78%) with a central ulcer had vision <3/60 on admission, of which 11 (24%) remained at that level 2 months after discharge. Only 7% of eyes with peripheral ulcers had vision <3/60 after the same duration of follow up. The BCVA was correlated to ulcer site (P<0.01) and size (P<0.01) but not to the age of the patient.
Hypopyon There were more corneal ulcers without hypopyon (59.8%) than with it (40.2%). 16 eyes (45%) in the contact lens group had hypopyon. Hypopyon was significantly correlated with central ulcers (P<0.05). There was no significant correlation between hypopyon ulcers with any of the ocular risk factors.
Ulcer site Of the ulcers, 51.7% were seen in the central cornea involving the pupillary area, 14.9% were in the paracentral region and 33.3% were in the peripheral cornea. The site of ulcer was not significantly correlated to any of the ocular risk factors.
Ulcer size Thirtyeight cases (43.6%) were 2 to 4mm in size, 28 (32.2%) larger than 4mm and 21 (24.1%) smaller than 2mm. There were statistically significant correlations between ocular surface disease and glaucoma with ulcer size.
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