Purpose

To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis.

Design

Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694).

Participants

Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus.

Methods

Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression.

Main Outcome Measures

The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign.

Results

Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non–adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age.

Conclusions

A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non–adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.

中文翻译：

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决定因素的腺病毒性角膜结膜炎

目的

在大型角膜结膜炎临床队列中确定可预测结局的宿主和病原体因素。

设计

回顾性分析来自耳嘧啶的角膜结膜炎随机，对照，掩盖试验的临床和分子数据（NVC-422 IIB期，NovaBay； clinicaltrials.gov标识符，NCT01877694）。

参加者

来自美国，印度，巴西和斯里兰卡的500名参与者患有角膜结膜炎的临床诊断和腺病毒快速检测阳性结果。

方法

在第1、3、6、11和18天获得临床体征和症状以及双侧结膜拭子。进行了聚合酶链反应（PCR）分析，以检测和定量所有样品中的腺病毒。回归模型用于评估各种变量与角膜结膜炎结局的相关性。通过腺病毒种类和Cox回归评估每种症状或体征消失的时间。

主要观察指标

第1天至第18天的临床体征综合评分差异，第1天至第18天的平均视力变化以及每种症状或体征消退的时间。

结果

在500名参与者中，有390名（78％）通过PCR显示出腺病毒的证据。在腺病毒阳性参与者中，腺病毒D种类最常见（占病例总数的63％），但总共检测到4种和21种不同类型的腺病毒。与所有其他腺病毒物种相比，腺病毒D与更严重的体征和症状，上皮下浸润发展的速率较高以及病毒载量下降较慢有关。所有患有非腺病毒D物种感染和腺病毒阴性角膜结膜炎的患者的临床过程均相似。在第1天到第18天之间，视力的平均变化为1.9个字母；视觉效果较差与年龄较大有关。

结论

很大比例的角膜结膜炎与可检测的腺病毒无关。腺病毒D角膜结膜炎的临床病程比非腺病毒D种类感染或腺病毒阴性角膜结膜炎的病程严重得多。演讲时病毒载量高和参与者来自美国以外地区与较差的临床结局有关。