Centre for Mathematical Biology, Mathematical Institute, University of Oxford, UK.
Prog Retin Eye Res. 2010 Jan;29(1):59-78. doi: 10.1016/j.preteyeres.2009.11.002. Epub 2009 Nov 26.
Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye. The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity. Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable.
泪液高渗被认为在干眼症的发病机制中起关键作用，干眼症是一种常见的症状性疾病，伴有视觉障碍、泪膜不稳定、炎症和眼表面损伤。我们构建了一个泪液质量和溶质平衡模型，该模型基于文献中的广泛数据进行参数估计，可用于研究泪液蒸发、泪液流量和眨眼率对泪液渗透压的影响。特别是，在水性缺乏性（ADDE）和蒸发性（EDE）干眼症中，估计了代偿事件的性质。该模型再现了健康眼的泪膜弯月面的观察渗透压，并预测了正常和干眼症状态下泪膜中的浓度高于弯月面。在正常眼中，这种差异很小，但在干眼症中差异显著，尤其是在弯月面浓度高和半径低同时存在的情况下。这可能会影响从弯月面样本中获得的渗透压值的解释，因为它们不一定能完全反映出泪膜高渗对眼表面造成的潜在损伤。模型分析表明，增加眨眼频率可能在 ADDE 中对升高的泪液渗透压的补偿作用有限，但增加泪液流量，同时增加眨眼频率，可能会延迟 EDE 中高渗透压的发展。尽管如此，预测在泪膜破裂之前，EDE 中的泪液渗透压可能会比 ADDE 升高到更高的水平，除非眼表面发生独立影响泪膜稳定性的事件。ADDE 中眼表前泪液与 EDE 或混合性疾病对特定条件的预测反应的差异表明，没有一个单一的、经验可获得的变量可以作为泪膜浓度和眼表面损伤的替代物。这强调了需要测量和整合多个诊断指标来确定结果和预后。模型预测还表明，进一步研究 EDE 中高泪液流量表型的可能性可能会有收益。
