Cataract surgery and the corneal endothelium: An appraisal of factors influencing endothelial cell losses during cataract surgery

A prospective investigation was designed to determine the factors that influence corneal endothelial cell losses during and after cataract surgery. An unselected cohort of patients due for routine cataract surgery were examined, by a single observer, one day prior to surgery and during the early (day 1 to 5) and late (week 10 to 30) postoperative period. Clinical assessment and endothelial specular photomicroscopy was performed for both the study eye and the partner eye; estimates of central corneal endothelial cell density being derived from the specular photomicrographs by a second, independent, observer. Two hundred and seventy patients were enrolled and 236 (84 male, 152 female) completed the study. The reproducibility of some clinical measurements was assessed by several tests, including variance analysis for repeated measurements in the partner (unoperated) eyes. The variability for estimates of central corneal thickness, anterior chamber depth and endothelial cell density were within accepted limits for these methods and a minor drift of some instrumental measurements was insufficient to impair subsequent results of investigation. Analysis of data by both paired comparisons and by multivariate variance analysis shows dense sclerosis of the lens nucleus to greatly increase cell losses after extracapsular surgery, or after intracapsular surgery with capsular rupture; this being the factor most influential in determining cell losses. The presence of diabetes further increases cell losses during extracapsular extraction of such cataracts. A peripheral corneal section used during extracapsular cataract surgery is associated with reduced cell losses, as would appear to be the absence of corneal guttata. The preoperative presence of a shallow anterior chamber or the loss of vitreous humour, however, both increase cell losses after intracapsular surgery. Mathematical functions characterizing the recovery of corneal thickness in the early and late postoperative period are proposed and formulae for the prediction of endothelial cell losses presented

Mathematical Models of Fluid Flows in the Human Eye

Fluids in the eye have many important functions, such as regulating the intraocular pressure, delivering nutrients to the avascular intraocular tissue of the cornea and the lens, and contributing to adhesion forces between the sensory retina and the retinal pigment epithelium. Failure of these functions may lead to a number of pathological conditions. Studying fluid flows in the eye is therefore relevant to improve our understanding of the physiology of the organ and to prevent or treat certain eye diseases. This thesis consists of two main parts. In the first part we propose mathematical models of the dynamics of the aqueous humour in the anterior segment of the eye. The problems considered are in the area of fluid mechanics and our approaches are based on the use of lubrication theory that is applicable for flows in thin domains. The second part is related to fluid transport across the retinal pigment epithelium and it concerns a multiphysics problem, which couples fluid and ion transport

Cell migration and capillary plexus formation in wounds and retinae

Cell migration is a fundamental biological phenomenon that is critical to the development and maintenance of tissues in multi-cellular organisms. This thesis presents a series of discrete mathematical models designed to study the migratory response of such cells when exposed to a variety of environmental stimuli. By applying these models to pertinent biological scenarios and benchmarking results against experimental data, novel insights are gained into the underlying cell behaviour. The process of angiogenesis is investigated first and models are developed for simulating capillary plexus expansion during both wound healing and retinal vascular development. The simulated cell migration is coupled to a detailed model of blood perfusion that allows prediction of dynamic flow-induced evolution of the nascent vascular architectures – the network topologies generated in each case are found to successfully reproduce a number of longitudinal experimental metrics. Moreover, in the case of retinal development, the resultant distributions of haematocrit and oxygen are found to be essential in generating vasculatures that resemble those observed in vivo. An alternative cell migration model is then derived that is capable of more accurately describing both individual and collective cell movement. The general model framework, which allows for biophysical cell-cell interactions and adaptive cell morphologies, is seen to have the potential for a range of applications. The value of the modelling approach is well demonstrated by benchmarking in silico cell movement against experimental data from an in vitro fibroblast scrape wound assay. The results subsequently reveal an unexplained discrepancy that provides an intriguing challenge for future studies

Morfologia e morfometria das células do endotélio da córnea de equinos utilizando a microscopia eletrônica de varredura

O conhecimento da morfologia endotelial nas diferentes regiões da córnea é de suma importância para avaliação de endotélios corneanos saudáveis e doentes e de suas respostas ao uso de medicações. O objetivo do presente estudo foi descrever a morfologia do endotélio nas regiões central e periférica superior da córnea saudável de equinos, medir a área média das células pentagonais, hexagonais e heptagonais presentes nas regiões avaliadas, calcular o polimegatismo de cada tipo celular e correlacionar estes parâmetros entre os diferentes formatos celulares. Foram estudados dez equinos, machos ou fêmeas, de diferentes idades, provenientes de um abatedouro licenciado. Imagens da superfície posterior do endotélio da córnea foram obtidas com uso de microscopia eletrônica de varredura. A morfologia do endotélio de diferentes regiões da córnea foi avaliada. Além disso, foi correlacionada a variabilidade do tamanho celular médio com a morfologia endotelial. A análise estatística foi conduzida usando o teste de análise de variância (ANOVA) seguido do teste de Tukey (Post-Hoc), com nível de significância de 5%. As amostras avaliadas foram compostas em sua maioria por células hexagonais (60,5%), pentagonais (21,4%) e heptagonais (16,9%), células com quatro, oito ou nove lados compuseram 1,3%. A área celular média das células pentagonais foi 203,58 μm², das hexagonais foi 223,84 μm² e nas heptagonais foi 270,54 μm². O polimegatismo encontrado foi de 16% nas células pentagonais e hexagonais e de 20% nas heptagonais. A morfologia das células endoteliais de equinos saudáveis não diferiu entre as regiões central e periférica superior da córnea, sugerindo que a região central é representativa da região periférica. As células com sete lados apresentaram polimegatismo maior em relação às células de seis e de cinco lados.The knowledge of the endothelial morphology in the different regions of the cornea is important for the evaluation of healthy and sick corneal endothelium and its response to drugs. In order to describe the endothelial morphology in the central and superior peripheral regions of the equines’ cornea, evaluate area from pentagonal, hexagonal and heptagonal cells present in the evaluated regions, calculate the polimegathism and correlate these parameters, two healthy corneas were collected of ten equine, male or female, of different ages. Images of the posterior surface of the corneal endothelium were taken with scanning electron microscope. The endothelial morphology was studied in the different regions of the equines’ cornea. In addition, the polimegathism and morphology was also correlated. A statistical analysis was conducted using the Analysis of Variance (ANOVA) followed by Tukey's Test (Post-Hoc), with a 5% level of significance. In the central region, the endothelium consisted of 58.8% hexagonal cells, 22.6% pentagon, 17.1% heptagonal and 1.4% cells with either four, eight or nine sides. In the superior peripheral region, 62.1% of the cells were hexagonal, 20.2% pentagon, 16.6% heptagonal and 1.1% cells with four or eight sides. The average cell area of the pentagonal cells was 210.77 ± 31.53 μm² in the central region and 196.39 ± 34.35 μm² in the superior peripheral region; in hexagonal cells, the average cell area found in the central region was 216.12 ± 37.09 μm² and 231.56 ± 34.95 μm² in the superior peripheral region; and in cells with seven sides, the average cell area was 261.76 ± 55.29 μm² in the central region and in the superior peripheral region was found 279.32 ± 52.37μm². When not considering the corneal regions, the polymegathism found was 16% in the pentagonal and hexagonal cells and 20% in the heptagonal cells. The morphology results obtained did not differ between the central and peripheral regions of the cornea, suggesting that the central region is representative of the peripheral region. The highest coefficient of variation was seen in cells with seven sides