Doenças da córnea estão entre as principais causas de cegueira e os mecanismos de lesão e reparação estão em grande parte concentradas no epitélio, porém os mediadores e alvos para possíveis intervenções terapêuticas são pouco conhecidos.Nas agressões ao epitélio da córnea, a ativação dos receptores vanilóides de potencial transitório 1 (TRPV1) leva a resposta inflamatória e cicatricial. O objetivo desse trabalho é identificar os mecanismos de sinalização e resposta do TRPV1 na córnea de animais experimentais. O cultivo de células epiteliais de córnea de ratos, a identificação de mediadores por western blot, medida do influxo de cálcio, resposta de citocinas medidas por ensaio quantitativo de PCR em tempo real (RNAm) e ELISA (proteína) após estímulos nocioceptivos ou inflamatórios; e a investigação histológica e imunohistoquimica em modelos animais, sejam ratos com diabetes mellitus (DM) por 8 semanas ou expostos a cloreto de benzalcônio a 0,2% (BAC) por 7 dias. Camundongos TRPV1-/- comparados aos controles C57 foram comparados sem estimulo, ou sob estimulo único com CAP a 1µM, BAC 0,2 % por 7 dias ou após queimadura alcalina com NaOH a 1M. Os resultados mostraram a presença de TRPV1 em epitélio de córnea em cultura primária, mostraram que essas células respondem com influxo de cálcio ao estímulo com o agonista Capsaicina a 1µM e aumento de TNF? e IL-1? (sendo máximo nas combinações CAP+CPZ e Win+CAP, respectivamente). Em ratos com DM e BAC ocorre a redução da expressão do RNAm de IL-1? (p=0,0269) na córnea, entre outras alterações. Os camundongos TRPV1-/- tem fenótipo físico e ocular normal, porém reduzida sensibilidade a CAP 1µM. O tratamento com BAC leva a diminuição da secreção lacrimal (p=0,0011) e de IL-1? e TNF? na glândula lacrimal (GL) de TRPV1-/- machos (p=0,0177, p=0,0245, respectivamente). A queimadura alcalina com NaOH 1M resultou em melhor cicatrização e maior espessura epitelial no grupo TRPV1-/-. Em ix conclusão, o TRPV1 está presente na córnea e atua em resposta a agressões externas. Situações adquiridas como DM e toxicidade por BAC, reconhecidas como neuropáticas diminuem a expressão de mediadores inflamatórios. A ausência genética e TRPV1 não altera o fenótipo, mas apresenta menor sensibilidade e melhor restauração da superfície ocular após queimadura alcalina / Corneal diseases are among the leading causes of blindness.Damage and repair mechanisms are largely concentrated in the epithelium, but the mediators and targets for possible therapeutic interventions are poorly understood. The aggressions to the corneal epithelium, the activation of vanilloid receptors transient potential 1 (TRPV1) leads to inflammatory and wound healing. The aim of this study is to identify the signaling mechanisms and TRPV1 response in the cornea of experimental animals.The culture of epithelial cells from rat cornea, to identify mediators by western blot analysis, measurement of calcium influx, cytokine response measured by PCR real time (mRNA) and ELISA (protein) nocioceptivos or after inflammatory stimuli; and the histological and immunohistochemical investigation in animal models are mice with diabetes mellitus (DM) for 8 weeks, and exposed to benzalkonium chloride at 0.2% (BAC) for 7 days. Mice TRPV1-/- compared to control C57 were compared with no stimulus, or under single stimulation with 1 µM Capsaicine (CAP), BAC 0.2% for 7 days or after the alkali burn with NaOH 1 M.The results showed the presence of TRPV1 in corneal epithelium in primary culture, showed that these cells respond to calcium influx the stimulus with capsaicin agonist 1?M and increase of TNF? and IL-1? (being maximum at the CAP + CPZ combinations and Win + CAP, respectively). In rats with DM and BAC occurs reducing the expression of IL-1? mRNA (p = 0.0269) in the cornea, among other changes. The TRPV1-/- mice have physical phenotype and normal ocular but low sensitivity to CAP 1?M. Treatment with BAC leads to decreased tear secretion (p = 0.0011) and IL-1? and TNF? in the lacrimal gland (GL) of TRPV1-/- mice (p = 0.0177, p = 0.0245, respectively) . The alkaline burn with NaOH 1M resulted in better healing and greater epithelial thickness in TRPV1-/- group .In conclusion, TRPV1 is present in the cornea and operates in response to external aggressions. Situations existing as DM and xi toxicity BAC recognized as neuropathic decrease the expression of inflammatory mediators. Genetic absence and TRPV1 does not alter the phenotype, but has lower sensitivity and better restoration of the ocular surface after alkaline burn

OBEJTIVOS: Analisar a segurança e eficácia da cirurgia de crosslinking (CXL) de córnea em pacientes com ceratocone em estágios avançados após um seguimento de 4 anos. MÉTODOS: Trata-se de um estudo retrospectivo de pacientes com ceratocone avançado em progressão (Estágio 3 e 4 da classificação de Amsler-Krumeich) que foram submetidos a cirurgia de CXL seguindo o protocolo padrão. Os parâmetros examinados foram acuidade visual com (AVCC) e sem (AVSC) correção, valores ceratométricos (média, plana, curva e apical), paquimetria, e contagem de células endoteliais no préoperatório e após 12, 24 e 48 meses do procedimento. RESULTADOS: Este estudo abrange quarenta olhos de 40 pacientes que foram submetidos a cirurgia de CXL. A média de idade foi 22,5 anos (Intervalo:15 a 37 anos). Tanto a AVSC quanto a AVCC permaneceram estáveis durante o período de seguimento, sem mudanças estatisticamente significativas. Apesar de todos os valores ceratométricos sofrerem uma leve diminuição, apenas a ceratometria apical atingiu uma mudança com significado estatístico (P=0,037) após 4 anos de seguimento. Uma redução significativa da espessura corneana foi também observada (paquimetria ultrassônica era de 388 ± 49 e passou para 379 ± 48 ?m, P < 0,0001; paquimetria através de tomografia de imagem em fenda era de 362 ± 48 e foi para 353 ± 51 um, P < 0,0001); embora essa diferença não seja clinicamente significativa. A contagem de células endoteliais não sofreu alterações significativas durante o seguimento. A taxa de falha do tratamento foi de 5% (dois pacientes) durante o seguimento. CONCLUSA?O: A cirurgia de CXL corneano em pacientes com ceratocone avançado se mostrou segura e capaz de manter os parâmetros visuais e topográficos pelo menos durante 4 anos / PURPOSE: To analyze the safety and efficacy of standard corneal collagen crosslinking (CXL) in advanced cases of progressive keratoconus (KC) after four years of follow-up. METHODS: A retrospective case series of patients with advanced progressive KC (stage 3 and 4 of Amsler-Krumeich classification) underwent standard CXL treatment. The parameters examined were changes in uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), keratometry values (mean K, flattest K, steepest K, and apical K), pachymetry, and endothelial cell count at the baseline and at 12-, 24- and 48-months postoperatively. RESULTS: Forty eyes of 40 patients were enrolled into the study. The mean patient age was 22.5 years (range: 15 to 37 years). Both mean UCVA and CDVA remained stable during the time points; no statistically significant change was noted. Although a slightly reduction was observed in all keratometric readings, a statistically significant reduction was only reached in the apical K (p=0.037) at four years after CXL. A significant reduction in the pachymetry was also found (from 388±49 to 379±48 um, P < 0,0001 and from 362±48 to 353±51 um, P < 0,0001, ultrasonic and slit-scanning readings, respectively) ; however this change is not likely clinically meaningful. Endothelial cell count was not significantly modified at the end of the study. Treatment failure or progression was noted in two patients (5%) over the followup period. CONCLUSION: Standard CXL treatment seems to be safe and able to stabilize both visual acuity and topographic parameters at four-year follow-up in advanced keratoconic eyes

Teng, Yufei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 175-193). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Os corantes vitais têm sido utilizados em diversas áreas da oftalmologia para melhorar a visibilização de diferentes tecidos. Com o objetivo de avaliar os efeitos imediatos do corante Azul brilhante a 0,05% no endotélio da córnea de equinos, foram utilizadas 38 córneas de 19 cavalos, machos ou fêmeas, de diferentes idades e provenientes de abatedouro comercial licenciado. As córneas foram aleatoriamente divididas em dois grupos. Grupo1: o endotélio da córnea foi exposto a solução salina balanceada por 60 segundos. Grupo 2: o endotélio da córnea foi exposto ao corante Azul brilhante 0,05% (Opht-Blue, Ophthalmos, São Paulo, Brazil) por 60 segundos seguido por lavagem com solução salina balanceada (BSS, Ophthalmos, São Paulo, Brazil). As córneas então foram excisadas com trépano de 8mm e preparadas para avaliação com microscopia óptica (24 córneas) e microscopia eletrônica de varredura (14 córneas). As áreas de dano endotelial foram mensuradas. Devido ao aparecimento de resíduos não normais na utilização de comparação de médias via ANOVA, optou-se pelo modelo linear generalizado e, com 5% de significância, o teste Qui-quadrado demonstrou que o fator tratamento não difere do controle. Conclui-se que o corante Azul brilhante em concentração de 0,05% não provocou danos ao endotélio da córnea de equinos. / Vital dyes have been used in many areas of ophthalmology for improving visualization of different tissues. With the objective of evaluating the immediate effects of 0,05% brilliant blue on corneal endothelium of horses, 38 corneas of 19 horses, both male and female of different ages obtained from a licensed Brazilian commercial slaughterhouse were studied. Corneas were randomly divided into two groups. In group 1, corneal endothelium was perfused with BSS for 60 seconds. In group 2, corneal endothelium was perfused with 0.3 mL of brilliant blue 0.05% (Opht-Blue, Ophthalmos, São Paulo, Brazil) for 60 seconds followed by rinsing with a balanced salt solution (BSS, Ophthalmos, São Paulo, Brazil). The corneas were, subsequently, excised with an 8mm trephine and prepared to analyze posterior endothelial surface using a light microscope (24 corneas) and a scanning electron microscope (14 corneas). Due to non-normal residuals at ANOVA mean comparison, a generalized linear model was utilized at 5% level of significance. Qui-square test stated that treatment and control group were not different statistically. The 0.05 % brilliant blue did not damage equine corneal endothelium.

Objetivo: Avaliar a função visual de pacientes submetidos a transplante lamelar anterior profundo (DALK) utilizando a dissecção com tunelizador manual e fio. Métodos: Foram incluídos 33 pacientes com ceratocone que apresentavam BCVA <= 0,60 LogMar, miopia e astigmatismo entre 8,00 e 10,00D, K central médio > 53,00D, ausência de cicatrizes, espessura corneana mínima entre 300 e 400 um. Foi feita avaliação oftalmológica completa no pré e no pós-operatório de 6 a 8 meses. Estas avaliações foram complementadas com exame topográfico da córnea, microscopia especular para avaliação da densidade das células endoteliais corneanas, aberrometria corneana e exame de tomografia de coerência óptica do segmento anterior. As variáveis BCVA, UCBA e os valores totais das aberrações corneanas de alta ordem foram correlacionadas com a espessura do leito estromal residual. Resultados: Os pacientes submetidos à DALK apresentaram BCVA de 0,68 ± 0,27 LogMar o que representa BCVA superior a 20/40 em 60% da amostra analisada. Não foram observadas micro ou macroperfurações. Houve diminuição na contagem endotelial de 2702,87 ± 548,87 células por mm2 para 2282,10 ± 525,66 células por mm2 . A dissecção do estroma profundo com o fio facilitou a remoção de tecido estromal posterior, fato corroborado com o achado de que o leito residual estromal aferido foi de 49,18 ± 18,36 ?m na região central e foi inferior a 80 ?m em grande parte dos pacientes estudados. No que se refere à regularidade da dissecção, observou-se tendência a valores mais elevados de espessura residual na periferia (60,09 ± 17,70 ?m). Não houve correlação da BCVA, UCVA e do total de aberrações de alta ordem da córnea com a espessura do leito estromal residual. Conclusão: A apreciação dos resultados desse estudo mostrou que com a técnica utilizada para realização de DALK em portadores de ceratocone obteve-se resultados topográficos e funcionais semelhantes a outras técnicas consagradas pela literatura. A facilidade na dissecção do estroma profundo, a regularidade da dissecção e a presença de baixíssimo índice de conversão para transplantes penetrantes são encorajadores / Objective: Evaluate the visual function of patients undergoing deep anterior lamellar keratoplasty (DALK) using a manual spatula and a wire dissection. Methods: Thirty three keratoconus patients were included, meeting the following inclusion criteria: BCVA logMAR <=0,60, myopia and astigmatism between 8.00 and 10,00D, K central average > 53.00D, no corneal scars and minimal corneal thickness between 300 and 400 um. Complete ocular evaluation was performed preoperatively and postoperatively in 6-8 months. These assessments were supplemented by topographical survey of the cornea, specular microscopy to evaluate the density of corneal endothelial cells, corneal wavefront analysis and examination of optical coherence tomography of the anterior segment (Visante). The BCVA variables, UCVA and the total amounts of corneal higher-order aberrations were correlated with the the residual stromal bed thickness. Results: Patients that undergone to DALK with the described technique presented a BCVA of 0.68 ± 0.27 logMAR which represents a BCVA of more than 20/40 at 60% of the analyzed sample. There were no micro or macroperforations. We observed a small decrease in the endothelial cell count from 2702.87 ± 548.87 cells per mm2 to 2282.10 ± 525.66 cells per mm2. The dissection of the deep stroma with a wire facilitated the posterior stromal tissue removal, thus the measured stromal bed thickness was 49.18 ± 18.36 ?m in the central region and less than 80 ?m in the majority of the studied patients. As regards the dissection regularity, we showed a tendency to higher values of residual thickness at the periphery (60.09 ± 17.70 ?m). There was no correlation of the BCVA, UCVA and total corneal higher-order aberrations with the residual stromal bed thickness. Conclusion: The assessment of the study data showed that the described technique achieved a topographical and functional result similar to other techniques consecrated by literature. The shallow learning curve, the ease to perform the dissection of the deep stroma, the postoperative stromal regularity and the presence of very low conversion rate for penetrating keratoplasty are encouraging

OBEJTIVOS: Analisar a segurança e eficácia da cirurgia de crosslinking (CXL) de córnea em pacientes com ceratocone em estágios avançados após um seguimento de 4 anos. MÉTODOS: Trata-se de um estudo retrospectivo de pacientes com ceratocone avançado em progressão (Estágio 3 e 4 da classificação de Amsler-Krumeich) que foram submetidos a cirurgia de CXL seguindo o protocolo padrão. Os parâmetros examinados foram acuidade visual com (AVCC) e sem (AVSC) correção, valores ceratométricos (média, plana, curva e apical), paquimetria, e contagem de células endoteliais no préoperatório e após 12, 24 e 48 meses do procedimento. RESULTADOS: Este estudo abrange quarenta olhos de 40 pacientes que foram submetidos a cirurgia de CXL. A média de idade foi 22,5 anos (Intervalo:15 a 37 anos). Tanto a AVSC quanto a AVCC permaneceram estáveis durante o período de seguimento, sem mudanças estatisticamente significativas. Apesar de todos os valores ceratométricos sofrerem uma leve diminuição, apenas a ceratometria apical atingiu uma mudança com significado estatístico (P=0,037) após 4 anos de seguimento. Uma redução significativa da espessura corneana foi também observada (paquimetria ultrassônica era de 388 ± 49 e passou para 379 ± 48 ?m, P < 0,0001; paquimetria através de tomografia de imagem em fenda era de 362 ± 48 e foi para 353 ± 51 um, P < 0,0001); embora essa diferença não seja clinicamente significativa. A contagem de células endoteliais não sofreu alterações significativas durante o seguimento. A taxa de falha do tratamento foi de 5% (dois pacientes) durante o seguimento. CONCLUSA?O: A cirurgia de CXL corneano em pacientes com ceratocone avançado se mostrou segura e capaz de manter os parâmetros visuais e topográficos pelo menos durante 4 anos / PURPOSE: To analyze the safety and efficacy of standard corneal collagen crosslinking (CXL) in advanced cases of progressive keratoconus (KC) after four years of follow-up. METHODS: A retrospective case series of patients with advanced progressive KC (stage 3 and 4 of Amsler-Krumeich classification) underwent standard CXL treatment. The parameters examined were changes in uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), keratometry values (mean K, flattest K, steepest K, and apical K), pachymetry, and endothelial cell count at the baseline and at 12-, 24- and 48-months postoperatively. RESULTS: Forty eyes of 40 patients were enrolled into the study. The mean patient age was 22.5 years (range: 15 to 37 years). Both mean UCVA and CDVA remained stable during the time points; no statistically significant change was noted. Although a slightly reduction was observed in all keratometric readings, a statistically significant reduction was only reached in the apical K (p=0.037) at four years after CXL. A significant reduction in the pachymetry was also found (from 388±49 to 379±48 um, P < 0,0001 and from 362±48 to 353±51 um, P < 0,0001, ultrasonic and slit-scanning readings, respectively) ; however this change is not likely clinically meaningful. Endothelial cell count was not significantly modified at the end of the study. Treatment failure or progression was noted in two patients (5%) over the followup period. CONCLUSION: Standard CXL treatment seems to be safe and able to stabilize both visual acuity and topographic parameters at four-year follow-up in advanced keratoconic eyes

De par son rôle dans de nombreuses fonctions biologiques, RAGE est une récepteur membranaire crucial du développement embryonnaire jusqu’à l’âge adulte. Ce récepteur multi-ligand est capable d’activer de nombreuses cascades de signalisation, lui permettant entre autres d’être impliqué dans les processus inflammatoires et cicatriciels. Bien que décrite, son action cellulaire et moléculaire dans les processus de régénération/cicatrisation reste encore à éclaircir, malgré des études déjà menées sur les épithéliums cutanée et pulmonaire. Concernant la cicatrisation de l’épithélium cornéen, l’action de ce récepteur et de ses ligands est peu documentée et largement controversé. Ce travail a permis de tester l’effet de 2 ligands de RAGE (HMGB1 et AGEs) sur la cicatrisation de l’épithélium cornéen en utilisant un modèle in vitro de cellules épithéliales de cornée humaine (HCE). Il visait aussi à étudier les cascades de signalisation et les processus cellulaire mis en jeu suite à l’activation de ce récepteur. Les résultats obtenus ont tout d’abord permis de démontrer que l’action pro-cicatrisante du récepteur RAGE sur des cellules de l’épithélium cornéen, était ligand et dose spécifique. Ainsi seul le ligand AGEs promeut la cicatrisation indépendamment des processus de migration et de prolifération cellulaire. Dans cette étude le couple AGEs/RAGE est capable d’activer la cascade de signalisation NF-κB et la transcription d’un gène cible Connexine 43, dont le rôle a déjà été décrit durant la cicatrisation.Malgré la complexité du « signal RAGE », les premières pistes apportées par cette étude permettent d’envisager dans un futur proche la caractérisation précise de son action pro-cicatrisante au niveau de la sphère oculaire. Ceci passera non seulement par l’étude exhaustive des cascades de signalisations activées et des gènes régulés mais aussi par l’utilisation du modèle animal souris sauvage et RAGE -/-. / Because of its role in many biological functions, RAGE is a crucial transmembranous receptor from development to adulthood. This multiligand receptor can activate numerous signaling pathways, and it is involved in inflammatory and wound healing processes. Although already describe, molecular and cellular processes involved during wound healing still to be clarify despite some studies conducted on skin and lung epithelium. In the corneal epithelium wound healing, RAGE and its ligands effects still poorly understood and widely controversial. This work allowed the test of 2 ligands (HMGB1 and AGEs) on corneal epithelium healing using an in-vitro model of human corneal epithelial cells (HCE). It also aims to study the signaling pathways and cellular processes involved after this receptor activation. Results obtained permit to demonstrate a ligand and dose-dependent action of RAGE during this pro-healing process. Thus, only AGEs ligand promotes wound healing independently of cellular migration and proliferation processes. In this study, AGEs/RAGE couple can activate NF-kB signaling pathway and Connexin 43 target gene expression, already describe to be involved in wound healing. Despite the “RAGE signal” complexity, first tracks brought by this study allow to plan in the near future the precise elucidation of its pro-healing properties in the ocular sphere. This will pass not only by the exhaustive study of the signaling pathways activated and the regulated genes but also by the use of wild-type and RAGE - / - mouse model.

Clinical wavefront-guided corneal ablation has been now the most technologically advanced method to reduce the dependence of glasses and contact lenses. It has the potential not only to eliminate spherocylindrical errors but also to reduce higher-order aberrations (HOA). Recent statistics show that more than 96% of the patients who received laser in situ keratomileusis (LASIK) treatment reported their satisfaction about the improvement on vision, six months after the surgery. However, there are still patients complaining that their vision performance did not achieve the expectation or was even worse than before surgery. The reasons causing the unexpected post-surgical outcome include undercorrection, overcorrection, induced HOA, and other postoperative diseases, most of which are caused by inaccurate ablation besides other pathological factors. Therefore, to find out the method to optimize the LASIK procedures and provide a higher surgical precision has become increasingly important. A proper method to calculate ablation profile and an effective way to control the laser beam size and shape are key aspects in this research to resolve the problem. Here in this Master of Philosophy degree thesis, the author has performed a meticulous study on the existing methods of ablation profile calculation and investigated the efficiency of wavefront only ablation by a computer simulation applying real patient data. Finally, the concept of a refractive surgery system with dynamical beam shaping function is sketched, which can theoretically overcome the disadvantages of traditional procedures with a finite laser beam size.

Recurrent corneal erosions are a common complication of superficial corneal wounds. They most commonly arise following a trauma, in association with various corneal dystrophies, or are idiopathic. The main aim of this thesis was to investigate two hereditary corneal diseases with recurrent erosions in order to find out if they had been described before, and more specifically to describe the clinical picture and the morphological changes, differentiate them from other known autosomal dominant corneal dystrophies with a clinical resemblance, and to exclude genetic linkage to known corneal dystrophies with autosomal-dominant inheritance and a clinical resemblance. The thesis is based on two families of subjects belonging to different phenotypes. The subjects from Småland (Dystrophia Smolandiensis) belonged to a six-generation family, which included 171 individuals of whom 44 were affected individuals, and the family from Hälsingland (Dystrophia Helsinglandica) included sevengenerations of 342 individuals, of whom 84 were affected. The individuals in both families were investigated by collection of medical history through medical records and questionnaires assessing different aspects of the diseases, pedigree analysis, and from clinical examination. Haplotype analysis was used to exclude genetic linkage of both diseases to known autosomal-dominant corneal dystrophies with a clinical resemblance. The morphological changes in Dystrophia Smolandiensis were investigated by examining affected individuals with in-vivo confocal microscopy and/or slit-lamp biomicroscopy, and examining corneal tissue samples using histopathology and immunohistochemistry. In Dystrophia Helsinglandica, the morphological changes were described using in-vivo confocal microscopy and/or slit-lamp biomicroscopy, but also using videokeratography and corneal sensitivity measurement. The main results were the findings of two new corneal disorders with autosomal dominant inheritance, characterized by recurrent corneal erosions. In Dystrophia Smolandiensis the symptoms often started within the first year of life. The number of recurrences per year was highest from the onset and for about 30-40 years, and the duration of recurrence could stretch up to 21 days. The frequency of recurrences was variable in the disease from continuous symptoms to once a year and tended to decrease later in life. The risk of having recurrences did not disappear completely with age. Typical precipitating factors of recurrence were draught and a common cold. About two thirds of the affected individuals responded well to oral vitamin B treatment, but no other therapy has so far been successful. In Dystrophia Smolandiensis development of corneal opacifications or secondary scarring of varying type and degree was seen in about half of the subjects. Opacifications were first noted at the age of about 7 years, but usually first seen at the age of 20-40 years. Corneal grafting was performed in nine individuals, and recurrences were seen in all grafts. The corneal buttons showed epithelial hyperplasia, partial or total loss of Bowman’s layer, and subepithelial fibrosis in the light microscope. The deeper stroma, Descement’s membrane, and endothelium were normal. Confocal microscopy confirmed loss of Bowman’s layer and revealed that the corneal nerves either were normal in their sub-basal plexa or showed signs of regeneration. None of the morphological findings were specific. We believe that the opacifications are reactive corneal changes to repeated erosive events. The onset in Dystrophia Helsinglandica was usually at the age of 4-7 years and late-developing subepithelial fibrosis not significantly affecting visual acuity was seen in all affected individuals over the age of 37 years. The number of recurrences per year was highest from the onset and for about 20-30 years, and the duration of recurrence was usually up to about a week. The frequency of recurrences tended to decrease in the disease with increasing age, but did not cease completely. The precipitating factor of recurrence was typically a minor trauma. No therapy has so far been successful in the family. The corneal changes of affected individuals were classified into different stages from a nearly normal cornea to progressive fairly discrete subepithelial fibrosis of the central cornea. Discrete localized Subepithelial fibrosis in the periphery or mid-periphery (stage I) was the sole finding in 12% of the individuals. A more widespread subepithelial fibrosis, mainly in the mid-periphery, was found in 31% of the individuals (stage II). In stage III, the subepithelial fibrosis engaged the central cornea but did not affect the vision to a significant degree. In late phases of stage III small jellylike corneal irregularities could be seen. We believe that the opacifications are reactive changes to repeated erosive events. In conclusion this thesis describes two new corneal disorders – Dystrophia Smolandiensis and Dystrophia Helsinglandica.

The purpose of this thesis is to describe the development of an anatomically based, young adult eye model, which includes a crystalline lens with a gradient refractive index (GRIN). This model will then be used to investigate the effect of laser refractive surgery. The first step in this process involved developing a symmetrical eye model that was found to be a better predictor of empirical longitudinal spherical aberration than any previous model. Myopia was simulated by either a purely axial or refractive technique. While these models were found to be good predictors of the spherical aberration measured in young adults, they did not predict the total amount of high-order aberrations. The techniques used to simulate a single type of myopia caused the myopic models to become anatomically inaccurate. To improve the eye models a biconic surface was used to quantify the anterior corneal shape as a function of myopia. A method to describe the refractive error and biconic shape parameters in Jackson Cross Cylinder terms was implemented to determine correlations. Results indicate that a biconic accurately models the average shape of the anterior corneal surface as a function of myopia. Adopting the biconic model for the anterior corneal surface and adding average misalignments of the ocular components transformed the models from symmetrical to asymmetrical. Refractive error was now simulated by the anatomically accurate changes in both the anterior corneal shape and axial length. The asymmetrical aberrations resulted from the misalignment of the ocular components and provided a good prediction of average empirical aberrations but underestimated the aberrations of individual subjects. Photorefractive keratectomy, a form of laser refractive surgery, was simulated by theoretically calculated and by empirically measured changes in the shape of the anterior corneal surface. Applying the change in anterior corneal shape to the asymmetrical models was used to develop postoperative models. Changes in corneal shape and model aberrations attributed to theoretical calculations do not match empirical observations. The prediction of increased high-order aberrations in postoperative models based on empirically measured changes in the anterior corneal topography was similar to clinical results. Average anatomically based, GRIN eye models have been developed that accurately predict the average aberrations of emmetropic and myopic young adults. These models underestimate the asymmetrical and total high-order aberrations that have been measured in individual subjects but are still useful for investigating the average effects of procedures like refractive surgery.