INTRODUÇÃO: É importante estudar a efetividade da trabeculectomia e estratégias para manter sua ação ao longo do tempo. Para melhorarmos o prognóstico das revisões cirúrgicas é imprescindível entendermos melhor a estrutura da bolha filtrante e suas possíveis causas de falência. Formas alternativas para se restabelecer a drenagem e o funcionamento da trabeculectomia não funcionante foram desenvolvidas, entre elas a Revisão Interna de Simmons. OBJETIVOS: Avaliar os efeitos da Revisão Interna de Simmons sobre a PIO; sobre o aspecto biomicroscópico da bolha no pós-operatório e sua correlação com achados biométricos obtidos pela biomicroscopia ultra-sônica. CASUÍSTICA E MÉTODOS: Foram incluídos e estudados de forma prospectiva por 6 meses, 29 pacientes portadores de glaucoma primário, submetidos a trabeculectomia prévia,há pelo menos três meses, que apresentavam PIO acima do esperado para o controle do glaucoma, apesar de medicação hipotensora utilizada. Foram fatores de inclusão a conjuntiva livre e o óstio interno da trabeculectomia patente à gonioscopia. O critério de sucesso foi: abaixamento da PIO, igual ou maior que 30% da PIO em relação à PIO pré-operatória e/ou pressão final menor ou igual a 15mmHg, com ou sem medicação antiglaucomatosa associada. RESULTADOS: Houve uma queda estatisticamente significante da PIO e do número de medicações utilizadas após a cirurgia. A PIO média antes da operação era de 23,72 ± 4,10 mmHg e ao término do estudo, de 15,04 ± 4,00 mmHg (p=0,000016). A média das pressões da curva tonométrica antes da cirurgia era de 22,36 ± 3,91mmHg, caindo para 15,01 ± 3,95mmHg no PO180d (p=0,0000001). Antes da cirurgia, a média do número de medicações usadas era de 2,1 ± 0,77 e ao término do estudo, 1,22 ± 1,01 (p=0,001117). Houve um aumento do tamanho da bolha filtrante, avaliado pela biomicroscopia. As bolhas apresentaram altura média de 0,28 ± 0,65 e terminaram o estudo com altura de 0,78 ± 0,85 (p=0,000016). Não houve diferença na altura da bolha, medida pela biomicroscopia ultra-sônica após a cirurgia. A pressão intra-ocular apresentou relação inversamente proporcional à dimensão da bolha filtrante, com significância estatística. As complicações mais encontradas foram: descolamento da membrana de Descemet, no local da incisão principal em 5 doentes (17,2%), abertura inadvertida da conjuntiva em 4 (13,8%), e descolamento de coróide, em 3 (10,3%). CONCLUSÕES: A Revisão Interna de Simmons proporcionou diminuição de 30% da PIO em 52% dos pacientes e redução do número de medicações antiglaucomatosas associadas, quando utilizadas. As bolhas se mostraram-se estatisticamente maiores após o procedimento. Houve uma correlação perfeita entre a classificação da altura da bolha entre a medida biomicroscópica baseada na escala de Indiana e a biométrica obtida pela biomicroscopia ultra-sônica. Não houve aplanamento da curva tonométrica apesar desta ter diminuído 32%. Não foi observada mudança significativa no vício de refração ou na acuidade visual após a operação. A biomicroscopia ultra-sônica demonstrou uma associação inversa entre um maior número de complicações pós-operatórias e o tamanho menor do óstio interno da trabeculectomia. / INTRODUCTION: It is important to study the trabeculectomy effectiveness and strategies to keep its action within long time. To improve the prognostic presented on glaucoma surgical reviews it is essential to understand better the bleb structure and its possible cause of failing. Alternative ways of restoring the drainage and the good performance of trabeculectomy have been studied, among them the Internal Revision of Simmons. PURPOSE: Evaluate the surgery effects on the IOP; on the biomicroscopic aspect of the bleb and its co-relation with biometric founding gotten through UBM. METHODS: For six months, 29 patients with open angle glaucoma who had been submitted to trabeculectomy before, for at least three months, with IOP above the expected to the control of glaucoma, despite the medication used, were included and studied in a prospective way. These patients should present the conjunctive tissue not too scarry and internal ostio of trabeculectomy present on the gonioscopia. The success criterion was: lowering the IOP, equal or above 30% on pre-operatory IOP and/or final pressure below 15 mmHg, with or without eye drops. RESULTS: There was a statistically fall of IOP and amount of medication used after the surgery. The average of IOP before surgery was 23.27 ± 4.10 mmHg and at the end of study was 15.04 ± 4.00 mmHg (p=0.000016). The average of the IOP curve pressure before surgery was 22.36 ± 3.91mmHg, dropped to 15.01 ± 4.0 mmHg at PO180d (p=0.0000001). Before the surgery the average of medication used was 2.1 ± 0.77 and at the end of the study it was 1.22 ± 1.01 (p=0.001117). There was an increase of the filtering bleb size clinically measured. The blebs had an average height of 0.28 ± 0.65 and at the end of the study their height was 0.78 ± 0.85 (p=0.000016). The UBM didn?t show any difference in the bleb size. The intra-ocular pressure presented an inversely proportional relation to the dimension of the filtering bleb, with statistic significance. The most frequently problems found were: detachment of Descemet membrane where the main incision was performed, in 5 (17.28%) patients; hole in the conjuntiva in 4 (13.88%), detachment of the choroid in 3 (10.38%). CONCLUSIONS: The surgery was effective, for provided 30% decrease of initial IOP in 52% without or with eye drops statistically in small number than in presurgery. The blebs have appeared, statistically, bigger after the procedure. There was a perfect correlation between the bleb height classification, within the clinical measurement, based on the Indian scale, and the biometric one, gotten by UBM. There was no flattening of the IOP curve pressure despite this one had been 32% lower than the initial one. No significant change has occurred in the vicious of refraction or in the visual accuracy after the surgery. The UBM demonstrated an association between a larger number of complications post-surgery and the internal size of the trabeculectomy ostio.

A diabetes mellitus (DM) causa alterações em todas as camadas da córnea. Córneas de pacientes diabéticos têm controle de sua hidratação prejudicado e são mais propensas à descompensação após injúria. A uveíte faco-induzida (UFI) ocorre em grandes proporções associada à catarata hipermatura em cães. A UFI também acarreta danos ao endotélio da córnea e pode levar ao edema estromal, usualmente transitório. Cães diabéticos são particularmente predispostos ao desenvolvimento de catarata e UFI associada. Os efeitos da DM e UFI podem potencialmente vir a se somar em córneas de cães com catarata diabética. A pressão intra-ocular (PIO) e paquimetria podem ser ferramentas úteis na determinação dessas alterações. O objetivo deste estudo foi determinar a relação entre pressão intra-ocular e paquimetria nos diferentes estágios de desenvolvimento das cataratas diabéticas e não diabéticas em cães da raça Poodle. Cento e vinte e dois cães adultos da raça Poodle, 134 fêmeas e 99 machos, com idades de 2 a 16 anos, foram admitidos no Serviço de Oftalmologia do Hospital Veterinário da Universidade de São Paulo e incluídos no trabalho. Afecções oculares concomitantes, ou doenças sistêmicas com manifestação ocular, foram consideradas fatores de exclusão. Após exame clínico oftalmológico, coletou-se dados referentes ao tempo de leucocoria e tempo de desenvolvimento da DM. Os cães tiveram a PIO mensurada por meio do TonoPen-XL® e a paquimetria mensurada com o uso do PachPen®. Para isso realizou-se anestesia tópica (colírio de Proximetacaína a 0,5% - Anestalcon®, Alcon). As comparações estatísticas entre as variáveis foram realizadas utilizando os testes de Spearman, Mc-Nemar e Mann-Whitney quando apropriados. As distribuições das variáveis entre os grupos foram avaliadas pelo test de Kruskal-Wallis, e quando significantes, o teste de Dunn foi utilizado para descriminar as diferenças encontradas. O nível de significância foi estabelecido em p<0,05. Dos 122 cães, 233 olhos foram incluídos e classificados em grupo controle (n=39), catarata incipiente (n=20), imatura (n=29), matura (n=20), hipermatura (n=80), catarata diabética imatura (n=9), diabética matura (n=11) e diabética hipermatura (n=25). As distribuições das variáveis (sexo, idade, peso, presença de uveíte, tempo de leucocoria, PIO e paquimetria) foram estatisticamente diferentes entre os diversos grupos. Fêmeas apresentaram-se mais acometidas por catarata diabética. A idade média dos animais variou de 7,03 a 10,73 anos entre os grupos, e os animais diabéticos foram estatisticamente mais velhos. A PIO foi estatisticamente menor e os sinais clínicos de UFI mais prevalentes nos grupos de cataratas hipermaturas, tanto diabéticas, quanto não diabéticas. A PIO correlacionou-se negativamente com a idade e a paquimetria. Houve correlação positiva da paquimetria com a idade e o peso; e correlação negativa com o tempo de leucocoria e a PIO. Olhos acometidos por UFI tiveram PIO estatisticamente menor e paquimetria maior, com diferença de 2 mmHg e 60 µm, respectivamente. Nos cães acometidos por catarata diabética, a paquimetria encontrou-se particularmente aumentada, e a UFI particularmente presente. Esse aumento possivelmente reflete a somatória dos efeitos da DM e UFI sobre a córnea. A hipermaturidade foi correlacionada à presença da UFI. A PIO e paquimetria mostraram-se instrumentos valiosos na determinação da UFI, principalmente se forem negativamente correlacionadas entre si. / Diabetes mellitus (DM) causes different alterations in all corneal layers, such as deficient control of hydration, what makes them prone to decompensate after injury. Lens induced uveitis (LIU) occurs mainly in dogs presenting hypermature cataracts, what causes irreversible damages to the corneal endothelium and may lead to stromal edema, usually transient. DM dogs are particularly predisposed to cataract with LIU associated. Intraocular pressure (IOP) and pachymetry measurements may be useful procedures capable to detect such alterations. The aim of this study was to determinate the relationship between intraocular pressure and pachymetry on diabetic and nondiabetic Poodles, presenting different stages of cataracts. One hundred twenty-two Poodles, 134 females and 99 males, with ages varying from 2 to 16 years, were admitted at the Ophthalmology Service, of the Veterinary Hospital, of the University of São Paulo. After complete identification of the animals, anamnese (time of DM and cataract formation) and ophthalmological exam, dogs were included in the study. Dogs affected by other systemic diseases inducing ocular manifestation or other primary ocular alteration were excluded. LIU was diagnosed by observation of congestion of the episcleral vases and resistence to midriasis after induction with Mydriacyl®. IOP was measured by TonoPen-XL® and pachymetry by PachPen® after instillation of anesthetic eyedrop (Proximetacaine 0,5% - Anestalcon, Alcon). Statistical comparison between factors were made using Spearman, Mc-Nemar and Mann-Whitney tests when appropriated. The distributions of the factors among the groups were compared by Krusskal-Walliss test, and when significant, Dunns test was used to describe the differences found. The level of significance was set at p<0,05. Two hundred thirty-three eyes of 122 Poodles were evaluated. Eyes were classified in different groups: healthy dogs without cataracts (n=39); dogs presenting incipient cataract (n=20); with immature cataracts (n=29); mature cataracts (n=20); or hypermature cataracts (n=80); DM dogs presenting immature cataract (n=9); DM with mature cataracts (n=11); and DM with hypermature cataracts (n=25). Distribution of factors, such as age, sex, weight, time of DM and cataract, presence of LIU, IOP and pachymetry were statistically different between groups. Female Poodles were more affected by diabetic cataract and diabetic dogs were older than the other ones. IOP was statistically lower and LIU alterations more prevalent in the hypermature cataract groups (diabetic and no diabetics). IOP was negatively correlated to age and pachymetry measures. Pachymetry was positively correlated to age and weight. Negative correlation was observed between pachymetry and time of cataracts formation. LIU eyes presented lower IOP and higher pachymetry. The difference found at pachymetry and IOP measurements in LIU and non LIU eyes were 60 µm and 2 mmHg respectively. In diabetic dogs, pachymetry was particularly higher and LIU particularly present. The higher corneal thickness may possible be related to the sum of alterations caused by DM and LIU to those corneas. Hypermaturity was directly related to LIU. We concluded that pachymetry and IOP measurements are important procedures to the LIU diagnosis, mainly when negatively correlated.

Objetivos: Avaliar a capacidade do eletrorretinograma de padrão reverso (PERG) macular e multifocal (mf) de diferenciar pacientes com suspeita de glaucoma (SG) e glaucoma com defeito de campo hemianópico (GH) de controles, comparar a capacidade de discriminação do PERG e tomografia de coerência óptica (TCO) fourrier domain, e avaliar a relação entre as medidas do PERG e TCO. Métodos: Medidas do campo visual (CV) computadorizado, respostas do PERG transiente e modo estacionário e PERGmf foram obtidos dos SG (n=14, 24 olhos), GH (n=5, 7 olhos) e controles (n=19, 22 olhos). Os seguintes parâmetros de TCO foram investigados: camada de fibras nervosas da retina peripapilar (CFNRpp), espessura total da mácula e espessuras das camadas segmentadas da mácula. As medidas foram analizadas utilizando-se modelos lineares de efeito misto. Também foi avaliada a relação entre as medidas e a performance diagnóstica de cada tecnologia. Resultados: Comparado aos controles, a média do tempo de pico de P50 da resposta do PERG transiente estava reduzida nos SG e GH, enquanto que a fase, a amplitude do modo estacionário e respostas do PERGmf estavam anormais apenas no GH. A média das medidas da TCO de espessura macular e da CFNRpp nos SG e GH diferiram significativamente dos controles. Uma significativa relação foi observada entre o PERG e a maior parte dos dos parâmetros do CV central e TCO. A análise por regressão e componentes principais revelou que a TCO de nervo óptico e mácula, assim como o PERG transiente e PERGmf tiveram estatisticamente capacidade similar em discriminar os SG dos controles. Conclusões: Os parâmetros do PERG e da TCO podem estar anormais, com significativa relação entre as medidas, em uma porcentagem alta de olhos com SG com CV normal. Nossos achados sugerem que as duas tecnologias podem ser úteis e complementares na detecção precoce de glaucoma / Purpose: To evaluate the ability of macular and multifocal (mf) pattern electroretinogram (PERG) to differentiate glaucoma suspects (GS) and glaucoma with hemifield loss (GHL) from controls, to compare the discrimination ability of PERG and fourier-domain optical coherence tomography (fdOCT), and to assess the relationship between PERG and fdOCT measurements. Methods: Standard automated perimetry (SAP), steady-state and transient PERG responses and mfPERG measurements were obtained from GS (n=14, 24 eyes), GHL (n=5, 7 eyes) and controls (n=19, 22 eyes). The following fdOCT parameters were investigated: circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula, and segmented macular layer thicknesses. Measurements were compared using mixed effects linear models. The relationships between measurements and the diagnostic performance of each technology were also assessed. Results: Compared to controls, average P50 peak time transient PERG responses were reduced in GS and GHL, whereas average phase and amplitude steady-state and mfPERG responses were abnormal only in GHL. The average fdOCT-measured cpRNFL and macular thickness measurements in GS and GHL differed significantly from controls. A significant relationship was found between PERG and most fdOCT or central SAP sensitivity parameters. Principal component regression analysis revealed that optic disc and macular OCT parameters, along with mfPERG and transient PERG parameters had statistically similar ability to discriminate GS from controls. Conclusions: PERG and OCT parameters may be abnormal, with significant correlations between measurements, in a high percentage of GS eyes with normal SAP. Our findings suggest that both technologies may be helpful and complementary in early glaucoma detection

INTRODUÇÃO: O blefaroespasmo essencial é uma distonia focal caracterizada por contrações involuntárias, espasmódicas e bilaterais dos músculos protratores das pálpebras. O glaucoma é a principal causa de cegueira irreversível em adultos de países desenvolvidos e a elevação da pressão intra-ocular é o maior fator de risco para o desenvolvimento da doença. A contração voluntária forçada das pálpebras pode causar aumentos da pressão intra-ocular de até 90 mmHg. Uma vez que pacientes com blefaroespasmo essencial apresentam contrações palpebrais freqüentes e de forte intensidade, eles poderiam compor um grupo de risco para o desenvolvimento do glaucoma. MÉTODOS: Vinte e oito pacientes com blefaroespasmo essencial e 28 pacientes de grupo controle, formado por indivíduos com doenças palpebrais ou no seu pós-operatório, foram submetidos a um exame oftalmológico completo. No grupo de pacientes com blefaroespasmo, a avaliação foi realizada em 8 a 11 dias após o tratamento com toxina botulínica. Efetuou-se exame de refração e medida de melhor acuidade visual corrigida com tabela de Snellen, biomicroscopia em lâmpada de fenda, tonometria de aplanação, campo visual computadorizado, teste de sobrecarga hídrica e biomicroscopia de fundo para avaliação da papila óptica. RESULTADOS: 1) A prevalência de glaucoma nos pacientes com blefaroespasmo foi significativamente maior do que nos indivíduos do grupo controle, sendo diagnosticada em 14,3% e 3,6% dos casos, respectivamente (p=0,008). 2) A pressão intra-ocular foi significativamente maior nos pacientes com blefaroespasmo (15,80 ± 3,80 mmHg) do que nos indivíduos do grupo controle (13,90 ± 2,75 mmHg) (p= 0,004). 3) O pico da pressão intra-ocular na prova de sobrecarga hídrica foi significativamente maior nos pacientes com blefaroespasmo essencial (18,82 ± 4,47 mmHg) do que nos indivíduos do grupo controle (16,27 ± 2,69 mmHg) (p=0,0421). DISCUSSÃO: Diversos estudos descreveram a influência da compressão palpebral sobre a pressão intra-ocular. A prova de sobrecarga hídrica tem sido considerada uma ferramenta indireta para se avaliar a capacidade do fluxo de drenagem do trabeculado, além de exibir correlação com os picos de pressão intra-ocular que muitas vezes não são detectados em exames de rotina. Os pacientes com blefaroespasmo essencial apresentaram pressões intra -oculares e picos de pressão intra-ocular na prova de sobrecarga hídrica mais elevados do que os pacientes do grupo controle, o que poderia indicar um baixo fluxo de drenagem. Estas altíssimas variações de pressão intra -ocular a que estes indivíduos são submetidos constantemente, em pacientes com menor fluxo de drenagem poderiam causar um aumento crônico da pressão intra -ocular e o desenvolvimento do glaucoma. CONCLUSÕES: Os resultados observados sugerem que estes pacientes compõem um grupo de risco para o desenvolvimento de glaucoma e esta doença deve ser pesquisada de maneira sistemática na avaliação inicial e durante o seguimento desses casos / INTRODUCTION: Essential blepharospasm is a focal distonia characterised by involuntary, spasmodic, bilateral contractions of eyelid protractors. Glaucoma is the most important cause of irreversible blindness in adults in developed countries and high intraocular pressure is the major risk factor for development of the disease. Voluntary forced eyelid closure can produce an intraocular pressure increase of 90 mmHg. As patients with essential blepharospasm present frequent and strong eyelid contractions, they could be at risk for glaucoma development. METHODS: Twenty eight patients with essential blepharospasm and 28 patients of a control group, with eyelid diseases or in the post-operative period, were submitted to a complete ophthalmic examination. In the group of patiens with blepharospasm, the evaluation was done between 8 to 11 days after botulinum toxin treatment. We performed refractometry and best corrected visual acuity with Snellen chart, slitlamp biomicroscopy, applanation tonometry, automated perimetry, water drinking test and dilated funduscopy to evaluate optic discs. RESULTS: 1) Prevalence of glaucoma in patients with blepharospasm (14,3%) was higher than in the individuals from control group (3,6%) (p=0,008). 2) Intraocular pressure was higher in patients with blepharospasm (15,80 ± 3,80 mmHg) than in the individuals from control group (13,90 ± 2,75 mmHg) (p=0,004). 3) Intraocular pressure peaks in the water drinking test were higher in patients with essential blepharospasm (18,82 ± 4,47 mmHg) than in the individuals from control group (16,27 ± 2,69 mmHg) (p=0,0421). DISCUSSION: Several studies reported the influence of eyelid compression over intraocular pressure. The water drinking test has been considered as an indirect tool to measure outflow facility and it has good correlation with intraocular pressure peaks which are frequently missed in routine examinations. Patients with essential blepharospasm had higher mean intraocular pressures and intraocular pressure peaks in the water drinking test than patients from control group, which could indicate low outflow facility. These high intraocular pressure variations in patients with low outflow facility could increase the intraocular pressure chronically and lead to development of glaucoma. CONCLUSION: Our results suggest that patients with essential blepharospasm be at higher risks for development of glaucoma and this disease should be always investigated at presentation and during follow-up of these cases

Glaucoma affects tens of millions of people and is the leading cause of irreversible blindness worldwide. Virtually all current glaucoma therapies target elevated intraocular pressure (IOP); however, the contribution of intracranial pressure (ICP) to glaucoma has recently garnered interest. Strain at the optic nerve head is now known to depend on the translaminar pressure difference (TLPD), which is the difference between IOP and ICP, rather than IOP alone. A better understanding of how IOP and ICP relate to glaucoma development and progression is essential for developing improved therapies and diagnostic tests. Glaucoma is commonly modeled in rats, yet aqueous humor dynamics are not well-documented in healthy nor diseased rat eyes. Moreover, because rats do not develop glaucoma spontaneously, it is essential to develop low-cost, reliable, and relevant models of glaucomatous pathology in the animal. The purpose of this dissertation work is to achieve the following goals: i) quantitatively assess aqueous humor dynamics in healthy, living rat eyes, ii) develop an ideal model of experimental glaucoma in rats, iii) quantitatively characterize aqueous humor dynamics throughout experimental glaucoma in living rats, and iv) investigate the effects of ICP manipulations on aqueous humor dynamics in living rats. Chapter 2 reports physiological parameters of aqueous humor dynamics for the first time in the eyes of living, healthy Brown-Norway rats, and presents a novel perfusion technique for efficiently and accurately estimating these parameters. Chapter 3 introduces the constant-pressure perfusion model of experimental glaucoma: a powerful new model which overcomes several limitations of existing techniques. The constant-pressure perfusion model induces IOP elevations which are prescribable and easily manipulated, does not directly target the trabecular meshwork or its vasculature, and offers continuous records of IOP rather than requiring regular animal handling and tonometry. Chapter 3 characterizes IOP-induced optic neuropathies in rats and demonstrates their resemblance to human glaucoma. Chapter 4 evaluates whether the constant-pressure perfusion model affects ocular physiology, specifically showing that resting IOP and conventional outflow facility are not permanently nor significantly altered in the model. Chapter 5 examines the effect of ICP manipulations on aqueous outflow physiology in living rats, and reports for the first time a graded effect of intracranial hypertension on conventional outflow facility. Evidence for a neural feedback mechanism that may serve to regulate the TLPD is also presented. Chapter 6 summarizes the results of this dissertation, provides recommendations for future work, and gives closing remarks. These collective projects provide insight into IOP regulation in both healthy and diseased rat eyes, advancing our understanding of glaucomatous development and damage in rats. A novel model of experimental glaucoma and several perfusion systems have been developed which are distinctly tailored for use in future glaucoma studies and will allow future investigators to study the disease with enhanced efficiency and exactitude. The results of this dissertation work suggest that detecting and correcting impairments of either IOP or ICP homeostatic capabilities may be of utmost importance for improving clinical outcomes in human glaucoma.

The murine eye naturally undergoes post-natal changes in eye size. This dissertation quantifies longitudinal structural and functional changes in control mice (C57BL/6J (B6), D2-Gpnmb+/SjJ) and in DBA/2J (D2) mice, which spontaneously develop elevated intraocular pressure (IOP). IOP elevation results in abnormal eye elongation, retinal nerve fiber layer (RNFL) thickness thinning and retinal ganglion cell (RGC) dysfunction and demise resembling human glaucoma. I measured structural changes with Optical Coherence Tomography (OCT), and RGC function with Pattern Electroretinogram (PERG). I also developed and refined provocation approaches (IOP elevation with changes in body posture; metabolic load with flickering light) to probe susceptibility of RGC function in D2 mice prone to glaucoma. Finally, I developed a novel system for recording, simultaneously but independently, the PERG from both eyes using asynchronous visual stimuli and deconvolution analysis. Simultaneous PERG recording from each eye was hitherto impossible due to the interocular cross-talk of the PERG signal. Altogether, the combination of these measures (OCT, PERG) and provocative conditions may represent powerful tools for glaucoma research using mouse models.

In most cases, myopia is characterized by an increase in axial length of the eye, but the exact mechanisms for the axial elongation are still unknown. Higher intraocular pressure (IOP) has been associated with myopia and could be involved in eye enlargement. Also, some investigators have argued that the mechanical stresses generated by the ocular muscles during near work cause the eye to stretch out of shape. The purpose of this work was to investigate the effect of IOP on eye geometry, build a finite element model of the corneo-scleral shell of a chick eye, and verify if the eye could elongate due to increased IOP and hence become myopic. In the present study, myopia was induced in the right eye of chicks using -15 dioptre (D) goggles. The in-vitro pressure-volume curves of normal and myopic chick eyes were obtained using a computer controlled syringe pump and a digital pressure gauge. The axial length and horizontal equatorial diameter of the chick eyes as pressure increased were measured from digital photographs. To build the finite element model, normal chick eyes were frozen, sliced using a microtome, and photographed. The image sequence was aligned using MATLAB software and imported into SolidWorks® and Mimics software packages for three-dimensional (3D) reconstruction. Three 3D models were constructed and imported into Abaqus/CAE® software for finite element analysis. Isotropic, homogeneous, linear elastic and exponentially stiffening material properties were used for the finite element models. The results of the finite element models were compared with the experimental data. The results showed that normal chick eyes elongated in the axial direction and initially contracted in the horizontal equatorial direction as IOP increased. Myopic chick eyes did not elongate as much in the axial direction and did not contract as much in the horizontal equatorial direction compared with normal eyes. The volumetric deformation of myopic eyes was similar to normal eyes suggesting that growth and remodelling of the ocular tissues was involved in experimental myopia in the chick. The 3D reconstructed geometry of a chick eye was similar to a real eye although small geometric inaccuracies were present. The finite element model with isotropic, homogeneous, and exponentially stiffening material properties agreed well with the experimental strains in spite of the fact that the anisotropy of the ocular tissues was not included in the finite element model. This suggests that the oblate geometry of the chick eye was the main parameter dictating its deformation under increased IOP. The natural tendency of chick eyes is to elongate in the axial direction as IOP increases and this suggests that IOP could play a role in myopia onset and progression. The way chick eyes deformed as pressure increased is probably due to their oblate geometry. The finite element model could be used in the future to study the effect of different parameters such as ocular muscle forces and ocular tissues material properties on eye geometry. This way, an eye configuration more prone to eye elongation and myopia could be determined.

In vivo, biomechanical stress plays an important role in tissue physiology and pathology, affecting cell and tissue behavior. Even though conventional outflow tissues in the eye are constantly exposed to dynamic changes in intraocular pressure (IOP), the effects of such biomechanical stressors on outflow tissue function have not been analyzed. In particular, changes in IOP with each heartbeat have been measured in human eyes approximating 2.7 mmHg/sec. The purpose of this dissertation is to determine the effect(s) of ocular pulse on conventional outflow tissue regulation and the effect that contractility plays in this mechanical stress-mediated response. The central hypothesis directing this research is that cyclic intraocular pulsations (i.e. ocular pulse) play a significant role in conventional outflow facility.In order to address our hypothesis we studied the effect of biomechanical stressors on conventional outflow physiology using three different strategies: (1) by comparing conventional outflow endothelial cells to blood and lymphatic capillary endothelia, we gained a better understanding of the effects of biomechanical stress on conventional outflow tissue physiology, (2) by modifying the anterior segment perfusion model, we were able to measure the effect of ocular pulse on conventional outflow facility, and (3) by exposing trabecular meshwork cell monolayers to cyclic biomechanical pressure oscillations in the presence of compounds known to affect trabecular meshwork contractility, we were able to analyze the effect of rho-kinase-mediated contractility on the ocular pulse-associated response.Perfused human and porcine anterior segments showed a significant ocular pulse-mediated decrease in outflow facility; in addition, perfused trabecular meshwork monolayers showed an increase in intra-chamber pressure when exposed to cyclic pressure oscillations. This effect was blocked by Y27632 inhibition of rho-kinase-mediated contraction.In conclusion, the work shown in this dissertation demonstrates for the first time that trabecular outflow tissues are capable of responding to a physiologically-relevant cyclic biomechanical stress. This response can be observed as an increase in outflow resistance that translates to lower baselines in outflow facility of anterior segments and lower hydraulic conductivity of trabecular meshwork monolayers. In addition, we concluded that the observed ocular pulse-mediated response of trabecular meshwork cells is regulated by rho-kinase-induced contractility.

In most cases, myopia is characterized by an increase in axial length of the eye, but the exact mechanisms for the axial elongation are still unknown. Higher intraocular pressure (IOP) has been associated with myopia and could be involved in eye enlargement. Also, some investigators have argued that the mechanical stresses generated by the ocular muscles during near work cause the eye to stretch out of shape. The purpose of this work was to investigate the effect of IOP on eye geometry, build a finite element model of the corneo-scleral shell of a chick eye, and verify if the eye could elongate due to increased IOP and hence become myopic. In the present study, myopia was induced in the right eye of chicks using -15 dioptre (D) goggles. The in-vitro pressure-volume curves of normal and myopic chick eyes were obtained using a computer controlled syringe pump and a digital pressure gauge. The axial length and horizontal equatorial diameter of the chick eyes as pressure increased were measured from digital photographs. To build the finite element model, normal chick eyes were frozen, sliced using a microtome, and photographed. The image sequence was aligned using MATLAB software and imported into SolidWorks® and Mimics software packages for three-dimensional (3D) reconstruction. Three 3D models were constructed and imported into Abaqus/CAE® software for finite element analysis. Isotropic, homogeneous, linear elastic and exponentially stiffening material properties were used for the finite element models. The results of the finite element models were compared with the experimental data. The results showed that normal chick eyes elongated in the axial direction and initially contracted in the horizontal equatorial direction as IOP increased. Myopic chick eyes did not elongate as much in the axial direction and did not contract as much in the horizontal equatorial direction compared with normal eyes. The volumetric deformation of myopic eyes was similar to normal eyes suggesting that growth and remodelling of the ocular tissues was involved in experimental myopia in the chick. The 3D reconstructed geometry of a chick eye was similar to a real eye although small geometric inaccuracies were present. The finite element model with isotropic, homogeneous, and exponentially stiffening material properties agreed well with the experimental strains in spite of the fact that the anisotropy of the ocular tissues was not included in the finite element model. This suggests that the oblate geometry of the chick eye was the main parameter dictating its deformation under increased IOP. The natural tendency of chick eyes is to elongate in the axial direction as IOP increases and this suggests that IOP could play a role in myopia onset and progression. The way chick eyes deformed as pressure increased is probably due to their oblate geometry. The finite element model could be used in the future to study the effect of different parameters such as ocular muscle forces and ocular tissues material properties on eye geometry. This way, an eye configuration more prone to eye elongation and myopia could be determined.

The discovery of the ocular hypotensive effect of topically applied prostaglandins (PGs) has raised a number of questions about the mechanisms of action involved. The aim of the present thesis was to answer some of these questions. PGs reduce the intraocular pressure (IOP) by increasing uveoscleral flow through the ciliary muscle, but the exact mechanism is not known. Morphological changes may be involved. PGs are also involved in the inflammatory response. In the first study the aim was to investigate the effect of latanoprost, a prostaglandin F2 a-analogue, on the blood-aqueous barrier and the IOP restoration after long-term treatment. 26 glaucoma patients were treated with latanoprost (50 pg/ml) once daily for 6-12 months. Aqueous protein concentration was followed with a laser flare meter in 16 patients throughout this period. No change was observed. IOP increased slowly after withdrawal of treatment. It was concluded that latanoprost has no clinically significant effect on the permeability of the blood-aqueous barrier and that the IOP will return to pretreatment levels within a few weeks, indicating that any changes in the ciliary muscle morphology are reversible. In 20 healthy volunteers it was attempted to prevent the ocular hypotensive effect of latanoprost by inhibiting uveoscleral flow by a pronounced ciliary muscle contraction. For this purpose a high dose of the cholinergic agonist, physostigmine (1 drop 8 mg/ml alternate hours) was used. However, the effects on IOP of the two drugs were mainly additive most likely due to a short-lasting effect of physostigmine on the ciliary muscle. The progressive IOP reduction by physostigmine in the second study raised the question as to whether the drug reduces aqueous flow apart from enhancing outflow. On the contrary, in the third study repeated administrations of physostigmine, in 20 normal subjects, increased aqueous flow, measured with fluorophotometry, by about 25%. From studies of patients it is known that latanoprost twice daily has less ocular hypotensive effect than once daily. This was the subject of the two remaining studies. The possibility that latanoprost causes a short-lasting increase in aqueous flow was examined in 18 healthy volunteers. Application of a second drop in the morning would blunt some of the early IOP lowering effect of latanoprost. Once or twice daily applications had similar effect on aqueous flow, a tendency to an increase without any difference between the dose regimens. The next study confirmed the difference in effect on IOP between once and twice daily applications in 40 normal subjects. The difference remained even when one of the two applications was omitted after two weeks’ treatment. The results indicate that applying latanoprost twice daily induces a modest receptor desensitisation. / <p>Diss. Umeå : Umeå universitet, 1997, härtill 5 uppsatser.</p> / digitalisering@umu