Introduction The ocular surface provides a unique opportunity to study hemodynamics since the vessels can be visualized directly, without treatment and non-invasively. The availability of instruments to measure various hemodynamic parameters on the ocular surface in an objective manner are lacking. The quantification of red blood cell velocity, blood oxygen saturation and conjunctival redness on the ocular surface using novel, validated techniques has the potential of providing useful information about vascular physiology. The specific aims of each chapter are as follows: Chapter 3: The objective was to design, develop and validate a system that would non-invasively quantify the red blood cell velocity in the conjunctival vessels. A tool was developed to automatically analyze video sequences of conjunctival vessels, digitally imaged with high enough magnification to resolve movement of the blood within the vessel. Chapter 4: The objective was to: a) design and develop a method in order to non-invasively quantify the changes in blood oxygen saturation (SO2) in the conjunctival vessels and demonstrate reliability of the measures and, b) demonstrate the application of the method by showing a response to an isocapnic hyperoxic provocation and compare those values to the results from a valid instrument. Chapter 5: The aim of this experiment was to examine variations in ocular redness levels, red blood cell velocities and oxygen saturation levels over time in clinically healthy participants and also to compare differences between two age groups. Chapter 6: The aim of this experiment was to examine the ocular redness levels, red blood cell velocities and oxygen saturation levels in clinically healthy participants when a topical ophthalmic decongestant was instilled onto the eye and to demonstrate the validity of the use of two novel techniques. Chapter 7: The aim of this experiment was to examine ocular redness, red blood cell velocity and oxygen saturation in participants who were habitual soft contact lens wearers (study) compared to those that did not (control) and also to compare differences in silicone (SH) and non-silicone hydrogel wearers. Methods Chapter 3: Simulations representing moving RBCs within a vessel and the random variation of each cell in terms of speed, shape and intensity were created in order to evaluate the performance of the algorithm. For each vessel, a signal that correlated to blood cell position was extracted from each frame, and the inter-frame displacement was estimated through a modified dynamic time warping (DTW) algorithm. This provided the red blood cell velocity over time in each point of the vessels. Thus, from these estimates, the mean red blood cell velocity for each vessel was easily evaluated. The true mean velocity from the simulation with the one estimated by the algorithm was compared and the system accuracy was determined. Chapter 4: a) Conjunctival vessels were imaged with two narrow-band interference filters with O2-sensitive and O2-insensitive peak transmissions using a Zeiss slit lamp at 32x magnification. Optical densities were calculated from vascular segments using the average reflected intensities inside and outside the vessels. Optical density ratios were used to calculate relative oxygen saturation values. Video images of the bulbar conjunctiva were recorded at three times of the day. Measurement repeatability was assessed over location at each time and across consecutive frames. b) Subjects initially breathed air for 10 minutes followed by pure oxygen (O2) for 20 minutes, and then air for a final 10 minute period using a sequential re-breathing circuit. Simultaneously, SO2 values measured with a pulse oximeter ear clip and finger clip were recorded. The validity of the dual wavelength method was demonstrated by comparing the values to those from the ear clip pulse oximeter. Chapter 5: Participants attended eight separate visits over the course of a day. Levels of bulbar conjunctival redness, red blood cell velocity and blood oxygen saturation were measured on a vessel of interest. Chapter 6: Participants attended three separate visits during an allotted 60 minute session. Bulbar conjunctival redness, red blood cell velocity and blood oxygen saturation were measured on a vessel of interest, pre-insertion, just after insertion and, 10 minutes after insertion of a topical ocular decongestant. Significant differences between the three measures were assessed and correlations between the three parameters were reported. Chapter 7: Participants were measured 8 times over the course of a day with their contact lenses in place. Bulbar conjunctival redness, red blood cell velocity and blood oxygen saturation were measured. Results Chapter 3: Results for the simulated videos demonstrated a very good concordance between the estimated and actual velocities supporting its validity. The mean relative error for the modified Dynamic Time Warping (DTW) method is 6%. Chapter 4: The intraclass correlations (ICCs) between the three locations at each time point were 0.93, 0.56 and 0.86 respectively. Measurements across 5 consecutive frames showed no significant difference for all subjects (ICC = 0.96). The ICCs between the two methods at each time point were 0.45, 0.10 and 0.11 respectively. a) There was no significant difference in SO2 between the three locations measured using the dual wavelength method for all subjects. There was also no significant difference between the three locations at any of the time points for the dual wavelength method. b) In response to isocapnic hyperoxic provocation using the dual wavelength method, blood oxygen saturation was increased from control values and subsequently recovered after withdrawal of hyperoxia. Blood oxygen saturation values recorded from the ear clip and finger clip of the pulse oximeter also showed an increase from control values and subsequently recovered after withdrawal of hyperoxia. SO2 comparison between the dual wavelength method and the ear-clip pulse oximeter method did not show a significant difference. The interaction between the two methods and time on SO2 was not significant. Chapter 5: From baseline, the group mean redness and oxygen saturation did not change significantly over time. There was a significant difference in the group mean red blood cell velocity values over time. There was no significant difference between age strata for all three measures. Chapter 6: After drop instillation redness values decreased significantly. There was no change in red blood cell velocity and oxygen saturation over time. There was a moderate significant correlation between SO2 and red blood cell velocity just after drop insertion. Chapter 7: When comparing the study and control groups, no significant difference in redness or SO2 over time was found. RBC velocity over time was found to be significantly different between groups. When comparing the two study groups (SH vs. hydrogel) no significant difference across either measure over time was found. Conclusions Chapter 3: Signal displacement estimation through the DTW algorithm can be used to estimate mean red blood cell velocity. Successful application of the algorithm in the estimation of RBC velocity in conjunctival vessels was demonstrated. Chapter 4: The application of the dual wavelength method was demonstrated and optical density ratios can be used in a reliable manner for relative oxygen saturation measurements. This valid method promises to enable the study of conjunctival O2 saturation under various experimental and physiological conditions. Chapter 5: The results of this study support the theory of metabolic regulation. The lack of any significant change across time for redness and oxygen saturation along with significant changes in red blood cell velocity substantiates this notion. Chapter 6: This study supports the literature regarding metabolic regulation of the microvasculature during the use of various stimuli. The results demonstrated that oxygen saturation levels remain stable even when a significant decrease in ocular redness is measured. The novel techniques used in this experiment demonstrated the expected action of the decongestant further contributing to their application and validity. Chapter 7: In summary, the participants in the study group were habitual contact lens wearers that had lower RBC velocities when compared to the control group supporting the notion that contact lenses initiate a hypoxic response. The lack of change in SO2 in either group supports the theory of metabolic regulation.

My PhD research involves multi-disciplinary areas of study such as measuring perfusion of blood vessels in hamster dorsal skin using laser speckle imaging technique. In this study the changes were measured in blood flow velocity and diameters of micro vasculatures after the influence of glycerol application. The second study identifies the changes in morphology and optical properties of eye tissue after applying hyper-osmotic agent such as 100% anhydrous glycerol. Further investigation on the reversal process was performed without any application of 0.9% saline. The third study identified the variation in fluorescence in hamster dorsal skin tissue and enucleated porcine eyes with temperature. This study investigated the variation in fluorescence intensity with temperatures starting at 14°C and compared in vivo and in vitro results for consistency. The fourth study investigated an implantable drug delivery package that was fabricated using PMMA and implanted between the sub-conjunctival and super-scleral space and release the content of the device by either mechanical pressure or light-activated ophthalmic Nd:YAG laser after optically clearing the eye tissue by topical application of a hyper-osmotic agent, 100% anhydrous glycerol. A hyper-osmotic agent creates a transport region in the conjunctiva and sclera to get visual access of the compartments in the drug delivery package. This new technology would provide the option to the patient of one time implantation of the carrier system containing the drug. Each time the patient requires medication a ND-YAG or other laser beam will propagate through the cleared eye tissue to release the drug in measurable doses at the discretion of the doctor from the package directly in to the vitreous humor. In this study we have measured half-life of the dye in the vitreous humor or posterior chamber and biocompatibility. The last study had drawn distinction between the fluorescence signals based on the location (anterior or posterior chamber) of the 10% Na fluorescence dye in the in vivo rabbit and ex vivo pig eyes. / text

A microbiota normal exerce função protetora na superfície ocular, competindo por nutrientes e secretando substâncias com propriedades bactericidas, o que dificulta a invasão de patógenos. Animais diabéticos apresentam diferentes alterações ceratoconjuntivais, tais como maior concentração de glicose no filme lacrimal, menor quantidade e qualidade da lágrima e diminuição da sensibilidade corneal, diferenças clinicamente relevantes que podem alterar essa microbiota. Traumas oculares também podem apresentar tal alteração por promoverem a quebra da barreira de proteção da superfície ocular. A correta identificação do agente etiológico, além de proporcionar um tratamento eficiente em alterações oculares, direciona a antibioticoterapia profilática tópica nos casos cirúrgicos e evita o uso abusivo de antibióticos, o que pode levar a destruição da microbiota normal da superfície ocular, facilitando assim o crescimento de bactérias e fungos patogênicos. Com o intuito de minimizar as complicações pós-operatórias das cirurgias intra-oculares, como as facectomias, freqüentemente realizadas nos cães diabéticos por serem predispostos a apresentarem catarata, este estudo visou avaliar a prevalência dos principais microrganismos da microbiota conjuntival de cães diabéticos. Foram avaliadas as microbiotas conjuntivais de 29 cães diabéticos, atendidos no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, totalizando 58 olhos. Estes, não estavam utilizando qualquer medicação tópica e não apresentavam alterações oculares ou doença sistêmica infecciosa que pudesse interferir nos resultados. As amostras foram colhidas do saco conjuntival com auxilio de zaragatoas, cuidando para que não houvesse contaminação pelo contato com pálpebras e cílios. As amostras foram inoculadas em meio enriquecedor Brain Heart Infusion (BHI) e caldo Sabouraud-dextrose e semeados em ágar sangue, MacConkey e Sabouraud-dextrose com cloranfenicol. Os microrganismos foram identificados por suas características morfológicas na bacterioscopia, pela coloração de gram e pelas características macro e microscópicas das colônias, além de testes bioquímicos. Houve maior prevalência de Staphylococcus (32,79%), principalmente coagulase negativos, que são os mais freqüentemente isolados nas infecções oculares: S. klosii, S. simulans, S. capitis, S. pasteuri, S. saprophyticus, S. haemolyticus. Também foram isolados Bacillus sp. (11,48%), S. intermedius (6,56%), Streptococcus sp (1,64%) e alguns fungos, como Cladosporium sp e Candida parapsilosis. Não houve crescimento de microrganismos gram negativos, anaeróbios estritos ou facultativos. Sugere-se que os resultados encontrados se relacionam diretamente às alterações ceratoconjuntivais dos animais analisados, local do exame, clima e diferentes raças. Sabendo-se que cães diabéticos são prováveis candidatos à facectomia, intervenção que promove quebra da barreira de proteção da superfície ocular e que existem microrganismos potencialmente patogênicos na conjuntiva destes animais, sugere-se análise da microbiota ocular antes da intervenção cirúrgica, para uso profilático de agentes antimicrobianos. / Normal ocular flora avoids infection depriving investor microorganisms of nutrients and by the secretion of bactericidal substances. Diabetic animals usually develop keratoconjunctival abnormalities, such as the higher concentration of glucose in the tear film; qualitative and quantitative tear deficiency and a decrease of the cornea sensitivity, what probably changes their conjunctival flora either. The same alteration may happen after ocular traumas, when the ocular barrier of protection is discontinued. The identification of agent etiology allows the efficient treatment of ocular infections, the prophylactic prescription of antibiotics before surgery and avoids destruction of normal ocular flora or multiplication of pathogens. Aiming to minimize complications on intraocular surgeries, such as facectomies, frequently realized in DM dogs for its predisposition to develop cataract, this study evaluated the prevalence of microorganisms in their conjunctival flora. The conjunctival flora of 29 diabetic dogs (58 eyes), attended at the Ophthalmology Service, of the Veterinary Hospital of the Veterinary College University of São Paulo were evaluated. These dogs werent using any kind of eyedrops, didnt present any ocular or systemic disease other than diabetes mellitus, what could change the results. Samples were taken with sterile swabs from the conjunctival sac and inoculated on Brain Heart Infusion (BHI) and Sabouraud-dextrose broth, then sown in blood agar, MacConkey and Sabouraud-dextrose-cloranfenicol. Contamination was avoided during procedure not touching the swab on eyelid or eyelashes. Microorganisms were identified by their morphological aspects at bacterioscopy, gram staining, macro and microscopy characteristics of the colonies and by biochemical tests. Staphylococcus presented the higher prevalence (32,79%), mostly the coagulase negative ones (S. klosii, S. simulans, S. capitis, S. pasteuri, S. saprophyticus, S. haemolyticus), which are frequently isolated from ocular infections. Either isolated, were Bacillus sp. (11,48%), S. intermedius (6,56%), Streptococcus sp (1,64%) and some fungus, such as Cladosporium sp and Candida parapsilosis. Gram negative bacteria, anaerobic stricts or facultative were not identified during the study. We suppose that these results are strictly correlated to keratoconjunctival alterations in DM dogs, procedure, weather and breed. We conclude that, as DM dogs presents potential pathogens on its conjunctiva and are probable candidates to cataract surgery, which discontinues the ocular barrier of protection, we suggest the identification of the agent etiology before surgery and the proper use of antibiotic before and after any intraocular intervention.

While much is known about the attachment of the chlamydiae to the host cell and intracellular events during the developmental cycle, little is known about the mechanism(s) by which elementary bodies exit the cell. In this report, we use the guinea-pig conjunctival model of Chlamydia caviae infection to present in vivo ultrastructural evidence supporting two mechanisms for release of chlamydiae from the mucosal epithelia. Four days after infection, histopathologic observation shows an intense infiltration of polymorphonuclear leukocytes (PMN) in the conjunctival epithelium. Using transmission electron microscopy, a gradient-directed PMN response to chlamydiae-infected epithelial cells was observed. As PMN infiltration intensifies, epithelial hemidesmosome/integrin/focal adhesion adherence with the basal lamina is disconnected and PMNs literally lift off and release infected superficial epithelia from the mucosa. Many of these infected cells appear to be healthy with intact microvilli, nuclei, and mitochondria. While lysis of some infected cells occurs with release of chlamydiae into the extracellular surface milieu, the majority of infected cells are pushed off the epithelium. We propose that PMNs play an active role in detaching infected cells from the epithelium and that these infected cells eventually die releasing organisms but, in the process, move to new tissue sites via fluid dynamics.

Background/aims Conjunctival squamous cell carcinoma (CSCC) is the most frequent malignant tumour of the conjunctiva, with scarce recurrence and infrequent metastasis. The purpose of this study is to describe the clinical and pathological characteristics of this neoplasm and to identify the prognostic factors for recurrence and metastasis in a cancer hospital in Peru. Materials and method A longitudinal, retrospective study of 176 consecutive patients diagnosed with SCC of the conjunctiva. Sociodemographic and clinical characteristics were evaluated. In addition, Kaplan-Meier curves were performed, and Cox regression was used to determine prognostic factors for recurrence and metastasis over time. Result Only 12.5% presented tumour size ≤5 mm. The highest proportion according to the histopathological type was the well-differentiated infiltrative forms (40.9%), and according to tumour, node, metastases (TNM), stage T3 was the most frequent (31.3%). The most performed initial treatment was orbital exenteration (38.6%). The proportion of recurrence was 6.8% and 8.0% for metastasis. The annual survival rate was 7% and the annual metastasis rate was 6%; for recurrence after 5 years, the survival rate was 11% and the metastasis rate was 14%. No prognostic factor evaluated was significant. Conclusion This is the most extensive patient study in Latin America with CSCC, with a high proportion of advanced histopathological grade, TNM stages, and radical treatments such as exenteration. Recurrence rates on average are similar to other reported studies, and it describes the rates of metastasis that have been poorly described in the literature. / Revisión por pares

Syfte: Syftet med denna studie var att undersöka om preservative-associated transient hyperfluorescens (PATH) förekommer mer vid användandet av en multipurposevätska kontra vid användandet av ett kontaktlinsskötselsystem med väteperoxid. Metod: Försökspersonerna, vana kontaktlinsbärare och ögonfriska, tillpassades den mjuka kontaktlinsen Biofinity.  Gradering av ögats främre segment utfördes med och utan infärgning av fluorescein. Därefter fick försökspersonerna två olika kontaktlinsvätskor, Refine One Step och BioTrue, att använda som skötselsystem. Lott drogs för att bestämma vilken lins som skulle skötas med vilket skötselsystem. Dagen efter kom försökspersonen tillbaka när kontaktlinserna suttit i ögonen exakt två timmar, ögonens yttre segment färgades in med fluorescein för att gradera conjunctival och corneal staining. Linserna sattes i igen och försökspersonen kom tillbaka efter fyra timmar för ytterligare en gradering, med fluorescein. Sju samt fjorton dagar senare upprepades samma procedur som vid dag två. Resultat: Medelvärden för PATH vid användandet av de båda kontaktlinsvätskorna (BioTrue och Refine One Step) togs fram och parat t-test användes för att analysera resultaten: BioTrue besök 1-2 (p<0,05), 3-4 (p<0,05) samt 5-6 (p<0,05); Refine One Step besök 1-2 (p=1), 3-4 (p=0,42) samt 5-6 (p=1). Detta visar statistiskt signifikant skillnad mellan PATH och en PHMB-baserad kontaktlinsvätska i kombination med silikonhydrogellins; ingen statistiskt signifikant skillnad visades vid användandet av ett väteperoxidsystem i kombination med en silikonhydrogellins. Slutsats: PATH förekommer vid kombinationen silikonhydrogel-lins och skötselsystem innehållandes konserveringsmedlet PHMB, men gav däremot ingen minskad komfort. För den kliniska verksamheten är PATH inget att oroa sig för då detta inte visar bioinkompatibilitet mellan kontaktlinsen och kontaktlinsvätskan. / The aim of this study was to evaluate if a greater amount of preservative-associated transient hyperfluorescence (PATH) is appearing when using a multipurpose-solution compared to using a hydrogen peroxide system as a cleaning and disinfecting scheme for contact lenses.   The subjects who participated in this study were contact lens wearers and had healthy eyes. Subjects were fitted with the soft contact lens Biofinity. The cornea and conjunctiva were examined with and without the color agent fluorescein using a slit lamp. The subjects received two different contact lens care systems: Refine One Step and BioTrue. The subjects were randomly assigned which lens that would go with which care system. The subjects came back the next day after having the contact lenses in the eyes for two hours. The contact lenses were removed, and fluorescein was instilled in order to grade corneal and conjunctival staining with the slit lamp. The contact lenses were then inserted again. The subject then came back after having the contact lenses in the eyes for four hours and another grading of corneal and conjunctival staining with the slit lamp was made. Seven and fourteen days later the subjects came back for the same procedure as day two.   Mean values for PATH when using both of the contact lens solutions (BioTrue and Refine One Step) were calculated and a paired t-test was used to analyze the results: BioTrue visit 1-2 (p<0.05), 3-4 (p<0.05) and 5-6 (p<0.05); Refine One Step visit 1-2 (p=1), 3-4 (p=0.42) and 5-6 (p=1). This shows a statistically significant difference between PATH and PHMB-based contact lens solutions and silicone hydrogel contact lenses; no statistically significant difference between PATH and contact lens care system containing hydrogen peroxide in combination with a silicone hydrogel contact lens.   PATH is appearing when combining a silicone hydrogel contact lens together with a multipurpose solution containing the preservative agent PHMB but gave no decreased comfort. In the clinical work PATH is non-significant, the presence of PATH does not show bio incompatibility between silicone hydrogel lenses and preservative agents but is simply the fluorescein which binds to the preservative agent PHMB.

O objetivo deste estudo foi comparar alterações histológicas induzidas por análogos de prostaglandinas e maleato de timolol na conjuntiva de coelhos. Cinqüenta coelhas da raça Nova Zelândia com idade e peso semelhantes foram divididos em cinco grupos de dez animais. Os olhos esquerdos foram tratados com uma gota diária de bimatoprosta 0,03%, travoprosta 0,004%, latanoprosta 0,005%, maleato de timolol 0,5% ou lágrimas artificiais contendo cloreto de benzalcônio (CBA) durante 30 dias. Os olhos contra-laterais serviram como controles. Realizaram-se biópsias na conjuntiva limbar superior com dimensões de 5 mm x 5 mm no oitavo e trigésimo dias em cinco coelhos de cada grupo. A conjuntiva foi imediatamente fixada com formaldeído a 10% por 24 horas, seguido de coloração por Hematoxilina-Eosina (HE) e Ácido Periódico de Shiff (PAS) e avaliação qualitativa por microscopia óptica. A avaliação histo-morfométrica quantitativa foi realizada usando o programa Image Pro-Plus 4.5. Os parâmetros avaliados foram: infiltrado inflamatório, espessura epitelial, número de células caliciformes, diâmetro e número de vasos sanguíneos. Observou-se leve infiltrado inflamatório focal no tecido conectivo subepitelial nos olhos controle e do grupo CBA, que consistia de aglomerados de linfócitos e raros neutrófilos. Todos os demais grupos exibiram no oitavo e trigésimo dias de tratamento infiltrado inflamatório moderado, composto por linfócitos e neutrófilos, que foi mais denso no grupo tratado com maleato de timolol do que nos grupos dos análogos de prostaglandinas. No trigésimo dia, o grupo que recebeu timolol mostrou aumento da densidade subepitelial de colágeno e aumento estatisticamente significante da espessura epitelial (P=0,004), que não foram observados nos demais grupos. Observou-se um aumento estatisticamente significante do número de vasos no grupo tratado com timolol (P=0,001). O diâmetro vascular no grupo que recebeu travoprosta apresentou aumento estatisticamente significante no oitavo dia de tratamento (P=0,008) e redução no 30º dia (P=0,035). A densidade de células caliciformes aumentou significativamente no grupo que recebeu travoprosta no oitavo dia (P=0,001) e no 30º dia nos grupos tratados com bimatoprosta (P=0,002) e latanoprosta (P=0,009). Conclui-se que, na conjuntiva de coelhos, o número de células caliciformes aumenta com o uso de análogos das prostaglandinas. O estudo sugere que essas drogas, entretanto, induzem menos alterações que o maleato de timolol na conjuntiva de coelhos / The purpose of this study was to compare histological changes induced by prostaglandin analogues and timolol maleate in the rabbit conjunctiva. Fifty New Zealand female rabbits with similar age and weight were divided in five groups of 10 animals. The left eyes were treated with one daily drop of bimatoprost 0,03%, travoprost 0,004%, latanoprost 0,005%, timolol maleate 0,5% or artificial tears containing benzalkonium chloride (BAC) for 30 days. The fellow eyes served as controls. Limbal superior conjunctival biopsies of 5 mm x 5 mm were performed at the 8th and 30th day in five rabbits of each group each time. The conjunctiva was immediately fixed with 10% formaldehyde for 24 hours, followed by Hematoxiline-Eosine (HE) and Periodic Acid Shiff (PAS) staining and optical qualitative microscopic evaluation. Morphohistometric quantitative analyses were conducted using the Image Pro-Plus 4.5 software. The evaluated parameters were: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels. A low level infiltration, consisting of localized clusters of lymphocytes and rare neutrophils, was observed in the subepithelial connective tissue of the control eyes and in the BAC group. At the 8th and 30th day post treatment, all other groups exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin analogue groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (P=0.004), which was not present in the other groups. A significant increase (P =0.001) in the number of blood vessels was observed in the group treated with timolol. An initial increase in the vascular diameter was observed at the 8th day in the travoprost group (P=0,008) although a significant reduction was observed at the 30th day (P =0,035). The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (P =0.001) and at the 30th day in those treated with bimatoprost (P =0.002) and latanoprost (P =0.009). We conclude that an increase in the number of goblet cell was initially observed with the use of all prostaglandin analogues. This study suggests that these drugs, however, induce fewer changes than timolol maleate in the rabbit conjunctiva

A neoplasia escamosa da superfície ocular constitui é uma das lesões mais frequentes que envolve a conjuntiva ou a córnea e tem como principais fatores de risco a exposição solar (radiação ultravioleta), a infecção pelo vírus do papiloma humano (HPV) e os estados de imunodeficiência, especialmente a infecção pelo vírus da imunodeficiência humana (HIV). Em suas formas mais avançadas, a neoplasia pode cursar com infiltração do globo ocular, da órbita e, mais raramente, com ocorrência de metástases para linfonodos ou a distância. O presente estudo teve como objetivo investigar os dados clínicos, histopatológicos, a presença de HPV e a expressão das proteínas p16 e p53 em 45 casos de neoplasia escamosa da superfície ocular diagnosticados no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, no período de 2005-2015. Avaliação histopatológica das lesões, estudo imuno-histoquímico para a detecção das proteínas e hibridização in situ cromogênica (CISH) para a detecção do DNA de HPV de alto e baixo grau foram realizados em todas as amostras. As lesões foram mais frequentes em homens de cor branca, com idade superior a 40 anos. A avaliação histopatológica revelou 31 casos (69%) de carcinoma invasivo e 14 casos (31%) de carcinoma in situ. Em 6 casos (13%) foi detectado DNA de HPV de alto grau por CISH. A frequência de expressão de proteínas p53 e p16 foi alta nas lesões, 89% e 53%, respectivamente. Em nosso estudo, a neoplasia escamosa da superfície ocular predomina em homens de cor branca, com idade acima dos 40 anos, com presença de HPV de alto grau em 13% dos casos. A expressão de p16 não apresentou um valor preditivo positivo alto quanto a possibilidade de associação com o vírus. / Ocular surface squamous neoplasia (OSSN) is one the most frequent lesions involving the conjunctiva or cornea and its main risk factors are solar exposure (ultraviolet radiation), human papilloma virus (HPV) infection and immunodeficiency states, especially human immunodeficiency virus (HIV) infection. In advanced cases one can observe eyeball or orbital infiltration and, rarely, lymph node or distant metastases. The present study aimed to investigate the clinical and histopathological data, as well as the presence of HPV and the expression of proteins p16 e p53 in 45 cases of OSSN diagnosed at the Clinics Hospital of Ribeirão Preto Medical School, University of São Paulo, from 2005 through 2015. Histopathological examination, immunohistochemical study for proteins p16 and p53, and chromogenic in situ hybridization (CISH) for low and high grade HPV were performed in all samples. Lesions were more frequent in white males, above 40 years old. Histopathological examination revealed 31 cases (69%) of invasive carcinoma and 14 cases (31%) of carcinoma in situ. In 6 cases (13%) high grade HPV was detected by CISH. The expressions of p53 and p16 were high, 89% and 53%, respectively. In our study, increased incidence of OSSN was observed in white males, above 40 years old, with high grade HPV in 13% of the cases. The expression of p16 did not show a high positive predictive value for HPV positivity in OSSN.

A neoplasia escamosa da superfície ocular constitui é uma das lesões mais frequentes que envolve a conjuntiva ou a córnea e tem como principais fatores de risco a exposição solar (radiação ultravioleta), a infecção pelo vírus do papiloma humano (HPV) e os estados de imunodeficiência, especialmente a infecção pelo vírus da imunodeficiência humana (HIV). Em suas formas mais avançadas, a neoplasia pode cursar com infiltração do globo ocular, da órbita e, mais raramente, com ocorrência de metástases para linfonodos ou a distância. O presente estudo teve como objetivo investigar os dados clínicos, histopatológicos, a presença de HPV e a expressão das proteínas p16 e p53 em 45 casos de neoplasia escamosa da superfície ocular diagnosticados no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, no período de 2005-2015. Avaliação histopatológica das lesões, estudo imuno-histoquímico para a detecção das proteínas e hibridização in situ cromogênica (CISH) para a detecção do DNA de HPV de alto e baixo grau foram realizados em todas as amostras. As lesões foram mais frequentes em homens de cor branca, com idade superior a 40 anos. A avaliação histopatológica revelou 31 casos (69%) de carcinoma invasivo e 14 casos (31%) de carcinoma in situ. Em 6 casos (13%) foi detectado DNA de HPV de alto grau por CISH. A frequência de expressão de proteínas p53 e p16 foi alta nas lesões, 89% e 53%, respectivamente. Em nosso estudo, a neoplasia escamosa da superfície ocular predomina em homens de cor branca, com idade acima dos 40 anos, com presença de HPV de alto grau em 13% dos casos. A expressão de p16 não apresentou um valor preditivo positivo alto quanto a possibilidade de associação com o vírus. / Ocular surface squamous neoplasia (OSSN) is one the most frequent lesions involving the conjunctiva or cornea and its main risk factors are solar exposure (ultraviolet radiation), human papilloma virus (HPV) infection and immunodeficiency states, especially human immunodeficiency virus (HIV) infection. In advanced cases one can observe eyeball or orbital infiltration and, rarely, lymph node or distant metastases. The present study aimed to investigate the clinical and histopathological data, as well as the presence of HPV and the expression of proteins p16 e p53 in 45 cases of OSSN diagnosed at the Clinics Hospital of Ribeirão Preto Medical School, University of São Paulo, from 2005 through 2015. Histopathological examination, immunohistochemical study for proteins p16 and p53, and chromogenic in situ hybridization (CISH) for low and high grade HPV were performed in all samples. Lesions were more frequent in white males, above 40 years old. Histopathological examination revealed 31 cases (69%) of invasive carcinoma and 14 cases (31%) of carcinoma in situ. In 6 cases (13%) high grade HPV was detected by CISH. The expressions of p53 and p16 were high, 89% and 53%, respectively. In our study, increased incidence of OSSN was observed in white males, above 40 years old, with high grade HPV in 13% of the cases. The expression of p16 did not show a high positive predictive value for HPV positivity in OSSN.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 12, 2007) Vita. Includes bibliographical references.