One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction. The application of FSLs in medical therapeutics is a recent development, and although they offer many benefits, FSLs also stimulate nonlinear optical effects (NOEs), many of which were insignificant with previously developed lasers. NOEs can change the laser characteristics during propagation through a medium, which can subsequently introduce unique safety concerns for the surrounding tissues. Traditional approaches for characterizing optical effects, laser performance, safety and efficacy do not properly account for NOEs, and there remains a lack of data that describe NOEs in clinically relevant procedures and tissues. As FSL technology continues to expand towards new applications, FSL induced NOEs need to be better understood in order to ensure safety as FSL medical devices and applications continue to evolve at a rapid pace. In order to improve the understanding of FSL-tissue interactions related to NOEs stimulated during laser beam propagation though corneal tissue, research investigations were conducted to evaluate corneal optical properties and determine how corneal tissue properties including corneal layer, collagen orientation and collagen crosslinking, and laser parameters including pulse energy, repetition rate and numerical aperture affect second and third-harmonic generation (HG) intensity, duration and efficiency. The results of these studies revealed that all laser parameters and tissue properties had a substantial influence on HG. The dynamic relationship between optical breakdown and HG was responsible for many observed changes in HG metrics. The results also demonstrated that the new generation of therapeutic FSLs has the potential to generate hazardous effects if not carefully controlled. Finally, recommendations are made to optimize current and guide future FSL applications.

Master of Science / Department of Clinical Sciences / Amy Rankin / Objective- To evaluate the use of a topical ophthalmic steroid (1% prednisolone acetate) and non-steroidal anti-inflammatory drug (0.1% diclofenac) on blood glucose concentrations, serum fructosamine concentrations, and clinical scores in diabetic dogs with cataracts using descriptive analysis. Animals- Twelve client-owned dogs with naturally-occurring, controlled (per history and physical examination), insulin-treated diabetes mellitus and cataract. A total of 40 dogs will be enrolled in the study, as determined by power analysis. Procedures- This was a prospective, randomized, double-masked, experimental study with 2 phases of data collection. Dogs were enrolled from October 2011 to March 2014 and were assigned to 1 of 2 treatments (Drug Red or Drug Blue) using blocked randomization; dogs received either 1% prednisolone acetate suspension or 0.1% diclofenac solution. Patient history, physical, and ophthalmic examinations were performed and a clinical score assigned at enrollment (Phase 1 [day 0]) and upon return (Phase 2 [day 32]). At these times, a complete blood count, serum chemistry, urinalysis, and serum fructosamine concentration were performed prior to hospitalization for up to 72 hours for continuous glucose monitoring. For 4 weeks (day 3 to 31), dogs returned home, and owners administered the dispensed ophthalmic medication 4 times daily to both eyes. Descriptive analysis of data was performed; statistical analysis will follow enrollment of 40 dogs. Results- Twelve dogs have completed the study, with 6 dogs assigned to each treatment group. Dogs received 4.44 or 0.44 mg/day of prednisolone acetate or diclofenac, respectively. Dogs assigned to Drug Red more commonly exhibited elevations in serum liver enzyme activity. Drug Red group showed a greater percent increase in fructosamine concentrations over time. Based on glucose curves alone (22 curves analyzed), an insulin dose increase was recommended for 12 curves. An insulin dose decrease and no dose change were recommended for 5 curves each. During treatment, 1 dog reportedly developed polyuria and polydipsia. Conclusions- Descriptive analysis revealed differences in some outcomes of interest among dogs treated with 2 different ophthalmic anti-inflammatory medications. Data collection is ongoing to determine if statistically significant differences exists for outcomes per group.

Foi desenvolvido um sistema inédito para diagnóstico e acompanhamento de Doenças Oculares Externas, particularmente de úlceras de córnea e que foi implementado num Hospital-Escola para uso diário. As úlceras de córnea, até então, eram avaliadas de forma subjetiva e qualitativa, estimando-se a extensão da área afetada. O indicativo de evolução do quadro clínico é basicamente a alteração da área afetada. Com o intuito de se poder avaliar a evolução desta patologia de forma quantitativa e padronizada, foi desenvolvido o presente sistema. O sistema consistiu em acoplar a uma Lâmpada de Fenda (biomicroscópio ocular) um divisor de feixes e um sistema ótico, no caminho ótico onde os feixes da Lâmpada de Fenda são paralelos, de forma que a imagem proporcionada nas oculares da Lâmpada de Fenda é simultaneamente proporcionada num detector do tipo CCD. Esta câmera CCD foi acoplada a um micro computador do tipo PC, via uma interface comercial, e as imagens são disponibilizadas num monitor. Um software dedicado foi desenvolvido e possui as seguintes funções e características: reconhecimento automático e medidas das áreas de ulceração, opcionalmente, medidas interativas de áreas quaisquer, medidas lineares interativas de comprimentos quaisquer e um amplo banco de dados dedicado a este setor da Oftalmologia. Ainda, todos os comandos podem ser realizados através do teclado ou do mouse, particularmente o de capturar imagem também pode ser acionado através de um pedal desenvolvido especialmente para o sistema. O sistema apresentou uma precisão de 5% (o método convencional, para medidas de úlceras perfeitamente elípticas proporcionava uma precisão de no máximo 13%). O protótipo do sistema está em uso no Hospital das Clínicas de Ribeirão Preto (ambulatório de Oftalmologia, setor de Doenças Oculares Externas), tem demonstrado excelente desempenho e estudos clínicos, agora proporcionados pela automação do sistema, começam a ser realizados / A system for diagnostic and follow up of External Ocular Diseases has been developed, particularly for Corneal Ulcers, and has been implemented in a Hospital-School for daily use. The corneal ulcers, until then, have been evaluated in a subjective and qualitative way, just by estimating the affected area. Its clinical evolution is indicated by the increasing/decreasing of the affected area. In order to evaluate quantitatively and standardize the evolution of this pathology we have developed the present system. The system consisted in attaching to a Slit Lamp (ocular biomicroscope) a beam splitter in the parallel rays optical path and an optical system, in order to provide simultaneously the ocular images to the Slit Lamp ocular lenses and to a CCD camera. The camera has been attached to a PC, via a commercial frame grabber and the images are displayed in a monitor. A dedicated software has been developed and it has the following functions and features: corneal ulcers self recognizing and area measurements, optional interactive area and extension measurement of any image and a data bank dedicated for this sector of the Ophthalmology. Also all the commands are available for keyboard or mouse clicking. Particularly, the image capturing command can also be turned ON/OFF by clicking a pedal, which was specially developed for the system. The precision of the measurements of the system is 5% (the conventional method, for perfect elliptical ulcer areas provides a maximum precision of 13%). The system\'s prototype is being used in the Hospital das Clínicas de Ribeirão Preto and it has presented excellent performance. Clinical studies are now being able to be done due to the automation of the clinical evaluations

As infecções adquiridas durante cirurgias oftalmológicas podem ter efeitos devastadores. O objetivo do presente estudo foi de comparar a proporção de culturas bacterianas negativas no fundo de saco conjuntival inferior após uma ou três gotas sequenciais de iodopovidona a 5% (PVPI). Os voluntários foram aleatoriamente designados para receber uma gota de PVPI (grupo PVPI) (no tempo 28 minutos) ou três gotas de PVPI (grupo PVPI+) (nos tempos 0, 20 e 28 minutos) no saco conjuntival inferior em olhos selecionados aleatoriamente. Um cotonete conjuntival foi identicamente obtido cinco minutos antes e 30 minutos após o tempo 0. A espessura corneana central foi medida da mesma maneira antes do tempo 0 e após o tempo 30 minutos. Os esfregaços conjuntivais foram incubados aerobicamente em meio líquido de tioglicolato enriquecido (caldo de carne) e em três meios de cultura sólidos (ágar chocolate, ágar de tripticase-soja com 5% de sangue de ovelha e ágar Sabouraud). No grupo PVPI (n=59), a proporção de olhos com culturas bacterianas negativas após o uso do PVPI (79,7%) não diferiu significativamente do valor basal (76,3%; p=0,7539). No grupo PVPI+ (n=61), a proporção de olhos com culturas bacterianas negativas após instilação de PVPI (85,3%) foi significativamente maior do que antes da intervenção (70,5%) (p=0,0177). No entanto, a análise estatística intergrupos não detectou esta diferença. Não houve diferença significativa na média da espessura corneana central antes e após a intervenção em ambos os grupos. A instilação de três gotas sequenciais de PVPI foi associada ao aumento na proporção de olhos com culturas conjuntivais negativas, enquanto que a instilação de uma única gota de PVPI não demonstrou este aumento. É necessário um estudo mais aprofundado para determinar se a diferença entre os regimes de administração da PVPI está associada a diferentes taxas de infecções oculares pós-operatórias. / Infections acquired during ophthalmic surgery can be devastating. The purpose of the current study is to compare the proportion of negative bacterial cultures after one versus three sequential drops of povidone-iodine (PI) 5% into the inferior conjunctival fornix. Patients were randomly assigned to receive 1 (PI group) drop (at time 28 minutes) or three (PI plus group) sequential drops (at time 0, 20 and 28 minutes) of PI 5% into the inferior conjunctival sac of one randomly selected eye. A conjunctival swab was identically obtained 5 minutes before and 30 minutes after time 0. Central corneal thickness (CCT) was measured in the same way before time 0 and after time 30. Conjunctival swabs were incubated aerobically in enriched Thioglycolate liquid medium (meat broth) and in three solid culture media (chocolate agar, trypticase soy agar with 5% sheep blood, and Sabouraud agar). In the PI group (n=59), the proportion of eyes with negative bacterial cultures after PI (79.7%) did not differ significantly from baseline (76.3%; p=0.7539). In the PI plus group (n=61), the proportion of eyes with negative bacterial cultures after PI (85.3%) was significantly higher than before PI (70.5%) (p=0.0177). However, the intergroup statistical analysis did not detect this difference.There was no significant difference in mean CCT before and after the intervention in both groups. Instillation of three sequential drops of PI was associated with an increase in the proportion of eyes with negative conjunctival cultures, while instillation of a single drop of PI did not demonstrate this increase.Further study is warranted to determine whether the difference between the PI administration regimens is also associated with differences in the rates of postoperative ocular infections.

As infecções adquiridas durante cirurgias oftalmológicas podem ter efeitos devastadores. O objetivo do presente estudo foi de comparar a proporção de culturas bacterianas negativas no fundo de saco conjuntival inferior após uma ou três gotas sequenciais de iodopovidona a 5% (PVPI). Os voluntários foram aleatoriamente designados para receber uma gota de PVPI (grupo PVPI) (no tempo 28 minutos) ou três gotas de PVPI (grupo PVPI+) (nos tempos 0, 20 e 28 minutos) no saco conjuntival inferior em olhos selecionados aleatoriamente. Um cotonete conjuntival foi identicamente obtido cinco minutos antes e 30 minutos após o tempo 0. A espessura corneana central foi medida da mesma maneira antes do tempo 0 e após o tempo 30 minutos. Os esfregaços conjuntivais foram incubados aerobicamente em meio líquido de tioglicolato enriquecido (caldo de carne) e em três meios de cultura sólidos (ágar chocolate, ágar de tripticase-soja com 5% de sangue de ovelha e ágar Sabouraud). No grupo PVPI (n=59), a proporção de olhos com culturas bacterianas negativas após o uso do PVPI (79,7%) não diferiu significativamente do valor basal (76,3%; p=0,7539). No grupo PVPI+ (n=61), a proporção de olhos com culturas bacterianas negativas após instilação de PVPI (85,3%) foi significativamente maior do que antes da intervenção (70,5%) (p=0,0177). No entanto, a análise estatística intergrupos não detectou esta diferença. Não houve diferença significativa na média da espessura corneana central antes e após a intervenção em ambos os grupos. A instilação de três gotas sequenciais de PVPI foi associada ao aumento na proporção de olhos com culturas conjuntivais negativas, enquanto que a instilação de uma única gota de PVPI não demonstrou este aumento. É necessário um estudo mais aprofundado para determinar se a diferença entre os regimes de administração da PVPI está associada a diferentes taxas de infecções oculares pós-operatórias. / Infections acquired during ophthalmic surgery can be devastating. The purpose of the current study is to compare the proportion of negative bacterial cultures after one versus three sequential drops of povidone-iodine (PI) 5% into the inferior conjunctival fornix. Patients were randomly assigned to receive 1 (PI group) drop (at time 28 minutes) or three (PI plus group) sequential drops (at time 0, 20 and 28 minutes) of PI 5% into the inferior conjunctival sac of one randomly selected eye. A conjunctival swab was identically obtained 5 minutes before and 30 minutes after time 0. Central corneal thickness (CCT) was measured in the same way before time 0 and after time 30. Conjunctival swabs were incubated aerobically in enriched Thioglycolate liquid medium (meat broth) and in three solid culture media (chocolate agar, trypticase soy agar with 5% sheep blood, and Sabouraud agar). In the PI group (n=59), the proportion of eyes with negative bacterial cultures after PI (79.7%) did not differ significantly from baseline (76.3%; p=0.7539). In the PI plus group (n=61), the proportion of eyes with negative bacterial cultures after PI (85.3%) was significantly higher than before PI (70.5%) (p=0.0177). However, the intergroup statistical analysis did not detect this difference.There was no significant difference in mean CCT before and after the intervention in both groups. Instillation of three sequential drops of PI was associated with an increase in the proportion of eyes with negative conjunctival cultures, while instillation of a single drop of PI did not demonstrate this increase.Further study is warranted to determine whether the difference between the PI administration regimens is also associated with differences in the rates of postoperative ocular infections.

<p>Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased.</p><p>In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done.</p><p>The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task.</p><p>As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed.</p><p>The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made.</p><p>The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.</p>

Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased. In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done. The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task. As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed. The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made. The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.

Microemulsions have gained interest from the pharmaceutical industry due to their ability to co-solubilize hydrophilic and lipophilic drugs, and to provide enhanced drug penetration. In this work, thermosensitive gelatin- and poloxamer 407-stabilized microemulsion-based gels (MBGs) were formulated using alcohol-free, low toxicity and low viscosity lecithin-based linker microemulsions. The addition of gelatin to water-rich bicontinuous microemulsions induced the formation of clear viscoelastic gels containing an oil-rich microemulsion as the gelatin seemed to dehydrate the original microemulsion. The addition of poloxamer 407 to water-continuous microemulsions produced MBGs with different gelation temperatures. High concentrations of lipophilic components in the microemulsion, particularly the oil, reduced sol-gel transition temperature, while hydrophilic components increased sol-gel transition temperature. Gelatin and poloxamer MBGs provided desirable viscoelastic properties for ophthalmic and transdermal applications with minimal impact on the transport properties of the original microemulsions.

Microemulsions have gained interest from the pharmaceutical industry due to their ability to co-solubilize hydrophilic and lipophilic drugs, and to provide enhanced drug penetration. In this work, thermosensitive gelatin- and poloxamer 407-stabilized microemulsion-based gels (MBGs) were formulated using alcohol-free, low toxicity and low viscosity lecithin-based linker microemulsions. The addition of gelatin to water-rich bicontinuous microemulsions induced the formation of clear viscoelastic gels containing an oil-rich microemulsion as the gelatin seemed to dehydrate the original microemulsion. The addition of poloxamer 407 to water-continuous microemulsions produced MBGs with different gelation temperatures. High concentrations of lipophilic components in the microemulsion, particularly the oil, reduced sol-gel transition temperature, while hydrophilic components increased sol-gel transition temperature. Gelatin and poloxamer MBGs provided desirable viscoelastic properties for ophthalmic and transdermal applications with minimal impact on the transport properties of the original microemulsions.

published_or_final_version / Anatomy / Master / Master of Philosophy