The purpose of this thesis was to investigate the effect of corneal swelling on the accuracy of Goldmann tonometry estimates of intraocular pressure (IOP). In the first experiment, central corneal thickness (CCT, ultrasonic pachymetry), IOP (Goldmann tonometry) and corneal curvature (keratometry) was measured in one eye of 25 subjects every two hours for 24 hours, except for 8 hours overnight (no measurements taken), and for the first two hours after awakening (measurement frequency 20 minutes). CCT (+20.1??10.9 pm) and IOP (+3.1??2.4 mmHg) peaked on eye opening, and then decreased at a similar rate (r=0.967, p<0.001) for the next two hours. Corneal swelling may have influenced the accuracy of Goldmann IOP measurements during this time. In the second and third studies, the CCT, IOP and corneal curvature were measured in both eyes of two groups of 25 subjects before and after the induction of corneal swelling, resulting from two hours of monocular closed eye contact lens wear. The increase in IOP was correlated to the increase in CCT at a rate of 0.33 to 0.48 mmHg per 10 pm, which signified an overestimation error in Goldmann IOP measurement. However, the change in IOP could not be accounted for solely by the change in CCT. In the fourth study, CCT, IOP and corneal curvature were used in conjunction with the Orssengo-Pye algorithm to determine the range of Young's modulus in the normal population, which was 0.29??0.06 MPa. Physiological variations in Young's modulus had a similar effect on Goldmann tonometry to CCT. In the fifth study, the data collected for studies 2 and 3 was used to calculate the Young's modulus changes associated with corneal swelling, again with the assistance of the Orssengo-Pye algorithm. No systematic change in Young's modulus was recorded after contact lens wear, but the model suggested that corneal biomechanical changes were responsible for the remainder of the change in IOP. All experimental results were combined to develop a model to calculate the diurnal variation of Goldmann IOP errors. The likely error in IOP due to overnight corneal swelling was 0.6 to 1.4 mmHg, which may explain as much as 45% (1.4 mmHg) of the 3.1 mmHg diurnal variation of IOP. In summary, small amounts of corneal swelling were shown to have a clinically significant impact on the accuracy of Goldmann tonometry. This may interfere with the measurement of the diurnal variation of IOP, particularly if measurements are taken prior to the resolution of overnight corneal swelling.

The purpose of this thesis was to investigate the effect of corneal swelling on the accuracy of Goldmann tonometry estimates of intraocular pressure (IOP). In the first experiment, central corneal thickness (CCT, ultrasonic pachymetry), IOP (Goldmann tonometry) and corneal curvature (keratometry) was measured in one eye of 25 subjects every two hours for 24 hours, except for 8 hours overnight (no measurements taken), and for the first two hours after awakening (measurement frequency 20 minutes). CCT (+20.1??10.9 pm) and IOP (+3.1??2.4 mmHg) peaked on eye opening, and then decreased at a similar rate (r=0.967, p<0.001) for the next two hours. Corneal swelling may have influenced the accuracy of Goldmann IOP measurements during this time. In the second and third studies, the CCT, IOP and corneal curvature were measured in both eyes of two groups of 25 subjects before and after the induction of corneal swelling, resulting from two hours of monocular closed eye contact lens wear. The increase in IOP was correlated to the increase in CCT at a rate of 0.33 to 0.48 mmHg per 10 pm, which signified an overestimation error in Goldmann IOP measurement. However, the change in IOP could not be accounted for solely by the change in CCT. In the fourth study, CCT, IOP and corneal curvature were used in conjunction with the Orssengo-Pye algorithm to determine the range of Young's modulus in the normal population, which was 0.29??0.06 MPa. Physiological variations in Young's modulus had a similar effect on Goldmann tonometry to CCT. In the fifth study, the data collected for studies 2 and 3 was used to calculate the Young's modulus changes associated with corneal swelling, again with the assistance of the Orssengo-Pye algorithm. No systematic change in Young's modulus was recorded after contact lens wear, but the model suggested that corneal biomechanical changes were responsible for the remainder of the change in IOP. All experimental results were combined to develop a model to calculate the diurnal variation of Goldmann IOP errors. The likely error in IOP due to overnight corneal swelling was 0.6 to 1.4 mmHg, which may explain as much as 45% (1.4 mmHg) of the 3.1 mmHg diurnal variation of IOP. In summary, small amounts of corneal swelling were shown to have a clinically significant impact on the accuracy of Goldmann tonometry. This may interfere with the measurement of the diurnal variation of IOP, particularly if measurements are taken prior to the resolution of overnight corneal swelling.

Made available in DSpace on 2014-06-11T19:23:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-16Bitstream added on 2014-06-13T20:50:54Z : No. of bitstreams: 1 renzo_r_me_jabo.pdf: 301706 bytes, checksum: 7ba09919044057e80244fe4b39f2b41e (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Estudaram-se a pressão intraocular, a densidade e a hexagonalidade de células endoteliais, níveis de Prostaglandina E2 e sua correlação com catarata senil madura (n=8) ou hipermatura (n=8). Adicionalmente, foram utilizados valores de Prostaglandina E2 do humor aquoso de cães oftalmologicamente saudáveis (n=7). Para avaliação da pressão intraocular empregou-se tonometria digital de aplanação. A avaliação da densidade e da hexagonalidade das células endoteliais foi realizada por meio de microscopia especular de não contato. Sob anestesia geral, 0,2mL de humor aquoso foram colhidos por meio de paracentese da câmara anterior. As amostras de aquoso foram congeladas e armazenadas à -80 oC para mensuração da concentração de PGE2, por imunoensaio enzimático competitivo. Os valores foram comparados estatisticamente, empregando-se análise de variância de via única, e o teste de múltiplas comparações de Bonferroni. Teste t não pareado foi utilizado para se avaliar os dados obtidos por microscopia especular. Possíveis correlações entre os resultados foram comparadas aplicando-se o teste de Person. Adotou-se nível de significância de p<0,05. Em ambos os grupos observou-se diminuição significativa da pressão intraocular (PIO), entretanto não houve diferença entre eles (p = 0,90). As médias dos valores de densidade celular (CD) e de hexagonalidade (HEX) foram 2253,363 cell/mm² e 59,03% para GSM e 2058,325 cell/mm² e 63,75% para GSH, respectivamente. Entretanto não houve diferença significativa entre ambos, tanto para CD (p=0,201), quanto para HEX (p=0,61). Observou-se incremento nos valores de PGE2 nos grupos com catarata em relação aos cães oftalmologicamente saudáveis (p<0,001), entretanto, não houve diferença significativa entre os grupos com catarata... / Intraocular pressure, endothelial cell density and hexagonality, and aqueous humor prostaglandin E2 (PGE2) were studied and correlated in dogs with mature (n=8) and hypermature (n=8) senil cataratcs. In addition, aqueous humor PGE2 values of ophthalmic healthy dogs (n=7) were used. Non contact specular microscopy was used to evaluate density and hexagonality of endothelial cells. 0.2mL of aqueous humor was collected by means of anterior chamber paracentesis. Aqueous humor samples were frozen at -80 oC and concentration of PGE2 were quantified by means of competitive enzyme immunoassay. PGE2 values were statistically compared with one way analysis of variance and Bonferroni´s multi comparison test. Specular microscopy data were assessed by means of unparied T test. Person´s test was used in order to assess possible correlations among data. Significance was set at value of P < 0.05. Values of endothelial cell density and hexagonality did not change significantly between groups (P = 0.61). PGE2 values were significantly higher in dogs with cataract, when compared with ophthalmic healthy dogs (P < 0.001), however, this parameter did not change significantly between mature and hypermature groups (P > 0.05). Is it possible tosay that cataract patients in stages of maturity or hipermaturity develop uveitis... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:23:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2004Bitstream added on 2014-06-13T19:30:13Z : No. of bitstreams: 1 borges_ag_me_botfmvz.pdf: 619936 bytes, checksum: 26f3dbd1632fca5d2ec5d73fee61d030 (MD5) / Dentre as doenças oculares diagnosticadas no cão, o glaucoma reveste-se de singular importância, como afecção potencial causadora de cegueira. O aumento da pressão intra-ocular (PIO) é o fator de risco primário para o desenvolvimento da neuropatia óptica glaucomatosa canina. A dorzolamida e o timolol, fármacos utilizados para o tratamento do glaucoma, reduzem a PIO pela diminuição da produção do humor aquoso, embora utilizem diferentes mecanismos de ação. O objetivo do trabalho foi avaliar o efeito do cloridrato de dorzolamida 2%, maleato de timolol 0,5% e da combinação de ambos na pressão intra-ocular de cães normais e verificar possíveis alterações na PIO do olho contra-lateral sem tratamento. Foram utilizados 60 cães, distribuídos em três grupos (G) aleatórios de 20 animais. Cada grupo recebeu tratamento tópico no olho esquerdo com timolol 0,5% (GT), dorzolamida 2% (GD) ou a combinação, timolol 0,5% e dorzolamida 2% (GTD). Em todos os grupos, a mensuração da PIO foi realizada utilizando-se tonômetro de aplanação (Tonopen). As medidas foram realizadas, em ambos os olhos, uma hora antes e uma, duas, quatro, seis e oito horas após a instilação de uma gota do colírio no olho esquerdo. No olho tratado percentual de redução máxima da associação timolol/dorzolamida foi numericamente superior (27%) comparado ao timolol (21,9%) e dorzolamida (22,4%) quando utilizados como monoterapia. O olho não tratado apresentou uma redução significativa da PIO, sendo que a redução máxima para o GT foi de 7%, para o GD de 13,8% e para o GTD de 13,6%. A dorzolamida e a associação timolol/dorzolamida promoveram uma ação redutora maior, após uma e seis horas da sua instilação no olho tratado. A administração tópica do timolol 0,5%, dorzolamida a 2% como monoterapia e a associação fixa destes fármacos resultou na redução significativa da PIO de cães clinicamente normais. / Glaucoma is one of the most important ocular diseases in the dog. Increased intraocular pressure (IOP) is the major risk factor for the development of glaucoma. Dorzolamide and timolol are drugs used for the treatment of glaucoma. Both drugs modify aqueous humor outflow by different mechanisms, resulting in decreased IOP. The aim of this work was to evaluate the efficacy of dorzolamide hydrochloride, timolol maleate and the combination of both drugs on IOP of healthy dogs. Sixty adult dogs were randomly and equally assigned to three groups (n = 20 per group). Each group received topical treatment in the left eye with 0,5% timolol, 2% dorzolamide or the combination (0,5% timolol / 2% dorzolamide). IOP measurements were made using aplanation tonometry (Tono-pen) after local instillation of 0,5% proparacaine in he both eyes. Measurements were performed 1 hour before (baseline) instillation of a single drop of the test drugs in the left eye, and at 1, 2, 4, 6 and 8 hours after treatment. Similar measurements were also performed in the right eye (nontreated eye). In the nontreated eye, IOP decreased over time, with a maximum decrease from baseline of 7%, 13,8% and 13,6% in the timolol, dorzolamide e timolol/dorzolamide groups, respectively. In the treated eye, there was a greater reduction in IOP for the combination (27% maximum decrease from baseline) when compared with timolol (21,9%) and dorzolamide (22,4%) groups. Dorzolamide and timolol/dorzolamide caused greater decreases in IOP at 1 and 6 hours after drug instillation. It was concluded that 0,5% timolol, 2% dorzolamide and the combination of these drugs are effective in reducing IOP in healthy dogs.

Orientador: Cláudia Valéria Seullner Brandão / Resumo: Dentre as doenças oculares diagnosticadas no cão, o glaucoma reveste-se de singular importância, como afecção potencial causadora de cegueira. O aumento da pressão intra-ocular (PIO) é o fator de risco primário para o desenvolvimento da neuropatia óptica glaucomatosa canina. A dorzolamida e o timolol, fármacos utilizados para o tratamento do glaucoma, reduzem a PIO pela diminuição da produção do humor aquoso, embora utilizem diferentes mecanismos de ação. O objetivo do trabalho foi avaliar o efeito do cloridrato de dorzolamida 2%, maleato de timolol 0,5% e da combinação de ambos na pressão intra-ocular de cães normais e verificar possíveis alterações na PIO do olho contra-lateral sem tratamento. Foram utilizados 60 cães, distribuídos em três grupos (G) aleatórios de 20 animais. Cada grupo recebeu tratamento tópico no olho esquerdo com timolol 0,5% (GT), dorzolamida 2% (GD) ou a combinação, timolol 0,5% e dorzolamida 2% (GTD). Em todos os grupos, a mensuração da PIO foi realizada utilizando-se tonômetro de aplanação (Tonopen). As medidas foram realizadas, em ambos os olhos, uma hora antes e uma, duas, quatro, seis e oito horas após a instilação de uma gota do colírio no olho esquerdo. No olho tratado percentual de redução máxima da associação timolol/dorzolamida foi numericamente superior (27%) comparado ao timolol (21,9%) e dorzolamida (22,4%) quando utilizados como monoterapia. O olho não tratado apresentou uma redução significativa da PIO, sendo que a redução máxima para o GT foi de 7%, para o GD de 13,8% e para o GTD de 13,6%. A dorzolamida e a associação timolol/dorzolamida promoveram uma ação redutora maior, após uma e seis horas da sua instilação no olho tratado. A administração tópica do timolol 0,5%, dorzolamida a 2% como monoterapia e a associação fixa destes fármacos resultou na redução significativa da PIO de cães clinicamente normais. / Abstract: Glaucoma is one of the most important ocular diseases in the dog. Increased intraocular pressure (IOP) is the major risk factor for the development of glaucoma. Dorzolamide and timolol are drugs used for the treatment of glaucoma. Both drugs modify aqueous humor outflow by different mechanisms, resulting in decreased IOP. The aim of this work was to evaluate the efficacy of dorzolamide hydrochloride, timolol maleate and the combination of both drugs on IOP of healthy dogs. Sixty adult dogs were randomly and equally assigned to three groups (n = 20 per group). Each group received topical treatment in the left eye with 0,5% timolol, 2% dorzolamide or the combination (0,5% timolol / 2% dorzolamide). IOP measurements were made using aplanation tonometry (Tono-pen) after local instillation of 0,5% proparacaine in he both eyes. Measurements were performed 1 hour before (baseline) instillation of a single drop of the test drugs in the left eye, and at 1, 2, 4, 6 and 8 hours after treatment. Similar measurements were also performed in the right eye (nontreated eye). In the nontreated eye, IOP decreased over time, with a maximum decrease from baseline of 7%, 13,8% and 13,6% in the timolol, dorzolamide e timolol/dorzolamide groups, respectively. In the treated eye, there was a greater reduction in IOP for the combination (27% maximum decrease from baseline) when compared with timolol (21,9%) and dorzolamide (22,4%) groups. Dorzolamide and timolol/dorzolamide caused greater decreases in IOP at 1 and 6 hours after drug instillation. It was concluded that 0,5% timolol, 2% dorzolamide and the combination of these drugs are effective in reducing IOP in healthy dogs. / Mestre

Previously, we showed that transcription factor activating protein 2-beta (AP-2β) deletion from the periocular mesenchyme (POM)-derived neural crest cells (NCCs) using Wnt1Cre (AP-2β NCC knockouts/AP-2β NCC KOs) resulted in anterior segment abnormalities and increased intraocular pressure (IOP). The present study investigated the role of AP-2β in development of structures of the conventional pathway including the trabecular meshwork and Schlemm’s canal, and the unconventional pathway including the ciliary muscle. Studies using NCC KOs revealed that the embryonic POM migrated appropriately, but a significant reduction in postnatal POM cell proliferation in the angle was observed, accompanied by reduced expression of trabecular meshwork and Schlemm's canal markers when compared to controls, which likely contributed to the elevated IOP in NCC KOs. However, since Wnt1Cre was expressed in multiple NCC derivatives, AP-2β was deleted specifically from the developing trabecular meshwork region (TMR) using Mgp-Cre knock-in (Mgp-Cre.KI) mice. Although migration of the POM giving rise to the trabecular meshwork was not affected, peripheral anterior synechia (PAS), a decrease in expression of trabecular meshwork and Schlemm’s canal markers, and significantly increased IOP was observed in TMR KOs compared to controls, paired with loss of retinal ganglion cells (RGCs), and reduced retinal thickness and function. However, treatment with latanoprost, a prostaglandin analog that increases outflow through the unconventional pathway, significantly reduced elevated IOP in TMR KOs. Overall, the results suggest that AP-2β plays a cell-autonomous role in trabecular meshwork development and a non-cell-autonomous role in Schlemm’s canal development, while also playing an indirect role in unconventional pathway function, and thus, is important for IOP homeostasis. Moreover, the AP-2β NCC KO and AP-2β TMR KO may serve as models of primary angle closure glaucoma that can be used to test IOP-lowering drugs, molecular targets and neuroprotective strategies to develop treatments for human glaucoma. / Thesis / Doctor of Philosophy (PhD) / Glaucoma is the leading cause of irreversible blindness worldwide. Primary angle closure glaucoma is one type of glaucoma resulting from abnormalities in structures that allow aqueous humour found in the front of the eye from exiting the eye through two major routes, including the conventional and unconventional pathways. Defects in these structures lead to increased intraocular pressure (IOP) that damages specialized cells important for vision. This project examines the role of transcription factor activating protein 2-beta (AP-2β) in development of structures responsible for IOP balance. Data from the current study showed that AP-2β is required for formation of the structures of the conventional pathway, but does not directly affect development of unconventional pathway structures. The two AP-2β deletion mutants used here can model human primary angle closure glaucoma to test the effect of various drugs and cell protection strategies aimed at treating glaucoma.

<p> In the work of this doctoral dissertation a new resonator sensor technique, first presented in 1989, has been further developed and evaluated with focus on technical characteristics and applications within the medical field.</p><p> In a first part a catheter-type tactile sensor using the resonator sensor technique was evaluated in a silicone model and applied to human prostate in vitro. The main finding was that different histological compositions of prostate tissue correlated with the frequency shift, .fS, of the resonator sensor and that the common property was the hardness of the tissue. The results indicated that hardness of the prostate tissue, and maybe hardness of human tissue in general, can be expressed according to a cone penetration standard (DIN ISO 2137) and that the hardness can be measured with this tactile sensor system. The tissue hardness application for the resonator sensor technique has to be further developed and evaluated in a larger study. The study also produced results that has led to the basic understanding of the resonator sensor system. One important result was that .fS of the sensor system was related to the contact area between sensor and sample. This indicated that the resonance sensor could be used for contact area measurement.</p><p> In a second part, containing three studies, the area-sensing capability from the first study was utilised in the development and evaluation of the applanation resonator sensor (ARS) for measurement of intraocular pressure (IOP). For the purpose of evaluating IOP-tonometers, an in vitro pig-eye model was developed, and it was shown that a saline column connected to the vitreous chamber could be used successfully to induce variations in IOP.</p><p> A ARS sensor with a flat contact surface was applied onto the cornea with constant force and .fS was measured. A mathematical model based on the Imbert-Fick law and the assumption that .fS was linearly related to contact area was proposed and verified with a convincing result. IOP measured with the ARS correlated well (r=0.92, n=360) with the IOP elicited by a saline column.</p><p> The ARS in a constant-force arrangement was evaluated on healthy human subjects in vivo. The results verified the sensor principle but revealed a nonnegligible source of error in off-centre positioning between the sensor and cornea. The sensor probe was redesigned and evaluated in the in vitro model. The new probe, with a spherical contact surface against the eye reduced the sensitivity to off-centre positioning. It was also shown that a .fS normalisation procedure could reduce the between-eye differences.</p><p> The ARS method for IOP measurement was further developed using combined continuous force and area measurement during the dynamic phase when the sensor initially contacts the cornea. A force sensor was included with the resonator sensor in one probe. Evaluation was performed with the in vitro pig-eye model. The hypothesis was that the IOP could be deduced from the differential change of force and area during that phase. The study showed good accuracy and good reproducibility with a correlation of r=0.994 (n=414) between measured pressure in the vitreous chamber and IOP according to the ARS. Measurement time was short, 77 ms after initial contact. Problems with inter-eye differences and low resolution at high pressures were reduced. The ARS method is the first to combine simultaneous, continuous sampling of both parameters included in the applanation principle. Consequently, there is a potential for reducing errors in the clinical IOP tonometry. </p>

In the work of this doctoral dissertation a new resonator sensor technique, first presented in 1989, has been further developed and evaluated with focus on technical characteristics and applications within the medical field. In a first part a catheter-type tactile sensor using the resonator sensor technique was evaluated in a silicone model and applied to human prostate in vitro. The main finding was that different histological compositions of prostate tissue correlated with the frequency shift, .fS, of the resonator sensor and that the common property was the hardness of the tissue. The results indicated that hardness of the prostate tissue, and maybe hardness of human tissue in general, can be expressed according to a cone penetration standard (DIN ISO 2137) and that the hardness can be measured with this tactile sensor system. The tissue hardness application for the resonator sensor technique has to be further developed and evaluated in a larger study. The study also produced results that has led to the basic understanding of the resonator sensor system. One important result was that .fS of the sensor system was related to the contact area between sensor and sample. This indicated that the resonance sensor could be used for contact area measurement. In a second part, containing three studies, the area-sensing capability from the first study was utilised in the development and evaluation of the applanation resonator sensor (ARS) for measurement of intraocular pressure (IOP). For the purpose of evaluating IOP-tonometers, an in vitro pig-eye model was developed, and it was shown that a saline column connected to the vitreous chamber could be used successfully to induce variations in IOP. A ARS sensor with a flat contact surface was applied onto the cornea with constant force and .fS was measured. A mathematical model based on the Imbert-Fick law and the assumption that .fS was linearly related to contact area was proposed and verified with a convincing result. IOP measured with the ARS correlated well (r=0.92, n=360) with the IOP elicited by a saline column. The ARS in a constant-force arrangement was evaluated on healthy human subjects in vivo. The results verified the sensor principle but revealed a nonnegligible source of error in off-centre positioning between the sensor and cornea. The sensor probe was redesigned and evaluated in the in vitro model. The new probe, with a spherical contact surface against the eye reduced the sensitivity to off-centre positioning. It was also shown that a .fS normalisation procedure could reduce the between-eye differences. The ARS method for IOP measurement was further developed using combined continuous force and area measurement during the dynamic phase when the sensor initially contacts the cornea. A force sensor was included with the resonator sensor in one probe. Evaluation was performed with the in vitro pig-eye model. The hypothesis was that the IOP could be deduced from the differential change of force and area during that phase. The study showed good accuracy and good reproducibility with a correlation of r=0.994 (n=414) between measured pressure in the vitreous chamber and IOP according to the ARS. Measurement time was short, 77 ms after initial contact. Problems with inter-eye differences and low resolution at high pressures were reduced. The ARS method is the first to combine simultaneous, continuous sampling of both parameters included in the applanation principle. Consequently, there is a potential for reducing errors in the clinical IOP tonometry.

Intraocular pressure (IOP) measurement is a routine procedure and a fundament in glaucoma care. Elevated IOP is the main risk factor for glaucoma, and to date, reduction of IOP is the only possible treatment. In a retrospective clinical material, the prevalence of open angle glaucoma was estimated on the west coast of Iceland. IOP measurement and optic nerve head examination were used to capture glaucoma suspects, within the compulsory ophthalmological examination for the prescription of eye glasses. The results were mainly in agreement with a recent prospective study in the same region. This indicated that retrospective data, under certain conditions, may contribute with useful information on the prevalence of glaucoma. However, normal tension glaucoma is underestimated if perimetry and/or fundus photography are not included in the examination. Three studies focused on the measurement of IOP. Goldmann applanation tonometry (GAT) is the standard method. GAT is affected by corneal properties, e.g. central corneal thickness (CCT) and corneal curvature (CC). Refractive surgery changes these properties. This has put focus on how corneal biomechanics translate into tonometric errors and stimulated the development of new methods. As a result, Pascal ® Dynamic Contour Tonometry (PDCT) and Icare® rebound tonometry have been introduced. A method under development by our research group is Applanation Resonance Tonometry (ART). It is based on resonance technology and estimates IOP from continuous measurement of force and contact area. Comparison of PDCT, Icare and GAT in a prospective study showed that the concordance to GAT was close to the limits set by the International Standard Organization (ISO) for PDCT, while Icare was outside the limits. To investigate if laser-assisted subepithelial keratectomy (LASEK) affects tonometry, a study was performed where measurements with GAT, PDCT and ART were obtained before, three and six months after LASEK. The hypothesis was that PDCT and ART would be less affected by LASEK than GAT. The results showed a statistically significant reduction of measured IOP three and six months after LASEK for all tonometry methods. Change in visual acuity and IOP between three and six months suggested a prolonged postoperative process. A servo-controlled prototype (ART servo) was developed. A study was undertaken to assess the agreement of ARTservo and a further developed v manual prototype (ART manual) with GAT. The study design was in accordance with the requirements of the ISO standard for tonometers. ARTmanual fulfilled the precision requirements of the ISO standard. ARTservo did not meet all the requirements of the standard at the highest pressure levels. Four tonometry methods, GAT, PDCT, Icare and ART, were investigated. None of them was independent of both CCT and CC. The inconsistencies in the results emphasize the importance of study design. A meta-analysis comprising healthy eyes (IOP ≤ 21 mmHg) in the three papers, revealed age as an important confounder. In summary, glaucoma prevalence in Iceland was investigated and the results indicated that a retrospective approach can contribute with meaningful information. ART and PDCT had a similar agreement to GAT. ART manual fulfilled the precision requirements set by the ISO-standard, ARTservo and PDCT were close, while Icare was distinctly outside the limits. All tonometry methods were affected by LASEK and no method was completely independent of corneal properties.

Background: Today corneal crosslinking with ultraviolet-A photoactivation of riboflavin is an established method to halt the progression of keratoconus. In some cases, when the refractive errors are large and the visual acuity is low, conventional corneal crosslinking may not be sufficient. In these cases it would be desirable with a treatment that both halts the progression and also reduces the refractive errors and improves the quality of vision. Aims:  The aims of this thesis were to determine whether mechanical compression of the cornea during corneal crosslinking for keratoconus using a sutured rigid contact lens could improve the optical and visual outcomes of the treatment, and also to find methods to evaluate the effect of different corneal crosslinking treatment regimens. Methods: In a prospective, open, randomized case-control study, 60 eyes of 43 patients with progressive keratoconus, aged 18-28 years, planned for routine corneal crosslinking, and a corresponding age- and sex-matched control group was included. The patients were randomized to conventional corneal crosslinking (CXL; n=30) or corneal crosslinking with mechanical compression of the cornea during the treatment (CRXL; n=30). Biomicroscopy, autorefractometry, best spectacle corrected visual acuity, axial length measurement, Pentacam® HR Scheimpflug photography, pachymetry, intraocular pressure measurements and corneal biomechanical assessments were performed before treatment (baseline) and at 1 month and 6 months after the treatment. One of the articles evaluated and compared the optical and visual outcomes between CXL and CRXL, while the other three articles focused on methods to evaluate treatment effects. In Paper I, the corneal light scattering was manually quantified from Scheimpflug images throughout the corneal thickness at 8 measurements points, 0.0 to 3.0 mm from the corneal centre, in patients treated with CXL. In Paper IV the corneal densitometry (light scattering) was measured with the Pentacam® HR software, in 4 circular zones around the corneal apex and at 3 different depths of the corneal stroma, in both CXL and CRXL treated corneas. Paper III quantified the biomechanical effects of CXL in vivo. Results: Corneal light scattering after CXL showed distinctive spatial and temporal profiles and Applanation Resonance Tonometry (ART) -technology demonstrated an increased corneal hysteresis 1 and 6 months after CXL. When comparing the refractive and structural results after CXL and CRXL, CRXL failed to flatten the cornea, and the treatment did not show any benefits to conventional CXL treatment, some variables even indicated an inferior effect. Accordingly, the increase in corneal densitometry was also less pronounced after CRXL. Conclusions: Analysis of corneal light scattering/densitometry shows tissue changes at the expected treatment location, and may be a relevant variable in evaluating the crosslinking effect. ART -technology is an in vivo method with the potential to assess the increased corneal hysteresis after CXL treatment. By refining the method, ARTmay become a useful tool in the future. Unfortunately, CRXL does not improve the optical and visual outcomes after corneal crosslinking. Possibly, stronger crosslinking would be necessary to stabilize the cornea in a flattened position.