Syfte: Syftet med studien var att, med hjälp av Optical Coherence Tomography (OCT), undersöka om det finns någon skillnad i central och perifer retinal tjocklek mellan olika ametropier. Metod: Studien omfattade 36 försökspersoner, som grupperades beroende på ametropi i en myop, emmetrop och hyperop grupp. Av de 36 försökspersonerna var det 15 myoper, 15 emmetroper och 6 hyperoper. En inledande mätning gjordes där försökspersonernas objektiva refraktion uppmättes med autorefraktor och därefter gjordes en avstämning i provbåge för att säkerställa refraktionen. Med OPKO Spectral OCT/SLO mättes retinas tjocklek både centralt och perifert på höger öga. För att analysera resultatet delades retina in i 15 olika zoner som jämfördes mellan de olika ametropierna. Resultat: Resultatet av studien visade en signifikant skillnad i foveal tjocklek mellan de olika ametropierna (p=0,03). Det var en siginifikant skillnad i retinal tjocklek mellan retinas zoner i alla tre ametropier (p<0,01), dock var det ingen signifikant skillnad i perifer retinal tjocklek mellan de tre olika ametropierna (p=0.07). Slutsats: Ingen skillnad i central och perifer retinal tjocklek kunde redovisas mellan de olika ametropierna. Då en tidigare studie har visat att den retinala tjockleken skiljer sig mellan olika ametropier kan resultatet av vår studie diskuteras då det i vår studie fanns brister som få antal personer, olika antal personer inom grupperna och en låg utbredning av synfel.

Purposes: To use optical coherence tomography (OCT) to image and quantify the effect of various corneal conditions, in terms of corneal, stromal and epithelial thickness, and light backscatter. To assess the changes caused by overnight orthokeratology (Corneal Refractive Therapy; CRT^TM) lens wear, keratoconus and laser in-situ keratomileusis (LASIK) refractive surgery, each of which may lead to topographical alterations in corneal thickness either by temporary moulding, degeneration, or permanent laser ablation, respectively. <br /><br /> Methods: Topographical thickness of the cornea was measured using OCT in all studies. The CRT^TM studies investigated myopic and hyperopic treatment, throughout the day. The myopic studies followed lens wear over a 4 week period, which was extended to 12 months, and investigated the thickness changes produced by two lenses of different oxygen transmissibility. CRT^TM for hyperopia (CRTH^TM) was evaluated after a single night of lens wear. <br /><br /> In the investigation of keratoconus, OCT corneal thickness values were compared to those obtained from Orbscan II (ORB) and ultrasound pachymetry (UP). A new fixation device was constructed to aid in the measurement of topographical corneal and epithelial thickness along 8 directions of gaze. Pachymetry maps were produced for the normal non-lens wearing cornea, and compared with the rigid gas permeable (RGP) lens wearing cornea and the keratoconic cornea. <br /><br /> Thickness changes prior to, and following LASIK were measured and monitored throughout six months. Myopic and hyperopic correction was investigated individually, as the laser ablation profiles differ for each type of procedure. The LASIK flap interface was also evaluated by using light backscatter data to monitor healing. <br /><br /> Results: Following immediate lens removal after myopic CRT^TM, the central cornea swelled less than the periphery, with corneal swelling recovering to baseline levels within 3 hours. The central epithelium decreased and mid-peripheral epithelium increased in thickness, with a more gradual recovery throughout the day. There also seemed to be an adaptation effect on the cornea and epithelium, showing a reduced amount of change by the end of the 4 week study period. The thickness changes did not alter dramatically during the 12 month extended study. In comparing the two lens materials used for myopic CRT^TM (Dk/t 91 vs. 47), there were differences in stromal swelling, but no differences in the central epithelial thinning caused by lens wear. There was a statistically insignificant asymmetry in mid-peripheral epithelial thickening between eyes, with the lens of lower Dk causing the greater amount of thickening. Hyperopic CRT^TM produced a greater increase in central stromal and central epithelial thickness than the mid-periphery. Once again, the stroma recovered faster than the epithelium, which remained significantly thicker centrally for at least six hours following lens removal. <br /><br /> Global pachymetry measurements of the normal cornea and epithelium found the periphery to be thicker than the centre. The superior cornea and epithelium was thicker than the inferior. In the measurement of the keratoconic cornea, OCT and ORB correlated well in corneal thickness values. UP measured greater values of corneal thickness. The keratoconic epithelium was thinner than normal, and more so over the apex of the cone than at the centre. The location of the cone was most commonly found in the inferior temporal region. Central epithelial thickness was thinner in keratoconics than in RGP lens wearers, which in turn was thinner than in non-lens wearers. <br /><br /> Following LASIK surgery for both myopia and hyperopia, the topographical OCT thickness profiles showed stromal thinning in the areas of ablation. The central myopic cornea showed slight regression at 6 months. During early recovery, epithelial thickness increased centrally in hyperopes and mid-peripherally in myopes. By the end of the 6 month study, mid-peripheral epithelial thickness was greater than the centre in both groups of subjects. The light backscatter profiles after LASIK showed a greater increase in backscatter on the anterior side of the flap interface (nearer the epithelium), than the posterior side (in the mid-stroma) during healing. The flap interface was difficult to locate in the OCT images at 6 months. <br /><br /> Conclusion: All the CRT^TM lenses used in this project produced more corneal swelling than that seen normally overnight without lens wear. In order for these lenses to be worn safely for long periods of time without affecting the health of the cornea, they need to be manufactured from the highest oxygen transmissible material available. The long-term effect of thinning on the epithelium's barrier properties needs to be monitored closely. <br /><br /> Global topographical thickness of the cornea and epithelium was measured using OCT in normal, RGP lens wearing and keratoconic eyes. Corneal and epithelial thickness was not symmetrical across meridians. The epithelium of RGP lens wearers was slightly thinner than normal, but not as thin as in keratoconics, suggesting that the epithelial change seen in keratoconus is mainly due to the condition. <br /><br /> Post-LASIK corneal and epithelial thickness profiles were not the same for myopic and hyperopic subjects, since the ablation patterns vary. Epithelial thickening in the mid-periphery had not recovered by six months in myopes or hyperopes, possibly indicating epithelial hyperplasia. Light backscatter profiles were used to monitor the recovery of the LASIK flap interface, showing the band of light backscatter around the flap interface to decrease as the cornea healed.

Purposes: To use optical coherence tomography (OCT) to image and quantify the effect of various corneal conditions, in terms of corneal, stromal and epithelial thickness, and light backscatter. To assess the changes caused by overnight orthokeratology (Corneal Refractive Therapy; CRT^TM) lens wear, keratoconus and laser in-situ keratomileusis (LASIK) refractive surgery, each of which may lead to topographical alterations in corneal thickness either by temporary moulding, degeneration, or permanent laser ablation, respectively. <br /><br /> Methods: Topographical thickness of the cornea was measured using OCT in all studies. The CRT^TM studies investigated myopic and hyperopic treatment, throughout the day. The myopic studies followed lens wear over a 4 week period, which was extended to 12 months, and investigated the thickness changes produced by two lenses of different oxygen transmissibility. CRT^TM for hyperopia (CRTH^TM) was evaluated after a single night of lens wear. <br /><br /> In the investigation of keratoconus, OCT corneal thickness values were compared to those obtained from Orbscan II (ORB) and ultrasound pachymetry (UP). A new fixation device was constructed to aid in the measurement of topographical corneal and epithelial thickness along 8 directions of gaze. Pachymetry maps were produced for the normal non-lens wearing cornea, and compared with the rigid gas permeable (RGP) lens wearing cornea and the keratoconic cornea. <br /><br /> Thickness changes prior to, and following LASIK were measured and monitored throughout six months. Myopic and hyperopic correction was investigated individually, as the laser ablation profiles differ for each type of procedure. The LASIK flap interface was also evaluated by using light backscatter data to monitor healing. <br /><br /> Results: Following immediate lens removal after myopic CRT^TM, the central cornea swelled less than the periphery, with corneal swelling recovering to baseline levels within 3 hours. The central epithelium decreased and mid-peripheral epithelium increased in thickness, with a more gradual recovery throughout the day. There also seemed to be an adaptation effect on the cornea and epithelium, showing a reduced amount of change by the end of the 4 week study period. The thickness changes did not alter dramatically during the 12 month extended study. In comparing the two lens materials used for myopic CRT^TM (Dk/t 91 vs. 47), there were differences in stromal swelling, but no differences in the central epithelial thinning caused by lens wear. There was a statistically insignificant asymmetry in mid-peripheral epithelial thickening between eyes, with the lens of lower Dk causing the greater amount of thickening. Hyperopic CRT^TM produced a greater increase in central stromal and central epithelial thickness than the mid-periphery. Once again, the stroma recovered faster than the epithelium, which remained significantly thicker centrally for at least six hours following lens removal. <br /><br /> Global pachymetry measurements of the normal cornea and epithelium found the periphery to be thicker than the centre. The superior cornea and epithelium was thicker than the inferior. In the measurement of the keratoconic cornea, OCT and ORB correlated well in corneal thickness values. UP measured greater values of corneal thickness. The keratoconic epithelium was thinner than normal, and more so over the apex of the cone than at the centre. The location of the cone was most commonly found in the inferior temporal region. Central epithelial thickness was thinner in keratoconics than in RGP lens wearers, which in turn was thinner than in non-lens wearers. <br /><br /> Following LASIK surgery for both myopia and hyperopia, the topographical OCT thickness profiles showed stromal thinning in the areas of ablation. The central myopic cornea showed slight regression at 6 months. During early recovery, epithelial thickness increased centrally in hyperopes and mid-peripherally in myopes. By the end of the 6 month study, mid-peripheral epithelial thickness was greater than the centre in both groups of subjects. The light backscatter profiles after LASIK showed a greater increase in backscatter on the anterior side of the flap interface (nearer the epithelium), than the posterior side (in the mid-stroma) during healing. The flap interface was difficult to locate in the OCT images at 6 months. <br /><br /> Conclusion: All the CRT^TM lenses used in this project produced more corneal swelling than that seen normally overnight without lens wear. In order for these lenses to be worn safely for long periods of time without affecting the health of the cornea, they need to be manufactured from the highest oxygen transmissible material available. The long-term effect of thinning on the epithelium's barrier properties needs to be monitored closely. <br /><br /> Global topographical thickness of the cornea and epithelium was measured using OCT in normal, RGP lens wearing and keratoconic eyes. Corneal and epithelial thickness was not symmetrical across meridians. The epithelium of RGP lens wearers was slightly thinner than normal, but not as thin as in keratoconics, suggesting that the epithelial change seen in keratoconus is mainly due to the condition. <br /><br /> Post-LASIK corneal and epithelial thickness profiles were not the same for myopic and hyperopic subjects, since the ablation patterns vary. Epithelial thickening in the mid-periphery had not recovered by six months in myopes or hyperopes, possibly indicating epithelial hyperplasia. Light backscatter profiles were used to monitor the recovery of the LASIK flap interface, showing the band of light backscatter around the flap interface to decrease as the cornea healed.

Purpose: To investigate whether retinal thickness varies with refractive error. Also secondary to see if there is any difference in retinal thickness between the right and left eye. Methods: The inclusion criteria for the study was subjects without any pathologies, age between 18-45 and refractive error of maximum +0.75 SER and the myopia had no limit, as well as no astigmatism higher then -1.00D. Subjects, which fitted the inclusion criteria for the study, was shown to the OCT room were retinal thickness measurements were acquired first on the right and then left eye. To get the same reading area, the same setup was used and the fixation point was always centered for each patient. After all subjects had undergone the same method the results were analyzed using t-test and regression analysis. Results: The analysis showed a difference between emmetropic eyes and myopic eyes in the peripheral retinal thickness, having the myopes being significantly thinner. The inter myopic analysis showed no difference in retinal thickness in any of the points. This could however be due to the smaller sample size. The comparison between right and left eye showed a good symmetry between the two eyes both in the emmetropic and the myopic group. Conclusions: From this study we can conclude that the myopic group has a thinner peripheral retinal thickness than the emmetropic group. Central retinal thickness is not significantly different but could be due to the smaller sample size. There is no difference in retinal thickness between right and left eye.

<p>Cancer is now the leading cause of death in developed countries. Despite advances in strategies aimed at the prevention and treatment of the disease, early detection of precancerous growths remains the most effective method of reducing associated morbidity and mortality. Pathological examination of physical tissues that are collected via systematic biopsy is the current "gold standard" in this pursuit. Despite widespread acceptance of this methodology and high confidence in its performance, it is not without limitations. Recently, much attention has been given to the development of optical biopsy techniques that can be used clinically and are able to overcome these limitations. This dissertation describes one such optical biopsy technique, angle-resolved low coherence interferometry (a/LCI), its adaptation to a clinical technology, and its evaluation in clinical studies.</p><p> The dissertation presents the theory that underlies the operation of the a/LCI technique, the design and validation of the clinical instrument, and its evaluation by means of two clinical trials. First, an account of the manner in which the depth-resolved angular scattering profiles that are collected by a/LCI can be used to determine nuclear characteristics of the investigated tissues is given. The design of the clinical system that is able to collect these scattering profiles through an optical fiber probe that can be passed through the accessory channel of an endoscope for <italic>in vivo</italic> use is presented. To demonstrate the ability of this system to accurately determine the size of cell nuclei, a set of validation experiments are described.</p><p> In order to evaluate the clinical utility of this a/LCI system, two clinical trials intended to assess the ability of a/LCI to detect the presence of early, pre-cancerous dysplasias in human tissues are presented. The first of these, an <italic>in vivo</italic> study of Barrett's esophagus (BE) patients undergoing routine surveillance for the early signs of esophageal adenocarcinoma, is described. This study represents the first use of the a/LCI technique in vivo, and confirms its ability to provide clinically useful information regarding the disease state of the tissue that it examines, with performance that compares favorably to other optical biopsy techniques. Next, an <italics>ex vivo</italics> study of resected intestinal tissue is presented. The results of this study demonstrate the ability of a/LCI to provide information that can be used to detect dysplasia in the lower gastrointestinal tract with high accuracy. This study will enable future development of the technology to allow conduction of <italic>in vivo</italic> trials of intestinal tissue. The results of these two clinical studies demonstrate the clinical utility a/LCI, illustrating its potential as an optical biopsy technique that has great potential to provide diagnostically relevant information during surveillance procedures. This is particularly relevant in the case of BE, where its successful use has been demonstrated <italic>in vivo</italic>.</p> / Dissertation

About 50% of cancer patients are treated with X-ray radiation therapy; however, with current treatment feedback, the effects and the efficacy of the treatment are generally detected several weeks/months after treatment completion. This makes the adjustment of the treatment based on early response, and identification of non-responding patients, nearly impossible. In this thesis a novel method combining optical coherence tomography and a gamut of image analysis methods is explored as a potential approach to detecting tissue variability. Applying texture analysis to the optical coherence tomography images may allow for the tracking of radiation therapy induced cell microstructural changes in cancer patients and help in the adjustment of treatment based on early response.

About 50% of cancer patients are treated with X-ray radiation therapy; however, with current treatment feedback, the effects and the efficacy of the treatment are generally detected several weeks/months after treatment completion. This makes the adjustment of the treatment based on early response, and identification of non-responding patients, nearly impossible. In this thesis a novel method combining optical coherence tomography and a gamut of image analysis methods is explored as a potential approach to detecting tissue variability. Applying texture analysis to the optical coherence tomography images may allow for the tracking of radiation therapy induced cell microstructural changes in cancer patients and help in the adjustment of treatment based on early response.

<p>Clinical imaging within ophthalmology has had transformative effects on ocular health over the last century. Imaging has guided clinicians in their pharmaceutical and surgical treatments of macular degeneration, glaucoma, cataracts and numerous other pathologies. Many of the imaging techniques currently used are photography based and are limited to imaging the surface of ocular structures. This limitation forces clinicians to make assumptions about the underlying tissue which may reduce the efficacy of their diagnoses. </p><p>Optical coherence tomography (OCT) is a non-invasive, non-ionizing imaging modality that has been widely adopted within the field of ophthalmology in the last 15 years. As an optical imaging technique, OCT utilizes low-coherence interferometry to produce micron-scale three-dimensional datasets of a tissue's structure. Much of the human body consists of tissues that significantly scatter and attenuate optical signals limiting the imaging depth of OCT in those tissues to only 1-2mm. However, the ocular anterior segment is unique among human tissue in that it is primarily transparent or translucent. This allows for relatively deep imaging of tissue structure with OCT and is no longer limited by the optical scattering properties of the tissue. </p><p>This goal of this work is to develop methods utilizing OCT that offer the potential to reduce the assumptions made by clinicians in their evaluations of their patients' ocular anterior segments. We achieved this by first developing a method to reduce the effects of patient motion during OCT volume acquisitions allowing for accurate, three dimensional measurements of corneal shape. Having accurate corneal shape measurements then allowed us to determine corneal spherical and astigmatic refractive contribution in a given individual. This was then validated in a clinical study that showed OCT better measured refractive change due to surgery than other clinical devices. Additionally, a method was developed to combine the clinical evaluation of the iridocorneal angle through gonioscopy with OCT.</p> / Dissertation

Preterm birth may lead to complications during the neonatal period that can cause visual dysfunctions. Retinopathy of prematurity (ROP) and neurological complications are well known reasons for visual dysfunctions, but preterm children with no or only mild ROP and no evident neurological problems may also be affected visually when they grow up. Retinal development starts early after gestation and continues long after birth. Major processes are underway during the second half of pregnancy when preterm children are born, and a preterm birth could possibly have a negative effect on normal retinal development. The aims of the studies were to evaluate retinal morphology and function in former preterm children and compare the results with children born at term. Former preterm children aged 5 to 17 years and born in a gestational age (GA) of 32 weeks or less were included in the different study groups. Children of similar ages who were born at term and with normal visual acuity (VA) acted as controls. Best corrected VA and refraction in cycloplegia were assessed in all children. Macular thickness and retinal nerve fiber layer (RNFL) thickness were measured with optical coherent tomography (OCT). Total retinal function was assessed with fullfield electroretinography (ffERG) and central macular function was assessed with multifocal electroretinography (mfERG). Preterm children had thicker central maculae than controls. There was a positive correlation between central macular thickness and GA at birth. RNFL thickness was reduced in the preterm children with severe ROP and treated ROP, but children with mild or no ROP did not differ from the fullterm children. The photoreceptor function measured with ffERG and the macular function measured with mfERG were reduced in the preterm group compared to controls. Preterm birth affects the retina both morphologically and functionally, and ROP has been suggested to be a reason for retinal changes. However, the results of this thesis indicate that children with no ROP also have retinal changes, suggesting an effect of prematurity itself. There were no correlations between any retinal changes and VA, but it is possible that larger studies using improved techniques may elucidate this further.

Organic cation (OC) secretion across renal proximal tubules (RPTs) involves basolateral OCT2- mediated uptake from the blood, followed by apical MATE1/2-mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H exchanger. OCs make up ~40% of all prescribed drugs and renal secretion plays a major role in clearing them. This study looked at two aims with the intent of resolving two outstanding issues dealing with the mechanism of MATE-mediated OC transport. First: Understanding the nature of intracellular sequestration of OC in cells that express hMATE1 as an integral part of characterizing 'the potential difference of substrate selectivity between the intracellular and extracellular face of MATE1.' Second: Testing whether structurally distinct MATE substrates can display different quantitative profiles of inhibition when interacting with structurally distinct ligands to determine 'the potential influence of the substrate on the profile of ligand interaction with MATE1.' All uptake experiments were realized with CHO cells that stably expressed hMATE1, hMATE2K or hOCT2. By epifluorescence microscopy cultured CHO-hMATE1 cells accumulated the fluorescent OC, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4- yl)amino]ethanaminium (NBD-MTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in hOCT2 expressing cells was restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC, 1-methyl-4-phenylpyridinium, [³H]MPP, from MATE1-expressing CHO cells. Punctate accumulation (20 min) of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of the V-Type H-ATPase, and 20 min accumulations of [³H]MPP and [³H]NBD-MTMA were reduced by >30% by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA (10-300 sec) suggesting that the effect of BAF was a secondary effect involving inhibition of the V-type H-ATPase. The 15 min accumulation of [³H]MPP by isolated single non-perfused rabbit RPTs was also reduced >30% by coexposure to 5 μM BAF. Thus, the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [³H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 μM BAF suggesting that vesicles loaded with OCs are not likely to recycle into the apical plasma membrane at sufficient rates to provide a parallel pathway for OC secretion. The uptake of three structurally distinct MATE substrates: MPP, triethylmethylammonium (TEMA) and NBD-MTMA into CHO-hMATE1 and CHO-hMATE2K cells was inhibited by three structurally similar cationic ionic liquids (ILs, salts in the liquid state: N-butylpyridinium, NBuPy; 1-methyl-3-butylimidazolium, Bmim; and N-butyl-N-methylpyrrolidinium, BmPy). The three ILs displayed a higher affinity for the pyridinium-based NBuPy (IC50 values, 2-4 μM) than for either the pyrrolidinium- (BmPy; 20-70 μM) or imidazolium-based ILs (Bmim; 15-60 μM). Inhibition of MPP, TEMA, and NBD-MTMA transport by NBuPy was competitive, with comparable Ki values against all substrates. Bmim also competitively blocked the three substrates but with Ki values that differed significantly (20 μM against MPP and 30 μM against NBD-MTMA versus 60 μM against TEMA). By trans-stimulation, all three ILs were transported by both MATE transporters. Together, these data indicate that renal secretion of ILs by the human kidney involves MATE transporters and suggest that the mechanism of transport inhibition is ligand-dependent, supporting the hypothesis that the binding of substrates to MATE transporters involves interaction with a binding surface with multiple binding sites. In order to further verify this hypothesis the uptake of four structurally distinct MATE substrates: MPP, NBD-MTMA, Cimetidine and Metformin into CHO-hMATE1 cells was characterized. Inhibition by ~400 drugs from the NIH clinical collection (NCC) was determined, and the rank order and level of inhibition seen were comparable against all substrates. IC₅₀ were measured for ~20 drugs selected from the NCC using principal component analysis (PCA); their IC₅₀ values were very similar against all four substrates, showing no systematic influence of substrate structure on inhibitory profile. The development and comparison of pharmacophores for each individual substrate revealed no substantial difference among them as proved by cluster analysis, leading to the conclusion that contrary to what was predicted based on the preliminary IL data, the substrates tested appear to have no influence on the inhibitory profile of ligands with hMATE1.