Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma. Since glaucoma is a leading cause of blindness, reliable methods for measuring the IOP are important. This doctoral dissertation presents a new method, applanation resonance tonometry (ART), for measurement of IOP. The method is based on resonance sensor technology combined with the novel multipoint analysis of continuously sampled data of both contact force and contact area. The ART was evaluated in in vitro porcine-eye studies as well as in clinic on both healthy volunteers and patients. A new symmetric probe with a larger sensor tip and improved aligning light was developed and evaluated in vitro. It showed that the error from off-centring was highly reduced. The new ART probe, used as a biomicroscope device (ARTBiom) and as a handheld device (ARTHand), was further evaluated in a clinical study designed in accordance with the International Standard Organisation’s (ISO) requirement. Both the ARTBiom and the ARTHand met the precision set by the requirements. Laser surgery is a common way to correct vision. The biomechanical effect of photorefractive keratectomy (PRK) on IOP measurements was evaluated using Goldmann applanation tonometry (GAT) and ART in an in vitro study. Both methods were affected, but to a different extent. The flat contact probe of GAT, as compared with the convex tip of ART, and single point vs. multipoint approach, provide explanation to the ART advantage regarding measurement error of IOP after PRK. In conclusion, resonance sensor technology has made it possible to introduce a new multipoint method for measuring IOP, and the method is relevant for measuring IOP in humans. It may be possible to reduce errors in the clinical measurement of IOP with this new method, especially after corneal surgery. The ART has the potential to become a useful clinical instrument for IOP measurement.

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.

Propósito: Determinar cuáles son los principales factores que influyen en la impermeabilidad intraoperatoria de las roturas retinianas en el desprendimiento rhegmatógeno primario (DRR). Los objetivos secundarios son, valorar si es posible hacer impermeables las roturas al paso de fluido sin necesidad de taponamiento postoperatorio, determinar si el estado del cristalino influye sobre la técnica quirúrgica. Analizar las complicaciones intraoperatorias, postoperatorias y resultados anatómicos y funcionales.Material y métodos: Estudio prospectivo de 82 ojos de 82 pacientes con DRR. Los pacientes fueron intervenidos mediante Vitrectomía vía Pars Plana (VPP), las roturas se trataron mediante la disección exhaustiva del vítreo con ayuda de perfluorocarbono líquido, un "secado" intenso de la interfase retina-epitelio pigmentario y la realización intraoperatoria de láser bajo aire. Al final de la intervención se realizó intercambio por solución salina balanceada (BSS) y se estudió el comportamiento de las roturas tratadas. Se estudió el éxito anatómico y funcional al mes, tres y seis meses después de la intervención. Las medidas de asociación entre variables categóricas se evaluaron mediante el test exacto de Fisher. Los contrastes de hipótesis de igualdad de medias se han llevaron a cabo tras transformación del logaritmo de la inversa de las variables (LogMAR) aplicandotanto el test de t Student y ANOVA de comparación de medias.Resultados: El éxito anatómico primario fue del 84,1%. No influyeron en la reaplicación el tipo, número o localización de las roturas. Tampoco influyó en la tasa de reaplicación el estado del cristalino, el tipo de cirugía utilizada o el tipo de fotocoagulación. Tuvieron menos tasa de reaplicación los pacientes con proliferación vitreorretiniana en grado B pero no fue estadísticamente significativo. La agudeza visual media preoperatoria fue de 20/80, y la postoperatoria de 20/40. El 46,4% de los pacientes con mácula desprendida antes de la intervención, obtuvieron agudezas visuales superiores a 20/50. La tasa de proliferación vitreorretiniana postoperatoria fue del 2,4%. El porcentaje de complicaciones fue inferior a otras series de DRR.Conclusiones: Mediante la disección exhaustiva del vítreo alrededor de las roturas, un taponamiento intraocular de corta duración y la realización intraoperatoria de láser de diodo es posible realizar un sellado de las roturas retinianas, que las impermeabiliza al paso de fluido, sin necesidad de dejar un taponador tras la intervención. Los principales factores que han influido en la impermeabilidad de las roturas son la visualización y el tratamiento completo de éstas. No influyeron el número de cuadrantes afectos, las roturas múltiples, la existencia de roturas superiores a una hora, las roturas inferiores o el tiempo de evolución del desprendimiento. El estado del cristalino no influyó en el sellado de las roturas. El índice de complicaciones, los resultados anatómicos y funcionales han sido similares a otras técnicas quirúrgicas para el desprendimiento de retina / Purpose: To evaluate factors associated with intraoperative sealing of retinal breaks in the primary rhegmatogenous retinal detachment (RRD). Secondary objectives are evaluate the possibility of retinal breaks sealing without postoperative tamponade, influence of lens status in retinal detachment surgery, avaluation of intraoperative and postoperative complications, anatomic and functional outcomes.Methods: Prospective study of 82 eyes in 82 patients with RRD. Pars plana vitrectomy was performed in all patients, retinal breaks were treated with intensive vitreous peeling around the breaks, and with diode laser under air. At the end of the surgery saline balanced serum was introduced into the vitreous cavity and a meticulous study of retinal breaks was performed. We evaluate anatomic and functional outcomes in the first month, third and sixth months after surgery. Results: Primary anatomic success was 84,1%. Kind, number or placement of retinal breaks didn't influence the anatomic success, neither lens status nor surgical procedure. Patients with vitreo-retinal proliferation (PVR) type B had less rate of success than the others but there was no statistical difference. Mean preoperative visual acuity was 20/80 and postoperative was 20/40. The 46,4% of macula-off patients ended the study with visual acuity over 20/50. Postoperative PVR rate was 2,4%. Conclusions: With intensive vitreous peeling around the breaks, intraocular short tamponade, and intraoperative diode laser is possible to seal retinal breaks, without using a postoperative tamponade. Main factors in surgical success are visualization and treatment of all breaks, kind of RRD, multiple, larger or inferior breaks, evolution time or lens status didn't show any influence in success rate. Rate of complications, anatomic and functional outcomes was similar than other studies.

Les malalties que causen ceguesa total o parcial afecten a milions de persones arreu del món. Una de les principals causas de ceguesa és el glaucoma, malaltia caracteritzada per un augment de la pressió intraocular (IOP) i una pèrdua de visió perifèrica. La fisiopatologia del glaucoma està estretament relacionada amb la fisiologia de l'humor aquós, fluid contingut a les cambres oculars (anterior i posterior). Des de la cambra anterior, l'humor aquós s'eliminarà a través de: 1) la via uveoescleral, que és minoritària, i 2) la via convencional o trabecular, on la major part de l'humor aquós (aprox. 80%) s'elimina travessant la xarxa trabecular cap el canal d'Schlemm i les venes aquoses. L'humor aquós té dues funcions: 1) nodrir les estructures avasculars (còrnia i cristal·lí) i 2) mantenir la IOP dins dels marges fisiològics (15-16 mmHg). Quan s'altera l'equilibri entre la producció i l'evacuació de l'humor aquós, l'humor aquós s'acumula i la IOP augmenta. La xarxa trabecular és un teixit d'estructura similar a una esponja organitzat en diferents regions i en contacte directe amb el canal d'Schlemm. La part més propera al canal d'Schlemm és la que presenta major resistència al pas de l'humor aquós. Alteracions en aquesta via suposaran un augment de la resistència i, en conseqüència, un augment de la IOP. La contractilitat cel·lular i la regulació del volum de la cèl·lula trabecular, són dos mecanismes claus en la regulació de la permeabilitat de la xarxa trabecular. Aquests dos mecanismes induirien deformacions a la membrana que activarien canals mecanosensibles.Un d'aquests canals mecanosensibles és el canal de K+ d'alta conductància dependent de Ca2+ (BKCa), que es caracteritza per la seva activació per voltatges despolaritzants i està modulat pel calci intracel·lula i del qual s'ha demostrat la seva mecanosensibilitat en diferents teixits.Per aquesta raó, s'ha caracteritzat electrofisiològicament el canal BKCa a la cèl·lula trabecular i s'ha estudiat la seva modulació per diferents factors, entre ells l'stretch mecànic. El canal BKCa ha demostrat ésser mecanosensible augmentant la seva probabilitat d'obertura tant per canvis en la tensió de la membrana cel·lular com per increments del volum cel·lular (swelling). En altres sistemes el canal està modulat per la pressió parcial d'oxigen (PO2), de manera que estímuls hipòxics disminueixen l'activitat del canal produïnt despolaritzacions com en les cèl·lules del cos carotidi. A l'ull, l'humor aquós aporta oxigen a les estructures avasculars i a la xarxa trabecular. Els valors de PO2 de l'humor aquós són més baixos (aprox. 55 mmHg) que en altres teixits més oxigenats (aprox. 95 mmHg). Per aquesta raó qualsevol procés que produeixi hipòxia a la cambra anterior tindrà un efecte més acusat. Per aquests motius s'ha estudiat quins mecanismes poden existir a les cèl·lules trabeculars per respondre a estats hipòxics. Els resultats obtinguts mostren com els corrents mitjançats pel canal BKCa disminueixen quan les cèl·lules trabeculars es tracten amb una solució hipòxica. Aquesta disminució dels corrents totals també s'observa en cèl·lules incubades en condicions d'hipòxia (5% O2).La hipòxia produeix alteracions a la mobilització del calci intracel·lular ([Ca2+]i) en diferents tipus cel·lulars. A les cèl·lules trabeculars s'ha estudiat l'efecte de la hipòxia sobre la [Ca2+]i i s'ha observat com la hipòxia modifica la resposta en relació al [Ca2+]i quan s'apliquen diferents substàncies vasoactives (bradikinina, endotel·lina-1) que influeixen sobre l'evacuació de l'humor aquós i que augmenten la [Ca2+]i a la cèl·lula trabecular. La hipòxia produeix entre d'altres efectes, un augment de la [Ca2+]i basal respecte les cèl·lules control (normòxiques) i disminueix l'increment de la [Ca2+]i produït per les substàncies agonistes. / SUBJECT: Electrophysiological characterization of a large conductance Ca2+-activated K+ channel (BKCa) in trabecular meshwork cells: modulation by membrane stretch and hypoxiaTEXT: The understanding of the physiology of the trabecular meshwork has advanced in the last few years, however few ionic channels have been characterized in this tissue. The large conductance Ca2+-activated K+ channel (BKCa) has been identified in the trabecular meshwork cells but its function is still unknown. BKCa channel is voltage dependent and its activity is modulated by intracellular calcium concentration ([Ca2+]i), with different functions depending on the cell type. In excitable cells it controls neuronal excitability, participates in neurotransmitter release and modulates contractile tone in vascular smooth muscle. In non-excitable cells it has been described its participation in cell volume regulation and its modulatory effect on different substances that mobilize [Ca2+]i.Besides [Ca2+]I, other substances such as cGMP or nitric oxide modulate the activity of BKCa channel in the trabecular meshwork. In other tissues, BKCa channel has shown mechanosensitive properties and it has also been described how its activity is modified by low PO2 values (hypoxia). Since trabecular meshwork cells are subjected to intraocular pressure and that aqueous humor contained in the anterior chamber presents PO2 values lower than other tissues, it is important to study the effects of these modulators on BKCa channel activity which will have a direct effect on the physiology of the trabecular meshwork.

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.

Η επίδραση της συστηματικής λήψης κορτικοστεροειδών στην ενδοφθάλμια πίεση είναι επαρκώς τεκμηριωμένη και εξαρτάται από σημαντικό αριθμό παραγόντων. Αντίθετα, ελάχιστες και αντικρουόμενες πληροφορίες υπάρχουν για την επίδραση των ρινικών κορτικοστεροειδών στην ενδοφθάλμια πίεση. Σκοπός της μελέτης ήταν η διερεύνηση της επίδρασης του ρινικού κορτικοστεροειδούς fluticasone υπό μορφή ρινικών ψεκασμών στην ενδοφθάλμια πίεση σε ασθενείς που έπασχαν από αλλεργική ρινίτιδα. Η ενδοφθάλμια πίεση μετρήθηκε πριν και κάθε πέντε ημέρες από τη χορήγηση του φαρμάκου. Η στατιστική ανάλυση δεν αποκάλυψε σημαντικές διαφορές, γεγονός που φανερώνει ότι το συγκεκριμένο κορτικοστεροειδές δεν επηρέασε την ενδοφθάλμια. / The effect of systemic administation on intraocular pressure is well established. However less attention has been paid to the effect of steroids when administered in a nasal spray. We conducted a study to investigate a possible association between nasal steroids and elevated IOP in 54 patients who were being treated for allergic rinitis. IOP was measured before the patients started therapy and thereafter every five days during that therapy. Follow up ranged from 27 to 35 days. Statistical analysis revealed no significant elavation in IOP after nasal steroid administration.

Purpose: To test the viability of implanting the Artisan®/VerisyseTM lens in a low-income monocular aphakic African population with insufficient capsular support where contact lens wear is expensive and spectacle correction is not possible, by assessing the postoperative visual functions. To further assess whether adverse effects (e.g.: pigment dispersion with secondary glaucoma, prolonged uveitis) in patients with highly pigmented irises would be as low as with patients in European and American trials. Methods: A prospective, randomised, controlled clinical trial comparing outcomes in two groups of unilateral aphakic patients. The patients in the first group received an Artisan intra-ocular iris-claw lens as a secondary procedure while the second group remained aphakic (the current treatment status quo for public patients in KwaZulu-Natal province in South Africa). Follow-up was done for 1 year. Results: The study was terminated early due to ethical and statistical reasons. Nine treated and five control patients were included. Monocular uncorrected vision was significantly higher in the treatment group (P=0,012) and patient satisfaction was higher (p=0,002). Changes in other variables (intraocular pressure, angle pigmentation, change in cup-to-disc ratio, iris pigment changes and best spectacle corrected vision) were not significantly different between the two groups. Conclusion: The Artisan®/VerisyseTM lens is a feasible option for aphakic African patients with regard to visual outcome, safety and patient satisfaction. This form of refractive correction should be the standard for patients with no capsular support and where other options are too expensive or carry greater risk. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2007.

Diss. Linköping : Univ., 2001.

Diss. (sammanfattning) Stockholm : Karol. Inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 5 uppsatser.