Testes oftálmicos, biometria ocular e cálculo do poder dióptrico da lente em corujas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Visual outcomes and pacient satisfaction follwing implantation of a supplementary multifocal IOL in patients undergoing cataract surgery

Purpose: To assess visual outcomes and patient satisfaction following implantation of the Sulcoflex® multifocal intraocular lens (IOL; Rayner Intraocular Lenses Ltd., Hove, UK) in a procedure combining capsular bag lens implantation with sulcus placement of the Sulcoflex® IOL. Setting: Instituto de Oftalmologia de Assis, Assis, SP, Brazil. Methods: Cataract patients > 45 years, with hyperopia ≥ 1.50 D and potential acuity measurement ≥ 20/30 undergoing Sulcoflex® multifocal IOL implantation were included. Monocular and binocular uncorrected near and distance visual acuity (VA) were evaluated at five days, one month, and three months postoperatively. Contrast sensitivity and refraction were measured in a subset of patients three months postoperatively. Patient satisfaction was assessed one month postoperative. Results: This non-consecutive case series comprised 25 eyes of 13 patients. Eleven eyes (52%) had pre-existing retinal pathologies. Monocular distance VA improved significantly at all follow-up visits. At final follow-up, 88% of eyes had monocular uncorrected distance VA (UDVA) of at least 20/25 and 24% had monocular UDVA of 20/20. All eyes had binocular UDVA of at least 20/25, and 58% had binocular UDVA of 20/20. Monocular uncorrected near vision (UNVA) was J1 in 68% of eyes and all patients had binocular UNVA of J1. Of all eyes studied, 92% and 58% achieved a spherical equivalent within 1 D and −0.5 D, respectively. The majority of patients reported satisfaction with visual outcomes. Complications included a postoperative intraocular pressure spike in four eyes. Conclusion: The Sulcoflex® multifocal IOL improves near and distance VA in cataract patients with retinal abnormalities and good VA potential.

Laminar Displacement and Prelaminar Tissue Thickness Change after Glaucoma Surgery Imaged with Optical Coherence Tomography

PURPOSE. To study changes in lamina cribrosa position and prelaminar tissue thickness (PTT) after surgical IOP reduction in glaucoma patients. METHODS. Twenty-two patients (mean age, 71.4 years) were imaged with spectral domain optical coherence tomography (SD-OCT; 24 radial B-scans centered on the optic nerve head [ONH]) before trabeculectomy or tube shunt implantation. Follow up images were acquired 1 week, 1 month, 3 months, and 6 months postsurgery. Bruch's membrane opening (BMO), the internal limiting membrane (ILM) and the anterior laminar surface (ALS) were segmented in each radial scan with custom software. Surfaces were fitted to the ILM and ALS with the extracted three-dimesional coordinates. PTT was the distance between the ILM and ALS, perpendicular to a BMO reference plane. Serial postsurgical laminar displacement (LD), relative to the BMO reference plane, and changes in PTT were measured. Positive values indicated anterior LD. RESULTS. Mean (SD) presurgery IOP was 18.1 (6.5) mm Hg, and reduced by 4.7 (5.5), 2.4 (7.7), 7.0 (6.2), and 6.8 (7.5) mm Hg at 1 week, 1 month, 3 months, and 6 months postsurgery, respectively. At the four postsurgery time points, there was significant anterior LD (1.8 [9.5], -1.1 [8.9], 8.8 [20.2], and 17.9 [25.8] mu m) and PTT increase (1.7 [13.3], 2.4 [11.9], 17.4 [13.7], and 13.9 [18.6] mu m). LD was greater in ONHs with larger BMO area (P = 0.01) and deeper ALS (P = 0.04); however, PTT was not associated with any of the tested independent variables. CONCLUSIONS. Both anterior LD and thickening of prelaminar tissue occur after surgical IOP reduction in patients with glaucoma. (Invest Ophthalmol Vis Sci. 2012;53:5819-5826) DOI:10.1167/iovs.12-9924

C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment

Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120 mmHg for 45 min, which was followed by 15 min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15 min. In the RBM exposed to 3 mM phosphate and/or 100 mu M Ca2+, C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment. (C) 2012 Elsevier Inc. All rights reserved.

Risk factors for blindness in patients with open-angle glaucoma followed-up for at least 15 years

Purpose: To determine the proportion of blindness and investigate the relationships between risk factors based on clinical characteristics and development of blindness in patients with primary open-angle glaucoma (POAG) treated for at least 15 years. Methods: A retrospective observational chart review was performed with 403 patients referred to a tertiary level hospital, each with a diagnosis of primary open-angle glaucoma, treated for at least 15 years. Blindness attributable to glaucoma was defined based on visual acuity and/or visual field tests. Variables considered to be possible risk factors for blindness were evaluated using odds ratio (OR), confidence interval (95% CI), and univariate and multivariate analyses. Results: Thirty-one patients became blind [13/53 (24.5%) - unilaterally and 18/53 (34%) - bilaterally] during the follow-up period of treatment (19.5 +/- 4.6 years, range 15-31 years). Multivariate statistics with regression analysis revealed that persistency on initial therapy <= 6 months was significantly associated with blindness, both unilateral (OR: 8.4; 95% CI: 1.3-56.4) and bilateral (OR: 7.2; 95% CI: 1.3-39.6). Other potential factors such as race, age, gender or number of medications were not associated with blindness. Conclusion: Blindness from primary open-angle glaucoma was not uncommon in this population of treated patients after the long follow-up period proposed. Persistence rates with the first therapy, as measured by a medical decision to change, were low. Persistence <= 6 months was statistically associated with the development of unilateral and bilateral blindness from glaucoma.

RAND-like Appropriateness Methodology Consensus for Primary Open-Angle Glaucoma in Latin America

PURPOSE: To report the results of a Latin American consensus panel regarding the diagnosis and management of primary open-angle glaucoma and to compare these results with those from a similar panel in the United States. DESIGN: A RAND-like (Research and Development) appropriateness methodology was used to assess glaucoma practice in Latin America. METHODS: The 148 polling statements created for the RAND-like analysis in the United States and 10 additional statements specific to glaucoma care in Latin America were presented to a panel of Latin American glaucoma experts. Panelists were polled in private using the RAND-like methodology before and after the panel meeting. RESULTS: Consensus agreement or disagreement among Latin American experts was reached for 51.3% of statements before the meeting and increased to 66.5% in the private, anonymous meeting after polling (79.0% agreement, 21.0% disagreement). Although there was a high degree of concordance (111 of 148 statements; 75%) between the results of this Latin American panel and the United States panel, there were some notable exceptions relating to diagnostic and therapeutic decision making. CONCLUSIONS: This RAND-like consensus methodology provides a perspective of how Latin American glaucoma practitioners view many aspects of glaucoma and compares these results with those obtained using a similar methodology from practitioners in the United States. These findings may be helpful to ophthalmologists providing glaucoma care in Latin America and in other regions of the world. (Am J Ophthalmol 2012;154: 460-465. (C) 2012 by Elsevier Inc. All rights reserved.)

Differences in early biomechanical properties after myopic and hyperopic lasik using mechanical microkeratome Sub-Bowman's Keratomileusis (SBK)

Purpose: To evaluate biomechanical changes measured with the ORA (Ocular Response Analyzer (R); Reichert Ophthalmic Instruments, Buffalo, New York, USA) after Lasik with the Moria One Use Plus and to compare the biomechanics changes after myopic and hyperopic ablations. Methods: Fourteeneyes for hyperopia (H) and 19 eyes for myopia (M) were evaluated with the ORA preoperatively and 1 month after Lasik with thin flap (100 microns) using SBK-OUP (Sub-Bowman Keratomileusis-One Use Plus, Moria (R)). CH (Corneal Hysteresis), CRF (Corneal Resistance Factor), IOPg (gold-standard, Goldmann correlated Intraocular pressure), IOPcc (Corneal compensated Intraocular pressure) and more 38 variables derived from the corneal biomechanical response signal of the ORA were analyzed. The Wilcoxon test was used to assess differences between the variables before and after surgery for each group and the differences between the pre and postoperative (1 month) myopic eyes were compared with those obtained in hyperopic eyes, using the Mann-Whitney test. Results: There was a significant difference before and after Lasik in myopic and hyperopic eyes in IOPg (Wilcoxon, p<0.05), but not in IOPcc. Only myopic eyes showed a significant difference in CH and CRF measurements before and after LASIK, as well as 9 other biomechanical parameters (aspect1, h1, dive1, path1, p1area1, W11, H11, and w2 path11; Wilcoxon, p<0, 05), 8 of these being related to the first sign of flattening. Five parameters related to the sign of the second applanation showed significant variation only in the eyes before and after hyperopic Lasik (aspect2, h2, dive2, mslew2 and H21; Wilcoxon, p<0,05). There was a difference in both myopic and hyperopic on three parameters related to the applanation signal areas (p1area, and p2area p2area1; Wilcoxon, p<0.05). Differences in IOPg and p1area, before and after surgery were significantly higher in myopic eyes than in hyperopic eyes (Mann-Whitey, p<0.05). Conclusion: There are several significant differences in biomechanical parameters after Lasik with Moria OUP_SBK. Overall, the impact of myopic LASIK on corneal biomechanics is higher than of hyperopic Lasik. The parameters derived from the first sign of the ORA are more affected in myopic LASIK, whereas parameters derived from the second applanation are more affected in hyperopic LASIK.

Optic Disc Margin Anatomy in Patients with Glaucoma and Normal Controls with Spectral Domain Optical Coherence Tomography

Objective: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). Design: Cross-sectional study. Participants: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. Methods: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruch's membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruch's membrane opening (BMO), defined as the innermost edge of Bruch's membrane; (2) Bruch's membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. Main Outcome Measures: The SD-OCT structures coinciding with the disc margin in stereophotographs. Results: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42-86) years and 63.5 (42-77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruch's membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruch's membrane and border tissue external to BMO. Bruch's membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. Conclusions: The clinically perceived disc margin is most likely not the innermost edge of Bruch's membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:738-747 (C) 2012 by the American Academy of Ophthalmology.

Rates of Change in the Visual Field and Optic Disc in Patients with Distinct Patterns of Glaucomatous Optic Disc Damage

Purpose: To investigate the rate of visual field and optic disc change in patients with distinct patterns of glaucomatous optic disc damage. Design: Prospective longitudinal study. Participants: A total of 131 patients with open-angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44) optic disc damage. Methods: Patients were examined every 4 months with standard automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT, Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany) for a period of 4 years. During this time, patients were treated according to a predefined protocol to achieve a target intraocular pressure (IOP). Rates of change were estimated by robust linear regression of visual field mean deviation (MD) and global optic disc neuroretinal rim area with follow-up time. Main Outcome Measures: Rates of change in MD and rim area. Results: Rates of visual field change in patients with focal optic disc damage (mean -0.34, standard deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean - 0.14, SD 0.77 dB/year) and diffuse (mean + 0.01, SD 0.37 dB/year) optic disc damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with focal optic disc damage (mean - 11.70, SD 25.5 x 10(-3) mm(2)/year) were faster than in patients with diffuse (mean -9.16, SD 14.9 x 10(-3) mm(2)/year) and sclerotic (mean -0.45, SD 20.6 x 10(-3) mm(2)/year) optic disc damage, although the differences were not statistically significant (P = 0.11). Absolute IOP reduction from untreated levels was similar among the groups (P = 0.59). Conclusions: Patients with focal optic disc damage had faster rates of visual field change and a tendency toward faster rates of optic disc deterioration when compared with patients with diffuse and sclerotic optic disc damage, despite similar IOP reductions during follow-up. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 294-303 (C) 2012 by the American Academy of Ophthalmology.

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

Elektrophysiologische Untersuchungen am experimentellen Autoimmun-Glaukom-Modell

Das Glaukom ist eine der führenden Erblindungsursachen weltweit. Trotzdem ist die Pathogenese, die zur Degeneration der retinalen Ganglienzellen führt, bisher nicht verstanden. In den letzten Jahren ergaben sich verschiedene Hinweise auf die Beteiligung einer immunologischen Komponente. Thema dieser Arbeit waren elektrophysiologische Untersuchungen, im Sinne von visuell evozierten Potentialen, am Tiermodell des Experimentellen Autoimmun Glaukoms und die Etablierung dieses Modells. Das Modell basiert auf einer Immunisierung von Lewisratten mit Pertussistoxin, inkompletten Freunds Adjuvant und potentiellen Antigenen, die zu einer Immunreaktion und einem Verlust von retinalen Ganglienzellen führen sollen. Zur Etablierung des Experimentellen Autoimmun Glaukom Modells wurde eine fünfwöchige Studie mit vier Gruppen durchgeführt. Als Antigene wurden Glia fibrilläres saures Protein (n= 10) und Myelin basisches Protein (n=10) verwendet, die beide in Studien zu Serum- und Kammerwasseranalysen bei Glaukompatienten eine Abweichung zur Kontrollgruppe gezeigt hatten. Außerdem wurde eine Gruppe mit selbst hergestelltem Sehnerv-Homogenat (n=12) immunisiert. Eine Gruppe erhielt keine Immunisierung und diente als Kontrolle (n=10). Zur Überprüfung der Effekte des Modells dienten verschiedene Untersuchungsmethoden, wie die Augeninnendruckmessung und die Untersuchung der Fundi. Des Weiteren wurden transiente und stationäre visuell evozierte Potentiale abgeleitet und die Latenzen, Amplituden und die Marker S (Steigung) und TR (Temporale Antworten) verglichen. Außerdem erfolgte nach Tötung der Tiere die Entnahme der Gehirne und Augen. Die Gehirne wurden nach Paraffineinbettung geschnitten, mit Luxol Fast Blue und Kresylviolett gefärbt und hinsichtlich etwaiger Entmarkungsherde oder anderer Pathologien unter dem Mikroskop bewertet. Der Verlauf des intraokulären Drucks zeigte sowohl zwischen den Gruppen als auch zwischen den verschiedenen Zeitpunkten keine signifikanten Unterschiede. Er bewegte sich im physiologischen Bereich mit durchschnittlich circa 12 mmHg. Die Funduskopien lieferten zu keinem Zeitpunkt krankhafte Veränderungen. Auch die visuell evozierten Potentiale lieferten zwischen den Gruppen keine signifikanten Unterschiede, sondern belegten normale visuelle Funktion bei allen Tieren. Die Auswertung der histologischen Untersuchung der Hirnschnitte zeigte keine Entmarkungsherde. Die erzielten Ergebnisse dieser Arbeit legen nahe, dass der retinale Ganglienzellverlust beim Experimentellen Autoimmun Glaukom Modell ohne eine Augeninnendruckerhöhung stattfindet. Die Fundusuntersuchung und die visuell evozierten Potentiale, wie in diesem Versuchsaufbau durchgeführt, scheinen nicht sensibel genug zu sein, diese Verluste nachzuweisen. In weiteren Arbeiten sollten andere Methoden zum Nachweis der retinalen Ganglienzellverluste erprobt werden. Neben elektrophysiologischen Methoden bieten sich für das weitere Vorgehen besonders immunhistologische Methoden an. Außerdem sollten die Mechanismen erforscht werden durch die es nach der Immunisierung zur Apoptose von retinalen Ganglienzellen kommt und welche Antikörper dazuführen können. Des Weiteren ist von Interesse, ob und wie eine zelluläre Komponente an der Pathogenese des Experimentellen Autoimmun Glaukoms beteiligt ist.

Identifizierung und Charakterisierung von Protein-Biomarkern beim Glaukom

Das Glaukom ist, nach dem Katarakt, die zweithäufigste Ursache für Erblindungen weltweit mit Milionen von Betroffenen, die von dieser zunächst weitgehend symptomfreien neurodegenerativen Erkrankung heimgesucht werden. Die Möglichkeiten auf dem Feld der Diagnose beschränken sich bislang weitestgehend auf die Messung des Augeninnendrucks und der Beurteilung des Augenhintergrundes durch einen erfahrenen Augenarzt. Eine labordiagnostische Prophylaxe ist bis heute nicht verfügbar, die Zahl unerkannter Erkrankungen dementsprechend hoch. Hierdurch geht wertvolle Zeit verloren, die man für eine effektive Therapie nutzen könnte.rnBezüglich der Pathogenese des Glaukoms geht man heute von mehreren, miteinander wechselwirkenden Pathomechanismen aus, zu denen neben mechanischen Einflüssen durch einen erhöhten IOD auch Hypoxie, verminderte Neutrophinversorgung, Exzitotoxizität, oxidativer Stress und eine Beteiligung autoimmuner Prozesse gezählt werden. Unabhängig vom Pathomechanismus folgt stets die Etablierung umfangreicher degenerativer Prozesse im Sehnervenkopf, den retinalen Ganglienzellen und den Axonen des Sehnerven, die letztlich im irreversiblen Untergang dieser Neuronen münden. Diese pathologischen Prozesse im ZNS hinterlassen auf Proteomebene Spuren, die mithilfe moderner massenspektrometrischer Methoden in Kombination mit multivariaten statistischen Methoden detektierbar und als sogenannte Biomarker-Kandidaten mit definiertem Molekulargewicht darstellbar sind. In dieser Arbeit wurde ein „Workflow“ entwickelt, der es ermöglicht, diese Biomarker-Kandidaten im Blutserum und in der Tränenflüssigkeit in einfachen, reproduzierbaren Schritten zu identifizieren und zu charakterisieren. Abweichend von der etablierten Methotik der Bottom-Up-Proteomics musste hierfür eine Methode entsprechend einer Top-Down-Philosophie entwickelt werden, die es erlaubt, die Spuren des Glaukoms im Proteom zu detektieren und zu charakterisieren.rnDies erfolgte in dieser Arbeit durch sowohl massenspektroskopischen Methoden wie SELDI-TOF® und MALDI-Tof-Tof als auch durch Bead-, Gel- und Flüssigkeits-chromatographisch-basierte Separations und Fraktionierungstechniken.rnDie erfolgreiche Kombination dieser Methoden führte zu Identifikationen einer ganzen Reihe von Biomarker-Kandidaten. Unter den identifizierten Proteinen, die bezüglich ihres korrespondierenden SELDI-Peaks im Massenbereich von Biomarker-Kandidaten liegen, finden sich Zytokine und Effektormoleküle der angeborernen Immunität, stressinduzierbare Kinasen, Faktoren, die zum Schutz der Telomeren dienen, Proliferationsmarker, neuronale Antigene und Transportproteine. Darüber hinaus wurden Komponenten identifiziert, die an der neuronalen Neutrophinversorgung beteiligt sind, neuronale Rezeptoren und Antigene, Komponenten des Komplementsystems und des MHC-I-Komplexes. All diese identifizierten Proteine sind bezüglich ihrer Funktion und möglichen Rolle innerhalb der Pathogenese des Glaukoms detailliert beschrieben und charakterisiert. Dies erlaubt einen umfassenden Einblick in alle Pathomechanismen, denen nach heutigem Kenntnisstand, eine Rolle an der Pathogenese des Glaukoms unterstellt wird.rn

Langzeitergebnisse nach Trabekulektomie bei Glaukompatienten

Hintergrund: Die antimetabolitgestützte Trabekulektomie stellt seit längeren denrnGoldstandard bei medikamentös nicht ausreichend therapierbaren Glaukomen dar. Kurz- und mittelfristige Erfolge wurden durch viele Studien bestätigt. Allerdings unterliegen diese sehr unterschiedlichen Erfolgsdefinitionen. Eine strikte Druckkontrolle ≤ 15 mm Hg ohne zusätzliche medikamentöse Therapie erscheint sinnvoll einen risikofreien Therapieerfolg zu bewerten. Es existieren nur wenige Langzeitstudien mit diesem Erfolgskriterium. Die durchgeführte Studie soll einen Eindruck der ophthalmologischen Versorgung trabekulektomierter Patienten an der Universitätsaugenklinik Mainz über einen bewusst langen Zeitraum bieten. Patienten und Methoden: In diese retrospektiven Studie wurden alle Patienten, die aufgrund einer fortgeschrittenen Glaukomerkrankung in den Jahren 1996, 2001 oder 2006 eine Trabekulektomie erhielten, aufgenommen. Von den 723 Augen der 664 Patienten dieser Jahrgänge konnten 447 (61,8%) nachverfolgt werden. Die Zusammensetzung der Patienten war mit anderen Studien vergleichbar. 28% konnten mindestens 7 Jahre, 10% sogar 10 Jahre nachverfolgt werden. Esrnwurde untersucht, ob ein signifikanter Zusammenhang zwischen dem ophthalomologisch-internistischem Entlassstatus (Visus, Tensio, Gesichtsfeld,rnGlaukomtyp, Voroperationen, Medikation, Vorerkrankungen, Art der Operation) undrnder erstrebten Kontrolle des Intraokulardruckes besteht. Ergebnisse: Die mittlere Nachbeobachtungszeit betrug 4,3 ± 3,4 Jahre. Nach 1, 3,rn5, 7 und 10 Jahren wiesen 217 (82,1%) (p < 0,001), 133 (67,7%) (p < 0,001), 70rn(50%) (p < 0,001), 59 (47,7%) (p = 0,056) und 16 (38,1%) (p = 0,06) Augen Intraokulardrücke ≤ 15 mm Hg ohne zusätzliche Antiglaukomatosa auf. Nichtrnstatistisch signifikant waren die 7- und 10-Jahresergebnisse. Mit Hilfe von Antiglaukomatosa waren es insgesamt, 225 (85,1%), 156 (79,7%), 87 (62,5%), 93 (75%) und 23 (54,7%) (alle p < 0,001). Die mediane Überlebenszeit für IOD ≤ 15 mm Hg ohne Medikation betrug 7,4 Jahre ± 5 Monate. Druckobergrenzen von ≤ 18 bzw. 21 mm Hg erfüllten bis zu 20% mehr Patienten. Der mittlere Visus von 0,32 ± 6 Stufen blieb nach einem mittleren postoperativen Abfall auf 0,25 ± 5 Stufen in den Folgeuntersuchungen stabil. Er zeigte ab dem 3-Jahresintervall keine statistisch signifikante Verschlechterung zum präoperativen Visus. 5,8 Jahre ± 80 Tage betrug die mediane Überlebenszeit für ein stabiles Gesichtsfeld. Gesichtsfelddaten, MD und PSD zeigten keine statistisch signifikante Verschlechterung (p > 0,05). Risikofaktoren für ein Scheitern der Operation waren Patientenalter (RR = 1,01, KI: 0,95 - 1,34, p = 0,043), arterielle Hypertonie (RR = 1,87, KI: 1,21-2,9, p = 0,005) und männliches Geschlecht (RR = 1,24; KI: 1,07 – 1,43; p = 0,004). Komplikationen waren passagere okuläre Hypotonien an 85 (19%), Fistulation an 46(10,2%), Aderhautschwellung an 29 (6,4%) –abhebung an 14 (3,1%), retinale Amotio an 9 (2%), hypotone Makulopathie an 5 (1,1%) und Hypertonien an 70 (15,6%) Augen. 150 (33,5%) Augen erhielten einen Folgeeingriff, 117 (26%) eine Phakoemulsifikation, 149 (33%) eine Fadenlockerung, 122 (27%) 5-FU-Injektionen, 42 (9,4%) eine Fadennachlegung, 33 (7,4%) ein Needling, 26 (5,8%) eine Zyklophotokoagulation, 19 (4,3%) eine Re-TE und 9 (2%) sonstige chirurgische Revisionen. Schlussfolgerung: Die Kontrolle des Augeninnendruckes ≤ 15 mm Hg ohne zusätzliche Medikation erreichten viele Patienten über einen langen Nachbeobachtungszeitraum. Die Häufigkeit der Komplikationen oder nötiger Folgeeingriffe war meist niedriger als in vergleichbaren Studien. Selbst Patienten mit hohem Risikoprofil hatten gute Ergebnisse. Aufgrund mangelnder Gesichtsfelddaten fanden sich keine Hinweise auf statistisch relevantes Fortschreiten des Glaukoms zur angestrebten medikationsfreien Druckkontrolle. Weitere Studien für einen Untersuchungszeitraum von 10 Jahren mit gleichen Erfolgskriterien wie in der vorliegenden Arbeit mit genauer Analyse der Gesichtsfelddaten wären wünschenswert, um zu belegen, dass die guten Langzeitergebnisse nach Trabekulektomie an der Universitätsaugenklinik Mainz auch eine Glaukomprogredienz dauerhaft verhindern. Damit stellt die an der Universitätsaugenklinik Mainz durchgeführte antimetabolitgestützte Trabekulektomie und deren postoperative Nachbetreuung an einer repräsentativen Population eine sichere und komplikationsarme Methode dar.

Numerical model of the human cornea based on stromal microstructure: identification of mechanical properties for two age groups

The optical quality of the human eye mainly depends on the refractive performance of the cornea. The shape of the cornea is a mechanical balance between intraocular pressure and tissue intrinsic stiffness. Several surgical procedures in ophthalmology alter the biomechanics of the cornea to provoke local or global curvature changes for vision correction. Legitimated by the large number of surgical interventions performed every day, the demand for a deeper understanding of corneal biomechanics is rising to improve the safety of procedures and medical devices. The aim of our work is to propose a numerical model of corneal biomechanics, based on the stromal microstructure. Our novel anisotropic constitutive material law features a probabilistic weighting approach to model collagen fiber distribution as observed on human cornea by Xray scattering analysis (Aghamohammadzadeh et. al., Structure, February 2004). Furthermore, collagen cross-linking was explicitly included in the strain energy function. Results showed that the proposed model is able to successfully reproduce both inflation and extensiometry experimental data (Elsheikh et. al., Curr Eye Res, 2007; Elsheikh et. al., Exp Eye Res, May 2008). In addition, the mechanical properties calculated for patients of different age groups (Group A: 65-79 years; Group B: 80-95 years) demonstrate an increased collagen cross-linking, and a decrease in collagen fiber elasticity from younger to older specimen. These findings correspond to what is known about maturing fibrous biological tissue. Since the presented model can handle different loading situations and includes the anisotropic distribution of collagen fibers, it has the potential to simulate clinical procedures involving nonsymmetrical tissue interventions. In the future, such mechanical model can be used to improve surgical planning and the design of next generation ophthalmic devices.