Structure-function Relationships Using the Cirrus Spectral Domain Optical Coherence Tomograph and Standard Automated Perimetry

Purpose: To evaluate the relationship between glaucomatous structural damage assessed by the Cirrus Spectral Domain OCT (SDOCT) and functional loss as measured by standard automated perimetry (SAP). Methods: Four hundred twenty-two eyes (78 healthy, 210 suspects, 134 glaucomatous) of 250 patients were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study and from the African Descent and Glaucoma Evaluation Study. All eyes underwent testing with the Cirrus SDOCT and SAP within a 6-month period. The relationship between parapapillary retinal nerve fiber layer thickness (RNFL) sectors and corresponding topographic SAP locations was evaluated using locally weighted scatterplot smoothing and regression analysis. SAP sensitivity values were evaluated using both linear as well as logarithmic scales. We also tested the fit of a model (Hood) for structure-function relationship in glaucoma. Results: Structure was significantly related to function for all but the nasal thickness sector. The relationship was strongest for superotemporal RNFL thickness and inferonasal sensitivity (R(2) = 0.314, P < 0.001). The Hood model fitted the data relatively well with 88% of the eyes inside the 95% confidence interval predicted by the model. Conclusions: RNFL thinning measured by the Cirrus SDOCT was associated with correspondent visual field loss in glaucoma.

Sulcus anatomy and diameter in pseudophakic eyes and correlation with biometric data: Evaluation with a 50 MHz ultrasound biomicroscope

PURPOSE: To evaluate the sulcus anatomy and possible correlations between sulcus diameter and white-to-white (WTW) diameter in pseudophakic eyes, data that may be important in the stability of add-on intraocular lenses (IOLs). SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Case series. METHODS: In pseudophakic eyes, the axial length (AL) and horizontal WTW were measured by the IOLMaster device. Cross-sectional images were obtained with a 50 MHz ultrasound biomicroscope on the 4 meridians: vertical, horizontal (180 degrees), temporal oblique, and nasal oblique. Sulcus-to-sulcus (STS), angle-to-angle (ATA), and sclera-to-sclera (ScTSc) diameters were measured. The IOL optic diameter (6.0 mm) served as a control. To test reliability, optic measurements were repeated 5 times in a subset of eyes. RESULTS: The vertical ATA and STS diameters were statistically significantly larger than the horizontal diameter (P=.0328 and P=.0216, respectively). There was no statistically significant difference in ScTSc diameters. A weak correlation was found between WTW and horizontal ATA (r = 0.5766, P<.0001) and between WTW and horizontal STS (r = 0.5040, P=.0002). No correlation was found between WTW and horizontal ScTSc (r = 0.2217, P=.1217). CONCLUSIONS: The sulcus anatomy had a vertical oval shape with the vertical meridian being the largest, but it also had variation in the direction of the largest meridian. The WTW measurements showed a weak correlation with STS. In pseudophakic eyes, Soemmerring ring or a bulky haptic may affect the ciliary sulcus anatomy.

Clinical Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops

Purpose: To report the clinical outcome of the treatment of dry eyes using 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) (Ophthalmos, Sao Paulo, Brazil). Methods: Sixteen eyes of 8 patients with Sjogren syndrome dry eyes (age, 51.13 +/- 9.45 years) were enrolled in this study (prospective noncontrolled interventional case series). Patients were instructed to use topical 0.03% tacrolimus eye drops twice a day (every 12 hours) in the lower conjunctival sac. Schirmer I test, break-up time, corneal fluorescein, and rose bengal staining score were performed in all patients 1 day before, and 14, 28, and 90 days after treatment with 0.03% tacrolimus eye drops. Results: The average fluorescein staining and rose bengal staining scores improved statistically significantly after 14 days of treatment and improved even more after 28 and 90 days. The average Schirmer I test did not improve statistically significantly after 28 days of treatment, although we did observe a significant improvement after 90 days of treatment with 0.03% tacrolimus eye drops. The average break-up time did not improve statistically after 14 days of treatment, although we observed a significant improvement after 28 and 90 days of treatment with 0.03% tacrolimus eye drops. Conclusions: Topical 0.03% tacrolimus eye drops successfully improved tear stability and ocular surface status in patients with dry eyes.

The Role of Dyslipidemia on Ocular Surface, Lacrimal and Meibomian Gland Structure and Function

Purpose: Dyslipidemia is characterized by high lipid blood levels that are risk factors for cardiovascular diseases, which are leading causes of death. However, it is unclear whether dyslipidemia is a cause of the dry eye syndrome (DES). Therefore we determined in transgenic mice models of dyslipidemia, whether there is an association with DES development. Methods: Dyslipidemic models included male and female adult mice overexpressing apolipoprotein CIII (Apo CIII), LDL receptor knockout (LDLR-KO) and ApoE knockout (ApoE-KO). They were compared with age-and gender-matched C57BL/6 mice. Ocular health was evaluated based on corneal slit lamp assessment, phenol red thread test (PRT) and impression cytology. Blood lipid profiles and histology of meibomian and lacrimal glands were also evaluated. Effects of high-fat diet and aging were observed in LDLR-KO and ApoCIII strains, respectively. Results: Body weight and lacrimal gland weight were significantly higher in male mice compared to females of the same strain (P < 0.05). Body weight was significantly lower in LDLRKO mice receiving high lipid diet compared to their controls (P = 0.0043). ApoE-KO were hypercholesterolemic and ApoCIII hypertriglyceridemic while LDLR-KO showed increases in both parameters. The PRT test was lower in male LDLR-KO mice with high-fat diet than control mice with standard diet (P = 0.0273). Aging did not affect lacrimal structural or functional parameters of ApoCIII strain. Conclusions: DES development is not solely dependent on dyslipidemia in relevant mice models promoting this condition. On the other hand, lacrimal gland structure and function are differentially impacted by lipid profile changes in male and female mice. This dissociation suggests that other factors beside dyslipidemia impact on tear film dysfunction and DES development.

In Vitro Effects of Bevacizumab Treatment on Newborn Rat Retinal Cell Proliferation, Death, and Differentiation

PURPOSE. Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on cell death, proliferation, and differentiation in newborn rat retina. METHODS. Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared. RESULTS. No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS. Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue. (Invest Ophthalmol Vis Sci. 2012;53:7904-7911) DOI:10.1167/iovs.12-10283

Portable light transmission measuring system for preserved corneas

Abstract Background The authors have developed a small portable device for the objective measurement of the transparency of corneas stored in preservative medium, for use by eye banks in evaluation prior to transplantation. Methods The optical system consists of a white light, lenses, and pinholes that collimate the white light beams and illuminate the cornea in its preservative medium, and an optical filter (400–700 nm) that selects the range of the wavelength of interest. A sensor detects the light that passes through the cornea, and the average corneal transparency is displayed. In order to obtain only the tissue transparency, an electronic circuit was built to detect a baseline input of the preservative medium prior to the measurement of corneal transparency. The operation of the system involves three steps: adjusting the "0 %" transmittance of the instrument, determining the "100 %" transmittance of the system, and finally measuring the transparency of the preserved cornea inside the storage medium. Results Fifty selected corneas were evaluated. Each cornea was submitted to three evaluation methods: subjective classification of transparency through a slit lamp, quantification of the transmittance of light using a corneal spectrophotometer previously developed, and measurement of transparency with the portable device. Conclusion By comparing the three methods and using the expertise of eye bank trained personnel, a table for quantifying corneal transparency with the new device has been developed. The correlation factor between the corneal spectrophotometer and the new device is 0,99813, leading to a system that is able to standardize transparency measurements of preserved corneas, which is currently done subjectively.

Keratometry device for surgical support

Abstract Background High astigmatisms are usually induced during corneal suturing subsequent to tissue transplantation or any other surgery which involves corneal suturing. One of the reasons is that the procedure is intimately dependent on the surgeon's skill for suturing identical stitches. In order to evaluate the influence of the irregularity on suturing for the residual astigmatism, a prototype for ophthalmic surgical support has been developed. The final intention of this prototype is to be an evaluation tool for guided suture and as an outcome diminish the postoperative astigmatism. Methods The system consists of hand held ring with 36 infrared LEDs, that is to be projected onto the lachrymal film of the cornea. The image is reflected back through the optics of the ocular microscope and its distortion from the original circular shape is evaluated by developed software. It provides keratometric and circularity measurements during surgery in order to guide the surgeon for uniformity in suturing. Results The system is able to provide up to 23D of astigmatism (32D - 55D range) and is ± 0.25D accurate. It has been tested in 14 volunteer patients intraoperative and has been compared to a commercial keratometer Nidek Oculus Hand-held corneal topographer. The correlation factors are 0.92 for the astigmatism and 0.97 for the associated axis. Conclusion The system is potentially efficient for guiding the surgeon on uniformity of suturing, presenting preliminary data indicating an important decrease on the residual astigmatism, from an average of 8D - for patients not submitted to the prototype guidance - to 1.4D - for patients who have actually been submitted to the prototype guidance - after the first 24 hours post-surgery and in the subsequent weeks. It also indicates that the surgeon should achieve circularity greater or equal to 98% in order to avoid postoperative astigmatisms over 1D. Trial Registration Trial registration number: CAAE - 0212.0.004.000-09.

Importância da tomografia de córnea para o diagnóstico de ectasia

OBJETIVO: Utilização da metodologia para interpretação da tomografia de córnea e segmento anterior para a detecção e diagnóstico de ectasia corneana. MÉTODOS: Descrição da interpretação clínica dos índices da tomografia de córnea e segmento anterior (Pentacam High Resolution - Oculus, Wetzlar,Germany); relato de 3 casos, demonstrando a importância da propedêutica no exame complementar, através do Pentacam HR®. CONCLUSÃO: Nossa experiência compatibiliza-se com os relatos de literatura na demonstração do incremento de sensibilidade e especificidade para a detecção precoce de susceptibilidade e diagnóstico de ectasia corneana, utilizando a tomografia de córnea e segmento anterior.

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.

Dangerous waters: outbreak of eye lesions caused by fresh water sponge spicules

Purpose To describe an extremely uncommon outbreak of eye lesions in a specific area of the Brazilian Amazonia. Methods Prospective noncomparative case series. Fifty-nine patients who developed eye lesions after swimming in the Araguaia river of Tocantins state in Brazil were examined. A team of ophthalmologists equipped with a slit-lamp, gonioscopic lenses, and indirect ophthalmoscopy performed full eye examination. Analysis of the flora and fauna of the river water was undertaken by a group of experts. Results and Conclusions Eighty-three eyes were affected. The most common lesions were corneal opacities seen in 34 eyes and conjunctival nodules diagnosed in 12 eyes. Severe visual acuity loss was detected in seven children with unilateral anterior chamber lesions. Spicules of the sponge species Drulia uruguayensis and Drulia ctenosclera were found inside three blind eyes that have been enucleated for diagnostic purposes. All eye lesions could be attributed to an outbreak of foreign bodies from fresh water sponges. Organic enrichment of the water resulting from the absence of sanitation probably was the key factor, which initiated a cycle of ecological imbalance that provoked human disease.

Lokalisation und Quantifizierung von 4-Hydroxynonenal in der Kochlea des Meerschweinchens nach Applikation von Gentamicin

Einleitung und Literaturdiskussion: Gentamicin ist ein aus Bakterien gewonnenes Aminoglykosid-Antibiotikum, das seit vielen Jahren im klinischen Alltag zur Therapie von bakteriellen Infektionen und zur Behandlung des Morbus Ménière eingesetzt wird. Ein bedeutender, jedoch noch nicht vollständig verstandener, Pathomechanismus ist dabei die Entstehung von 4-HNE durch Lipid Peroxidation und die konsekutive Schädigung durch das gebildete Aldehyd. Ziel dieser Arbeit war es, die Beeinflussung der Expression von 4-HNE in sieben verschiedenen Regionen der Kochlea (SV, SL, CO, NF, LF, IDZ und SGZ) durch Gentamicin zu beschreiben und quantitativ zu ermitteln.rnMaterial und Methoden: Die Meerschweinchen wurden in vier Gruppen unterteilt: eine unbehandelte Kontrollgruppe und je eine Gruppe 1, 2 und 7 Tage nach Gentamicin-Applikation. Nach Ablauf der Inkubationszeit wurden die Kochleae den Tieren entnommen, das Gewebe fixiert, geschnitten und auf Objektträgern aufgebracht. Die Schnitte wurden mit 4-HNE-Antikörpern behandelt und die Immunreaktion mikroskopisch lokalisiert und zelluläre quantitative Unterschiede am Computer berechnet.rnErgebnisse: Die Auswertung der Daten ergab signifikante Anstiege der Immunreaktion auf 4-HNE von der Kontrollgruppe zu allen drei Behandlungsgruppen in vier der sieben untersuchten Regionen (Stria vascularis, Spirales Ligament, Cortisches Organ und Nervenfasern). In zwei Bereichen (Fibrozyten im Limbus und Interdentalzellen) kam es zwischen Kontrollgruppe und nur einer Behandlungsgruppe D (7d) zu einer signifikanten Erhöhung. Lediglich die Spiralganglionzellen erbrachten keine signifikanten Differenzen. Der Vergleich der Einzelwindungen erbrachte für die Stria vascularis, das Spirale Ligament, das Cortische Organ und die Nervenfasern signifikante Anstiege innerhalb der drei Windungen von der Kontrollgruppe zu den drei Behandlungsgruppen. Bei der Stria vascularis zeigte sich als einzige Region eine signifikant erhöhte Immunfärbung in allen drei Einzelwindungen von der Kontrollgruppe zu allen Behandlungsgruppen. Beim Vergleich der Gesamtwindungen ließ sich ausschließlich für die Region der Stria vascularis von der ersten zur dritten Windung ein Anstieg der Braunfärbung feststellen. Zudem konnten Korrelationen der Färbeintensitäten einerseits zwischen den beiden Regionen der Lateralen Wand und andererseits zwischen zwei Zelltypen im Limbus aufgezeigt werden.rnDiskussion: Die durch Gentamicin-gesteigerte 4-HNE-Expression kann durch genomische und nicht-genomische Prozesse hervorgerufen werden.

Prävalenz dentaler Pathologien vergangener und rezenter Bevölkerungen : dentalpathologische Untersuchungen an einem frühmittelalterlichen Reihengräberfeld aus Mannheim

Pathologische Veränderungen des stomatognathen Systems haben die Menschheit seit jeher geplagt. Etliche dieser dentalen Pathologien hinterlassen Spuren, die auch an Skelettmaterial noch erkannt werden können. Die vorliegende Studie beschäftigt sich mit der Aufnahme dentaler Pathologien an Skelettmaterial eines frühmittelalterlichen Gräberfelds aus dem Bösfeld in Mannheim. Hierbei werden die Individuen in Hinblick auf AMTL, PMTL, Karies, marginale Parodontopathien, periapikale Läsionen, Zahnabnutzung, Zahnstein und Hypoplasien untersucht. In Folge werden die Häufigkeit der Pathologien innerhalb verschiedener Untergruppen der Bösfelder Population und zwischen anderen zeitgleichen und rezenten Populationen verglichen.rnrnBei der Prävalenz von AMTL und Karies ist ein signifikanter Anstieg mit dem Alter der Individuen zu beobachten, während sich kein Unterschied zwischen den Geschlechtern ergibt. Marginale Parodontopathien sind signifikant weniger bei frühadulten Individuen zu finden als bei der Gruppe der über 30 Jährigen. In der Gesamtpopulation ergeben sich keine Unterschiede zwischen den Geschlechtern. Altersabhängig betrachtet sind jedoch die über 40-jährigen Männer signifikant häufiger von marginalen Parodontopathien betroffen, während bei der Altersgruppe der Frühadulten die weiblichen Individuen häufiger betroffen sind. Unabhängig von Geschlecht und Alter kann bei den marginalen Parodontopathien ein Zusammenhang zwischen den alveolaren Entzündungsreaktionen und dem Abstand zwischen Schmelz-Zement Grenze und Limbus alveolaris festgestellt werden. Die männlichen Individuen des Bösfelds sind signifikant häufiger von periapikalen Läsionen betroffen. Bei dem Zahnverschleiß wird ein solcher Unterschied zwischen den Geschlechtern nicht festgestellt. Lediglich eine Zunahme des Verschleißes mit dem Alter liegt vor. Auch der Zahnsteinbefall steigt mit dem Alter an. Ein Unterschied bei dem Zahnsteinvorkommen zwischen den Geschlechtern ist nicht zu finden. Nur die frühmaturen Männer zeigen im Vergleich zu den Frauen einen signifikant geringeren Befall. Diese höhere Zahnsteinablagerung bei den frühmaturen Frauen kann mit deren Eintritt in das Klimakterium erklärt werden. Die Hypoplasien des Enamels lassen ein durchschnittliches Entstehungsalter von 3 bis 4 Jahren erkennen. Dieses kann mit dem, im Frühmittelalter sehr späten, Abstillalter in Verbindung gebracht werden. Die an der Bösfelder Serie beobachteten Häufigkeiten der Patholgien sind zu einem großen Teil vergleichbar mit anderen zeitgleichen Skelettserien. rnrnDie vorliegende Studie gibt einen Einblick in die Epidemiologie dentaler Pathologien im Frühmittelalter, kann Rückschlüsse ziehen auf damalige Lebensumstände und kann Unterschiede zwischen damaliger und heutiger Prävalenz verschiedener Erkrankungen darstellen. Zukünftige Studien an der Bösfelder Skelettserie können mit einem Fokus auf die archäologische Auswertung der Grabbeigaben weitere Erkenntnisse liefern und so das Verständnis dieser merowingerzeitlichen Population vertiefen. rn

Biomechanical model of human cornea based on stromal microstructure

The optical characteristics of the human cornea depends on the mechanical balance between the intra-ocular pressure and intrinsic tissue stiffness. A wide range of ophthalmic surgical procedures alter corneal biomechanics to induce local or global curvature changes for the correction of visual acuity. Due to the large number of surgical interventions performed every day, a deeper understanding of corneal biomechanics is needed to improve the safety of these procedures and medical devices. The aim of this study is to propose a biomechanical model of the human cornea, based on stromal microstructure. The constitutive mechanical law includes collagen fiber distribution based on X-ray scattering analysis, collagen cross-linking, and fiber uncrimping. Our results showed that the proposed model reproduced inflation and extensiometry experimental data [Elsheikh et al., Curr. Eye Res., 2007; Elsheikh et al., Exp. Eye Res., 2008] successfully. The mechanical properties obtained for different age groups demonstrated an increase in collagen cross-linking for older specimens. In future work such a model could be used to simulate non-symmetric interventions, and provide better surgical planning.

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.

Pressure-cornea-vascular index (PCVI) for predicting disease progression in normal tension glaucoma

It has been shown that the pressure-to-cornea index (PCI), which estimates the relative effects of intraocular pressure (IOP) and central corneal thickness (CCT), may differentiate between glaucoma and non-glaucoma states. The authors investigated the utility of the pressure-cornea-vascular index (PCVI) in predicting field-progression in patients with normal tension glaucoma (NTG).