Bilateral Circumscribed Posterior Keratoconus: Visualization by Ultrasound Biomicroscopy and Slit-Scanning Topography Analysis

This paper documents a rare nonprogressive developmental disorder—bilateral circumscribed posterior keratoconus—in a 60-year-old man referred for a cataract surgery. For the first time ultrasound biomicroscopy was used to visualise the local anterior bulging of the posterior corneal surface with concomitant thinning of the stroma. The amount of localized posterior depression, corneal thickness and the refractive power of both the posterior and anterior corneal curvature were measured using slit-scanning topography analysis (Orbscan)

Role of Corneal Stromal Cells on Epithelial Cell Function during Wound Healing

Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs) and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM) on corneal epithelial cell function along with substance P (SP). Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK), paxillin, vimentin, β-catenin and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT) regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits α4, α5, αV, β1 and β3 whereas SFCM increased α4, α5, αV, β1 and β5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained activation of ZEB1, Slug in combination with upregulated migration-associated integrins and ERK (Extracellular signal-regulated kinase)-FAK-paxillin axis, may lead to induce type 2 EMT-like changes during corneal epithelial wound healing

Longitudinal stability of the diurnal rhythm of intraocular pressure in subjects with healthy eyes, ocular hypertension and pigment dispersion syndrome

Background The diurnal fluctuation of intraocular pressure may be relevant in glaucoma. The aim of this study was to find out whether the timing of diurnal fluctuation is stable over the years. Methods Long-term IOP data from the Erlangen Glaucoma Registry, consisting of several annual extended diurnal IOP profiles for each patient, was retrospectively analyzed. Normal subjects, patients with ocular hypertension and with pigment dispersion syndrome were included because these subjects had not been treated with antiglaucomatous medications at the time of data acquisition. A cosine curve was fitted to the IOP data and the stability of individual rhythms over the years was tested using the Rayleigh test. To compare the peak times among groups, means were calculated only from subjects with a significant Rayleigh test. Results Of the fifty-two eligible subjects, a total of 364 extended diurnal IOP profiles measured in a sitting position had been collected over a period of 114 ± 39 months. The Rayleigh test indicated intraindividual stability of phase timing only in 19 subjects (36%). In subjects with pigment dispersions syndrome, peak IOP occurred on average two hours and seven minutes later during the day compared with subjects without this condition (p = 0.05). Conclusions Fitting of cosine curves to the clinical IOP profiles was generally feasible, although careful interpretation is warranted due to lack of measurements in supine position and between midnight and 7 am. The interesting observation of a phase lag in eyes with pigment dispersion syndrome warrants confirmation and exploration in future prospective studies. The analysis of the IOP data showed no stable individual rhythm in the long term in a majority of patients

Outcomes of Sutureless Iris-Claw Lens Implantation

Purpose. To evaluate the indications, refraction, and visual and safety outcomes of iris-claw intraocular lens implanted retropupillary with sutureless technique during primary or secondary operation. Methods. Retrospective study of case series. The Haigis formula was used to calculate intraocular lens power. In all cases the wound was closed without suturing. Results. The study comprised 47 eyes. The mean follow-up time was 15.9 months (SD 12.2). The mean preoperative CDVA was 0.25 (SD 0.21). The final mean CDVA was 0.46 (SD 0.27). No hypotony or need for wound suturing was observed postoperatively. Mean postoperative refractive error was −0.27 Dsph (−3.87 Dsph to +2.85 Dsph; median 0.0, SD 1.28). The mean postoperative astigmatism was −1.82 Dcyl (min −0.25, max −5.5; median −1.25, SD 1.07). Postoperative complications were observed in 10 eyes. The most common complication was ovalization of the iris, which was observed in 8 eyes. The mean operation time was 35.9 min (min 11 min, max 79 min; median 34, SD 15.4). Conclusion. Retropupilary iris-claw intraocular lens (IOL) implantation with sutureless wound closing is an easy and fast method, ensuring good refractive outcome and a low risk of complication. The Haigis formula proved to be predictable in postoperative refraction

Role of Bone Morphogenetic Protein 7 (BMP7) in the Modulation of Corneal Stromal and Epithelial Cell Functions

In the cornea, healing of the wounded avascular surface is an intricate process comprising the involvement of epithelial, stromal and neuronal cell interactions. These interactions result to the release of various growth factors that play prominent roles during corneal wound healing response. Bone morphogenetic proteins (BMPs) are unique multi-functional potent growth factors of the transforming growth factor-beta (TGF-β) superfamily. Treatment of corneal epithelial cells with substance P and nerve growth factor resulted to an increase in the expression of BMP7 mRNA. Since BMP7 is known to modulate the process of corneal wound healing, in this present study, we investigated the influence of exogenous rhBMP7 on human corneal epithelial cell and stromal cell (SFs) function. To obtain a high-fidelity expression profiling of activated biomarkers and pathways, transcriptome-wide gene-level expression profiling of epithelial cells in the presence of BMP7 was performed. Gene ontology analysis shows BMP7 stimulation activated TGF-β signaling and cell cycle pathways, whereas biological processes related to cell cycle, microtubule and intermediate filament cytoskeleton organization were significantly impacted in corneal epithelial cells. Scratch wound healing assay showed increased motility and migration of BMP7 treated epithelial cells. BMP7 stimulation studies show activation of MAPK cascade proteins in epithelial cells and SFs. Similarly, a difference in the expression of claudin, Zink finger E-box-binding homeobox 1 was observed along with phosphorylation levels of cofilin in epithelial cells. Stimulation of SFs with BMP7 activated them with increased expression of α-smooth muscle actin. In addition, an elevated phosphorylation of epidermal growth factor receptor following BMP7 stimulation was also observed both in corneal epithelial cells and SFs. Based on our transcriptome analysis data on epithelial cells and the results obtained in SFs, we conclude that BMP7 contributes to epithelial-to-mesenchymal transition-like responses and plays a role equivalent to TGF-β in the course of corneal wound healing

Increased Homocysteine Levels in Tear Fluid of Patients with Primary Open-Angle Glaucoma

Aims: We assessed homocysteine (Hcy) levels in tear fluid and plasma of patients with primary open-angle glaucoma (POAG). We determined the association between Hcy levels, dry eye syndrome and B vitamin status. Methods: This prospective case-control study included 36 patients with POAG and 36 controls. Hcy concentrations were measured by highperformance liquid chromatography. Results: Patients with POAG had significantly higher mean Hcy levels both in tear fluid (205 8 84 nmol/l; p ! 0.001, t test) and in plasma (13.43 8 3.53 _ mol/l; p = 0.001, t test) than control subjects (130 8 53 nmol/l and 10.50 8 3.33 _ mol/l, respectively). Hcy in tear fluid was significantly correlated with plasma Hcy in POAG patients (r = 0.459; p = 0.005, Pearson’s correlation), but not in controls (r = 0.068; p = 0.695). POAG patients with dry eye disease had significantly higher Hcy levels both in tear fluid and plasma than POAG patients without dry eye disease. There was no association between Hcy levels and B vitamin status in subjects with POAG. Conclusions: The study suggests increased Hcy levels in tear fluid and plasma of patients with POAG. Elevated Hcy levels might be a risk factor for POAG and dry eye syndrome in subjects with glaucoma

Levels of aqueous humor trace elements in patients with non-exsudative age-related macular degeneration: a case-control study.

Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD. For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards. Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 µmol/L, IQR: 0.40-0.84 vs. 0.06 µmol/L; IQR: 0.01-.018; p = 0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62-3.15 vs. 1.17 µmol/L; IQR: 0.95-1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289-329 vs. 129 µmol/L; IQR: 111-145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9-32.6 vs. 5.1 µmol/L; IQR: 4.4-9.4; p = 0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4-31.3 vs. 49.9 µmol/L; IQR: 32.0-.142.0; p = 0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD. Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD

Novel Mutations in the MYOC/GLC1A Gene in a Large Group of Glaucoma Patients

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 2002. Por políticas de la revista en la que el artículo fue publicado no es posible descargar la versión del editor/PDF; no obstante, se pone a disposición el enlace de la publicación original.Mutations at the myocflin (MYOC) gene within the GLC1A locus have been revealed in 2- 4% of patients suffering primary open angle glaucoma (POAG) worldwide. In our ongoing glaucoma study sixhundred eighty two persons have been screend for MYOC mutations. The first group consisted of 453 patients from a long-term clinical study diagnosed either with juvenile OAG (JOAG), POAG, ocular hypertension (OHT) or normal tension glaucoma (NTG) plus 22 cases of secondary glaucoma. This group, and additional 83 healthy controls, is part of a long term study with repeated clinical examinations at the University of Erlangen-Nurnberg. An additional sample of 124 glaucoma patients or at risk persons referred from other sources were included in the mutation screening. Five novel mutations, namely Gly434Ser, Asn450Asp, Va1251Ala, 11e345Met and Ser393Asn, could he identified as cause of preperimetrk POAG, JOAG, normal tension POAG and POAG. Myocilln mutations were identified similar with previous reports with other ethnic populations at the rate of 11/341 (3.2%) probandsUniversidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Instrumental settings for Inductively-Coupled-Plasma-Mass-Spectrometry (ICP-MS).

<p>Instrumental settings for Inductively-Coupled-Plasma-Mass-Spectrometry (ICP-MS).</p