bluuebunny/crossref_metadata_2025 huggingface dataset:
The protective effect of anti‐blue lens against photo‐induced cell death
Authors: Yu W.Y. , Shan S.W. , To C.H. , Chan H.H.L.
Published: September 2015

Purpose

Anti‐blue lenses that selectively block the harmful portion of the blue light spectrum become commercially available recently. This study aimed to evaluate the protective effect of anti‐blue lens on cultured porcine primary retinal pigmented epithelial (RPE) cells against photo‐irradiation.

Methods

Primary RPE cells were isolated from porcine eyes and cultured to confluence. The cells were characterised by RPE65 using Western Blot. White and blue light emitting diode (LED) light sources as well as the transmittance of the anti‐blue and anti‐UV lenses were characterised by a spectroradiometer. The RPE cells were exposed to ~1.8 × 104 cd/m2 white (peak wavelength at 443 and 533 nm) or blue (peak wavelength at 448 and 523 nm) LED light for 16 hours, with anti‐blue, anti‐UV lens or without lens. Control cells were incubated in the dark. Cellular viability under the different lighting conditions with the anti‐blue or anti‐UV lenses were compared using trypan blue staining and MTT assay.

Results

Trypan blue staining showed that the RPE cellular viability under no light, white light and blue light conditions without any lenses were 94.8 ± 0.4%, 93.7 ± 1.1% and 88.7 ± 2.0% respectively. Blue light irradiation significantly induced more cell death when compared to no light (p = 0.001) and white light (p = 0.005) conditions. MTT assay also revealed significant difference under blue light when compared to no light (p = 0.002) and white light (p = 0.014) conditions. When comparing the effect of anti‐blue and anti‐UV lenses on cell survival, we found that anti‐blue lens showed significantly elevated viability (93.4 ± 1.4% vs 90.6 ± 1.4%) using trypan blue (p = 0.022) and MTT assay (p = 0.029).

Conclusions

Blue light exposure induced significant cytotoxicity on RPE cells. The anti‐blue lens significantly reduced the harmful blue spectrum and showed protective effect on RPE cell survival.
In‐vivo microdialysis as a new technique to assess ocular pharmacokinetics of topically applied drugs in a rabbit model
Authors: Garhofer G. , Klaus R. , Jäger W. , Zeitlinger M. , Richter‐Müksch S. , Schmetterer L.
Published: September 2015

Purpose

Although topical drug delivery is the most widely used ocular drug administration route, the in‐vivo pharmacokinetic profile of topically applied drugs is only inadequately described. This is mainly caused by the fact that in the eye the assessment of in‐vivo pharmacokinetics is difficult and technically demanding. Here, we propose a new technique for the in‐vivo assessment of pharmacokinetic parameters of topically applied drugs using in‐vivo microdialysis in a rabbit model.

Methods

8 Female New Zealand White rabbits were included in the experiments. A linear microdialysis probe (30 kDa molecular weight cut off [MWCO]) was implanted in the anterior chamber, a concentric probe (20 kDa MWCO) in the posterior segment of the same eye. After a run‐in period to obtain stabile conditions, a single drop of ciprofloxacin eye drops was administered on the cornea. Microdialysis samples were collected every 30 min for 6 h. Probes were analyzed using HPCL.

Results

In the anterior chamber, the maximum total drug concentration was reached after 116 ± 36 minutes (Tmax) and amounted to 0.373 ± 0.281 μg/ml (Cmax). AUC (0‐n) for ciprofloxacin in the anterior chamber was 78.8 ± 47 μg min/ml. In the vitreous, drug concentration was considerably lower. A Cmax of 0.02 ± 0.03 μg/ml was reached after 106 ± 60 min. AUC (0‐n) for ciprofloxacin in the vitreous was 0.286 ± 370 μg min/ml.

Conclusions

Here, we present in‐vivo microdialysis as a new method for the in‐vivo assessment of pharmacokinetic profiles. Maximum drug concentration in the anterior chamber was reached approximately 2 hours after single drug administration. Although the drug concentration in the vitreous was considerably lower, time course of drug concentration was comparable. In summary, our data show that microdialysis is an excellent method to assess in‐vivo pharmacokinetics with a high temporal resolution.
Comparison between i‐gel and endotracheal tube in corneal grafts: a randomized clinical trial
Authors: Guerrier G. , Rondet S. , Hallal D. , Levy J. , Boutboul D. , Sjögren L. , Legeais J.M. , Nicolau R. , Mehanna C. , Bourges J.L. , Samama C.M.S.
Published: September 2015

Purpose

To assess the safety of the laryngeal mask I‐Gel® in keratoplasty (KP) performed under general anaesthesia.

Methods

Patients with indications for KP (n = 110) were enrolled in a prospective study and randomly assigned to I‐Gel® (n = 55; 30 lamellar KP and 25 penetrating KP) or tracheal tube (n = 55; 29 lamellar KP and 26 penetrating KP). Peri‐operative complications and recovery time were compared between two groups using t‐test or χ2 test. Contraindications to elective use of the laryngeal mask airway were exclusion criteria (oesophageal reflux, extreme obesity, oropharyngeal pathology, expected difficult intubation).

Results

No surgical peri‐operative complications were reported in either group. There was a significantly greater incidence of coughing at extubation and after extubation in the tracheal group (25/55; 45%) than in the laryngeal mask group (3/55; 5%) (p < 0.001). Recovery time was shorter in the I‐Gel® group (80 min; 95%CI [75–86]) compared with the tracheal tube group (88 min; 95%CI [82–95]) (p = 0.03). There were no significant differences in the incidence of sore throat and hoarseness between the two devices.

Conclusions

The use of I‐Gel® for keratoplasty under general anaesthesia is safe, reduces the risk of potential ocular hypertension during recovery and saves recovery time.
Lack of tone response in retinal arterioles secondary to electrical field stimulation
Authors: Kratholm N. , Simonsen U. , Jensen P.S. , Kringelholt S. , Bek T.
Published: September 2015

Purpose

The retinal vascular system is devoid of autonomic nervous supply and therefore retinal blood flow is autoregulated. However, it is unknown to what extent electrical activity in the retina during the visual process contributes to this flow regulation. The purpose of the present study was to study changes in vascular tone in retinal arterioles during electrical field stimulation (EFS) simulating neuronal activity around the vessels.

Methods

Porcine ciliary arteries and retinal arterioles were mounted in a myograph system and the tone was measured during: A) Six series of bipolar field stimulations with a frequency of 1 Hz successively doubled to reach 32 Hz. In each series 30 mA pulses with a duration of 0.3 msec were applied during 20 sec, followed by a resting period of 5 min. B) The successive addition of the Na+ channel opener veratridine in the concentrations: 10−6, 3 ×10−6, 10−5 and 3 × 10−5 mM. The experiments were repeated after addition of the Na+ blocker tetrodotoxin (TTX) and after removal of the perivascular retinal tissue.

Results

EFS had no significant effect on the tone of retinal arterioles (p > 0.66), whereas veratridine showed a concentration dependent relaxation of these vessels (p < 0.01). The effect was partially reduced by TTX which depended on the presence of perivascular retinal tissue.

Conclusions

EFS has no effect on the tone of porcine retinal arterioles in vitro, whereas veratridine induces relaxation of these vessels. The findings are in accordance with a lack of autonomic nervous supply in retinal arterioles.
Adjunctive photodynamic therapy for type 1 choroidal neovascularization associated with thickened choroid
Authors: Kim N. , Lee W.K.
Published: September 2015

Purpose

To evaluate the treatment outcomes of adjunctive photodynamic therapy (PDT) in patients with type 1 choroidal neovascularization (CNV) associated with thickened choroid and refractory to anti‐vascular endothelial growth factor (VEGF) monotherapy.

Methods

Data on 28 eyes of 28 patients with type 1 CNV with a minimum subfoveal choroidal thickness of 300 μm were reviewed. All showed persistent subretinal and/or intraretinal fluid after at least 4 anti‐VEGF injections in the 6 months before adjunctive PDT. No eyes had certain polypoidal lesions on indocyanine green angiography. The main outcomes measured included the rates of complete fluid absorption at 3 months and the change in best‐corrected visual acuity (BCVA) at 12 months.

Results

At 3 months, complete fluid absorption was observed in 24 eyes (85.7%). The mean central macular thickness significantly reduced from 342 ± 63 μm to 242 ± 60 μm, and the mean subfoveal choroidal thickness from 386 ± 80 μm to 350 ± 91 μm compared to baseline (P < 0.001, P < 0.001, respectively). Over the 1‐year follow‐up period, 17 eyes (60.7%) were free from recurrent fluid accumulation. Anti‐VEGF injection was mainly used in the re‐treatment of persistent or recurrent exudation (mean: 1.5). At 12 months, the mean BCVA significantly improved compared to baseline (20/53 to 20/44, P = .039), and the logarithm of the minimal angle of resolution BCVA improved by ≥0.3 or maintained in 27 eyes (96.4%).

Conclusions

Adjunctive PDT in eyes with type 1 CNV with thickened choroid refractory to anti‐VEGF monotherapy resulted in complete fluid absorption in most eyes, which translated to visual improvement up to 1 year.
MMP‐9 null mice display elevated IOP due to reduced aqueous humor drainage from the trabecular meshwork
Authors: De Groef L. , Siwakoti A. , Geeraerts E. , Billen J. , Stalmans I. , West‐Mays J. , Moons L.
Published: September 2015

Purpose

Aqueous humor outflow resistance depends on a complex equilibrium of extracellular matrix biosynthesis versus proteolysis in the trabecular meshwork. Several members of the MMP family, including MMP‐9, are essential to the regulation of aqueous humor outflow resistance, i.e. to intraocular pressure (IOP) homeostasis. Here, we characterized the baseline ocular phenotype of MMP‐9 null mice, with emphasis on the dysregulation of IOP homeostasis.

Methods

MMP‐9 null and wild type mice, from 3 to 13 months of age, were studied. IOP and central corneal thickness were measured via rebound tonometry and pachymetry, resp. Anterior chamber morphology and trabecular meshwork organization were studied (1) in vivo with OCT, (2) via light microscopy and (3) by means of transmission electron microscopy (TEM), and its collagen composition was studied using Sirius Red and immunostainings. Integrity of the retina and optic nerve were evaluated with OCT and histological stainings on tissue sections and retinal flatmounts.

Results

MMP‐9 null mice present with early‐onset ocular hypertension, and fluorophotometric measurements of aqueous humor turnover revealed a reduced aqueous humor drainage. While OCT, light microscopy and TEM analysis did not disclose any abnormalities in the cellular organization of the trabecular meshwork, collagen staining indicated that there is an aberrant extracellular matrix composition in MMP‐9 null mice. Remarkably, the observed IOP elevation in MMP‐9 null mice did not result in a glaucomatous phenotype at the level of the retina and optic nerve at the ages studied.

Conclusions

Our observations corroborate the role of MMP‐9 as an important remodeler of the trabecular meshwork, and evidence for a causal link between MMP‐9 deficiency, trabecular meshwork composition and IOP elevation is revealed.
Use of retinal oximetry in estimating cerebral tissue oxygenation
Authors: Van Keer K. , Abegão Pinto L. , Stalmans I. , Vandewalle E.
Published: September 2015

Purpose

To investigate the correlation between cerebral tissue oxygenation (SctO2) and retinal vessel oxygen saturation (SO2) using non‐invasive spectroscopy in healthy individuals.

Methods

Retinal and cerebral oxygen saturations were measured in dark‐adapted, healthy volunteers breathing ambient air in a seated position using dual wavelength retinal oximetry and transcranial near‐infrared spectroscopy (NIRS) respectively. Correlations between SO2 and SctO2 were analyzed using Pearson correlation coefficients. Multivariate analysis was performed to determine the relative contribution of the arterial and venous vessels to SctO2. Using this model, SctO2 was estimated based on retinal arterial and venous oxygen saturation. Pearson correlation coefficients, paired sample t‐test and Bland‐Altman analysis were used to assess the agreement between the measured and the predicted SctO2.

Results

Twenty‐one young healthy individuals aged 26.4 ± 2.2 years were analyzed. SctO2 showed a significant positive correlation with both arterial and venous SO2 (r = 0.442, P = 0.045 and r = 0.434 P = 0.049 respectively). In multivariate analysis, the relative contribution of arterial and venous SO2 to SctO2 was significantly correlated with diastolic blood pressure, retinal venous oxygen saturation and retinal venous diameter (R2=0.60, P < 0.001). The measured SctO2 (72.2 ± 3.5%, range 67.3–80.1) correlated well with estimated SctO2 (72.2 ± 2.6%, range 67.6–77.5) (r = 0.774, P < 0.001). Bland–Altman plots showed 95% agreement within ±6.8%.

Conclusions

In this pilot study, retinal oximetry showed promising as an estimate of cerebral tissue oxygenation as measured by NIRS.
Long‐term results of the phase I/II clinical trial: standardized, non‐xenogenic, cultivated limbal stem cell transplantation
Authors: Behaegel J. , Ni Dhubhgaill S. , Koppen C. , Tassignon M.J. , Zakaria N.
Published: September 2015

Purpose

To evaluate the long‐term success rate of transplanted non‐xenogenic, bio‐engineered, composite grafts of cultured limbal epithelial stem cells on standardized amniotic membranes in patients with limbal stem cell deficiency.

Methods

We report the extended outcome of standardized cultivated limbal stem cell transplantations of our previous phase I/II trial. Between July 2008 and May 2012, 18 patients with partial or total limbal stem cell deficiency received either autologous (n = 15) or allogenic (n = 3) stem cell explants, using a protocol free from xenogenic products and a reduced manipulation surgical technique.

Results

Six of the 18 patients were lost to follow‐up. The remaining 12 patients had a mean follow‐up of 46.6 months. Two of 10 patients experienced an evisceration, not related to the stem cell transplantation. 7 of the remaining 8 (87.5%) patients retained a persistent intact epithelium. Although we did see a significant reduction in corneal neovascularization of the corneas post transplantation, we did not see a significant improvement in visual acuity of the total cohort, although one patient gained a visual acuity from finger counting to 0.5 post limbal stem cell transplantation and post penetrating keratoplasty.

Conclusions

This standardized culture system and surgical approach is safe and effective in restoring a functional epithelial cell layer, with satisfying long‐term results. Due to the limited number of patients and the comorbidities, we did not see a significant improvement in visual acuity of the total cohort. We maintain that in selected cases this technique, followed by a penetrating keratoplasty can significantly improve visual acuity.
Computerized analysis of human corneal endothelium morphology
Authors: Ruggeri A. , Scarpa F.
Published: September 2015

Purpose

Corneal images acquired by in‐vivo microscopy provide clinical information on the cornea endothelium health state. The reliable estimation of the 3 clinical morphometric parameters (endothelial cell density, pleomorphism, polymegethism) requires the accurate detection of cell contours in a large number of cells. Thus for the practical application of this analysis in clinical settings an automated method is needed.

Methods

The contours of cells are detected using a genetic algorithm. It randomly modifies individuals from the current population to produce the children for the next generations, which evolve toward an optimal solution. We start with a small set of vertexes forming regular hexagons, which in successive generations evolve into polygons with possibly different number and positions of vertexes. Each vertex is positioned by considering both its correspondence with the actual image (pixels intensity) and the regularity of the resulting polygons. The goal is to obtain a final population of vertexes forming polygons that best fit the cells contours in the actual image.

Results

15 images were acquired with a specular endothelial microscope (SP‐3000P, Topcon Co, Japan) in healthy and pathological subjects. Ground truth values for the 3 parameter were obtained from manually drawn cell contours. Differences between this manual estimation of the parameters and the automated one were always less than 8%.

Conclusions

These preliminary results show the ability of the proposed algorithm to adapt to different shapes and sizes of cells and to allow the reliable estimation of the morphometric parameters used in clinical practice.
Randomised, controlled study of the efficacy and safety of a new eye‐drop formulation for moderate to severe dry eye syndrome
Authors: Doan S. , Baudouin C. , Khairallah M.
Published: September 2015

Purpose

The aim of this study was to compare the efficacy and safety in Dry Eye Disease (DED) of T2762, a new product containing an innovative bioprotective molecule trehalose (molecule finds in plants resistant to dissication with osmoprotectant properties) and hyaluronic acid, to Vismed®.

Methods

Phase III, randomized, active‐controlled, Investigator‐masked, multicentric study in France and Tunisia. 105 Adult patients (≥18 years) with moderate to severe DED were included and received one drop of either T2762 (N = 52) or Vismed® (N = 53) 3‐6 times per day for 84 days. The primary efficacy variable was the Oxford grading score at Day 35. Ocular Surface Disease Index (OSDI), dry eye symptoms, Schirmer test, TBUT, conjunctival hyperaemia, and global performance were assessed as secondary efficacy criteria at baseline, Day 35 and Day 84. Safety assessments were standard.

Results

Non‐inferiority of T2762 to Vismed® for Oxford grading score was demonstrated at Day 35. For secondary efficacy parameters, reductions in OSDI, dry eye symptoms and investigator/patient assessments of global performance were better for T2762. There were no clinically meaningful between‐group differences for the other secondary criteria. Both treatments were well tolerated. Interestingly, there were fewer ocular symptoms upon instillation and fewer AEs with T2762.

Conclusions

T2762 is effective and safe, with better patient satisfaction than existing hyaluronate‐only eye drops, and offers a therapeutic advancement in the treatment of moderate to severe DED.
The pathophysiology of pseudoexfoliation syndrome is affected by interaction of TGF‐β1 and LOXL1
Authors: Liravi P. , Zenkel M. , Kruse F.E. , Schlötzer‐Schrehardt U.
Published: September 2015

Purpose

The cross‐linking enzyme lysyl oxidase‐like 1 (LOXL1) and profibrotic transforming growth factor (TGF)‐ß1 play key roles in pathophysiology of pseudoexfoliation (PEX) syndrome/glaucoma. The purpose of this study was to investigate the interaction between LOXL1 and TGF‐ß1 with respect to the PEX‐specific disordered matrix metabolism.

Methods

Primary human Tenon's capsule fibroblasts (hTCF) obtained from patients were treated with TGF‐ß1 (0‐10 ng/ml) for 12‐72 hours without or with preincubation with inhibitors of TGF‐β signalling pathways. Expression of LOXL1 and PEX‐specific extracellular matrix components was examined by using quantitative RT‐PCR and Western immunoblot analysis. Direct binding of LOXL1 to TGF‐ß1 was analyzed by blot overlay assay and solid phase ELISA using purified LOXL1, recombinant human TGF‐ß1, TGFß1‐LAP. The effect of LOXL1 on TGF‐ß1 signaling was analyzed using TGF‐ß receptor signaling real time PCR assays (BioRad) after transient transfection of hTCF with a full‐length pCMV6‐LOXL1 vector construct/with empty vector .

Results

TGFß1 significantly increased LOXL1 expression, secretion and enzymatic activity and correlated with enhanced expression of BMP‐1, elastin, fibrillin‐1, fibulin‐4 and fibulin‐5 with peak effects at 10 ng/ml for 48 hours. This induction was blocked by TGF‐β receptor inhibitors and inhibitors of the canonical Smad and non‐canonical signaling pathways. Direct binding between LOXL1 and TGFß1‐LAP was demonstrated by Blot overlay assays and ELISA. LOXL1 overexpression temporarily upregulates different transcriptional regulators and some protein kinases of p38‐MAPK signalling pathway after 12 to 24 hours post‐transfection.

Conclusions

The results of this study indicate that the interaction of LOXL1 and TGF‐ß1 plays an important role in the PEX‐associated abnormal matrix metabolism and fibrosis.
Ocular Chronic Graft Versus Host Disease after Bone Marrow Transplantation
Authors: Jeppesen H. , Sengeloev H. , Lindegaard J. , Julian H. , Prause J.U. , Heegaard S.
Published: September 2015

Purpose

Allogeneic bone marrow transplantation (BMT) is a curative therapy for a number of hematological diseases. Ocular chronic graft versus host disease (cGVHD) is a major contributor to long‐term morbidity after BMT. The purpose of this study was to report the frequency of ocular cGVHD after BMT and onset in relation to systemic cGVHD.

Methods

Retrospective examination of medical records of patients who underwent consecutive allogeneic BMT from 1980‐2011 at Copenhagen University Hospital (Rigshospitalet). This study included adults (>16 years) with no dry eye disease prior to BMT. The patients were seen by an ophthalmologist before BMT and annually after BMT. The ophthalmological examination included tear break‐up time, Schirmers test, corneal fluorescein stain, slit lamp examination and ophthalmoscopy. The criteria proposed by the “International Chronic Ocular GVHD Consensus Group” was used to diagnose ocular cGVHD.

Results

Out of the 939 patients included, 222 patients (23.6%) developed ocular cGVHD. We found no significant difference between gender and the development of ocular GVHD (p = 0.67). Median age at time of BMT was 41 years (rage 16–73) and 46 years (17–68) in the group who developed ocular cGVHD. Median time of onset of ocular cGVHD was 20 months (0.4–196) after BMT. Diagnosis of ocular cGVHD preceded systemic cGVHD in 33 cases (15%). Twenty‐seven patients (12%) had ocular cGVHD without systemic cGVHD. Ocular cGVHD was significantly higher in patients with systemic cGVHD involving the skin (p < 0.001).

Conclusions

Ocular cGVHD is common after BMT. It can occur at any age, but is more common in elder patients. Ocular cGVHD can occur in patients without systemic cGVHD. We recommend ophthalmological examinations in all patients before and after allogeneic BMT due to the high frequency of ocular cGVHD.
The STZ‐induced diabetic rat as a model for studying neuronal pathologies of diabetic retinopathy
Authors: Herrmann R. , Zippel N. , Haller J. , Streicher R.
Published: September 2015

Purpose

Diabetic retinopathy (DR) is a sight‐threatening complication of diabetes and a leading cause of blindness in adults. Current therapies target late‐stage vascular dysfunction of DR. However, DR is not a vascular disease per se, but is also characterized by chronic neurodegeneration. To identify neuroprotective treatments, it is critical to utilize appropriate animal models reflecting a hyperglycemia‐dependent loss of retinal function. Here we report a comprehensive characterization of the STZ‐induced diabetic rat as a model for neuronal dysfunction in DR.

Methods

Hyperglycemia was induced in Brown Norway rats upon STZ treatment. Blood glucose levels were monitored regularly and insulin levels were measured at study termination. To investigate different aspects of retinal function, dark‐ and light‐adapted flash and flicker electroretinograms were recorded at 4 and 7 weeks post STZ application, respectively. One group of animals received insulin treatment for antagonizing the effects of hyperglycemia.

Results

STZ treatment led to decreased insulin and increased blood glucose levels. Hyperglycemia caused functional impairments of both rod‐ and cone‐driven pathways on the level of the outer as well as the inner retina, which could be partially rescued by insulin treatment. Overall, the degree of functional impairments correlated with increasing blood glucose levels.

Conclusions

The STZ‐induced diabetic rat model is characterized by a hyperglycemia‐dependent dysfunction of retinal neurons. Thus, this model is an attractive tool for investigating novel mechanisms underlying DR.
Surface modification of intraocular lenses towards controlled drug delivery
Authors: Filipe H.P. , Bozukova D. , Pimenta A. , Vieira A.P. , Alves P. , Coimbra P. , Guiomar A.J. , Gil M.H. , Mata J.L.G. , Serro A.P.
Published: September 2015

Purpose

Ocular drug delivery systems replacing or complementing the usual therapeutics after cataract surgery have been the focus of several studies. A possible solution could be implanting intra‐ocular lenses (IOLs) also acting as drug carriers. The main challenge is to obtain IOLs that besides providing the best refractive outcome release the drug at a suitable rate. The purpose of our research was to design an effective strategy to incorporate the drug and study the release profile.

Methods

IOL surface was modified with PHEMA [poly(2‐hydroxyethyl methacrylate)] by treatment with argon plasma and subsequent immersion in a HEMA solution with moxifloxacin (MFX; Vigamox®), followed by a final immersion in an MFX solution. Drug release profiles were obtained in vitro under hydrodynamic conditions, which simulate those found in the eye for the aqueous humor. A microfluidic cell with a volume of 250 μL was designed and used with a continuous flow of saline solution, at 37°C, with a renovation rate similar to the physiological one.

Results

Results showed that MFX was released with concentrations above the minimum inhibitory concentrations for S. aureus, S. epidermidis and S. pneumoniae for 11 days.

Conclusions

In the conditions described, IOLs surface modification with PHEMA has allowed an extended drug release effective to prevent post cataract surgery endophthalmitis.
Surgically induced corneal astigmatism after fornix‐based trabeculectomy
Authors: Van Keer K. , Willekens K. , Abegão Pinto L. , Delbeke H. , Vandewalle E. , Stalmans I.
Published: September 2015

Purpose

To evaluate the degree of surgically induced corneal astigmatism (SIA) following trabeculectomy and to investigate the relation of SIA with long‐term reduction of intraocular pressure (IOP).

Methods

Fourty‐four eyes of 44 patients undergoing fornix‐based trabeculectomy were included in this single center, prospective trial. IOP, visual acuity (VA), corneal astigmatism, medication use and adverse events were recorded preoperatively and at 1, 3, 6 and 18 months postoperatively. Changes in corneal astigmatism were analysed using vector analysis. Pre‐ and postoperative parameters were compaired using one‐sample t‐test. Correlation between SIA and IOP were assessed using Pearson correlation coefficients.

Results

Vector analysis of corneal astigmatism revealed a significant increase in with‐the‐rule corneal astigmatism, reaching a maximum at 1 month postoperatively (1.15 ± 0.8 D, P < 0.001) followed by a gradual decline (0.87 ± 0.8 D, P < 0.001 at month 18). SIA at 1 month showed a borderline significant correlation with IOP reduction at 3 months (r = 0.315, P = 0.051). SIA at 3, 6 and 18 months did not correlate with reduction in IOP (P > 0.05). After a transient decline at 1 month after surgery, VA recovered to preoperative values at month 3 without need for adjustment of the optical correction.

Conclusions

Fornix‐based trabeculectomy induces statistically significant with‐the‐rule astigmatism without affecting long term VA. In our population, maximum SIA, measured at 1 month postoperatively, showed a borderline significant correlation with reduction of IOP at 3 months.
Sarilumab for the treatment of posterior segment non‐infectious uveitis (NIU): The SATURN (SARIL‐NIU) study
Authors: Heissigerova J. , Sundaram P.A. , Erickson K. , Varona R. , Corp‐dit‐Genti V. , Vitti R. , Buggage R. , Rihova E. , Nguyen Q.D.
Published: September 2015

Purpose

Interleukin‐6 (IL‐6) and/or its soluble receptor are detected in the vitreous and aqueous humors of patients with uveitis. Inhibition of IL‐6 signaling in a murine model of experimental autoimmune uveitis suppresses the development of uveitis. We designed an exploratory Phase 2 study to evaluate the efficacy and safety of sarilumab, a human monoclonal antibody directed against the alpha subunit of the IL‐6 receptor complex in the management of posterior segment NIU.

Methods

SATURN is a 52‐week, multicenter, double‐masked, placebo‐controlled, parallel arm, randomized trial to evaluate the efficacy and safety of sarilumab (200 mg) administered subcutaneously every 2 weeks in patients with posterior NIU, who are treated with systemic steroids (as single therapy or with methotrexate). Efficacy and safety are assessed at each visit. The study primary endpoints are reduction from baseline in vitreous haze or systemic‐steroid sparing effects, both measured at week 16. Other key endpoints assessed at week 16 include the change from baseline in: central retinal thickness, best‐corrected visual acuity, and percentage of patients with retinal vessel leakage on fluorescein angiography.

Results

The study has completed enrollment. As of April 6, 2015, 58 patients have been randomized and treated.

Conclusions

The SATURN study may help clarify the role of IL‐6 in the pathogenesis of NIU and the potential for IL‐6 inhibition in the management of posterior segment NIU.
Microfluidic in vitro Drug Release from Contact Lens Materials
Authors: Filipe H.P. , Paradiso P. , Valente A.R.B. , Mata J.L.G. , Saramago B. , Henriques J.M. , Serro A.P.
Published: September 2015

Purpose

Over 90% of ophthalmic drugs are commonly applied as eye drops. However, drug tear film residence time is less than 5 min, and only 5% of the administered drug is absorbed, leading to a final poor drug bioavailability and eventual side effects Efforts have been made to develop more effective drug delivery systems. Therapeutic contact lenses (CLs) have demonstrated to be a good vehicle for a controlled release of a variety of drugs owing to their biocompatibility, high degree of comfort, and prolonged contact with the eye.

Methods

CLs materials were prepared as a) a conventional hydroxyethylmethacrylate (HEMA) based hydrogel and as b) a silicone based hydrogel. The different materials were loaded with an antibiotic‐ levofloxacin (LVF), and one of two non‐steroidal anti‐inflammatory drugs (NSAID) ‐diclofenac (DCF) and ketorolac (KET). To simulate physiological human eye conditions such as temperature, tear volume and flow rate, drug release tests were carried out in a novel microfluidic cell.

Results

Results showed that a) HEMA based hydrogel allows a drug release up to 10 hours with predicted concentrations in the eye as >129 µg/mL for LVF, >918 µg/mL for DCF and > 251 µg/mL for KET whereas b) Silicone based hydrogel releases both NSAID for at least 4 days, with concentrations >163 µg/mL for DCF and >31 µg/mL for KET.

Conclusions

Drug eluted CLs biomaterials can be used as a platform for ocular drug delivery applications.
Management of acute submacular haemorrhage: Royal free hospital experience
Authors: Sim S.Y. , Elhousseini Z. , Maragkos I. , Asaria R.
Published: September 2015

Purpose

To evaluate visual outcomes of patients presenting with acute submacular haemorrhage (SMH) secondary to neovascular Age Related Macular Degeneration (nAMD) treated with pars plana vitrectomy (PPV), subretinal recombinant tissue plasminogen activator (rTPA) and air.

Methods

Retrospective, clinical case series. 7 patients with acute SMH secondary to nAMD, underwent PPV, instillation of 50 μg/0.1 ml subretinal alteplase and air tamponade. Data was obtained from Electronic Medical Records (EDRM) of the Royal Free Hospital from October 2013 to March 2015. Patient demographics (age, gender, and laterality), duration between onset and treatment, visual acuity (VA) and any concurrent treatment were recorded.

Results

7 patients were included in our study with mean age ‐ 69.1 years (Range: 60–87). 3 patients had cataract. No other ocular comorbidities. Mean period between onset of symptoms to treatment was 13.7 days (Range: 1–56). At presentation, six patients had hand movement (HM) VA and one patient had counting fingers (CF) VA. At one month post‐operatively, 6 patients (85.7%) demonstrated VA improvement ≥1 line, of whom 3 (42.9%) improved by ≥2 lines. At 6 months post‐operatively however, only 3 (42.9%) patients had sustained VA improvement. Post‐operative OCT demonstrated complete displacement of SMH in 4 patients (57.1%), while 3 patients had residual submacular organised blood.

Conclusions

Subretinal rTPA following vitrectomy with air tamponade may be used to dissolve submacular blood mass enabling physicians to resume NHS funded anti‐VEGF therapy. Long‐term visual outcome is often limited by underlying disease progression.
Ocular Sarcoidosis Surgery as the most effective option to avoid blindness
Authors: Martinez M. , Del Buey M. , Perez I. , Idoate A. , Sánchez J.I. , Ascaso J. , Cristobal J.
Published: September 2015

Purpose

To present the clinical evolution and diagnosis of a patient with binocular and no simultaneous affection of posterior synechiae, associated to bombe iris and neovascular glaucoma, without medical treatment response.

Methods

Clinical case: A 63 year‐old male is assisted in the ER because of progressive and painless visual loss in his left eye; visual acuity was only light perception. Anterior segment (AS) showed a synechia, ambarin atypical membranous tissue and neovascularization in the pupillary area, causing an iris bombe with no acute inflammatory signs and an IOP of 60 mmhg. Ocular sonogram and ultrasound bio microscopy didn't show tumor growth. The treatment with anti‐inflammatory, hypotensive and mydriatic eye drops could not break the synechiae nor reach normal IOP. One year later, the patient came to the ER because of right eye visual loss. AS showed a similar synechial tissue, no tyndall effect and IOP of 20 mmhg. Due to the left eye experience, we decided to practice surgery in the right eye.

Results

We took aqueous humor sample + synechiotomy + iridian biopsy + phacoemulsification with IOL. 20/20 visual acuity after surgery. After many medical tests and the anatomopathological study, the patient was released from the hospital with probable pulmonary and ocular sarcoidosis.

Conclusions

If we have a patient with atypical progressive posterior synechiae without inflammatory signs and with no treatment response, we should think about sarcoidosis ocular as the diagnosis. Our experience shows that an early surgery is the most effective option to avoid blindness in these cases.
Immune Responses at the Ocular Surface
Authors: Saban D.R.
Published: September 2015

Immune‐mediated diseases of the ocular surface are relatively broad in their respective etiologies, which can involve infection, autoimmunity, or allergy. Despite this range, immune responses often converge upstream at the level of the dendritic cell (DC)—a highly specialized group of antigen presenting cells required in the activation of naïve T cells. Our lab has established a novel mouse model of allergic eye disease (AED), which leads to severe clinical manifestations, sustained ocular inflammation, and eosinophilic infiltration at levels seen in patients with atopic keratoconjunctivitis. Use of the AED model has led to identification of classical CD11b+ DCs as the key subset responsible for activating allergen reactive T cells. In addition, the AED model has uncovered the importance of CCR7 as the master chemokine receptor in homing of ocular surface DCs to the regional lymph nodes. Additionally, CCR7 has recently been shown to contribute to activation of Th17 cells in the mouse model of dry eye disease. Likewise, similar to the dry eye disease model, AED involves corneal lymphangiogenesis—potentially suggesting a role for corneal DCs in allergic immune responses. Thus, efforts to progress the current understanding of DC biology holds tremendous promise for advancement of novel and effective medicines in immune mediated diseases of the ocular surface.
Study of Xailin night physical Properties versus marketed ocular lubricant products
Authors: Pilotaz F. , Pecout A. , Do M.
Published: September 2015

Purpose

Xailin Night is a multi‐dose preservative free lubricating eye ointment for night‐time relief of dry eye sensations. It contains white soft paraffin 57.3% w/w, white mineral oil 42.5% w/w and lanolin alcohols 0.2% w/w. Comparative studies were performed with Xailin Night against other marketed products in the EU in order to assess its key physical properties.

Methods

Tested products cover the whole range of ocular lubricants from oily formula to aqueous compositions. The parameters studied were the following: Viscosity and rheological behaviour (25°C and 35°C), capacity to slow down evaporation at 40°C and 70°C, spreading capacity at room temperature and 35°C, long‐lasting assessment. The products marketed in the EU assessed in this study were: Viscotears liquid gel, Lipolac, Celluvisc 4 mg/0.4 mL, Siccafluid 2.5 mg/g, Bepanthen, Vismed multi, Hyabak 0.15%, Artelac Nighttime Gel.

Results

At room temperature, Xailin Night viscosity shows an intermediate profile included between low viscosity gels (Siccafluid) and very highly viscous products (Bepanthen, Viscotears and Lipolac). As expected, temperature has an effect on the rheological behaviour of ointments but not on the other products. No evaporation is observed for Xailin Night whatever the temperature, while all the other tested products show a slight evaporation. Lipolac and Viscotears have a superior spreading capacity compared to pure aqueous‐based products but remain significantly lower than ointments. As an ointment, Xailin Night has a superior long‐lasting effect than aqueous products.

Conclusions

Xailin Night is an ocular ointment with a strong long lasting effect and shows no evaporation compared to aqueous based ocular lubricants.
New management of peri‐ocular basal cell carcinoma using in vivo and ex vivo confocal microscopes
Authors: Espinasse M. , Grivet D. , Perrot J.L. , Cinotti E. , Labeille B. , Forest F. , Gain P. , Thuret G.
Published: September 2015

Purpose

We have been using a handheld dermatology in vivo reflectance confocal microscopy (IVCM) for the imaging of the whole ocular surface and ocular adnexa for more than two year (JAmAcadDermatol2014;71:912, AJO2015;159:324), mainly for noninvasive diagnosis before surgery. Ex vivo confocal microscopy (EVCM) is a new device that allows pseudo histology in freshly excised tissue. Aim: to assess a new management strategy for eyelids lesions suspected to be basal cell carcinoma (BCC) using these two complementary confocal microscopes (CM).

Methods

IVCM and EVCM, both using vivascope CM (Lucid Inc, NY) were performed by 3 skilled dermatologists having more than 500 CM diagnoses each with pathology confirmation. Forty consecutive peri‐ocular BCC were diagnosed by IVCM. Two millimetre‐margin incisions were made during surgery. Freshly excised tissues were mounted, unstained, between two glass slides and analysed “en face” with EVCM to delimitated the tumour and the clearance of margins. Diagnosis and margins were confirmed by standard pathology and immunolabeling on fixed tissues.

Results

We obtained the first “en face” EVCM to delimitated the tumour. The acquisition of the whole tumour took less than 3 minutes. Tissues were not damaged by flat mount nor by exposure to laser beam. Histology confirmed all IVCM diagnosis of BCC and all clear margins.

Conclusions

Association of IVCM and EVCM allowed accurate management of peri ocular BCC, using micrographic surgery to reduced surgical margins. GRANT: project INNOVEYE GIRCI RAA.
Canaloplasty with the Stegmann Canal expander – two years results
Authors: Grieshaber M. , Schoetzau A. , Stegmann R.
Published: September 2015

Purpose

To assess the safety and efficacy of circumferential viscocanalostomy (canaloplasty) using a new canal expander in Caucasians with primary open‐angle glaucoma (POAG).

Methods

Thirty‐five eyes of 35 consecutive patients with medically uncontrolled POAG underwent primary canaloplasty and implantation of the Stegmann Canal Expander into Schlemm's canal. Schlemm's canal was unroofed ab externo, and dilated with viscoelastic material and microcatheter. The Stegmann Canal Expander was implanted into the canal lumen, and the superficial scleral flap was closed watertight. Laser goniopuncture of the trabeculo‐Descemet's membrane window was performed if postoperative intraocular pressure (IOP) exceeded 16 mmHg.

Results

The mean IOP dropped from 26.6 ± 4.2 mm Hg preoperatively to 12.1 ± 2.6 mm Hg at 1 month, 13.1 ± 1.9 mmHg at 6 months, 13.0 ± 1.9 mm Hg at 12 months, and 13.4 ± 2.4 mm Hg at 24 months (p < 0.001). Laser goniopuncture was performed on 5 eyes (14.7%) 6.4 months after surgery; the mean IOP was 19.1 mm Hg before and 14.1 mm Hg after goniopuncture. The number of medications dropped from 2.9 ± 0.3 before surgery to 0.08 ± 0.3 after surgery (p < 0.001). The postoperative BCVA at last visit (0.12 ± 0.09; range, 0–0.39) was comparable to preoperative values (0.16 ±  SD 0.10; range, 0–0.39) (p = 0.35). Complications were minor and included microhyphema (14 eyes) and transient elevated IOP (steroid responder; 4 eyes), partial peripheral Descemet's membrane detachment (2 eyes).

Conclusions

Canaloplasty with implantation of the Stegmann Canal Expander reduced IOP significantly in POAG with a low risk for complications.
The study of needle tip aspirates and entry sites after intravitreal injections with different needle types
Authors: Lytvynchuk L. , Savytska I. , Sergiienko A. , Binder S. , Petrovski G.
Published: September 2015

Purpose

To compare the entry site and study the cellular content of different needle tip aspirates after transscleral intravitreal injection (IVI) on rat eyes.

Methods

The intravitreal injections (IVI) were performed on 20 white outbred rat eyes (10 IVI with 30‐gauge subcutaneous needles (SCN), 10 with 27‐gauge Pencan needle (PCN) (B.Braun)). The 1.0 cc syringes were preloaded with 0.02 cc of balanced salt solution (BSS) and connected to the needles. The penetration was performed 1 mm posterior to the limbus, followed by aspiration of 0.01 cc vitreous body. Aspirated material was evacuated onto glass slides and stained by Azure‐2‐Eosin. Enucleation and histological analysis of the IVI entry site was performed at magnification 100 and 400 times.

Results

Cellular content of the aspirated material was revealed in all cases. The aspirated cells represented conjunctival epithelial‐, ciliary body non‐pigmented epithelial‐, sclerocyte‐like cells and vitreous crystallised specimens. The amount of conjunctival epithelial cells prevailed in 27‐gauge PCN IVI cases. The stained granular proteins were less significant in the case of 27‐gauge PCN tips. The entry sites after 30‐gauge SCN injection showed concrete cut of all tissues, while partial reassembling of the sclerocyte bindings was seen after 27‐gauge PCN injections.

Conclusions

The use of 30‐gauge SCN and 27‐gauge PCN needles for transscleral IVI has resulted in trauma of all layers of the rats’ eye wall. Histological analysis of the needle tip aspirates showed less tissue damage by 27‐gauge PCN; moreover, the SCN tips created complete cuts due to their sharp edges, in contrast to the PCN tips.
Mitochondrial DNA haplogroups associated with neovascular age‐related degeneration in a Spain population
Authors: Esteban O. , Ascaso F. , Calvo T. , Montoya J. , Ruiz‐Pesino E. , Martinez M. , Almenara C. , Del Buey M. , Cristobal J.
Published: September 2015

Purpose

To investigate whether mtDNA haplogroups are associated with neovacular AMD in a geographically defined area north east of Spain.

Methods

AMD patients were ascertained at the Department of Ophthalmology of Lozano Blesa University Clinic Hospital, Zaragoza, Spain. We assessed the association between mtDNA haplogroups and neovascular AMD in 91 AMD patients and 656 unrelated controls residing in the same city. Late‐stage neovascular AMD was defined as described in the international AMD calssification. Genetic analysis for mtDNA haplogroups was performed at the Department of Biochemistry and Molecular and Celular Biology at University of Zaragoza.

Results

Haplogroup HV was the most frequent in AMD patients ( 54.9%) and controls (57.5%), followed by haplogroups U (20.9% and 22.6%, respectively), J (4.4% and 8.9%, respectively), and T (7.7% and 6.9%, respectively). There were no statistical significant differences between both groups (P > 0.05, chi‐square test).

Conclusions

Although findings of associations between different mtDNA haplogroup types and AMD lesions have been previously reported, suggesting that these haplogroups may be genetic markers indicative of an individual's susceptibility to AMD, present study did not show such association in our population.
Focal choroidal changes on diabetic macular edema
Authors: Duarte L. , Ruão M. , Gallego R.
Published: September 2015

Purpose

With the increasing interest in choroidal changes in Diabetes, we performed a pilot and prospective study to evaluate the morphological choroidal findings in diabetic macular edema detected with SD‐OCT, compared with normal or non‐macular edema diabetic eyes.

Methods

Two groups of patient were selected: Diabetic patients with no or any stage of diabetic retinopathy with no history of ocular treatment; and non‐diabetic patients as normal controls. Patients with other ocular diseases or surgery where not included. Complete ophthalmological exam was performed. A retinography, blood pressure measurement and OCT with the EDI or choroidal acquisition protocol was performed to all patients. For the analysis choroidal thickness was measured using automated calculation after manual segmentation. OCT images were analyzed for morphological changes in the choroidal space and vasculature, and findings were recorded.

Results

47 eyes were included in this study: 11 with macular edema, 16 with non‐proliferative diabetic retinopathy, 10 from diabetic patients with no retinopathy and 10 control. Age ranged from 41 to 80 and matched for the sub‐groups. Choroidal thickness varied from 75 µm to 383 µm and no correlation was found with age, blood pressure or diabetic stage, except for advanced stages of retinopathy and macular edema where it appears to have a change in the architecture of the choroidal vessels with a tendency of vanishing of the large vessels in favor to the choriocapillaris, well related to the subjacent area of retinal active disease and edema.

Conclusions

As a pilot study, the results only can direct to larger sample studies in order to look for the meaning of choroidal changes that are being reported in diabetic patients and other ocular diseases. It suggests that thickness changes may be due to specific vascular changes.