bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing an innovative bioreactor destined to improve the endothelial viability of stored corneas
Authors: Rageade D. , Bernard A. , Nangoum‐Fosso T. , Herbepin P. , He Z. , Perrache C. , Piselli S. , Acquart S. , Thuret G. , Gain P.
Published: September 2015

Purpose

Loss of intraocular pressure (IOP) after death and after corneo‐scleral procurement triggers a stromal swelling causing posterior folds in which endothelial mortality is increased. We hypothesized that restoration of IOP after procurement will be key for long‐term corneal storage with preserved endothelial functions.

Methods

We designed two bioreactors (BR) (for human and porcine corneas) and their control units. The BR presented as a sterile disposable cassette comprising a corneal chamber with transparent windows surrounded by the fluidic system. Sterile sampling sites were added in the circuit for monitoring physiochemical parameters as well as sterility without risk of contamination.

Results

After insertion of the corneo‐scleral rim, the system was closed and the cassette connected to its control unit, comprising a peristaltic pump driven by a microcontroller. In a comparative study (ongoing) on paired corneas, the BR maintained a normal corneal thickness and transparency during the storage, while reducing the number of endothelial folds and increasing the endothelial viability.

Conclusions

The innovative BR restores IOP while ensuring a continuous medium renewal in a fully transparent chamber. The BR will be available for eye banks, research laboratories, contract research organizations, and cosmetic industry. GRANTS: AP looks for from ANSM, EFS, UJM.
Interventions against VEGF overexpression, available strategies and future developments
Authors: Amadio M. , Bucolo C. , Govoni S. , Drago F. , D'Agata V. , D'Amico A.G. , Cupri S. , Pignatello R. , Pascale A.
Published: September 2015

Purpose

Neovascular diabetic retinopathy (DR) and age‐related macular degeneration (AMD) are characterized by increased VEGF signaling. VEGF can be targeted using monoclonal antibody‐based drugs (e.g. ranibizumab, aflibercept) or by modified oligonucleotides (e.g. pegaptanib). The main difference between the two classes is that antibodies recognize all VEGF isoforms while oligonucleotides may be more specific for certain isoform such as VEGF165. New ways of intervention stem out from the observation that VEGF expression can be post‐transcriptionally regulated by the RNA‐binding HuR/Elav‐like1 protein. We evaluated if targeting HuR is a potential tool to hinder VEGF overexpression.

Methods

2.5 µM HuR siRNA (naked or delivered by nanocarriers) was intravitreally administered in a DR model. Rats were sacrificed 48 h after siRNA injection and retinal tissues collected for Western blot, ELISA, histological examination.

Results

HuR siRNA treatment blunts both HuR and VEGF increase, restating normal VEGF content in DR retina. HuR siRNA exerts its protective effect when included in liposomal nanocarriers, since the naked molecule does not prevent diabetic retinal damage.

Conclusions

An HuR‐based strategy may be a target in the chain of events controlling VEGF expression synergizing with oligonucleotide‐based interventions having the potential to modulate the expression of VEGF without fully blocking it.
Clinical evaluation of video imaging technology during visual field exams
Authors: Charlier J. , Zanlonghi X. , Defoort‐Dhellemmes S.
Published: September 2015

Purpose

Video imaging consists in recording the entire visual field process in synchrony with the video of the patient's head. Several clinical applications have been investigated to evaluate the clinical usefulness of this new technology.

Methods

The study included results from 48 visual field exams performed on a MonCvONE full field projection perimeter with synchronized video recording.The video from a large viewing field camera was recorded in synchrony with the position of the visual stimulus, with other test parameters such as luminance and size and with the patient's response obtained from the patient's press button or from the operator judgment. The study included patients who were unable to perform automated perimetry due to young age or handicap, patients with abnormal eye movements, head posture or ptosis and controls performed after automated perimetry.

Results

Video recording was extremely useful in the majority of clinical cases. 24 exams were performed on young children (age between 2 and 5 years) using attraction perimetry. The eye orientation responses could be interpreted and validated after the exam. In other cases, the video recording facilitated the interpretation and documentation of visual field results with the inclusion of video snapshots in the examination report. Additional applications included the recording of cardinal eye gaze positions and of the fusion visual field.

Conclusions

Synchronized video imaging performed during visual field exams is a clinically useful tool for the examination of patients who cannot perform automated perimetry and for the documentation of artefacts and situations such as ptosis, abnormal eye movements, abnormal head posture and incorrect position of refraction.
Assessment of deviation angle and oblique muscle function in strabismus patients using analysis of two‐dimensional eye globe pictures in diagnostic gaze positions
Authors: Bushuyeva N. , Romanenko D.
Published: September 2015

Purpose

To develop simple and fast method of deviation angle and extraocular muscle (EOM) function examination in strabismus patients.

Methods

Pictures of eye globes in 12 diagnostic gaze positions were taken. They were analyzed using developed software: for both eyes the program calculated pupil center shift relative to pupil center position in primary gaze for each gaze position in millimeters. 140 volunteers (70 adults and 70 children) without EOM pathology and refraction anomalies were examined to create reference interval database for each gaze position. 148 strabismus patients were examined using developed method and conventional ones: Hirschberg and Fresnel prism tests for deviation measurement, 0–4 scale was used to assess oblique muscle function.

Results

Eye globe shifts in healthy adults and children mainly ranged from 3 to 4.5 mm, maximal shifts equaled 6.5 mm in adults and 5.5 mm in children. Correlation coefficient between deviation angle measured with the method and Hirschberg test was 0.797, mean difference between measurements was 1.1º. Correlation coefficient between the method and Fresnel prism test was 0.881, mean difference between measurements was 3.8 PD. Cluster analysis sorted out 3 degrees of oblique muscle disfunction measured with the developed method. They in 80% correlated with conventional scale.

Conclusions

Developed automated method of deviation angle and EOM function assessment simplifies and objectifies examination of strabismus patients.
Comparison of CKC‐ and BAK‐cationic emulsions in a rat model of corneal wound healing
Authors: Daull P. , Feraille L. , Elena P.P. , Garrigue J.S.
Published: September 2015

Purpose

Dry eye disease (DED) is a chronic disorder that afflicts 20% of the population. One prominent feature of DED is the ubiquitous presence of inflammatory cells and corneal epithelium damages in DED patients. The aim of the present study is to compare the efficacy of unpreserved cationic emulsions (CEs) with cetalkonium (CKC) or benzalkonium (BAK) chloride as cationic agents on debrided rat corneas healing and inflammatory response.

Methods

The CEs were assessed in a rat model of corneal scraping. The upper part of the corneal epithelium was scraped prior to a 5‐day treatment with the CEs. Paces of corneal recovery and clinical evaluations (in vivo confocal microscopy (IVCM) and Draize tests) were used to evaluate the healing process. Inflammatory cells count in the corneal stroma was assessed by IVCM.

Results

Corneal healing was only marginally affected by the different treatments, and was almost complete at day 5. However, cornea wounds closed more rapidly when treated with CKC‐CEs than with BAK‐CEs. Interestingly, both Draize and IVCM scores indicate that treatments with the CKC‐CEs resulted in a better healing process when compared to BAK‐CEs. The number of inflammatory cells was also at its lowest following treatments with CKC‐CEs.

Conclusions

By restoring a hydrated ocular surface the different treatments promote corneal healing. Inflammatory cells count in the stroma was at its lowest with the preservative‐free CKC‐CEs, suggesting that CKC and BAK have indeed different properties and effects on the ocular surface. Hence, Ikervis®, a CKC‐CE of cyclosporine, represents a promising treatment option for the management of corneal lesions and inflammation in DED patients.
Longterm outcomes of cyclodiode treatment for patients with neovascular glaucoma
Authors: Weston K. , Lockwood A. , Penwarden A. , Kirwan J.
Published: September 2015

Purpose

To investigate the outcomes following cyclodiode treatment for patients with refractory neovascular glaucoma. Outcome measures were sustained IOP reduction, symptom relief, number of medications and progression to pthysis, over a 10 year period. Visual acuity data was also collected.

Methods

A consecutive retrospective series of 15 eyes of 14 patients in a single eye unit, undergoing cyclodiode treatment between May 1999 to July 2005. Case notes were reviewed.

Results

Four patients died before completion of 10 year follow up but are included in the 5 year follow up data. Symptomatic relief was achieved in all eyes. Four eyes required a single further treatment with cyclodiode at 2 months to 3 years. Mean IOP prior to treatment was 42 mmHg. Following treatment, mean IOP was 18.5 mmHg at 1 month, 19.6 mmHg at 6 months, 15.33 mmHg at 1 year, 15.07 mmHg at 2 years, 12.92 mmHg at 3 years, 14.38 mmHg at 5 years and 10.1 mm/Hg at 10 years (75.95% reduction). 88% of eyes did not require any medication at 10 years. The mean reduction in number of medications used was 2 (2.8–0.8). Pthysis occurred in 5 eyes. In 3 eyes this occurred within 1 year of cyclodiode and in the remaining 2 eyes by 4 years. No patients progressed to evisceration or enucleation. 60% of eyes were NPL at 10 years, with pre‐cyclodiode acuities in this group of HMs to PL. One eye remained the same, with PL vision, and one eye improved from CF to 1/60. The vision in 2 eyes dropped from CF to HMs.

Conclusions

Cyclodiode laser treatment is effective for both pain control and maintaining IOP in the long term. It allowed a reduction in the number of topical treatments required.
Interleukin 33/ST2 signaling regulates inflammatory response in choroidal stroma and ocular angiogenesis: implications for age‐related macular degeneration
Authors: Theodoropoulou S. , Doyle S. , Copland D. , Liu J. , Wu J. , Campbell M. , Dick A.
Published: September 2015

Purpose

Age‐related macular degeneration (AMD) is a leading cause of irreversible blindness. We wished to elaborate mechanisms that regulate RPE‐choroidal microenvironment in AMD. We hypothesize that retinal pigment epithelial cells (RPE) produce interleukin 33 (IL‐33) and regulate choroidal stromal fibroblasts and mast cell activation and angiogenesis in an ST2‐dependent manner. Through such mechanisms, change in choroidal architecture may contribute to AMD phenotypes observed clinically.

Methods

Upon treatment, RPE cells, human choroidal fibroblasts and bone‐marrow‐derived mast cells (BMMC) were assayed by RT‐PCR, Western Blot and ELISA. Choroidal sprouting assay and laser‐induced choroidal neovascularization (CNV) were used as models of ocular angiogenesis.

Results

TLR‐stimulation of RPE significantly up‐regulated IL‐33 expression. ST2+ BMMC generated a spectrum of inflammatory cytokines when cultured with IL‐33 rich RPE supernatant. Pretreatment with IL‐33 antagonist markedly inhibited the ability of BMMC to produce inflammatory mediators. Importantly, activation of inflammatory cascade upon RPE supernatant treatment was abrogated in ST2‐/‐ BMMC. In a wound‐healing assay, recombinant IL‐33 treatment of human choroidal fibroblasts impaired their ability to migrate and contract collagen gel. Furthermore, IL‐33 treatment promoted vascular choroidal sprouting in WT and IL33‐/‐ explants. CNV was also regulated by exogenous and endogenous IL‐33 in WT and IL33‐/‐ mice respectively.

Conclusions

Our data illuminate an endogenous IL‐33/ST2 pathway between RPE function and choroidal stroma, influencing tissue remodeling and regulating angiogenesis. Our findings support IL‐33/ST2 axis as a therapeutic target in AMD.
The effect of PAXgene fixation on preservation of morphology and nucleic acids in microdissected retinal tissue
Authors: Edward D. , Liu Y.
Published: September 2015

Purpose

To compare the effect of the 2 fixatives on tissue morphology and to obtain good quality nucleic acids for molecular analysis from micro‐dissected retinal samples

Methods

Enucleated specimens from NZ white rabbits were fixed in formalin or PAXgene fixative using standard protocols, and then processed and embedded in paraffin for sectioning. H&E stained were used to assess the structural integrity of the retina. Retinal tissue on slides was micro dissected using a 27 gauge needle under a dissection microscope. DNA/RNA were extracted and assessed for preservation of quality and quantity of the retinal tissue.

Results

The retinal morphology was well preserved with both PAXgene and formalin fixation. The RNA yield from both fixation methods was similar, but RNA from PAXgene fixed samples had a better purity than that extracted from formalin fixed paraffin embedded samples (FFPE). For DNA, there was a twofold greater yield in PAXgene fixed samples (PFPE) compared to FFPE but with similar purity. Quantitative reverse transcription polymerase chain reaction analyses from two assays showed that the mean Cycle threshold values for beta‐actin, beta‐microglobin, Opsin 1‐sw, Rhodopsin and 18S RNA of PFPE group was significantly lower than those of FFPE group (suggesting better RNA integrity) (p < 0.01 for all groups). A greater than 10‐fold level of gene expression was detected in PFPE relative to FFPE for the above genes in both assays. Furthermore, the number of tissue sections required for these studies suggested that this technique could be applied to study retinal macular molecular pathology.

Conclusions

PAXgene fixed tissue retinal morphology is comparable to FFPE tissue. PAXgene may be a good alternative to formalin, providing good tissue morphology and ability to isolate high quality nucleic acids from micro‐dissected paraffin embedded retinal samples.
Impact of intracamerular Cefuroxime on post‐operative endophthalmitis in Languedoc Roussillon, France from 2010 to 2014
Authors: Daien V. , Papinaud L. , Lacombe S. , Daures J.P. , Villain M.
Published: September 2015

Purpose

Post‐operative endophthalmitis remains the most severe complication of cataract surgery. The purpose of this study was to determine the incidence of post‐operative endophthalmitis in Languedoc Roussillon between 2010 and 2014. Secondary objective was to assess the correlation between the use of intracamerular injection of cefuroxime and post‐operative endophthalmitis incidence.

Methods

All patients >40 years old who underwent a primary cataract surgery in Languedoc Roussillon (France) between January 2010 and December 2014 were collected from the regional administrative database of medical care. Incidence rate of post‐operative endophthalmitis was estimated. Spearman coefficient was used to assess the correlation between the incidence of post‐operative endophthalmitis and the use of intracamerular cefuroxime at the end of cataract surgery.

Results

In 5 years, 179 515 eyes underwent a cataract surgery in Languedoc Roussillon. A total of 182 patients had a post‐operative endophthalmitis owing to a 1 year incidence of 0.10% after cataract surgery. The incidence of endophthalmitis decreased over the study: 0.16%, 0.12%, 0.11%, 0.07% and 0.05% in 2010, 2011, 2012, 2013 and 2014, respectively. The use of cefuroxime prophylactic injection at the end of cataract surgery increased over the study: 3.27%, 7.65%, 32.04%, 75.67% and 85.36% in 2010, 2011, 2012, 2013 and 2014, respectively. The incidence of post‐operative endophthalmitis was negatively correlated with the use of intracamerular injection of cefuroxime (r = −0.96, p = 0.008).

Conclusions

This study provides information on the decrease of post‐operative endophthalmitis incidence and its correlation with the increased use of cefuroxime intracamerular injection to prevent the risk of infection in the real world. This observational study confirms the promising results of the ESCRS study.
Indocyanine green angiography findings in Stargardt disease
Authors: El Matri L. , Chebil A. , Charfi H. , Largueche L. , Hassairi A.
Published: September 2015

Purpose

To evaluate indocyanine green angiography (ICGA) findings in Stargardt disease (STGD).

Methods

We reported a retrospective and descriptive study of 20 patients (40 eyes) with Stargardt's disease with different stages. All patients underwent a complete ophthalmic examination, fluorescein angiography, indocyanine green angiography (ICGA). Spectral‐domain optical coherence tomography (SD‐OCT) and fundus autofluorescence were also executed.

Results

In 27.5% of eyes affected by STGD, ICGA showed hypocyanescence from the areas of atrophy, more evident in the late phases. SD‐OCT revealed morphologically intact choroid in STGD patients with ICGA‐imaged dark atrophy. All the remaining eyes showed isocyanescence or mild hypercyanescence from the areas of atrophy in the late phase of ICGA.

Conclusions

The ICGA‐imaged dark atrophy may be the presence of material that obscures ICGA cyanescence. However, this hypothesis seems unlikely, since SD‐OCT images failed to show any deposit between the choroid and the retina. This finding suggests a possible selective damage of the choriocapillaris in STGD.
New device to applanate full thickness eyelid tumours for ex vivo confocal microscopy
Authors: Grivet D. , Cinotti E. , Perrot J.L. , Labeille B. , Cambazard F. , Bernard A. , Forest F. , Gain P. , Thuret G.
Published: September 2015

Purpose

Immediate confirmation of the suspected diagnosis and verification of margin clearances are of crucial importance during surgery of eyelid tumours. In a multidisciplinary approach with Dermatologist, Ophthalmologist and Pathologist to increase treatment efficiency of these patients, we use a combination of handheld Dermatology in vivo confocal microscope to obtain pseudo histology and ex vivo confocal microscopy (EVCM, Lucid, NY) on fresh tissue to better study margins. Tissues are always fixed for standard pathology. In our first uses of the EVCM, tissue thickness and irregularity hinder from obtaining a full map of the tumour because some parts were not in contact with the glass slide. We designed a specific device to applanate the tissue.

Methods

The prototype device was composed of a 3D printed plastic slide comprising 2.5 mm diameter tapped holes, and a slider destined to a standard glass slide. Thirty screws allowed precisely adjusting the distance between both plans. The tissue was placed on the glass slide, covered by a thin plastic sheet and by the slide with screws. By gently adjusting individual screws, the tissue could be evenly applanated in front of the EVCM. The pathologist assessed whether the device damaged the tissue.

Results

Without controlled applanation all tissues were only partially mapped. The applanator allowed obtaining a full map of the tissue in all cases with gentle local adjustments directly controlled by the image quality obtained in live. No significant damage was noted.

Conclusions

This simple applanator is useful to improve image quality obtained with the EVCM on full thickness complex tissue like eyelids tumours.
Wide‐Field Angiography in the management of retinal vasculitis
Authors: El Matri Hassairi A. , Chebil A. , Bouladi M. , Kort F. , El Matri L.
Published: September 2015

Purpose

To study the value of Wide‐Field angiography in the management of patients with retinal vasculitis.

Methods

A total of 48 eyes of 24 patients with systemic vasculitis underwent complete ophthalmic exam, followed by wide‐field retinal angiography (WF‐FA) with the Heidelberg Angiograph SLO using the Staurenghi contact lens. The primary outcome was diagnosing the extent of retinal vasculitis (RV) and monitoring disease activity. The secondary outcome was the percentage of patients whose management changed, based on the availability of WF–FA.

Results

WF‐FA assisted in revealing retinal vasculitis in 5 of 24 patients (20.8%), in 2 cases retinal vasculitis was not clinically evident. The extent was quantified in the 5 patients and the disease activity monitored in 3 patients. Three of 24 patients (12.5%) had management change: planning medical treatment or laser photocoagulation.

Conclusions

WF‐FA is a valuable technology in the management of patients with systemic vasculitis and can be used for the diagnosis, treatment and follow up of retinal vasculitis.
Uveal melanoma and other cancers
Authors: Desjardins L. , Villaret J. , Cassoux N. , LumbrosoLeRouic L. , Levy C. , Plancher C. , Savignoni A.
Published: September 2015

Purpose

We evaluated in a retrospective study the frequency and nature of other cancers in uveal melanoma patients.

Methods

Patients and method

A prospective registry of uveal melanoma patients is pêrformed in our center including usual datas on patients and tumor characteristics and since 2000 cancer past history. Each patient is followed during ten years after initial treatment and occurence of second cancer after uveal melanoma is registered.

Results

there are 6262 patients in the database with uveal melanoma and for 3934 history of previous cancer was registered. We had 548 cases of associated cancer: 423 had a past history of cancer before uveal melanoma was diagnosed and 102 patients développed a second cancer after the diagnosis of uveal melanoma. Cutaneous melanoma and renal carcinoma were found to be more frequent than expected.

Conclusions

Recent genetic improvments led to new discovery of germinal mutations responsible for cancer. As known for BRCA mutations and breast cancer or Rb1 gene and retinoblastoma, BAP 1 mutations has been found to predispose to mesothelioma, clear cells renal cancer and cutaneous and uveal melanoma. For young patients or patients with multiple cancers or family high frequency of cancer genetic counseling has became essential.
Selecting uveal melanoma for PRAME‐TCR T cell immunotherapy
Authors: Jager M.J. , Krijgsman D. , Luyten G.P.M. , Luk S.J. , der Velden P. Van , Heemskerk M.H.M.
Published: September 2015

Purpose

To determine which uveal melanoma may be candidates for PRAME‐directed immunotherapy using TCR‐modified autologous T cells.

Methods

Expression of PRAME was determined in uveal melanoma by an Illumina array. HLA polymorphisms were determined on peripheral blood leukocytes. Clinical and histological characteristics of UM were derived from clinical charts and pathology reports.

Results

PRAME expression was highly variable; tumor size, thickness, and the presence of an inflammatory phenotype were associated with PRAME expression. 20/37 monosomy 3 cases expressed PRAME, and 8/20 disomy 3 tumors. 10‐year survival data on 60 UM showed worse survival of UM with high PRAME compared to those with a low PRAME. However, six of the eight PRAME‐positive disomy 3 cases died from metastases. With this information, all cases with PRAME‐positive primary tumors who carry the HLA‐A2 antigen should be followed closely for the development of metastases, as they can be candidates for PRAME‐TCR autologous T cell therapy.

Conclusions

Uveal melanoma may be good candidates for treatment with autologous T cells that have been modified so that they carry PRAME‐specific T cell receptors. Large uveal melanoma with a high PRAME expression (independent of chromosome 3 status) in HLA‐A2 positive patients are potential candidates for PRAME‐TCR autologous T cell therapy. A high PRAME expression, also in disomy 3 tumors, was associated with an inflammatory phenotype and with death due to metastases.
Selective laser trabeculoplasty: Results on intraocular pressure and number of topical antiglaucoma medications
Authors: Bonnel S. , Fenolland J.R. , Marill A.F. , Gaillard R. , Rosenberg R. , Theillac V. , Mazharian A. , Mouinga A. , Giraud J.M. , Renard J.P.
Published: September 2015

Purpose

To evaluate results at one year of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) and assess if differences are related to number of topical treatments in ocular hypertension (OHT) and open angle glaucoma (OAG) patients.

Methods

We performed a retrospective chart review of 106 eyes treated by SLT. Indications for SLT treatment were insufficient IOP control, allergy, discomfort or non‐compliance to antiglaucoma treatment. Only patients with at least 1 year of follow‐up after SLT were included. IOP was measured before and at 1, 6 and 12 months after SLT. All IOP measurements were performed with Goldmann applanation tonometry.

Results

106 eyes of 68 patients untreated (n = 13), or treated with one (n = 25), two (n = 39) or three (n = 28) topical antiglaucoma medications were included. Mean preoperative IOP was 19.4 ± 3.6 mmHg (respectively 21.1 ± 2.7, 19.8 ± 3.1, 19.1 ± 4.2 and 18.9 ± 3.4 mmHg corresponding to the group without, one, two or three treatments) and 15.7 ± 3.1 mmHg at 12 months (respectively 16.2 ± 3.5, 15.6 ± 2.6, 15.6 ± 3.4 and 15.5 ± 2.8 mmHg for each groups) which corresponds to an average decrease of 18.3% (respectively 23.7%, 19.7%, 17.2% and 16.1% for each groups). At 1 year, 62.2% (n = 66) were responders (≥3 mmHg reduction from baseline IOP = 15.5% of IOP baseline): 92.3% without treatment (n = 12), 68% with one (n = 17), 59% with two (n = 23) and 50% with three treatments (n = 14). The average IOP of responders decreased from 20.7 ± 3.4 to 15.2 ± 2.9 mmHg (26.6%), respectively from 20.8 ± 2.6 to 15.8 ± 3.2 (25%) without treatment, from 20.6 ± 3.2 to 14.9 ± 3.7 (27.3%) with one, from 20.8 ± 4.1 to 15.5 ± 3.3 (25.1%) with two and from 20.7 ± 3.2 to 14.4 ± 2.4 mmHg (29.7%) with three treatments.

Conclusions

Lowering of IOP and number of responders after SLT appears to be more important un OHT and OAG patients with less topical antiglaucoma treatment.
Impact of Storage Temperature on Gene Expression of Cultured ARPE‐19 Cells
Authors: Pasovic L. , Eidet J.R. , Olstad O.K. , Chen D.F. , Lyberg T. , Utheim T.P.
Published: September 2015

Purpose

The development of a suitable storage method for retinal pigment epithelium (RPE) is necessary in the establishment of future RPE replacement therapy, and storage temperature has proven to be pivotal for cell survival. We analyzed the gene expression profile of cultured human RPE cells after storage at 4°C, 16°C, and 37°C.

Methods

ARPE‐19 cells were cultured until confluence and stored in Minimum Essential Medium at 4°C, 16°C, and 37°C for seven days. DNA microarrays validated by qRT‐PCR were used to determine the gene expression profile.

Results

The gene expression profile of cultures stored at 4°C cluster closest to the control cultures that were not stored and display the least change in gene expression after storage (157 differentially expressed genes compared to controls), while cultures stored at 16°C and 37°C display much larger changes compared to controls (1787 and 1357 differentially expressed genes, respectively). Expression levels of key genes involved in phagocytosis, pigment synthesis, the visual cycle, cell junctions, and cellular transport were maintained close to control levels in cultures stored at both 4°C and 16°C in contrast to 37 °C.

Conclusions

RPE cell cultures stored at 16°C appear to modulate their gene expression profile in a manner that supports cell survival during storage, while maintaining the expression levels of genes important for key RPE functions.
Occult non‐metallic intraocular foreign body causing recurrent anterior uveitis
Authors: Morreale Bubella R.
Published: September 2015

Purpose

To describe the case of textile worker with recurrent anterior uveitis following the traumatic penetration of nylon thread into the anterior segment of the eye.

Methods

Examination by slit‐lamp of the affected eye B‐scan ultrasonography during the inflammatory episode and after the resolution of the uveitis. Visual Acuity Measurement during the inflammatory episode and after the resolution of the uveitis.

Results

The use of topical therapy together with antibiotic systemic therapy led to the regression of the inflammatory symptoms (intense epibulbar and tarsal hyperemia with perikeratic reaction, corneal sub‐oedema with some folds in the Descemet's membrane, Tyndall 2+ and a layer of lower hypopyon associated with a filamentous foreign body with a spiral shape at the base of the lower chamber. In miosis the pupil did not react to a light stimulus) and pain. Removal of the foreign body allowed the rapid resolution of the recurrent uveitis.

Conclusions

This case underlines the need for an accurate search for possible foreign bodies in cases of ocular traumas, even apparently slight ones, once penetration into the posterior chamber has been excluded.
Sarcoidosis of orbita and central nervous system presenting as a non‐arteritic ischemic optic neuropathy
Authors: De Bruyn D. , Ninclaus V. , Leroy B.P. , De Schryver I. , De Zaeytijd J.
Published: September 2015

Purpose

To describe a patient who presented with non‐arteritic ischemic optic neuropathy (NA‐AION) as an initial manifestation of neurosarcoidosis.

Methods

A case of a 70‐year‐old woman who presented with loss of vision in the left eye and normal neuroimaging, was initially diagnosed as a NA‐AION. An extensive workup included MRI orbita and PET/CT scan.

Results

At the initial presentation, the left eye showed loss of vision and papilloedema. Further ophthalmological examination was normal, as was a CT scan of the brain. A diagnosis of NA‐AION was entertained. After 4 months, she had no light perception vision. Fundoscopy of the LE showed papilloedema with retinal infiltrates and severe ischaemia. MRI of the brain showed mass infiltration of the intraorbital and the intracranial optic nerve up to the optic chiasm. A complete systemic workup revealed a monoclonal gammopathy with cervical and hilar lymph nodes noted on PET/CT scan. Mediastinoscopy with biopsy of the hilar lymph nodes demonstrated a non‐caseating granulomatous lesion and a diagnosis of sarcoidosis was confirmed.

Conclusions

Sarcoidosis is a multisystemic disease characterized by granulomatous inflammation. Ocular involvement is seen in approximately 25% of patients with sarcoidosis. Uveitis is the most common ocular manifestation. Orbital and CNS manifestations of sarcoidosis are uncommon. Involvement of the optic nerve, chiasm and visual tract only represent 1–5% of neurosarcoidosis cases. In the latter, sarcoidosis can be initially misdiagnosed as NA‐AION, before involvement of the orbit and the CNS. Systemic involvement should be ruled out in any case of AION with an atypical evolution.
Repeatability of wide‐field autofluorescence lifetime imaging at the human retina in healthy volunteers
Authors: Klemm M. , Dietzel A. , Nagel E. , Schweitzer D.
Published: September 2015

Purpose

The detection of metabolic changes in the retina is the goal of fluorescence lifetime ophthalmoscopy (FLIO). We performed an observational clinical study in young healthy volunteers to examine the usability of 55° wide‐field fluorescence lifetime images.

Methods

The time‐resolved retina autofluorescence was measured (scanning laser ophthalmoscope: 55° of fundus, 62 µm resolution; excitation: diode laser with pico‐second pulses, 473 nm, 80 MHz repetition rate; detection: spectral channels 500–560 nm (ch1) and 560–720 nm (ch2), time‐correlated single photon counting method) in the right eye of 11 healthy volunteers (28.7 ± 3.6 years). Three repetitive measurements (m1–m3) on different days within one week at a similar time have been performed. All subjects had a crystalline lens and an undilated pupil. A modified 3‐exponential approach was applied to determine the fluorescence lifetimes τ. τ were computed on the ETDRS grid and in a 15 × 15 pixel region 25° superior to the fovea.

Results

49% of the measurements had shadowing effects in the inferior image region caused by eye lashes. τ (mean ± std) over all volunteers are: outer ring ETDRS gridsuperior regionch1ch2ch1ch2m1: 350 ± 25 ps255 ± 11 ps 348 ± 20 ps260 ± 7 psm2: 357 ± 27 ps257 ± 12 ps 357 ± 20 ps261 ± 7 psm3: 350 ± 26 ps257 ± 12 ps 327 ± 17 ps254 ± 5 ps

Results for the inner ring of the ETDRS grid are similar to the outer ring. The coefficient of variation in the superior region is 5.5% in ch1 and 2.5% in ch2. τ of repetitive measurements as well as of ETDRS grid's outer ring and the superior region are within the standard deviation.

Conclusions

FLIO measurements in young healthy volunteers using a 55° lens are repeatable. Spectral channel 2 is preferable because of its lower variability.
Choroidal Thickness and Systemic Examination in Diabetic Patients without Diabetic Retinopathy
Authors: Cardigos J. , Vicente A. , Costa L. , Crisóstomo S. , Marques N. , Cunha J.P. , Pinto L.A. , Ferreira J.
Published: September 2015

Purpose

The choroidal circulation receives nearly 95% of ocular blood flow and it is essential for a normal retinal structure and function. Recently, several clinical studies showed a variation in choroidal thickness (CT) even before the presence of diabetic retinopathy (DR), which the meaning remains uncertain and questionable. Our objective was to analyze and correlate the CT with the disease duration, systemic blood pressure (SBP) and analytic evaluation.

Methods

Prospective, observational case‐control study. A complete ophthalmological examination was performed, including dynamic contour tonometry and axial length. CT was assessed by a non‐invasive procedure using an OCT (Spectralis Heidelberg Engineering) with an enhanced depth mode (EDI) at 13 different locations (subfoveal and 3 measurements 500 μm apart in all 4 directions – nasal, temporal, superior and inferior). The SBP was measured and an analytical evaluation was performed, including glycemia, glycosylated hemoglobin – HbA1c, lipid parameters, renal function, ionogram and microalbuminuria. Correlation between variables was explored using Spearman correlations.

Results

The study included 65 diabetic patients without DR (36 females; mean age 67.23 ± 9.08 years), with an average disease duration of 90.42 ± 81.82 months. The CT didn't showed a correlation with disease duration, SBP, glycemia, HbA1c, renal function, lipid parameters, homocysteinemia, natremia or microalbuminuria. However, the CT was positively correlated with potassium and chlorine serum levels in 5 points, with statistic significance (r between 0.26 and 0.31, p < 0.05).

Conclusions

CT may be positively influenced by serum levels of potassium‐chlorine in diabetic patients but not in healthy controls. These abnormal CT relationships can be detected even with no visible DR. Further studies are needed to explore these differences.
Analysis of Mp‐1 audio‐biofeedback impact on fixation in low vision patient with maculopathy
Authors: Sato G. , Rizzo R. , Villani G.M. , Camerucci C.
Published: September 2015

Purpose

To study the impact of a low vision rehabilitation strategy based on Nidek MP‐1 auditory biofeedback (BFB).

Methods

Retrospective study of 39 eyes/26 consecutive patients referred for low vision rehabilitation. Patients received 8 monocular training sessions of BFB, each of 10 minutes duration, 7–14 days apart. Microperimetry, ETDRS VA and Pelli‐Robson was performed at the beginning and at the end of the sequence. BFB employs a sound to train the patient to keep a specific gaze position.

Results

Age median was 70. Pre‐BFB logMAR VA was 1, logCS 0.60. Post‐BFB logMAR VA was 1, logCS 0.75. Dense central scotomas and eccentric fixation locations were detected in 35 eyes/24 patients, and relative scotomas with central fixations in 4 eyes/2 patients. Mean sensitivity was 7.60 dB pre‐BFB, and 8 db post‐BFB. Pre‐BFB fixation stability was 24% within 2°, and 67% within 4°; post‐BFB, it was 25% within 2°, and 64% within 4°. BCEA analysis showed pre‐BFB values for 68.2% BCEA to be 3.6, and 4.46 post‐BFB. After BFB, no significant difference was found for any of the above‐mentioned parameters in the sample as a whole. Nevertheless, grouping cases by change in pre‐vs post‐BFB BCEA (group A: decrease in BCEA, n = 21; group B: increase in BCEA, n = 18) showed a significant difference in terms of BCEA itself, and in the related fixation stability (p < 0.05).

Conclusions

Although no significant difference in VA, CS, mean sensitivity, fixation stability at 2° and 4°, and BCEA was found after BFB in the sample as a whole, still there was an improvement in 21 eyes (53.8%) in terms of BCEA and fixation stability. Grouping analysis demonstrated that, while other tested outcome measures were not affected, some cases did respond significantly to BFB improving their fixation stability.
The effect of macular edema on the measurement of retinal nerve fiber layer thickness and the thickness of peripapillary retina
Authors: Kim S. , Lee S. , Lee J.
Published: September 2015

Purpose

With advanced in accuracy and reproducibility of spectral domain optical coherent tomography, It issuggested that the serial changes of retinal nerve fiber layer (RNFL) thickness could reflect the progression of glaucoma. But, patient may have accompany disease that affect retinal structure such as diabetes, venular occlusive diasese and macular degenerative diasese. So, we investigated the factors that influence the measurement of RNFL and peripapillaryretina.

Methods

In this retrospective controlled case series, we reviewed the eyes with macular edema. Analyzed factorsassociated RNFL thickness and peripapillary retina ranging from 3 mm and 5 mm of optic disc included age, IOP, visualacuity, central macular thickness (CMT), central macular thickness changes and kinds comorbid diasese. All themeasured values were obtained at initial presentation and the presentation when macular edema was relieved. The RNFL thickness and peripapillary retinal thickness were measured by SD‐OCT (Spectralis OCT).

Results

The measured value RNFL thickness and peripapillary retina were significantly fluctuate with the macularedema. The initial CMT, CMT changes were quantitively correlated with RNFL thickness alteration (p < 0.01). The initialCMT, CMT changes also significantly correlated with peripapillary retina ranging from 3 and 5 mm of optic disc, butthere was distinction associated with geographic difference. In the subgroup analysis, there were difference associations according to kinds comorbid diasese.

Conclusions

The macular edema effected the RNFL and the peripapillary retina. The measurements of RNFL andperipaillary retina were quantitively correlated in some kinds of comorbid diasese. The central macular thickness shouldbe considered in clinical application of detection about decreased RNFL thickness in patients who have macular edema.
Topical treatment with a new matrix therapy agent (RGTA, CACICOL) improves epithelial wound healing after penetrating keratoplasty in a rabbit model
Authors: Crouzet E. , He Z. , Olmiere C. , Perrache C. , Piselli S. , Jullienne R. , Gain P. , Thuret G.
Published: September 2015

Purpose

Epithelial wound healing is a milestone in the early post‐operative care after penetrating keratoplasty (PKP). It reduces the infectious risk, allows safe instillation of steroids, and conditions discharge from hospitalization. The present study assessed a new matrix therapy agent, for the management of post PKP epithelial defects in a preclinical rabbit model of PKP.

Methods

New Zealand white rabbits received a 7.1/7 mm PKP with a desepithelialized rabbit cornea from the same sibling. Immunosuppression was obtained thanks to subconjonctival corticosteroid. Rabbits were randomized to receive either CACICOL (n = 3) or a placebo (n = 3). Investigators were masked. Eyedrops were instilled immediately after graft and repeated on alternate day until complete reepithelilalization. The epithelial wound healing was monitored fluorescein staining. Corneal thickness was monitored using AS‐OCT. Rabbits were euthanatized and corneas were analyzed using histological cross sections, confocal microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

Results

Corneas receiving CACICOL healed in 6, 6 and 8 days versus 8, 8 and 10 days with the placebo (P = 0.099). Epithelial thicknesses were 45, 32 et 23 μm with CACICOL and 25, 29 et 19 μm with the placebo. In SEM superficial cells of the CACICOL group were similar to normal corneas and had more numerous microvilli with the placebo. MET showed normal epithelial ultrastructure in the CACICOL group with more hemidesmosomes than with the placebo.

Conclusions

RGTA seems a potentially useful, noninvasive therapeutic approach in PKP management.
Cell penetrating peptide constructs: A novel drug delivery to the eye
Authors: Scott R. , Hill L. , de Cogan F. , O'Neill J. , Logan A.
Published: September 2015

Purpose

In neovascular age‐related macular degeneration (AMD) blood vessels grow from the choroid under the retina causing macular damage and scarring. Anti‐VEGF drugs such as, ranibizumab or aflibercept are administered by intravitreal injection to treat AMD related neovascularisation, We present a novel cell‐penetrating peptide construct (CPPC) topical delivery system to deliver Ranibizumab to the retina using drops.

Methods

Peptides were produced using standard solid‐phase peptide synthesis. They were analysed using mass spectrometry and purified using high‐pressure liquid chromatography and used at a purity of >95%. CPPC were built around the drugs by vortexing for 10 seconds and incubating at room temperature. Drug delivery experiments were carried out ex‐vivo in freshly enucleated porcine eyes. In vivo experiments were carried out in C57 mice. Mice had a three 100 μm laser burns to the choroid to model neo‐vascularisation in AMD. They then received a single intravitreal injection of an anti‐VEGF agent or CPPC/Ranibizumab applied topically to the conjunctival sac twice daily for the duration of the experiment. Choroidal neovascularisation was measured by immunohistochemistry.

Results

Ex vivo delivery to enucleated porcine eyes demonstrated that a single 60 μL drop could deliver 1.7 ± 0.4 μg/mL of ranibizumab to the vitreous cavity. Confocal images of immunohistochemistry on retinal wholemounts showed ranibizumab within the retina. In vivo experiments demonstrated both intravitreal injection and CPPC bound Ranibizumab reduced neovascularisation equally, compared to controls

Conclusions

CPPC can be used topically to deliver therapeutic levels of Ranibizumab to the posterior segment.
BAP1 correlates with metastasis in polyploid uveal melanoma
Authors: Kilic E. , Yavuzyigitoglu S. , Mensink H. , Vaarwater J. , Naus N. , Paridaens D. , de Klein A.
Published: September 2015

Purpose

Most of the Uvea melanoma (UM) display a near‐diploid karyotype with only a few chromosomal changes. In contrast to these simple aberrations 10% of the UM samples show a polyploid character (> 58 chromosomes) and were associated with unfavorable prognosis. This study attempts to gain insight in polyploidy in UM and supplement the old data with the current knowledge on mutations in UM specific genes.

Methods

Fluorescence‐In‐Situ‐Hybridization (FISH) and/or Single‐Nucleotide‐Polymorphism (SNP) array was used to determine the ploidy status. Tumors showing signs of polyploidy (range tri‐ tetraploidy) were further investigated. Immune‐histochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) or the hotspots for the GNAQ, GNA11, SF3B1 and EIF1AX genes was carried out using Sanger Sequencing .

Results

Polyploidy was seen in 23 tumor samples. Fourteen of the UM patients developed metastases with a median follow‐up of 35 months. Thirteen tumors showed loss of BAP1 expression and all genetically tested polyploid tumors harbored a GNAQ or GNA11 mutation. SF3B1 mutations were found in three UM specimens and one of the tumors harbored an EIF1AX mutation. Univariate analyses showed a significant association with decreased survival for chromosome 1, 3 and 8 aberrations, SF3B1 wild type and a loss of BAP1 expression. In the multivariate analyses, BAP1 expression was the only independent prognostic marker within the polyploid tumors (HR 10.1; p = 0.008).

Conclusions

Also for the tumors displaying polyploidy loss of BAP1 expression is associated with an increased risk of metastatic disease.
Resolution of postoperative macular hole with topical nepafenac: a case report
Authors: Idoate A. , Honrrubia A. , Ascaso J. , Cristobal J. , Perez I. , Almenara C. , Esteban O. , Martinez M. , Sanchez J.I.
Published: September 2015

Purpose

Macular hole (MH) is a rare complication of cataract extraction. Various etiologies are discussed but it seems that the combination of vitreous traction and pseudophakic macular edema are the causes most likely involved in its pathogenesis. Pars plana vitrectomy (PPV) and internal limiting membrane peeling is the gold standard treatment option for patients with postoperative MH. Medical treatment has not been very effective in resolving this pathology. We present a case of post‐surgical MH treated with topical Nepafenac.

Methods

Interventional case report showing the role of topical Nepafenac as a therapeutic tool in post‐surgical MH.

Results

An 81‐year‐old female with a history of uncomplicated cataract surgery in RE. Four weeks after surgery there was a progressive visual deterioration with a best corrected visual acuity (BCVA): 0.05. SD‐OCT revealed a full‐thickness MH. Nepafenac 0.1 mg/ml, 3 times a day, was administered for 8 weeks in RE. Four months later, an improvement of her visual acuity (BCVA: 0.4) and a recovery of the retinal structure were observed. No recidive has been observed in a follow‐up of 1 year.

Conclusions

We propose the therapeutic use of topical NSAIDs as a possible alternative to surgery for macular holes whose etiology is related to inflammatory processes.
Experience with the monoclonal anti IgE antibody Omalizumab in severe refractory vernal keratoconjunctivitis in children
Authors: Doan S. , Amat F. , Gabison E. , Just J. , Cochereau I.
Published: September 2015

Purpose

Vernal keratoconjunctivis (VKC) is a severe form of pediatric ocular allergy, characterized by acute and chronic corneoconjunctival inflammation that may lead to visual sequelae. Although topical cyclosporine is usually effective, severe forms may be refractory and require prolonged steroid therapy. Omalizumab is a monoclonal anti IgE antibody, administered systematically and authorized for severe asthma. We report our clinical experience with omalizumab in severe VKC children.

Methods

We retrospectively reviewed the files of 4 boys treated with omalizumab because of severe VKC, defined as persistent corneal inflammation despite continuous topical 2% cyclosporine and steroid eye drops.

Results

Four boys, aged 7 to 13 years old, were treated. All children had asthma and 1 had severe lid eczema. Two patients had required supratarsal steroid injections. Omalizumab was administered every 2 weeks by subcutaneous injections, at doses varying from 450 to 600 mg per injection. Three patients out of 4 responded to the treatment, with a decrease in frequency and in duration of the inflammatory flares, and also a decreased need for topical steroid. However, the response was incomplete and they still had inflammatory corneoconjunctival flares despite continuous topical cyclosporine. On the other hand, asthma and lid eczema were completely controlled in these 3 patients. The fourth child did not respond to o and needed oral steroids for his VKC and his asthma. Noticeably, this patient did not have detectable sensitization to any allergen, contrary to the other cases. The treatment was stopped in this refractory case, but is still ongoing in all other cases, with a median duration of 16 months (6 to 26 months).

Conclusions

Omalizumab is an interesting treatment in severe refractory forms of VKC, but its efficacy is incomplete in these very severe cases.