bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging and Biopsies
Authors: Van Ginderdeuren R.
Published: September 2015

Imaging is necessary before taking a biopsy for diagnostic purposes, to delineate the extension, find the correct location and plan the most adequate procedure for the biopsy. In case of suspicion for conjunctival/palpebral lymphoma a CT scan is performed to exclude bilaterality and delineate the exact proportions. For orbital/lachrymal gland tumors with differential diagnosis of lymphoma a CT/MRI shows the exact location and dimensions of the tumor. In case of a tumor with easy access a large biopsy is preferred over fine needle aspiration biopsies. Special precaution is necessary not to crush the specimen to prevent artefacts of the fragile lymphoma cells The biopsy is divided in a fresh portion for frozen sections and for genetic analysis; the bulk of the tumor is fixed in formalin for the standard stainings Retinal/choroidal lymphomas can be diagnosed by fundus examination, OCT, ultrasound and fluoangiography. Biopsies require special surgical skills and adapted laboratory techniques because of the paucity of cells. Steroids must be discontinued for at least 10 days. A vitreal above a scleral approach is preferred because of the possibility to obtain also a retinal sample.
Healthcare delivery, not just about the doctor and the patient
Authors: Mazy R.
Published: September 2015

In this paper we explore the evolution of a classic hospital in a static building to a patient‐focused “concept” of healthcare delivery system where the healthcare provider can exercises high quality medicine with the necessary structural and organizational support. An organizational support for each individual(ist) healthcare provider who wants to perform “independently” the excellence in his work and be patronage and protected by its organization. As Wegener described “doctors are not manageable” but they should be supported and encouraged. Lean implementation, teamwork, promoting healthcare pathways, enriching the resources for all professionals to prevent Burn‐out are some of the aspect of a modern supportive organization to improve the quality of care AND the quality of life for the healthcare provider. Promoting the excellence and the professionals in order to increase the financial resources is one of the “jobs” of the manager of the hospital in his extensive list of To Do's.
Laboratory work‐up and specialized investigations
Authors: Pleyer U.
Published: September 2015

Based on the anatomical involvement of the eye intraocular inflammation is classified into anterior, intermediate, posterior and panuveitis. All subtypes of uveitis are potentially related to infectious and noninfectious etiologies. This presentation will assist the participants in accurately diagnosing uveitis in a step latter approach including physical and laboratory investigations. In addition, a tailored approach based on confounding clinical observations with specialized investigations will help to further differentiate clinical entities. In cases of suspected intraocular infections the option of intraocular fluid evaluation for antibody testing and polymerase chain testing against the causative agent will be presented. Taken together, this part of the course will provide a rational decision‐making strategy for diagnosis of patients with uveitis.
Recent advantages in the imaging of human corneal endothelial cells
Authors: Thuret G.
Published: September 2015

Sixty years after the understanding of their crucial role in corneal transparency maintenance, endothelial cells (ECs) are back under the spotlight since the development of endothelial keratoplasty and since new drugs and bioengineering techniques are in the pipeline. Accurate and informative imaging techniques are necessary to objectively assess the efficacy of each new therapeutic option. We will describe 3 recent advances in this field. 1/a simple laboratory assay coupled with image analysis that facilitates the assessment of toxicity of any kind of process liable to interfere with ECs. 2/a software that uses optimized algorithms of 3D reconstruction and of cell segmentation in order to increase the accuracy of EC count in eye banks by avoiding parallax errors that occur when ECs are counted in the deep posterior folds of stored corneas. 3/a 3D mapping of the subcellular localization of a set of proteins characteristic of ECs (in absence of a unique marker). We used confocal imaging of fluorescence immunolabelling of structural and functional proteins of normal human ECs. This 3D map could prove useful to characterize cells obtained during bioengineering processes that are candidate to become advanced‐therapy medicinal products.
Development pathway
Authors: Cordeiro M.F.
Published: September 2015

One of the biggest hurdles in ophthalmology, particularly glaucoma, in recent years has been the successful translation of laboratory advances to the clinic. This is not unique to glaucoma – such a problem has been well‐described in different spheres of medicine. In fact, a search in PubMed on this subject reveals over 1000 references. A major identifiable bottleneck is the developmental pathway and the adherence to regulatory requirements. Regulatory issues and common problems will be provided, using examples that are well‐documented in the field of glaucoma.
Scheimpflug analysis in an epidemiological study
Authors: Wegener A.
Published: September 2015

Radiation cataract enhances age‐related scattering increase. Radiation induces formation of subcapsular and cortical cataracts. Light scattering changes in lens layers evidences radiation damage to lens proteins. Scheimpflug imaging today offers standardized recording procedures minimizing the operator influence. The initial disadvantage of Scheimpflug imaging of only a few optical sections, has been overcome by the number of images recorded by the Pentacam® (25/50 images/eye). Densitometric and biometric image analysis needs a 3D data localization in the lens. This type of image analysis has been proven suitable for nuclear and cortical cataracts. Subcapsular cataracts pose more problems because of their 2D extension. Scheimpflug imaging with 50 images per eye partly compensates this, but retroillumination imaging can be superior in this case. OCT has been developed for imaging of the retina, but is now also used for the anterior eye segment. However, in radiation cataract and epidemiological studies, this technique is not useful, because optical coherence tomography detects coherence shifts at interfaces not particle related light scattering. It detects clearly shaped cataracts, but not changes in lens light scattering.
Descemets membrane endothelial keratoplasty (DMEK)
Authors: Katamish T.
Published: September 2015

Descemet's membrane endothelial keratoplasty (DMEK) has emerged as the superior technique for endothelial keratoplasty (EK) in routine cases to selectively replace diseased endothelium in patients with Fuchs endothelial dystrophy and pseudophakic bullous keratopathy. Despite all the advantages of DMEK the overall procedure is challenging for the surgeon. Crucial yet difficult steps of DMEK include: (1) Preparation of an intact donor lamella (D.M. and endothelium), (2) Transfer of the graft into the anterior chamber, (3) Unfolding and orientation of the graft, and (4) Final successful attachment after air filling. In my presentation I will demonstrate clearly how to perform these different steps safely and reproducibly.
Improving vision and comfort of patients with corneal deformations with implementation of ultraHealth and ultraHealth FC S‐H Hybrid Lenses
Authors: Manczak H.
Published: September 2015

In spite of the quadrant specific lens designs, fitting GP lenses to protruded corneas is a greater fitting compromise compared with fitting regular shaped corneas with GP corneal lenses. Also as GP corneal lenses have direct mechanical impact on unhealthy, more vulnerable KC epithelium, they are more likely to induce erosions, abrasions and other mechanical changes. Additionally, due to lack of centration evoked by misalignment of the tip of the cone and optical axis of the cornea, the visual outcome of GP corneal lens wear in patients with corneal irregularity in comparison to GP wear in regular shape corneas patients is usually worse. Synergeyes UltraHealth and UltraHealth Flat Curve hybrid lenses are designed to reduce or eliminate interaction between the part of the cornea within the area of the protrusion, and the back surface of the lens. In addition, size of Synergeyes hybrid lenses is 14.5 mm what usually results in better centration over the visual axis which leads to a reduction of HOA; thus they give a better visual quality outcome. Hypoxia, one of major drawbacks of former hybrid lenses, is greatly alleviated with the new materials that are available. Therefore, currently it is possible to diminish or in some cases entirely exclude complications enhancing the visual outcome at the same time.
Candidate Retinal Biomarkers in CNS Neurodegenerative Disease
Authors: Hudson C.
Published: September 2015

To institute early prevention of the common CNS neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Lewy Body Disease and Vascular Cognitive Disorders, cost‐effective, non‐invasive early diagnostic biomarkers are essential. Early detection of these diseases is critical given the growing evidence that new therapies will only be effective in pre‐symptomatic or prodromal stages of the degenerative process. Retinal imaging by spectral domain optical coherence tomography is currently used to evaluate morphological neurodegenerative changes caused by ophthalmic disease. Evidence suggests that this technique may also provide a biomarker in AD and PD, revealing changes in the retinal nerve fibre layer that correlate with cortical thinning and possibly prior to emergence of clinical symptoms. This presentation will up‐date the evidence supporting the use of non‐invasive retinal imaging as a pre‐symptomatic prognostic biomarker of CNS neurodegenerative disease.
Imaging in uveitis: techniques and indications
Authors: Herbort C.P.
Published: September 2015

This tutorial will address the main complementary imaging techniques used in the field of (posterior) uveitis. In case imaging work‐up is decided, fluorescein angiography (FA) is performed routinely since a few decades. FA gives information on the superficial structures and lesions of the fundus including pathology of the retina, retinal vessels, optic disc, and subretinal fluid collection, as well as the RPE for which it is the examination method of choice, and the choriocapillaris in the first seconds of angiography. Most of the time it only confirms and gives the precise extension of lesions already identified by the clinical examination. The choroid is however involved at least as often as the retina and often all or part of choroidal lesions are occult and not detected by the clinical exam or FA. Only indocyanine green angiography (ICGA) gives visual access to choroidal inflammatory pathology where it can distinguish stromal choroidits (birdshot, VKH) from choriocapillaritis (MEWDS, APMPPE, etc). So if angiography is deemed necessary during initial appraisal of a case dual FA/ICGA should be performed as choroiditis can not be excluded à priori. Other methods addressed will be OCT, UBM, FAF as well as anterior segment OCT.
Comparison of corneal topographic indices of keratoconus versus normal eyes by using pentacam imaging
Authors: Yekta A.A. , Khabazkhoob M. , Hashemi H. , Bakhshi S. , Ostadimoghaddam H. , Heravian J. , Rezvan F. , Yekta R.
Published: September 2015

Purpose

To compare the corneal topographic indices of keratoconus versus normal eyes by using pentacam imaging.

Methods

One hundred and fifty patients (300 eyes) from keratoconus clinic based on inclusion criteria and 149 nominees (298 eyes) for refractive surgery with normal cornea were selected from the Noor Eye Hospital, Tehran, Iran. Pentacam scheimflug measurements were performed for both groups based on standard measurement factors. Pentacam topography indices were recorded for each case.

Results

Average of topographic indices were evaluated and compared between two groups with T‐test. The difference between two groups was significant. Effective indices in discrimination suspect from normal were evaluated by logistic regression. Sensitivity and specificity of indices were plotted by ROC curve. In order to diagnose suspect keratoconus, index of height decentration (IHD) and index of height asymmetry (IHA) had the most sensitivity and specificity values.

Conclusions

The results of this study showed that the index of IHD and IHA were the most sensitive and specific criteria in the diagnosis and discrimination between keratoconus and normal eyes. Based on sensitivity and specificity criteria, the given cut‐points for each indices play an important role in detecting subclinical keratoconus from normal eyes.
Detecting and managing blindness risk in glaucoma
Authors: McNaught A.
Published: September 2015

Glaucoma patients are sometimes described as a homogeneous disease group, with the implication that the ‘a priori’ lifetime risk of visual impairment is similar for all patients, or that predicting the eventual risk of visual impairment is problematic. This is an oversimplification of the true situation. The risk of eventual visual impairment can be substantially different between individual patients, with these differences being evident at the first visit to the glaucoma clinic: a diagnosis of secondary glaucoma e.g. PXF, or angle closure glaucoma, is a an important adverse risk factor, as is the initial severity of visual field loss, height of presenting IOP, and, perhaps most important of all, the age of the patient at presentation. The risk of eventual significant visual loss for patients presenting as OHT is low, though, research work, notably the OHTS study, has highlighted risk factors evident at diagnosis which aid more accurate estimation of the visual prognosis. The prognostic importance of the initial findings at diagnosis, and a review of the literature is presented: including new insights from a recent UK audit of a countywide clinical population detailing the annualised relative risk of individual glaucoma patients requiring glaucoma surgery, segregated by presenting diagnosis.
Involvement of mitochondrial dynamics in the physiopathology of Dominant Optic Atrophy
Authors: Lenaers G.
Published: September 2015

Dominant Optic Atrophy is a blinding disease due to the degeneration of the Retinal Ganglion Cells (RGC) that form the optic nerve. Since our discovery of OPA1 gene in 2000 and novel genes more recently, we now know that mitochondrial dynamic is a key process for RGC physiology, as all DOA genes are primarily or secondarily related to mitochondrial dynamics. I shall present these genes and their respective involvement in mitochondrial fusion or fission, and then put emphasis on the importance of mitochondrial dynamics for the maintenance of RGC physiology, taking into account the two different myelinisation status of RGC axons in the retina and optic nerve. Analysis of these parameters in wild type mice and animals mutated for the DOA genes will be presented to illustrate the consequences of impairing mitochondrial dynamics on mitochondrial structure in axons and RGC survival. We believe that our data provide the first example of a mitochondrial disease, for which a clear rational explanation can justify the high specificity of the cell type affected in this disease.
OCT in assessing glaucoma progression
Authors: Garway‐Heath D.
Published: September 2015

OCT imaging enables the measurement of various structures in the optic nerve head (ONH) and retina which may be progressively damaged in glaucoma. Examples include the neural rim and lamina cribrosa at the ONH and the retinal nerve fibre layer (RNFL) in the peripapillary region of the retina and ganglion cell layer (and associated structures) in the macula. Most of these can be measured with high precision (low variability), which makes them good candidates for identifying progression and quantifying rates of progression. The presentation will provide a critical review of the literature for the application of OCT imaging to measure progression in glaucoma, considering the various potential anatomical targets. The application of OCT imaging in clinical practice will be discussed, including pitfalls in relation to image quality and artifacts. The presentation will also discuss the clinical relevance of OCT‐measured change in relation to vision function and how imaging outcomes should be interpreted.
En Face OCT and OCT‐Angiography in ocular oncology
Authors: Zografos L.
Published: September 2015

En Face OCT and OCT Angiography are two innovative diagnostic modalities which were adapted for the diagnosis, therapeutic decision and observation of the evolution following conservative management in ocular oncology. En Face OCT is particulary useful for (1) The definition of the extend of serous retinal detachment and the documentation of its variations (2) The definition of the internal anatomical structure of unpigmented choroidal tumors (3) The definition of the limits of flat and diffused choroidal melanomas in order to define the target volume of the irradiation. Angio‐OCT in ocular oncology is mainly used for the definition of retinal vascular lesions observed in radiation induced optic neuropathy and radiation induced maculopathy. This allows a better definition of the therapeutic strategies with anti‐VEGF drugs in order to preserve visual function.
Corneal nerves maintain the immune privilege of the cornea
Authors: Hamrah P.
Published: September 2015

The aim of the current study is to investigate if neuronal dysfunction leads to the loss of corneal immune privilege. After trigeminal axotomy, corneal cytokines were measured by multiplex bead assay. Corneal hem‐ (HG) and lymph‐angiogenesis (LG), as well as immune cell infiltration and phenotype were assessed by immunohistochemistry staining. Trigeminal axotomy was performed in recipient mice one week prior to corneal transplantation and allospecific delayed‐type hypersensitivity (DTH) was used to compare results between groups. Axotomy resulted in significant increase of CD45+ cells and up‐regulation of MHC‐2. Pro‐inflammatory cytokines in the cornea were significantly increased. The area of corneal HG and LG were significantly increased by 6.3 fold and 5.7 fold respectively. Axotomy before corneal transplantation resulted in rejection of all grafts, and donor‐specific DTH response in these mice was positive at 2 weeks, as compared to transplanted mice without prior axotomy.Neurogenic immune homeostasis is a critical process, whereby the peripheral nervous system directly maintains corneal immune privilege.
Uveitis ‐ the classic masquerade in adults
Authors: Kivelä T.
Published: September 2015

The classic masquerade syndrome in adults is vitreoretinal lymphoma mimicking bilateral uveitis – in about one third of cases, before any evidence of an intracranial lymphoma. It is, however, not the sole neoplastic disease that can lure the clinician to diagnose uveitis. Other examples include posttransplant lymphoproliferative disorder, multiple myeloma, leukemia, histiocytosis, and carcinoma or another amelanotic tumour metastatic to the anterior segment of the eye, and certain paraneoplastic disorders. Making the correct diagnosis needs prior knowledge, a high index of suspicion, careful systemic workup and, quite often, a confirmatory fine needle aspiration biopsy. A further caveat is that in some of these disorders, immunosuppressive treatment may initially appear to be effective. Notably, this apparent effect will prove only temporary, whereas posttransplant lymphoproliferative disorder actually calls for less intensive immunosuppression. This talk will introduce these principles using clinical examples.
Endothelial cell loss after phacoemulsification according to different anterior chamber depths measured by IOL master
Authors: Hwang H. , Lyu B. , Yim H. , Lee N.
Published: September 2015

Purpose

To compare the loss of corneal endothelial cells after phacoemulsification according to different anterior chamber depths (ACDs), as measured with the IOL Master.

Methods

We conducted a prospective, randomized clinical study on 135 eyes of 135 patients with senile cataracts. Eyes with nuclear density grades of 2 to 4 were divided into three groups according to ACD: ACD I, 1.5 < ACD < 2.5 mm; ACD II, 2.5 < ACD < 3.5 mm; or ACD III, 3.5 < ACD < 4.5 mm. Intraoperative ultrasound time (UST), mean cumulative dissipated energy (CDE), and balanced salt solution (BSS) use were measured. Clinical examinations included central corneal thickness (CCT), endothelial cell count (ECC), and corrected distance visual acuity (CDVA) preoperatively, and 1 day, 1 month, and 2 months postoperatively.

Results

There were no significant differences in CDE among the ACD groups (P > 0.05). The percentage of endothelial cell loss was significantly higher in ACD I than ACD III in the grade 3 and 4 cataract density groups 2 months after phacoemulsification (P < 0.05). There were also more changes in CCT in all of the cataract density groups in the ACD I group compared to the ACD II and III groups 2 months postoperatively, but the difference was not statistically significant.

Conclusions

Eyes with shallow ACDs, especially those with relatively hard cataract densities, can be vulnerable to more corneal endothelial cell loss in phacoemulsification surgery. Thus, more attention is needed to avoid corneal decompensation in cataract surgery on patients with shallow ACDs and hard nucleus densities.
Biomechanical properties of eyes with asymmetrical glaucoma defect
Authors: Cellini M. , Gizzi C. , Finzi A. , Campos E.C.
Published: September 2015

Purpose

To evaluate biomechanical properties in eyes of patients affected by primary open angle glaucoma (POAG) with marked asymmetrical defects by means of Ocular Response Analyzer (ORA) and Spectral Domain OCT with Enhanced Depth Imaging (EDI SD‐OCT) function.

Methods

We studied 20 patients (mean age: 56 ± 12) with asymmetrical POAG. One eye was classified as mild glaucoma (MG) and the sound eye as severe glaucoma (SG) by visual field indexes: MD −4.21 ± 1.51 vs −16.56 ± 5.76 dB; p = 0.011 and PSD 3.54 ± 0.87 vs 10.95 ± 3.51 dB; p = 0.007. An EDI SD‐OCT centered on the optic nerve head and an ORA examination were performed on each eye of every subject before and during a IOP increase of 12.5 ± 2.1 mm/Hg induced by a compression of the globe with an ophthalmodinamometer. Corneal histeresis (CH), corneal resistence factor (CRF) and laminar displacement (LD) were statistically analyzed by Wilcoxon's rank sum test and Spearman's correlation test considering significant a p < 0.05.

Results

After IOP increase we found a decrease of CH: 9.3 ± 3.66 vs 6.92 ± 3.04 mm/Hg; p = 0.012 in SG and 8.62 ± 2.16 vs 7.23 ± 2.29 mm/Hg; p = 0.176 in MG. CRF instead increase: 8.61 ± 2.31 vs 12.38 ± 3.65 mm/Hg; p = 0.016 in SG and 9.02 ± 1.48 vs 12.22 ± 5.68 mm/Hg; p = 0.041 in MG. LD was positive in MD: 29.08 ± 19.28 μm and negative in AG‐6.58 ± 16.09 μm. In AG eyes we found a correlation between LD and CRF (r = −0.658; p = 0.019) and between LD and Scleral Rigidity (r = −0.693; p = 0.012).

Conclusions

This study demonstrates that in asymmetrical glaucoma the IOP increase changes the eye biomechanics with stiffening of the eye structures that involves not only the lamina cribrosa but also the corneal tissue.
HLA‐A*02:06 and PTGER3 polymorphism exerts additive effects in cold medicine‐related Stevens‐Johnson syndrome with severe ocular complications in Japanese and Korean populations
Authors: Ueta M. , Tokunaga K. , Sotozono C. , Sawai H. , Yoon K.C. , Kim M.K. , Seo K.Y. , Joo C.K. , Kinoshita S.
Published: September 2015

Purpose

We reported that PTGER3 SNPs were associated with Stevens‐Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). We also reported that about 80% of our SJS/TEN patients had taken cold medicines within several days before disease onset and designated them cold medicine related‐SJS/TEN (CM‐SJS/TEN) patients, and that HLA‐A*02:06 was significantly associated with CM‐SJS/TEN in Japanese and Korean populations. Moreover, we documented that HLA‐A*02:06 with TLR3 polymorphisms exerted more than additive effects in SJS/TEN with SOC. In the current study we focused on CM‐SJS/TEN with SOC and analyzed an interactive effect between PTGER3 SNPs and HLA‐A*02:06 in Japanese and Korean populations.

Methods

Samples from 132 Japanese patients with CM‐SJS/TEN with SOC were collected and 221 healthy Japanese volunteers were also recruited as controls. Samples from 30 Korean patients with CM‐SJS/TEN with SOC were collected and 120 healthy Korean volunteers were also recruited as controls. Genotyping of PTGER3 gene SNPs was performed using the TaqMan SNP genotyping assay or the DigiTag2 assay. HLA‐A genotyping was performed using using commercial bead‐based typing kits, WAK Flow.

Results

In Japanese population, we found an interaction with additive effects between HLA‐A*02:06 and the high‐risk genotypes PTGER3 rs1327464 GA or AA (OR = 10.8, p = 2.56 × 10−7). Moreover, we also found an additive effect between HLA‐A*02:06 and the high‐risk genotypes PTGER3 rs1327464 GA or AA (OR = 14.2, p = 5.58 × 10−6).

Conclusions

These finding might show that the combination of these two polymorphisms could give improvements for a genetic testing as compared to using only one susceptibility gene.
Expression of Tissue inhibitor of metalloproteinase in ocular Stevens‐Johnson Syndrome: An Immunohistochemical Study
Authors: Venugopal R. , Sen S. , Kashyap S. , Sharma A. , Agarwal T. , Sharma N.
Published: September 2015

Purpose

Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) forms complexes with Matrix Metalloproteinases to inhibit tissue degradation and extracellular matrix (ECM) accumulation. Involvement of TIMP‐1 in Stevens ‐Johnson syndrome (SJS) ocular pannus formation remains unexplored. Therefore, this study aims to evaluate the expression of TIMP‐1 in SJS ocular sequelae patients.

Methods

Pannus tissues of 18 SJS patients excised during ocular surface reconstruction surgeries were collected. Clinical and histopathological parameters were examined. Immunohistochemistry (IHC) was performed on all cases for TIMP‐1 and evaluated on the basis of epithelial/stromal staining intensity. Expression of TIMP‐1 was statistically correlated with the histopathological and clinical parameters.

Results

Mean age was 25.6 ± 13.10 years. There was a male preponderance. Antipyretics (38%) were the most common cause of ocular SJS. Mean duration from onset of systemic episode to first presentation was 8.3 ± 6.2 years. Mean BCVA was 2.72 logMAR ± 0.47, mean Schirmer's value was 0.27 ± 1 mm. Epithelial hyperplasia was found histologically in 88.8% and stromal vascularization in 55%. Stromal fibrosis was indentified in 22%. TIMP‐1 expression was found in pannus epithelium in 13 cases and in stroma in 15 cases. Epithelial TIMP‐1 expression was statistically significant with epithelial hyperplasia, epithelial keratinization, squamous metaplasia, inflammation and stromal fibrosis (p < 0.05). Stromal TIMP‐1 positivity correlated significantly with epithelial keratinization (p = 0.0134).

Conclusions

TIMP‐1 protein expression correlated with the histopathological factors in ocular manifestations of SJS. This indicates TIMP‐1's contribution in pannus formation which involves ECM modifications. This may help TIMP‐1 to be considered as a possible therapeutic target in SJS.
Rescue of photoreceptor degeneration by progesterone in an animal model of retinitis pigmentosa
Authors: Miranda M. , Benlloch‐Navarro S. , Trachsel‐Moncho L.C. , Ramírez D.T. , López‐Pedrajas R. , Almansa I. , Silvestre D.
Published: September 2015

Purpose

Retinitis Pigmentosa (RP) is a neurodegenerative disease, resulting in progressive death of photoreceptors. rd10 mice are a model of RP that have a mutation on the cGMP phosphodiesterase codifying gene. The aim of this study is to evidence the neuroprotective role on photoreceptors of progesterone.

Methods

Progesterone was orally administered (150 mg/kg at postnatal days 15, 17, 19 and 21). The last day, eyes were enucleated and sectioned or homogenized. Sections were stained with hematoxilyn‐eosin and TUNEL assay was performed. Alterations of different proteins (pCREB, CREB, BDNF, TNFα and LC3) were determined by western blot (WB). Oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)) were determined by HPLC. To explore PG mechanism, ARPE‐19 PG treated cells were exposed to H2O2 and cell viability was measured. Tissue homogenates were also exposed to a biochemical induction of lipid peroxidation, and the effect of PG was studied.

Results

Hematoxilyn‐eosin and TUNEL assays revealed that histological degeneration decreased with PG. No differences were obesrved in WB analyzed proteins between control and rd10 retinas. Retinal GSH/GSSG ratio was decreased and MDA increased in rd10 mice, and PG restored these alterations. After H2O2 stress, major viability was detected on ARPE‐19 PG treated cells and inhibiton of lipid peroxidation was observed in tissue when PG was added.

Conclusions

Results suggest that progesterone protection could be related with its antioxidant ability.
Dexamethasone 0.7‐mg intravitreal implant in patients with radiation macular edema after proton beam therapy for choroidal melanoma: 2‐year results
Authors: Baillif S. , Maschi C. , Caujolle J.P.
Published: September 2015

Purpose

To evaluate over a 2‐year period, the efficacy of dexamethasone 0.7‐mg intravitreal implant in patients with radiation macular edema after proton beam therapy for choroidal melanoma.

Methods

Nine patients’ charts were retrospectively reviewed. The main outcome measures were visual acuity and mean central retinal thickness.

Results

All patients received a radiation dose of 60 cobalt gray equivalent. Radiation macular edema occurred within a mean time of 41 months after irradiation. Mean preinjection visual acuity was 50 ETDRS letters. Mean central retinal thickness was 461.7 μm. Two months after injection, mean visual acuity was 57 ETDRS letters. It improved for 5 patients (+4, +9, +15, +15, and +19 letters) and remained unchanged for 4. Two months after injection, mean central retinal thickness was 321.6 μm. A complete resolution of radiation macular edema was observed for 7 patients. Four patients underwent several injections of dexamethasone performed 4 to 5 months after the last injection. Intraocular pressure increased for 2 patients over a mean follow‐up period of 24 months. Two patients underwent cataract surgery after the third injection of dexamethasone implant.

Conclusions

Intravitreal dexamethasone implant can improve visual acuity in radiation macular edema. The observed beneficial effect lasted up to 5 months.
Transcription factors involved in cell death and regeneration in AGEs exposed retinal neurons
Authors: Oshitari T. , Bikbova G. , Yamamoto S.
Published: September 2015

Purpose

To examine the role of transcription factors in neuronal cell death and regeneration in advanced glycation end‐products (AGEs) exposed rat retinas.

Methods

The retinas of six SD rats were cultured in three dimensional collagen gels and incubated in serum‐free control media, AGEs‐BSA media, AGEs‐BSA + several neurotrophic factors (neurotrophin‐4, hepatocyte growth factor, glial cell line‐derived neurotrophic factor, tauroursodeoxycholic acid) supplemented media. After 7 days, the numbers of TUNEL positive cells and regenerating neurites were counted. The explants were immunostained for nuclear factor‐kB (NF‐kB) and specific protein 1 (SP1) and counted the number of immunopositive cells in the explants.

Results

In retinas incubated with AGEs, the numbers of TUNLE positive cells were more and the numbers of neurites were fewer than in control. All of the neurotrophic factors decreased TUNEL positive cells and increased the number of neurites, and the survival and regenerative effect was more significant in the neurotrophin‐4 group. The numbers of NF‐kB and SP1 immunopositive cells were higher in AGEs exposed retinas than in control. All of the neurotrophic factors decreased the number of NF‐kB immunopositive cells but did not significantly affect SP1 expression.

Conclusions

These results give the clue to understand the role of transcriptional factors involved in cell death and regeneration in AGEs exposed retinal neurons.
Correlation of Different Circulating Endothelial Progenitor Cells to Stages of Diabetic Retinopathy in patients with type 2 diabetes mellitus
Authors: Wu Z. , Ty M. , Wang F.
Published: September 2015

Purpose

To investigate vasculogenic endothelial progenitor cells (EPCs) in patients with type 2 diabetes mellitus (T2DM) with or without diabetic retinopathy (DR).

Methods

A case‐control study comparing 20 normal controls (CO) and 60 patients with T2DM with and without DR was performed. Patients with DR were studied and staged according to ETDRS severity scale. 60 patients were included: 20 without DR (NDR), 20 with nonproliferative DR (NPDR), and 20 with proliferative DR (PDR). EPCs (CD34/CD309) were enumerated by flow cytometry.

Results

The content of EPCs in PDR group (0.0316 ± 0.0294) % was significantly higher than that of the other three groups (χ2 = 43.780, P < 0.05). The content of EPCs of CO group (0.0179 ± 0.0047) % was higher than that of the NPDR group (0.0123 ± 0.1137) % and the NDR group (0.0151 ± 0.0086) % too,but the difference was not significant(χ2 = 5.244, P = 0.73), There was no significant difference of content of EPCs between NPDR group and the NDR group (χ2 = 6.016, P = 0.12).

Conclusions

In patients with T2DM with DR, EPCs undergo stage‐related regulation. In nonproliferative retinopathy, a reduction of EPCs was observed, and in proliferative retinopathy,a dramatic increase of mature EPCs was observed.
Role of macrophages in the course of an in vivo murine model of Anterior Ischemic Optic Neuropathy
Authors: Kokona D. , Häner N.S. , Ebneter A. , Zinkernagel M.S.
Published: September 2015

Purpose

Anterior Ischemic Optic Neuropathy (AION) is a common cause of vision loss and is characterized by degeneration of the optic nerve and retinal ganglion cells. Recently, inflammation has been proposed to play a role in the course of AION, and we wanted to investigate the contribution of circulating and/or resident microglia.

Methods

We examined the role of macrophages in the course of AION, employing an in vivo murine model of laser‐induced AION. AION was induced in BALB/c mice and three and six days after, OCT was performed and the number of infiltrating cells in the vitreous body was quantified. Bone marrow chimeras were generated using bone marrow derived cells that express GFP under the promoter of CX3CR1, specifically labelling macrophages. Cells were injected intravenously in lethally irradiated BALB/c mice which were subjected to AION two weeks later. Three and seven days after the AION induction, the eyes were subjected to OCT. The mice were euthanized at day 7 and their eyes were prepared for immunohistochemical studies against GFP and Iba‐1. FACS analysis of the retina was also performed in AION subjected BALB/c mice 3, 7 and 14 days after AION induction.

Results

Three and six days after AION induction, quantification of the OCT data showed a statistically significant elevation of infiltrating cells in the vitreous of AION subjected eyes compared to control eyes. This finding was substantiated by FACS analysis. The chimeras experiments revealed infiltration of circulatory macrophages into the retina.

Conclusions

Our data support a role of circulating and/or resident macrophages in the course of AION.
Evaluation of a portable manual stretching device to simulate accommodation
Authors: D'Antin J.C. , Pinilla Cortés L. , Montenegro G.A. , Barraquer R.I. , Michael R.
Published: September 2015

Purpose

To evaluate the performance of a manual lens stretching device using clinical scanners to analyze variations in lens topography and cross sections.

Methods

The stretching device consists of 6 pulling elements, attached to an external ring, which act like an aperture. The anterior segment of enucleated eyes from six months old pigs were glued to the device, then the cornea and the posterior segment of the eye were removed; finally, the whole setup was placed inside a container, which controls the stretching process. Different clinical scanners (Casia OCT, Orbscan and Pentacam) were used to analyze variations in lens shape. Calibrations were achieved using an artificial lens of known dimensions and refractive index.

Results

The device allows for a radial increase of 1.8 mm. Lens topography could be analyzed using the Orbscan and the Pentacam. While lens cross sections were obtained using the Casia OCT and the Pentacam. The posterior surface of the lens could not be correctly visualized. With our tests we observed changes in porcine lens diameter, shape, surface topography and dioptric power during stretching.

Conclusions

This stretching device allows for the analysis of the anterior surface and cross sections of the lens. Its capabilities are comparable to larger static stretchers, but has the advantage of being portable, allowing it to be used with the clinical scanners the center already has destined to patients, making it a cheaper alternative. However, the forces can't be measured.
Retinal thickness in children with anisohypermetropic amblyopia
Authors: Tomo N. , Nahoko O.
Published: September 2015

Purpose

To determine the retinal thickness in eyes of children with anisohypermetropic amblyopia, their fellow eyes, and eyes of age‐matched controls. To assess the effects of optical treatment on the foveal thickness in eyes with anisohypermetropic amblyopia.

Materials and Methods

Twenty‐five patients (6.0 ± 2.2 years, mean ± standard deviation) with anisohypermetropic amblyopia and 25 age‐matched controls (5.6 ± 1.9 years) were studied. Spectral‐domain optical coherence tomography (SD‐OCT) was used. The foveal thickness and the thickness of the outer nuclear (ONL), photoreceptor inner segment (IS) layer, and outer segment (OS) layer were measured by the embedded OCT software.

Results

The length of the OS was significantly longer in the fellow eyes (48.2 ± 5.9 µm) than in the amblyopic eyes (42.9 ± 4.6 µm, P = 0.03). One year after the optical treatment of the anisohypermetropia, the best‐corrected visual acuity (BCVA) improved and the length of the OS was significantly increased (P = 0.0001). After optical treatment there was no more significant difference in the OS length between in the amblyopic eyes and fellow eyes (P = 0.94). The change of BCVA was significantly correlated with the change of the length of the OS one year after the treatment (r = 0.54; P = 0.0004).

Conclusions

We found anisohypermetropic amblyopic eyes had qualitative and quantitative differences in the microstructures of the retinal photoreceptor layers from control eyes. An increase in the OS length was detected in the amblyopic eyes after the optical treatment. There was a significant correlation between the increased OS length and better BCVA.
Epithelial wound healing in a model of porcine corneas stored in an innovative bioreactor
Authors: Guindolet D. , He Z. , Bernard A. , Regeade D. , Piselli S. , Perrache C. , Forest F. , Peoch M. , Gain P. , Gabison E. , Thuret G.
Published: September 2015

Purpose

Experimental models of corneal epithelial healing are critically important to study cellular mechanisms and new therapeutics. We designed a bioreactor (BR) for exvivo corneal storage. It restores a pressure equivalent to the intraocular pressure in the endothelial chamber while allowing continuous renewing of media in both epithelial and endothelial chambers. It comprised 2 transparent windows for direct observation of epi and endo layers. Initially designed for human corneas, we adapted a prototype for porcine corneas to develop a new experimental platform. Aim: to study epithelial wound healing in the BR compared to a standard ex‐vivo model of porcine corneas.

Methods

Porcine eyeballs were obtained from a local slaughterhouse within 4 hours after death. Excised corneas were stored either in a BR or in a Petri dish with culture medium and agar for 4 weeks. A 5 mm epithelial debridmentulcer was performed. Exposition of the epithelium to various conditions was assessed in parallel: air‐lifting, immersion in different media, alternating media and air. Experiments were done in triplicate. Healing rate was monitored with fluorescein staining, digital pictures, and image analysis with ImageJ. After complete healing, corneas were processed for histology and immunolabelling with K3‐K12, laminin‐5, 5‐ethynyl‐2′‐deoxyuridine (EdU), ABCB5, and PAX6.

Results

Faster epithelial healing was observed for cornea stored in bioreactor. In bioreactor epithelial layer was mature (K3‐K12 immunostaining) and multi‐layered. Basement membrane was also restored (laminin‐5 immunostaining). Repeated epithelial debridement successfully healed indicating adequate survival of progenitors

Conclusions

This innovative porcine bioreactor could be a new ex‐vivo assay to study corneal wound healing and to assess efficacy or toxicity of new therapeutics. Grant: UJM, ANSM.
Intratarsal injection of kenacort in the treatment of severe cases of VKC
Authors: Lazreg S.
Published: September 2015

Purpose

To treat refractory cases of Vkc with intratarsal injections of trialcinolone.

Methods

We treated Severe cases of Vkc that have already experienced different anti allergic treatments and topical steroids with frequent relapses and dependancies to steroids with intratarsal injection of 40 mg of dexametasone, the follow up visits were performed at D0, D 3, D7 and D30 ( slit lamp examination, corneal staining, ocular pressure).

Results

87 severe cases of Vkc 63 males, mean age 10.4 ± 3.5 years, 90% bilateral, and 100% of corneal involvement. 70% mixed forms and 15% of tarsal forms, the mean follow up was 20+/‐7 months. at D3 we had a decrease of all ocular signs (photophobia, redness and pruritis) at D7 decrease of corneal staining and trantas nods, and at d30, total remission of the Vkc, the mean duration of the efficacy of the treatment was 10.4 ± 2.6 months, no adverse event was observed.

Conclusions

Intratarsal injection of steroids is very effective in severe and resistant cases of Vkc, especially in our countries where this disease is very severe, frequent and when topical cyclosporine is not available.
Glaucoma patients have a significant decrease in retrobulbar blood flow velocities during general anesthesia
Authors: Abegao Pinto L. , Vandewalle E. , Willekens K. , Van keer K. , Van Calster J. , Stalmans P. , Vertommen J. , Deckers K. , Marques‐Neves C. , Stalmans I.
Published: September 2015

Purpose

Glaucoma patients are known to have an underlying vascular dysfunction and General anesthesia (GA) significantly decreases blood pressure, which might decrease ocular perfusion. This study was conducted to investigate the effects of GA on ophthalmic flow velocities and blood pressure.

Methods

Prospective, case‐control study. Glaucoma patients were scheduled for trabeculectomy or drainage device implantation; non‐glaucomatous patients undergoing vitrectomy for macular hole or epiretinal membrane peeling were recruited as control subjects. Color Doppler imaging of the ophthalmic artery (OA) was performed immediately before and 1 minute after GA induction. The following parameters were analyzed: OA blood velocities and resistivity index, as well as cardiovascular parameters (diastolic and systolic blood pressure and heart rate). Statistical analysis was performed using Studentâ€™s paired t test, Mann‐Whitney, Fisher's exact test and Spearman's correlation.

Results

53 patients were included (glaucoma group: 25; control group: 28). The magnitude in blood pressure decrease after GA induction was similar between the two groups (p value 0.61–0.70). However, the decrease in OA blood velocities was significantly larger in the glaucoma groups than in the control group (p < 0.03 in all comparisons). Unlike the control subjects, in the glaucoma group there was a significant association between the magnitude of blood pressure decrease and the lowering of the OA mean blood velocity (r = 0.69, 95% IC: 0.36–0.87, p < 0.001).

Conclusions

These results suggest that glaucoma patients are unable to keep a stable blood velocity in the OA when subjected to acute significant decreases in blood pressure (such as the ones seen after GA induction).
Changes of intraocular pressure and cornea biomechanical properties after cataract phacoemulsification
Authors: Yugay M. , Ryabtzeva A.
Published: September 2015

Purpose

Cataract phacoemulsification is accompanied by changes in intraocular pressure and biomechanical parameters of the eye. Corneal hysteresis characterizies the visco‐elastic properties of the cornea. Our purpose was to analyse the changes of intraocular pressure and corneal hysteresis during 3 months after phaco.

Methods

The study included 80 eyes of 80 patients who underwent uncomplicated phacoemulsification throught clear corneal incision with IOL implantation. Preoperative examination included standard techniques and measurement of corneal hysteresis, central corneal thickness (CCT), corneal compensated intraocular pressure (IOP) and Goldman IOP by Ocular Response Analyzer, repeated before surgery, 1 day, 2 weeks, 1 and 3 months after surgery.

Results

Corneal hysteresis decreased on the first day after cataract phacoemulsification from 9.90 ±0.24 mm Hg to 8.88 ± 0.26 mm Hg and after 2 weeks to 7.91 ± 1.13 mm Hg (p < 0.05). Then corneal hysteresis increased and after 3 months after surgery returned to preoperative values (9.78 ± 0.29 mm Hg). Intraocular pressure raised after surgery by 3 mm Hg, decreased to preoperative values by 1 month after phaco, and continued to decrease by 1.5–2 mm Hg up to 3 months after phacoemulsification. Central corneal thickness increased after phaco from 539 ± 21 mcm to 559 ± 33 mcm the first day after surgery and 659 ± 28 mcm in 2 weeks. It decreased to 552 ± 26 mcm in 1 month and returned to preoperative values in 3 months.

Conclusions

Corneal hysteresis decreased in the early postoperative period after phaco, dropping to a minimum 2 weeks after surgery. Then corneal hysteresis gradually increased, reaching preoperative values at 3 months after surgery. Changes of intraocular pressure are opposite to changes of corneal hysteresis. CCT increased after phaco, reached maximum in 2 weeks and returned to preoperative values in 3 months.
Immunohistochemical characterization of a retinal hamartoma
Authors: Van Ginderdeuren R. , Stalmans P.
Published: September 2015

Purpose

To describe the immunohistochemical features of a retinal hamartoma.

Methods

A 38 y old man was referred for preretinal fibrosis on his right eye. There was loss of vision for more than 8 years with metamorphopsia. The left eye was normal. Oct imaging showed an epiretinal fibrosis with extensive macular oedema. A 27Gauge vitrectomy was performed. The lamina limitans interna (ilm) was peeled after staining with Membrane Blue Dual and sent for histopathology.

Results

After removal the epiretinal membrane was immediately fixed with PreservCyt® in a ThinPrep® container. The specimen was routinely processed by the Cellient® embedding system. Microscopy showed a folded Pas positive membrane, recognized as ilm with on one side some glial remnants and on the other side a cuboidal non‐pigmented epithelium. The glial remnants stained with glial fibrillar protein (gfap), the epithelium with prekeratin AE1/AE3. CD 34 stain was positive in preretinal capillaries.

Conclusions

A strange retinal fibrosis consisted of glial tissue and a row of superficial cuboidal non‐pigmented epithelium cells. This kind of hamartoma with immunohistological description was never investigated or published.