bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of High resolution Gabor‐Domain optical coherence microscopy for early diagnosis of corneal disease
Authors: Courrier E. , Tankam P. , He Z. , Hindman H. , Lepine T. , Gain P. , Thuret G. , Rolland J.
Published: September 2016

Purpose

We investigate the capability of a high volumetric‐resolution imaging modality, Gabor‐Domain Optical Coherence Microscopy (GD‐OCM), to identify key features in the structural modification of the cornea in three frequent diseases.

Methods

Host corneal buttons were excised during penetrating keratoplasty from patients with Fuchs’ endothelial corneal dystrophy (FECD), type IIIA lattice corneal dystrophy (LCD) and keratoconus. We sutured them onto cadaver corneal rims to preserve their shape, mounted onto a corneal artificial chamber and pressurized under a pressure of 20 mmHg. We imaged them using GD‐OCM in a non‐contact mode, combining optical coherence tomography's high sectioning capability with confocal microscopy's high lateral resolution. The system achieved high‐contrast imaging with a field of view of 1 × 1 mm2 and volumetric cellular resolution of 2 μm across a tissue up to 2 mm thick.

Results

GD‐OCM produced high resolution and high‐contrast 3D images of the cornea's different layers. For FECD: the Descemet's membrane and stroma thickened and the density and size of keratocytes increased, along with associated guttae. Change in keratocytes seems to start in the posterior stroma in the early disease process and later heads toward the anterior stroma. For LCD: lattice linear deposits were identified in the anterior stroma, and for keratoconus, folds were identified in the posterior stroma, presumably Vogt's striae. For both, keratocytes and endothelial cells morphology was preserved.

Conclusions

The GD‐OCM revealed key pathologic features of several important corneal diseases and can be applied toward studying corneal diseases.
Müller cells increase survival of retinal ganglion cells – a coculture model of primary retinal ganglion cells and primary Müller cells
Authors: Toft‐Kehler A.K. , Skytt D. , Brændstrup C. , Gurubaran I. , Kolko M.
Published: September 2016

Purpose

Müller cells are considered to be vital in the maintenance of retinal ganglion cells (RGCs), and since RGCs are essential to maintain the neuronal function of the retina, a functioning symbiotic partnership between Müller cells and RGCs is fundamental. The present study evaluates glia‐neuron interactions in a coculture model of primary Müller cells and primary RGCs.

Methods

To investigate the Müller cell‐RGC interaction we developed a coculture model, in which primary Müller cells from mice were grown in inserts on top of pure primary RGC cultures likewise from mice. The impact of 24 h of starvation on the ability of Müller cells to protect RGCs was evaluated. Moreover, changes in glutamate uptake were studied in Müller cells as well as cell viability in response to starvation.

Results

The presence of Müller cells significantly increased the survival of RGCs during normal conditions as well as during 24 h of pre‐starvation. Glutamate uptake capacity was significantly increased during starvation along with an increased Vmax. Starvation induced significantly reduced cell viability both in Müller cells and RGCs with a significantly greater reduction of cell viability in Müller cells.

Conclusions

The present study reveals an increased survival of RGCs in presence of Müller cells and herewith we confirm Müller cells as being key players in RGC homeostasis. Moreover, we verify the coculture model as being a unique approach to study the glia‐neuron partnership in inner retinal diseases.
Electroporation enhances chemosensitivity of uveal melanoma cells
Authors: Fiorentzis M. , Katopodis P. , Kalirai H. , Seitz B. , Viestenz A. , Coupland S.E.
Published: September 2016

Purpose

Electrochemotherapy (ECT) is increasingly being used for tumour ablation with reduced systemic toxicity, in cancers refractory to current treatments. Metastatic UM is characterised by its innate chemoresistance to many widely used cytotoxic drugs; however, there are no reports of the use of ECT in this disease. We investigated the cytotoxic effect of bleomycin in combination with electroporation on three human uveal melanoma (UM) cell lines in vitro.

Methods

Mel270, 92‐1 and OMM‐1 UM cell lines were treated with either: a) electroporation alone (pulse amplitude 300–750 V/cm, 8–10 pulses, 100 μs, 5 Hz); b) bleomycin alone (0–10 μg/ml) or; c) in combination. Cell survival was analyzed by MTT viability assay after 36 h.

Results

Electroporation alone reduced cell viability in all UM cell lines with increasing pulse amplitude as compared with untreated control cells; maximum reduction in viability across all UM cell lines was 27% at 750 V/cm for 10 pulses. All UM cell lines were resistant to the cytotoxic effects of bleomycin (0–10 μg/ml) alone. ECT of the UM cell lines with 750 V/cm, 8 pulses, 100 μs, 5 Hz and bleomycin showed a dose‐dependent reduction in cell viability; 1 μg/ml bleomycin reduced viability by 57%, 46% and 51% in the Mel270, 92‐1 and OMM‐1 UM cell lines, respectively.

Conclusions

In vitro ECT with bleomycin was more effective than the highest concentration of the antineoplastic drug or electroporation alone, opening new perspectives in the treatment of UM.
Correlation between choroidal and retinal thickness in diabetic patients without diabetic retinopathy
Authors: Cardigos J. , Proenca R. , Vicente A. , Marques N. , Cunha J.P. , Abegao Pinto L. , Ferreira J.
Published: September 2016

Purpose

This study was design to examine the correlation between retinal and choroidal thickness in diabetic patients without diabetic retinopathy.

Methods

125 type 2 diabetic patients without diabetic retinopathy underwent a complete ophthalmological examination. Retinal total thickness and retinal layer automatic segmentation were assessed by using spectral domain optic coherence tomography (Spectralis Heidelberg Engineering). Retinal measures were made at fovea and at 3 mm temporal (T3), nasal (N3), superior (S3) and inferior (I3) to the fovea. Choroidal Thickness (CT) was assessed with enhanced depth mode (EDI) software (subfoveal and at 1,000 μm temporal, nasal, superior and inferior to the fovea). Pearson correlations were analyzed between CT and RT (total and by layer) at the five locations of study: subfoveal CT with central RT; and CT at the 1,000 μm temporal, nasal, superior and inferior to fovea's center with RT at the T3, N3, S3 and I3, respectively.

Results

Diabetic patients were in average 66.9 ± 9.33 years old with an average disease duration of 93.50 ± 81.74 months. Except for the pigmented epithelium retinal layer, which showed a positive, but weak correlation with CT at N3, S3 and I3 (r between 0.25 and 0.32, p < 0.05), the analyze didn't showed a statistical significant correlation between CT and the thickness of the other retinal layers.

Conclusions

Recent studies empathize the role of a choroidal vasculopathy in diabetic retinopathy pathogenesis. The absence of correlation between CT and RT may be related to changes in the choroid occur in earlier stages of the disease. Future longitudinal studies are needed in patients at different stages of diabetic retinopathy.
Hypoxia and retinal blood flow changes: a study using OCT‐Angiography
Authors: Cordeiro Sousa D. , Moreira S. , Leal I. , Dionísio P. , Abegão Pinto L. , Marques‐Neves C.
Published: September 2016

Purpose

The raising number of commercial flights means a routinely exposure to hypoxic conditions by the crew and passengers. Aircrafts’ cabins are pressurized to a value of 565 mmHg, equivalent to breathing 15.1% oxygen at sea level. We aimed to study the relationship between normobaric hypoxia and retinal blood flow.

Methods

Prospective cohort study. The Hypoxia Challenge Test was performed at sea level, according to the British Thoracic Society protocol. OCT‐Angiography (AngioVue®) was done at three time‐points (baseline, hypoxia and 30’ post‐hypoxia). Foveal and parafoveal flow densities were assessed using built‐in AngioAnalytics®. To guarantee data independence, right and left eyes were compared separately. Only images with high‐quality acquisition signal were included. Repeated‐measures ANOVA and mean comparison analysis were performed using STATA 13.0.

Results

Studied population included 30 subjects (14 women), with a mean age of 28.8 ± 4.2 [range 22–37] years. There was no statistically significant within‐subject difference in foveal flow density in both right and left eyes. However, within‐subject differences in parafoveal flow density were recognized for both right (p = 0.05) and left eyes (p = 0.03). Paired analysis confirmed a significant difference (p < 0.05) in mean parafoveal flow density between the three time‐points: baseline (OD = 55.7 ± 0.46, OS = 57.1 ± 0.44), hypoxia (OD = 56.7 ± 0.38; OS = 57.9 ± 0.35) and post‐hypoxia (OD = 56.1 ± 0.35, OS = 57.0 ± 0.39).

Conclusions

To our knowledge, there is no published data specifically addressing flight cabin hypoxia and eye hemodynamics. Our work in healthy subjects may help to establish normality thresholds and identify individuals at risk and their need for personalized screening and therapeutic air‐travel recommendations.
Peripheral vessel leakage in diabetic retinopathy using Wide field retinal angiography
Authors: Maamouri R. , Bouraoui R. , Fedra K. , Hassairi A. , El Matri L.
Published: September 2016

Purpose

To evaluate the peripheral vessel leakage in patients with non proliferative diabetic retinopathy (NPDR) using a wide field fluorescein angiography

Methods

In a retrospective study, consecutive wide‐field angiographs obtained using the Heidelberg Retina Angiograph 2 with a contact lens system Staurenghi, were graded in: peripheral vascular leakage, areas of retinal non perfusion, retinal neovascularization observed overly of conventional 7 standard fields.

Results

A total of 71 eyes in 39 diabetic patients were included. Distribution of NPDR severity was: mild NPDR in 6% of eyes, moderate NPDR in 21% and severe NPDR in 73%. Findings included angiographic peripheral vessel leakage in 85%, peripheral non perfusion in 87% of eyes, neovascularization in 14%, macular edema in 53%, and macular ischemia in 4%. Peripheral vessel leakage was associated with peripheral non‐perfusion (p < 0.001) but not with retinal neovascularization (53 vs. 35%, p = 0.01), neither with macular edema (p = 0.449).

Conclusions

This study had characterized peripheral vessel leakage (PVL), and shown a correlation with peripheral non‐perfusion. Peripheral non‐perfusion and PVL appeared to be markers of active diabetic retinopathy.
Contribution of wide field angiography to diabetic macular edema
Authors: Maamouri R. , Bouraoui R. , Kort F. , Falfoul Y. , El Matri K. , El Matri L.
Published: September 2016

Purpose

To evaluate diabetic macular edema in non proliferative diabetic retinopathy (NPDR) using a wide field fluorescein angiography.

Methods

In a retrospective study, consecutive wide‐field angiographs using the Heidelberg Retina Angiograph 2 with a contact lens system Staurenghi and SD‐OCT were performed in diabetic patients with non proliferative diabetic retinopathy.

Results

A total of 71 eyes in 39 diabetic, average age was 58 years (SD 12). Most of the patients had type 2 diabetes mellitus (92%) and average duration since diabetes diagnosis was 10 years. Mean HA1c was 7.4%. Distribution of NPDR severity was: mild NPDR in 6% of eyes, moderate NPDR in 21% and severe NPDR in 73%. Macular edema was found in 53%. A thicker retina was observed in eyes with peripheral non perfusion (353 vs. 254 μm p = 0.006). Retinal non perfusion was associated with macular edema (97 vs. 76%, p = 0.01) and poor visual acuity (p < 0.001).

Conclusions

Diabetic macular edema seems to be strongly associated with peripheral retinal non perfusion. So treatment and management of diabetic macular edema may be reconsidered using either a targeted laser treatment in the area of retinal non perfusion or anti‐VEGF intravitreal injection.
In vitro evaluation of anti HSV‐1 siRNAs and in vivo evaluation of electroporation to transfect siRNAs on murine cornea
Authors: Rousseau A. , Escriou V. , Roy P. , Poccardi N. , Takissian J. , Bigey P. , Labetoulle M.
Published: September 2016

Purpose

HSV‐1 keratitis (HSK) is a leading cause of infectious blindness in developed countries. Massive use of nucleosidic DNA polymerase inhibitors, used as curative or prophylactic treatments, may favor the emergence of resistance. Anti‐HSV1 small interfering RNAs (siRNA) may be efficient to overcome this issue, but their transfection into corneal cells remains a challenge. The purpose of this study was to assess the in vitro efficacy of siRNA targeting HSV‐1 DNA polymerase to reduce HSV‐1 replication, and the in vivo efficacy of electroporation to transfect siRNA into corneal cells on the murine cornea.

Methods

Three different anti HSV‐1 DNA polymerase siRNAs (S1–S3) and one control siRNA were transfected into vero cells using cationic lipids, which were secondarily infected with the SC16 strain of HSV‐1. Efficacy on viral replication was assessed using flow cytometry, quantitative PCR (qPCR) and plaque assay technique. On murine cornea, fluorescent siRNAs were injected subconjunctivally and electroporation was performed with custom made electrodes applied on the conjunctiva. The eyes were enucleated, and observed under fluorescence microscopy.

Results

The three siRNAs were able to inhibit viral replication. Compared to the control siRNA, S3 was the most efficient siRNA, decreasing by 60% the number of infected cells as measured with flow cytometry, by 59% the number of plaques and by 75% the viral load estimated with qPCR. Electroporation improved siRNA penetration into the corneal epithelium compared to subconjunctival injection alone.

Conclusions

These results demonstrate that siRNA directed against HSV‐1 DNA polymerase efficiently inhibits HSV‐1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative to treat HSK. Besides, intracorneal penetration may be facilitated by electroporation.
Normal range of eye movement and its relationship to age
Authors: Shin Y. , Lim H.W. , Kang M.H. , Seong M. , Cho H. , Kim J.H.
Published: September 2016

Purpose

To determine the range of eye movement in normal human subjects and to investigate the effect of age on eye movement.

Methods

We enrolled 261 healthy subjects, 5–91 years of age for this prospective observational study. Photographs were obtained in the cardinal gaze positions and processed using Photoshop. The processed images were analyzed using the Image J program to measure the angle of eye movement. The angle of eye movement was quantified using a modified limbus test. We measured the angle of eye movement in adduction, abduction, elevation, and depression.

Results

The normal ranges of eye movement were 44.9 ± 7.2° in adduction, 44.2 ± 6.8° in adduction, 27.9 ± 7.6° in elevation, and 47.1 ± 8.0° in depression. There were significant negative correlations between the angles of horizontal and upward gazes and age (R = −0.294 in adduction, R = −0.355 in abduction, and R = −0.506 in elevation, all p < 0.001). However, the angle of downward gaze was not significantly correlated with age (R = 0.017, p = 0.722).

Conclusions

The normal ranges for the angle of horizontal gaze were symmetric, whereas the range of upward gaze angle was smaller than that for the downward gaze among all ages. Unlike the age‐related decline of range in other gazes, only downward gaze was not impaired by increasing age. Differences in eye‐movement range based on gaze direction and their associated aging mechanisms should be considered when assessing eye movements.
Surgical treatment of pediatric strabismus (PS): series of 148 patients
Authors: Rahmania N. , Van Rompay T. , Morfeq H. , Promelle V. , Milazzo S.
Published: September 2016

Purpose

Surgical management of Pediatric Strabismus (PS) is a frequent reason of consultation in current ophthalmic practice. The aim of this study is to describe the PS epidemiology in patients consulting for surgery.

Methods

This 3 years observational descriptive retrospective study was led in ophthalmological department of university hospital. 148 patients <18 years were included. All patients received complete ophthalmological and orthoptic evaluations to determine the clinical form of strabismus.

Results

The sex ratio was: 49.3% females vs. 50.7% of males. Exotropia was found in 46.4% of females and 53.4% of males. Esotropia was the predominant etiology (79.6%), then 19% of exotropia and 1.4% of vertical deviation. Mean age at first consultation was 6.6 years (6.3 for esotropia vs. 9.3 for exotropia). 36% had infantile forms, 26% had accommodative strabismus, 13% had an exotropia, 7% had an acquired esotropia. For amblyopia we found only 3% of severe forms whereas moderate and low forms were found in 7.4 and 11.8% of patients. Risk factors of PS identified were neurological diseases (8.1%), hyperopia (+2.33 diopters in average), complicated pregnancy (16.3%) or delivery (27%), prematurity (13 .4%), birth weight lower than 2.5 kg (14.6%) and pedigree of strabismus (74.1%).

Conclusions

The epidemiology of PS in our study is related to other European studies but different from American or Asian studies. The hypothesis are possible ethnic differences and different therapeutic management. Better understanding of these risks factors will enhance the prevention and treatment of this pathology.
Onset‐offset visual evoked potentials in the diagnosis of ocular albinism in infantile nystagmus
Authors: Bouladi M. , Bouraoui R. , Limaiem R. , Chaker N. , Mghaieth F. , El Matri L.
Published: September 2016

Purpose

To study the contribution of onset‐offset visual evoked potentials (VEP) in the diagnosis of ocular albinism in infantile nystagmus.

Methods

Case report.

Results

Observations: Two girls aged respectively three‐year old and six‐year old presented with infantile nystagmus. Ophthalmic examination showed visual acuity of 2/10 bilaterally, a brown iris, with positive transillumination and depigmented fundus without any other depigmentation of skin or hair. Flash VEP showed probable crossed asymmetry of P2 amplitude. P100 wave was unrecordable in 60’ Pattern VEP. 60’ onset‐offset VEP were performed and showed evident crossed asymmetry in C1 and C2 waves which confirmed the diagnosis of ocular albinism. SD‐OCT was also performed and showed foveal hypoplasia.

Conclusions

Ocular albinism is more difficult to diagnose than the oculo‐cutaneous albinism since it is limited to ophthalmic manifestations. Onset‐offset VEP are very useful in nystagmus patients because they are less sensitive to ocular oscillations and showed more evident crossed asymmetry than flash or pattern VEP.
Anterior segment parameters measured by ultrasound biomicroscopy in the subtypes of angle‐closure
Authors: Kim Y.Y. , Yoo C. , Cho S.Y. , Lee T.E.
Published: September 2016

Purpose

To compare anterior segment parameters in primary angle closure suspect (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM P60, Paradigm Inc, Utah, USA).

Methods

59 eyes of 59 patients with PACS, 41 eyes of 41 patients with PAC, and 51 eyes of 51 patients with PACG were investigated. Definitions of PACS, PAC, and PACG were based on the recommendation from the International Society for Geographic and Epidemiological Ophthalmology. In each participant, slit lamp examination, funduscopy, gonioscopy, Goldmann applanation tonometry and UBM were performed. Anterior segment parameters such as anterior chamber depth (ACD), anterior chamber width (ACW), lens vault (LV), angle opening distance 500 (AOD500), trabecular meshwork‐ciliary process distance (TCPD), iris thickness (IT) and iris zonular distance (IZD) were evaluated.

Results

AOD500 were significantly different among the angle‐closure subtypes in nasal, inferior, and temporal quadrants (PACS > PACG > PAC; p < 0.05). TCPD were significantly different among the subtypes in all quadrants (PACG > PACS > PAC; p < 0.05). ACD were significantly different among the subtypes (PACG > PACS > PAC; p < 0.05). ACW, LV, IT and IZD were not significantly different among the subtypes (p > 0.05).

Conclusions

AOD500, TCPD, and ACD were the smallest in PAC, and ACW, LV, IT, and IZD were similar among the angle‐closure subtypes. There may be a consequence in the development of angle‐closure from mild to severe damages (from PACS to PAC to PACG) in terms of intraocular pressure, angle status, and optic nerve head status. However, our results suggested that such consequence may not exist in anterior segment morphology measured by UBM.
Retinal venous oxygen saturation in healthy, atrophic and retinal vascular diseases
Authors: Olafsdottir O.B. , Hardarson S. , Vandewalle E. , Pinto L.A. , Eysteinsson T. , Eliasdottir T. , Gottfredsdottir M.S. , van Keer K. , Bek T. , Stalmans I. , Stefánsson E.
Published: September 2016

Purpose

Mean retinal venous oxygen saturation (VSatO2) has been found to be different from normal in several retinal diseases. There are speculations that metabolic imaging of the retina could be helpful in monitoring such diseases and perhaps help with diagnosis. The aim of the study was to characterize normal range of retinal VSatO2 and to further examine patients that fall outside normal range.

Methods

Retinal vessel oxygen saturation was measured in healthy individuals (n = 89), patients with glaucoma (n = 78), retinitis pigmentosa (RP, n = 10), diabetic retinopathy (DR, n = 54) and central retinal vein occlusion (CRVO, n = 14). Measurements were performed with a spectrophotometric retinal oximeter, Oxymap T1.

Results

Fifty‐four healthy individuals were age‐ and gender matched with DR and CRVO patients. For this healthy group, 5% of VSatO2 were below 38 and 5% of VSatO2 were above 63%. Eleven CRVO patients (79%) had lower than 38% VSatO2. Twenty‐five DR patients (46%) had VSatO2 above 63% and the ratio of those outside normal limits increased with severity of retinopathy. Mean VSatO2 was lower in CRVO patients and higher in DR compared to healthy (p < 0.0001 for both comparisons). Eighty‐nine healthy individuals that were 60 years and older were compared to glaucoma and RP patients. In this healthy group, 5% of VSatO2 were above 64%. Six glaucoma (8%) and two RP patients (20%) had VSatO2 higher than 64%. Mean VSatO2 was higher in advanced glaucoma (p = 0.007) and RP (p = 0.05) compared to healthy.

Conclusions

Most CRVO patients have VSatO2 below the normal limit. Although there is overlap in VSatO2 between patients with DR and normal, a considerable proportion of DR patients fall outside the normal range. Most of the patients with glaucoma and RP were within normal limits for VSatO2.
Peter's anomaly in twins: a rare incidence with novel associations
Authors: Khayat H. , Tayyib A. , Alsulami R. , alkahtani A. , alzahrani S. , Almarzoki H.
Published: September 2016

Purpose

Peter's anomaly is a rare developmental malformation involving the anterior segment of the eye culminating in congenital blindness, with or without systemic associations. herein, we report an incidence of this anomaly in twins with novel associations.

Methods

Chart review, clinical and radiological assessment.

Results

The probands are 2 year old Saudi boys (twin I and twin II) born to consanguineous mates at 36 weeks following uneventful pregnancy. On examination: both twins were not blinking in response to light and were not able to fixate and follow a moving object with prominent horizontal nystagmus. Slit lamp examination demonstrated varying degrees of central leukoma (corneal opacity) associated with iridocorneal adhesion characteristic of type I peter anomaly in both twins. No catarctous changes were observed. A normal intraocular pressure with intact retinas were seen in both twins. Striking pupillary abnormalities include bilaterally underdeveloped pupil (twin I) and bilateral absence of the pupil (twin II). Ocular ultrasound: revealed bilateral vitreous hemorrhage mostly linked to deranged coagulation. Ocular MRI: showed bilateral microophtalmia and optic nerves hypoplasia with small optic chiasm in both twins. Systemic associations: both twins have coarse facial features and a thrombophilia state secondary to homozygous protein C deficiency; a rare thrombotic condition seen in 1\4,000,000 live birth. Twin II developed bilateral inguinal hernia and cryptorchidism

Conclusions

The novel concordance of peter's anomaly in these twins is probably an emerging evidence supporting the genetic basis of this defect. Optic nerve and optic chiasm hypoplasia along with the severe protein C deficiency and bilateral absence of the pupil are all important associations which have never been reported previously with this anomaly.
Modern aspects of demodex blepharitis treatment
Authors: Rykov S. , Petrenko O. , Shargorodskaya I.
Published: September 2016

Purpose

The aim of conducted study was to evaluate the modern eyelid hygiene procedures effectiveness in treatment of demodex blepharitis.

Methods

Sixty patients with blepharitis and proved presence of Demodex mites were randomized into two groups: Group 1 (n = 30) received the standard treatment of blepharitis (antimicrobial, anti‐allergic, non‐steroidal therapy, artificial tears as required); Group 2 received the standard treatment in complex with eyelid hygiene procedures twice a day during at least one month: applying sterile wipes (Blephaclean®, Thea), warm compresses and eyelid massage. Effectiveness of treatment for each patient in both groups was assessed by means of subjective daily 3‐grade scale of patient's comfort, and objective 3‐grade scales: level of eyelids edge inflammation daily, condition of tarsal glands by meibomiography weekly, presence of Demodex mites, eggs, larvas in acarogramm every 2 weeks.

Results

There was no significant difference in the average general grade of the clinical complaint between the groups at baseline. Both groups improved clinically with treatment but the subjective level of comfort was greater and appeared sooner in Group 2. By day 3, the grade of clinical complaints was significantly lower in Group 2 compared to Group 1 (1.3 vs. 2.6, p < 0.05). Similar average level (1.3) was gained in Group 2 only to 7th day. Redness and eyelid swelling reduced for at least 80% of subjects after 14 days in Group 1, but after only 10 days in Group 2. After 3 months Demodex specimens were still found in 28 (46.7%) patients in Group 1, but only in 10 (16.7%) in Group 2. There were no significant visual functions changes in both groups of patients during all follow‐up period.

Conclusions

The study demonstrated the important advantages of comprehensive eyelid hygiene procedures in addition to standard therapy of demodex blepharitis.
Classification and heritability of macular pigment spatial profile phenotypes using two‐wavelength fundus autofluorescence
Authors: Huntjens B. , Ctori I. , Mahroo O. , Williams K. , Hammond C.
Published: September 2016

Purpose

We investigated the frequency and heritability of macular pigment (MP) spatial profile phenotypes determined by objective and subjective profile classification based on fundus autofluorescence (FAF).

Methods

Between scans Coefficient of Repeatability (CoR) of MP optical density (MPOD) was calculated from two FAF scans (Spectralis, Heidelberg, Germany) of 40 participants (39 ± 8.6 years) acquired in a single session. We then analyzed two FAF scans acquired in a single session from 314 twins (157 pairs; 39 ± 8.8 years) and classified each MP profile as exponential, ring‐like or central dip by subjective visual assessment. Profiles were also classified objectively based on deviations larger than the CoR away from the exponential fit. We calculated kappa agreement of the profiling methods, case‐wise concordance of non‐exponential profiles for the 88 mono‐ (MZ) and 69 dizygotic (DZ) twin pairs, and profile heritability.

Results

Following visual subjective profiling, 64% showed an exponential profile, 27% presented ring‐like and 9% central dip profiles; case‐wise concordance was 0.80 for MZ and 0.41 for DZ twins. Following objective classification, 71% showed an exponential profile, 29% ring‐like profile and no central dip profiles were identified; case‐wise concordance was 0.74 for MZ and 0.36 for DZ twins. Heritability was calculated as 81.5% (95% CI 61.1–93.1). Between scan repeatability of profile classification showed good agreement objectively (κ = 0.85, 95% CI 0.69–1.00; p < 0.0005) and moderate agreement visually (κ = 0.48, 95% CI 0.23–0.73; p < 0.0005). Agreement of subjective versus objective profiling was low (κ = 0.23, 95% CI 0.04–0.42; p = 0.02).

Conclusions

MP profiles showed high heritability. Compared to visual assessment, objective profile classification is a more reliable method for future experimental studies using two‐wavelength FAF.
Metallothionein polymorphisms in a Northern Spanish population with Age‐Related Macular Degeneration (AMD)
Authors: Garcia M. , Álvarez L. , Fernandez Á. , Gonzalez‐Iglesias H. , Escribano J. , Fernandez‐Vega B. , Fernandez‐Vega Á. , Villota E. , Fernandez‐Vega L. , Coca‐Prados M.
Published: September 2016

Purpose

To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with aged‐related macular degeneration (AMD).

Methods

A case‐control study of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls matched by age and ethnicity were enrolled. DNA was isolated from peripheral blood and genotyped for fourteen MT SNPs (MT1A: rs11076161, rs 11640851, rs8052394 and rs7196890; MT1B: rs8052334, rs964372 and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636 and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software.

Results

The allelic frequency analysis revealed that rs28366003 in MT2A gene, showed the unique significant association with AMD (dry form; p = 4.40 × 10−4), increased disease susceptibility ranged from approximately 9.80 for the allele G (OR = 9.80, 95% CI: 1.11–86.25). The frequency of genotype AA at SNP rs28366003 was significantly lower in dry AMD cases than in control under a recessive association model (p = 2.65 × 10−4; AA vs. AG+GG) conferring protection from the disease (OR = 0.82, 95% CI: 0.71–0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the thirteen SNPs analyzed.

Conclusions

The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 in the MT2A gene with susceptibility to the dry form of AMD in the Northern Spanish population.
4 Gy radiotherapy in 6 patients with orbit marginal zone lymphoma: A small case series
Authors: Graeff E.
Published: September 2016

Purpose

To demonstrate therapeutic approach with low dose radiotherapy of 4 Gy in 6 cases of marginal zone lymphoma (2 lacrimal gland cases, 1 conjunctival case and 3 orbital cases itself)

Methods

Small case series of 6 patients with ocular marginal zone lymphoma, including diagnostic and therapeutic options

Results

In 6 patients (58–86 years) a marginal zone lymphoma of the orbit was diagnosed. A proptosis of the eye could be observed in one patient with lacrimal gland tumour as well as in three patients with orbital lesions itself. Two patients showed additional eye movement retraction accompanied by diplopia. In addition to a thorough ophthalmological examination, the staging of patient included ultrasound of the orbit, MRI of the head, gastroscopic examination and a PET‐CT of the whole body was performed. In all cases the diagnosis was made by ocular pathology. A focal radiotherapy with 4 Gy in two fractions was the only treatment in 5 cases. In one case a combination with additional systemical rituximab was necessary. A regression of all lesions could be observed and no tumour relapses occured until 7–29 months later.

Conclusions

In cases of orbit MALT lymphoma a gold standard radiotherapy of 30 Gy in 15 fractions was established. However in our small case series of 6 patients a complete regression of tumour mass was shown using 4 Gy in two fractions. Depending on the general state of the patient a reduced radiation therapy remains a usefull alternative.
Age related changes in axon guidance cues in the optic chiasm
Authors: Gomes Alves Da Conceicao R. , Barber A.C. , Martin K.R.
Published: September 2016

Purpose

Adult mammalian retinal ganglion cells (RGC) usually fail to regenerate axons post injury. Axon regeneration can be facilitated by several approaches but misguidance of regenerating axons at the optic chiasm is often observed and has been attributed to intrinsic proprieties of RGCs and/or a lack of extrinsic guidance cues in the adult visual system. This study characterizes the guidance cues present in the adult optic chiasm compared to the embryonic visual system.

Methods

Known guidance cues were examined in embryonic and adult optic chiasms of C57 mice by IHC. Radial glial markers (RC2/BLBP/Slit1) and developmental markers (Shh/Pax2) were assessed. RC2, BLBP, Slit1 and Shh are known as inhibitory guidance cues while Pax2 is a permissive guidance cue.

Results

Staining for glial markers RC2 & BLBP was detected immediately superior to the optic chiasm in coronal E15.5 samples. In coronal adult brain samples, RC2 & BLBP staining was observed in the optic chiasm midline; a very different distribution to E15.5 samples. No staining was observed in E15.5 or adult horizontal samples. Slit1 showed expression in the optic chiasm midline and optic tract at E15.5, but no staining was detected in the adult. Shh showed the same pattern as Slit 1 in the optic nerve at E15.5. Pax2 was present in optic nerves of both embryonic and adult samples.

Conclusions

Here the profile of guidance cues in the embryonic and adult visual system was characterized. In the developing embryo all markers, known to be crucial for establishing axonal pathways along the optic stalk and optic tract, were present. In the adult visual system Slit1 and Shh were absent, RC2 and BLBP were ectopically expressed, and Pax2 expression was low. These results may explain misguidance of regenerating RGC axons in the adult optic chiasm, highlighting the importance of understanding this environment.
Quantitative assessment of retinal permeability in the diabetic Akimba mouse: validation of a promising animal model for diabetic retinopathy
Authors: Hu T.T. , Vanheukelom V. , De Vriese A. , Feyen J.H.M.
Published: September 2016

Purpose

Unravelling the pathogenesis of diabetic retinopathy (DR) remains largely elusive, mainly due to lack of reliable diabetic animal models. The Akimba mouse (Ins2AkitaVEGF+/−) was generated by crossing Akita (T1D) with hVEGF‐overexpressing Kimba mice. The aim of this study was to validate this innovative diabetic model as a quantitative in vivo screening tool for anti‐leakage therapeutics in the context of DR.

Methods

Fluorescein angiography (FA) and OCT were implemented to assess retinal permeability and edema in Akimba compared to WT. FITC‐BSA perfusion and immunohistochemistry (IHC) were performed as well. Metamorph software (Leica) was used for quantitative analysis. The efficacy of anti‐VEGF therapy was investigated in Akimba mice via intravitreal injection of anti‐VEGF or vehicle.

Results

We report for the first time that quantitative analysis of FA images and FITC‐BSA perfused flatmounts revealed a significant increase of vascular leakage in the Akimba eye compared to WT. Analogous to the clinical DR situation, edema can be discerned in OCT scans of Akimba eyes. The effect of anti‐VEGF was monitored via longitudinal FA follow‐up before and 2–4 weeks after treatment. Anti‐VEGF treatment induced a significant decrease in vascular leakage (approx. 35%). IHC stainings confirmed that Akimba also exhibits other DR hallmarks such as inflammation, angiogenesis and fibrosis.

Conclusions

Current study demonstrated that the Akimba mouse is a powerful model for screening therapeutics against sight‐threatening retinal edema. This diabetic model also exhibits other main DR‐related processes, signifying the relevance of the Akimba model for DR research. Further validation will be crucial to strengthen the toolbox of in vivo DR models and ultimately to address the unmet need for effective next generation therapies for DR.
Coats' syndrome is associated with reduced pressure autoregulation in retinal arterioles
Authors: Herborg A. , Bek T. , Petersen L.
Published: September 2016

Purpose

Coats’ disease is a rare condition characterised by dilatation and hyperpermeability of retinal vessels typically affecting one eye, which may lead to severe visual loss. The disease is treated by retinal photocoagulation, but there is a need for a treatment more targeted at the pathogenic mechanisms of the disease, which are presently unknown.

Therefore, the purpose of the present study was to study the contribution of disturbed pressure and metabolic autoregulation to the pathogenesis of Coats’ disease.

Methods

Seven patients, three males and four females aged 34.1, 11–69 years (mean, range) affected by Coats’ disease in one eye were studied in both eyes using the Dynamic Vessel Analyzer (DVA). Video recordings were used to measure the diameter of larger retinal arterioles during rest, during an increase in the arterial blood pressure by lifting a hand weight and during stimulation of retinal metabolism by flickering light.

Results

The resting diameter of retinal arterioles was non‐significantly larger (mean ± SEM) in the affected eye (133.9 ± 8.3 μm) than in the unaffected eye (118.2 ± 8.6). The contraction of retinal arterioles during increased blood pressure secondary to isometric exercise was not significantly different from zero in arterioles, neither from the affected (0.1 ± 0.3%) nor from the unaffected (0.2 ± 0.6%) eye (p = 0.93).

Conclusions

Coats’ disease is accompanied with impaired pressure autoregulation in retinal arterioles, but there is no significant difference between the response in the affected and the non‐affected eye. The pathogenesis of Coats’ disease is due to other factors than diameter autoregulation in the larger retinal arterioles.
DNA methylation patterns in uveal melanoma derived FFPE samples correlate with survival
Authors: Ness C. , Grüner C.C. , Meza Zepeda L. , Moe M.C. , Noer A.
Published: September 2016

Purpose

To examine correlation of DNA methylation patterns of human uveal melanoma with survival.

Methods

FFPE samples from 24 UM patients undergoing enucleation of the eye in the period 1976–1989 were included. Inclusion was based on histopathological data, data from the Norwegian Cancer Registry and the Norwegian Cause of Death Registry. DNA was isolated from the FFPE samples and further bisulphite converted and restored according to Illuminas recommendations. Bisulphite converted DNA was then run on The Infinium HumanMethylation450 BeadChip assay (HM‐450K). Bioinformatics analyses were conducted in R statistical software, including analysis of copy number variation.

Results

Our data shows subclustering correlated with survival and mortality, additionally our data informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of UM.

Conclusions

The methylation profile of a given cancer can elucidate therapeutic targets, reveal biomarkers for early detection or identify high risk tumours. The present study is the first to report methylation changes in FFPE samples derived from UMs.
The change of Ganglion cell layer and Inner plexiform layer thickness in Type 2 DM with non‐proliferative diabetic retinopathy
Authors: Choi C. , Mun S.J.
Published: September 2016

Purpose

To evaluate each retinal layer's thickness change in Type2 DM patients with non‐proliferative diabetic retinopathy by using Optical Coherence Tomography (OCT)

Methods

We compared the thickness of each retinal layers by using OCT in 102 eyes, composed of normal control 60 eyes and NPDR 42 eyes. The thickness of these 7 layers were measured; retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE). We excluded the patient who had refraction rate <−6D or greater than +3D, patients who had retinal disease other than diabetic retinopathy, and patient who had preretinal membrane, macular edema,. The each layer's thickness was measured in 4 different regions, 3 mm away from central fovea; superior, inferior, nasal, and temporal direction.

Results

The thickness of each layer at all 4 different regions of GCL was thicker in normal control group than in NPDR. The average difference was 4.92㎛ and the result showed statistical significance in all four regions. Also, normal control group have thicker thickness in all four regions of IPL and the average difference was 2.67 μm. The nasal, temporal, superior regions showed statistically significant correlation, but the inferior region did not. However, normal control group and NPDR group had no significant difference in layer's thickness at RNFL, INL, OPL, ONL, RPE layers.

Conclusions

When we compared and measured each retinal layer's thickness by OCT, the normal group showed thicker layer's thickness in GCL, IPL layers than NPDR group but had no significant difference in RNFL, INL, OPL, ONL, RPE layers. In conclusion, the thinning of Inner retinal layers such as GCL, IPL might be used as a useful tool to diagnose and follow‐up in early diabetic retinopathy.
Systematic assessment of clinical methods to diagnose and monitor diabetic retinal neuropathy
Authors: Jenkins K.S. , Rowan A. , Layton C.
Published: September 2016

Purpose

Background and Purpose: Diabetic retinal neuropathy refers to retinal neural tissue damage occurring before diabetic retinopathy and fulfils many of the criteria for causality for the subsequent vasculopathy. Developing reliable means of measuring neuronal damage in diabetes may be important in efforts to prevent retinopathy. This study aimed to systematically assess current clinical measurements of diabetic retinal neuropathy.

Methods

A systematic search of the medical literature since 1984 was performed on PUBMED and EMBASE and the evidence supporting each identified method as an indicator for clinically important diabetic retinal neuropathy was graded relatively as strong, medium or weak according to criteria assessing its relationship to subsequent diabetic retinopathy, quality of supporting studies and published reproducibility.

Results

The systematic search yielded 6,421 results. Subsequent assessment by two independent investigators identified 601 multiple subject studies in humans assessing clinical aspects of retinal structure, function or psychophysics in the pre‐diabetic retina. Clinical methods assessed as being supported by relatively ‘strong’ evidence included FM‐100 hue colour vision changes, flash ERG b‐wave latency, flash multifocal b‐wave latency, scotopic flash ERG oscillatory potential amplitude and contrast sensitivity.

Conclusions

Conclusions/Discussions: The results showed moderately poor quality of extant evidence and indicate the best clinical methods for assessing diabetic retinal neuropathy remain to be confirmed. This is the first systematic assessment of the medical literature aiming to assess the breadth and validity of these methods and represents an early step in identifying and developing endpoints for use in trials designed to identify at risk patients or prevent diabetic retinopathy.
HuR/ELAVL1 expression in the human cataractous lens
Authors: Amadio M. , Marchesi N. , Govoni S. , Pascale A. , Petrovski G.
Published: September 2016

Purpose

Cataract is a common age‐related ocular disease having as major determinants oxidative stress, accumulation of protein aggregates and inflammation. It has been previously reported that the expression of the RNA‐binding HuR/ELAVL1 (Embryonic Lethal Abnormal Vision‐Like 1) protein, a master regulator of many cellular functions including cell stress response, is altered in various ocular disorders. Here we develop a method to assess, by means of several techniques, the expression of HuR/ELAVL1 in human lens.

Methods

Human anterior lens capsules (aLCs) were collected from patients undergoing uneventful cataract surgery for mixed nuclear and cortical cataracts after informed consent was obtained. Control aLCs were obtained from non‐cataractous lenses derived from human cadaver eyes removed within 24 h of death. The samples collected were snap frozen for further processing. Quantitative real‐time PCR, Western blotting and ELISA assay were used to determine the expression and distribution of HuR/ELAVL1 in the lenses.

Results

HuR/ELAVL1 is expressed at both mRNA and protein level in the epithelial cells and aLC from age‐related cataract patients and healthy subjects.

Conclusions

This is the first study documenting the expression of HuR/ELAVL1 in human lens. Considering the importance of oxidative stress in the development of cataract, further experiments will allow to determine whether HuR/ELAVL1, which exerts in other ocular pathologies a post‐transcriptional control of stress response genes, may play a role in cataract pathogenesis.
First cases of ocular dirofilariasis caused by drofilaria repens in Belgium
Authors: Smets M. , De Potter P.
Published: September 2016

Purpose

To report two different clinical ocular presentations of dirofilariasis caused by Dirofilaria repens and to illustrate the symptoms resulting from this rare condition.

Methods

A case series of 2 patients.

Results

The first patient was a 26 years old Romanian man complaining of 1 month‐duration painless swelling and redness of the right eye. Slit lamp examination revealed a scleral nodule located nasally with conjonctival hyperhemia. This condition was diagnosed as nodular scleritis and was initially treated with systemic nonsteroidal anti‐inflammatory medication and later, with systemic corticosteroids. Few weeks later, the patient came back to our clinic with the complaint of ‘something coming out of the eye’. The examination of the right eye revealed a partial extrusion of a whitish living worm. Excisionnal biopsy was performed under general anesthesia with complete removal of the parasitic cyst wich was adherent to the medial rectus muscle.

The second case was a 61 years old man complaining about a slowly growing and slightly painful nodule located at the internal portion of the left superior eyelid that as been diagnosed as an inflammatory versus infectious anterior orbital cyst. A B‐scan ultrasonography of the lesion documented an encapsulated cyst containing a living worm. The MRI confirmed the cystic component of this preseptal orbital and well‐defined lesion with heterogenous signal. Through transcutaneous approach, excisionnal biopsy of the cyst was performed. The opened cyst showed a living parasite.

Conclusions

Ocular Dirofilariasis is a rare condition that can easily be confused with tumoral and/or inflammatory lesion.