bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term prognosis of visual acuity in eyes with retinal pigments epithelial tears
Authors: Cha D.M. , Yoon S.W.
Published: September 2016

Purpose

To evaluate the long‐term prognosis of visual acuity in the eyes with retinal pigment epithelial (RPE) tears treated with anti‐vascular endothelial growth factor (VEGF) repeatedly.

Methods

Six eyes of 4 patients diagnosed with RPE tear were studied retrospectively. All the patients were followed up at least for 24 months. If there was evidence of active leaking from choroidal neovascular membrane despite RPE tear, anti‐VEGF injection was done repeatedly at the discretion of ophthalmologists.

Results

The mean visual acuity was 20/500 in the break of RPE tear, and the final visual acuity was 20/200. Foveal involvement of RPE tear was the most important factor of the final visual acuity. Four eye with RPE tears involved foveola, although final visual acuity remained more than 20/200 in the two eyes. Anti‐VEGF injection varied from zero to 19. More anti‐VEGF injection was associated with the better final visual acuity.

Conclusions

In our study, RPE tear did not suggest poor visual acuity in the long‐term follow up known to be different. Active anti‐VEGF injection might be needed to improve visual acuity in the long term follow up.
Mitochondrial inhibition of retinal Müller cells alter glutamate homeostasis and their ability to sustain retinal ganglion cells
Authors: Skytt D.M. , Vohra R. , Toft‐Kehler A.K. , Gurubaran I.S. , Bergersen L.H. , Kolko M.
Published: September 2016

Purpose

Glia‐neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing neurons with energy sources. In this study, we evaluated consequences of mitochondrial inhibition on retinal Müller cells and their ability to sustain RGCs.

Methods

The human Müller glial cell line, MIO‐M1, as well as mono‐ and co‐cultures of primary C56Bl/6 mouse Müller cells and RGCs, was used as cellular models. Cells were treated with 10 uM antimycin A to inhibit mitochondrial function. Changes in glutamate uptake in Müller cells were examined by kinetic assays with 3H‐l‐glutamate. Cell viability was evaluated by LDH assays. Regulations in gene and protein expression were evaluated by qPCR and western blotting.

Results

Mitochondrial inhibition significantly reduced protein‐ and mRNA expression of the major glutamate transporter, EAAT1, in Müller cells. Moreover, mitochondrial inhibition significantly decreased Müller cell glutamate uptake. Mitochondrial inhibition solely did not effect cell viability neither in Müller cells nor in RGC. However, simultaneous mitochondrial inhibition and starvation significantly decreased survival of both cell types. The protective effect of Müller cells in co‐cultures of primary RGCs and MCs were attenuated during mitochondrial inhibition.

Conclusions

Inhibition of mitochondrial function alter the neuroprotective characteristics of Müller cells by decreasing the expression of glutamate transporter and functional reduction of glutamate uptake. Furthermore, the impaired mitochondrial activity may affect the ability of Müller cells to maintain a cellular homeostasis in such way that their ability to protect RGCs may to suffer.
The Soft Shell Technique To Prevent Leakage of Perfluorocarbon Liquid Into The Subretinal Space
Authors: Hussain R. , Chan Y.K. , Lu Y. , Wu J. , Cheung H.C. , Shum H.C. , Sakamoto T. , Wong D.
Published: September 2016

Purpose

Perfluorocarbon liquid (PFCL) can be used to unfold the retina during vitreoretinal surgery. The subretinal migration of PFCL is an undesirable complication of its use in cases with posterior retinal breaks particularly with associated proliferative vitreoretinopathy. The ‘soft shell’ technique, which is the use of hyaluronate (HA) to cover the break, has been described to prevent such migration. Our aim is to assess the scientific basis of this technique.

Methods

A porcine retina model with two holes on a transwell was used to mimic the retinal breaks in vivo. HA solution was used to cover one of the holes. Perfluoro‐n‐octane (PFO) was added on top of the retina model incrementally using a syringe pump. The liquid level of PFO required to cause rupture of the PFO/aqueous interface with or without the HA coating at the two holes was measured. The interfacial tensions between the PFO against water and against HA solution with different aqueous concentrations were measured using pendant drop analysis.

Results

The interfacial tension between PFO and aqueous with HA coating (68.3 ± 1.29 mN/m) is statistically significant higher than the PFO/aqueous interface without hyaluronate (37.4 ± 3.40 mN/m) (p < 0.05). A higher PFCL level is required to cause the rupture of the PFO/aqueous interface at the hole with HA coating.

Conclusions

A greater hydrostatic pressure is needed to rupture the PFO/aqueous interface in the presence of HA coating at the break. The increase may due to the increase in interfacial tension at the interface. This study provides the scientific explanation how the soft shell technique may work.
Upregulated expression of heparanase in the vitreous of patients with proliferative diabetic retinopathy originates from activated endothelial cells and leukocytes
Authors: Abu El Asrar A. , Nawaz M.I. , Mohammad G. , Van den Eynde K. , Siddiquei M.M. , Mousa A. , de Hertogh G. , Geboes K. , Opdenakker G.
Published: September 2016

Purpose

To determine and interrelate the levels of heparanase, syndecan‐1 and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR), and to study the production of heparanase by human retinal microvascular endothelial cells (HRMEC) and its effect on HRMEC barrier function.

Methods

Vitreous samples from 33 PDR and 27 nondiabetic patients, epiretinal membranes from 16 patients with PDR and HRMEC were studied by enzyme‐linked immunosorbent assay, immunohistochemistry, and Western blot analysis. The effect of heparanase on HRMEC barrier function was evaluated by transendothelial electrical resistance.

Results

We showed a significant increase in the expression of heparanase, syndecan‐1 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls. (p < 0.0001 for all comparisons). Significant positive correlations were found between the levels of heparanase and the levels of syndecan‐1 (r = 0.75, p < 0.0001) and VEGF (r = 0.91, p < 0.0001) and between the levels of syndecan‐1 and the levels of VEGF (r = 0.78, p < 0.0001). In epiretinal membranes, heparanase was expressed in vascular endothelial cells and CD45‐expressing leukocytes. High‐glucose, TNF‐α and the combination of TNF‐a and IL‐1b, but not cobalt chloride induced upregulation of heparanase in HRMEC. Heparanase reduced transendothelial electrical resistance of HRMEC.

Conclusions

Our findings suggest a link between heparanase, syndecan‐1 and VEGF in the progression of PDR and that heparanase is a potential target for therapy of diabetic retinopathy.
EyeOP1 as a novel non‐invasive surgical treatment of glaucoma: an Italian multicenter study
Authors: Giannaccare G. , Bagnis A. , Gizzi C. , Vagge A. , Fresina M. , Del Noce C. , Sebastiani S. , Dormi A. , Traverso C.E. , Campos E.
Published: September 2016

Purpose

To evaluate safety and efficacy of a new non‐invasive ultrasound device for the surgical treatment of glaucoma.

Methods

This is a multicenter prospective study conducted at the University of Bologna and Genoa including 30 eyes of 30 patients with uncontrolled glaucoma. Of these, 15 patients were affected by primary open angle glaucoma (POAG), 10 by angle closure glaucoma (ACG) and 5 by neovascular glaucoma (NVG). The procedure was performed by an ultrasound generator probe with 6 piezoeletric transducers activated for 4, 6 or 8 sec (EyeOP1, EyeTechCare, Rillieux‐la‐Pape, France). Intraocular pressure (IOP) measurements were performed before and 1 day, 1–2 weeks, 1–3–6 months after the procedure. Primary outcomes were mean IOP reduction, qualified success (IOP reduction ≥20% without hypotensive medication adjunction) and complete success (as above plus IOP < 21 mmHg). Secondary outcomes were the correlations with glaucoma subtypes and exposure treatment time.

Results

The mean pre‐operative IOP was 30.1 mmHg (mean numbers of hypotensive drops and acetazolamide tablets were 2.7 and 0.8 respectively). Six months after treatment, mean IOP value was 20.2 mmHg (mean number of hypotensive drops and acetazolamide tablets were 2 and 0.3 respectively). IOP reduction was significant regardless glaucoma subtypes and exposure time (p < 0.001). In particular, higher IOP reductions were found in patients affected by ACG or treated with 8 sec exposure time (always p < 0.05). Qualified success was reached in 18 eyes, complete success in 6 eyes. Two patients had no IOP reduction with the need of subsequent surgery or increased number of drops. No major complications occurred.

Conclusions

This procedure appear to be safe and effective in reducing IOP in all glaucoma subtypes. In particular, IOP reduction was shown to be higher in ACG and 8 sec exposure groups.
Surface chemistry of the interactions of cationic nanoemulsions with human meibum films
Authors: Daull P. , Yokoi N. , Nencheva Y. , Georgiev G.A.
Published: September 2016

Purpose

Ikervis® (IKV) cationic nanoemulsions (CNE) were demonstrated to enhance tear film stability in vivo possibly via effect on tear film lipid layer (TFLL). Therefore the interactions of IKV and of binary and ternary mixtures of its constituents were studied with human meibum (MGS) films. The binary mixtures consisted of 2% mid chain triglycerides (MCT) blended with 0.005% cetalkonium chloride (CKC) and 0.3% Tyloxapol (e.g. MCT/CKC and MCT/Tylo respectively). The ternary mixture contained MCT/CKC/Tylo (2%/0.005%/0.3%). The impact of 0.1 μM bovine submaxillary mucin (BSM) on CNE/MGS interactions was also evaluated.

Methods

MGS and CNE oils were spread at the air/water interface of a Langmuir surface balance in range of 2D ratios (20/1, 10/1, 5/1, 3/1, 2/1 and 1/1) at two measurement regimes: with (i) MGS or (ii) total lipid amount kept constant. The films capability to reorganize during dynamic area cycling was evaluated. The layers dilatational rheology was probed via the step/relaxation method. Films structure was monitored with Brewster Angle microscopy.

Results

The binary mixtures showed limited spreading and miscibility with MGS resulting in poor mechanical properties. The ternary mixture and IKV spread and mixed well with MGS. At fixed MGS amount, the inclusion of CNEs enhanced the structure, properties and elasticity of the layers. At fixed total lipid, the films remained primarily elastic, but at high (≤3/1) CNE content the elasticity slightly decreased and heterogeneities in layers structure were observed. BSM enhanced the ternary mixture (IKV)/ MGS interactions.

Conclusions

At physiologically relevant MGS/CNE ratios MCT/CKC/Tylo and IKV interact favorably with MGS films. The positive effect of BSM suggests that polyanionic polysaccharides can enhance CNE/TFLL interactions in vivo.

Support: Collaborative study grant by Santen SAS, Evry, France.
Novel tissue‐targeted localized gene therapy for corneal scarring and neovascularization
Authors: Mohan R. , Gupta S. , Sharma A. , Anumanthan G. , Sinha P. , Fink M. , Tripathi R. , Raikwar S. , Giuliano E. , Rieger F. , Hesemann N. , Sinha N. , Chaurasia S.
Published: September 2016

Corneal scarring and neovascularization (NV) due to trauma, injury and/or infection are leading cause of global blindness. This presentation will provide an overview of corneal gene therapy and stipulate novel bench‐to‐bedside translational strategies for human application. The talk will include information about identified potent adeno‐associated virus (AAV) and nanoparticle vectors, simple and minimally invasive vector delivery techniques for delivering genes into desired corneal cells, and defined gene therapy approaches for introducing therapeutic genes selectively into corneal keratocytes or endothelium in vivo through single application of vector employing customized delivery techniques. Further, talk will discuss cornea‐specific mechanisms driving pathologic process, novel molecular targets for interrupting TGFβ1 signaling pathways, and therapeutic genes identified from basic‐science corneal wound healing investigations performed in my lab laboratory using established small and large animal and donor human corneas. Finally, it will show potential of single‐ and two‐gene combination therapy given locally in the cornea via optimized methods in inhibiting and eliminating corneal scarring and neovascularization in vivo in preclinical rabbit studies. The optimized gene therapy approaches could be easily applied in a clinical setting, if safety and toxicity are proven.
Why risking the satisfaction and the compliance of your newly diagnosed glaucoma patient? – The PASSY survey
Authors: Munoz‐Negrete F.J. , Erb C. , Stalmans I. , Lemij H.
Published: September 2016

Purpose

Preserved latanoprost eyedrops efficacy have been demonstrated in intraocular pressure lowering. New marketed first formulation of a preservative‐free (PF) latanoprost (Monoprost®) was a further step to improve tolerance. Relatively little is known about newly diagnosed patient's tolerance to their first prostaglandin treatment. That's why naive patients were included in the PASSY survey (PAtient Satisfaction SurveY).

Methods

PASSY is an epidemiological, retrospective survey carried out in 6 European countries (BE, DE, NL, PT, SP, CH). Newly diagnosed OHT/glaucoma patients (naïve) treated with a preservative‐free latanoprost (Monoprost®) for 3 months were included. The results of naive patients are reported here for the first time.

Results

23.8% of the total number patient (1,872) were naïve patients (435) with 59% female and 41% male. Their average age was 64.2 ± 12.96 years (SD). Based on automated visual field damage, 79.1% had mild glaucoma, 17.7% moderate and 3.2% advanced. As for tolerance, 97.3% of the naïve patients declared to be satisfied (50.1%) or very satisfied (47.2%) with PF latanoprost. Mean tolerance of evaluated with a Visual Analog Scale (VAS; 0 mm: very bad tolerance – 100 mm: very good tolerance) was 86.7 ± 13.93 mm for PF latanoprost. Of those naive patients using PF latanoprost, only 1.5% developed an OSD (82.1% mild, 14.3% moderate and 1.6% severe).

Conclusions

After 3 months of Monoprost® treatment, 97.3% of naïve patients were satisfied by their first PF formulation latanoprost treatment. Ocular surface disease occurred in as littel as 1.5% of naïve patients. Because glaucoma management is severely hindered by non‐compliance with medication and given that PF latanoprost is now available at a modest cost, this seems like a suitable first‐choice therapy for glaucoma.
Immunosuppression with a subconjunctival implant releasing dexamethasone in a rabbit model of penetrating keratoplasty
Authors: Crouzet E. , He Z. , Perrache C. , Basset T. , Delavenne X. , Peoc'h M. , Gain P. , Thuret G.
Published: September 2016

Purpose

Rejection occurs in 20–30% of cases after penetrating keratoplasty (PK). Most often, its prevention relies only on steroid eyedrops but topical treatments expose to limited therapeutic adherence. Aim: to assess efficacy of continuous immunosuppression using a subconjunctival implant releasing dexamethasone (SCIRD) in a rabbit model of PK.

Methods

7.5 mm PK were performed in NZW rabbits. After randomisation they received either a SCIRD (Ozurdex, Allergan) (n = 8), dexamethasone eyedrops (1 mg/ml, Dexafree, Thea) 3 times a day (n = 6), or 0.9% NaCl (n = 6). The running suture was left in place to stimulate angiogenesis. Weekly follow‐up by digital slit lamp and anterior segment OCT. Images were analysed blind to the treatment for transparency, neovessels, and central corneal thickness (CCT). After 5 or 6 weeks, animals were killed and corneas were processed for standard histology.

Results

Placebo group: constant early neovascularization growing to neovessels penetrating the graft on >270° after 5 weeks + rejection (opaque graft, 360° neovessels, CCT > 500 μm) in 50% of cases. Eye drops and implants groups: similar evolution, without rejection after 6 weeks and normal CCT. Moderate neovascularization occurred in 5/6 rabbits treated with eyedrops and 6/8 treated with the implant. Histology confirmed clinical diagnosis in all cases. The implants disappeared after 3–5 weeks. No adverse effect.

Conclusions

Despite a severe rejection model, a SCIRD was not less efficient than eye drops to prevent rejection during the first 6 weeks. These findings highlight the potential benefit of subconjunctival implants of steroids after corneal graft.
Optical coherence tomography to distinguish Parkinson disease versus supranuclear progressive palsy
Authors: Rebolleda G. , Sanchez Sanchez C. , Martinez Castrillo J.C. , Gonzalez Lopez J.J. , Oblanca Llamazares N. , Muñoz‐Negrete F.J.
Published: September 2016

Purpose

The aim of the study was to examine patterns of peripapillary andretinal layer damage as a potential marker of neurodegeneration in Parkinson'sdisease (PD) compared to progressive supranuclear palsy (PSP) with 2 SD‐ OCTdevices.

Methods

Peripapillary retinal nerve fiber layer (pRNFL), macular thickness (MT)and ganglion cell layer inner plexiform analysis (GCA) by Cirrus and pRNFL analysis and automaticsingle retinal layers macular segmentation by Spectralis were used to evaluate38 patients with PD and 15 patients with PSP.

Results

Mean average and superior RNFL by Cirrus were thicker in PD compared to PSP (p = 0.001). The mean central, superior, supero‐temporal and infero‐temporal RNFL thicknesses by Spectralis were also significantly higher in PD compared to PSP (p < 0.05). Using Cirrus OCT, mean MT and all measurements by GCA were significantly higher in PD compared to PSP (p < 0.002). The AUC was larger for minimum GCIPL (0.912) than for average GCIPL thickness (0.850). A minimum GCIPL thickness cut‐off value of 69 μm, was able to differentiate PSP from PD (Sensitivity: 91.7%; Specificity: 72.7%). Minimum and average GCIPL thicknesses significantly correlated with Hoehn and Yahr score (p < 0.05), and with UPDRS (Unified Parkinson's Disease Rating Scale) (p < 0.005).

Conclusions

Thedifferential diagnosis of Parkinsonian disorders is clinical one and not alwayseasy, especially at the onset of disease. In thecurrent study, the minimum GCIPL thickness was the most sensitiveparameter to differentiate PD from PSP and it was significantly correlated withneurological score. These findings may facilitate the differential diagnosisand give insight into the degenerative processes of atypical parkinsonian syndromes.
Corneal imaging and densitometry measurements to monitor fuchs progression and treatments outcomes
Authors: Alzahrani K. , Carley F. , Brahma A. , Morley D. , Hillarby M.C.
Published: September 2016

Purpose

Fuchs’ dystrophy is a degenerative disease of the corneal endothelium leading to corneal edema and eventually to loss of vision. There are several treatment options including corneal transplantation, which can be full (Penetrating Keratoplasty) or partial (Descemet's stripping automated endothelial keratoplasty) thickness. Disease progression and treatment out comes are normally monitored by corneal thickness and visual acuity. In this study, we have used the new densitometry software for the Oculus Pentacam to compare the corneal clarity measurement between Penetrating Keratoplasty (PK) and Descemet's Stripping Endothelial Keratoplasty (DSAEK) in patients with Fuchs dystrophy

Methods

A retrospective comparative study was carried out at Manchester Royal Eye Hospital. Data collection of one year after the corneal transplantation for 23 Fuchs dystrophy patients, including; best corrected visual acuity (BCVA), corneal densitometry, central corneal thickness (CCT) was analysed

Results

Analysis of densitometry measurements found higher corneal densitometry after PK than DSAEK in the posterior layer between 2 and 6 mm from the centre but it was not significant. There were no significant correlation between CCT and corneal densitometry. Corneal densitometry was found to be significantly correlated with BCVA inthe central 0–2 mm zone. This correlation differed in corneal depth, in PK it was with the posterior layer but in DSAEK it was with the anterior stroma These difference were found to be significant between the two group (p˂005.).

Conclusions

There were different outcomes in the corneal densitometry measurement after different type of corneal transplantation. Oculus Pentacam provides an objective evaluation to monitor the cornea status. Further investigation with prospective design, a longer study period and larger sample size are now underway.
Molecular study of the MFRP gene in patients with posterior microphthalmia (MCOP) supports its role in autosomal recessive MCOP pathogenesis
Authors: Almoallem B. , Arno G. , De Zaeytijd J. , Hull S. , Suzani M. , de Ravel T.J.L. , Webster A. , Leroy B.P. , Moore T. , De Baere E.
Published: September 2016

Purpose

Posterior microphthalmia (MCOP) is a rare developmental disease restricted to the posterior segment of the eye. To date, mutations in the MFRP gene, encoding a frizzled‐related protein, reported in autosomal recessive MCOP (arMCOP).Here, we aimed to identify the genetic cause of arMCOP in seven patients from different ethnicity.

Methods

All patients underwent detailed ophthalmological evaluations and Sanger sequencing of the of MFRP (NM_031433.2). Two patients originating from a consanguineous marriage underwent homozygosity mapping using SNP arrays.

Results

MFRP was found in a homozygous region of 10.2 and 6.2 Mb in two patients respectively. Overall, eight distinct MFRP mutations were found in the patients studied. Five patients were homozygous for:two missense variants with predicted pathogenic effect (c.1231T > C, novel;c.1549C > T, known) and three frameshift mutations (c.1090_1094del, novel; c.498del and c.498dup, known). Moreover, a sixth patient was compound heterozygous for a nonsense mutation (c.955C > T, novel) and novel deletion of 6.2 kb (c.16088_54+40delinsA),predicted to abolish the transcription initiation site. The seventh patient was heterozygous for a known frameshift mutation (c.491_492insT),no second mutation was found so far. All patients had short axial length (13–16.5 mm),reduced visual acuity (0.15–0.8 logMAR) and hyperopia (+13D to +17.25D).Crowded optic discs were noticed in 7/7 and macular folds in 3/7 patients. Optical coherence tomography showed intraretinal cysts in 5/7 patients. Peripheral pigmentary changes were observed in 5/7 patients.

Conclusions

Eight distinct MFRP mutations four of which novel and the first report of a genomic rearrangement. No clear genotype‐phenotype correlations could be observed. This identification might offer opportunities for potential gene‐based therapies suggested by Dinculescu et al (2012).
Trabeculectomy: long term visual field stability
Authors: Bobat H. , Lockwood A. , Kirwan J.F.
Published: September 2016

Purpose

Evaluation of 10 year visual field (VF) stability following trabeculectomy for open angle glaucoma (OAG).

Methods

Consecutive visual fields (VFs) of patients who had undergone primary trabeculectomy for OAG were reviewed for evidence of glaucomatous progression. Progression rate was determined by the difference between the better of the last two Mean Deviations (MDs) and the better of the first two MDs (or first and last MD if <4 VFs were available), divided by time. <0.3 dB/year was classified as stable, ≥0.3 dB/year as borderline progression and ≥0.5 dB/year as definite progression. Eyes with <3 reliable VFs over <2 years were excluded.

Results

143 eyes (120 patients) underwent trabeculectomy; 84 (66 patients) met the inclusion criteria. Mean follow‐up was 11.2 ± 1.71 years; IOP (mean ± SD) at final review was 11.5 ± 4.2 mmHg. Mean progression rate was 0.14 dB/year; 66.7% (56/84) eyes were stable, 15.5% (13/84) showed evidence of borderline progression and 19% (16/84) definite progression.

Of those with definite progression, 62.5% (10/16) failed to achieve good IOP control post‐operatively (final IOP was >13 mmHg) or had VF loss attributable to causes other than glaucoma. Only 6 (7.1%) eyes progressed despite good IOP control.

Conclusions

In the majority of cases, current trabeculectomy surgery can achieve VF stability or markedly curtailed progression for at least 10 years.
Augmentation of corneal graft tissue with UV‐riboflavin crosslinking: a pilot study in glaucoma drainage device patients
Authors: Stone D. , Ahmad S. , Craven R. , Owaidhah O.
Published: September 2016

Purpose

Glaucoma drainage device (GDD) surgery has gained popularity, with outcomes equivalent to trabeculectomy in some studies. However, erosion of the tube through the overlying conjunctiva may occur in 5–10% of patients. Donor cornea tissue has been utilized as a patch graft for GDD surgery, with positive short‐term results. We report interim results of an ongoing pilot study to determine the feasibility and safety of utilizing the anterior lenticule from Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) corneas, with augmentation by corneal crosslinking.

Methods

Prospective study of 10 patients undergoing GDD surgery. The anterior corneal lenticule (300–350 μm) from a DSAEK donor tissue was placed epithelial side down in a well, and allowed to soak in riboflavin solution (Vibe‐X, Avedro) for 15 min. Then 8 mW/cm2 ultraviolet irradiation was applied for 15 min, for a total energy of 7.2 J/cm2. The tissue was then bisected and placed in Optisol GS media at 4°C. When ready to be implanted, the tissue was sutured over the glaucoma device, then covered with recipient conjunctiva as per the usual technique. Representative sections were examined with H&E and Masson Trichrome histological stains. Intraoperative and postoperative findings and complications were documented, with all subjects reaching the 3 month visit of an anticipated 36 month study.

Results

After 15 min the grafts demonstrated complete saturation with riboflavin. Histology revealed no apparent demarcation line, supporting a full‐thickness treatment effect. There were no intraoperative complications, no postoperative infections, and no unexpected surgical difficulties.

Conclusions

UV‐riboflavin crosslinking of corneal tissue appears to be a safe modification of GDD surgery, and warrants ongoing study.
Genetic and phenotypic traits of staphylococcus epidermidis strains causing post‐cataract endophthalmitis compared to commensal conjunctival flora
Authors: Chiquet C. , Aptel F. , Musson C. , Boisset S. , Maurin M.
Published: September 2016

Purpose

The aim of this study was to evaluate the virulence and antibiotic resistance traits of S. epidermidis strains causing post‐cataract endophthalmitis compared to those of the normal conjunctival flora in non‐infected control patients.

Methods

This prospective study included 22 patients (22 eyes) with acute post‐cataract endophthalmitis and 72 uninfected control patients (72 eyes). Antibiotic susceptibilities were evaluated using the Vitek II® automated system. These strains were then tested for the presence of eight virulence genes (icaA, icaB, icaC, icaD, atlE, aap, and capA), the insertion sequence IS256, and the mecA gene coding for methicillin‐resistance.

Results

Culture of 72 conjunctival samples collected from 41 patients allowed isolation of 43 S. epidermidis strains. The strains from the endophthalmitis group patients displayed higher prevalence rates for aap, atlE and mecA genes carriage compared to those of the control group (77% vs. 42%, p = 0.007; 100% vs. 79%, p = 0.02; and 54% vs. 11%, p < 0.001, respectively) and more frequently harbored simultaneously the mecA and icaA genes (13%) compared to the control group (2.3%, p = 0.01). They were also significantly more resistant than control strains to methicillin, fluoroquinolones, and the aminoglycosides.

Conclusions

A higher capacity of adhesion to intraocular lens and formation of biofilms, and a higher resistance to antibiotics were found in S. epidermidis strains causing post‐cataract endophthalmitis compared to those of the normal conjunctival flora. The selection of such strains in endophthalmitis patients could be related to their specific virulence traits and/or their resistance to antibiotics used for prophylaxis of endophthalmitis.
Does macular pigment optical density really matter in children?
Authors: Erkan Turan K. , Cankaya A.B. , Taylan Sekeroglu H. , Inam O. , Karahan S.
Published: September 2016

Purpose

To evaluate macular pigment optical density (MPOD) in healthy children and to compare with strabismic children.

Methods

The study included 54 healthy children and 41 children with strabismus. All underwent ophthalmological evaluation, macular pigment optical density measurement (Macular Densitometer, Macular Metrics II, Rehoboth, MA, USA) and questionnaire about food habits. Children with strabismus were graded in terms of fixation preference. Gestational age, birth weight and body mass index of the participants were matched.

Results

The mean age was 9.87 ± 2.39 years in healthy children and 9.07 ± 2.07 years in children with strabismus (p > 0.05). Mean MPOD was 0.23 ± 0.25 in healthy eyes and 0.25 ± 0.27 in non‐preferred eyes of strabismic children (p > 0.05). MPOD was significantly higher in preferred eyes of strabismic children (0.43 ± 0.34, p = 0.001). There was a significant difference of MPOD between both eyes in patients with different grades of fixation as patients with grade 1, 2, 3 preference had interocular difference of MPOD whereas patients with grade 4 preference (free alternation) had similar MPOD in both eyes (p = 0.008). No relation between MPOD and age, food habits, gestational age, birth weight and body mass index was demonstrated. Furthermore, interocular visual acuity difference, type of strabismus and angle of deviation were found to have no effect on MPOD.

Conclusions

Preferred eyes of children with strabismus seem to have higher MPOD compared to non‐preferred eyes. This difference may emerge from the higher tendency of pushing the button while preferred eye is under testing. Similar MPOD in healthy and non‐preferred eyes remain unexplained and deserve further investigation. This result should been enlightened and it should be kept in mind that MPOD measurement require good cooperation and its results should be carefully interpreted.
Two novel KERA mutations causing cornea plana in a Czech family and associated phenotypes
Authors: Skalická P. , Dudakova L. , Liskova P.
Published: September 2016

Purpose

To identify the molecular genetic cause in a previously not reported Czech family with the occurrence of cornea plana in two siblings.

Methods

Detailed ophthalmological examination and direct sequencing of the KERA coding region in the proband followed by target analysis of the identified mutations in other family members.

Results

The family was not aware of any consanguinity. Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887‐1G>A in KERA were detected in both affected individuals. The mother was a heterozygous carrier of c.887‐1G>A and the father of c.209C>T. In silico analysis supported the pathogenicity of both mutations. The younger brother, aged 13 years, had typical ocular phenotype of cornea plana with keratometry readings bellow 30 D, shallow anterior chamber, indistinct limbus and central corneal opacity. Corneal endothelial cell morphology was normal in the right eye; in the left eye specular microscopy images could not be taken. In the older brother, aged 20 years, marked thinning with protrusion in the superior part of the left cornea was present resulting into mean keratometry of 47.2 D. No corneal endothelial cell pathology was observed by specular microscopy bilaterally.

Conclusions

The identification of two novel heterozygous mutations in the second Czech family with cornea plana does not support the hypothesis of a founder effect. Marked corneal thinning and protrusion in cornea plana is a very rare finding and longitudinal follow‐up evaluation needs to be performed to determine its possible progressivity.
Primary intraocular lymphoma and flow cytometry analysis of the vitreous – a case report
Authors: Romanowska Dixon B. , Karska Basta I. , Kubicka‐Trzaska A.
Published: September 2016

Purpose

To present a case of chronic bilateral uveitis which preceded diagnosis of B‐cell intraocular lymphoma based on the results of a vitreous flow cytometry analysis.

Methods

We conducted a retrospective and interventional case report.

Results

A 46‐year‐old woman was admitted to the Department of Ophthalmology of Jagiellonian University in Krakow witha 6‐months history of deterioration of vision in both eyes. Clinical examination showed the presence of bilateral chronic uveitis with the presence of subretinal multiple yellow lesions. The standard screening panel laboratory tests for uveitis showed no pathology. MRI of a central nervous system was within normal limits. Because of no improvement in BCVA andthe presence of active intraocular inflammation inspite of long‐term systemic steroids and immunosuppressant therapy a diagnostic 25G pars planavitrectomy was performed. A 1.5 cc of non‐diluted vitreous was taken and analyzed using a flow‐cytometry. The cytometric analysis of the vitreous aspirate showed the presence of 67.5% of lymphocyte B population (CD3+; CD2+, CD5+; CD7+, CD45RO+; CD38+, HLADR+/−; CD45RA−) with CD4/CD8 = 8.5. The diagnosis of B‐cell lymphoma was established.

Conclusions

Flow cytometry analysis of vitreous aspirate may be a precious diagnostic tool in unclear clinical cases of intraocular inflammation, in eyes suspected for intraocular neoplastic process.
Outer retinal reflectivity on En‐face OCT as a new tool to detect early stage hydroxychloroquine maculopathy
Authors: Viotte A. , Bigan G. , Flores M. , Girard C. , Delbosc B. , Saleh M.
Published: September 2016

Purpose

Hydroxychloroquine (HCQ) maculopathy can cause irreversible vision loss. Alteration of the parafoveal photoreceptors has been reported to be one of the earliest histopathological sign. The relationship between the ellipsoid zone reflectivity and cone density was recently demonstrated. The main objective of the study was to measure the outer retinal reflectivity in patients taking a HCQ regimen without proven toxicity on routine screening tests. The second objective was to investigate the relationship between the reflectivity measured and the screening tests outcomes.

Methods

Consecutive patients visiting for HCQ toxicity screening in the Besançon University Hospital were included. All patients underwent a complete ophthalmic examination with a 10‐degrees automated perimetry (with measurement of the foveal threshold and the mean 2–5°), fundus autofluorescence, multifocal electroretinogram (with measurement of N1, P1 and N2 amplitudes in a 2–5° range) and spectral‐domain optical coherence tomography with en‐face reconstruction of the ellipsoid zone and the retinal pigment epithelium (with measurement of the absolute reflectivity expressed in greyscale in the 2–5° range).

Results

76 eyes were studied (39 patients). None of them displayed a toxic maculopathy. The cumulative dose for HCQ ranged from 24 to 2,400 g (706 g ± 620). Bivariate analysis showed a decreased in ellipsoid reflectivity with escalating cumulative doses of HCQ (linear regression, p < 0.0001, r²: 0.3). Reflectivity was also correlated with N1, P1 and N2 amplitudes (p < 0.05). Finally, reflectivity was statistically correlated with 5 degrees threshold perimetry (p < 0.005).

Conclusions

Parafoveolar ellipsoid reflectivity with en face OCT could be a rapid, repeatable and quantifiable biomarker allowing to detect the HCQ maculopathy earlier than any other screening method currently used.
Introducing and measuring cornea and sclera deformability parameters on the basis of Schiøtz tonometry: mathematical modeling and clinical evaluation in Primary Open Angle Glaucoma (POAG)
Authors: Iomdina E.N. , Lyubimov G. , Moiseeva I. , Stein A. , Kiseleva O. , Archakov A.
Published: September 2016

Purpose

To obtain additional information on the biomechanical status of the eyeball on the basis of static loading by the Schiøtz tonometer, to be applied to POAG.

Methods

Earlier, we proposed a mechanically correct theory of Schiøtz tonometry, which represents the eyeball as a shell characterized by two elastic constants separately responsible for the cornea and the sclera properties, and used the theory here. We examined 41 patients (43 eyes) aged 55–72 (mean age 64 ± 4.0 years) with non‐operated POAG, including 20 eyes with early and 23 eyes with advanced stage of POAG. 15 patients with no eye pathology of the same age group served as control. The examination included differential Schiøtz tonometry using a GlauTest 60 tonograph.

Results

Applicability limits are estimated for the standard relations used in processing the clinical data. Based on differential tonometry, we introduced a coefficient γ, equal to the ratio of the IOP difference to the plunger weight difference, and looked at how γ depends on the cornea and sclera stiffness and the true IOP. The γ coefficient, which mainly characterizes the scleral rigidity, was determined at 1.65 ± 0.25 mm Hg/g for the early stage of POAG and 1.88 ± 0.13 mm Hg/g for the advanced POAG stage, with a control group average of 1.47 ± 0.10 mm Hg/g (p < 0.05). On average, γ was 27% greater for the POAG patients, whereas the mean Friedenwald's rigidity coefficient only differed from the norm by 7%.

Conclusions

Changes in the mechanical parameter proposed testify to changes in the elastic characteristics of the eyeball in POAG. The coefficient γ reflects individual abnormalities of the biomechanical status of the sclera for the glaucomatous eye more adequately than Friedenwald's rigidity coefficient. Practical recommendations are proposed.

The study was supported by RFBR (project No. 14‐01‐00475).
MiRNA‐126 regulation in corneal neovascularization
Authors: Zhang H.
Published: September 2016

A microRNA (abbreviated miRNA) is a small non‐coding RNA molecule (containing about 22 nucleotides) that functions in RNA silencing and post‐transcriptional regulation of gene expression. miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins and resemble the small interfering RNAs (siRNAs) of the RNA interference (RNAi) pathway. The human genome may encode over 1,000 miRNAs, which appear to target about 60% of the genes of humans and other mammals. A miRNA is complementary to the 3′ UTR of one or more messenger RNAs (mRNAs) and has post translational regulation of the mRNAs. MiRNAs are known to be involved in the normal functioning of eukaryotic cells as well as many diseases. However, little is known about the role of microRNA in ocular diseases. We tested the microRNA expression in both corneal neovacualrization patients and animal models.
Normative values of retinal vessel oximetry in healthy children against adults
Authors: Waizel M. , Kazerounian S. , Türksever C. , Todorova M.G.
Published: September 2016

Purpose

Retinal oximetry (RO) has been established as a non‐invasive method to analyze oxygen saturation in retinal vessels. The aim of our study was to compare metabolic (oxygen saturation) and anatomical (retinal vessel diameter) RO parameters of healthy children against adults.

Methods

A total of 157 eyes of 79 healthy subjects were examined: 20 eyes of children (7–18 year) were compared to adults of different age groups [20–29 year (n = 16); 30–39 year (n = 46); 40–49 year (n = 38); 50–59 year (n = 25), 60–87 year (n = 12)]. RO was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A‐SO2) and venules (V‐SO2) were measured and their difference (A‐V SO2) was calculated. In addition, we evaluated the corresponding diameter in retinal arterioles (D‐A) and venules (D‐V). For statistical evaluation non‐parametric tests (Friedman test for multiple comparisons, paired Wilcoxon rank sum test for pairwise comparisons) were performed.

Results

Children showed statistically significant lower arterial oxygen saturation values (A‐SO2) compared to all adult subgroups (Friedman test, p = 0.0005). Although not statistically significant, the values of V‐SO2 (p = 0.06) and A‐V SO2 (p = 0.30) showed a trend to be lower in children. The D‐A (p = 0.49) and D‐V (p = 0.82) values were not significantly different between groups.

Conclusions

These data indicate that the retinal oxygen metabolism changes throughout lifetime. Therefore, normative data for different age groups are mandatory.
Ultrafiltration rate in hemodialysis does not affect mean ocular perfusion pressure or intraocular pressure in end‐stage renal disease
Authors: Leal I. , Cordeiro Sousa D. , Couceiro R. , Bigotte Vieira M. , Noélia L. , Resina C. , Neves F. , Gomes da Costa A. , Pinto F. , Marques‐Neves C. , Proença H.
Published: September 2016

Purpose

Ultrafiltration rate (UFR), the rate at which fluid is removed during hemodialysis (HD), has been increasingly recognized as a potential modifiable cardiovascular risk factor in HD patients. High UFR has been shown to promote non‐physiological fluid shifts and hemodynamic instability, which may contribute to tissue ischemia. Our goal was to evaluate if changes in mean ocular pressure perfusion (MOPP) and intraocular pressure (IOP) could be related to UFR.

Methods

Prospective cohort study including 16 eyes of 16 black patients (8 women) with end‐stage renal disease (ESRD) under HD. Haemodynamic data and IOP (measured with Tonopen®) were obtained 1 h before and after HD. MOPP was calculated as MOPP = 2/3(MAP) − IOP. STATA v.13.0 was used as statistical package and a p‐value of 0.05 was considered statistically significant.

Results

Mean age of ESRD patients was 46.81 ± 7.72 [range 28–60] years. The mean time under HD was 17.38 ± 14.67 months. MOPP before and after HD were 52.7 ± 13.0 and 51.4 ± 13.1 mmHg, respectively. The difference between MOPP before and after HD was not statistically significant (p = 0.15). UFR applied to these patients was 673.6 ± 198.7 [range 250–1000] ml/h. When applying a regression model, this difference in MOPP was not associated with the UFR (p = 0.56), in both crude and adjusted analysis.

Conclusions

In patients with ESRD, changes in MOPP do not seem to be related with UFR. Although UFR has been claimed to be culprit of tissue ischemia, still ill‐defined vaso and barorregulatory mechanisms may play a role in protecting the eye from ischemia during this hemodynamic challenge.
Lamina cribrosa displacement after trabeculectomy in pseudoexfoliation and primary open angle glaucoma
Authors: Kadziauskiene A. , Strelkauskaite E. , Asoklis R. , Lesinskas E. , Schmetterer L.
Published: September 2016

Purpose

To compare the changes in lamina cribrosa depth between eyes with pseudoexfoliation glaucoma (PEXG) and primary open angle glaucoma (POAG) following trabeculectomy.

Methods

The prospective study included 37 glaucomatous eyes (23 PEXG and 14 POAG). The lamina cribrosa depth was measured using enhanced depth imaging spectral domain optical coherence tomography before trabeculectomy and three months after the surgery. The postoperative displacement of the lamina cribrosa (LCD) was compared between the PEXG and POAG groups. The relationship between LCD and intraocular pressure (IOP) reduction was analysed.

Results

There was a significant reduction in the mean (±SD) IOP in PEXG and POAG eyes following the trabeculectomy (14.2 ± 7.2 mmHg, p < 0.001, 14.4 ± 7.5 mmHg, p < 0.001; respectively). In total, the median (IQR) depth of the lamina cribrosa decreased from 469.4 (209.3) μm at baseline to 443.7 (145.5) μm three months after the surgery (p < 0.001). No significant difference in median (IQR) postoperative lamina cribrosa displacement between the PEX and POAG patients was found (42.1 (50.8) μm and 22.8 (53.9) μm, respectively; p = 0.186). The anterior displacement of lamina cribrosa after trabeculectomy did correlate significantly neither with the baseline IOP nor with the IOP reduction in the examined groups.

Conclusions

In glaucomatous eyes the anterior displacement of the lamina cribrosa occurred after the IOP reduction following trabeculectomy. However, no differences in the decrease of the lamina cribrosa depth were found between the pseudoexfoliation glaucoma and primary open angle glaucoma patients. The association between the lamina cribrosa displacement and IOP reduction was not significant.
In the search of biomarkers for thyroid associated orbitopathy (TAO)
Authors: Kishazi E. , Dor M. , Eperon S. , Gracià M.D.L.A. , Fouda C. , Oberic A. , Hamédani M. , Turck N.
Published: September 2016

Purpose

Tears are known as lubricating the eyes and ensuring nutrition and protection of the surrounding ocular tissues. However, its composition is the result of a dynamic system, which is dependent on various stimuli, including ocular and systemic diseases. Here, we propose that, tears could represent an innovative source of biomarkers in thyroid‐associated orbitopathy (TAO) disease.

Methods

Schirmer's test was adopted to collect tears from TAO [n = 20, 3 males, mean age (±SD): 46.0 years (±13.0)] and healthy patients [n = 18, 8 males, 45.4 years (±18.7)]. Independent isobaric proteomics experiments were carried out and analyzed on a linear trap quadrupole Orbitrap Velos Pro. Easyprot software was used to obtain protein identification and quantification (2 unique peptides, 1% FDR, ratio<0.66 or >1.5, p‐value>0.05). Biological process and pathways were analyzed using Ingenuity pathway analysis software (6.7 version). Verification of proteins was performed by Western Blot or immunoassays.

Results

Globally, 646 proteins were identified and 62 were considered as differentially expressed (27 up‐and 35 downregulated). Interestingly, among them, the acute phase response signalling and glycolysis pathways were mainly represented. Verification is ongoing for these candidates. In parallel, we observed that the levels of IL‐6, IL‐10, IL‐12 and TNF‐α, were significantly upregulated in tears of TAO patients.

Conclusions

These results confirmed tears as a suitable source to discover biomarkers for TAO disease. Moreover, the emergence of proteins involved in the glycolysis, associated to inflammation, could bring new general knowledge about TAO that still remains not well characterized. This study is kindly supported by the Provisu foundation and the SNF_MHV (PMPDP3_158370).