bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel role of PELI3 as a potential biomarker for Sjogren's syndrome related dry eyes
Authors: Pilson Q. , Ni Gabhann J. , Murphy C.C.
Published: September 2015

Purpose

In Sjogren's syndrome (SS) related dry eyes (SS‐KCS), reduced aqueous tear production and tear hyperosmolarity leads to inflammatory damage to the ocular surface. microRNAs (miR) are known to alter the expression of cytokines, which plays an important role in the pathogenesis and progression of SS. The aim of this study was to isolate miRs and mRNA from conjunctival epithelial cells (CEC) of patients with primary SS (pSS) to identify potential biomarkers that might aid diagnosis and future therapy in pSS.

Methods

Confirmed SS‐KCS and healthy controls were recruited to this study. mRNA isolated from conjunctival impression cytology was sent for miR and mRNA microarray. Bioinformatic analysis was performed to identify predicted targets and comparison was made with the mRNA microarray data. Validation experiments were performed in HeLa cells following transfection with selected miR mimics and predicted genes were detected using qPCR.

Results

miR and mRNA microarray found 32 differentially expressed novel miRs and 136 differentially expressed genes in pSS patients compared to healthy controls. Following bioinformatic analysis, novel miR‐A was chosen for further analysis. miR‐A was significantly increased in pSS (p = 0.0079) and bioinformatics suggested Pellino3 (PELI3), a negative regulator of inflammatory cytokines, as a predicted target. The mRNA microarray showed a decrease in PELI3 in pSS patients compared to healthy controls (p = 0.0731). Overexpression of miR‐A mimic in HeLa cells resulted in decreased expression of PELI3, suggesting that it is a direct target for miR‐A.

Conclusions

We have identified differentially expressed miRs and gene targets from CEC in pSS. PELI3, a potential target of novel miR‐A which is over expressed in pSS, is a negative regulator of cytokines that might have biomarker and therapeutic potential for pSS related dry eyes.
Posterior corneal surface: new insights in curvature and astigmatism
Authors: Patel S. , Wacker K.
Published: September 2015

Purpose

In normal eyes, a fixed relationship between anterior and posterior corneal astigmatism is assumed, especially for lens power calculations. This study assessed the association between anterior and posterior corneal astigmatism and thickness.

Methods

Normal corneas were examined by slit‐lamp microscopy and Scheimpflug imaging. The differences between vertical and horizontal thicknesses at 4‐mm and 6‐mm‐diameters were calculated. Anterior and posterior astigmatism were calculated as the difference between steep and flat powers based on the corresponding radii of curvature and refractive indices. Comparisons and significances of correlations were assessed by using generalized estimating equation models.

Results

Fifty‐four subjects (101 corneas) aged 18–80 years were included. Peripheral corneas were thicker vertically than horizontally (p < 0.001) at 4 mm by 13.4 ± 9.4 µm (mean ± standard deviation) and at 6 mm by 8.6 ± 4.8 µm. Anterior corneal astigmatism was 1.08 ± 0.57 D and was aligned vertically (73%), horizontally (6%), or obliquely (21%). Posterior corneal astigmatism was −0.31 ± 0.13 D and was aligned vertically (94%) or obliquely (6%). Anterior and posterior astigmatism were correlated in eyes with vertical anterior astigmatism (r = 0.65; p < 0.001), but not in eyes with oblique or horizontal anterior astigmatism. The difference between vertical and horizontal corneal thickness correlated with posterior astigmatism at 4 mm (r = −0.58; p < 0.001) and at 6 mm (r = −0.61; p < 0.001).

Conclusions

The posterior cornea is normally ellipsoid in shape with a steep vertical meridian that corresponds to the cornea being thicker in the vertical paracentral region. Understanding the normal relationship between anterior and posterior corneal surfaces is important when assessing the same in corneal diseases.
Effect of intravitreal bevacizumab on choroidal thickness in eyes with retinal vein occlusion and diabetic macular oedema
Authors: Kuoliene K. , Malysko K. , Cimbalas A. , Asoklis R.
Published: September 2015

Purpose

To evaluate choroidal thickness (CT) before and after intravitreal bevacizumab injections in eyes with macular oedema due to retinal vein occlusion and diabetic maculopathy.

Methods

In this pilot study, 18 eyes of 16 patients were treated with intravitreal bevacizumab injections. The central macular thickness was measured at baseline and after treatment with intravitreal bevacizumab using spectral domain optical coherence tomography (SD‐OCT). The choroid was evaluated using SD‐OCT with EDI mode (Spectralis® HRA+OCT, Heidelberg Engineering) at the fovea before and after intravitreal bevacizumab.

Results

18 eyes were treated with 1.25 mg of intravitreal bevacizumab every 4 weeks, with at least three injections per eye and then continued if oedema persisted. The mean number of intravitreal bevacizumab injections per eye was three. The subfoveal choroidal thickness was significantly thinner after intravitreal anti‐VEGF treatment (214.82 ± 62.67 μm) than at baseline (265.52 ± 87.67 μm, P < 0.001). The mean central macular thickness decreased significantly after treatment with intravitreal bevacizumab (265.53 ± 83.20 μm) compared to baseline (522.63 ± 305.62 μm, P < 0.005). Decrease in central macular thickness did not correlate with decrease in subfoveal choroidal thickness.

Conclusions

In eyes with macular oedema due to retinal vein occlusion and diabetic maculopathy, treatment with intravitreal bevacizumab significantly reduced subfoveal CT and central macular thickness.
Ptosis and diplopia after incidental botulinum powder exposure
Authors: Cho M.
Published: September 2015

Purpose

To report the occurrence of an unilateral ptosis and diplopia not direct injection of botulinum but incidental botulinum power exposure.

Methods

This is a case report of botulinum powder's local effect.

Results

Thirty years old woman visited our hospital due to ptosis and diplopia. She did botulinum powder purification at her laboratory and incidentally botulinum power was spattered to her right eye. Two days later, right lid ptosis was developed and the next day, diplopia was occurred. She also showed right eye pupil dilatation and hypotropia. She was taken brain MRI and we couldn't find pathologic lesion. One month later, the diplopia was disappeared and ptosis was much improved.

Conclusions

In addition to direct periocular injection, only botulinum power exposure can also make local effect, such as ptosis, muscle paresis, pupil dilatation.
Inflammasome activation by UVB irradiation in human corneal epithelial cells
Authors: Kauppinen A. , Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K.
Published: September 2015

Purpose

Cornea is the outermost layer of the eye and mainly responsible for the absorption of ultraviolet B (UVB) radiation. An acute painful inflammatory damage caused by UVB radiation on the corneal epithelium is known as photokeratitis, snow blindness, or welder's burn. We have previously shown that UVB induces inflammation by increasing the production of cytokines IL‐6 and IL‐8 in human corneal epithelial (HCE) cells and now, we have continued this study by exploring the effects of UVB on the inflammasome signaling.

Methods

In vitro‐cultured HCE cells were exposed to UVB radiation after priming with TNF‐α. Thereafter, inflammasome components and cytokines were determined using the ELISA, western blot, and activity assays.

Results

Our results suggest that UVB is capable of activating inflammasome signaling in HCE cells.

Conclusions

In addition to traditional pathways, UVB induces the activation of more recently found pro‐inflammatory signaling system in the human corneal epithelium.
Ultrastructural maintenance of decellularized corneas using dextran
Authors: Lynch A. , Wilson S. , Ahearne M.
Published: September 2015

Purpose

Corneal decellularization has emerged as a promising alternative to traditional tissue‐engineering strategies for the creation of corneal replacements for transplantation. However, decellularization methods can lead to swelling of the cornea, limiting its potential use as a scaffold. In this study, we propose the use of a complex polysaccharide, dextran, to reduce this swelling and maintain the native dimensions and architecture of the cornea.

Methods

Porcine corneal buttons were treated with Triton X‐100, SDS and nucleases under constant rotation followed by a washing step. To prevent corneal swelling, the decellularization solution was supplemented with dextran. This solution was added to one group throughout the decellularization process and to a second group during the washing cycle. The resulting acellular scaffolds were systematically evaluated by histological and biochemical analyses, in addition, the ultrastructure of the cornea was examined by transmission electron microscopy (TEM).

Results

Results demonstrated that the combination of detergents and nucleases effectively removed the majority of cellular material from the cornea. Furthermore, the addition of dextran prevented significant swelling when used throughout the protocol or only during the washing process. After soaking in glycerol a degree of transparency was returned to all decellularized corneas suggesting maintenance of the extracellular matrix. However, TEM analysis confirmed that dextran must be present throughout the decellularization process to preserve the native ultrastructure of the cornea.

Conclusions

The findings of this study indicate that the addition of dextran to the decellularization process not only prevents significant corneal swelling but also enhances the maintenance of the native ultrastructure of the cornea.
The prevalence and incidence of glaucoma in Denmark in a fifteen year period: A nationwide study
Authors: Kolko M. , Horwitz A. , Thygesen J. , Jeppesen J. , Torp‐Pedersen C.
Published: September 2015

Purpose

The purpose of the present study was to describe the prevalence, incidence and demographic variation of glaucoma patients in Denmark in the period from 1996 to 2011. Moreover, the aim was to identify the treatment pattern of glaucoma medication within the studied period.

Methods

The study population comprised all individuals living in Denmark in the period 1996‐2011. The National Prescription Registry was used to identify all claimed prescriptions for glaucoma medication.

Results

A total of 116,592 incident glaucoma patients were identified. Average age at onset was 66 years (range: 0‐105 year), 55% were women. The over all prevalence of glaucoma increased from 0.79% to 1.72% during the investigated period. In 2011, glaucoma affected 3.76% of the population above 50 years and 10% in patients above 80 years.The highest prevalence of glaucoma was found in capital region of Denmark. Within the studied period the use of prostaglandin analogs and combination drugs increased, whereas the use of b‐blockers, carbon anhydrase inhibitors and parasympathomimetic drugs decreased (p < 0.001). Finally, the use of a2‐adrenergic agonists remained unchanged within the studied period. A total of 75% of the patients were treated with two or more glaucoma medications.

Conclusions

Over all, the present study is the first assessment of the frequency and the development of glaucoma in Denmark over a 15‐year period. Glaucoma affects a little less than 2% of the total population and increases with age to reach a prevalence of more than 10% amongst people above 80 years.
Optic nerve head hemorrhage and vitreous traction
Authors: Willekens K. , Pinto L.A. , Vandewalle E. , Stalmans P. , Stalmans I.
Published: September 2015

Purpose

During posterior vitreous detachment (PVD) the posterior hyaloid remains, for a certain period, attached to the optic disc. It can exert traction with development of optic nerve head hemorrhages (ONHH). ONHH are known to be associated with glaucomatous progression and retinal nerve fiber layer (RNFL) defects. Therefore this study aims at investigating the relationship between PVD formation and ONHH in open angle glaucoma patients.

Methods

Patients presenting with an ONHH, from November 2014 on, were included. They underwent a comprehensive ophthalmological investigation, automated visual field test, confocal scanner (HRT III), OCT (HRT‐Spectralis) scan and stereographic photos of the optic nerve head. This study is part of a larger, clinicaltrial.gov (NCT02290795) registered, study investigating vitreopapillary traction (VPT).

Results

Eighteen eyes of 18 patients (11 normal tension, 6 primary open angle and 1 secondary open angle glaucoma) were included. Seven out of 18 (38.9%) eyes had concomitant VPT and 7 had a complete PVD. Seven ONHH were located infero‐, 5 supero‐ and 6 temporal. In the non‐VPT subgroup 5 out of 11 (45.5%) eyes showed matching retinal nerve fiber layer defects, with 2 out of 7 (28.6%) in the VPT subgroup.

Conclusions

VPT could be a confounding factor in glaucoma assessment and ONHH development.
The improvement of Spoke‐Wheel pattern foveoschisis in a patient with X‐linked retinoschisis treated with topical dorzolamide observed by high‐resolution adaptive optics camera
Authors: Gocho K. , Akeo K. , Kameya S. , Yamaki K. , Mizota A. , Takahashi H.
Published: September 2015

Purpose

The purpose of the study is to report the improvement of foveomacular cavities and spoke‐wheel pattern retinoschisis observed by spectral‐domain optical coherence topmography (SD‐OCT) and high‐resolution adaptive optics fundus camera in a patient with XLRS treated with topical dorzolamide.

Methods

A 42 y.o. man with XLRS underwent detailed ophthalmic examinations. A mutation of RS1 gene was detected earlier. The ophthalmological examinations included SD‐OCT, fundus autofluorescence imaging, and full‐field and multifocal ERGs. Fundus images with microscopic resolution were obtained using the AO retinal camera (rtx1, Imagine Eyes, France). He was treated with topical dorzolamide three times a day. Transverse foveomacular cavities was observed by SD‐OCT and the en‐face images of spoke‐wheel pattern foveoschisis was observed by AO fundus camera during a follow‐up period.

Results

His BCVA was 0.15 in the right eye and 0.3 in the left eye. The right eye showed atrophic macular degeneration and left eye showed spoke‐wheel pattern foveoschisis. SD‐OCT showed the thinning of retinal thickness in the right eye and cystoid foveoschisis in the left eye. AO images showed spoke‐wheel pattern retinal fold in the left eye. The spoke‐wheel pattern in AO was sharper compared to the images obtained by fundus photography and autofluorescence imaging. After 14 month of treatment with topical dorzolamid, improvement of foveomacular cavities in SD‐OCT was observed. The spoke‐wheel pattern retinal fold in AO become obscure after treatment, however still detectable even after foveomacular cavities in SD‐OCT was almost disappeared.

Conclusions

AO imaging showed detailed microstructure of spoke‐wheel pattern foveoschisis and their improvement during a follow‐up period. AO imaging may be helpful in clarifying the pathology of the foveoschisis in XLRS.
Long‐term results orthokeratological therapy in patients with myopia
Authors: Bushuyeva N. , Maliieva O.
Published: September 2015

Purpose

The potential impact of the peripheral refraction on the refractogenesis and development of myopia is validating for using orthokeratologicaltherapy to form a peripheral myopic defocus in patients with myopia. The purpose of the research was to study the long‐term results of orthokeratologicaltherapy in patients with myopia.

Methods

21 patients (42 eyes) with myopia from ‐0.75 D to ‐4.5 diopters σ = (−2.35 ± 1.22) D, with average age (12.43 ± 6.09), used the night contact lenses Paragon CRT 100 were followed up for 3 years. Methods of examination included visometry, keratometry and refractometry after cycloplegy with Cyclomed 1% with using KR‐8900, Topcon and HRK‐7000, Huvitz; ultrasonic eye`s biometry with Desmin M (thickness of cornea and lens, depth of anterior chamber, length of vitreous) before and after 3 years using OK‐ therapy. We have used (patent Ukraine № 91371, 24.06.2014) coefficient K = ((AC+L/2)/(V+L/2)) × 100, AC ‐ anterior chamber, L ‐ thickness of lens, length of vitreous.

Results

The long‐term results of orthokeratological therapy showed the positive effect to slow of the myopic process. After 3 years OK‐ therapy myopia was stabilized in 27 eyes (64.29%). The date 31 and more of coefficient K showed the refractive type of myopia and less then 31 ‐ showed axial type of myopia. The refractive type of myopia was in 22 eyes (52.38%) and axial type of myopia was in 20 eyes (47.62%).

Conclusions

The most positive effect of orthokeratological therapy observed in patients with refractive component due to the curvature of the cornea. Coefficient have showed the type of axial or refractive myopia (Patent Ukraine № 83299U, 27.08.2013). The coefficient can be used for prognosis of progression myopia.
Analysis of molecular mechanisms that predispose patients to develop post‐PRK haze
Authors: Rajiv Kumar N. , Ghosh A. , Shetty R. , Pahuja N.
Published: September 2015

Purpose

Factors that predispose certain patients to develop post‐surgical haze remain unknown.We analyzed gene expression in corneal epithelium collected from patients prior to haze development following PRK. We further developed an in‐vitro model to study haze using TGFβ that mimics pre‐disposed and post haze conditions.

Methods

Corneal epithelium was collected intraoperatively from patients undergoing PRK. 4 eyes that developed haze postoperatively and 10 eyes of age matched controls without haze were analysed. Microarray analysis was followed by bioinformatics and validation. In vitro studies were performed on HCE cells on differential doses of TGFβ with or without wound for inflammatory markers, structural & pro‐fibrotic genes and regulators of signaling cascades.

Results

Microarray analysis revealed 1100 up regulated and 1700 down regulated genes in haze patients. ECM‐ Receptor interactions were elevated in patients prior to haze induction while Wnt signaling genes and CXC motif chemokines were reduced. Structural genes (Col I, Col IV, MMP2 & 14, TIMP1) were reduced in haze patients which correlated with in‐vitro model. Inflammatory factors TNFα, IL‐11 were elevated, but IL6 and IL1 did not show appreciable changes. Regulators of signaling cascades EGFR and Wnt3a were reduced in haze patients & in vitro. We propose a signal transduction network including few novel genes like PREX1, PXDN, SOX17, WNT3A, CXCL10 etc which can be factors that predispose patients to haze.

Conclusions

Our study shows that molecular factors poise the cornea in some patients to developing corneal haze after surgery.
Integrated multi‐omic analysis of human retinoblastoma identifies novel regulatory networks
Authors: Sureshbabu V. , Mallipatna A. , Guha N. , SA D. , Lateef S. , Gundimeda S. , Padmanabhan A. , Shetty R. , Ghosh A.
Published: September 2015

Purpose

a) Elucidate the differential expression profiles in tumors & invitro models. b) Identify novel signal transductions and key regulators in retinoblastoma.

Methods

Institutional Ethics Committee approval was obtained prior to sample collection. We used enucleated eyes of 9 case samples & 2 pediatric deceased controls. Total RNA was extracted from tumor & control retina samples for mRNA, miRNA microarray and RT‐PCR for gene expression validation in tumors. Patient's aqueous, vitreous and tears were analysed by LC/GC‐MS to validate metabolic profiles of retinoblastoma. RB invitro models were developed using cell lines MCF‐7, Y79 & Weri, for correlative analysis with patient data.

Results

We identified 8 key differentially regulated pathways and genes, from the mRNA expression profile. The miRNA expression profile helps to discover 18 novel miRNAs which regulates key target genes identified by mRNA microarrays. Multi‐ omics analysis of metabolomics data with gene expression profiles revealed key regulators belonging to common pathways. RB1 silenced MCF‐7 showed significant overlap in key cell cycle genes & RB1 complemented retinoblastoma cell line Y79 mimics gain of function of molecular signature.

Conclusions

Overall, the study identifies molecular mechanisms driving retinoblastoma and provides an in‐vitro modelling framework for further studies.
Effects of selective retina therapy on retinal oxygen saturation compared to conventional photocoagulation in rabbits
Authors: Kim J.R. , Roh Y.J.
Published: September 2015

Purpose

Subvisible selective retina therapy (SRT) was designed to target retinal pigment epithelium (RPE) without damaging adjacent photoreceptors. This study evaluated the changes in retinal oxygen saturation and retina histology after SRT compared to conventional photocoagulation(PC) in rabbits.

Methods

One eye in each of 10 chinchilla bastard rabbits was treated with 144 spots of SRT (527 nm) or conventional laser treatment (577 nm), respectively. After treatment, fundus photography, optical coherence tomography, and fluorescein angiography were performed to detect lesions. At 1 week post‐treatment, retinal oxygen saturation in untreated, SRT‐treated, and PC‐treated areas was evaluated in five eyes. Histologic evaluation was performed using light and electronic microscopy. At 4 weeks post‐treatment, the same procedures were performed in the remaining five eyes.

Results

At 1 week post‐treatment, mean retinal oxygen saturation in the PC‐treated area (23.3 ± 7.2 mm Hg) was relatively higher than in the untreated (16.6 ± 4.3) and SRT (15.34 ± 5.3) areas. Similar results were found at 4 weeks post‐treatment (PC‐treated, 25.3 ± 8.5; untreated, 14.4 ± 5.2, SRT‐treated, 15.2 ± 4.6). OCT and histological examinations revealed selective RPE damage while sparing photoreceptors in the SRT lesion. In contrast, broad damage in multiple retinal layers including the photoreceptors was observed in conventional PC lesions.

Conclusions

Increased retinal oxygen saturation after conventional PC might be due to widespread destruction of retinal layers including photoreceptors which is most oxygen consuming structure in retina. In contrast, relatively unchanged retinal oxygen saturation was observed in SRT lesions with intact retinal layers and photoreceptors. SRT can be used as an photoreceptor saving laser therapy in RPE dysfunction diseases such as DME or CSC.
Assessment of the performances of a handheld in vivo confocal microscope for the analysis of human corneal innervation
Authors: Brehon A. , Perrot J.L. , Cinotti E. , Labeille B. , Grivet D. , Crouzet E. , Gain P. , Thuret G.
Published: September 2015

Purpose

We previously reported, for the first time, the use of a dermatological handheld in vivo confocal microscope (IVCM), VivaScope 3000 (Lucid, NY), for the imaging of the ocular surface and ocular adnexa (AmJOphthalmol2015;159:324). Aim: to further assess its performances for qualitative and quantitative analysis of corneal innervation.

Methods

Clinical interventional prospective single‐center study comparing the first version of the handy handheld VivaScope 3000 with the Heidelberg Retina Tomograph (HRTIII‐RCM) as a reference. The right central subbasal plexus (SBP) of healthy corneas of non‐diabetic patients, diabetic patients without peripheral neuropathy and diabetic patients with peripheral neuropathy was analyzed the same day with both IVCMs by the same observer. The three best images were selected for each device and the nerve density, the number of nerves by frame, the number of branch per frame, and tortuosity of the nerves of the central SBP were calculated using NeuronJ. Analyzes were done on similar areas, blind to the IVCM type, then on full fields.

Results

The VivaScope provided 920 × 920 μm images versus 400 × 400 μm for the HRTIII‐RCM. Images of the SBP were easily obtained but the 4 parameters were significantly lower in the 3 populations with the VivaScope despite a larger field of view. Comparisons between populations are ongoing.

Conclusions

This handheld dermatological IVCM is able to image the SBP but is less informative than the static HRTIII‐RCM. For SBP, the larger field is not an advantage because most of the field is out of focus. Improvements of the IVCM objective are proposed. GRANT: project INNOVEYE GIRCI RAA.
Correlation between radiation dose and damage to optic disc and macula in eyes treated with ruthenium brachytherapy
Authors: Espensen C.A. , Fog L.S. , Klemp K. , Aznar M.C. , Specht L. , Kiilgaard J.F.
Published: September 2015

Purpose

Poor visual acuity and blindness due to retinal damage are challenging side effects to 106Ru‐plaque treatments of malignant melanomas. In this study, we evaluated the dose to fovea and to the optic nerve and investigated the link between dose and the occurrence of macular and optic nerve damage.

Methods

The study included 54 patients treated in 2005 and 2006 in Copenhagen University Hospital, Denmark. Six patients were excluded due to missing information on ocular outcome. Using dedicated commercial software, the tumour was retrospectively contoured on pre‐treatment fundus images. The position of the plaque was determined from the radiation scar in post‐treatment fundus images and enabled to recreate the dose distribution. The presence of ocular damage was determined from the same post‐treatment fundus images. The dose to the fovea and optic nerve were reported and compared to the presence of ocular damage.

Results

The estimated dose to the macula for patients with macular damage (median: 64 Gy, range: 7–668 Gy) was significantly larger than for patients with no macular damage (me‐ dian: 7, range: 0‐31 Gy) (p = 1.8·10−7). Optic nerve doses for patients with optic nerve damage (median: 87 Gy, range: 38–257 Gy) similarly differed significantly from those for patients without damage (median: 17 Gy, range: 0–122 Gy) (p = 1.7·10−4).

Conclusions

After 106Ru‐plaque treatment, patients where ocular damage was identified had received a significantly higher dose to the macula and optic nerve compared to patients with no signs of ocular damage.
Investigation of genotype‐phenotype correlation of TGFBI mutations reveals c.1868G>A; p.(Gly623Asp) is associated with a variable clinical phenotype, including epithelial basement membrane dystrophy
Authors: Evans C. , Davidson A. , Carnt N. , Veli N. , Tuft S.J. , Hardcastle A.
Published: September 2015

Purpose

Autosomal dominant mutations in TGFBI cause a range of clinically distinct corneal dystrophies. We investigated the TGFBI mutation spectrum in our cohort and correlated genotype with phenotype.

Methods

TGFBI exons 4, 11, 12, 13, 14 and 16 were Sanger sequenced in 59 unrelated probands attending Moorfields Eye Hospital with a diagnosis of a potential TGBFI‐associated corneal dystrophy.

Results

The majority of individuals, 86%, carried a mutation at one of the two known hotspot residues for TGFBI‐associated corneal dystrophies: Arg‐124 and Arg‐555. Mutations affecting either of these residues demonstrated genotype‐phenotype correlation. A c.1868G>A; p.(Gly623Asp) mutation was identified in five unrelated probands; one with a clinical diagnosis of lattice corneal dystrophy, two with a Bowman's layer dystrophy (Reis‐Bϋcklers or Thiel‐Behnke corneal dystrophy) and two with epithelial basement membrane dystrophy (EBMD). The clinical variability associated with this mutation indicates that other genetic or environmental factors can influence phenotypic expression.

Conclusions

This is the first time the c.1868G>A; p.(Gly623Asp) mutation has been associated with EBMD, although other mutations in TGFBI have previously been identified in a small number of EBMD patients. These results demonstrate that the c.1868G>A; p.(Gly623Asp) mutation is responsible for a significant proportion of the disease burden for TGFBI‐associated corneal dystrophies in the UK and highlights the need for patients with EBMD to be screened for mutations in TGFBI.
Impact of Intravitreal Aflibercept (IVT‐AFL) on Diabetic Retinopathy in the VIVID‐DME and VISTA‐DME Studies
Authors: Larsen L.M. , Metzig C.
Published: September 2015

Purpose

Post‐hoc analysis to assess changes in the diabetic retinopathy severity scale (DRSS) score and the development of proliferative diabetic retinopathy (PDR) in VIVID‐DME and VISTA‐DME.

Methods

Patients (pts) were randomized to IVT‐AFL 2 mg every 4 weeks + sham laser (2q4), IVT‐AFL 2 mg every 8 weeks (after 5 initial monthly doses) + sham laser (2q8), or laser + sham injections. Primary efficacy endpoint was mean change from baseline (BL) in visual acuity at week (W)52; the proportion of pts with a ≥ 2‐step improvement from BL on the DRSS was a secondary endpoint at W100. Pts were considered to have developed PDR if BL DRSS score was <61 and there was ≥1 post‐baseline DRSS score ≥61. Results are presented for pooled IVT‐AFL 2q4 and 2q8 treatment arms.

Results

The proportion of pts receiving IVT‐AFL vs. laser with a ≥ 2‐step improvement in DRSS at W100 was 31.0% vs. 8.2% (VIVID‐DME) and 37.0% vs. 15.6% (VISTA‐DME). The proportion of pts receiving IVT‐AFL vs. laser who developed PDR through W100 was 1.8% vs. 5.3% (VIVID‐DME) and 2.6% vs. 12.3% (VISTA‐DME); when data were integrated across the two trials, the respective proportions were 2.4% vs. 9.4% (nominal P ≤ 0.0001). The most common ocular serious AE in IVT‐AFL‐treated pts was cataract (VIVID‐DME, 2.2%, VISTA‐DME, 1.3%).

Conclusions

A greater proportion of pts treated with IVT‐AFL experienced ≥step improvements in DRSS scores at W100 compared with laser‐treated pts. A smaller proportion of IVT‐AFL‐treated pts in both studies developed PDR compared with laser. These findings demonstrate the beneficial impact of IVT‐AFL not only on DME, but also on the underlying diabetic retinopathy.
Comparison of Humphrey visual field perimetry and new invented PC‐based visual field testing system in healthy people and glaucoma patients
Authors: Kim Y.G. , Lee J. , Lee B. , Kim S. , Lee N. , Kim S. , Park J. , You H. , Kang J.H.
Published: September 2015

Purpose

The aim of this study was to compare the visual field test in healthy people and glaucoma patients with Humphrey visual field perimetry (HFA) and new invented PC‐based visual field testing system (PCVF).

Methods

This prospective study included 48 healthy people and 37 glaucoma patients who underwent both HFA and PCVF. Pattern standard deviation (PSD), mean deviation (MD) were compared between the 2 tests using Pearson correlation. Areas under receiver operating characteristics curve (AUCs) for discriminating healthy from glaucoma, sensitivity and cut‐off value at 80% and 90% specificity of MD and PSD were determined in HFA and PCVF.

Results

MD and PSD were correlated in glaucomatous eyes (r = 0.48, 0.50 p < 0.002, <0.002). The AUCs of MD and PSD from HFA were 0.882, 0.903 and those from PCVF were 0.676, 0.813. The sensitivity at 80% specificity of MD was 81.1% in HFA, 43.2% in PCVF, with the cut off value of PSD at 80% specificity at −2.86 dB in HFA and −4.40 dB in PCVF.

Conclusions

MD and PSD data from HFA and PCVF significantly correlated in glaucomatous eyes. PCVF can be comparable to HAF for visual field testing system.
Anterior segment changes after femtosecond cataract surgery measured with optical coherence tomography and scheimpflug imaging technology
Authors: Perez Carrasco M.J. , Fernández‐Cuenca S. , Lorente‐Hevia M.P. , Álvarez de Rementería L. , Aldaham S. , Puell M.
Published: September 2015

Purpose

To determine changes in anterior chamber depth (ACD), iridocorneal angle size (IAS) and central corneal thickness (CCT) using optical coherence tomography (OCT) and Scheimpflug imaging technology (SIT) in subjects implanted with multifocal intraocular lens (IOL) after femtosecond cataract surgery.

Methods

Prospective study of 36 healthy eyes (68.8 ± 7.9 years) undergoing femtosecond laser assisted‐cataract surgery and AcrySof REsTOR SN6AD1 IOL implantation. The anterior segment parameters were measured preoperatively and 1 month after surgery with the Visante‐OCT (Zeiss) and the Oculyzer™ II (WaveLight® AG) systems. Analysis of agreement and interchangeability of the preoperative 2 systems measurements was performed by the Bland‐Altman method.

Results

After femtosecond cataract surgery, the ACD and IAS measured with Oculyzer™ II showed a significant mean increase of 1.54 ± 0.28 mm and 10.2 ± 4.23 respectively. Also, using the Visante‐OCT there was a significant mean increase: 1.27 ± 0.34 mm for ACD and 9.38 ± 6.52 (Temporal) and 8.29 ± 7.13 (nasal) for IAS. CCT showed no significant changes. The range of agreement indicated that the 2 techniques cannot be used interchangeably for preoperative measurement of ACD and IAS.

Conclusions

After cataract surgery with femtosecond laser, ACD and IAS increased significantly when measured using OCT and SIT. Visante‐OCT and Oculyzer™ II systems can be used interchangeably for CCT evaluation but not for ACD and IAS.
Effect of Preconditioning Intraocular Lenses in Moxifloxacin Solution
Authors: Filipe H.P. , Bozukova D. , Pimenta A. , Mata J.L.G. , Colaço R. , Saramago B. , Serro A.P.
Published: September 2015

Purpose

The goal of our research was to investigate the possibility of using drug loaded intra‐ocular lenses (IOLs) as an alternative to topical antibiotic usually prescribed after cataract surgery.

Methods

Although widely used in drug release studies due to its simplicity in comparing systems, static conditions are far from reproducing biological conditions. A microfluidic cell mimetizing chamber's aqueous humor hydrodynamic is a much closer approach. With a volume of 250 µL, the cell is fed with a continuous flow of saline solution at a physiological similar rate.

Results

Results showed that 30 days preconditioned IOLs were able to maintain a MXF concentration above the minimum inhibitory concentrations for Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pneumoniae for 20 days.

Conclusions

Further investigation in using moxifloxacin loaded IOls as effective to prevent post cataract surgery endophthalmitis is encouraged.
Three optic disc pit maculopathy case studies by optical coherence tomography images supporting the role of cerebrospinal fluid in this pathology
Authors: Martinez M. , Ascaso J. , Arias L. , Filloy A. , Almenara C. , Esteban O. , Del Buey M. , Cristobal J.
Published: September 2015

Purpose

Optic disc pit (ODP) is a rare congenital optic disc abnormality characterized by a localized grayish‐white depression usually in the center or inferotemporal part of the optic nerve head. It is generally unilateral (85‐90%) and its prevalence is estimated to be 1 in 11,000. Unless the ODP develops maculopathy, patients remain asymptomatic. Serous macular detachment may occur in up to 50% of cases,leading to significant decrease in visual acuity. Although the pathogenesis of ODP maculopathy is unclear, various theories about its onset have implicated fluid entry either from the vitreous cavity or from leakage of cerebrospinal fluid through the peripapillary subarachnoid space. The aim of this study was to evaluate the source of subretinal fluid under the macula in three patients with ODP.

Methods

Three different optical coherence tomography equipments (EDI‐OCT Spectralis, Heidelberg; Swept‐source OCT, Topcon and Spectral‐domain 3D OCT‐2000, Topcon) were used.

Results

These OCT images revealed a direct communication between a prominent serous macular detachment and the subarachnoid space through the ODP.

Conclusions

These three cases support the theory that in some cases the source of serous macular detachment could be cerebrospinal fluid passing into the retina through the ODP due to an incomplete closure of the embryonic fissure.
Analysis of the efficacy of the tissue regenerating agent (RGTA) 0.01% poly‐carboxymethylglucose sulfate in the treatment of neurotrophic corneal ulcers and persistent epithelial defects
Authors: Del Buey M.A. , Casas P. , Caramello C.M. , Esteban O. , Martinez M. , Sánchez N. , Pinilla I. , Lanchares E.
Published: September 2015

Purpose

To report the results obtained in a series of 58 eyes with chronic corneal ulcers and persistent epithelial defects resistant to conventional therapy and treated with 0.01% poly‐carboxymethylglucose sulfate based on tissue regenerating agent technology (RGTA, Cacicol®).

Methods

A prospective study was made of 58 eyes. The ulcers were essentially chronic and slow‐evolving, with mean vertical and horizontal diameters of 2.4 and 2.7 mm, respectively (range 1‐5.5 mm). The patients received an initial dose of one drop every 48 hours during 10 days. After evaluation of the effects of treatment, new dosing schemes were prescribed for those patients who had improved their clinical condition though without complete resolution of the disease.

Results

Important variation was observed in the time to recovery of corneal integrity, ranging from a few days to some weeks, depending on the severity and etiology of the case. Full healing was recorded in 50 patients. The patients with large neurotrophic ulcers showed improvement of the lesions, with a decrease in lesion size after 15 days of treatment. All patients reported subjective improvement. The drug showed immediate efficacy in 11 eyes with epithelialisation disorders following PRK or trauma, with recovery of tissue integrity after the first treatment period.

Conclusions

The tissue regenerating agent (RGTA Cacicol®) is an interesting and effective topical adjuvant product for the treatment of severe and chronic corneal ulcers resistant to conventional treatment. Its efficacy remains to be confirmed in the context of double‐blind, randomised clinical trials.
Immediate Effect of Ultraviolet‐A Collagen CXL Therapy on Biomechanics and Histology of Human Cornea
Authors: Del Buey M.A. , Lanchares E. , Calvo B. , Lavilla L. , Almenara C. , Pérez I. , Idoate A. , Pinilla I. , Ascaso J. , Cristobal J.
Published: September 2015

Purpose

To evaluate the immediate effect of the CXL treatment on the biomechanical properties and histological microstructure of healthy human corneal tissue. With this purpose, in vitro mechanical tests and histological observation of cross‐linked and untreated human corneal tissue were performed.

Methods

Mechanical tensile test and histological analysis were performed in de‐epithelialized healthy human corneal tissue treated with riboflavin solution (0.01% riboflavin‐5‐phosphate and 20% dextranT‐500) – 30 min UVA irradiation (treated sample TS). A similar study was performed to untreated de‐epithelialized healthy human corneal tissue (control sample, CS). Both histological and mechanical analyses were performed immediately after treatment.

Results

The analysis of the stress‐strain curves showed a different corneal response between treated (TS) and untreated (CS) samples. TS showed a stiffer behaviour than CS. The treated corneal tissue (TS) resulted 1.8, 1.6, 1.7 and 1.5 fold stiffer than the untreated sample (CS) at 6, 8, 10 and 12% stretch, respectively. The histological analysis of TS showed an increased fibrillar density with decrease of interlamellar space in comparison with CS. Keratocyte apoptosis was observed in TS even at deep stromal level.

Conclusions

The UVA‐induced CXL has an immediate biomechanical and histological effect over the treated healthy human corneal tissue. Stiffening of the tissue, keratocyte apoptosis and stromal compacting were observed.
Generic Drugs‐ are they as good as brand‐names?
Authors: Kolko M. , Ali N. , Jensen P.K.
Published: September 2015

Purpose

The aim of the present study was to investigate different characteristics of six Latanoprost generics.

Methods

Prize, drop size and volume in each generic were determined. The hardness of each bottle was further evaluated using a fish weight and a hook. Finally, pH was measured and the buffer capacity evaluated by addition of NaOH.

Results

Price, drop size and volume varied significantly between the brand version (xalatan) and the generic latanoprost products. Hence, drops sized were in the range 40–47 µl and the number of drops in each generic bottle varied between 95 and 111 drops. The embalages of each latanoprost product were different in both size and hardness. The control value of pH in the brand version (Xalatan) was 5.99 ± 0.01 (mean ± SD), whereas the generic latanoprost products had significantly higher values within the range 6.70–6.82. Hence, titration of 2.5 µl Xalatan to neutrality required 70.4 ± 0.4 nmol NaOH compared to the generic latanoprost products which required within the range 28.1–33.7 nmol NaOH.

Conclusions

The present study identifies differences among latanoprost generics such as different pH values and different buffer capacities. Moreover, the emballages varies significantly, thereby leading to critical variations in the handling of the generics. Finally, the number and size of drops in each generic were different, not to mention the prize variations between the brand version and the generics. Over all, generic eye drops should not be considered identical. Therefore, re‐evaluation of the requirements for introducing generic drugs seems reasonable.
Study of XAILIN HA Physical Properties versus Marketed Hyaluronate Based Ocular Lubricants
Authors: Pilotaz F. ,  Saldo J. ,  Boix M.
Published: September 2015

Purpose

Xailin HA is a multi‐dose lubricating eye drop for alleviating symptoms of moderate to severe dry eye sensations. It contains sodium hyaluronate (HA) 0.2% w/w and sodium perborate in aqueous buffered vehicle. Perborate is a disappearing preservative that turns into water and oxygen upon contact with the ocular surface.

Comparative studies were performed with Xailin HA against other EU marketed HA products in order to assess its key physical properties.

Methods

The parameters studied were the following: Macroscopic appearance, pH, osmolality, viscosity at 25°C, drop size and surface tension. The marketed products assessed in this study were: Xailin HA, Vismed multi, Hyabak, Hyalistil, Optive Fusion, Hylo‐Comod, Hylo‐vision HD, Artelac Splash MDO, Hylo‐Gel.

Results

All products are clear and colourless and their pH range is between 6.8 and 7.4. The tested products remain in the common range of osmolality for topical ophthalmic forms except Vismed multi (hypotonic, 150 mOsm/kg). Xailin HA presents the next lower osmolality (260 mOsm/kg). Four categories from less to more viscous products are observed: (i) Hyabak and Hylo‐Vision (ii) Artelac Splash MDO, Hyalistil, Optive Fusion, Hylo‐Comod and Vismed Multi (iii) Xailin HA (iv) Hylo‐Gel Xailin HA is significantly different from all others products with the lowest surface tension recorded.

Conclusions

Xailin HA is a new hyaluronan‐based ocular lubricant. Its low surface tension property should reflect a better distribution and spreading capacity on corneal surface than the other marketed products tested.
Optical Coherence Tomography and Fundus Autofluorescence evaluation in an animal model of Retinal Degeneration
Authors: Segura F. , Fernandez‐Sanchez L. , Sánchez‐Cano A. , Tamarit J.M. , Fuentes‐Broto L. , Del Buey M. , Cuenca N. , Pinilla I.
Published: September 2015

Purpose

To evaluate fundus autofluorescence (FAF) and OCT changes comparing with immunohistochemical (ICC) analysis in long term degeneration of P23H rat and to investigate retinal and choroidal vascularization using fluorescein and indocianin green angiography.

Methods

Twenty‐albino homozygous P23H line 1 rats aging from 18 postnatal days (P18) to 27 months and wild‐type albino Sprague‐Dawley (SD rats) (2 and 15 months old) were used for this study. Normal pigmented Long Evans (LE) 2 months old rats were used to compare FAF findings. ICC was performed to correlate with the findings of OCT and AF changes.

Results

FAF pattern varied from not findings at P18 to a mosaic of hyperfluorescent dots in the rats of 6 months or older. Retinal thicknesses diminished during the time: 205.2–183.18 μm in SD rats and 189.88–58.15 μm in P23H rats. In long term degeneration, OCT showed severe changes at the retinal layers; ICC helped to identify the cell loss and remodeling changes.

Conclusions

Autofluorescent ophthalmoscopy is a non‐invasive method that can detect changes in metabolic activity at the RPE in animal models of retinal degeneration in vivo. Retinal vascular plexus changed with aging. OCT showed a diminution of retinal thickness and retinal layer changes with the degeneration. ICC shows a good correlation.
Assessment of corneal layers thickness with spectral‐domain optical coherence tomography
Authors: Segura F. , López de la Fuente C. , Sáchez‐Cano A. , Orduna E. , Del Buey M. , Pinilla I.
Published: September 2015

Purpose

To assess the corneal layers thickness in healthy young adults using spectral‐domain anterior segment optical coherence tomography (AS‐OCT).

Methods

There were 86 eyes of 86 healthy volunteers, 55 females and 31 males, which were included in the study. The mean age ± standard deviation (SD) was 22.87 ± 3.90 years (range, 20–43). Spectral‐domain AS‐OCT was performed using Spectralis OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Measurements of central corneal thickness, and central thickness of epithelium, Bowman's layer, stroma and the complex Descemet‐endothelium were performed.

Results

Mean central corneal thickness, epithelium, Bowman, stroma and Descemet‐endothelium were 555.50 ± 29.64 µm (range 510–624), 54.60 ± 4.25 µm (range 45–63), 16.70 ± 1.73 µm (range 14–20), 467.51 ± 28.91 µm (range 420–533) and 16.74 ± 1.66 µm (range 14–20), respectively.

Conclusions

Spectralis OCT can be easily used to non‐invasive measurements of the anterior segment parameters and this study establishes a normal database for corneal thickness and all its layers in healthy young adults.
Intravitreal Aflibercept (IVT‐AFL) for Diabetic Macular Edema (DME): 3 Year Data from VIVID‐DME and VISTA‐DME
Authors: Staurenghi G. , Metzig C.
Published: September 2015

Purpose

To evaluate long‐term outcomes with IVT‐AFL injection in the treatment of DME.

Methods

406 patients (VIVID‐DME) and 466 patients (VISTA‐DME) were randomized to IVT‐AFL 2 mg every 4 weeks + sham laser (2q4), IVT‐AFL 2 mg every 8 weeks (after 5 initial monthly doses) + sham laser (2q8), or laser + sham injections. From week (W)100 to W148, laser patients could receive IVT‐AFL if retreatment criteria were met. Primary efficacy endpoint was the mean change from baseline (BL) in best corrected visual acuity (BCVA) at W52. Outcomes at W100 and W148 are described.

Results

At W100, mean BCVA gains from BL in the IVT‐AFL 2q4, 2q8 and laser groups were +11.4, +9.4 and +0.7 letters (VIVID‐DME; P < 0.0001), and +11.5, +11.1 and +0.9 letters (VISTA‐DME; P < 0.0001). In VISTA‐DME, improvements in BCVA were maintained to W148 in the IVT‐AFL 2q4 (+10.4 letters) and 2q8 (+10.5 letters) groups. Cataract was the most frequent ocular serious AE in both studies through 100 weeks (VIVID‐DME: 2.2%; VISTA‐DME: 1.3%); incidence of Antiplatelet Trialists’ Collaboration‐defined arterial thromboembolic events with IVT‐AFL was similar across the studies (VIVID‐DME: 4.8%; VISTA‐DME: 7.8%). Safety outcomes at W148 in VISTA‐DME were consistent with W100 data with no new safety signals observed. The third year of VIVID‐DME is ongoing.

Conclusions

In both studies, IVT‐AFL demonstrated superior outcomes compared with laser through W100, with similar efficacy in the 2q4 and 2q8 groups. In VISTA‐DME, BCVA gains from BL with both IVT‐AFL regimens were sustained through W148. Through 100 weeks the incidence of AEs was consistent with the known safety profile of IVT‐AFL.