bluuebunny/crossref_metadata_2025 huggingface dataset:
Resvega induces autophagy and prevents ARPE‐19 cell damage during proteasome inhibition
Authors: Koskela A. , Reinisalo M. , Olmiere C. , Petrovski G. , Sinha D. , Karjalainen R. , Kaarniranta K.
Published: September 2016

Purpose

Impaired autophagic and proteasomal cleansing has been documented in retinal pigment epithelial (RPE) cells and age‐related macular degeneration (AMD) pathology. Omega fatty acids and resveratrol has been shown to be cytoprotective in RPE cells. We examined effects of commercial Resvega on the regulation of autophagy and cytoprotection in ARPE‐19 cells under proteasome inhibition.

Methods

Protein aggregation was induced with 1 mM MG‐132 and autophagy was inhibited with bafilomycin A1. Resvega that includes vitamin C 240 mg, E 30 mg, zinc 12.5 mg, copper 1 mg, omega‐3 665 mg, lutein 10 mg, zeaxanthin 2 mg and resveratrol 30 mg was used solely and together with proteasome inhibition up to 48 h. p62 (SQSTM1), LC3 (microtubule‐associated protein 1A/1B‐light chain 3) and Hsp70 (Heat shock protein 70) were analyzed by Western blotting (WB). Tandem fluorescently tagged LC3 (GFP‐mCherry‐LC3) transfection was used to study autophagy flux in fluorescence microscopy.

Results

Inhibition of proteasomes with MG‐132 upregulated Hsp70, autophagy markers p62 and LC3 detected in WB. Simultaneous treatment with MG‐132 and Resvega corresponding 25 μM resveratrol concentration highly increased amount of LC3‐II, but decreased p62 and Hsp70. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. Fluorescence microscopy showed increased autophagy flux with GFP‐mCherry‐LC3 Resvega treatment and autophagy inhibition resulted accumulation of p62 and LC3‐II.

Conclusions

This data showed how Resvega was able to induce autophagy and clear protein waste caused by proteasome inhibition in ARPE‐19 cell line. Resvega has a potential in the prevention and treatment of RPE damage and AMD.
Correlating myopia severity with visual performance in a young Asian male population
Authors: Ang B.C.H. , Tan M.M.H. , Cheong K.X. , Lim E.W.L. , Yang A.H. , Tey F.L.K. , Tan C.S.H. , Tan M.C.L.
Published: September 2016

Purpose

To examine the visual performance in a young Asian male population with severe myopia.

Methods

A cross‐sectional study of right eyes of 564 severe myopes [Spherical Equivalent (SE) ≤−6.00 D] and 148 emmetropes (SE −0.50 to +1.00 D). The severe myopes were categorised into three groups (Group 1: SE −6.00 to >−8.00D; Group 2: SE −8.00 to >−10.00D; and Group 3: SE ≤−10.00D). Multivariate regression analyses adjusting for age and ethnicity were performed to examine the relationship between Corrected Distance Visual Acuity (CDVA) [photopic, mesopic and Night Vision Goggles (NVG)] and Contrast Sensitivity (CS) (mesopic and NVG) with SE and Axial Length (AL).

Results

The mean age of subjects was 21.07 ± 1.17 years and majority were Chinese (91.9%). The mean SE was 0.10 ± 0.23D for emmetropes and −8.76 ± 2.04D for severe myopes (p < 0.001). Higher degrees of myopia were associated with reduced CDVA and CS and increased AL (all p < 0.001 among groups). Among the severe myopes, Group 1 had the highest proportion of subjects with good CDVA (photopic ≥6/6, mesopic ≥6/6, and NVG ≥6/7.5 LogMAR) and CS (mesopic ≥0.75 and NVG ≥0.35 LogCS) compared to Groups 2 and 3 (all p < 0.001). Among severe myopes with good VA (photopic ≥6/6, mesopic ≥6/6, or NVG ≥ 6/7.5 LogMAR), Group 1 also had the highest proportion of subjects who achieved mesopic CS of ≥0.75 and NVG CS ≥0.35 LogCS (both p < 0.001). Multivariate analyses also demonstrated that reduced VA and CS were significantly associated with decreased SE and increased AL (all p < 0.001).

Conclusions

Higher degrees of myopia are associated with reduced VA and reduced CS.
Ganglion cell‐inner plexiform layer thickness and visual improvement after vitrectomy for rhegmatogenous retinal detachment
Authors: Lee J.Y. , Kim D.Y. , Kim J.Y.
Published: September 2016

Purpose

To evaluate the association of postoperative macular ganglion cell‐inner plexiform layer (GCIPL) thickness with postoperative visual outcomes in patients undergoing vitrectomy for macular–off rhegmatogenous retinal detachment (RRD) using spectral domain optical coherence tomography.

Methods

Data from 22 eyes with macular‐off RRD who were followed for more 6 months after successful pars plana vitrectomy were analyzed. Macular GCIPL thickness in eyes with RRD was compared with that of the normal contralateral eyes 6 months after surgery. The correlation between the interocular difference in GCIPL thickness and postoperative best corrected visual acuity (BCVA) was evaluated.

Results

Preoperative and postoperative central macular thickness were 538.09 ± 318.42 μm, 230.77 ± 34.69 μm. Mean GCIPL thickness was significantly decreased with time after surgery (3 vs. 6 months, p < 0.01). Mean GCIPL thickness in eyes with RRD 6 months after surgery were 61.04 ± 12.04 μm and in the unaffected contralateral eyes were 73.67 ± 6.73 μm. The interocular difference in macular GCIP thickness was significantly correlated with postoperative BCVA. Among patients with intact photoreceptor layers, a greater decrease in GCIPL thickness was correlated with a worse postoperative BCVA (r = 0.629; p = 0.02). No significant correlation were identified between interocular macular GCIPL thickness difference and age (r = 0.629; p = 0.85), axial length (r = 0.874; p = 0.43).

Conclusions

Macular GCIPL thickness decreased after vitrectomy to repair for RRD. The decrease in GCIPL thickness was significantly correlated with postoperative visual outcomes.
Ultrasound treatment in patients with Primary Open‐Angle Glaucoma with a second generation probe: Results of a Multicenter Clinical Trial
Authors: Aptel F. , Rouland J.F. , Stalmans I. , Denis P.
Published: September 2016

Purpose

To evaluate the efficacy and safety of the Ultrasound Ciliary Plasty (UCP) procedure with a second generation probe.

Methods

Fifty‐two eyes of 52 patients with primary open‐angle glaucoma were treated between April 2015 and August 2015 in 4 University Hospitals with a second generation therapy probe comprising 6 piezoelectric transducers with increased lesion volume. All patients were treated with a 8 sec exposure time. Complete ophthalmic examinations were performed before the procedure, and at 1 day, 1 week, 3 and 6 months after. Primary outcomes were surgical success (defined as IOP reduction from baseline ≥20% and IOP > 5 mmHg) at the last follow‐up visit, and vision‐threatening complications. Secondary outcomes were mean IOP at each follow‐up visits compared to baseline, medication use, complications, and re‐interventions.

Results

IOP was significantly reduced (p < 0.02), from a mean preoperative value of 24.3 ± 7.0 mmHg to a mean value of 16.8 ± 7.6 mmHg at last follow‐up. Success (IOP reduction >20%) was achieved in 67% of eyes at last follow‐up. Four patients were ret‐treated. No major intra‐ operative complications occurred. Transitory hypotony (IOP < 5 mmHg) occurred in 3 patients, choroidal detachment in 1 patient and macular edema in 1 patient during the follow‐up.

Conclusions

Ultrasonic Circular Cyclo Coagulation seems to be an effective method to reduce intraocular pressure in patients with OAG. Increasing the lesion volume seems to increase the efficacy and rate of responders.
Neuroprotective effects of EPA and DHA fatty acids in the DBA/2J hereditary glaucoma mouse model
Authors: Kalogerou M. , Prokopiou K. , Kolovos P. , Malas S. , Papagregoriou G. , Deltas C. , Georgiou T.
Published: September 2016

Purpose

To determine whether omega‐3 (ω‐3) supplementation used alone or in combination with timolol, protect against inflammation and RGC loss in DBA/2J mouse model

Methods

DBA/2J mice were assigned to the following treatment groups (n = 20/group) with balanced sex:ω‐3 plus timolol, ω‐3,timolol and untreated. All treatments were started at the age of 8.5 months and continued until sacrifice at 11.5 months of age. Mice received daily gavage administration of fish oil (EPA/DHA = 2:1) and/or topical instillation of timolol (0.5%) once a day. The dosage of EPA/DHA was adjusted so that the AA/EPA blood ratio was within therapeutic range of 1–1.5 using Gas chromatography. RGC densities were counted using Brn3a antibody. Real‐time polymerase chain reaction was performed to determine the gene expression of TNF‐α, IL‐1β and IL‐18 inflammatory molecules in the retinas. Western blot analysis was used to test the protein expression of IL‐18 in the retinas.

Results

RGC densities were found significantly higher in the groups of ω‐3 plus timolol (p = 0.0041),ω‐3 (p = 0.0097) and timolol (p = 0.0011) compared to that of untreated group. No significant differences were seen in the gene expression levels of TNF‐α (p = 0.0790, p = 0.0742, p = 0.1006),IL‐1β (p = 0.1242, p = 0.4865, p = 0.5280) and IL‐18 (p = 0.6320, p = 0.3351, p = 0.3663) in the retinas between the groups of ω‐3 plus timolol, ω‐3 or timolol and the untreated group. Protein expression of IL‐18 was significantly reduced in the retinas of ω‐3 treatment group compared to that of untreated (p = 0.0367)

Conclusions

Our findings suggest not only that ω‐3 supplementation (AA/EPA ratio <1.5) has a neuro‐protective effect in the DBA/2J, as demonstrated by the RGC density analysis, but also provide insight into the role of inflammation in the pathogenesis of glaucoma and indicate that ω‐3 administration could be beneficial in controlling inflammation in the retina.
Early changes in mild Alzheimer's disease in the neuroretinal rim segmentation
Authors: Salobrar‐Garcia E. , Leal M. , Hoyas I. , Salazar J.J. , Ramirez A.I. , de Hoz R. , Rojas B. , Gil P. , Yubero R. , Triviño A. , Ramirez J.J.
Published: September 2016

Purpose

The purpose of the present study was to analyze in detail the peripapillary area divided into 12 sectors in order to identify the first sector that thins in Alzheimer's disease (AD) patients compared with controls.

Methods

A total of 23 mild AD patients and 28 controls were examined. Patients underwent a complete ophthalmologic exam. The peripapillary RNFL thickness parameters evaluated were thickness for each 12‐o'clock hour position with the 3‐o'clock position as nasal, 6‐o'clock position as inferior, 9‐o'clock position as temporal, and 12‐o'clock position as superior. Patients were required to have a visual acuity better than 0.6 and no retinal pathology.

Results

Compared to controls, the eyes of patients with mild‐AD patients showed no statistical difference in peripapillary RNFL thickness (p > 0.05); however, sectors 2, 3, 4, 8, 9, and 11 of the papilla showed thinning, but thickening in sectors 1, 5, 6, 7, and 10.

Conclusions

Despite the fact that peripapillary RNFL thickness did not statistically differ in comparison to control eyes, the increase in peripapillary thickness in our mild‐AD patients could correspond to an early neurodegeneration stage and may entail the existence of an inflammatory process that could lead to progressive peripapillary fiber damage.
Short‐term efficacy of intravitreal aflibercept depending on subtypes of polypoidal choroidal vasculopathy: polypoidal choroidal neovascularization or idiopathic choroidal vasculopathy
Authors: Sagong M. , Jeong S.
Published: September 2016

Purpose

To compare the short‐term efficacy of intravitreal aflibercept treatment for polypoidal choroidal neovascularization (CNV) and idiopathic polypoidal choroidal vasculopathy (PCV).

Methods

Twenty‐nine patients (29 eyes) with treatment‐naïve subfoveal PCV were consecutively enrolled in this institutional study. The subjects were classified into two subtypes (type 1, polypoidal CNV, 16 eyes; and type 2, idiopathic PCV, 13 eyes) based on the presence or absence of both feeder and draining vessels on indocyanine green angiograph. Intravitreal aflibercept was administered at baseline and at 1, 2, and 4 months. The primary outcome was the polyp regression percentage after 3 monthly injections. Changes in the best‐corrected visual acuity and subfoveal choroidal thickness (CT) were evaluated at 3 and 6 months

Results

The complete polyp regression percentage was higher in type 1 than type 2 patients after 3 monthly injections (81 vs. 30%, respectively; p = 0.008). Type 1 patients showed better visual improvement at 3 months than type 2 patients (−0.34 vs. −0.08 logarithm of the minimum angle of resolution [logMAR], respectively; p = 0.050). Although subfoveal CT was significantly decreased after injections in both groups, type 2 patients with a thicker choroid at baseline showed a greater decrease than type 1 patients (−43.5 μm vs. −19.6 μm, respectively; p = 0.032) at 3 months.

Conclusions

There was a difference in early treatment response with aflibercept between two subtypes of PCV. Type 1 polypoidal CNV showed better visual improvement with a higher percentage of polyp regression than type 2 idiopathic PCV.
Angiogenic potential of orbital adipose derived stromal cells
Authors: Afanasyeva D. , Gushchina M. , Borzenok S.
Published: September 2016

Purpose

Orbital fat contains adipose‐derived stromal cells (ADSC), many therapeutic effects of which have been showed during last years. One line of research is studying of their secretory potential and their role in orbital volume augmentation. It is known that ADSC from subcutaneous adipose tissue secrete some angiogenic and antiapoptotic factors. Nevertheless, there is no information on this, regarding the orbital ADSC. The purpose of this study was to define the secretion of angiogenic factors by orbital ADSC.

Methods

Samples of orbital adipose tissue were resected during standard reconstructive and plastic surgery. We isolated orbital ADSC and then collected samples of culture medium on Day 2 and 5 for further quantification of VEGF‐A and TGF‐ß2 with ELISA.

Results

VEGF‐A was determined in most samples of culture medium on Day 2. In 4 samples primary negative for VEGF A, this factor was determined on Day 5. In other samples we noticed decrease of VEGF‐A concentrations up Day 5 (p = 0.025). In samples of culture medium of orbital ADSC from nasal fat pad on Day 2 we detected TGF‐ß2, in contrary to the samples from other orbital fat pads. In samples of culture medium primary negative for TGF‐ß2, on Day 5 we have noticed the secretion of this factor. There we no significant difference in VEGF‐A and TGF‐ß2 concentrations in culture medium of orbital ADSC isolated from patients of different age and orbital condition.

Conclusions

In vitro orbital ADSC secrete VEGF‐A and TGF‐ß2. It points out their potential to regulate angiogenesis in orbital tissues and may play positive role at fat transplantation into the orbit.
Taurine exerts antioxidant and osmoprotecting activity: an in vitro and in vivo study
Authors: Bucolo C. , Fidilio A. , Platania C.B.M. , Geraci F. , Drago F.
Published: September 2016

Purpose

To evaluate the effects of ophthalmic solutions based on sodium hyaluronate (SH) with or without taurine (TAU) in experimental dry eye disease models.

Methods

Rabbit corneal epithelial cells (SIRCs) were exposed to oxidative stress (1 mM H2O2) and treated with the following formulations: 0.2% SH, 0.4% SH, 0.4% SH + 0.5% TAU. Reactive oxygen species (ROS) were assessed by commercial kit (ab113851). Dry eye was induced in albino rabbits by topical application (4 times per day) of 1% atropine eye drops. Fifteen minutes after atropine instillation we treated the eyes with test formulations (0.2% SH, 0.4% SH, 0.4% SH + 0.5% TAU). The following endpoints were evaluated: tear breakup time (TBUT), Schirmer's test, ferning test, tear osmolarity. Results were compared to negative (CTR‐; normal eye) and positive control groups (CTR+; atropine‐treated eye).

Results

Taurine significantly (p < 0.01) quenched ROS production in SIRC after oxidative stress. The effect of taurine, in terms of ROS quenching, was significantly (p < 0.01) higher compared to SH‐treated cells. Topical administration of atropine in the rabbit eye significantly (p < 0.01) reduced tear volume and TBUT. Ferning test and tear osmolarity were also significantly (p < 0.01) modified by atropine treatment. All the altered parameters were significantly (p < 0.01) reversed by 0.4% SH + 0.5% TAU treatment. Furthermore, treatment with SH‐TAU formulation was more effective compared to SH formulations.

Conclusions

All together these data demonstrated that taurine has a potent antioxidant activity preventing the negative effect elicited by atropine on tear stability. Therefore, our findings support the hypothesis that the formulation containing taurine may be more useful than SH formulations in clinical practice to manage ocular surface diseases related to dry eye.
Retrospective review of pressure reducing effect of iStent and Trabectome procedures combined with cataract surgery
Authors: Toth M. , Bazeer S. , Gazzard G.
Published: September 2016

Purpose

To evaluate the intraocular pressure (IOP) reducing effect of cataract operation combined with either trabecular bypass microstent (iStent) implantation or internal trabeculectomy (Trabectome).

Methods

A retrospective interventional case series involving 61 eyes who underwent cataract surgery combined with either iStent implantation or Trabectome. Outcomes included short term (1–3 months) and long term (6–12 months) changes of intraocular pressures and number of glaucoma medications.

Results

For all cases, mean preoperative IOP of 19.9 ± 5.2 mmHg decreased by 17% to 15.8 ± 4.9 mmHg short term and by 12% to 16.4 ± 3.73 mmHg long term. For iStent cases, short term and long term IOP reduction was 21.7 and 17.7%, respectively (from 20.6 ± 6.3 mmHg to 15.2 ± 3.3 and to16.5 ± 3.8 mmHg). For Trabectome cases, short term and long term IOP reduction was 14.6 and 10.5%, respectively (from 19.5 ± 4.5 mmHg to 16.2 ± 5.7 and to 16.4 ± 3.8 mmHg). Long‐term IOP changes were significant in both subgroups (p < 0.005). There was no significant change in the number of glaucoma medications in either groups (2.0 ± 1.1 preoperative, and 1.7 ± 1.3 long term postoperative for all cases, p = 0.09.)

Conclusions

Cataract surgery combined with iStent or Trabectome provided a significant but only modest reduction in intraocular pressure.
In vivo measurement of increased vascular permeability after STZ induction of diabetes in rats by fluorescence angiography using the Micron IV
Authors: Allen C. , Bates D.
Published: September 2016

Purpose

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness. Chemically induced diabetic rodent models mimic some phenotypic changes in DR, but quantitative assessment of increased vascular permeability seen in diabetes usually requires invasive and terminal experiments. The Micron IV provides enhanced sensitivity, resolution, real‐time capture and a non‐invasive platform compared to comparable systems. This study tests the hypothesis that retinal vascular leakage can be assessed in vivo over time, using the Micron IV.

Methods

FA was carried out in non and diabetic rats on day 0 and 7 using the Micron IV. Animals received a single dose of PBS (n = 6) or streptozotocin i.p., 50 mg/kg (n = 6) on day 1 and blood glucose levels were measured on day 4. Angiograms were converted to 8‐bit images in ImageJ and the intensity of sodium fluorescein in an area of the vascular interstitium and the retinal vessel were measured over time. The ratio of interstitial to vascular fluorescence intensities were plotted against time to give rate of increase in intensity per unit time.

Results

Retinal vascular leak was measured in the same focal position of the retina on day 0 and 7 using the Micron IV. Retinal leak was shown to significantly increase (p < 0.05) in the STZ induced diabetic group (13.3 ± 3.30 × 10−4 s−1) compared to non‐diabetic controls (7.5 ± 3.7 × 10−4 s−1), on day 7. This was supported by fundus images showing increased capillary leakage and the formation of multiple micro‐aneurysms in the retina.

Conclusions

The Micron IV system provides a standardised, real‐time and non‐invasive platform to measure retinal permeability in a rat model of diabetes. Advanced quantitative assessments such as this could substantially contribute to a better understanding of the pathogenesis of DR and identify potential drugs for treatment.
Development of novel electrospun scaffolds for corneal tissue engineering
Authors: Kador K. , Ahearne M.
Published: September 2016

Purpose

Blindness due to corneal disease or injury is one of the leading causes of blindness worldwide. Tissue engineering techniques are currently developed to create whole corneal replacement including corneal substitutes constructed from compressed collagen, electrospun fibres and decellularized corneal extracellular matrix (ECM). Here we combine these methods to develop electrospun scaffolds with different fibre alignments while incorporating ECM into the scaffolds to enhance the cell's environment and maintain the native cell phenotype.

Methods

Porcine corneas were dissected, decellularized and milled to a fine powder. Gelatin or Polycaprolactone (PCL) were dissolved with or without ECM and electrospun in different alignments. Scaffolds were characterized by infrared spectroscopy (FTIR), water contact angle, fibre diameter, light absorbance and transparency. Human stromal cells were cultured for seven days and then analysed for survival, morphology and biochemical markers through immunohistochemistry and PCR.

Results

New peaks corresponding to polypeptide bonds were observed in FTIR scans from PCL/ECM when compared to PCL along with a decrease in the water contact angle. No change was observed with the incorporation of ECM to gelatin fibers. Aligned fibre scaffolds from all samples absorbed less light and were more translucent. Random fibres resulted in a greater distortion of test images while PCL and PCL/ECM random samples were completely opaque. No change in survival was observed but fibre orientation and ECM did affect the cell morphology while orientation affected ALDH3a1 expression.

Conclusions

Incorporating corneal ECM into aligned electrospun fibres mimics the cornea's native structure and environment while helping to maintain the keratocyte morphology and protein markers.
Filtering blebs after XEN implantation and trabeculectomy: a clinical and in vivo confocal microscopy study
Authors: Cardigos J. , Crisostomo S. , Costa L. , Anjos R. , Vieira L. , Cardoso M. , Reina M. , Gomes T.
Published: September 2016

Purpose

The aim of this study was to evaluate and compare macroscopic and microscopic morphological features of functioning filtering blebs after XEN Gel Stent (XEN) implantation and trabeculectomy.

Methods

Prospective, observational case‐control study of 10 eyes submitted to XEN implantation, 10 eyes submitted to trabeculectomy and 11 control eyes treated medically. A complete ophthalmological examination was performed, including Goldmann applanation tonometry, slit‐lamp examination, anterior segment photography and in vivo confocal microscopy (IVCM – Heidelberg Retina Tomograph II, Rostock Cornea Module). Photographs were analyzed with Moorfields bleb grading system classification. The IVCM images were analyzed for the density of intraepithelial microcysts, the density of subepithelial connective tissue, the number, diameter and tortuousity of blood vessels and the presence of inflammatory cells. The examinations were performed from 6 to 16 months postoperatively and only blebs resulting from a surgery with total success were included (Intraocular pressure <21 mmHg without therapy).

Results

The analyze of anterior segment photographs didn't showed diferences between blebs's features after XEN implantation and trabeculectomy. The IVCM showed an increase in the density of intraepithelial microcysts and subepithelial connective tissue in XEN and trabeculectomy blebs comparing with the controls (p < 0.05). All morphological findings were similar when comparing the group of XEN and trabeculectomy blebs.

Conclusions

Functioning blebs after XEN implantation showed similar features comparing with functioning blebs after trabeculectomy. Further longitudinal studies are needed to increase the postsurgery understanding and management of filtering blebs.
Outcomes after surgical resection of lower eyelid tumors and reconstruction using a septal chondromucosal graft and an upper eyelid skin flap
Authors: Lemaitre S. , Levy‐Gabriel C. , Couturaud B. , Gardrat S. , Cassoux N. , Desjardins L.
Published: September 2016

Purpose

Surgical excision of large malignant lower eyelid tumors may cause important full‐thickness eyelid defects. The reconstruction of such defects must reestablish an acceptable aesthetic result and also restore the physiologic function of the eyelid.

Methods

We report the outcomes of full‐thickness excision of tumors extending over half of the horizontal lid length, followed by reconstruction using a septal chondromucosal graft (coming from the ipsilateral nasal cavity) and an upper eyelid skin flap. Histological analysis of the specimen identified the tumor type and surgical margins for each patient.

Results

25 patients were operated with this technique between March 2009 and June 2015: 17 basal cell carcinomas, 3 spindle cell carcinomas and 5 conjunctival melanomas (out of which 2 were associated with lentigo malignant melanoma). Mean duration of follow‐up after surgery was respectively 36, 41 and 17 months for each of these 3 tumor types. We found a single local tumor recurrence and it was a basal cell carcinoma in a xeroderma pigmentosum patient. We describe some of the possible surgical complications and functional sequelae.

Conclusions

In the case of eyelid tumors, the need to perform complete oncologic excision with margins adapted to tumor type may result in the removal of an important part of the eyelid. Several surgical techniques are available for lower eyelid reconstruction; the choice of the technique and its results depend mainly on the surgeon's experience.

In malignant tumors, complete surgical excision with margins adapted to tumor type prevents local recurrence in most cases. Our repair strategy gives good aesthetic and functional results.
Reduced post‐illumination pupil response in patients with mild‐moderate cataracts is associated with impaired sleep quality
Authors: Roemer S. , Munch M. , Ladaique M. , Hashemi K. , Kawasaki A.
Published: September 2016

Purpose

Cataracts absorb light, especially in the blue‐range of the visible light spectrum, and reduce retinal illumination. Recent studies showed improved sleep and faster reaction times following cataract extraction. These non‐visual benefits are perhaps due to increased blue light transmission and melanopsin‐dependent photoreception. We compared visual function, pupil responses, sleep quality and sleep‐wake cycle in patients with cataracts and controls.

Methods

30 patients with cataracts and 22 age‐matched pseudophakic controls were tested during the winter season. Ophthalmologic examination with automated perimetry and optical coherence tomography was performed. Pupil responses were recorded to a 1s red or blue light having pre‐selected intensities. All participants completed a questionnaire for subjective sleep quality (Pittsburgh Sleep Quality Index; PSQI). They were asked to maintain a regular sleep‐wake rhythm with approximately 8 h of sleep. Rest‐activity cycles were recorded for one week by wrist worn activity watches.

Results

Mean acuity was 1.0 ± 0.1 for both groups. The pupil contraction amplitude to dim blue light and the post‐illumination pupil response to bright blue light were significantly reduced in patients with cataracts (p < 0.05). This was associated with a significantly higher PSQI score relative to controls (p = 0.02), indicating impaired sleep, and a lower post‐illumination response to bright blue light (R = 0.43; p < 0.05). Sleep analysis from the activity watches revealed a significantly lower sleep efficiency in cataract patients than in controls (78.6 ± 8.3 vs. 83.2 ± 4.5; %; mean ± SD; p = 0.02).

Conclusions

Patients with cataracts, not visually impaired, demonstrate reduced melanopsin activity, as assessed by the pupil response. This latter is correlated with impaired subjective sleep quality and greater sleep fragmentation.
Use of glaucoma medications in Portugal: a cross‐sectional nationwide study
Authors: Cordeiro Sousa D. , Leal I. , Nascimento N. , Abegão Pinto L.
Published: September 2016

Purpose

There is scarce data about antiglaucomatous prescribing patterns in Portugal. We aim to describe and analyze the nationwide prescription of glaucoma medications in Portugal in the year of 2015. Ultimately, our goal is to identify improvement opportunities for the system and the patient, in particular.

Methods

Cross‐sectional study. A common electronic drug prescription system is used by all hospitals and clinics in Portugal. We used this national database and included all hypotensive drug prescriptions in 2015. Demographic data, medications prescribed (in isolation and fixed combination) and healthcare related costs were provided in an encrypted form and anonymously extracted. Statistical analyses were performed using STATA 13.0.

Results

A total of 236.234 subjects (56.8% women) were prescribed one or more drugs. Mean age was 71.6 ± 13.3 [range 0; 108] years. Of the ~800.000 prescriptions, 52.3% were from general practitioners and 38.7% from ophthalmologists. The most prescribed drugs were latanoprost (20.0%), timolol/dorzolamide (13.7%), brimonidine (9.0%) and timolol (8.8%). Single‐dosed preparations were prescribed in significantly younger patients (mean age = 68.7 ± 0.07) than other formulations (mean age = 71.8 ± 0.01), p < 0.001. Single‐agent and combination therapies accounted for 14.5€ M and 8.5€ M in costs for the healthcare system, respectively.

Conclusions

This nationwide study revealed prescription's trends and disclosed the burden of the disease in terms of its medical management. A cost‐effective approach in glaucoma is essential for the whole system sustainability and should be promoted by every healthcare stakeholder.
In vitro activity of Cacicol® on herpes simplex virus type 1: a promising adjunct therapy of herpetic corneal infections?
Authors: Labetoulle M. , Rousseau A. , Breckler M. , Molet L. , Boutolleau D. , Burrel S. , Deback C.
Published: September 2016

Purpose

Herpes simplex keratitis (HSK) remains the leading cause of infectious blindness in developed countries. Cacicol®, a topical eye biopolymer containing a poly‐carboxymethyl sulfate solution is a recent licensed regenerating agent used for matrix repair therapy, intended for wound healing of corneal epithelial defects. According to its chemical composition, we hypothesized that Cacicol® could compete with natural heparan sulfate which initiates cell surface attachment of herpes simplex virus type 1 (HSV‐1) and that Cacicol® could have unexplored antiherpetic activities.

Methods

Cacicol® was tested in vitro against both cell free HSV‐1 SC16 strain and HSV‐1 PSL‐R, a clinical isolate resistant to both acyclovir and foscarnet due to mutations in both thymidine kinase and DNA polymerase, and compared to the activity of vehicle, equivalent to active drug minus the active component. The reduction of the initial viral inoculum by Cacicol® or vehicle, during 1 h adsorption was determined by plaque reduction assays on Vero cells.

Results

A dose dependent effect was demonstrated when both SC16 and PSL‐R were pre‐treated with Cacicol® during adsorption. Initial inoculums of 1,104 PFU were significantly decreased to 160 PFU (±26.6) and 117 PFU (±22.3) for SC16 and PSL‐R respectively, while vehicle has no effect on viral replication.

Conclusions

Cacicol® has a significant in vitro antiherpetic activity and seems particularly interesting for the management of HSV‐1 resistant to acyclovir or foscarnet, especially in tissues that can receive Cacicol® by topical application (such as the cornea). Clinical studies are necessary to determine its in vivo activity and its usefulness as a promising adjunct or alternative therapy of recurrent HSK.
Modern diagnostic methods used in macular telangiectasia
Authors: Romanowska Dixon B. , Karska Basta I. , Lesniak A.
Published: September 2016

Purpose

Presenting an assessment of new, various diagnostic methods used in patients with macular telangiectasia – an idiopathic, uncommon disorder characterized bytelangiectatic vessels in the juxtafoveolar region.

Methods

The study included 5 patients with macular telangiectasia treated in theDepartment of Ophthalmology and Ocular Oncology, Jagiellonian University, CollegiumMedicum in Cracow. The patients were enrolled in an observational study and evaluatedusing various diagnostic and treatment methods. The examination included BCVA, funduscolor photo, fundus autofluorescence, fluorescein angiography, DRI OCT‐1 AtlantisTOPCON and OCT‐angiography (AngioVue). Retinal layers, the region bounded by the outer retina, Bruch's membrane, choriocapillaris, and the remaining choroidal vasculature were assessed.

Results

In all 5 patients with macular telangiectasia, the telangiectatic vessels wereidentified in fluorescein angiography, showing leakage in late phase. DRI OCT‐1 allows to abetter assessment of the neurosensory retina and demonstrate small foveal cystoid cavitieswith destruction of inner and outer layers, which is typical of this disease. This isvery useful in differentation with choroidal neovascularization in the wet type of AMD orcystoid macular oedema and helps to determin the severity of the disease. In all the patients OCT‐angiography (AngioVue) enabled a visualization of very small retina vessels, but not a diagnosis of the neovascularization and leakage.

Conclusions

The results of our observation indicate that fluorescein angiography and DRIOCT‐1 seem to be the most useful diagnostic methods in macular telangiectasia, but OCT‐angiography can provide an alternative assessment method especially in patients with contraindications for fluorescein angiography. Further studies comprising a wider group of patients are necessary.
5‐year Incidence of Lubricant Dependence in Medically and Surgically Treated Glaucoma Patients
Authors: Iyer J. , Lim F. , Yang Z. , Tong L. , Wong T.
Published: September 2016

Purpose

Chronic use of intraocular pressure (IOP) lowering medications is associated with ocular surface disease. Glaucoma surgery has also been associated with ocular surface disturbances. In this study we assess the incidence of topical lubricant use in glaucoma patients who are medically controlled or who have had glaucoma surgery over 5 years of followup.

Methods

Retrospective chart review was performed for patients on medications for primary open angle glaucoma. Some of these patients required subsequent glaucoma surgery. Primary outcome measure was the incidence and onset of topical lubricant use in these patients.

Results

505 cases patients with POAG were reviewed. Mean age was 63.9 years (SD: 11.1) and 42.8% were women. 122 of these patients required a MMC‐augmented phacotrabeculectomy (n = 97) or trabeculectomy (n = 25) over the course of followup. 5‐year incidence of lubricant use was 39% in glaucoma subjects. Females were more likely to use topical lubricants (p < 0.01). Incidence of lubricant use increased from 21.3% preoperatively to 71.3% postoperatively in subjects who subsequently underwent trabeculectomy or phacotrabeculectomy.

Conclusions

Glaucoma medications, surgery and female gender are predisposing factors for ocular lubricant use. Notably MMC‐augmented trabeculectomy and phaco‐trabeculectomy increased the need for topical lubricants by more than threefold.
Normobaric hypoxia induces changes in mean ocular perfusion pressure
Authors: Leal I. , Cordeiro Sousa D. , Moreira S. , Dionisio P. , Abegao Pinto L. , Marques‐Neves C.
Published: September 2016

Purpose

It is still unclear how a normobaric hypoxic stimulus affects mean ocular perfusion pressure (MOPP) in healthy subjects. The Hypoxia Challenge Test (HCT), performed according to the British Thoracic Society (BTS) protocol, mimics the hypoxia levels in medium/long‐haul flights, in which cabins are pressurized to a value of around 565 mmHg, equivalent to breathing 15.1% oxygen at sea level. We aimed to study the relationship between hypoxia and MOPP.

Methods

Prospective cohort study. All volunteers answered a health questionnaire and HCT was performed, according to the BTS protocol. Oxygen desaturation index (ODI) was assessed using the built‐in software. Intraocular pressure was measured in three timepoints (baseline, hypoxia, post‐hypoxia) using iCare® tonometer. The MOPP was calculated as MOPP = 2/3(mean arterial pressure) − IOP. To guarantee data independence, right and left eyes were compared separately. Statistical analyses were performed using STATA 13.0.

Results

Studied population included 30 subjects (14 women), with a mean age of 28.8 ± 4.2 [range 22–37] years. There was a within‐subject statistically significant difference in MOPP for both right and left eyes (p < 0.01). Paired analysis confirmed a significant difference (p < 0.05) in MOPP values (in mmHg): baseline (OD = 46.6 ± 6.7, OS = 47.0 ± 6.6), hypoxia (OD = 43.5 ± 6.7; OS = 43.1 ± 6.6) and post‐hypoxia (OD = 46.7 ± 6.2, OS = 47.3 ± 5.9). Controlling for age and axial length, a multivariate linear regression model analysis revealed a relationship between MOPP and ODI, for right (p = 0.01) and left (p = 0.07) eyes.

Conclusions

To our knowledge, there is no published data specifically addressing flight cabin hypoxia and MOPP. These results in healthy subjects may help to establish normality responses to a hypoxic stress.
Macular thickness in diabetic eyes without clinical macular edema
Authors: García Zamora M. , Montero Moreno J.A. , Gonzalez Uruena C. , Frances Caballero E. , Fernandez‐Munoz M.
Published: September 2016

Purpose

To evaluate macular thickness of individuals with moderate diabetic retinopathy (DR) without macular edema (DME).

Methods

Retinal thickness was calculated by automated segmentation of spectral domain‐optical coherence tomography scans of patients with moderate DR without DME and compared with an age‐matched population of non‐diabetic individuals. Mean values and multiple linear regression analysis were used to determine the relationship between retinal layers thickness and age, sex, diabetes type and concentration of glycosylated hemoglobin (HbA1c).

Results

A total of 66 eyes were studied, 34 eyes with moderate DR without DME or previous treatment and 32 eyes from non‐diabetic individuals. The mean retinal nerve fiber layer (RNFL) thickness in the superior parafoveal area of patients with DR was 29.88 μm vs. 23.18 μm in the non‐diabetic group (p = 0.01). The mean inner nuclear layer thickness in the central fovea area in the DR group was 28.26 μm vs. 22.87 μm in the non‐diabetic control group (p = 0.01). There was a significant linear correlation (R = 0.353, p = 0.04) between HbA1c and the inner nuclear layer thickness in the superior parafoveal area.

Conclusions

According to our findings, DR patients showed an increase of macular thickness compared with the non‐diabetic control group in the superior parafoveal and central foveal area. Increased HbA1c levels may play a role in the increased macular thickness.
Treatment of neovascular age‐related macular degeneration with anti‐VEGF agents: predictive factors of long‐term visual outcomes
Authors: Pedrosa A.C. , Sousa T. , Pinheiro‐Costa J. , Beato J. , Falcão M. , Falcão‐Reis F. , Carneiro Â.
Published: September 2016

Purpose

To evaluate the predictive factors of long‐term visual outcomes in neovascular age‐related macular degeneration (nAMD) treated with anti‐VEGF agents.

Methods

Unicentric retrospective review of patients with nAMD treated with anti‐VEGF agents. Visual outcomes, 12 and 60 months after diagnosis, were evaluated: visual acuity (VA), VA variation, VA ≥65 ETDRS letters and VA variation >0 ETDRS letters. In the attempt to identify predictive factors of visual outcomes, the following variables were analyzed: at baseline, age, gender, VA, choroidal neovascularization subtype, central foveal thickness, presence of subfoveal hemorrhage or fibrosis, and treatment delay; during follow‐up, frequency of medical examinations, missed medical examinations, intravitreal injections, missed injections and of treatment suspension, as well as the development of retinal atrophy, subretinal fibrosis, sudden massive retinal hemorrhage and retinal pigment epithelium tear.

Results

One hundred and seventeen patients were included. In multivariate analysis, the only predictive factor of visual outcomes at 12 months was baseline VA: a higher baseline VA was associated with a higher final VA and a higher likelihood of final VA ≥65 ETDRS letters, but a smaller VA variation and a lower likelihood of VA increase. Baseline VA remained a predictive factor of all visual outcomes 60 months after diagnosis. Additionally, at 60 months, higher final VA was also predicted by a higher number of injections and no subretinal fibrosis during follow‐up, and VA increase was more frequent in younger and female patients.

Conclusions

Baseline VA influences absolute VA and VA variation at 12 and 60 months, while number of injections, development of subretinal fibrosis, age at diagnosis and gender are predictive factors at 60 months.
The effect of silica nanoparticle exposure on cultured human keratocytes
Authors: Yim B. , Park J. , Park C.Y.
Published: September 2016

Purpose

Silica nanoparticles (SiNPs) are closely related to our daily life including drug delivery, cosmetics and fine dust. However, the influence of SiNPs on human corneal keratocyte cells has not yet been widely studied. In this study, we investigated the effect of SiNPs on cultured human keratocytes.

Methods

Human keratocytes were cultured in DMEM/F12(1:1) medium containing 10% FBS and Antibiotic‐Antimycotic. SiNPs exposure was performed by adding 50, 100 and 150 nm of non‐porous SiNPs into culture media with different concentrations (10, 20, 50, 100 μg/ml) for 24 and 48 h. Keratocytes viability was measured using CCK‐8 reagent after 24 and 48 h exposure of SiNPs. Release of Lactate Dehydrogenase (LDH) was measured by LDH cytotoxicity detection kit. The measurement of intracellular reactive oxygen species (ROS) generation was performed using Fluorometric Intracellular Ros Kit. Cellular autophagy activity (LC3B and Beclin 1) and mTOR pathway activation (p‐mTOR and mTOR) were detected by Western Blot.

Results

In human keratocytes, significant cellular cytotoxicity and membrane damage were not detected after exposure to three different sizes of SiNPs for 24 and 48 h. Intracellular ROS generation was slightly increased at high concentration (100 μg/ml) of three sizes of SiNPs. And Cellular autophagy was significantly activated in concentration‐dependent manner after exposure to SiNPs for 24 h with increase of western blot for LC3A/B. The upstream of autophagy signaling, the mTOR pathway, was slightly activated after exposure to three sizes of SiNPs.

Conclusions

SiNPs (50, 100, 150 nm) induced no significant cytotoxicity in cultured human keratocytes.
Factors affecting the prognosis of visual acuity and visual fields in pituitary adenoma patients treated with endonasal endoscopic transsphenoidal surgery
Authors: Liinamaa J. , Luomaranta T. , Raappana A. , Saarela V.
Published: September 2016

Purpose

The objective of this study was to evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endonasal endoscopic transsphenoidal surgery (EETS), with special attention to the prognostic factors such as the tumors’ suprasellar dimension (SSD) and volume.

Methods

A total of forty‐seven patients with pituitary adenomas operated by EETS were retrospectively evaluated. VA, VF and visual impairment score (VIS) calculated from VA and VFs were determined pre‐ and postoperatively. Tumors’ SSD and chiasmal contact were evaluated and correlation of tumor volume and SSD with pre‐ and postoperative visual function (VA, VF and VIS) was assessed.

Results

VA improved in 42% of eyes (n = 21) after EETS and 79% (n = 38) had normal VA postoperatively. Postoperative recovery in VF was observed in 86.5% (n = 32) eyes with VF defect. Mean VIS change was 11.6 (95% CI 7.3–16.0) and it improved in 96.0% of the patients (n = 24) with preoperative visual impairment. The mean SSD in patients with VF defect (n = 20) was 16.3 mm (95% CI 13.2–19.3) and in patients with no VF defects (n = 23) 7.5 mm (95% CI 5.9–9.2) (p < 0.001). A cut‐off value of 10 mm for visual perturbations was determined for SSD and 5.1 ml for tumor volume (p < 0.001 for both). A significant correlation between the tumor's SSD and volume with pre‐ and postoperative visual function was found.

Conclusions

The visual outcome after EETS for pituitary adenomas was excellent and significant complications were rare. The size (suprasellar dimension and volume) of pituitary adenoma was the most important predictor of visual outcome after EETS.
Combination of global electroretinogram and sd‐oct in the etiology of infantile nystagmus
Authors: Bouladi M. , Bouraoui R. , Limaiem R. , Chaker N. , Mghaieth F. , El Matri L.
Published: September 2016

Purpose

To study the combination of global electroretinogram (ERG) and SD‐OCT in the etiology of infantile nystagmus.

Methods

Sixteen children with infantile nystagmus, and no evident etiology in the normal ophthalmic examination underwent ERG with ISCEV guidelines and SD‐OCT.

Results

Median age was 8.7 ± 2.9 years (3.4–14.6 years). ERG and SD‐OCT were both normal in 6 children. In 9 children, ERG showed cone dysfunction and OCT allowed differentiation between achromatopsia in 4 children and cone dystrophy in 5 children. Two children had rod and cone dysfunction in ERG and OCT was normal. Dysfunction in inner‐layer retina was found in one child who had X‐linked juvenile retinoschisis diagnosed with OCT.

Conclusions

ERG is useful in the etiologic diagnosis and prognosis of infantile nystagmus. Its combination with SD‐OCT allows better characterization of the etiology of nystagmus especially in diseases involving the macula which may guide molecular study, help performing genetic counseling, and facilitate future gene therapy.
Exploration of human tear proteome
Authors: Turck N. , Dor M. , Eperon S. , Salvisberg C. , Fouda C. , Hainard A. , Guex‐Crozier Y. , Hamedani M.
Published: September 2016

Purpose

The tear film is a complex structure which constitutes an interface between our eyes and the external environment. Its protein, lipid and metabolite composition is highly regulated depending on several factors. Despite its attractive characteristics, this fluid is still poorly studied. Here we present an in‐depth human tear proteome based on a mass spectrometry approach.

Methods

In this study, tears of two healthy controls (two women aged 59 and 61 years) were collected with Schirmer's papers. After trypsin digestion and off‐gel electrophoresis fractionation, two proteomic analyses were performed by mass spectrometry (using LTQ Orbitrap Velos Pro coupled to a liquid chromatography). Resulting files were searched against the UniProt‐SwissProt/TrEMBL database (version 2014_10) and a false discovery rate of 1% was selected. The protein list was analysed using Ingenuity Pathways Analysis and Cytoscape software.

Results

Globally 2105 and 825 proteins were identified with 1 and 2 unique peptides respectively after removing keratins and immunoglobulins. Regarding the 825 proteins, the top three pathways that we highlighted were the acute phase response signalling, the remodelling of epithelial adherens junctions and the clathrin‐mediated endocytosis signalling. Moreover, we identified 203 proteins that were not found in the previous published studies. By comparing our tears with others fluids, only 26.9% were identified in vitreous humor and 45.7% in plasma, confirming that tears have a specific composition.

Conclusions

Thanks to this study, we are able to propose an expanded tear proteome. Both specific proteins of the tears and correlations with other fluids give them a great potential for biomarker research.

This study is kindly supported by the Provisu Foundation and the SNF_MVH (PMPDP3_158370).