bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of intravitreal aflibercept and ranibizumab on retinal vessel diameter measured using fluorescein angiography
Authors: Cho A.R. , Min J.K. , Park J.H. , Yang H.S.
Published: September 2017

Purpose

To investigate the effect of intravitreal (IVT) aflibercept and ranibizumab on retinal vessel diameter in patients with neovascular age‐related macular degeneration (N‐AMD).

Methods

Forty eyes of 40 consecutive participants with treatment‐naïve N‐AMD were included. Two groups of 20 eyes received three consecutive monthly treatments of IVT aflibercept or ranibizumab. Retinal vessel diameter was measured using fluorescein angiography (FA) before the first IVT injection and 1 month after the third injection. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were calculated to represent average retinal vessel diameters.

Results

Retinal vessel diameter significantly decreased in aflibercept‐treated patients; CRAE and CRVE reduced from 106.7 ± 22.9 μm to 96.1 ± 24.1 μm (P = 0.028) and from 148.8 ± 19.6 μm to 140.8 ± 19.6 μm (P = 0.003), respectively. Pre‐injection and post‐injection arteriovenous ratios were 0.71 ± 0.08 and 0.71 ± 0.11, respectively (P = 0.733). However, retinal vessel diameter was not significantly reduced in ranibizumab‐treated patients; CRAE changed from 107.1 ± 23.3 μm to 104.4 ± 22.0 μm (P = 0.073) and CRVE from 139.0 ± 13.8 μm to 139.2 ± 14.2 μm (P = 0.794). Pre‐injection and post‐injection arteriovenous ratios in the ranibizumab‐treated group were 0.74 ± 0.14 and 0.72 ± 0.14, respectively (P = 0.163).

Conclusions

IVT aflibercept treatment had a significant vasoconstrictive effect in eyes treated for N‐AMD; on the other hand, IVT ranibizumab did not significantly affect retinal vessel diameter. The aflibercept‐mediated reduction in diameter was not vessel‐specific.
Acute macular neuroretinopathy type 2: an unusual case
Authors: Cellini M. , Sebastiani S. , Campos E.
Published: September 2017

Purpose

Acute Macular Neuroretinopathy (AMN) is a rare retinal disease distinguished in two different types. In type 1 the lesion occurs above the outer plexiform layer (OPL) interesting the inner nuclear layer (INL), differently in type 2 the lesion occurs below the OPL interesting the outer nuclear layer (ONL). Type 1 is more common among elderly, males, and associated with cardiovascular risk factors while type 2 is more usual in young and females.

Methods

A 68 years‐old white man presented to Ophthalmic Emergency Room complaining the acute‐onset of a paracentral superonasal scotoma in his left eye. His medical history was significant for systemic arterial hypertension in good control with diuretics and sartans. He also refers primary open angle glaucoma in treatment with prostaglandin analogous in both eyes. We performed fluorescein and indocyanine green angiographies, spectral domain‐Optical Coherence Tomography (SD‐OCT), OCT angiography (OCTA), standard automated perimetry (SAP), microperimetry, and multifocal electroretinogram (mfERG).

Results

Fluorescein and indocyanine green angiographies were unremarkable. SD‐OCT revealed a focal hyperreflective band that involved the OPL and ONL localized in the parafoveal inferior region. The SAP showed a superonasal scotoma that was confirmed by the mfERG trace decrease and the inferotemporal reduced retinal sensibility at microperimetry. OCTA revealed a deep retinal capillary plexus perfusion defect area inferotemporally to the fovea.

Conclusions

Our case describes an unusual AMN type 2 that occurs in an elderly male patient affected by systemic arterial hypertension typical for type 1. These evidences suggest a closer pathogenic relationship between the two forms of AMN. Further studies will be able to determine whether AMN type 1 and AMN type 2 rapresent single or multiple entities.
Regenerative therapies with combined axoprotectants in AGE‐exposed retinas
Authors: OSHITARI T. , Bikbova G. , Baba T. , Yamamoto S.
Published: September 2017

Purpose

To examine the best effective combination of axoprotectants in AGE‐exposed rat retinas in culture.

Methods

Seven SD rats were used in this study. Retinal explants were three‐dimensionally cultured in collagen gel and incubated in serum free media, AGEs, AGEs+100 mM citicoline, AGEs+100 mM TUDCA, AGEs+10 ng/ml NT‐4, AGEs+citicoline+TUDCA, and AGEs+citicoline+TUDCA+NT‐4. The numbers of neurites were counted after 7 days of culture, followed by TUNEL staining and immunostaining of phosphorylated JNK and active‐form of caspase‐9.

Results

All of the axoprotectants decreased TUNEL‐positive cells, p‐JNK and caspase‐9 immunopositive cells, and increased the numbers of neurites. However, the number of neurites was significantly higher in the retinas incubated with combined three agents.

Conclusions

Combination solutions containing citicoline, TUDCA, and NT‐4 should be considered regenerative therapy for AGE‐related retinal degeneration.
The changing sphingolipidome of retinal ganglion cells in response to stress
Authors: Trzeciecka A.M. , Piqueras M.C. , Bhattacharya S.K.
Published: September 2017

Purpose

To capture dynamic sphingolipid profile of retinal ganglion cells (RGC) subjected to stress.

Methods

RGCs from P0‐P8 C57BL/6 mice were purified using 2‐step immunopanning method: after initial anti‐macrophage depletion retinal suspension was enriched for Thy1.2 +  cells. RGCs, cultured on poly‐D‐lysine and laminin substrate in defined serum‐free medium with addition of BDNF, CNTF and forskolin, were subjected to 2 psi (~100 mmHg) hydrostatic pressure by addition of carbon dioxide, resulting in additional stress components of acidosis and mild hypoxia. Samples were spiked with internal standards and lipids extracted using Bligh&Dyer method. Untargeted profiling analysis was carried out using reverse phase liquid chromatography coupled to high‐resolution mass spectrometer (Q Exactive). Subsequently, peak extraction, identification and alignment were performed in Lipid Search 4.1 software. Quantification is based on the ratio to respective internal standard and normalized to total DNA content.

Results

Based on MS/MS spectra we identified a total of 725/839 species at 4/24 h stress exposure, respectively, from 7 sphingolipid subclasses of which 76/174 (10.5%/20.7%): 31/81 ceramide, 14/35 hexosyl‐ceramide, 2/20 dihexosyl‐ceramide, 13/18 ceramide 1‐phosphate, 6/13 sphingomyelin, 10/6 sphingoid base, 0/1 sphingoid base 1‐phosphate species changed significantly when compared to time‐matched controls (t.test p < 0.05). We did not find changes in total levels of metabolites in any of the subclasses. 67% of the early (4 h) altered species displayed increase, while 71% of the late (24 h) ones ‐ decrease.

Conclusions

Levels of particular RGC sphingolipid species change upon acute stress. It may suggest that individual sphingolipids have distinct roles in cell fate decisions. The great challenge now lies in understanding biological significance of these alterations.
Effects of trypan blue on corneal endothelial cell viability;Optimal time of Trypan Blue Dye Application to DMEK donor tissue
Authors: kim E.Y. , Kim S.Y.
Published: September 2017

Purpose

The purpose of this study was to evaluate the corneal endothelial cell toxicity of the trypan blue dye used in Descemet membrane endothelial keratoplasty(DMEK) donor corneal tissue to enhance visibility before transplant.

Methods

Human cadaver eyes with healthy endothelial cells that were unsuitable for transplantation were obtained. The mean endothelial cell density was 2679±232.76(2273‐2994)cells/mm2 and the mean age was 61±13.37(35‐73)years. The tissue samples were divided into 3 subgroups based on the application time of trypan blue dye(control, 4,and 6 minutes). Trypan blue dye 0.06%(Vision Blue®) was applied to the endothelium for 30seconds(Control). Descemet membrane was then stripped from the posterior stroma so a sheet of DM with the endothelial monolayer(DMEK donor tissue) was obtained. From the endothelial side, a trephination was made with a 8.25mm corneal trephine. Each sample tissue was stained with 0.06%trypan blue for a duration of 4, 6 minutes. Live/Dead assays using calcein AM and ethidium homodimer was performed to assess endothelial cell viability of DMEK donor tissue using fluorescent microscope.

Results

Endothelial cell damage was expressed as the percent of dead cells/ (live + dead cells). The mean values(cell death rate) were 52.95±10.54%(control); 61.23±12.96%(4min.); 81.85±15.17%(6min.)

Conclusions

Endothelial cell toxicity of staining of DMEK donor tissue with trypan blue(0.06%) up to 4 minutes was similar to that of the control group. However, the endothelial cell death rate was relatively higher in the group for 6 minutes staining than in the group for 4miniutes staining or control. As the staining time of trypan blue increased, the endothelial cell death rate tended to increase(Jonckheere‐terpstratest,p<0.05).
Discomfort self‐perception in contact lens wearers
Authors: Pastor‐Zaplana J.A. , Morales‐Villellas M. , Gallar J. , Acosta M.C.
Published: September 2017

Purpose

Chronic use of contact lenses (CLs) disturb ocular surface, leading to loss of corneal epithelium integrity and ocular discomfort. In many patients, there is no correlation between the severity of ocular surface disturbances and the perceived discomfort. In the present work, we analyzed the correlation between discomfort self‐perception and ocular surface disease index in contact lens wearers.

Methods

Forty contact lens wearers of both sexes, 18‐25 years old participated voluntarily in the study. An ad‐hoc questionnaire (Likert scale survey type) was used to score the frequency and intensity of ocular surface discomfort and dryness sensation. Ocular Surface Disease Index (OSDI) adapted for Spanish speakers was also administered. An equivalent group of age and sex‐matched volunteers with similar refractive errors that never wore CLs served as control.

Results

Significant differences were found between CL and eyeglasses wearers in medium‐high intensity discomfort sensations (72.5% vs 32.5%, CL vs spectacle wearers, p=0.003), eye dryness sensation (87.5% vs 57.5%, p= 0.001), presence discomfort sensation during the day (92.5% vs 77.5%, p=0.011) and frequency of watering eye sensation (90% vs 27.5%, p=0.001). There were no significant differences in the frequency of headache nor in the need to use artificial tears. Surprisingly, no differences were found in OSDI questionnaire between CL and eyeglasses wearers.

Conclusions

Contact lens wearers most frequently perceive eye surface alterations than eyeglass wearers, although there are no significant differences in OSDI questionnaire.

(Supported by SAF2014‐54518‐C3‐1‐R, MINECO, Spain, and ERDF, European Commission)
Corneal haze in juvenile and adult keratoconus patients after corneal cross‐linking
Authors: Alzahrani K. , Carley F. , Brahma A. , Mofty H. , Biswas S. , Lin Y. , Morley D. , Hillarby C.
Published: September 2017

Purpose

Densitometry software for the Oculus Pentacam was used to investigate the treatment outcomes of corneal cross linking (CXL) in adult and juvenile keratoconus patients.

Methods

A retrospective comparative study was carried out at Manchester Royal Eye Hospital. Corneal densitometry measurements collected before and after CXL treatment for 32 eyes from KC patients, aged between 13 and 39, were divided to 2 groups 13‐18 years(juvenile group) and 19‐39 years (adult group) was compared to pre and post treatment at 3, 6 and 12 months for each group and between both groups.

Results

Analysis of densitometry measurements found higher corneal densitometry after CXL which peaks at 3 months post treatment in both groups. There was significant diversity in corneal densitometry measurements at stromal zone 0‐2 and 2‐6 mm for all layer except the posterior layer for each group p<0.05). Significant differences were found between both groups at six months in the central (p=0.006), posterior (p=0.004) and full depth (p=0.02) layers for zone 0‐2 mm.The same layers differed significantly in the 2‐6 mm zone in all layers (p=0.01). One year post treatment significant differences were shown in corneal densitometry level between both groups in the 0‐2 mm zone of the central layer (p=0.007), posterior layer (p=0.01) and full depth (p=0.03).The central layer in zone 2‐6 mm was significantly different between both groups (p=0.04).

Conclusions

Haze levels post CXL differing in severity in different corneal zones and between both groups.The 0‐2 mm and 2‐6 mm zones were found to be the most affected area post treatment.Haze reached its maximum level at three months post treatment then appears to differ significantly in improvement level between adult and juvenile group, with the later never returning to pre‐treatment clarity in the most anteriorly central zone in juvenile group
The use of corneal scrubbing associated with matrix therapy in the treatment of chronic ulcers
Authors: Lazreg S. , Christophe B.
Published: September 2017

Purpose

to treat refractory chronic ulcers with corneal scrubbing and matrix therapy; In dermatology practice, the same method is used in severe burns, the cutaneous scrubbing removes necrotic tissues and helps healthy tissues to progress faster

Methods

Retrospective study on chronic corneal ulcers evolving for several week refractory to conventional treatments; All the corneal ulcers were scrubbed with cotton buds, most of them received matrix therapy at the dose regimen of a drop every other day until corneal healing and preservative free lubricants 3 times a day, for the painful cases, we performed bandage contact lenses, and the remaining patients received the bandage contact lenses without matrix therapy; ocular examination was performed at D0, D3, D7, D15 and D30, with slit lamp examination, fluorescein coloration and measurement of the size of the ulcers,

Results

18 patients were included and divided on 3 groups Group 1: corneal scrubbing, matrix therapy, lubricant and contact lenses Group 2: corneal scrubbing, matrix therapy, lubricant without contact lenses Group 3: corneal scrubbing; lubricant and contact lenses All the ulcers healed at D30, in the group1 and 2, corneal healing was faster between 7 and 10 days. No complications were reported despite the occurrence of one case of descemetocele at D3, with a good outcome at D15

Conclusions

Corneal scrubbing may accelerate corneal healing and therefore allows matrix therapy to be more efficient.
The efficacy of heating devices to warm the lids
Authors: Almutairi R. , Hagan S. , Madden L.C. , Pearce E.I.
Published: September 2017

Purpose

To investigate commercially available warming devices for their ability to effectively warm the lids by looking at heat distribution along the lid using thermography.

Methods

Devices that warm the eyelids are a standard treatment for MGD and blepharitis patients. Four commercial devices were tested: Medibeads a microwave activated eye mask, hot flannel, Eyebag instant disposable air activated heating pads, and a faical sauna.

Fifteen normal healthy subjects were recruited and acclimated for 15 min in a controlled environment chamber at 25°C and 65% RH. Each device was used for 10 min over four separate sessions. Lid surface temperature was observed for 3 min before and then after treatment using a FLIR ThermaCAM P620.

Results

The mean lid temperature before applying devices was (35.77 ± 0.55°C). Immediately after treatment, there was a significant increase in lid temperature (p < 0.05) for all the devices. The Medibeads (38.54 ± 0.53°C) was significant warmer than the Eyebags (37.96 ± 0.46°C) (p < 0.03) and facial sauna (37.62 ± 0.60°C) (p = 0.008). The hot flannel (38.57 ± 0.79°C) was significantly warmer than the facial sauna (p = 0.007).

The facial sauna and the hot flannel leave the skin wet. The wetness may cause evaporative cooling and thereby reduce the beneficial warming effect. The wet devices showed a larger spread. Furthermore, the temperature 1 min after sauna treatment had returned to the pre‐treatment value (p = 0.23).

The dry devices showed less spread and a longer lasting effect. In addition, the temperature after Medibeads treatment was warmer than after the Eyebags (p = 0.01).

Conclusions

The dry warming devices were shown to be more consistent. The Medibeads showed the most effective heating. This suggests that the Medibeads offer the most consistent warming for the treatment of MGD and blepharitis patients.
Mushroom keratoplasty
Authors: Nahas S. , Silvana M.
Published: September 2017

Purpose

To report the visual out comes and graft survival rate of mushroom keratoplasty using femto second laser for the treatment of full thickness cornea opacities and healthy endothelium.

Methods

Retrospective chart view of 23 eyes (low risk of immunologic reactions n = 12; high risk n = 11) undergone femtosecond assisted mushroom keratoplasty. The mushroom shaped graft consisted of a large top hat (9 mm diameter + 250 microns in thickness) and small stalk (6–6.5 mm). The wavelight FS200 laser parameters used on this platform for the donor and recipient corneas are described. Outcome measures were BCVA best corrected visual acuity refraction, corneal topography, endothelial cell density, graft rejection and graft failure at 1, 3, 6 and 12.

Results

Average follow up was 9 months (range 6–15) months. All grafts were clear at the last follow up visit. Excluding eyes with pre existing ocular co‐morbidities. The percentage of patients achieving BCVA of 20/40 or better at 1, 3, 6 and 12 months was 66.7%, 90.50%, 95.2% and 100%, respectively. At last follow up the refractive cylinder was 6 diopters (D) or less in all eyes, averaging 3.7 D. Two eyes (8.7%) had rejection that were easily reversed with topical steroids.

Conclusions

Femtosecond‐assisted mushroom keratoplasty (FAMK) shows faster visual recovery, better visual acuity and limited postoperative astigmatism with no increase risk of rejection.
Complete corneal ring (MyoRing) implantation combined with corneal collagen crosslinking in keratoconus treatment
Authors: Emin U. , Mukharram B. , Gyulli K. , Guzel B.
Published: September 2017

Purpose

To evaluate functional results of complete corneal ring (MyoRing) implantation with corneal collagen crosslinking (CXL) for progressive keratoconus

Methods

MyoRing implantation with corneal CXL was performed in 39 eyes with progressive keratoconus of the II‐III disease degree according to the Amsler classification. Implantation of a MyoRing in the corneal pocket was performed using a PocketMaker microkeratome and corneal intrastromal implantation system. Saturation of the cornea was performed with a solution of 0.1% riboflavin injected into the corneal pocket through the incision tunnel within 10–15 minutes. Standard surface UV irradiation (370 nm, 3 mW/cm2) was carried out for 30 minutes. The follow‐up was 36 months.

Results

Significant improvements in uncorrected distance visual acuity and corrected distance visual acuity were observed. Keratometry was reduced for 9.43 D, the spherical equivalent decreased from from 9.43 D to 6.25 D. The cylinder decreased to 3.31. Corneal thickness decreased from baseline (from 426.93 ± 46.58 μm to 401.24 ± 39.12 μm) 36 months postoperatively, which corresponds with pachymetry reduction after conventional CXL. Dynamic observation after 36 months showed stabilization of clinical and functional results.

Conclusions

Combination of CXL and MyoRing implantation was effective for keratoconus treatment. Complete corneal ring implantation combined with corneal collagen crosslinking allows not only correct the keratoconus followed ametropia but also slow down the progression of the disease.
Short‐term in vivo morphologic changes of amniotic membrane after fibrin glue‐assisted pterygium surgery on anterior segment optical coherence tomography: a case series
Authors: Lim S.
Published: September 2017

Purpose

The evaluations of morphologic changes of amniotic membrane (AM), even after successful AM transplantation surgery without complications, may be difficult. Moreover, there was no report regarding morphologic changes after fibrin glueassisted AM transplantation with pterygium excision. Here, we highlight and describe the use of spectral domain optical coherence tomography (OCT) for the evaluation of the morphologic features of amniotic membrane (AM) and of associated in vivo structural changes after fibrin glue‐assisted pterygium surgery.

Methods

Retrospective Case Series.

Results

All three patients underwent cryo‐preserved AM transplantation using the permanent inlay technique (epithelial side up) with fibrin glue. In vivo morphologic changes of AMs were evaluated using a spectral domain OCT equipped with an anterior segment imaging module (RTVue‐100, Optovue, Inc., Fremont, CA, USA). Anterior segment OCT examinations demonstrated morphologic changes, that is, re‐absorption of fibrin glue or subconjunctival hemorrhage, migration of epithelium, and integration of AM into sclera, of AMs over first postoperative months.

Conclusions

Anterior segment OCT might provide additional structural information, including quantitative and qualitative data, on AMs after pterygium surgery as compared with conventional slit‐lamp examination.
Computational fluid dynamics simulations of aqueous flow through the CyPass® Micro‐Stent
Authors: Vidal Aroca F. , Vera L.F. , Missel P. , Sarangapani R.
Published: September 2017

Purpose

In normotensive eyes, aqueous humor is eliminated through Schlemm's canal and through the iris root in approximately equal fractions. But in glaucomatous eyes, the hydraulic resistance of the trabecular meshwork restricts outflow through the canal and causes the IOP to rise. The CyPass® supraciliary micro‐stent is a device implanted by minimally invasive glaucoma surgery (MIGS) which is designed to reduce IOP by allowing an alternative pathway for aqueous humor outflow. The device, a fenestrated polyimide tube, is inserted between the sclera and the ciliary muscle creating an adjacent fluid space which communicates directly with the suprachoroidal outflow pathway.

Methods

To better understand and illustrate the mechanism of action for this device, computational fluid dynamics simulations of aqueous flow were conducted in human eye models with and without implanted devices. The configuration of the device and fluid space in the eye was obtained from a separate mechanical simulation of device implantation using an explicit solver. Hydraulic resistances of the vitreous and sclera were obtained from the literature.

Results

The resistances of the trabecular meshwork and ciliary muscle were adjusted to produce an IOP of 24.4 mmHg (the mean untreated IOP in the COMPASS trial) and a suprachoroidal elimination fraction of 80%. With the device implanted the hydraulic resistance of the fluid in the space adjacent to the device was reduced ~4 orders of magnitude to achieve the post‐surgical IOP of 16.8 mmHg observed in the COMPASS study. It was found that the device reduces IOP by decreasing the overall resistance of the eye to hydraulic flow by more than 30%.

Conclusions

The model confirms that substantial IOP lowering is achievable through aqueous egress via a supracilliary stent even when there is substantial trabecular resistance.
Wait before extrapolating rather than wait between two eyedrops! … The 1974 Chrai et al.'s study on the albino rabbit may not apply to humans
Authors: Bailleul H. , Beraud G. , Denion E.
Published: September 2017

Purpose

The recommendation of having patients waiting 5 minutes between two eyedrops instillation is based on an experimental work conducted by Chrai et al. in 1974 on the albino rabbit. In this work, instillation of pilocarpine eyedrops was followed by instillation of saline eyedrops after 30 seconds and 2 minutes with as few as 4 rabbits and permitted a decreasing of the maximum difference in pupillary diameter respectively by 44% and 17.5%. The present study was undertaken to assess the validity of these findings in humans.

Methods

Twenty‐four healthy volunteers were enrolled from March 2016 to April 2017. Eyeballs were photographed in a completely dark room with an infrared camera at baseline, 40 minutes after instillation of 1% pilocarpine and 40 minutes after instillation of 1% pilocarpine eyedrops followed by the instillation of saline eyedrops immediately afterwards or 5 minutes later. Pupil to iris surface ratios were calculated and differences of ratios between baseline and 40 minutes (i.e. myosis gain) were compared with Wilcoxon test.

Results

The mean (SD) myosis gain was 0.176 (0.089) with 1% pilocarpine alone; 0.165 (0.086) with 1% pilocarpine immediately followed by saline eyedrops (p = 0.652) and 0.167 (0.087) with pilocarpine followed 5 minutes later by saline eyedrops (p = 0.731). Only some eye colours significantly influenced the myosis gain in multivariate analysis.

Conclusions

Despite using pupil/iris surface ratios (more sensitive than diameter measurements), and more subjects (24 versus 4) our study fails to confirm the results found by Chrai et al.'s in the albino rabbits. While awaiting for the issue of the time interval between eyedrops in humans to be further investigated, one should be cautious with extrapolation of Chrai et al.'s conclusions in the albino rabbits to humans.
Missed opportunities of optimizing glaucoma medical therapy – A nationwide cross‐sectional analysis of glaucoma topical therapy in Portugal (PEM Study)
Authors: Pimenta G. , Sousa D.C. , Leal I. , Barata A. , Marques‐Neves C. , Abegão Pinto L.
Published: September 2017

Purpose

Approximately 2.2% of the Portuguese population are under intraocular pressure(IOP)‐lowering medication. However, an analysis based on the number of drugs may neglect how fixed combinations can minimize the burden of topical therapy and adherence to treatment. We aimed to analyse the prescription pattern of these drugs in Portugal and to identify improvement opportunities on the daily topical antiglaucomatous therapy.

Methods

Cross‐sectional nationwide study, resorting to the PEM database from 2015 – which retrieved prescription data from all hospitals and clinics in the country. All data was provided in an encrypted form and anonymously extracted. Statistical analyses were performed for only one‐month data (January) to guarantee a cross‐sectional view and reduce the likelihood of misinterpreting changes in medication during the year. STATA was used as statistical package.

Results

In January 2015, a total of 53.053 people were prescribed IOP‐lowering drugs in Portugal, with only 4,5% of these being preservative‐free formulations. The vast majority of the patients instilled up to two drops a day (72%), either using monotherapy (63%) or fixed‐combination (9%). Among the remaining 28%, half could have reduced at least two daily drops by using more fixed combinations.

Conclusions

Although most patients were under either monotherapy or one fixed combination, instilling up to 2 drops a day, the use of preservative‐free drugs is far from the ideal scenario. Our results also suggested the number of daily drops may be significantly reduced in as many as 14% of the patients, thus potentially reducing ocular surface side effects and improving adherence.
Calcium signaling in human lens epithelial cells after mechanical stimulation
Authors: Andjelic S. , Gosak M. , Gojic D. , Hawlina M.
Published: September 2017

Purpose

The purpose of this study is to explore and identify intra‐ and inter‐cellular calcium (Ca2+) signaling in human lens epithelial cells (LECs) upon local mechanical stimulation, to understand better the role of Ca2+ in intercellular communication related to cataract formation, lens regeneration and posterior capsular opacification (PCO).

Methods

The anterior lens capsule (aLC: basement membrane and associated LECs) were obtained from cataract surgery. Primary human LEC cultures were established by placing adherently the intact human aLC onto Petri dishes. LECs were stained with Fura‐2 dye, the fluorescence of which was imaged to monitor spatio‐temporal changes in cytosolic free Ca2+ concentrations in response to localized, micropipette induced mechanical stimulation.

Results

Analysis of the intra‐ and inter‐cellular Ca2+ signaling from postoperative aLCs and cultures showed that the Ca2+ signal spreads radially and its propagation speed increases with the degree of cataract. While in aLC Ca2+ signals travels between the first few neighbor LECs in the order of seconds, in confluent culture the propagation is slower and it covers smaller distances. LECs from aLC with less developed cataracts exhibit faster and bigger changes in intracellular Ca2+ concentration. Moreover, in aLC and in LEC cultures, the duration of Ca2+ transients prolongs with increasing distance from stimulation site, whereas their amplitude decreases.

Conclusions

The modifications of Ca2+ homeostasis in LECs, which are associated with different degrees of cataract, affect Ca2+ signaling upon the local mechanical stimulation. Impairment of Ca2+ signaling might be the basis of cataract formation. LEC's cultures have less developed Ca2+ signaling capabilities, what might be reflected on lens regeneration and PCO.
Autophagy induction decreases protein aggregation in response to polyphenolic pinosylvin and heat shock exposures in ARPE‐19 cells
Authors: Amirkavei M. , Koskela A. , Koskelainen A. , kaarniranta K.
Published: September 2017

Purpose

Impaired protein degradation and increased protein aggregation in retinal pigment epithelium (RPE) cells associate with the age‐related macular degeneration (AMD) pathology. Heat shock proteins (Hsps) refold misfolded proteins and attempt to prevent the accumulation of detrimental cytoplasmic protein aggregates. Once Hsps capacity is exceeded the protein aggregates are secondarily degraded by autophagy or proteasomes. The Hsps and clearance mechanisms are important to prevent RPE damage and AMD development. We showed recently that stilbenoid polyphenol, pinosylvin has strong cytoprotective power against oxidative stress in ARPE‐19 cells. Here, we investigated the effects of pinosylvin and/or heat shock on the regulation of autophagy in ARPE‐19 cells in the protein aggregation model.

Methods

ARPE‐19 cells were solely or simultaneously treated with 15 µM pinosylvin and/or heat shock at 42˚C for 30 min with or without proteasome inhibitor MG‐132 (1 µM) or autophagy inhibitor bafilomycin A1 (50 nM) and followed up to 48 h. Autophagy markers p62/SQSTM1 (sequestosome 1), LC3 (microtubule‐associated protein 1A/1B‐light chain 3) and Hsp70 (heat shock protein 70) were analyzed by Western blotting (WB). Cytotoxicity was analysed by LDH assay.

Results

Inhibition of proteasomes with MG‐132 or heat shock highly upregulated Hsp70, p62 and LC3 detected in WB. Simultaneous treatment with pinosylvin and heat shock showed stronger autophagy induction and cytoprotection rather than theirs single treatments during proteasome inhibition.

Conclusions

Combination of polyphenolic pinosylvin and thermotherapy may provide improved autophagy and cytoprotective response in RPE cells.
An educational information platform on the ocular surface and dry eye disease ‐ OSCB‐Berlin.org
Authors: Knop E. , Knop N.
Published: September 2017

Purpose

The OCULAR SURFACE is an important part of the eye for the first steps of vision and thus for everything that comes later. The complexity and the ever‐increasing wealth of new scientific findings makes it increasingly difficult for many to understand the ocular surface and its diseases – in particular DRY EYE DISEASE.

Methods

Experienced scientists have collected relevant research‐based information, from the literature & own results and experience. It is intended to provide useful, reliable understandable information for all stake‐holders from laymen & patients, over clinical practitioners to the fellow scientists in the field that is also suitable for academic teaching.

Results

This educational OSCB‐WebSite‐ Homepage of the Ocular Surface Center Berlin (OSCB‐Berlin.org) follows a newly developed didactic style that is image‐driven in the user interface & content. Text is in parallel with images like a text book ‐ but in addition the information is intensely cross‐linked by hyperlinks and supplemented by Animations, so that the reader can enter from any starting point and dig deeper until the information interest is satisfied. The Website is based on pictographic images that illustrate the content. When it becomes more complex, static images are supplemented with Animations in the same style that make even complex content easily understandable. Every topic is covered in three different formats with increasing depth of information to satisfy different interest groups.

Conclusions

Conclusion. The new online INFORMATION PLATFORM on the OCULAR SURFACE and DRY EYE DISEASE covers many aspects of the ocular surface and its alterations with a focus on Dry Eye Disease. It contains reliable, science‐based, unbiased information & constitutes a public information platform for all stakeholders in the field.and is supported by hundreds of colleagues world‐wide.
Assessment of the visual acuity, contrast sensitivity, color vision and visual integration in the Alzheimer's Disease progression according to the scale GDS
Authors: Salobrar‐Garcia E. , Hurtado L. , Lopez‐Cuenca I. , de Hoz R. , Salazar J.J. , Ramirez A.I. , Yubero R. , Gil P. , Ramirez J.M.
Published: September 2017

Purpose

Alzheimer's disease (AD) is characterized by an accumulation of abnormal plaques and tangles in the brain with cortical atrophy most pronounced in the medial temporal and posterior temporoparietal regions. The process is estimated to begin years before the appearance of clinical symptoms. The aim of this work was to investigate the potential use of ophthalmological psychophysical tests as AD follow‐up.

Methods

Twenty‐six mild AD patients, 12 moderate AD and 32 controls underwent visual acuity (VA), contrast sensitivity (CS), colour perception tests and perception visual test (PDT). All patients were classified according the Global Deteriorate Scale (GDS).

Results

In comparison with control: i) patients with mild AD presented a significant decrease in the VA, in the CS (for all the spatial frequencies), in the blue colour perception and in PDT; ii) patients with moderate AD showed the same result as the mild AD, compared with controls, furthermore a significant increase of the total number of errors in the colour test (p < 0.05 in all instances). In comparison with mild AD, moderate AD patients had no statistical differences in CS, VA and PDT (p > 0.05) but significant differences in the colour perception (total number of errors and unspecific blue axis errors) (p < 0.05).

Conclusions

In comparison with the control group, patients with mild and moderate AD presented a statistically significant decrease in CS, for all the spatial frequencies (the higher the spatial frequency, the greater the loss of CS perception), and in the colour perception. Therefore AD patients, show alterations in the M, P, and K visual pathways. Psychophysical tests could be useful tools to diagnose support and follow‐up in mild AD.
Optical coherence tomograpy in cerebral amyloidosis
Authors: Van Keer K. , Schaeverbeke J. , Barbosa Breda J. , Evenepoel C. , Abegão Pinto L. , Stalmans I. , Vandenberghe R. , Vandewalle E.
Published: September 2017

Purpose

To correlate structural and vascular optical coherence tomography (OCT) parameters with cerebral amyloid burden in cognitive intact (Control) and mild cognitive impairment patients (MCI).

Methods

Controls and MCI patients were recruited from an ongoing longitudinal cohort of cognitively intact older adults and a memory clinic‐based cohort of amnestic MCI patients respectively. Retinal nerve fiber layer (RNFL) thickness and parafoveal vessel density were measured using Angio‐OCT. Amyloid burden was quantified on [18F]flutemetamol or florbetaben PET scans as standard uptake value ratio (SUVR) and categorized as positive (Aβ+) or negative (Aβ‐). For statistical analyses, univariate correlation coefficients and one‐way ANOVA with LSD post‐hoc comparisons were performed.

Results

35 Controls (16 Aβ+, 19 Aβ‐) and 28 MCI patients (20 Aβ+, 8 Aβ‐) were recruited. Parafoveal vessel density and inferior RNFL showed a significant negative correlation with SUVR (spearmans ρ  =  ‐0.296, P = 0.020; and ‐0.336, P = 0.008 respectively). Inferior RNFL was significantly lower in the Aβ+ MCI group compared to the Aβ‐ Controls, Aβ+ Controls and Aβ‐ MCI patients (P = 0.007, P = 0.023 and P = 0.015 respectively) with no significant differences being found between the other subgroups.

Conclusions

This pilot study demonstrates that lower parafoveal vessel density values, as assessed with angio‐OCT, are correlated with higher cerebral amyloid burden. The reduced inferior RNFL thickness in MCI, previously reported in other studies, appears to be confined to Aβ+ MCI patients. These findings provide further support for a potential role of OCT in the early diagnosis of Alzheimer's disease.
Retinal nerve fibre layer thickness associates with cognitive impairment and physical disability in multiple sclerosis
Authors: Birkeldh U. , Zahavi O. , Manouchehrinia A. , Hietala A. , Hillert J. , Wahlberg‐Ramsay M. , Brautaset R. , Nilsson M.
Published: September 2017

Purpose

Reductions in the retinal nerve fibre layer (RNFL) have been indicated even in early‐stages of multiple sclerosis (MS). The aim was to assess the potential of the RNFL quadrant measurements in differentiating disease phenotypes and their association with cognitive impairment and physical disability.

Methods

Four hundred and sixty‐five MS patients and 168 healthy controls (HCs) were included. MS subjects were divided in subgroups according to disease phenotype. All subjects underwent optical coherence tomography (OCT) examination of all retinal quadrants using Canon OCT HS‐100. Associations were tested using linear mixed effect models.

Results

The global RNFL thickness was 6.4 μm thinner (95% CI: −8.5 to −4.3, p < 0.001) in relapsing‐remitting MS (RRMS), 11.6 μm thinner (95% CI: −14.4 to −8.8 μm, p < 0.001) in secondary progressive MS (SPMS) and 10.7 μm thinner (95% CI: −16.0 to −5.5, p < 0.001) in primary progressive MS (PPMS) compared with HCs. Global RNFL and temporal quadrant showed high correlation to cognitive impairment and physical disability in MS.

Conclusions

We report that RNFL thickness reduction is significantly associated with physical and cognitive disability and OCT measurements are useful for axonal loss. We suggest the use of temporal quadrant RNFL thickness as a more sensitive outcome as oppose to the global RNFL thickness.
Optical coherence tomography outcomes in patients with Friedreich ataxia
Authors: Rojas Lozano P. , Ferreras Amez A. , Monsalve B. , García‐Salobrar E. , Muñoz Blanco J.L. , Urcelay J.L. , Salazar J.J. , Ramirez A.I. , de Hoz R. , Ramírez J.M.
Published: September 2017

Purpose

To compare the ETDRS macular thicknesses (MT), the ganglion cell complex plus inner plexiform layer thicknesses (GCC) and the peripapillary retinal nerve fiber layer (RNFL) thicknesses between patients with Friedreich ataxia (FA) and age‐matched healthy individuals.

Methods

Seven FA patients and 19 age‐matched controls were prospectively selected. All participants underwent a neurological evaluation, a comprehensive ophthalmological assessment and imaging with spectral domain Cirrus OCT (Carl Zeiss Meditec, Dublin, CA). Both eyes were included, left eyes were converted to a right eye format. The OCT parameters were compared between groups with the Mann‐Whitney U test. A p < 0.05 was considered significant.

Results

Mean age was 44.73 ± 11.9 and best‐corrected visual acuity (BCVA) was 0.97 ± 0.1 for the control group, while mean age was 37.85 ± 10.2 years and BCVA was 0.76 ± 0.2 for the AF group. The central macular thickness was similar in both groups, but the macular thicknesses of the inner ring of the ETDRS grid, except the temporal area, were reduced in FA ataxia compared to healthy controls. The nasal and inferior thicknesses of the outer ring were also lower in AF patients. All the GCC measurements and the RNFL thicknesses around the optic disc, except the eight clock‐hour position, were decreased in FA individuals.

Conclusions

In AF patients, the macular, GCC and RNFL thicknesses were lower than in healthy controls, presumably because of the loss of the ganglion cells. More studies are needed to evaluate the changes in the retina due to AF.
Visual impairment in combined pathology: multiple sclerosis and pituitary adenoma
Authors: Ioyleva E. , Makarenko I.
Published: September 2017

Purpose

To study the changes of visual function in patients with combined pathology: multiple sclerosis and pituitary adenoma.

Methods

Four females from 18 to 41 years old were examined.They complained of decrement of visual acuity, pain with eye movement. We identified decrease in visual acuity from 0.01 to 0.1, visual field central defect.To exclude organic pathology, the patient was sent for MRI of the brain, confirmed the diagnosis: MS and pituitary adenoma. For identify the root cause of reduced visual acuity, patients were examined by Cirrus HD‐OCT; Humphrey HFA II‐750i; Microperimetry on MP‐1, MRI of the brain and orbits.

Results

144 patients were examined in the S. Fyodorov “Eye Microsurgery” Complex, Moscow, 4 of them were diagnosed and confirmed a combined pathology:MS and pituitary adenoma. According ophthalmoscopy in three patients was marked optic disk hyperemia and swelling of the disc margin, one patient – temporal optic disk pallor. According microperimetry we received a decrease in overall photosensitivity from 8.3 to 11 dB. OCT: in 3 patients revealed a slight an increase average retinal nerve fiber layer thickness (A RNFL) from 110 to 113 μm. In 1 patient revealed a decrease A RNFL thickness to 76 μm. To confirm demyelinating cause of optic neuritis was scheduled MRI of orbits. In two patients were found nidus of demyelination in the optic nerve. Hormonal activity of pituitary microadenomas in the blood serum: cortisol from 350 to 400 mME/l, prolactin from 190 to 315 nmol/l.

Conclusions

Visual impairment caused by demyelinating process that is confirmed by special methods of examination. Identified pituitary microadenomas is hormone‐inactive tumor, therefore they do not affect the clinical course of MS. Combined pathology requires a change in tactics of patient's management with the participation of the endocrinologist and neurosurgeon.
Idebenone is effective and well tolerated in Leber's hereditary optic neuropathy (LHON): Long‐term results of real world clinical practice
Authors: Llòria X. , Catarino C. , Silva M. , Klopstock T.
Published: September 2017

Purpose

LHON is a mitochondrial disease resulting in progressive, severe central vision loss, which is caused by 1 of 3 mitochondrial DNA mutations in >95% of patients. Idebenone, at a dose of 900 mg/day, is effective and safe in patients with LHON. Here, we report long‐term treatment outcomes in real world clinical practice.

Methods

The Expanded Access Program (EAP) assessed idebenone's therapeutic potential in patients with onset of symptoms within 1 year prior to enrollment. Efficacy was assessed as clinically relevant recovery (CRR) or clinically relevant stabilization (CRS). CRR is defined as improvement from off‐chart to reading 5 letters on the ETDRS chart, or as an improvement of 10 letters. CRS is defined as maintenance of VA <1.0 logMAR (20/200).

Results

85 patients carried one of the 3 most common mutations and had at least 1 post‐baseline (BL) visual acuity (VA) assessment. At BL, median age was 23.6 years and median treatment duration at last observation was 17.3 months. A subset of 25 patients presented with VA <1.0 logMAR, from which 52% experienced CRS. CRR from nadir was observed in 51% of patients. The number of eyes which remained on chart increased from 51% at nadir to 67% at last observation, and those <1.0 logMAR increased from 7% to 27%. At BL, 9% of patients were <1.0 logMAR in both eyes, which increased to 23% following treatment. The proportion of patients with CRR increased with treatment duration, with approximately 50% observed up to 6 months, but extending up to 18 months. CRR and CRS were observed, to different degrees, regardless of mutation.

Conclusions

Idebenone has a good safety profile for the long‐term treatment of LHON, and when initiated early, can stabilize good residual vision and prevent severe vision loss and blindness in a large proportion of patients. Maximal benefit may be achieved by prolonged treatment.
Prediction of ophthalmological problems in 6.5 year‐old prematurely born children
Authors: Holmstrom G. , Hreinsdottir J. , Kaul Fredriksson Y. , von Hofsten C. , Rosander K. , Hellström Westas L.
Published: September 2017

Purpose

The aim of the study was to describe the ophthalmological outcome at 6.5 years and to identify possible predictive factors visual problems at this age.

Methods

This is a prospective, population‐based study, including all infants born ≤32 weeks gestational age (GA) in Uppsala County, Sweden, during 2004 to 2007. The children were screened for ROP in the neonatal period, visual tracking test were performed at 4 months tests of, and at 2.5 years, ophthalmological, visuospatial and cognitive testing were performed. At 6.5 years, 84 prematurely born and 64 children born at term participated in ophthalmological and visual testing. Of the preterm children, 24 (29%) had ROP and 9 had IVH 3‐4 and/or PVL in the neonatal period.

Results

Mean visual acuity (VA) did not differ between preterm and full‐term children, but a “subnormal” VA of ≤0.8 was more common in the preterm than the control group (31% versus 14%) (p < 0.05). No prematurely born child was blind, but two had VA < 0.5. A contrast sensitivity of < 0.5 was more common (36% versus 19%, p < 0.05) and strabismus was also more common in the pre‐terms (8% versus 0%, p < 0.05). Within the preterm group, logistic regression analyses revealed GA, ROP, PVL/IVH, and mild cognitive disability (Bayley III test), to be predictive factors for ophthalmological and visual problems at 6.5 years age.

Conclusions

Prematurely born children had an increased prevalence of ophthalmological problems at 6.5 years age. Treated ROP and early neurological problems were risk factors for later ophthalmological dysfunctions. This study also showed that reduced cognitive function at 2.5 years appeared to predict such problems.