bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitreous and subretinal VEGF levels in fresh rhegmatogenous retinal detachment
Authors: Sozen‐Delil F.I. , Cekic O.
Published: September 2016

Purpose

To explore the levels of vascular endothelial growth factor (VEGF) in vitreous and subretinal fluid in eyes with rhegmatogenous retinal detachment.

Methods

Overall 16 eyes of 16 patients (mean age, 49) with fresh rhegmatogenous retinal detachment were included into this study. There was no systemic or ocular disease other than the retinal detachment that might contribute to results in the patients. Vitreous samples (n = 9) were obtained during pars plana vitrectomy whereas subretinal fluid samples (n = 7) were obtained via external drainage during encircling sclera buckle surgery. Serum and vitreous VEGF levels were analyzed using enzyme‐linked immunosorbent assay. Total vitreous or subretinal fluid proteins and total serum proteins were also measured. Mann–Whitney U and Spearman correlation tests were performed to compare the VEGF concentrations.

Results

Median VEGF level was found higher in subretinal fluid when compared to vitreous (545.80 pg/ml vs. 106.08 pg/ml, p = 0.05). The difference was still significant after adjusting the results with total protein (p = 0.05). Subretinal fluid VEGF level was similar to serum VEGF level (410.30 pg/ml) in buckling group (p = 0.95) while serum VEGF level (221.20 pg/ml) was significantly higher than that of vitreous in vitrectomy group (p = 0.019). There was no correlation between serum and subretinal VEGF (p > 0.05) or serum and vitreous VEGF levels (p > 0.05).

Conclusions

The retinal pigment epithelium is the major source of VEGF in the eye. The current study confirmed that VEGF level in subretinal fluid is higher than that of in the vitreous in eyes with fresh retinal detachment, most probably due to the retinal pigment epithelium is in closer vicinity to the subretinal fluid, compared to vitreous humor.

Acknowledgement

This project was supported by Marmara University, Scientific Research Projects Committee.
Visualization of neovascular changes by swept source OCT angiography
Authors: Szaflik J.P. , Szaflik M.
Published: September 2016

Purpose

Instruments for using OCT angiography have recently become available. The aim of this paper is to report the possibilities, advantages and disadvantages of OCT angiography in the clinical diagnosis of retinal and choroidal neovascular diseases.

Methods

The OCT angiography images were obtained in patients with retinal neovascular diseases such as AMD and diabetic neovascular retinopathy and in patients with doubtful macular changes. OCT angiography was also performed as a follow up after intravitreal injections.

Results

OCT angiography images might be helpful in proper diagnostic process of neovascular changes. The examination is quick, harmless and performed without intravenous contrast. The quality of OCT angiography images depends on patients compliance and translucency of eye optical system. The movement artefacts are the most common.

Conclusions

OCT angiography is a new diagnostic tool which might be useful in visualization of pathological vessels and solving diagnostic problems of doubtful changes. It's worth to perform OCT angiography before traditional angiography. It would also be useful in patients with intolerance to fluorescein or indocyanine.
Collagen biomaterials for cornea regeneration – how does it work
Authors: Griffith M. , Reddy J. , Liszka A. , Lewis P.N. , Hayes S. , Meek K.M.
Published: September 2016

We have previously shown in animal models and in early clinical studies that collagen‐based biomaterials promoted functional regeneration of corneal epithelium, stroma and nerves. Recently, we showed that these fabricated implants were made of collagen fibrils that were fine and aligned, like those in human corneas. There were noticeable differences such as the uniaxial alignment of the implant fibrils compared to the biaxial alignment in the cornea, and the lack of D‐banding of collagen fibrils in the implants. Nevertheless, the aligned fibrils facilitated an orderly in‐growth of corneal stromal cells to form a neo‐stroma. TEM examination showed the presence of extracellular vesicles (EVs) in the regenerating corneas. Immunohistochemistry showed that the EVs were positively stained for collagen amongst other cargoes. In implants made from short peptide analogs of collagen, alignment of short fibrils was observed. However these implants had a much higher number of EVs. This suggests that a combination of a scaffold comprising highly aligned fibrils mimicking the highly ordered corneal ECM together with elaboration of collagen and other ECM macromolecules is required for regeneration of a functional neo‐cornea and not scar tissue.
Cases
Authors: Audo I.
Published: September 2016

Inherited retinal diseases are a heterogeneous group of disorders both clinically and genetically. Comprehensive analysis have helped better define phenotype correlations and also indentify novel clinical associations. Interesting cases will be presented to illustrate the spectrum of these disorders and diagnostic chanlenges.
Weill‐Marchesani syndrome: displaced lens, displaced pupil, displaced diagnosis
Authors: Hussain N. , Jeyabaladevan S. , Macapagal M. , Tumbocon J.
Published: September 2016

Purpose

Weill‐Marchesani Syndrome (WMS) is a rare, multi‐system, connective tissue disorder characterised by short stature, brachydactyly and ocular disturbance in late childhood. The cardinal ophthalmic feature is a microspherophakic lens which commonly results in lens subluxation, lenticular myopia, cataract formation and chronic glaucoma. Corectopia is a finding associated with lens subluxation but can also be a complication of ocular surgery. Until now, there are no reported cases of corectopia in WMS.

Methods

We describe the case of a 26‐year‐old female who presented with progressive blurring of vision on a background of high myopia, glaucoma and bilateral cataracts. The patient had undergone multiple procedures to control intraocular pressures, including bilateral trabeculectomy and glaucoma valve insertion in the left eye. She was diagnosed with WMS two years ago, but was lost to follow up.

Results

Examination revealed inferior subluxation and opacification of the lens bilaterally. Interestingly, the left pupil was displaced nasally and corneal bullae were noted on the inferior surface of the left eye. She was listed for bilateral phacoemulsification and intraocular lens insertion following this consultation, however re‐presented with sudden deterioration in vision within one week. Her right lens was displaced anteriorly but there was no corneal oedema. She subsequently underwent emergency lensectomy and was left aphakic in that eye.

Conclusions

WMS often goes undiagnosed in childhood. A greater awareness of the presenting features of the condition is important for early recognition and referral onto secondary care for specialist ophthalmic input. Our experience demonstrates that screening for complications is of paramount importance and early lensectomy may prevent irreversible ocular damage and improve visual outcomes.
Possible association with obesity‐related loci and outcome of wet AMD
Authors: Kaarniranta K. , Helisalmi S. , Birling A. , Saavalainen L. , Tolppola O. , Vajanto V. , Uusitupa M. , Paterno J.J.
Published: September 2016

Purpose

To investigate whether obesity‐related genes affect a visual outcome of anti‐VEGF‐treatment in wet AMD.

Methods

Thirty‐seven patients with wet AMD (mean age: 77.0 years) in Kuopio University Hospital, Finland, solely treated with anti‐VEGF as needed, were genotyped for 40 recently associated obesity‐related loci using the Sequenom iPlex platform. Diabetes and other causes of macular oedema diagnosed by ophthalmologist were exclusion criteria. Obesity‐loci were examined with respect to retrospective clinical monitoring data, including also visual acuity (VA) measured by Snellen decimals.

Results

Visual outcome was associated with rs10938397 (GNPDA2), rs1555543 (PTBP2), and rs7359397 (SH2B1). Mean differences in VA between the two homotsygotes were 0.25 (p = 0.03), 0.25 (p = 0.002), and 0.26 (p = 0.003), respectively. Genotypes did not differ by age, baseline VA, body mass index (BMI), gender, the number of anti‐VEGF injections, smoking, or the use of dyslipidemia medication, expect for rs10938397 (mean BMI difference 3.2 kg/m2, p = 0.38) and rs7359397 (mean age difference 8.5 years, p = 0.14).

Conclusions

Our data suggest, that at least rs1555543 (PTBP2) might have some effect on the visual outcome of anti‐VEGF‐treatment in wet AMD. The present study may be affected by the small sample, and it need to be replicated in a larger prospective setup. Diseases associated with PTBP2 include cancer‐associated retinopathy. Nevertheless, the potential role of the abundant genetic variation in modifiying drug responses in wet AMD should be further investigated.
The ON/OFF system pathway of the retina
Authors: Castelo‐Branco M.
Published: September 2016

The ON/OFF pathways in the retina represent parallel systems with asymmetric properties. Here we discuss the basic anatomy and function of these pathways in health and disease, from the point of view of luminance, contrast and motion perception. We will also highlight how receptive field properties are shaped within each of these pathways and how they cross‐talk within other parallel streams in the retina. Finally, we will address experimental and disease models that dissect the function of each of these pathways.
Grading iris color of post‐mortem human eyes
Authors: Madigan M. , Cionaca V. , Sitiwin E. , Ton H.T.
Published: September 2016

Purpose

Iris colour encompasses a continuum from pale blue to very dark brown and is usually classified via a descriptive three colour scale: blue, green‐hazel or brown. Digital imaging technologies provide an opportunity to quantify iris colour, and are increasingly used for studies of genetic variations in iris colour. We explored the use of digital imaging and colour space information for grading of iris colour in post‐mortem eyes, including eyes with choroidal naevi.

Methods

Post‐mortem adult human irises (n = 25) were examined and photographed using a Jenoptik digital camera and ProgResCaptureProv2.8.9 software. Standard lighting (colour temperature) and parameters for imaging were established and used for all specimens. Iris colour was graded (n = 5) (using a nine‐category system; Mackey et al. Clin Exp Ophthalmol, 2011). We also developed a method in Photoshop to express iris colour as Hue in the Hue, Saturation, Brightness (HSB) colour space, for comparison with the category grading.

Results

Using the nine‐category grading end‐point grades (light blue and dark brown) were consistently graded. Intermediate grades were categorised differently for some observers, usually with adjacent categories. Green irises were not observed in this small series. Digital imaging using standard iris images and an averaging filter, provided colour information (Hue) for each iris. This allowed discrimination of iris colour compared to category grading.

Conclusions

As expected category‐grading was not always consistent between observers. We developed a digital imaging approach using HSB color space to give a H value for each iris. We are exploring the utility of processing functions such as gaussian blur. This approach provides a standard iris colour for post‐mortem tissue and will be used for comparison with fundus colour.
Regression of corneal neovascularization associated with corneal epithelial defect after treatment with regenerating agents (Cacicol®)
Authors: Del Buey M.A. , Esteban O. , Lanchares E. , Martinez M. , Casas P. , Ascaso F.J. , Cristobal J.A.
Published: September 2016

Purpose

Corneal neovascularization is formed in response to inflammation and hypoxia. It is secondary to different conditions such as herpes simplex stromal keratitis, persistent corneal epithelial defects, contact lens use, keratoplasty of infections. The use of Regenerating Agents (RGTA) is a new treatment that mimics the function of extracellular matrix components. It makes extracellular matrix resistant to inflammatory molecules, restoring the properties and the micro‐‐environment needed for the normal corneal tissue regeneration. We report number of cases showing the role of Cacicol® in the regression of severe corneal neovascularization in patients with neurotrophic keratitis.

Methods

Interventional number of cases (N = 5) treated with RGTA (Cacicol®) for two months. The patients presented central corneal epithelial defect caused by neurotrophic keratopathy. These defects showed superficial and deep stromal neovascularization. The patients was treated with conventional therapy. We decided to combine this conventional treatment with RGTA (Cacicol®) one every two days for one month. After that period, we spread the dose to once a week for one month more.

Results

After first month, we observed that the dimensions of the epithelial defect decreased in two cases and it had disappeared in three cases. After second month, all patients had complete corneal healing and we also observed a regression of superficial and deep stromal vascularization. In three cases, neovascularization had decreased considerably and it had disappeared in two cases.

Conclusions

RGTA (Cacicol®) improves corneal melting and epithelial defects associated to corneal neurotrophic pathology. Moreover, in cases with corneal neovascularization associated, we find an important decrease of superficial and deep neovessels.
SD‐OCT for study of retinal layers segmentation in patients under Hydroxychloroquine treatment
Authors: Costa L. , Basílio A.L. , Proença R. , Cunha J.P. , Vieira L. , Flores R. , Santos A.
Published: September 2016

Purpose

Hydroxychloroquine has been used for decades in treatment of rheumatic disorders. Macular toxicity is an adverse effect dependent to duration of treatment and daily dosage. Although, the exactly retinal structure under this toxic effect is not yet totally understandable.

To study the sectorial effect of Hydroxychloroquine in all retinal layers in 1st, 2nd, 3th and 6th mm centered on fovea by automatic segmentation using Spectral‐Domain Optical Coherence Tomography.

Methods

Retrospective, non‐randomized study involving 44 eyes of 44 patients under treatment with Hydroxychloroquine. The authors have created two age‐matched groups. A group 1 of patients in treatment duration under 10 years (n = 30) and a group 2 above 10 years of treatment (n = 14).

Results

The inner retinal layers thickness of 1st and 2nd mm is impaired in group 2 but the results did not showed significant difference between groups. The automatically segmentation of layer by layer did not prove a sectorial defect in inner retina. The thickness of Outer Nuclear Layer (ONL) was impaired in group 2, in opposition to Outer Plexiform Layer (OPL). This analysis has demonstrated a tendency for inversion of ONL and OPL thickness values in both groups.

Conclusions

The toxicity of Hydroxychloroquine apparently was not responsible for significant alterations in inner retinal thickness. That is a tendency for reduction in ONL thickness. The higher thickness of OPL in group 2 is a surprising aspect that needs additional analysis. The outcomes were very dependent to the limited number of patients in our sample. Further longitudinal studies about this topic will be necessary.
Mid‐term clinical outcomes of collagen‐phosphorylcholine cornea substitutes for therapeutic anterior lamellar keratoplasty
Authors: Buznyk O. , Islam M.M. , Iakymenko S. , Pasyechnikova N. , Griffith M.
Published: September 2016

Purpose

To assess safety and efficacy of biosynthetic collagen‐phosphorylcholine implants as corneal substitutes in patients with severe pathologies for whom human donor cornea transplantation carries a high risk of rejection.

Methods

Recombinant human collagen type III and 2‐methacryloyloxyethyl‐phosphorylcholine were fabricated into collagen‐MPC corneal substitutes (CMCS). CMCS were implanted into the corneas of 8 patients (3 Phase 0, 5 Phase 1 patients) by anterior lamellar keratoplasty (ALK). The pathologic areas were excised and replaced with CMCS grafts. Benchmark patients were grafted by conventional ALK and human amniotic membrane (HAM). Follow‐up ranged from 12 to 36 months.

Results

Pre‐operatively, CMCS patients had persistent ulcers or recurrent erosions from chemical or thermal burns, keratitis or failed penetrating grafts. All patients were relieved of pain and photophobia post‐operation. 7/8 CMCS grafted corneas epithelialized within 4–50 weeks leading to improved visual acuity in 4/8 patients. Neovascularisation developed in 2/8 patents. Ten patients with similar conditions grafted by conventional ALK took 2–12 weeks to epithelialize. Neovascularisation developed in 9/10 patients, and visual acuity improved in 3/10 patients. In HAM patients, corneas epithelialized within 2–3 weeks, neovascularization developed in 7/10 patients, vision improved in 4/10 patients.

Conclusions

These results suggest that CMCS are safe in patients. In addition, they appeared to withstand the adverse microenvironment within corneas with severe pathology, and restored corneal integrity in high risk keratoplasty patients. Further clinical testing is needed to verify these early results.
Proton beam radiotherapy (PBR) for the treatment of retinal capillary haemangioblastoma
Authors: Hussain R. , Hassan S. , Ho V. , Kacperek A. , Errington D. , Heimann H.
Published: September 2016

Purpose

We describe the treatment of retinal haemangioblastomas with proton beam radiotherapy as a primary treatment for juxtapapillary lesions, and as a secondary treatment in refractory cases.

Methods

Retrospective analysis of patients from Jan 1997–Dec 2011 with retinal haemangioblastomas treated in the Clatterbridge Cancer Centre Douglas Cyclotron. Patients were treated with reduced dose 18 Gy.

Results

Seven patients were treated, 4 with Von Hippel Lindau syndrome. Five cases had juxtapapillary lesions; 5 had previous failed therapy; argon laser photocoagulation‐3, photodynamic therapy‐3, intravitreal anti‐VEGF (bevacizumab/abflibercept)‐4, ruthenium‐106 plaque brachytherapy‐2, vitrectomy with endolaser‐1. Tumour diameter was 4.0–7.2 mm (mean 4.8 mm) and thickness 1.2–4.2 mm (mean 2.2 mm) with visual acuity logMAR 0.0‐hand movements (mean 0.9). Mean follow up was 24 months (12–48 m). Within three months, all lesions regressed which continued over 18 months; tumour diameter decreased by 2.7 mm (1.5 mm depth). All cases demonstrated resolution of subretinal fluid within 3–6 months; however 3 developed radiation maculopathy at 12–22 months and were treated with intravitreal bevacizumab with good effect. Five patients had visual stabilisation; one case had visual improvement and another lost vision (HM to PL) (mean 0.8) due to radiation maculopathy.

Conclusions

PBR is an effective treatment for retinal haemangioblastomas with good regression of tumours; side effects are fewer and less severe than that reported with external beam radiotherapy, however our rates of radiation maculopathy were >40% despite a dose of 18 Gy. Although the expense and difficulty with access may limit its use, PBR ought to be considered in refractory cases unresponsive to alternative therapies, and in juxtapapillary lesions where alternative treatments cause rapid and severe visual loss.
Relationship between immune response and ocular inflammation after intravitreal injection of rAAV2/2–ND4 (GS010) in Leber hereditary optic neuropathy (LHON) patients
Authors: Vignal Clermont C. , Bouquet C. , Uretsky S. , Galy A. , Thomasson N. , Fitoussi S. , Combal J.P. , Sahel J.
Published: September 2016

Purpose

rAAV2/2‐ND4 vector (GS010), under development by GenSight‐Biologics as a treatment for vision loss in LHON patients bearing ND4 mutation, is administered via intravitreal injection (IVI). Immune response to intraocular AAV administration may impact safety and efficacy of AAV‐delivered ocular gene therapy. We investigated the relationship between systemic anti‐AAV2 antibody levels pre‐ and post‐IVI and ocular inflammatory reactions after GS010 injection.

Methods

Fifteen LHON‐ND4 patients (Phase I/IIa; ClinicalTrials.gov NCT02064569) underwent IVI of GS010 with four escalating dose levels (9E9; 3E10; 9E10; 1.8E11 vg/eye). Ocular examinations were performed up to 48 weeks. Serum anti‐AAV2 IgG were quantified by ELISA and Neutralizing antibodies (Nab) were quantified using a seroneutralization luciferase cell‐based assay. The complete data at 48 weeks will be presented

Results

At baseline, NAb levels in serum were undetectable in 7 patients and above 1:1,000 titer for 2. After 2 weeks, IgG titers increased up to 19 times baseline levels in 7 patients and NAbs up to 39 times in 10. At week 8, NAb titers remained above 1:1,000 titer for 6 patients; then titers tended to decrease progressively overtime. 13 patients experienced mild to moderate ocular inflammation (anterior chamber and/or vitritis), that resolved with standard therapy, without apparent correlation with the humoral serum response.

Conclusions

A humoral serum response against AAV2 was observed from 2 weeks post‐injection of GS010 in LHON patients. Ocular inflammation was reported, with no consistent correlation with anti‐AAV2 antibody levels and non‐detectable impact on pharmacodynamics trends. Additional follow‐up of humoral and cellular immunogenicity in Phase III trials will confirm these observations and delineate the potential predictable impact for contralateral eye injection.
A descriptive subgroup analysis of within hospital glaucoma referral in a tertiary center in Portugal
Authors: Leal I. , Cordeiro Sousa D. , Marques‐Neves C. , Abegao Pinto L.
Published: September 2016

Purpose

Glaucoma is a progressive and irreversible optic neuropathy carrying tremendous burden in healthcare systems. The aim of our study was to characterize the population referred to a glaucoma subspecialty department (GSD) in a university hospital.

Methods

We analyzed retrospectively the within‐hospital referral to the GSD. Electronic medical records and referral letters between Jan and Dec 2014 were screened. Data was screened for ancillary exams, type of tonometry, number of IOP‐lowering medications and extent of the disease (HODAPP classification). Statistics were performed with STATA v13.0.

Results

A total of 151 patients (78 males) were referred. Mean age was 68.2 (range 18–91). Thirty‐six patients (23.8%) were referred with visual field, pachimetry and OCT. Of those with a visual field, 38 (55.1%) had a mean defect >6 db (of which 17 had >12 dB), with 34 patients having at least two exams. In contrast, 16 (10.6%) were referred with no ancillary exam performed and 67 (50%) had all IOP measurements performed with pneumotonometry. Sixteen patients (10.6%) had a description of a gonioscopy. All patients were under IOP‐lowering treatment, of which 83 (55%) were under 2 or more IOP‐lowering medications. The number of patients referred with more than 80 years old was 29 (19.2%), 5 (18.52)% of which had a complete documentation of the disease. In this subset of patients, 6 (42.8%) had an advanced form of the disease.

Conclusions

Better understanding of our population characteristics will lead to a more accurate referral system. In a significant part of GDS referrals there was insufficient or poor quality clinical data. Our study raises awareness on the importance of an efficient within hospital subspecialist referral, leading to economic and health gain in Ophthalmology departments.
Difference between manifest and cycloplegic refraction in healthy non‐presbyopic patients
Authors: Del Buey M.A. , Lanchares E. , Pinilla I. , Almenara C. , Perez I. , Minguez E. , Cristobal J.A.
Published: September 2016

Purpose

To study the variation of objective refraction between manifest and cycloplegic conditions in healthy myopic patients younger than 40 years.

Methods

Sixty‐six myopic eyes of healthy patients under the age of forty years were included in this study. Manifest refraction, mean corneal power, white‐to‐white measurement, pupil diameter, central corneal thickness and anterior chamber depth weremeasured. Following the evaluation, 1% cyclopentolate was applied to induce cycloplegia and autorefractometer refraction was determined again. A statistical analysis was accomplished to investigate the relation ofthe mentioned parameters with the variation between manifest and cycloplegic refraction.

Results

Twenty‐eight eyes showed no difference between non‐cycloplegic and cycloplegic refraction. Thirty‐eight eyes presented a relevant difference (over 0.5D) between both measurements. The statistical analysis showed no differences between these two groups in age, non‐cycloplegic refraction, keratometry, white‐to‐white, central corneal thickness or anterior chamber depth. The only significant difference found between groups was the pupil diameter. Those patients with smaller pupil diameters presented greater changes in refraction. On the contrary, patients with wider pupils had negligible changes of refraction.

Conclusions

According to our outcomes, not only hyperopic patients and children, but also myopic patients may require refraction assessment under cycloplegic conditions when autorefraction is used, since many of them show a significant modification with respect to manifest refraction. Our results show a relation between this change in autorefractometer refraction with and without cycloplegia and the pupil diameter.
Semi‐fluorinated alkanes for topical delivery of Cyclosporine
Authors: Agarwal P. , Scherer D. , Günther B. , Rupenthal I.
Published: September 2016

Purpose

Cyclosporine A (CsA) is an anti‐inflammatory agent that has been frequently used to treat ocular inflammatory conditions, such as dry eye syndrome. However, the poor water solubility of CsA makes it difficult to formulate into an acceptable ocular dosage form. Semi‐fluorinated alkanes (SFAs) are a novel class of inert, non‐toxic and amphiphilic liquids that form clear solutions with CsA and have been suggested as efficient carriers for topical administration of CsA. The aim of this study was to assess the corneal bioavailability of CsA from SFAs compared to currently marketed formulations.

Methods

An ex vivo porcine eye model was used to study the penetration of a) Restasis® (0.05% CsA ophthalmic emulsion), b) Ikervis® (0.1% CsA ophthalmic emulsion), and c) 0.05% or 0.1% CsA in SFAs. The amount of drug penetrated per gram of cornea between 0.5 and 4 h after application was assayed by HPLC and statistically compared using a two‐way ANOVA. Drug distribution in different layers of the cornea was also visualized by substituting CsA with a lipophilic fluorescent dye and viewing corneal sections under a fluorescent microscope.

Results

Significant improvement in corneal penetration of CsA could be observed for 0.05% CsA in SFAs (C1 h = 5.844 ± 2.408 ng/g) over Restasis (C1 h = 761 ± 221 ng/g), with the area under curve (AUC) being more than 8‐folds greater. The AUC of 0.1% CsA in SFAs (C1 h = 12.556 ± 4.017 ng/g) was 3.6 folds greater than Ikervis (C1 h = 2.900 ± 341 ng/g). Microscopic examinations revealed that the dye incorporated into SFAs tended to accumulate mainly in the corneal epithelium.

Conclusions

Overall, this study showed that SFAs can significantly improve the corneal absorption of lipophilic drugs, such as CsA, and could therefore be a promising platform for drug delivery to the eye.
A curry a day keeps glaucoma away? – A curcumin study
Authors: Balendra S.I. , Davis B.M. , Guo L. , Cordeiro M.F.
Published: September 2016

Purpose

Curcumin's neuroprotective potential is challenged by its low solubility and stability at physiological pH. We aimed to solubilise curcumin into a formulation with high encapsulation efficiency (EE) and stability in phosphate buffer solution and to demonstrate its neuroprotective efficacy in vitro and in vivo upon topical administration in the well‐established ocular hypertensive (OHT) rat model of glaucoma.

Methods

A thin‐film hydration technique was employed to manufacture curcumin‐loaded micelles which were characterised for size and dispersity using dynamic light scattering and transmission electron microscopy. EE was assessed spectroscopically. Stability of the formulation was assessed by measuring changes in particle physical properties and EE over time. Assessment of curcumin mediated neuroprotection in vitro was achieved using an alamarBlue cell‐viability assay in paraquat‐treated primary retinal ganglion cells (RGCs). In vivo assessment of topical curcumin micelle mediated neuroprotection was assessed in the OHT model with primary endpoint of whole retinal Brn3a histology.

Results

A solubilised micellar formulation was developed containing 4.5 mg/ml of curcumin with >90% EE. This was found to be stable at room temperature for >45 days, increasing to >6 months with lyophilisation in presence of a cryoprotectant. Curcumin versus vehicle‐only pre‐treated RGCs had a significantly higher IC50 in vitro (p < 0.05). Curcumin‐treated versus untreated OHT eyes had a significantly higher RGC density on Brn3a histology (p < 0.001).

Conclusions

A novel curcumin formulation is described which increases its solubility 100‐fold to 4.5 mg/ml and is stable for >60 days at room temperature and >6 months on lyophilisation. This formulation elicited significant neuroprotection in vitro and on 3 weeks of topical ocular instillation in vivo, with no toxicity findings.
En‐face imaging of epiretinal membrane using swept source optical coherence tomography
Authors: Kim J.T. , Chung H.
Published: September 2016

Purpose

To define morphologic features of epiretinal membrane (ERM) using en face images from swept‐source optical coherence tomography (SS OCT).

Methods

Consequtive patients with idiopathic ERM were analyzed for en face imaging analysis within a 6‐month period. All patients had undergone 3D volume scan of swept source OCT (Triton OCT, Topcon, Japan). The patients were devided into 3 groups, retinal thickening without retinal hole (Group 1); retinal thickening with lamellar macular hole (Group 2); retinal thickening with macular pseudohole (Group 3). Secondary ERM were excluded from analysis. En face imaging was analyzed on and under the level of ILM.

Results

Mean patient age was 63.6 ± 10.8 years (n = 77). Mean central retinal thickness (CRT) in group 1, 2, and 3 was 422.3 ± 73.3 μm (n = 51), 334.1 ± 39.6 μm (n = 34) and 277.7 ± 58.6 μm (n = 12). En face imaging under ILM level well visualized central tractional membrane (CTM), and imaging on the ILM level showed well radiating folds (RF) over the posterior pole. Group 1 had CTM over the fovea (100%), however Group 2 had CTM outside the fovea (94.1%). Group 3 had better BCVA and lesser CRT than the other groups (ANOVA p < 0.05).

Conclusions

En face SS OCT provides an useful tool to visualize the pathologic features in epiretinal membrane. Lamellar macular hole might be associated with perifoveal or extrafoveal epiretinal membrane and it's tractional force. Macular pseudohole might be associated with ERM or prior macular traction. En face SS OCT provides an useful tool to visualize the pathologic features in epiretinal membrane.
Communication between the researcher and the researched. Designing an application based study regarding effects of air pollution on ocular surface diseases
Authors: Czak W. , Nowakowski J. , Mulak M. , Łaba A. , Misiuk‐Hojło M.
Published: September 2016

Purpose

To inform application users about current air pollution and their ocular surface state. To gather data concerning correlation between air pollution and ocular surface diseases.

Methods

AirPoll is a mobile application that serves as a gateway to a nation‐wide air pollution study. We designed it using Apple's Research Kit – an open source software framework for medical researchers. After all the permissions are granted and consent form is signed digitally, the application uses phone's Global Positioning System to determine user's location and then connects to the server of US Environmental Protection Agency to determine the level of various air pollutants. The built in questionnaire module allows us to gather data related to user's health, including past medical history and OSDI Dry Eye questionnaire. To raise user's engagement in the study and provide an information feedback, every user has access to his or her data presented in an easy to understand manner. Both current pollutants in the user's location and his approximate health state are displayed in a simple graph form.

Results

Data concerning current air pollutants levels basing on geolocation of the application user (including particulate matter with a mean aerodynamic diameter of 2.5 μm and 10 μm, ozone, sulfur oxides and volatile organic compounds) and results concerning ocular surface obtained using OSDI Dry Eye questionnaire.

Conclusions

This innovative approach to sharing information in medical research not only raises user's involvement in the study, but also fulfils an educational purpose.
Nanophthalmos clinical features and specific outcome
Authors: Bremond‐Gignac D.
Published: September 2016

Nanophthalmos is a rare genetic eye disease. Anterior and posterior segment of the eyeball are significantly reduced without major structural anomaly. Otherwise than in microphthalmia, the eye is functional, visually functional with an extreme farsightedness or hyperopia. The high hyperopia is usually the first sign detected. In nanophthalmos, ultrasound shows markedly reduced axial lengths. They also present thickening of scleral tissues with fibronectin level. Although they may suffer problems associated with the extreme small size. An increased risk of glaucoma especially by closure angle may be observed. Uveal effusion represents the major complication and ocular surgery should be avoided as far as possible. Complications may lead to amblyopic vision loss. These seem secondary to the actual disease state, which may be viewed as one extreme on the spectrum of refractive errors. Nanophthalmic patients in infancy present a relatively good visual acuity but the pathology may lead to severe visual impairment.
Specificities of corneal infectious diseases in children
Authors: Bremond‐Gignac D.
Published: September 2016

Infectious keratitis in children is not common but can cause a severe visual impairment if late diagnosed with delayed treatment established or with weak efficacy. Corneal infections in children can affect subjects of all ages with a high frequency in newborns and infants. In infant, children and teenagers the most common ocular pathogens, that differ from the adult, are Haemophilus Influenzae, Staphylococcus aureus, Streptococcus pneumonia and also Moraxella species. These infections infections could lead to ulcers and sight‐threatening complications. In children corneal infections can be difficult to diagnose because the pathology can develop without pain. In addition, the examination may be difficult to perform. Identification of the pathogen must be performed as far as possible. The treatment should be provided earlier and aims to eliminate the bacteria, virus or fungus pathogens. Specific epidemiology of pathogens will be detailed according to age. Risks of visual impairment and amblyopia must be integrated. An update on topical antibiotics and current options will be reviewed with practical aspects, diverse clinical cases and considering quality of life of children and parents.
Topical cyclosporine‐A in dry eye associated with chronic graft versus host disease
Authors: Atilla H.
Published: September 2016

Graft‐versus‐host disease (GVHD) is a major complication of bone marrow transplantation and seen in 50–70% of cases. It is a complex clinical disease with many organ and system involvement. Acute form is seen in the first 3 months after transplantation, mainly as hepatitis and chronic form is mostly seen after acute GVHD. Ocular manifestations can be classifed as anterior and posterior findings but dry eye syndrome is the most frequent ocular finding and seen in 40–90% of patients with chronic GVHD. Corneal vascularization, keratitis and perforation can be seen. Topical cyclosporine‐A might be an effective and safe treatment option in dry eye related to chronic GVHD in combination with topical steroids, autologous serum, lubricant eye drops and ointments.
Trans‐scleral delivery of novel anti‐angiogenic small molecule inhibitors of SRPK1
Authors: Batson J. , Toop H.D. , Allen C. , Rowlinson J. , Babaei‐Jadidi R. , Gibbons B. , Zhang J. , Wearmouth S.F. , Knapp S. , Morris J.C. , Bates D.O.
Published: September 2016

Purpose

Development of non‐invasive, novel therapies for wet age‐related macular degeneration (wAMD) and diabetic macular oedema (DME) is hindered by insufficient delivery to the retina. SRPK1 is a novel target that regulates VEGF‐A splicing. We used a rational medicinal chemistry approach to specifically design novel inhibitors with properties required for trans‐scleral delivery.

Methods

Freshly enucleated porcine eyes were dissected, and eye tissue was clamped into a scaffold with inhibitors in the upper chamber facing the sclera. Tissue was dissected at 24 h and compound measured by mass spectrometry. Compounds were screened based on structure, potency, selectivity, molecular weight, cLogP and SAR to inform further development. Efficacy and PK were evaluated in vivo in C57/Bl6 mice. New Zealand White rabbits received 3× daily eye drop for 6 days then eyes were dissected, compounds analysed by mass spectrometry.

Results

Potent SRPK1 inhibitors had improved permeability ex vivo compared to pazopanib (SPHINX‐A 1.47 × 10−6 cm/s, Pazopanib 0.07 × 10−6 cm/s p < 0.0005). Modifications of the R1 and R2 domains, based on crystal structure analysis, led to enhanced permeability (SPHINX‐B 3.46 cm/s*10−6). Permeability did not correlate with molecular weight or cLogP but could be affected by additional parameters such as melanin binding. SPHINX‐A was detected at 0.008% of the total applied dose (84 μg) and above its target IC50 value in rabbit eyes. SRPK1 inhibitor eye drops inhibited laser‐CNV (EC50s < 0.5 μM, n = 6–8, p < 0.05, One‐way ANOVA).

Conclusions

With increased specificity, potency and trans‐scleral permeability, novel SRPK1 inhibitors have potential to reach therapeutic levels in posterior eye segments following eye drop administration and improve treatment for patients with wAMD and DME.
Static and dynamic retinal vessel analyses in patients with stroke as compared to healthy control subjects
Authors: De Boever P. , Palkovits S. , Pertl L. , Fazekas F. , Kneihsl M. , Trozic I. , Goswami N. , Weger M.
Published: September 2016

Purpose

The retinal microcirculatory bed shares anatomical and physiological characteristics with the cerebral circulation. Static and dynamic changes in the retinal blood vessels can mirror cardio‐ and cerebrovascular events. The aim of the study was to underpin the relevance of retinal analysis for stroke research.

Methods

18 stroke patients and 16 age‐matched healthy control subjects were included in the present study. Retinal image acquisition was done with a Zeiss fundus camera FF 450plus. Static vessel analysis was done using IFLEXIS software provided by VITO (www.iflexis.com). Retinal vessel dimensions and geometric dimensions were determined. A retinal arteriole and a retinal venule were examined before and after flicker light stimulation for 60 sec. Flicker response, the relative change of vessel diameter due to flicker light stimulation, was calculated using Dynamic Vessel Analysis by imedos (www.imedos.de).

Results

Central Retinal Arterial Equivalent (CRAE) was significant smaller in stroke patients when compared to the control group, whereas Central Retinal Venular Equivalent (CRVE) was comparable between the groups. Arteriovenous ratio (AVR) was significantly smaller in the stroke group. The analysis further showed significantly smaller daughter arteriolar branches and larger venular branch angles in stroke patients. Dynamic vessel analysis found reduced arteriolar diameters in stroke patients. Response to flicker light was smaller in stroke patients but this difference did not reach level of significance.

Conclusions

Our pilot study indicates that retinal analysis is a non‐invasive and convenient tool that is relevant to study microvascular changes in stroke patients The importance of retinal changes as a risk factor for stroke or for patient stratification is now being addressed in follow‐up studies.
Manufacturing of an ocular prosthesis based on the 3D printed anophthalmic socket
Authors: Ruiters S. , Sun Y. , De Jong S. , Politis C. , Mombaerts I.
Published: September 2016

Purpose

In anophthalmos, the ideal ocular prosthesis restores the facial appearance and eye motility, and is comfortable to wear. This can best be achieved with a bespoke prosthesis. The initial step usually involves injection of dental impression material to obtain a mould of the anophthalmic socket. However, the socket impression method distorts the soft tissues, so that additional alterations to the prosthesis are required via the trial and error method. Developing an impression‐free method of the anophthalmic socket.

Methods

A cone‐beam CT of the anophthalmic orbit is taken, and with computer‐aided design and computer‐aided manufacturing (CAD/CAM) the anophthalmic socket is printed three dimensionally (3D). The 3D‐printed socket is subsequently used as a trial working prosthesis in the conventional way.

Results

With this novel technique, a prosthesis was successfully fitted in a 68‐year‐old male who had undergone a recent evisceration.

Conclusions

Computer‐aided design and 3D printing can accurately outline the anophthalmic cavity. Validating the impression‐free moulding technique is subjected to further studies.
Systematic review of patient preference and adherence to the correct use of graduated compression stockings to prevent deep vein thrombosis in surgical patients
Authors: Wade Ros , Paton Fiona , Woolacott Nerys
Published: September 2016

Aim

The aim of this study was to explore patient preference and adherence to thigh and knee length graduated compression stockings for the prevention of deep vein thrombosis in surgical patients.

Background

Hospitalised patients are at risk of developing deep vein thrombosis. Mechanical methods of prophylaxis include compression stockings, available as knee or thigh length. Patient adherence to correct stocking use is of critical importance to their effectiveness.

Design

Systematic review of quantitative evidence.

Data sources

Eleven databases were searched from inception to 2013 for systematic reviews of compression stockings. Reviews were screened for relevant primary studies and update searches of eight electronic sources were undertaken (2010–2014).

Review methods

Randomised controlled trials and observational studies of surgical patients using compression stockings were quality assessed and data were extracted on patient adherence and preference. A narrative summary is presented.

Results

Nine randomised controlled trials and seven observational studies were included in the systematic review. There was substantial variation between studies in terms of patient characteristics, interventions and methods of outcome assessment.

Conclusion

Patient adherence was generally higher with knee length than thigh length stockings. However, the studies reflect patient adherence in a hospital setting only, where patients are observed by healthcare professionals; it is likely that adherence reduces once patients have been discharged from hospital. Patients preferred knee length stockings over thigh length stockings. In many clinical settings, any difference in efficacy between thigh length and knee length stockings may be rendered irrelevant by patient preference for and likely better adherence to knee length stockings.
Understanding Special Olympics Experiences from the Athlete Perspectives Using Photo‐Elicitation: A Qualitative Study
Authors: Weiss Jonathan A. , Burnham Riosa Priscilla , Robinson Suzanne , Ryan Stephanie , Tint Ami , Viecili Michelle , MacMullin Jennifer A. , Shine Rebecca
Published: September 2016

Background

Many individuals with intellectual disabilities experience challenges to participating in organized sport, despite its known benefits. The aim of this qualitative study was to understand the experiences of participating in sport (Special Olympics) from the perspectives of athletes with intellectual disabilities.

Methods

Five participants (13‐33 years of age) took part in a photo‐elicitation project during a 1‐month period.

Results

Our thematic analysis of participant photographs and descriptions revealed the following athlete themes: ‘Connectedness’ and ‘Training in Sport’.

Conclusion

Photo‐elicitation was a useful and important tool in assisting athlete participants to communicate their motivations to participate in sport in ways that using traditional verbal interviewing would not.
Content Validity and Psychometric Characteristics of the “Knowledge about Older Patients Quiz” for Nurses Using Item Response Theory
Authors: Dikken Jeroen , Hoogerduijn Jita G. , Kruitwagen Cas , Schuurmans Marieke J.
Published: September 2016

Objectives

To assess the content validity and psychometric characteristics of the Knowledge about Older Patients Quiz (KOP‐Q), which measures nurses' knowledge regarding older hospitalized adults and their certainty regarding this knowledge.

Design

Cross‐sectional.

Setting

Content validity: general hospitals. Psychometric characteristics: nursing school and general hospitals in the Netherlands.

Participants

Content validity: 12 nurse specialists in geriatrics. Psychometric characteristics: 107 first‐year and 78 final‐year bachelor of nursing students, 148 registered nurses, and 20 nurse specialists in geriatrics.

Measurements

Content validity: The nurse specialists rated each item of the initial KOP‐Q (52 items) on relevance. Ratings were used to calculate Item‐Content Validity Index and average Scale‐Content Validity Index (S‐CVI/ave) scores. Items with insufficient content validity were removed. Psychometric characteristics: Ratings of students, nurses, and nurse specialists were used to test for different item functioning (DIF) and unidimensionality before item characteristics (discrimination and difficulty) were examined using Item Response Theory. Finally, norm references were calculated and nomological validity was assessed.

Results

Content validity: Forty‐three items remained after assessing content validity (S‐CVI/ave = 0.90). Psychometric characteristics: Of the 43 items, two demonstrating ceiling effects and 11 distorting ability estimates (DIF) were subsequently excluded. Item characteristics were assessed for the remaining 30 items, all of which demonstrated good discrimination and difficulty parameters. Knowledge was positively correlated with certainty about this knowledge.

Conclusion

The final 30‐item KOP‐Q is a valid, psychometrically sound, comprehensive instrument that can be used to assess the knowledge of nursing students, hospital nurses, and nurse specialists in geriatrics regarding older hospitalized adults. It can identify knowledge and certainty deficits for research purposes or serve as a tool in educational or quality improvement programs.