bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate transport and receptor actions: Potential roles in inner retinal function and disease
Authors: Vohra R. , Vosborg F. , Henriksen U. , Gurubaran I.S. , Hasan‐Olive M. , Holm E. , Skytt D. , Gjedde A. , Storm‐Mathisen J. , Kolko M. , Bergersen L.H.
Published: September 2015

Purpose

In the brain and in adipose tissue activation of the lactate receptor GPR81 is known to promote downregulation of cAMP. Lactate is hereby involved in excitability, metabolism and inflammation. Neurodegenerative diseases in retina may in a similar manner be linked to disturbed lactate homeostasis.

Methods

qPCR was performed on retina and brain extracts to investigate whether the lactate receptor GPR81 is expressed in the retina. Immunocytochemistry was performed on primary cell cultures of Müller cells (MC) and retinal ganglion cells (RGC) from mice to evaluate the presence of lactate receptors in neuronal and glial cells in the retina. Lactate assays were made to show the changes in lactate concentrations during different conditions of stress.

Results

GPR81 mRNA was twice as high in retina as in hippocampus or cerebral cortex. Immunocytochemistry indicated lactate receptors in both RGC and MC. Lactate assays showed a decreased release of lactate from MC upon energy restriction. Interestingly, the combination of inhibited mitochondrial function and energy restriction significantly increased the amount of released lactate.

Conclusions

The presence of lactate receptors in the retina as well as the changed levels of lactate in response to stress support the suggestion that lactate could be of great importance in retinal homeostasis and as such in the pathogenesis of inner retinal diseases.
Anatomical digital image analysis of the angle and optic nerve – a novel method for glaucoma imaging
Authors: Russell G. , Szabó Á. , Sziklai P. , Facskó A. , Kolko M. , Petrovski G.
Published: September 2015

Purpose

To devise a simple, fast and low‐cost method for glaucoma imaging using anatomical digital image analysis of the angle and optic nerve in human subjects.

Methods

A pilot study included 10 open‐angle glaucoma patients attending the glaucoma services at the Department of Ophthalmology, University of Szeged, Hungary; colour photographs of the fundus, standard optic nerve images with OCT and additional digital slit lamp images of the angle where collected. Digital image conversion and analysis of the angle using Image J (NIH, USA) and adaptive histogram equalization Contrast Limited AHE (CLAHE) to prevent noise amplification. Angle and optic nerve images, were analyzed separately in the Red, Green and Blue (RGB) channels, then 3D volumetric analysis of the degrees of angle, cup volume of the optic nerve took place. Horizontal tomogram reconstitution and nerve fiber detection methods were developed and compared to a standard Topcon 3D OCT.

Results

Angle measurements from digital angle images by gonioscopy all fitted within one standard deviation of Anterior OCT measurements. Comparative analysis of RGB channels produced volumetric cup and Horizontal tomogram results closely resembling those of OCT 3D appearance and B‐scan of the cup, respectively. Similar RGB channel splitting and image subtraction produced a map closely resembling that of the thickness RNFL map on OCT.

Conclusions

While spectral domain OCT is rapidly progressing in the area of optic disc and chamber angle assessment, rising health care costs and lack of availability of the technology, opens demand for alternative forms of image analysis of glaucoma. Volumetric, geometric and segmentational data obtained through digital image analysis correspond well to those obtained by high definition OCT imaging. A larger number of subjects is needed to further validate the method.
Eyelid disorders evaluation in the Ophthalmic current practice in Belgium, Denmark, France, Netherland, Portugal and Turkey: The Meibum Study
Authors: Diaz Valle D. , Doan S. , Yagmur M. , Benitez del Castillo J.M.
Published: September 2015

Purpose

To determine the incidence and characteristics of eyelid inflammatory disorders during general ophthalmological consultations and to demonstrate the association between palpebral pathologies and ocular surface pathologies in 6 of the 9 European countries involved in the MEIBUM survey.

Methods

Multi‐center, international, transversal and epidemiological survey. The primary objective was to assess the percentage of eyelid disorders in patients attending a current ophthalmologic consultation. The secondary objectives were to assess the association between palpebral pathologies and ocular surface pathologies, the impact of eyelid disorders on patient's daily life (on vision, on daily life activities/work, on leisure, on contact lens wearing, on emotions and on sleep).

Results

A total of 1398 were included by ophthalmologists from Belgium, Denmark, France, Netherland, in Portugal and Turkey.The mean age was 56.2 (±17.5). At least an ocular history was found in 78.4% of the patients. The main antecedents were “Dry eye” (25%), “Glaucoma” (15.7%) and “Cataract” (19.8%). The percentage of eyelid disorders was 73.4%. The diagnostic of Meibomian Gland Dysfunction (MGD) was established in 45.4% of the total patients and dry eye in 63.4%. The impact of MGD on daily life was mainly on vision for 60.2% of the patients, on daily activities/work (49.7%), on leisure (40.8%), but also on emotions (22.1%) and sleep (15.8%). MGD were treated by eyelid hygiene recommendations: warming (68.5%), massaging (67.7%) cleansing (78.9%), and eye drops for dry eye (79.5%).

Conclusions

MGD was diagnosed in nearly half of the patients with a strong link to dry eye. The impact on daily life is notable. Only dry eye symptoms seem to be taken in charge more often than MGD.
Combination of Resveratrol with omega‐3 fatty acids synergize to counteract VEGF‐R pathway in sick retinal pigment epithelium cells mimicking AMD
Authors: Chalons P. , Scagliarini A. , Courtaut F. , Olmière C. , Delmas D.
Published: September 2015

Purpose

The aim of this work is to assess whether RSV (Resveratrol) can act synergistically with omega‐3 fatty acids to modulate VEGF (Vascular Endothelial Growth Factor) signaling pathway in order to identify a new and more effective therapy for the treatment of AMD (Age‐Related Macular Degeneration).

Methods

In this study, undifferentiated and differentiated human retinal pigment epithelial cells (ARPE‐19) were used. The cells were treated with an omega‐3/RSV preparation (Resvega®), or a RSV‐free formulation or RSV alone for 24 h. The expression of key proteins in VEGF signaling pathway was evaluated by Western Blotting.

Results

We observed that the combination omega‐3/RSV preparation (Resvega®) induces a stronger inhibition of the VEGF‐R pathway activation than the RSV‐free formulation or RSV alone in sick retinal cells. Surprisingly, Resvega® maintains and increases the functional VEGF‐R pathway in normal retinal cells.

Conclusions

This work brings a new insight into the mechanism by which omega‐3/RSV could counteract AMD and could protect the other eye when AMD is already present.

Financial Support: This work is supported by Théa laboratory.
Effects of recurring intraocular pressure elevations on the retina and the autoimmune component
Authors: Teister J. , Gramlich O. , Neumann M. , Tao X. , Pfeiffer N. , Grus F.
Published: September 2015

Purpose

In glaucoma, complex changes of IgG serum autoantibody (Aab) repertoire highlight the possible contribution of an autoimmune component in the pathogenesis of this neurodegenerative disease. An elevated intraocular pressure (IOP) and its fluctuations are considered as major risk factors. The aim of the study was to identify the systemic influence of fluctuations using recurring pressure peaks and drops in a glaucoma animal model.

Methods

Sedated male Long Evans rats experienced a unilateral, intermittent IOP manipulation using a silicone loop adjusted around the eye globe for 1 hour during 27 treatments. The pressure profile included pressure peaks to 35 and 45 mmHg and drops to a physiologic value of 8 mmHg. Contralateral (n = 12) and untreated eyes (n = 14) served as controls. Neurodegeneration was determined after paraphenylenediamine staining and Brn3a staining. Microglia activation was identified after Iba1 staining in retinal cross‐sections. Changes of serum immunoreactivities were identified using a microarray approach with a glaucoma‐specific antigen Setup.

Results

A loss of axon density (as axons/0.05 mm2) of treated eyes (19624 ± 1709) compared to contralateral (21943 ± 1510; p < 0.01) and untreated eyes (22267 ± 1408; p < 0.01) occured, which was confirmed by retinal ganglion cell count. Next to an activation of microglia, upregulated Aab reactivities for GST, transferrin, and NSE were identified in serum of treated animals in comparison to control serum.

Conclusions

This animal model including pressure peaks and drops allows the establishment of individual IOP profiles. The retina and the optic nerve sustained a significant damage and an altered autoimmune repertoire could be induced. A significant influence of recurring pressure fluctuations could be demonstrated using this sophisticated glaucoma animal model.
Corneal nerve activity during ocular inflammatory processes
Authors: Luna C. , Quirce S. , Belmonte C. , Gallar J. , Acosta M.C.
Published: September 2015

Purpose

To study the changes in sensory nerve activity of the eye associated with ocular inflammation in two different experimental models developed in the guinea‐pig.

Methods

Allergic keratoconjunctivitis (AK): Ovalbumin sensitization was induced and blinking and tearing rate was measured before and after the allergic challenge. UV photokeratitis: One eye of the anesthetized guinea‐pig was exposed to 254 nm radiation during different times. Blinking rate and tear secretion were measured before and 48 h after UV. In both models, nerve activity was recorded in vitro in the whole eye or the excised cornea superfused with physiological saline at a controlled temperature. Spontaneous (SA) and stimulus‐evoked electrical activity were recorded. Mechanical, thermal and chemical sensitivity were tested in control and inflamed eyes.

Results

In AK model tearing and blinking rate increased significantly. In nociceptors, mechanical threshold decreased, the percentage of units with SA increased and the impulse response to chemical stimulation increased significantly in inflamed eyes compared with controls. On the contrary, SA and response to cold of cold thermoreceptors decreased during inflammation.

Conclusions

In ocular pathological processes primarily characterized by local inflammation, nociceptors became sensitized while cold thermoreceptors became desensitized, due to changes in the expression and/or activity of ion channels present in sensory nerve terminals. Disbalance in the sensory input from the different functional types of sensory nerve fibers innervating the ocular surface in inflammatory conditions may be in the bases of the unpleasant sensations evoked by inflammatory pathological processes affecting the ocular surface in humans.
Heterogeneous choroidal thickness pattern in diabetic patients without diabetic retinopathy
Authors: Vicente A. , Costa L. , Cardigos J. , Santos A. , Amado D. , Cunha J.P. , Abegao Pinto L. , Ferreira J.
Published: September 2015

Purpose

The authors intend to present an analysis and comparison of the choroidal thickness in more distant superior regions. Choroidal thickness is increased in a heterogeneous pattern superiorly to the fovea in diabetic patients without diabetic retinopathy.

Methods

Observational case‐control study of 60 eyes of 60 patients with diabetes mellitus type 2 without diabetic retinopathy. A control group of 31 eyes of 31 patients without diabetes with similar demographic features was also created. All the patients were recruited from the same outpatient clinic. Enhanced depth imaging spectral‐domain optical coherence tomography (EDI SD‐OCT SPECTRALIS®) was performed and high‐resolution macular scans were obtained. Choroidal thickness was evaluated 2000 μm superiorly to the fovea by manual layer segmentation. Previous studies have validated the validity of using a manual layer segmentation procedure in OCT. Statistical analysis was done with SPSS Statistics. A p value <0.05 was considered statistically significant.

Results

Diabetic patients were in average 67.0 ± 9.6 years old and 56.7% were male. Average choroidal thickness 2000 μm superiorly to the fovea was 287.77 ± 74.32 μm in diabetic patients and 249.81 ± 53.96 μm in non‐diabetic patients. There was a significant increase in choroidal thickness in diabetic patients when compared to non‐diabetic patients (T‐student, p = 0.014).

Conclusions

Choroidal thickness can be accurately measured using high‐definition macular OCT scans. This study documented structural differences in the choroid associated with diabetes mellitus type 2 that are not only present in the central foveal area as reported in previous studies. Diabetes Mellitus is associated with multiple microvascular dysfunctions that are probably coupled with choroidal vascular modifications that induce changes in thickness.
Macular diseases in myopia
Authors: Creuzot C.
Published: September 2015

Pathologic myopia is a leading cause of blindness wordlwide with macular degeneration often related to a posterior ectasia named staphyloma. This degeneration leads to a progressive thinning of the retinal pigment epithelium and choroid. The main signs of macular diseases due to myopia can vary from yellow‐white breaks in Bruch's membrane called lacquer cracks, subretinal hemorrhages and secondary neovascularisation that can be associated. The diagnosis can be made with visual acuity measurement, fundus exam, OCT, autofluorescence and angiography to differentiate isolated hemorhhages and choroidal neovascularisation. The prognosis of myopic choroidal neovascularisation has been greatly improved with antiangiogneic agents.
Outcomes of using intravitreal ranibizumab to treat patients with ischaemic diabetic maculopathy
Authors: Begum S. , Lockwood A. , Mourtzouko S.
Published: September 2015

Purpose

To report the functional and anatomical outcomes of using intravitreal ranibizumab (IR) for patients with ischaemic diabetic maculopathy (IDM).

Methods

Retrospective analysis of 11 consecutive patients treated with IR for IDM from Nov 2008 to May 2015. The number of injections, fluorescein fundus angiography (FFA) results, visual acuity (VA) and central retinal thickness (CRT) prior to commencing IR were recorded. VA was assessed with logMAR.

Results

Three eyes were excluded as one had a history of vein occlusion, one was amblyopic and the other patient had multiple vitreous haemorrhages and vitrectomy.There were equal numbers of females and males, the average age was 67 (34–82 years) and patients had on average 5 (range 3–11) injections of IR. Average length of follow up was 13 months (5–18 months). On FFA 4 patients had enlargement of foveal avascular zone (FAZ), 1 patient had fragmentation of FAZ, 1 patient had deregulation of FAZ and 1 patient had an increase in FAZ. The average initial VA was +0.9 (+0.3 to +1.78) and the average final VA was +1.05 (+0.6 to +1.78). The average change between initial and final VA was +0.15. Initial average CRT was 558 (306–785) reducing to an average of 447 (197–892) at the final follow up. The average CRT reduction was 111 between initial and final CRT.

Conclusions

Anatomical thickness appears to be reduced with IR injections, but without improvement in visual acuity. No adverse complications were noted with this regimen.
Clinical Experience with the Ruthenium‐ plaque Brachytherapy in Case of Choroidal Melanoma
Authors: Grajewski L. , Kneifel C. , Ciernik I. , Ebrahimi F. , Krause L.
Published: September 2015

Purpose

The brachytherapy with β‐ emitting ruthenium‐ plaques is a well‐established treatment for patients with choroidal melanoma. This treatment modality has been used in our department since January 2011.

Methods

A retrospective study of 104 eyes with choroidal melanoma that were treated with ruthenium‐ brachytherapy between January 2011 and December 2014. Patients were followed for regression and associated side‐ effects. The study included patients that had a follow‐ up time of at least 3 months.

Results

Of the 104 melanomas nine also showed an infiltration of the ciliary body, 32 manifested at a central location and 59 eyes showed an exudative retinal detachment prior to brachytherapy. The mean sclera contact dose was 519 Gy, the mean apical dose applied was 105 Gy. The mean apical depth of the melanoma prior to therapy was 4.3 mm and after 12 months 2.2 mm. In three cases a movement of the plaques was necessary since the plaque did not cover the tumour margins in total because of the diameter of the melanomas. In eight cases the tumour showed regrowth after an initial regression was noticed. All together four eyes had to be removed. In eight cases distant metastasis were detected and two eyes showed a radiation retinopathy.

Conclusions

For the treatment of choroidal melanoma the β‐ emitting ruthenium‐ plaques represent a therapy with a local tumour control rate of 92.3% and eye salvaging rate of 96.2%.
Neurotrophic keratitis (NK) in carotid cavernous fistulae (CCF)
Authors: Stephan S. , Rouger H. , Doan S. , Lamirel C. , Cochereau I. , Gabison E.
Published: September 2015

Purpose

Carotid cavernous fistulae (CCF) are rare, with a poor visual outcome. In addition, lesions of trigeminal nerve induced by an elevated venous pressure in the cavernous sinus may induce a neurotrophic keratitis (NK). Embolization is the standard care.

The objective of this study was to assess NK in a group of patients treated by embolization of their CCF using in vivo confocal microscopy.

Methods

Patients treated for an indirect CCF from January 2004 to May 2013 were prospectively included. The diagnostic of NK was assessed by Oxford's test, Cochet‐Bonnet's esthesiometry and a study of corneal nerves by in vivo confocal microscopy. Results were compared using Student t‐test.

Results

13 patients, 5 men and 8 women, with a median age of 67 years old were included with a median follow‐up of 51 months: 38% (5/13) had a NK, of which 40% (2/5) bilateral. 60% (3/5) were clinically cured, with a minimal to moderate NK; and 40% (2/5) had persisting CCF symptoms with a moderate to severe NK.

Conclusions

To our knowledge, NK resulting of a compression of the trigeminal nerve by CCF has never been studied. On the other hand, NK is a challenging diagnosis because of a poor clinical presentation. Recently, in vivo confocal microscopy has been developed for corneal nerves analysis and should therefore be considered as an interesting tool to assess NK in patients treated for a CCF.

NK are frequent (38%) in patients treated for CCF. NK are minime to moderate and sometimes bilateral. Early diagnosis using in vivo confocal microscopy should avoid corneal complication.
Proteomic analysis of the uveal melanoma (UM) secretome reveals novel insights and potential biomarkers
Authors: Angi M. , Kalirai H. , Coupland S.
Published: September 2015

Purpose

UM is the most common primary intraocular tumour in adults. Despite successful ocular treatment, 50% of patients develop fatal metastatic spread, usually involving the liver. UM patients are stratified into high risk (HR) or low risk (LR) metastatic groups, according to clinical, histopathological and genetic features of their tumours. Blood biomarkers are urgently needed to detect the early development of metastatic disease. The aims of this work were to increase our understanding of UM metastasis processes, and to identify secreted biomarkers of UM metastatic disease.

Methods

Comparative analysis of the secretome from short‐term cultures of HR and LR UM patient samples was performed by nanoLC‐MS/MS‐based label‐free quantitative proteomics. Normal (N) controls included the secretome of cultured normal choroidal melanocytes. Secreted proteins were predicted based on their sequences. Bioinformatic analyses were performed using Partek and Ingenuity Pathway Analysis software.

Results

Eighteen UM (4LR; 14HR) and 5N cultures were established and their secretomes analysed. 1917 proteins were identified, and 1857 quantified in all subgroups. 627/1857 (34%) were classically and non‐classically secreted, and 554/1857 (30%) represented exosomal proteins. 947 proteins were differentially expressed between UM and N; pathway analysis demonstrated upregulation of proteins involved in mTOR signalling amongst others. An 18‐protein signature that discriminated between HR and LR UMs was identified.

Conclusions

Our comparative study of the secretome of N versus UM has identified cancer‐associated proteins linked to cell proliferation and cancer progression. Moreover, a UM secretome signature of metastatic risk was identified. Further studies on the exosomal fraction are also being performed.
Novel SRPK1 inhibitors specifically target alternative splicing in human primary retinal epithelial cells
Authors: Rowlinson J. , Batson J. , Toop H. , Allen C. , Gibbons B. , Babaei‐Jadidi R. , Zhang J. , Wearmouth S. , Knapp S. , Morris J. , Bates D.
Published: September 2015

Purpose

Specifically altering the splicing of VEGF‐A from pro‐angiogenic VEGF‐A165a to anti‐angiogenic VEGF‐A165b could prove effective in the treatment of wet AMD. VEGF‐A alternative splicing is controlled through RNA binding protein SRSF1 which when phosphorylated by the serine kinase SRPK1 induces pro‐angiogenic VEGF‐A165a expression. We aimed to use novel SRPK1 inhibitors that specifically alter splicing in retinal pigment epithelial (RPE) cells.

Methods

RPE cells were treated with novel compounds, synthesized based on the structure of SRPK1, followed by extraction of RNA and protein. RT‐PCR and digital PCR was used to examine splicing of genes expressed in the eye or known targets of SRPK1, and ELISA and immunoblotting were used to detect VEGF‐A isoform expression.

Results

Novel SRPK1 inhibitors dose‐dependently increased the expression of the anti‐angiogenic VEGF‐A165b isoform. RT‐PCR showed that SRPK1 inhibition altered alternative splicing of MKNK2, a known splicing target of SRSF1, resulting in a 2 fold change to isoform a in RPE cells. No change in splicing was observed for BCL2L1, ARR1, CAMK2D, RAC1, FN1 or hnRNPB1/A2. Other SRSF1 targets such as TEAD1, BIM and MST1R were not expressed in RPE cells.

Conclusions

We have developed novel SRPK1 inhibitors that specifically target splicing within the retina and offer an alternative more specific therapeutics for patients with exudative AMD.
Stimulation of TLR4 Increases Angiogenic and Anti‐Angiogenic Gene Expression in Choroidal Endothelial Cells
Authors: Stewart E. , Wei R. , Uribe M. , May S. , Amoaku W.
Published: September 2015

Purpose

The Toll‐like receptor (TLR) family initiate the innate immune response in reaction to invading microbes. Studies confirm the expression of TLRs in a variety of ocular tissues and cells, and it has also been suggested that selected TLRs may be associated with geographic atrophy and neovascularisation in age‐related macular degeneration, diabetic retinopathy and other vascular and inflammatory diseases of the ocular posterior segment. However, the exact mechanisms of TLR stimulation and the mechanism of endothelial inflammatory and angiogenic effects have not been defined.

Methods

Microarray analysis was performed on primary human choroidal endothelial cells stimulated with LPS, a specific TLR ligand. Microarray results were validated using qPCR and the functional significance of increased factors were investigated using proliferation and migration assays.

Results

Microarray indicated a large increase in expression of angiogenic (e.g. CCL2, IL‐8) and anti‐angiogenic (e.g. CXCL10, CXCL11) molecules. The fold change in expression of these molecules was validated using qPCR and the secretion using ELISA. Reported angiogenic molecules were confirmed to have a pro‐angiogenic effect in vitro.

Conclusions

This profiling of factors increased during TLR4 stimulation will help inform our understanding of inflammation in choroidal vascular diseases, as well as the development of future treatments for intraocular vascular diseases.
Two Sisters with Congenital Blindness caused by Osteoporosis‐pseudoglioma Syndrome due to new Mutations in the LPR5 Gene
Authors: Welinder L. , Robitaille J.M. , Boerkoel C.F. , Rupps R. , Lyons C.
Published: September 2015

Purpose

To discover the reason behind two sisters being born blind with retinal detachment and microphthalmia with later findings of severe osteoporosis with low impact fractures.

Methods

Molecular testing identified biallelic lipoprotein receptor‐related protein 5 (LRP5) mutations (NM_002335.3:c. [889dupA]; [2827 + 1G4A]) confirming a diagnosis of osteoporosis–pseudoglioma (OPPG) syndrome.

Results

Two new mutations in the LPR5 gene were each found in the unrelated parents of the girls and were found heterozygote in the girls. Both parents were then discovered to have osteopenia, as did several relatives, who all started preventive treatment.

Conclusions

OPPG is a autosomal recessive disease almost uniformly causing blindness from very early age with severe osteoporosis and low impact fractures, which was also the case of our two sisters. The diagnosis of OPPG was confirmed by sequencing the LPR5 gene, where two new mutations were found.
Significance of Camouflage, Chromatic Acuity and Contour in the Design of Pseudoisochromatic Plates
Authors: Krastel H. , Schultze‐Lutter S. , Mothes N. , Udodov E. , Kahlert C. , Jonas J.B.
Published: September 2015

Purpose

Pseudoisochromatic plates use a pseudo‐chaotic pattern of image dots to conceal the contour of colour optotypes. By our study we wantto improve the understanding of functional principles of pseudoisochromatic plates.

Methods

The circular elements of red/green pseudoisochromatic plates were varied in size and degree of pseudo‐chaotic arrangement. Illuminated by standard white D 65, colour optotypes were presented to daltonians and to normal observers, and the rates of failure and success in recognition were recorded.

Results

Recognition of pseudoisochromatic optotypes is related to the size of elements in a non‐ linear way. Towards small visual angles, colour optotype recognition may improve due to fusion of the perceived colour of adjacent small elements. Towards large visual angles, colour optotype recognition may again improve due to detection of the individual colours of elements. Weakening of contours by defocus may improve the recognition of colour optotypes due to loss of camouflage. Loss of camouflage also occurs with a more regular, less pseudo‐chaotic arrangement of image dots, thus facilitating the recognition of colour optotypes.

Conclusions

Besides the colours themselves, arrangement and size of coloured elements need careful consideration in designing pseudoisochromatic plates. In application of the plates defocusing has to be avoided.
The “complete vitrectomy performed early” treatment philosophy
Authors: Rocha De Sousa A. , Gouveia P. , Correia‐Pinto J. , Alves P. , Falcao‐Reis F.
Published: September 2015

Purpose

To compare the impact of early versus late complete vitrectomy in the management of acute postoperative endophthalmitis (PE).

Methods

Retrospective study.

Results

57 eyes from 57 patients were included in this study. 49.1% of patients were males. Baseline characteristics were similar in all groups (VIT, NVIT, VIT_early and VIT_late). Mean visual acuity at presentation was hand movements (2.3 logMAR) in all groups. After treatment mean visual acuity was 1.2 ± 1.1 logMAR in the NVIT group and 1.9 ± 1.2 logMAR in the VIT group (p = 0.075). The differences between visual outcomes in VIT_early and VIT_late groups, however, achieved statistical significance (p = 0.012): 0.8 ± 1.1 logMAR in the VIT_early group whereas in the VIT_late group it was 2.2 ± 1.0 logMAR. Significant differences between visual outcomes were also encountered when comparing NVIT and VIT_late groups (p = 0.008). The difference in final visual acuity between VIT_early and NVIT didn't not attain statistical difference (p = 0.459).

Conclusions

This study highlights the impact of a complete early vitrectomy in the management of PE. A complete vitrectomy didn't surpass the visual results of intravitreal antibiotics alone (p = 0.075). Howeverm a complete vitrectomy performed within the first 24 hours after presentation was clearly beneficial when compared to vitrectomy performed later (p = 0.012). Furthermore, our series suggests that a late vitrectomy is detrimental to visual results when compared to intravitreal antibiotics (p = 0.008).
Intra and inter‐rater agreement of anterior lamina cribrosa depth measurements using enhanced‐depth imaging optical coherence tomography
Authors: Leal I. , Cordeiro Sousa D. , Couceiro R. , Barata A. , Abegao Pinto L. , Pinto F. , Marques‐Neves C.
Published: September 2015

Purpose

To determine intra and inter‐rater agreement of anterior lamina cribrosa depth (ALCD) manual measurements using enhanced depth imaging spectral‐domain optical coherence tomography (EDI‐OCT).

Methods

Double blind prospective observational study between December 14 and May 15. EDI‐OCT of optic nerve head was performed in subjects with an irrelevant ophthalmologic history (2 cross scans: vertical and horizontal). ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane and the anterior border of the lamina cribrosa, at the maximum depth point. Two double‐blinded experienced operators manually measured ALCD twice, with a one‐month interval. Intra and inter‐rater agreement was evaluated using intraclass correlation coefficients (ICC), concordance correlation coefficients (CCC) and Bland‐Altman (BA) plots for the right eye vertical (RV) and horizontal (RH) scans and left eye vertical (LV) and horizontal (LH) scans. Statistical analyses were performed using STATA 13.0.

Results

Studied population included 44 subjects (26 women), with a mean age of 62.9 ± 14.3 years. Mean vertical and horizontal maximum ALCD was 453.3 ± 88 μm and 436.1 ± 78.7 μm, respectively. Intra‐rater ICC for ALCD in RV, RH, LV and LH were 0.98, 0.94, 0.97 and 0.96, respectively. Inter‐rater ICC for ALCD in RV, RH, LV and LH were all 0.99. Intra‐rater CCC for ALCD in RV, RH, LV and LH were 0.98, 0.93, 0.97 and 0.96. Inter‐rater CCC for ALCD in RV, RH, LV and LH were all 0.99. Bland–Altman plots suggested that almost all observations were within the 95% limits of agreement.

Conclusions

ALCD manual measurements with EDI‐OCT showed high agreement among intra and inter‐rater measurements in healthy eyes. EDI‐OCT is a reliable tool for ALCD measurement, which can provide potentially useful information for integrated glaucoma management.
Testing of an automated tablet‐based method for the determination of low contrast near visual acuity in ophthalmic patients
Authors: Mirza N. , Tahir H.J. , Wang Y. , Parry N.R.A. , Murray I.J. , Aslam T.M.
Published: September 2015

Purpose

To test an automated, tablet‐based self‐testing method for the determination of low contrast near visual acuity in ophthalmic patients.

Methods

The Mobile Assessment of Vision by intERactIve Computer (MAVERIC) system consists of a calibrated tablet computer (Samsung Galaxy Tab S 8.4) running purpose‐built software housed in a bespoke physical booth. Near low contrast (25%) visual acuity was measured in one eye using the MAVERIC system and a near ETDRS chart at a distance of 40 cm on a population of ophthalmic patients with various retinal conditions. Patients independently completed testing using the MAVERIC system once an explanation of its use had been given. Repeat measures of near acuity were also conducted using the MAVERIC system.

Results

The MAVERIC system displayed excellent repeatability. Bland Altman analysis of data showed reasonable agreement between measurements obtained using MAVERIC and the near ETDRS chart. The degree of difference between data sets was consistent.

Conclusions

This study demonstrates the potential viability of the MAVERIC self‐testing system as a means to test low contrast near visual acuity in ophthalmic patients with a high degree of reliability and thus a potential method of both initial assessment and monitoring of near visual acuity in such patients.
Assessing the microstructures of the human cornea using Gabor‐Domain optical coherence microscopy with large field of view and high resolution
Authors: Thuret G. , Tankam P. , He Z. , Lanis M. , Canavesi C. , Lepinet T. , Hindman H. , Topham D. , Gain P. , Rolland J.P.
Published: September 2015

Purpose

To investigate the performances of a new large field of view and high volumetric‐resolution Gabor‐Domain Optical Coherence Microscope (GD‐OCM) in imaging human corneal microstructures

Methods

The GD‐OCM combined the high sectioning capability of optical coherence tomography with the high lateral resolution of confocal microscopy. We developed a system that achieved high‐contrast imaging with a field of view of 1 ± 1 mm2 and volumetric cellular resolution of 2 μm across a thickness of up to 2 mm in tissue. The system fitted on a movable cart and the handheld scanning probe was attached to an articulated arm that may be adjusted to image different locations of the cornea without contact. For real time visualization, we implemented a parallelized Multi‐Graphic Processing Units architecture to speed up the processing of data. In this investigation, we focused on imaging the microanatomy of the corneal stroma keratocytes as well as corneal endothelial cells of ex vivo human corneas maintained in an innovative bioreactor

Results

The overall time to 3D visualization, including acquisition that is 1.5 minutes, processing and rendering of a 1000 × 1000 × 400 voxels, was <2 minutes compared to 2 hours on a conventional CPU. The system produced 3D high‐resolution images of the distribution of epithelial cells, stromal keratocytes and endothelial cells, comparable to standard in vivo confocal microscopy

Conclusions

This innovative GD‐OCM allows pseudo histology of the cornea in an unprecedented wide field and a short acquisition time compatible with analysis of ex vivo living corneas
Ocular surface improvement after conjunctivochalasis (CCH) surgery
Authors: Caramello C.M. , Mateo Orobia A.J. , Peiro C. , Del Buey M. , Perez Navarro I. , Almenara C. , Esteban O. , Ascaso J. , Cristobal J.
Published: September 2015

Purpose

To evaluate symptomatology and ocular surface changes in patients with CCH grade III after excision surgery.

Methods

Prospective, interventional study in which 15 patients with CCH grade III were enrolled.

Patients underwent CCH excision surgery: 8 patients underwent semiperitomy perilimbic with cauterization technique and 7 paste‐pinch‐cut conjunctivoplasty.

The following ocular surface properties were studied preoperatory and 6 weeks after surgical intervention:

– Symptoms by using Ocular Surface Disease Index questionnaires (OSDI)

– Tear Osmolarity by using Tearlab Osmolarity System®.

– Tear Break Up Time (BUT)

– Tear clearance and Tear Function Index by using fluorescein test measure by schirmer strip stain. (Vico and Benitez del Castillo technique)

– Corneal and conjunctival stain:Lissamin green (0–3 grades) and Fluorescein: (0–3 grades)

Results

OSDI questionnaire confirm symptomatology improvement after surgery. Fluorescein Test measure by Schirmer strip stain reveal a better tear clearance. Fluorescein corneal stain and lissamine green corneal stain decrease. Osmolarity ocular surface values and tear BUT normalise after surgery. There was not significant difference between semiperitomy perilimbic with cauterization technique and paste‐pinch‐cut conjunctivoplasty.

Conclusions

CCH patients have an increase proteolytic activitiy in ocular surface. Conjunctival excess interfere with appropriate meniscus tear formation and translate to a deficient corneal tear film. Inflammation control and conjunctival mechanical restore by surgery decrease ocular surface symptomps, improve tear clearance and tear stability and normalize osmolarity values.
Prevalence of diabetic retinopathy in children and adolescents with type 1 diabetes in Helsinki, Finland, 7–15 years after diagnosis
Authors: Gräsbeck S. , Gräsbeck T. , Miettinen P.J. , Summanen P.A.
Published: September 2015

Purpose

The study focuses on the prevalence of diabetic retinopathy (DR) in children and adolescents who were diagnosed from 1999 to 2004 in Helsinki with type 1 diabetes (T1D) under the age of 15 years and subsequently photographed in 2011–2014.

Methods

Fundus images of the patients were taken as a part of clinical follow‐up at the Department of Pediatrics if aged 10–18 years, and at Herttoniemi Hospital if older than 18 years. Of the 238 patients, 201 (84%) were included in this retrospective study (another 23 patients had moved from Helsinki, one patient never attended the fundus photography sessions, two had not yet been photographed due to young age, 10 patients who were transferred to adult care did not attend screening as planned, and one patient had died). The presence and severity of DR was determined from 60° fundus images taken with a digital Canon CF‐60UD camera with a green filter by one observer (SG) using ETDRS classification. The eye with more advanced DR level represented the patient.

Results

Of the 201 patients, 106 (53%) were males. The median age at diagnosis of T1D was 8 (range, 0.8–14) years. At the time of fundus imaging the median age was 19 (range, 10–28) years, and the median T1D duration was 11 (range, 7–15) years. Altogether 123 (61%; 95%CI, 54–68) patients had DR of whom the majority (113; 92%; 95%CI, 86–96) had mild DR (level 20 or 35). One patient had neovascularization on the retina. The age of the youngest patient with DR was 10 years. Of the 10 patients who did not attend fundus imaging in adult care, nine had had no DR and one had level 20 DR when analyzed in the pediatric unit.

Conclusions

Our results indicate that over half of the young T1D patients in Helsinki have DR after a median duration of 11 years.
The added value of undiluted vitreous biopsy samples processed by the Cellient® tissue processor (Hologic) in unsolved uveitis
Authors: Van Calster J. , Van Ginderdeuren R.
Published: September 2015

Purpose

In this prospective study, the added value of undiluted vitreous biopsy samples in the diagnosis of unsolved uveitis was evaluated. Vitreous biopsies are difficult to handle because of the paucity of cells and the gelatinous structure of the vitreous. Histopathological analysis of the vitreous is useful in challenging cases to differentiate uveitis from lymphoma or infection and to define the type of cellular reaction.

Methods

97 consecutive undiluted vitreous samples were isolated in patients with unsolved intermediate or posterior uveitis. A 1.5‐2.5cc sample was taken through a single 23G or 27G port using the EVA vitrectomy platform (DORC) with a twin duty cycle high speed cutter. The samples were analysed with the Cellient® tissue processor (Hologic). This machine is a fully automated processor starting from a specified container with PreservCyt® (fixative fluid) with cells to paraffin. Routine histochemical and immunostainings were evaluated.

Results

In 94.8% of the cases, sufficient material was found to provide an added value in the diagnostic workup. In 34%, a Cytolyt® mucolytic wash was necessary to prevent clotting of the tubes in the Cellient® tissue processor due to the viscosity of the sample. In 7% the diagnosis was an acute inflammation (presence of granulocytes), in 42% chronic active inflammation (presence of T‐lymphocytes), in 36% low‐grade inflammation (presence of CD68 cells, with <5% T‐lymphocytes); and in 9% a malignant process (lymphoma). In 5% no diagnosis was found. In the chronic active inflammation group 39% was a granulomatous inflammatory process.

Conclusions

This standardized protocol for sampling and handling undiluted vitreous biopsies gives a superior result in morphology, number of cells, and possibility of immuno‐histochemical stainings. The diagnosis can be established or confirmed in 94.8% of cases.
Cyclin kinase inhibitor p27 is downregulated in conjunctival melanoma
Authors: Moulin A. , Schalenbourg A. , Zografos L. , Nicolas M.
Published: September 2015

Purpose

As loss of cyclin dependent kinase inhibitors p27 and p21 have been identified in cutaneous melanoma and associated with a poorer prognosis, we decided to assess the expression of p27 and p21 in benign and malignant conjunctival melanocytic proliferations.

Methods

The expression of p27 and p21 was assessed by immunohistochemistry in 35 conjunctival naevi and 32 conjunctival melanomas. Statistical analysis was performed with JUMP 8.0 software. Immunohistochemistry was evaluated independently by two observers.

Results

There was a concordance in 94.02% and 92.54% of the cases in the evaluation of the expression of p27 and p21, respectively. Discrepant cases were simultaneously reviewed to achieve complete agreement.

There were 13 subepithelial nevi and 22 compound nevi. There were 14 females and 21 males with a mean age was 36.9 ± 3.6 yo (SEM). Nuclear expression of p27 was found in all the nevi. p21 was identified in only 4 nevi (11.4%).

The melanoma group was composed of 18 females and 14 males with a mean age of 65.9 ± 3.38 yo (SEM). p27 and p21 were respectively lost in 18 cases (56.25%) and in 24 cases (75%). There was a significant downregulation of p27 in conjunctival melanoma compared to benign conjunctival nevi (p > 0.0001).

In the melanomas, there was a correlation between loss of p27 expression and depth of invasion (p = 0.0141) as well as non‐bulbar tumor localization (p = 0.0279). Although the proliferation index was more elevated in melanomas with p27 loss, this was not significant.

Conclusions

The downregulation of p21 in benign melanocytic proliferations identified in the skin appears also to occur in the conjunctiva. Our results also demonstrate in vivo a significant downregulation of p27 in conjunctival melanoma. Restauration of p27 function in conjunctival melanoma might represent a potential therapeutical option for this tumor.
Meibomian Gland Dysfunction (MGD) and Tear Cytokines after Cataract Surgery according to Preoperative Meibomian Gland Status
Authors: Jung J.W. , Cho D. , Kyoung Yul S.
Published: September 2015

Purpose

To investigate the possible mechanisms by which cataract surgery aggravates meibomian gland dysfunction (MGD), we evaluated the changes in tear cytokines and ocular surface parameters after cataract surgery according to the preoperative MGD grade.

Methods

Fifty patients who underwent cataract surgery were enrolled and classified into two groups: Group I had no or minimal MGD, and group II had grade 2–4 MGD. Ocular surface parameters were measured, including tear film break‐up time (TBUT), Schirmer I test, ocular surface staining, and Ocular Surface Disease Index (OSDI), and tear cytokine levels were measured.

Results

In group II, preoperative MGD grade, ocular surface staining, TBUT, and OSDI were worse and mean interleukin (IL)‐2, IL‐6, and TNF‐α levels were higher than those of group I. MGD and ocular surface parameters were worsened to a greater degree after surgery in group II than in group I (P < 0.050). In group II, IL‐6 and TNF‐α levels significantly increased at postoperative 1 month, and there were significant correlations between changes in ocular surface parameters and tear cytokines (IL‐2, IL‐6, and TNFα; P < 0.050).

Conclusions

The extent to which the MGD grade was aggravated following cataract surgery differed based on preoperative MGD grade. In patients with definite MGD, which was associated with high cytokine levels, an increase of tear cytokines indicated an aggravation of severe MGD after cataract surgery. Preoperative MGD and ocular surface status should be carefully evaluated.
Evaluation of the Variation in Thickness of the Different Retinal Layers in Diabetic Patients with OCT
Authors: Vicente A. , Cardigos J. , Lívio C. , Proença R. , Santos A. , Cunha J.P. , Abegão Pinto L. , Ferreira J.
Published: September 2015

Purpose

To present a comparison of the thickness variation of the different retinal layers in diabetic patients without diabetic retinopathy.

Methods

A prospective observational study was performed. 175 eyes of 175 patients: 125 diabetic patients without diabetic retinopathy and 50 subjects without diabetes (age and gender matched) from the ophthalmology outpatient clinic were included. Optical Coherence Tomography (OCT SPECTRALIS®) was performed with high‐resolution macular scans. Automated retinal layer segmentation was performed using validated software and layers thicknesses were determined. The coefficient of variation of the different layers was calculated. A p value < 0.05 was considered statistically significant.

Results

Diabetic patients were in average 66.9 ± 9.3 years old. There weren't significant differences in the coefficients of variation between diabetic and non‐diabetic patients: total retinal thickness (9.3% vs. 9.3%; p = 0.39), RNFL (41.09% vs. 42.25%; p = 0.33), GCL (30.39% vs. 31.13%; p = 0.20), IPL (23.62% vs. 24.13; p = 0.40), ILN (21.26% vs. 19.86; p = 0.44).

Conclusions

Previous studies have demonstrated that choroidal thickness coefficient of variation is lower in diabetic patients. Nevertheless, in retinal layers no difference was found in diabetic patients without macular edema. There is a combination of choroid with diminished thickness coefficient of variation and retinal layers with normal thickness coefficient of variation. This suggests that vascular choroidal pathology precedes retinal layers dysfunction. Exudation and lipid accumulation associated with microvascular retinal dysfunction and changes in axonal homeostasis only appear at a second step. This study emphasizes the importance of the retinal layer thickness measurement with OCT in the evaluation of diabetic patients.
Nanomedicine and Ophthalmology: looking forward
Authors: Cordeiro Sousa D. , Ferreira Q. , Araujo M. , Morgado J. , Ferreira J. , Leal I. , Abegao Pinto L. , Marques‐Neves C.
Published: September 2015

Purpose

Nanomedicine has been receiving greater attention in recent years due to the ability to use materials and devices at the size of intracellular structures and molecules, involving systems in the order of <100 nm. In particular, nanosized materials can provide substantial advantages when compared to current therapeutics that are used in the treatment of ocular diseases. Nanotechnology‐based approaches are being explored in order to enhance drug permeation, to control mechanisms of drug release and to improve the action of nanocarriers with specific targeting moieties. From biopharmaceuticals to continuous intraocular pressure biosensors and tissue regeneration, nanotechnology provides an impressive range of possibilities to explore and improve patient care.

Methods

Herein, we review the most recent literature regarding nanotechnology applications in ophthalmology, highlighting their advantages and challenges to overcome, prospecting them in terms of clinical utility.

Results

Nanocarriers, nanodevices and nanostructured biocoatings with applications in the treatment of ocular diseases are resumed and their impact in the evolution of ophthalmology is discussed. We present a recent study about nanostructured films composed of drugs encapsulated in nanocarriers with applications in glaucoma treatment. Our results suggest that nanocarriers improve drug delivery and that specific drug amounts can be released during controlled periods of time.

Conclusions

Our research emphasizes new trends and applications of nanodevices in ophthalmology. Nanomedicine is definitely part of a paradigm shift in healthcare providing, making it possible to reach excellence in ophthalmological diagnosis and therapeutics.

Acknowledgements

The authors thank FCT–Portugal for financial support under the project UID/EEA/50008/2013 and Post‐Doc grant to QF.