bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of screening tests for sight‐threatening eye disease in a UK population
Authors: Lawrenson John , Fidalgo Bruno , Dabasia Priya , Jindal Anish , Edgar David , Ctori Irene , Peto Tunde
Published: December 2019

Background/Aims

To determine the performance of combinations of structural and functional screening tests in detecting sight‐threatening eye disease in a cohort of elderly subjects recruited from primary care

Methods

505 subjects ≥ 60 years underwent: Frequency Doubling Technology (FDT) perimetry; iVue OCT (iWellness® and peripapillary retinal nerve fibre layer (RNFL) scans); IOP with the Ocular Response Analyzer (ORA), all performed by an ophthalmic technician. The reference standard was a full ophthalmic examination by an experienced clinician who was masked to the index test results. Subjects were classified as presence or absence of sight‐threatening eye disease (clinically significant cataract, primary open angle glaucoma, intermediate or advanced AMD and significant diabetic retinopathy). Univariate and multivariate logistic regression was used to determine the association between abnormal screening test results and the presence of sight‐threatening eye disease.

Results

171 subjects (33.8%) had one or more sight‐threatening eye disease(s). The multivariate analysis found significant associations with any of the target conditions for visual acuity < 6/12, an abnormal FDT and peripapillary RNFL thickness outside the 99% normal limit. The sensitivity of this optimised screening panel was 61.3% (95% CI 53.5‐68.7); specificity 78.8% (CI 74.0‐83.1), positive predictive value 59.5% (CI 53.7‐65.2) and an overall diagnostic accuracy of 72.9% (CI 68.8‐76.8).

Conclusion

A subset of screening tests may provide an accurate and efficient means of population screening for significant eye disease in the elderly. This study provides useful preliminary data to inform the development of further larger, multicentre screening studies to validate this screening panel.
Efficacy of echinomycin in hypoxia‐inducible factor‐mediated ocular angiogenesis
Authors: Plastino Flavia , Santana Garrido Álvaro , Aronsson Monica , Barrero Alfonso Mate , Kvanta Anders , Cueto Carmen Maria Vázquez , André Helder
Published: December 2019

Purpose

Echinomycin (EKN), an inhibitor of hypoxia‐inducible factor (HIF)‐1 DNA‐binding activity, has been implied as a possible therapeutic agent in ischemic diseases. We assessed EKN in hypoxia‐driven responses in vitro using human primary adult retinal pigment epithelium cells (aRPE), and in vivo using the laser‐induced mouse choroidal neovascularization (CNV) model.

Methods

Adult retinal endothelial were kept at normoxia (20% O2) or exposed to hypoxia (1% O2), in the presence or absence of EKN. Epithelial wound‐healing was used to determine the dose of EKN. Effects of EKN on hypoxia‐mediated pathways were analyzed by western blot for HIF‐1a, qPCR of HIF‐target genes, and proteome array for soluble angiogenic factors. Inhibition of angiogenesis by EKN was determined in human primary adult retinal endothelial cells (aREC), exposed to EKN‐treated hypoxic conditioned aRPE medium by spheroid sprouting assay. 8‐week‐old C57BL/6J mice underwent laser‐induced CNV, as a model of HIF‐associated ocular neovascularization. Animals were treated with EKN and compared to a mouse VEGFR1‐Fc chimera protein (equivalent of aflibercept). CNV lesion area was determined by fluorescein angiography.

Results

Adult retinal endothelial treated with EKN demonstrated hypoxia‐dependent decreased cell proliferation in the wound‐healing assay. Lower HIF‐mediated transcripts were detected in hypoxic aRPE cells treated with EKN compared with non‐treated controls. These results were confirmed by proteome profiler for angiogenic factors, and subsequently reduced hREC sprouting. Laser‐induced mice treated with 1 mg of intravitreally injected EKN demonstrated a significant decrease in vascular lesion area when compared with 1 mg of VEGFR1 chimera or vehicle‐treated controls.

Conclusions

Our data suggest EKN as a potent inhibitor of HIF‐mediated angiogenesis in retinal cells and in the mouse model of CNV, which could have future implications in the treatment of patients with neovascular age‐related macular degeneration.
The effect of systemic blood pressure on optical coherence tomography angiography in glaucoma patients with optic disc hemorrhage
Authors: Won Bae Hyoung , Keum Park Chan , Yeop Lee Sang , Je Seong Gong , Yun Kim Chan
Published: December 2019

Purpose

The association between retinal microvascular structure and glaucoma has been revealed in multiple studies using optical coherence tomography angiography (OCTA). Recently, the vessel density (VD) of the macular area has been studied for various applications such as diagnosis, assessment, and estimation of visual function in glaucoma. In this study, we tried to identity the factors that affected macular VD (mVD) in glaucomatous eyes.

Methods

Optical coherence tomography and OCTA images were collected in a retrospective, cross‐sectional observational study. Glaucomatous eyes were further divided into two groups according to history of disc hemorrhage (DH). Association between mVD and demographic characteristics, ganglion cell‐inner plexiform layer (GCIPL) thickness, visual field mean deviation (MD) and systemic blood pressure was analyzed in each group.

Results

Ninety‐two eyes from 58 healthy subjects and 179 eyes from 103 patients with glaucoma were included. In both healthy and glaucomatous eyes, mVD was inversely associated with the age of the eyes (β = −0.035, p = 0.025; β = −0.039, p = 0.018). In the glaucomatous eyes, mVD was significantly decreased as the MD value was worse (β = 0.109, p = 0.002). In the glaucomatous eyes with DH, the mVD decreased as the blood pressure increased (β = −0.080, p = 0.002; β = −0.104, p = 0.007; β = −0.105, p = 0.003, for systolic BP, diastolic BP and mean arterial pressure, respectively) but the other factors were not significantly associated with mVD.

Conclusions

Reduced mVD is more common in older individuals in both healthy and glaucomatous eyes. mVD also correlates with the severity of MD value in glaucomatous eyes. In glaucomatous eyes with DH, high systemic BP is associated with a reduction in mVD. This may indicate that patients with glaucoma are more susceptible to vascular damage secondary to hypertension.
Evolution of AMD drusenoid deposits Lipid Type, “L” density, structure, volume, complications study
Authors: Gonzalez Corinne
Published: December 2019

Purpose

To study evolution of AMD drusenoid deposits “L”: density, structure, volume parameters with Morphology‐structural software, complications with OCT, Multimodal exam. 6 years follow‐up.

Methods

84 eyes of 74 patients with AMD drusenoid deposits“L”, Lipid Type (soft Drusen, Drusenoid PED “L”).Deposits were evaluated by Multimodal exam, OCT (Spectralis spectral domain HRA‐OCT) and Morphology‐Structural software (M‐S software). Multimodal exam, OCT let analyze deposit, evolution, itself and its environment. M‐S software let drusenoid deposit contents analyze, discrimination, differentiation, let grading (volume, contours analyze), let measurements:volume (in µm3),density(grey levels of deposits),structure(structural measures, texture parameters),so evaluation, characterization of those “L” deposits evolution. Evaluation, comparison for each eye, each patient, between all studied patients was done every 6 months, during 6 years.

Results

AMD Drusenoid Deposit “L” density, structure evolution was with less density, structure, 2 years cycle evolution with stepwise regression for density parameter, bell‐shaped curve for structure parameter; for volume evolution:decrease, 1 year ½ cycle with bell‐shaped curve. Evolution: 55% rather unchanged, (slightly more dense, heterogeneous), No Neovascular Complication, 45% to Atrophy (flattening deposit, abnormal facing Photoreceptor layer, Pigment Epithelium layer: granular, irregular, crumbled, less thick, thinner and thinner to disappear). M‐S Software reliable, relevant for characterization, evolution study of deposit; Density:good criteria to characterize drusenoid deposit and evolution, too for Structure to study contents, modifications, evolution; Volume: interesting criteria for lesion, eye, patient study but no or less according whole studied patients.

Conclusion

Evolution of AMD Drusenoid deposits Lipid Type, “L”, allow to and improve AMD knowledge,its complication understanding and gain AMD biomarker feature.
Orbital fibroblasts from thyroid‐associated ophthalmopathy patients secret IL‐6 via up‐regulation of IGF‐1 by activating the NF‐kB pathway
Authors: Kim Jihyun , Kim Sung Eun , Yang Suk‐Woo
Published: December 2019

Purpose

Interleukin (IL)‐6 plays as a modulator for functions of lymphocytes. Significantly higher level of IL‐6 has been observed in primary orbital tissue cultures of thyroid‐associated ophthalmopathy (TAO) patients compared to those of non‐TAO patients. In the current study, we investigated the issue of whether of how orbital fibroblasts (OFs) from TAO patients significantly secret higher level of IL‐6.

Methods

Human OFs were obtained from orbital fat from decompression surgery in patients with TAO or from upper lid blepharoplasties in patients with no prior history of thyroid disease. The levels of IL‐6 and insulin‐like growth factor (IGF)‐1 in culture media of OFs were determined by using an ELISA kit. The NF‐kB activity of OFs was determined by measuring the level of IkB degradation and IKKa/ IKKb/NF‐kBp65 phosphorylation.

Results

Cultured OFs from TAO patients significantly secreted higher level of IL‐6 and IGF‐1, compared with those of control groups. In addition, treatment with IGF‐1 induced secretion of IL‐6 in OFs from TAO patients. The levels of IkB degradation and IKKa/IKKb/NF‐kBp65 phosphorylation were higher in non‐treated OFs of TAO patients than those of control groups. Furthermore, treatment with Bay 11‐7082, an inhibitor of NF‐kB pathway, reduced the secretion of IL‐6 and IGF‐1 in OFs from TAO patients.

Conclusions

These results suggest that IL‐6 secretion is dependent on NF‐kB/IGF‐1 pathway in OFs from TAO patients. These findings also show that NF‐kB/IGF‐1/IL‐6 pathway may be a reasonable target of therapeutic intervention in the case of TAO.
Bacterial nanocellulose compared to the amniotic membrane as a potential corneal bandage material
Authors: Anton‐Sales Irene , Christopher D’Antin Justin , Fernandez Jorge , Charoenrook Victor , Barraquer Rafael I. , Laromaine Anna , Roig Anna , Michael Ralph
Published: December 2019

Purpose

To compare bacterial nanocellulose (BNC) patches produced by K.xylinus, against the amniotic membrane (AM) as a bandage material for ocular surface disorders. Based on previous structural characterizations of our BNC patches, and detailed cytocompatibility tests of BNC with human dermal fibroblasts; we hypothesise that BNC is viable as a bandage material for corneal surface disorders.

Methods

We tested the mechanical resistance of BNC (n = 6) and AM (n = 5) samples by using progressively weighted sutures to tear the samples. In order to test material stability, 6 samples of each type were maintained in culture media at physiological conditions for 30 days. Then any change in the morphology, nanostructure and light absorbance were analysed. Finally, in order to study the effects of corneal tissue on the samples, we sutured 3 of each type to ex‐vivo porcine corneas and cultured them in physiological conditions for 2 weeks. After which, morphology, fibre nanostructure and transparency were evaluated.

Results

BNC resisted tearing at the suture point until an average weight of 41g while AM resisted <4.5 g. After 30 days in culture, both sample types lost some mass, BNC maintained transparency while AM became more opaque and had some crystal formations. After culture with a cornea; BNC presented no obvious nanostructure degradation, while AM did show some areas with more pores. Macroscopically, BNC samples remained more transparent than AM.

Conclusions

Based on the results, BNC is more resistant mechanically to sutures, equally conformable to the dome shape of the eye, and more stable than AM. Overall these results support BNC as a promising new ocular bandage material.
Opposing neurological responses to autologous peripheral blood stem cell transplantation in two patients with POEMS syndrome
Authors: Ota Jin , Yokouchi Hirotaka , Baba Takayuki , Yamamoto Shuichi
Published: December 2019

Purpose

We present our findings in two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, one with and one without optic disc edema (ODE), after autologous peripheral blood stem cell transplantation.

Method

Both patients underwent an autologous peripheral blood stem cell transplantation. The peripapillary retinal thickness (pRT) was determined by spectral‐domain optical coherence tomography (SD‐OCT) to assess the degree of optic disc edema. The SD‐OCT examinations consisted of a 3.45 mm diameter circular scan centered on the optic disc. The pRT thickness was measured at the baseline and at 12 months after beginning the treatment. The serum level of VEGF was determined by enzyme‐linked immunosorbent assays (ELISAs) at the baseline and at 12 months after beginning the treatment. Neurological examinations, e.g., grip strength and compound muscle action potentials (cMAPs) of the upper limb, were also measured at the baseline and 12 months after the transplantation.

Result

The pRT in the case without ODE was 310 μm at the baseline. At 12 months after the transplantation, the serum levels of VEGF decreased from 7050 to 511 pg/ml, the grip strength increased from 13 kg to 19 kg, and the cMAP amplitudes increased from 4.31 mV to 7.02 mV. On the other hand, the pRT in the case with severe ODE was 1167 μm at the baseline, and it did not change after the transplantation. The serum levels of VEGF decreased from 9060 pg/ml to 99 pg/ml after the transplantation, the grip strength decreased from 32 kg to 29 kg, and the amplitudes of the cMAP decreased from 2.16 mV to 0.32 mV at 12 months after the transplantation.

Conclusion

These results suggest that the baseline degree of ODE before an autologous peripheral blood stem cell transplantation might be a predictive marker on the effectiveness of the transplantation on patients with the POEMS syndrome. However, further studies with a larger sample size are needed.

Keywords: POEMS syndrome, vascular endothelial growth factor (VEGF), peripapillary retinal thickness (pRT), autologous peripheral blood stem cell transplantation, predictive marker
Improving endothelial cell migration by novel in vitro 3D culture of corneal grafts
Authors: Miron Alina , Spinozzi Daniele , Lie Jessica , Oellerich Silke , Melles Gerrit R.J. , Ní Dhubhghaill Sorcha
Published: December 2019

Purpose

Studying in vitro cell migration of endothelial sheets is challenging since capacity for cell migration needs to be maintained while the tissue must remain fixed on a rigid substrate. Here, a 3D culture technique is designed to maintain cellular viability and reduce tissue handling in order to analyze in vitro endothelial cell migration from corneal grafts.

Methods

Twelve Quarter‐Descemet membrane endothelial keratoplasty (Q‐DMEK) grafts obtained from four corneas with intact and viable endothelial cells but ineligible for transplantation were included for explant culture. Graft quadrants were embedded in temperature‐reversible hydrogel and cultured over 2–3 weeks. Cell movement was assessed by light microscopy at fixed standardized time intervals. After gel removal, immunohistochemistry analysis was performed to characterize the phenotype of the migrating cells. Cell viability was assessed by Trypan Blue and Calcein‐AM.

Results

All grafts embedded in the 3D hydrogel system maintained cell viability and displayed a capacity for cell migration. The migration pattern was asymmetric as endothelial cells moved as a sheet only from the radial cut graft edges, while no activity was seen in the peripheral graft area. Immunostaining performed on the samples after removing the gel showed the presence of proliferation and migration markers in the endothelial cell monolayers expanded from the radial graft edges. The endothelial cells maintained the expression patterns of phenotypical markers.

Conclusions

Temperature‐reversible hydrogel proved to be a very useful matrix for studying in vitro endothelial cell migration from explant grafts and allowed for subsequent immunohistochemistry analysis after gel removal. Studying in vitro endothelial cell migration from customized endothelial grafts should result in a better understanding of cellular migration mechanisms which play an important role in achieving faster corneal clearance in patients after corneal transplantation.
Optic nerve glioma – a case study
Authors: Dutta Udbuddha
Published: December 2019

Purpose

To evaluate a 5 year old boy with painless progressive enlargement of the left eye since the past 1 year. He also complained of a loss of vision in the left eye.

Methods

Study Design: Case Study.

Duration of Study: 1 year.

The patient was evaluated over 1 year and investigations were carried out as deemed necessary.

Investigations

Slit lamp biomicroscopy with 90 D Volk lens was done for anterior and posterior segment examination. Gonioscopy, Applanation Tonometry, Automated Perimetry and Indirect Ophthalmoscopy were done. CT and MRI of the orbit was also carried out.

Results

Presenting visual acuity was absence of light perception in the left eye and the proptosis was measured of 25 mm which was in the downward and outward direction. A relative afferent pupillary defect was noticed in the left eye and extraocular movements were restricted superiorly and medially. Funduscopy of the left eye revealed a pale disc, blurring of the disc margins and presence of optociliary shunt vessels. CT scan of the left eye showed a fusiform optic nerve swelling. MRI showed a fairly large fusiform swelling in left optic nerve, pressure effect on ocular bulb with proptosis, no extension of the lesion in optic canal. This was consistent with the diagnosis of optic nerve glioma.

Conclusion

Optic nerve glioma is an important cause of unilateral proptosis in children. Early diagnosis is mandatory and management should involve an integrated approach of neurosurgeons, plastic surgeons, ophthalmologists and radiologists.
Retinal neurodegeneration in systemic lupus erythematosus: layer by layer retinal study using optical coherence tomography
Authors: Dias‐Santos Arnaldo , Ferreira Joana , Pinheiro Sofia , Cunha João Paulo , Alves Marta , Papoila Ana Luísa , Moraes‐Fontes Maria Francisca , Proença Rui
Published: December 2019

Purpose

To find early signs of retinal neurodegeneration by comparing the thickness of peripapillary retinal nerve fiber layer (pRNFL) and of all macular layers between systemic lupus erythematosus (SLE) patients without ophthalmologic manifestations and healthy controls. The effect of disease duration and systemic comorbidities was also studied.

Methods

Cross‐sectional study, in which retinal segmentation analysis with spectral domain‐optical coherence tomography (SD‐OCT) was performed. For pRNFL thickness, the global and six peripapillary sectors were determined. Each retinal layer thickness was calculated in the nine early treatment diabetic retinopathy study (ETDRS) subfields. Multiple regression analysis was performed.

Results

Sixty‐eight eyes of 68 SLE patients and 50 eyes of 50 healthy controls were considered. pRNFL was significantly thinner in the SLE group globally (p = 0.026), in temporal superior (p = 0.007) and temporal (p = 0.037) sectors. Multivariable analysis in the SLE group revealed that chronic medication with antihypertensives, statins and anticoagulants were associated with a thinner pRNFL in some sectors (p < 0.05). SLE patients presented a significant thinning in the photoreceptor (PR) layer in five ETDRS areas (p < 0.05). Shorter disease duration was associated with greater photoreceptor thinning in all ETDRS subfields. Neuropsychiatric SLE, higher disease activity index and cardiovascular risk factors were associated with a thinner PR layer. No differences were observed in the remaining macular layers.

Conclusion

This was the first study to perform OCT segmentation analysis of all retinal layers in SLE patients. These patients present a significant reduction in pRNFL and macular PR layer thickness. These differences were more pronounced in patients with poor systemic disease control, neuropsychiatric SLE and higher cardiovascular risk burden. Thus, there is evidence for the presence of early signs of retinal neurodegeneration in SLE.
Kimura disease: familial and ocular occurrence
Authors: Georgelin Denis , Robert Matthieu , Putterman Marc , Gignac Dominique , Bremond‐Gignac Dominique
Published: December 2019

Purpose

Kimura disease is a sporadic disease of unknown etiology, that mostly affects young Asian males. Major signs are subcutaneous nodules and parotitis, but cases can be revealed by lid or caruncle swelling. We report the case of a child with a caruncle lesion that results from Kimura disease.

Methods

A 12‐year‐old boy born to a Caucasian father and a Vietnamese mother was referred for a bilateral caruncle swelling developing over 18 months. Family history revealed a Kimura disease in father’s history. The ophthalmological examination showed a painless bilateral salmon‐colored swelling of the caruncles. The pediatric examination found an ongoing parotitis, and no dermatological lesion. Orbital MRI was normal and biology showed an increased level of total blood IgE. A surgical removal of the lesions was performed. Anatomopathological analysis was consistent with a Kimura disease: a follicular lymphoid hyperplasia with germinal centers and fibrosis. A few months later, the child developed a nephrotic syndrome.

Results

Besides the problem of the complex diagnosis raised by this case, the other issue is the pathophysiology of this condition, so far known as sporadic. Indeed, the present two cases in a father and his child may suggest a genetic predisposition. Few studies head in that direction showing clonal rearrangements on the T‐cell receptor genes in Kimura disease.

Conclusions

Major signs of Kimura disease are dermatological, but uncommon sites can be seen, such as the caruncle. An accurate diagnosis is essential due to its possible association with nephrotic syndrome, but is difficult and supported by the anatomopathological analysis. The familial cases we report challenge the formerly postulated hypothesis of a sporadic condition.
Relationship between mean transit time of retina and various hemodynamic factors using automatic image analysis technique and high speed fluorescein angiography
Authors: Hee Kim So , Eun Lee Ji , Kwon Hanjo
Published: December 2019

Purpose

Mean transit time (MTT) is defined as the volume/flow ratio of a capillary bed and reflects tissue perfusion delay. Using high speed fluorescein angiography (FA), image registration algorithm and deconvolution method, MTT of retina was automatically calculated and analyzed with other perfusion factors.

Methods

A camera type FA capable of recording an image of 1920 square pixels at 20 frames per second was constructed. Sodium fluorescein (4.0 mL of a 10%) was injected into the antecubital vein to all 6 normal subjects. Automatic image registration was performed to correct saccadic eye movements with the nonlinear diffusion feature extraction (KAZE) method. After selection of the specific major arteries and veins, MTT was calculated by deconvolution method using time series of the fluorescein intensity of each vessel. The relationship between arteriovenous passage time (AVP), arteriovenous transit time (AVT), peak arterial time (PA), peak venous time (PV) and MTT was investigated using correlation analysis.

Results

The mean age of subjects was 35.2 ± 6.1 years and 24 major arteries and veins were selected. The mean MTT was 1.970 ± 0.898 s. The mean AVP, AVT, PA, and PV were 1.450 ± 0.454, 11.227 ± 1.339, 5.400 ± 1.113, and 7.280 ± 1.368 s. MTT showed a strong correlation with AVP (r = 0.736, p = 0.006), PA (r = 0.637, p = 0.026), and PV (r = 0.769, p = 0.003), but no significant correlation with AVT. AVT was only correlated with PV (r = 0.666, p = 0.018).

Conclusions

In normal subjects, MTT of retina correlated with retinal arterial, venous, and tissue transit times. MTT seems to reflect the perfusion status of all vascular components compared with AVT. A comparative study of patients expected to delay retinal MTT need to be conducted to investigate the clinical significance of MTT.
Risk of corneal transplantation after phacoemulsification in patients with cornea guttata
Authors: Viberg Andreas , Samolov Branka , Armitage Margareta Claesson , Behndig Anders , Byström Berit
Published: December 2019

Purpose

To investigate the risk of corneal transplantation after phacoemulsification related to cornea guttata.

Methods

In this retrospective registry‐based cohort study, patient data from the Swedish National Cataract Register for years 2010‐2012 were linked with data from the Swedish Cornea Transplant Register for years 2010‐2017. Altogether, data from 276,354 cataract patients was linked with data from 2,091 patients with primary and secondary endothelial failure as indication for corneal transplantation. Other surgical methods for cataract extraction than phacoemulsification were excluded. If both eyes had surgery, one eye was randomly selected to obtain unrelated samples. A Kaplan‐Meier curve and Cox regression analysis were used to investigate the risk for corneal transplantation due to endothelial failure after phacoemulsification.

Results

Out of the 3,346 phacoemulsification patients with cornea guttata, 153 underwent corneal transplantation within 6.2 years in median. The cumulative transplantation rate, 6 years after the phacoemulsification was 4.8% in the group with cornea guttata and 0.08% in the group without. The annual transplantation rate among the cornea guttata patients during the first year was 1.64% and diminished the following 5 years to 0.55% in average. The annual transplantation rate among the patients without cornea guttata was 0.01% in average after phacoemulsification during the same period of time. The transplantation hazard ratio for cornea guttata present at the phacoemulsification was 67.6 (95% CI: 53.6.0‐85.3, p < 0.001), when adjusting for potential confounders.

Conclusions

The hazard of corneal transplantation after phacoemulsification was 67.6 times higher with cornea guttata than without. Still, the great majority of the patients with cornea guttata did not undergo corneal transplantation during the study period.
Hydrophilic polymers: interactions with lipid layers and ferning patterns
Authors: Eftimov Petar , Daull Philippe , Georgiev Georgi
Published: December 2019

Purpose

To evaluate (i) the mucomimeticity of pharmaceutically applicable hydrophilic polymers (HP) as well as (ii) their interactions with human meibum films.

Methods

Four HP were used‐hyaluronic acid (HA), cross‐linked hyaluronic acid (CHA), carboxymethyl cellulose (CMC) and gellan gum (GG)‐ at the concentrations of 0.0001, 0.001,0.01,0.05, 0.1%. HP mucomimeticity was probed by the formation of tear‐like ferning patterns (TFP) after HP solution drop evaporation. The interactions between HP and meibum at the air/water interface were examined in vitro at blink‐like compression/expansion of the film area by Langmuir surface balance. Surface pressure (π)‐area (A) isocycles and stress relaxations were used to assess the sample’s lateral elasticity and reorganization during area cycling. Films morphology was monitored by Brewster Angle Microscopy (BAM).

Results

Significant differences were observed in the capability of HP to form ferning patterns: CHA (≥0.001%) > HA (≥0.01%) = CMC (≥0.01%) > GG (≥0.05%). CHA, HA, CMC and GG enhanced the uniform spreading of meibomian layers as well as their elasticity and rapid reorganization at blink like area cycling in concentration dependent manner. BAM micrographs revealed considerable thickening of the meibomian films in the presence of HP.

Conclusions

The combination of tear ferning and Langmuir surface balance studies allows to simultaneously evaluate the mucomimetic and the lipid interaction properties of HP. TFP forming polymers enhanced both (i) the uniform spreading and structure of meibomian layers and (ii) their dynamic surface properties. Cross‐linking HA was particularly efficient both in ferning pattern and meibomian film systems.
Identifying risk factors for severity & activity of Graves Orbitopathy – a multi‐centre analysis of the characteristics and treatment of patients with Thyroid Eye Disease
Authors: Farag Soma , Feeney Claire , Lee Vickie , Akishar Rashmi , Nagendran Sonali , Jain Rajni , Aziz Ahmad , Robinson Stephen , Meeran Karim , Bravis Vassiliki
Published: December 2019

Purpose

Early diagnosis and treatment of Graves Orbitopathy (GO) is essential to prevent sight‐threatening complications and long‐term disability and therefore establishing a standard of care is highly desirable. Establishing predictors of a severe disease course are also vital to allow for early intervention.

Methods

A retrospective patient‐cohort study of 236 patients referred to three GO multidisciplinary (MDT) clinics between 2012–2019. Derived from this cohort, audit standards were compared against TEAMeD‐5 guidelines, looking in particular at; (i) time between referral and specialist review (ii) offering of smoking cessation and selenium supplementation where appropriate (iii) time from referral to treatment for moderate‐severe active disease. Patient characteristics were also analysed to investigate for any groupwise differences and correlations between variables collected at baseline to help predict subsequent disease activity.

Results

Median patient age was 48.0 years, 77.5% female, 30.1% White Caucasian. Median initial clinical activity score (CAS) was 1 (range 0–7). Additionally, 80.5% had positive TSH antibody titre. The median time between referral and first MDT clinic was 50.0 days. Of the 254 patients, 80/236 received IVMP for active moderate‐severe GO and the mean time to treatment was 9.3 days. All patients with sight‐threatening GO were seen and treated within 2 weeks. There were 52/236 (22.0%) current smokers, all of whom received documented smoking cessation advice. A positive correlation was found between TSH antibody titre (R = −0.2902, p = 0.0545).

Conclusion

The increasing recognition that an MDT approach is optimal for the management of GO requires a strong clinical governance framework. This work will further define the TEAMeD guidelines before the national implementation. Novel findings relating to the association of disease activtiy with biomarkers of diabetes and antibody titres are worth further investigation.
Expression of factors related with lymph‐/hem‐angiogenesis in the cornea and conjunctiva during dry eye induction
Authors: Lee Sang‐Mok , Hyun Jo Dong , Oh Jun hyoung , Joo Lee Byung , Jae Lee Seok , Sik Cho Chang , Jeung Kim Mi , Kong Mingui , Hun Kim Jeong
Published: December 2019

Purpose

Corneal lymphangiogenesis is known to play an important role in the pathogenesis of dry eye disease (DED). And the low‐grade inflammation associated with DED is known as an inducer of lymphangiogenesis without accompanying hemangiogenesis. This study is to evaluate the expression of known factors related with lymph‐/hem‐angiogenesis in the cornea and conjunctiva in the murine DED model.

Methods

DED was induced by housing 8‐week‐old female C57BL/6 mice in a controlled environmental chamber that allowed for the relative low humidity (< 25%), continuous regulation of airflow, and temperature (21 to 23ºC) for 3 weeks. Corneal fluorescein score was evaluated to confirm the efficacy of DED induction. Fluorescence images from the corneal whole mounts after immunohistochemical stain for lymphatic vessel endothelial hyaluronan receptor (lyve)‐1 were used for analysis. The expression of m‐RNA of the VEGF‐A, VEGF‐C, VEGF‐D (Figf), Angiopoietin‐2 (Angpt2), and VEGFR3 (flt4) were evaluated by real‐time PCR in the cornea and conjunctiva.

Results

Percentage of the area of lyve‐1+ area of the whole corneal area increased significantly in DED group (5.55 ± 1.45% in DED group versus 3.88 ± 0.74% in control, P=0.015, Mann‐Whitney U test). The expression of Angiopoietin‐2 increased significantly in the cornea (1.38 folds, 95% confidence interval [CI]: 1.03~1.84) and in the conjunctiva (1.36 folds, 95% CI: 1.04~1.77). And the expression of VEGF‐C increased significantly only in the conjunctiva (1.64 folds, 95% CI: 1.21~2.21). However, the expression of VEGF‐D significantly decreased both in the cornea (0.40 folds, 95% CI: 0.32~0.49) and in the conjunctiva (0.44 folds, 95% CI: 0.37~0.52).

Conclusions

Unique lymphangiogenesis without hemangiogenesis in DED may be associated with increased expression of Angiopoietin‐2 and VEGF‐C and decreased expression of VEGF‐D. However, the exact interaction of these key factors should be studied further.
The inhibitory effect of D2 dopaminergic agonists on VEGF and VEGF‐R genes expression and blood vessels formation
Authors: Oseka Maciej , Swiech‐Zubilewicz Anna , Danieluk Katarzyna , Mackiewicz Jerzy
Published: December 2019

Purpose

VEGF and its receptor VEGF‐R play an important role in high vascular permeability and new blood vessels formation in various retinal diseases as wet Age‐related Macular Degeneration (wAMD), Diabetic Macular Oedema (DMO) or Proliferative Diabetic Retinopathy (PDR). The aim of this study was to evaluate the influence of selected D2 dopaminergic agonists: bromocriptine, cabergoline and pergolide on VEGF‐A and VEGF receptor‐2 (VEGFR‐2) genes expression and blood vessels formation in Danio rerio (Zebrafish) larvae.

Methods

VEGF‐A and VEGFR‐2 genes expression was measured in real‐time polymerase chain reaction (rt‐PCR) 5 days post fertilization (dpf) after blood vessels formation stimulated by cobalt chloride (CoCl2). The inhibitory effect of bromocriptine, cabergoline, pergolide on VEGF‐A and VEGFR‐2 genes expression were compared with the inhibitory effect of bevacizumab (VEGF inhibitor). The inhibitory effect of bromocriptine, cabergoline, pergolide and bevacizumab on angiogenesis of Sub‐Intestinal Vessels Plexus (SIVP), Retinal Vessels (RV) and Tail Vessels (TV) was assessed in 72, 96 and 120 hours post fertilization (hpf).

Results

Bromocriptine, cabergoline, pergolide and bevacizumab decreased VEGF‐A and VEGFR‐2 genes expression 5 dpf. Bromocriptine, cabergoline, pergolide and bevacizumab inhibited stimulated angiogenesis of SIVP, RV and TV.

Conclusions

D2 dopaminergic agonists inhibit VEGF and VEGFR‐2 genes expression and stimulated angiogenesis in larvae of Danio rerio. This effect is comparable with bevacizumab – clinically used VEGF inhibitor. D2 dopaminergic agonists can be a potential group of drugs with anty‐VEGF effect.
An unusual case of intradural haemangioma of the optic nerve mimicking optic neuritis
Authors: Hopkins Abigail , Airody Archana , Gale Richard
Published: December 2019

Purpose

Vascular malformations of the anterior optic pathways are very rare. We report an unusual case of intradural haemangioma involving the optic nerve mimicking optic neuritis.

Methods

A 31 year old male patient presented with a 6 day history of dizziness, reduced vision in the left eye and pain on eye movements. He had a left relative afferent pupillary defect (RAPD) along with dyschromatopsia. Dilated fundoscopy revealed a swollen left optic disc. An initial diagnosis of optic neuritis was made. A couple of months later, he represented with deteriorating vision. An MRI head revealed enlargement but not enhancement of the intracranial optic nerve on the left side and no other abnormality. Two weeks later the patient was seen again with deterioration in his vision, he was treated with steroids with no improvement in vision.

Results

Further MRI imaging showed a left optic nerve sheath tumour with progression in serial scans, which did not involve the cavernous sinus or extend intracranially, making the most likely diagnosis optic nerve sheath meningioma. The patient successfully underwent surgical excision of the optic nerve. Histology revealed a very unusual intradural haemangioma of the left optic nerve which was causing pain and repeated episodes of intradural bleeding.

Conclusion

This case highlights the diagnostic difficulties in distinguishing between neoplastic and inflammatory optic nerve processes leading to a delay in initiation of appropriate treatment. Histopathologic examination is recommended and remains gold standard in establishing a diagnosis, especially when the course of treatment or surgical management may differ.
Progressive impairment of visual function in fibromyalgia
Authors: Ordunahospital Elvira , Viladés Palomar Elisa , Cordón Ciordía Beatriz , Pérez Velilla Javier , José Vicente Altabás María , Satué Palacián María , García Campayo Javier , Jesús Rodrigo Sanjuán María , García Martín Elena
Published: December 2019

Objectives

To evaluate visual fuction affectation in patients with fibromyalgia during 5 years of follow‐up.

Methods

One hundred and eighteen eyes of 118 patients (96.7% women) with fibromyalgia were analysed at a baseline visit and another at 5 years of follow‐up. They underwent visual acuity (VA) measurement with the best correction and with the ETDRS test at 100% and 2.5% of saturation, contrast sensitivity evaluation with Pelli Robson and CSV1000E tests, chromatic vision analysis with the Farnsworth test 15D and Lanthony 15D (using the Color Vision Recorder software), intraocular pressure (IOPmeasurement, visual field with the Easyfield perimeter, stereopsis with TNO test and macular ganglion cell thickness with optica coherence tomography (OCT) of Fourie Domain (Cirrus, Zeiss). All measurements were made by the same observer. In addition, epidemiological and clinical variables such as age at diagnosis, duration of the disease, and quality of life scale (with EQ‐5D test), were recorded.

Results

The average age at the baseline visit was 52.01 ± 8.81 years with an average duration of fibromyalgia of 7.88 ± 4.25 years, and an average of quality of life EQ‐5D of 45.08 ± 18.84 out of 100. When comparing the baseline visit with the 5‐year visit, no significant differences were found in VA measurements, butsignificant differences were found (p value <0.05) in constrast sensitivity (with Pelli Robson and CSV1000E tests, in A, B, C and D frequencies), in stereopsis, in color vision (with AC CCi indext of the Farnsworth and the Lanthony tests), in visual field (MS and MD indexes). There were no significant differences during the 5 years follow‐up in the ganglion cell layer thickness measured with OCT.

Conclusions

The patients with fibromyalgia present an visual function reduction during the progression of the pathology, but without retinal or ganglion cell layer thinning in OCT.
Conjunctival lymphoma a case report
Authors: Boned Ana , Diaz Maria Dolores , del Buey Maria Angeles , Marco Sara , López Isabel , Karlsruher Gisela , Montes Paula , Ascaso Francisco Javier
Published: December 2019

Purpose

Orbital lymphomas are not frequent within orbital pathologies; they are commonly found associated to systemic diseases. Lymphomas affecting only the conjunctiva are even less frequent and their bilateral manifestation are uncommon. The characteristic lesion of conjunctival lymphomas is an orange‐pink mass at the bottom of the bag, without adhesion to deep planes. Patients are often asymptomatic but they may also complain of irritation of the eye. Painful proptosis or ptosis may appear if the affectation extends to the orbit. The average age of presentation is 60–70 years and it is more common in women. The diagnosis is confirmed by biopsy of the lesion.

Methods

We report the case of a 55‐year‐old woman with a conjunctival bilateral mucosa associated lymphoid tissue (MALT) lymphoma, not associated to systemic disease. The patient came to the service complaining of one month of epifora and itching in both eyes, with a salmon patch conjunctival mass in the temporal tarsal conjunctiva of the left eye, without any inflammatory signs or decreased visual acuity.

Results

A partial exeresis and biopsy of the left eye subconjunctival mass was performed. An extranodal lymphoma of the lymphoid tissue associated with mucosa was diagnosed (MALT lymphoma), CD20: positive, BCL2: positive and Ki67: 5%. Ocular ECO and MRI demonstrated infiltration of the external rectus muscle, being in contact with the superior rectus muscle, and PET CT confirmed a normal metabolic pattern. The patient was followed up for several months in the departments of Ophthalmology and Oncology, treatment was initiated with radical radiotherapy 30 Gy, fractionation cGy 200 in the left conjunctiva, which started on January 30 2017 and ended on February 18 2017.

Conclusion

Biopsy offers an early diagnosis for conjunctival lymphoma, being its prognosis very good. Because of this, ophthalmologists should be aware of this pathology, its characteristics and diagnosis.
A step towards pigmentation independent retinal vessel oximetry
Authors: Hirsch Katrin , Heitmar Rebekka , Cubbidge Robert P.
Published: December 2019

Purpose

Retinal vessel oximetry is a promising tool to gain information on the microcirculation of the retina. Due to the ratio of reflectance’s of the vessel plane and the neighbouring tissue, computation of oxygen saturation values (SO2) varies between individuals. The aim of this study was to develop a data transformation approach to overcome pigmentation‐ dependency, allowing for inter‐subject comparison of SO2 values.

Methods

Arterial and venous SO2 results of 67 healthy subjects (mixed ethnicities) were related to the pigmentation value (RP) provided by the Vesselmap software (RVA Imedos, Jena). After normalization of the axis values, a regression line was rotated around the intercept with the y‐axis applying a rotation matrix (clockwise rotation).

Results

Regression lines before rotation were aSO2=0.808*RP+84.61 (R2 = 0.74) and vSO2 = 0.358*RP+39.17 (R2 = 0.56) for arteries and veins, respectively. Transformed arterial and venous regression lines were aSO2 = 0.066*RP+84.57 (R2 = 0.05) and vSO2 = 0.028*RP+39.09 (R2 = 0.01), respectively.

Conclusion

Clockwise rotation of the regression lines for arteries and veins was able to reduce R2 from 0.74 to 0.05 for arteries and from 0.56 to 0.01 for veins, confirming that the data transformation resulted in retinal pigmentation independent SO2 results. The proposed approach might improve comparability of inter‐subject results and allow for determination of normative data.
Review of endogenous endophthalmitis in a tertiary eye centre; can we spot the trends?
Authors: Mathews Namita , Barry Robery J. , Butt Gibran F.
Published: December 2019

Purpose

Endogenous endophthalmitis is a rare but sight‐threatening infection due to haematogenous spread of pathogens. Early diagnosis and appropriate treatment reduces morbidity. This study aimed to identify pathogenic similarities and visual outcomes.

Method

A retrospective audit of all endogenous endophthalmitis cases between January 2010 and December 2016 at the Birmingham and Midlands Eye Centre (BMEC) was undertaken. All patients coded as having a diagnosis of endophthalmitis in the electronic patient records system, were identified and the case notes reviewed. Details of each case (microbiology, source of infection and outcome) were recorded. Cross‐tabulations were performed to identify trends and prognostic factors.

Results

Ten males and six females (range 38–96 years) were identified. This constituted 6% of all endophthalmitis cases at BMEC in the study period. Eyes affected: six left, four bilateral and six right. Twelve cases (75%) had identifiable risk factors (e.g. bacterial endocarditis, malignancy, immunodeficiency). Seven (44%) cases were culture positive from vitreous or aqueous samples: four bacterial and three fungal. Initial broad‐spectrum therapy covered for six of these of these cases (86%) from sensitivity data. Six patients were found to be culture positive from a non‐ocular sample. A source of infection was identified in 13 patients (76%). After treatment, four patients (25%) achieved driving‐standard vision or better, eight patients (50%) had no perception of light, of whom 3 (38%) underwent evisceration.

Conclusion

Patients with risk factors and clinical suspicion of endogenous endophthalmitis should be reviewed and treated promptly. Our results demonstrate that less than half of cases are culture positive from vitrectomy samples therefore it is important to assess thoroughly for the source and send all available ocular and non‐ocular microbiology samples. Visual outcome remains poor for this condition and patients should be forewarned of the prognosis.
Analysis of microstructural changes of the retina at different localization of the optic nerve head drusen
Authors: Ioyleva Elena , Kabanova Evgenya , Zinov’eva Aleksandra
Published: December 2019

Purpose

Identification of microstructural changes of the retina at different localization of the optic nerve head drusen (ONHD).

Methods

The study included 108 patients (216 eyes) with bilateral ONHD in age from 18 to 60 years. The control group included 28 healthy individuals. All patients underwent standard ophthalmologic examination and optical coherence tomography (OCT) on a Cirrus HD‐OCT 5000 instrument (Carl Zeiss Meditec Inc).

Results

According to the OCT data, three types of localization of ONHD in relation to the Bruch’s membrane are identified: superficial (above the Bruch’s membrane), deep (below the Bruch’s membrane) and combined (superficial and deep). The combined location of the drusen is determined in 48.6% of cases, deep ‐ in 40.3%, superficial ‐ in 11.1%. Younger patients (35.52 ± 13.09 years) were more likely to have deep ONHD, in the middle age group (42.03 ± 13.2 years) ‐ combined ONHD, and in older age (51.67 ± 12.78 years) ‐ superficial ONHD. In superficial and combined ONHD a significant (p <0.05) decrease thickness of mGCIPL (GCL+IPL) in all sectors (superior, superonasal, inferonasal, inferior, inferotemporal, superotemporal), minimal and average thickness of mGCIPL was diagnosed; a significant (p <0.05) decrease of average thickness of ILM‐RPE and the cubic volume of ILM‐RPE was determined. With deep ONHD, the changes of mGCIPL were less pronounced and statistically insignificant.

Conclusion

Minimal changes in the mGCIPL and ILM‐RPE at deep ONHD are characterized as the initial stage of the pathological process. With combined and superficial ONHD, there is a pronounced decrease thickness of the mGCIPL and neuroepithelium, which allows us to conclude that this localization of the drusen is associated with a progressive degenerative process.