bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding and perceptions of inherited eye diseases and attitudes to genetic testing and gene therapy in a primary eye care setting
Authors: Ganne P. , Votruba M. , Garrioch R.
Published: September 2015

Purpose

To explore the level of understanding and perceptions of inherited eye diseases and attitudes to genetic testing and gene therapy in a primary eye care setting.

Methods

This study was undertaken as a part of an EVER foundation fellowship at the School of Optometry and Vision Sciences, Cardiff University, UK in 2014. Participant groups were surveyed by questionnaire. The groups were: undergraduate students of optometry, primary eye care professionals and the members of general public attending the optometry practice to have a routine eye test or a routine annual follow‐up. Four focus groups were conducted to design the questionnaire. A preliminary study aimed to understand perceptions and to explore the level of knowledge about genetics, inherited eye diseases and gene therapy. A second questionnaire was designed to explore attitudes to genetic testing and gene therapy.

Results

The majority of participants (82%) perceived genetics as an important science. However, the level of understanding of genetics and inherited eye diseases was relatively low among all groups of participants. Undergraduate students and primary eye care professionals were better informed about inherited eye diseases than the general public (p = 0.001). The majority (80%) across all three groups had a positive attitude to genetic testing and gene therapy. There was a lack of knowledge about the genetic services available among all groups of participants.

Conclusions

This study shows a broadly supportive attitude to genomic medicine among the public albeit a poor level of knowledge of genetics and genetic eye diseases. Improving public awareness and education in inherited eye diseases can improve the utility of genetic testing and therapy.
Reduced retinal nerve fibre layer thickness in multiple sclerosis patients with and without history of optic neuritis
Authors: Birkeldh U. , Wahlberg‐Ramsay M. , Hietala A. , Brautaset R. , Nilsson M.
Published: September 2015

Purpose

Compare the retinal nerve fibre layer (RNFL) thickness in multiple sclerosis (MS) patients, with and without previous episodes of optic neuritis (ON), to disease‐free controls, using optical coherence tomography (OCT).

Methods

The RNFL was measured with a spectral domain OCT (Canon HS‐100) in 433 MS patients and in 70 controls. The MS eyes were sorted into three groups: MS non ON eyes (MSON−), MS ON eyes (MSON+) and the fellow eye of MS ON (MSON_fellow). One eye of each patient in the MSON‐group and in the control group was selected randomly for analysis.

Results

Seventy control eyes, 327 MSON‐ eyes, 106 MSON+ eyes and 106 MSON_fellow eyes were analysed in a linear regression adjusting for age. The average RNFL thickness was found to be statistically thinner in the MSON− group (88.2 ± 13.0 µm) compared to the controls (98.1 ± 9.0 µm; p < 0.00).The average RNFL was thinner in the MSON+ group (77.3 ± 15.2 µm) compared to MSON− eyes and the controls (p < 0.00). A paired t‐test showed a significant decrease in RNFL thickness in the MSON+ eyes compared to MSON_fellow.

Conclusions

Multiple sclerosis causes RNFL loss. A mean reduction of ~10 µm was found in MS patients without history of ON and a mean reduction of 20 µm was found in MS patients with history of ON compared to healthy controls. This study showed that OCT is a useful tool that provides evidence of neural degeneration in MS patients, with or without the presence of ON.
Clinical evaluation of Nidek autorefractometer AR‐360A
Authors: Stoor K. , Karvonen E. , Liinamaa J. , Saarela V.
Published: September 2015

Purpose

A clinical evaluation of the Nidek AR‐360A autorefractometer was performed to examine its accuracy in measuring refraction and visual acuity, in a pilot study for a clinical screening trial (the Northern Finland Birth Cohort Eye Study).

Methods

Measurements of the refractive error were obtained from 160 eyes of 80 subjects (mean age 48.9), first objectively with the AR‐360A and then subjectively by an optometrist. Agreement with the subjective refraction was calculated for sphere, cylinder, mean spherical equivalent (MSE), cylindrical vectors J45 and J0, and presbyopic correction (add). Visual acuity was measured using an ETDRS chart and the autorefractometer. The central corneal thickness (CCT) was measured with pachymetry.

Results

The refractive error measured with the AR‐360A was lower than the subjective refraction performed by the optometrist for sphere (−0.13D ± 0.31D p < 0.0005), and higher for cylinder (0.11D ± 0.18D p < 0.0005). The bias between the measurements of MSE, J45 and J0 was very low; −0.08D ± 0.31D p = 0.002, 0.00D ± 0.43D p = 0.89, and 0.19D ± 0.36D p = 0.51, respectively. The amount of add measured by the autorefractometer was slightly higher at 0.16D ± 0.23D p < 0.0005. There was no statistically significant correlation with either visual acuity (p = 0.650) or CCT (p = 0.054) and the difference between the subjective and objective refraction. In 99.4% of the measurements of visual acuity using the ETDRS chart and the autorefractometer, values were within one Snellen line of each other.

Conclusions

The Nidek AR‐360A autorefractometer is a reliable tool for determining the refraction and visual acuity in a clinical screening trial.
Abnormal lymphatic‐like differentiation and endothelial progenitor cell activation in hemi retinal vein occlusion
Authors: Loukovaara S. , Gucciardo E. , Repo P. , Lohi J. , Salven P. , Lehti K.
Published: September 2015

Purpose

Pathological vascular differentiation in retinal vein occlusion‐related neovessel formation remains poorly characterized. The role of the intraocular lymphatic‐like differentiation or endothelial progenitor cell activity has not been studied in this disease.

Methods

An eye with hemi retinal vein occlusion (RVO) underwent vitrectomy, neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α‐smooth muscle actin and pan‐endothelial cell adhesion molecule (CD31). Expression of lymphatic endothelial cell (LEC) markers was studied by lymphatic vessel hyaluronan endothelial receptor‐(LYVE)‐1, podoplanin (PDPN), and prospero homeobox protein (Prox)‐1. Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67) and expression of the stem cell marker CD117.

Results

Specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE‐1 and Prox‐1 was detected, with Prox‐1 being more widely expressed in the vessels. PDPN expression was found in the extravascular structures representing potentially monocyte‐ or bone‐marrow derived cells. Expression of stem cell marker CD117 in actively proliferating Ki67‐expressing ECs suggested for vascular endothelial stem cell activity.

Conclusions

Intraocular lymphatic‐like differentiation coupled with endothelial stem/progenitor cell activation may be involved in the pathology of neovessel formation in ischemia‐induced human hemi‐RVO.
Correlation between peripapillary retinal thickness and serum level of vascular endothelial growth factor in patients with POEMS syndrome
Authors: Yokouchi H. , Baba T. , Oshitari T. , Yamamoto S.
Published: September 2015

Purpose

To determine whether there is a significant correlation between the peripapillary retinal thickness (pRT) and the serum level of vascular endothelial growth factor (VEGF) in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.

Methods

This was a cross sectional, observational case series. We studied 34 eyes of 17 treatment‐naïve patients with POEMS syndrome whose intracranial pressure (ICP) was within the normal range. The spectral‐domain optical coherence tomographic (SD‐OCT) examinations consisted of circle scans around the optic disc (3.45 mm in diameter). The pRT was automatically measured in the SD‐OCT images, and the average pRT was used for the statistical analysis. The serum level of VEGF was measured by Enzyme‐linked immunosorbent assays (ELISAs), and the correlation between the pRT and the serum level of VEGF was determined.

Results

The mean serum level of VEGF in all POEMS patients was 6085 ± 3332 pg/ml with a range of 1380 to 12000 pg/ml. The correlation between the pRT and the serum level of VEGF was significant (right eye, r = 0.85, P < 0.0001; left eye, r = 0.65, P = 0.004, Spearman's rank‐correlation coefficient), and there was a strong positive correlation between the pRT of the right eyes and left eyes (r = 0.83, P < 0.0001, Spearman's rank‐correlation coefficient).

Conclusions

The significant correlation between the pRT and the serum level of VEGF suggests that the higher serum level of VEGF might be associated with the development of the optic disc edema in patients with POEMS syndrome.
Intravitreal Cysticercosis
Authors: Halfeld Furtado De Mendonca R. , De Oliveira Maia O.
Published: September 2015

Purpose

To describe a very interesting vitrectomy in a case of intravitreal cysticercosis.

Setting

Cysticercosis is the most common ocular helminthic infection in man.

Methods

A 14 year old Brazilian girl complained of blurred vision in her right eye over the past 6 months. During this period she had several episodes of hyperaemia. Visual acuity in the right eye was hand motion and in the left eye 20/20. The intraocular pressure was normal. Fundus examination of the left eye was normal. Fundus examination of the right eye showed a floating cyst in the vitreous cavity.

Results

The patient underwent 23‐gauge vitrectomy without any complications. Perfluorocarbon liquid was used to facilitate the removal of the cyst in the vitreous cavity. Laser photocoagulation was carried out around the retinal break, followed by silicone oil implantation. Light and electron microscopic studies suggested Cysticercus cellulosae as the infecting agent.

Conclusions

The complete and active aspiration of the Cysticercus Cellulosae in the vitreous cavity was very interesting and efficient. We believe that the success of the surgery was due to the fact that the cyst was removed intact by pars plana vitrectomy.
Optic disc drusen with subretinal hemorrhage
Authors: Halfeld Furtado De Mendonca R. , De Oliveira Maia O.
Published: September 2015

Purpose

To report a rare and interesting case of optic disc drusen with subretinal hemorrhage.

Setting

The hemorrhagic complications of the optic disk drusen are rare and interesting.

Methods

A 25 year old white man complained of an acute blurred vision in his left eye over the past 6 days. Visual acuity in the right eye was 20/20 and in the left eye 20/200. He had photoreactive and anisocoric pupils (left > right). Fundus examination in both eyes showed an elevated optic nerve head with blurred and irregular disc margins. In the left eye was present a subretinal hemorrhage.

Results

The neurological examination and brain computed tomography were normal. Fluorescein angiography (FA) of the left eye showed hypofluorescence (blocked) due to subretinal hemorrhage. No fundus autofluorescence was detected. Indocyanine green angiography was performed to exclude a neovascular choroidal membrane. Goldmann visual field exam showed in the right eye enlargement of the blind spot and paracentral scotoma and in the left eye a small constriction of the isopters and central scotoma. Ocular ultrasound demonstrates an echogenic focus within the optic nerve head. No treatment was performed. Spontaneous resolution of the subretinal hemorrhage was observed. At 3‐months follow‐up the visual acuity of the right eye was 20/20 and left eye 20/25.

Conclusions

Optic disc drusen may be associated with subretinal hemorrhage as a result of direct mechanical compression and rupture of subretinal vessels at the optic disc. Optic disc drusen often mimic papilledema and must be distinguished from true papilledema. The subretinal hemorrhage can resolve spontaneously.
Dietary interventions for age‐related macular degeneration: a review of the evidence
Authors: Lawrenson J. , Evans J.
Published: September 2015

Purpose

To summarise the findings of three recently published Cochrane systematic reviews, conducted by the authors that investigated whether taking nutritional supplements can prevent or slow the progression of age‐related macular degeneration (AMD).

Methods

The systematic reviews were performed using standard Cochrane methodology. We included randomised controlled trials (RCTs) where increased dietary intake of omega 3 fatty acids or antioxidant vitamin or mineral supplements were compared to placebo or no intervention with the aim of preventing the development of AMD, or slowing its progression.

Results

There is no good evidence from RCTs that the general population should be taking antioxidant vitamin supplements to reduce their risk of developing AMD later on in life. By contrast, there is moderate quality evidence that people at high risk of developing advanced AMD may experience a delay in progression by taking specific antioxidant vitamin and mineral supplements. This finding is drawn from trials conducted in the USA in a relatively well‐nourished population. Although observational studies have shown that the consumption of dietary omega 3 fatty acids may reduce the risk of progression to advanced AMD, two recently published RCTs failed to show any benefit of omega 3 supplements on AMD progression.

Conclusions

There is no high quality experimental evidence that nutritional supplementation is beneficial for the primary prevention of AMD. However, people at high risk of developing advanced AMD may benefit from taking antioxidant vitamins. There is currently no evidence to support increasing levels of omega 3 long chain polyunsaturated fatty acids in the diet for the explicit purpose of preventing or slowing the progression of AMD.
Neuroprotection as a therapeutic target in diabetic retinopathy: a basic approach
Authors: Dal Monte M. , Amato R. , Biagioni M. , Cammalleri M. , Casini G.
Published: September 2015

Purpose

To test the hypothesis that protecting retinal neurons from apoptosis elicited by diabetic stress may prevent the increase of vascular endothelial growth factor (VEGF) in the retina.

Methods

Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing diabetic retinopathy (DR), i.e. high glucose (HG), oxidative stress (OS) or advanced glycation end‐products (AGE). Retinal cell death was antagonized with octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well‐documented neuroprotectants. Data were obtained with real time RT‐PCR, Western blot, ELISA and immunohistochemistry.

Results

Control explants remained viable up to 10 days. Increased apoptosis was observed after HG, OS or AGE, and it was paralleled by increases in VEGF expression and release. Both OCT and PACAP reduced retinal apoptosis. At the same time, they also reduced VEGF expression and release. To get indications about the biological significance of VEGF release by stressed retinal cells, a VEGF trap (VT) was administered to HG, OS or AGE treated retinal explants. The effect of the VT was to further increase cell death induced by treatments.

Conclusions

Protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. This suggests that the retina in early DR releases VEGF as a pro‐survival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.
The use of matrix therapy in the Treatment of corneal perforation
Authors: Lazreg S.
Published: September 2015

Purpose

Corneal perforation may be the most severe complication of ocular surface and corneal inflammation, the purpose of this study is to treat these small perforations.

Methods

Patients with corneal perforation in Sjögren's syndrome disease, we're treated by Cacicol at the dose regiment of one drop every other day for 3 weeks associated to an hydrophilic contact lens, the follow up visits were performed every day the first week, than every week the first month.

Results

5 cases of corneal perforation were treated, 4 females, mean age 73+/‐ 23 years, the size of the perforation was less than 1 mm in all cases, and the time between the perforation and the onset of the treatment was less than 24 hours, all the patients were treated for severe dry eye in Sjögren's disease since many years, the perforation were no painful in all cases, The beginning of corneal healing was observed between D 3 and D7, and the total cicatrization of the perforation was observed at d 15 for all patients.

Conclusions

Matrix therapy can be helpful in small size corneal perforation associated to contact lens bandage in the absence of amniotic membrane.
Comparison of preservative‐free latanoprost and bimatoprost in a multicenter, randomized, investigator‐masked cross‐over clinical trial
Authors: Stalmans I. , Cordeiro F. , Hommer A. , Oddone F. , Ribeiro L. , Sunaric Mégevand G. , Rossetti L.
Published: September 2015

Purpose

To investigate the efficacy and safety of Bimatoprost Unit Dose Preservative Free (BUDPF) and Latanoprost Unit Dose Preservative Free (LUDPF) in a clinical setting.

Methods

Prospective, randomized, investigator‐masked, cross‐over comparison. Patients with ocular hypertension or open angle glaucoma (OAG) with an IOP less than or equal to 21 mmHg with a preserved prostaglandin monotherapy at screening were washed out and randomized to receive BUDPF or LUDPF for 3 months and were then switched to the other respective treatment for another 3 months. IOP curves were performed at baseline and after each treatment period, and safety and tolerability were assessed at the two latter timepoints.

Results

Both drugs were effective in lowering IOP, both at 3 and at 6 months (estimated differences compared to baseline pressures: −4.0 ± 0.5 for both BUDPF and LUDPF, p < 0.01 at 3 months; −5.2 ± 0.5 for BUDPF, −3.4 ± 0.5 for LUDPF, both p < 0.01 at 6 months). Analysis at 6 months (primary endpoint) showed a difference of 1.6 ± 0.5 mmHg between the two groups, favoring BUDPF (p < 0.01). An intra‐subject IOP difference of 0.9 ± 0.2 mmHg in favor of BUDPF was observed (p < 0.01).

Conclusions

This study demonstrate a superior efficacy of BUDPF over LUDPF in lowering IOP.
Concordance between ophtalmologists and paramedical professionals in screening for retinal abnormalities with ultrawide field imaging
Authors: Durbant E. , Vardi K. , Bordet J. , Barbe C. , Garcia T. , Angioi K. , Arndt C.
Published: September 2015

Purpose

The decreasing number of ophthalmologists leads to evaluate preliminary screening procedures performed by paramedical professionnals. The ultrawide field retinography is a recent technique allowing to obtain, simply and reproducibly, central and peripheral retinal images with or without mydriasis.The main objective of this study was to evaluate the diagnostic agreement between the reading of the ultra wide field images by a paramedical professional compared to a doctor.

Methods

A prospective diagnostic two‐center study was performed in the ophthalmological departments of two University Hospitals (Reims and Nancy) including all patients eligible in an outpatient clinic. For each patient, an ultra wide field retinography was taken with an Optomap (Optos) and an image analysis was performed by both a paramedical professional and an ophthalmologist. The agreement (kappa coefficient) between both image readings was evaluated.

Results

901 patients were included from July 2011 to November 2014. A good agreement was found between paramedical professionals and ophthalmologists for the global analysis (normal or abnormal image) (k = 0.62 [0.59 to 0.66]).This good concordance was also found for retinal lesions, including the macula (k = 0.70 [0.66 to 0.73]) and particularly for the analysis of red lesions such as hemorrhages, dilated veins and retinal detachment. However, the agreement was poor for optic disc analysis (k = 0.38 [0.32 to 0.44]).

Conclusions

In screening procedures, paramedical professionals were able to identify retinal abnormalities on ultra wide field image in a significant number of cases. However, the correct identification of optic disc abnormalities was poor.
Looking for the best mouse model to study retinoblastoma
Authors: Lemaitre S. , Poyer F. , Cassoux N. , Fréneaux P. , Thomas C.
Published: September 2015

Purpose

Retinoblastoma is the most common primary intraocular tumor in children. Current therapies have many adverse effects. New approaches must therefore be developed and evaluated on animal models. Retinoblastoma mouse models include transgenic mice and patient‐derived xenografts. We report our experience with orthotopic xenograft models of retinoblastoma using different mice strains.

Methods

Human retinoblastoma tumors were established and maintained by xenografted cells from enucleated eyes on immunodeficient mice. The orthotopic model was obtained by subretinal injection of cells in suspension in the right eye of immunodeficient (nude, SCID) and immunocompetent mice (C57BL6N, B6ALB). Tumor growth was monitored by SD‐OCT imaging and histology was also performed.

Results

Tumor growth was observed both in immunocompetent and in immunodeficient mice. Chronic retinal detachment may occur after the subretinal injection. Retinal, subretinal and vitreal tumor growth were achieved in four different strains. Retinal anatomy (thickness and number of layers) is different in nude mice. Mouse strains include immunocompetent and immunodeficient mice, albino and pigmented mice. Albino mice suffer from light‐induced retinal degeneration and a retinal degeneration mutation is present in the C57Bl6 strain. Consequently, visual function after treatment can be difficult to interpret in these mice. Retinal anatomy in nude mice may be responsible for chronic retinal detachment after the subretinal injection.

Conclusions

The genetic background of a given mouse can influence on its visual properties but it does not seem to influence the establishment of a xenograft model.
Comparison of the lamina cribrosa thickness of patients with unilateral branch retinal vein occlusion and normal subjects
Authors: Sagong M. , Lim S.H. , Kim M. , Chang W.
Published: September 2015

Purpose

We compared the lamina cribrosa thickness (LCT) of normal subjects and patients with unilateral branch retinal vein occlusion (BRVO), and investigated the correlation between the LCT and the BRVO subtypes.

Methods

A total of 46 eyes of 46 patients with naïve untreated BRVO and 31 eyes of 31 normal control subjects were included in this study. The occlusion site was divided into 2 BRVO types: arteriovenous crossing BRVO (AV‐BRVO) and optic nerve BRVO (ON‐BRVO). The optic nerve head (ONH) was scanned using enhanced‐depth imaging (EDI) with the Spectralis OCT system. The mean LCT was defined at the centers of the mid‐superior, central, and mid‐inferior horizontal B‐scans. The inter‐eye differences and intra‐eye differences in the LCT in BRVO were analyzed using the paired t‐test.

Results

The mean LCT of both eyes in the patients with BRVO was thinner than that of the normal subject eyes (both P < .001). Although the LCT of the BRVO‐affected eyes were slightly thinner than that of the fellow eyes (237.0 µm vs. 241.4 µm), there was no statistically significant difference. Moreover, there were no significant LCT differences according to site of occlusion (AV‐BRVO 237.6 µm vs. ON‐BRVO 234.4 µm, P > .05).

Conclusions

The lamina cribrosa was thinner in both eyes of the unilateral BRVO patients than in those of the normal subjects, but there was no difference in the LCT regardless of the anatomical site of the occlusion. These findings suggest that BRVO and glaucoma may have a common structural pathogenic mechanism.
The effects of nitroglycerine and COX‐inhibition on retinal vessel diameters during hypoxia
Authors: Kaya M. , Petersen L. , Bek T.
Published: September 2015

Purpose

Retinal hypoxia plays a role in the pathophysiology of retinal vascular diseases such as diabetic retinopathy. Previous studies have shown that nitric oxide (NO) and cyclooxygenase (COX) products are involved in hypoxia‐induced dilatation of the retinal vessels. Therefore, the purpose of this study was to examine the effect of an NO donor and inhibition of COX products on the diameter regulation of retinal vessels during hypoxia in healthy subjects.

Methods

Twenty normal persons were examined with the Dynamic Vessel Analyzer (DVA). Retinal vessel diameters were measured at rest, and during isometric exercise and flicker stimulation. The measurements were performed during normoxia and hypoxia before and after sublingual administration of the NO donor nitroglycerine, and were repeated on a second study day after topical administration of the COX‐inhibitor diclofenac.

Results

Hypoxia alone and combined with nitroglycerine significantly reduced both arteriolar constriction during isometric exercise and dilatation during flicker stimulation (p < 0.0001). Diclofenac further reduced the arteriolar constriction induced by isometric exercise during hypoxia (p = 0.005). Nitroglycerine alone had no effect on the retinal vessel diameters.

Conclusions

Diameter regulation of retinal vessels during hypoxia in normal persons is affected by inhibition of COX products but not by increased NO. The results contribute to understanding of retinal flow regulation and thereby to the identification of possible new strategies for intervention on diseases characterized by disturbances in retinal blood flow.
Correlation of Osmolarity Measurements with Signs and Symptoms in the Norwegian Dry Eye Clinic
Authors: Badian R.A. , Eidet J.R. , Ræder S. , Utheim Ø. , Chen X. , Stojanovic A. , Utheim T.P.
Published: September 2015

Purpose

To evaluate the relationship between osmolarity and signs and symptoms of dry eye disease (DED) in a Norwegian cohort of patients with DED.

Methods

Clinical signs and symptoms were evaluated for 365 subjects at the Norwegian Dry Eye Clinic. All patients received an extensive ophthalmological work‐up, including tear meniscus height, blink rate, corneal sensibility, tear film break‐up time, Ocular Protection Index, vital staining, Schirmer I, meibum quality and meibum expressibility. Pearson correlations between signs and symptoms were performed. P values below 0.05 were considered significant.

Results

High osmolarity correlated with lower ocular protection index (0.32) and higher blink interval (0.12), but no other parameters.

Conclusions

Osmolarity did not correlate strongly with any parameters of dry eye disease.
Mass production of high quality corneal endothelial cells from old donors
Authors: He Z. , Forest F. , Perrache C. , Cognasse F. , Cognasse H. , Gain P. , Thuret G.
Published: September 2015

Purpose

In vitro expansion of human corneal endothelial cells (CECs) possessing differentiation status and high endothelial cell density (ECD) is the key for the future cell therapies addressing endothelium dysfunctions. A few recent successes were reported using young donors (<30 years old (yo), by definition scarce), but an efficient technique is lacking for current donors over 55 yo. We present a protocol for mass production of very high quality CECs from old donors.

Methods

The Descemet membrane of 35 organ cultured corneas from donors over 55 yo were peeled and digested in collagenase to separate the CECs. Primary cultures were grown in fibronectin‐coated wells for 1 month with low concentrations of growth factors. Cells were then trypsinized and subcultivated for 1 month in a second medium enriched with growth factors. The whole process was animal compound free. Only cultures with small regular cells without mesenchymal transition were further subcultured in T25 flasks. At 5th passage, the culture yield and cell characteristics were assessed.

Results

Cultures with monolayer of small polygonal cells were obtained for 7 donors (mean age 71 ± 13 yo). ECD was ≥4000 cells/mm2. At 5th passage, each cornea gave more than 160 million of CECs. They strongly expressed ZO1, Na/K ATPase, NCAM, Ncadherin and Vimentin as expected. After ex vivo re‐endothelialization of denuded corneas of their own CECs, a new endothelium with high ECD (>2500 cells/mm2) was obtained. Alizarin red staining showed typical morphology of CECs.

Conclusions

This new protocol provided a very high quality of cultured CECs from old donors. The satisfying yield and high ECD allows us to plan its transfer to a clinical grade process.
cis‐Urocanic acid prevents inflammation and cell death in UVB‐treated ARPE‐19 cells
Authors: Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K. , Kauppinen A.
Published: September 2015

Purpose

cis‐Urocanic acid (cis‐UCA) is an endogenous ultraviolet (UV) absorbing chromophore that is mainly produced in the upper layers of epidermis. The aim of our study was to investigate the cytoprotective capacity of cis‐UCA in UVB‐irradiated ARPE‐19 cells.

Methods

ARPE‐19 cells were pretreated with IL‐1α ± and cis‐UCA and then exposed to UVB radiation. Secretion of IL‐1β and ‐18 was measured using the ELISA method. Moreover, the cells were observed under an inverted microscope and cell viability was measured by lactate dehydrogenase (LDH) release assay. The proper cis‐UCA concentration was evaluated comprehensively beforehand using MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide), neutral red, and LDH tests.

Results

Our results show that UVB after IL‐1α ± priming activates IL‐1β and ‐18 secretion in ARPE‐19 cells and cis‐UCA clearly alleviates that. cis‐UCA also improves cellular viability.

Conclusions

cis‐UCA shows anti‐inflammatory and cytoprotective properties in ARPE‐19 cells.
A case of significant refractive change in nodular posterior scleritis
Authors: Yoon S. , Jeong H. , Kim H. , You T.
Published: September 2015

Purpose

The aim of this study is to report refractive change in a patient with nodular posterior scleritis.

Methods

A 43‐year‐old woman visitied clinic with a complaint of near vision discomfort associated with ocular pain and conjunctival injection. Her past ocular history was myopia of both eye, refractive error was ‐1.00D and uncorrected visual acuity was 20/40.

Results

On ocular examination, uncorrected visual acuity was 20/20 in her right eye. But, refrective error of right eye changed ‐1.00D to +0.25D. Fundus examination revealed an large submacular mass associated with subretinal fluid surrounding it. B‐scan ultrasonography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography findings confirmed a nodular posterior scleritis. But, brain and orbit MRI was normal finding except posterior scleritis. As treatment, nepafenac eye drops 3 times a day, and flurbiprofen tablet 100 mg twice a day were prescribed. After 4 weeks of treatment, the ocular pain was relieved, refractive error was changed +0.25D to ‐1.00D and subretinal mass totally regressed.Conclusions

In case of severe nodular posterior scleritis, refractive error changes can appear at chief complain. So, In the case of refractive error change associated with ocular pain, nodular posterior scleritis should be evaluated.
Effect of dexamethasone intravitreal implant in the treatment of noninfectious uveitis
Authors: Frère A. , Janssens X. , Makhoul D. , Judice L. , Postelmans L. , Lefèbvre P. , Caspers L. , Willermain F.
Published: September 2015

Purpose

To investigate the effect of dexamethasone intravitreal implant (Ozurdex; Allergan, Inc) in noninfectious uveitis.

Methods

Charts of patients with noninfectious uveitis treated by dexamethasone intravitreal implants were reviewed in a retrospective study. Uveitis etiologies, treatment indications, visual acuity, central retinal thickness measured by optical coherence tomography, intraocular pressure and number of injections were collected. Parameters were analyzed before injection (29 ± 6 days), after 5–6 weeks (49 ± 10 days) (short follow‐up) and 4–5 months (134 ± 2 days) (long follow‐up) post Ozurdex injection.

Results

We included 14 patients (20 eyes, 26 implants injections). Before injections, mean visual acuity was 0.5 ± 0.5 logMAR and improved to 0.3 ± 0.4 logMAR at short time follow‐up and to 0.3 ± 0.5 logMAR at long time follow‐up. Macular thickness has decreased by 101 ± 126 µm at short time follow‐up and 83 ± 162 µm at long time follow‐up. Mean intraocular pressure was 16 ± 5 mmHg before injections, 17 ± 6 mmHg at short time follow‐up and 15 ± 3 mmHg at long time follow‐up.

Conclusions

In noninfectious uveitis, dexamethasone implant can improve visual acuity and decrease macular thickness without significant increase of intraocular pressure. Although the effect seems limited in time.
Autophagy stimulus affects different kinase pathways and promotes HuR protein activation and SQSTM1/p62 protein synthesis in ARPE‐19 cells
Authors: Amadio M. , Marchesi N. , Govoni S. , Pascale A. , Kaarniranta K.
Published: September 2015

Purpose

Age‐related macular degeneration (AMD) pathogenesis is characterized by protein degradation impairment in retinal pigment epithelial (RPE) cells. We previously found that the expression of autophagy receptor SQSTM1/p62 is positively regulated by the RNA‐binding HuR/ELAV protein. We investigated the effects of AICAR (autophagy inducer, 5‐aminoimidazole‐4‐ carboxamide‐1‐β‐D‐ribofuranoside) and MG‐132 (proteasome inhibitor) co‐treatment on HuR activation, p62 expression, and the kinases potentially involved.

Methods

ARPE‐19 cells were treated with MG‐132 (1 µM) and/or AICAR (2 mM) for increasing times (up to 2 h) and subjected to cell fractionation. SQSTM1/p62 mRNA and protein levels were measured by qRT‐PCR and Western blotting, respectively. HuR protein levels and its phosphorylated status were evaluated by Western blotting. The effects of puromycin (1 mM, protein synthesis inhibitor) and various kinase inhibitors were also tested.

Results

AICAR+MG‐132 co‐treatment for 2 h induces HuR protein up‐regulation, its cytoplasmic translocation and phosphorylation, as well as increased expression of p62 protein, being the latter one blunted by puromycin. AICAR+MG‐132 co‐treatment affects various kinases with differential outcomes.

Conclusions

AICAR+MG‐132 co‐treatment leads to HuR activation and p62 protein translation. Different protein kinase pathways are likely involved in these events.
The Repeatability of straylight measurements using the C‐Quant in young and older adults
Authors: Puell M. , Barrio A.R. , Antona B.
Published: September 2015

Purpose

To assess the repeatability of retinal straylight measurements using the C‐Quant straylight‐meter and to evaluate the effect of age on repeatability.

Methods

Twenty nine young (35.6 ± 9.6 years old) and twenty three older (61.8 ± 8.7 years old) subjects participated in the study. They were examined with the C‐Quant straylight‐meter. Two readings were taken in two different sessions with a time interval between them from 1 to 3 weeks. Inclusion criteria were distance best‐corrected VA of at least 0.8 decimal and without manifest ocular diseases. The repeatability of the straylight was estimated by the Bland‐Altman method whereby the mean difference (MD) and the 95% limits of agreement were determined as the coefficient of repeatability (COR).

Results

Mean retinal straylight was 0.97 ± 0.12 log units and 1.21 ± 0.21 in the young and the older group, respectively. Repeatability of straylight measurements in the entire sample was high (MD: −0.003 log units, COR = ±0.21 log units). The repeatability was better in the younger group (MD: +0.024 log units, COR = ±0.15 log units) than in the older group (MD: −0.021 log units, COR = ±0.24 log units). There were not any significant differences between the two repeated measurements in each group and also in the entire sample.

Conclusions

The measurement of retinal straylight using the C‐Quant showed a good repeatability, although was worse in the older group. The impact of changes in straylight caused by intraocular scatter in the older eye should be considered when measuring straylight in age‐related diseases such as cataract.
Wide field imaging in patients treated with vigabatrin
Authors: Vardi K. , Brugniart C. , Motte J. , Ducasse A. , Arndt C.
Published: September 2015

Purpose

The purpose of this study was to evaluate the occurrence of retinal changes on wide field imaging and to compare the results with ERG recordings in patients treated with vigabatrin.

Methods

Seven consecutive patients treated with vigabatrin were followed up with ERG and wide field imaging using scanning laser ophthalmoscopy (Optomap)

Results

Three patients had abnormal ERG recordings and presented with peripheral pigmentary changes. Three patients had normal ERG recordings with no peripheral changes on wide field imaging. One patient had abnormal ERG with no peripheral pigmentary changes.

Conclusions

The follow‐up with ERG in children treated with vigabatrin is complicated because the recordings are regularly repeated. A follow‐up protocol combining electrophysiological recordings and wide field imaging could simplify screening for retinal toxicity but it remains to be demonstrated with a prospective study.
Nonarteritic anterior ischemic optic neuropathy (NAION): A misnomer. A non‐ischemic papillopathy caused by vitreous separation
Authors: Parsa C. , Hoyt W.
Published: September 2015

Purpose

Vascular abnormalities such as disc hemorrhages and swelling present at the time of visual loss in NAION, followed by peripapillary vascular narrowing and ensuing disc pallor is enticing, but not etiologically conclusive for ischemia. Optic disc as well as retinal findings of whiteness with disc swelling is indicative of axoplasmic stasis that may also occur simply from anatomic distortion of axons rather than occlusion of vessels. It may also occur from mechanical stretching with fracture of the axonal cytoskeleton.

Methods

Review of the literature regarding (1) vitreous attachments and effects of separation from the optic disc, (2) dynamic shear force stretch injury to axons.

Results

Within the normal population and in the age‐goup in which NAION occurs, 10% have complete PVD, 70% partial PVD, and 20% no PVD. In those with acute NAION, however, either total vitreous separation from the disc, or complete parapapillary detachment, is always present. Any teleangectatic vessels on the disc surface correspond to areas of visual field sparing and encompass areas of unseparated vitreous still under tension.

Conclusions

Where internal limiting membrane is absent over the disc and peripapillary retina, most notably in cupless discs where epipapillary membrane adhesions are strongest, vitreous separation may momentarily stretch and elongate axons, breaking the cytoskeleton in more aged and less distensible axons, leading to immediate axoplasmic accumulation and atrophy in the prelaminar sites of separation. Vitreous synchysis occurs more precociously in diabetics. Ischemic pathophysiology need not be invoked in so‐called NAION, better termed papillary vitreous detachment, or PVD‐N. In those at risk, the timely and controlled release of vitreous connections to the optic disc may prevent such optic disc injury.
Assessment of choroidal thickness in high myopic glaucomatous eyes using SD OCT
Authors: El Matri L. , Chebil A. , Hassairi A. , Maamouri R. , Kort F. , Chaker N.
Published: September 2015

Purpose

To measure macular choroidal thickness (CT) using spectral domain optical coherence tomography (OCT) in high myopic eyes with primary angle‐open glaucoma (POAG), and to investigate whether the choroid is thinner in these eyes compared to high myopic eyes without glaucoma.

Methods

We conducted a cross‐sectional study of 68 eyes with high myopic glaucoma matched with 68 highly myopic eyes without glaucoma by age, central corneal thickness and axial length (AL). OCT scans were performed with the spectral domain OCT (Topcon 2000). The subfoveal CT was measured between the Bruch membrane and the internal aspect of the sclera.

Results

In the subgroup without glaucoma, matched with the subgroup with glaucoma by age (P = 0.48), central corneal thickness (P = 0.28) and AL (P = 0.14), the mean subfoveal CT was 98.56 μm ± 31.37 μm. In the subgroup with glaucoma, the mean subfoveal CT was 51.32 μm ± 18.44 μm. The comparison between the two subgroups found a statistically significant difference in subfoveal CT (P < 0.0001).

Conclusions

Foveal choroidal thickness is reduced in highly myopic eyes with glaucoma. The choroidal thinning can be a useful parameter for the diagnosis and the follow‐up of highly myopic patients with glaucoma.
Modulation of the contrast response function of V1 neurons by the pulvinar
Authors: Casanova C. , Lai J. , Thomas S.
Published: September 2015

Purpose

The pulvinar establishes reciprocal connections with nearly all the visual cortices and is thus in a strategic position to influence analyses taking place at the cortical level. Projections from the pulvinar to the primary visual cortex (V1) are considered to be modulatory, altering decoding properties of neurons without changing their basic receptive field properties. Results from our laboratory, based on optical imaging, have supported this assumption (Soc. Neurosci. Abst. 2011. Vanni et al.).

Methods

Here, we investigate further by studying V1 single unit responses during reversible deactivation of the lateral posterior (LP) – pulvinar complex in the cat through microinjections of gamma‐aminobutyric acid. Recording and injection electrodes were positioned to obtain overlapping thalamic and cortical receptive fields.

Results

No change in the preferred orientation or direction selectivity of V1 neurons was observed during pulvinar deactivation. However, for 67% of the cells tested (n = 39/58), the response amplitude to the optimal stimulus was reduced by a mean of 65%. The contrast response function of neurons was modeled with the Naka‐Rushton function and analysis of the effects of pulvinar deactivation revealed at least three types of modulation based on the function parameter predominantly affected: 24% of cells had a decrease in Rmax, 13% had an increase in the exponential factor and 11% had a C50 increase.

Conclusions

Our results suggest that the pulvinar modulates activity of neurons in the primary visual cortex in a contrast‐dependent manner. Consequently, this extrageniculate nucleus is likely to contribute to cortical processing in shaping spatiotemporal activity patterns of V1 neurons.
Microbiology of conjunctiva sac in intravitreal injections
Authors: Grzybowski A. , Gaca‐Wysocka M. , Paluch M.
Published: September 2015

Purpose

To evaluate the conjunctival sac flora before and after intravitreal injection (IVI) in eyes with no prophylactic antibiotic use.

Methods

37 eyes of 37 patients not using systemic or local antibiotics for at least 30 days were included. Microbiological culture from conjunctiva sac to nutrient media was taken twice: before IVI and before any topical medications were given and 30 minutes after anty‐VEGF IVI. Topical antibiotics were not used neither before, nor after IVI. Shortly before IVI conjunctival sac was rinsed with 5% povidone‐iodine (PVI). Control group constituted eyes not treated with IVI of the same patients.

Results

Negative microbiological cultures before and after IVI were noted in the studied group in 15 patients (40.5%) and in 9 control eyes (24.3%). Coagulase‐negative Staphylococci (CNS) were cultured in 13 eyes (35.1%) before IVI and in 8 eyes (21.6%) after IVI. In 3 eyes (8.1%) Staphylococcus aureus was shown before IVI, with subsequent negative cultures. In the control group CNS was shown in 14 eyes (37.8%) before IVI and in 7% (18.9%) after IVI. Microbiological flora was identical in studied and control groups in 14 cases (37.8%). There was no case of post‐IVI endophthalmitis.

Conclusions

About 50% of cultures were negative, in 35% ‐ CNS, and in 15% ‐ other bacteria were cultured, including Staphylococcus aureus in 8%. The number of negative cultures after IVI (the use of PVI) was higher than before IVI, and all Staphylococcus aureus were eliminated. The eye antisepsis based on PVI in IVI is an effective and efficient prophylaxis method.
Using reaction time in visual search and decision making task to measure visual field thresholds in multifixation perimetry
Authors: Leinonen M. , Mäntysalo T. , Sampinen K. , Ojala M.
Published: September 2015

Purpose

The ability to make eye movements to point the fovea toward object perceived in peripheral visual field is a fundamental feature of human visual system. We studied if reaction time (RT) in visual search task can be used for deciding if a peripheral visual field stimulus is visible when measuring visual field thresholds.

Methods

Ocusweep™ ambient light perimeter was programmed to display peripheral 0.2° stimulus of 100 ms duration for triggering a reflex saccade to point the fovea towards the location of the stimulus which was replaced with a faint arrow figure for reporting its direction with a button press and thus confirming foveal fixation. Next peripheral stimulus followed by a new arrow was then displayed. RT between button presses were recorded. Thresholds of the right eye of eight experienced healthy persons (mean age 43, range 22–58 years) using Humphrey 30–2 grid were measured with a staircase algorithm adjusting the intensity of the stimulus in response to the RT. Measurement reliability was estimated with catch trials, viewing distance controlled using ultrasonic rangers and variation in ambient room lighting (94–240 cd/m²) compensated using ambient light sensors of Ocusweep™.

Results

Thresholds measured with RT perimetry were close to normal age corrected values of Octopus perimeter: mean MD was 0.7 dB and mean sLV 2.5 dB. The RT difference between positive (no stimulus, pure visual search, mean RT 1980 ms) and negative catch trials (suprathreshold stimulus, reflex saccade, mean RT 649 ms) was 1331 ms (SD 369 ms).

Conclusions

Reaction time perimetry can be used to measure visual field thresholds and also to assess reflex saccades.
The Silk‐protein Sericin Induces Rapid Melanization of Cultured Retinal Pigment Epithelial Cells by Activating the NF‐κB Pathway
Authors: Pasovic L. , Utheim T.P. , Reppe S. , Lyberg T. , Olstad O.K. , Eidet J.R.
Published: September 2015

Purpose

Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients suffering from age‐related macular degeneration represents one of the most promising novel treatment modalities in regenerative medicine. Development of RPE transplants in the laboratory, however, is a lengthy process requiring up to 3 months of cell differentiation. We explored whether the silk protein sericin can be used as a culture medium supplement to induce differentiation of human RPE.

Methods

Microarray analysis determined the expression of RPE‐associated transcripts in control cultures and cultures supplemented with sericin. Quantitative immunofluorescence (QIM), spectrophotometry and transmission electron microscopy (TEM) validated the findings.

Results

Sericin supplementation increased the expression of RPE‐associated transcripts (RPE65 and CRALBP). The NF‐kB pathway was identified as one of the top sericin‐induced regulators. Increased levels of RPE‐associated proteins (including CRALB and the pigment melanin) in the sericin‐supplemented cultures were confirmed by QIM, spectrophotometry and TEM. Sericin supplementation also increased cell survival following serum starvation. Inclusion of NF‐kB agonists and antagonists in the culture medium showed that activation of the NF‐kB pathway appears to be necessary, but not sufficient, for sericin‐induced RPE pigmentation.

Conclusions

Sericin promotes pigmentation of cultured human RPE by activating the NF‐kB pathway.