bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesopic Visual Acuity in Type2 Diabetes without Retinopathy
Authors: Aldaham S. , Martín‐Ridura M.D.C. , Barrio A.R. , Antona B. , Carballo‐Álvarez J. , Puell M.
Published: September 2015

Purpose

Today, the information about the extent to which mesopic visual acuity (VA) is altered in diabetics without retinopathy is lacking. The purpose of this study was to evaluate distance high contrast VA (HC‐VA) and low contrast VA (LC‐VA) under mesopic luminance conditions in type 2 diabetics without any signs of retinopathy.

Methods

Thirty‐six control subjects and twenty‐three diabetics (well controlled glucose level) without retinopathy (mean onset duration 8.5 ± 4.42 yrs) were tested. All subjects had best corrected VA of 20/20 or better. VA was measured using the HC (96% contrast) and LC (10% contrast) Baily‐Lovie charts under photopic (85 cd/m2) and mesopic (0.10 cd/m2) luminance conditions with best distance correction worn. The subject was left to dark adapt for 10 minutes in the dark before testing mesopic VA.

Results

Mean photopic VA's (logMAR) were significantly worse in diabetics than controls (HC‐VA 0.03 ± 0.08 and −0.03 ± 0.08, p < 0.01; LC‐VA 0.17 ± 0.08 and 0.11 ± 0.11, p < 0.05, respectively). Mean mesopic HC‐VA was also worse in diabetics than controls (0.56 ± 0.11 and 0.48 ± 0.09, p < 0.05, respectively), but with less extent than photopic VA. Mesopic LC‐VA was not significantly different between diabetics and controls (0.94 ± 0.11 and 0.91 ± 0.06).

Conclusions

Distance photopic high contrast and low contrast VA, and mesopic HC‐VA were able to detect the worsening of VA in type 2 diabetics before any signs of retinopathy can be detected.
The effect of panretinal photocoagulation and additive Intravitreal bevacizumab injections on central retinal vessel diameters in diabetic retinopathy
Authors: Park J.M. , Lee S.J.
Published: September 2015

Purpose

To evaluate the effect of Panretinal photocoagulation and additive Intravitreal bevacizumab injections on Central retinal vessel diameters in Diabetic retinopathy.

Methods

Changes on central retinal vessel diameters were restrospectively analyzed before and 6 month after panretinal photocoagulation with or without additive Intravitreal bevacizumab injections in patients first diagnosed with diabetic retinopathy. Vessel diameters were measured using IVAN soft ware and Big6 fornula.

Results

21 patients were enrolled, mean age 54.9 years. There were significant decreases in central retinal artery diameters in both groups, with and without additive Intravitreal bevacizumab injections, 6 months after completion of panretinal photocoagulation(p < 0.05), but no significant changes in central retinal vein diameters. Additive Intravitreal bevacizumab injections did not bring the significant changes in central retinal vessel diameters before and after 6 months, compared to vessel diameters treated with panretinal photocoagulation only (p < 0.05).

Conclusions

Panretinal photocoagulation has effects on changes of central retinal artery diameters but not central retinal vein diameters, and additive Intravitreal bevacizumab injections did not cause significant additive changes on central retinal vessels in this study. meters before and after 6 months, compared to vessel diameters treated with panretinal photocoagulation only(p < 0.05).
Research on ophthalmic examination apparatus to diagnose multiple diseases which result in loss of eyesight
Authors: Suzuki N. , Yamane K.
Published: September 2015

Purpose

In Japan, the four major diseases which cause the loss of eyesight are glaucoma, diabetic retinopathy, pigmentary retinal degeneration, and age‐related macular degeneration. We developed an ophthalmic examination apparatus having the functions of fundus camera, microperimetry, electroretinography, and visual acuity testing, designed to diagnose multiple diseases which result in loss of eyesight.

Methods

We constructed the experimental device with the same optical system as a fundus camera. The device has previously been used for research involving the diagnosis of early diabetic retionopathy. The microperimetry optical system was calculated using the optical engineering software OpTalix‐LT and was added to the experimental device. In addition, we added an Edmund infrared camera EO‐0413, a lens with a focal length of 25 mm, a 45‐degree cold mirror, a 12V/50W halogen lamp, and an 8‐inch monitor. The artificial eye consists of a plane‐convex lens, a black spacer, and a hemispherical cup. A small section paper was stuck on the bottom of the hemispherical cup. The artificial eye was photographed for 10 times using the experimental device. The software was generated to show the examination target on the monitor and save examination data using C++Builder XE6.

Results

The device was able to show the retinal fundus on the monitor, at a length and width of 1 mm with a resolution of 63.25 ± 3.51 and 64.13 ± 6.10 pixels, respectively.

Conclusions

We succeeded in adding the function of microperimetry to the experimental ophthalmic device.
Exome sequencing confirms ZNF408 mutations as a cause of familial retinitis pigmentosa
Authors: Habibi I. , Chebil A. , Kort F. , Munier F. , Schorderet D. , El Matri L.
Published: September 2015

Purpose

The aim of this study was to identify the gene causing retinitis pigmentosa (RP) in a Tunisian family.

Methods

Three members of a consanguineous Tunisian family were clinically examined and were given best‐corrected visual acuity (BCVA), slit lamp biomicroscopy, fundus photography and optical coherence tomography scanning (OCT) testing. Blood samples were collected for DNA extraction. Regions of homozygosity were further analyzed in the index case and whole exome sequencing was performed. All detected mutations in candidate genes were validated by Sanger sequencing.

Results

The phenotype was characterized by hemeralopia starting in the first decade of life. BCVA ranged from 20/100 to 20/40. Fundus examination revealed typical RP changes with bone spicule‐shaped pigment deposits in the mid periphery along with atrophy of the retina, narrowing of the vessels and waxy optic discs. Tomograms showed macular edema. They also had high myopia and posterior subcapsular cataract. Mutation analysis in the region of homozygosity identified a c.653‐1G>T mutation in the canonical splice site of exon 5 of the zinc finger protein 408 (ZNF408) gene. All three affected members were homozygous for this mutation.

Conclusions

So far, only two different mutations have been identified (Avila‐Fernandez et al, Hum Mol Genet. 2015). This family represents the third case of ZNF408 mutations and further expands the clinical spectrum ofmutations.
Hypoxia induces an inflammatory response in ARPE‐19 cells
Authors: Arjamaa O. , Aaltonen V. , Piippo N. , Kaarniranta K. , Kauppinen A.
Published: September 2015

Purpose

To characterize further the link between hypoxia and inflammation in retinal diseases, we studied here the effects of hypoxic exposure on the secretion of inflammatory cytokines from ARPE‐19 cell culture, pretreated with lipoplysaccharide (LPS, to induce inflammation).

Methods

ARPE cell culture was exposed to 24 h hypoxia, 24 h hypoxia followed by 24 h reoxygenation, and 24 h or 48 h normoxia with or without LPS. Experiments were performed using culture medium DMEM/F‐12 supplemented with penicillin, streptomycin and L‐glutamin without or serum and with or without LPS. Each treatment was repeated 6 times. Hypoxia (37 C, 1% O2, 5% CO2, 90% moisture) was induced in Ruskinn Invivo2 workstation, and normoxia and reoxygenation (37C, air, 5% CO2, 90% moisture) in a standard cell culture incubator. The culture media and cell lysates were collected under hypoxic or normoxic atmosphere, centrifuged and snap frozen for storage and further analyses. VEGF and cytokines were measured with ELISA and intracellular proteins (autophagy markers p62, LC3 and oxidative stress marker Nrf2) with immunoblotting.

Results

As expected, hypoxic conditions increased significantly the secretion of VEGF from ARPE‐19 cell culture as compared to the secretion in normoxic conditions. Also, the secretion of IL‐6 and IL‐8 showed a significant increase in hypoxia when measured at 24 h. The intracellular protein levels were changed: p62 increased while LC3 and Nrf2 decreased in hypoxia (at 6 h).

Conclusions

An acute exposure to hypoxia induced an inflammatory response in ARPE‐19 cell culture as characterized with an increased IL‐6 and IL‐8 secretion from cell culture. Intracellularly, the autophagic response decreased (seen with the increase of p62 and with the decrease of LC3) and the oxidative stress increased (seen with the decrease of Nrf2).
Female heterozygotes of X‐linked ocular disease in the era of molecular diagnostics
Authors: KREPS E.O. , De Zaeytijd J. , De Baere E. , Leroy B.P.
Published: September 2015

Purpose

To investigate the accuracy of recognizing female heterozygotes for X‐linked retinitis pigmentosa (XLRP) and choroideraemia (CHM) using fundoscopy and blue‐light fundus autofluorescence (FAF).

Methods

Retrospective analysis revealed 26 female XLRP heterozygotes from 17 different families (age 3–77 years) and 8 CHM heterozygotes from 5 families (age 14–65 years). Molecular diagnosis has been obtained for all subjects.

Results

In XLRP, 17 of 26 patients (65.4%) mentioned nyctalopia. RPGR mutations were identified in 18 subjects – 9 of which in ORF15 – whereas a causative mutation was found in RP2 in the remaining 8 subjects. Dilated fundoscopy showed no abnormalities in 8 subjects, a tapetoid reflex in 2, regional pigmentary changes in 16 and full‐blown RP features in 2 patients. An abnormal FAF pattern was found in 18 of 26 patients (69.2%). Of the 26 molecularly proven heterozygotes, 23 (88.5%) showed abnormalities on fundoscopy and/or FAF. In CHM, only 1 of 8 patients – aged 40 – mentioned visual difficulties at night. In each of the 8 subjects, equatorial mottled pigmentary changes were evident. FAF revealed multiple hyper‐ and hypoautofluorescent flecks in all 8 patients. In both XLRP and CHM, clinical findings were independent of age or specific mutation.

Conclusions

Female heterozygotes of XLRP show abnormalities on dilated fundoscopy and/or blue‐light fundus autofluorescence in 88.5% of cases with a molecularly proven diagnosis. The most characteristic feature is a radial pattern of alternating areas of hyper‐ and hypoautofluorescence. In CHM, all carriers exhibit pigmentary changes in the retinal midperiphery and scattered autofluorescence changes, despite a lack of visual symptoms.
The P2X7 receptor is a potential therapeutic target for the treatment of Uveitis
Authors: Tempest‐Roe S. , Tam F. , Taylor S.
Published: September 2015

Purpose

Adenosine‐5′‐triphosphate (ATP) functions as an important extracellular messenger and plays a critical role as a danger signalling molecule during inflammation. In pathological conditions damaged cells leak high concentrations of ATP into the extracellular milieu, activating P2 Purinergic receptors which are highly expressed on immune cells. Pathological stimulation of the P2X7 receptor may be involved in the development of autoimmune disease, so we explored the impact of P2X7R antagonist treatment on the development of Experimental Autoimmune Uveitis (EAU) in mice.

Methods

EAU was induced in P2X7‐/‐ and wild‐type mice using IRBP peptide 1‐20(GPTHLFQPSLVLDMAKVLLD) with adjuvant Bordetella pertussis toxin. All procedures were performed under a Home Office License in accordance with the regulations of UK ASPA (1986). EAU was then induced in B10.rIII mice with RBP‐3 161‐180 (SGIPYIISYLHPGNTILHVD) and adjuvant Bordetella pertussis toxin. P2X7R antagonist A439079275 or vehicle were injected i.p. twice daily from day 12. p.i when clinical features of EAU manifested. Disease activity was observed through TEFI imaging and animals were treated until peak disease and termination at day 16 p.i.

Results

P2X7R deficiency protected against the development of EAU, with disease scores significantly lower in P2X7‐/‐ animals compared to control animals. P2X7R antagonist treatment with A439079 prevented development of severe EAU with disease scores in A439079 treated animals significantly lower than vehicle treated animals.

Conclusions

P2X7R deficiency protects against the development of EAU in mice and P2X7R antagonist can ameliorate established disease. The P2X7R may represent a viable therapeutic target for ocular inflammatory disease.
Estimated cerebrospinal fluid pressure and trans‐lamina cribrosa pressure difference in open angle glaucoma. The Korea National Health and Nutrition Examination Survey 2009‐2012
Authors: Lee S.H. , Kwak S.W. , Kang E.M. , Hong S. , Seong G.J. , Kim C.Y.
Published: September 2015

Purpose

To investigate associations of estimated cerebrospinal fluid pressure (CSFP) and trans‐lamina cribrosa pressure difference (TLCPD) with glaucomatous optic neuropathy in a population‐based setting.

Methods

A total of 6656 adults (≥40 years) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Subjects were divided into non‐glaucomatous and glaucomatous group, and glaucomatous subjects were further divided into normal tension glaucoma (NTG) group and high tension glaucoma (HTG) group. Based on a previous study with lumbar CSFP measurements, CSFP was estimated as CSFP (mmHg) = 0.55 Body Mass Index(kg/m2) + 0.16 Diastolic Blood Pressure(mmHg)‐0.18 × Age(years)−1.91. TLCPD was calculated as intraocular pressure (IOP)‐CSFP. Differences in estimated CSFP and TLCPD were assessed between the non‐glaucomatous and glaucomatous groups.

Results

In the non‐glaucomatous population (n = 6016), mean estimated CSFP was 11.38 ± 3.11 mmHg and mean TLCPD was 2.54 ± 3.83 mmHg. When compared to the glaucoma group (n = 640), lower IOP (p < 0.001), higher CSFP (p < 0.001), and lower TLCPD (p < 0.001) were observed in the non‐glaucomatous group. Differences between glaucomatous subjects and non‐glaucomatous subjects in estimated CSFP, TLCPD, and IOP were greater for the HTG subjects than for the NTG subjects.

Conclusions

Estimated CSFP and TLCPD may play a significant role in pathogenesis of NTG and HTG.
An algorithm combining two lesion‐detection methods of retinal microaneurysms for the reduction of human workload
Authors: Ometto G. , Bek T. , Al‐Diri B. , Hunter A.
Published: September 2015

Purpose

Reduction of workload in the detection of microaneurysms (MA) from retinal photographs is crucial for the diagnosis and screening of diabetic retinopathy. Automatic algorithms for the detection of retinal lesions can help reduce human intervention especially when the lesions are present in large numbers.

Methods

Two methods for lesion detection were combined in a single algorithm, one based on the analyses of the contrast between dark peak‐points and surrounding circular regions, and a second one based on the correlation between the intensity values in the photographs and a MA‐template. The two individual methods and the two methods combined were tested separately to compare their performance on retinal images from 26 high‐risk patients.

Results

Both individual lesion‐detection methods missed clustered MAs. With the exclusion of grouped lesions, the two methods combined showed higher sensitivity and precision than the contrast and template methods alone, identifying 22% and 13% more lesions respectively.

Conclusions

The combination of the two methods can provide repeatable detection of unclustered MAs in photographs from high‐risk patients. Manual intervention is only required to select grouped MAs and to adjust the automatic results, considerably reducing human workload.
The role of dendritic cells in non‐infectious anterior uveitis
Authors: O'Rourke M. , Canavan M. , Sweeney C. , Fletcher J. , Fearon U. , Murphy C.
Published: September 2015

Purpose

Noninfectious uveitis is characterised by influx of inflammatory cells into the immune‐privileged ocular microenvironment. Dendritic cells (DC) are powerful antigen presenting cells (APCs) and thereby initiate and perpetuate inflammation. Animal models of uveitis have suggested alterations in DC contribute to pathogenesis. Firstly, we examine the phenotype of circulating DC in anterior uveitis (AU). Secondly, we characterise the influxing inflammatory cells in the local micro‐environment of inflamed aqueous humor (AqH). Finally, the effect of this inflamed microenvironment on a DC model is examined.

Methods

Circulating DC were defined as HLA‐DR+, Lineage‐ and CD11c+. CD40, CD80 and CD83 cell surface expression was used to assess activation and maturation of circulating DC. Cells isolated from AqH obtained from AU patients (n = 5) and HC were assessed by flow cytometry based on cell size, granularity and cell surface expression. 1:2 dilution of AqH supernatant was cultured with monocyte derived DC (moDC) model obtained from a healthy donor for 48 hours and activation and maturation markers on moDC assessed.

Results

There is a decrease in circulating DC in AU patients compared to HC (p < 0.01). Circulating AU DC express higher CD40 (p < 0.05). Inflamed AqH contains >98% CD45+ cells. Populations of neutrophils (CD15+ HLA‐DR‐), T cells (CD3+ and either CD4+ or CD8+) and APCs (HLA‐DR+ CD11c+) were identified. HC AqH is devoid of CD45+ cells. AU AqH induces CD40 (p < 0.01) and CD80 (p < 0.01) expression on moDC compared to HC.

Conclusions

These results suggest that DC are recruited from the circulation to the eye during AU. AqH from AU patients can activate DC which will lead to initiation and propagation of inflammation. Current work examines functional effects on allogenic CD4+ T cell cocultures. These results suggest DC may be a useful therapeutic target in AU.
Reversal of ischemic retinopathy in ocular ischemic syndrome following carotid artery stenting
Authors: Esteban O. , Nuñez E. , Ascaso J. , Perez I. , Idoate A. , Sanchez J. , Cristobal J.
Published: September 2015

Purpose

Ocular ischemic syndrome (OIS), also known as hypoperfusion retinopathy is a rare ocular disease determined by chronic arterial hypoperfusion. The risk factors include age between 50–80 years, male gender (M:F = 2:1), arterial hypertension, diabetes mellitus, coronary disease (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The reported incidence is 7.5 cases per million persons every year and the five‐year mortality rate is 40%.

Methods

Interventional case report showing the role of the early diagnosis and treatment with carotid artery stenting in a patient with OIS.

Results

A 58‐year‐old patient with primary arterial hypertension, hypercholesterolemia obstruction of right renal artery presented with multiple episodes of amaurosis fugax with a 5–10 min of duration since three months ago in right eye. Physical examination revealed uncorrected distant visual acuity of 20/20 in each eye. Fundus examination showed dilated retinal veins and multiples microhemorrhages in the right eye. Peripheral retinal ischemia was identified with fluorescein angiography. Doppler ultrasound examination revealed a more than 90% stenosis of the right internal carotid artery. Retinal signs of ischemia improved and amaurosis fugax episodes disappeared two months following internal carotid artery stenting

Conclusions

The early diagnosis and treatment of patients with OIS have a major effect on their visual prognosis.
From devastation to restoration: trichosporon asahii can be beaten
Authors: Aydin Yaz Y. , Yildirim N. , Oz Y. , Sahin A. , Yaz Y.
Published: September 2015

Purpose

To report the first case of fungal keratitis caused by T. asahii which is treated succesfully with penetran keratoplasty.

Methods

A 79‐year‐old woman was attended to our clinic with pain and hyperemia in her left eye. The patient had undergone phacoemulsification and intraocular lens implantation surgery from her left eye 9 months ago, and after the surgery visual acuity had been reported 0,8. 4 months after the surgery bullous keratopathy was occurred and treated with bandage contact lens and topical steroids. When she was evaluated visual acuity was light perception and slit lamp examination showed in anterior segment a large keratitis area, central of keratitis area was melted, anterior chamber was shallow and hypopyon was occurred. In direct examination hyphae formation was seen.

Results

Fluconazole 200 mg 2 × 1, Cefazolin 50 mg/ml gtt per hour, Voriconazole %1 gtt per hour, Cyclopentolate %1 3 × 1, Phenilephrin %2.5 3 × 1, Tropicamide %1 3 × 1, Acetozolamide 250 mg 2 × 1 treatment were started empirical until the culture and antibiograme were resulted. Culture was resulted and Trichosporon asahii was isolated. The microorganism was sensitive for voriconazole and fluconazole, resistant for amphotericin B. According to the antibiograme results, systemic fluconazole and topical voriconazole treatment were continued. The keratitis area was healed with medical treatment but cornea was spontaneously perforated in 15th day of treatment and penetrating keratoplasty was performed immediately. After penetrating keratoplasty visual acuity was reached 0.1 and corneal graft was clear.

Conclusions

Fungal keratitis is vision threatening corneal disease causing by corneal ulceration. Trichosporon is one of the uncommon agent for fungal keratitis. This is the first case reported as a fungal keratitis caused by T. asahii treated successfully with penetrating keratoplasty.
Systemic IL‐1β production as a consequence of corneal HSV‐1 infection – contribution to the development of Herpes Simplex Keratitis
Authors: Murphy C. , de Chaumont C. , Shahnazaryan D. , Malone C. , Jefferies C. , Smith S. , Ni Gabhann J.
Published: September 2015

Purpose

Herpes Simplex Virus type‐1 (HSV‐1) infection can result in keratitis, a sight‐threatening disease that is the leading cause of infectious corneal blindness in the western world. HSV‐1 can invade the cornea and remain latent after treatment in the trigeminal ganglia. The pathogenesis of HSK involves a complex interaction between cytokines, chemokines and growth factors, either brought in by inflammatory cells or produced locally. Avoidance of these innate anti‐viral responses can cause lifelong recurrent infection, which in turn can cause progressive corneal scarring, vascularisation, thinning and the need for corneal transplantation to recover vision, often with poor long‐term outcome. This study aimed to investigate peripheral cytokine production in HSK patients with active and inactive infection to identify potential therapeutic targets.

Methods

Peripheral blood mononuclear cells and serum were prepared from whole blood taken from both healthy controls and HSK patients during active infection or following treatment. Protein expression levels were analysed by Western Blot. Cytokine levels were determined by multiplex ELISA.

Results

Active corneal HSV‐1 infection resulted in significantly elevated peripheral levels of the pro‐inflammatory cytokine IL‐1b in patients compared to healthy controls. IL‐1β levels remained significantly increased in these patients following treatment. Impaired production of pro‐inflammatory cytokines (including IL‐6, IL‐8 and TNF‐a) and anti‐viral factors (including IL‐12 and IFN‐g) was associated with significantly reduced expression of the transcription factors IRF3 and STAT1 in active patients compared to inactive patients.

Conclusions

Our data suggest that dysregulated peripheral production of pro‐inflammatory cytokines and anti‐viral factors may have implications for HSV‐1 viral clearance and recurrent keratitis.
Correlation of hyperreflective foci, status of photoreceptor layer, and visual acuity in diabetic macular edema
Authors: Chebil A. , Ben Abdallah M. , Kort F. , Hassairi A. , Maamouri R. , El Matri L.
Published: September 2015

Purpose

To investigate the correlation ofhyperreflective foci, photoreceptor integrity and visual acuity (VA) in patients with diabetic macular edema (DME).

Methods

Seventy‐eight patients (114 eyes) with DME were analyzed retrospectively with Spectral‐domain optical coherence tomography (SD‐OCT).

Results

SD‐OCT showed that 28 eyes (24.5%) had hyperreflective foci in the inner retinal layers, and 66 eyes (57.9%) had hyperreflective foci in the outer retinal layers. The logMAR VA was significantly (P < .0001) worse in eyes with hyperreflective foci in the outer retinal layers than in eyes without them (0.478 ± 0.241 vs 0.133 ± 0.233, respectively). Disruption of the ellipsoid zone and ELM line on OCT were significantly (respectively P < .0001 and P < .0001) associated with both hyperreflective foci in the outer retinal layers and poor logMAR VA.

Conclusions

The presence of hyperreflective foci in the outer retina is closely associated with a disrupted ELM and ellipsoid zone on SD‐OCT images and decreased VA in DME.
Prognostics factors of poor functionally response in ranibizumab treatment for diabetic macular edema
Authors: Jullien M. , Deken‐Delannoy V. , Labalette P.
Published: September 2015

Purpose

Purpose was to identify prognostics factors of poor functional response to anti‐ VEGF (ranibizumab) in diabetic macular edema (DME).

Methods

This retrospective study enrolled 36 eyes with DME treated with intravitral ranibizumab injections. The main outcome measures where the change in best corrected visual acuity (BCVA) after 12 months of treatment and its correlations with clinical findings.

Results

BCVA at baseline examination was 61 +/‐ 16 letters. In the final control after 12 months following injection, the median value of BCVA increased to 67 +/‐ 18 letters. Two groups were analyzed: the responder group (22 eyes or 61%) corresponding to patients with an increase in visual acuity at 12 months and non‐responders (39%). Sex, age, number of IVT, the focal laser history, blood pressure and diabetes duration evolution were similar in both groups. The median HbA1c was not significantly different between the 2 groups (p = 0.80). Patients who have received prior treatment (over 3 months before the first injection of ranibizumab) i.e. intravitreal injections of bevacizumab or intravitreal or sub‐Tenon triamcinolone acetonide injections were significantly more numerous in the non‐responder group (71.43% versus 27.3%, p = 0.0093). Best visual acuity was significantly different between the 2 groups at 3 months and 6 months compared to baseline (10.4 versus 2 letters, p = 0.02 at 3 months and 5 letters versus −2, p = 0.0004 at 6 months). Nine of the 19 eyes with available pictures of the fundus (47%) had extra‐foveal exudates. 89% of these patients were responders but the small number of patients did not allow statistical analysis.

Conclusions

In our study, the presence of previous treatments and the lack of response at 3 and 6 months are associated with poor functional response that could justify a management change.
Blepharitis and thin corneal thickness: An unexpected association
Authors: Trechot F. , Conaert J.B. , Perone J.M. , Angioi K.
Published: September 2015

Purpose

The aim of this study is to measure central corneal thickness in patients with blepharitis associated with meibomian gland dysfunction. Local inflammation and alteration of the tears film might result to corneal thinning.

Methods

All consecutive patients seen in consultation with blepharitis in our Department of Ophthalmology in November 2014 were included. Blepharitis clinic criteria were those reported by MGD workshop. Meanwhile a control group was set up. Patients with ophthalmic associated pathology, or recent history of ophthalmic surgery were excluded. The central corneal thickness was measured with a non contact pachymeter (NT 530P, Nidek, Jp).

Results

The study group was made of 40 eyes of 20 patients (11 men) with blepharitis, mean age was 58.5 ± 14.4. Forty eyes of 20 healthy patients (9 men) were used as a control group, mean age was 56.75 ± 13.39. The study group and the control group were comparable in gender and in age. In the study group, the mean central thickness was 527.5 μm ± 29.8 and in the control group mean central corneal thickness was 554.9 μm ± 24.7. There was statistically significant difference between the two groups using a Z normal distribution test.

Conclusions

Blepharitis may be associated with a thinner corneal thickness. Increased of osmolarity in the tear fluid and ocular surface inflammation are likely to be the cause of this decrease.
Standardising the Schirmer Test by Enclosing the Strip in a Waterproof Sheath
Authors: Willshire C. , Buckley R. , Bron A.J.
Published: September 2015

Purpose

Holly et al. (1984) showed that the wetting length of the Schirmer strip is influenced by evaporation and may be affected by ambient humidity. This could explain poor reproducibility in different environmental conditions. We therefore studied how preventing evaporation affected wetting length in different conditions of relative humidity.

Methods

A closed‐eye Schirmer test was performed bilaterally in 8 subjects with normal eyes (3 male; mean age 35.5 years SD ± 25), in a Weiss‐Gallenkamp controlled environmental chamber, at a temperature of 23°C and with a laminar airflow of 0.08 m/s. Tests were conducted at relative humidities (RH) of 25%, 15% and 5%, with a 10 min break between each test. Eyes received either a standard Schirmer paper (Whatman No. 41 – Biotech®), or a Schirmer paper clad in a waterproof sheath, on a random basis. Sheaths were constructed from a double layer of laminating plastic (Fellowes® ImageLast – outer layer: polyethylene terephthalate; inner layer: ethylene‐vinyl acetate), heat‐sealed to form a lightweight pouch. Papers were inserted, first on the right eye and then on the left. Wetting length was measured at 5 minutes. If full wetting occurred before this time, the time was noted.

Results

The wetting length was greater on the sheathed side in 23/24 tests. At 25% RH the mean difference in wetting length was 39.3% SD ± 14.7 (n = 8), at 15% RH the mean difference was 44.3% SD ± 17.8 (n = 8) and at 5% RH the mean difference was 56.3% SD ± 17.7 (n = 7). However, no significant difference was found in % means at different RH, P (0.287) > α ± (0.05) using a repeated measures ANOVA test.

Conclusions

Sheathing of the Schirmer strip frees the test from a dependence on ambient conditions that can vary seasonally, geographically and locally from clinic to clinic. Such standardisation would improve the performance and utility of the test.
Nuclear factor‐erythroid 2‐related factor‐2 (Nrf2) and peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) regulates proteolysis in cornea
Authors: Smedowski A. , Paterno J.J. , Amadio M. , Levonen A.L. , Tavi P. , Kaarniranta K. , Wylegala E.
Published: September 2015

Purpose

The cornea is exposed to constant oxidative stress that may lead to protein homeostasis imbalance and tissue damage during aging process. The ubiquitin‐proteasome pathway and the lysosomal pathway including autophagy are the major proteolytic systems to clean damaged proteins in cells. Our aim was to investigate the role of the Nrf2 and PGC‐1α, the central transcription factors of the regulation of cellular detoxification and defense against oxidative stress, in corneas of double knockout mice (Nrf2‐/PGC1α‐).

Methods

After fixation in 4% PFA, eyeballs were embedded in paraffin and 5 μm cross sections were cut using microtome. Tissue sections were deparaffinized, rehydrated and processed for immunostaining with primary antibodies against Beclin, HuR, p62 and LC3. Results were compared with age matching wild type controls.

Results

Deficiency of Nrf2 and PGC‐1α evoked accumulation of proteasomal ubiquitin and autophagy markers p62, Beclin and LC3 in one year old animals. Moreover, HuR that regulates p62 expression was highly up‐regulated in the cornea epithelium.

Conclusions

These results suggest that Nrf2 and PGC‐1α deficiency associates with the impaired proteasomal and autophagy clearance in the corneal epithelium. This might be linked to corneal diseases, such as macular dystrophy (Kaarniranta et al., 2015).
Investigating the blue sclera in osteogenesis imperfecta by in vivo confocal microscopy
Authors: Jullienne R. , Brehon A. , Perrot J.L. , Forest F. , Cinotti E. , Labeille B. , Peoc'h M. , Thuret G. , Gain P.
Published: September 2015

Purpose

The blue sclera appearance is a distinctive clinical sign for osteogenesis imperfecta (OI), a connective tissue disorder caused by an abnormality of type I collagen. It is a challenging diagnosis because multiple bone fractures, occurring in early childhood, can be the only sign of the non‐lethal forms of OI. In these situations, child abuse is a major concern for Paediatricians.

Aim

To investigate the in vivo confocal microscopy (IVCM) of the sclera and its characteristics as a diagnostic test for OI.

Methods

A father and his daughter suffering from OI gave informed consent for non‐invasive ocular examination. The cornea and sclera were examined with a handheld dermatological IVCM (VivaScope 3000, MAVIG GmbH/Lucid), which we pioneered for ophthalmological examination. The examination of two age matched healthy volunteers and corneoscleral donor tissues served as a control.

Results

The IVCM in OI shows a very specific and reproducible pattern where the collagen fibres have a well organised parallel alignment as would be expected within the clear corneal stroma. Collagen fibres were cross striated in the control.

Conclusions

These findings were consistent with the electron‐microscopic features previously described. The blue appearance results from the visualisation of the underlying choroid through the translucent sclera, which displays a specific parallel orientation of the collagen fibres. To the best of our knowledge, this is the first report of IVCM of the blue sclera. This rapid and non‐invasive imaging technique is an interesting diagnostic tool for challenging cases, especially in children, with multiple bone fractures.

GRANT: GIRCI RAA
Choroidal Thickness in Diabetic Patients without Diabetic Retinopathy
Authors: Ferreira J. , Vicente A. , Proença R. , Dias‐Santos A. , Santos B. , Cunha J.P. , Abegão Pinto L.
Published: September 2015

Purpose

To evaluate choroidal thickness (CT) in diabetic patients without diabetic retinopathy (DR) using enhanced depth imaging spectral‐domain optical coherence tomography (EDI SD‐OCT). To correlate CT with disease duration, systemic blood pressure (BP), glycemia, intraocular pressure (IOP) and ocular pulse amplitude (OPA).

Methods

Prospective, observational case‐control study. A complete ophthalmological examination was performed (visual acuity, refraction, Goldmann applanation and dynamic contour tonometries, fundoscopy and axial length). CT was assessed by a non‐invasive procedure using an EDI‐OCT (Spectralis Heidelberg) at 13 locations (subfoveal and 3 measurements 500 μm apart in all 4 directions – nasal, temporal, superior and inferior).

Results

180 patients were recruited: 130 diabetic patients with no DR and 50 healthy controls; one eye per patient included in the study. CT at 1500 μm above the fovea was significantly thicker in the diabetic group (239.9 ± 56 μm vs 268.2 ± 67.7 μm, p = 0.001). None of the other topographic region comparisons were statistically different (p > 0.05). In diabetic patients CT was not correlated with disease duration, BP, glycemia or IOP. CT was positively correlated with OPA in 12 points in diabetic patients (r between 0.19 and 0.27, p < 0.05) but not in the control group. CT variation coefficients in the diabetic group were statistically lower than in the control group (p < 0.01).

Conclusions

The thickening of the choroid at 1500 μm superior of the fovea in diabetic patients without DR may correspond to the diabetic choroidopathy in mid‐periphery presented before DR. Moreover, this tissue may be functionally different, as the pattern of correlations seems to differ between groups. Further studies are needed to explore these differences and the potential of the CT in the clinical setting.
A case report of eyelid basal cell carcinoma with orbital invasion: an alternative to exenteration
Authors: Jeancolas A.L. , Maalouf J. , Baudot A. , Ameloot F. , George J.L. , Angioi K.
Published: September 2015

Purpose

Basal cell carcinoma (BCC) is the most common periocular skin cancer affecting eyelids. Lateral canthus location is very rare. The gold standard treatment consists in an extensive surgery which allows the lowest recurrence rate. We report the case of a man suffering of a lateral canthus eyelid BCC with intraorbital invasion and who declined exenteration.

Methods

A 78‐year old man consulted his ophthalmologist for a painless right ptosis associated with a tumefaction of the external orbital angle. He had neither oculomotor disorders nor decreased visual acuity. He was refered to our clinic 6 months later; we noticed a worsening of the ptosis up to visual axis and an abduction limitation. Visual acuity was steady. Pathological analysis revealed the diagnosis of BCC. Orbital tomography showed a location near the lacrimal gland with posterior invasion along the lateral rectus muscle. Multidisciplinary meeting suggested performing an exenteration. The patient refused this treatment. A conservative surgery was then suggested. The patient has been informed about risks of dissemination.

Results

We performed a tumorectomy with large excision including the lateral part of upper and lower eyelids, the tumor itself, the lacrimal gland and the lateral orbital wall adjacent to the tumor. Pathological analysis revealed clear resection margins on all samples.The 4‐month control revealed no complications.

Conclusions

Exenteration is the gold standard treatment of orbital invasive BCC. In case of lateral canthus lesions, radiotherapy is not recommended because of major risks of orbital recurrences and side effects. Several authors showed that in case of bone‐adjacent tumors, bone resection is necessary, because tomography is not specific enough to rule out bone invasion. Despite a complete tumor resection, a long term follow‐up is mandatory patients with invasive BCC.
The influence of lingering fusional adaptation on the Bielschowsky head tilt test in superior oblique paresis
Authors: Irsch K. , Guyton D. , Ying H.
Published: September 2015

Purpose

To investigate how fusion influences the Bielschowsky head tilt test (BHTT) in unilateral superior oblique paresis (SOP).

Methods

In eight fusing patients, we correlated haploscopic‐determined fusion mechanisms with BHTT differences (BHTTD).

Results

Five patients used the vertical recti for vertical fusional vergence and had a mean±SD BHTTD of 22 ± 8PD. After a 30‐minute patch test one of those, in whom the test was performed, showed a decrease of 10PD. Two patients used the “paretic” superior oblique muscle (SOM) and the contralateral superior rectus muscle (SRM) to fuse, and had a mean ± SD BHTTD of 6 ± 8PD. The BHTTD of one, in whom a patch test was performed, increased by 11PD. The remaining patient used the “paretic” SOM and contralateral inferior oblique muscle (IOM) to fuse, and had a BHTTD of only 3PD, increasing to 21PD after patching.

One explanation for this behavior in the last patient involves lingering vergence adaptation of the “paretic” SOM and contralateral IOM, which makes these muscles more effective when activated on ipsilateral head tilt, lessening the expected increase in hyperdeviation. Similarly, in our patients with oblique/rectus‐mediated fusion, the vergence‐adapted “paretic” SOM and contralateral SRM are activated on ipsilateral and contralateral tilt respectively, lessening the hyperdeviation in both directions. In the other five patients, however, the vergence‐adapted ipsilateral IRM and contralateral SRM are activated on contralateral tilt, accentuating the BHTTD.

Conclusions

Fusion influences the BHTTD, either decreasing or increasing it depending on the particular muscles used for fusion. The absence of a positive BHTT should not be relied upon to rule out the diagnosis of SOP. In suspected SOP patients with fusion, performing the BHTT after a patch test may be necessary to bring out the BHTTD supporting the diagnosis.
Downregulating the Myocardin‐related transcription factor/ Serum response factor (MRTF/SRF) pathway is a novel therapeutic approach to prevent post‐surgical fibrosis in glaucoma
Authors: Yu‐Wai‐Man C. , Treisman R. , Khaw P.T. , Bailly M.
Published: September 2015

Purpose

Glaucoma is the first leading cause of irreversible blindness worldwide and fibrosis is the main cause of failure of glaucoma surgery. There are currently no available anti‐fibrotic treatments in the eye. We have previously described how the MRTF/SRF transcription pathway is intricately linked to all the key pathways in ocular fibrosis. We thus hypothesised that inhibiting the MRTF/SRF pathway would be a good therapeutic target to prevent fibrosis in the eye.

Methods

MRTF and SRF expression were knocked down in human Tenon's fibroblasts using small interfering RNAs, and three‐dimensional fibroblast‐populated collagen gels were used to measure contraction in vitro. Cytotoxicity was assessed using the live‐dead assay. Live cell imaging was used to study the cell protrusive behaviour during contraction and quantification was performed using a custom parameter, the dynamic index. Reflection confocal microscopy and DQ collagen were also used to measure matrix degradation. Real‐time qPCR was used to compare the gene expression of key matrix metalloproteinases in contracting gels.

Results

MRTF and SRF silencing significantly decreased collagen matrix contraction by 80% and 87% respectively. MRTF silencing did not impair cell viability compared to controls. Knocking down MRTF markedly reduced the protrusive behaviour of human Tenon's fibroblasts (dynamic index = 0.19 as compared to 0.66 for controls). MRTF silencing also significantly decreased matrix degradation and the expression of MMP‐1, MMP‐2, MMP‐9, and MMP‐14 genes.

Conclusions

Our study is the first to show that inhibiting the MRTF/SRF pathway significantly decreases collagen matrix contraction, cell protrusive behaviour of fibroblasts, and matrix degradation in the conjunctiva, and thus represents a promising new therapeutic approach to prevent post‐surgical fibrosis in glaucoma.
Semi‐automated reconstruction of inflammatory infiltration in infectious keratitis
Authors: Smedowski A. , Tarnawska D. , Wylegala E.
Published: September 2015

Purpose

To perform reconstruction of inflammatory cells infiltration in infectious keratitis.

Methods

First we performed in vivo confocal microscopy (HRT III, Rostock Cornea Module) in 118 patients diagnosed for the infectious keratitis (45 viral, 40 bacterial, 23 fungal, 10 amoebal). Inflammatory cytology has been analyzed according to morphology and size of cells forming infiltration. Microscopic scans were then processed with stereological software (MicroBrightField Inc, VT, USA) to track inflammatory cells within scans. Representative reconstructions of inflammatory cells infiltration has been created for each etiology of keratitis based on previous characterization of cells.

Results

Overall inflammatory cells densities showed no specificity for keratitis etiology, however there was clearly different participation of morphological types of cells depended on keratitis etiology. Leukocyte‐like, round cells represented approximately 4.4% of inflammatory cells in viral, 91.2% in bacterial, 50.4% in fungal and 54.4% in amoebal keratitis. Rest of cells were represented by different forms of dendritic cells, which were possible to track in stereology.

Conclusions

In vivo analysis of corneal epithelial cytology provides useful information about keratitis etiology. Reconstruction of inflammatory cells infiltration can help to create diagnostic algorithm for infectious keratitis diagnosis.
Management of unexplained haemorrhagic PVD at Southampton Eye Casualty Clinic
Authors: Shalaby A. , Tossounis C. , Andrew M.
Published: September 2015

Purpose

To assess the management of unexplained haemorrhagic PVDs at the Eye Casualty Clinic and compare it with suggested management plans in the literature. Finally suggest possible changes which could improve outcomes.

Methods

A retrospective review of patient electronic records at HICCS, e‐Documents and MEDISOFT databases over a 5‐month period (August 2014‐December 2014). All patients attending eye casualty clinic with a diagnosis of a haemorrhagic PVD were included. Patients with pre‐existing retinal neovascularisation or haemorrhagic ARMD and Macroaneurysms were excluded.

Results

There were 43 patients recorded with unexplained haemorrhagic PVDs in 5 months. 28/43 (65.1%) patients were seen and Discharged at the Eye Casualty Clinic in Max 2 visits. The remaining 15/43 (34.9%) patients were referred to VR OPD for further review. Of these, 7/15 patients had a retinopexy performed prior to VR OPD visit. The patients were seen by different doctors every time and of varying clinical experience (SHO, SpR, Fellow, Associate Specialist, Locum Consultant).

Conclusions

The retinal break was missed in 3/8 (37.5%) of the patients presenting at the Eye Casualty Clinic with an unexplained haemorrhagic PVD and a break despite the presence of a good fundus view.A significant number of patients (28/43, 65.1%) were managed solely at the Eye Casualty Clinic effectively.All the patients that had a laser retinopexy were referred to the VR OPD in 2 weeks for a review.

Suggestions

All patients with unexplained haemorrhagic PVDs and no fundal view should be referred to the VR service the same day for possible early vitrectomyAll patients with no obvious retinal break and reasonable view of their fundus (unless having a very clear view) must be referred to the VR OPD within 1 week for a more detailed fundoscopy.
Hyperreflective Dots in Spectral Domain Optical Coherence Tomography as Phenotypic Marker in Uveitis‐Associated Cystoid Macular Edema
Authors: Sellam A. , Massamba N. , Fel A. , LeHoang P. , Bodaghi B.
Published: September 2015

Purpose

To evaluate the agreement between hyperreflective dots (HRD) in retina layers by spectral domain optical coherence tomography (SD‐OCT) and laser flare photometry associated with best‐corrected visual acuity (BCVA) results in patients with uveitic cystoid macular edema (CME).

Methods

All patients referred to our tertiary care center for posterior uveitis had full examination including: BCVA, laser flare photometry, SD‐OCT, fluorescein and infracyanine angiography. §Causes of uveitis were multiple: infectious, inflammatory and unknown. The characteristics of the HRD were evaluated in all SD‐OCT scans. HRD were defined as small focal hyperreflective material scattered mainly in outer retinal layers but also spreading to all retinal layers observed in at least one available scan. Two different ophthalmologists counted HRD using a horizontal B scan cross section through the fovea. They were classified on the basis of quantity (i.e. absent, few if less than 10, moderate if between 10 and 20, or numerous if more than 20). Central macular thickness (CMT) was also evaluated.

Results

24 eyes of 18 patients were included. 8 men and 10 women with posterior uveitis were examined. Mean flare measurement was 25.1 (3–62). Mean BCVA was 20/63. Mean central macular thickness was 463 μm. 2 subgroups were identified. 13 eyes presented decreased BCVA, normal or elevated Flare, numerous HRD and increased CMT, corresponding to active posterior uveitis. Other 11 eyes presented decreased BCVA, increased CMT, normal laser Flare photometry, those results corresponding to chronic posterior uveitis. The difference with the two groups was numerically significant.

Conclusions

HRD are correlated to CMT and BCVA but not with anterior chamber flare in active posterior uveitis. A large prospective study is needed in order to confirm these results.