bluuebunny/crossref_metadata_2025 huggingface dataset:
Long term efficacy and tolerability of anti‐TNFα therapy in the treatment of non‐infectious uveitis – a surveillance study
Authors: DAMATO EM , DICK A , LEE RJW , SHARMA SM
Published: August 2012

Purpose To report the efficacy and tolerability of anti‐TNFα agents in the management of non‐infectious uveitis and scleritis in adult patients

Methods Forty adult patients treated for at least twelve months with anti‐TNFα therapy for non‐infectious uveitis or scleritis were identified using an online biologics registry. Data were collected regarding prednisolone doses, immunosuppressive agents, adverse effects and steroid rescues. The main outcome measures were 1. rates of reduction of daily prednisolone dose to 10mg, 5mg or less; 2. rates of reduction in concomitant immunosuppression 3. steroid rescues and 4.adverse events

Results In this patient cohort the use of anti‐TNFα therapy enabled the daily prednisolone dose to be maintained at 10mg or less per day in 80% of patients. The rate of steroid rescue was reduced from 0.79 rescues per person per year (PPY) to 0.29PPY following the use of anti‐TNFα therapy. In patients requiring more than 2 immunosuppressive agents at baseline, it was possible to reduce this to 1 or 0 in 80%

Conclusion This study supports the current use of anti‐TNFα agents in the management of adult patients with non‐infectious uveitis, whilst awaiting results of current on going randomized controlled trials. . Their use enables steroid sparing, a reduction in concurrent immunosuppressive agents and is associated with a lower risk of relapse. This is achieved with a low rate of adverse events.
Final results of an investigator initiated, multicenter randomised controlled trial of the efficacy of Adalimumab in active uveitis refractoty to standard treatment (ADUR)
Authors: MACKENSEN F , BECKER MD , JAKOB E , DOBNER BC , HEINZ C , LORENZ HM , HEILIGENHAUS A , MAX R
Published: August 2012

Purpose TNF alpha inhibitors have revolutionized the care of autoimmune diseases, among them severe cases of non‐infectious uveitis. Randomized clinical trials are lacking for this indication except for etanercept. We aimed to close this gap by initiating a randomized clinical trial testing Adalimumab (ADA) in severe forms of uveitis.

Methods Local and federal authorities approval has been obtained. Patients with active uveitis despite 0,1mg/kg/bodyweight of prednisone and already one immunosuppressive medication were eligible. Patients were randomized into either a therapy with ADA 40 mg s.c. every other week and high dose corticosteroids in a tapering regime or to increase the corticosteroids only. At three months main outcome parameters are assessed and efficacy determined. In case of treatment failure switch to the other arm was possible.

Results 25 patients were enrolled. The last patient will finish the trial in september 2012. 20 patients have been evaluated to date. The primary outcome criterion (Visual accuity improvement > 2 lines) was reached by 63.3% patients in the ADA group (mean improvement 0.29 logMar). In the control arm only 25% of patients improved > 2 lines. In parallel the control arm showed less reduction in inflammatory activity (reduction in activity score by a mean 2.89) as compared to the ADA group (mean reduction by 15.3 points).

Conclusion The results oft he trial show clear superiority of ADA over control in the treatment of severe uveitis forms in termy of visual accuity and inflammatory activty.

Commercial interest
New treatments for age related macular degeneration
Authors: MILLER JW
Published: August 2012

Treatment of age related macular degeneration (AMD) has progressed dramatically in the last 10 years, particularly in the neovascular stage of the disease. This has been accomplished in part through greater understanding of the pathophysiology of neovascular AMD and the role of VEGF in vessel growth and leakage. Anti‐VEGF treatment halts vision loss in more than 90% of patients, and leads to vision improvement in a third. Ideally, however, we would like to develop treatments that can prevent AMD or halt its progression as well as to prevent any vision loss, and this requires greater understanding of the earliest events in AMD. Genetic studies have identified associations with the CFH gene and HTRA‐1 gene amongst others, suggesting key pathways in the disease process. Delineating the dysfunction in these pathways through additional genetic and functional studies, and then developing effective interventions, is the current goal of AMD research. In addition, investigators seek to refine our current therapies as well as to improve current diagnostic modalities in order to better characterize the phenotype of AMD patients. Finally, since photoreceptor loss is the ultimate cause of vision loss in patients with AMD as well as other retinal disorders, investigations are ongoing to identify the molecular pathways of photoreceptor cell death and test therapies that might be used for neuroprotection.

Commercial interest
How to detach vitreous in macular diseases
Authors: GANDORFER A
Published: August 2012

Abstract not provided
ILM peeling in macular surgery: side‐effect
Authors: TADAYONI R
Published: August 2012

Purpose Discussing data on side effects of ILM peeling.

Conclusion ILM peeling induces anatomical and functional alteration of the retina that should be weigh up against its benefits.
An update on the vision simulator
Authors: CHATEAU N
Published: August 2012

Abstract not provided
Shack‐Hartmann aberrometry vs OQAS : the quarrel of the ancients and the moderns ?
Authors: GICQUEL JJ , PISELLA PJ
Published: August 2012

The Optical Quality Analysis System (OQAS) has the advantage over Hartmann‐Shack aberrometers of being capable of measuring both wavefront aberrations and scatter. In patients with eyes with mild scatter, both techniques give similar results. However in eyes severe amount of scatter, Hartmann‐Shack aberrometry may overestimate the quality of vision. On the other hand, the OQAS suffers from a certain level of background noise, generated by the choroid. During this presentation we will determine the current indications for those two techniques.
Scleritis: general concepts
Authors: PAVESIO C
Published: August 2012

Inflammation of the sclera may be a very serious condition, not only because it can produce structural damage to the globe and eventually result in blindness, but also because it may be a manifestation of a life‐threatening systemic disease. It is predominantly a disease of the middle aged and elderly, probably reflecting the age group of the commonly associated systemic diseases. Females are more likely to be affected, and no geographical or racial differences have been detected, either in incidence or prevalence. There is also no evidence of any genetic predisposition. The disease may start in one eye only but becomes bilateral in one third of the patients, the second eye becoming involved from three months to six years after the first. It is typically a very painful condition, but painless scleritis can occur. Clinical features of anterior and posterior scleritis will be discussed.
Infectious scleritis
Authors: WATSON P
Published: August 2012

Scleritis can occur as a result of an immunological response in systemic infectious diseases such as tuberculosis, leprosy, syphilis and lyme disease. These diseases are becoming more common and, as under‐treatment in many countries leads to incomplete elimination of the underlying infection, scleritis is becoming more common. Scleritis can also result from an immunological reponse to a systemic infection by bacteria, viruses , parasites or fungi. More rarely the sclera can be infected directly through the introduction of the organism into the sclera by trauma or from the spread of infection from adjacent sources. This is much more likely to happen if the tissue has been previously irradiated or surgically treated particularly after pterygium surgery. Infectious scleritis is less common than immunologically induced scleritis , diagnosis is difficult so treatment is often delayed and frequently incorrectly treated with steroids with sometimes disastrous consequences. Therefore in all patients with scleritis it is important to ask oneself: Could this be infective?
Scleritis and systemic diseases
Authors: LEE R
Published: August 2012

Abstract not provided
Is spectral domain optical coherence tomography useful in improving the contour line with the Heidelberg Retina Tomograph?
Authors: BRON A , FRANCOZ A , NICOT F , KOEHRER P , AHO S , CREUZOT‐GARCHER C
Published: August 2012

Purpose To compare the measurements of the optic disc in glaucoma patients and glaucoma suspects with spectral domain optical coherence tomography (SD‐OCT) and confocal scanning laser ophthalmoscopy (HRT) before and after adjustment of the contour line with the help of the OCT.

Methods In 109 consecutive patients (109 eyes), optic disc parameters were compared prospectively between the 2 devices before and after adjustment of the optic disc area (ODA) on the HRT3 with ODA obtained with the Cirrus SD‐OCT as a reference. Intraclass correlation coefficients (ICC) and the 95% limits of agreement (LoA) with Bland‐Altman plots were used to compare the agreement of the pre and post‐adjustment measurements with the OCT and the HRT.

Results The ICC for the optic disc area (ODA) was better after adjustment of the contour line on the HRT3 with the help of ODA obtained with the OCT, 0.785 and 0.985, respectively. However the ICC for the rim area (RA) was still moderate after the adjustment, 0.543 and 0.627 respectively. Other parameters C/D ratio, cup area and cup volume were almost unchanged. The 95% limits of agreement (LoA) with Bland‐Altman analysis were narrowed after the adjustment of the ODA, from ‐0.52 to + 0.71 mm2 to ‐0.12 to + 0.15 mm2. However the LoA remained wide for the RA even after correction of the contour line on the HRT with the help of the OCT, ‐0.32 to + 0.74 mm2 vs ‐0.23 to +0.61 mm2.

Conclusion SD‐OCT is an additional valuable tool in improving the placement of the contour line on the HRT. However the parameters of the optic disc measured by the 2 methods are not interchangeable.
The relationship between standard automated perimetry and retinal ganglion cell–inner plexiform layer thickness measured by the cirrus spectral domain optical coherence tomograph
Authors: SHIN HY , PARK HY , JUNG KI , PARK CK
Published: August 2012

Purpose To evaluate the strength and pattern of the relationship between the ganglion cell–inner plexiform layer (GCIPL) thickness measured with Cirrus high‐definition (HD)‐OCT and visual field (VF) assessed by standard automated perimetry (SAP).

Methods Ninety‐three eyes of 49 glaucoma patients were enrolled. In all patients, parameters of both GCIPL and the peripapillary retinal nerve fiber laye(pRNFL) thickness were measured by Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, CA). Mean sensitivity(MS) was recorded on the decibel (dB) and 1/L scales. The relationship between function and structure (GCIPL, pRNFL) was sought.

Results Correlations were seen between GCIPL sectors and RNFL sectors patients with glaucoma. (r = 0.38–0.792). Average GCIPL thickness and MD correlated most strongly of a strength similar to that demonstrated between average pRNFL thickness and MD. The highest correlations were observed between superior VF cluster (in dB scale) and inferior GCIPL thickness(R2=0.49) or inferior RNFL thickness (R2 = 0.51). Correlations were slightly greater with dB scale than 1/L scale.

Conclusion There was a moderate association between the GCIPL thickness and SAP. Cirrus HD‐OCT measurements of the GCIPL relate well with functional loss in patients with glaucomatous optic neuropathy.
A mutation in peroxidasin causes microphalmia and anterior segment dysgenesis in mice
Authors: YAN X , GRAW J
Published: August 2012

Purpose The purpose of this study was to analyze the phenotype of ENU induced Pxdn‐/‐ eyes in mice(KTA48 mutants) and investigate the molecular mechanisms of peroxidasin in eye development and disease.

Methods The eyes of the mutants were analyzed by morphologically and histologically. The molecular expression was measured by immunofluorescence, in situ hybridization and real time PCR.

Results The genome‐wide linkage analysis mapped the KTA48 mutation on chromosome 12; positional candidate gene analysis detected a mutation in the Pxdn gene (encoding peroxidasin) co‐segregating with the mutation. The Pxdn‐mRNA of the KTA48 mutants contains a T‐>A mutation at pos. 3816 (T3816A) creating a new Alw26I restriction site; the mutation converts the Cys at codon 1272 into a stop codon (Cys1272X).Whole mount immunostaining showed that peroxidasin is mainly expressed in the eye at E9.5. Immunostaining study showed peroxidasin is mainly express in the eye lids, developing cornea, lens, inner retina at embryonic stages. At E15.5, the phenotype of the homozygous mutant is most obvious but varies little, with its different tissues (especially anterior segment) severely impaired. At P11 Pxdn‐/‐ mice showed further anomalies in addition to the phenotype in embryonic eyes, including congenital corneal opacity, congenital cataract and congenital glaucoma. Real‐time PCR showed the expression of Pax6 is dramatically increased at E15.5 Pxdn‐/‐ eyes compared to wild‐type eyes, which was confirmed by immunofluorescence and in‐situ hybridization.

Conclusion Our findings demonstrate a requirement for peroxidasin in normal eye development, which may be through regulating Pax6 expression.
Polymorphism of endothelial nitric oxide synthase T786C in patients with normal tension glaucoma and primary open angle glaucoma
Authors: LUKASIK U , KOSIOR‐JARECKA E , WROBEL‐DUDZINSKA D , KUSMIREK K , KOCKI J , ZARNOWSKI T
Published: August 2012

Purpose Comparison of allelic variant frequency of eNOS gene T786C in patients with normal tension glaucoma and primary open angle glaucoma.

Methods The studied group constituted 97 patients with NTG and 49 patients with POAG. DNA was isolated from peripheral blood and T786C polymorphism was studied by RT‐PCR method.

Results In NTG patients TT genotype was present in 36% patients, TC in 52.6% and CC in 11.3%. In POAG patients genotype TT was detected in 42.9% persons, TC in 48.9% and CC in 8.2%. The difference in allelic frequency was not statistically significant (p=0.75). In women with NTG the allelic frequency was similar to men (respectively, in women: TT‐35.9%, TC‐48.4%, CC‐15.6% and men TT‐36.4%, TC‐60.6%, CC‐3%; p=0.92). In group of women with POAG the allelic frequency was also similar to men (in women: TT‐41.2%, TC‐50%, CC‐8.8% and men: TT‐46.7%, TC‐46.7% a CC‐6.7%; p=0.09). Comparing the difference in genotype frequencies between both glaucoma types no significant difference was detected in women (p=0.9) and men (p=0.7). The CC genotype was most frequently present in NTG women (15.6%), comparing to NTG men (3%) and POAG women (8.8%).

Conclusion The frequency of particular genotypes of T786C polymorphism of eNOS gene did not significantly differ in patients with NTG and POAG, yet the mutated allelic form is most frequent in NTG women.
Non invasive tear film break‐up time and blinking
Authors: NEPP J
Published: August 2012

Purpose The break‐up time of the tear film for evaluation of dry eyes is performed with fluorescein in blue light of the slit lamp. Errors may occure by the observer and has to be repeated for accurat results. The BUT can also be seen with a Keratograph 4 (KG‐BUT). In this pilot‐study we want to evaluate the measurements with KG‐BUT in patients with dry eyes. The Fluorescein‐BUT (FL‐BUT) and the KG‐BUT was compared and we observed the correlation of both kinds of BUT with the Lid‐opening‐time LOT. So we wanted to find out, if the KG‐BUT is more accurate compared to the FL‐BUT.

Methods 17 eyes of 10 patients were observed. The keratograph 4 of Oculus was used for measurements, five times for each eye. Than the measurement of the LOT was done in ten blink‐intervalls. At last the FL‐BUT was measured at the slit lamp, three time repeated. The BUT was performed single blinded by two different observers. We compared the mean time of each patient of KG‐BUT with Fl‐BUT and both with the LOT . For statistic analysis the Pearson correlation was used.

Results The Fl‐BUT was 4,2 sec average, (0,7‐8sec for single patients, stdev 1,8) the KG‐BUT 5,6 sec average (1,2‐14,5sec; stdev 4,13). The LOT was 3,6 sec average (1,75 ‐6,3sec; stdev 1,8). There was no significant correlation between Fl‐BUT and KG‐BUT (R: ‐20),no correlation between LOT and KG BUT (R:8). There was a positive correlation between Fl‐BUT and LOT (R: 50).

Conclusion This pilot study point at a relation of Fl‐BUT with the lid opening time LOT. The clinic observation seemes to be more accurate than the measurement with the Keratograph. But as the KG‐BUT is independent from the observer and without contact further observations have to be performed additionally.
The lid margin and Demodex
Authors: HORWATH‐WINTER J , RABENSTEINER DF , SCHWANTZER G , BOLDIN I , FISCHL M , WACHSWENDER C , HALLER‐SCHOBER EM , SCHMUT O
Published: August 2012

Purpose Demodex infestation can be associated with blepharitis. To date, the pathogenic potential of these mites in Meibomian Gland Dysfunction (MGD) remains unclear. The purpose of this study was to determine the relationship between the prevalence of Demodex in eyelashes and changes of the anterior and posterior lid margin.

Methods Between October 2011 and March 2012, 229 consecutive patients with ocular discomfort from the dry eye unit of the Ophthalmological Department, Medical University Graz, Austria, were investigated for the presence of Demodex mites on sampled eyelashes. Lid margins were evaluated according to scales, vascularisation, Marx line, expressibility and quality of meibomian gland secretion.

Results Demodex spp. were found in 40.2% of patients with ocular discomfort. The presence of Demodex mites was significantly associated to blepharitis. No difference in Demodex occurrence was found between the sexes. Compared to the non‐infested, patients with Demodex mites had significantly more scales formed as sleeves, a higher Marx line score and a lower quality of the meibomian gland secretion. No significant association was observed with vascularisation of the lid margins and expressibility of meibomian glands. Within the infested patients the mean Demodex count per patient was 3.28 ± 2.89 and Demodex count was found to increase with increasing age.

Conclusion Demodex mites are associated with changes of the anterior and posterior lid margin and therefore may play a pathogenic role in blepharitis and MGD.
Ocular surface in surgery
Authors: DUA H
Published: August 2012

Abstract not provided
Coats disease: fluorescein angiography guided management
Authors: SUZANI M , MOORE AT
Published: August 2012

Purpose To study the anatomical and visual outcome of patients (pts) with Coats disease treated with laser or cryotherapy on the basis of fluorescein angiography (FA) findings.

Methods 28 children, mean age at diagnosis 6 ys, have been included. They all underwent examination under anaesthesia, fluorescein angiography (FA) with RetCam and laser treatment or cryotherapy. Changes in best corrected visual acuity (VA) pre and post treatment were recorded. Retinal imaging was repeated when possible.

Results 6 pts were classified as Stage 2a, 17 as Stage 2b, 4 as stage 3Ai, one as Stage 3b. In the 25 patients who had FA, 15 had telangectatic vessels for less than 6 clock hours, mainly in the temporal periphery, and in 10 they involved more than 6 clock hours. FA showed areas of capillary bed closure starting from the area of the telangectasia up to 360 degree in the retinal periphery. 21 patients were treated with laser photocoagulation, 2 with cryotherapy and 4 with cryotherapy and laser to the telangectatic vessels and peripheral ischaemic areas. After treatment, 22 pts showed reduced exudation or no change, 6 pts had an increase in exudation and required further laser or cryo therapy. 9 pts with stage 2b showed improvement or stabilization of VA, in 4 VA deteriorated. All pts with stage 2a maintained good VA.

Conclusion FA provides useful information about the distribution of telangectasia and of ischaemic areas in Coats disease. Laser treatment to the telangectatic vessels and ischaemic area is effective in improving the anatomical outcome and preserve vision. FA is helpful in guiding treatment and reduces the number of treatments necessary.
Influence of cataract in reproducibility of Optical Coherence Tomography measurements
Authors: BAMBO M , FERRANDEZ B , GARCIA‐MARTIN E , GIL‐ARRIBAS L , ARA M , SATUE M
Published: August 2012

Purpose To evaluate the effect of lens opacities in quality of images and reproducibility of retinal nerve fiber layer (RNFL) thickness measurements using Spectralis Optical Coherence Tomography (OCT).

Methods Fifty eyes of 50 subjects (25 men and 25 women; aged from 62 to 88 years) underwent three 360° circular scans centred on the optic disc by the same experienced examiner using the “RNFL Fast” Glaucoma Application and the “RNFL‐N Fast” Axonal Application of Spectralis OCT instrument one month before and one month after cataract surgery. Comparison between the two visits and changes in reproducibility (using intra‐class correlation coefficients and coefficients of variation) were analyzed. The quality of images was also compared between both visits.

Results RNFL and RNFL‐N differences were detected between both visits for average thickness, temporal and nasal quadrants (p<0.05) using Glaucoma Application and for inferior and nasal quadrants (p<0.05) with Axonal Application. RNFL average thickness was 99.6 µm in pre‐surgery visit and 102.4 µm in post‐surgery visit using Glaucoma Application; and 94.3 and 94.7 µm, respectively, with Axonal Application. Reproducibility shows better values in post‐surgery evaluation (mean coefficient of variation of 5.55% in pre‐surgery visit vs 4.32% in post‐surgery). Intra‐class correlation coefficients were higher than 0.834 in all visits and parameters, so reliability of Spectralis measurements was high with both Spectralis OCT applications. The quality of images was better in post‐surgery evaluations.

Conclusion The measurements of RNFL thickness and the reproducibility of Spectralis OCT are affected by lens opacity.
European Vision Award 2012: From chickens to humans ‐ learning about the puzzles of myopia
Authors: SCHAEFFEL F
Published: August 2012

After it was found that the growing vertebrate eye uses the focus of the retinal image to fine‐tune its axial length to the focal length of the optics, it seemed as if the solution of the problem of myopia was in close reach. While a lot was learned about the fascinating details of biological mechanisms coordinating eye growth by vision from animal experiments, it is still a puzzle why eyes of children start to deviate from the correct path and become too long. Currently, a major challenge is to find out which details of visual experience in kids may have a similar effect as wearing a negative lens or a diffuser ‐ since these are the two treatments that induce axial myopia in animal models. The talk will also review some current attempts to slow down the progression of myopia once it had already started.
Cis‐urocanic acid inhibits conjunctivitis and blepharitis in rat model of acute eye irritation
Authors: JAUHONEN HM , VIIRI J , KAARNIRANTA K , LAIHIA JK , LEINO L
Published: August 2012

Purpose In vitro studies have shown anti‐inflammatory and cytoprotective effects of cis‐urocanic acid (cis‐UCA) in human ocular epithelial cells exposed to UV‐B irradiation. In this study, we aimed to investigate the efficacy of topical cis‐UCA against compound 48/80 induced eye irritation in a rat model.

Methods Adult Wistar rats in groups of six animals were treated with 1000 µg/ml compound 48/80 in both eyes. Cis‐UCA 0.5% solution, corticosteroid dexamethasone 1 mg/ml (Oftan® Dexa), antihistamine ketotifen 0.25 mg/ml (Zaditen), or PBS was applied in both eyes at time points 0.5, 6, and 12 h after application of compound 48/80. Clinical signs of ocular inflammation were evaluated by scoring from photographs by ophthalmologist 1, 6, 12, and 24 h after the last drug application.

Results Cis‐UCA solution attenuated conjunctival hyperemia in compound 48/80 irritated eyes equally well compared to dexamethasone and ketotifen. At time points 12 and 24 h, the mean decrease in severity score was 50% and 40%, respectively, for the cis‐UCA group. Redness of the eyelid margin was prevented best by ketotifen at 1‐h time point, whereas cis‐UCA and dexamethasone almost completely abolished lid redness at 6, 12, and 24 h.

Conclusion These results suggest that cis‐UCA has an anti‐inflammatory effect in acute eye irritation, which is comparable to corticosteroid dexamethasone and antihistamine ketotifen.
Scleritis, clinical features, etiological diagnosis and treatment : a review of 32 cases
Authors: LEAL C , LE ROUX K , RAHMI A , SèVE P , DENIS P , KODJIKIAN L
Published: August 2012

Purpose To evaluate the various clinical presentations, etiological diagnosis and prognosis of patients with scleritis at a tertiary care eye center.

Methods Retrospective, monocentric and analytical study on a series of 32 patients with scleritis seen in the departments of Ophthalmology and Internal Medicine at Croix‐Rousse University Hospital, Lyon, France from 2004 through 2011.

Results The mean age of patients with scleritis was 46.8 years (range 22‐77years). Nineteen of the patients were women and 13 were men. Twenty‐six patients (81%) had anterior scleritis (15 nodular, 8 diffuse and 3 necrotizing), six (19%) had posterior scleritis. Unilateral inflammation was present in 24 patients (75%). Twelve of the 32 patients (37.5%) had a systemic disease : Wegener's granulomatosis (n = 3),Behçet's disease (n = 2), unspecified inflammatory arthritis (n = 2), psoriatic arthritis (n = 1),ankylosing spondylitis (n = 1), sarcoidosis (n = 1), Cogan's syndrome (n = 1), ulcerative colitis (n = 1). Six patients (18.8%) were suspected of having infectious disease with herpes : clinical context and positive treatment response with oral valacyclovir. Systemic agents and topical agents were required in 28 patients (87.5%). The first line therapy was mainly oral non steroidal anti‐inflammatory drugs in 15 patients (47%) and oral corticosteroids in 8 (25%). Immunosuppressive drugs were required in 6 patients, 4 with systemic disease. The mean follow‐up was 16.3 months.

Conclusion The number of systemic disease in our series is similar to the main series in the literature. Treatment with valacyclovir might be effective in patients with suspected herpes simplex scleritis.
Ocular toxoplasmosis: patient age and other risk factors for a severe course of disease
Authors: PLEYER U , MäNZ M , FELS G , METZNER S , HAZIROLAN D , JOHNSEN J
Published: August 2012

Purpose Atypical disease courses of ocular toxoplasmosis (OT) have been reported in elderly patients. The aim of this study was to determine whether patient age is correlated with relevant clinical parameters.

Methods A retrospective clinical study and statistical analysis was conducted on patients (n=180) with active OT.

Results The age of first disease manifestation showed a clear unimodal distribution with a median incidence peak at age 26 while recurrences did not follow an age specific pattern (median= 35 years). First manifestation of OT or recurrence occurring after the age of 35 are associated with larger lesion size (2‐3 PD; contingency coefficient [CC]=0.304; p=0.047; n=60) and (CC=0.32; p=0.009) respectively. Additionally, older patients displayed uveitis anterior (63.2%; p=0.055; n=56) and vitreous involvement (89.5%; p=0.054; n=78) more frequently. Complications during OT (secondary IOP, macula and peripapillary edema, ablatio) did not correlate with patient age, but were attributable to localisation of lesions (central= 29.2% vs. peripheral=9%; p=0.039). Recurrences were present in 70% of patients (47.9%:1‐3 episodes vs. 21.8%:4‐7 episodes), whereas bi‐ocular OT always predisposes for recurrences. Standard therapy consisted of clindamycin. Large OT lesions more frequently required systemic steroid treatment (72.9% in 2‐3 PD cases vs. 48.3% in 1 PD cases; CC=0.271; p=0.007; n=124).

Conclusion Patient age was significantly correlated with lesion size and inflammatory involvement of the anterior part of the eye. Localisation of lesions is a predictor for complications.
Miltefosine and polyhexamethylene biguanide, a new drug combination for the treatment of Acanthamoeba keratitis. Results from in‐vivo toxicological and efficacy studies
Authors: OBWALLER A , POLAT ZA , WALOCHNIK J , VURAL A , DURSUM A , ARICI MK
Published: August 2012

Purpose Miltefosine (MLT) and combinations of Miltefosine and polyhexamethylene biguanide (PHMB), chlorhexidine (CHX), and propamidine isethionate (PI), respectively, have been tested in a rat efficacy model for treatment of Acanthamoeba keratitis. In a second step, the most promising treatment regimens from efficacy studies have been tested for local tolerance in a fully GLP‐compliant toxicological study in pigmented rabbits.

Methods The cornea of rats were infected with Acanthamoeba hatchetti. Cornea infections were graded microscopically. Nine groups were treated with varous treatment regimens for 28 days (8 times per day during the first week, and 3 times per day for the last three weeks). Efficacy of treatment was examined by determination of the degree of infection and culturing of excised eyes after the end of the treatment period. On day 28 the eyes were inspected under the microscope, re‐graded and were then compered with the grades before starting the therapy.

Results Best treatment results were obtained from PHMB‐MLT group. The ratio of fully recovered eyes was 28.4%. The highets therapeutic activity was yielded by the combination MLT‐PHMB (86%), followed by MLT, CHX, or PI (72%) and the combination MLT–PI (70%. The fully GLP‐compliant study in pigmented rabbits (28 days, 8 treatments per day) showed excellent local tolerance.

Conclusion Thus the combination of Miltefosine and PHMB can be seen as a highly effective and save option for treatment of AK.
Time profile of viral DNA in aqueous humor of patients treated for VZV acute retinal necrosis using quantitative real‐time PCR
Authors: CHIQUET C , LABETOULLE M , GERMI R , BERNHEIM D , MORAND P , ROMANET JP
Published: August 2012

Purpose To evaluate the kinetics of varicella zoster virus (VZV) load using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Design: Cohort study, evaluation of diagnostic test or technology.

Methods Six patients (52±13 years) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from all eyes for qPCR evaluation. The patients were treated with intravenous aciclovir and intravitreal injections of antiviral drugs. The mean follow‐up was 17.6±16.4 months.

Results Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8±24.9 days) followed by a decrease in the number of viral genome copies. The mean baseline viral load was 3.4×107±4.45×107copies/ml (6×106 to 1.2×108). The viral load decreased following a logarithmic model, with a 50% reduction obtained in 3±0.7 days. There was a significant viral load (> 102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs.

Conclusion qPCR use demonstrated reproducible VZV DNA kinetics with a two‐phase evolution: plateau followed by logarithmic decrease. These data suggest that high‐dosage antiviral therapy during the conventional 10 days duration is insufficient in most patients. This patient's series responded with a similar decrease in viral load once initiated, this may be used to predict the progression of future patients. The correlation of the viral load threshold with clinical improvement needs to be more clearly defined.
Aquaporins in glaucoma eyes
Authors: TRAN TL , BEK T , HAMANN S , HEEGAARD S
Published: August 2012

Purpose Glaucoma is a neurodegenerative disorder with loss of retinal ganglion cells and axons. Elevated intraocular pressure is a significant risk factor in the development of glaucoma. Aqueous humour secretion is in part maintained by the aquaporins (AQPs) and AQPs also regulate fluid homeostasis in the retina. We investigate the expression of AQP1, ‐3, ‐4, ‐5, ‐7 and ‐9 in human glaucoma eyes compared to control normal eyes.

Methods Immunohistochemistry for AQP1, ‐3, ‐4, ‐5, ‐7 and ‐9 was performed on human paraffin embedded eyes. Nine glaucoma eyes were examined comprising three eyes diagnosed with simplex glaucoma, three eyes with neovascular glaucoma and three eyes with chronic angle closure glaucoma. The six control eyes had normal intraocular pressure without glaucoma. From each immunohistochemical slide representative fields (x20 objective) within the eye were captured. Using Photoshop software optical densities were generated and indices of staining intensity were calculated.

Results Immunostaining showed labeling of AQP7 in the Müller cell endfeet with an increased intensity in glaucoma eyes (p=0,02). AQP9 labeling of the retinal ganglion cells showed decreased intensity per cell (p=0,005). In the optic nerve there were no difference in AQP1, AQP4 and AQP9 labeling in the optic nerve astrocytes between normal and glaucoma eyes

Conclusion This is the first study investigating the AQPs in human glaucoma eyes. We found a reduced expression of AQP9 in retinal ganglion cells in glaucoma eyes. Glaucoma also induced increased AQP7 expression in the Müller cell endfeet. These results suggest that changes in retinal AQP expression are associated with the development of glaucoma
Ocular perfusion pressure – a risk factor for open‐angle glaucoma or a statistical artifact?
Authors: JANSONIUS NM , RAMDAS WD , WOLFS RCW , HOFMAN A , DE JONG PTVM , VINGERLING J
Published: August 2012

Purpose Epidemiological studies have reported ocular perfusion pressure (OPP) as a risk factor for open‐angle glaucoma (OAG). OPP is essentially the difference between blood pressure and intraocular pressure (IOP). IOP is thus part of OPP. As IOP itself is a strong OAG risk factor, the crucial question is whether the linear adjustment for IOP as commonly used in statistical models is sufficient to remove all confounding by IOP ‐ a prerequisite to consider OPP an independent risk factor if significant after adjustment for IOP. This question was addressed in our study.

Methods We performed Cox regression on longitudinal data from the Rotterdam Study comprising 103 incident OAG cases and 3779 controls. All models were adjusted for age, gender and IOP. First, we entered diastolic OPP (DOPP) in the model as tertiles. Next, we entered systolic OPP (SOPP). Subsequently, we replaced the blood pressure values in DOPP and SOPP by normally distributed random numbers. Based on the diastolic and systolic blood pressure distributions in our data, we used standard deviation (SD) values of 10 and 20 mmHg. For both SD values, the analyses were repeated 10 times.

Results The hazard ratio (HR) for the lowest tertile of DOPP was 1.11 (95% confidence interval 0.68‐1.83) and of SOPP 1.21 (0.74‐1.98). The median (range) HR of the lowest tertile of the resampled DOPPs (diastolic blood pressure replaced by noise with a SD of 10 mmHg) was 1.27 (1.03‐1.97) and of the resampled SOPPs (systolic blood pressure replaced by noise with a SD of 20 mmHg) 0.99 (0.72‐1.35).

Conclusion Residual confounding by IOP can reveal a significant spurious association between a low DOPP and incident OAG with HRs similar to those reported in the literature.
Analysis of eye hydrodynamics on the basis of tests with a mechanical load applied
Authors: STEIN A , LYUBIMOV G , MOISEEVA I , IOMDINA E , NAZARENKO L
Published: August 2012

Purpose To use the results of tonography and other measurements on the mechanically loaded eye for obtaining information about its hydraulic system.

Methods We carried out tests of two types: standard 4 min tonography using a digital indentation tonograph Glautest‐60 and discrete IOP measurements for up to 20 min after the load was removed. The experimental data were processed on the basis of our model of the eyeball as an elastic water‐filled shell, which makes it possible to correctly estimate the individual elastic properties. The entire pressure vs. time tonography curve was used.

Results We introduce two parameters measurable from tonography: the IOP stabilization time and the limiting pressure in the loaded eye (the standard processing method yields one parameter). This and comparison with other data, including those available from literature, enabled us to test different hypotheses that specify the model and make it possible to calculate the hydraulic characteristics, e.g., the outflow facility coefficient. It is shown that the set of assumptions commonly used in processing the tonography data is inconsistent with the facts. The most intriguing are the apparent increase in the output (episcleral vein) pressure and the presence in the system of two characteristic times. Possible mechanisms to which these observations can be attributed are the pressure dependence of the outflow resistance and the capacitance of the outflow system.

Conclusion Under mechanical actions, in the hydraulic system of the eye substantial changes occur. The correct interpretation of these, strongly individual, changes may be important for diagnostics. Tonography may be a useful tool but the method of processing its data needs modification.
Who wants it?
Authors: HALL G
Published: August 2012

Purpose Until recently, genetic testing in retinal dystrophy has been limited to a small proportion of families. Next Generation Sequencing is now being developed within clinical laboratories to deliver genetic testing to a much greater number of families. Retinal dystrophy is a very heterogenous condition affecting 1 in 3,000 people, but with new NGS technology, we now estimate that mutations can be identified in around 60‐70% of families.

Results Understanding the clinical utility and applicability of testing in the care and management of families will be very important. Research suggests that patients want genetic testing in order to confirm the inheritance pattern in the family, identify those at risk and to give hope of future gene‐based therapies in the future.

Conclusion We report on our experience in the genetic eye clinic since the introduction of NGS testing, the impact on families and some of the complexities including the identification of de‐novo dominant mutations in sporadic cases as well as unexpected syndrome diagnoses.
Foveal changes during ocular movements in normal eyes. A prospective study.Kinetics of posterior pole during ocular movements in various diseases:a videomorphing technique
Authors: THEOCHARIS IP
Published: August 2012

Purpose To reveal the structural changes of the fovea and the posterior pole during ocular movements (OM) and specifically from the temporal gaze to nasal gaze.Videomorphing is proposed to study the kinetics of posterior pole during OM in various diseases.

Methods A prospective controlled study.The right normal eye of healthy individuals was enrolled. SD OCT cube scans were used. The central fovea thickness (CFT) was chosen as the primary measurement.The measurements were obtained at the primary positions and at the temporal and nasal gaze.Four CFT values were recorded:the CFTtemp at the temporal gaze with a vertex1 distance ,the CFTnasal at the nasal gaze with a vertex2 distance,the CFT1 at the vertex1 and the straightforward position and the CFT2 at the vertex2 and the straightforward position.The absolute difference between the CFT temp‐CFT nasal was compared with the absolute difference between CFT1‐CFT2 at the straightforward position of every patient . Paired t‐test was used.Videomorphing of the OCT images with the same method was used to animate the posterior pole deformation during horizontal OM in healthy individuals,in patients with dry and wet AMD,with CSC and with high myopia.

Results 20 patients were included.The |CFT1‐CFT2| ranged from 1μm to 4μm with mean value 1.6μm. |CFTtemp‐CFTnasal| ranged from 1μm to 10μm with mean 5.8μm.(p= 0.0013). Videomorping revealed oscillation of the posterior pole during OM with specific characteristics for every disease.

Conclusion CFT showed significant fluctuation during ocular movements. Animation of posterior pole deformation during OM show different characteristics between normal eyes , AMD , CSC and high myopic eyes.
Vascular network of the human macula from OCT
Authors: RODRIGUES P , GUIMARAES P , BERNARDES R , SERRANHO P
Published: August 2012

Purpose To compute the vascular network of the human macula from spectral‐domain optical coherence tomography (OCT) to an extent similar to that of color fundus photography (CFP).

Methods Macular cube protocol scans of 512x128x1024 and 200x200x1024 voxels of 20 eyes from 13 type 2 diabetic patients and 10 eyes from 10 healthy volunteers were collected from the Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, CA, USA) database. Additionally, CFPs and fluorescein angiograms (FAs) from the patients' eyes were gathered from the imaging database. Three distinct fundus references were computed from the OCT volumes after proper preprocessing. An additional OCT fundus image (OCTref) is computed as the principal component of these 3 OCT fundus references. The visible vascular network was manually segmented on CFP, FA and OCTref for comparison. Finally, a support vector machine (SVM) pattern classification algorithm was used to classify each pixel of the OCTref image into the vessel or non‐vessel classes from a set of 14 features computed from the OCT fundus references.

Results Over 67% (67.8(7.2)%, average(SD)) of the vascular network manually segmented from the FA was manually segmented from the CFP, while this percentage raises to 69.2(8.9)% for OCT. In this way, the OCTref allows to compute an extended vascular network as compared to the CFP (102.8(14.4)%). When comparing the automatic versus the manual vascular segmentation, a specificity of 99.4(0.2)% and a sensitivity of 83.9(4.0)% were obtained. Overall, the accuracy of the automatic classification is of 98.0(0.4)%.

Conclusion The proposed algorithm allows for the segmentation of the vascular network from OCT scans of the ocular fundus to a level similar to that of color fundus photography.
Observation of fundus using a novel high‐speed and high resolution optical coherent tomography: a preliminary report
Authors: YONEYA S , BABA M , SUZUKI M , KURODA H
Published: August 2012

Purpose to evaluate capability of femto‐second white laser in observing the fundus when applying it to optical coherent tomography (OCT) as a light source.

Methods We have successfully developed 8 fs cw mode0locked Titanium Sapphire (TiS) laser which had broad band with ranging from 650 nm down to 950 nm. Using this laser, over 200 nm bandwidth portion ranging from 750 nm down to 950 nm pulse was created.. Acquistion time of one OCT image is o.o2 second and vertical resolution in the air is 2 μm in the air. Horizontal resolution is less than1 μm. High‐speed acquisition time allows us to observe time sequential OCT images like an OCT movie for one second using a computer soft ware. Fundus examination using this OCT system was performed in eyes of healthy volunteers and patients with age‐related macular degeneration (AMD) under approval of IRB. Effect of indocyanine green (ICG) in OCT images was also evaluated in the AMD patients when who has a routine ICG examination at clinic.

Results Pulsative movement of choroidal vasculature and retinal vessels at the optic disc head could be observed in motion OCT images. Single scan OCT image of healthy macula delineated four distinctive lines in stead of three when observed with a conventional SD‐OCT, particularly in images scanned through extra fovea. Furthermore, as structure of the optic nerve head was clearly illustrated, so a manner of optic nerve how getting through the lamina cribrosa was well appreciated.

Conclusion Femto‐second laser OCT is a promising tool to explore a new dimension of clinical ophthalmology particularly in examining AMD as well as glaucoma patients.

Commercial interest
The STRONG study
Authors: LORENZ K
Published: August 2012

Neovascular glaucoma (NVG) is a very aggressive, rare type of glaucoma but contributes disproportionately to blindness from all eye diseases. NVG is also the second most common cause for the removal of the eye‐ball across all eye diseases, usually for intractable pain. The major cause of NVG is Ischaemic Central Retinal Vein Occlusion (CRVO) leading to neovascularisation and obstruction of aqueous humour outflow and increased intraocular pressure. Today’s therapeutic approaches are insufficient and include destruction of the retina by coagulation, or off‐label anti‐VEGF injection into the eye. Clearly, there is a need for better treatments. Aganirsen is an antisense oligonucleotid that can interrupt the production of Vascular Endothelial growth factor, which plays a major role in the pathogenesis of NVG and is developed by GENE SIGNAL. A Phase II/III randomised, double‐masked, 3‐group, placebo‐controlled trial (STRONG) is proposed to assess Aganirsen’s efficacy in reducing the rate of anterior and posterior segment neovascularisation and NVG development after CRVO. Aganirsen is manufactured by AMATSI, another SME. Involving 333 subjects at 35 sites, the study is operationalized via a disease specific network (EVICR.net). The study aims at assessing a new therapeutic approach for NVG for which conditional authorization will be sought at the end of the project. STRONG also delivers new insights into the natural course of the disease and its risk factors analysing one of the largest patient cohorts ever. Also, it allows for a novel classification of NVG, yields image analysis tools, and proposes biomarkers able to differentiate between high‐ and low‐risk patients and drug responders.
Compressive lesions
Authors: KAWASAKI A
Published: August 2012

Purpose To learn about compressive lesions which can mimic optic neuritis

Methods Case presentations

Results Idiopathic demyelinating optic neuritis is an acute unilateral optic neuropathy associated with pain. Compressive lesions are typically distinguished by chronic, progressive visual loss that is painless. Sometimes, a compressive lesion will manifest itself acutely and can be mistaken for optic neuritis. Focal inflammatory mass at the orbital apex (orbital pseudotumor) , lesions of the optic canal , expanding ophthalmc artery aneurysm, and infarction of an undiagnosed pituitary tumor (apoplexy) are examples of a compressive mass lesion that can present as an acute painful optic neruopathy. The clinical features of these entities will be discussed along with pearls for. suspecting the correct diagnosis.

Conclusion Careful history and examination can reveal important clues for distinguishing compressive lesion from optic neuritis

Commercial interest