bluuebunny/crossref_metadata_2025 huggingface dataset:
Human retinal pigment epithelium expressed tight junction markers in spheroid cultures
Authors: PINILLA I , WRIGHT LS , GARCIA MARTIN E , GAMM DM , CUENCA NICOLAS
Published: September 2009

Purpose To determine if spheroid cultures generated from human prenatal retinal pigment epithelium (RPE) express markers for mature RPE and tight‐junction proteins and secrete components of the Bruchs membrane.

Methods RPE was dissected from human prenatal donor eyes, chopped into 200 µm sections and place in suspension culture in serum‐free defined medium containing the commercially formulated supplement B27. Cultures were grown as spherical aggregate suspensions. At various times darkly spheroids were removed from the suspension and fixed with 4% PFA for one hour and cryoprotected with sequential sucrose solution. The spheroids were embedded in OCT, cut in 16 µm cryosections, and stained for different RPE and membrane markers including RPE65, CRALBP, PEDF, Occludin, Ezrin, Zo‐1 and laminin. EM was also performed.

Results Inside the spheroids, RPE cells were located around a central space containing secreted laminin without a clear structure. Cells expressed tight‐junctions markers including ZO‐1, ezrin and occludin. Some of the cells had intracytoplasmic expression on CRALBP, RPE65 and PEDF. Long term culture spheroids showed a decrease in the number of RPE cells and increased pigment and debris. When examined with EM, RPE cells were located over a layer of fibroblasts, showing microvilli towards the outside of the spheroid and intracellular pigment.

Conclusion Prenatal RPE maintained as spheriods show some RPE mature markers expression as well as tight junction markers. The cells are able to secrete laminin, an important component of the Bruch membrane.
Evaluation of anterior chamber depth in aphakic and pseudophakic patients with Boston type 1 keratoprosthesis
Authors: DE LA CRUZ J , GUPTA S , ELDERKIN S , GARCIA J
Published: September 2009

Purpose To assess anterior chamber depth in aphakic and pseudophakic patients with Type 1 Boston Keratoprosthesis using anterior segment optical coherence tomography.

Methods Sixteen patients who underwent Boston Type 1 Keratoprosthesis implantation were evaluated for anterior chamber depth by the non‐contact technique of AS‐OCT. Longitudinal cuts were used in evaluation of AC depth. Functional AC depth was defined as the distance between the back plate of the KPro and the anterior surface of the iris. Anatomic AC depth was defined as the distance from the posterior surface of donor cornea to the iris. Both functional and anatomic AC depths were measured nasally and temporally. The distance between the back plate of the KPro and anterior surface of the posterior chamber intraocular lens (PCIOL) was also measured in pseudophakic patients.

Results A total of 16 patients were included in this study. There were 9 pseudophakic and 7 aphakic patients. Anatomic AC depths ranged between 0.86mm to 3.2mm. Functional AC depths ranged from 0mm to 2.2mm. Pseudophakic patients had anatomic AC depths between 0.92mm and 3.1mm and functional AC depths between 0mm and 2.2mm. Aphakic patients had anatomic AC depths between 0.86mm and 3.2mm, and functional AC depths between 0mm and 2.2mm. The distance between the back plate of the KPro and PCIOL in pseudophakic patients ranged from 0.14mm to 2mm.

Conclusion Anterior chamber depth measurement, combined with AC angle data provide valuable information in the setting of KPro implantation. This may be helpful in monitoring patients post‐operatively for anterior segment complications such as crowding of the AC, or occlusion of the angle.
Screening for retinal detachment using a wide field scanning laser ophthalmoscope
Authors: BONNAY G , NGUYEN F , NABHOLZ N , BOUSQUET E , DUCASSE A , ARNDT C
Published: September 2009

Purpose The development of non‐mydriatic retinal photography has changed the clinical practice, allowing detection of abnormalities in the posterior pole without clinical examination in mydriasis. However the field of view does not exceed 60° and peripheral retinal detachments are likely to be missed on these images. The purpose of this study was to evaluate a wide field (200°) imaging system (Optos, UK ) using a scanning laser ophthalmoscope (SLO) for screening purposes in retinal detachment.

Methods All patients referred for retinal detachment from November 2007 to April 2008 were examined by one retinal surgeon who also performed the fundus drawing. An SLO image was taken by an orthoptist in training. A masked image lecture of the entire data base was performed by a resident. Both were unaware of the details of the retinal examination. The number of breaks and the extent of the detachment on the drawing were compared with the findings detected on the SLO image.

Results 56 eyes with retinal detachment were documented. In 40 out of 56 eyes the retinal breaks could be detected on the SLO images obtained. The retinal breaks situated superiorly between 11 and 1o’clock or inferiorly between 5 and 7 o’clock and two retinal detachments, one superior and one inferior, were not detected on the SLO images. SLO image analysis enabled correct diagnosis of retinal breaks in more than 7/10 cases. Retinal detachments were detected in more than 9/10 cases.

Conclusion Although the wide field SLO imaging system is not suitable as a diagnostic tool of retinal breaks and retinal detachment replacing the fundus examination by a retinal specialist, it represents a reliable screening method.

Commercial interest
Phenotype‐genotype relationship of TGFβI corneal dystrophies among Polish families
Authors: NOWINSKA A , WYLEGALA E
Published: September 2009

Purpose To analyze clinical, histologic and genetic features of TGFβI corneal dystrophies.

Methods 43 patients from 14 unrelated families were recruited. The clinical examination consisted of inheritance pattern and medical history analysis, slit lamp biomicroscopy and anterior segment optical coherence tomography. Light microscopy was performed on 9 corneal specimen obtained during keratoplasty. PCR and sequencing of all coding exons of TGFβI was performed.

Results Based on the study we diagnosed 3 families with GCD1. The clinical pattern of all families with GCD1 was similar. OCT revealed hiperreflective focal changes in the stroma and distinct irregularity of Bowman layer. Histological analysis showed Masson trichrome positive deposits. R555W mutation was revealed. 1 family was diagnosed with TBCD. We noticed increased reflectivity, irregularity of Bowman layer and increased central corneal thickness (CCT) to 608 µm during OCT exam. R555Q mutation was revealed. Two mutations were detected in patients with LCD. Patients from 8 families had R124C mutation. Those patients had thin lattice lines in anterior stroma and CCT increased to 628 µm. Two families had atypical LCD with H626R mutation. There were differences in phenotype between those two families. The first one had asymmetric, late‐onset dystrophy with thin fragile lines extending to DM on OCT scan, while the other family had both eyes involved with thick, distinct lines accompanied with stromal haze, also extended to DM. Corneal buttons of LCD patients showed Congo red positive deposits.

Conclusion Among Polish families R124C TGFBI mutation is the most common genetic pattern coexisting clinically with increased CCT. Genetic analysis plays an important role in corneal dystrophy diagnosis.
Rarebit visual field follow‐up in pediatric glaucoma
Authors: MARTIN L , LUNDVALL NILSSON A
Published: September 2009

Purpose To evaluate the long term change of the Rarebit (RB) visual fields and optic disc images in a group of children, maximally treated for paediatric glaucoma of various origin and severity, and compare them to normal RB visual field development during adolescence.

Methods Thirteen subjects (24 eyes) with pediatric glaucoma and 14 control subjects from the total group of 15 glaucoma and 15 control subjects in a previous study were included in the current follow‐up study. For comparison, RB visual field data from 4 other studies including healthy children were used. Data regarding best corrected visual acuity, refraction (spherical equivalent), intra‐ocular pressure, optic nerve appearance, diagnosis and treatment in the glaucoma group was collected from the medical records. In the control children, best corrected visual acuity was measured after determination of the refractive errors using an autorefractor. All participating subjects underwent RB visual field test and optic disc topography measurements using the Heidelberg Retina Tomograph.

Results A majority of both glaucoma eyes and control eyes showed visual field improvement. Using the same limit of normality as in the previous study (MHR above 90% and less than 5 depressed locations), 6 out of the 23 RB visual fields, previously classified as pathological, were now classified as normal. Some visual fields, both in the control and the glaucoma group showed slight deterioration, not leading to re‐classification. Twenty‐one of 26 eyes in the glaucoma group were examined with both RBP and HRT3. The concordance between the methods was 0.6 (Cohen´s kappa).

Conclusion In adolescents, maximally treated for glaucoma, both the optic nerve heads and the visual fields remain stable during 5 years of follow‐up.
Zone‐I retinopathy of prematurity, progression and scheduling of treatment
Authors: AKKOYUN I , OTO S , YILMAZ G , TARCAN A , AKOVA AY
Published: September 2009

Purpose To evaluate the progression celerity and scheduling of suitable treatment time for Zone‐I Retinopathy of Prematurity (ROP).

Methods Records of 36 eyes (18 infants) with Zone‐I ROP, which were screened for ROP at the Neonatal Intensive Care Unit of Baskent University, Ankara, Turkey, between January 2004‐March 2009, were evaluated retrospectively. Birth weight ranged between 480‐1000g, gestational age ranged from 24‐28 weeks. First fundus examination was performed at 29‐31 weeks gestational age, and was repeated once or more per week. The first treatment was performed using laser photocoagulation and the progression criteria for laser photocoagulation treatment were: (1) Zone‐I ROP less than stage‐3 with plus disease (ETROP‐type 1); (2) Zone‐I stage 3 ROP with or without plus disease (ETROP‐type 1).

Results Twenty eyes of 10 infants showed criterion (1) and 16 eyes of 8 infants criterion (2). Corneal opacity, pupillary rigidity, tunica vasculosa lentis and vitreous haze were observed until 31‐33 weeks gestational age. The time period for the progression of stage‐1 to stage‐3 retinopathy ranged between 0.7‐3.7 weeks. The mean age at the first treatment was 33 weeks (range 30‐35 weeks). The mean time between the development of stage‐1 retinopathy and the laser treatment was 9.8 days in mean (5‐23 days), and 69.3 % of the infants were treated within 12 days after the diagnosis of stage‐1 ROP. Additional treatments were performed in 7 eyes, scleral buckling+cryotherapy in 5 eyes, vitrectomy in 2 eyes.Thirty‐two eyes had favorable and 4 eyes had unfavorable outcomes.

Conclusion The diagnosis of Zone‐I ROP requires close‐meshed follow‐up and immediate treatment.
Efficacy of systemic ganciclovir as a therapeutic strategy for cytomegalovirus‐associated anterior uveitis in immunocompetent patients
Authors: ANGI M , CASSOUX N , FARDEAU C , LE HOANG P , BODAGHI B
Published: September 2009

Purpose Cytomegalovirus (CMV)‐associated anterior uveitis is a newly recognized entity that accounts for half of patients with Posner‐Schlossman syndrome. To date, the therapeutic management of these patients remains controversial. The aim of this study was to assess the efficacy of systemic Ganciclovir as a treatment for PCR‐proven CMV‐associated hypertensive anterior uveitis.

Methods Retrospective interventional study of 27 consecutive patients treated in a single centre between 2002 and 2008. Main outcome measures included intraocular pressure (IOP) and anterior chamber inflammation.

Results All patients responded to systemic Ganciclovir, with mean IOP dropping from 32 to 14 mmHg (p<0,05). Relapses occurred in 50% of cases within one year from the first antiviral course. Repeated treatment allowed control of the disease in 75% of cases (follow‐up range: 12‐78 months).

Conclusion Ganciclovir is effective but remains a suspensive therapeutic strategy.
DSAEK grafted corneas remain clear with low endothelial cell counts
Authors: OLESEN H
Published: September 2009

Purpose Presentation of observations on endothelial viability and visual outcome in 30 consecutive eyes operated with Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK)

Methods DSAEK for Fuchs' dystrophy was introduced in October 2006 at the Eye Dept. at Rigshospitalet. The first 7 eyes were grafted with pre‐cut donor tissue, the remaining operations involved tissue preparation with a Moria keratome. All patients were monitored at regular post‐operative intervals for an average of 20 months (range 7 ‐ 34 months). Donor tissue condition was evaluated in terms of detachment rate, primary graft failure and rejection events. Endothelial cell counts (ECC) were done with a digital Topcon SP‐3000P specular microscope camera. Final visual outcome was recorded.

Results A fairly large loss of endothelial cells during transplantation was noted. Average cell density of the donor buttons was 2400/mm². At one year follow‐up the recorded ECC had declined to 1129/mm² on average. At two years the average cell density was 1083/mm² indicating a slow progressive cell loss. At the latest follow‐up cell counts ranged from 429 to 2332/mm². Nonetheless all corneas were clear except for one, which was developing secondary bullous keratopathy. Patient satisfaction and visual performance and comfort did not seem correlated to the ECC. Median acuity was 20/40. No case of classical rejection was seen.

Conclusion DSAEK is a tempting alternative to PKP in Fuchs' dystrophy. The learning curve, however, is steep even for experienced surgeons at the cost of endothelial cells during the tissue handling. Corneal clarity as well as visual funtion is retained even with very low cell densities.
Interventions via the NO system and tachyphylaxia
Authors: PRASANNA G
Published: September 2009

Abstract not provided
Anatomy of the Meibomian gland
Authors: KNOP E , KNOP N
Published: September 2009

Purpose The Meibomian gland (MG) is a large sebaceous gland in the eye lid that produces the lipids for the superficial tear film layer. Although it is an indispensable component of the functional anatomy of the ocular surface, its importance is still underestimated. Increasing evidence points to a high impact of MG dysfunction (MGD) as a major cause of a dysfunctional tear film and evaporative dry eye disease. Increasing new information has occurred in recent years an will be explained.

Methods Results of a Pubmed based literature review on the anatomy, cell biology and physiology are explained together with own results.

Results The Meibomian gland shares distinct similarities in embryology with the pilo‐sebaceous unit of the cilia. The keratinised skin epithelium extends into the terminal part of the central duct. Signs of incipient keratinisation continue downstream in the central duct and ductules. The innervation of the MG is characterized by the structure of a dense network of nerve fibres and terminals around the basement membrane of the secretory acini and ducts. The MG is, similar to the lacrimal gland, mainly under parasympathetic control. The orifice of the central duct opens onto the free lid margin close to the posterior lid border and directly anterior to the line of Marx, that represents the surface of the muco‐cutaneous junction which is followed proximally by the epithelial lip of the lid wiper

Conclusion The MG is the provider of the superficial lipid layer of the tear film and is regulated similar to the lacrimal gland which may allow coordinated secretion. It preserves a commitment to keratinisation which explains why hyper‐keratinisation of the MG is an important cause for obstructive MGD. Deeper knowledge of the MG will allow better understanding of MGD and its therapy.
Physiological impact of the Meibomian gland on ocular surface integrity
Authors: BRON AJ
Published: September 2009

Purpose To review Meibomian gland physiology, including the secretory process, role of the Meibomian lipids, their delivery to the tear film and the maintenance and stability of the tear film lipid layer.

Methods A Review

Results The Meibomian gland is innervated and possesses androgen and oestrogen receptors. The latter play a part in secretory regulation. Current evidence suggests that Meibomian oil is delivered in the absence of blinking but that delivery is aided by the blink. Only a proportion of the glands are active at any one time, which may reflect their holocrine nature; secretion involves total disgorgement of acinar contents.It may be envisioned that the glands go through a cycle in which some are active all of the time (maybe less than 50%) while all of the glands are inactive, some of the time. Studies of gland expressibility suggest that, for the lower lid, a far greater proportion of the nasal than temporal glands are active at any one time. Ninety percent of the meibomian oil consists of non‐polar lipids while the rest is polar, phospholipid, thought to be essential for lipid spread across the aqueous tear film. Secretion maintains a basal level of about 300 mg of lipid in the oil reservoirs, of which about a tenth is delivered to the TFLL. Lipid is drawn across the tear film in the upstroke of each blink to form a lipid layer that stabilizes in about 1 second and remains stable for the remainder of the interblink. In the normal eye, the structure of the TFLL remains almost unchanged from blink to blink and then changes abruptly as the lipid from the TFLL mixes with that of the two oil reservoirs.

Conclusion These events ensure that the TFLL retards evaporative water loss from the tear film and conserves moisture at the surface of the eye.

Commercial interest
CFH, C3 and ARMS2 are significant risk loci for age‐related macular degeneration but not for late stage disease progression
Authors: SCHOLL HPN
Published: September 2009

Purpose Variants in the genes encoding complement factor H (CFH), complement component 3 (C3) and age‐related maculopathy susceptibility 2 (ARMS2) have repeatedly been shown to confer significant risks for age‐related macular degeneration (AMD). However, their role in disease progression and thus their relevance for the design of targeted therapeutic intervention remains unknown.

Methods Association between variants in CFH, C3 and ARMS2 and disease progression of late atrophic AMD was analyzed. Patients were selected from the multicenter FAM study cohort (n=619) and compared with 612 matched controls. A quantitative phenotype of disease progression was computed based on longitudinal observations by fundus autofluorescence imaging.

Results In a subset of 99 cases with pure bilateral geographic atrophy (GA), variants in CFH (Y402H), C3 (R102G), and ARMS2 (A69S) are associated with disease (P=1.6×10‐9, 3.2×10‐3, and P=2.6×10‐12, respectively). Median progression rate of GA over a mean follow‐up period of 3.0 years was 1.61 mm2/year with high concordance between fellow eyes. No association between the quantitative progression variable and any of the genetic risk variants at the three loci was observed (P>0.13).

Conclusion Variants at CFH, C3, and ARMS2 confer significant risks for atrophic AMD; however there is no association with disease progression. Consequently, treatment options targeted at ameliorating pathogenic effects mediated by any one of the three susceptibility factors are likely to fail once atrophic manifestations of AMD have developed. Other, as yet unknown susceptibilities may influence disease progression.
EUPO courses
Authors: SPILEERS W
Published: September 2009

EUPO (European Professors of Ophthalmology)organizes yearly courses especially for European residents in ophthalmology. The actual status and the planning for the near future of the activities of EUPO will be highlighted. The close conjunction with SOE, EBO and EVER will be outlined.
Myopic choroidal neovascularization treated by intravitreal bevacizumab: comparison of two different initial doses
Authors: MONTERO MORENO JA , RUIZ‐MORENO JM
Published: September 2009

Purpose To report the anatomical and visual outcome of myopic choroidal neovascularization (CNV) treated by two different schedules with intravitreal bevacizumab.

Methods Prospective, comparative, consecutive, non randomized, multicentric, interventional pilot study. Two groups of highly myopic patients with subfoveal and juxtafoveal CNV were treated by monthly intravitreal injections with 1.25 mg bevacizumab. Group 1 comprised 19 eyes treated by three consecutive monthly intravitreal injections. Group 2 comprised 20 eyes treated by one single intravitreal injection. Patients were evaluated for best corrected visual acuity (BCVA) and optical coherence tomography (OCT) at baseline and then monthly. Fluorescein angiography was performed at baseline and when CNV activity was suspected. Further intravitreal injections were performed if CNV activity was detected.

Results Both groups were matched for age, spherical equivalent, LogMAR BCVA, central foveal thickness (CFT) as determined by OCT at baseline and number of eyes with previous PDT treatment. The average number of letters gained was 6.3 in Group 1 vs 7.2 in Group 2 (p=0.001 and 0.09 respectively, Student t test for paired data). Changes in OCT were not significant for either group by the end of follow up. The mean number of total injections were 3.2 (Group 1) vs 1.7 (Group 2) (p=0.00, Mann‐Whitney test). Four recurrences (four eyes) occurred in Group 1 vs fifteen (seven eyes) in Group 2 (p=0.001; Fisher exact test).

Conclusion Both initial treatment have similar results improving BCVA. Group 1 was treated by a higher number of injections achieving a longer lasting inactivation of myopic CNV, reducing the number of recurrences during the first year.
Apoptotic activity of intravitreal bevacizumab on rabbit retina
Authors: TURKCU MF , ALP MN , TURKCU G , KULACOGLU S , KURAL G
Published: September 2009

Purpose To evaluate the safety and the apoptotic activity of intravitreal (IV) injection of bevacizumab in rabbit eyes by histopatological analysis.

Methods Fourteen rabbits were divided into three groups, 8 rabbits in the first and 3 rabbits in each of the second and the third groups. We applied 1.25 mg/0.05 ml IV bevacizumab to the right eyes of each subject in the first and the second groups and the same volume of saline to the left eyes of each subject in the first and the third groups. The left eyes in the second group and the right eyes in the third group were left untreated and used as the control group. After 14 days, all animals were sacrificed and all eyes were enucleated for histological examination.

Results There was no evidence of ocular inflammation, cataract, or retinal toxicity in any of the sections examined by light microscopy. We observed inflammatory cell infiltration that includes plasma cells in 3 of 11 eyes which received bevacizumab, 4 of 11 eyes which received saline, and 2 of 6 eyes which were left untreated. In all groups, we observed some vacuolization in the ganglion cell layer and some distinctive dispersion and detachment of retinal layers, including rod and cone cells and the retinal pigment epithelium. After immuno‐histochemical staining with Caspase 3 and p53, there was no histological evidence of toxicity to the retina and the optic nerve in any of the sections that were analyzed in all three groups.

Conclusion According to the results of this study, IV injection of bevacizumab with the dose of 1.25 mg/0.05 ml caused no histological sign of toxicity or apoptotic activity on rabbit retina.

Commercial interest
Photodynamic therapy for symptomatic circumscribed choroidal hemangioma
Authors: MAYER CF , WACKERNAGEL W , LACKNER EM , SCHNEIDER MR , HAAS A , WEGER M , LANGMANN G
Published: September 2009

Purpose Photodynamic therapy (PDT) is a well established treatment option for symptomatic choroidal hemangioma. We present seven patients treated with PDT at our department.

Methods Seven patients (2 female, 5 male) with a mean age of 46 Years (range 44 ‐ 69 years) have been treated between October 2005 ‐ March 2007. Best corrected visual acuity at first visit was minimum 0.25 and maximum 0.8 (Snellen). Indirect ophthalmoscopy showed a choroidal hemangioma with subretinal fluid. Ancillary examinations included angiography, OCT and A‐ and B‐scan ultrasonography. Largest basal diameter was 8 mm (median; range 5.5 ‐ 10.2 mm) and tumor height 3 mm (median; range 2.2 ‐ 4 mm). One or more PDTs had to be done. Median follow up was 19 months (range 3 to 39 months).

Results In 3 patients one PDT was sufficient to obtain good and stable visual acuity. Three patients needed a second PDT twelve months after the initial treatment. In one patient six PDTs were necessary over a period of 20 months and additional vitrectomy had to be done. Five patients showed a gain in visual acuity (median 4 lines; range 1 to 6 lines). One patient showed unchanged visual acuity and one patient showed a loss of 3 lines after six PDTs and vitrectomy.

Conclusion In six out of seven patients stable visual acuity could be obtained. In one patient multiple PDTs and vitrectomy were necessay to achieve stable clinical results. Our findings confirm that PDT is an effective treatment modality for choroidal hemangioma.
Effects of moxaverine on ocular blood flow in patients with age‐related macular degeneration, patients with primary open angle glaucoma and in healthy controls
Authors: PEMP B , GARHOFER G , LASTA M , SCHMIDL D , SCHMETTERER L
Published: September 2009

Purpose Several common eye diseases including age‐related macular degeneration (AMD) and primary open angle glaucoma (POAG) are associated with ocular perfusion abnormalities. Moxaverine has been shown to increase ocular blood flow in young, healthy volunteers after intravenous administration. The present study investigated whether moxaverine alters ocular blood flow in elderly patients with AMD or POAG and in healthy control subjects.

Methods 20 patients with AMD, 20 patients with POAG and 20 age‐matched healthy subjects were included in this trial. 150 mg moxaverine (Ursapharm, Saarbrücken, Germany) was administered intravenously over 30 minutes. Systemic haemodynamics, retinal vessel diameters, choroidal, optic nerve head and retrobulbar blood flow were measured before and up to 90 minutes after drug administration.

Results Administration of moxaverine increased choroidal blood flow by 8.7 ± 21.8% (p=0.012) and optic nerve head blood flow by 12.9 ± 33.3% (p=0.021). Additionally, an increase in the mean flow velocities of posterior ciliary arteries (24.8 ± 34.7%, p<0.001) and in the ophthalmic artery (23.3 ± 33.5%, p<0.001) was found after administration of moxaverine. However, no differences were found between the 3 study groups. No significant change of retinal vessel diameters was observed.

Conclusion The present study indicates an increase of ocular blood flow after systemic administration of a single dose of moxaverine in patients with POAG, patients with AMD and in age‐matched healthy controls. Further studies are needed to investigate possible beneficial effects after long‐term treatment in patients with ocular diseases associated with hypoperfusion.
Effect of glaucoma and glaucoma risk factors on choroidal hemodynamics
Authors: ABOU SAMRA W , RIVA CE , POURNARAS CJ , EMARAH M
Published: September 2009

Purpose a) to determine subfoveal choroidal hemodynamics in patients with primary open angle glaucoma (POAG) and patients with ocular hypertension (OH); b) to assess the effects of diabetes (DM), systemic hypertension (SHT) and myopia on subfoveal choroidal hemodynamics

Methods Laser Doppler flowmetry (LDF) was used to determine the subfoveal choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) in 1) patients with POAG (n=85) and patients with OHT (n=25); 2) patients with glaucoma risk factors which were further subdivided into three subgroups; DM (n=93), SHT (n=57) and myopia (n=29) respectively. Subjects with each risk factor were further subdivided into two subgroups (without and with POAG), 3) age matched healthy controls (n=100).

Results All LDF parameters were significantly reduced in all groups of patients compared with age matched controls. No statistically significant differences in the LDF parameters among HTG, NTG and OHT subgroups were detected. No significant difference in the LDF parameters between the two subgroup of each risk factor (without and with POAG) was noted.The LDF data of glaucomatous patients with risk factors demonstrated a significant reduction of ChBF and an increase in resistance in comparison to glaucomatous patients without risk factors

Conclusion Subfoveal choroidal LDF parameters are reduced in subjects with POAG, OHT and patients with glaucoma risk factors, such as DM, SHT (under antihypertensive therapy) and myopia when compared with age matched healthy controls. However, the role of these choroidal circulatory alterations in the development or progression of the glaucomatous optic neuropathy remains to be clarified.
Wavefront aberrometry advances in refractive surgery
Authors: COCHENER B
Published: September 2009

Wavefront aberrometry has been adapted from optical astronomy in order to analyze complex image distortions caused by the human optical system, called higher order aberrations. The aberrations increase with larger pupil size or during nocturnal vision when the pupil dilates. They may have a significant impact on vision, even in a patient with 20/20 visual acuity. Most Shack Hartman aberrometers can be used as a super auto refracto‐keratometer during refractive surgery pre‐operative evaluations. They can capture the full amount of astigmatism and so will minimize the need for retreatment due to undercorrection. Modern Shack Hartman aberrometers give also the refractive surgeons the possibility to measure aberrations induced by flap creations. In addition they will be useful for performing customized excimer laser ablation (data coming from the aberrometer mapping out a path for the laser in reshaping the cornea). This technique has been shown to improve the correction of lower order aberrations (90% of the aberrations of the human eye), but is there a real benefit for treating higher order aberrations? Is a Shack Hartman aberrometer needed for every day refractive surgery practice? Thru an evidence based review of the literature confronted to personal experience we will try to answer these questions.
Sympathetic influence on intraocular pressure
Authors: MARQUES‐NEVES C , GONçALVES C , LARANJO S , SANTOS M , ROCHA I
Published: September 2009

Purpose To apply wavelet analysis to investigate the sympathetic modulation upon intraocular pressure(IOP)of the cold pressure test

Methods In an autonomic dedicated lab continuous and simultaneous recording of(IOP) with Pascal(DCT) and arterial blood pressure(BP) were made in 11 healthy individuals,of both sexes,in basal conditions and during 1minute of cold‐pressure test(CPT).The tests were in the morning period and in the 24h previous individuals were told not to smoke and to avoid xanthines or other stimulants ingestion. Individuals under medication or with other pathology that could affect the autonomic nervous system were excluded. Data analysis of IOP and systolicBP (SBP) in the time‐scale domain with wavelets(DB12)was performed, for both variables, during the last minute prior to test and during one minute upon test. In this last case,periods of 10s where individually analysed and the period with the largest value was the chosen for statist analysis using t‐Student test, Welch corrected(Ducla‐Soares et al, 2007).LFIOP and LFSBP were calculated and differences between basal and CPT values were considered significant where p<0.05. Data were expressed as mean±SEM., and for LF mmHg2

Results Data refer to 6 male and 5 female with a mean age of 49[40‐70] On CPT, a sympathetic challenging manoeuvre, an increase of SBP was observed. Wavelet analysis of both signals showed a significant increase of LFIOP and LFSBP from 0.13±0.15 and 8.66±1.51 to 0.37±0.26 mmHg2 and 18.7±4.5mmHg2, respectively, and a not significant change in IOP 17.0±2.6 to18.0±1.5

Conclusion Our data show a sympathetic signature on IOP correlated with that observed in BP. We show that wavelets are a suitable tool for the evaluation of sympathetic signature on short periods of IOP recorded by DCT
Factors affecting ocular rigidity in normal human eyes
Authors: DASTIRIDOU AI , GINIS H , KARYOTAKIS NG , TSILIMBARIS M , PALLIKARIS IG
Published: September 2009

Purpose To measure the ocular rigidity coefficient and evaluate its relation with axial length (AL), age and mean systemic blood pressure (SBP).

Methods Sixty three patients (63 eyes) undergoing cataract surgery, with different refractive errors and no ocular or systemic pathology were enrolled in this study. An invasive, computer controlled device comprising a microdosimetric pump and a pressure sensor, is connected to the anterior chamber under topical anaesthesia with drops. The system is used to raise the intraocular pressure (IOP) from 15 to 40mmHg, by infusing the eye with a saline solution. After each 4 ul infusion step, the IOP is continuously recorded for 2 seconds. From an initial level of 40mmHg an IOP decay curve of 1 minute is obtained. SBP and pulse rate are measured during the procedure. The rigidity coefficient is calculated by an exponential fit to the pressure volume data after correction for outflow. The study was approved by the Institutional Board and performed under the patient’s informed consent.

Results Mean AL was 24.8 (range 21.2‐32.5). Mean age and SBP was 59 (12) years and 93.7 (10.5) mmHg respectively. The mean ocular rigidity coefficient was 0.021 (0.005) ul‐1. Increasing axial length is associated with a decrease in the rigidity coefficient (r=‐0.61, p<0.01). A positive correlation between the rigidity coefficient and age of the patients is found (r=0.31, p=0.01), whereas similar findings were not observed for SBP (p>0.05).

Conclusion This manonetric approach of measuring ocular rigidity provides a normative database of this parameter in living human eyes. Axial length and age influence ocular rigidity. These results may have implications on tonography and ocular pulse studies.
Nitric oxide synthesis is related to astroglial cell cycle in the mouse retina via p53 gene regulation
Authors: GALLEGO‐PINAZO R , DIAZ‐LLOPIS M , RAMIREZ AI , SALAZAR JJ , RAMIREZ JM , ZANON‐MORENO VC , PONS‐VAZQUEZ S , PINAZO‐DURAN MD
Published: September 2009

Purpose To analyze the influence of p53 gene in retinal astrocytes morphology and function.

Methods Adult mice of the strain C57BL/6 were distributed into two groups: 1) wild type TP53, as the controls (cp53; n=20) and 2) mice with an extra copy of p53 (sp53; n=22). Both eyeballs were enucleated, after death by ether narcosis, to obtain the retinas. Right retinas were frozen (‐85ºC) until processing to assess nitric oxide (NO) synthesis. Left retinas were obtained and proccesed to perform immunohistochemical localization of the glial fibrillary acidic protein (GFAP). Data are expressed as the mean ± SD. Statistical analysis was carried out using Student’s t‐test. Confidence interval was taken at 95%.

Results The NO levels were significantly higher in the sp53 retinas than in the cp53 ones (145 + 15 vs 111 + 10 μM; p<0,05). Strong GFAP expression was detected and mapped by fluorescence microscopy in the whole retinas. GFAP+ stellate cells were located throughout the peripheral, equatorial and central retina. Astroglial density was significantly higher in the sp53 retinas as compared to the cp53 group (72 + 8 vs 49 + 6 cells/retinal area; p<0,001).

Conclusion All data suggest a complex set of p53 actions: 1) to regulate NO production (probably recruiting a latent retinal astrocytic population), 2) to regulate the sensitivity toward NO in the retina by protecting astrocytes from oxidative attack. Increasing p53 activity may be an outstanding therapeutic strategy for certain retinal diseases.
The role of the professor as leader and promotor of science
Authors: PRAUSE JU
Published: September 2009

Purpose To present essential aspects of the role of the professor as promotor and leader of science

Methods Key elements are presented and illustrated by examples: The creative scientific milieu The typical flow of a young talent in Copenhagen Creating the team spirit Internal courses: Fund raising – list of good funds Statistics How to prepare an article Internal social relationships: Journal club The ”professors Court” or the ”gossip club” Scientific lines ‐ Buffer funds

Results The effect is a high number of completed PhD projects per professor

Conclusion When you share ideas, dreams, knowledge ‐ like with love, you do not loose any part of it ‐ you gain
Differential association of cataract sub‐types with obesity and FTO polymorphisms
Authors: LIM L , TAI E , AUNG T , TAY W , SAW SM , SEIELSTAD M , WONG TY
Published: September 2009

Purpose Investigating a possible link between genetic variants associated with obesity and cataract may validate the causal link between obesity and cataract suggested by epidemiological studies. This study assessed the associations of obesity and genetic variants in the FTO locus, a human susceptibility locus for obesity, with cataract.

Methods This was a population‐based cross‐sectional study on adults aged 40‐80 years. Cataract was assessed by standardized slit‐lamp examination according to the Lens Opacity Classification System III (LOCS III). Obesity was defined by BMI≥30kg/m2. The SNP rs9939609 at the FTO locus was selected for analysis. Additive and recessive models were constructed for the association between FTO polymorphisms and cataract.

Results 3069 subjects were included, of which 1476 (48.1%) had any cataract, 927(30.2%) had nuclear cataract, 1012(33.0%) had cortical cataract and 308(10.0%) had PSC cataract. After multivariable adjustment, obesity was significantly associated with cortical (OR1.34(95% CI,1.04‐1.73)) and PSC (OR 1.53(1.07‐2.18)) cataracts, but not nuclear cataract. In the additive model, each copy of the minor allele of rs9939609 was associated with nuclear cataract (OR 1.33(1.11‐1.58)). This association persisted in multivariate analyses controlling additionally for BMI, diabetes, hypertension and smoking (OR 1.30(1.08‐1.55)). There was no association with cortical or PSC cataract. In the recessive model, rs9939609 was associated with nuclear but not cortical or PSC cataract.

Conclusion Obesity is associated with cortical and PSC cataract while the SNP rs9939609 in the FTO gene is associated with nuclear cataract. The contrasting associations may reflect differences in the pathophysiology of cataract subtypes.
Intravitreal L‐arginine injection reverses the retinal arteriolar vasoconstriction that occurs after experimental acute branch retinal vein occlusion
Authors: MENDRINOS E , PETROPOULOS IK , MANGIORIS G , PAPADOPOULOU DN , POURNARAS CJ
Published: September 2009

Purpose To investigate the effect of L‐Arginine on the retinal arteriolar diameter following acute branch retinal vein occlusion (BRVO) in minipigs.

Methods Under general anesthesia, 10 eyes of 10 minipigs were evaluated. Two hours after BRVO, an intravitreal juxta‐arteriolar microinjection of 30 µl L‐Arginine 1 mM (pH=7.4) was performed in 7 eyes. Three eyes received a microinjection of 30 µl of the solvent (pH=7.4) that was used to prepare the solution of L‐Arginine and served as controls. Retinal arteriolar diameter changes were measured using a Retinal Vessel Analyzer.

Results Overall (n=10), two hours after BRVO there was a 10.5 ± 1.9 % decrease in the retinal arteriolar diameter in the affected territories compared to baseline (p<0.05). An increase of 16.0 ± 3.0 % (p< 0.01) and 21.0 ± 7.0 % (p<0.05) of the arteriolar diameter was evidenced 10 and 15 minutes respectively after L‐Arginine injection (n = 7) compared to the diameter prior to L‐Arginine injection. Thereafter, the vasodilatory effect of L‐Arginine started to decrease but persisted and remained significant at the end of the study period (5.0 ± 1.5 % at 30 min, p<0.05). Microinjection of the solvent that was used to prepare the solution of L‐Arginine (n=3) did not produce any significant effect on the retinal arterioles, which remained constricted at all time‐points (p>0.1).

Conclusion We found a significant vasodilation after intravitreal juxta‐arteriolar L‐Arginine microinjection in eyes with experimental BRVO. L‐Arginine microinjection can be a beneficial therapeutic option in acute BRVO, reversing the arteriolar vasoconstriction by stimulating NO production.
A rat model to study choroidal blood flow
Authors: STROHMAIER C , RUNGE CW , BOGNER B , GRABNER G , REITSAMER HA
Published: September 2009

Purpose To develop a model for the investigation of blood flow of in the choroid of rats. Due to their similarities in ocular blood supply und availability, rats are becoming increasingly interesting models in ocular blood flow research. The ability of choroidal autoregulation during changes in perfusion pressure has been shown in various species already. The presented study aims to show autoregulation in the choroid in a new model for blood flow measurement in the choroid of rats.

Methods Male Brown‐Norway rats were anesthetised with Ketamin Hydrochloride (100 mg/kg) i.p.. A catheder for blood pressure measurement was inserted into the right femoral artery and advanced to the aorta, another catheter was inserted into the right femoral vein for drug administration. Pentobarbital was used to provide adequate anaesthesia for the following procedures, subsequently the animal was respired via a tracheotomy. Endtidal CO2 was kept in the range between 35 – 45 mmHg and airway pressure was limited to 6 cm H2O. A thoracotomy was performed through the 8th intercostal space and a hydraulic occluder was placed around the inferior vena cava just above its passage through the diaphragm. Choroidal blood flow was measured with a custom‐made, non‐invasive laser Doppler Flowmeter.

Results Blood pressure was reduced through a mechanical reduction of venous return, typically from 80 mmHg to 20 mmHg. Between 80 and 50 mmHg, blood flow remained virtually constant, between 50 mmHg and 20 mmHg, a linear relationship between blood pressure and blood flow was observed.

Conclusion The presented model is appropriate for the investigation of blood flow in the choroid of rats. Autoregulation in the choroid of rats could be demonstrated.
Differential effects of ageing on foveal and peripheral colour vision
Authors: RAUSCHER F , EDGAR D , BARBUR J
Published: September 2009

Purpose Colour sensitivity was assessed to establish aging effects both at the fovea and 6 deg away from fixation, in each of the four quadrants.

Methods 65 normal healthy subjects (from 20 to 80 years of age) took part in the study. All subjects had Visual Acuity (VA) of 6/6 or better. Fixation accuracy was monitored using infrared imaging of the pupil and the tests were carried out on the P_SCAN system. Target size was adjusted for parafoveal locations to account for retinal and cortical magnification. Yellow‐blue (YB) and red‐green (RG) colour discrimination was assessed using the CAD (colour assessment and diagnosis) test (http://www.caa.co.uk/docs/33/200904.pdf).

Results RG and YB colour thresholds were analysed separately for all five locations tested and showed no significant effect with ageing below the age of 60 years. Two age bands were formed based on statistical analysis (20‐59.9 and 60‐79.9). The decline in performance with age was more rapid at the fovea and exhibited a steeper gradient when compared with results in the periphery for both RG and YB discrimination. Foveal YB discrimination showed the largest ageing effect. No significant difference was found between the four parafoveal locations. YB discrimination at the fovea also exhibited the largest inter‐subject variability.

Conclusion These findings may have clinical significance in the very early detection of disease processes that remain subclinical in many subjects. Differences between foveal and peripheral locations help to differentiate between the normal effects of ageing and disease. For example, higher foveal and normal peripheral YB thresholds in normal subjects from high peripheral thresholds in early glaucomatous subjects.
On the effectiveness of cone mosaic geometry in sampling patterns near the Nyquist frequency
Authors: GINIS H , PERDIKARIS K , PALLIKARIS A
Published: September 2009

Purpose The cone mosaic is characterised by a quasi‐periodic hexagonal organization. The purpose of this work was to develop a mathematical model of cone mosaic including irregularities and to employ this model to evaluate its effectiveness in sampling simple patterns including optotypes (letters) of different sizes and gratings.

Methods Cone mosaic images were analyzed using purposely‐developed computer programs and a stochastic model of the human cone mosaic was created. The computer‐generated mosaics were used to sample sequences of patterns translated to positions randomly extracted from experimental data of fixational eye movements. The sampling efficiency was evaluated as the RMS difference between the initial and the sampled pattern. Similar simulations were performed using a periodic mosaic of equal average cone size.

Results Sampling efficiency (as described by the minimum RMS difference) was better for the quasi‐perioding sampling compared to the periodic sampling especially when the sampled pattern involved spatial frequencies higher than 20 cpd. The periodic sampling performed better only in the case where the spatial frequencies in the Fourier spectrum of the sampled pattern exactly matched the spatial frequency associated to the cone spacing (divided by an integer). However the quasi‐periodic sampling was more effective in all other pattern sizes and orientations.

Conclusion Although the trichromatic nature of the human cone mosaic as well as the neural organization in the retina after phototransduction were not taken into account, our simulations demonstrate that the geometric irregularities at the cone mosaic may result to more efficient sampling of simple patterns of arbitrary size and orientation.
Distribution of amyloid and BIG‐H3 in the cornea and limbus of a patient with lattice corneal dystrophy. Unique findings in donated eyes
Authors: AKHTAR S , ALMUBRAD T , BRON AJ , BONSHEK R
Published: September 2009

Purpose The lattice corneal dystrophies (LCDs) are hereditary diseases involving the formation of opaque or refractile, amyloid‐containing filaments in the corneal stroma. We report the distribution of amyloid and big‐h3 protein in cornea and limbus in a patient suffering with LCD.

Methods An 84 year‐old patient with lattice corneal dystrophy died and donated her eyes for further study. The corneal and limbal tissue of the patient processed for light and electron microscopy. The primary polyclonal antibody big‐h3 was located by secondary, goat anti‐rabbit antibody conjugated with gold.

Results In cornea amyloid deposits were observed below epithelium, and in the anterior and middle stroma. The epithelium was thin and invaginated by the amyloid deposits. In the limbus, large numbers of amyloid deposits were observed in sub‐epithelial region, and in the mid and deep stroma. Subepithelial amyloid was also present in the substantia propria beneath the bulbar conjunctival epithelium. The amyloid deposits contained very thin amyloid fibrils and strongly stained with big‐h3 antibody. There were also numerous long spacing collagen fibrils observed in the mid stroma, which also labelled with the antibody.

Conclusion This is the first report of structural changes in the peripheral cornea and limbus in LCD. It is thought that mutated big‐h3 protein diffuse into the stroma from the corneal epithelium to form amyloid deposits. The presence of amyloid and big‐h3 at the limbus and in the adjacent bulbar conjunctiva and perilimbal cornea, suggests that Big‐h3 is overproduced in these regions, which are normally free from clinically detectable disease.