Exfoliation Glaucoma Patients Research Articles

Growth Factors, Oxidative Damage, and Inflammation in Exfoliation Syndrome.

Exfoliation syndrome (XFS) produces deleterious ocular aging and has protean systemic manifestations. Local ocular production of TGFβ1 is of central importance in XFS. TGFβ1 appears to induce the expression of LOXL1 and the production of other extracellular matrix components which are known to be present in exfoliation material. Furthermore, results from several studies find that the aqueous humor of exfoliation glaucoma patients exhibits a decreased antioxidant defense and increased oxidative stress systems. Finally, studies show that the levels of interleukin-6 and interleukin-8 in the aqueous humor of XFS patients were 3-fold higher than in controls. Overall TGFβ1, as well as a prooxidative and proinflammatory environment seems to play an important role in XFS.

Lack of Association between Serum Vitamin B₆, Vitamin B12, and Vitamin D Levels with Different Types of Glaucoma: A Systematic Review and Meta-Analysis.

Although vitamins play a major role in health, and their deficiency may be linked to symptoms of optic-nerve dysfunction, the association between serum vitamin levels and glaucoma in humans remains controversial. In this study, articles in the PubMed, Web of Science, and EMBASE databases were searched up to 25March 2017. Nine studies on primary open-angle glaucoma (POAG), four studies on normal tension glaucoma (NTG), and six studies on exfoliative glaucoma (EXG) were retrieved. The combined results showed no differences in the levels of serum vitamin B6 between POAG (p = 0.406) and EXG (p = 0.139) patients and controls. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were 2.792 ng/mL (−3.793 to 9.377) and 1.342 ng/mL (−3.120 to 0.436), respectively. There was no difference between POAG (p = 0.952), NTG (p = 0.757), or EXG (p = 0.064) patients and controls in terms of serum vitamin B12. The WMDs with 95% CIs were 0.933 pg/mL (−31.116 to 29.249), 6.652 pg/mL (−35.473 to 48.777), and 49.946 pg/mL (−102.892 to 3.001), respectively. The serum vitamin D levels exhibited no differences (p = 0.064) between POAG patients and controls; the WMD with 95% CI was 2.488 ng/mL (−5.120 to 0.145). In conclusion, there was no association found between serum vitamin B6, vitamin B12, or vitamin D levels and the different types of glaucoma.

Oxidized low-density lipoprotein, lipid and calcium aggregates reveal oxidative stress and inflammation in the conjunctiva of glaucoma patients.

Conjunctival specimens from primary open-angle glaucoma (POAG), exfoliation glaucoma (ExG) patients and controls were histologically analysed for oxidized low-density lipoprotein (ox-LDL), lipid and calcium aggregates. Our goal was to use them as biomarkers of oxidative stress and inflammation and to evaluate their correlation with glaucoma and impact on surgical outcome. Conjunctival samples were obtained from POAG (n=14) and ExG (n=17) patients and from control subjects (n=11) operated for macular hole, retinal detachment or strabismus. Immunohistochemistry was performed using the antibody against ox-LDL. Lipids and calcium were analysed by histochemical stainings with Nile red and Alizarin red S, respectively. Immunoreaction for ox-LDL was significantly increased in POAG (p= 0.049) and the number of lipid aggregates was significantly higher in ExG (p=0.009) when compared to control. When POAG and ExG patients were grouped according to the outcome of deep sclerectomy (DS) surgery, the number of lipid (p<0.001) and calcium aggregates (p=0.014) were significantly higher in the conjunctival stroma of patients whose surgery failed within a three-year follow-up period. The lipid-mediated alterations suggested the presence of oxidative stress and inflammation in the conjunctiva of glaucoma patients. The present data further support the role of oxidative stress and inflammation in the wound healing process leading to excessive scarring and failure in DS surgery.

The relationship between self-reported habitual exercise and visual field defect progression: a retrospective cohort study

BackgroundExercise reduces intraocular pressure (IOP) in the short term. However, it is not known whether exercise contributes to slower glaucomatous visual field defect progression.MethodsTwenty-four primary open-angle glaucoma or exfoliation glaucoma patients who were evaluated by the Humphrey Field Analyzer (HFA) 24–2 program ≥ four times in 3 years were enrolled. Patients with a history of intraocular surgery in past 3 years or other eye diseases threatening visual fields were excluded. Patients were classified into two groups whether they had exercise habits or not.ResultsEleven patients had exercise habits. The mean ± standard error of IOP and MD slope were 14.8 ± 0.9 mmHg and +0.20 ± 0.20 dB/year in the exercise group and 13.3 ± 0.8 mmHg and −0.53 ± 0.18 dB/year in the non-exercise group (P = 0.24 and P = 0.01, respectively). Higher IOP [odds ratio (OR) = 0.44/1 mmHg increase; P = 0.02] and habitual exercise (OR = 0.04; P = 0.02) reduced the visual field defect progression risk in logistic regression analyses.ConclusionsPatients with self-reported exercise habits had slower glaucoma progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12886-016-0326-x) contains supplementary material, which is available to authorized users.

Comment on Comparison of ocular response analyzer parameters in primary open angle glaucoma and exfoliative glaucoma patients

Sir, Recently, Beyazyıldız et al.[1] investigated ocular response analyzer (ORA) parameters in primary open angle glaucoma (POAG), exfoliative glaucoma (EXG) patients and control subjects. We congratulate the authors that they found impressive results with such a simple-design study. The authors found (i) significantly lower corneal hysteresis (CH) and corneal resistance factor (CRF) in EXG patients than other groups, (ii) insignificant difference in CRF between POAG and control subjects, (iii) significant positive correlation between CH and central corneal thickness in EXG patients and control subject but not in POAG patients. The results really have clinical significance in terms of diagnosis and management. However, we wander whether the authors performed adjustments for multiple comparisons in the statistical analyses. We also wander about the relation between functional parameters and ORA results. Are visual field losses in the groups related with CH and CRF? Does lower CH result in higher mean deviation values despite normal intraocular pressure? What is the correlation between CH/CRF and visual field parameters? The answers of these questions are very important and will increase our understanding about the progression of glaucoma in POAG and EXG patients. We kindly ask to the authors about the answers of these questions.

Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients

Chronic conjunctival inflammation, caused by various reasons, for example long-term use of topical drugs and/or their preservatives, affects the outcome of glaucoma surgery by interfering with wound healing. Matrix metalloproteinases (MMPs) remodel extracellular matrix (ECM) and are involved in the wound healing process. This study was designed to evaluate the conjunctival expression of MMPs and their tissue inhibitors (TIMPs) in the normal eye, primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and whether there is an association between staining intensities and deep sclerectomy outcome. Immunohistochemical procedures were performed on conjunctival samples which were obtained from POAG (n=11) and ExG (n=14) patients as well as normal (n=7) subjects. Antibodies against MMPs (MMP-1, -2, -3 and -9) and TIMPs (TIMP-1, -2 and -3) were used. In conjunctival stroma, expression levels of MMP-2 (p=0.047), MMP-3 (p=0.009), MMP-9 (p<0.001), TIMP-1 (p=0.003), TIMP-2 (p<0.001) and TIMP-3 (p<0.001) in ExG and MMP-9 (p=0.008), TIMP-2 (p=0.02) and TIMP-3 (p=0.002) in POAG were significantly increased compared to control. We further found correlations between expression of MMP-1 and MMP-3 and the length of pilocarpine treatment. The expression of MMPs and TIMPs is increased in the conjunctiva of POAG and ExG patients having a long history of topical antiglaucoma drops. Antiglaucoma agents and/or their preservatives alter the remodelling balance of ECM in conjunctiva of POAG and ExG eyes. The balance between MMPs and TIMPs may play a crucial role in the conjunctival wound healing process and the outcome of glaucoma surgery.

Novel common variants and susceptible haplotype for exfoliation glaucoma specific to Asian population.

The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). However, the risk allele of a variant in LOXL1 has been found to be inverted between Asian and Caucasian populations. Therefore, we newly performed a genome-wide association study using 201 XFS/XFG and 697 controls in Japanese, and identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs) distributing in not only LOXL1 but also TBC1D21 and PML at the 15q24.1 locus. These SNPs were confirmed by an independent population consisted of 121 XFS/XFG and 263 controls in Japanese. Moreover, further analyses revealed a unique haplotype structure only from the combination of TBC1D21 and LOXL1 variants showing a high XFS/XFG susceptibility specific for the Asian population. Although there still should be other gene(s) in the other region(s) contributing to the disease process, these results suggested that the combination of newly discovered variants in these genes might be useful for precise XFG risk assessment, as well as for elucidating the molecular mechanism of XFG pathogenesis through XFS.

Elevated Levels of Multiple Biomarkers of Alzheimer's Disease in the Aqueous Humor of Eyes With Open-Angle Glaucoma

To investigate levels of biomarkers of Alzheimer's disease in the aqueous humor in patients with open-angle glaucoma (OAG). Aqueous humor samples were collected from 38 patients with cataracts, 20 patients with POAG, and 32 patients with exfoliation glaucoma. Aqueous levels of apolipoprotein (Apo) AI, ApoCIII, ApoE, transthyretin (TTR), complement factor H, complement C3, and α2-macroglobulin (α2M) were determined by multiplex bead immunoassay. Clinical data were obtained from medical charts. Age and sex did not differ significantly among groups. POAG patients had significantly higher aqueous levels of Apo AI, ApoCIII, ApoE, TTR, and α2M compared with cataract patients (P < 0.001, P = 0.036, P < 0.001, P < 0.001, and P < 0.001, respectively). Corresponding values for exfoliation glaucoma patients were also significantly higher compared with those for cataract patients (P = 0.003, P = 0.009, P < 0.001, P < 0.001, and P < 0.001), and those levels correlated positively with each other in eyes with OAG (P < 0.001 for all combinations). Complement factor H and complement C3 levels did not differ among groups. Mean deviation values for the Humphrey visual field test correlated positively with levels of Apo AI, ApoE, TTR, and complement factor H in OAG patients (P = 0.026, 0.012, 0.008, and 0.027, respectively), but age and IOP values were not correlated with protein levels. OAG patients had elevated levels of multiple biomarkers of Alzheimer's disease in the aqueous humor.

Review of the Influence of Pigment Dispersion and Exfoliation Glaucoma Diagnosis on Intraocular Pressure in Clinical Trials Evaluating Primary Open-angle Glaucoma and Ocular Hypertension

To evaluate published, randomized, prospective, parallel clinical trials utilizing currently approved glaucoma medications to determine what influence, if any, pigment dispersion (PD) or exfoliation glaucoma (XFG) patients had on the intraocular pressure. A review of clinical trial articles evaluating currently used topical glaucoma medicines. Articles were published between January 1995 and April 2011. If the articles met the inclusion/exclusion criteria, they were analyzed for PD and XFG. Twenty-four articles were included, containing 49 treatment arms that included PD or XFG patients. The range of PD patients was 0% to 4.5%, with a mean of 1.5±0.9%, and for XFG patients 0% to 6.3%, with a mean of 2.2±2.1%. The treatment arms with PD showed a difference in the intraocular pressures (IOPs), for all studies analyzed together, for the baseline IOPs between clinical trials that did and did not include PD patients (8 AM IOPs: with PD 26.5±0.9 mm Hg and without PD 25.8±1.3 mm Hg, P=0.024; and diurnal curve mean IOPs: with PD 25.3±1.1 mm Hg and without PD 24.5±1.3 mm Hg, P=0.024). The XFG treatment arms showed that there was a difference in the IOPs for all studies analyzed together for diurnal baseline IOPs between clinical trials that did and did not include XFG patients (with XFG 25.2±1.2 mm Hg and without XFG 24.3±1.0 mm Hg, P=0.016). Trial designs for prospective, parallel, glaucoma clinical studies that are performed in the United States generally can include PD and XFG patients with only a small impact on the IOP and a low number of such subjects enrolled.

24-hour efficacy of the bimatoprost–timolol fixed combination versus latanoprost as first choice therapy in subjects with high-pressure exfoliation syndrome and glaucoma

AimTo compare the 24-h intraocular pressure (IOP) control obtained with the bimatoprost–timolol fixed combination (BTFC) versus latanoprost in newly diagnosed, previously untreated exfoliation syndrome (XFS) or exfoliative glaucoma (XFG) patients...

Comparison of 24-Hour Intraocular Pressure Reduction Obtained with Brinzolamide/Timolol or Brimonidine/Timolol Fixed-Combination Adjunctive to Travoprost Therapy

To determine the adjunctive 24-h efficacy obtained with brinzolamide/timolol, or brimonidine/timolol fixed combinations (FCs) in open-angle glaucoma patients insufficiently controlled on travoprost monotherapy. Prospective, observer-masked, active controlled, crossover, comparison. Qualified primary open-angle or exfoliative glaucoma patients with a baseline intraocular pressure (IOP) >18 mm Hg at 10:00 on travoprost monotherapy were randomized for 3 months to either brinzolamide/timolol, or brimonidine/timolol FC therapy adjunct to travoprost. Patients were then crossed-over to the opposite therapy for another 3 months. At baseline and at the end of each treatment period, the patients underwent 24-h IOP monitoring. Fifty patients completed the study. The mean 24-h baseline IOP on travoprost monotherapy was 20.1 mm Hg [95% confidence interval (CI): 19.6, 20.7 mm Hg]. Both adjunctive FC therapies significantly reduced the IOP at each time point and for the mean 24-h IOP (P<0.001) compared with travoprost monotherapy. Brinzolamide/timolol FC provided a significantly lower mean 24-h IOP (17.2 mm Hg, 95% CI: 16.4, 17.9 mm Hg) than brimonidine/timolol FC (18.0 mm Hg, 95% CI: 17.3, 18.8 mm Hg) (P<0.001). For all the 3 timepoints between 18:00 and 02:00, the brinzolamide/timolol FC provided a significantly lower IOP than the brimonidine/timolol FC (P≤0.036). For the other 3 timepoints, no significant differences were detected. This study demonstrated that both FCs provide statistically and clinically significant incremental 24-h IOP lowering to travoprost monotherapy. The brinzolamide/timolol FC however achieves a better mean 24-h IOP control owing to the greater efficacy in late afternoon and during the night.

Risk Factors Associated with Progression in Exfoliative Glaucoma Patients

Purpose: To evaluate exfoliative glaucoma (XFG) patients over 5 years, determining risk factors associated with progression or non-progression of glaucoma. Methods: A retrospective, observational study. Patients were chosen from consecutive charts and data collected from each available visit included in the follow-up period. Data were abstracted for non-progressed XFG patients for 5 years and for progressed patients until glaucoma worsened. Progression was determined from patient records and by disc photographs. Results: There were 71 (53%) progressed and 63 (47%) non-progressed XFG patients.Baseline parameters demonstrated worse visual field damage (p = 0.014) and more prescribed medicines (p = 0.03) in progressed patients. The mean intraocular pressure (IOP) for progressed patients was 18.7 ± 4.3 and 17.3 ± 3.4 mm Hg for non-progressed patients (p = 0.047). The mean IOP that best separated the groups was 17 mm Hg with 60% staying non-progressed at or below this level and 30% above this level. At the last visit, progressed patients had more medicines prescribed (1.7) than non-progressed patients (1.3, p = 0.005). A multivariate regression analysis showed higher mean, peak and variance of IOP, number of glaucoma medications at the final visit and presence of a disc hemorrhage (n = 5) as independent risk factors for progression (p ≤ 0.05). Conclusion: IOP reduction in XFG may be essential in reducing disease progression. The presence of disc hemorrhage in XFG may suggest an increased probability of progression despite treatment to within the normal IOP range.

Ocular response analyzer to assess corneal biomechanical properties in exfoliation syndrome and exfoliative glaucoma

The aim of this work was to investigate the differences in corneal biomechanical parameters between healthy and exfoliation syndrome (EXS) and exfoliative glaucoma (EXG) patients. Two hundred and forty-four eyes of 102 healthy, 64 EXS, and 78 EXG patients were included in the study. Corneal biomechanical parameters were measured using an ocular response analyzer (ORA). Central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The differences in ORA parameters between study and control group participants were analyzed using Student's t test. In healthy subjects, EXS and EXG eyes mean corneal hysteresis (CH) values were 9.4 ± 1.4mmHg, 8.5 ± 1.5mmHg and 6.9 ± 2.1mmHg, respectively. The difference in mean CH between the EXG and the other two groups were statistically significant (p < 0.01 for both comparisons). CH was significantly lower in EXS patients than that of healthy eyes (p < 0.001). Mean corneal resistance factor (CRF) values were 9.8 ± 1.6mmHg, 9.3 ± 1.8mmHg and 9.5 ± 2.6mmHg, respectively. Except for the difference between the control and EXS eyes (p = 0.004), no statistically significant difference was found between the groups in relation to mean CRF. There were no significant differences in CCT between the control eyes and exfoliative eyes with or without glaucoma. In this study, CH was found to be significantly lower in eyes with exfoliation. Further studies are needed to establish the relationships between exfoliation, ocular biomechanics, and glaucoma.

Conjunctival Inflammatory Cells and Their Predictive Role For Deep Sclerectomy in Primary Open-angle Glaucoma and Exfoliation Glaucoma

To investigate the conjunctival inflammatory alterations of patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and correlate the findings with the success of deep sclerectomy (DS) surgery and with the patients' medical history. Altogether 25 POAG and ExG patients of the prospective DS study were divided, based on the diagnosis and success of the operation, into 4 groups, POAG S (success), POAG F (failure), ExG S, and ExG F. Controls were obtained from other ophthalmologic surgery patients who did not have glaucoma, and their conjunctiva was examined to be normal. Inflammatory cell subtypes in the conjunctiva were identified and quantified by using immunohistochemistry and monoclonal antibodies: CD3 (T-lymphocyte marker), CD4 (T-helper lymphocyte marker), CD8 (T-cytotoxic lymphocyte marker), CD20 (pan-B cell marker), CD38 (plasma cell marker), CD45RA (naïve T-cell marker), and CD68 (macrophage marker). Higher numbers of inflammatory cells were found in the conjunctiva of the glaucoma patients on medical treatment compared with the normal conjunctiva of the controls. Moreover, T-lymphocytes, T-helper lymphocytes, T-cytotoxic lymphocytes, B cells, plasma cells, and macrophages were found in significantly higher numbers in patients in whom DS failed during the follow-up period of 2.5 years than those with surgical success. High numbers of cytotoxic and helper T-lymphocytes, plasma cells, and macrophages indicate a chronic inflammatory reaction in the conjunctiva of glaucoma patients. The chronic inflammation is most probably owing to the chronic topical treatment of the patients and seems to be a significant risk factor for DS surgery failure.

Is There Any Difference in Target Intraocular Pressure for Exfoliative Glaucoma Patients with Cardiovascular Disease History?

To investigate if patients with exfoliation glaucoma (XFG) with cardiovascular disease (CVD) require different target intraocular pressure (IOP) compared to patients with XFG with no CVD for long-term stability. A retrospective, multicenter, observational cohort analysis included consecutive patients with XFG from 9 European academic centers, with a minimum of 5 years follow-up. In 201 patients, there was a statistical difference between progressed and non-progressed patients in mean (p=0.0049) and peak (p=0.015) IOP, variance of IOP (p=0.028), and number of medicine changes/year (p=0.0037). At a mean IOP ≥22 mmHg, patients progressed in 84% (32/38), between 14 and 21 mmHg in 54% (81/151), and at ≤13 mmHg in 33% (4/12). There was no difference in the rate of progression between groups based on CVD history (p=0.65). However, IOP that allowed ≤50% progression rate for patients with mild or no CVD was ≤20-21 mmHg and ≤18 mmHg for patients with severe disease. Further, at IOP ≥20 mmHg, 8% (1/12) of patients with severe CVD remained stable in contrast to 38% (16/42) of patients with mild and 21% (4/19) with no CVD history (p=0.0093). By multivariant regression analysis of the IOP and CVD measures, mean IOP was a risk factor for progression (p=0.0097). Although IOP is the main determinant of progression in XFG under treatment, history of severe CVD should be further investigated as potential risk factor for glaucomatous progression.

Lysyl Oxidase-like 1 Gene Polymorphisms in German Patients With Normal Tension Glaucoma, Pigmentary Glaucoma and Exfoliation Glaucoma

To evaluate the association between lysyl-oxidase-like 1 (LOXL1) gene polymorphisms and exfoliation glaucoma, pigmentary glaucoma and normal tension glaucoma in a case-control cohort of German patients. Six single nucleotide polymorphisms in a 22 kb genomic region encompassing the LOXL1 gene plus an additional "outlier" single nucleotide polymorphism located approximately 1.1 Mb upstream of LOXL1 were genotyped in 128 exfoliation glaucoma patients, 88 pigmentary glaucoma patients, 273 normal tension glaucoma patients, and 280 healthy control subjects either with TaqMan allelic discrimination assays or by direct sequencing, and a genetic association study was performed. For the exfoliation glaucoma cases, case-control allelic association for 6 single nucleotide polymorphisms were highly significant. In contrast, there were no genotypic differences between pigmentary glaucoma cases, normal tension glaucoma cases and controls. However, an association between rs1048661 genotype and age at disease onset was suggested for pigmentary glaucoma patients. Our study reveals that in the German population the LOXL1 genetic predisposition is limited to exfoliation glaucoma and does not include normal tension glaucoma. In addition, our study implicates that LOXL1 polymorphisms are not likely to have a major influence on the pathophysiology of pigmentary glaucoma. However, 1 nonsynonymous polymorphism may serve as a predictor of age at disease onset in pigmentary glaucoma.

Mitomycin‐C‐augmented deep sclerectomy in patients with primary open‐angle glaucoma and exfoliation glaucoma: a 1‐year prospective study

To investigate the efficacy and safety of mitomycin C (MMC)-augmented deep sclerectomy with implant (DSCI) in patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG). A total of 68 eyes of 68 patients with POAG and ExG were enrolled consecutively to undergo DSCI with MMC (0.4 mg/ml for 2 min). The intraocular pressure (IOP), number of antiglaucoma medications, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser goniopunctures and complications were compared postoperatively. Surgery was considered as a complete success when IOP was < 18 mmHg without antiglaucoma medication. Preoperatively, the mean IOPs were 23.1 +/- 5.8 and 25.4 +/- 8.3 mmHg, and 13.8 +/- 6.1 and 11.2 +/- 5.6 mmHg in the POAG and ExG groups, respectively, at 12 months. 77.4% and 75.7% of surgeries were a complete success in the POAG and ExG groups, respectively [not significant (NS)]. Five patients (16.1%) in the POAG group but none in the ExG group (0%) were receiving antiglaucoma medication at 12 months (NS). Nd:YAG laser goniopuncture was performed in 29.0% of eyes in the POAG group and in 55.6% of eyes in the ExG group (p = 0.047). Postoperatively, choroidal detachment occurred in 16.1% of eyes in the POAG group and in 10.8% of eyes in the ExG group (NS). We encountered no serious complications related to MMC use. DS with MMC augmentation appears to be equally effective in ExG and POAG patients in lowering IOP to target levels, at least in the short term, with few immediate postoperative complications.

This issue of Acta

The illustration on the cover shows bilateral upper lid masses that happen to be encapsulated contact lenses as reported by Perera et al. in this issue of Acta. Stefánsson et al. suggest that ethics rules in medical research have become too strict and should be relaxed in retrospective clinical studies. Professor Morten la Cour in Copenhagen was the 2007 Acta-EVER lecturer and contributes a review paper on the physiology of the retinal pigment epithelium and its role in health and disease. Tarkkanen et al. in Helsinki found no difference in the prevalence of hypertension or ischemic heart disease between patients with primary open angle glaucoma and those with exfoliative glaucoma. However diabetes mellitus was less frequent among the exfoliative glaucoma patients. The same authors also contribute a letter to the editor where they suggest that the prevalence of age-related macular degeneration is similar in patients with primary open angle and exfoliative glaucoma. Saarela and Airaksinen in Oulu suggest that the Heidelberg retina tomograph may be used to detect small changes in optic nerve head and progressive retinal nerve fiber layer defects. Sato et al. in Japan find a strong association between retinal nerve fiber layer thickness and retinal sensitivity, but only when the atrophy of nerve fibers is relatively severe. Gauti Jóhannesson et al. in Umeå find a reasonable correlation and concordance between IOP measurements with Pascal, ICare and Goldman applanation tonometry. The ICare showed significantly dependency on central corneal thickness whereas Goldman applanation tonometry and Pascal tonometry showed significant dependency on corneal curvature. Vuori and Mäntyjärvi in Turku found that an exact correction of myopia is important to prevent false visual field interpretation in patients with tilted disc syndrome. Nakazawa et al. in Japan looked at changes in optic disc deviation and peripapillary crescent in eyes with mild or moderate myopia. They found the optic disc to deviate mostly nasally with the progression of myopia. Yu-Wai-Man et al. in Newcastle found no evidence of auditory dysfunction in 10 patients with Leber’s hereditary optic neuropathy. Puell and Barrio in Madrid suggest that distraction, such as cell phones, may impair a drivers useful visual field, whereas low concentrations of alcohol do not. Weeber and van der Heijde in the Netherlands created a computer model of the deformation of the lens during accommodation. Falck et al. in Oulu found that only one out of 220 persons over 60 years old in Finland was in current need of cataract surgery. This suggests that the supply of cataract surgery is extremely good. Akhtar et al. in United Kingdom, Switcherland and Austria describe the ultrastructural details of collagen fibrils and proteoglycan development in the zebrafish cornea, and suggest that this may be useful in the understanding of human corneal physiology and genetics. Kashiwabuchi et al. in Brazil suggest that penetrating keratoplasty may be useful for difficult cases of acanthamoeba keratitis. Gíavina-Bianchi et al. in Brasil have developed a mouse model for allergic conjunctivitis. Banat et al. in Germany examined light evoked responses from photoreceptor cells and other retinal cells in mouse and bovine retina in vitro. Minnella et al. in Rome found intravitreal bevacizumab to be safe and effective in 15 eyes with proliferative diabetic retinopathy and vitreous haemorrhages. Islam et al. in London discuss saccadic Lateropulsion. Malandrini et al. in Italy used confocal microscopy in a patient with recurrent conjunctival neoplacia. I hope the readers enjoy this issue of Acta.

Meta-analysis of 24-Hour Intraocular Pressure Studies Evaluating the Efficacy of Glaucoma Medicines

To evaluate efficacy and safety data of currently available ocular hypotensive medicines derived from 24-hour studies, of similar design, in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma, or ocular hypertension (OH). Meta-analysis of published articles evaluating patients with POAG, exfoliative glaucoma, or OH. We included articles that were randomized, prospective, single- or double-masked, comparative studies of ocular hypotensive therapies over 24 hours. Each article selected contained an untreated baseline, >or=4-week treatment period, >/=20 patients per treatment arm, and >or=6 time points not spaced >5 hours apart and used Goldmann applanation or Tonopen tonometry (supine measurements) to measure intraocular pressure (IOP). Twenty-four-hour IOP efficacy. This analysis included 864 separate 24-hour treatment curves from 386 patients in 28 treatment arms from 11 studies. A statistical difference in the mean diurnal pressure decrease existed between monotherapy treatments for POAG/OH patients, with bimatoprost (29%) and travoprost (27%) showing the greatest 24-hour reduction (P = 0.026). Timolol 0.5% was less effective than latanoprost (24% vs. 19% reduction) but decreased the pressure at each night time point (P = 0.0003). Dorzolamide showed a 19% 24-hour pressure reduction and brimonidine 0.2% a 14% one. In exfoliative glaucoma patients, latanoprost and travoprost showed higher baseline and treatment pressures, although the pressure reductions (29% and 31%, respectively) were greater generally than observed with POAG/OH. An evening-dosed latanoprost/timolol fixed combination reduced the pressure 33%, and the dorzolamide/timolol fixed combination (DTFC), 26%. However, the power to detect a difference for this specific comparison was probably low, due to the limited number of patients (n = 20) in the DTFC group. A statistical difference between evening-dosed (24%) and morning-dosed (18%) latanoprost (P<0.0001) was noted, but not between evening (27%) and morning (26%) travoprost (P = 0.074). The mean reduction of night time points was statistically lower than day time points for latanoprost (P = 0.031), timolol (P = 0.032), and brimonidine (P = 0.050), but not for dorzolamide. Dorzolamide (P = 0.60), travoprost (P = 0.064), and bimatoprost (P = 0.057) did not demonstrate nighttime pressures lower than daytime ones. The mean reduction of night time points was statistically lower than that of day time points for latanoprost (P = 0.031), timolol (P = 0.032), and brimonidine (P = 0.050), but not for dorzolamide (P = 0.60), bimatoprost (P = 0.057), travoprost (P = 0.064). Similar relative efficacies generally exist in various classes of ocular hypotensive agents during night and day hours.

Phospholipases A2 in normal human conjunctiva and from patients with primary open-angle glaucoma and exfoliation glaucoma

Chronic situations like long-term use of topical medications induces conjunctival inflammation and is also a significant risk factor for failure of filtering surgery. We evaluated conjunctival expression of group IIA secretory PLA(2) (sPLA(2)-IIA), group V secretory PLA(2) (sPLA(2)-V), calcium-independent PLA(2) (iPLA(2)) and cytosolic PLA(2) (cPLA(2)). Samples were obtained from non-glaucomatous patients (control subjects), and patients with either primary open-angle glaucoma (POAG) or exfoliation glaucoma (ExG). All the glaucoma patients had been treated with antiglaucomatous medication, and underwent deep sclerectomy surgery. Antibodies against sPLA(2)-IIA, sPLA(2)-V, iPLA(2) and cPLA(2) were used for immunohistochemical staining of frozen tissue sections. In the human conjunctiva of non-glaucomatous patients, immunostaining of sPLA(2)-IIA, sPLA(2)-V or cPLA(2) was low and positively stained cells were mainly localized in the surface of the epithelium. In contrast, iPLA(2) was found to predominate in human normal conjunctiva and it demonstrated strong labeling throughout the epithelium. The stromal staining of iPLA(2) was weak. Expression of sPLA(2)-IIA was significantly increased in stromal fibers of patients with POAG or ExG. No changes were found in levels of sPLA(2)-V, iPLA(2) or cPLA(2) between the patient groups and controls. These findings demonstrate that sPLA(2)-IIA, sPLA(2)-V, iPLA(2) and cPLA(2) are expressed in the conjunctiva of non-glaucomatous patients. In the epithelium, sPLA(2)-IIA, sPLA(2)-V, and cPLA(2) may participate in protection against risks caused by mechanical wear and tear stress whereas iPLA(2) may regulate remodeling and maintenance of membrane phospholipids. sPLA(2)-IIA may also have the important role in the degradation of bacteria. In conjunctival stroma of POAG and ExG patients, sPLA(2)-IIA may play a role in the development of scar tissue after glaucoma filtration surgery.