The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome.

LOXL1 (lysyl oxidase-like 1) has been identified as the major effect locus in pseudoexfoliation (PEX) syndrome, a fibrotic disorder of the extracellular matrix and frequent cause of chronic open-angle glaucoma. However, all known PEX-associated common variants show allele effect reversal in populations of different ancestry, casting doubt on their biological significance. Based on extensive LOXL1 deep sequencing, we report here the identification of a common non-coding sequence variant, rs7173049A>G, located downstream of LOXL1, consistently associated with a decrease in PEX risk (odds ratio, OR = 0.63; P = 6.33 × 10-31) in nine different ethnic populations. We provide experimental evidence for a functional enhancer-like regulatory activity of the genomic region surrounding rs7173049 influencing expression levels of ISLR2 (immunoglobulin superfamily containing leucine-rich repeat protein 2) and STRA6 [stimulated by retinoic acid (RA) receptor 6], apparently mediated by allele-specific binding of the transcription factor thyroid hormone receptor beta. We further show that the protective rs7173049-G allele correlates with increased tissue expression levels of ISLR2 and STRA6 and that both genes are significantly downregulated in tissues of PEX patients together with other key components of the STRA6 receptor-driven RA signaling pathway. siRNA-mediated downregulation of RA signaling induces upregulation of LOXL1 and PEX-associated matrix genes in PEX-relevant cell types. These data indicate that dysregulation of STRA6 and impaired retinoid metabolism are involved in the pathophysiology of PEX syndrome and that the variant rs7173049-G, which represents the first common variant at the broad LOXL1 locus without allele effect reversal, mediates a protective effect through upregulation of STRA6 in ocular tissues.

Diffuse brain damage in normal tension glaucoma.

Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP <21 mm Hg despite the typical glaucomatous findings, represents the most suitable model of glaucoma to test the validity of this hypothesis. We acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc.

Hydrus microstent compared to selective laser trabeculoplasty in primary open angle glaucoma: one year results.

BACKGROUND: To compare the reduction of intraocular pressure (IOP) and glaucoma medications following selective laser trabeculoplasty (SLT) versus stand-alone placement of the Hydrus microstent, a microinvasive glaucoma surgery device. DESIGN: Prospective interventional case-series. University practice. PARTICIPANTS: Fifty six eyes (56 patients) with uncontrolled primary open-angle glaucoma. METHODS: Patients received either SLT (n = 25) or Hydrus implantation (n = 31) in two centres. Patients were evaluated at baseline and 1, 7 days, 1, 3, 6 and 12 months after surgery. MAIN OUTCOME MEASURES: Intraocular pressure and number of glaucoma medications variations inter-groups and intra-groups. RESULTS: There were no significant differences at baseline between groups, but the mean deviation was worse in the Hydrus group (-8.43 ± 6.84 dB, confidence limits (CL)-2.8/-3.3 vs.-3.04 ± 0.65 dB, CL-6/-10.8; P < 0.001). After 12 months, there was a significant decrease in IOP and medications in the Hydrus group compared with baseline values. In the SLT group, only the decrease in IOP was significant. There was 3-fold greater reduction in medication use in the Hydrus group compared with SLT (-1.4 ± 0.97 vs.-0.5 ± 1.05, P = 0.001). 47% of patients were medication free at 12 months in the Hydrus group (4% in the SLT group). No complications were recorded in the SLT group. In the Hydrus group, three patients experienced a temporary reduction of visual acuity post-operatively, and two patients had post-operative IOP spikes that resolved within one week. CONCLUSIONS: Both SLT and Hydrus implantation reduced IOP without serious adverse events. Hydrus implantation led to a significant and further reduction in medication dependence at 12 months.

Early changes of brain connectivity in primary open angle glaucoma.

Our aim was to assess in primary open angle glaucoma (POAG), a major cause of irreversible blindness worldwide, whether diffuse brain changes recently shown in advanced stage can be detected since the early stage. We used multimodal magnetic resonance imaging (MRI) in 57 patients with the three POAG stages and in 29 age-matched normal controls (NC). Voxelwise statistics was performed with nonparametric permutation testing. Compared with NC, disrupted anatomical connectivity (AC) was found in the whole POAG group along the visual pathway and in nonvisual white matter tracts (P < 0.001). Moreover, POAG patients showed decreased functional connectivity (FC) in the visual (P = 0.004) and working memory (P < 0.001) networks whereas an increase occurred in the default mode (P = 0.002) and subcortical (P < 0.001) networks. Altered AC and FC were already present in early POAG (n = 14) in both visual and nonvisual systems (P ≤ 0.01). Only severe POAG (n = 30) showed gray matter atrophy and this mapped on visual cortex (P < 0.001) and hippocampus (P < 0.001). Increasing POAG stage was associated with worsening AC in both visual and nonvisual pathway (P < 0.001), progressive atrophy in the hippocampus and frontal cortex (P < 0.003). Most of the structural and functional alterations within and outside the visual system showed correlation (P < 0.001 to 0.02) with computerized visual field and retinal nerve fiber layer thickness. In conclusion, the complex pathogenesis of POAG includes widespread damage of AC and altered FC within and beyond the visual system since the early disease stage. The association of brain MRI changes with measures of visual severity emphasizes the clinical relevance of our findings. Hum Brain Mapp 37:4581-4596, 2016. © 2016 Wiley Periodicals, Inc.

Repeatability and reproducibility of applanation resonance tonometry: a cross-sectional study.

BACKGROUND: To assess repeatability (intra-observer variability) and reproducibility (inter-operator variability) of intraocular pressure (IOP) measurements with servo-controlled Bioresonator Applanation Resonance Tonometry (ART) and to evaluate possible influential factors. METHODS: The study included 178 patients (115 glaucoma and 63 controls; one eye per subject). IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by ART (ART1, ART2), in randomized sequence, by a single operator to assess intra-operator variability. Each ART measurement consisted on 3 readings. To assess inter-operator variability 2 evaluators performed 2 measurements each (in random order) on the same patient. Repeatability and reproducibility were assessed by the coefficient of variation (CoV) and intraclass correlation coefficient (ICC). RESULTS: In the entire cohort, ART1 was 0.4 ± 2.2 mmHg (-7.0 to 5.7 mmHg) higher than ART2 (p = 0.03) regardless of test order. Intra-operator CoV was 7.0% ± 6.3%, and ICC was 0.80-0.92. Inter-operator CoV ranged between 5.7% ± 6.1% and 8.2% ± 7.2%, and ICC between 0.86 and 0.97. ART1 and 2 were respectively 1.7 ± 3.1 and 1.3 ± 3.1 mmHg higher than GAT (p < 0.01). Test-retest difference with ART fell within ±1 mmHg in 41% of cases, within ±2 mmHg in 70%, within ±3 mmHg in 85%. 15% had a test-retest difference higher than ± 3 mmHg; Bland-Altman 95% intervals of confidence were -3.9 and +4.6 mmHg. Results were unaffected by age, diagnosis, central corneal thickness, keratometry, operator, randomization sequence. CONCLUSIONS: In most cases ART repeatability and reproducibility were high, with no differences due to patients' characteristics. ART measurements overestimated GAT by a mean of 1.3-1.7 mmHg.

Variants in ASB10 are associated with open-angle glaucoma.

The molecular events responsible for obstruction of aqueous humor outflow and the loss of retinal ganglion cells in glaucoma, one of the main causes of blindness worldwide, remain poorly understood. We identified a synonymous variant, c.765C>T (Thr255Thr), in ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) in a large family with primary open angle glaucoma (POAG) mapping to the GLC1F locus. This variant affects an exon splice enhancer site and alters mRNA splicing in lymphoblasts of affected family members. Systematic sequence analysis in two POAG patient groups (195 US and 977 German) and their respective controls (85 and 376) lead to the identification of 26 amino acid changes in 70 patients (70 of 1172; 6.0%) compared with 9 in 13 controls (13 of 461; 2.8%; P = 0.008). Molecular modeling suggests that these missense variants change ASB10 net charge or destabilize ankyrin repeats. ASB10 mRNA and protein were found to be strongly expressed in trabecular meshwork, retinal ganglion cells and ciliary body. Silencing of ASB10 transcripts in perfused anterior segment organ culture reduced outflow facility by ∼50% compared with control-infected anterior segments (P = 0.02). In conclusion, genetic and molecular analyses provide evidence for ASB10 as a glaucoma-causing gene.

Common sequence variants in the LOXL1 gene in pigment dispersion syndrome and pigmentary glaucoma.

BACKGROUND: Single nucleotide polymorphisms (SNPs) within the LOXL1 gene are associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The aim of our study is to investigate a potential involvement of LOXL1 gene in the pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). METHODS: A cohort of Caucasian origin of 84 unrelated and clinically well-characterised patients with PDS/PG and 200 control subjects were included in the study. Genomic DNA from whole blood was extracted and the coding and regulatory regions of LOXL1 gene were risequenced in both patients and controls to identify unknown sequence variations. Genotype and haplotype analysis were performed with UNPHASED software. The expression levels of LOXL1 were determined on c-DNA from peripheral blood lymphocytes by quantitative real-time RT-PCR. RESULTS: A significant allele association was detected for SNP rs2304722 within the fifth intron of LOXL1 (Odds ratio (OR = 2.43, p-value = 3,05e-2). Haplotype analysis revealed the existence of risk and protective haplotypes associated with PG-PDS (OR = 3.35; p-value = 1.00e-5 and OR = 3.35; p-value = 1.00e-4, respectively). Expression analysis suggests that associated haplotypes can regulate the expression level LOXL1. CONCLUSIONS: Haplotypes of LOXL1 are associated with PG-PDS independently from rs1048661, leading to a differential expression of the transcript.

Changes in the morphological and functional patterns of the ocular surface in patients treated with prostaglandin analogues after the use of TSP 0.5%® preservative-free eyedrops: a prospective, multicenter study.

AIM: To investigate and compare the effects of topical benzalkonium chloride-preserved prostaglandins (PGAs) on the ocular surface in patients with primary open-angle glaucoma before and after 3 months of treatment with additional 0.5% preservative-free tamarind seed polysaccharide single-dose eyedrops (TSP®, Oftagen, Pisa, Italy). METHODS: This was a prospective, longitudinal, multicenter study. From 5 different Italian glaucoma centers, 10 glaucomatous patients were recruited in each center. All the patients were treated with a PGA with preservative for at least 1 year. Preservative-free artificial tears 3 times per day were prescribed. The participants were subjected to clinical and instrumental evaluation at baseline, after 1 month and after 3 months of treatment. All patients were examined with a digital corneal confocal laser scanning microscope (HRT II Rostock Cornea Module). RESULTS: After 3 months of TSP 0.5% treatment, an improvement of some ocular signs and symptoms was found. The percentage of conjunctival hyperemia decreased from 67 to 13%. Schirmer's test and breakup time significantly changed from the baseline after 3 months. Confocal microscopy showed a significant increase in conjunctival goblet cells. CONCLUSION: Artificial substitutes, in particular TSP 0.5%, might protect the ocular surface hence giving higher compliance, adherence and quality of life to the patients.

Short-term changes in intraocular pressure after phacoemulsification in glaucoma patients.

PURPOSE: To evaluate short-term intraocular pressure (IOP) changes after phacoemulsification in glaucoma and normal patients and the effect of oral acetazolamide (Diamox) to control IOP in these patients. METHODS: 120 patients undergoing cataract surgery were included in this prospective multicenter study involving 6 University Eye Clinics: 60 patients with well-controlled primary open-angle glaucoma (POAG) and 60 controls. Half of the study participants received oral acetazolamide, 250 mg, 1 and 6 h after surgery. The treated and untreated groups were matched for age and density of cataract. All patients underwent a standard phacoemulsification procedure and were checked for IOP with Goldmann tonometry in the morning before surgery and then at 3, 6, 21 and 24 h postoperatively by a masked evaluator. RESULTS: The group with POAG showed a significant postsurgical increase in IOP (p < 0.001) at all time points. Six of thirty (20%) untreated POAG patients showed at least 1 IOP reading above 30 mm Hg whereas acetazolamide significantly reduced postoperative IOP at all time points (p < 0.01) and in no case was IOP >30 mm Hg. The control group had high IOP during the first 6 h (p < 0.01), but normal values thereafter. CONCLUSION: A significant short-term IOP increase may be found after phacoemulsification both in POAG and normal patients; this is not dangerous in normal subjects, but can be potentially dangerous in POAG patients. The use of systemic acetazolamide provided significant control of IOP and could be considered a 'possible standard' management of cataract surgery in POAG patients.

Retinal nerve fiber layer thinning in CADASIL: an optical coherence tomography and MRI study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a genetic form of small-vessel disease causing subcortical dementia. A relevant role of axonal injury was recently proposed to explain disability and cognitive decline in this disease. The retinal nerve fiber layer (RNFL) is the only part of the brain where unmyelinated axons can be visualized and quantified in vivo. Their assessment may be an easily reproducible marker of neurodegenerative processes. The aim of this study was to investigate axonal degeneration in CADASIL by measuring RNFL thickness and correlating it with MRI measures of global and regional cerebral atrophy. METHODS: RNFL thickness was measured using optical coherence tomography in 17 CADASIL patients. Average values per quadrant (temporal, superior, nasal, inferior) and overall values were compared with those of normal sex- and age-matched subjects. Data of 13 patients were analyzed for correlations with MRI-based global and regional brain volumes normalized for head size. RESULTS: RNFL thickness was significantly reduced in CADASIL patients with respect to controls (p < 0.05). No significant correlations were found between RNFL thinning and brain atrophy. CONCLUSIONS: RNFL thinning suggests that retinal axonal loss occurs in CADASIL, even in the absence of subjective visual deficit.

Use of amniotic membrane transplantation in isolated conjunctival Bowen disease: a case report.

PURPOSE: To report a case of isolated conjunctival Bowen disease treated with surgical resection and amniotic membrane transplantation. METHODS: Interventional case report. RESULTS: A 70-year-old man was admitted to our clinic with a large conjunctival verrucous plaque well-demarcated in the correspondence of the bulbar conjunctiva in the superior quadrant of the left eye with involved limbal and corneal surface. Ophthalmologic examination on slit-lamp examination and color fundus photographs were carried out before surgery and the results were evaluated. CONCLUSIONS: Treatment options and treatment studies of Bowen disease are difficult because there are a variety of different protocols and the success of the management depends on several factors (body site, lesion size, number of lesions, and thickness). In the conjunctival localization of the lesion, amniotic membrane transplantation appears to be a useful therapeutic choice after surgical resection of the lesion used to reconstruct ocular and conjunctival surface.

Altered Large-Scale Brain Functional Connectivity in Ocular Hypertension.

We hypothesized that assessment of brain connectivity may shed light on the underpinnings of ocular hypertension (OHT), characterized by raised intraocular pressure (IOP) and no typical glaucomatous findings. OHT carries a risk for future glaucoma development, thus representing a model of presymptomatic condition. In previous studies on glaucoma, we showed altered brain connectivity since the early stage and in case of normal IOP. In this pilot study, we used a multimodal MRI approach by modeling voxelwise measures of gray matter volume, anatomical connectivity along white matter(WM) tracts, and large-scale functional connectivity in OHT subjects (n = 18, age: 58.3 ± 9.8 years) and demographically matched normal controls (n = 29). While OHT brain had no structural alterations, it showed significantly decreased functional connectivity in key cognitive networks [default mode network, frontoparietal working memory network (WMN), ventral attention network (VAN), and salience network (SN)] and altered long-range functional connectivity, which was decreased between default mode and SNs and increased between primary and secondary visual networks (VN). Overall, such findings seem to delineate a complex neuroplasticity in the OHT brain, where decreased functional connectivity in non-visual networks may reflect a type of temporarily downregulated functional reserve while increased functional connectivity between VN may be viewed as a very early attempt of adaptive functional reorganization of the visual system.

Exploring the gap between diagnostic research outputs and clinical use of OCT for diagnosing glaucoma.

AIMS: To explore the gap between diagnostic research outputs and clinical use of optical coherence tomography (OCT) in glaucoma and assess the reliability of a specific reference database when applied to a morphological imaging parameter for diagnostic purposes. METHODS: Consecutive subjects enrolled in the Multicenter Italian Glaucoma Imaging Study (MIGIS) have been included in this cross-sectional, comparative evaluation of diagnostic tests study. Patients underwent measurement of global and sectorial peripapillary retinal nerve fibre thickness (pRNFL) and minimum rim width (MRW) by OCT. The sensitivity and specificity of reference-database categorical classifications were calculated by means of 2×2 tables and sensitivity was compared with that of the corresponding continuous parameter extracted from the receiver operating characteristic (ROC) curves by matching the specificity. RESULTS: 280 Caucasian subjects have been included. At matched specificities, the sensitivity of pRNFL categorical classifications was statistically similar to that of the corresponding continuous parameters, whereas the sensitivity of the MRW categorical classifications was significantly lower than that of the corresponding continuous parameters. CONCLUSIONS: The diagnostic accuracy of reference database classifications might be lower than that extrapolated from the ROC curves of continuous parameters used in diagnostic research. The gap between the accuracy of these two approaches may be used to estimate the reliability of a specific reference database when applied to a continuous parameter for diagnostic purposes.

Macular versus nerve fibre layer versus optic nerve head imaging for diagnosing glaucoma at different stages of the disease: Multicenter Italian Glaucoma Imaging Study.

PURPOSE: To compare the diagnostic accuracy of minimum rim width (MRW), peripapillary retinal nerve fibre layer (pRNFL) and multilayered macular analysis by Spectralis SD-OCT (Heidelberg Engineering, Germany) in discriminating perimetric glaucoma at different stages of the disease from healthy eyes. METHODS: In this multicentre, prospective, evaluation of diagnostic tests study, multilayered macular analysis and MRW and pRNFL were obtained from one eye of 197 glaucoma (76 early, 68 moderate and 53 advanced) and of 83 healthy controls from the Multicenter Italian Glaucoma Imaging Study (MIGIS). The reference standard for classifying eyes as glaucomatous and for staging the disease was the visual field. The main outcome measures were area under the ROC curve (AUC) and sensitivity at fixed specificity (95%). RESULTS: Average MRW and average pRNFL showed the highest and similar diagnostic accuracy in both the whole study population (AUC 0.968 and 0.939) and early glaucoma (AUC 0.956 and 0.929). Among the macular parameters, the three innermost retinal layers combined as the Ganglion Cell Complex provided the highest diagnostic accuracy (AUC 0.931) in the whole population, which was statistically similar to that of average pRNFL but inferior to that of average MRW. Compared to both average MRW and pRNFL, all macular parameters showed statistically significant lower accuracy in early glaucoma, but accuracy in moderate and advanced glaucoma showed no statistically significant differences among three protocols. CONCLUSION: The diagnostic accuracy of MRW, pRNFL and macular analysis by Spectralis SD-OCT is overall good. MRW and pRNFL analysis performs statistically and clinically better than macular analysis to discriminate early glaucoma from healthy eyes.

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1.

Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.

In Vivo Goblet Cell Density as a Potential Indicator of Glaucoma Filtration Surgery Outcome.

PURPOSE: We analyzed the preoperative conjunctival goblet cell density (GCD), MUC5AC, and HLA-DR in glaucomatous patients undergoing trabeculectomy, using laser scanning confocal microscopy (LSCM) and impression cytology (IC). METHODS: We enrolled 57 patients undergoing trabeculectomy. At baseline LSCM and IC were performed at the site planned for surgery; LSCM was repeated after 12 months at the bleb site. The main outcomes were: GCD, mean microcyst density (MMD) and area (MMA) at LSCM, MUC5AC, and HLA-DR positivity at IC, and IOP. The relationships between baseline GCD, and 12-month IOP, MMD, and MMA were analyzed. RESULTS: Trabeculectomy was successful in 39 patients (complete success in 27, Group 1; qualified in 12, Group 2), and unsuccessful in 18 (Group 3). At baseline IOP (mm Hg) was 27.2 ± 3.12, 27.5 ± 2.23, and 27.7 ± 1.90 in Groups 1 to 3, respectively; GCD and MUC5AC positivity were higher in Group 1 compared to Groups 2 and 3 (P < 0.05); HLA-DR, MMD, and MMA were not significantly different among the groups. At 12 months, IOP reduced by 45.3%, 35.4%, and 12.8% in Groups 1 to 3, respectively. Goblet cell density did not change in Group 1, whereas it was reduced in Groups 2 and 3 (P < 0.05), with values lower in Group 3. Mean microcyst density and MMA increased in Groups 1 and 2 (P < 0.05), with values higher in Group 1 (P < 0.05). Baseline GCD positively correlated with 12-month IOP reduction (P < 0.001, r = 0.641), MMD (P < 0.05, r = 0.454), and MMA (P < 0.001, r = 0.541). CONCLUSIONS: Goblet cells positively affect the filtration ability after trabeculectomy; therefore, preoperative GCD could be considered as a potential in vivo biomarker of surgical success.

Health-related quality of life in patients with primary open-angle glaucoma. An Italian multicentre observational study.

PURPOSE: As a progressive condition, glaucoma may impair health-related quality of life (HRQoL), due to vision loss and other factors. This study evaluated HRQoL in a cohort of patients treated for primary open-angle glaucoma (POAG) and assessed its association with clinical features. METHODS: This was an Italian, multicentre, cross-sectional, observational study with the subgroup of newly diagnosed patients with POAG prospectively followed up for one year. Patients with previous or new diagnosis (or strong clinical suspicion) of POAG aged >18 years were considered eligible. Information was collected on demographic characteristics, medical history, clinical presentation and POAG treatments. HRQoL was measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and Glaucoma Symptom Scale (GSS). Subscale and total scores were obtained and a Pearson correlation coefficient between instruments' scores calculated. RESULTS: A total of 3227 patients were enrolled from 2012 to 2013 and 3169 were analysed. Mean age was 66.9 years. A total of 93.8% had a previous diagnosis (median duration: 8.0 years). Median values for mean deviation and pattern standard deviation were 3.9 and 3.6 dB, respectively. Mean scores on most subscales of the NEI-VFQ-25 exceeded 75.0 and mean GSS subscale scores ranged between 70.8 and 79.7 (with a total mean score of 74.8). HRQoL scores on both scales were significantly inversely associated with POAG severity. CONCLUSION: In this large sample of Italians treated for POAG, disease severity was limited and HRQoL scores were high. QoL decreased with advancing disease severity. These findings confirm the role of vision loss in impairing QoL in POAG, underlying the importance of timely detection and appropriate treatment.

Brinzolamide 1%/timolol versus dorzolamide 2%/timolol in the treatment of open-angle glaucoma or ocular hypertension: prospective randomized patient-preference study.

PURPOSE: The objective of this study was to assess preference for fixed-combination brinzolamide 1%/timolol 0.5% (BTFC) versus fixed-combination dorzolamide 2%/timolol 0.5% (DTFC) in patients with open-angle glaucoma or ocular hypertension. METHODS: In this prospective, single-masked crossover study, patients were randomized 1:1 to BTFC-DTFC or DTFC-BTFC treatment sequences. Patients self-administered each medication for 7 days, with a 48-hour washout period between treatments, and rated ocular discomfort after each treatment period. Medication preferences based on ocular comfort (primary endpoint) and anticipated adherence were assessed. Safety outcomes included adverse events and intraocular pressure. Between-group differences in treatment preference and ocular discomfort scores were analyzed using chi-square and Wilcoxon-Mann-Whitney tests, respectively. Adherence, intraocular pressure, and adverse events were summarized descriptively. RESULTS: In total, 112 patients were enrolled (mean ± SD age, 66±11 years), and 109 patients completed the study. Numerically, more patients in the intent-to-treat dataset preferred BTFC versus DTFC (59.3% versus 40.7%); however, this result was not statistically significant (treatment difference, 18.6%; P=0.0670). Mean ocular discomfort scores (range, 0-9) were statistically significantly lower with BTFC versus DTFC (2.6 versus 3.7; P=0.0002, Wilcoxon- Mann-Whitney test). More patients who preferred BTFC over DTFC were confident that they would adhere to their preferred medication. Treatment-related adverse events included blurred vision with BTFC and eye irritation or eye pain with DTFC. CONCLUSION: BTFC and DTFC were preferred by approximately 60% and 40% of patients, respectively, and BTFC was associated with less patient-reported ocular discomfort. Greater ocular comfort of glaucoma medications may improve treatment adherence.

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes.

OBJECTIVE: To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. METHODS: One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. RESULTS: ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. CONCLUSIONS: The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression.

Circadian intraocular pressure patterns in healthy subjects, primary open angle and normal tension glaucoma patients with a contact lens sensor.

PURPOSE: To examine the circadian intraocular pressure (IOP) patterns in healthy subjects, in primary open angle and normal tension glaucoma (POAG; NTG) using a contact lens sensor (CLS; Sensimed Triggerfish, Lausanne, Switzerland). METHODS: This was an observational, nonrandomized study. Ten healthy subjects (Group 1, 10 eyes) and 20 glaucomatous patients [20 eyes, 10 with POAG (Group 2) and 10 with NTG (Group 3)] were enrolled. All patients were controlled with prostaglandin analogues. The 24-hr IOP pattern was the main outcome. The morning (6AM-11AM), afternoon/evening (noon-11PM) and night (midnight-5AM) subperiod patterns, peaks and prolonged peaks (>1 hr) were secondary outcomes. RESULTS: Mean 24-hr IOP pattern showed a nocturnal acrophase in all groups. Patterns were significantly different among groups (p = 0.02), with highest nocturnal IOP values in POAG. Prolonged peaks were more common in patients with glaucoma (70%) than in healthy subjects (33.3%) (p < 0.001). Significant differences were found for Groups 2 and 3 in the morning versus afternoon/evening (p = 0.019 and p = 0.035, Bonferroni correction), morning versus night (p = 0.005 and p < 0.0001) and afternoon/evening versus night periods comparisons (p < 0.0001 for both groups). In Group 1, patterns significantly differed in the morning versus night and afternoon/evening versus night period comparisons (p < 0.0001). CONCLUSIONS: Continuous 24-hr IOP monitoring with the CLS revealed a nocturnal acrophase in healthy subjects and, more markedly, in glaucoma. Because the diurnal IOP profile seems not to predict the nocturnal rhythm, the circadian IOP pattern should be evaluated in clinical practice. These findings may be worthwhile for the management of glaucoma.