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Poor adherence to topical glaucoma medications has been linked to worse visual field outcomes in glaucoma patients. Therefore, identifying and overcoming the adherence barriers are expected to slow down the progression of disease. The most common barriers to adherence, in addition to the lack of knowledge, include forgetfulness, side effects of medications, difficulties with drop instillation and low self-efficacy. Symptoms and signs of ocular surface disease, which importantly reduce patients’ quality of life, are decreased by using preservative-free topical medications. Sustained drug delivery systems using different vehicles seem promising for relieving the burden of drop administration. Currently, only the bimatoprost sustained-release intracameral implant is available for clinical use and single administration. In the era of digitalization, smart drug delivery-connected devices may aid adherence and, by sharing data with care providers, improve monitoring and adjusting treatment. Selective laser trabeculoplasty as first-line treatment delays the need for drops, whereas minimally invasive glaucoma procedures with and without devices combined with cataract surgery increase the likelihood of patients with early-to-moderate glaucoma to remain drop free or reduce the number of drops needed to control intraocular pressure. The aim of this narrative review is to present and discuss devices and treatments that may improve adherence by reducing the need for drops and side effects of medications and aiding in glaucoma monitoring. For the future, there is a need for studies focusing on clinically important outcomes, quality of life and the cost of intervention with longer post-interventional follow up.

Purpose To investigate the value of pattern electroretinography (PERG) and photopic negative response (PhNR) in monitoring glaucoma compared to standard clinical tests (standard automated perimetry (SAP) and clinical optic disc assessment) and structural measurements using spectral-domain OCT. Methods A prospective study included 32 subjects (32 eyes) with ocular hypertension, suspect or early glaucoma monitored for progression with clinical examination, SAP, PERG, PhNR and OCT for at least 4 years. Progression was defined clinically by the documented change of the optic disc and/or significant visual field progression (EyeSuite™ trend analysis). One eye per patient was included in the analysis. Results During the follow-up, 13 eyes (40.6%) showed progression, whereas 19 remained stable. In the progressing group, all parameters showed significant worsening over time, except for the PhNR, whereas in the stable group only the OCT parameters showed a significant decrease at the last visit. The trend of change over time using linear regression was steepest for the OCT parameters. At baseline, only the ganglion cell complex (GCC) and peripapillary retinal nerve fibre (pRNFL) thicknesses significantly discriminated between the stable and progressing eyes with the area under the ROC curve of 0.72 and 0.71, respectively. The inter-session variability for the first two visits in the stable group was lower for OCT (% limits of agreement within ± 17.4% of the mean for pRNFL and ± 3.6% for the GCC thicknesses) than for ERG measures (within ± 35.9% of the mean for PERG N95 and ± 59.9% for PhNR). The coefficient of variation for repeated measurements in the stable group was 11.9% for PERG N95 and 23.6% for the PhNR, while it was considerably lower for all OCT measures (5.6% for pRNFL and 1.7% for GCC thicknesses). Conclusions Although PERG and PhNR are sensitive for early detection of glaucomatous damage, they have limited usefulness in monitoring glaucoma progression in clinical practice, mainly due to high inter-session variability. On the contrary, OCT measures show low inter-session variability and might have a predicting value for early discrimination of progressing cases.

Introduction: Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. Methods: Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol® (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. Results: All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; p = 0.93), 71% for DS (0.0075% BAK; p = 0.067), 70% for OP (0.01% BAK; p = 0.054), and 69% for LT (0.02% BAK; p = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (p = 0.217), 52% for DS (p = 0.011), 34% for OP (p = 0.017), and 31% for LT (p = 0.0007). Conclusion: LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.

Purpose: The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops. Design: Modified Delphi method. Methods: Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in two sequential web-based surveys administered from June 27 to August 29, 2021. A total of 91 clinical experts were invited to participate. Of these, 71 (78%) experts from 23 different countries accepted the invitation and answered the first questionnaire. The importance of items was ranked using a 10-point scale (1 as not important, 10 as very important). Results: A total of 84 items were rated in round one by 71 participants. Of these, 68 (81%) reached consensus. In round two, 19 items, including three additional items, were rated by 53 (75%) participants. Consensus was reached in 98% of investigated items. Eight outcomes were agreed as important to assess when conducting future trials: ocular surface, dryness, epithelial damage, local adverse effects related to eye drops as reported by patients, periocular surroundings and eyelids, quality of life questionnaires, hyperemia, visual acuity, tear film, and anterior chamber inflammation. Conclusion: We propose a consensus-based series of outcomes and assessment methods to be used in clinical trials assessing adverse effects of anti-glaucomatous eye drops. This will hopefully improve the comparability of results from future trials and thus facilitate meta-analyses and progress in this field.

To examine the physicochemical properties of five preservative-free (PF) 0.005% latanoprost ophthalmic products; MonoprostThe pH value, osmolality, and surface tension were examined. Cell survival was analyzed using lactate dehydrogenase and tetrazolium dye colorimetric assays. Mucin production was analyzed with immunohistochemical staining.MonoprostSignificant differences in pH value, osmolality, and surface tension were observed. However, this did not affect the viability of the goblet cells or the release of mucin. Clinical studies are required to evaluate the long-term effects of use on efficacy and safety.

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.

Glaucoma is a common ocular neurodegenerative disease characterized by the progressive loss of retinal ganglion cells and their axons. It is the most common cause of irreversible blindness. With an increasing number of glaucoma patients and disease progression despite treatment, it is paramount to develop new and effective therapeutics. Emerging new candidates are the receptor agonists of the incretin hormone glucagon-like-peptide-1 (GLP-1), originally used for the treatment of diabetes. GLP-1 receptor (GLP-1R) agonists have shown neuroprotective effects in preclinical and clinical studies on neurodegenerative diseases in both the brain (e.g., Alzheimer’s disease, Parkinson’s disease, stroke and diabetic neuropathy) and the eye (e.g., diabetic retinopathy and AMD). However, there are currently very few studies investigating the protective effects of GLP-1R agonists in the treatment of specifically glaucoma. Based on a literature search on PubMed, the Cochrane Library, and ClinicalTrials.gov, this review aims to summarize current clinical literature on GLP-1 receptor agonists in the treatment of neurodegenerative diseases to elucidate their potential in future anti-glaucomatous treatment strategies.

Purpose: To determine the value of self-monitoring of diurnal intraocular pressure (IOP) by Icare Home rebound tonometer in patients with glaucoma and ocular hypertension. Methods: Patients with open-angle glaucoma or ocular hypertension, controlled IOP at office visits, and at least 3 years of follow-up in the glaucoma clinic were included. Progression of glaucoma was based on medical records and defined by documented structural and/or visual field change. Patients were trained to correctly perform self-tonometry and instructed to measure diurnal IOP in a home setting for 3 days. IOP characteristics (mean, peak IOP, fluctuation of IOP as range, and SD of IOP) were documented and compared between the progressive and stable eyes. Results: Ninety-four patients (50 females) with a mean (SD) age of 57.1 (14.7) years were included. Among the 94 eyes from 94 subjects, 72 (76.6%) eyes had primary open-angle glaucoma, ten (10.6%) had pigmentary glaucoma, four (4.3%) had exfoliative glaucoma, and eight (8.5%) eyes had ocular hypertension. Thirty-six eyes showed progression and 58 eyes were stable. Patients with progression were older than those with stable disease (mean (SD) 65.8 (8.4) years vs 51.7 (15.3) years, P

Purpose: To evaluate and compare the accuracy of self-measurement of intraocular pressure using Icare Home rebound tonometer with Goldmann applanation tonometer and assess acceptability of self-tonometry in patients with glaucoma and ocular hypertension. Methods: In the study, 117 subjects were trained to use Icare Home for self-measurement. Icare Home tonometer readings were compared with Goldmann applanation tonometer, including one eye per patient. Agreement between the two methods of measurement was evaluated by Bland and Altmann analysis. Questionnaire was used to evaluate patients’ perception of self-tonometry. Results: One hundred and three out of 117 patients (88%) were able to measure their own intraocular pressure and 96 (82%) fulfilled the requirements for certification. The mean (SD) difference Goldmann applanation tonometer minus Icare Home was 1.2 (2.4) mmHg (95% limits of agreement, –3.4 to 5.9 mmHg). The magnitude of bias between the two methods depended on central corneal thickness, with greater bias at central corneal thickness Conclusion: Icare Home tonometry tends to slightly underestimate intraocular pressure compared to Goldmann applanation tonometer. Most patients were able to perform self-tonometry and found it acceptable for home use. Measurements using rebound self-tonometry could improve the quality of intraocular pressure data and optimize treatment regimen.

BackgroundTo investigate the outcomes of glaucoma referrals across different European countries.Methods250 patients newly referred to tertiary referral glaucoma specialist practices in the UK, Hungary, Slovenia, Italy and Greece were prospectively enrolled (50 consecutive patients per centre). Referral accuracy and predictive value of referral criteria for an intervention or further monitoring (positive predictive value) were analysed.ResultsSame-day discharges occurred in 43% (95% CI 39% to 75%) (12/28) of optometrist-initiated referrals (UK only), 37% (95% CI 30% to 45%) (59/158) of ophthalmologist-initiated referrals (all centres) and 54% (95% CI 40% to 68%) (26/48) of self-referrals (Hungary, Italy and Greece). The percentages from all referral sources were 46% (95% CI 32% to 60%) in the UK, 56% (95% CI 44% to 70%) in Hungary, 30% (95% CI 17% to 43%) in Slovenia, 22% (95% CI 11% to 34%) in Italy and 60% (95% CI 46% to 74%) in Greece (p21 mm Hg, 56% (95% CI 43% to 69%) (33/59) for a suspicious optic disc and 61% (95% CI 45% to 77%) (22/36) for a suspicious visual field, with large between-country differences (p21 mm Hg only. By combining the IOP criterion with any other referring criterion, the positive predictive value increased from 56% (95% CI 45% to 67%) to at least 89% (95% CI 68% to 100%). In the UK, a hypothetical IOP threshold of >26 mm Hg, as a requirement for IOP-only referrals, would reduce IOP-only referrals by 44%, while not missing any definite glaucoma cases.ConclusionThe accuracy of referrals was poor in the UK and the other countries. Requiring a combination of criteria and raising the IOP threshold for IOP-only referrals are needed to cut waste in clinical care.

To evaluate discrimination ability of pattern electroretinography (PERG) and photopic negative response (PhNR) between early glaucoma and healthy controls, and their relationship with structural measurements using spectral-domain optical coherence tomography (SD-OCT). Cross-sectional study with 34 patients with ocular hypertension (n = 7), suspect glaucoma (n = 17), and early glaucoma (n = 10), plus 24 age-matched controls. The following parameters were analyzed: P50 and N95 amplitude of the PERG, PhNR amplitude and PhNR/b-wave ratio, peripapillary retinal and macular nerve fiber layer (NFL) thicknesses, and ganglion cell complex (GCC) thickness. Data from only one eye per individual were included in the statistical analysis. Descriptive statistics, ANOVA, receiver operating characteristics (ROC) curves, and correlation tests were used for analysis of the variables. PERG N95 and PhNR amplitudes were significantly reduced in suspect and early glaucoma eyes versus controls. Significant differences across ocular hypertensive, suspect, and early glaucoma eyes were found for macular NFL and GCC thickness, but not for any of the ERG parameters. The mean PhNR amplitude did not differ across these groups and was already reduced on average by 46% in ocular hypertensive and early glaucoma eyes and by 52% in suspect glaucoma eyes. The P50 and N95 amplitudes showed similar reduction in suspect and early glaucoma eyes on average by 15 and 26%, respectively. Of the ERG parameters, PhNR amplitude distinguished best between glaucoma and control groups, with an area under ROC curve of 0.90 for suspect glaucoma, and 0.86 for early glaucoma. PhNR/b-wave ratio showed strongest association in suspect glaucoma eyes with peripapillary retinal (r, 0.61) and macular NFL (r, 0.76) thicknesses. In eyes with early glaucoma, peripapillary retinal NFL thickness correlated best with PhNR amplitude (r, 0.71) and PERG P50 amplitude (r, 0.67). In eyes with suspect glaucoma, important decrease in PhNR amplitude is associated with small changes in peripapillary retinal and macular NFL thicknesses. These findings suggest that PhNR may be a useful and sensitive test in eyes with diagnostic dilemma, although further follow-up of such eyes is required for definitive confirmation.

Patients with glaucoma have an increased prevalence of dry eye (DE) compared to age-matched population without glaucoma. Clinical presentation of DE varies among individuals and may significantly reduce quality of life. The onset and deterioration of DE is caused by the toxic-inflammatory effects of preservatives in eye drops, active substance itself, and added, pharmacologically inactive substances or excipients. Ocular surface changes most frequently include superficial punctate keratitis, tear film instability, and allergic reactions. Despite the lack of symptoms, clinical signs may indicate ocular surface damage. The discordance between signs and symptoms is partly caused by decreased corneal sensitivity induced by neurotoxicity of the preservative benzalkonium chloride (BAK). Therefore, it is also important to evaluate ocular surface before initiating glaucoma therapy and during follow-up in asymptomatic patients. A preservative-free and/or BAK-free therapy is indicated in patients with severe DE and allergy to preservatives, and recommended in patients with DE of moderate severity, blepharitis, in symptomatic patients, before filtering surgery to reduce preoperative inflammation, in those with moderate fluorescein staining of grade 2 according to Oxford scheme, and reduced tear film break-up time.

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.

Purpose 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. Methods A retrospective, multicenter, observational cohort analysis included consecutive patients with XFG from 9 European academic centers, with a minimum of 5 years follow-up. Results In 201 patients, there was a statistical difference between progressed and nonprogressed 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). Conclusions 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.

To measure retinal nerve fibre layer (RNFL) thickness with spectral-domain OCT (SD-OCT) in patients with glaucoma, and to evaluate the correlation between visual field parameters and RNFL thickness. Two hundred twelve subjects—55 normal, 37 with preperimetric glaucoma (PPG) and 119 with different stages of primary open angle glaucoma (POAG) were enrolled in this study. Standard automated perimetry was performed in all eyes. RNFL thickness was measured for 6 segments of the 3.4 mm diameter circle and for 8 areas corresponding to the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, both centred on the optic disc. RNFL thickness values were calculated for the inner ring surrounding the optic disc border and the outer ring of the ETDRS grid. The association between visual field parameters and RNFL thickness was evaluated with regression analysis and Pearson correlation coefficients. In the normal group, mean RNFL thickness was 93 ± 9 μm for circle and 91 ± 14 μm for inner ring, for the POAG group the values were 58 ± 21 μm for circle and 40 ± 21 μm for inner ring, and for the PPG group the values were 77 ± 15 μm and 59 ± 15 μm, respectively. The differences in RNFL thickness between normal and glaucoma eyes were significant (p

The aim was to investigate the effects of monochromatic and broadband stimuli on the amplitude of the photopic negative response (PhNR) and to compare the sensitivities of these stimuli for the detection of ganglion cell damage in glaucoma patients. Forty-one healthy subjects were studied, along with 16 patients with open-angle glaucoma. Photopic electroretinograms (ERGs) were elicited with monochromatic red, amber, green, and broadband white stimuli of progressively brighter intensities in a blue background. Pattern ERGs were also recorded using a 0.8 degrees checkerboard pattern on a 21.6 degrees x 27.8 degrees screen. In the photopic ERGs of the control subjects, the PhNR amplitude was significantly higher (P0.01) to red than to monochromatic amber, green, and broadband white stimuli of the same intensity. In glaucoma patients, the percentage of amplitude reduction was greater for the PhNR to red (68%, P0.001) than to the broadband stimulus (38%, P = 0.001). The PhNR to red monochromatic stimulus appeared to be a more sensitive parameter, with a larger area enclosed by the receiver-operating characteristic curve (0.97) than for the PhNR to broadband stimulus (0.76). Also, the PhNR to red stimulus showed a more significant correlation with the pattern ERG and the visual field defects (P0.05) than the PhNR elicited with broadband stimulus. These findings suggest that ganglion cell activity can be more efficiently evaluated with the PhNR elicited with a red than with a broadband stimulus. The PhNR thus appears to be a promising test for the diagnostics of the ganglion cell dysfunction.

Purpose: The efficacy of dorzolamide/timolol fixed combination (DTFC) versus latanoprost/timolol fixed combination (LTFC) in open-angle glaucoma or ocular hypertensive patients. Methods: Patients were randomized to DTFC or LTFC for 6 weeks and switched to opposite treatment for Period 2. Results: Thirty-two completed patients had a mean diurnal IOP of 19.5 ± 3.2 mmHg for DTFC and 18.9 ± 3.4 mmHg for LTFC (p = 0.12), with no significant difference found between DTFC and LTFC at any timepoint following a Bonferroni correction (p ≥ 0.01). Conclusions: Patients treated with DTFC and LTFC have a statistically similar ocular hypotensive effect.

In glaucoma patients, lasers are used to increase aqueous humor outflow, treat internal block of aqueous flow, and reduce aqueous humor production. The indications, techniques, and efficacy of various

To compare optic nerve head topographies measured using a Heidelberg retina tomograph I (HRT) and a retinal thickness analyzer (RTA) and thereby to determine clinical agreement between the two devices. Also, to investigate the reproducibility of optic nerve head measurements using the HRT and RTA.The study included 50 normal left eyes of 50 white adults. Ophthalmologic examination, keratometry, fundus photography, and examination with HRT and RTA were performed. To determine reproducibility, 10 volunteers had repeated examinations after a week. Mean (SD), median, and 5th and 95th percentiles were calculated for the HRT and RTA measurements and differences in measurements between HRT and RTA were tested for statistical significance. Clinical agreement was assessed with limits of agreement and reproducibility by a repeatability coefficient and intraclass correlation coefficient (ICC).Statistically significant differences (P0.05) between measurements by HRT and RTA were observed for all topographic parameters, except for rim area (P = 0.051) and height variation contour (P = 0.054). The limits of agreement between HRT and RTA were wide. The repeatability coefficient for HRT was good (or =0.10) for all parameters, except for retinal nerve fibre layer (RNFL) cross-sectional area (0.28). The repeatability coefficient for RTA was0.10 for cup area (0.15), rim area (0.19), maximum cup depth (0.13), height variation contour (0.11), and RNFL cross-sectional area (0.14). The ICC was good (or =90%) for all parameters, except for mean RNFL thickness (89%) for HRT, and height variation contour (84%) for RTA.The observed differences within the limits of agreement were clinically important. Therefore, the two devices cannot be used interchangeably in clinical practice.

PURPOSE To compare the efficacy and safety of timolol maleate 0.5% versus brinzolamide 1% when added to travoprost 0.004% in patients with ocular hypertension or primary open-angle glaucoma. DESIGN A prospective, double-masked, randomized, active-controlled, parallel comparison. METHODS Qualified patients at Visit 1 were placed on travoprost dosed every evening for 4 weeks and then were randomized at baseline (Visit 2) to the addition of timolol maleate or brinzolamide each given twice daily. Patients returned to clinic at Week 4 (Visit 3) for a safety visit and Week 12 (Visit 4) for an efficacy visit. At Visits 2 and 4 the intraocular pressure (IOP) was measured at 08:00, 12:00, and 16:00 hours. RESULTS Ninety-seven patients on brinzolamide had a baseline diurnal IOP of 21.5+/-2.2 mmHg and 95 on timolol maleate had 21.3+/-2.5 mmHg, each added to travoprost. The diurnal mean IOP at Week 12 was 18.1+/-2.7 mmHg for brinzolamide and 18.1+/-3.0 mmHg for timolol maleate (p=0.96). There was no statistical difference found between treatment groups in the absolute level of pressure, or in the reduction in IOP from baseline, at each time point or for the diurnal curve (p>0.05). There was no significant difference for any adverse event between groups (p>0.05), with the most common side effect being conjunctival hyperemia in 15/97 (16%) brinzolamide and 6/95 (6%) timolol treated patients (p=0.06). CONCLUSIONS This study showed that brinzolamide provides similar safety and efficacy compared to timolol maleate when added to travoprost.

Background and Objectives To compare the histopathological changes in the human trabecular meshwork after low power argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) with a Q-switched, frequency-doubled, neodymium:yttrium–aluminium–garnet (Nd:YAG) laser. Study Design/Materials and Methods In gonioscopically normal trabecular meshwork of three patients awaiting enucleation due to malignant melanoma of the choroid, SLT and ALT were performed 1–5 days prior to enucleation. In each eye, the lower half of trabecular meshwork received SLT, one quadrant low power (460 mW) ALT and one quadrant was left untreated. Specimens were evaluated with light and transmission electron microscopy. Results A sharp demarcation line was visible between the laser treated and untreated intact trabecular meshwork after ALT and SLT. Both lasers caused disruption of trabecular beams, but the extent of the damage was smaller after SLT. The collagen component of trabecular beams was mostly amorphous, the long-spacing collagen was scanty after ALT, but more abundant after SLT. In the intertrabecular spaces fragmented cells and tissue debris with only a few pigmented cells were observed. Some endothelial cells were desquamated, but appeared slightly better preserved after SLT than ALT. Conclusions Our ultrastructural comparison of the morphological changes after low power ALT and SLT in patients demonstrated that both lasers caused splitting and fragmentation of the trabecular beams of the trabecular meshwork, but the extent of the damage was smaller and the preservation of long-spacing collagen better after SLT than after ALT. Lasers Surg. Med. 33:204–208, 2003. © 2003 Wiley-Liss, Inc.

PURPOSE To correlate clinical bleb characteristics and the expression of human leukocyte antigen (HLA)-DR by conjunctiva with the outcome of trabeculectomy. PATIENTS AND METHODS In this cross-sectional study, bleb morphology was assessed at slit lamp using the Moorfields Bleb Grading System in 85 eyes of 85 patients. Conjunctival specimens were collected from superior conjunctiva by impression cytology and analyzed for the expression of HLA-DR on epithelial and antigen-presenting cells. The success of trabeculectomy was defined as intraocular pressure

Purpose. To investigate the influence of inflammatory molecules in the aqueous humour and on the ocular surface on the outcome of glaucoma surgery.Methods. Thirty patients who needed antiglaucomatous surgery were included. The interleukin- (IL-) 8, IL-1, IL-6, IL-10, tumour necrosis factor- (TNF-) ; and IL-12 were determined from aqueous humour preoperatively and the imprints of conjunctiva were analysed for expression of human leukocyte antigen- (HLA-)-DR after surgery by flow cytometry. The success of trabeculectomy was defined as intraocular pressure less than 21 mmHg without antiglaucoma medication.Results. Eyes with trabeculectomy failure at 3 months showed significantly higher TNF- and IL-6 levels in the aqueous than eyes with successful surgery. Increased expression of HLA-DR on epithelial cells and antigen-presenting cells was not associated with the trabeculectomy outcome.Conclusions. Higher preoperative levels of TNF- and IL-6 in aqueous humour may contribute to the development of inflammatory milieu and were associated with worse outcome of glaucoma surgery.

To determine the incidence of glaucomatous progression at mean intraocular pressure (IOP) levels in patients with ocular hypertension (OHT).A retrospective, multicentre, cohort analysis of 230 OHT patients with 5 years of follow-up evaluated for risk factors associated with progressive optic disc and visual field loss to determine the incidence of glaucomatous progression.Forty percent of patients with IOPsor = 24 mmHg, 18% of patients with IOPs of 21-23 mmHg, 11% of patients with IOPs with 18-20 mmHg, and 3% of patients with IOPs ofor = 17 mmHg progressed to glaucoma. The mean IOP was 19.8+/-2.4 mmHg in the stable group and 21.7+/-2.6 mmHg in the progressed group (P=0.0004). The highest average peak IOP was 23.4+/-4.0 mmHg in the stable group and 25.2+/-3.1 mmHg in the progressed group (P=0.006). Based on the pachymetry values for central corneal thickness, patients with thinner corneas more often progressed to glaucoma (P0.0001). A multivariant regression analysis to determine risk factors for progression was positive primarily for higher peak IOPs, older age, male gender, argon laser trabeculoplasty, visual acuityor = 20/50, and no topical medical therapy or beta-blocker therapy prior to the study.IOP reduction within the normal range over 5 years of follow-up reduces the chance of progression to primary open-angle glaucoma in OHT patients.

Barbara Cvenkel,1 Špela Štunf,1 Irena Srebotnik Kirbiš,2 Margareta Strojan Fležar2 1Department of Ophthalmology, University Medical Center Ljubljana, Ljubljana, Slovenia; 2Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Purpose: The aim of this study was to assess signs and symptoms of ocular surface disease (OSD) and the cytomorphological changes of ocular surface in glaucoma patients using preserved antiglaucoma drops.Methods: In this cross-sectional study, 109 participants (79 patients with topical medication and 30 untreated controls) completed the Ocular Surface Diseases Index (OSDI) questionnaire and underwent an ophthalmic examination, including Schirmer test, tear film breakup time (TBUT), and fluorescein staining. Conjunctival specimens were collected by impression cytology and analyzed by light microscopy using Nelson’s grading scheme (grades 0–3). This classification is based on the nucleus-to-cytoplasm ratios of epithelial cells and the numbers of goblet cells, with grade 2 considered abnormal.Results: The medication group had significantly shorter TBUT (median [interquartile range]: 6.0seconds [5.0–8.0 seconds] vs 9.5seconds [6.0–12.3 seconds]; P

Ganglion cells with nerve fibre layer contribute a substantial fraction to the retinal thickness (RT). In contrast to the analysis of papillary and peripapillary area, which have shown large variability in normal eyes, the variation of retinal cell density in the perifoveal region is reported to be less than 10%. By measuring RT at the posterior pole we wanted to detect retinal changes due to glaucoma and determine their correspondence with visual field (VF) changes.The Retinal Thickness Analyzer (RTA) was used to obtain RT maps in 21 normal eyes, 20 eyes with ocular hypertension and 22 eyes with glaucoma. A green laser slit (540 nm) of the RTA was focused on the retina at an angle and its intersection with the retina was imaged. The distance between the reflections from the vitreo-retinal and retina-retinal pigment interface is directly proportional to the RT. Five locations covering the central 20 degrees were scanned, generating 10 optical cross sections that were transformed into colour-coded RTA maps. Numerical data were presented for the perifoveal and posterior pole region.In glaucomatous eyes significant localised thinning of the retina was present, identified as the increased number of clusters including at least four points that are 2 standard deviations below normal. The minimum retinal thickness was decreased in glaucoma eyes and the perifoveal temporal modulation and perifoveal temporal/nasal asymmetry--indicators of greater RT loss in the temporal and the nasal quadrant, respectively--were higher in eyes with glaucoma, but with overlapping global indices between the groups. In 16 of 22 eyes with glaucoma there was good agreement of RT changes with VF defects. In two eyes with typical glaucomatous damage at the optic disc but without VF defects localised changes of RT were detected.The RTA enables objective noninvasive evaluation of the posterior pole and could become helpful in diagnosis of glaucoma before the onset of functional damage. However, at present its clinical usefulness is limited by overlapping values of retinal thickness between normal and glaucomatous populations.

Background: Selective laser trabeculoplasty (SLT) targets the pigmented trabecular meshwork (TM) cells without damage to the adjacent non-pigmented tissue. A study was conducted to evaluate the efficacy and safety of SLT in the treatment of uncontrolled open-angle glaucoma. Methods: In a prospective non-randomized study 44 eyes of 31 patients with uncontrolled open-angle glaucoma were treated with a frequency-doubled, Q-switched Nd:YAG laser. A total of approximately 50 spots were placed over 180° of the TM at energy levels ranging from 0.7 to 0.9 mJ. Intraocular pressure (IOP) was measured 1, 2, and 24 h, 1 and 2 weeks and 1, 2, 3, 6, 9, and 12 months after treatment. Results: The average pre-operative IOP was 25.6 (SD 2.6) mm Hg (range 22–34). The mean IOP reduction from baseline at 24 h, 3, 6 and 12 months was 7.1 mm Hg (SD 3.5) or 27.6%; 4.2 mm Hg (SD 3.5) or 16.4%; 4.7 mm Hg (SD 4.2) or 18.6%, and 4.4 mm Hg (SD 3.8) or 17.1%, respectively. The percent of eyes with IOP reduction of 3 mm Hg or more at 3, 6 and 12 months was 66, 78 and 62%. A pressure spike of 8 mm Hg or more was detected in 4 eyes (9.1%). Anterior chamber reaction was seen 1 h after SLT and was mild to moderate in 16 eyes (40.4%) and marked in 3 eyes (6.8%). Conclusions: SLT has shown reasonable efficacy in lowering IOP over 1-year follow-up, but there was a tendency for IOP to increase with a longer follow-up. Long-term follow-up studies with a large sample size are needed to determine whether the IOP lowering effect is sustained over time, and to assess the efficacy of repeated SLT.

Purpose: To investigate the expression of inflammatory markers HLA-DR in impression cytology specimens from patients receiving topical antiglaucoma monotherapy. Methods: Impression cytology specimens were obtained from patients taking no topical medication (n = 13) and from primary open-angle glaucoma or ocular hypertensive patients taking one topical medication for at least 3 months (latanoprost n = 14; betaxolol n = 12; timolol n = 14). None of the patients had any signs of ocular surface inflammation as detected by slit-lamp examination, a normal Schirmer’s test and tear breakup time. The expression of HLA-DR on epithelial cells and T lymphocytes was analysed by flow cytometry. Results: A significant increase in HLA-DR on epithelial cells in patients on monotherapy was detected (latanoprost p < 0.05; betaxolol p < 0.01; timolol p < 0.01). Although the duration of treatment differed significantly between individual groups, there was no significant correlation between the length of monotherapy and the expression of inflammatory markers by epithelial cells and T lymphocytes. In the latanoprost group, the increased expression of HLA-DR was associated with a shorter duration of treatment. Conclusions: The flow-cytometric results indicate that administration of a single topical medication preserved with benzalkonium chloride, irrespective of type, for 3 months or more induced a significant degree of subclinical inflammation detected as increased expression of HLA-DR on conjunctival epithelial cells.