Search

Prcis: The lamina cribrosa (LC) pores of patients with high-tension glaucoma (HTG) appear to take a more tortuous pathway than the LC pores of patients with non-glaucomatous (NG)., Objective: To compare the LC pore microarchitecture in patients with HTG, normal tension glaucoma (NTG), and NG, by reconstructions of the LC made from tomographic images., Patients and Methods: Spectral domain-optical coherence tomography images of 52 eyes (18 NG, 18 HTG, and 16 NTG) of 29 patients were analyzed. Pores were traced using segmentation software. Pore length, tortuosity, and verticality were the 3 quantitative parameters compared among the 3 groups. Correlation analyses were performed to determine the effects of covariates on the 3 quantitative parameters., Results: Pore tortuosity in HTG (1.419 ± 0.093) was significantly higher ( P = 0.011) than in NG (1.347 ± 0,034) but did not differ from that of NTG eyes ( P = 0.251). In addition, NTG had significantly shorter pores ( P = 0.005) than NG. No difference in pore tortuosity or verticality was found between NG and NTG ( P = 0.587 and P = 0.120, respectively). Pore verticality and length in HTG eyes did not significantly differ from that of NG eyes ( P = 0.049 and P = 0.033, respectively) and NTG eyes ( P = 0.827 and P = 0.968, respectively). All of the quantitative parameters measured were not correlated with age but were associated with glaucoma severity (Visual Field Index, mean deviation, retinal nerve fiber layer, and ganglion cell complex), except for pore verticality, which was not correlated with retinal nerve fiber layer., Conclusion: The LC pores of patients with HTG appear to be more tortuous than the pores of patients with NG, and the pores of patients with NTG are shorter than those of patients with NG. Changes in pore parameters appear to be associated with the severity of glaucomatous optic neuropathy., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, is closely linked to increased intraocular pressure (IOP), with the trabecular meshwork (TM) playing a critical role in its regulation. The TM, located at the iridocorneal angle, acts as a sieve, filtering the aqueous humor from the eye into the collecting ducts, thus maintaining proper IOP levels. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of primary open-angle glaucoma POAG particularly, in the dysfunction of the TM. This study utilizes human TM explants to closely mimic in vivo conditions, thereby minimizing transcriptional changes that could arise from cell culture enabling an exploration of the transcriptomic impacts of TGF-β2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-β2 exposure (5 ng/ml for 48 h). Bulk RNA sequencing identified significant upregulation in genes linked to extracellular matrix (ECM) regulation and fibrotic signaling. Immunohistological analysis further elucidated the morphological alterations, including cytoskeletal rearrangements and ECM deposition, providing a visual confirmation of the transcriptomic data. Notably, the enrichment analysis unveils TGF-β2's influence on both bone morphogenic protein (BMP) and Wnt signaling pathways, suggesting a complex interplay of molecular mechanisms contributing to TM dysfunction in glaucoma. This characterization of the transcriptomic modifications on an explant model of TM obtained under the effect of this profibrotic cytokine involved in glaucoma is crucial in order to develop and test new molecules that can block their signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The relationship between glaucoma and Obstructive Sleep Apnea Syndrome (OSAS) has long been discussed, with conflicting study findings. OSAS appears in the most recent studies to be more of an aggravating factor than an independent risk factor for glaucoma. Patients with OSAS may develop a more rapid progression of primary open-angle glaucoma (POAG). OSAS may damage the optic nerve not only by increasing the intraocular pressure (IOP) but also by altering the blood supply to the optic nerve as shown by more recent work with OCT-Angiography. Although the systemic benefits of Continuous Positive Airway Pressure (CPAP) have been demonstrated, few studies have evaluated its effect on the optic nerve. CPAP might act on glaucomatous neuropathy by improving the blood supply to the optic nerve. The study of this mechanism of action might provide new insights into the relationship between OSAS and glaucoma., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Prcis: The iStent inject W implanted during phacoemulsification effectively reduces IOP., Purpose: The purpose of this study was to evaluate the efficacy and safety of iStent inject W combined with phacoemulsification in patients with controlled open angle glaucoma undergoing cataract surgery., Patients and Methods: We conducted a retrospective, bicentric study of patients with controlled chronic open angle glaucoma who underwent phacoemulsification combined with the injection of 2 iStent inject Ws. Patient characteristics, including intraocular pressure (IOP) and the number of glaucoma medications, were evaluated preoperatively and 1 week, 1 month, and 6 months postoperatively. The primary end point was IOP reduction, and the secondary end point was the reduction in the number of glaucoma medications., Results: In this study, 85 eyes were included. The majority of patients had primary open angle glaucoma (85% of eyes). Preoperative mean IOP was 16.1±2.0 mm Hg with a mean of 2.3±0.5 glaucoma medications. At 1 week postoperatively, the mean IOP was 16.7±3.1 mm Hg with a mean of 2.0±0.7 hypotensive medications. At 1 and 6 months, the mean IOP was 14.2±2.1 and 13.0±1.5 mm Hg, with a mean of 2.0±0.6 and 1.8±0.5 glaucoma medications, respectively. The percentage IOP reduction at 1 and 6 months was 11.6% ( P =0.001) and 19.3% ( P <0.0001), respectively. Regarding glaucoma medications, at 1 and 6 months, the reduction in the number of medications was 12.9% ( P =0.025) and 22.4% ( P =0.003), respectively. The most frequent significant postoperative adverse events were corneal edema in 7%, IOP spikes in 6%, and hyphema in 6% of eyes, which resolved spontaneously., Conclusions: The iStent inject W implanted during phacoemulsification effectively reduces IOP and the number of glaucoma medications needed at 6 months of follow-up, with a favorable safety profile in patients with controlled open angle glaucoma., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To provide an overview of the existing alternative models for studying trabecular meshwork (TM)., Methods: Literature review., Results: The TM is a complex tissue that regulates aqueous humor outflow from the eye. Dysfunction of the TM is a major contributor to the pathogenesis of open-angle glaucoma, a leading cause of irreversible blindness worldwide. The TM is a porous structure composed of trabecular meshwork cells (TMC) within a multi-layered extracellular matrix (ECM). Although dysregulation of the outflow throughout the TM represents the first step in the disease process, the underlying mechanisms of TM degeneration associate cell loss and accumulation of ECM, but remain incompletely understood, and drugs targeting the TM are limited. Therefore, experimental models of glaucomatous trabeculopathy are necessary for preclinical screening, to advance research on this disease's pathophysiology, and to develop new therapeutic strategies targeting the TM. Traditional animal models have been used extensively, albeit with inherent limitations, including ethical concerns and limited translatability to humans. Consequently, there has been an increasing focus on developing alternative in vitro models to study the TM. Recent advancements in three-dimensional cell culture and tissue engineering are still in their early stages and do not yet fully reflect the complexity of the outflow pathway. However, they have shown promise in reducing reliance on animal experimentation in certain aspects of glaucoma research., Conclusion: This review provides an overview of the existing alternative models for studying TM and their potential for advancing research on the pathophysiology of open-angle glaucoma and developing new therapeutic strategies.

Prostaglandin analogue topical medications are one of the most effective therapeutic approaches for the chronic management of glaucoma and ocular hypertension, through the reduction of elevated intra ocular pressure (IOP). While many of the first generations of anti-glaucoma eye drops were preserved with benzalkonium chloride, their repeated use may induce chronic ocular surface toxicity that leads to ocular surface disease (OSD) signs and symptoms. As a result, soft-preservatives and preservative-free formulations have been developed with the goal to avoid the long-term iatrogenic toxicity of the preservative agents. In addition, it has been suggested that OSD and its associated inflammation may negatively impact the efficacy of the IOP-lowering medications, including treatment adherence and compliance. Hence, it may be particularly interesting that glaucoma medications can concomitantly protect and "heal" the ocular surface and its environment while lowering elevated IOP, for the greater benefit of glaucoma patients. The objective of the present review is to briefly present the preclinical data of the cationic oil-in-water emulsion of latanoprost (latanoprost-CE) to shed some light on its mechanisms of action. It overall supports the following hypothesis: the restoration of a healthy ocular surface environment and treatment of the OSD signs and symptoms will allow for an improved elevated IOP reduction and glaucoma management. This would be achieved with a once daily dosing regimen to preserve glaucoma patients' vision, ocular surface, and quality-of-life and wellness.

Background: The goal of this study was to assess the efficacy and safety of phacoemulsification combined with iStent Inject® implantation for the treatment of chronic open-angle glaucoma controlled on topical anti-glaucoma medications and associated with cataract., Methods: This study was a retrospective analysis of patients who underwent phacoemulsification and implantation of an iStent Inject® for chronic open-angle glaucoma associated with cataract. For all patients, pre- and postoperative characteristics, including number of glaucoma medications and intraocular pressure (IOP), were compared using Paired-sample t-tests and Wilcoxon signed-rank tests, respectively. Postoperative visits were scheduled at 7 days and 1, 3, 6, and 12 months after surgery., Results: Forty-nine eyes of 39 patients were included in the study. Mean preoperative IOP at baseline was 16.3±4.3mmHg (range, 10-29mmHg) with a mean of 2.2±1.0mmHg antiglaucoma medications. At 1 month, the mean IOP reduction was 16% (P<0.05) along with an 18.7% reduction in the mean number of medications. At 6 months, the mean IOP was 12.8±2.6, with a mean of 1.1±0.9 antiglaucoma medications. The mean IOP reduction at 6 months was 22% (P<0.05) along with a 49% reduction in the mean number of medications. At 12 months, the mean IOP was 13.8±2.5 with a mean of 1.1±1.2 medications. The mean IOP reduction at 12 months was 15% (P<0.05) along with a 47% reduction in the mean number of medications. No severe device-related side effects were observed., Conclusions: iStent Inject® implantation combined with phacoemulsification resulted in effective IOP reduction and medication burden in patients with mild to advanced chronic open-angle glaucoma and preoperative IOP well controlled with topical hypotensive medications., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: PreserFlo® MicroShunt (PM) (also known as InnFocus® MicroShunt) is a subconjunctival stent implanted ab externo via a minimally invasive surgical procedure. The current indication is progressive, mild to moderate, open angle glaucoma uncontrolled on topical medications. According to the literature, adverse events are rare, mild and transient., Case Presentation: Two cases of stand-alone PreserFlo MicroShunt® implantation in patients with uncontrolled open-angle glaucoma are reported. Exposure occurred 7 days and 3 months respectively after implantation. These cases shared common features including preexisting blepharitis and the lack of a Tenon's flap. In both cases, removal of the device was required after several attempts at repair., Conclusions: PreserFlo MicroShunt® exposure is a potentially vision-threatening complication because of the risk of endophthalmitis. Potential risk factors include the absence of a Tenon's flap and pre-existing ocular surface inflammation. Ocular surface inflammation should be detected and treated prior to PM implantation. If a deficiency in Tenon's capsule is noted intraoperatively, close monitoring should be performed because of the higher risk of PM exposure., (© 2021. The Author(s).)

The pathophysiology of glaucoma is complex, multifactorial and not completely understood. Elevated intraocular pressure (IOP) and/or impaired retinal blood flow may cause initial optic nerve damage. In addition, age-related oxidative stress in the retina concurrently with chronic mechanical and vascular stress is crucial for the initiation of retinal neurodegeneration. Oxidative stress is closely related to cell senescence, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, which are involved in glaucoma progression. Accumulating evidence from animal glaucoma models and from human ocular samples suggests a dysfunction of the para-inflammation in the retinal ganglion cell layer and the optic nerve head. Moreover, quite similar mechanisms in the anterior chamber could explain the trabecular meshwork dysfunction and the elevated IOP in primary open-angle glaucoma. On the other hand, ocular surface disease due to topical interventions is the most prominent and visible consequence of inflammation in glaucoma, with a negative impact on filtering surgery failure, topical treatment efficacy, and possibly on inflammation in the anterior segment. Consequently, glaucoma appears as an outstanding eye disease where inflammatory changes may be present to various extents and consequences along the eye structure, from the ocular surface to the posterior segment, and the visual pathway. Here we reviewed the inflammatory processes in all ocular structures in glaucoma from the back to the front of the eye and beyond. Our approach was to explain how para-inflammation is necessary to maintain homoeostasis, and to describe abnormal inflammatory findings observed in glaucomatous patients or in animal glaucoma models, supporting the hypothesis of a dysregulation of the inflammatory balance toward a pro-inflammatory phenotype. Possible anti-inflammatory therapeutic approaches in glaucoma are also discussed., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: The study aimed to detect and describe glaucoma-related pseudocystic abnormalities at the internal nuclear layer (INL) of the macula using OCT, in relation with visual field defects and other clinical data., Patients and Methods: Primary open-angle glaucoma patients presenting for a follow-up visit were consecutively included over 5 months and underwent clinical examination, OCT imaging, and central 10-2 visual field testing. OCT measures included the thickness of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), together with an analysis of B-Scans and en-face images. All data provided by OCT were analyzed and compared with the visual field testing., Results: Fourteen patients out of 216 showed pseudocysts in the INL of the macula. These cysts were hyporeflective, fusiform, and of variable size (15 to 25μm) and were always associated with a thinning of both the RNFL and GCC. En-face OCT showed evidence of a distribution of cysts in the macular region, based on the appearance of numerous, dense hyporeflective pits whose localization matched precisely with the vision loss as assessed by central 10-2 visual field testing. No other correlations were found., Discussion: Pseudocysts of the internal nuclear layer of the macular region are found in some cases of chronic glaucoma. Their presence is always associated with a scotoma in the visual field and appear to constitute a marker for glaucoma progression. Glaucoma-related central pseudocysts could result from Müller cell changes, excitotoxicity, and/or trans-synaptic retrograde degeneration. The presence of pseudocysts could be a marker of a particular subpopulation whose features remain to be determined., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: To compare the tolerability and efficacy of a preservative-containing latanoprost (PCL) to a preservative-free formulation of latanoprost (PFL) in patients with open-angle glaucoma or ocular hypertension., Methods: A pooled analysis was performed of data from five published studies. The primary outcome was tolerability as evaluated by the severity of hyperemia. The secondary objectives were patient tolerance based on a composite ocular surface disease (OSD) score arising from ocular signs and symptoms, patient and investigator satisfaction, and a comparison of IOP-lowering efficacy., Results: There were three randomized controlled trials and two observational studies included in the analysis. Conjunctival hyperemia improved significantly in 25.6% (388) of patients switched to the PFL group versus 11.7% (117) of patients switched to the PCL group (p < 0.001). PFL was two times superior to PCL in reducing ocular hyperemia (odds ratio = 1.96; p < 0.001). The mean OSD composite score decreased by 32.2% in patients switched to the PFL group and 14.1% in the PCL group (p < 0.001). At 3 months, the mean IOP was similar between groups (p = 0.312)., Conclusion: This post hoc pooled analysis confirmed the findings of the individual studies that PFL is as efficacious at reducing IOP as PCL but better tolerated. After switching to PFL, there was twice the improvement in the OSD composite score. PFL was twice as effective at reducing ocular hyperemia and other ocular signs. These findings suggest that PFL has features that may improve patient compliance, thereby potentially improving the IOP-lowering efficacy on a long-term basis.

Radius-Maumenee syndrome is a rare cause of severe secondary open-angle glaucoma. The ocular hypertension is due to episcleral venous hypertension. This syndrome consists of open angle glaucoma and episcleral venous dilatation without orbital or systemic abnormalities. It is diagnosis of exclusion after ruling out carotid-cavernous fistula, thyroid orbitopathy and an invasive orbital process that might explain the elevated episcleral venous pressure. Treatment begins with glaucoma eyedrops and, in case of failure, filtering surgery. Uveal effusion syndrome and postoperative choroidal detachment are frequent complications of filtering surgery in patients with this syndrome. We present the case report of a 59-year-old woman with Radius-Maumenee syndrome., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma., Methods: We conducted a prospective observational study in the glaucoma department at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 min before and after VF testing. Sub analyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations., Results: There was no significant change in IOP after VF testing, with IOP's 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R 2  = 0.12), whether based on duration of the VF test (P = 0.18) or the MD (P = 0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (P = 0.36), chronic angle closure glaucoma (P = 0.85) and OHT (P = 0.42). The subgroup of patients with an IOP elevation ≥2 mmHg had a significantly higher VF test duration (P = 0.002)., Conclusion: VF testing does not influence IOP as measured with a non-contact tonometer.

Background: To compare the efficacy of phacoemulsification (PKE) combined with nonpenetrating deep sclerectomy (NPDS) with mitomycin C (MMC) versus XEN® gel stent with MMC., Methods: In this nonrandomized, retrospective, comparative, single-center pilot study, 105 consecutive eyes of 75 patients with uncontrolled primary open-angle glaucoma (POAG) and cataract who underwent PKE combined with either XEN implantation (n = 47) or NPDS (n = 58) between May 2013 and November 2018 were included. The primary outcome was complete success at 9 months, which was defined as intraocular pressure (IOP) ≤18, 15 or 12 mmHg without treatment; qualified success was IOP ≤18, 15 or 12 mmHg with antiglaucoma medications. Secondary outcome measures included the number of antiglaucoma medications, visual acuity (VA), and postoperative adverse events., Results: Using the 18 mmHg threshold, complete or qualified success was achieved in 69.6 and 89.1% in the PKE + XEN group, and 63.8 and 89.7% in the PKE + NPDS group (p = .54 and p = .93), respectively, at 9 months. The mean IOP decreased from 20.8 ± 6.8 mmHg to 16.2 ± 2.8 mmHg in the PKE + XEN group (p < .001, 18.9% mean drop), and from 21.5 ± 8.9 mmHg to 14.9 ± 3.9 mmHg in the PKE + NPDS group (p < .001, 25.6% mean drop). Best-corrected VA significantly improved (p < .001) in both groups. The mean number of antiglaucoma medications was significantly reduced from 2.66 ± 1.1 to 0.49 ± 1.0 in the PKE + XEN group (p < .001) and from 2.93 ± 0.9 to 0.69 ± 1.2 in the PKE + NPDS group (p < .001)., Conclusions: The XEN stent combined with PKE seemed to be as effective and safe as PKE + NPDS at 9 months in this pilot study.

Background: The effect of cataract surgery on IOP in patients with primary open-angle glaucoma (POAG) is a subject of debate. We investigated the effect of cataract surgery by phacoemulsification on intraocular pressure (IOP) in patients with medically POAG ., Methods: Seventy eyes of 40 POAG patients undergoing cataract surgery by phacoemulsification were retrospectively evaluated. All patients had their POAG medically controlled without prior glaucoma surgery. Baseline demographics and clinical characteristics were recorded. IOP and the number of glaucoma medications were evaluated before and for 1 year after cataract surgery. We analyzed IOP variations from baseline with a Student t-test for a paired sample. We used a Pearson correlation coefficient and linear regression to study the relation between IOP change from baseline and preoperative characteristics., Results: One year after phacoemulsification, IOP decreased by a mean 1.15 ± 3 mmHg (6.8 ± 18.1%) (P = 0.01) and the number of glaucoma medications remained unchanged with a difference of - 0.1 ± 0.43 (P = 0.09). Higher preoperative IOP was associated with a greater IOP decrease after 1 year of follow-up (P < 0.001). One and 7 days after cataract surgery, 12.9 and 4.2% of the eyes had IOP spikes > 30 mmHg, respectively. One year after cataract surgery, 75.7% of the POAG eyes maintained the same number of glaucoma medications while 17.1% had a decrease and 7.2% of the eyes required adding glaucoma medications., Conclusion: Cataract surgery by phacoemulsification in eyes with medically controlled POAG resulted at 1 year in a very small IOP decrease without a change in the number of glaucoma medications. A drop in IOP should not be expected after performing phacoemulsification alone in POAG patients.

Primary open-angle glaucoma is a progressive chronic optic neuropathy, typically bilateral, that occurs after the age of 40 years. It is the second leading cause of irreversible blindness in the world. Primary open-angle glaucoma corresponds to a progressive loss of retinal ganglion cell characterized by an excavation of the optic disc associated with typical visual field defects. Elevated intraocular pressure is the main risk factor of primary open-angle glaucoma. Diagnosis and monitoring of primary open-angle glaucoma arebased on both analysis of structural alteration, by clinical examination of optic disc completed by imaging tests (Ocular Coherence Tomography), and functional alterations, by visual field tests. The only effective treatment to slow primary open-angle glaucoma progression is the reduction of the intraocular pressure with anti-glaucomatous eye drops, laser or surgical treatments., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The purpose of this study was to analyze the change in intraocular pressure (IOP) and glaucoma medications using the XEN ® Gel Stent as a solo procedure or in association with phacoemulsification in patients with chronic open angle glaucoma (OAG)., Methods: We included cohort studies with at least one year of follow-up in patients with primary open angle glaucoma (POAG), pseudo-exfoliative glaucoma (PXG) or pigmentary glaucoma (PG) who received a XEN® gel stent. The main outcome measure was IOP reduction at 12 months follow-up. Secondary outcomes were the decrease in glaucoma medications 12 months after surgery, frequency and type of postoperative interventions and complication rate., Results: A total of 8 case series published between 2016 and 2018 were included; six were prospective studies, and two were retrospective. There was no randomized controlled trial. The data concerned a total of 958 eyes of 777 patients. The various studies showed a mean IOP at 12 months between 13 and 16mmHg, which represented an IOP reduction between 25 and 56% (mean: 42%). This decrease was associated with a reduction in glaucoma medications in all studies. The decrease in IOP was significantly greater in XEN ® implantation as a stand-alone procedure (44%) than in combined surgery (32%) (P<0.05). Transient hypotony (<1 month) (3%), choroidal detachment or choroidal folds (1.5%), hyphema (1.9%), bleb leak (1.1%) and shallow anterior chamber (1.1%) were the most frequent complications. As for severe complications, four cases of malignant glaucoma (0.4%) and one case of retinal detachment have been reported. In the follow-up period, needling has been required in 32% of cases, and a total of 55 eyes (5.7%) required repeat filtering surgery or cyclodestructive procedure., Conclusion: XEN ® Gel Stent appears effective for reducing IOP and the number of medications in OAG patients within 1 year postoperatively with an acceptable safety profile. However, vigilant postoperative follow-up and frequent postoperative maneuvers are required., (Copyright © 2019. Published by Elsevier Masson SAS.)

Purpose:: To assess tolerability and efficacy following a switch from benzalkonium chloride-latanoprost to preservative-free latanoprost in patients with glaucoma or ocular hypertension., Methods:: A total of 140 patients with glaucoma or ocular hypertension controlled with benzalkonium chloride-latanoprost for at least 3 months were switched to treatment with preservative-free latanoprost. Assessments were made on days 15, 45, and 90 (D15, D45, and D90) and included best-corrected visual acuity, intraocular pressure, slit lamp examination, fluorescein staining, tear film break-up time, patient symptom evaluation, and subjective estimation of tolerability., Results:: Mean best-corrected visual acuity remained unchanged during the study. Mean intraocular pressure compared with baseline (D0) remained stable throughout the study (D0, 15.9 mmHg (standard deviation = 2.6); D90, 15.3 mmHg (standard deviation = 2.4); p < 0.006). Tear film break-up time improved or remained unchanged relative to baseline in 92% of patients at D45 and in 93% at D90. Moderate-to-severe conjunctival hyperemia was seen in 56.8% of patients at D0, but this figure decreased to 13.7%, 2.2%, and 1.6% at D15, D45, and D90, respectively. Subjective assessment of tolerability (0-10 scale) indicated improvement with change of therapy (mean score: 5.3 (standard deviation = 2.2) at D0 versus 1.9 (standard deviation = 1.7) at D90; p < 0.0001)., Conclusion:: Preservative-free latanoprost has at least the same intraocular pressure-lowering efficacy as benzalkonium chloride-latanoprost, with a better tolerability profile. This may translate into greater control of treatment and improved quality of life.

Background: The purpose of this study was to evaluate the changes in choroidal thickness and lamina cribrosa position after nonpenetrating deep sclerectomy (NPDS) and trabeculectomy., Methods: Twenty-three eyes with glaucoma that required filtering surgery were included (12 NDPS and 11 trabeculectomies) in this prospective observational study. OCT-enhanced depth imaging (OCT-EDI) was used to measure choroidal thickness, prelaminar tissue thickness and lamina cribrosa position before and 7 days and 1 month after surgery. All results are shown as median (interquartile range values)., Results: Intraocular pressure (IOP) was significantly lower 1 week after surgery than at baseline (7 (6/10) mmHg vs. 21 (18/26) mmHg; p < 0.001) with a mean 64% decrease. IOP remained significantly lower at 1 month with a 55% mean decrease as compared to baseline (10 (8/12) mmHg; p < 0.001). One week after surgery, the subfoveolar choroidal thickness (SFCT) significantly increased (372 (306/523) μm vs. 317 (227/413) μm; p = 0.04) and the prelaminar tissue (PLT) was significantly thicker (269 (162/360) μm vs. 138 (87/268) μm; p = 0.02) as compared to preoperative measurements. These changes were not statistically significant at one month. There were no differences concerning these parameters between the NPDS and trabeculectomy groups. During the first week, the SFCT increase was correlated with IOP reduction (r = - 0.41; p = 0.04)., Conclusions: OCT-EDI allowed the visualization of structural changes at the level of the optic nerve and choroidal vascularization during acute IOP changes. No difference was observed between NPDS and trabeculectomy concerning these structural modifications.

Goals: To assess the efficacy and safety of preservative-free timolol 0.1% gel in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT)., Methods: In this multicenter, open-label, non-controlled clinical trial in Algeria, treatment-naïve patients with intraocular pressure (IOP)>20mmHg and<31mmHg (treatment-naïve patients, group 1) and patients with IOP controlled by current ocular monotherapy but presenting with local intolerance in at least one eye (intolerant patients; group 2) were eligible. Timolol gel was administered once daily in the morning for 84 days. The primary efficacy criteria were reduction in IOP (group 1) and maintenance of baseline IOP (group 2)., Results: Overall, 93 patients were included (53 in group 1, 40 in group 2). All patients in group 2 had been previously treated with preserved eye drops. In group 1, patients showed a significant reduction in IOP with mean changes in the worse eye of -10.3±3.0mmHg at D28 and -10.8±2.5mmHg at D84 (P<0.0001). In group 2, the maintenance of efficacy on IOP at D84 was satisfactory in 91.7% of patients (worse eye). Preservative-free timolol gel was well tolerated in both groups. In group 2, the overall symptom score was significantly reduced from 8.6±5.1 to 0.9±1.6 at D28 and 0.7±1.2 at D84 (P<0.0001), and the overall ocular sign score from 3.7±2.1 to 0.8±1.0 at D28 and 0.6±0.8 at D84 (P<0.0001)., Conclusions: This preservative-free timolol 0.1% gel was effective in decreasing IOP in treatment-naïve patients and in controlling IOP and reducing ocular signs and symptoms in patients intolerant to their previous preserved medications., (Copyright © 2018. Published by Elsevier Masson SAS.)

Purpose: The purpose of this study was to evaluate the effect of treating ocular surface disease (OSD) in patients with medically uncontrolled primary open-angle glaucoma (POAG) associated with OSD., Methods: We compiled a retrospective observational case series of 10 patients with POAG that remained uncontrolled with topical treatments and who were referred for filtering glaucoma surgery. All patients underwent a complete assessment of their glaucoma and ocular surface for both eyes. The main treatments were change of topical antiglaucoma medications to preservative-free equivalents, removal of allergenic treatments or those identified as causing side effects, switch to another therapeutic class with the same efficacy but with a better safety profile and treatment of OSD., Results: After a minimum follow-up of 6 months, we observed improved ocular surface in all patients, associated with an intraocular pressure (IOP) decrease or stabilization even if some antiglaucoma medications were removed. The mean IOP significantly decreased from 23.75±9.98 mm Hg to 15.15±4.75 mm Hg (-36.2%; P=0.0001). The mean number of IOP-lowering medications was 3.7±1.06 at presentation and 2.8±0.63 after treatment (P=0.01). The Oxford score also decreased from a mean 1.7±0.67 to 0.4±0.51 (-76.5%; P<0.001). For 2 patients, IOP was not sufficiently reduced after treatment and they finally underwent filtering surgery., Conclusions: The prevalence of OSD in POAG patients is very high, particularly in patients with uncontrolled glaucoma with multiple topical medications. Careful management of the ocular surface associated with a reduction of the toxicity of eyedrops may result in improvement of ocular surface health and better IOP control.

Purpose: The purpose of this study was to evaluate the efficacy of nonpenetrating deep sclerectomy (NPDS) on posture-induced intraocular pressure (IOP) changes in open-angle glaucoma (OAG)., Materials and Methods: Twenty-five eyes of 25 patients with OAG that underwent NPDS were included in this study. IOP was measured with the IcarePro (ICP) tonometer in the sitting, supine, dependent lateral decubitus position (DLDP), and nondependent lateral decubitus position (NDLDP) before surgery, and at 1 and 3 months after surgery., Results: The mean baseline IOP measured in the sitting position was 20.5±8.4 mm Hg with Goldmann applanation tonometry and 19.6±6.5 mm Hg with ICP. At 1 and 3 months after NPDS, mean IOP decreased significantly in each position (P<0.001). At each time point, mean IOP was higher in all lying positions than in the sitting position (P<0.001) and higher in the DLDP than in the supine and NDLDP positions (P<0.001 and P=0.001). Posture-induced IOP changes between the sitting and supine position, DLDP, and NDLDP, respectively, were significantly reduced by 77% (P=0.009), 60% (P=0.001), and 82% (P=0.01) at 1 month and by 79% (P=0.004), 70% (P<0.001), and 79% (P<0.001) at 3 months after surgery. The IOP fluctuation reduction was significantly inferior when considering sitting-DLDP than other postural changes., Conclusions: NPDS is effective in lowering the mean IOP in all body positions and also the postural IOP fluctuations. The mean IOP in the DLDP remained higher than in the other body positions. This posture should be avoided in patients with asymmetric OAG.

Purpose: The purpose of the current study was to evaluate the efficacy and adverse event profile of 2 trabecular micro-bypass stents implanted during standard phacoemulsification cataract surgery in patients with mild to advanced open-angle glaucoma whose intraocular pressure (IOP) was well controlled by topical medications., Patients and Methods: This study was a retrospective analysis of patients with mild to advanced chronic open-angle glaucoma who underwent phacoemulsification and implantation of 2 stents. For all patients, preoperative and postoperative characteristics were evaluated, including number of medications and IOP. Postoperative visits were scheduled at 7 days and at months 1, 6, 12, and 24 after surgery. At each visit, IOP and the number of medications were noted., Results: In total, 63 eyes of 41 patients were included in the study. The vast majority of eyes (85.7%) were diagnosed with primary open-angle glaucoma. Preoperative mean IOP at baseline was 16.8±3.0 mm Hg (range, 10 to 24 mm Hg) with a mean of 2.3±0.9 medications. The mean IOP reduction represented a 13% decrease at 1 month (P<0.001), 13% at 6 months (P<0.001), 12% at 1 year (P<0.001), and 10% at 2 years (P<0.001), concomitant with a 23% reduction in the mean number of medications (P<0.001), 35% (P<0.001), 40% (P<0.001), and 40% (P<0.001), respectively, at each scheduled follow-up visit. At 24 months postoperatively, 19 of 23 (83%) patients experienced an IOP decrease compared with the preoperative visit. No severe device-related adverse events were observed., Conclusions: Patients with mild to advanced glaucoma can benefit from micro-bypass implantation even if their IOP is well controlled with topical hypotensive medications. Expectations for these reductions should be moderate.

Purpose: Pigment dispersion syndrome (PSD) is characterized by a structural abnormality of the posterior surface of the iris causing contact with the zonular fibers. It can lead to an open-angle glaucoma secondary to pigment dispersion into the trabecular meshwork. Laser peripheral iridotomy (PI) has been proposed as a treatment for pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS) by reducing the dispersion of pigment. The goal of this review was to assess the effects of PI for PSD and PG., Methods: We included six randomized controlled trials and two cohort studies (286 eyes of 218 participants). Four trials included participants with PG, and 4 trials enrolled participants with PSD with or without elevated intraocular pressure (IOP)., Results: Among patients with PG, at an average of 9 months of follow-up, the mean difference in IOP between groups was 2.69mmHg less in the PI group (95 % CI: -6.05 to 0.67; 14 eyes). In patients with PDS, the average IOP was statistically lower after PI as compared to baseline (Student test, t=11.49, P<0.01). With regard to visual field progression in participants with GP, after an average follow-up of 28 months, the risk of progression was not influenced by PI (RR 1.00 95 %: CI 0.16 to 6.25; 32 eyes). No trials that enrolled patients with PSD showed a diminution of the risk of glaucoma conversion at mid- and long-term., Conclusion: PI decreases the biomechanical factor causing contact between the iris and zonular fibers and may lower IOP over the long-term. Nevertheless, the effects of PI on visual field changes or progression have not been established in PG and PDS. There is no scientific evidence as of yet to advocate PI as a treatment for PDS or PG., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: To measure the influence of surgically induced intraocular pressure lowering on peripapillary and macular vessel density in glaucoma patients using optical coherence tomography angiography., Methods: Twenty-one eyes of 21 patients with open-angle glaucoma scheduled for filtering surgery were enrolled prospectively. Using optical coherence tomography angiography, vessel density was quantified within the peripapillary and macular regions, before and 1 month after filtering surgery. Change in vessel density was calculated for all analyzed areas., Results: One month after surgery, the mean intraocular pressure reduction was 44.2%±4.8% (range, 15.2% to 77.1%). The mean change in vessel density for the whole peripapillary area was 0.065±0.88% (P=0.788). In the macular region, the mean change in vessel density was -0.022%±0.691% (P=0.405) with significant changes only within the inferotemporal area of patients with predominantly superior visual field defects (-1.86%±1.43%, P=0.024)., Conclusions: Optical coherence tomography angiography allowed very limited measurement of intraocular pressure lowering-induced changes on the vessel density of the peripapillary and macular regions in glaucoma patients.

Purpose: To report a case of severe pigmentary glaucoma (PG) in a 13-year-old boy of a family affected by pigment dispersion syndrome (PDS)., Patients and Methods: A 13-year-old child was referred to our hospital for severe bilateral glaucoma. A complete ophthalmologic evaluation including refraction, intraocular pressure, central corneal thickness, slit-lamp biomicroscopy, gonioscopy, fundus examination, and ultrasound biomicroscopy was performed. Family members were also examined and a family pedigree was obtained., Results: Ophthalmologic examination revealed a severe bilateral PG with Krukenberg spindle and a widely open heavily pigmented iridocorneal angle. Ultrasound biomicroscopy showed a deep anterior chamber with pronounced iris concavity in both eyes. Within his family, his 15-year-old sister and 7-year-old brother were both affected by PDS diagnosed on gonioscopy findings., Conclusions: We report for the first time a severe case of pediatric PG with a family history of PDS. This case demonstrates that accurate screening is necessary in cases of familial PDS and PG, even in the pediatric population.

Purpose: To compare characteristics of functioning blebs (FBs) and nonfunctioning blebs (NFBs) with en-face spectral-domain optical coherence tomography (OCT)., Methods: We evaluated 41 blebs of 38 patients after a first-time trabeculectomy. Eyes were classified into 2 groups: FBs (22 eyes) and NFBs (19 eyes). En-face OCT images were analyzed semiquantitatively for the density of intraepithelial microcysts (0 to 3), internal fluid-filled cavity (0 to 3), and bleb vascularization (0 to 2). Presence of conjunctival fibrosis and visualization of the scleral flap were also analyzed., Results: FBs showed significantly more intraepithelial microcysts than did NFBs: the mean grading of microcyst density was 1.86 for FBs and 0.11 for NFBs (P<0.0001). None of the FBs were rated 0 and none of the NFBs were rated 2 or 3 for the density of intraepithelial microcysts. NFBs presented more conjunctival fibrosis than FBs (63% vs. 32%, P<0.05). There was no significant difference between FBs and NFBs for bleb vascularization, visualization of the scleral flap, and presence of subepithelial fluid-filled cavities. There was a direct correlation between postoperative intraocular pressure and intraepithelial microcyst density (r=-0.7655, P<0.0001). The long-term administration of preserved eyedrops before surgery was associated with fewer intraepithelial microcysts (r=-0.5436; P=0.0006)., Conclusions: FBs were associated with a higher number of intraepithelial microcysts evaluated with en-face OCT. A higher density of microcysts was associated with a lower intraocular pressure and a shorter duration of preserved topical treatment before surgery. En-face OCT provides a simple, noninvasive, and reproducible method to analyze blebs after filtering surgery.

Purpose: To characterize the in vivo morphology of human lamina cribrosa pores in healthy and glaucoma eyes., Patients and Methods: In this cross-sectional, observational study, a flood-illumination adaptive optics fundus (FIAO) camera was used to perform in vivo, high-resolution, noninvasive imaging of the optic disc and lamina cribrosa in 30 patients diagnosed with primary open-angle glaucoma (POAG), in 15 healthy controls and in 14 healthy subjects with at least one direct relative with POAG. Two masked graders measured each visible lamina cribrosa pore along the major and minor axes in order to categorize pores as oval (minor/major axis ratio<0.75) or round. We used these same measurements to calculate pore surface area as a best-fit oval., Results: Lamina cribrosa pores were visible in 95.2% of the subjects. In 52% of controls, the pores were visualized under the neuroretinal rim. In POAG patients, 78% of visible pores had an oval shape versus 19.4% in controls (P<0.01). Average pore surface area was significantly different (1561 px(2) versus 724 px(2); P<0.01). In healthy subjects with at least one direct relative with POAG, 21% had pores with an appearance comparable to that of subjects in the glaucoma group., Conclusion: On average, lamina cribrosa pores are elongated in POAG eyes and also in healthy eyes of POAG relatives. In vivo characterization of lamina cribrosa pore morphology by FIAO imaging may enhance our understanding of glaucoma, and offer new means for its early detection., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) cyclocoagulation in reducing intraocular pressure (IOP) in patients with refractory glaucoma by using a novel miniaturized delivery device (EyeOP1)., Methods: We conducted a 12-month open-label multicenter prospective study (EyeMUST1 Study). Patients with primary (primary open-angle glaucoma [POAG]) or secondary refractory glaucoma were treated in two groups depending on the duration of each ultrasound shot (group 1: 4 seconds; group 2: 6 seconds). The primary efficacy outcome was based on IOP reduction at 6 and 12 months., Results: Fifty-two patients were enrolled: 36 (69%) had POAG and 16 (31%) had secondary glaucoma. Group 1 (n = 24) and group 2 (n = 28) had similar demographics and baseline characteristics. In group 1, IOP was reduced from a mean preoperative value of 29.7 ± 7.7 mm Hg (n = 3.5 glaucoma medications) to a mean postoperative value of 21.3 ± 6.7 mm Hg (n = 3.5 glaucoma medications) and 20.1 ± 6.7 mm Hg (n = 3.2 glaucoma medications) at 6 and 12 months, respectively. In group 2, IOP was reduced from a mean preoperative value of 29.0 ± 7.4 mm Hg (n = 3.3 glaucoma medications) to a mean postoperative value of 20.2 ± 7.4 mm Hg (n = 3.4 glaucoma medications) and 18.5 ± 6.6 mm Hg (n = 3.5 glaucoma medications) at 6 and 12 months, respectively. At 12 months, the IOP reduction was sustained in both groups (32% IOP reduction in group 1 and 36% IOP reduction in group 2). The overall tolerance of the technique was good, with no serious adverse events., Conclusions: The new miniaturized HIFU EyeOP1 delivery device seems to be effective in decreasing IOP in patients with refractory glaucoma. The technology offers a good safety profile. (ClinicalTrials.gov number, NCT01338467.)., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Objective: To analyze the effect of preserved antiglaucoma eye drops on the expression of extracellular matrix (ECM) metalloproteinase inducer (EMMPRIN) in conjunctival epithelial cells., Methods: A total of 18 patients treated for primary open-angle glaucoma with benzalkonium chloride (BAK) preserved eye drops and eight age-matched controls were included in this study. Glaucoma patients were divided into two groups according to their daily exposure to BAK: high-exposure (HE) group and low-exposure (LE) group. HLA-DR and EMMPRIN were quantified on conjunctival impression cytology specimens using flow cytometry. In parallel, IOBA-NHC conjunctival epithelial cells were exposed to different BAK concentrations, in the presence or absence of cyclosporine A (CsA), and their total and surface expressions of EMMPRIN were assessed by flow cytometry and results are given in relative fluorescence intensities (RFIs)., Results: Compared to the control group (1.71 ± 0.39 RFI), EMMPRIN was significantly increased in the HE (4.19 ± 1.50 RFI, p < 0.001) and LE groups (2.55 ± 0.40 RFI, p = 0.029). Similar increase was observed in HLA-DR expression in the HE (4.58 ± 1.38 RFI, p < 0.001) and LE groups (2.52 ± 0.47 RFI, p = 0.046) as compared to control subjects (1.75 ± 0.27 RFI). Across all subjects enrolled in the study, there was a significant correlation between HLA-DR and EMMPRIN (R(2) = 0.875, p < 0.0001). IOBA-NHC cells exposed to BAK presented a significant increase in EMMPRIN, which was proportional to the concentration of BAK. The surface expression of EMMPRIN was inhibited by CsA., Conclusions: The increased expression of EMMPRIN in patients topically treated with multiple antiglaucoma BAK-preserved eye drops suggests a matrix metalloproteinase-related modification of conjunctival ECM remodeling. In vitro results suggest that CsA has the potential to limit BAK effects on EMMPRIN.

Introduction: Micro-invasive glaucoma surgical implantation of trabecular micro-bypass stents, previously shown to be safe and effective for open-angle glaucoma (OAG) subjects during cataract surgery, was considered for evaluation as a sole procedure. The aim of this study was to evaluate the safety and intraocular pressure (IOP)-lowering efficacy after ab interno implantation of two Glaukos Trabecular Micro-Bypass iStent inject second generation devices in subjects with OAG. This study was performed at sites in France, Germany, Italy, Republic of Armenia, and Spain., Methods: In this pan-European, multi-center prospective, post-market, unmasked study, 99 patients with OAG on at least two topical ocular hypotensive medications who required additional IOP lowering to control glaucoma disease underwent implantation of two GTS400 stents in a stand-alone procedure. Patients were qualified if they presented with preoperative mean IOP between 22 and 38 mmHg after medication washout. Postoperatively, subjects were assessed at Day 1, Months 1, 3, 6, 7, 9, and 12. IOP, medication use and safety were assessed at each visit., Results: Sixty-six percent of subjects achieved IOP ≤18 mmHg at 12 months without medication, and 81% of subjects achieved Month 12 IOP ≤ 18 mmHg with either a single medication or no medication. Mean baseline washout IOP values decreased by 10.2 mmHg or 39.7% from 26.3 (SD 3.5) mmHg to 15.7 (SD 3.7) mmHg at Month 12. Mean IOP at 12 months was 14.7 (SD 3.1) mmHg in subjects not using ocular hypotensive medications. Reduction from preoperative medication burden was achieved in 86.9% of patients, including 15.2% with reduction of one medication and 71.7% with reduction of two or more medications. Postoperative complications occurred at a low rate and resolved without persistent effects., Conclusion: In this series, implantation of two trabecular micro-bypass second generation stents in subjects with OAG resulted in IOP and medication reduction and favorable safety outcomes.

Purpose: To evaluate known and potential risk factors, including nutritional, lifestyle and environmental factors, differentiating patients with high-tension primary open-angle glaucoma (POAG) from control subjects with ocular hypertension (OHT)., Methods: In 2006-2007, 111 French ophthalmologists prospectively enrolled 339 cases of POAG and 339 age-matched controls with OHT. After a clinical examination with assessment of ocular risk factors, the ophthalmologist filled, during face-to-face interview, a detailed questionnaire developed by nutritionists and epidemiologist on lifestyle and environmental risk factors, including socio-demographic variables, dietary habits related to omega-3 fatty acids intake, smoking and alcohol drinking and professional exposure to pesticides and other chemicals. Associations of POAG with risk factors were estimated using conditional logistic regression, with adjustment for age, gender and duration of disease., Results: In the final multivariate model, by comparison with OHT, POAG was significantly associated with more frequent use of pesticides during the professional life [OR = 2.65, 95% confidence interval (CI): 1.04-6.78, p = 0.04] and with low consumption of fatty fish (OR = 2.14, 95% CI: 1.10-4.17, p = 0.02) and walnuts (OR = 2.02, 95% CI: 1.18-3.47, p = 0.01). POAG was also associated with higher frequency of heavy smoking (40 pack-years or more, OR = 3.93, 95% CI: 1.12-13.80, p = 0.03) but not with moderate (20-40 pack-years) and light smoking (<20 pack-years)., Conclusions: These exploratory observations suggest a protective effect of omega-3 fatty acids and a deleterious effect of heavy smoking and professional exposure to pesticides in POAG. This will need to be confirmed in future studies., (© 2012 The Author. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Thanks to recent progress in imaging techniques, the anatomy of the anterior segment can be measured accurately and noninvasively. The objective of this study was to assess early postoperative changes induced by non penetrating deep sclerectomy (NPDS) on anterior chamber depth, anterior chamber angle and central corneal thickness., Patients and Methods: Twenty eyes of 20 patients with primary open-angle glaucoma (POAG) that underwent NPDS were studied. All patients underwent ophthalmologic examination including non invasive analysis of the anterior segment architecture. Visante(®) OCT was used to determine anterior chamber depth, central corneal thickness, scleral spur angle (SSA), angle opening distance at 500μm (AOD 500), and trabecular-iris space area at 500 μm (TISA 500) in the nasal and temporal quadrants. These evaluations were performed at 1 day preop, then day 1, day 7 and day 30 after surgery., Results: Preoperatively, SSA, AOD 500 and TISA 500 were 37.24 ± 12.67°, 0.42 ± 0.25 mm and 0.15 ± 0.1 mm(2), respectively, in the nasal quadrant, and 39.62 ± 12.41°, 0.46 ± 0.25 mm and 0.16 ± 0.08 mm(2), respectively, in the temporal quadrant. Mean anterior chamber depth, central corneal thickness and intraocular pressure (IOP) were 3.09 ± 0.54 mm, 530 ± 34.3 μm and 20.43± 7.25 mmHg respectively. After NPDS, aside from IOP being significantly decreased on day 1 (5.57 ± 2.78 mmHg, P<0.0001), day 7 (8.2 ± 3.12 mmHg, P<0.0001) and day 30 (13.4 ± 3.47 mmHg, P=0.001), none of the other study parameters was significantly modified., Conclusion: No relationship was found between IOP and anterior chamber architecture after NPDS. NPDS appears to significantly reduce IOP while maintaining the architecture of the anterior chamber, and in particular, the anterior chamber angle., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Given the growing number of ocular hypotensive medications available, it is important to be able to predict a positive response to therapy. The purpose of the present study was to identify predictors of an additional 10% intraocular pressure (IOP) reduction after 12 weeks of treatment with latanoprost/timolol fixed combination (FC) in patients requiring a change in their previous ocular hypotensive medication., Methods: This multicenter, open-label, prospective, phase IIIb study included subjects >or=18 years of age with open-angle glaucoma (OAG) or ocular hypertension (OHT). Eligible subjects had baseline IOP >or=21 mmHg and insufficient response to current beta-blocker monotherapy. The primary efficacy analysis (logistic regression) identified predictors of a positive response after 12 weeks of latanoprost/timolol FC., Results: The intent-to-treat (ITT) population included 383 subjects treated with >or=1 drop of FC and having >or=1 follow-up IOP assessment. Mean IOP was 22.19 +/- 2.16 mmHg at baseline and was reduced by 5.42 +/- 2.71 mmHg at study end. In all, 325 (84.9%) subjects had a positive response to latanoprost/timolol FC; the response rate was similar across groups: OAG (n = 208; 82.7%); OHT (n = 161; 87.6%); OAG+OHT (n = 14; 85.7%). Higher baseline IOP (odds ratio: 1.284; 95% confidence interval [CI]: 1.101, 1.497; p = 0.0014) and absence of adverse events (odds ratio: 0.318; 95% CI: 0.161, 0.629; p = 0.0010) were significant predictors of positive response. Age, gender, ethnic origin, diagnosis, family history of OAG/OHT, corneal thickness, and concomitant systemic beta-blocker were not significant predictors of a positive response in the ITT analysis. The FC was well tolerated. The most common adverse events were related to the eye and were consistent with known adverse events associated with latanoprost and timolol., Conclusions: These results support the use of latanoprost/timolol FC in patients whose IOP is insufficiently controlled on beta-blocker monotherapy. Patients with higher baseline IOP levels and who do not experience adverse events while on therapy are most likely to achieve a positive response to latanoprost/timolol FC.

Background: Prospective, multicenter, randomized, double-masked trials have shown latanoprost instilled once daily to be at least as effective as and generally superior to timolol administered twice daily and to be as effective as other frequently prescribed prostaglandin analogues. This study prospectively assessed the efficacy of latanoprost monotherapy in a large cohort of treatment-naive patients with a broad range of baseline intraocular pressure (IOP) levels treated in actual clinical practice settings., Methods: This prospective, open-label, multicenter, uncontrolled, phase IV study included treatment-naive ocular hypertension or open-angle glaucoma subjects initiating latanoprost once daily (evening). IOP levels were measured at baseline and after 1 and 3 months. The primary efficacy outcome was mean change in IOP from baseline to month 3. Analyses were stratified by baseline IOP: > or = 20 and <24 mmHg vs > or = 24 mmHg., Results: Efficacy analyses (intent to treat) included 572 subjects: 20 to <24 mmHg group, N = 252; > or = 24 mmHg group, N = 320. Mean baseline IOP levels were 22.2 +/- 0.9 mmHg and 26.7 +/- 2.8 mmHg, respectively. At month 3, significant IOP reductions were seen in both groups (p < 0.0001, within-group differences); reductions were smaller in the 20 to <24 mmHg group (-6.3 +/- 2.4 vs -9.2 +/- 3.7 mmHg, respectively; -28.0 +/- 10.6% vs -34.1 +/- 11.9%, respectively). An IOP reduction of > or = 30% from baseline to month 3 was noted in 48.4% and 65.6% of subjects, respectively (p < 0.0001). At month 3, targets IOPs of < or = 18 mmHg were achieved by > or = 70% of subjects in both groups. Latanoprost was well tolerated with an adverse event profile similar to that reported in the literature., Conclusions: This "real world" study found once-daily latanoprost to be effective and safe in treatment-naive ocular hypertension or open-angle glaucoma patients. Patients with baseline IOP levels of 20 to <24 mmHg as well as > or = 24 mmHg benefitted from initial latanoprost therapy., Trial Registration Number: NCT00647101.

Purpose: To measure the impact of the Xal-Ease delivery device on ease of eyedrop administration and on treatment compliance and satisfaction., Methods: This prospective, multicenter, randomized, comparative, crossover study was conducted at 43 sites in France. Eligible subjects were >18 years of age, were diagnosed with primary open-angle glaucoma or ocular hypertension, had been treated with latanoprost or fixed-combination latanoprost/timolol for >or=3 months prior to enrollment, and did not require a therapy change. Subjects used either Xal-Ease or the dropper bottle for 4 weeks and then switched to the alternate delivery method for the next 4 weeks. Subjects completed questionnaires after 1 and 4 weeks in each treatment period., Results: In all, 211 subjects were enrolled, 107 to the Xal-Ease/dropper bottle group and 104 to the dropper bottle/Xal-Ease group. Baseline demographic and ocular characteristics were similar. Use of Xal-Ease made it significantly less likely that the subject would need someone to help with drop instillation (6.9% vs 18.1%, respectively; p<0.001) and reduced the problem of the tip of the bottle touching the eye (3.2% vs 35.6%, respectively; p<0.001). Reported compliance rates were very high and similar across groups during both treatment periods. After 1 month of use during both treatment periods, more than 70% of subjects reported global satisfaction with Xal-Ease to their physicians. No adverse events associated with the use of Xal-Ease were noted., Conclusions: Xal-Ease generally makes administration of latanoprost or fixed-combination latanoprost/timolol easier compared with the dropper bottle.

Objectives: To evaluate satisfaction and compliance in glaucoma and ocular hypertensive patients receiving a fixed combination treatment., Materials and Methods: After instilling a fixed combination, patients were asked to fill out a questionnaire about their satisfaction and compliance at baseline and 15 days after the onset of new therapy., Results: 1693 glaucoma patients (G) and 621 ocular hypertensive (OHT) patients were included. Mean age was 65.6+/-11.7 years. Onset of disease was 7.2+/-6.6 years and 5.2+/-4.9 years for G and OHT patients, respectively. Insufficient efficacy of the previous topical treatment (monotherapy in 55% of cases) was the main cause for shifting to a fixed combination in 70% of cases. Satisfaction was increased in 15% of the patients and compliance was increased in 25% of the patients., Discussion: Fixed combination provides an easier regimen and therefore encourages better compliance, a key issue in a chronic disease such as glaucoma.

Objective: To characterize and understand, at the cellular level, the aqueous humor pathways after filtering surgery, using in vivo confocal microscopy and impression cytology (IC)., Design: Observational case series., Participants: Thirty-two blebs of 29 patients after trabeculectomy were retrospectively evaluated., Methods: In vivo confocal microscopy and immunofluorescence staining of IC samples taken on and around the bleb area were performed. Impression cytology samples were examined under confocal microscopy after goblet cell and inflammatory cell immunostaining with anti-MUC5AC and antivimentin antibodies, respectively. Eyes were classified into 3 groups: (1) functioning blebs (11 eyes), (2) nonfunctioning blebs (10 eyes), and (3) functioning blebs after mitomycin C application (12 eyes). Impression cytology specimens and in vivo confocal microscopy images were analyzed and compared in a masked manner., Main Outcome Measures: Conjunctival epithelium changes of each type of bleb were analyzed using both impression cytology specimens and in vivo confocal microscopy and correlated to clinical outcomes., Results: In all IC specimens, numerous MUC5AC-positive cells were observed outside the edges of the blebs. Few MUC5AC-positive cells were observed at the surface of nonfunctioning blebs. Numerous goblet cells with immunostaining that was weak or limited to the membrane were clearly visible morphologically at the surface of functioning blebs (with and without adjunctive mitomycin C). Using in vivo confocal microscopy, all functioning blebs showed numerous intraepithelial optically empty microcysts, whereas nonfunctioning blebs had none or only a few. All blebs contained dendritiform inflammatory cells, especially after mitomycin C application., Conclusion: Impression cytology and in vivo confocal microscopy provide a new approach to filtering blebs. Microcysts observed at the surface of functioning blebs seemed to correspond to goblet cells, mostly containing aqueous humor instead of highly hydrophilic gel-forming mucins. Although this hypothesis requires further confirmation, the transcellular pathway of the aqueous humor could be hypothesized to occur at the level of goblet cells toward the ocular surface.

Purpose: To investigate the expression of CCR5 and CCR4, two chemokine receptors, as markers of the T helper (Th) 1 and Th2 pathways, respectively, and class II antigen HLA-DR as a hallmark of inflammation on conjunctival cells obtained from patients receiving long-term glaucoma treatment., Design: Case-control study., Participants: A total of 18 normal subjects and 70 glaucoma patients treated with topical antiglaucoma drugs for more than 1 year: 14 receiving a beta-blocker as monotherapy, 38 treated with a prostaglandin analog alone (19 with latanoprost, 6 with travoprost, 13 with bimatoprost), and 18 receiving multiple treatments., Methods: Impression cytologic specimens (ICSs) were obtained from 1 eye of the patients and processed for flow cytometry. Conjunctival cells were extracted and incubated with monoclonal antibodies against CCR4, CCR5, HLA-DR, or their specific controls to measure, in a masked manner, the percentages of conjunctival cells positive for the 3 markers., Main Outcome Measures: HLA-DR and chemokine receptors (CCR4 and CCR5) in ICSs., Results: Compared with all other groups, HLA-DR expression was raised significantly in the multitreatment group, whereas all monotherapies showed slight and nonsignificant increases. Both CCR4 and CCR5 were increased significantly in all 5 glaucoma groups compared with normal subjects, with no between-group differences., Conclusions: This study demonstrates the overexpression of 2 chemokine receptors in the conjunctival epithelium of glaucoma patients treated over the long term. These results show the simultaneous overexpression of CCR4 and CCR5, suggesting that the chronic use of topical treatments may stimulate both the Th1 and Th2 systems simultaneously. These results also suggest that inflammatory mechanisms combining allergy with toxicity are at work and illustrate the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.

Purpose: To evaluate the utility of the Visante OCT in the follow-up of filtering surgery., Material: and methods: In this study, we evaluated 38 filtering blebs in 31 patients following trabeculectomy (4) and nonpenetrating deep sclerectomy (NPDS). In 11 cases, mitomycin C was used during surgery. In patients who underwent NPDS, a collagen implant was placed within the scleral site in eight eyes and seven eyes had goniopuncture during follow-up. All patients had complete ophthalmologic examination with morphological evaluation of the bleb and intraocular pressure measurement as well as Visante OCT evaluation., Results: The trabeculectomy site as well as the trabeculodescemetic membrane (in NPDS), the scleral flap, the conjunctival flap, the iris, and the relationship between these structures were analyzed. Functioning blebs had a hyporeflective and irregular conjunctival tissue associated with a route for aqueous humor under the scleral flap from the anterior chamber toward the subconjunctival space. This filtration route was also observed within nonfunctioning encapsulated blebs. Flat and encapsulated nonfunctioning blebs had dense and hyperreflective conjunctival tissue. In the particular case of nonfunctioning flat blebs, there was no route for aqueous humor filtration under the scleral flap., Conclusion: The Visante OCT is a simple and noninvasive imaging technique with good resolution, allowing the analysis of morphologic changes occurring in eyes after filtering surgery.

Objectives: The aim of this study was to assess the changes in intraocular pressure (IOP) and ophthalmic symptoms with the Glaucoma Symptom Scale in patients suffering from open-angle glaucoma (OAG) or ocular hypertension (OHT) after 3 months of treatment with latanoprost., Materials and Methods: This multicentric open study was carried out in adult patients suffering from OAG or simple OHT (naive or previously treated with monotherapy) and needing a change or initiation of anti-glaucomatous treatment. One drop of latanoprost 0.005% was instilled every evening for 12 weeks in each affected eye. Efficacy was assessed by the variation in IOP and ophthalmic symptomatology at the end of treatment. Prognosis factors associated with a relative IOP reduction of at least 30% were sought (using a logistic regression model)., Results: A total of 920 patients suffering from OAG (54%) or OHT (44%), either previously treated (69%) or naive (31%), were included. The male:female ratio was 0.78 and the mean age was 63+/-13 years. At inclusion, the mean IOP was 22.1+/-3.8 mmHg. After treatment, IOP was significantly decreased by 5.1+/-4 mmHg, corresponding to a 22% reduction. IOP reduction was 7.1+/-4 mmHg, corresponding to 29% in naive patients and 4.2+/-4 mmHg, corresponding to 19% in previously treated patients. A relative IOP reduction of at least 30% was reached by 47% of naive patients and 21% of previously treated patients. In previously treated patients, a relative IOP reduction of at least 30% had a greater chance of being reached in men with previous ophthalmic history and high IOP at inclusion (above 21 mmHg). IOP reduction was similar in patients with OAG and OHT. A significant improvement in ophthalmic symptoms was observed after treatment in previously treated patients. A total of 7% of the patients presented an adverse event affecting the visual system: eye irritation (2%), eye pain (2%), or eye hyperemia (1%). Compliance was good for 94% of the patients., Conclusion: Latanoprost given as first or second-line treatment at the recommended dose effectively decreases IOP in patients with OAG or OHT. This treatment also improves visual and nonvisual symptoms in previously treated patients and presents a good safety profile.

Purpose: The aim of this work was to study, using flow cytometry, the expression of two chemokine receptors, CCR4 and CCR5, known to be related to the TH2 and TH1 systems, respectively, and the expression of HLA-DR, a hallmark of inflammation, on conjunctival impression cytology specimens (ICS) of glaucomatous patients treated over the long term., Patients and Methods: In this case-control study, ICS were taken in a series of 35 glaucomatous patients treated with topical antiglaucoma drugs for more than 1 year (seven with beta-blockers, ten with prostaglandins, and 18 receiving multiple treatments), and 20 normal subjects. Conjunctival cells were collected and incubated with specific monoclonal antibodies directed against CCR4, CCR5, and HLA-DR, in order to measure, in a masked manner using flow cytometry, the percentage of cells positive to each marker in the conjunctival epithelium., Results: Compared to normal subjects, HLA DR expression was significantly elevated in glaucomatous patients, with a tendency toward higher levels in the multitreatment group and lower levels in patients treated with prostaglandins, which did not differ significantly from control values. Both CCR4 and CCR5 significantly increased in glaucoma patients on multitreatment or monotherapy compared with normal subjects., Conclusion: This study demonstrates the overexpression of these two chemokine receptors in the conjunctival epithelium of patients treated for more than 1 year. Our results showing the simultaneous overexpression of CCR4 and CCR5 thus suggest that the chronic use of topical treatments may concurrently stimulate the TH1 and TH2 systems. These results evoke inflammatory mechanisms, combining allergy and toxicity, and confirm the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.

Objective: To analyze bleb structure after filtering surgery at the cellular level using a new generation in vivo confocal microscope., Design: Observational case series., Participants: We retrospectively evaluated 17 filtering blebs of 13 patients after trabeculectomy., Methods: Ophthalmologic examinations included slit-lamp examination, applanation tonometry, and in vivo confocal microscopy (Heidelberg Retina Tomograph II, Rostock Cornea Module). Eyes were classified into 3 groups: (1) functioning blebs (6 eyes), (2) nonfunctioning blebs (6 eyes), and (3) functioning blebs after application of mitomycin C (5 eyes). Cellular patterns, morphologic appearance, and functional aspects of functioning and nonfunctioning blebs were compared in a masked manner., Main Outcome Measures: In vivo confocal microscopy images were analyzed for number of intraepithelial microcysts, density of subepithelial connective tissue, presence of blood vessels, or encapsulation., Results: All functioning blebs had numerous intraepithelial optically-empty microcysts, whereas all nonfunctioning blebs had none or few. Subepithelial connective tissue was widely spaced in all functioning blebs, whereas the tissue was dense in 83.3% of nonfunctioning blebs. Functioning blebs with mitomycin C had numerous microcysts and loosely arranged subepithelial connective tissue as compared with nonfunctioning blebs., Conclusions: In vivo confocal microscopy study of blebs is an original method that agrees well with ex vivo histologic examination. The number of microcysts and the density of the subepithelial connective tissue observed with in vivo confocal microscopy are correlated with bleb function. By providing details of the structures of filtering blebs at the cellular level, in vivo confocal microscopy constitutes a new promising way to understand wound healing mechanisms after filtering surgery.

Purpose: To compare the conjunctival epithelial cell expressions of inflammatory cytokines in normal subjects and in glaucoma patients treated over the long term., Design: Case-control study., Participants: A total of 69 glaucoma patients treated over the long term and 15 normal subjects with no ocular abnormality or topical treatment., Methods: Amongst the 69 glaucoma patients, 27 were treated with preserved beta-blockers, 24 with unpreserved 0.5% timolol, and the other 18 patients with an association of > or =2 preserved drugs. All patients were treated for more than 1 year with the same treatment, with no significant differences between groups for mean ages and durations of treatment at the time of the study. Impression cytology specimens were taken and processed for immunofluorescence techniques. Conjunctival cell expressions of HLA DR, as a standard for inflammatory level, and the interleukins IL-6, IL-8, and IL-10 were obtained and quantified using flow cytometry., Main Outcome Measures: Immune markers and proinflammatory cytokines in impression cytology specimens., Results: We found a significantly increased expression of all immunoinflammatory markers and mediators in the conjunctival epithelium of glaucoma patients compared with normal eyes. Human leukocyte antigen DR was significantly higher in the 2 groups receiving preserved drugs than in the unpreserved timolol group. The 3 interleukins were similarly overexpressed in all glaucoma groups, with no significant between-groups differences except for the expression level of IL-8, which was significantly higher in the multitreatment group than in the preservative-free one., Conclusions: The present study confirms the increased expression of immunoinflammatory markers by the conjunctival epithelium of glaucoma patients treated over the long term. The development of nontoxic preservatives or preservative-free solutions is therefore of great interest.

Purpose: Several recent clinical studies have shown the benefit of lowering intraocular pressure in both ocular hypertensive and glaucoma patients. However, in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), there is no consensus on the value of intraocular pressure (IOP) to be reached to prevent the progression of visual field defects. This IOP value, called target IOP, is defined by the ophthalmologist according to the patient and the progression of the disease, without a clear explicit justification of this decision. In France, ophthalmologists' education is mainly based on scientific meetings and the European Guidelines. This study was conducted to investigate the position of the IOP target in the treatment strategy for patients with glaucoma or OHT., Material: and methods: A cross-sectional descriptive survey was conducted in France among ophthalmologists in private practice. Patients with simple OHT or with OAG who required an initiation or a modification of treatment were included., Results: We included 1735 patients (805 males, 46.4%) in the study. An OAG was diagnosed in 1338 patients (77.1%) and a simple OHT in 397 patients (22.9%). The patients with OAG were older than the OHT patients (65 years vs 61.7 years, p<0.0001). Most patients (73.5%) were included for treatment modification (77.5% of the patients with OAG and 59.9% of the patients with simple OHT; p<0.0001). The main reason for treatment change was an unsatisfactory IOP value. The main therapeutic objective was to reach a target IOP in 46.0% of the patients. The choice of the ocular hypotensive drugs depended on the IOP value in 51.9% of the patients. When the treatment was modified, monotherapy was preferred in 60.8% of the patients., Conclusion: Among ophthalmologists, the main objective for the treatment of patients with simple OHT or with OAG was to reach a target IOP. About half the participants were used to set up a target pressure for their patients. This fairly good ratio shows the comprehensiveness and the adaptation of our colleagues to relatively new concepts in treating and managing patients with ocular hypertension or chronic open-angle glaucoma. If a modification in the treatment was necessary, then monotherapy was preferred. This decision was motivated by the efficacy of the treatment but also by expected better patient compliance.

Aims: The aim of the ab externo trabeculectomy (AET) is to remove the external portion of the trabecular meshwork (ETM) responsible for the main aqueous outflow resistance in glaucoma patients, with no opening of the anterior chamber. ETM characteristics were evaluated with a confocal microscope., Methods: A prospective comparative observational case series was performed in 60 consecutive medically treated patients with primary open angle glaucoma and eight postmortem normal donors' eyes that underwent AET. Once deroofing the Schlemm' s canal (SC), a deeper dissection led to removal of a coherent membrane (ETM) which allowed satisfactory aqueous egress through the remaining intact internal trabecular meshwork (TM) layers. After fixation with acetone and immunostaining with anti-vimentin antibody, ETM were analysed with a confocal microscope., Results: Glaucomatous ETM (mean thickness: 29.5 (7.6) micro m) were characterised by a severe paucicellularity compared with the controls (respectively 37.3 (9.7) cells/area and 167.5 (24.9) cells/area, p<10(-4)). ETM analysis showed involvement of both cribriform and corneoscleral layers. ETM cell density was significantly decreased in case of preoperative fluorometholone instillation., Conclusion: Paucicellularity of glaucomatous TM is confirmed by this original technique. Structural characteristics of the ETM, whose removal allows satisfactory aqueous egress, suggest that aqueous outflow resistance not only involves inner wall of SC and juxtacanalicular meshwork but also corneoscleral trabecular layers.

Chronic glaucoma is a severe disease that can induce blindness.Early diagnosis and symptomatic treatment reduce the risk of blindness. Treatment that will be started before the onset of clinical signs and will remain lifelong thereafter is troublesome, and therapeutic compliance is usually poor. Thus, quality of life (QOL) measurement in patients with chronic glaucoma has a particular purpose: to measure patients' perception of the disease and treatment in order to maintain good treatment compliance to ensure therapeutic management efficacy and to preserve visual function. No glaucoma-specific instrument is available in the medical and QOL literature. Various generic(SF-36, SF-20 and SIP) and specific(VAQ, VF-14, NEI-VFQ) QOL questionnaires,one glaucoma-specific symptomatic scale (GSS),and one treatment preference scale (COMTol) have been used to measure QOL in glaucoma patients. These instruments do not sufficiently measure the psychosocial dimension of the disease and the QOL impact of treatment. An instrument able to measure all dimensions needs to be developed in order to help ophthalmologists in the therapeutic management of their patients and to measure QOLin patients in the successive stages of the disease.

Purpose: Recent histologic studies of conjunctival tissues in patients who have had long-term treatment for glaucoma have shown in situ an abnormal infiltration by inflammatory cells. In this study, conjunctival inflammatory antigens were investigated in impression cytology specimens from patients who have been and those who have not been treated for glaucoma., Methods: This study included 107 eyes from 55 patients with primary open-angle glaucoma. Of these, 48 had received prolonged topical treatments, all containing benzalkonium chloride as a preservative. Seven glaucomatous eyes could be examined before any treatment. In addition, the authors examined 11 patients (21 eyes) receiving anticataract eye drops preserved with chlorhexidine and 15 normal untreated subjects (30 eyes). In all patients, immunocytochemistry was performed in impression cytology specimens, using two monoclonal antibodies against HLA-DR antigens and receptor to IgE CD23., Results: None of the untreated eyes showed reactivity for either monoclonal antibody. In contrast, HLA-DR expression by conjunctival cells was found in 43 of 88 treated eyes (mean percentage of reactive cells, 70% +/- 28%) and positive staining for receptor to IgE in 26 of 68 eyes (52% +/- 28% of conjunctival cells). Results were not related to a specific treatment or combination of anti-glaucoma drugs. However, the proportion of positive specimens (3/14 for both antigens) in the group receiving chlorhexidine-containing eye drops was significantly lower than that found in the patients with glaucoma., Conclusion: This study showed abnormal expression of inflammatory markers without clinical inflammation at the level of conjunctival cells in repetitive contact with various anti-glaucomatous treatments and their common preservative, benzalkonium chloride. Failure in filtering glaucoma surgery was found to be related to prolonged medical treatment; therefore, a topical sensitization to preservatives and/or anti-glaucoma drugs has been hypothesized. An immunocytologic test thus could be useful for qualitative and quantitative investigation of drug-induced conjunctival inflammation and predict high-risk patients.