[Biomechanics of the lamina cribrosa: A determining factor in glaucomatous neuropathy. A review of the literature]. / Biomécanique de la lame criblée : un facteur déterminant de la neuropathie glaucomateuse. Une revue de la littérature.

Glaucoma is a chronic optic neuropathy characterized by progressive sclero-laminar remodeling. The main factor at the origin of these deformations is the intraocular pressure (IOP), the effect of which varies according to the biomechanical properties of the individual lamina cribrosa (LC). In this environment, the LC represents a malleable zone of weakness within a rigid corneoscleral shell. It is a dynamic structure whose movements play a key role in the pathogenesis of glaucoma: displacing it posteriorly, in addition to contributing to the characteristic appearance of glaucomatous cupping, would increase constriction on the nerve fibers and the laminar capillaries. Often incorrectly considered permanent in adults, these deformations have a certain degree of reversibility, which is currently better characterized thanks to progress in imaging techniques. The occurrence of anterior displacement and laminar thickening following a reduction in IOP could thus constitute a good prognostic factor by reducing mechanical stress on this region. These changes would tend to reduce laminar pore tortuosity and shear forces, which are probably key mechanisms of axonal loss in glaucoma.

Safety and efficacy of iStent Inject trabecular micro-bypass stents in combination with phacoemulsification for chronic open angle glaucoma associated with cataract.

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.

[Role of the lamina cribrosa in the pathogenesis of glaucoma. A review of the literature]. / Rôle de la lame criblée dans la pathogenèse du glaucome. Une revue de la littérature.

Located within the scleral canal, the lamina cribrosa is a sieve-like structure separating the intraocular and retrobulbar portions of the optic nerve. Identified as the main site of axonal damage in glaucomatous optic neuropathy, the study of the lamina cribrosa has been of great interest for many years. Numerous studies have explored the histological and morphological characteristics of the laminar region in healthy subjects as well as glaucoma patients. More recently, the development of adaptive optics systems and new generations of OCT has allowed great progress in the understanding of the pathogenesis of glaucoma and has opened new perspectives for the improvement of diagnostic procedures.

[The trabecular meshwork: Structure, function and clinical implications. A review of the littérature (French translation of the article)]. / Le trabéculum : structure, fonction et implications cliniques. Une revue de la littérature.

Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal angle, is the main pathway for drainage of aqueous humor (AH) out of the eye, and its dysfunction is responsible for the IOP elevation. The trabecular meshwork is a complex, fenestrated, three-dimensional structure composed of trabecular meshwork cells (TMC) interdigitated into a multilayered organization within the extracellular matrix (ECM). The purpose of this literature review is to provide an overview of current understanding of the trabecular meshwork and its pathophysiology in glaucoma. Thus, we will present the main anatomical and cellular bases for the regulation of aqueous humor outflow resistance, the pathophysiological mechanisms involved in trabecular dysfunction in the various types of glaucoma, as well as current and future therapeutic strategies targeting the trabecular meshwork.

The trabecular meshwork: Structure, function and clinical implications. A review of the literature.

Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP). The trabecular meshwork, located within the iridocorneal angle, is the main pathway for drainage of aqueous humor (AH) out of the eye, and its dysfunction is responsible for the IOP elevation. The trabecular meshwork is a complex, fenestrated, three-dimensional structure composed of trabecular meshwork cells (TMC) interdigitated into a multilayered organization within the extracellular matrix (ECM). The purpose of this literature review is to provide an overview of current understanding of the trabecular meshwork and its pathophysiology in glaucoma. Thus, we will present the main anatomical and cellular bases for the regulation of aqueous humor outflow resistance, the pathophysiological mechanisms involved in trabecular dysfunction in the various types of glaucoma, as well as current and future therapeutic strategies targeting the trabecular meshwork.

[Perception of glaucoma and therapeutic adherence: A multicenter observational study]. / Perception du glaucome et observance thérapeutique : une étude observationnelle multicentrique.

INTRODUCTION: The purpose of this study was to evaluate medication adherence of glaucoma patients through the "Glaucoma treatment compliance assessment tool (GTCAT)" questionnaire and to correlate the results with clinical parameters. PATIENTS AND METHODS: This multicenter prospective observational study was performed in the Département hospitalo-universitaire (DHU) Sight Restore, Paris, France. All patients had been followed for chronic open angle glaucoma (COAG) for at least 3 years. A French version of the GTCAT questionnaire was administered to patients. The results were correlated with clinical parameters of glaucoma, such as duration of disease, medications used, intraocular pressure (IOP) and mean deviation (MD) of the most recent visual field. RESULTS: Seventy-three patients were included in our study, with 60.9% declaring that they fully adhered to the treatment. There was a correlation between the amount of days missing treatment and difficulties using the eye drops. The main cause of missing the drops was forgetfulness (75%), followed by unavailability of the drop when it was time to take it (37.5%). The impact of glaucoma on quality of life was correlated to the amount of adverse effects of topical medications. The patient's perception of the importance of preserving vision was correlated to the level of confidence in the physician concerning the diagnosis of glaucoma. CONCLUSION: In glaucoma patients, the use of the GTCAT questionnaire confirmed the complex relationship between the patient, the disease and its treatment, and even his or her relationship with the ophthalmologist. These results emphasized the importance of therapeutic education but also the negative role of side effects of the eye drops on treatment adherence in glaucoma patients.

Loss of p300 accelerates MDS-associated leukemogenesis.

The role that changes in DNA methylation and histone modifications have in human malignancies is poorly understood. p300 and CREB-binding protein (CBP), two distinct but highly homologous lysine acetyltransferases, are mutated in several cancers, suggesting their role as tumor suppressors. In the current study, we found that deletion of p300, but not CBP, markedly accelerated the leukemogenesis ofNup98-HoxD13 (NHD13) transgenic mice, an animal model that phenotypically copies human myelodysplastic syndrome (MDS). p300 deletion restored the ability of NHD13 expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew in vitro, and to expand in vivo, with an increase in stem cell symmetric self-renewal divisions and a decrease in apoptosis. Furthermore, loss of p300, but not CBP, promoted cytokine signaling, including enhanced activation of the MAPK and JAK/STAT pathways in the HSPC compartment. Altogether, our data indicate that p300 has a pivotal role in blocking the transformation of MDS to acute myeloid leukemia, a role distinct from that of CBP.

[Assessment of anterior segment anatomy by OCT after non penetrating deep sclerectomy]. / Analyse de l'architecture du segment antérieur par OCT après sclérectomie profonde non perforante.

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.

[Corneal sensitivity in patients treated medically for glaucoma or ocular hypertension]. / Évaluation de la sensibilité cornéenne chez les patients traités médicalement pour un glaucome ou une hypertonie oculaire.

PURPOSE: To evaluate the corneal sensitivity in patients treated with intraocular pressure (IOP)-lowering medications. INTRODUCTION: Chronic administration of anti-glaucoma drops is associated with numerous tissue changes on the ocular surface. The purpose of this study was to investigate the effect of these medications and their preservative, benzalkonium chloride (BAK), on corneal sensitivity. PATIENTS AND METHODS: Thirty-nine patients treated for glaucoma or ocular hypertension (OHT) and nine untreated patients were included in this study. Treated patients were divided into three groups according to the daily number of preserved eyedrops (0, 1 and ≥2). Corneal sensitivity was assessed using the Cochet-Bonnet esthesiometer. All patients underwent a complete examination of the ocular surface including Schirmer testing, tear film breakup time (BUT) and corneal and conjunctival fluorescein staining. The Ocular Surface Disease Index (OSDI) questionnaire was used to evaluate symptoms. RESULTS: Corneal sensitivity was 58.8±2.8mm, 56.2±5.2mm, 50.3±12.5mm and 44.3±13.6mm in untreated patients, in patients treated with none, one and two or more instillations of preserved eyedrops, respectively. Corneal sensitivity in patients treated with preserved eyedrops was significantly lower as compared to untreated patients (P<0.001) and patients treated with preservative-free eyedrops (P=0.012). Corneal sensitivity of patients treated with intraocular pressure-lowering medications was negatively correlated to the number of instillations of preserved eyedrops (r=-0.390 ; P<0.001) as well as to the duration of treatment (R=-0.357 ; P=0.001). BUT and fluorescein staining were significantly altered in treated patients compared to the untreated control group ; however, no significant difference was observed between the treated groups. There was no significant difference for OSDI or Schirmer testing between the various groups. CONCLUSION: Chronic administration of BAK-containing anti-glaucoma eyedrops appears to alter corneal sensitivity. These results could explain the absence of correlation between clinical signs and symptoms sometimes observed in patients treated for glaucoma or OHT.

[The influence of ocular surface diseases in the management of glaucoma]. / Influence des pathologies de la surface oculaire sur le traitement du glaucome.

INTRODUCTION: The medical treatment of glaucoma is frequently used as a first-line treatment. Often effective, this treatment is administered over the long term. Chronic administration of eye drops is implicated in ocular surface disease. The objective of this study was to determine the prevalence of ocular surface diseases (OSDs) in patients treated for glaucoma or ocular hypertension (OHT) as well as their influence on therapeutic management. PATIENTS AND METHODS: Eighty-eight patients followed at the Quinze-Vingts National Ophthalmology Hospital for glaucoma or OHT were evaluated. All patients had a complete ocular examination including an evaluation of the ocular surface. A questionnaire derived from the Ocular Surface Disease Index (OSDI) was used to assess ocular surface symptoms and the related impairment of quality of life. According to the clinical evaluation of the ocular surface, patients were classified into three groups (A, no OSD; B, moderate OSD; C, severe OSD. The patients for whom ocular surface disease had modified the therapeutic management of glaucoma were identified. RESULTS: In this study, 72 patients (82 %) showed significant symptoms of OSDs (OSDI score>22). A moderate or severe OSD was observed in 67 patients (76 %). For 33 patients (38 %), the OSD influenced the choice of glaucoma or OHT treatment. Among these patients, six had glaucoma surgery, one had laser trabeculoplasty, and 26 required one or several changes in eyedrops. CONCLUSION: This study confirmed the high prevalence of OSDs in patients treated for glaucoma or OHT. For numerous patients, these pathologies influenced not only their quality of life but also their therapeutic management.

[What to do if the intraocular pressure measurement does not appear reliable]. / Que faire si la mesure de la pression intraoculaire semble peu fiable ?

Among the various intraocular pressure (IOP) measurement methods available today, Goldmann applanation tonometry (GAT) remains the gold standard for in-office routine IOP measurement. However, numerous factors may affect IOP measurement with GAT, namely corneal features. Before any interpretation of an IOP value, the measurement conditions should be checked and the central corneal thickness evaluated, since GAT overestimates IOP in thick corneas and underestimates IOP in thin ones. When GAT is not applicable, other IOP measurement devices, which have their own limits, are available. For example, the ocular response analyzer (ORA) and dynamic contour tonometry (DCT) provide IOP readings that are less influenced by corneal properties and may be useful after refractive surgery. Regardless of the choice of tonometer, the IOP value must not be considered alone but from a clinical point of view, including, namely, multiple IOP measurements over a day since the IOP fluctuates over a 24-h time period. A complete clinical examination is necessary in each case to search for glaucomatous neuropathy.

[New diagnosis approaches: iridocorneal angle in optical coherence tomography]. / L'angle irido-cornéen en tomographie de coherence optique.

Gonioscopy remains a standard technique to evaluate anterior segment and iridocorneal angle. However, new imaging techniques, particularly high resolution optical coherence tomography (OCT), permit to optimally visualize the anterior segment. Use of OCT in glaucoma diagnosis and follow-up will increase with technical progress and new high speed ultrahigh-resolution OCT.

[Application of anterior segment OCT to the study of glaucoma]. / Application de l'OCT de segment antérieur dans l'étude des glaucomes.

Anterior segment OCT is a noninvasive and simple imaging technique providing high-resolution images of the anterior segment of the eye. Glaucoma is a large domain of application for anterior segment OCT. In addition to the morphologic and morphometric analysis of anterior segment structures and of the iridocorneal angle in particular, numerous new applications such as the follow-up of filtering surgery have been developed.

[Clinical key points. Gonioscopy]. / Les points-clés de la clinique. La gonioscopie.

Gonioscopy should be performed in all patients with glaucoma or suspected of having glaucoma. Four points are systematically evaluated: the width of the angle, the degree of trabecular pigmentation, the iridotrabecular appositions or synechia, and the level of iris insertion and the shape of the peripheral iris profile.

[Surgical key points. Nonpenetrating sclerectomy]. / Les points-clés de la chirurgie. La sclérectomie non perforante.

Deep sclerectomy is a true external sclerotrabeculectomy. By selectively increasing the aqueous humor outflow through the trabecula and Schlemm's canal without anterior chamber penetration, deep sclerectomy is the most physiological surgical technique in glaucoma. Nevertheless, this technique requires accurate knowledge of anterior chamber anatomy and accurate dissection.

[Utility of the Visante OCT in the follow-up of glaucoma surgery]. / Apport de l'OCT-Visante dans le suivi de la chirurgie du glaucome.

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.