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.

[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.

[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.

Blood flow rate in the microvasculature of the optic nerve head in primary open angle glaucoma. A new approach.

In order to evaluate the optic nerve head perfusion in patients with primary open-angle glaucoma (POAG), we measured the velocity of the red blood cells (RBCs) in the capillaries of the optic nerve head with a laser-Doppler velocimeter and evaluated the blood viscosity by determining the capacity of the RBCs to disaggregate with an erythroaggregameter. Our results showed that in POAG patients optic nerve blood velocity was reduced and that the aggregability of the RBCs was increased. The two parameters were not significantly correlated, possibly because of local papillary autoregulation and anatomical variability in the papilla vessels. These two factors could explain why the same rheological anomaly in two subjects could lead to different responses in blood velocity. The RBC hyperaggregability cannot be explained by quantitative modifications of the plasma proteins. Modifications in the membrane of the RBCs could indeed be responsible for hyperaggregability, since our data suggest that deformability of the RBCs is impaired in glaucoma.

Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma.

Optic disc blood flow velocity was measured in healthy patients, those with primary open angle glaucoma (POAG), and patients with normal pressure glaucoma (NPG). The velocity of the red blood cells (RBCs) in the capillaries of the optic nerve head (ONH) has been measured with a laser Doppler velocimeter (LDV), and blood viscosity has been evaluated notably by determining the aggregability of the RBCs with an erythroaggregameter. Our results in POAG patients and NPG patients showed that their optic nerve blood flow velocity was reduced and that the aggregability of the RBCs was increased. The hyperaggregability of the erythrocytes is responsible for the increase of the local viscosity in the papillary capillary network. These haemodynamic modifications observed in patients with glaucoma support the hypothesis of a vasogenic mechanism that could impair the optic nerve in glaucoma patients.

Confocal microscopic examination of trabecular meshwork removed during ab externo trabeculectomy.

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.

[Hemo-rheology of glaucomatous neuropathy]. / Hémorhéologie de la neuropathie glaucomateuse.

The vascular participation to the optic nerve pathogenesis has been contradicted. The red blood cell velocity in the optic nerve capillary with a laser Doppler velocimeter, an atraumatic and reliable method, and the aggregability was determined with an erythroaggregameter to know whether an erythrocyte hyperaggregability could slow down the optic nerve blood flow as it has been previously demonstrated in an experimental study. The experiment on the open angle glaucoma patients showed that their optic nerve blood flow was reduced, and their erythrocyte aggregability significantly increased. The two parameters were not significantly correlated, certainly because of a local papillary autoregulation and of the papilla vessels variability, those two factors could modulate the blood flow response to blood qualitative changes. The erythrocyte hyperaggregability could be explained by erythrocyte membrane modifications that could agree with the glaucoma heredity.

[Management of non penetrating surgery failure]. / Que faire en cas d'échec d'une sclérectomie profonde?

Failure of deep sclerectomy with external trabeculectomy is defined as intraocular pressure (IOP) elevation in the post-operative period. This IOP increase is related to obstacles on the outflow pathway, which may be hindered either by internal obstacles (iris incarceration, internal trabecular layers insufficiently permeable to aqueous humor), or by external obstacles (excessive conjunctival scar such as fibrosis or cysts). These obstacles require specific treatment that is not always successful. Pre-, intra- and post-operative care that reduces the incidence of these complications is detailed.

[What strategy after three trabeculectomy failures?]. / Que faire en cas d'échec d'une triple trabéculectomie ?

Three trabeculectomy failures raises the delicate problem of refractory glaucoma with unresponsive ocular hypertony. The therapeutic strategy requires first a careful assessment of the reasons for the previous failures (internal or external obstacles to filtration which might have responded to preventive treatment), then, depending on the patient's age, type of glaucoma, anatomic status of the ocular structures and the visual potential of the eye, a choice has to be made between different surgical techniques aimed at favoring aqueous humor evacuation (trabeculectomy associated with antimetabolites or drainage implant) or destruction of the ciliary body to reduce intraocular pressure by limiting the production of aqueous humor. Choosing between these two possibilities is not an easy task as success rates are highly variable on such eyes and complications are frequent, leading to lower visual acuity in 30 % of the cases. These salvage procedures recall that first line trabeculectomy must be optimized in all cases.

[Non penetrating filtering surgery, evolution and results]. / La chirurgie filtrante non perforante: évolution du concept, réalisation, résultats.

Trabeculectomy is currently the standard filtration procedure for glaucoma surgical treatment. Despite several advantages over full-thickness procedures, trabeculectomy can be responsible for early postoperative complications related to sudden ocular decompression that can lead to hypotony with its sight-threatening complications. Nonpenetrating glaucoma surgeries, namely viscocanalostomy and deep sclerectomy with external trabeculectomy, have been developed in recent years in order to improve the safety of conventional filtering procedures. The goal of these procedures is to reduce intraocular pressure (IOP) by enhancing the natural aqueous outflow channels, while reducing outflow resistance, attributed for 75% to the trabecular meshwork and for 25% to the outer wall of Schlemm's canal (SC) or tissue surrounding it. In these procedures, the anterior chamber is not opened so that complications related to full thickness procedures are mainly avoided. In the last few years, viscocanalostomy and deep sclerectomy with external trabeculectomy have become the most popular nonpenetrating filtering procedures. Both involve the removal of a deep scleral flap, the external wall of SC, and corneal stroma behind the anterior trabecula and Descemet membrane, thus creating a scleral lake. The aqueous humor leaves the anterior chamber through the intact trabeculodescemetic membrane and reaches the scleral lake, from where it will egress into different pathways. In viscocanalostomy, a high-molecular viscoelastic substance is injected into the ostia of the SC in order to enlarge the SC and its collector channels. In deep sclerectomy with external trabeculectomy, the main goal is to remove the inner wall of the SC and the adjacent trabecular layers involved in aqueous outflow resistance, while leaving the innermost trabecular layers intact so that the anterior chamber does not open during operation. Different surgical adjuvants designed to maintain the scleral lake open are commercially available. Retrospective and prospective published studies have reported similar midterm results with trabeculectomy and nonpenetrating filtering procedures in terms of IOP control, with fewer postoperative complications and better visual acuity recovery with the nonpenetrating procedures. This article reviews the current nonpenetrating surgical procedure techniques, their mechanism of action, and their outcome.

[Consensus on neovascular glaucoma]. / Consensus sur le glaucome néovasculaire.

Neovascular glaucoma is a dreadful pathology with a rapid spontaneous evolution responsible for painful and blind eye. The main cause is an anterior neovascular proliferation following a broad retinal ischemia. Early diagnosis and treatment are required in order to maintain a good visual status and a satisfactory IOP control with medical, surgical or cylodestructive procedures. In any case, the treatment of the retinal ischemia has to be performed. One must keep in mind that the most efficient way to avoid the incidence of neovascular glaucoma is a strict control of clinical situations potentially responsible for retinal ischemia, namely VRO in elderly patients and diabetic retinopathy in younger patients.

[Familial complicated optic disc drusen in a child]. / Drüses familiales compliquées chez un enfant.

We report a case of a 15-year-old child with optic disc drusen with known familial inheritance and disc swelling. Inheritance and visual field defects are discussed.

[Leber's idiopathic stellate neuroretinitis. Apropos of 9 cases]. / La neurorétinite stellaire idiopathique de Leber. A propos de neuf cas.

Leber's optic neuroretinitis is a particular form of optic neuropathy characterized by swelling of the optic disc and a stellate pattern of exsudative deposits in the macula. It occurs most often in healthy young subjects who have acute monolateral visual loss, often preceded by presumed viral illness. The etiology is unknown and viral infection has been suggested in the pathogenesis of this condition. The prognosis for visual recovery is reported to be excellent, but late visual sequelae have been described: loss of vision or visual field loss. This entity should be recognized and distinguished from more serious diseases causing septic neuroretinitis or papillitis.

[Evaluation of confocal microscopy in the analysis of the external trabecular membrane during deep nonpenetrating sclerectomy]. / Apport de la microscopie confocale dans l'analyse de la membrane trabéculaire prélevée au cours de la chirurgie filtrante non perforante.

PURPOSE: Deep non penetrating sclerectomy (DNPS) is a new filtering surgical procedure whose aim is a selective ablation of the external portion of the trabecular meshwork (TM) which is involved in the aqueous outflow resistance, i.e. the inner wall of Schlemm's canal (SC) and the external trabecular layers, especially the cribriform TM. We evaluated, with a confocal microscope, the structural characteristics of this part of the TM in glaucomatous patients. METHODS: Thirty-six external trabecular membranes (ETM) were obtained from 33 consecutive glaucomatous patients (mean age: 56.5+/-14.5 years) and from four post-mortem normal donors (60.5 +/-7.7 years), which underwent DNPS according to the same surgical procedure. Under conjunctival and scleral flaps, the roof of the SC was opened and removed. A deeper dissection led to the removal of the inner wall of the SC and the adjacent ETM, i.e the TEM, which allowed a satisfactory aqueous flow through the remaining internal TM layers. After fixation with acetone or triton X100 and immunostaining with anti-fibronectin or vimentin antibodies, the samples were analyzed with a confocal microscope (Nikon EZ 2000). RESULTS: The mean thickness of the ETM was 34.4+/-7.3 microm in glaucomatous eyes, not significantly different from the controls (39.0+/-10.7 microm). The main characteristic of the glaucomatous ETM membrane is a paucicellularity as compared to the controls (respectively 21.6+/-12.1 cells/area and 156.1+/-28.8 cells/area). The confocal microscope analysis shows that the ETM involves two different portions of the trabecular meshwork. The architectural characteristics of the outermost portion of the ETM with its star-shaped cells arranged in a homogenous extra-cellular matrix, suggest that it is the trabecular cribriform meshwork. The inner portion of the ETM shows cells arranged regularly in a fibrillar extra-cellular matrix as described in the corneoscleral trabecular meshwork. CONCLUSION: These results confirm the previous reported histopathological changes of the glaucomatous TM. The thickness of the removed ETM and its structural characteristics show that the ablation of the TM layers necessary to obtain a satisfactory aqueous filtration, not only involves the cribriform layers but also one of the inner parts of the TM, i.e. the corneoscleral TM. This result suggests that aqueous humor resistance not only involves the cribriform trabecular meshwork but also a part of the corneoscleral trabecular meshwork.

[Acute ischemic optical neuropathy which became bilateral in 3 days in Horton disease]. / Neuropathie optique ischémique aiguë bilatéralisée en 3 jours dans le cadre d'une maladie de Horton.

We report a case of a 71-year-old man with sequential visual loss within 3 days due to giant cell arteritis confirmed by a temporal artery biopsy. The anterior ischemic optic neuropathy was associated with cilioretinal artery occlusion on the right eye. He improved after intravenous corticosteroid therapy. Clinical characteristics and treatment are discussed.

[Trans-scleral diode laser cyclophotocoagulation for the treatment of refractory pediatric glaucoma]. / La cyclophotocoagulation transsclérale au laser diode dans le traitement des glaucomes réfractaires du sujet jeune.

PURPOSE: To evaluate the success rate of contact diode transscleral cyclophotocoagulation (TSCPC) in pediatric refractory glaucoma. PATIENTS: and method: Twenty-eight eyes of 28 patients (age range 5 months to 26 years) with medical and surgical refractory pediatric glaucoma due to primary congenital glaucoma (group 1, 20 eyes) or aphakic congenital glaucoma (group 2: 8 eyes), were included in this retrospective study. All eyes underwent one or more TSCPC with the diode laser (Oculight SLX, Iris Medical) with a minimal follow-up of 2 months. Success was defined as intraocular pressure (IOP) between 6 and 20 mmHg after one or more procedures, with no increase in medical hypotensive therapy, and no progression to another hypotensive procedure. RESULTS: Mean baseline IOP was 29.4 +/- 7.8 mmHg (range 25 to 60 mmHg) and mean follow-up was 10.3 +/- 6.9 months (range 2 to 26 months). Success rates evaluated at 6 and 12 months (Kaplan Meier survival curves) were 54.4% and 27.7% respectively, with one-third of the eyes retreated once or more. These success rates were similar in both groups with a mean baseline IOP decrease of 38.9 +/- 15.9%. Postoperative uncontrolled hypertony occurred in the first 3 months in 6 (21.4%) eyes, leading to surgical IOP management. Other complications were decrease in visual acuity (14.3%), inflammation (25.5%) and phthisis (3.5%). CONCLUSION: TSCPC with the diode laser is a disappointing procedure for the management of refractory pediatric glaucoma, with poor mid-term IOP control and high incidence of complications including severe uncontrolled IOP increase. For these reasons, this cyclodestructive procedure should be considered as a last resort therapy for patients with refractory pediatric glaucoma.