Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious).

INTRODUCTION: Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG). METHODS AND ANALYSIS: This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 months. Secondary outcomes include mean percentage reduction in IOP at 3, 6 and 12 months; proportion of participants with at least 20% reduction in IOP from baseline at 6 months; change in ocular hypotensive medications at 12 months and evaluation of safety. Participants were aged >= 40 years with OAG, including exfoliative or pigmentary glaucoma, or ocular hypertension with untreated or washed out IOP 22-35 mm Hg. TREATMENTS: DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4-1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3-2.6 mJ. A sample size of 164 is sufficient to detect a non-inferiority margin of 1.95 mm Hg for change from baseline IOP. CLINICAL TRIAL REGISTRATION NUMBER: NCT03750201, ISRCTN14033075.

Reoperations for complications within 90 days after gel stent implantation or trabeculectomy.

PURPOSE: To describe reoperations in the operating room for complications that occurred within the first 90 days after gel stent implantation or trabeculectomy at a single institution over 5 years. METHODS: In this retrospective chart review, patients who have undergone gel stent implantation with mitomycin C (MMC) or trabeculectomy with MMC were enrolled. Postoperative complications that required reoperations within the first 90 days were evaluated. RESULTS: A total of 510 surgeries were performed on 392 patients over a 57-month period by 2 glaucoma surgeons. Of these, 284 were gel stent implantation, and 226 were trabeculectomy. Combined phacoemulsification was performed in 52/284 (18.3%) in the gel stent group and in 26/226 (11.5%) of eyes in the trabeculectomy group (p = 0.03). Reoperations took place in 13/510 (2.5%) eyes, including 4/284 (1.4%) in the gel stent group, 9/226 (4.0%) in the trabeculectomy group (p = 0.07). In the gel stent group, indications for reoperation were bleb failure (2), suprachoroidal hemorrhage (1), bullous keratopathy (1). In the trabeculectomy group, indications for reoperation were bleb failure (3), overfiltration (2), persistent wound leak (2), aqueous misdirection (2). CONCLUSIONS: The rates of reoperation for early postoperative complications after gel stent or trabeculectomy was low and comparable with previous studies. A slightly higher number of reoperations within 90 days was observed in the trabeculectomy group than the gel stent group despite the more significant number of combined procedures in the latter group. Bleb failure was the most common indications for reoperation in both groups. Excessive outflow was a cause of reoperation mostly in the trabeculectomy group.

Bilateral choroidal detachment and myopic shift after acetazolamide intake for laser capsulotomy.

INTRODUCTION: To report a case of bilateral choroidal effusion after laser capsulotomy. CASE DESCRIPTION: A healthy 85 years old white woman was referred to our hospital with a diagnosis of posterior capsule opacification in the left eye. The patient was treated with laser capsulotomy and oral acetazolamide was administered after the procedure. The day after, the patient visited the emergency room complaining bilateral blurred vision. A myopic shift and peripheral choroidal detachment was noted in both eyes. Discontinuation of acetazolamide and treatment with topical steroid and cyclopentolate resulted in a significant improvement in visual acuity and the complete resolution of the choroidal detachment in 1 week. CONCLUSION: To the best of our knowledge, this is the first reported case of choroidal detachment and acute transient myopia following the administration of oral acetazolamide after laser capsulotomy.

Nail-Patella Syndrome and Glaucoma: A Case Report and Review of the Literature.

Nail-patella syndrome (NPS) is a rare autosomal dominant disease characterized by nail dysplasia, aplastic or hypoplastic patellae, elbow dysplasia, and presence of iliac horns. Renal or ocular abnormalities are also associated with the disease. We report the case of a 57-year-old woman affected by NPS and having haploinsufficiency of the LMX1B gene who experienced severe bilateral chronic angle-closure glaucoma in both eyes and that was successfully managed with a flap-express procedure in the right eye. The left eye had no light perception, and medical treatment was considered. Glaucoma is the most frequent ocular abnormalities observed in association with NPS and usually presents with an open angle. Glaucoma associated with NPS typically has an early onset open-angle phenotype. In fewer cases, it may present with an angle-closure phenotype. Therefore, we emphasize the need for glaucoma case-finding protocols comprehensive of gonioscopy in NPS patients and their relatives.

Moving beyond the Slit-Lamp Gonioscopy: Challenges and Future Opportunities.

After almost a century from its introduction in clinical practice, slit-lamp gonioscopy is still considered the reference standard for evaluating the anterior chamber angle (ACA). Gonioscopy is essential for diagnosing angle closure disease, and ACA features are included in glaucoma's diagnostics and treatments algorithms. However, shortcomings of slit-lamp gonioscopy include a steep learning curve, lack of agreement between examiners and poor documentation. Thanks to advances in miniaturization and computing, new instruments for digital gonioscopy have been developed and marketed. This narrative review focuses on the Gonioscope GS-1, which permits semi-automated circumferential documentation of the ACA in real-colour photographs. Advantages and disadvantages of GS-1 compared with slit-lamp gonioscopy and other ACA imaging technologies such as optical coherence tomography are discussed. Finally, potential opportunities offered by this device for telemedicine, virtual clinics, and automatic classification with deep learning are presented.

A 2-year prospective multicenter study of ultrasound cyclo plasty for glaucoma.

Ultrasound cyclo plasty (UCP) is a recently developed surgical technique for glaucoma allowing a selective and controlled coagulation of the ciliary body. We herein investigated the long-term efficacy and safety of UCP for the treatment of glaucoma. This prospective study included patients with primary and secondary glaucoma. All surgeries were performed using the EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France). Sixty-six patients were included, and 60 completed regularly the 2-year follow-up. Preoperative IOP was 28.5 ± 9.6 mmHg and significantly decreased to 17.0 ± 5.4 at 2 years (p < 0.001). The daily number of both hypotensive eye drops and acetazolamide tablets decreased significantly (respectively, from 2.6 ± 1.1 to 1.7 ± 1.2 and from 0.7 ± 0.8 to 0.2 ± 0.5; both p < 0.001). At 2 years, 68.1% of patients met the definition of qualified success (IOP < 21 mmHg regardless of glaucoma medications) and 10.3% of patients met the definition of complete success (IOP < 21 mmHg without glaucoma medications). No major intra- or postoperative complications occurred; however, 15 eyes required additional glaucoma surgery. These results suggest that UCP is an effective and safe procedure to reduce IOP in glaucoma patients through a 2-year follow-up period.

Early Postoperative Intraocular Pressure is Associated With Better Pressure Control After XEN Implantation.

PRéCIS:: Gel stent implantation is a bleb-forming surgery designed to achieve predictable pressure drop. An early low intraocular pressure (IOP) is associated with the long-term success of the procedure. PURPOSE: To identify the variables associated with the success of the XEN procedure. PATIENTS AND METHODS: This was part of a prospective, uncontrolled, consecutive case series study. Patients with primary open-angle glaucoma or pseudo-exfoliative glaucoma were included. All the patients underwent surgical XEN implant procedure with mitomycin-C subconjunctival injection 20 minutes before surgery. Success criteria were an off-medication IOP of 6 to 16 mm Hg 12 months after surgery; no additional glaucoma surgery; no visual threatening complications, no visual acuity loss >1 Snellen line. One eye per patient was considered for statistical analysis. A univariate Cox proportional hazard regression analysis was performed to identify potential risk factors for surgical failure. Then, a multivariate Cox model was built. RESULTS: One hundred twenty-three patients were recruited in this study: 93 patients underwent XEN implantation alone whereas 30 the combined procedure with phacoemulsification and intraocular lens implantation. Univariate Cox regression showed that the day after surgery intraocular lens>9 mm Hg was associated with surgical failure (P=0.02) and a postoperative number of needlings ≥2 in the follow-up was also predictive of surgical failure (P<0.01). These data were confirmed by a multivariate model too. At 1 year the surgical success criteria were 76% in the group with 24-hour IOP≤9 mm Hg, whereas it was 43% when above 9 mm Hg (P=0.026). CONCLUSIONS: Our study shows that an early IOP≤9 mm Hg is predictive of the efficacy of the procedure during 1-year follow-up, whereas more than 2 needlings are predictive of failure.

CFSE: A New Method for Identifying Human Limbal Stem Cells and Following Their Migration in Human Cornea.

AIM: To develop a method capable of identifying human corneal limbal stem cells (LSCs) and follow their proliferation and migration in the epithelium. MATERIALS AND METHODS: Ten fresh matched pairs of cadaveric normal human corneas were obtained from donors. Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to target LSCs. The distribution of CFSE-positive cell clusters was analyzed by fluorescence microscopy by counterstaining with 4',6-diamidino-2-phenylindole (DAPI). Fluorescence was digitally recorded for seven days, and the rate of cell movement was determined. RESULTS: CFSE-labeled cells were tracked in corneas. Analysis of time sequences revealed that they moved centripetally. Daily average CFSE-labeled LSC movement was 0.073±0.01 cm (±SD). CONCLUSION: CFSE allowed us to identify LSCs and to track their centripetal migration from the limbal basal layer to the anterior ocular surface. This experimental system appears to be a valuable tool for further studies on corneal epithelial cell migration and proliferation.

Predictors of Endothelial Cell Loss after Phacoemulsification for the Treatment of Primary Angle Closure.

PURPOSE: To investigate demographic and anatomical factors associated with a reduction in endothelial cell density (ECD) after phacoemulsification (PE) for the treatment of primary angle closure (PAC). METHODS: In this prospective case series, ECD was evaluated by noncontact specular microscopy and biometric parameters by both noncontact optical biometry and anterior segment optical coherence tomography, preoperatively and at 12 months after surgery. Anterior segment biomicroscopy and gonioscopy were also performed. The change in ECD and its relation to clinical characteristics and biometric parameters were evaluated by linear regression analysis. RESULTS: 44 patients with PAC were included in the study. The mean (SD) patient age was 71.6 (10.2) years; thirty-one (70.5%) of them were women. Coexistence of exfoliation syndrome (XS) was observed in 4 cases (9.1%). The mean (SD) ECD (cells/mm2) changed from 2275 (463) preoperatively to 1964 (613) postoperatively with a mean reduction of -310 (95% CI -445 to -176; p < 0.001). In the multivariate regression model, after correction for age and lens status, XS was the only parameter associated with ECD percentage change (B = -36.00; p=0.001). CONCLUSION: PE in angle closure causes a significant ECD reduction. In our population of PAC patients, XS is significantly associated with ECD change. In this group of patients, a careful preoperative endothelial evaluation should be performed.

Chorioretinal folds: a proposed diagnostic algorithm.

PURPOSE: To create a diagnostic algorithm for the management of chorioretinal folds. METHODS: We reviewed the existing literature about chorioretinal folds focusing our attention on three specific conditions and created a diagnostic algorithm in order to otpimize the choice and the number of investigations. RESULTS: Chorioretinal folds are visible striations of the fundus usually arranged in parallel lines and disposed horizontally. They may be either unilateral or bilateral, symptomatic or asymptomatic and are often associated with different possible ocular and extra ocular pathologies, including systemic diseases like autoimmune disorders and intracranial hypertension. They are named idiopathic when no apparent cause for their development is detectable. However, with improved diagnostic testing, the patients with idiopathic choroidal folds are likely to represent only a smaller portion of the total. CONCLUSIONS: Since choroidal folds be the sole sign of an underlying disease possibly requiring a multidisciplinary approach, an appropriate work-up varying according to the specific clinical features of each case is needed to define the etiology and the treatment. A diagnosting algorithm may be useful in order to optimize the diagnostic approach and management.

EX-PRESS Ab Externo Revision With a 41-G Needle.

The EX-PRESS Glaucoma Filtration Device is a stainless steel, nonvalved filtration device that channels aqueous humor through a secure lumen to a half-thickness scleral flap, creating a subconjunctival filtration bleb. Elevated postoperative intraocular pressure may indicate occlusion of the device lumen or episcleral fibrosis, and it is essential to reestablish the flow in a timely manner to prevent bleb formation failure. We report the successful use of an extendible 41-G subretinal injection needle to rapidly restore device patency when the conventional bleb revision was not effective.

Prospective evaluation of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C.

PURPOSE: Our purpose was to evaluate the clinical safety and efficacy of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C (MMC) in open angle glaucoma (OAG). METHODS: This was a prospective, uncontrolled, interventional case series. All subjects underwent CLASS procedure by a single surgeon. After the dissection of a partial thickness scleral flap, topical MMC 0.2 mg/ml was applied to the sclera and the conjunctiva for 3 min. The CO2 laser with a beam-manipulating system was used to ablate the scleral tissue and expose the Schlemm's canal area. Primary outcomes: intraocular pressure (IOP) change, number of IOP-lowering medicaments change. Adverse events were evaluated as secondary outcomes. RESULTS: Twenty-one eyes of 21 patients underwent the CLASS procedure. Thirteen were primary OAG (62%), two normal pressure glaucoma (10%), three exfoliative glaucoma (14%) and three others secondary OAG. With a mean (SD) follow-up of 15.3 (5.9) months, the IOP changed from 25.4 (6.7) mmHg at baseline to 10.9 (3.4) mmHg al the last visit. Mean reduction of IOP was -14.5 mmHg (95% CI, -17.7 to -11.2, P < 0.001). The median (IQR) number of IOP-lowering medication decreased from 3 (3-3) at baseline to 1 (0-1) at the last visit (P < 0.001). Visual acuity did not change significantly. Adverse events: five eyes (24%) developed iris adhesion to the filtration area that was successfully managed with office-based procedures. In one case (5%), CLASS was converted to trabeculectomy due to intraoperative perforation of the ablated area. There was one case of hypotony maculopathy successfully treated with placement of additional transconjunctival scleral flap sutures. CONCLUSIONS: The CLASS procedure with MMC is clinically safe and effective maintaining a large reduction in IOP and in the number of IOP-lowering medications with a mean follow-up of 15 months. Iris adhesion at the filtrating area warrants further evaluation and possibly reflects the surgeon's learning curve.

Comparison of Central Corneal Thickness Measurements Using Ultrasonic Pachymetry, Anterior Segment OCT and Noncontact Specular Microscopy.

PURPOSE: To evaluate and compare central corneal thickness (CCT) values measured with anterior segment optical coherence tomography (AS-OCT), noncontact specular microscopy (NCSM), and ultrasound pachymetry (USP). MATERIALS AND METHODS: CCT was measured in 182 healthy eyes without ocular abnormalities other than refractive errors. Three consecutive measurements of CCT by the same examiner were obtained during the same session. The testing sequence of AS-OCT and NCSM was randomly selected. The USP always was performed after the noncontact examinations. RESULTS: The average CCT measured by AS-OCT, NCSM, and USP were 535.8±35.5, 547.7±38.2, and 537.4±37.5 µm, respectively. The mean differences between modalities were 11.8±14.7 µm (P<0.01) between NCSM and AS-OCT, 10.3±17.7 µm (P<0.01) between NCSM and USP and 1.6±8.6 µm (P=0.02) between USP and AS-OCT. CONCLUSIONS: AS-OCT, NCSM, and USP showed an overall strong agreement in measuring CCT. However, CCT measurements with AS-OCT showed a good correlation to those obtained by USP, NCSM tended to give statistically significant higher CCT readings than either alternative and showed the worse repeatability indices. On the basis of our results, CCT measurement obtained with different instruments cannot be considered directly interchangeable.

From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma.

Glaucoma is a degenerative disease of the eye. Both the anterior and posterior segments of the eye are affected, extensive damage being detectable in the trabecular meshwork and the inner retina-central visual pathway complex. Oxidative stress is claimed to be mainly responsible for molecular damage in the anterior chamber. Indeed, oxidation harms the trabecular meshwork, leading eventually to endothelial cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility and (ultimately) increased IOP. Moreover, free radicals are involved in aging and can be produced in the brain (as well as in the eye) as a result of ischemia, leading to oxidation of the surrounding neurons. Glaucoma-related cell death occurs by means of apoptosis, and apoptosis is triggered by oxidative stress via (a) mitochondrial damage, (b) inflammation, (c) endothelial dysregulation and dysfunction, and (d) hypoxia. The proteomics of the aqueous humor is significantly altered in glaucoma as a result of oxidation-induced trabecular damage. Those proteins whose aqueous humor levels are increased in glaucoma are biomarkers of trabecular meshwork impairment. Their diffusion from the anterior to the posterior segment of the eye may be relevant in the cascade of events triggering apoptosis in the inner retinal layers, including the ganglion cells.

The Outflow Pathway: A Tissue With Morphological and Functional Unity.

The trabecular meshwork (TM) plays an important role in high-tension glaucomas. Indeed, the TM is a true organ, through which the aqueous humor flows from the anterior chamber to Schlemm's canal (SC). Until recently, the TM, which is constituted by endothelial-like cells, was described as a kind of passive filter. In reality, it is much more. The cells delineating the structures of the collagen framework of the TM are endowed with a cytoskeleton, and are thus able to change their shape. These cells also have the ability to secrete the extracellular matrix, which expresses proteins and cytokines, and are capable of phagocytosis and autophagy. The cytoskeleton is attached to the nuclear membrane and can, in millionths of a second, send signals to the nucleus in order to alter the expression of genes in an attempt to adapt to biomechanical insult. Oxidative stress, as happens in aging, has a deleterious effect on the TM, leading eventually to cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility, and (ultimately) increased IOP. TM failure is the most relevant factor in the cascade of events triggering apoptosis in the inner retinal layers, including ganglion cells. J. Cell. Physiol. 231: 1876-1893, 2016. © 2016 Wiley Periodicals, Inc.

Tafluprost for glaucoma.

INTRODUCTION: Lowering intraocular pressure (IOP) is, at present, the only therapeutic approach to the treatment of glaucoma. Good compliance is essential in every chronic therapy; therefore, the development of IOP-lowering eye drops that are well tolerated and have an easy administration schedule is essential for the treatment of glaucoma. Prostaglandins are a first-choice drug class for the treatment of glaucoma. AREAS COVERED: This review provides a background on tafluprost, a newly synthesized prostaglandin analogue, and summarizes the existing data on its efficacy and safety, including comparative data with the other prostaglandin derivatives now available on the market. A review of the literature was performed. EXPERT OPINION: Current research focuses not only on the efficacy of the drugs but also on their tolerability. The importance of obtaining good compliance by the patient is increasingly relevant; therefore, new formulations are studied to provide fewer side effects and an easier schedule. Tafluprost is a new prostaglandin analogue that has been marketed in some European countries and in Japan for more than 2 years and was recently (July 2009) approved in 21 countries. Besides a well-demonstrated IOP-lowering effect, tafluprost is the first topical prostaglandin available as a preservative-free formulation.