Search

PURPOSE To evaluate the effectiveness and safety of the Preserflo MicroShunt implant (Santen) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). DESIGN Retrospective, open-label, multicenter study. PARTICIPANTS Patients with insufficiently controlled primary POAG or PXG who underwent a standalone MicroShunt implantation procedure. METHODS Consecutive patients with POAG and PXG who underwent surgery with the ab externo minimally invasive glaucoma surgery device Preserflo MicroShunt with mitomycin C. MAIN OUTCOME MEASURES Primary end points were mean change in intraocular pressure (IOP) and number of hypotensive medications from baseline through month 12. Success was defined as an IOP of 18 mmHg or less and an IOP reduction of 20% or more, with (qualified) or without (complete) any hypotensive medication. RESULTS Among the 130 patients who underwent MicroShunt implantation, 104 fulfilled the inclusion and exclusion criteria and were included in the analysis. Eighty-one eyes (77.9%) were diagnosed with POAG and 23 eyes (22.1%) were diagnosed with PXG. The mean age was 71.4 ± 12.6 years, and 45 patients (43.3%) were women. Mean IOP was lowered significantly from 25.1 ± 6.5 mmHg at baseline to 14.1 ± 3.4 mmHg at month 12 (P < 0.0001). At month 12, 27 eyes (26.0%) were categorized as complete successes and 61 eyes (58.7%) were categorized as qualified successes. The mean number of hypotensive medications was reduced significantly from 3.0 ± 1.0 medications at the preoperative visit to 0.77 ± 0.95 medication at month 12 (P < 0.001). Throughout the study, 19 eyes (18.3%) required needling and 14 eyes (13.5%) underwent surgical revision. Eight eyes (7.7%) showed hyphema and 5 eyes (4.8%) showed choroidal detachment. These were resolved with medical therapy without sequelae. Four patients underwent subsequent surgeries, and 2 patients underwent trabeculectomy (at months 3 and 6): One patient underwent transscleral cyclophotocoagulation at month 3 and 1 patient underwent MicroPulse cyclophotocoagulation at month 4. CONCLUSIONS In this retrospective study, the MicroShunt effectively lowered IOP and the need for IOP-lowering medications.

Background Glaucoma is a disease characterized by progressive damage of the optic nerve. Several therapeutic options are available to lower intraocular pressure (IOP). In primary open-angle glaucoma (POAG) patients with inadequate IOP control (or controlled with multiple medical therapies or for whom medical therapy is contraindicated), the implantation of micro-invasive glaucoma surgery devices (MIGS) and concomitant cataract surgery has proved to be more effective in reducing intraocular pressure (IOP), as compared to cataract surgery alone. The objective of this study was to assess the cost-effectiveness of iStent inject® device with concurrent cataract surgery vs. cataract surgery alone, in patients with mild-to-moderate POAG, adopting the Italian National Health Service (NHS) perspective. Methods Simulation of outcomes and costs was undertaken using a Markov model with 4 health states and one-month cycles, that is used to simulate the prognosis of these patients. Efficacy data were obtained from the randomized clinical trial (RCT). A lifetime horizon was adopted in the analysis. A discount rate of 3.5% was applied to both costs and effects. The Italian National Healthcare Service (NHS) perspective was considered, therefore only healthcare direct costs (acquisition of main interventions and subsequent procedures; medications; monitoring and follow-up; adverse events). Model robustness was tested through sensitivity analyses. Results Results of the base-case analysis showed that the total lifetime costs were higher in the iStent inject® + concurrent cataract surgery, compared with the cataract surgery alone group (€8368.51 vs. €7134.71 respectively). iStent inject® + concurrent cataract surgery was cost-effective vs. cataract surgery alone, with an incremental cost-effectiveness ratio of €13,037.01 per quality-adjusted life year (QALY) gained. Both one-way deterministic and probabilistic sensitivity analyses confirmed robustness of base-case results. The cost-effectiveness accessibility curve (CEAC) showed that iStent inject® + cataract surgery would have a 98% probability of being cost-effective, compared to cataract surgery alone, when the willingness to pay (WTP) is equal to €50,000 per QALY gained. Conclusions The results of the cost-utility analysis confirm that iStent inject® + cataract surgery is a cost-effective option for the treatment of patients affected by mild-to-moderate POAG, compared with cataract surgery alone, when evaluated from the Italian NHS perspective.

Medical therapy is the first treatment choice for most patients with glaucoma; however, in a relevant proportion of patients, intraocular pressure (IOP) reduction is achieved with multi-therapy and/or high therapeutic doses. Conventional surgery is the standard alternative to medical therapy when this is not effective or not tolerated. Recently, selective laser trabeculoplasty (SLT) has been advocated as first-line therapy, and "minimally invasive glaucoma surgery" (MIGS) has been developed as safer and less traumatic surgical intervention for patients with glaucoma. Schlemm's canal surgery has emerged as one of the approaches with the most favorable risk-benefit profile for glaucoma patients in need of cataract surgery. However, despite the promising results, use of MIGS in Italy has been extremely low. We aimed to investigate the reasons of the lower-than-expected use of Schlemm's canal-based MIGS devices in Italy, share our perspective on their potential place in therapy, and give practical suggestions to improve the management of glaucoma patients.

The XEN Gel Microstent is a subconjunctival microinvasive glaucoma surgical device developed with the aim of improving the predictability and safety profile of bleb-forming glaucoma surgical procedures. The stent is a hydrophilic tube composed of a porcine gel cross-linked with glutaraldehyde with good stability and biocompatibility with minimal tissue reaction. This device has demonstrated promising outcomes with fewer risks compared to traditional surgeries. The aim of the review is to present early studies on different designs of the XEN Gel Stent, to summarize different surgical techniques of implantation and to analyze more comprehensively the results, complications and rates of needling of the commercially available device (Xen 45). The review will address separately special cases (PXG, UVG, ICE, congenital glaucoma) and describe small series and case reports.

Objectives To assess and describe current utilisation, characteristics and perspectives on virtual glaucoma clinics (VGCs) amongst European glaucoma specialists. Methods Cross-sectional, anonymized, online questionnaire distributed to all European Glaucoma Society-registered specialists. Questions were stratified into five domains: Demographics, Questions about VGC use, Questions for non-VGC users, COVID-19 effects, and VGC advantages/disadvantages. Results 30% of 169 participants currently use VGCs, with 53% based in the United Kingdom. Of those using VGCs, 85% reported higher patient acceptance compared to traditional care. The commonest virtual model was asynchronous remote monitoring (54%). Nurses (49%) and ophthalmic technicians (46%) were mostly responsible for data collection, with two-thirds using a mixture of professionals. Consultant ophthalmologists were the main decision-makers in 51% of VGCs. Preferred cohorts were: ocular hypertension (85%), glaucoma suspects (80%), early/moderate glaucoma in worse eye (68%), stable glaucoma irrespective of treatment (59%) and stable glaucoma on monotherapy (51%). Commonest investigations were: IOP (90%), BCVA (88%), visual field testing (85%) and OCT (78%), with 33 different combinations. Reasons for face-to-face referral included: visual field progression (80%), ‘above-target’ IOP (63%), and OCT progression (51%). Reasons for not using VGCs included: lack of experience (47%), adequate systems in place (42%), no appropriate staff (34%) and insufficient time/money (34%). 55% of non-VGC users are interested in their use with 38% currently considering future implementation. 83% stated VGC consultations have increased during the COVID-19 pandemic; 86% of all participants felt that the pandemic has highlighted the importance of VGCs. Conclusions A significant proportion of European glaucoma units are currently using VGCs, while others are considering implementation. Financial reimbursement and consensus guidelines are potentially crucial steps in VGC uptake.

The new XEN63 implant is a minimally invasive glaucoma surgery device with limited experience in real life. This retrospective study included open-angle glaucoma patients who underwent XEN63 implant, either alone or in combination with cataract surgery. Primary endpoints were the intraocular pressure (IOP) at month 3 and the incidence of serious adverse events. Twenty-three eyes of 23 patients were included. Mean age was 67.8 ± 15.3 years and 15 (65.2%) were women. Mean IOP was significantly lowered from 27.0 ± 7.8 mmHg at baseline to 12.2 ± 3.4 mmHg at month 3 (p &lt, 0.0001). Mean IOP lowering was 40.8 ± 23.5%, with 14 (60.9%) and 16 (69.6%) eyes achieving an IOP lowering ≥30% and ≥20% without hypotensive medication, respectively. The number of hypotensive medications (NHM) was significantly reduced from 2.27 ± 0.94 drugs at baseline to 0.09 ± 0.42 drugs at month 3, p &lt, 0.0001. Four (17.4%) eyes had hypotony (IOP ≤ 6 mmHg) at postoperative day one, which was successfully resolved without sequelae. Four (17.4%) eyes had choroidal detachment (3 at day 7 and 1 at day 15), which was successfully resolved with medical treatment, at the month 1 visit. Three (13.0%) eyes required needling (mean time for needling 35.6 ± 9.7 days). XEN63 significantly lowered IOP and reduced the NHM, with a good short-term safety profile.

To evaluate the effectiveness and safety of the Preserflo MicroShunt implant (Santen) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG).Retrospective, open-label, multicenter study.Patients with insufficiently controlled primary POAG or PXG who underwent a standalone MicroShunt implantation procedure.Consecutive patients with POAG and PXG who underwent surgery with the ab externo minimally invasive glaucoma surgery device Preserflo MicroShunt with mitomycin C.Primary end points were mean change in intraocular pressure (IOP) and number of hypotensive medications from baseline through month 12. Success was defined as an IOP of 18 mmHg or less and an IOP reduction of 20% or more, with (qualified) or without (complete) any hypotensive medication.Among the 130 patients who underwent MicroShunt implantation, 104 fulfilled the inclusion and exclusion criteria and were included in the analysis. Eighty-one eyes (77.9%) were diagnosed with POAG and 23 eyes (22.1%) were diagnosed with PXG. The mean age was 71.4 ± 12.6 years, and 45 patients (43.3%) were women. Mean IOP was lowered significantly from 25.1 ± 6.5 mmHg at baseline to 14.1 ± 3.4 mmHg at month 12 (P0.0001). At month 12, 27 eyes (26.0%) were categorized as complete successes and 61 eyes (58.7%) were categorized as qualified successes. The mean number of hypotensive medications was reduced significantly from 3.0 ± 1.0 medications at the preoperative visit to 0.77 ± 0.95 medication at month 12 (P0.001). Throughout the study, 19 eyes (18.3%) required needling and 14 eyes (13.5%) underwent surgical revision. Eight eyes (7.7%) showed hyphema and 5 eyes (4.8%) showed choroidal detachment. These were resolved with medical therapy without sequelae. Four patients underwent subsequent surgeries, and 2 patients underwent trabeculectomy (at months 3 and 6): One patient underwent transscleral cyclophotocoagulation at month 3 and 1 patient underwent MicroPulse cyclophotocoagulation at month 4.In this retrospective study, the MicroShunt effectively lowered IOP and the need for IOP-lowering medications.

The suprachoroidal space has most certainly been a fascinating yet frustrating space for glaucoma specialists. Much effort has been made to explore the potential of uveoscleral outflow with variable success. Its pharmacologic manipulation using prostaglandin analogues has been a significant achievement in glaucoma medication development. On the other hand, surgical exploration of the suprachoroidal space in glaucoma has been met with disappointments. Cyclodialysis cleft offers significant yet unpredictable IOP lowering. Supraciliary drainage devices have led to complications and failure due to fibrotic response. This chapter describes the latest developments in the exploration of the suprachoroidal space for the treatment of glaucoma.

Exogenous fungal endophthalmitis (EXFE) represents a rare complication after penetrating ocular trauma of previously unresolved keratitis or iatrogenic infections, following intraocular surgery such as cataract surgery. The usual latency period between intraocular inoculation and presentation of symptoms from fungal endophthalmitis is several weeks to months as delayed-onset endophthalmitis. Aspergillus spp., is the most common causative mould pathogen implicated in this ocular infection and early diagnosis and prompt antimicrobial treatment, concomitantly in most cases with expert surgical attention, reduce unfavorable complications and increase the possibility of eye function preservation. Topical, intravitreal and systemic antifungal molecules are the mainstay of a medical approach to the disease and azoles, polyenes and in particular cases echinocandins are the pharmacological classes most commonly used in clinical practice. This review discusses pharmacokinetics and pharmacodynamic of antifungal agents in their principal modes of administration with a focus on their ability to achieve high drug concentration in the vitreous and ocular tissues.

Minimally invasive glaucoma surgery (MIGS) has fulfilled an unmet need in the management of glaucoma. This chapter highlights some controversial issues regarding the use of MIGS in clinical practice, including (1) whether there is sufficient evidence to advocate combining MIGS with cataract surgery over cataract surgery alone, (2) the merits and drawbacks of different approaches to trabecular bypass and canal-based MIGS procedures, (3) the effect of MIGS on endothelial cell loss, (4) suprachoroidal MIGS devices and whether there is still a role for these procedures, and (5) a comparison between subconjunctival MIGS and trabeculectomy. Several questions are still left unanswered and hopefully, further research and more clinical experience with these new technologies will help improve surgical outcomes for patients.

Background Excimer laser trabeculostomy (ELT) is a microinvasive glaucoma surgery (MIGS) that creates multiple laser channels through the trabecular meshwork using a cold laser system, which minimizes tissue fibrosis and aids in bypassing the main area of resistance to aqueous outflow. The purpose of this review is to evaluate the current body of evidence surrounding ELT in terms of efficacy and review the safety profile of the procedure. Main text Studies screened had to show clear inclusion and exclusion criteria as well as well-defined outcome measures. PubMed, MEDLINE, EMBASE and the Cochrane Controlled Trial Database were searched. Preferred Reporting Items of Systematic Reviews (PRISMA) guidelines were used to assess for study quality and for any bias. Sixty-four articles were initially identified with 18 meeting preliminary screening criteria. Ultimately, 8 studies met inclusion criteria and 2 additional non-referenced publications were also included: 1 randomized control trial, 4 prospective case series and 5 retrospective studies. Overall studies showed moderate intraocular pressure (IOP) lowering of between 20% and 40% from baseline without medication washout and mostly a decrease in glaucoma medications with few complications. Conclusion Current literature shows a significant IOP-lowering effect of ELT with a favorable safety-profile in standalone cases or combined with cataract surgery. Limitations to these studies are the lack of controls and washout IOP. Overall, ELT is an attractive MIGS option that does not require any residual device remaining in the angle.

The aqueous humor (AH) outflow pathways definition is still matter of intense debate. To date, the differentiation between conventional (trabecular meshwork) and unconventional (uveoscleral) pathways is widely accepted, distinguishing the different impact of the intraocular pressure on the AH outflow rate. Although the conventional route is recognized to host the main sites for intraocular pressure regulation, the unconventional pathway, with its great potential for AH resorption, seems to act as a sort of relief valve, especially when the trabecular resistance rises. Recent evidence demonstrates the presence of lymphatic channels in the eye and proposes that they may participate in the overall AH drainage and intraocular pressure regulation, in a presumably adaptive fashion. For this reason, the uveolymphatic route is increasingly thought to play an important role in the ocular hydrodynamic system physiology. As a result of the unconventional pathway characteristics, hydrodynamic disorders do not develop until the adaptive routes cannot successfully counterbalance the increased AH outflow resistance. When their adaptive mechanisms fail, glaucoma occurs. Our review deals with the standard and newly discovered AH outflow routes, with particular attention to the importance they may have in opening new therapeutic strategies in the treatment of ocular hypertension and glaucoma.

Purpose: Bacterial ocular infections can result in loss of all or part of the ocular structures, contributing to a high disability charge. Local surveillance of etiology and susceptibility patterns is crucial for an appropriate empiric management of ocular infections. The aim of this study was to analyze of bacterial spectrum in culture-proven ocular infections and trends of antimicrobial susceptibility patterns. Methods: A monocentric retrospective study was performed including ocular infection cases diagnosed at the Microbiology Unit of Turin Ophthalmic Hospital between 1988 and 2017. Spectrum of pathogens that caused bacterial culture-proven ocular infections and trends of antimicrobial susceptibility patterns were analyzed. Results: A total of 15,517 culture-positive isolates were identified as causative agents of ocular infections. Gram-positive bacteria were deemed to cause infection in 73.5% of cases. Staphylococcus spp. and Pseudomonas spp., coagulase-negative staphylococci, Staphylococcus aureus were the leading causative pathogens of keratitis, endophthalmitis, and conjunctivitis, respectively. Statistically significant changes in temporal trends were observed for all analyzed microorganism groups except for Enterobacteriaceae group. Overall, fluoroquinolones and chloramphenicol demonstrated to be the most effective antimicrobials in vitro toward bacterial ocular infections, followed by tetracycline, ampicillin, and aminoglycosides. Enterobacteriaceae isolates showed higher multi-drug resistance rate, followed by coagulase-negative staphylococci. Analysis of resistance rates over time highlighted increasing resistance trend for aminoglycosides among Gram-negative and for both aminoglycosides and fluoroquinolones among Gram-positive pathogens, especially for S. aureus. Conclusion: This study provided a 30-year assessment of bacterial ocular infections in an urban area of Italy, giving support to epidemiological consciousness and guiding empiric antimicrobial therapy.

Purpose: We present the case of a 22-year-old woman, diagnosed as having atypical hemolytic uremic syndrome with a hypertensive crisis, who presented a bilateral serous retinal detachment. Case Description: A 22-year-old woman, diagnosed as having atypical hemolytic uremic syndrome, was referred for blurred vision in both eyes, evolving over 7 days. Treatment including hemodialysis, plasma exchange, systemic steroids, antihypertensive medications and eculizumab was started 1 month prior to referral. At presentation, best-corrected visual acuity was 20/40 in the right eye and 20/25 in the left eye. Retinal examination revealed bilateral serous retinal detachment in the posterior pole and some small, flat, variably pigmented lesions. Optical coherence tomography confirmed marked serous retinal detachment in both eyes. Fluorescein and indocyanine green angiography was performed. Treatment for systemic hypertension was changed. Seven days later, dilated fundus examination and optical coherence tomography demonstrated a significant regression of the serous retinal detachment. Her visual acuity improves in both eyes at the last control, showing at fundus examination a complete resolution of the exudative detachment but a persistence of variable flat pigmented lesion. Conclusion: Although multiple organ systems are commonly affected in hemolytic uremic syndrome, ocular involvement has only been described in very few cases. Ocular manifestations in atypical hemolytic uremic syndrome include retinal, choroidal and vitreal hemorrhages, retina and/or ischemic signs. Bilateral serous retinal detachment may also be a sign of atypical hemolytic uremic syndrome or even the first manifestation of a hypertensive event.

Endophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxis after cataract surgery. This procedure is controversial because of both the low efficacy and the low adherence to therapy by elderly patients. A unique slow release antibiotic intravitreal injection could solve these problems. The objective of the present study was to design ophthalmic nanocomposite delivery systems based on in situ gelling formulations that undergo sol-to-gel transition upon change in temperature to prolong the effect of CEF. Oil in water (O/W) microemulsion (&micro, E) and solid lipid nanoparticles (SLN), obtained with an innovative formulation technology called cold microemulsion dilution, were evaluated as ocular drug delivery systems for CEF. Drug entrapment efficiency up to 80% was possible by esterifying CEF with 1-dodecanol to obtain dodecyl-CEF (dCEF). Both dCEF-loaded SLN and &micro, E were then added with Pluronic&reg, F127 (20% w/v) to obtain a nanocomposite hydrogel-based long acting system. The prepared thermosensitive formulations were evaluated for their physical appearance, drug content, gelation temperature, injectability and rheological properties, in vitro release studies and stability studies. Moreover, cell proliferation assays on human retinal pigment epithelial ARPE-19 cells were performed to evaluate the influence of this innovative system on the cellular viability. In addition, minimal inhibitory concentration (MIC) was assessed for both CEF and dCEF, revealing the need of dCEF hydrolysis for the antimicrobial activity. Although further experimental investigations are required, the physico-chemical characterization of the nanocomposite hydrogels and the preliminary in vitro release studies highlighted the potential of these systems for the sustained release of CEF.

L Jay Katz,1 Carl Erb,2 Amadeu Carceller Guillamet,3 Antonio M Fea,4 Lilit Voskanyan,5 Jane Ellen Giamporcaro,6 Dana M Hornbeak6 1Glaucoma Service, Wills Eye Hospital, Philadelphia, PA, USA; 2Glaucoma Service, Eye Clinic Wittenbergplatz, Berlin, Germany; 3Department of Ophthalmology, Hospital Quirón, Barcelona, Spain; 4Department of Surgical Sciences, University of Torino, Torino, Italy; 5Glaucoma Service, S.V.Malayan Ophthalmology Centre, Yerevan, Armenia; 6Department of Clinical Research and Medical Affairs, Glaukos Corporation, San Clemente, CA, USA Purpose: Evaluate long-term outcomes after one, two, or three trabecular micro-bypass stents implanted in a standalone procedure in eyes with open-angle glaucoma taking ocular hypotensive medication.Patients and methods: Prospective randomized ongoing study of 119 subjects (109 with 42-month follow-up) with open-angle glaucoma, preoperative intraocular pressure (IOP) 18–30 mmHg on one to three glaucoma medications, and unmedicated (post-washout) IOP 22–38 mmHg. Subjects were randomized to receive one (n=38), two (n=41), or three (n=40) iStent trabecular micro-bypass stents in a standalone procedure. Postoperatively, IOP was measured with medication and annually following washout. Data included IOP, medications, gonioscopy, pachymetry, visual field, visual acuity, adverse events, and slit-lamp and fundus examinations.Results: Preoperative mean medicated IOP was 19.8±1.3 mmHg on 1.71 medications in one-stent eyes, 20.1±1.6 mmHg on 1.76 medications in two-stent eyes, and 20.4±1.8 mmHg on 1.53 medications in three-stent eyes. Post-washout IOP prior to stent implantation was 25.0±1.2, 25.0±1.7, and 25.1±1.9 mmHg in the three groups, respectively. Postoperatively, Month 42 medicated IOP was 15.0±2.8, 15.7±1.0 and 14.8±1.3 mmHg in the three groups, and post-washout IOP (Months 36–37) was 17.4±0.9, 15.8±1.1 and 14.2±1.5 mmHg, respectively. IOP reduction ≥20% without medication was achieved in 89%, 90%, and 92% of one-, two-, and three-stent eyes, respectively, at Month 12; and in 61%, 91%, and 91% of eyes, respectively, at Month 42. The need for additional medication remained consistent at Months 12 and 42 in multi-stent eyes (four two-stent eyes and three three-stent eyes at both time points), whereas it increased in single-stent eyes (four eyes at Month 12 versus 18 eyes at Month 42). Safety parameters were favorable in all groups.Conclusion: The standalone implantation of either single or multiple iStent® device(s) produced safe, clinically meaningful IOP and medication reductions through 42 months postoperatively, with incrementally greater and more sustained reductions in multi-stent eyes. Keywords: microinvasive glaucoma surgery/MIGS, iStent, surgery, standalone, multiple

Importance There is a lack of information about long term results of chronic angle closure glaucoma (CACG) following an acute primary angle closure (APAC) in Caucasian patients Purpose To report morphological and functional long-term data of CACG eyes following a monolateral APAC attack and to provide a comparison with their fellow eyes Design Observational retrospective case series (Clinica Oculistica Universitaria, Ospedale Oftalmico, Turin) Participants 57 consecutive patients (114 eyes) underwent long term follow-up analysis. Methods Patients underwent ophthalmic assessment more than 5 years since the APAC attack. Main Outcome Measures Intraocular pressure (IOP), number of antiglaucoma medications, best corrected visual acuity (BCVA), angle assessment with gonioscopy, Vertical Cup-To-Disc ratio (VCDR), Standard automated perimetry (SAP). Comparisons were made between APAC attack eyes and fellow eyes and between phakic and pseudophakic eyes as observed at follow up. Results Mean follow-up time was 5.86 ± 1.19 years. Outcomes showed a significant greater damage in the APAC eyes compared with fellow eyes both in structural (mean VCDR 0.61± 0.16; p

International audience; Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations,and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR= 25, P=2.9 x 10-14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10-8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

We report the 3-year IOP efficacy of the implantation of the Schlemm’s canal Hydrus® Microstent (Ivantis®) combined with phacoemulsification versus phacoemulsification alone

PURPOSE: To evaluate the effectiveness of an ab interno subconjunctival gelatin implant as primary surgical intervention in reducing intraocular pressure (IOP) and IOP-lowering medication count in medically uncontrolled moderate primary open-angle glaucoma (POAG). METHODS: In this prospective, non-randomized, open-label, multicenter, 2-year study, eyes with medicated baseline IOP 18-33 mmHg on 1-4 topical medications were implanted with (phaco + implant) or without (implant alone) phacoemulsification. Changes in mean IOP and medication count at months 12 (primary outcomes) and 24, clinical success rate (eyes [%] achieving ≥ 20% IOP reduction from baseline on the same or fewer medications without glaucoma-related secondary surgical intervention), intraoperative complications, and postoperative adverse events were assessed. RESULTS: The modified intent-to-treat population included 202 eyes (of 218 implanted). Changes (standard deviation) in mean IOP and medication count from baseline were - 6.5 (5.3) mmHg and - 1.7 (1.3) at month 12 and - 6.2 (4.9) mmHg and - 1.5 (1.4) at month 24, respectively (all P

BACKGROUND To compare the reduction of intraocular pressure (IOP) and glaucoma medications following selective laser trabeculoplasty (SLT) versus stand-alone placement of the Hydrus microstent, a microinvasive glaucoma surgery device. DESIGN Prospective interventional case-series. University practice. PARTICIPANTS Fifty six eyes (56 patients) with uncontrolled primary open-angle glaucoma. METHODS Patients received either SLT (n = 25) or Hydrus implantation (n = 31) in two centres. Patients were evaluated at baseline and 1, 7 days, 1, 3, 6 and 12 months after surgery. MAIN OUTCOME MEASURES Intraocular pressure and number of glaucoma medications variations inter-groups and intra-groups. RESULTS There were no significant differences at baseline between groups, but the mean deviation was worse in the Hydrus group (-8.43 ± 6.84 dB, confidence limits (CL)-2.8/-3.3 vs.-3.04 ± 0.65 dB, CL-6/-10.8; P

Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity.

Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy.

Purpose. To assess inflammatory involvement of cornea in dry eye by means of confocal microscopy, evaluating the presence and distribution of Langherans cells (LCs). Methods: 98 eyes of 49 subjects were enrolled: 18 subjects affected by Sjögren Syndrome Dry Eye (SSDE), 17 with Non-Sjögren Syndrome Dry Eye (NSSDE), 14 healthy volunteeers. Dry eye symptoms, tear film, ocular surface damage and corneal confocal microscopy were analized. Results: A significant increase of LCs density was observed at sub-basal nerve plexus (SSDE = 79 cells/mm2 and NDE = 22 cells/mm2; p = 0,0031) and sub-epithelial nerve plexus (SSDE = 38 cells/mm2 and NDE = 3 cells/mm2; p = 0,0169) in central cornea of SSDE group. An increased number of LCs from the center to the periphery of the cornea was observed, significant only in healthy volunteers group. In dry eye patients there was an increase in LCs density in both peripheral and central cornea with a significant difference between NDE (14,66 cells/mm2) and SSDE (56,66 cells/mm2) only in central cornea (p = 0,0028). In SSDE group, mean density of LCs in central cornea results also superior to NSSDE group (29,33 cells/mm2). There was no correlation between LCs density and dry eye symptoms, tear film deficiency and ocular surface damage. Conclusion: This study demonstrates the activation of an inflammatory and immunological reaction in cornea of NSSDE and SSDE patients. Confocal microscopy can be an important diagnostic tool in evaluation and follow-up of dry eye disease.

Objective. To evaluate the efficacy and safety of the Xen Gel Stent and provide a macro- and microscopic analyses of bleb morphology. Methods. A prospective 12-month study on patients with primary open-angle glaucoma. Patients underwent implantation of the XEN Gel Stent (Allergan INC, Dublin, Ireland) either alone or combined with a cataract surgery. Biomicroscopy, in vivo confocal microscopy (IVCM), and anterior segment-optical coherence tomography (AS-OCT) were used to assess bleb morphology. Safety parameters were adverse events, best corrected visual acuity, visual field, and corneal endothelial cell loss. A postoperative IOP ≤ 18 mmHg without or on medications was respectively defined as complete and qualified success while an IOP ≥ 18 mmHg was defined as failure. Results. Twelve eyes of 11 patients were evaluated. At one year, 5 out of 10 patients available achieved a complete success while five were qualified success. AS-OCT showed that bleb wall reflectivity was significantly higher in the failure group; IVCM revealed that stromal density was significantly lower in the success group. No safety issues were recorded. Conclusion. Implantation of the XEN Gel Stent appears to be a safe and effective procedure. AS-OCT and IVCM may be helpful in bleb assessment.

Marta Zola, Cristina Briamonte, Umberto Lorenzi, Federica Machetta, Federico M Grignolo, Antonio M Fea Ophthalmic Eye Hospital, Department of Surgical Sciences, University of Turin, Italy Purpose: The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema.Methods: Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180days with best-corrected visual acuity (BCVA), complete slit-lamp examination, intraocular pressure (IOP), optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results: BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p30 mmHg 30 days after the second implant, treated topically.Conclusion: Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. Keywords: uveitis, macular edema, dexamethasone, intavitreal implant

Background MIGS have been developed as a surgical alternative for glaucomatous patients. Purpose To analyze the change in intraocular pressure (IOP) and glaucoma medications using different MIGS devices (Trabectome, iStent, Excimer Laser Trabeculotomy (ELT), iStent Supra, CyPass, XEN, Hydrus, Fugo Blade, Ab interno canaloplasty, Goniscopy-assisted transluminal trabeculotomy) as a solo procedure or in association with phacoemulsification. Methods Randomized control trials (RCT) and non-RCT (non randomized comparative studies, NRS, and before-after studies) were included. Studies with at least one year of follow-up in patients affected by primary open angle glaucoma, pseudoexfoliative glaucoma or pigmentary glaucoma were considered. Risk of Bias assessment was performed using the Cochrane Risk of Bias and the ROBINS-I tools. The main outcome was the effect of MIGS devices compared to medical therapy, cataract surgery, other glaucoma surgeries and other MIGS on both IOP and use of glaucoma medications 12 months after surgery. Outcomes measures were the mean difference in the change of IOP and glaucoma medication compared to baseline at one and two years and all ocular adverse events. The current meta-analysis is registered on PROSPERO (reference n° CRD42016037280). Results Over a total of 3,069 studies, nine RCT and 21 case series with a total of 2.928 eyes were included. Main concerns about risk of bias in RCTs were lack of blinding, allocation concealment and attrition bias while in non-RCTs they were represented by patients' selection, masking of participants and co-intervention management. Limited evidence was found based on both RCTs and non RCTs that compared MIGS surgery with medical therapy or other MIGS. In before-after series, MIGS surgery seemed effective in lowering both IOP and glaucoma drug use. MIGS showed a good safety profile: IOP spikes were the most frequent complications and no cases of infection or BCVA loss due to glaucoma were reported. Conclusions Although MIGS seem efficient in the reduction of the IOP and glaucoma medication and show good safety profile, this evidence is mainly derived from non-comparative studies and further, good quality RCTs are warranted.

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. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0095-y) contains supplementary material, which is available to authorized users.

International audience; Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities.This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder ('controls'). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°.Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p0.001), initial IOP (p0.001), older age at the beginning of follow-up (p0.001), whereas final IOP was found to be protective (p0.05).In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.

Purpose. To investigate retinal function using microperimetry in patients affected by idiopathic epiretinal membrane (iERM) and cataract who underwent combined surgery: 4-year follow-up.Design. Prospective, interventional case series.Methods. 30 eyes of 30 consecutive patients with iERM and age-related cataract underwent 25-gauge vitrectomy and cataract surgery. At baseline, 90 and 180 days, and 1 and 4 years, we examined retinal mean sensitivity (MS), retinal mean defect (MD), fixation stability, and frequency of microscotomas using MP1 microperimetry. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) using a spectral domain optical coherence tomography (SD-OCT) were also performed.Results. All patients completed 1-year follow-up, while 23 patients reached last follow-up. Baseline MS and MD (10.48 ± 4.17 and −9.18 ± 4.40 dB) significantly changed at one year (12.33 ± 3.66 and −7.49 ± 3.31 dB,p<0.01), at four years (14.18 ± 3.46 and −4.66 ± 2.85,p<0.01), and between one and four years (p<0.01) after surgery. Compared to baseline, CRT and BCVA significantly changed at one year and remained stable at four years. No variations were observed in fixation stability and frequency of microscotomas compared to baseline.Conclusions. Long-term follow-up using microperimetry seems useful to evaluate patients after iERM surgery: retinal sensitivity changes even when BCVA and CRT remain stable.

Purpose To compare phacoemulsification alone and phacoemulsification with micro-bypass stent implantation in eyes with primary open-angle glaucoma. Setting Instituto di Fisiopatologia Clinica, Clinica Oculistica, Universita' di Torino, Torino, Italy. Methods In this prospective double-masked randomized clinical trial, patients had phacoemulsification alone (control group) or phacoemulsification with iStent implantation (combined group). Primary outcomes were intraocular pressure (IOP) and reduction in medication use over 15 months and IOP after a 1-month washout of ocular hypotensive agents (ie, 16 months postoperatively). Results The baseline IOP was similar between groups (combined group: 17.9 mm Hg ± 2.6 [SD]; control group: 17.3 ± 3.0 mm Hg) ( P = .512). Three patients in the control group were lost to follow-up. The mean IOP was 14.8 ± 1.2 mm Hg in the combined group and 15.7 ± 1.1 mm Hg in the control group at 15 months and 16.6 ± 3.1 mm Hg and 19.2 ± 3.5 mm Hg, respectively, after washout; the IOP was statistically significantly lower in the combined group than in the control group at both time points ( P = .031 and P = .042, respectively). At 15 months, the mean number of medications was lower in the combined group than in the control group (0.4 ± 0.7 and 1.3 ± 1.0, respectively; P = .007), as was the proportion of patients on ocular hypotensive medication (33% and 76%, respectively). Conclusions Phacoemulsification with stent implantation was more effective in controlling IOP than phacoemulsification alone; the safety profiles were similar. Financial Disclosure The author has no financial or proprietary interest in any material or method mentioned.