Laura Dallorto

Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and meta-analysis

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.

Retinal nerve fibre layer and macular thickness analysis with Fourier domain optical coherence tomography in subjects with a positive family history for primary open angle glaucoma

Aim To detect early structural changes of retinal nerve fibre layer (RNFL) and macular ganglion cell complex (GCC) in subjects with a positive family history for primary open angle glaucoma (POAG) using Fourier domain optical coherence tomography (FD-OCT) (RTVue-100). Methods This was a cross-sectional observational study. First and second degree relatives of POAG patients, healthy subjects, and subjects with preperimetric glaucoma (PPG) without a family history for glaucoma, were enrolled. All participants underwent complete ophthalmic examination, visual field test and FD-OCT (RTVue-100) imaging. Average RNFL and GCC thicknesses were measured and a pattern analysis was applied to the GCC map. Analysis of variance (ANOVA), least significant difference post-hoc test, and multiple ANOVA were used. Results The final analysis included 271 eyes divided into several groups: 163 eyes of first and second degree relatives (85 healthy, 40 with ocular hypertension and 38 with PPG); and 108 eyes of subjects without a positive family history (60 healthy and 48 PPG). RNFL and GCC thickness values of these five groups were statistically different (p<0.001). RNFL superior, GCC average, GCC superior, and GCC inferior were found to be significantly thinner and the global loss volume was higher in normal relatives than in healthy subjects without a positive family history of POAG (p=0.04, p=0.001, p=0.005, p=0.004, p=0.009). RNFL and GCC thicknesses obtained by dividing the family members by the degree of consanguinity showed statistically significant thinning in siblings of glaucomatous subjects than in offspring. Conclusions Our study shows that the eyes of subjects with a positive family history for POAG have significantly thinner RNFL and GCC than normal eyes and a more accurate follow-up has to be performed.

Retinal and Macular Ganglion Cell Count Estimated With Optical Coherence Tomography RTVUE-100 as a Candidate Biomarker for Glaucoma

Purpose To evaluate the ability of total and macular estimated retinal ganglion cell (RGC) counts to discriminate between healthy and glaucomatous eyes. To determine threshold markers of the estimated RGCs taking into account age dependence. Methods This was a cross-sectional, observational study. The study group consisted of 176 eyes subdivided in three groups: 32 healthy, 91 preperimetric (PPG), and 53 primary open-angle glaucoma (POAG) eyes. The estimate of total and macular number of RGCs was obtained using a model described later. To account for the inverse correlation of RGC count with age, we considered two age subgroups (≤55 and >55 years) for both total and macular estimated RGC counts. We computed frequency distributions and receiver operating characteristic (ROC) curves to measure the discriminating ability and derive the cut-offs between two different conditions with their relative diagnostic parameters. Results The total and macular estimated RGC counts showed highly significant differences among the three groups (P < 0.0001). The estimated RGC counts performed fairly well in distinguishing healthy from glaucomatous (PPG+POAG) eyes (area under the curve [AUC] = 0.79-0.92) with no statistically significant difference between total and macular RGCs. The approach allowed a good discrimination also between PPG and POAG eyes (AUC = 0.86-0.92). Cutoffs for the older age bracket were found to be lower in all cases. Conclusions Retinal ganglion cell counts estimated with empirical formulas with RTVue-100 could be used as a valid surrogate for neural losses in glaucoma.

Long-term outcomes after acute primary angle closure of Caucasian chronic angle closure glaucoma patients: Five years outcomes after acute primary angle closure

There is a lack of information about long‐term results of chronic angle closure glaucoma following an acute primary angle closure attack in Caucasian patients.

Long-term efficacy of deep sclerectomy in Posner-Schlossman syndrome

The Posner-Schlossman syndrome (PSS) is an elusive disease that can lead to serious consequences such as glaucomatous damage. Deep sclerectomy has been proven thus far to be the most effective surgical intervention to keep intraocular pressure (IOP) elevation under control compared with other surgical techniques, because it presents the least amount of postoperative complications. The aim of this case report is to demonstrate the efficacy of deep sclerectomy with T-Flux and the long-lasting effects that persist after 7 years in an eye affected by PSS. This case report demonstrates that an intervention of deep sclerectomy can lead to excellent results in terms of visual acuity as well as IOP lowering early in the history of the patient affected by PSS so that it can preclude establishment of glaucomatous damage.

Diagnostic Ability and Discriminant Values of OCT-Angiography Parameters in Early Glaucoma Diagnosis

Purpose: To evaluate papillary, peripapillary, and macular vasculature with optical coherence tomography angiography in preperimetric (PPG), primary open-angle glaucoma (POAG), and normal eyes, and to assess diagnostic ability and associations among the vasculature and structural damage. Methods: This was an observational, cross-sectional study. Retinal nerve fiber layer (RNFL), ganglion cell complex thickness, whole-image (wiVD), inside disc (idVD), peripapillary (ppVD), and macular vessel densities were obtained. Analysis of variance, post hoc test, and Pearson coefficient were used. The areas under the receiver operating characteristic curve (AUC) and cut-offs were calculated. Results: Thirteen healthy, 39 PPG, and 19 POAG eyes were included. Papillary and peripapillary VD were lower in POAG eyes in all parameters analyzed. wiVD in PPG eyes (52.37 ± 5.04%) was significantly decreased compared to healthy eyes (58.02 ± 2.02%, p < 0.05). AUC ranged from 0.62 to 0.90; the established cut-off values were 56% for wiVD, 55% for idVD, and 62% for ppVD. Pearson’s correlation coefficient showed a direct correlation between the papillary or peripapillary VD and RNFL thickness. Conclusions: Vessel densities in POAG eyes are significantly lower than in healthy eyes, and they show good discriminatory abilities. A diminished microvascular network is associated with RNFL thinning more strongly in POAG than in PPG eyes.

Changes of Visual Pathway and Brain Connectivity in Glaucoma: A Systematic Review

Background: Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is due to the implications in recent therapies, such as neuroprotection and neuroregeneration. Objective: In this review, we outline the current understanding of brain structural, functional, and metabolic changes detected with the modern techniques of neuroimaging in glaucomatous subjects. Methods: We screened MEDLINE, EMBASE, CINAHL, CENTRAL, LILACS, Trip Database, and NICE for original contributions published until 31 October 2017. Studies with at least six patients affected by any type of glaucoma were considered. We included studies using the following neuroimaging techniques: functional Magnetic Resonance Imaging (fMRI), resting-state fMRI (rs-fMRI), magnetic resonance spectroscopy (MRS), voxel- based Morphometry (VBM), surface-based Morphometry (SBM), diffusion tensor MRI (DTI). Results: Over a total of 1,901 studies, 56 case series with a total of 2,381 patients were included. Evidence of neurodegenerative process in glaucomatous patients was found both within and beyond the visual system. Structural alterations in visual cortex (mainly reduced cortex thickness and volume) have been demonstrated with SBM and VBM; these changes were not limited to primary visual cortex but also involved association visual areas. Other brain regions, associated with visual function, demonstrated a certain grade of increased or decreased gray matter volume. Functional and metabolic abnormalities resulted within primary visual cortex in all studies with fMRI and MRS. Studies with rs-fMRI found disrupted connectivity between the primary and higher visual cortex and between visual cortex and associative visual areas in the task-free state of glaucomatous patients. Conclusions: This review contributes to the better understanding of brain abnormalities in glaucoma. It may stimulate further speculation about brain plasticity at a later age and therapeutic strategies, such as the prevention of cortical degeneration in patients with glaucoma. Structural, functional, and metabolic neuroimaging methods provided evidence of changes throughout the visual pathway in glaucomatous patients. Other brain areas, not directly involved in the processing of visual information, also showed alterations.

Efficacy and Safety of Combined Intravitreal Bevacizumab and Retrobulbar Corticosteroids for Neovascular Age-Related Macular Degeneration

Introduction: Inflammation plays an important role in age-related macular degeneration (AMD) pathogenesis and progression. Thus, corticosteroids have been used for macular edema associated with exudative AMD. The purpose of this study was to evaluate the efficacy and safety of combined therapy of Intravitreal Bevacizumab (IVB) with Retrobulbar (RB) injection of triamcinolone or dexamethasone (RBTA or RBDEX) in eyes with Choroidal Neovascularization (CNV) in AMD. Secondary, we compared the results with the efficacy of single intravitreal injection of bevacizumab, ranibizumab and aflibercept.Methods: In this retrospective interventional comparative case series, patients with CNV were treated with IVB (1.25 mg) and RBTA or RBDEX. Control groups included patients who underwent IV injection of Bevacizumab (IVB), Ranibizumab (IVR) and Aflibercept (IVA). The primary purpose was the change of Central Retinal Thickness (CRT) at the Optical Coherence Tomography (OCT) and of Best Corrected Visual Acuity (BCVA) at 1 year.Results: A total of 123 eyes were divided into Group 1 (31 eyes treated with IVB+RBTA); Group 2 (31 IVB +RBDEX); Group 3 (25 IVB), Group 4 (24 IVA); Group 5, (12 IVR). All 5 groups showed a statistically significant improvement at 1 year in terms of visual acuity and CRT reduction. Group 1 showed significant greater gain of letter at 1-year (13.06 letters) compared to group 3 (8.24 letters, p=0.04) and to group 5 (6.58 letters, p=0.045). Combined therapy showed statistically significantly greater CRT reduction compared to the IVB (mean CRT reduction at 1-year: 71.39 μm, 75.84 μm and 38.44 μm in group 1, 2 and 3) with a lower number of injections per year.Conclusions: In AMD patients, combined therapy (IVB+RBTA or RBDEX) improved visual acuity with a minimum number of treatments during the 1-year follow-up. Prospective studies with a larger sample are needed to confirm these results and determine the long-term efficacy of this therapy.