Anti-vascular endothelial growth factor for neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG. OBJECTIVES: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more types of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 19 October 2021; metaRegister of Controlled Trials to 19 October 2021; and two additional trial registers to 19 October 2021. We did not use any date or language restrictions in the electronic search for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of people treated with anti-VEGF medications for NVG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion. MAIN RESULTS: We included five RCTs (356 eyes of 353 participants). Each trial was conducted in a different country: two in China, and one each in Brazil, Egypt, and Japan. All five RCTs included both men and women; the mean age of participants was 55 years or older. Two RCTs compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP alone. One RCT randomized participants to receive an injection of either intravitreal aflibercept or placebo at the first visit, followed by non-randomized treatment according to clinical findings after one week. The remaining two RCTs randomized participants to PRP with and without ranibizumab, one of which had insufficient details for further analysis. We assessed the RCTs to have an unclear risk of bias for most domains due to insufficient information to permit judgment.   Four RCTs examined achieving control of IOP, three of which reported our time points of interest. Only one RCT reported our critical time point at one month; it found that the anti-VEGF group had a 1.3-fold higher chance of achieving control of IOP at one month (RR 1.32, 95% 1.10 to 1.59; 93 participants) than the non-anti-VEGF group (low certainty of evidence). For other time points, one RCT found a three-fold greater achievement in control of IOP in the anti-VEGF group when compared with the non-anti-VEGF group at one year (RR 3.00; 95% CI:1.35 to 6.68; 40 participants). However, another RCT found an inconclusive result at the time period ranging from 1.5 years to three years (RR 1.08; 95% CI: 0.67 to 1.75; 40 participants).  All five RCTs examined mean IOP, but at different time points. Very-low-certainty evidence showed that anti-VEGFs were effective in reducing mean IOP by 6.37 mmHg (95% CI: -10.09 to -2.65; 3 RCTs; 173 participants) at four to six weeks when compared with no anti-VEGFs.  Anti-VEGFs may reduce mean IOP at three months (MD -4.25; 95% CI -12.05 to 3.54; 2 studies; 75 participants), six months (MD -5.93; 95% CI -18.13 to 6.26; 2 studies; 75 participants), one year (MD -5.36; 95% CI -18.50 to 7.77; 2 studies; 75 participants), and more than one year (MD -7.05; 95% CI -16.61 to 2.51; 2 studies; 75 participants) when compared with no anti-VEGFs, but such effects remain uncertain. Two RCTs reported the proportion of participants who achieved an improvement in visual acuity with specified time points. Participants receiving anti-VEGFs had a 2.6 times (95% CI 1.60 to 4.08; 1 study; 93 participants) higher chance of improving visual acuity when compared with those not receiving anti-VEGFs at one month (very low certainty of evidence). Likewise, another RCT found a similar result at 18 months (RR 4.00, 95% CI 1.33 to 12.05; 1 study; 40 participants).  Two RCTs reported the outcome, complete regression of new iris vessels, at our time points of interest. Low-certainty evidence showed that anti-VEGFs had a nearly three times higher chance of complete regression of new iris vessels when compared with no anti-VEGFs (RR 2.63, 95% CI 1.65 to 4.18; 1 study; 93 participants). A similar finding was observed at more than one year in another RCT (RR 3.20, 95% CI 1.45 to 7.05; 1 study; 40 participants).  Regarding adverse events, there was no evidence that the risks of hypotony and tractional retinal detachment were different between the two groups (RR 0.67; 95% CI: 0.12 to 3.57 and RR 0.33; 95% CI: 0.01 to 7.72, respectively; 1 study; 40 participants). No RCTs reported incidents of endophthalmitis, vitreous hemorrhage, no light perception, and serious adverse events. Evidence for the adverse events of anti-VEGFs was low due to limitations in the study design due to insufficient information to permit judgments and imprecision of results due to the small sample size. No trial reported the proportion of participants with relief of pain and resolution of redness at any time point. AUTHORS' CONCLUSIONS: Anti-VEGFs as an adjunct to conventional treatment could help reduce IOP in NVG in the short term (four to six weeks), but there is no evidence that this is likely in the longer term. Currently available evidence regarding the short- and long-term effectiveness and safety of anti-VEGFs in achieving control of IOP, visual acuity, and complete regression of new iris vessels in NVG is insufficient. More research is needed to investigate the effect of these medications compared with, or in addition to, conventional surgical or medical treatment in achieving these outcomes in NVG.

Treatment with citicoline eye drops enhances retinal function and neural conduction along the visual pathways in open angle glaucoma.

PURPOSE: To evaluate the retinal function and the neural conduction along the visual pathways after treatment with citicoline eye drops in patients with open angle glaucoma (OAG). METHODS: Fifty-six OAG patients (mean age 52.4 ± 4.72 years, IOP <18 mmHg with beta-blocker monotherapy only) were enrolled. Of these, 47 eyes completed the study: 24 OAG eyes were treated with topical citicoline (OMK1®, Omikron Italia, 3 drops/day) (GC eyes) over a 4-month period (month 4) followed by a 2-month period of citicoline wash-out (month 6), and another 23 OAG eyes were only treated with beta-blocker monotherapy (GP eyes). In GC and GP eyes, pattern electroretinogram (PERG) and visual evoked potentials (VEP) were assessed at baseline and at months 4 and 6 in both groups. RESULTS: At baseline, similar (ANOVA, p > 0.01) PERG and VEP values in GC and GP eyes were observed. After treatment with topical citicoline, a significant (p < 0.01) increase of PERG P50-N95 and VEP N75-P100 amplitudes, and a significant (p < 0.01) shortening of VEP P100 implicit times were found. In GC eyes, the shortening of VEP P100 implicit times was correlated significantly (p < 0.01) with the increase of PERG P50-N95 amplitudes. After a 2-month period of topical Citicoline wash-out, PERG and VEP values were similar (p > 0.01) to baseline ones. GP eyes showed not significant changes of PERG and VEP values during the entire follow-up. CONCLUSIONS: Topical treatment with citicoline in OAG eyes induces an enhancement of the retinal bioelectrical responses (increase of PERG amplitude) with a consequent improvement of the bioelectrical activity of the visual cortex (shortening and increase of VEP implicit time and amplitude, respectively).

Evaluating the effect of pupil dilation on spectral-domain optical coherence tomography measurements and their quality score.

BACKGROUND: Spectral-domain optical coherence tomography (SD-OCT) provides fast scan speed and high scan resolution improving its diagnostic accuracy. The purpose of this study was to evaluate if SD-OCT measurements and their quality score are influenced by pupil dilation. METHODS: Retinal nerve fiber layer thickness (RNFL), ganglion cell complex (GCC) and optic nerve head (ONH) were measured in one eye of 57 glaucoma patients and 36 healthy subjects using spectral domain optical coherence tomography (SD-OCT) before and after pupil dilation. Comparisons were made between measurements and their quality score pre- and post dilation (Signal Strength Index, SSI). Overall RNFL, average GCC and ONH rim volume were considered in the analysis. RESULTS: No statistically significant differences were found between pre- and post-dilation measurements in both groups (glaucoma: RNFL 80 ± 15 µm vs 80 ± 16 µm, p = 0.87; GCC 81.35 ± 13.4 µm vs 81.10 ± 13.14 µm, p = 0.92; ONH 0.05 ± 0.11 mm(3) vs 0.04 ± 0.07 mm(3), p = 0.74; controls RNFL 99 ± 12 µm vs 98 ± 14 µm, p = 0.70; GCC 92.12 ± 6.7 µm vs 91.54 ± 7.05 µm, p = 0.72; ONH 0.11 ± 0.1 mm(3) vs 0.04 ± 0.07 mm(3), p = 0.36) nor between pre- and post-dilation quality score (glaucoma SSI RNFL 54.3 ± 10.3 vs 51.7 ± 18.1, p = 0.12; SSI GCC 58 ± 9.5 vs 57 ± 8.09, p = 0.55; SSI ONH 48.5 ± 7.6 vs 46.6 ± 7.2, p = 0.16; controls SSI RNFL 57 ± 10.3 vs 54 ± 9.31, p = 0.2; SSI GCC 60.9 ± 8.1 vs 58.8 ± 7.3, p = 0.3; SSI ONH 51.5 ± 8.9 vs 50.4 ± 8.3, p = 0.59). CONCLUSION: Pupil dilation doesn't affect SD-OCT measurements and their quality score.

Cytidine 5'-Diphosphocholine (Citicoline) in Glaucoma: Rationale of Its Use, Current Evidence and Future Perspectives.

Cytidine 5'-diphosphocholine or citicoline is an endogenous compound that acts in the biosynthetic pathway of phospholipids of cell membranes, particularly phosphatidylcholine, and it is able to increase neurotrasmitters levels in the central nervous system. Citicoline has shown positive effects in Parkinson's disease and Alzheimer's disease, as well as in amblyopia. Glaucoma is a neurodegenerative disease currently considered a disease involving ocular and visual brain structures. Neuroprotection has been proposed as a valid therapeutic option for those patients progressing despite a well-controlled intraocular pressure, the main risk factor for the progression of the disease. The aim of this review is to critically summarize the current evidence about the effect of citicoline in glaucoma.

Nerve growth factor modulation of retinal ganglion cell physiology.

Nerve growth factor (NGF) is an endogenous neurotrophin involved in the development, maintenance and regeneration of mammalian sympathetic and sensory neurons. Additionally, NGF is known to have trophic and differentiating activity on several populations of cholinergic neurons of the central nervous system (CNS), and to act as a differentiation factor in the development of the visual cortex. The paramount functions of NGF in the visual system are also highlighted by the presence of this neurotrophin and both its receptors TrkA and p75 in most intra-ocular tissues, including lens, vitreous, choroid, iris, and trabecular meshwork. In the retina, NGF is produced and utilized specifically by retinal ganglion cells (RGC), bipolar neurons and glial cells, and is thought to have crucial protective effects in several disease states. Studies on the role of NGF on RGCs survival following optic nerve transection, ischemic injury, ocular hypertension and glaucoma are discussed in this review.

Effectiveness and safety of XEN45 implant over 12 months of follow-up: data from the XEN-Glaucoma Treatment Registry.

OBJECTIVES: To evaluate the 1-year effectiveness and safety of the XEN45, either alone or in combination with phacoemulsification, in glaucoma patients. METHODS: This multicentre, prospective, observational study included consecutive eyes of glaucoma patients from the Italian XEN-Glaucoma Treatment Registry (XEN-GTR) who underwent XEN45 alone or in combination with phacoemulsification, with at least 1 year of follow-up. Surgical success was defined as intraocular pressure (IOP) < 18 mmHg and ≥20% reduction from preoperative IOP, over 1 year of follow-up. RESULTS: Two hundred thirty-nine eyes (239 patients) were analyzed, 144 (60.2%) eyes in the XEN-solo and 95 (39.8%) eyes in the XEN+Phaco groups. One hundred-sixty-eight (70.3%) eyes achieved overall success, without statistically significant differences between study groups (p = 0.07). Preoperative IOP dropped from a median (IQR) of 23.0 (20.0-26.0) mmHg to 14.0 (12.0-16.0) mmHg at month 12 (p < 0.001), with overall 39.9 ± 18.3% IOP reduction. The mean number of preoperative ocular hypotensive medications (OHM) was significantly reduced from 2.7 ± 0.9 to 0.5 ± 0.9 at month 12 (p < 0.001). Preoperative IOP < 15 mmHg (HR: 6.63; 95%CI: 2.61-16.84, p < 0.001) and temporal position of the surgeon (HR: 4.25; 95%CI: 2.62-6.88, p < 0.001) were significantly associated with surgery failure. One hundred-forty-six (61.1%) eyes had no intraoperative complications, whereas 91 (38.1%) and 56 (23.4%) eyes experienced at least one complication, respectively early (< month 1) and late (≥ month 1), all self-limiting or successfully treated without sequelae. Needling occurred in 55 (23.0%) eyes at least once during follow-up. CONCLUSION: Over 1-year follow-up, XEN45 alone or in combination with phacoemulsification, had comparable success rates and effectively and safely lowered IOP and the need for OHM.

Retinal thinning in Gaucher disease patients and carriers: results of a pilot study.

Both Gaucher disease patients and heterozygous glucocerebrosidase mutation carriers are at increased risk of Parkinson's disease. Retinal thinning has been reported in early Parkinson's disease. Here we used optical coherence tomography to demonstrate thinning of the retinal ganglion cell layer in Gaucher disease patients and carriers who manifest clinical markers of potential early neurodegeneration. Optical coherence tomography may help identify Gaucher disease patients and carriers at increased risk of developing Parkinson's disease.

Ubiquitin proteasome system and glaucoma: A survey of genetics and molecular biology studies supporting a link with pathogenic and therapeutic relevance.

Glaucoma represents a group of progressive neurodegenerative diseases characterized by the loss of retinal ganglion cells (RGCs) and their axons with subsequent visual field impairment. The disease develops through largely uncharacterized molecular mechanisms, that are likely to occur in different localized cell types, either in the anterior (e.g., trabecular meshwork cells) or posterior (e.g., Muller glia, retinal ganglion cells) segments of the eye. Genomic and preclinical studies suggest that glaucoma pathogenesis may develop through altered ubiquitin (Ub) signaling. Ubiquitin conjugation, referred to as ubiquitylation, is a major post-synthetic modification catalyzed by E1-E2-E3 enzymes, that profoundly regulates the turnover, trafficking and biological activity of the targeted protein. The development of new technologies, including proteomics workflows, allows the biology of ubiquitin signaling to be described in health and disease. This post-translational modification is emerging as a key role player in neurodegeneration, gaining relevance for novel therapeutic options, such as in the case of Proteolysis Targeting Chimeras technology. Although scientific evidence supports a link between Ub and glaucoma, their relationship is still not well-understood. Therefore, this review provides a detailed research-oriented discussion on current evidence of Ub signaling in glaucoma. A review of genomic and genetic data is provided followed by an in-depth discussion of experimental data on ASB10, parkin and optineurin, which are proteins that play a key role in Ub signaling and have been associated with glaucoma.

Glaucoma Progression Diagnosis: The Agreement between Clinical Judgment and Statistical Software.

Background: To explore the agreement between clinical judgment and Guided Progression Analysis II (GPAII) in the evaluation of visual fields (VF) progression in patients with glaucoma. Methods: Three glaucoma experts and three general ophthalmologists were asked to rate the VF series by classifying them as progressive through the observation of the overview report. The agreement between clinical judgment and GPAII event analysis (EA) and trend analysis (TA) was assessed by Cohen statistic. The sensitivity and specificity of clinical judgment in detecting the presence of progression was evaluated considering the results of GPAII as the reference standard. Results: 66 VF series were included in the study. Glaucoma experts, general ophthalmologists, GPAII EA, and GPAII TA found progression in 39%, 38%, 15%, and 21% of the VF series (p < 0.05). The clinical judgment of glaucoma experts and general ophthalmologists was discordant with GPAII EA in 27.2% and 28.7% (k = 0.35, 95% CI 0.15−0.56 and k = 0.30, 95% CI 0.09−0.52) and with GPAII TA in 21.2% and 25.7% of the VF series examined (k = 0.51, 95% CI 0.31−0.72 and k = 0.41, 95% CI 0.18−0.62). Considering the GPAII EA and TA as reference standard, glaucoma experts showed a sensitivity of 90% and 92.8% and a specificity of 69.6% and 75%, while general ophthalmologists showed a sensitivity of 80% and 78.5% and a specificity of 69.6% and 73%. Conclusions: The agreement between clinical judgment and GPAII ranges from fair to moderate. Glaucoma experts showed better ability than general ophthalmologists in detecting VF progression.

Italian Candidates for the XEN Implant: An Overview from the Glaucoma Treatment Registry (XEN-GTR).

Background The Italian XEN Glaucoma Treatment Registry (XEN-GTR) was created to acquire a comprehensive prospective dataset that includes the patient characteristics, intraoperative variables, and postoperative management of glaucoma patients undergoing the XEN gel stent implantation. Methods This was a prospective observational, longitudinal clinical study involving 10 centres throughout Italy. The baseline examination included a comprehensive evaluation of demographic parameters (age, sex, ethnicity, and systemic condition), specific ophthalmological parameters, and quality of life questionnaire score collection. Results The baseline data of 273 patients were analysed. The median (IQR) age was 72 (65.0 to 78.0) years. Of the 273 patients, 123 (45%) were female and 150 (55%) were male. A total of 86% of the patients had open-angle glaucoma with a mean intraocular pressure of 24 ± 6 (range 12.0-60.0) mmHg. The mean number of medications was 2.7 ± 0.9 at baseline for the patients with a prevalence of prostaglandin analogues combined with a beta-blocker and anhydrase carbonic inhibitor (31.8%). The mean scores of the NEI-VFQ 25 and GSS questionnaires were 78 ± 18 (range 26.5-100) and 85 ± 14 (range 79-93), respectively. Combined XEN/cataract surgeries were scheduled in 73.7% of the patients. The preferred place for the XEN implant was the supero-nasal quadrant (91.6%). Conclusions Observing the baseline characteristics of the typical Italian candidates for the XEN gel implant shows that they are patients affected by POAG and cataracts, with moderate to severe glaucoma damage, all of which has an impact on their quality of life.

Levels of plasma homocysteine in pseudoexfoliation glaucoma.

BACKGROUND: To examine levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with pseudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and healthy control subjects. METHODS: This study included 36 patients with PEXG, 40 with POAG, and 40 age-matched healthy subjects. Fasting plasma Hcy concentrations and levels of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay; values exceeding 14 µm/l were considered elevated. RESULTS: Mean plasma Hcy was significantly higher in PEXG (16.55 ± 7.23 µm/l) compared with POAG (13.91 ± 3.61 µm/l) and controls (13.12 ± 5.13 µm/l) (p = 0.03 and p = 0.0007 respectively). There were no statistical differences in serum vitamin B12 and folic acid levels among PEXG, POAG and control subjects (p > 0.05). A moderate, although statistically significant, relationship between Hcy and folic acid levels was found in the PEXG group (R(2) = 0.23, p = 0.003). Hcy levels were found not to be related with folic acid or vitamin B12 in either POAG or control subjects. CONCLUSIONS: In this study, plasma Hcy is significantly higher in PEXG group than the POAG and control groups. Hyper-Hcy might play a role in the pathogenesis of PEXG. Hyper-Hcy may be an independent factor stressing vasculopathy in addition to pseudoexfoliation, so might be a modifiable risk factor for PEXG.

Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review.

Cytidine 5'-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer's disease, Parkinson's disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials).

Neural Conduction Along Postretinal Visual Pathways in Glaucoma.

Purpose: This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes. Methods: Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24-2 Humphrey mean deviation (MD) between -2.5 and -20 dB and IOP <21 mmHg on pharmacological treatment (OAG group) and 20 age-matched controls (control group) were enrolled. In both groups, simultaneous pattern electroretinograms (PERG) and visual evoked potentials (VEP), in response to checks stimulating macular or extramacular areas (the check edge subtended 15' and 60' of visual arc, respectively), and RNFL-T (measured in superior, inferior, nasal, and temporal quadrants) were assessed. Results: In the OAG group, a significant (ANOVA, p < 0.01) reduction of 60' and 15' PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60' and 15' PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly (p < 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson's test, p < 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation (p < 0.01) with RNFL-T (overall or temporal) values was detected. Conclusions: In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60' and 15' RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction.

Confocal Microscopy and Anterior Segment Optical Coherence Tomography Imaging of the Ocular Surface and Bleb Morphology in Medically and Surgically Treated Glaucoma Patients: A Review.

Glaucoma patients often suffer from ocular surface disease (OSD) caused by the chronic administration of topical anti-glaucoma medications, especially in cases of long-term therapy with preserved or multiple drugs. Additionally, glaucoma surgery may determine ocular surface changes related to the formation and location of the filtering bleb, the application of anti-mitotic agents, and the post-operative wound-healing processes within the conjunctiva. Recently, several studies have evaluated the role of advanced diagnostic imaging technologies such as in vivo confocal microscopy (IVCM) and anterior segment-optical coherence tomography (AS-OCT) in detecting microscopic and macroscopic features of glaucoma therapy-related OSD. Their clinical applications are still being explored, with recent particular attention paid to analyzing the effects of new drug formulations and of minimally invasive surgical procedures on the ocular surface status. In this review, we summarize the current knowledge about the main changes of the ocular surface identified at IVCM and AS-OCT in glaucoma patients under medical therapy, or after surgical treatment.

Endothelial Cell Density After XEN Implant Surgery: Short-term Data From the Italian XEN Glaucoma Treatment Registry (XEN-GTR).

PRECIS: XEN implant was associated with low endothelial cell density (ECD) reduction. In fact, when combined with phacoemulsification, the reduction in ECD was similar to that expected after phacoemulsification alone. PURPOSE: The purpose of this study was to assess the impact of XEN implant, either alone or in combination with phacoemulsification, on ECD. METHODS: Multicenter, prospective, observational study conducted on consecutive open-angle glaucoma patients, who were enrolled in the Italian XEN Glaucoma Treatment Registry and have complete endothelial cell count data at baseline and at 6 months after implantation. The primary endpoint was the mean percentage change in ECD between baseline and month 6. RESULTS: The study included 108 open-angle glaucoma eyes (68 in the XEN-solo and 40 eyes in the XEN+phaco groups) and 60 control eyes (phaco-solo group). As compared with baseline, mean (95% confidence interval, CI) ECD reduction was -5.6% (-7.0% to -4.9%), -11.3% (-13.8% to -10.9%), and -13.0% (14.8% to -11.8%) in the XEN-solo, XEN+phaco, and phaco-solo groups, respectively (P=0.0004, <0.0001, and <0.0001, respectively). As compared with the XEN-solo group, the ECD reduction was significantly greater in the XEN+phaco group (mean difference=5.7%; 95% CI: 4.1%-7.3%, P<0.0001) and in the phaco-solo group (mean difference=7.4%; 95% CI: 5.7%-9.1%, P<0.0001). ECD reduction was similar in XEN+phaco and phaco-solo groups (P=0.9). In absolute terms, ECD reduction was significantly greater in the XEN+phaco (mean difference=169±306, P=0.021) and in the phaco-solo (mean difference=192±302, P=0.0022) groups than in the XEN-solo group. CONCLUSIONS: The mean ECD reduction 6 months after XEN implantation was low. The ECD reduction in the XEN+phaco group was larger than in the XEN-solo group but was similar to that observed in the phaco-solo group.

Steroid-induced glaucoma: Epidemiology, pathophysiology, and clinical management.

Glucocorticoids are a class of anti-inflammatory drugs commonly used to treat various ocular and systemic conditions. Although the role of glucocorticoids in the treatment of numerous serious inflammatory diseases is pivotal, their prolonged use may increase intraocular pressure resulting in steroid-induced glaucoma. We provide a detailed update on steroid-induced glaucoma as a preventable cause of blindness in the adult and pediatric population and describe its epidemiology, social impact, and risk factors. Furthermore, we explore the propensity of different steroids to increase the intraocular pressure, the role of different routes of steroid administration, dosage and duration of treatment, as well as the clinical features, genetics, and management of steroid-induced glaucoma.

Enhancement of Retinal Function and of Neural Conduction Along the Visual Pathway Induced by Treatment with Citicoline Eye Drops in Liposomal Formulation in Open Angle Glaucoma: A Pilot Electrofunctional Study.

INTRODUCTION: To evaluate the retinal function and the relative neural conduction along the visual pathway after treatment with citicoline in liposomal formulation (CLF) eye drops in patients with open angle glaucoma (OAG). METHODS: Twelve OAG patients (mean age ± standard deviation 52.58 ± 11.39 years, intraocular pressure < 18 mmHg under topical hypotensive treatment, Humphrey field analyzer mean deviation - 4.49 ± 2.46 dB) were enrolled. Only one eye of studied patients was treated with CLF eye drops (OMK1-LF®, Omikron Italia, 3 drops/day) (CLF group, 12 eyes) over a period of 4 months. In CLF eyes, pattern electroretinogram (PERG), visual evoked potentials (VEP), and visual field test were assessed at baseline and at the end of treatment (month 4). RESULTS: After treatment with CLF eye drops, a significant increase of PERG P50-N95 amplitude and a significant shortening of VEP P100 implicit time were found. In CLF eyes, the shortening of VEP P100 implicit time was significantly correlated with the increase of PERG P50-N95 amplitude. CONCLUSION: Data from this pilot study suggest that treatment with CLF eye drops induces an enhancement of the retinal bioelectrical responses (increase of PERG amplitude) with a consequent improvement of the bioelectrical activity of the visual cortex (shortening of VEP implicit time). FUNDING: Omikron Italia S.r.l. and Opko Health Europe.

Tear Film, Conjunctival and Corneal Modifications Induced by Glaucoma Treatment.

Ocular surface disease is characterized by tear film instability and histopathologic and clinical changes of the ocular surface. Glaucoma patients often suffer from ocular surface disease caused by the chronic use of preserved medical treatment to reduce intraocular pressure. Benzalkonium chloride is the preservative most frequently used in glaucoma medications. Its effect on tear film, conjunctiva and cornea and the consequences in glaucoma management are discussed in this mini-review.

Human vitreous concentrations of citicoline following topical application of citicoline 2% ophthalmic solution.

PURPOSE: To evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo. METHODS: Twenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography. RESULTS: The overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 µg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 µg/mL, 44.45 ± 10.19 µg/mL and 330.41 ± 75.8 µg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 µg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 µg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 µg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 µg/mL, 6.24 ± 3.6 µg/mL and 172.80 ± 99.76 µg/mL, respectively. CONCLUSION: Citicoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.