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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

Influence of Sociodemographic Factors on Disease Characteristics and Vision-related Quality of Life in Primary Open-angle Glaucoma Patients: The Italian Primary Open Angle Glaucoma Study (IPOAGS).

PURPOSE: The purpose of this article was to evaluate the potential association between sociodemographic factors with clinical characteristics, vision-related quality of life (QoL), and glaucoma-related symptoms scores in a large cohort of primary open-angle glaucoma patients. MATERIALS AND METHODS: Multicenter, cross-sectional study involving academic and nonacademic centers. Previously diagnosed primary open-angle glaucoma patients aged >18 years were enrolled. At baseline, information on demographic characteristics, social, medical and ocular history, clinical presentation and treatments was collected. Vision-related QoL was evaluated by means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), while glaucoma-related symptoms were evaluated using the Glaucoma Symptom Scale (GSS) questionnaire. The associations between sociodemographic factors with clinical characteristics (mean deviation, pattern standard deviation, best-corrected visual acuity), NEI-VFQ-25, and GSS scores were evaluated by means of univariate and multivariate general linear models. RESULTS: A total of 3227 patients were enrolled. Older age and male sex were significantly associated with lower mean deviation (P<0.01) and higher pattern standard deviation (P<0.01), whereas older age was associated with lower best-corrected visual acuity (P<0.01). The composite GSS score was related to age (P=0.02), sex (P<0.01), employment (P=0.01), and profession (P=0.04), while the total NEI-VFQ-25 score was associated with sex (P<0.01), marital status (P=0.02), and employment (P=0.02). CONCLUSIONS: Age and sex were significantly associated with almost all indicators of glaucoma severity at baseline. Other variables, such as employment, profession, and marital status were significantly associated with vision-related QoL scores.

Prospective, Randomized, Single Masked, Parallel Study Exploring the Effects of a Preservative-Free Ophthalmic Solution Containing Hyaluronic Acid 0.4% and Taurine 0.5% on the Ocular Surface of Glaucoma Patients Under Multiple Long-Term Topical Hypotensive Therapy.

INTRODUCTION: To compare the effects of a preservative-free (PF) ophthalmic solution containing hyaluronic acid (HA) 0.4% and taurine (TAU) 0.5% with those of a PF ophthalmic solution containing HA 0.2% on ocular surface signs, symptoms, and morphological parameters in glaucoma patients under multiple long-term topical hypotensive therapy. METHODS: Eligible patients underwent evaluation of ocular surface parameters by ocular surface disease index (OSDI) and glaucoma symptom scale (GSS) questionnaires, breakup time test (BUT), Schirmer I test, corneal and conjunctival staining (Oxford scale), and conjunctival in vivo confocal microscopy (Heidelberg Retina Tomograph 3, Heidelberg Engineering GmbH, Heidelberg, Germany). After the baseline visit, patients were randomized to use a PF ophthalmic solution containing HA 0.4% and TAU 0.5%, QID, in both eyes (group 1) or to use a PF ophthalmic solution containing HA 0.2%, QID (group 2) in addition to the ongoing preserved hypotensive treatment. Follow-up visits were scheduled at 30 and 90 days. RESULTS: Thirty-nine eyes of 39 glaucoma patients were included in the study. At baseline, results of study tests of both groups were similar. After 90 days in group 1 the BUT (p = 0.01), the Oxford score (p = 0.03), the conjunctival goblet cells (CGC) density (p = 0.0005) ,and the two questionnaires score significantly improved (OSDI, p = 0.003; GSS, p = 0.003) compared to baseline values, while in group 2 all these parameters did not differ from baseline (BUT, p = 0.39; Oxford score, p = 0.54; CGC density, p = 0.33, OSDI p = 0.65, GSS, p = 0.25). The BUT and the CGC density were statistically different between groups both at 30 and 90 days (p = 0.04 and p = 0.04, respectively). The Schirmer I test did not statistically change after 90 days in both groups. CONCLUSIONS: The PF ophthalmic solution with HA 0.4% and TAU 0.5% seems to improve CGC density and reduce signs and symptoms of dry eye in glaucoma patients under long-term multiple preserved hypotensive therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03480295.

Citicoline and Retinal Ganglion Cells: Effects on Morphology and Function.

BACKGROUND: Retinal ganglion cells (RGCs) are the nervous retinal elements which connect the visual receptors to the brain forming the nervous visual system. Functional and/or morphological involvement of RGCs occurs in several ocular and neurological disorders and therefore these cells are targeted in neuroprotective strategies. Cytidine 5-diphosphocholine or Citicoline is an endogenous compound that acts in the biosynthesis of phospholipids of cell membranes and increases neurotransmitters' levels in the Central Nervous System. Experimental studies suggested the neuromodulator effect and the protective role of Citicoline on RGCs. This review aims to present evidence of the effects of Citicoline in experimental models of RGCs degeneration and in human neurodegenerative disorders involving RGCs. METHODS: All published papers containing experimental or clinical studies about the effects of Citicoline on RGCs morphology and function were reviewed. RESULTS: In rodent retinal cultures and animal models, Citicoline induces antiapoptotic effects, increases the dopamine retinal level, and counteracts retinal nerve fibers layer thinning. Human studies in neurodegenerative visual pathologies such as glaucoma or non-arteritic ischemic neuropathy showed a reduction of the RGCs impairment after Citicoline administration. By reducing the RGCs' dysfunction, a better neural conduction along the post-retinal visual pathways with an improvement of the visual field defects was observed. CONCLUSION: Citicoline, with a solid history of experimental and clinical studies, could be considered a very promising molecule for neuroprotective strategies in those pathologies (i.e. Glaucoma) in which morpho-functional changes of RGCc occurs.

Use of Topical Cannabinomimetic Palmitoylethanolamide in Ocular Surface Disease Associated with Antiglaucoma Medications.

PURPOSE: Chronic use of topical hypotensive therapies in glaucoma patients leads to chronic inflammation of the ocular surface, which decreases the success rate of long-term glaucoma management. The aim of this study is to evaluate the effect of topical palmitoylethanolamide (PEA) (Defluxa©), a well-known anti-inflammatory and analgesic agent, in suppressing the ocular surface inflammation associated with the use of hypotensive eye drops. METHODS: In a pilot clinical trial, we enrolled 15 glaucomatous patients who received topical PEA (Defluxa) in addition to the current antiglaucoma drugs, while 15 glaucomatous patients did not receive any additional treatment. At 3 different time points (day 0, 15, and 30), signs of ocular surface involvement, adverse events, visual acuity, and intraocular pressure were assessed. RESULTS: Topical PEA (Defluxa) was effective in increasing the Schirmer test (P < 0.05) and the tear film breakup time (T-BUT) (P < 0.0001), and improving the conjunctival hyperemia (P < 0.0001) by day 30, compared to baseline. Compared to control, by day 15, the conjunctival hyperemia score was significantly decreased in the PEA (Defluxa) group (P < 0.01), while the T-BUT and the Schirmer Test achieved a significant improvement by day 30 (P < 0.05; P < 0.01). DISCUSSION: Our data suggests that topical PEA (Defluxa) is a safe, effective, and generally well-tolerated treatment to prevent or suppress ocular surface inflammation attributable to chronic glaucoma treatment.

Detection of central visual field defects in early glaucomatous eyes: Comparison of Humphrey and Octopus perimetry.

PURPOSE: To compare the detection rate of central visual field defect (CVFD) between the 30-degree Octopus G1 program (Dynamic strategy) and the HFA 10-2 SITA-Standard test in early glaucoma eyes not showing any CVFD on the HFA 24-2 SITA-Standard test. METHODS: One eye of 41 early glaucoma patients without CVFD in the central 10° on HFA 24-2 test was tested with both the HFA 10-2 test and the Octopus G1 program 15 minutes apart, in random order. The primary outcome measure was the comparison of CVFD detection rates. Secondary outcome measures comprised the agreement in detecting CVFD, and the comparison of test durations and the numbers of depressed test points outside the central 10-degree area between the HFA 24-2 test and the Octopus G1 program. RESULTS: The mean age of the population was 65.2±10.1 years, and the mean deviation with HFA 24-2 was -3.26±2.6 dB. The mean test duration was not significantly different between the tests (p = 0.13). A CVFD was present in 33 (80.4%) HFA 10-2 test and in 23 (56.0%) Octopus G1 tests (p = 0.002). The overall agreement between the HFA 10-2 and Octopus G1 examinations in classifying eyes as having or not having CVFD was moderate (Cohen's kappa 0.47). The Octopus G1 program showed 69.6% sensitivity and 100% specificity to detect CVFD in eyes where the HFA 10-2 test revealed a CVFD. The number of depressed test points (p<5%) outside the central 10° area detected with the Octopus G1 program (19.68±10.6) was significantly higher than that detected with the HFA 24-2 program (11.95±5.5, p<0.001). CONCLUSION: Both HFA 10-2 and Octopus G1programs showed CVFD not present at HFA 24-2 test although the agreement was moderate. The use of a single Octopus G1 examination may represent a practical compromise for the assessment of both central and peripheral visual field up to 30° eccentricity without any additional testing and increasing the total investigation time.

A Review of the Ahmed Glaucoma Valve Implant and Comparison with Other Surgical Operations.

The Ahmed glaucoma valve (AGV) is a popular glaucoma drainage implant used for the control of intraocular pressure in patients with glaucoma. While in the past AGV implantation was reserved for glaucoma patients poorly controlled after one or more filtration procedures, mounting evidence has recently encouraged its use as a primary surgery in selected cases. AGV has been demonstrated to be safe and effective in reducing intraocular pressure in patients with primary or secondary refractory glaucoma. Compared to other glaucoma surgeries, AGV implantation has shown favorable efficacy and safety. The aim of this article is to review the results of studies directly comparing AGV with other surgical procedures in patients with glaucoma.

Ahmed glaucoma valve implant: surgical technique and complications.

Implantation of Ahmed glaucoma valve is an effective surgical technique to reduce intraocular pressure in patients affected with glaucoma. While in the past, the use of this device was reserved to glaucoma refractory to multiple filtration surgical procedures, up-to-date mounting experience has encouraged its use also as a primary surgery for selected cases. Implantation of Ahmed glaucoma valve can be challenging for the surgeon, especially in patients who already underwent previous multiple surgeries. Several tips have to be acquired by the surgeon, and a long learning curve is always needed. Although the valve mechanism embedded in the Ahmed glaucoma valve decreases the risk of postoperative hypotony-related complications, it does not avoid the need of a careful follow-up. Complications related to this type of surgery include early and late postoperative hypotony, excessive capsule fibrosis around the plate, erosion of the tube or plate edge, and very rarely infection. The aim of this review is to describe surgical technique for Ahmed glaucoma valve implantation and to report related complications.