Gloria Roberti

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. J. Cell. Physiol. 229: 1130–1133, 2014.

A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy

Purpose: To study the neuroprotective effect of topical citicoline. Materials and Methods: Experimental phase to evaluate the ability of citicoline eye drops to reach the vitreous and the retina: The right eyes of 5 mice CD1 were treated with two drops per day for three days of citicoline 1% and 2% (OMK1, Omikron Italia s.r.l.), and then the vitreous was analyzed with the liquid chromatography and spectrometry mass (LC-MS/MS). Clinical phase to determine if topical citicoline is able to delay glaucoma progression, considering perimetric parameters and electro functional tests. Patients were randomized in two groups, OMK1 and OAG. The first group was treated with OMK1 three times per day, plus hypotensive therapy for two months and one month of wash out. The second group was treated only with hypotensive treatment for three months. Results: LC-MS/MS detected the molecule very well, and only OMK1 showed systemic absorption. Thirty-four patients were enrolled, 16 in the OMK1 and 18 in the OAG group. Perimetric parameters showed a positive trend in individual eyes of patients in OMK1 group, but these values were not statistically significant in the whole group. Retinal ganglion cells function improved as shown by reduced P50 latency (P = 0.04) and increased P50-N95 amplitude (P < 0.0001) of pattern electroretinogram, up to 30 days after the washout (P = 0.01; P = 0.002). Visual evoked potential and retino-cortical time improvement regressed after 30 days of washout. In OAG group, there was any change during the follow-up. No adverse reactions were reported in both groups. Conclusions: Topical citicoline seems to have a neuroprotective action.

Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages.

Purpose To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters. Materials and Methods 45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated. Results Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03). Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019) and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04) but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06) compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01). Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008) and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001) but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32) compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004). Conclusions BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that both factors could be further investigated as potential circulating biomarkers for the early detection of 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.

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.

Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP, Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized, Double Masked, Placebo-Controlled Clinical Trial.

Purpose To compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects. Methods In this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability. Results Mean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure. Conclusion Both Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure. Trial Registration EU Clinical Trial Register and EudraCT# 2010-024272-26

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.

Comparing Optic Nerve Head Analysis Between Confocal Scanning Laser Ophthalmoscopy and Spectral Domain Optical Coherence Tomography

Abstract Purpose/aim of the study: Confocal scanning laser ophthalmoscopy, HRT3, and spectral domain optical coherence tomography (OCT), RTVue-100, are able to give 3-dimensional (3D) topography images of optic nerve head (ONH) and to derive stereometric parameters and sectorial analysis. The purpose of the study is to evaluate the agreement of these two devices and their diagnostic accuracy to discriminate eyes with glaucoma from those without. Materials and methods: Glaucoma patients and healthy control subjects were included. All of them underwent a complete ophthalmological examination, including slit lamp evaluation and visual field (VF) test. After pupil dilatation, HRT3 and RTVue-100 were performed. The following stereometric parameters were recorded: disc area, rim area, rim volume, cup volume, cup area, cup/disk ratio, and the following sectors, superotemporal, superonasal, inferotemporal, inferonasal. Results: Forty-six eyes of 46 glaucoma patients and 58 eyes of 58 healthy subjects were included in the study. In both groups, HRT3 rim area and rim volume were statistically higher than RTVue-100 (glaucomas: 0.95 ± 0.38 versus 0.44 ± 0.33 and 0.19 ± 0.13 versus 0.02 ± 0.03, p < 0.01. controls: 1.41 ± 0.30 versus 1.08 ± 0.37 and 0.37 ± 0.13 versus 0.14 ± 0.11, p < 0.01), while cup area was statistically higher by RTVue-100 (glaucomas: 1.42 ± 0.57 versus 1.14 ± 0.58, p < 0.01. controls: 1.05 ± 1.35 versus 0.65 ± 0.48). Bland and Altman plots confirmed the presence of a fixed bias. The parameters with largest AUROC were rim volume, rim area and cup/disk ratio for both instruments. HRT3 inferotemporal sector had the highest sensitivity (80.43%, at 75.9% specificity), while for RTVue-100, the superotemporal sector had the highest sensitivity (76.1%, at 81% specificity). The agreement was moderate for inferotemporal sector and fair for the others. Conclusions: HRT3 and RTVue-100 are not interchangeable for ONH analysis. They both have good diagnostic accuracy, but RTVue-100 shows slightly better performance, at least with regard to rim area volume.

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.