Rehabilitative strategies after filtering procedure in glaucoma.

Glaucoma is one of the leading causes of non-reversible blindness worldwide, and almost 6 million people are estimated to be impaired visually in advanced stage of glaucoma. Recently, several studies on glaucoma has been focused towards new therapeutic approaches based on mechanisms independent from IOP control. Effects of new therapeutic agents, visual psychophysical training, or complementary medications targeting optic pathways today seem to be a relevant and effervescent field of research. The goal of the study is to evaluate in glaucoma patients if a rehabilitative strategy with a biofeedback training with microperimetry may be useful after surgery in recovery visual performance even when visual field defects are present in IOP is well controlled environment. Were enrolled 24 patients (28 eyes) with Primary Open Angle Glaucoma (POAG) (mean 63 range: 49-75 years) from our Glaucoma Center after filtering surgery. All patients after one months from surgical intervention underwent to a complete ophthalmologic examination: IOP measurement, gonioscopy, visual field and SD-OCT at baseline of RNFL thickness. In some cases, were included in the study both eyes because in POAG frequently clinical conditions are different in each eye, and secondarily new fixation target retinal location (TRL) was chosen based on single eye retinal sensitivity. Best corrected visual acuity was significantly increased after the training from 0.61 to 0.479 (p = 0.00058) with no change in refractive error. After the biofeedback patients presented increased value in Mean retinal sensitivity from 14.91 to 15.96 (p = 0.0078).Fixation stabilitywas improved either according to Fuji classification (increased from 75.1 to 81.3% p = 0.0073) or BCEA value, reduced from 8.7 to 6.0 square degrees (p = 0.013) we noted a marked increase in this parameter with better performances and satisfaction by the patient. RFNL thickness: no change was noted (p = 0.505) in this value as an indicator of disease's stability. Our data indicate that MP-3 Biofeedback may be a good strategy to reduce the impairment of the Glaucoma Patient.

Oxidative Stress Implication in Retinal Diseases-A Review.

Oxidative stress (OS) refers to an imbalance between free radicals (FRs), namely highly reactive molecules normally generated in our body by several pathways, and intrinsic antioxidant capacity. When FR levels overwhelm intrinsic antioxidant defenses, OS occurs, inducing a series of downstream chemical reactions. Both reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced by numerous chemical reactions that take place in tissues and organs and are then eliminated by antioxidant molecules. In particular, the scientific literature focuses more on ROS participation in the pathogenesis of diseases than on the role played by RNS. By its very nature, the eye is highly exposed to ultraviolet radiation (UVR), which is directly responsible for increased OS. In this review, we aimed to focus on the retinal damage caused by ROS/RNS and the related retinal pathologies. A deeper understanding of the role of oxidative and nitrosative stress in retinal damage is needed in order to develop targeted therapeutic interventions to slow these pathologies.

Anti-inflammatory role of curcumin in retinal disorders (Review).

Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione], the main component of turmeric (Curcuma longa, a flowering plant of the ginger family, Zingiberaceae), is known to possess different pharmacological activities, particularly anti-inflammatory and antioxidant properties. Since an underlying inflammatory process exists in several ocular conditions, such as anterior uveitis, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), the aim of the present review was to summarize the pleiotropic effects exerted by this molecule, focusing in particular on its beneficial role in retinal diseases. The anti-inflammatory activity of curcumin has also been described in numerous systemic inflammatory pathologies and tumors. Specifically, the biological, pharmaceutical and nutraceutical properties of curcumin are associated with its ability to downregulate the expression of the following genes: IκBα, cyclooxygenase 2, prostaglandin E2, interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor-α. According to this finding, curcumin may be useful in the treatment of some retinal disorders. In DR, proliferative vitreoretinopathy and AMD, beneficial effects have been observed following treatment with curcumin, including slowing down of the inflammatory process. Despite the aforementioned evidence, the main disadvantage of this substance is that it possesses a low solubility, as well as poor oral bioavailability due to its reduced absorption, rapid metabolism and rapid elimination. Therefore, several curcumin analogues have been synthesized and tested over the years, in order to improve the possible obtainable therapeutic effects. The purpose of the present review was to identify new aspects that could guide future research on this important traditional medicine, which is a well-tolerated natural product, and is widely considered safe and economical.

Mesenchymal stem and non-stem cell surgery, rescue, and regeneration in glaucomatous optic neuropathy.

BACKGROUND: Glaucomatous optic neuropathy (GON) is an anatomofunctional impairment of the optic nerve triggered by glaucoma. Recently, growth factors (GFs) have been shown to produce retinal neuroenhancement. The suprachoroidal autograft of mesenchymal stem cells (MSCs) by the Limoli retinal restoration technique (LRRT) has proven to achieve retinal neuroenhancement by producing GF directly into the choroidal space. This retrospectively registered clinical study investigated the visual function changes in patients with GON treated with LRRT. METHODS: Twenty-five patients (35 eyes) with GON in progressive disease conditions were included in the study. Each patient underwent a comprehensive ocular examination, including the analysis of best corrected visual acuity (BCVA) for far and near visus, sensitivity by Maia microperimetry, and the study of the spectral domain-optical coherence tomography (SD-OCT). The patients were divided into two groups: a control group, consisting of 21 eyes (average age 72.2 years, range 50-83), and an LRRT group, consisting of 14 eyes (average age 67.4, range 50-84). RESULTS: After 6 months, the BCVA, close-up visus, and microperimetric sensitivity significantly improved in the LRRT-treated group (p<0.05), whereas the mean increases were not statistically significant in controls (p>0.5). CONCLUSIONS: Patients with GON treated with LRRT showed a significant increase in visual performance (VP) both in BCVA and sensitivity and an improvement of residual close-up visus, in the comparison between the LRRT results and the control group. Further studies will be needed to establish the actual significance of the reported findings.

Antioxidant and Biological Properties of Mesenchymal Cells Used for Therapy in Retinitis Pigmentosa.

Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenges in the field of ophthalmological research. Although this inherited retinal dystrophy is still an incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidence regarding the effectiveness of cell therapies in RP, especially those based on mesenchymal cells, and we focus on their therapeutic action: limitation of both oxidative stress and apoptotic processes triggered by the disease and promotion of cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP.

Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects.

PURPOSE: To assess whether treatment with the Limoli Retinal Restoration Technique (LRRT) can be performed in patients with retinitis pigmentosa (RP), grafting the autologous cells in a deep scleral pocket above the choroid of each eye to exert their beneficial effect on the residual retinal cells. METHODS: The patients were subjected to a complete ophthalmological examination, including best corrected visual acuity (BCVA), close-up visus measurements, spectral domain-optical coherence tomography (SD-OCT), microperimetry (MY), and electroretinography (ERG). Furthermore, the complete ophthalmological examination was carried out at baseline (T0) and at 6 months (T180) after surgery. The Shapiro-Wilk test was used to assess the normality of distribution of the investigated parameters. A mixed linear regression model was used to analyse the difference in all the studied parameters at T0 and T180, and to compare the mean change between the two groups. All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). RESULTS: LRRT treatment was performed in 34 eyes of 25 RP patients recruited for the study. The eyes were classified in two groups on the basis of foveal thickness (FT) assessed by SD-OCT: 14 eyes in Group A (FT≤190µm) and the remaining 20 ones in Group B (FT > 190µm). Although it had not reached the statistical significance, Group B showed a better improvement in BCVA, residual close-up visus and sensitivity than Group A. CONCLUSIONS: Previous studies have described the role of LRRT in slowing down retinal degenerative diseases. Consequently, this surgical procedure could improve the clinical and rehabilitative prognostic parameters in RP patients. On the other hand, further clinical research and studies with longer follow-up will be needed to evaluate its efficacy.

Abnormal stereopsis and reduced retinal sensitivity in patients with retinitis pigmentosa.

PURPOSE: The aim of the study was to evaluate retinal sensitivity and stereoacuity (SA) in retinitis pigmentosa (RP) patients. METHODS: Twenty-six patients with RP were examined, mean age 36.4 ± 7.21 (SD) years old and best corrected visual acuity better than 0.15 logMAR. The control group (CG) included 25 healthy subjects matching the RP group by age and sex. Every patient and healthy control underwent a complete ophthalmologic examination: Titmus, Lang, TNO stereotests and microperimetry (MP-1) (Nidek Technologies). Results were subjected to factor analysis using Varimax rotation, and p values < 0.05 were considered statistically significant. RESULTS: With the Titmus stereotest, the mean SA was 136.52 ± 26.5 (SD) arcsec in the RP group and 67.2 ± 11.5 (SD) in CG; Lang SA was 391.39 ± 53.72 (SD) in RP group and 1150 ± 33.4 (SD) in CG; and TNO SA was 69.3 ± 14.39 (SD) in the RP group and 15.97 ± 3.7 (SD) in CG. Factor analysis showed significant correlation between visual acuity and SA (p = 0.0001) in RP group. MP-1 demonstrated that in RP patients, inter-ocular difference in retinal sensitivity and fixation stability was related to anomalous stereopsis (p values < 0.05). CONCLUSION: Progressive RP degeneration in the cone system could determine a significant impairment in the binocular vision due to anomalous inter-ocular retinal sensitivity and incomplete Panum's area utilization, causing an incongruent retinal localization. These findings suggest a possible reason why RP patients with a central retinal involvement, even if minimal, perceive a damaged stereoscopic perception that produces a severe disability.

Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review.

To evaluate whether grafting of autologous mesenchymal cells, adipose-derived stem cells, and platelet-rich plasma into the supracoroideal space by surgical treatment with the Limoli retinal restoration technique (LRRT) can exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and were divided based on retinal foveal thickness (FT) ≤ 190 or > 190 µm into group A-FT and group B-FT, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed a non-significant improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of retinitis pigmentosa (RP), it was concluded that further research is needed on tapeto-retinal degenerations, both from a clinical and molecular point of view, to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation timeframes, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

Therapeutic Approaches with Intravitreal Injections in Geographic Atrophy Secondary to Age-Related Macular Degeneration: Current Drugs and Potential Molecules.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy.

Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report.

This study is aimed at examining whether a suprachoroidal graft of autologous cells can improve best corrected visual acuity (BCVA) and responses to microperimetry (MY) in eyes affected by dry Age-related Macular Degeneration (AMD) over time through the production and secretion of growth factors (GFs) on surrounding tissue. Patients were randomly assigned to each study group. All patients were diagnosed with dry AMD and with BCVA equal to or greater than 1 logarithm of the minimum angle of resolution (logMAR). A suprachoroidal autologous graft by Limoli Retinal Restoration Technique (LRRT) was carried out on group A, which included 11 eyes from 11 patients. The technique was performed by implanting adipocytes, adipose-derived stem cells obtained from the stromal vascular fraction, and platelets from platelet-rich plasma in the suprachoroidal space. Conversely, group B, including 14 eyes of 14 patients, was used as a control group. For each patient, diagnosis was verified by confocal scanning laser ophthalmoscope and spectral domain-optical coherence tomography (SD-OCT). In group A, BCVA improved by 0.581 to 0.504 at 90 days and to 0.376 logMAR at 180 days (+32.20%) postoperatively. Furthermore, MY test increased by 11.44 dB to 12.59 dB at 180 days. The different cell types grafted behind the choroid were able to ensure constant GF secretion in the choroidal flow. Consequently, the results indicate that visual acuity (VA) in the grafted group can increase more than in the control group after six months.

Visual field improvement in non-arteritic posterior ischemic optic neuropathy in a patient treated with intravenous prostaglandin E1 and steroids.

Non-arteritic posterior ischemic optic neuropathy (NA-PION) is a disorder of reduced blood flow to the retrobulbar optic nerve. There is usually an acute loss of visual acuity and field. Previous studies have noted an improvement in visual acuity and in ocular and retrobulbar blood flow with the use of a potent vasodilator of the microcirculation, prostaglandin E1 (PGE1), and steroids. The current report describes immediate improvement in the visual fields and visual acuity in a patient with NA-PION treated with intravenous PGE1 and steroids 66 hours after onset. An 89-year-old white female was first seen in December 2016 with a sudden loss of vision in the right eye. After a complete eye exam and visual fields, the patient was diagnosed with NA-PION. Treatment was immediately started with steroids and intravenous PGE1. This was repeated once again the next morning. Visual acuity in the right eye improved from 1/10 + 1 to 7/10 + 3 at 5 days. The mean deviation of the visual field improved from - 7.10 decibels (dB) with a central scotoma of - 22 dB to - 2.97 dB with a central scotoma of - 19 dB. After 2 weeks, her visual acuity was 7/10 + 1 and visual field testing of the right eye revealed a mean deviation of - 2.54 dB with a central scotoma of - 9 dB. The left eye was unchanged. In cases of NA-PION, PGE1 and steroids should be considered to immediately restore blood flow to help improve visual acuity and visual fields.

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study.

BACKGROUND: The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. RESULTS: 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. METHODS: Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (µm) and group B with RTA equal to or more than 250 µm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). CONCLUSIONS: The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity.

Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration.

Evolving atrophic macular degeneration represents at least 80% of all macular degenerations and is currently without a standardized care. Autologous fat transplantation efficacy was demonstrated by several studies, as these cells are able to produce growth factors. The aim of the work was to demonstrate possible therapeutic effect of the joined suprachoroidal graft of adipocytes, adipose-derived stem cells (ADSCs) in stromal vascular fractions (SVFs) of adipose tissue, and platelet-rich plasma (PRP). Twelve eyes in 12 dry age-related macular degeneration (AMD) patients, aged 71.25 (SD ± 6.8) between 62 and 80 years, were analyzed. A complete ocular evaluation was performed using best corrected visual acuity (BCVA), retinographic analysis, spectral-domain optical coherence tomography, microperimetry, computerized visual field, and standard electroretinogram (ERG). Each eye received a cell in graft between choroid and sclera of mature fat cells and ADSCs in SVF enriched with PRP by means of the variant second Limoli (Limoli retinal restoration technique [LRRT]). In order to test if the differences pre- and post-treatment were significant, the Wilcoxon signed-rank test has been performed. Adverse effects were not reported in the patients. After surgery with LRRT, the most significant increase in the ERG values was recorded by scotopic rod-ERG (answer coming from the rods), from 41.26 to 60.83 µV with an average increase of 47.44% highly significant (P < 0.05). Moderately significant was the one recorded by scotopic maximal ERG (answer coming from the rods and cones), from 112.22 to 129.68 µV with an average increase of 15.56% (P < 0.1). Cell-mediated therapy based on growth factors used appears interesting because it can improve the retinal functionality responses in the short term. The ERG could, therefore, be used to monitor the effect of cell-mediated regenerative therapies.