Retinitis Pigmentosa: From Pathomolecular Mechanisms to Therapeutic Strategies.

Retinitis pigmentosa is an inherited disease, in which mutations in different types of genes lead to the death of photoreceptors and the loss of visual function. Although retinitis pigmentosa is the most common type of inherited retinal dystrophy, a clear line of therapy has not yet been defined. In this review, we will focus on the therapeutic aspect and attempt to define the advantages and disadvantages of the protocols of different therapies. The role of some therapies, such as antioxidant agents or gene therapy, has been established for years now. Many clinical trials on different genes and mutations causing RP have been conducted, and the approval of voretigene nepavorec by the FDA has been an important step forward. Nonetheless, even if gene therapy is the most promising type of treatment for these patients, other innovative strategies, such as stem cell transplantation or hyperbaric oxygen therapy, have been shown to be safe and improve visual quality during clinical trials. The treatment of this disease remains a challenge, to which we hope to find a solution as soon as possible.

Gene Therapy in Hereditary Retinal Dystrophies: The Usefulness of Diagnostic Tools in Candidate Patient Selections.

PURPOSE: Gene therapy actually seems to have promising results in the treatment of Leber Congenital Amaurosis and some different inherited retinal diseases (IRDs); the primary goal of this strategy is to change gene defects with a wild-type gene without defects in a DNA sequence to achieve partial recovery of the photoreceptor function and, consequently, partially restore lost retinal functions. This approach led to the introduction of a new drug (voretigene neparvovec-rzyl) for replacement of the RPE65 gene in patients affected by Leber Congenital Amaurosis (LCA); however, the treatment results are inconstant and with variable long-lasting effects due to a lack of correctly evaluating the anatomical and functional conditions of residual photoreceptors. These variabilities may also be related to host immunoreactive reactions towards the Adenovirus-associated vector. A broad spectrum of retinal dystrophies frequently generates doubt as to whether the disease or the patient is a good candidate for a successful gene treatment, because, very often, different diseases share similar genetic characteristics, causing an inconstant genotype/phenotype correlation between clinical characteristics also within the same family. For example, mutations on the RPE65 gene cause Leber Congenital Amaurosis (LCA) but also some forms of Retinitis Pigmentosa (RP), Bardet Biedl Syndrome (BBS), Congenital Stationary Night Blindness (CSNB) and Usher syndrome (USH), with a very wide spectrum of clinical manifestations. These confusing elements are due to the different pathways in which the product protein (retinoid isomer-hydrolase) is involved and, consequently, the overlapping metabolism in retinal function. Considering this point and the cost of the drug (over USD one hundred thousand), it would be mandatory to follow guidelines or algorithms to assess the best-fitting disease and candidate patients to maximize the output. Unfortunately, at the moment, there are no suggestions regarding who to treat with gene therapy. Moreover, gene therapy might be helpful in other forms of inherited retinal dystrophies, with more frequent incidence of the disease and better functional conditions (actually, gene therapy is proposed only for patients with poor vision, considering possible side effects due to the treatment procedures), in which this approach leads to better function and, hopefully, visual restoration. But, in this view, who might be a disease candidate or patient to undergo gene therapy, in relationship to the onset of clinical trials for several different forms of IRD? Further, what is the gold standard for tests able to correctly select the patient? Our work aims to evaluate clinical considerations on instrumental morphofunctional tests to assess candidate subjects for treatment and correlate them with clinical and genetic defect analysis that, often, is not correspondent. We try to define which parameters are an essential and indispensable part of the clinical rationale to select patients with IRDs for gene therapy. This review will describe a series of models used to characterize retinal morphology and function from tests, such as optical coherence tomography (OCT) and electrophysiological evaluation (ERG), and its evaluation as a primary outcome in clinical trials. A secondary aim is to propose an ancillary clinical classification of IRDs and their accessibility based on gene therapy's current state of the art. MATERIAL AND METHODS: OCT, ERG, and visual field examinations were performed in different forms of IRDs, classified based on clinical and retinal conditions; compared to the gene defect classification, we utilized a diagnostic algorithm for the clinical classification based on morphofunctional information of the retina of patients, which could significantly improve diagnostic accuracy and, consequently, help the ophthalmologist to make a correct diagnosis to achieve optimal clinical results. These considerations are very helpful in selecting IRD patients who might respond to gene therapy with possible therapeutic success and filter out those in which treatment has a lower chance or no chance of positive results due to bad retinal conditions, avoiding time-consuming patient management with unsatisfactory results.

Visuo-Acoustic Stimulation's Role in Synaptic Plasticity: A Review of the Literature.

Brain plasticity is the capacity of cerebral neurons to change, structurally and functionally, in response to experiences. This is an essential property underlying the maturation of sensory functions, learning and memory processes, and brain repair in response to the occurrence of diseases and trauma. In this field, the visual system emerges as a paradigmatic research model, both for basic research studies and for translational investigations. The auditory system remains capable of reorganizing itself in response to different auditory stimulations or sensory organ modification. Acoustic biofeedback training can be an effective way to train patients with the central scotoma, who have poor fixation stability and poor visual acuity, in order to bring fixation on an eccentrical and healthy area of the retina: a pseudofovea. This review article is focused on the cellular and molecular mechanisms underlying retinal sensitivity changes and visual and auditory system plasticity.

Update on Gene Therapy Clinical Trials for Choroideremia and Potential Experimental Therapies.

Background and objectives: Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations involving the CHM gene. Gene therapy has entered late-phase clinical trials, although there have been variable results. This review gives a summary on the outcomes of phase I/II CHM gene therapy trials and describes other potential experimental therapies. Materials and Methods: A Medline (National Library of Medicine, Bethesda, MD, USA) search was performed to identify all articles describing gene therapy treatments available for CHM. Results: Five phase I/II clinical trials that reported subretinal injection of adeno-associated virus Rab escort protein 1 (AAV2.REP1) vector in CHM patients were included. The Oxford study (NCT01461213) included 14 patients; a median gain of 5.5 ± 6.8 SD (-6 min, 18 max) early treatment diabetic retinopathy study (ETDRS) letters was reported. The Tubingen study (NCT02671539) included six patients; only one patient had an improvement of 17 ETDRS letters. The Alberta study (NCT02077361) enrolled six patients, and it reported a minimal vision change, except for one patient who gained 15 ETDRS letters. Six patients were enrolled in the Miami trial (NCT02553135), which reported a median gain of 2 ± 4 SD (-1 min, 10 max) ETDRS letters. The Philadelphia study (NCT02341807) included 10 patients; best corrected visual acuity (BCVA) returned to baseline in all by one-year follow-up, but one patient had -17 ETDRS letters from baseline. Overall, 40 patients were enrolled in trials, and 34 had 2 years of follow-up, with a median gain of 1.5 ± 7.2 SD (-14 min, 18 max) in ETDRS letters. Conclusions: The primary endpoint, BCVA following gene therapy in CHM, showed a marginal improvement with variability between trials. Optimizing surgical technique and pre-, peri-, and post-operative management with immunosuppressants to minimize any adverse ocular inflammatory events could lead to reduced incidence of complications. The ideal therapeutic window needs to be addressed to ensure that the necessary cell types are adequately transduced, minimizing viral toxicity, to prolong long-term transgenic potential. Long-term efficacy will be addressed by ongoing studies.

Role of CD 20+ T cells and related cytokines in mediating retinal microvascular changes and ocular complications in chronic-plaque type psoriasis.

OBJECTIVE: To assess the role of CD3+ CD20+ CD4- CD8- double-negative (DN) or CD3+CD20+ CD4/CD8+ T cells and the related pro-inflammatory cytokines in the humor aqueous, in mediating retinal microvascular changes in patients with chronic plaque-type moderate to severe psoriasis. DESIGN: A total of 76 patients (57.6 ± 11.7 years) with chronic plaque-type psoriasis were initially evaluated. Nineteen patients (19 eyes) and 19 healthy volunteers (19 eyes) were subjected to dermatological evaluation with Psoriasis Area Severity Index (PASI) and the Dermatology life quality index (DLQI). Retinal images were processed using an automatized software. On the same day, a venous sample was collected and analyzed using multiparametric flow cytometry. Three out of 6 patients who presented cataract, consented to perform surgery with humor aqueous collection. The samples were analyzed using a Multi-Analyte ELISA kit for the simultaneous quantification of IL1α, IL1ß, IL2, IL4, IL6, IL8, IL10, IL12, IL17A, IFNγ, TNF-α, GMCSF. RESULTS: The CD3+CD4+/CD8+CD20+CD56- T cells expression was greater in the psoriatic patients (+73.9%, P < 0.001) compared to controls, but not the DN T cells (-8.2%, P = 0.30). Ocular complications were diagnosed in 61.1% of patients, microvascular parameters including artero-venous ratio (P = 0.04), subfoveal choriocapillaris/Sattler's layer, and choroidal thickness (CT, both P < 0.001) were significantly altered in psoriasis subgroup. The increased circulating levels of the CD3+CD4+/CD8+CD20+CD56- T cells were associated with thinning of subfoveal CT (P = 0.03) and Haller's layer (P = 0.01). Instead, the DN T cells presented an inverse relationship with disease duration (P = 0.02), DLQI score (P = 0.02), and the use of biological therapy (P = 0.05). The related cytokine patterns possibly modified in this cellular context have been investigated. No significant differences were observed in cytokines levels between psoriasis and controls, the most significant difference was detected on IL-6, without reaching statistical significance (fold change of 1.4, P = 0.13). CONCLUSION: Our findings demonstrated that CD20+ T cell subpopulation is highly represented in psoriasis regardless of the use of immunomodulatory therapies, and the diffuse microvascular alterations suggested possible endothelial damage as mainstream for the genesis of psoriatic-mediated complications as further supported by the comparable concentrations of cytokines, at least as humor aqueous content, with respect to healthy eyes.

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.

Vitreo-macular interface disorders in retinitis pigmentosa.

PURPOSE: To investigate the prevalence and progression of vitreo-macular interface disorders (VMID) phenotypes and their natural history in retinitis pigmentosa (RP). METHODS: A total of 257 eyes of 145 RP patients with VMID were retrospectively evaluated. Patients were divided according to the VMID subtypes into epiretinal membranes (ERMs), vitreo-macular traction (VMT) group, and macular hole (MH). Serial eye-tracked spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA) changes were analyzed for a mean follow-up of 36.95 months. The status of posterior vitreous cortex was also considered. A control group of 65 eyes belonging to 65 RP patients with no macular changes was also recruited. RESULTS: VMID and control groups had the same baseline BCVA (0.50 vs 0.44 LogMAR) and did not differ in terms of phakic status. Different VMID groups had similar BCVA at baseline (p = 0.98). ERM represented the most prevalent disorder (207/257 eyes, 80.5%), followed by 35/257 (13.6%) VMT, and 15/257 Lamellar MH (LMH) eyes (5.8%). There were no cases of full thickness MH. Throughout the 36.9 months of follow-up, BCVA decreased an average 0.09 LogMAR from 0.31 to 0.4 in VMID patients and 0.01 in controls. VMID subgroup analysis showed a significant BCVA decrease in ERM patients (- 20.29%, p < 0.001), while VMT and LMH did not change significantly. Foveal thickness also remained stable over time. Complete PVD was present in 11 eyes in ERM, VMT, and LMH. CONCLUSIONS: Our study confirms the high prevalence of VMID in RP patients; however, only ERMs determined a significant loss of vision over 24 months. The high prevalence of VMID in RP patients suggests that macular alteration other than edema represents part of disease spectrum.

Factors Influencing Fixation Stability Area: A Comparison of Two Methods of Recording.

SIGNIFICANCE: The authors analyze factors influencing bivariate contour ellipse area (BCEA) in healthy and pathologic eyes and how such factors may affect isolated (static BCEA) or microperimetric fixation (dynamic BCEA). They conclude that aging increases both dynamic BCEA and examination time, whereas static BCEA offers less variance and the maximum distinction with pathologic eyes. PURPOSE: The aim of this study was to assess factors influencing BCEA and the recording method that offer less variability and thus maximum distinction between healthy and pathologic eyes. METHODS: A total of 136 eyes were retrospectively reviewed, 85 eyes without ophthalmic disorders (logMAR acuity ≦0.0) and 51 eyes with late age-related macular degeneration (AMD) were enrolled. All patients underwent two consecutive examinations, a 30-second isolated fixation (static BCEA) and a microperimetric test with continuous fixation recording (dynamic BCEA). All the examinations were carried out using MP1 microperimeter (NAVIS software version 1.7.6; Nidek Technologies, Padova, Italy). RESULTS: Dynamic BCEA was significantly correlated with age (r = 0.38, P < .001), total (r = 0.32, P = .03), and tracking time (r = 0.33, P = .02) in controls, whereas no significant relationships were found in the AMD group. The greatest difference between static and dynamic BCEA was observed in 70- to 79-year decade in healthy subjects (P < .01). Logistic regression analysis showed that late AMD status was significantly predicted by ±2 SD and ±3 SD static BCEA (both P = .03). CONCLUSIONS: Dynamic BCEA is influenced by a certain degree of variability in advanced-age healthy subjects. In such cases, the use of ±2 SD and ±3 SD static BCEAs seems to offer a more accurate detection of fixation stability changes in the AMD group with respect to normal subjects.

The face of Ebola: changing frequency of haemorrhage in the West African compared with Eastern-Central African outbreaks.

BACKGROUND: The West-African (WA) Zaire Ebolavirus disease (EVD) outbreak was characterized by an exceptionally high number of cases and deaths as compared with the Eastern-Central African (ECA) outbreaks. Despite the Zaire Ebolavirus being the most lethal for humans, case-fatality rate, close to 80 % in ECA outbreaks, almost halved to 47 % in Guinea-Liberia-Sierra Leone (WA). Such an improvement was due to the remarkable implementation of international humanitarian aids. Some studies also suggested that the long human-to-human transmission cycle occurred in WA, gave rise to human adaptation and consequent immune escape. Haemorrhage, the main feature in seriously infected EVD patients, is due to the immune system that triggers the infected endothelial cells which expose the spike-like glycoprotein (GP) of the virion on their surface. If the human adaptation hypothesis holds true, the proportion of EVD patients with haemorrhage in the WA outbreak should be lower than in the ECA outbreaks due to immune escape. Therefore, the aim of this meta-analysis was to compare the relative frequencies of three typical haemorrhagic symptoms (conjunctival -CB, nasal -NB, gingival -GB- bleedings) in the ECA and WA outbreaks. METHODS: Literature searches were performed through PubMed and Scopus using generic keywords; surveys including at least ten patients reporting CB, NB, GB relative frequencies were extracted and split into ECA and WA. The meta-analytical methods chosen were based on the levels of between-study heterogeneity and publication bias. Pooled CB, NB, GB relative frequencies in ECA and WA were estimated and compared. Subgroup analysis including only studies on Zaire Ebolavirus also was performed. RESULTS: Fifteen studies (10 ECA, 5 WA) were located with 4,867 (CB), 3,859 (NB), 4,278 (GB) EVD patients overall. GB pooled relative frequency was 45.3 % (95 % confidence interval -95 CI, 34.7-56.1 %) and 18.0 % (95 CI, 6.0-34.5 %), in ECA and WA; NB was 10.6 % (95 CI, 5.7-16.8 %) and 1.3 % (1.0-1.8 %); GB was 24.2 % (95 CI, 11.9-39.2 %) and 1.9 % (95 CI, 1.4-2.4 %). Subgroup analysis confirmed these results. CONCLUSIONS: During the WA outbreak the relative frequency of GB decreased by two thirds, while NB and GB almost disappeared, suggesting that the Zaire Ebolavirus human adaptation hypothesis is plausible.

Corneal collagen cross-linking followed by phacoemulsification with IOL implantation for progressive keratoconus associated with high myopia and cataract.

PURPOSE: To evaluate the visual and topographic outcomes of a two-stage approach treatment for progressive keratoconus (KC) associated with high myopia and cataract. METHODS: Two patients, a 50-year-old man and a 54-year-old woman with high myopia (spherical equivalent greater than -10D), cataract, and progressive KC with poor spectacle-corrected vision and contact lens intolerance underwent a 2-stage approach treatment: first corneal collagen cross-linking (CXL) followed after at least 6 months by phacoemulsification with intraocular lens (IOL) implantation in both eyes. RESULTS: In both patients after a mean follow-up of 3.5 years (from 2 to 4) uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and corneal topography pattern improved in both eyes, and the patients were satisfied with the visual improvement and happy with tolerable glasses. CONCLUSION: This 2-stage approach reported no complications and was effective in improving visual acuity and corneal patterns in patients with high myopia, cataract, and progressive KC.

Corneal sensitivity in keratoconus: a review of the literature.

Corneal sensitivity has recently received much attention given the crucial role the corneal nerves play in maintaining normal corneal structure and function. An increased understanding of the corneal sensitivity and dry eye disease in keratoconus, including alterations of the conjunctival cells, may help explain the pathogenesis of this disorder. There is histological evidence of the involvement of corneal nerves in the pathology of keratoconus and it has been suggested that this plays a role in the pathophysiological features and progression of the disease. In this review, the impaired corneal sensitivity found on keratoconus and corneal sensitivity changes after cross-linking performed in patients with keratoconus are reported.

A standardized laboratory and surgical method for in vitro culture isolation and expansion of primary human Tenon's fibroblasts.

Good manufacturing practices guidelines require safer and standardized cell substrates especially for those cell therapy products to treat ocular diseases where fibroblasts are used as feeder layers. However, if these are unavailable for stem cells culturing, murine fibroblasts are regularly used, raising critical issues as accidentally transplanting xenogenous graft and adversely affecting stem cell clinical trials. Moreover, human fibroblasts play a significant role in testing novel ophthalmologic drugs. Accordingly, we developed a standardized laboratory and surgical approach to isolate normal and undamaged Tenon's fibroblasts to implement the setting up of banks for both stem cells-based ocular cell therapy and in vitro drug testing. A 2-3 cm(2) undamaged Tenon's biopsy was surgically obtained from 28 patients without mutually correlated ocular diseases. Nineteen dermal biopsies were used as control. Fibroblasts were isolated with or without collagenase, cultured in autologous, fetal bovine or AB serum, tested for viability by trypan blue, vimentin expression and standardized until passage 6. Successful Tenon's fibroblasts isolation was age dependent (P = 0.001) but not sex, pathology or surgery related. A significant rate of successful cultures were obtained when biopsies were not digested by collagenase (P = 0.013). Moreover, cultures in autologous or fetal bovine serum had comparable proliferative properties (P = 0.77; P = 0.82). Through our surgical and laboratory standardized procedure, we elucidated for the first time key points of this human primary culture system, the role of the autologous serum, comparing Tenon's and dermal fibroblasts. Our protocol may be clinically useful to reduce the risk above mentioned and may be potentially more effective for ophthalmological clinical purposes.

Identifying Meibomian Gland Dysfunction Biomarkers in a Cohort of Patients Affected by DM Type II.

(1) Background: Meibomian gland dysfunction (MGD) among patients with diabetes mellitus (DM) is a common manifestation of dry eye syndrome (DES). (2) Methods: The purpose of this study is to identify clinical parameters and biomarkers useful to improve the follow-up and the treatment of these patients. We have used an ocular surface disease index (OSDI) questionnaire, Schirmer test I/II, tear film break-up time (TF-BUT), fluorescein plus lissamine green staining, Marx's line (ML), and meibomian gland (MGs) morphology using Sirius® Topographer (CSO, Costruzione Strumenti Oftalmici, Florence, Italy). Blood sample analysis included glucose, glycated hemoglobin, lipid profile, cortisol, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (ASD) and testosterone. (3) Results: Cortisol and ASD were positively correlated with an increase of MG tortuosity, and an Increased level of triglycerides was associated with a reduction of MGs length. DHEAS levels lowered with age and were associated with ocular surface staining. (4) Conclusions: Future studies, perhaps including meibum lipid analysis and tear cytokine levels, may also further elucidate the connection between these parameters, MG architecture and function.

Potential Role of Biofeedback Visual Training in High-Speed Motorbike Drivers.

Purpose: In several sports, appropriate training strategies remain a challenge for athletes and coaches, with the goal of improving performance. Extensive research has proposed several technical tools for obtaining parametric evaluations before competition in real life. This study aimed to assess whether some retinal performances might be improved using psychophysical techniques in health professionals involved in motorcycle sports (FIM MotoE). Methods: Two MotoE drivers were screened at baseline using complete ophthalmological examinations and evaluation of retinal reaction times, followed by a biofeedback training program. After 4 months of training, the subjects underwent a control visit using the same protocol as the baseline. Results: Central reaction time was shorter for 75% of drivers, with a consistent reduction (mean value of 20%). The peripheral reaction time showed an increasing trend after visual training. In both drivers, fixation stability improved dramatically (in 30% increments). Conclusion: The potential role of advanced technology was applied to high-speed drivers. Our results may be due to an attentional shift from the peripheral retina to the central retina during training. In our opinion, training potentiates the most useful pathways at the expense of less involved retinal and cortical areas, thus improving driving abilities and safety.

COVID-19 Vaccines in Inherited Retinal Degenerations (IRD), Fears, Ideas and Real Interactions.

Purpose: In the COVID-19 pandemic era, vaccines are one of the most efficient weapons, as well established by WHO, that humans have, in all their variants (mRNA, AAV or others). Unfortunately, in western nations skepticism within different groups has been generated by the fast approval processes, driven by the urgent need to confront the rapid increase of hospitalized patients and number of deaths by regulation authorities as FDA and EMA. Moreover, several scientific and non-scientific perplexity, also amplified by the media, created hard no-vax strategies, that lead many patients to refuse vaccine administration. Also in this selected population higher rate of COVID-19 infections and severe diseases are registered and consequently there was an increase of death number. Furthermore, to avoid vaccine shots, people frequently ask exemption querying ophthalmological and systemic diseases, in this situation most patients affected with orphan ophthalmological conditions as inherited retinal degenerations have profound fears and doubt. The goal of our study was to ascertain if these fears are based on real facts and if there are interactions or severe visual impairment after each shot of vaccinations. Methods: Five hundred randomically selected patients affected by IRD at each patient was asked anonymously, number of vaccine administrations and eventually reported side effects. Results: Of 500 selected patients 61 (12,2%) did not underwent to Covid-19 vaccination, reasons were various (fear, laziness, caregiver unavailability etc.). Remaining 439 patients (87,8%) had first shot of vaccine. Only 30% of patients complained side effects of vaccine, none of them was serious. Conclusion: The number of patients is wide enough to draw some considerations: In IRD vaccination is safe, in all doses ocular side effects were reported only in one third of subjects and this is not different from the percentage shown by normal people, COVID-19 effects may be more dangerous than vaccine.

WAMD: From Pathophysiology to Therapeutic Treatments.

Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life [...].

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.

New insight into visual function with aspherical intraocular lenses (IOLs): Tecnis ZCB00 and Acrysof SN60WF.

In this study, we investigated the visual performance of two aspherical intraocular lenses (IOLs), Tecnis ZCB00 and Acrysof SN60WF, by measuring high-order aberration, visual evoked potentials (VEP), retinal sensitivity, and fixation stability by MP-1 microperimetry and contrast sensitivity values. Twenty-two patients with age-related cataract were randomly allocated to either the Tecnis or the Acrysof group. All measurements were taken from patients of both groups 2 months postoperatively. Statistical analysis was performed with Student's t test, where P-values < 0.05 were considered significant. Results were not statistically significant with regard to high-order aberration, VEP, retinal sensitivity, and fixation stability. However, the contrast sensitivity values varied significantly between Tecnis ZCB00 and Acrysof SN60WF, with Tecnis ZCB00 performing better. The anterior aspherical surface design of the Tecnis IOL indicated better mesopic contrast sensitivity at mediate and high frequencies, ensuring a better quality of vision after cataract surgery.

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.