Uveoscleral Outflow Routes after MicroPulse Laser Therapy for Refractory Glaucoma: An Optical Coherence Tomography Study of the Sclera.

To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography (AS-OCT). Forty-two candidate patients for MP-TLT were consecutively enrolled and underwent AS-OCT at baseline and after six months. MP-TLT success was defined as an intraocular pressure (IOP) reduction by one-third. The main outcome measures were the mean superior (S-), inferior (I-), and total (T-) intra-scleral hypo-reflective space area (MISHA: mm2) and scleral reflectivity (S-SR, I-SR, T-SR; arbitrary scale) as in vivo biomarkers of uveoscleral aqueous humor (AH) outflow. The IOP was the secondary outcome. The relations between the baseline-to-six months differences (D) of DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, DT-SR, and DIOP, were investigated. At 6 months, the median IOP reduction was 21% in the failures and 38% in the successes. The baseline S-MISHA, I-MISHA, and T-MISHA did not differ between the groups, while S-SR and T-SR were higher in the successes (p < 0.05). At six months, successful and failed MP-TLTs showed a 50% increase in S-MISHA (p < 0.001; p = 0.037), whereas I-SR and T-SR reduced only in the successes (p = 0.002; p = 0.001). When comparing DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, and DT-SR, there were no significant differences between the groups. In the successful procedures, DIOP was positively correlated with DT-MISHA and DI-MISHA (ρ = 0.438 and ρ = 0.490; p < 0.05). MP-TLT produced potentially advantageous modifications of the sclera in refractory glaucoma. Given the partial correlation between these modifications and post-treatment IOP reduction, our study confirmed that the activation of the uveoscleral AH outflow route could significantly contribute to the IOP lowering after MP-TLT.

A deep learning approach to investigate the filtration bleb functionality after glaucoma surgery: a preliminary study.

PURPOSE: To distinguish functioning from failed filtration blebs (FBs) implementing a deep learning (DL) model on slit-lamp images. METHODS: Retrospective, cross-sectional, multicenter study for development and validation of an artificial intelligence classification algorithm. The dataset consisted of 119 post-trabeculectomy FB images of whom we were aware of the surgical outcome. The ground truth labels were annotated and images splitted into three outcome classes: complete (C) or qualified success (Q), and failure (F). Images were prepared implementing various data cleaning and data transformations techniques. A set of DL models were trained using different ResNet architectures as the backbone. Transfer and ensemble learning were then applied to obtain a final combined model. Accuracy, sensitivity, specificity, area under the ROC curve, and area under the precision-recall curve were calculated to evaluate the final model. Kappa coefficient and P value on the accuracy measure were used to prove the statistical significance level. RESULTS: The DL approach reached good results in unraveling FB functionality. Overall, the model accuracy reached a score of 74%, with a sensitivity of 74% and a specificity of 87%. The area under the ROC curve was 0.8, whereas the area under the precision-recall curve was 0.74. The P value was equal to 0.00307, and the Kappa coefficient was 0.58. CONCLUSIONS: All considered metrics supported that the final DL model was able to discriminate functioning from failed FBs, with good accuracy. This approach could support clinicians in the patients' management after glaucoma surgery in absence of adjunctive clinical data.

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.

Managing the ocular surface after glaucoma filtration surgery: an orphan topic.

BACKGROUND: Ocular surface (OS) disorders before glaucoma filtration surgery (GFS) have been considered to play a crucial role influencing the surgical outcome. Conversely, the impact of surgery itself on the OS is almost completely overlooked, though evidence suggest that ocular surface disease (OSD) may be induced in patients by GFS. This review analyzes the determinants involved in the OSD development after GFS, the clinical features and related consequences, the main diagnostic hallmarks, as well as the therapeutic strategies for its management. METHODS: The PubMed database was utilized for the literature examination. Keywords that were searched included ocular surface disease, glaucoma filtration surgery, filtration bleb, post-surgical management, and quality of life. RESULTS: After GFS, OSD is promoted by peri- and post-operative factors, such as the filtration bleb (FB) development, combined surgical approach with phacoemulsification, the use of antifibrotic agents and the reintroduction of antiglaucoma medications. This particular form of OSD that present similar clinical features to mild to moderate dry eye, can be named as post-glaucoma surgery-OSD (PGS-OSD). PGS-OSD may negatively affect the FB functionality, thus potentially hindering the disease control, and significantly worsen the patient quality of life (QOL). CONCLUSIONS: Clinicians are encouraged to routinely include the OS evaluation after GFS and to consider proper management when the occurrence of PGS-OSD worsen the patient's QOL or exert negative effects to the FB functionality. An outline summarizing the main risk factors and the most appropriate therapeutic options to mitigate the PGS-OSD was proposed to support the routine practice.

A machine learning approach to predict the glaucoma filtration surgery outcome.

This study aimed at predicting the filtration surgery (FS) outcome using a machine learning (ML) approach. 102 glaucomatous patients undergoing FS were enrolled and underwent ocular surface clinical tests (OSCTs), determination of surgical site-related biometric parameters (SSPs) and conjunctival vascularization. Break-up-time, Schirmer test I, corneal fluorescein staining, Meibomian gland expressibility; conjunctival hyperemia, upper bulbar conjunctiva area of exposure, limbus to superior eyelid distance; and conjunctival epithelial and stromal (CET, CST) thickness and reflectivity (ECR, SCR) at AS-OCT were considered. Successful FS required a 30% baseline intraocular pressure reduction, with values ≤ 18 mmHg with or without medications. The classification tree (CT) was the ML algorithm used to analyze data. At the twelfth month, FS was successful in 60.8% of cases, whereas failed in 39.2%. At the variable importance ranking, CST and SCR were the predictors with the greater relative importance to the CART tree construction, followed by age. CET and ECR showed less relative importance, whereas OSCTs and SSPs were not important features. Within the CT, CST turned out the most important variable for discriminating success from failure, followed by SCR and age, with cut-off values of 75 µm, 169 on gray scale, and 62 years, respectively. The ROC curve for the classifier showed an AUC of 0.784 (0.692-0.860). In this ML approach, CT analysis found that conjunctival stroma thickness and reflectivity, along with age, can predict the FS outcome with good accuracy. A pre-operative thick and hyper-reflective stroma, and a younger age increase the risk of FS failure.

Expert consensus on the management of patients undergoing cataract surgery: A Delphi study.

PURPOSE: To define the management of patients undergoing cataract surgery. SETTING: Panel of experts on cataract surgery and members of the Italian Association of Cataract and Refractive Surgery (AICCER) participated in the Delphi study. DESIGN: A restricted panel of experts defined the statements concerning the topic and identified a larger panel of experts who voted the statements. The statements concerned a series of practical issues concerning the management of patients undergoing cataract surgery. METHODS: An initial web round-table served to develop the statements. The larger panel was constituted by 15 experts which anonymously voted the statements, presented in a web platform, using a 5- point Likert scale. Consensus was defined as at least 80% of agreement. RESULTS: All participants completed the questionnaire. Globally, the total percentage of agreement of all statements was 90.4%. The total mean score was 4.5. Score 4 and score 5 accounted for the 27% and the 68% of the total votes, respectively. CONCLUSIONS: The participants felt they could largely agree with and approve the statements proposed by the board. In addition, the Delphi study identified some points that are highly shared and endorsed. In particular, a new model approach can be based on a seven-day course using a fixed high-potency corticosteroid combination with a broad-spectrum antibiotic. At the end of this cycle, the patient should be re-evaluated in some way to continue any treatment in the most appropriate and personalized way possible.

Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning - The 2022 Ophthalmologica Lecture.

Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the "postreceptor neuronal loss" theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber's hereditary optic neuropathy.

The Effect of Varied Microperimetric Biofeedback Training in Central Vision Loss: A Randomized Trial.

SIGNIFICANCE: This investigation reports for the first time the effects of different microperimetric biofeedback strategies in visually impaired subjects with central field loss. PURPOSE: This study aimed to evaluate the effects of two MP-3 microperimeter biofeedback strategies on the visual performance of subjects with central vision loss. Moreover, changes between the groups were compared to provide indications of practice with biofeedback stimulation in subjects with central vision loss. METHODS: Using simple randomization, 19 participants were trained according to two different biofeedback stimulation approaches using the MP-3 microperimeter. Patients were assigned to two different groups: subjects trained for 2 days a week (group A) and 3 days a week (group B). The patients in each group were randomized to perform a total of 10 or 15 sessions. RESULTS: Fixation stability increased from 4.5 ± 2.8 to 2.3 ± 2.2° 2 and from 8.2 ± 6.9 to 1.4 ± 1° 2 after 2 and 3 weekly biofeedback training sessions, respectively ( P < .05). Biofeedback training induced a significant improvement of 40.7 and 29.4% in reading speed for groups A and B, respectively ( P < .05). A comparison of two weekly biofeedback training sessions with three weekly biofeedback sessions demonstrated greater fixation stability in group B ( P < .05). CONCLUSIONS: This study concludes that a biofeedback intervention is effective in enhancing oculomotor control in patients with central vision loss. In our study, a more intensive biofeedback strategy seemed to produce significantly better results in terms of functional vision parameters.

Refractive surgery and dry eye.

Refractive surgery is one of the most common elective surgeries performed worldwide. The incidence of dry eye disease (DED) after corneal refractive surgery varies among different studies. Pre-existing untreated DED has been identified as a risk factor for postsurgical dry eye symptoms. On the basis of both evidence and clinical experience, some recommendations for ocular surface and DED management pre- and post-refractive surgery are described. In aqueous deficiency Dry Eye Disease, preservative-free lubricating drops should be preferred, in addition to ointment and gel forms. Topical anti-inflammatory agents (Cyclosporine 0.1%, hydrocortisone phosphate, fluorometholone) should be used for 3-6 months in cases of ocular surface damage. The therapy of evaporative DED includes lifestyle modifications, lid hygiene (either performed by the patient or offered as professional lid hygiene by the physician), use of lubricating eye drops with lipid components, topical and/or systemic antibiotic treatment with anti-inflammatory properties and Intense Pulsed Light (IPL-) Treatment for meibomian gland dysfunction.

Innovation in the Development of Synthetic and Natural Ocular Drug Delivery Systems for Eye Diseases Treatment: Focusing on Drug-Loaded Ocular Inserts, Contacts, and Intraocular Lenses.

Nowadays, ocular drug delivery still remains a challenge, since the conventional dosage forms used for anterior and posterior ocular disease treatments, such as topical, systemic, and intraocular administration methods, present important limitations mainly related to the anatomical complexity of the eye. In particular, the blood-ocular barrier along with the corneal barrier, ocular surface, and lacrimal fluid secretion reduce the availability of the administered active compounds and their efficacy. These limitations have increased the need to develop safe and effective ocular delivery systems able to sustain the drug release in the interested ocular segment over time. In the last few years, thanks to the innovations in the materials and technologies employed, different ocular drug delivery systems have been developed. Therefore, this review aims to summarize the synthetic and natural drug-loaded ocular inserts, contacts, and intraocular lenses that have been recently developed, emphasizing the characteristics that make them promising for future ocular clinical applications.

Efficacy and Patients' Satisfaction with the ORCAM MyEye Device Among Visually Impaired People: A Multicenter Study.

To evaluate usability of and satisfaction with OrCam MyEye, a finger-size wearable assistive technology device for visually impaired during real-world tasks. This prospective multicenter study was conducted on visually impaired people recruited from 5 vision rehabilitation centers. Patients performed real-world tasks such as near and distance reading, money handling, colour identification and face recognition in 2 different scenarios: without using any low vision aid and with OrCam. System Usability Scale (SUS), Patient's Global Impression of Change (PGIC), the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0) and the Psychosocial Impact of Assistive Devices Scale (PIADS) were administered after the use of the OrCam device. Among the 100 participants, use of OrCam MyEye device improved many daily-living tasks (F = 1.67, P < .05), and in particular reading and face recognition. Multivariate logistic regression showed that age and visual field defect explained 89% of the variation in efficacy of the device. Nearly half (45%) of the participants indicated a positive rating with the SUS. The PGIC rates showed a minimal improvement with a mean score of 4.2 (SD:1.8). The most highlighted parameter with the QUEST 2.0 test was "ease of use" in 58% (48 subjects). The PIADS indicator showed that the device positively impacted on the daily-living tasks of users (r2 = 0.72, P < .05). Regression modelling demonstrated a good relation between the questionnaires scores and demographic, disease and visual factors (P < .05). OrCam MyEye allowed visually impaired people to read, handle money and face recognition independently. This device may offer to these subjects to be independent.

Two-surgeon, two-center evaluation of a new combined EDOF intraocular lens approach.

PURPOSE: To evaluate visual performance and quality of life after bilateral implantation of 2 extended depth-of-focus intraocular lenses (EDOF IOLs). SETTING: Ophthalmology Clinic, Department of Medicine and Science of Ageing, University "G. d'Annunzio" Chieti-Pescara, Italy, and Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy. DESIGN: Prospective clinical study. METHODS: 60 eyes of 30 patients with senile cataract were enrolled in this study. Patients underwent phacoemulsification and bilateral implantation of the Mini WELL IOL in the dominant eye and the Mini WELL PROXA IOL in the nondominant eye within a month. The main outcome measures over a 3-month follow-up period were uncorrected and corrected visual acuity at different distances (33 cm, 60 cm, and 4 m), defocus curve, contrast sensitivity, and patient satisfaction (evaluated by mean of the National Eye Institute Refractive Error Quality-of-Life instrument-42 questionnaire). RESULTS: Binocular uncorrected visual acuity at 90 days was 0.03 ± 0.11 logMAR for long distance, 0.05 ± 0.10 logMAR for intermediate distance, 0.03 ± 0.08 logMAR at 40 cm, and 0.06 ± 0.08 logMAR at 33 cm. Statistically significant differences between the 2 EDOF IOLs in favor of Mini WELL PROXA IOL were observed for uncorrected near visual acuity at 40 and 33 cm ( P < .001 and P < .001, respectively) and for distance-corrected near visual acuity at 40 cm ( P < .001). Significant differences between the 2 IOLs in the defocus curves were reported. CONCLUSIONS: In this small pilot study, bilateral implantation of Mini WELL IOL and Mini WELL PROXA IOL achieved good quantity and quality of vision.

Management of patients undergoing cataract surgery: An Italian survey.

PURPOSE: To investigate the management of patients undergoing cataract surgery in Italy. SETTING: Italian ocular surgeons, members of the Italian Association of Cataract and Refractive Surgery (AICCER), were invited to participate to this survey. DESIGN: Participants had to respond to a questionary including a series of practical questions concerning the management of patients undergoing cataract surgery. METHODS: A designed questionnaire explored the main issues concerning the practical problems involved in managing patients undergoing cataract surgery. The questionnaire was sent by e-mail and analyzed by descriptive statistics. RESULTS: Preoperative prophylaxis was performed by most surgeons. After surgery, several products were used, even simultaneously. Fixed antibiotic-corticosteroid combination (87.2%; 89) and NSAIDs (88.2; 90) were chosen as the most commonly used drug classes. The average duration of prescribed post-surgical therapies was more than two weeks for 52.9% (54) of participants, two weeks for 29.4% (30), and only one week for 5.9% (6). CONCLUSION: This survey confirmed a discrete adherence to the main guidelines but at the same time highlights a discrete inhomogeneity in the use of medications, duration of treatments, and follow-up visits. For this reason, it is appropriate to continue updating and implementing the guidelines and educational pathways. This thought is consistent with the Precision Medicine approach. Every patient should be carefully evaluated to determine the best medication, dosage, and duration. A Personalized Medicine strategy is used on a single patient to optimize treatment clinical efficacy while minimizing side effects.

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.

Bioengineered Human Stromal Lenticule for Recombinant Human Nerve Growth Factor Release: A Potential Biocompatible Ocular Drug Delivery System.

Small incision lenticule extraction (SMILE), is a surgical procedure for the myopia correction, during which a corneal stromal lenticule is extracted. Given that we have previously demonstrated how this discarded tissue could be repurposed as a bio-scaffold for stromal engineering, this study aimed to explore its use as an ocular drug delivery system of active molecules, using neurotrophic factor Nerve Growth Factor (NGF). We employed human stromal lenticules directly collected from healthy donors undergoing SMILE. Following a sodium dodecylsulfate (SDS) treatment, decellularized lenticules were incubated with a suspension of polylactic-co-glycolic-acid (PLGA) microparticles (MPs) loaded with recombinant human NGF (rhNGF-MPs). Fluorescent MPs (Fluo-MPs) were used as control. Data demonstrated the feasibility to engineer decellularized lenticules with PLGA-MPs which remain incorporated both on the lenticules surface and in its stromal. Following their production, the in vitro release kinetic showed a sustained release for up to 1 month of rhNGF from MPs loaded to the lenticule. Interestingly, rhNGF was rapidly released in the first 24 h, but it was sustained up to the end of the experiment (1 month), with preservation of rhNGF activity (around 80%). Our results indicated that decellularized human stromal lenticules could represent a biocompatible, non-immunogenic natural scaffold potential useful for ocular drug delivery. Therefore, combining the advantages of tissue engineering and pharmaceutical approaches, this in vitro proof-of-concept study suggests the feasibility to use this scaffold to allow target release of rhNGF in vivo or other pharmaceutically active molecules that have potential to treat ocular diseases.

Topical Steroids and Glaucoma Filtration Surgery Outcomes: An In Vivo Confocal Study of the Conjunctiva.

(1) Background: The purpose of this study is to investigate the effects of topical steroids on conjunctiva in patients undergoing filtration surgery (FS) for glaucoma by using confocal microscopy (CM); (2) Methods: One hundred and four glaucomatous patients were randomized to fluorometholone or lubricants four weeks before FS. CM was performed before treatments and pre-operatively. Dendritic and goblet cell densities (DCD, GCD), stromal meshwork reflectivity (SMR), vascular tortuosity (VT), and intra-ocular pressure (IOP) were the main outcomes. By evaluating treatments and outcomes (12-month success/failure) as categorical variables, patients were grouped into Group 1, 2, 3, or 4 (success/failure with fluorometholone, or lubricants); (3) Results: Twelve-month IOP was reduced in Groups 1 and 3 (p < 0.001). After treatments, DCD and SMR were reduced in Groups 1 and 2 (p < 0.01), and 1 and 3 (p < 0.05), respectively. Pre-operative DCD was lower in the steroid compared to lubricant group (p < 0.001), whereas SMR was lower in successful (1 and 3) compared to failed groups (2 and 4) (p = 0.004). There were no significant differences between the fluorometholone and lubricant groups for success percentages. The number of bleb management procedures and IOP lowering medications were lower in Group 1 compared to Groups 2−4 (p < 0.05); (4) Conclusions: Topical steroids mitigate conjunctival inflammation and lower the stromal density in patients undergoing FS. These modifications lead to less intensive post-operative management.

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress.

BACKGROUND: The present study aimed to investigate the rationale and efficacy of using a citicoline, coenzyme Q10 (CAVAQ10) and vitamin B3 fixed combination in combating inflammation and oxidation in neuronal cells exposed to oxidative stress. METHODS: HypoE22 cells and isolated hypothalamic specimens were selected as in vitro models to conduct the experiments. The efficacy of citicoline, CAVAQ10, and vitamin B3, with their fixed combination, were assayed after the exposure of hypothalamic cells to hydrogen peroxide (concentration range 1 nM-10 µM), in order to evaluate the biocompatibility of treatments. The activity of neuroprotective and pro-inflammatory factors, namely, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα), involved in the neuronal cell damage in neurodegenerative diseases, were assayed in isolated hypothalamus. RESULTS: Neither citicoline, CAVAQ10, nor vitamin B3 significantly altered hypothalamic cell viability, thus suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. In the same condition, citicoline and CAVAQ10 were also effective in reducing the gene expression of monoaminoxidase-B, involved in dopamine degradation. However, only citicoline demonstrated an ability to reduce dopamine levels. Conversely, all compounds were effective in reducing the gene expression of IL-6, and TNFα, and in inducing the gene expression of BDNF, with the co-administration of citicoline/CAVAQ10/vitamin B3 being generally more effective than single ingredients. CONCLUSIONS: The present findings support the beneficial and synergistic effects of citicoline, CAVAQ10, and vitamin B3 in fixed combination in reducing inflammation and oxidation, and in stimulating neurotrophin production in neuronal cells.

Preparing the ocular surface for glaucoma filtration surgery: an unmet clinical need.

The mutual relationship among medical therapy, ocular surface (OS) and filtration surgery (FS) represents one of the most crucial issues in glaucoma management. As the long-term use of intraocular pressure-lowering medications significantly affect the OS health, patients with an uncontrolled disease frequently undergo glaucoma surgery in less-than-ideal conditions. As we known, OS changes strongly affect the post-operative bleb filtration capability. Therefore, improving the OS conditions before proceeding with FS is needed. Currently, given the rapid diffusion of new surgical procedures, this need is even more perceived. Nevertheless, despite surgeons retain the OS preparation of primary importance, and recognize the OS disease (OSD) as the only modifiable risk factor for filtration failure, there is no agreement on which strategies should be preferred to prepare patients. This is largely due to the lack of validated guidelines, which forces clinicians to adopt personal approaches based on evidence derived from low-quality studies. In this review, we provided an overview of risk factors involved in the FS failure, with particular attention to those depending on OS changes, and how OSD negatively affects the aqueous humor resorption after surgery. Moreover, we reported the most exploited measures to mitigate the OSD before surgery, the possible reasons underlying the absence of shared approaches, and the upcoming area of intervention to preserve the OS health during glaucoma management. Finally, based on the current evidence, we proposed a pre-operative outline reporting the main risk factors that should be considered before surgery, and the therapeutical options available to improve the OS.

Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy.

Neurotrophic Keratopathy (NK), classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe specific medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative to the neurotization surgery. However, few studies have been conducted to the molecular mechanism underlying the response to the treatment. Here, we carried out tears proteomics to highlight the protein expression during pharmacological treatment of NK (Data are available via ProteomeXchange with identifier PXD025408).Our data emphasized a proteome modulation during rhNGF treatment related to an increase in DNA synthesis, an activation of both BDNF signal and IL6 receptor. Furthermore, the amount of neuronal Extracellular Vesicles EVs (CD171+) correlated with the EVs carrying IL6R (CD126+) together associated to the inflammatory EVs (CD45+) in tears. Such scenario determined drug response, confirmed by an in vivo confocal microscopy analysis, showing an increase in length, density and number of nerve fiber branches during treatment. In summary, rhNGF treatment seems to determine an inflammatory micro-environment, mediated by functionalized EVs, defining the drug response by stimulating protein synthesis and fiber regeneration.