Development and preliminary evaluation of a novel preoperative index for quantitative analysis of photoreceptor loss in full-thickness macular holes.

PURPOSE: To identify novel quantitative parameters for evaluating photoreceptor loss in full-thickness macular holes (FTMH), exploring their potential clinical impact on postoperative functional and anatomical recovery. METHODS: This pilot study enrolled 38 eyes from 38 patients diagnosed with FTMH. Preoperatively, eyes underwent analysis and were subsequently followed for six months post-surgery. Best-corrected visual acuity (BCVA) was recorded, and cross-sectional images of FTMH were obtained using B-scan optical coherence tomography (OCT) and en-face OCT. Quantitative assessment of ellipsoid zone (EZ) and external limiting membrane (ELM) integrity changes was conducted and correlated with postoperative anatomical and functional recovery. The photoreceptor Integrity Index (PIIN), calculated as the ratio of photoreceptor area to lumen hole area measured at customized segmentation, was correlated with the minimum and base diameters of the hole, positive change in BCVA, preoperative EZ defect (EZd), preoperative ELM defect (ELMd), and changes in EZ and ELM over the six-month follow-up period (∆-EZ and ∆-ELM). The main outcome measures focused on evaluating the effectiveness of PIIN in predicting postoperative anatomical and functional changes. RESULTS: A higher PIIN correlated with a greater BCVA change over six months (p < 0.001). Univariate regression analysis using the PIIN as a predictor for positive change in BCVA (|∆-BCVA| [logMAR]) over time yielded significant results (p < 0.001). Additionally, the PIIN significantly correlated with EZd at baseline, ELM at baseline, and ELMd change over the six-month follow-up period. CONCLUSION: The PIIN shows promise as a tool for evaluating photoreceptor loss in macular holes and estimating postoperative functional and anatomical recovery. KEY MESSAGES: What is known Previous studies have extensively used optical coherence tomography (OCT) to investigate various biomarkers for assessing patients with full-thickness macular hole (FTMH), without considering detailed MH ultrastructural features Existing indexes used to predict surgical outcomes for FTMH primarily depend on geometrical parameters and do not integrate detailed ultrastructural characteristics, such as cellular components.  What is new A novel concept introduces the quantitative measurement of residual photoreceptors located at the edge of FTMH. The Photoreceptor Integrity Index (PIIN) integrates different ultrastructural components of macular holes, aiming to become a valuable clinical tool to predict both anatomical and functional recovery outcomes following surgical intervention for FTMH.

Is the Advent of New Surgical Procedures Changing the Baseline Features of Patients Undergoing First-Time Glaucoma Surgery?

Background: The aim of this study was to determine if the rise in new surgical procedures for glaucoma is changing the baseline features of patients. Methods: In this retrospective study, we reviewed the baseline features of patients undergoing their first glaucoma surgery in 2011 and 2021, collecting data regarding intraocular pressure (IOP), visual field (VF) parameters, stage of disease, and the type of surgery. Results: In the study, 455 patients were included in the analysis. From these, 230 eyes had glaucoma surgery performed in 2011 (Group A) and 225 eyes in 2021 (Group B). When considering the baseline features, Group A was older than Group B (72.7 ± 10.7 and 70 ± 12.4 years; p = 0.02, respectively), and showed a significantly more advanced VF mean defect (-16.4 ± 8.8 and -13.8 ± 8.7 dB; p < 0.01, respectively) and a higher IOP (25.9 ± 6.6 and 24.9 ± 7.8 mmHg; p = 0.02, respectively). Overall, severe VF damage at the time of surgery was more frequent in Group A (74.3%) than in Group B (60.8%) (p < 0.01). The overall number of traditional glaucoma surgeries was 211 in 2011, reducing to 94 ten years later, with similar severe pre-operative VF defects. In 2021, minimally invasive bleb surgery (MIBS) represented 58% of all surgeries. Conclusions: In the last ten years, patients receiving glaucoma surgery for the first time were younger, had less severe disease, and a more contained IOP. The baseline feature modifications were probably related to the diffusion of new procedures, especially MIBS, which allowed for treating patients at an earlier stage, reserving traditional procedures for advanced cases.

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.

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.

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.

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.

Ubiquitin proteasome system and glaucoma: A survey of genetics and molecular biology studies supporting a link with pathogenic and therapeutic relevance.

Glaucoma represents a group of progressive neurodegenerative diseases characterized by the loss of retinal ganglion cells (RGCs) and their axons with subsequent visual field impairment. The disease develops through largely uncharacterized molecular mechanisms, that are likely to occur in different localized cell types, either in the anterior (e.g., trabecular meshwork cells) or posterior (e.g., Muller glia, retinal ganglion cells) segments of the eye. Genomic and preclinical studies suggest that glaucoma pathogenesis may develop through altered ubiquitin (Ub) signaling. Ubiquitin conjugation, referred to as ubiquitylation, is a major post-synthetic modification catalyzed by E1-E2-E3 enzymes, that profoundly regulates the turnover, trafficking and biological activity of the targeted protein. The development of new technologies, including proteomics workflows, allows the biology of ubiquitin signaling to be described in health and disease. This post-translational modification is emerging as a key role player in neurodegeneration, gaining relevance for novel therapeutic options, such as in the case of Proteolysis Targeting Chimeras technology. Although scientific evidence supports a link between Ub and glaucoma, their relationship is still not well-understood. Therefore, this review provides a detailed research-oriented discussion on current evidence of Ub signaling in glaucoma. A review of genomic and genetic data is provided followed by an in-depth discussion of experimental data on ASB10, parkin and optineurin, which are proteins that play a key role in Ub signaling and have been associated with glaucoma.

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.

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.

Ultrasound Cyclo Plasty in Patients with Open Angle Glaucoma and High Myopia.

PRCIS: Ultrasound cyclo plasty (UCP) using high-intensity focused ultrasound is an effective and safe procedure in lowering intraocular pressure (IOP) in patients with glaucoma, even in those with high myopia. PURPOSE: This study aimed to evaluate the efficacy and safety of UCP in glaucoma patients with high myopia. MATERIALS AND METHODS: In this retrospective, single-center study, we enrolled 36 eyes divided into 2 groups based on axial length: group A (≥26.00 mm) and group B (<26.00 mm). We collected data about visual acuity, Goldmann applanation tonometry, biomicroscopy, and visual field before the procedure and at 1, 7, 30, 60, 90, 180, and 365 days after the procedure. RESULTS: Mean IOP significantly decreased in both groups after treatment ( P <0.001). Mean IOP reduction from baseline to the last visit was 9.8±6.6 mmHg (38.7%) in group A and 9.6±6.3 mmHg (34.8%) in group B ( P <0.001). Mean IOP at the last visit was 15.8±4.1 mmHg in the myopic group and 18.1±5.6 mmHg in the non-myopic one. Regarding the number of IOP-lowering eyedrops being taken by our patients, statistically significant differences were found between groups A and B neither at baseline (2.8±0.9 and 2.6±1.0; P =0.568) nor 1 year after the procedure (2.5±1.1 and 2.6±1.1; P =0.762). No major complications occurred. All minor adverse events resolved within a few days. CONCLUSION: UCP seems to be an effective and well-tolerated strategy to lower IOP in glaucoma patients with high myopia.

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.

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.

In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma.

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

Long-term outcome of supraciliary gold micro shunt in refractory glaucoma.

PURPOSE: To evaluate the 10-year follow-up efficacy and safety of gold micro shunt (GMS) in patients with refractory glaucoma, and the potential risk factors for failure. METHODS: Retrospective data analyses based on medical records from 55 patients who underwent GMS implant for refractory glaucoma between March 2007 and April 2008. The primary outcome measure was the cumulative probability of success defined as intraocular pressure (IOP) below 21 mmHg together with a 33% lowering of the baseline IOP with (qualified) or without (complete) topical medications, no reoperation for glaucoma or loss of light perception. RESULTS: Mean IOP 10 years after the GMS implantation was 21.6 ± 5.1 mmHg with 2.7 ± 0.7 drugs. Qualified success was achieved in 8/55 patients (14.5%) with a mean of 2.9 ± 0.8 drugs at 5 years and in 2/55 patients (3.6%) with a mean of 2.7 ± 1.0 drugs at 10 years. None of the patients reached complete success at five years from surgery. The cumulative probability of complete success was 14%, 9% and 0% at 1, 2 and 5 years, respectively, and 72%, 67%, 36% and 3.6% at 1, 2, 5 and 10 years, respectively, for qualified success criterion. Baseline IOP for complete success, number of baseline medication for qualified success and age at the time of GMS implantation for both criteria were risk factors significantly associated with failure. CONCLUSION: A very low long-term survival rate of GMS in refractory glaucoma was found. Most patients did not reach the IOP success criteria of the study, even with the re-introduction of medications, leading to the need for further surgical procedures.

Confocal Microscopy and Anterior Segment Optical Coherence Tomography Imaging of the Ocular Surface and Bleb Morphology in Medically and Surgically Treated Glaucoma Patients: A Review.

Glaucoma patients often suffer from ocular surface disease (OSD) caused by the chronic administration of topical anti-glaucoma medications, especially in cases of long-term therapy with preserved or multiple drugs. Additionally, glaucoma surgery may determine ocular surface changes related to the formation and location of the filtering bleb, the application of anti-mitotic agents, and the post-operative wound-healing processes within the conjunctiva. Recently, several studies have evaluated the role of advanced diagnostic imaging technologies such as in vivo confocal microscopy (IVCM) and anterior segment-optical coherence tomography (AS-OCT) in detecting microscopic and macroscopic features of glaucoma therapy-related OSD. Their clinical applications are still being explored, with recent particular attention paid to analyzing the effects of new drug formulations and of minimally invasive surgical procedures on the ocular surface status. In this review, we summarize the current knowledge about the main changes of the ocular surface identified at IVCM and AS-OCT in glaucoma patients under medical therapy, or after surgical treatment.