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The purpose of this study was to evaluate corneal epithelium and stromal remodelling with anterior segment optical coherence tomography in patients who have undergone stromal lenticule addition keratoplasty (SLAK) for advanced keratoconus. This was a prospective non-comparative observational study. Fifteen eyes of 15 patients with advanced keratoconus underwent implantation with a cadaveric, donor negative meniscus-shaped intrastromal lenticule, produced with a femtosecond laser, into a stromal pocket dissected in the recipient cornea at a depth of 120 μm. Simulated keratometry, central corneal thickness (CTT), corneal thinnest point (CTP), central epithelial thickness (CET), central and peripheral lenticule thickness, anterior and posterior stromal thickness were measured. Regional central corneal epithelial thickness (CET) and variations in the inner annular area (IAT) and outer annular area (OAT) were also analysed. All parameters were measured preoperatively and 1, 3, and 6 months postoperatively. The average anterior Sim-k decreased from 59.63 ± 7.58 preoperatively to 57.19 ± 6.33 D 6 months postoperatively. CCT, CTP, CET, and OAT increased and IAT decreased significantly after 1 month. All parameters appeared unchanged at 6-months except that of OAT that further increased. Lenticule thickness was stable. In conclusion we observed that SLAK reshapes the cornea by central flattening with stromal thickening and epithelial thickness restoration.

To compare functional and morphological outcomes of femtosecond laser clear corneal incision (CCI) versus manual CCI during cataract surgery. Sixty eyes of 60 patients who underwent CCI during cataract surgery were randomized into two groups: femtosecond laser CCI (30 eyes) and manual CCI (30 eyes). There were no significant between-group differences in uncorrected distance visual acuity, corrected distance visual acuity, surgically induced astigmatism, and corneal aberrations. Keratometric astigmatism was significantly lower in the femtosecond laser CCI group compared to the manual CCI group at 30 and 180 days (P < .05). Central endothelial cell count was significantly higher in the femtosecond laser CCI group compared to the manual CCI group at 7 and 30 days postoperatively (P < .05). A lower increase of corneal thickness at the incision site was observed at 30 and 180 days postoperatively in the femtosecond laser CCI group compared to the manual CCI group (P < .05). In addition, femtosecond laser CCI showed a better morphology (lower percentage of endothelial and epithelial gaping and endothelial misalignment) compared to manual CCI at different time points. Total phacoemulsification time was significantly lower in the femtosecond laser CCI group (P < .05). The femtosecond laser procedure was safe, efficient, and less damaging, as evidenced by lower central endothelial cell loss, lower increase of corneal thickness at the incision site, and better tunnel morphology compared to the manual technique.

AimsTo investigate associations between changes in retinal vessels and alterations detected by spectral domain optical coherence tomography (SD-OCT) scans in intermediate stage age-related macular degeneration (AMD).MethodsThirty eyes of 30 patients with intermediate dry AMD were enrolled in the study. Of the cohort study, 15 eyes (changes-AMD group) showed OCT changes preceding the development of drusen-associated atrophy. A control group of healthy subjects was selected for statistical comparisons. All patients underwent an ophthalmologic evaluation, including OCT angiography (OCTA) and SD-OCT scans. Main outcome measures were superficial vessel density, deep vessel density, macular thickness.ResultsFoveal macular thickness was 215.2±32.9 μm in changes-AMD patients and was significantly thinner than no changes-AMD patients (248.3±23.3 μm, p=0.002) and healthy subjects (268.1±19.2 μm, p<0.0001). Furthermore, in the parafoveal area, the thicknesses of both the inner retina and the outer retina were reduced in the changes-AMD group, after comparison with the two other groups. Parafoveal superficial vascular plexus flow density was 43.3±2.7% in changes-AMD patients and was decreased compared with the no changes-AMD group (48.7±3.3%, p=0.003) and healthy controls (50.4±6.1%, p=0.001). A direct correlation of the superficial plexus flow density with the inner retina parafoveal macular thickness (R2=0.761, p=0.028) was found.ConclusionsWe demonstrated an association between SD-OCT signs and retinal blood supply in patients with intermediate AMD and we showed that patients with signs predicting development of geographic atrophy have a reduced flow in superficial vascular plexus and damage of the inner and the outer retina.

Introduction To describe the advantages of the ARTEVO ® 850 digital color assistant (DCA) for enhancing visualization during vitreoretinal surgery. Methods All surgical procedures were conducted under the expertise of a single surgeon utilizing the ARTEVO ® 850 heads-up microscope from ZEISS. During the surgeries, images were contemporaneously recorded with and without the application of the DCA across key phases: core vitrectomy, peripheral vitrectomy, epiretinal membrane (ERM) peeling, and internal limiting membrane (ILM) peeling. This approach enabled a direct comparison to evaluate the impact of the filter on visualization quality during each specific surgical maneuver. Results The application of the “vitrectomy blue” filter on the ARTEVO ® 850 surgical microscope provided advantages, particularly during core and peripheral vitrectomy. The “vitrectomy blue” filter improved visualization of the vitreous, allowing for clearer identification and removal of residual vitreous strands and opacities. In surgeries involving ERM, the “peeling blue” filter provided enhanced contrast and clarity in visualizing the membrane, facilitating thorough peeling. Furthermore, when used in conjunction with dye staining techniques, it further amplified the visualization of ERM in high myopic eyes. This combination reduced the need for additional re-staining during surgery, streamlining the procedure and potentially minimizing intraoperative complications related to dye toxicity. In macular hole surgery, the “peeling blue” filter contributed to improving the characterization and delineation of the hole edges and surrounding tissues. Conclusions The ARTEVO ® 850 DCA can potentially enhance tissue visualization during vitreoretinal surgeries, particularly in scenarios with compromised visibility. Our observation underscored the efficacy of the blue filter in improving the clarity and contrast of vitreous, ERM and macular hole visualization. This enhancement was particularly evident when the DCA was used in combination with dye staining techniques, which further improved the visualization of ERM in high myopic eyes.

Primary open-angle glaucoma (POAG) represents the leading cause of irreversible blindness worldwide and is a multifactorial, chronic neurodegenerative disease characterized by retinal ganglion cell and visual field loss. There are many factors that are associated with the risk of developing POAG, with increased intraocular pressure being one of the most prevalent. Due to the asymptomatic nature of the disease, the diagnosis of POAG often occurs too late, which necessitates development of new effective screening strategies for early diagnosis of the disease. However, this task still remains unfulfilled. In order to provide further insights into the pathophysiology of POAG, we applied a targeted metabolomics strategy based on a high-throughput screening method for the determination of tear amino acids, free carnitine, acylcarnitines, succinylacetone, nucleosides, and lysophospholipids in naïve to therapy glaucomatous patients and normal controls. Also, we conducted proteomic analyses of the whole lacrimal fluid and purified extracellular vesicles obtained from POAG patients and healthy subjects. This multi-omics approach allowed us to conclude that POAG patients had lower levels of certain tear amino acids and lysophospholipids compared with controls. These targeted analyses also highlighted the low amount of acetylcarnitine (C2) in POAG patient which correlated well with proteomics data. Moreover, POAG tear proteins seemed to derive from extracellular vesicles, which carried a specific pro-inflammatory protein cargo.

To evaluate ocular surface and eyelid modifications occurring in glaucomatous patients diagnosed with glaucoma therapy-related ocular surface disease (GT-OSD) and retinal comorbidities who previously underwent serial Intravitreal injections (IVIs) of aflibercept. Thirty-two eyes of 32 patients with a diagnosis of GT-OSD and concomitant retinal diseases were enrolled in a two-center retrospective observational study. The main outcome measures were: Noninvasive tear film break-up time (NIBUT), Tear meniscus height (TMH), Bulbar redness score (BRS), fluorescein Tear film Break Up Time (TBUT), Corneal Fluorescence Staining (CFS), Schirmer test I (ST), and inferior eyelid Meibomian Glands (MGs) dropout. Differences between treated and fellow eye (TE, FE), were considered. The median number of IVIs (aflibercept) in TE was 4 (interquartile range (IQR) 3-6.50). Mean BRS was significantly lower ( p  = 0.011) and median TBUT higher ( p  = 0.037) in TE compared to FE. Despite CFS and NIBUT did not significantly differ between eyes, their median values showed a marginal tendency for better results in TE compared to FE. Serial IVIs of aflibercept positively affected some features of the GT-OSD, reducing conjunctival hyperemia and improving the tear film stability. These preliminary results could open to new strategies for ocular surface management in glaucoma, whether confirmed in larger prospective studies.

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.

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.

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.

PurposeTo describe and compare the conjunctival filtering bleb features after XEN gel implantation and trabeculectomy using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM).MethodsFifty-two patients who underwent completely successful trabeculectomy (24 eyes) or completely successful XEN gel implantation (28 eyes) were consecutively enrolled. At the sixth-month follow-up, filtering blebs were analyzed with AS-OCT and IVCM. The main outcomes were the following: (i) bleb-wall epithelium cyst-like structure density and area (BECSD, BSCSA), (ii) bleb-wall sub-epithelium cyst-like structure density and area (BSCSD, BSCSA,), (iii) bleb-wall thickness (BT), (iv) bleb-wall epithelial thickness (BET), (v) bleb-wall reflectivity (BR), and (vi) bleb height (BH), for AS-OCT. Mean microcyst density (MMD) and area (MMA) and stromal meshwork reflectivity (SMR) were the IVCM outcomes.ResultsSix-month intraocular pressure was 11.46 ± 3.09 and 10.06 ± 3.39 mmHg in the XEN gel implantation and trabeculectomy, respectively (p > 0.05). At AS-OCT, XEN gel blebs showed lower BH, BT, BET, BR, (p < 0.001), and BECSA values (p < 0.005), and a higher BECSD (p < 0.05) compared with trabeculectomy blebs. At IVCM, MMA and SMR values were lower in the XEN gel implantation, compared with trabeculectomy (p < 0.05). BECSD and BSCSD negatively correlated with BR (p < 0.01; r = − 0.110; p < 0.01; r = − 0.249), whereas BR strongly correlated with SMR (p < 0.001; r = 0.819).ConclusionSuccessful filtering blebs after XEN gel implantation appeared flatter and thinner, with a higher number of epithelial cysts and a hypo-reflective bleb wall compared with trabeculectomy. These aspects may depend on the different intra-operative tissue manipulation and/or on different aqueous humor dynamics in the sub-conjunctiva between surgeries.