Thyroid Hormone Signaling in Retinal Development and Function: Implications for Diabetic Retinopathy and Age-Related Macular Degeneration.

Thyroid Hormones (THs) play a central role in the development, cell growth, differentiation, and metabolic homeostasis of neurosensory systems, including the retina. The coordinated activity of various components of TH signaling, such as TH receptors (THRs) and the TH processing enzymes deiodinases 2 and 3 (DIO2, DIO3), is required for proper retinal maturation and function of the adult photoreceptors, Müller glial cells, and pigmented epithelial cells. Alterations of TH homeostasis, as observed both in frank or subclinical thyroid disorders, have been associated with sight-threatening diseases leading to irreversible vision loss i.e., diabetic retinopathy (DR), and age-related macular degeneration (AMD). Although observational studies do not allow causal inference, emerging data from preclinical models suggest a possible correlation between TH signaling imbalance and the development of retina disease. In this review, we analyze the most important features of TH signaling relevant to retinal development and function and its possible implication in DR and AMD etiology. A better understanding of TH pathways in these pathological settings might help identify novel targets and therapeutic strategies for the prevention and management of retinal disease.

Current Evidence for a New Surgical Technique for Scleral Fixation: The Implantation of a Carlevale Lens, a Systematic Review.

Background: The Carlevale lens (FIL SSF, Soleko IOL Division, Italy) is a new lens for suture-less scleral fixation. This paper aimed to systematically review articles on this lens, the surgical techniques used for its implantation, complications and outcomes. Methods: This systematic review was performed following the PRISMA guidelines. The search string used was "Carlevale" AND "scleral fixation" from inception until March 2024. For completeness, either case-control studies, case reports or case series written in English were included. The authors used the Newcastle-Ottawa scale for the case-control studies and the JBI Critical Appraisal Checklist for case reports and case series. Results: Twenty-nine articles were included. Scleral fixation with Carlevale lens can be performed by creating scleral flaps or, alternatively, by using scleral pockets. The two sclerotomies must be diametrically opposed, and are preferably created by 25-gauge trocars. A pars plana vitrectomy should be performed every time, and the design of the lens should be suitable for self-anchoring to the sclera; the most accredited strategy to achieve this is to avoid scleral sutures. There were only a few intraoperative and postoperative complications reported; vitreous hemorrhages were the most frequent intraoperative events, while the most relevant postoperative complications were vitreous hemorrhages, cystoid macular oedema and transient variations in the intraocular pressure. Excellent results have been obtained in terms of BCVA, IOL centration and stability, mean intraocular pressure, postoperative spherical equivalent, separation between anterior and posterior chamber and the distance of the IOL from anterior chamber structures. Conclusions: The foldable hydrophilic design of the Carlevale lens has shown good effectiveness, IOL stability and few intra and post-operative complications.

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.

A pilot study on Langerhans cells in keratoconus patients by in vivo confocal microscopy before and after corneal cross-linking and correlation with eye rubbing.

PURPOSE: The aim of this study was to investigate the corneal microstructure and Langerhans cells using in vivo confocal microscopy in keratoconus patients before and after cross-linking, and to correlate the morphologic findings with clinical and patient-reported outcomes, including eye rubbing (ER) behavior. METHODS: Patients with progressive keratoconus undergoing iontophoresis-assisted epithelium-on cross-linking (I-CXL) were consecutively enrolled. In vivo confocal microscopy was performed before and 6 months after treatment. Patients were asked to quantify their ER behavior on a Visual Analogue Scale (VAS) and completed the Keratoconus Outcomes Research Questionnaire and the Ocular Surface Disease Index questionnaires at the same time points. Visual acuity, tear osmolarity, topography, aberrometry, and pachymetry of both eyes were assessed. RESULTS: Thirteen patients were included in this pilot study. Preoperatively, the mean Langerhans cells density was 35,615 cells per mm2, and the median morphology was 3. The mean ER VAS before treatment was 7,077 out of 10. The ER VAS showed significant positive correlations with both Langerhans cells density and morphology of the study eye. After treatment, a statistically significant reduction in ER VAS and in Langerhans cells variables was observed. The mean sub-basal plexus nerve density was comparable to pre-operative values 6 months after I-CXL. CONCLUSIONS: Based on this preliminary evidence, the presence of high density of mature Langerhans cells in the central cornea of keratoconus patients and its correlation with eye rubbing support the role of inflammation in keratoconus. The reduction in these markers after treatment may suggest a potential of CXL in moderating immune-related inflammation and eye rubbing in the medium term.

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.

Ocular surface and glaucoma, a mutual relationship. Practical suggestions for classification and management.

The chronic use of glaucoma medications could improve the development of an ocular comorbidity, the glaucoma therapy-related ocular surface disease. This could be related to the exposure of the conjunctiva to preservatives, but also active compounds such as prostaglandin analogues may improve the risk of ocular surface inflammation. Inflammation has a negative impact on tolerability and adherence to eyedrops and to the outcome of filtration surgery as well. A stratification of glaucoma patients based not only on visual field progression but also on glaucoma therapy-related ocular surface disease would be desirable for a strategic management. Early diagnosis, individualized treatment, and safe surgical management should be the hallmarks of glaucoma treatment. One of the main issues for the proper and successful management of patients is the right timing, effectiveness and safety for both medical and surgical treatment options leading to a precision medicine in glaucoma disease as the best modern treatment.

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.

Impact of corneal collagen cross-linking on vision-related quality of life measured with the keratoconus outcomes research questionnaire (KORQ) in patients with keratoconus.

PURPOSE: To assess the impact of corneal collagen cross-linking on self-reported vision-related quality of life (VR-QoL) in keratoconus patients by means of the Keratoconus Outcomes Research Questionnaire (KORQ), a new disease-specific patient reported outcomes measures (PROMs) tool. METHODS: Patients with progressive keratoconus undergoing corneal collagen cross-linking were consecutively enrolled. Patients completed the KORQ before and after the treatment, at 1, 3 and 6 months. Data were collected regarding the visual acuity and the topographic, aberrometric and pachymetric parameters of both eyes. Patients were also asked to quantify their eye rubbing behavior on a Visual Analogue Scale (VAS) from 0 to 10, before and 6 months after treatment. The KORQ scores were associated with the visual acuity, topographic, aberrometric and pachymetric data by means of the Spearman correlation coefficient. RESULTS: The Activity Limitation (AL) subscale score was higher after surgery. Preoperatively, negative correlations were observed between the KORQ AL score and Best Corrected Visual Acuity (logMAR), maximum keratometry, flattest keratometry, steepest keratometry, symmetry index front and higher order aberrations (HOA) of the treatment eye. Postoperatively, we observed a shift toward the fellow eye, with stronger correlation of the KORQ scores with the fellow eye parameters. The Symptoms subscale score correlated with the aberrometric parameters of both eyes at various time points. Statistically significant correlations were observed between the change in KORQ scores and the change in aberrometric parameters. A statistically significant reduction in the eye rubbing behavior was detected (p < 0,0001). CONCLUSIONS: These results suggest that the corneal cross-linking treatment is effective both in improving the subjective perception of the disease by the patient and in stabilizing the objective indicators of disease progression. Keratometric, aberrometric and visual acuity values showed a significant impact on self-reported VR-QoL. Corneal cross-linking, by halting the worsening of these parameters, may bear a beneficial effect on VR-QoL.

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.

Choroidal Vascularity Index in Central and Branch Retinal Vein Occlusion.

(1) Background: we aimed to evaluate choroidal vascularity change in eyes with central and branch retinal vein occlusion (RVO). (2) Methods: in this retrospective cross-sectional study, we reviewed the records of 47 patients with recent-onset, naïve, unilateral retinal vein occlusion. Enhanced-depth imaging optical coherence tomography scans were binarized using the ImageJ software; luminal area (LA) and total choroidal area (TCA) were measured. The choroidal vascularity index (CVI) was calculated as the proportion of LA to TCA. Depending on the pattern of macular oedema, eyes were classified as having no macular oedema (nME), cystoid macular oedema (CME), cystoid macular oedema with serous retinal detachment (mixed). (3) Results: CVI, TCA and LA were greater in eyes with RVO than in fellow, unaffected eyes. No difference was found between central and branch RVO except for central macular thickness (CMT). When compared with controls, eyes with CME presented a significant increase in subfoveal choroidal thickness, CMT, TCA, LA and CVI; eyes with mixed macular oedema had greater CMT and CVI than contralateral eyes; no significant differences in any of the considered parameters were observed in eyes with nME. (4) Conclusions: The results suggest that RVO alters the vascularity of the choroid that varies according to the type of macular oedema.

Outcomes of XEN 63 Device at 18-Month Follow-Up in Glaucoma Patients: A Two-Center Retrospective Study.

Background: Glaucoma surgery has significantly evolved over the last years. This paper aims to evaluate the midterm clinical outcomes of the XEN63 device in a real-world scenario. Methods: A retrospective clinical study was conducted on consecutive patients who underwent an XEN63 implant insertion, either alone or in combination with phacoemulsification. The primary endpoint was the mean intraocular pressure (IOP) at the month 18 visit. Results: Twenty-three eyes (23 patients) were included in the analysis. The preoperative IOP was significantly lowered from 27.0 ± 7.8 mmHg to 14.1 ± 3.4 mmHg at month 18 (p < 0.0001). At month 18, 14 (77.8%) and 11 (61.1%) eyes had an IOP ≤ 16 mmHg and ≤ 14 mmHg, respectively, without ocular hypotensive medication. The mean number of ocular hypotensive medication taken was significantly reduced from 2.3 ± 0.9 drugs at baseline to 1.0 ± 1.4 drugs at month 18 (p = 0.0020). Four (17.4%) eyes had hypotony at postoperative day 1, which was successfully resolved without sequelae. Four (17.4%) eyes underwent a needling procedure and four (17.4%) eyes underwent additional surgeries. Conclusions: The XEN63, either alone or in combination with cataract surgery, significantly lowered the IOP and reduced the need for ocular hypotensive drugs over a period of 18 months.

Intraoperative Anterior Segment Optical Coherence Tomography in the Management of Cataract Surgery: State of the Art.

BACKGROUND: The introduction of non-invasive diagnostic tools in ophthalmology has significantly reshaped current clinical practice in different settings. Recently, different anterior segment (AS) intraoperative optical coherence tomography (i-OCT) systems have been employed for different interventional procedures including cataract surgery. MATERIALS AND METHODS: A review on the use of AS i-OCT in the management of cataract surgery, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were assessed for all included articles. RESULTS: Out of 6302 articles initially extracted, 6302 abstracts were identified for screening and 32 of these met the inclusion/exclusion criteria for full-text review; 19 articles were excluded. CONCLUSIONS: The use of AS i-OCT in cataract surgery, even if only a few studies have a high level or grade of evidence, may represent a useful tool for novel surgeons approaching phacoemulsification but also for expert ones for teaching purposes and to plan and manage complicated cases.