Targeted next-generation sequencing analysis in Italian patients with keratoconus.

OBJECTIVE: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC). SUBJECTS/METHODS: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC. A purpose-developed Next Generation Sequencing (NGS) panel was used to identify and analyse the coding exons and flanking exon/intron boundaries of 26 genes known to be associated with KC and corneal dystrophies. Interpretation of the pathogenic significance of variants was performed using in silico predictive algorithms. RESULT: The targeted NGS research identified a total of 167 allelic variants of 22 genes in the study population; twenty-four patients had stable keratoconus (n. 54 variants) and forty patients had progressive disease (n. 113 variants). We identified genetic variants of certain pathogenic significance in five patients with progressive KC; in addition, eight novel genetic variants were found in eight patients with progressive KC. Mutations of FLG, LOXHD1, ZNF469, and DOCK9 genes were twice more frequently identified in patients with progressive than stable disease. Filaggrin gene variants were found in 49 patients (76% of total), of whom 32 patients (80% of progressive KC group) had progressive disease. CONCLUSIONS: Targeted NGS research provided new insights into the causative effect of candidate genes in the clinical phenotype of keratoconus. Filaggrin mutations were found to represent a genetic risk factor for development of progressive disease in Italy.

Safety of an Intracameral Fixed Combination for Mydriasis and Intraocular Anaesthesia During Cataract Surgery.

Purpose: To compare the safety of a standardized, commercially available intracameral combination of mydriatics and anesthetic (ICMA) with a reference topical mydriatic regimen for cataract surgery. Patients and Methods: The safety results from two international, randomized, controlled clinical studies were combined to compare ICMA at the beginning of cataract surgery (ICMA group) to the reference topical mydriatic regimen (reference group). Data were collected on ocular and systemic adverse events, corneal and anterior chamber examination, endothelial cell density, retinal thickness and visual acuity. Analysis was performed on a pooled safety set from both studies, preoperatively and up to 1 month postoperatively. Results: 342 patients received ICMA and 318 the reference topical regimen. Ocular adverse events were reported in 17.0% of patients in the ICMA group and 18.6% in the reference group. No difference was shown between groups in endothelial cell density (2208 ± 498 cells/mm2 for ICMA group versus 2241 ± 513 cells/mm2 for the reference group; p=0.547) and retinal thickness (change from baseline less than 50 µm in 94.7% versus 95.0% of patients, respectively) at 1 month postoperatively. At 1-day post-surgery, less patients in the ICMA group had moderate or severe (Grades 2 and 3) superficial punctate corneal staining (3.9% versus 7.0% for the reference group; p=0.064). Postoperatively, some ocular symptoms were also less frequently reported in the ICMA group. Best-corrected visual acuity increased in 96.0% of patients in the ICMA group and 95.8% in the reference group at 1 month. Conclusion: ICMA injection at the beginning of cataract surgery was demonstrated to be safe and may also provide perioperative and postoperative advantages over the standard topical mydriatic regimen.

Systematic review for the development of a core outcome set for monofocal intraocular lenses for cataract surgery.

Introduction: The aim of the study was to define a core outcome set (COS) to be measured following cataract surgery for the postoperative evaluation of monofocal intraocular lenses (IOLs). Compared to current COSs, the present work provides updates considering the advances in the technology due to the development of new generation monofocal IOLs, which are characterized by a safety profile comparable to standard monofocal IOLs but with an extended range of intermediate vision. Methods: Healthcare professionals (ophthalmologist surgeons) and patients were involved in the selection of outcomes to be included in the COS, starting from a list of indicators retrieved from a systematic literature search. The search considered observational studies with both a retrospective or prospective design, case studies and classic randomized controlled trials (RCTs). A mixed methodology integrating a Delphi-driven and an expert panel approach was adopted to reach an agreement among clinicians, while patients were involved in the completion of a questionnaire. Results: The final COS included 15 outcomes. Eleven outcomes, all clinical, were considered for inclusion after a joint discussion among ophthalmologists; seven outcomes were linked to visual acuity, while the remaining to contrast sensitivity, refractive errors, aberrations and adverse events. Measurement metrics, method of aggregation and measurement time point of these outcomes were specified. The most important aspects for the patients were (1) quality of life after cataract surgery, (2) the capacity to perform activities requiring good near vision (e.g., reading), (3) spectacle independence, and (4) safety of movements without fear of getting hurt or falling (intermediate vision). Discussion: In a context with limited healthcare resources, it is important to optimize their use considering also the preferences of end-users, namely patients. The proposed COS, developed involving both ophthalmologists and patients, provides an instrument for the postoperative evaluation of different technologies in the context of monofocal IOLs, which can be used not only in clinical trials but also in clinical practice to increase the body of real-world evidence.

Real-time monitoring of riboflavin concentration using different clinically available ophthalmic formulations for epi-off and epi-on corneal cross-linking.

PURPOSE: To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. METHODS: Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. RESULTS: At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. CONCLUSIONS: Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols.

Pharmacological Stimulation of Soluble Guanylate Cyclase Counteracts the Profibrotic Activation of Human Conjunctival Fibroblasts.

Conjunctival fibrosis is a serious clinical concern implicated in a wide spectrum of eye diseases, including outcomes of surgery for pterygium and glaucoma. It is mainly driven by chronic inflammation that stimulates conjunctival fibroblasts to differentiate into myofibroblasts over time, leading to abnormal wound healing and scar formation. Soluble guanylate cyclase (sGC) stimulation was found to suppress transforming growth factor ß (TGFß)-induced myofibroblastic differentiation in various stromal cells such as skin and pulmonary fibroblasts, as well as corneal keratocytes. Here, we evaluated the in vitro effects of stimulation of the sGC enzyme with the cell-permeable pyrazolopyridinylpyrimidine compound BAY 41-2272 in modulating the TGFß1-mediated profibrotic activation of human conjunctival fibroblasts. Cells were pretreated with the sGC stimulator before challenging with recombinant human TGFß1, and subsequently assayed for viability, proliferation, migration, invasiveness, myofibroblast marker expression, and contractile properties. Stimulation of sGC significantly counteracted TGFß1-induced cell proliferation, migration, invasiveness, and acquisition of a myofibroblast-like phenotype, as shown by a significant downregulation of FAP, ACTA2, COL1A1, COL1A2, FN1, MMP2, TIMP1, and TIMP2 mRNA levels, as well as by a significant reduction in α-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein expression. In addition, pretreatment with the sGC stimulator was capable of significantly dampening TGFß1-induced acquisition of a contractile phenotype by conjunctival fibroblasts, as well as phosphorylation of Smad3 and release of the proinflammatory cytokines IL-1ß and IL-6. Taken together, our findings are the first to demonstrate the effectiveness of pharmacological sGC stimulation in counteracting conjunctival fibroblast-to-myofibroblast transition, thus providing a promising scientific background to further explore the feasibility of sGC stimulators as potential new adjuvant therapeutic compounds to treat conjunctival fibrotic conditions.

Enhanced Monofocal Intraocular Lenses in Fuchs' Endothelial Dystrophy Patients: Results from Triple Descemet Membrane Endothelial Keratoplasty Procedure.

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) is currently regarded as the most effective surgical procedure for addressing Fuchs Endothelial Corneal Dystrophy (FECD), frequently performed in conjunction with cataract surgery. In this retrospective study, we present a comparison of visual performance, clinical outcomes, and optical quality between two types of monofocal Intraocular Lenses (IOLs): one standard and one enhanced intermediate vision model, implanted in patients who underwent combined phacoemulsification and DMEK surgery. METHODS: This single center comparative retrospective study was conducted at the Eye Clinic of the University of Florence (Italy) and included a total of 48 eyes of 48 patients affected by FECD and cataract. All patients underwent combined DMEK with phacoemulsification procedures. The patients' data were analyzed and divided into two groups: one group (standard group) consisted of 24 eyes that underwent phaco-DMEK with implantation of a monofocal IOL, and the second group (enhanced monofocal group) included 24 eyes that underwent phaco-DMEK with implantation of an enhanced monofocal IOL. In both groups, the following monocular visual outcomes were evaluated 6 months after surgery: Uncorrected Distance Visual Acuity (UDVA) and Best-Corrected Distance Visual Acuity (BCDVA) at 4 mts; Uncorrected Intermediate Visual Acuity (UIVA), Distance-Corrected Intermediate Visual Acuity (DCIVA) at 66 cm; Uncorrected Near Visual Acuity (UNVA) and Best Corrected Near Visual Acuity (BCNVA). Monocular defocus curves were also assessed. Furthermore, optical quality in terms of Contrast Sensitivity (CS) in photopic conditions, Higher-Order Aberrations (HOAs) at a pupil size of 5 mm. Modulation Transfer Function (MTF), Objective Scatter Index (OSI), and Strehl ratio, were also analyzed. A Patient-Reported Spectacle Independence Questionnaire was revised to evaluate spectacle independence outcomes. RESULTS: the two groups did not exhibit statistically significant differences in terms of UDVA, BCDVA, UNVA and BCNVA, photopic CS, HOAs, OSI, Strehl ratio, and MTF. However, in the phaco-DMEK enhanced monofocal IOL group, significantly better results were observed in terms of UIVA and DCIVA as well as a different defocus curve profile at 1.50 D, providing better defocus results at intermediate distance compared with the ZCB00 IOL. CONCLUSION: In our study, we found that enhanced monofocal lens performed favorable visual outcomes, even in cases of FECD, compared to standard monofocal IOLs. Comparable optical quality observed in the Eyhance group could allow surgeons to consider these lenses as a viable option for selected patients with FECD.

Effectiveness of a New Active Tear Substitute Containing 0.2% Hyaluronic Acid and 0.001% Hydrocortisone on Signs and Symptoms of Dry Eye Disease by Means of Low- and High-Tech Assessments.

INTRODUCTION: An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog®, Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph®) assessments. METHODS: This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score. RESULTS: Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15 days (6.4 ± 3.6 vs 5.4 ± 3.7 s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45 days (6.8 ± 2.6 vs 5.6 ± 2.3 s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage. CONCLUSION: These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3-6 months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests.

Accuracy of an Air-Puff Dynamic Tonometry Biomarker to Discriminate the Corneal Biomechanical Response in Patients With Keratoconus.

PURPOSE: The aim of this study was to assess accuracy of the mean corneal stiffness ( kc , N/m) parameter to discriminate between patients with keratoconus and age-matched healthy subjects. METHODS: Dynamic Scheimpflug imaging tonometry was performed with Corvis ST (Oculus Optikgeräte GmbH, Germany) in patients with keratoconus (n = 24; study group) and age-matched healthy subjects (n = 32; control). An image processing algorithm was developed to analyze the video sequence of the Corvis ST air-puff event and to determine the geometric and temporal parameters that correlated with the corneal tissue biomechanical properties. A modified 3-element viscoelastic model was used to derive the kc parameter, which represented the corneal tissue resistance to deformation under load. Receiver operating characteristic curves were used to assess the overall diagnostic performance for determining the area under the curve, sensitivity, and specificity of the kc in assessing the corneal tissue deformation to the Corvis ST air-puff event in keratoconus and control eyes. The Corvis Biomechanical Index ( CBI ) was analyzed for external validation. RESULTS: The kc parameter was significantly different between keratoconus and controls ( P < 0.001), ranging from 24.9 ±3.0 to 34.2 ±3.5 N/m, respectively. It was highly correlated with CBI (r = -0.69; P < 0.001); however, the kc parameter had greater specificity (94%) than CBI (75%), whereas the 2 biomarkers had similar area under the curve (0.98 vs. 0.94) and sensitivity (96% vs. 92%) in predicting the occurrence of keratoconus. CONCLUSIONS: The kc parameter extracted by video processing analysis of dynamic Scheimpflug tonometry data was highly accurate in discriminating patients with clinically manifest keratoconus compared with controls.

Hypochlorous acid hygiene solution in patients affected by blepharitis: a prospective randomised study.

BACKGROUND/AIMS: To investigate the clinical outcomes and antimicrobial activity of an hypochlorous acid hygiene solution compared with hyaluronic acid wipes for blepharitis treatment in patients with dry eye disease (DED). METHODS: This study involved 48 eyes of 48 patients affected by blepharitis with mild to moderate DED. 24 patients were treated with a hypochlorous acid hygiene solution (HOCL group) and 24 patients were treated with hyaluronic acid wipes (HYAL group) for a period of 4 weeks. The following clinical outcomes were assessed before (V0) and after the treatment period (V1): non-invasive keratograph break up time (NIK-BUT), tear film BUT (TF-BUT) tear meniscus height (TMH), Keratograph meibography, Meibomian Gland Yield Secretion Score (MGYSS), Corneal Staining Score (CSS), Schirmer test I, Keratograph conjunctival redness score and Ocular Surface Disease Index (OSDI). Moreover, microbiological analysis of upper and lower eyelid margins was performed at V0 both before and 5 min after treatment. RESULTS: After 1-month NIK-BUT and TF-BUT significantly increased in HOCL group, while they did not show a statistically significant difference in HYAL group compared with baseline. OSDI, TMH and MGYSS showed a significant difference in both groups, while Schirmer test, meibography, CSS and conjunctival redness score did not significantly change in both groups. Bacterial load showed a significant reduction in both groups, more pronounced in HOCL group compared with HYAL group. CONCLUSIONS: Hypochlorous acid hygiene solution can be securely employed in blepharitis treatment considering the satisfying clinical outcomes and antimicrobial activity compared with hyaluronic acid wipes.

Dupilumab-Associated Blepharoconjunctivitis: Clinical and Morphological Aspects.

PURPOSE: To describe the clinical and morphologic changes in the ocular surface microstructure of patients affected with moderate-to-severe Atopic Dermatitis (AD) before and during Dupilumab treatment. METHODS: This is a monocentric observational study on thirty-three patients affected with AD before and during Dupilumab treatment. All patients underwent a slit-lamp examination: complete clinical assessment, Break Up Time test (BUT), Schirmer test, and corneal staining grading (Oxford scale) were performed. Meibomian Glands Dysfunction (MGD) evaluation (Meibography), Non-invasive Keratograph Break Up Time test (NIKBUT), Tear Meniscus Height (TMH), and ocular Redness Score (RS) have been investigated using an OCULUS Keratograph. In vivo images of the conjunctiva, cornea, and meibomian glands have been acquired by confocal microscopy. RESULTS: Sixty-six eyes were included in our study: twenty-two eyes of 11 naive patients with indication for treatment but not in therapy yet (Group 1) and forty-four eyes of 22 patients treated with Dupilumab for at least 4 months (subcutaneous administration of 300 mg every 2 weeks) (Group 2). Either patients treated with Dupilumab or naive patients with moderate-to-severe forms of AD had a tear film instability (TBUT and NIKBUT reduced), whereas the quantity of the tear film was overall normal (Schirmer test and TMH), without statistically significant differences between the two groups. When Meibography was performed with the Keratograph, the difference between Group 1 and Group 2 was statistically significant in terms of Meiboscore (p = 0.0043 and p = 0.0242, respectively), as well as the difference in terms of mean RS. These results paired well with the confocal microscopy results in which we found a decrease in the goblet cell population in the conjunctival epithelium in the treated group (5.2 cells/mm), along with inflammatory cells that were more concentrated around the adenoid lumina of the meibomian glands. CONCLUSIONS: In recent years, the use of Dupilumab has been increasing, but mild-to-severe conjunctivitis is a common side effect. Our major results demonstrate a loss of meibomian glands at the Keratograph examination: we can assume a reduced meibum secretion and an evaporative dry eye with MGD. We suggest that the inflammation of the ocular surface may involve not only the cornea and the conjunctiva, but also the meibomian glands, and Dupilumab may play a role. However, the frequency of clear conjunctivitis is not as common as reported in the literature.

Artificial intelligence for detecting keratoconus.

BACKGROUND: Keratoconus remains difficult to diagnose, especially in the early stages. It is a progressive disorder of the cornea that starts at a young age. Diagnosis is based on clinical examination and corneal imaging; though in the early stages, when there are no clinical signs, diagnosis depends on the interpretation of corneal imaging (e.g. topography and tomography) by trained cornea specialists. Using artificial intelligence (AI) to analyse the corneal images and detect cases of keratoconus could help prevent visual acuity loss and even corneal transplantation. However, a missed diagnosis in people seeking refractive surgery could lead to weakening of the cornea and keratoconus-like ectasia. There is a need for a reliable overview of the accuracy of AI for detecting keratoconus and the applicability of this automated method to the clinical setting. OBJECTIVES: To assess the diagnostic accuracy of artificial intelligence (AI) algorithms for detecting keratoconus in people presenting with refractive errors, especially those whose vision can no longer be fully corrected with glasses, those seeking corneal refractive surgery, and those suspected of having keratoconus. AI could help ophthalmologists, optometrists, and other eye care professionals to make decisions on referral to cornea specialists. Secondary objectives To assess the following potential causes of heterogeneity in diagnostic performance across studies. • Different AI algorithms (e.g. neural networks, decision trees, support vector machines) • Index test methodology (preprocessing techniques, core AI method, and postprocessing techniques) • Sources of input to train algorithms (topography and tomography images from Placido disc system, Scheimpflug system, slit-scanning system, or optical coherence tomography (OCT); number of training and testing cases/images; label/endpoint variable used for training) • Study setting • Study design • Ethnicity, or geographic area as its proxy • Different index test positivity criteria provided by the topography or tomography device • Reference standard, topography or tomography, one or two cornea specialists • Definition of keratoconus • Mean age of participants • Recruitment of participants • Severity of keratoconus (clinically manifest or subclinical) SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), Ovid MEDLINE, Ovid Embase, OpenGrey, the ISRCTN registry, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 November 2022. SELECTION CRITERIA: We included cross-sectional and diagnostic case-control studies that investigated AI for the diagnosis of keratoconus using topography, tomography, or both. We included studies that diagnosed manifest keratoconus, subclinical keratoconus, or both. The reference standard was the interpretation of topography or tomography images by at least two cornea specialists. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the study data and assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When an article contained multiple AI algorithms, we selected the algorithm with the highest Youden's index. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included 63 studies, published between 1994 and 2022, that developed and investigated the accuracy of AI for the diagnosis of keratoconus. There were three different units of analysis in the studies: eyes, participants, and images. Forty-four studies analysed 23,771 eyes, four studies analysed 3843 participants, and 15 studies analysed 38,832 images. Fifty-four articles evaluated the detection of manifest keratoconus, defined as a cornea that showed any clinical sign of keratoconus. The accuracy of AI seems almost perfect, with a summary sensitivity of 98.6% (95% confidence interval (CI) 97.6% to 99.1%) and a summary specificity of 98.3% (95% CI 97.4% to 98.9%). However, accuracy varied across studies and the certainty of the evidence was low. Twenty-eight articles evaluated the detection of subclinical keratoconus, although the definition of subclinical varied. We grouped subclinical keratoconus, forme fruste, and very asymmetrical eyes together. The tests showed good accuracy, with a summary sensitivity of 90.0% (95% CI 84.5% to 93.8%) and a summary specificity of 95.5% (95% CI 91.9% to 97.5%). However, the certainty of the evidence was very low for sensitivity and low for specificity. In both groups, we graded most studies at high risk of bias, with high applicability concerns, in the domain of patient selection, since most were case-control studies. Moreover, we graded the certainty of evidence as low to very low due to selection bias, inconsistency, and imprecision. We could not explain the heterogeneity between the studies. The sensitivity analyses based on study design, AI algorithm, imaging technique (topography versus tomography), and data source (parameters versus images) showed no differences in the results. AUTHORS' CONCLUSIONS: AI appears to be a promising triage tool in ophthalmologic practice for diagnosing keratoconus. Test accuracy was very high for manifest keratoconus and slightly lower for subclinical keratoconus, indicating a higher chance of missing a diagnosis in people without clinical signs. This could lead to progression of keratoconus or an erroneous indication for refractive surgery, which would worsen the disease. We are unable to draw clear and reliable conclusions due to the high risk of bias, the unexplained heterogeneity of the results, and high applicability concerns, all of which reduced our confidence in the evidence. Greater standardization in future research would increase the quality of studies and improve comparability between studies.

Early Outcomes of an Artificial Endothelial Replacement Membrane Implantation After Failed Repeat Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to report the outcomes of a novel artificial endothelial replacement membrane implant for treating corneal edema after failed repeat endothelial keratoplasty (EK). DESIGN: This was a retrospective interventional case series. METHODS: Patients with chronic corneal edema underwent removal of the EK graft and implantation of an artificial endothelial replacement membrane (EndoArt, EyeYon Medical, Israel) several months after 2 or more Descemet stripping endothelial keratoplasty procedures. The implant was secured to the posterior corneal surface using an air-gas bubble. Outcome measures included corrected distance visual acuity (logMAR), central corneal thickness, device-related complications, and ocular discomfort. RESULTS: Five eyes of 5 patients underwent EndoArt implantation. Six months after surgery, the synthetic endothelial replacement membrane was well-centered and adherent to the posterior corneal surface, with improvement in central corneal transparency in all patients. Corrected distance visual acuity increased from mean 1.26 ± 0.25 (logMAR) preoperatively to 0.74 ± 0.44 (logMAR) postoperatively (P = 0.06). Central corneal thickness significantly decreased from a mean of 805 ± 135 µm (excluding the EK graft) preoperatively to 588 ± 60 µm (excluding the EndoArt) postoperatively (P = 0.015). No severe device-related complications developed after surgery, although most patients required more than 1 air-gas bubble injection to achieve complete implant adhesion. All patients experienced preoperative reduction in subjective ocular pain. CONCLUSIONS: Synthetic endothelial replacement membrane implantation improves central corneal transparency and visual acuity in patients with failed EK and guarded prognosis for repeat keratoplasty. No significant implant-related adverse events occurred after surgery.

Enhanced Monofocal Intraocular Lenses: A Retrospective, Comparative Study between Three Different Models.

The purpose of this study was to compare the visual performance and optical quality between three new enhanced monofocal intraocular lenses (IOLs). This retrospective study included patients affected by cataracts with corneal astigmatism less than 0.75 D and no ocular comorbidities who underwent cataract surgery with bilateral implantation of Tecnis Eyhance ICB00 (Johnson & Johnson Vision Care, Inc., Jacksonville, FL, USA), Vivinex Impress XY1-EM (Hoya Surgical Optics, Singapore) or IsoPure 123 (PhysIOL, Liege, Belgium) IOLs. Three months postoperatively, monocular and binocular uncorrected and corrected distant, and intermediate and near visual acuities were measured. Binocular defocus curve, photopic contrast sensitivity, Point Spread Function (PSF), low order aberrations (LOAs), high order aberrations (HOAs), objective scatter index (OSI), halo and glare perception were also evaluated. This study included a total of 72 eyes from 36 patients. Visual acuity outcomes, PSF, LOAs, HOAs and OSI were similar between groups. There were no statistically significant differences in terms of photopic contrast sensitivity, halo or glare perception. In patients without ocular comorbidities, the Eyhance ICB00 IOL, the Vivinex Impress IOL and the Isopure IOL-even though based on different optical properties-provided similar results in terms of visual acuity, contrast sensitivity and intraocular aberrations, with no influence on photic phenomena.

Beyond vision:Cataract and health status in old age, a narrative review.

Cataract is a leading cause of visual impairment in old age. Lens opacification is notoriously associated with several geriatric conditions, including frailty, fall risk, depression and cognitive impairment. The association is largely attributable to visual impairment, while other mechanisms, associated with extraocular comorbidity and lifestyle, might partly explain this correlation. Available literature suggests that cataract surgery may be effective in decreasing fall risk, improving depressive symptoms and limiting the risk of cognitive impairment and dementia incidence, although intervention studies on these outcomes are still limited. In this review we also emphasize the need to move from the concept of visual acuity to functional vision, especially in the context of the geriatric patient. Research is needed regarding the effect on the cited outcomes of different cataract treatment strategies, such as systematic bilateral versus monolateral surgery and use of different intraocular lenses.

Efficacy of vector thermal pulsation treatment in reducing postcataract surgery dry eye disease in patients affected by meibomian gland dysfunction.

PURPOSE: To evaluate the effect of a single LipiFlow vector thermal pulsation treatment performed before cataract surgery in reducing signs and symptoms of postoperative dry eye disease (DED) in patients with mild-moderate meibomian gland dysfunction (MGD). SETTING: Eye Clinic, Careggi Hospital, University of Florence, Florence, Italy. DESIGN: Prospective unmasked randomized controlled clinical trial. METHODS: This study included patients affected by age-related cataract and mild-moderate MGD, who were randomized into 2 groups: (1) a single LipiFlow treatment performed at 5 preoperative weeks and (2) warm compresses and eyelid massages twice a day for 1 preoperative month (control group). Noninvasive break-up time (NI-BUT), Schirmer test, Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, and MG functionality parameters were evaluated at visit 0 (5 preoperative weeks), visit 1 (1 preoperative week), and visit 2 (1 postoperative month). Confocal microscopy of the MG of lower eyelids was performed at visit 0 and visit 2. RESULTS: A total of 46 patients (46 eyes) were enrolled. In the LipiFlow group (n = 23), NI-BUT, SPEED questionnaire, and MG functionality parameters significantly improved at visit 1 ( P < .05) and visit 2 ( P < .05) compared with baseline and remained stable postoperatively. In the control group (n = 23), they did not significantly improve after treatment, while worsened postoperatively. Moreover, the changes in all parameters from baseline were significantly different between the 2 groups. Confocal microscopy imaging highlighted lower postoperative MG alterations in the LipiFlow group. CONCLUSIONS: A single preoperative LipiFlow treatment was effective in preventing postcataract surgery DED in patients with mild-moderate MGD. Postoperatively, treated patients displayed a better ocular surface status compared with warm compresses.

Corneal Sub-Basal Nerve Plexus in Non-Diabetic Small Fiber Polyneuropathies and the Diagnostic Role of In Vivo Corneal Confocal Microscopy.

In vivo corneal confocal microscopy (IVCM) allows the immediate analysis of the corneal nerve quantity and morphology. This method became, an indispensable tool for the tropism examination, as it evaluates the small fiber plexus in the cornea. The IVCM provides us with direct information on the health of the sub-basal nerve plexus and indirectly on the peripheral nerve status. It is an important tool used to investigate peripheral polyneuropathies. Small-fiber neuropathy (SFN) is a group of neurological disorders characterized by neuropathic pain symptoms and autonomic complaints due to the selective involvement of thinly myelinated Aδ-fibers and unmyelinated C-fibers. Accurate diagnosis of SFN is important as it provides a basis for etiological work-up and treatment decisions. The diagnosis of SFN is sometimes challenging as the clinical picture can be difficult to interpret and standard electromyography is normal. In cases of suspected SFN, measurement of intraepidermal nerve fiber density through a skin biopsy and/or analysis of quantitative sensory testing can enable diagnosis. The purpose of the present review is to summarize the current knowledge about corneal nerves in different SFN. Specifically, we explore the correlation between nerve density and morphology and type of SFN, disease duration, and follow-up. We will discuss the relationship between cataracts and refractive surgery and iatrogenic dry eye disease. Furthermore, these new paradigms in SFN present an opportunity for neurologists and clinical specialists in the diagnosis and monitoring the peripheral small fiber polyneuropathies.

A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol.

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination.

Ocular Surface Features in Patients with Parkinson Disease on and off Treatment: A Narrative Review.

Parkinson disease (PD) is a progressive, neurodegenerative disease of the central nervous system. Visual disturbance is one of the most frequent nonmotor abnormalities referred to by patients suffering from PD at early stages. Furthermore, ocular surface alterations including mainly dry eye and blink reduction represent another common finding in patients with PD. Tears of PD patients show specific alterations related to protein composition, and in vivo confocal microscopy has demonstrated profound changes in different corneal layers in this setting. These changes can be attributed not only to the disease itself, but also to the medications used for its management. In particular, signs of corneal toxicity, both at epithelial and endothelial level, are well described in the literature in PD patients receiving amantadine. Management of PD patients from the ophthalmologist's side requires knowledge of the common, but often underdiagnosed, ocular surface alterations as well as of the signs of drug toxicity. Furthermore, ocular surface biomarkers can be useful for the early diagnosis of PD as well as for monitoring the degree of neural degeneration over time.

The Soluble Guanylate Cyclase Stimulator BAY 41-2272 Attenuates Transforming Growth Factor ß1-Induced Myofibroblast Differentiation of Human Corneal Keratocytes.

Corneal transparency, necessary for vision and depending on the high organization of stromal extracellular matrix, is maintained by keratocytes. Severe or continuous corneal injuries determine exaggerated healing responses resulting in the formation of irreversible fibrotic scars and vision impairment. Soluble guanylate cyclase (sGC) stimulation demonstrated antifibrotic effects in both experimental fibrosis and human lung and skin fibroblasts. Here, we assessed whether sGC stimulation with BAY 41-2272 could attenuate transforming growth factor ß1 (TGFß1)-induced myofibroblast differentiation of human corneal keratocytes. Cells were challenged with TGFß1, with/without BAY 41-2272 preincubation, and subsequently assessed for viability, proliferation, migration, chemoinvasion, as well for the expression of myofibroblast/fibroblast activation markers and contractile abilities. Treatment with BAY 41-2272 did not affect keratocyte viability, while preincubation of cells with the sGC stimulator was able to inhibit TGFß1-induced proliferation, wound healing capacity, and invasiveness. BAY 41-2272 was also able to attenuate TGFß1-induced myofibroblast-like profibrotic phenotype of keratocytes, as demonstrated by the significant decrease in ACTA2, COL1A1, COL1A2, FN1 and PDPN gene expression, as well as in α-smooth muscle actin, α-1 chain of type I collagen, podoplanin, vimentin and N-cadherin protein expression. Finally, BAY 41-2272 significantly counteracted the TGFß1-induced myofibroblast-like ability of keratocytes to contract collagen gels, reduced phosphorylated Smad3 protein levels, and attenuated gene expression of proinflammatory cytokines. Collectively, our data show for the first time that BAY 41-2272 is effective in counteracting keratocyte-to-myofibroblast transition, thus providing the rationale for the development of sGC stimulators as novel promising modulators of corneal scarring and fibrosis.