Assessment of the predictive ability of theranostics for corneal cross-linking in treating keratoconus: a randomized clinical trial.

PURPOSE: To validate the ability of theranostic imaging biomarkers in assessing the propensity of corneal cross-linking (CXL) in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (epi-off; 25 eyes) and epithelium-on (epi-on; 25 eyes) CXL protocols using UV-A medical device incorporating theranostic software module. The device used controlled UV-A light both for performing CXL and for estimating the corneal riboflavin concentration (riboflavin score) and assessing treatment effect (theranostic score) in real time. A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epi-off and epi-on protocols respectively. All eyes underwent 9 minutes UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to correctly classify eyes and positively predict a Kmax flattening at 1 year after CXL. Other outcome measures were the change of Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction, and central corneal thickness one year after CXL. RESULTS: Accuracy and precision of the combined use of theranostic imaging biomarkers in predicting eyes that had more than 0.1 diopter (D) Kmax flattening at 1 year were 91% and 95% respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR: -2.11, -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 LogMAR (IQR: -0.3, 0.0 LogMAR; P < 0.001 and IQR: -0.2, 0.0 LogMAR; P < 0.001 respectively). There were no significant changes in endothelial cell density (P = 0.33) and central corneal thickness (P = 0.07) 1 year postoperatively. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epi-off and epi-on CXL protocols. The concentration of riboflavin and its UV-A light mediated photo-activation in the cornea are the primary factors determining CXL treatment efficacy.

Marine Natural Products Rescuing the Eye: A Narrative Review.

Different degrees of visual impairment lead to a decrease in patient wellbeing, which has an adverse effect on many facets of social and professional life. Eye disorders can affect several parts of the eye, most notably the retina and the cornea, and the impacted areas might share a common form of cellular damage or dysfunction (such as inflammation, oxidative stress and neuronal degeneration). Considering that marine organisms inhabit a broad variety of marine habitats, they display a great degree of chemical diversity. As a result, molecules with a marine origin are receiving more and more attention in the hopes of developing novel therapeutic approaches. For instance, fucoxanthin has been demonstrated to be effective in protecting the retina against photo-induced damage, while largazole, astaxanthin and spirulina have all shown antioxidant, anti-inflammatory and antiapoptotic activities that can be useful for the management of several ocular diseases, such as age-related macular degeneration and ocular surface disorders. The aim of this review is to analyze the scientific literature relating to the therapeutic effects on the eye of the main natural marine products, focusing on their mechanism of action and potential clinical uses for the management of ocular diseases.

A Systematic Quality Assessment of Online Resources on Eyelid Ptosis Using the Modified Ensuring Quality Information for Patients (mEQIP) Tool.

BACKGROUND: Eyelid ptosis is an underestimated pathology deeply affecting patients' quality of life. Internet has increasingly become the major source of information regarding health care, and patients often browse on websites to acquire an initial knowledge on the subject. However, there is lack of data concerning the quality of available information focusing on the eyelid ptosis and its treatment. We systematically evaluated online information quality on eyelid ptosis by using the "Ensuring Quality Information for Patients" (EQIP) scale. MATERIALS AND METHODS: Google, Yahoo and Bing have been searched for the keywords "Eyelid ptosis," "Eyelid ptosis surgery" and "Blepharoptosis." The first 50 hits were included, evaluating the quality of information with the expanded EQIP tool. Websites in English and intended for general non-medical public use were included. Irrelevant documents, videos, pictures, blogs and articles with no access were excluded. RESULTS: Out of 138 eligible websites, 79 (57,7%) addressed more than 20 EQIP items, with an overall median score of 20,2. Only 2% discussed procedure complication rates. The majority fail to disclose severe complications and quantifying risks, fewer than 18% clarified the potential need for additional treatments. Surgical procedure details were lacking, and there was insufficient information about pre-/postoperative precautions for patients. Currently, online quality information has not improved since COVID-19 pandemic. CONCLUSIONS: This study highlights the urgent requirement for improved patient-oriented websites adhering to international standards for plastic and oculoplastic surgery. Healthcare providers should effectively guide their patients in finding trustworthy and reliable eyelid ptosis correction information. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Nanoparticles from Microalgae and Their Biomedical Applications.

Over the years, microalgae have been a source of useful compounds mainly used as food and dietary supplements. Recently, microalgae have been used as a source of metabolites that can participate in the synthesis of several nanoparticles through inexpensive and environmentally friendly routes alternative to chemical synthesis. Notably, the occurrence of global health threats focused attention on the microalgae application in the medicinal field. In this review, we report the influence of secondary metabolites from marine and freshwater microalgae and cyanobacteria on the synthesis of nanoparticles that were applied as therapeutics. In addition, the use of isolated compounds on the surface of nanoparticles to combat diseases has also been addressed. Although studies have proven the beneficial effect of high-value bioproducts on microalgae and their potential in medicine, there is still room for understanding their exact role in the human body and translating lab-based research into clinical trials.

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.

Outcomes of serial sessions of Activa mask combined with intense pulsed light therapy in patients with Meibomian gland dysfunction.

BACKGROUND: To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD). METHODS: Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire. RESULTS: Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 µm (all P < 0.001), while MGL and tear osmolarity decreased from 21.1 ± 17.3 to 17.0 ± 14.1% and from 302.0 ± 8.5 to 295.7 ± 6.9 mOsm/L (respectively, P = 0.004 and P < 0.001). In parallel, OSDI score decreased significantly from 49.8 ± 13.5 to 29.8 ± 10.6 (P < 0.001). In the historical control group of patients who underwent only IPL, NIBUT, LLT, tear osmolarity and OSDI improved significantly but not MGL and TMH. CONCLUSIONS: Serial sessions incorporating the application of an eye mask producing heating and vibration immediately followed by IPL therapy are able to improve all ocular surface parameters as well as ocular discomfort symptoms in MGD patients.

Wide Range Applications of Spirulina: From Earth to Space Missions.

Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.

Exploring the Healthy Eye Microbiota Niche in a Multicenter Study.

PURPOSE: This study aims to explore and characterize healthy eye microbiota. METHODS: Healthy subjects older than 18 years were selected for this descriptive cross-sectional study. Samples were collected with an eSwab with 1 mL of Liquid Amies Medium (Copan Brescia, Italy). Following DNA extraction, libraries preparation, and amplification, PCR products were purified and end-repaired for barcode ligation. Libraries were pooled to a final concentration of 26 pM. Template preparation was performed with Ion Chef according to Ion 510, Ion 520, and Ion 530 Kit-Chef protocol. Sequencing of the amplicon libraries was carried out on a 520 or 530 chip using the Ion Torrent S5 system (Thermo Fisher; Waltham, MA, USA). Raw reads were analyzed with GAIA (v 2.02). RESULTS: Healthy eye microbiota is a low-diversity microbiome. The vast majority of the 137 analyzed samples were highly enriched with Staphylococcus, whereas only in a few of them, other genera such as Bacillus, Pseudomonas, and Corynebacterium predominate. We found an average of 88 genera with an average Shannon index of 0.65. CONCLUSION: We identified nine different ECSTs. A better understanding of healthy eye microbiota has the potential to improve disease diagnosis and personalized regimens to promote health.

Special Issue "Diagnosis and Management of Dry Eye Disease and Ocular Surface Inflammation".

It is estimated that a wide proportion of the world's population (5% to 50%) may suffer from dry eye disease to a various extent [...].

Retinal microcirculation abnormalities in patients with systemic sclerosis: an explorative optical coherence tomography angiography study.

OBJECTIVES: To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A). METHODS: A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries. RESULTS: The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients. CONCLUSION: We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.

Automated digital analysis of intraoperative keratoscopy and its correlation with postoperative astigmatism after big-bubble deep anterior lamellar keratoplasty.

PURPOSE: To investigate the correlation between postoperative corneal astigmatism (PCA) and values of intraoperative keratoscopy analyzed with a newly developed automated technique in patients undergoing big-bubble (BB) deep anterior lamellar keratoplasty (DALK). METHODS: Photographs of keratoscope rings taken at the end of BB-DALK were analyzed using ImageJ for the calculation of "roundness" (R): values = 1 indicate a perfect circle. Pearson's correlation was used to evaluate the relationship between R and PCA that measured 1 week (V1), 3 months (V2), and 18 months (V3), postoperatively. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the accuracy of R for identifying patients with PCA < 3 diopters (D). The point on the ROC curve nearest to the coordinate (0,100) was used as a cutoff to determine sensitivity and specificity. RESULTS: Data from 121 patients were included. The mean value of R*was 0.93 ± 0.04 (range 0.76-0.99). R showed a significant correlation with PA at V3 (R = - 0.42, P < 0.01). The ROC curve had an AUC of 0.69 (95% CI 0.59-0.79). A cutoff value of R = 0.93 had a sensitivity of 70.3% and specificity of 61.0% for identifying patients with PA < 3D at V3. CONCLUSIONS: This new digital analysis of keratoscope rings allows to identify with reasonably good diagnostic accuracy patients with low values of post-DALK astigmatism correctable with spectacles.

Short-term choroidal vascular changes after aflibercept therapy for neovascular age-related macular degeneration.

INTRODUCTION: The purpose of this study was to evaluate choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept injection over a 3-month period. METHODS: Enhanced depth imaging optical coherence tomography scans of 60 eyes with treatment-naïve nAMD and 60 unaffected fellow eyes were retrospectively analyzed. Data was collected at baseline and after 3 monthly intravitreal injections of aflibercept. The ImageJ software was used to binarize OCT scans and measure total choroid area (TCA), luminal area (LA), and stromal area (SA). Choroidal vascularity index (CVI) was defined as the ratio of LA to TCA. RESULTS: After treatment, subfoveal choroidal thickness (CT) in nAMD eyes significantly decreased from 210. 6 ± 61.6 to 194.6 ± 58.7 µm (P < 0.001), TCA from 1.620 ± 0.502 to 1.500 ± 0.451 mm2 (P < 0.001), LA from 1.075 ± 0.335 to 0.985 ± 0.307 mm2 (P < 0.001), SA from 0.545 ± 0.176 to 0.516 ± 0.153 mm2 (P = 0.005), and CVI from 66.36 ± 2.89 to 65.46 ± 2.87% (P = 0.009). The decrease of CVI after treatment was significantly correlated with baseline CVI (Rs = 0.466, P < 0.001), but not with the change in BCVA and presence of dry macula after treatment (always P > 0.05). CONCLUSION: Choroidal thickness and vascularity significantly decreased after treatment with aflibercept in nAMD eyes. Besides the pharmacologic effect on the neovascular lesion, aflibercept may induce vascular changes also on the underlying choroid.

Multimodal imaging of Hypotrichosis with juvenile macular dystrophy: a case report.

BACKGROUND: To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging. CASE PRESENTATION: An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD). Fundus examination showed several alterations of the retinal pigment epithelium and circular pigmented area of chorioretinal atrophy. Structural spectral domain optical coherence tomography (OCT) showed some backscattering phenomenon with several alterations of retinal pigment epithelium and photoreceptor layer in both eyes. Moreover, OCT showed hyperreflective lesion beneath the neuroepithelium in left eye. OCT angiography (OCT-A) revealed a pathologic neovascular network in choriocapillaris plexus, probably the result of a fibrovascular membrane. Multifocal electroretinograms (MfERGs) showed functional alterations in 12.22° of the central retina. In order to confirm the suspicion of HJMD, the child and both parents underwent genetic testing. Both parents resulted to be heterozygous healthy carriers of a single variation. CONCLUSION: Multimodal imaging, in particular OCT-A, is a useful aid, along to clinical findings and genetics, for the diagnosis of inherited retinal dystrophies.

CHOROIDAL VASCULARITY INDEX QUANTIFICATION IN GEOGRAPHIC ATROPHY USING BINARIZATION OF ENHANCED-DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHIC SCANS.

PURPOSE: To evaluate choroidal structural changes occurring over time in geographic atrophy (GA) secondary to age-related macular degeneration using choroidal vascularity index (CVI). METHODS: Enhanced-depth imaging optical coherence tomography scans of 34 patients with GA and 32 control subjects were retrospectively analyzed. Data were collected at baseline and after a mean follow-up of 18.3 ± 8.3 months. Choroidal images were binarized using the ImageJ software, and the luminal area and stromal area were segmented. Choroidal vascularity index was defined as the ratio of luminal area to total choroid area. RESULTS: Patients with GA showed significantly lower values of CVI, total choroid area, luminal area, and subfoveal choroidal thickness compared to control subjects (65.83 ± 3.95 vs. 69.33 ± 3.11, P < 0.001; 0.400 ± 0.239 mm vs. 0.491 ± 0.132, P = 0.006; 0.263 ± 0.152 mm vs. 0.340 ± 0.094, P = 0.002; 185.2 ± 79.8 µm vs. 216.8 ± 58.8 µm, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = -0.509; P = 0.002). During the follow-up period in patients with GA, subfoveal choroidal thickness decreased from 185.2 ± 79.8 to 152.2 ± 73.1 (P = 0.001), stromal area increased from 0.138 ± 0.090 mm to 0.156 ± 0.068 (P = 0.028), and CVI decreased from 65.83 ± 3.95 to 62.24 ± 3.63 (P < 0.001). CONCLUSION: This study showed for the first time that CVI is reduced in patients with GA, and that this metric further worsened during the follow-up period.

Obstructive Sleep Apnea and Keratoconus: A Systematic Review and Meta-analysis.

BACKGROUND: Despite the increasing number of studies focused on the association between obstructive sleep apnea (OSA) and keratoconus (KC), to date, no comprehensive meta-analysis or systematic review was published. OBJECTIVE: The objective of this study was to evaluate the association between OSA and KC. DATA SOURCES: Sources of data were PubMed, Scopus, and Web of Science databases. STUDY ELIGIBILITY CRITERIA: The criteria for study eligibility were case-control studies and cohort studies reporting data on the association of OSA with KC with risk ratio, odds ratio, or hazard ratio with 95% confidence intervals or sufficient raw data for calculation. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was conducted with a random-effects model using odds ratio with 95% confidence interval as the effect size. Heterogeneity was evaluated using the Q and I tests. Sensitivity analysis and assessment of publication bias were performed. RESULTS: Five studies (four case-control studies and one cohort study) published between 2012 and 2016 and involving 33,844 subjects (16,922 patients with KC, 16,922 controls) were included in this meta-analysis. A significant association between OSA and KC has been shown (pooled odds ratio, 1.841; 95% confidence interval, 1.163 to 2.914; P = .009). A significant heterogeneity was observed (Q = 15.8, I = 74.6%). There was no evidence of significant publication bias (P = .07). The sensitivity analyses indicated the stability of results. LIMITATIONS: Heterogeneity across the studies was observed. Data from four hospital-based case-control studies and one large population-based cohort study were combined. Most of the included studies ascertained OSA by the Berlin Questionnaire, which is a screening tool. CONCLUSIONS: This meta-analysis provides significant evidence that OSA is associated with KC. Therefore, a proper screening for OSA is warned for KC patients for the prevention of various cardiovascular comorbidities. Further prospective studies are warranted to explore more in-depth the casual relationship between the two conditions.

Clinical Applications of Astaxanthin in the Treatment of Ocular Diseases: Emerging Insights.

Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in microalgae and seafood such as salmonids, shrimps and lobsters. Due to its unique molecular structure, astaxanthin features some important biologic properties, mostly represented by strong antioxidant, anti-inflammatory and antiapoptotic activities. A growing body of evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases, ranging from the anterior to the posterior pole of the eye. Therefore, the present review aimed at providing a comprehensive evaluation of current clinical applications of astaxanthin in the management of ocular diseases. The efficacy of this carotenoid in the setting of retinal diseases, ocular surface disorders, uveitis, cataract and asthenopia is reported in numerous animal and human studies, which highlight its ability of modulating several metabolic pathways, subsequently restoring the cellular homeostatic balance. To maximize its multitarget therapeutic effects, further long-term clinical trials are warranted in order to define appropriate dosage, route of administration and exact composition of the final product.

Impact of cataract surgery on depression and cognitive function: Systematic review and meta-analysis.

IMPORTANCE: In elderly people, visual impairment is associated with depressive symptoms and cognitive decline. However, the impact of cataract surgery on depression and cognitive impairment is still controversial. BACKGROUND: To evaluate the effect of cataract surgery on depression and cognitive status in the elderly. DESIGN: This study was a meta-analysis. PARTICIPANTS: Patients with age-related cataract who underwent cataract surgery were recruited for this study. METHODS: A literature search was performed on PubMed, Scopus and Web of Science. Data were extracted from selected studies by two independent reviewers. The pooled standardized mean difference (SDM) was estimated using a random-effects model. Heterogeneity was evaluated using the Q and I2 tests. Multiple sensitivity analyses and assessment of publication bias were performed. MAIN OUTCOME MEASURES: The main outcome was a report of a measure of depression or cognitive impairment before and after surgery. RESULTS: Sixteen studies were included: 14 of them reported data on depression and 9 of them on cognitive function. Depression significantly decreased after surgery (SDM = 0.460; 95% CI: 0.223-0.697; P < .001). In six controlled studies, the reduction of depression was higher in the surgery group than in the control group (SDM = 0.161; 95% CI: 0.027-0.295; P = .019). Cognitive function significantly improved after surgery (SDM = 0.254; 95% CI: 0.120-0.388; P < .001). In four controlled studies, the improvement of cognitive function was higher in the surgery group than in the control group (SDM = 0.188; 95% CI: 0.002-0.374; P = .048). Results were stable after sensitivity analyses. CONCLUSIONS AND RELEVANCE: This meta-analysis provides evidence that cataract surgery has a positive effect on depression and cognitive function in the elderly.

Biomarkers in Tears and Ocular Surface: A Window for Neurodegenerative Diseases.

OBJECTIVES: The purpose of this review is to briefly outline current scientific evidence on the potential role of tear analysis and ocular surface evaluation in diagnosis and monitoring of neurodegenerative diseases, especially Alzheimer disease, Parkinson disease, and glaucoma. METHODS: A systematic computerized search in the electronic databases PubMed, MEDLINE, and the Cochrane Collaborations was conducted to find eligible articles which their main topic was to investigate the tear and ocular surface in neurodegenerative diseases. After a first screening of titles and abstracts and a full-text review, 26 articles met the inclusion criteria (1 about the neurodegenerative diseases, 3 about the Alzheimer disease, 11 about the Parkinson disease, 11 about glaucoma, and 1 about amyotrophic lateral sclerosis). RESULTS: The ocular surface picture seems to be altered in the setting of neurodegenerative diseases with specific characteristics according to each disease. They seem to be associated with reduced corneal sensitivity and abnormal tear function, and each one presents the expression of specific biomarkers in tears. CONCLUSIONS: The study of tears and ocular surface appears to be a new and noninvasive promising way to assist in the diagnosis and monitoring of neurodegenerative diseases.

Therapeutic Effects of Lactoferrin in Ocular Diseases: From Dry Eye Disease to Infections.

Lactoferrin is a naturally occurring iron-binding glycoprotein, produced and secreted by mucosal epithelial cells and neutrophils in various mammalian species, including humans. It is typically found in fluids like saliva, milk and tears, where it reaches the maximum concentration. Thanks to its unique anti-inflammatory, antioxidant and antimicrobial activities, topical application of lactoferrin plays a crucial role in the maintenance of a healthy ocular surface system. The present review aims to provide a comprehensive evaluation of the clinical applications of lactoferrin in ocular diseases. Besides the well-known antibacterial effect, novel interest has been rising towards its potential application in the field of dry eye and viral infections. A growing body of evidence supports the antimicrobial efficacy of lactoferrin, which is not limited to its iron-chelating properties but also depends on its capability to directly interact with pathogen particles while playing immunomodulatory effects. Nowadays, lactoferrin antiviral activity is of special interest, since lactoferrin-based eye drops could be adopted to treat/prevent the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which has conjunctivitis among its possible clinical manifestations. In the future, further data from randomized controlled studies are desirable to confirm the efficacy of lactoferrin in the wide range of ocular conditions where it can be used.