Short Wavelength Automated Perimetry, Standard Automated Perimetry, and Optical Coherence Tomography in Dominant Optic Atrophy.

Background: Blue-yellow axis dyschromatopsia is well-known in Autosomal Dominant Optic Atrophy (ADOA) patients, but there were no data on the correlation between retinal structure and short-wavelength automated perimetry (SWAP) values in this pathology. Methods: In this cross-sectional case-control study, we assessed the correlation between best corrected visual acuity (BCVA), standard automated perimetry (SAP), SWAP, and optical coherence tomography (OCT) parameters of 9 ADOA patients compared with healthy controls. Correlation analysis was performed between BCVA, mean deviation, pattern standard deviation (PSD), and fovea sensitivity (FS) values and the OCT thickness of each retinal layer and the peripapillary retinal nerve fiber layer (pRNFL). Results: The following significant and strong correlations were found: between BCVA and ganglion cell layer (GCL) and the global (G) pRNFL thicknesses; between SAP FS and GCL and the G-pRNFL thicknesses; between SWAP PSD and total retina, GCL, inner plexiform layer, inner nuclear layer, inner retinal layer and the temporal pRNFL thicknesses. We found a constant shorter duration of the SITA-SWAP compared with the SITA-STANDARD strategy. Conclusions: SWAP, SAP, and BCVA values provided relevant clinical information about retinal involvement in our ADOA patients. The perimetric functional parameters that seemed to correlate better with structure involvement were FS on SAP and PSD on SWAP.

Non-Invasive High-Resolution Imaging of In Vivo Human Myelinated Axons.

This work aims to reveal the microscopic (2-3 micrometer resolution) appearance of human myelinated nerve fibers in vivo for the first time. We analyzed the myelinated retinal nerve fibers of a male patient without other neurological disorders in a non-invasive way using the transscleral optical phase imaging method with adaptive optics. We also analyzed the fellow eye with non-myelinated nerve fibers and compared the results with traditional ocular imaging methods such as optical coherence tomography. We documented the microscopic appearance of human myelin and myelinated axons in vivo. This method allowed us to obtain better details than through traditional ocular imaging methods. We hope these findings will be useful to the scientific community to evaluate neuro-retinal structures through new imaging techniques and more accurately document nerve anatomy and the pathophysiology of this disease.

EBEI: A new index of eye bank efficiency.

PURPOSE: To describe a new proxy of the Eye Bank (EB) activity named "Eye Bank Efficiency Index" (EBEI), calculated as the ratio between the number of corneal tissues distributed by an EB within a certain time period, and the difference between the number of procured and discarded tissues. METHODS: To demonstrate the effectiveness of the new metric as compared to traditional statistics, an analysis was conducted using data from the largest Italian Eye Bank (Fondazione Banca degli Occhi del Veneto Venice, Italy). Collected data included: the number of corneas retrieved, the number of discarded grafts, and the number of distributed tissues. The analysis focused on three defined timeframes: January to December, March to May (the "Italian Lockdown period"), and June to December (the "Italian post-lockdown period"). RESULTS: In 2020, the annual variation of the EBEI showed a significant increase of up to 3.4% compared to the previous year (0.986 in 2019; 1.020 in 2020), but then gradually decreased to 0.993 in 2022. However, during the months of lockdown in 2020, there was a significant decline of -13.8% in the EBEI compared to the same period in the previous year. The variation in the EBEI during the post-lockdown months was minimal in 2020 and 2021, with the lowest EBEI value of 0.976 being reached in 2022 (-7.8% compared to 2019). CONCLUSION: The EBEI is a simple and reliable new measure of the EB activity. Its widespread adoption could ensure a more accurate and reliable analysis of EB data for academic, political, and economic purposes.

Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE.

OBJECTIVES: Patients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in patients with SLE than in HCs. Retinal microvascular impairment detected through optical coherence tomography angiography (OCTA) was investigated as a marker of systemic vascular involvement in SLE.The aim of the study was to evaluate the relationship between retinal vascular impairment and IMT in SLE. METHODS: Cross-sectional study recruiting patients with SLE and HCs. Data of the study population were collected. CV risk was evaluated through the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, Framingham and QRESEARCH risk estimator V.3 (QRISK3) scores. Both groups underwent OCTA and carotid ultrasound with IMT assessment.Statistical analysis was accomplished using Pearson/Spearman, t-test/Mann-Whitney or χ2 test. Variables statistically significant at univariate regression analysis were tested in an age-corrected and sex-corrected multivariate regression model. RESULTS: 43 patients with SLE and 34 HCs were recruited. Patients with SLE showed higher triglycerides (p=0.019), Triglycerides-Glucose (TyG) Index (p=0.035), ACC/AHA guidelines (p=0.001), Framingham Risk Scores (p=0.008) and a reduced superficial (p<0.001) and deep (p=0.005) whole retinal vessel density (VD) compared with HCs.In SLE univariate analysis, deep whole VD showed a negative correlation with IMT (p=0.027), age (p=0.001), systolic blood pressure (p=0.011), QRISK3 Score (p<0.001), Systemic Lupus International Collaborating Clinics Damage Index (p=0.006) and apolipoprotein B (p=0.021), while a positive correlation was found with female sex (p=0.029). Age-adjusted and sex-adjusted multivariate analysis confirmed QRISK3 Score (p=0.049) and IMT (p=0.039) to be independent risk factors for reduced retinal VD. CONCLUSIONS: Patients with SLE showed lower retinal VD and higher CV risk indicators compared with HCs. Among patients with SLE, QRISK3 Score and IMT were found to be independent risk factors for retinal vascular impairment, suggesting a role of OCTA in evaluating preclinical CV involvement in SLE. Moreover, TyG Index could represent a biomarker of CV risk in patients with SLE compared with HCs.

Framing Effects on Willingness and Perceptions towards COVID-19 Vaccination among University Students in Italy: An Exploratory Study.

Vaccine hesitancy is a diffused psychological phenomenon that has been increasingly addressed in several studies since the COVID-19 pandemic. Communication campaigns play a pivotal role influencing recipients' perceptions and may affect the likelihood to vaccinate or to show hesitancy. In the context of communicating risks during the COVID-19 pandemic, we hypothesized that highlighting different aspects of data on the effectiveness of vaccines would influence people's willingness and attitudes to vaccinate. In this exploratory study, we administered two versions of a survey to a convenience sample of students from three universities in Italy. In the first version, salience was placed on the effectiveness of the vaccine in terms of reducing the probability of infection. In the second version, salience was placed on the effectiveness of the vaccine in terms of reducing the probability of hospitalization after being infected by COVID-19. The results confirmed our hypothesis: participants reported that they were more willing to become vaccinated when exposed to the hospitalization frame (main dimension). Conversely, we found mixed effects of the frame on the following sub-dimensions: reliability, trust, protection, safety, and confidence. Taken together, we show that it is possible to influence, to some extent, university students' attitudes and perceptions toward COVID-19 vaccination by acting on how information is framed. We discuss the implications of these findings for the development of behaviorally informed policies.

Assessment of microvascular involvement in lupus nephritis patients by retinal OCT-angiography and kidney biopsies.

OBJECTIVES: Ocular and renal microvascular damage in lupus nephritis (LN) share similar physiopathological pathways that have investigated using traditional fundus examination and high-resolution colour electroretinography. Optical coherence tomography angiography (OCTA) is a recent, non-invasive technique for imaging the microvasculature of retina and choroid. Aim of the study was to investigate through OCTA analysis the relationship between retinal microvascular alterations and renal functional and histologic features. METHODS: Systemic lupus erythematosus (SLE) patients with LN, SLE without renal involvement and healthy controls were recruited and accomplished an ophthalmological evaluation, including OCTA. SLE-LN patients underwent a rheumatological evaluation, including disease-related clinical and laboratory features collection and kidney biopsy examination. RESULTS: This cross-sectional study enrolled forty-six eyes of 23 LN patients, thirty-two eyes of 16 SLE patients and forty-two eyes of 21 controls. Thirteen SLE-LN patients (56.5%) displayed lupus retinopathy, 10 at moderate (77%) and 3 at severe stage (23%) by fundus oculi examination. Analysis of OCTA data showed with high/moderate accuracy a reduction of retinal capillary vessel density in both SLE and SLE-LN patients compared to controls in superficial and deep plexi. A reduction in fovea thickness and an increase in foveal avascular zone were also detected. OCTA data of LN patients correlated with LN duration, disease activity, kidney function and the presence of LN-vascular lesions at kidney biopsy. CONCLUSIONS: Our results suggest the role of OCTA in early detection of systemic vascular involvement in SLE-LN patients and related kidney functional-histological impairment.

Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) prevalence in obstructive sleep apnea syndrome (OSA) patients: a systematic review and meta-analysis.

PURPOSE: Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) represent two distinct conditions which have been associated with several ocular and systemic comorbidities. The main aim of this systematic review and meta-analysis is to explore the available literature to estimate the prevalence rate of LEC and FES in obstructive sleep apnea (OSA). METHODS: The protocol of this systematic review and meta-analysis has been registered in PROSPERO. Four electronic databases (PubMed/MEDLINE, Google Scholar, Cochrane Library, Web of Science) were searched from inception to December 24, 2021. A random intercept logistic regression model was carried out for the analysis of overall proportions. Odds ratio and mean difference were reported as measures of the effect size in the presence of binary and continuous outcomes, respectively. The estimated numbers of LEC/FES patients in OSA were calculated by multiplying the prevalence rate determined by our random-effects model and the corresponding Benjafield et al.'s population prospect. RESULTS: We included 11 studies comprising 1225 OSA patients of whom 431 and 153 affected by LEC and FES, respectively. Our model estimated a pooled prevalence rate for LEC and FES in OSA patients of 40.2% (95%CI: 28.6-53.1%) and of 22.4% (95%CI: 13.8-34.2%), respectively. The number of LEC/FES affected individuals among OSA patients is expected to peak up to 376 and to 210 million, respectively. OSA patients appeared to have a 3.4 (95%CI: 2.2-5.2) and a 3.0 (95%CI: 1.7-5.5) increased risk of developing LEC and FES than the healthy counterpart. CONCLUSION: Prevalence of LEC and FES is higher in OSA-affected patients compared to controls. More studies are warranted to investigate the mechanisms leading to the development of LEC and/or FES in OSA patients, as well as the feasibility of the adoption of these clinical findings as screening tools for OSA.

Primary Open Angle Glaucoma Prevalence in Europe: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to evaluate the prevalence of POAG in Europe. METHODS: Two authors independently conducted a systematic literature search on PubMed/MedLine, Web of Science, and Google Scholar to identify papers analyzing the prevalence of POAG in European countries. After removal of duplicates, title and abstract screening, and full-text analysis, data from selected articles were entered in an Excel spreadsheet. We performed risk of bias assessment using the Joanna Briggs Institute Prevalence Critical Appraisal Tool and conducted a meta-analysis using the R software (version 1.4.1106). RESULTS: We retrieved 9348 eligible papers from the initial electronic search and included 10 of them in the qualitative and quantitative analyses. A total of 26,993 patients were included in this meta-analysis (11,927 male and 14,556 female). We identified 755 POAG cases (397 male and 348 female), with a pooled prevalence estimate in Europe of 2.60% (95% confidence interval: 1.90%-3.56%). Increasing odds for POAG were related to increasing age and some geographic differences in the disease distribution in the continent were identified. Statistically significant sex-related differences in the prevalence rate of POAG were not observed in this cohort. CONCLUSION: POAG is a neurodegenerative disease that affects a large proportion of the older European population. In the future, the prevalence of POAG is expected to grow in Europe because of the progressive aging populations of Western countries. Future high-quality epidemiological studies for the evaluation of POAG prevalence rates are warranted.

Global Prevalence of Fuchs Endothelial Corneal Dystrophy (FECD) in Adult Population: A Systematic Review and Meta-Analysis.

Purpose: To evaluate the global prevalence of Fuchs endothelial corneal dystrophy (FECD). Design: Systematic review and meta-analysis. Methods: A systematic electronic literature search was conducted on PubMed/MedLine, Cochrane Library, and Google Scholar, in order to select papers analysing the prevalence rate of FECD. Two authors independently conducted the electronic search. After removal of duplicates, title and abstract screening, and full-text analysis, data from selected articles were archived in a customized Excel spreadsheet. Risk of bias assessment was performed using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. Meta-analysis was conducted using R (version 1.4.1106, package "meta"). Results: A total of 6660 eligible articles were retrieved from the initial electronic search. Only 4 original works were included in the qualitative and quantitative analysis. Of the 4746 patients included in this meta-analysis (i.e., 2232 male (M) and 2322 female (F)), we retrieved 269 FECD cases (81 M; 188 F), with a pooled prevalence estimates of 7.33% (95% CI: 4.08-12.8%). Statistically significant gender-related differences in the prevalence of FECD emerged by the analysis (OR: 2.22; 95% CI: 1.66-2.96, p=0.0016). While the total number of people aged >30 years with FECD is nowadays estimated at nearly 300 million, an increase of 41.7% in the number of FECD-affected patients is expected by 2050, when the overall figure is supposed to rise up to 415 million. Conclusion: This study provides a reliable figure of the present and future epidemiological burden of FECD globally, which might be useful for the design of FECD screening, treatment, rehabilitation, and related public health strategies.

The effectiveness of nudging interventions to promote healthy eating choices: A systematic review and an intervention among Italian university students.

Nudges are changes in choice architecture (i.e., the environment in which people make decisions) aiming to steer a person's decision to a particular choice, without restricting alternative options or changing financial incentives. These strategies have been extensively used to promote healthy eating, above all among youths, whose behaviors can still be easily shaped compared to older people's. The current paper describes two studies aiming to investigate the effectiveness of nudging interventions in promoting healthy eating among university students. The first study consisted of a systematic review mapping all the published studies which describe the effectiveness of this kind of intervention worldwide. Twelve eligible records were selected after a search of three different databases. Information about the publication of the record, the adopted research methods and the described intervention was retrieved from each selected record. Based on this review's results, a new nudging intervention was developed to promote healthy food choice among Italian university students. The intervention aimed to modify students' choice for each of the Italian meal courses: first course (pasta, rice or soup), second course (meat, fish, cheese or cured meat), side dish, bread, and fruit. An Italian university cafeteria was observed in two phases: a pre-intervention phase (baseline) and a post-intervention phase (nudging strategies were implemented in the cafeteria's architecture). The applied nudging intervention was effective in promoting healthy choices in relation to the second course, the side dish, and the bread, but it did not significantly affect choices related to the first course or the fruit. Implications of these results and suggestions for future interventions are discussed.

Optical coherence tomography angiography in the multimodal assessment of the retinal posterior pole in autosomal dominant optic atrophy.

PURPOSE: To assess retinal vascular involvement in patients with autosomal dominant optic atrophy (ADOA) genetically confirmed by the presence of the OPA1 (Optic Atrophy 1) gene mutation using a multimodal protocol of investigation of retinal posterior pole. METHODS: In this cross-sectional, case-control, observational study, both eyes of 13 patients with a genetic diagnosis of ADOA were compared with both eyes of 13 healthy controls (HCs). All subjects underwent full ophthalmological examination, spectral domain-optical coherence tomography (SD-OCT), fundus perimetry (FP) and OCT angiography (OCTA). RESULTS: Vessel density (VD) of the superficial and deep macular vascular plexi and of the radial peripapillary capillary plexus were significantly decreased (p ≤ 0.001) in ADOA patients compared with HCs. The area under the receiver operating characteristics analysis also revealed high values of sensitivity and specificity of OCTA parameters in distinguish between patients and HCs. A strong correlation (Pearson Coefficient, r = 0.91) emerged between OCTA VD of the superficial retinal plexus and the average Ganglion Cell Layer (GCL) thickness as measured by SD-OCT; a slightly lower correlation (Pearson Coefficient, r = 0.89) was also found between VD of the deep plexus and the average GCL thickness of the same eyes in patients with ADOA. The correlation among values of differential light sensitivity (DLS) measured by FP with VD and GCL thickness parameters was also investigated. The correlation analysis among DLS and the VD parameters showed from low-to-moderate correlation (ranging from r = 0.29 for the deep fovea VD to r = 0.59 for the deep whole image VD). The correlation coefficient between the mean DLS and the average thickness of GCL was more significant (Pearson Coefficient, r = 0.75). A significant correlation emerged also between the VD and the visual acuity, in terms of LogMAR BCVA (best-corrected visual acuity), especially for the VD of the deep capillary plexus (Pearson Coefficient for the Deep whole Image VD and LogMAR BCVA r = -0.75; for the Deep parafovea VD and LogMAR BCVA r = -0.78). CONCLUSION: Retinal microvascular assessment by OCTA angiography can provide relevant clinical information on retinal involvement in ADOA patients. In patients with genetically confirmed OPA1-related ADOA, there is a decrease in retinal vessel density associated with GCL thinning and DLS reduction.

Combined use of coenzyme Q10 and citicoline: A new possibility for patients with glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide. Several risk factors have been involved in the pathogenesis of the disease. By now, the main treatable risk factor is elevated intraocular pressure. Nevertheless, some patients, whose intraocular pressure is considered in the target level, still experience a progression of the disease. Glaucoma is a form of multifactorial ocular neurodegeneration with complex etiology, pathogenesis, and pathology. New evidence strongly suggests brain involvement in all aspects of this disease. This hypothesis and the need to prevent glaucomatous progression led to a growing interest in the pharmacological research of new neuroprotective, non-IOP-lowering, agents. The aim of this paper is to report evidence of the usefulness of Coenzyme Q10 and Citicoline, eventually combined, in the prevention of glaucomatous neurodegeneration.

Subclinical Signs of Retinal Involvement in Hereditary Angioedema.

To explore retinal abnormalities using spectral domain optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A) in a highly selective cohort of patients with type I hereditary angioedema (HAE). This prospective case-control study included 40 type I HAE patients and 40 age-/sex-matched healthy subjects (HC). All participants underwent SD-OCT-scanning of retinal posterior pole (PP), peripapillary retinal nerve fiber layer (pRNFL), and optic nerve head (ONH). Superficial/deep capillary density was analyzed by OCT-A. A total of 80 eyes from 40 HAE and 40 eyes from HC were evaluated. The pRNFL was thicker in HAE than in HC in nasal superior (p < 0.0001) and temporal quadrants (p = 0.0005 left, p = 0.003 right). The ONH thickness in HAE patients was greater than in HC in the nasal (p = 0.008 left, p = 0.01 right), temporal (p = 0.0005 left, p = 0.003 right), temporal inferior (p = 0.007 left, p = 0.0008 right), and global (p = 0.005 left, p = 0.007 right) scans. Compared to HC, HAE showed a lower capillary density in both superficial (p = 0.001 left, p = 0.006 right) and deep (p = 0.008 left, p = 0.004 right) whole images, and superficial (p = 0.03 left) and deep parafoveal (p = 0.007 left, p = 0.005 right) areas. Our findings documented subclinical retinal abnormalities in type I HAE, supporting a potential role of the retinal assessment by SD-OCT/OCT-A as a useful tool in the comprehensive care of HAE patients.

Complex Rearrangement of the Entire Retinal Posterior Pole in Patients with Relapsing Remitting Multiple Sclerosis.

There are consolidated data about multiple sclerosis (MS)-dependent retinal neurodegeneration occurring in the optic disk and the macula, although it is unclear whether other retinal regions are affected. Our objective is to evaluate, for the first time, the involvement of the entire retinal posterior pole in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) unaffected by optic neuritis using Spectral Domain-Optical Coherence Tomography (SD-OCT). The study protocol was approved by Tor Vergata Hospital Institutional Ethics Committee (Approval number 107/16), and conforms to the tenets of the Declaration of Helsinki. After a comprehensive neurological and ophthalmological examination, 53 untreated RRMS patients (aged 37.4 ± 10) and 53 matched controls (aged 36.11 ± 12.94) were enrolled. In addition, each patient underwent an examination of the posterior pole using the SD-OCT built-in Spectralis posterior pole scanning protocol. After segmentation, the mean thickness, as well as the thickness of the 64 single regions of interest, were calculated for each retinal layer. No statistically significant difference in terms of average retinal thickness was found between the groups. However, MS patients showed both a significantly thinner ganglion cell layer (p < 0.001), and, although not statistically significant, a thinner inner nuclear layer (p = 0.072) and retinal nerve fiber layer (p = 0.074). In contrast, the retinal pigment epithelium (p = 0.014) and photoreceptor layers p < 0.001) resulted significantly thicker in these patients. Interestingly, the analysis of the region of interest showed that neurodegeneration was non-homogeneously distributed across each layer. This is the first report that suggests a complex rearrangement that affects, layer by layer, the entire retinal posterior pole of RRMS retinas in response to the underlying neurotoxic insult.

The Retinal Posterior Pole in Early Parkinson's Disease: A Fundus Perimetry and SD-OCT Study.

PURPOSE: To assess the structure and function of the retinal posterior pole in patients with early Parkinson's disease (PD) and to identify possible biomarkers correlated with clinical features. PATIENTS AND METHODS: A cross-sectional case-control study of 21 patients with PD and 22 age-matched healthy controls (HC) was conducted. All subjects underwent full ophthalmological examinations, fundus perimetry (FP) and spectral domain-OCT (SD-OCT) of the entire retinal posterior pole and peripapillary retinal nerve fiber layer (pRNFL). RESULTS: We analyzed 41 eyes from 21 patients (14 males and 7 females) with early PD (Hoehn and Yahr scale (H&Y) equal to or less than stage 2) and 41 eyes from 22 HC (12 males and 10 females). We found no significant difference in the pRNFL thickness between patients with PD and HC. The statistical analysis of the SD-OCT posterior pole area, consisting of 64 values for each retinal layer, revealed a decrease in the outer nuclear layer (ONL) thickness in patients with PD (p < 0.0001). On the contrary, a significant increase in the thickness of the outer plexiform layer (OPL) (p < 0.0001) and of the retinal pigmented epithelium (RPE) (p= 0.002) compared to healthy controls was detected. Other retinal layers showed no significant statistical differences. The differential light sensitivity (DLS) values measured by FP were significantly lower in patients than the healthy controls (15 [13-16.2] vs 17.95 [16.08-18.96] p<0.0001). CONCLUSION: Our results showed that DLS and retinal structure differed in the posterior pole between patients with early PD and controls. Thickening of the OPL may represent accumulation of α-synuclein in the OPL of patients with PD.

Combined Low-Level Light Therapy and Intense Pulsed Light Therapy for the Treatment of Dry Eye in Patients with Sjögren's Syndrome.

PURPOSE: To evaluate the effects of combined intense pulsed light therapy (IPL) and low-level light therapy (LLLT) in dry eye disease (DED) in patients affected by Sjögren's syndrome. Patients and Methods. This is a monocentric, prospective, interventional study. At baseline, all the study patients (n = 20) were on tear substitute therapy and underwent Schirmer type-1 test and breakup time (BUT) test. After baseline measurements, tear substitute therapy was suspended, and patients underwent IPL and LLLT. The same investigations were carried out at one (T1) and at three (T3) months after treatment. The Ocular Surface Disease Index (OSDI) survey was used to measure the severity of DED. RESULTS: BUT test showed an increase in tear film breakup time in patients with DED 1 month after the beginning of the treatment (T0 vs T1: p=0,01). This increase was even more statistically significant after 3 months of the IPL and LLLT treatment (T0 vs T3: p < 0.0001). Schirmer test values increased too, but there was not statistically significance between values at T0 and T1 or T3. The patients perceived an improvement in their condition, which resulted in a lower score on the OSDI survey. The OSDI score was lower at T1 than T0 (T0 vs T1: p=0.0003), while it tended to increase again after 3 months although it was still lower than baseline (T0 vs T3: p=0.02). No facial or ocular side effects were reported. CONCLUSIONS: The use of combined IPL/LLLT for the treatment of DED in patients affected by Sjögren's syndrome appears to be beneficial.

CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing.

The endocannabinoid system (ECS) is a complex regulatory system, highly conserved among vertebrates. It has been widely described in nearly all human tissues. In the conjunctiva and cornea, the ECS is believed to play a pivotal role in the modulation of the local inflammatory state as well as in the regulation of tissue repair and fibrosis, neo-angiogenesis and pain perception. This review aims to summarize all the available data on ECS expression and its function in ocular surface structures to provide a specific insight concerning its modulation in dry eye disease, and to propose directions for future research.

Reorganization of the structural connectome in primary open angle Glaucoma.

Primary open angle Glaucoma (POAG) is one of the most common causes of permanent blindness in the world. Recent studies have suggested the hypothesis that POAG is also a central nervous system disorder which may result in additional (i.e., extra-ocular) involvement. The aim of this study is to assess possible structural, whole-brain connectivity alterations in POAG patients. We evaluated 23 POAG patients and 15 healthy controls by combining multi-shell diffusion weighted imaging, multi-shell, multi-tissue probabilistic tractography, graph theoretical measures and a recently designed 'disruption index', which evaluates the global reorganization of brain networks. We also studied the associations between the whole-brain structural connectivity measures and indices of visual acuity including the field index (VFI) and two Optical Coherence Tomography (OCT) parameters, namely the Macula Ganglion Cell Layer (MaculaGCL) and Retinal Nerve Fiber Layer (RNFL) thicknesses. We found both global and local structural connectivity differences between POAG patients and controls, which extended well beyond the primary visual pathway and were localized in the left calcarine gyrus (clustering coefficient p = 0.036), left lateral occipital cortex (clustering coefficient p = 0.017, local efficiency p = 0.035), right lingual gyrus (clustering coefficient p = 0.009), and right paracentral lobule (clustering coefficient p = 0.009, local efficiency p = 0.018). Group-wise (clustering coefficient, p = 6.59∙10-7 and local efficiency p = 6.23·10-8) and subject-wise disruption indices (clustering coefficient, p = 0.018 and local efficiency, p = 0.01) also differed between POAG patients and controls. In addition, we found negative associations between RNFL thickness and local measures (clustering coefficient, local efficiency and strength) in the right amygdala (local efficiency p = 0.008, local strength p = 0.016), right inferior temporal gyrus (clustering coefficient p = 0.036, local efficiency p = 0.042), and right temporal pole (local strength p = 0.008). Overall, we show, in patients with POAG, a whole-brain structural reorganization that spans across a variety of brain regions involved in visual processing, motor control, and emotional/cognitive functions. We also identified a pattern of brain structural changes in relation to POAG clinical severity. Taken together, our findings support the hypothesis that the reduction in visual acuity from POAG can be driven by a combination of local (i.e., in the eye) and more extended (i.e., brain) effects.