Peripheral and ocular microvascular alterations in systemic sclerosis: observations from capillaroscopic assessments, perfusion peripheral analysis, and optical coherence tomography angiography.

To investigate the correlations between finger microvascular morphology and function in patients with systemic sclerosis (SSc) and the status of ocular microcirculation, as detected by nailfold videocapillaroscopy (NVC), laser speckle contrast analysis (LASCA), and optical coherence tomography angiography (OCTA). The enrollment included 32 SSc patients, classified according to the 2013 ACR/EULAR criteria, and 27 sex- and age-matched healthy controls. The participants underwent comprehensive rheumatological and ophthalmological examinations, as well as NVC, LASCA, and OCTA analysis on the same day at a single center from March to October 2022. SSc patients receiving intravenous prostanoids cycles were assessed at least 1 month after infusion. Statistical analysis was conducted using Stata® 15.1. Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p < 0.05). In addition, a significantly reduced retinal and choroidal perfusion was detected in SSc patients vs controls (all p < 0.05). Interestingly, diffuse cutaneous SSc (dcSSc) patients exhibited a lower choroidal perfusion (p = 0.03) but an increased choroidal thickness (CT) than limited cutaneous SSc patients (p < 0.001). CT was increased also in patients with positive Scl70 antibodies and with a history of digital ulcers directly correlating with disease duration (r = 0.67, p = 0.001). Finally, the combination of LASCA and OCTA parameters showed a significant discrimination capacity between SSc patients and controls, with an area under the curve of 0.80 [95% CI (0.74, 0.87)]. Peripheral microvascular damage is correlated with impaired ocular microcirculation in SSc. The increased choroidal thickness observed in dcSSc may be related to local sub-endothelial extracellular matrix deposition. The combined analysis of choroidal and fingertip perfusion offers preliminary insights that may complement traditional diagnostic methods for SSc.

Macular Choroidal Thickness: Evaluation of Variability among Measurements and Assessment of Predictive Value of Glaucomatous Visual Field Damage.

INTRODUCTION: This study aimed to investigate the relationship between the choroidal circulation and glaucoma, assessing macular choroidal thickness (MCT) as a predictive value of glaucomatous visual field damage. METHODS: Twenty primary open-angle glaucoma patients were recruited. Patients underwent 2 SS-OCT scans: one with DRI OCT (Topcon) and the other with PLEX Elite 9000 (Zeiss). Standard OCT parameters were acquired by DRI OCT, while MCT was manually measured in 5 points on Plex ELITE 9000 images. The relationship among MCT, standard OCT parameters, and visual field indices was evaluated. Pearson's r correlation was calculated to evaluate these relationships. Reproducibility of measurements was analyzed. RESULTS: MCT measurements showed a good intra- and interobserver repeatability. A negative correlation appeared between MCT and BMI (r = -0.518, p = 0.023). Mean deviation showed a statistically significant correlation with MCT measured at subfoveal and at 1,000 µm nasally (r = 0.50, p = 0.03, and r = 0.52, p = 0.023). A correlation was found between the 2 MCT (Zeiss vs. Topcon) measurements and between MCT and peripapillary choroidal thickness (r = 0.944 and r = 0.740, p < 0.001, respectively). CONCLUSIONS: A good intra- and interobserver reproducibility was found. MCT showed a weak predictive value of glaucomatous visual field damage. A significant correlation was found between MCT and BMI.

Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update.

BACKGROUND: Uveitis is one of the most frequent ophthalmologic manifestations in rheumatology. Uveal inflammation can underlie a systemic inflammatory rheumatic disease (SIRD) in approximately 30% of cases with a significant burden on the quality of life since it represents a cause of blindness in up to 20% of cases in Western countries. METHODS: In this review, we provide a comprehensive overview of the pathophysiology of uveitis associated with SIRDs. According to our literature survey on the epidemiology of uveitis among SIRDs, spondyloarthritides, Behçet's disease and sarcoidosis get the major impact. RESULTS: In Behçet's uveitis, the key players are highly polarized Th1 and Th17 lymphocytes, natural killer T cells and γδ T cells. All contribute to a great destructive inflammatory environment with the most serious visual damage resulting from the involvement of the posterior segment of the eye. In contrast, spondyloarthritides-related uveitis derives from a complex interaction between genetic background and extra-ocular inflammatory mediators originating from enthesitis, arthritis, psoriatic lesions and microbiome pro-inflammatory alterations. In such conditions, the immune infiltration of CD4+ T cells, Th17 and natural killer cells along with pro-inflammatory cytokines, TNF-α among all, leads to intraocular inflammation. Lastly, granuloma formation represents the primary hallmark lesion in sarcoid uveitis. This suggests a profound link between the innate system that mainly recruits activated macrophages and adaptive system involving by Th1, Th17 and Th17.1 cells. CONCLUSIONS: Awareness among rheumatologists of a potential severe ocular involvement generates new insights into targeted therapeutic approaches and personalized treatments for each patient.

Visual Defects and Ageing.

Many diseases are related to age, among these neurodegeneration is particularly important. Alzheimer's disease Parkinson's and Glaucoma have many common pathogenic events including oxidative damage, Mitochondrial dysfunction, endothelial alterations and changes in the visual field. These are well known in the case of glaucoma, less in the case of neurodegeneration of the brain. Many other molecular aspects are common, such as the role of endoplasmic reticulum autophagy and neuronal apoptosis while others have been neglected due to lack of space such as inflammatory cytokine or miRNA. Moreover, the loss of specific neuronal populations, the induction of similar mechanisms of cell injury and the deposition of protein aggregates in specific anatomical areas are very similar events between these diseases. Intracellular and/or extracellular accumulation of protein aggregates is a key feature of many neurodegenerative disorders. The existence of abnormal protein aggregates has been documented in the RGCs of glaucomatous patients such as the anomalous Tau protein or the ß-amyloid accumulations. Intra-cell catabolic processes also appear to be common in both glaucoma and neurodegeneration. They also help us to understand how the basis between these diseases is common and how the visual aspects can be a serious problem for those who are affected.

Chorioretinal folds: a proposed diagnostic algorithm.

PURPOSE: To create a diagnostic algorithm for the management of chorioretinal folds. METHODS: We reviewed the existing literature about chorioretinal folds focusing our attention on three specific conditions and created a diagnostic algorithm in order to otpimize the choice and the number of investigations. RESULTS: Chorioretinal folds are visible striations of the fundus usually arranged in parallel lines and disposed horizontally. They may be either unilateral or bilateral, symptomatic or asymptomatic and are often associated with different possible ocular and extra ocular pathologies, including systemic diseases like autoimmune disorders and intracranial hypertension. They are named idiopathic when no apparent cause for their development is detectable. However, with improved diagnostic testing, the patients with idiopathic choroidal folds are likely to represent only a smaller portion of the total. CONCLUSIONS: Since choroidal folds be the sole sign of an underlying disease possibly requiring a multidisciplinary approach, an appropriate work-up varying according to the specific clinical features of each case is needed to define the etiology and the treatment. A diagnosting algorithm may be useful in order to optimize the diagnostic approach and management.

Prospective evaluation of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C.

PURPOSE: Our purpose was to evaluate the clinical safety and efficacy of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C (MMC) in open angle glaucoma (OAG). METHODS: This was a prospective, uncontrolled, interventional case series. All subjects underwent CLASS procedure by a single surgeon. After the dissection of a partial thickness scleral flap, topical MMC 0.2 mg/ml was applied to the sclera and the conjunctiva for 3 min. The CO2 laser with a beam-manipulating system was used to ablate the scleral tissue and expose the Schlemm's canal area. Primary outcomes: intraocular pressure (IOP) change, number of IOP-lowering medicaments change. Adverse events were evaluated as secondary outcomes. RESULTS: Twenty-one eyes of 21 patients underwent the CLASS procedure. Thirteen were primary OAG (62%), two normal pressure glaucoma (10%), three exfoliative glaucoma (14%) and three others secondary OAG. With a mean (SD) follow-up of 15.3 (5.9) months, the IOP changed from 25.4 (6.7) mmHg at baseline to 10.9 (3.4) mmHg al the last visit. Mean reduction of IOP was -14.5 mmHg (95% CI, -17.7 to -11.2, P < 0.001). The median (IQR) number of IOP-lowering medication decreased from 3 (3-3) at baseline to 1 (0-1) at the last visit (P < 0.001). Visual acuity did not change significantly. Adverse events: five eyes (24%) developed iris adhesion to the filtration area that was successfully managed with office-based procedures. In one case (5%), CLASS was converted to trabeculectomy due to intraoperative perforation of the ablated area. There was one case of hypotony maculopathy successfully treated with placement of additional transconjunctival scleral flap sutures. CONCLUSIONS: The CLASS procedure with MMC is clinically safe and effective maintaining a large reduction in IOP and in the number of IOP-lowering medications with a mean follow-up of 15 months. Iris adhesion at the filtrating area warrants further evaluation and possibly reflects the surgeon's learning curve.

Reproducibility of retrobulbar blood flow velocity measurements in normal subjects using two different CDI devices.

PURPOSE: This study was done to evaluate the intra- and inter-operator reproducibility of colour Doppler imaging (CDI) in assessing blood flow velocity in the ophthalmic (OA), central retinal (CRA) and short posterior ciliary arteries (SPCA) in healthy subjects. MATERIALS AND METHODS: The right eye of two groups of eight healthy volunteers was examined. Two radiologists and two ophthalmologists, divided into pairs, measured peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) of each vessel using a different CDI device for each group. The concordance between two measurements was evaluated with Lin's concordance correlation coefficient (CCC). RESULTS: Globally, very good degrees of intra-operator concordance were obtained for the PSV (0.859 cm/s), EDV (0.834 cm/s) and RI (0.859) of the OA. There was moderate concordance for PSV (0.574 cm/s) and EDV (0.594 cm/s) and good concordance for RI (0.694) for the CRA. Good degrees of concordance were obtained for the SPCA measurements. However, inter-operator concordance was found globally poor. CONCLUSIONS: These data show that CDI measurements in retrobulbar vessels are operator dependent. To increase the intra-operator and inter-operator concordance, rules should be adopted for timing of the examination and positioning of the probe to minimise the pressure applied on the eye.

Autonomous artificial intelligence versus teleophthalmology for diabetic retinopathy.

Purpose: To assess the role of artificial intelligence (AI) based automated software for detection of Diabetic Retinopathy (DR) compared with the evaluation of digital retinography by two double masked retina specialists. Methods: Two-hundred one patients (mean age 65 ± 13 years) with type 1 diabetes mellitus or type 2 diabetes mellitus were included. All patients were undergoing a retinography and spectral domain optical coherence tomography (SD-OCT, DRI 3D OCT-2000, Topcon) of the macula. The retinal photographs were graded using two validated AI DR screening software (Eye Art TM and IDx-DR) designed to identify more than mild DR. Results: Retinal images of 201 patients were graded. DR (more than mild DR) was detected by the ophthalmologists in 38 (18.9%) patients and by the AI-algorithms in 36 patients (with 30 eyes diagnosed by both algorithms). Ungradable patients by the AI software were 13 (6.5%) and 16 (8%) for the Eye Art and IDx-DR, respectively. Both AI software strategies showed a high sensitivity and specificity for detecting any more than mild DR without showing any statistically significant difference between them. Conclusions: The comparison between the diagnosis provided by artificial intelligence based automated software and the reference clinical diagnosis showed that they can work at a level of sensitivity that is similar to that achieved by experts.

Risk Factors for Failure in Glaucoma Patients Undergoing Microshunt Implantation.

PURPOSE: To evaluate risk factors for failure of Microshunt in glaucoma patients. DESIGN: Multicenter retrospective cohort study. METHODS: The study included 220 eyes from 220 consecutive glaucoma patients undergoing Microshunt implantation at six glaucoma units. Four intraocular pressure (IOP) success criteria were defined: (A) IOP ≤21 mm Hg with ≥20% IOP reduction; (B) IOP ≤18 mm Hg with ≥20% IOP reduction; (C) IOP ≤15 mm Hg with ≥25% IOP reduction; and (D) IOP ≤12 mm Hg with ≥30% IOP reduction from baseline. Kaplan-Meier analysis was used to estimate success rates according to the criteria above, and multivariable Cox models were used to identified risk factors for failure according to criterion A. RESULTS: Success rates varied based on different criteria, ranging from 43.3% to 62.5% (overall success for criteria D and A, respectively) and from 35.3% to 44.4% (complete success for criteria D and A, respectively) at 1-year follow-up. Higher intraoperative MMC concentration was associated with reduced risk of failure to maintain complete (0.4 vs 0.2 mg/mL: hazard ratio [HR] = 0.441, P < .001) and overall (0.4 vs 0.2 mg/mL: HR = 0.360, P = .004) success. For complete success, other risk factors for failure were pseudoexfoliation glaucoma/pigmentary glaucoma (HR = 1.641, P = .004), primary angle closure glaucoma (HR = 1.611, P < .001), and previous non-glaucomatous ocular surgeries (HR = 2.301, P = .002). For overall success, other risk factors for failure were lower preoperative IOP (for 1-mm Hg increase, HR = 0.934, P = .005), higher number of preoperative antiglaucoma agents (HR = 1.626, P < .001), and Microshunt combined with cataract surgery (HR = 1.526, P = .033). CONCLUSIONS: This study identified risk factors for Microshunt failure, highlighting the importance of high intraoperative MMC dose and careful patient selection to optimize surgical success.

Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious).

INTRODUCTION: Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG). METHODS AND ANALYSIS: This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 months. Secondary outcomes include mean percentage reduction in IOP at 3, 6 and 12 months; proportion of participants with at least 20% reduction in IOP from baseline at 6 months; change in ocular hypotensive medications at 12 months and evaluation of safety. Participants were aged >= 40 years with OAG, including exfoliative or pigmentary glaucoma, or ocular hypertension with untreated or washed out IOP 22-35 mm Hg. TREATMENTS: DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4-1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3-2.6 mJ. A sample size of 164 is sufficient to detect a non-inferiority margin of 1.95 mm Hg for change from baseline IOP. CLINICAL TRIAL REGISTRATION NUMBER: NCT03750201, ISRCTN14033075.

Bilateral choroidal detachment and myopic shift after acetazolamide intake for laser capsulotomy.

INTRODUCTION: To report a case of bilateral choroidal effusion after laser capsulotomy. CASE DESCRIPTION: A healthy 85 years old white woman was referred to our hospital with a diagnosis of posterior capsule opacification in the left eye. The patient was treated with laser capsulotomy and oral acetazolamide was administered after the procedure. The day after, the patient visited the emergency room complaining bilateral blurred vision. A myopic shift and peripheral choroidal detachment was noted in both eyes. Discontinuation of acetazolamide and treatment with topical steroid and cyclopentolate resulted in a significant improvement in visual acuity and the complete resolution of the choroidal detachment in 1 week. CONCLUSION: To the best of our knowledge, this is the first reported case of choroidal detachment and acute transient myopia following the administration of oral acetazolamide after laser capsulotomy.

Nail-Patella Syndrome and Glaucoma: A Case Report and Review of the Literature.

Nail-patella syndrome (NPS) is a rare autosomal dominant disease characterized by nail dysplasia, aplastic or hypoplastic patellae, elbow dysplasia, and presence of iliac horns. Renal or ocular abnormalities are also associated with the disease. We report the case of a 57-year-old woman affected by NPS and having haploinsufficiency of the LMX1B gene who experienced severe bilateral chronic angle-closure glaucoma in both eyes and that was successfully managed with a flap-express procedure in the right eye. The left eye had no light perception, and medical treatment was considered. Glaucoma is the most frequent ocular abnormalities observed in association with NPS and usually presents with an open angle. Glaucoma associated with NPS typically has an early onset open-angle phenotype. In fewer cases, it may present with an angle-closure phenotype. Therefore, we emphasize the need for glaucoma case-finding protocols comprehensive of gonioscopy in NPS patients and their relatives.

Trabeculectomy versus Xen gel implant for the treatment of open-angle glaucoma: a 3-year retrospective analysis.

OBJECTIVE: To compare the two surgical techniques in terms of efficacy, safety, and postoperative management over 36 months of follow-up. METHODS: This retrospective clinical cohort study compared the outcome of trabeculectomy surgery and Xen gel implant in patients having uncontrolled glaucoma. Patients were recruited using the following inclusion criteria: uncontrolled intraocular pressure (IOP) on maximally tolerated medical therapy, healthy conjunctiva freely mobile in the superior sector, open-angle, glaucomatous visual field damage, full follow upfollow-up of at least 36 months. Thirty-four patients were submitted to trabeculectomy and 34 to Xen gel implant. We set the lower limit at 6mmHg mm Hg and the upper limit ≤12 mm Hg for criteria A, upper limit to ≤15 mm Hg for criteria B and upper limit ≤18 mm Hg for criteria C. Criteria for success have been characterizedcharacterised according to whether or not this has been achieved without (complete success) or with IOP -lowering medications (qualified success). RESULTS: For all survival curves, trabeculectomy was superior to Xen gel implant. When considering complete success, the log-rank test for criteria A was statistically significant (pp=0.006), marginally significant for criteria B (pp=0.065) and not significant for criteria C (pp=0.23). When qualified success was considered, trabeculectomy was superior to Xen gel for criteria A, B, and C (pp=0.012, pp=0.033 and pp=0.025, respectively). Higher number of post-operative flat chamber and bleb leakage was observed in the trabeculectomy group. CONCLUSION: Xen gel implant techniques offer a better safety profile but a lower IOP reduction compared to compared with the gold -standard technique.

Choroidal Detachment after XEN Gel Stent Implantation.

BACKGROUND: The purpose of this study is to estimate the incidence of choroidal detachment (CD) after XEN gel stent implant surgery and to evaluate the associated factors. METHODS: We reviewed the clinical charts of 126 patients who underwent XEN implantation between March 1, 2016, and December 31, 2018 at the University Eye Clinic of Genoa. Ocular, demographics, and perioperative factor were registered and analysed. Univariate and multivariate logistic analysis were performed to investigate factors associated with CD occurrence. RESULTS: Of the 126 patients, 25 (19.8%) developed a choroidal detachment after XEN gel stent implant surgery. The mean period between surgery and CD detection was 5.84 ± 1.77 days. The mean intraocular pressure (IOP) at the time of CD diagnosis was 6.4 ± 3.1 mmHg. Age (OR = 1.10, p < 0.019), early postoperative IOP (OR = 0.70, p < 0.001), and number of preoperative IOP-lowering drugs (OR = 5.70, p < 0.001) were significantly associated with CD presence. Complete resolution was observed in all the cases. Wide-field imaging and ultrasonography were useful tools to diagnose and follow up CD until resolution. CONCLUSIONS: When carefully investigated, CD is a relatively common complication after XEN gel stent implant procedure. Older age, lower postoperative IOP, and higher number of preoperative IOP-lowering drugs were significantly associated with the development of CD.

Recombinant Human Nerve Growth Factor (Cenegermin)-Driven Corneal Wound Healing Process: An Evidence-Based Analysis.

Purpose: To evaluate anterior segment optical coherence tomography (AS-OCT) to detect the wound healing process as per monitoring the effectiveness of cenegermin to treat moderate to severe neurotrophic keratoplasty. Methods: A retrospective chart review was realized to identify patients treated with cenegermin at the Clinica Oculistica, University of Genoa, Italy. All patients underwent careful examinations at baseline and follow-up visits. AS-OCT scans centered on the minimum corneal thickness (CT) area were always performed. We compared findings of AS-OCT with the findings from the slit-lamp examination. A linear regression analysis was used to evaluate factors associated with corneal healing. A further analysis, including a control group treated with 50% autologous serum (AS), was done to investigate and compare the efficacy of cenegermin. Results: Data from 16 eyes were studied. The average patients' age was 60.9 ± 21.1 years; five (31.2%) eyes experienced persistent epithelial defect and 11 (68.8%) eyes had neurotrophic corneal ulcer. The average reepithelialization time was 3.9 ± 0.5 weeks in the cenegermin group versus 5.9 ± 1.9 weeks in the AS group (p < 0.01). The AS-OCT scans revealed an average CT at the thinnest point of 276.3 ± 74.1 µm before treatment with an average increase of 176.5 ± 60.3 µm at the end of the cenegermin treatment (B = -0.15; p = 0.035). The AS-OCT percentage increase in corneal thickness between the two groups was statistically significant (p < 0.02). Conclusion: Understanding the cascade of events involved in the nerve growth factor-driven corneal wound healing process is clinically meaningful for the clinician. AS-OCT is an effective tool for systematic anterior segment imaging, allowing the detailed detection of the front-to-back layered corneal structure for quantitative analysis and monitoring of the healing process.

Moving beyond the Slit-Lamp Gonioscopy: Challenges and Future Opportunities.

After almost a century from its introduction in clinical practice, slit-lamp gonioscopy is still considered the reference standard for evaluating the anterior chamber angle (ACA). Gonioscopy is essential for diagnosing angle closure disease, and ACA features are included in glaucoma's diagnostics and treatments algorithms. However, shortcomings of slit-lamp gonioscopy include a steep learning curve, lack of agreement between examiners and poor documentation. Thanks to advances in miniaturization and computing, new instruments for digital gonioscopy have been developed and marketed. This narrative review focuses on the Gonioscope GS-1, which permits semi-automated circumferential documentation of the ACA in real-colour photographs. Advantages and disadvantages of GS-1 compared with slit-lamp gonioscopy and other ACA imaging technologies such as optical coherence tomography are discussed. Finally, potential opportunities offered by this device for telemedicine, virtual clinics, and automatic classification with deep learning are presented.

Delayed Re-epithelialization After Epithelium-Off Crosslinking: Predictors and Impact on Keratoconus Progression.

Purpose: To investigate the demographic and corneal factors associated with the occurrence of delayed reepithelialization (DRE) after epithelium-off crosslinking (epi-off CXL). Design:Retrospective case series. Methods:A chart review was performed to identify patients treated with epi-off CXL. DRE was defined as a corneal epithelial defect detected by fluorescein staining that persisted for more than 10 days. Slit-lamp examination, anterior segment optical coherence tomography, corneal topography, and corneal in vivo confocal microscopy (IVCM) were always performed preoperatively and at each follow-up visit (1, 3, 6, 12 months). A generalized estimating equation was used to assess the baseline factors associated with DRE. Results:Data from 153 eyes were analyzed. The mean age of patients was 24.9 ± 8.5 years, and 47 (30.7%) were women. The average reepithelization time was 4.7 ± 1.8 days. Six eyes (3.9%) experienced DRE. In the multivariate model, both the age of the patient (OR = 1.30; p = 0.02) and the corneal steepest meridian (OR = 0.44, p = 0.047) were associated with DRE. Baseline nerve count was also associated with DRE (0.87, p = 0.03). Male gender was associated with a slower early nerve regrowth (1-6 months) (p = 0.048), but not with the occurrence of DRE (p = 0.27). Preoperative central corneal thickness was not related to DRE (p = 0.16). DRE was not associated with keratoconus progression after epi-off CXL (p = 0.520). Conclusions:The association between DRE and age may reflect the age-related decrease in the corneal healing response. Also, low baseline corneal nerve count is associated with DRE. Gender seems to affect reinnervation measured by IVCM but not the reepithelization time. DRE does not seem to affect the efficacy of epi-off CXL.

Ocular microvascular damage in autoimmune rheumatic diseases: The pathophysiological role of the immune system.

Pathological eye involvement represents a quite common finding in a broad spectrum of autoimmune rheumatic diseases (ARDs). Ocular signs, often occur as early manifestations in ARDs, ranging from symptoms related to the mild dry eye disease to sight-threatening pathologies, linked to the immune response against retinal and choroidal vessels. Retinovascular damage driven by markedly inflammatory reactivity need a prompt diagnosis and treatment. Immune-complexes formation, complement activation and antibody-mediated endothelial damage seem to play a key role, particularly, in microvascular damage and ocular symptoms, occurring in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Conversely, early alterations of retinal and choroidal vessels in the asymptomatic patient, often detectable coincidentally, might be indicators of widespread vascular injury in other connective tissue diseases. Particularly, endothelin-induced hypoperfusion and pathological peri-choroidal extracellular matrix deposition, might be responsible for the micro-architectural alterations and loss of capillaries detected in systemic sclerosis (SSc). Instead, interferon alpha-mediated microvascular rarefaction, combined with endothelial lesions caused by specific autoantibodies and immune-complexes, appear to play a significant role in retinal vasculopathy associated to inflammatory idiopathic myopathies (IIM). The immuno-pathophysiological mechanisms of ocular microcirculatory damage associated with the major ARDs will be discussed under the light of the most recent achievements.

Semantic segmentation of gonio-photographs via adaptive ROI localisation and uncertainty estimation.

OBJECTIVE: To develop and test a deep learning (DL) model for semantic segmentation of anatomical layers of the anterior chamber angle (ACA) in digital gonio-photographs. METHODS AND ANALYSIS: We used a pilot dataset of 274 ACA sector images, annotated by expert ophthalmologists to delineate five anatomical layers: iris root, ciliary body band, scleral spur, trabecular meshwork and cornea. Narrow depth-of-field and peripheral vignetting prevented clinicians from annotating part of each image with sufficient confidence, introducing a degree of subjectivity and features correlation in the ground truth. To overcome these limitations, we present a DL model, designed and trained to perform two tasks simultaneously: (1) maximise the segmentation accuracy within the annotated region of each frame and (2) identify a region of interest (ROI) based on local image informativeness. Moreover, our calibrated model provides results interpretability returning pixel-wise classification uncertainty through Monte Carlo dropout. RESULTS: The model was trained and validated in a 5-fold cross-validation experiment on ~90% of available data, achieving ~91% average segmentation accuracy within the annotated part of each ground truth image of the hold-out test set. An appropriate ROI was successfully identified in all test frames. The uncertainty estimation module located correctly inaccuracies and errors of segmentation outputs. CONCLUSION: The proposed model improves the only previously published work on gonio-photographs segmentation and may be a valid support for the automatic processing of these images to evaluate local tissue morphology. Uncertainty estimation is expected to facilitate acceptance of this system in clinical settings.

On Clinical Agreement on the Visibility and Extent of Anatomical Layers in Digital Gonio Photographs.

Purpose: To quantitatively evaluate the inter-annotator variability of clinicians tracing the contours of anatomical layers of the iridocorneal angle on digital gonio photographs, thus providing a baseline for the validation of automated analysis algorithms. Methods: Using a software annotation tool on a common set of 20 images, five experienced ophthalmologists highlighted the contours of five anatomical layers of interest: iris root (IR), ciliary body band (CBB), scleral spur (SS), trabecular meshwork (TM), and cornea (C). Inter-annotator variability was assessed by (1) comparing the number of times ophthalmologists delineated each layer in the dataset; (2) quantifying how the consensus area for each layer (i.e., the intersection area of observers' delineations) varied with the consensus threshold; and (3) calculating agreement among annotators using average per-layer precision, sensitivity, and Dice score. Results: The SS showed the largest difference in annotation frequency (31%) and the minimum overall agreement in terms of consensus size (∼28% of the labeled pixels). The average annotator's per-layer statistics showed consistent patterns, with lower agreement on the CBB and SS (average Dice score ranges of 0.61-0.7 and 0.73-0.78, respectively) and better agreement on the IR, TM, and C (average Dice score ranges of 0.97-0.98, 0.84-0.9, and 0.93-0.96, respectively). Conclusions: There was considerable inter-annotator variation in identifying contours of some anatomical layers in digital gonio photographs. Our pilot indicates that agreement was best on IR, TM, and C but poorer for CBB and SS. Translational Relevance: This study provides a comprehensive description of inter-annotator agreement on digital gonio photographs segmentation as a baseline for validating deep learning models for automated gonioscopy.