"Anterior Segment Optical Coherence Tomography for Cases of High Intraocular Pressure Following XEN Implant for Glaucoma".

PRECIS: This study showed that the XEN patency should be verified by OCT imaging in cases of encapsulated blebs. Although fibrosis plays the principal role, humour aqueous flow reduction could affect the "spacer" effect that inhibits the fibroblast attachments. PURPOSE: To evaluate the application of the AS-OCT imaging in studying the relationship between a low flow rate through the XEN63 and the development of a cystic bleb. METHODS: Retrospective case series of three eyes presenting a cystic bleb after a XEN63 implantation for uncontrolled IOP. Demographic and clinical data were obtained from medical records. The imaging findings, complications and managements following the surgery were evaluated. RESULTS: Three patients, with an average age of 67.3 years, initially showed a patent stent lumen and a functional bleb after surgery. The IOP of all eyes increased on average at 28.3 days from the surgery, with a mean value of 39.66 mmHg. The slit lamp examination showed a cystic bleb. The AS-OCT imaging confirmed the previous finding and revealed either a partial or total occlusion of the stent internal ostium. A Nd:YAG laser, in proximity of the ostium, was performed in order to resolve the obstruction. Although the AS-OCT imaging showed the device patency and the IOP immediately decreased, the latter became elevated again. Consequently, in all the cases a further needling procedure was needed to achieve an adequate IOP reduction. Six months after the two-step procedure, the IOP averaged 13.33 mmHg, the XEN63 lumens appeared cleared and the blebs showed a functional morphology. No adverse events were observed. CONCLUSION: The development of a cystic bleb may result from an altered balance between the flow-rate through the XEN63 and the fibrosis development in the postoperative healing process. A proper follow up based on slit lamp biomicroscopy, IOP measurement and AS-OCT imaging is advisable to estimate and manage a cystic bleb following XEN63 implantation.

Blepharospasm as a tardive manifestation of COVID-19 disease: A case report.

We report three cases of blepharospasms developed after a symptomatic COVID-19 infection, in order to describe a possible association between COVID-19 infection and essential blepharospasm. Blepharospasm could represent a late sign of COVID-19 infection (more than four weeks after the contagion) and may be triggered by the neurotropism of the coronavirus.

X-linked retinoschisis: OCT-angiography in two brothers from a four-generation family with a p.Arg197Cys pathogenic variant in the RS1 gene.

INTRODUCTION: X-linked juvenile retinoschisis (XLRS) is a rare genetic disease causing retinal splitting. The aim of this work is to describe the optical coherence tomography angiography (OCTA) features in two brothers affected by an hemizygous c.589C>T (p.Arg197Cys) pathogenic variant in exon 6 of the RS1 gene. CASE DECRIPTION: Each patient underwent a complete ophthalmological examination, including measurement of best corrected visual acuity, slit-lamp biomicroscopy, fundus color photographs, fundus autofluorescence and infrared imaging, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). En Face SD-OCT and OCTA revealed the presence of two different pattern of cystic lesions, fusiform and oval, disposed on a petaloid or irregular manner in the perifoveolar area. A widening of the foveal avascular zone with interruption of the vascular arcades was clearly evident. Furthermore, a capillary drop-out was observed in the superficial plexus of the central retina, other than capillary ectasia in the deep capillary plexus. Straight gray lines were visible among the cysts. CONCLUSIONS: OCTA data herein described allow a detailed morphological evaluation of XLRS other than a quantitative assessment of retinal capillary flow in this disease. The retinal alterations that we have reported may be helpful to better understand this rare condition with OCTA being a sensitive technique to monitor the evolution of the disease and the response to potential future therapeutic approaches aimed to restore vision.

Compass Fundus-Guided Perimetry in Geographic Atrophy.

Purpose: To evaluate compass (CMP), a recently introduced device that combines scanning ophthalmoscopy, automated perimetry, and eye tracking, for fundus-guided perimetry (microperimetry) with the purpose of correlating perimetric retinal sensitivity (PRS) and retinal geographic atrophy (GA) features. Materials and Methods: A retrospective, cross-sectional study was performed in 56 eyes of 43 patients affected by GA. All patients underwent compass 10-2 perimetry, consisting of a full-threshold visual field on fundus photography and an infrared (IR) image of the central 30° of the retina. Data were exported to an Excel sheet. Binarization with black/white (B/W) variables was applied on the compass photo fundus and matched with visual field scores. Patients underwent autofluorescence (AF) and IR images (Heidelberg, Germany): CMP and Heidelberg IR images were homologated by using GIMP software (https://www.gimp.org), and then atrophic areas were manually measured with the ImageJ program. CMP perimetric grid was overlapped with AF and IR pictures by using GIMP, obtaining composite TIFF images, which were then analyzed with the ImageJ greyscale score (GSS) tool. A hyperautofluorescent halo was identified on the GA edges of some patients. Pearson's correlation between GA size on IR compass and IR Heidelberg and between GSS and PRS values has been calculated; the independent t-test was realized to calculate the correlation between GSS and B/W variables identified on the CMP photo fundus. The Spearman correlation between total deviation and pattern deviation was calculated. Results: The AUC-ROC score between CMP scores and B/W variables was 93,4%. The Spearman correlation between total deviation and pattern deviation was highly significant (p = 0,00). The correlation between AF GSS values and PRS was significant (p value = 0,00), the correlation between GSS of hyperautofluorescent points and PRS was significant (p value = 0,00), and the correlation between IR GSS and PRS was significant (p value = 0,00). The correlation between AF GSS and B/W variables was significant (p value = 0,002), the correlation between hyperautofluorescent points and B/W was not significant (p value = 0,40), and the correlation between IR GSS and B/W was significant (p = 0,00). Conclusions: Based on our preliminary results, compass seems to be a reliable, quick, and safe device for the anatomical and functional study of GA. The direct visualization of the visual field on the fundus photography as a background allows a precise assessment and clinical monitoring of this disease.

The Influence of Eyelid Position and Environmental Conditions on the Corneal Changes in Early Postmortem Interval: A Prospective, Multicentric OCT Study.

In the current study, using portable optical coherence tomography, we evaluated 46 corneas of 23 individuals in a multicenter setting during the first 17 h after death. Twenty-three eyes were kept open, and twenty three were kept closed. Furthermore, the experiment was carried out for 12 samples in summer and 11 in winter. Our data show that postmortem corneal alterations largely depend on the phenomena of dehydration (in particular in open eyes) and swelling of the stroma in closed eyes, probably due in the first phase to hypoxia/anoxia and subsequently to the passage by osmosis of the aqueous humor from the anterior chamber to the corneal tissue. Our findings could have significant repercussions in forensic pathology for estimating the postmortem interval and transplantation to optimize the conservation of the tissue before the explant.

Non-infectious uveitis burden on quality of life and work impairment assessed through different psychometric questionnaires.

BACKGROUND: The purpose of this study was to evaluate the association between a novel psychometric 12-item questionnaire (U-qest) and other validated questionnaires to assess quality of life and work impairment in patients with non-infectious uveitis. METHODS: Data were collected at baseline and 3 months postbaseline using U-qest and two other validated questionnaires: The National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and the 12-Item Short-Form Health Survey (SF-12). RESULTS: A total of 136 patients (52.2% female) aged 47.9 ± 14.8 years (mean ± SD) were enrolled in 14 uveitis referral centres. U-qest correlated moderately with VFQ-25 and SF-12 at baseline and at 3 months. Both U-qest and VFQ-25 scores improved as disease improved; however, U-qest also detected improvement in patients for whom VFQ-25 scores did not improve. Disease activity was shown to significantly affect activity impairment. Patients and physicians expressed positive perceptions regarding the use and benefit of this instrument. U-qest showed very good reliability in terms of internal consistency (Cronbach's alpha = 0.91). CONCLUSIONS: U-qest can be considered a useful tool to assess the burden of uveitis on quality of life.

Xen45 gel stent ab interno trimming for ostium occlusion: case report.

BACKGROUND: Despite the XEN gel stent low-risk profile, various complications following the implant have been described, including internal and external occlusion, with a consequent postoperative rise in intraocular pressure (IOP). In this case report we aimed to present a XEN45 stent internal occlusion successfully treated by trimming in situ its proximal end with a 25 G vitreous scissors using a bimanual technique. CASE PRESENTATION: A 63-year-old male patient affected by primary open angle glaucoma (IOP = 25 mmHg) and a full thickness macular hole in his right eye, underwent ab-interno Xen gel stent implantation and, 1 month later, a 25 G vitrectomy surgery. Despite a significant IOP reduction after stent implant, 6 days after vitrectomy, IOP increased (25 mmHg) and the conjunctival bleb flattened following occlusion of stent internal ostium by a clot of presumed fibrinous material. The Nd:YAG laser failed to remove the clot, so that we decided to snip a small bit of the proximal end of the Xen tube (about 0,5 mm length) with a 25 G vitreous scissors, using a bimanual technique. In the postoperative day 1 and month 1, the IOP was 8 mmHg and 12 mmHg, respectively. The Anterior Segment OCT confirmed a functional, layered, filtering bleb, and the normal appearance and patency of the XEN proximal segment. No side effects from the intervention were observed. CONCLUSIONS: Ab interno trimming with vitreous scissors of the occluded proximal end of the XEN stent may represent a safe, rapid and efficient method to restore aqueous humor subconjunctival drainage.

Dual Corneal-Graft Rejection after mRNA Vaccine (BNT162b2) for COVID-19 during the First Six Months of Follow-Up: Case Report, State of the Art and Ethical Concerns.

Present mass vaccination against Coronavirus Disease-19 (COVID-19) is the most widely used health policy and the most promising approach to curb the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic globally. However, new side effects are emerging from the mass vaccination not described during the experimental stages. In the present study, we discuss a case of acute corneal graft rejection, which has occurred 25 years after transplantation and 13 days after the administration of the BNT162b2 vaccine (Comirnaty, BioNTech/Pfizer), which was followed-up for a period of six months. In this period, the corneal inflammation appeared twice but was successfully managed with topical therapy and supplementation of Vitamin D. A risk of corneal graft rejection must be included in the list of potential vaccine complications, in order to inform the transplanted patient to undergo a preliminary and a follow-up ocular examination, and eventually to include corneal graft in the list of contraindications to vaccination.

The "Quarantine Dry Eye": The Lockdown for Coronavirus Disease 2019 and Its Implications for Ocular Surface Health.

The pandemic of coronavirus disease 2019 (COVID-19) has led many countries of the world to impose a series of containment measures such as lockdowns (mass quarantines), curfews or similar restrictions (eg, stay-at-home orders, or shelter-in-place orders). All these restrictions were established in order to limit spread of COVID-19. Thus, approximately 3.9 billion people worldwide were under lockdown by early April 2020. During this time (home confinement), some solutions have been proposed by experts to improve work and school productivity, including smart working and online school lessons. However, many of the restrictive measures are likely to act as predisposing factors for dry eye disease (DED), directly or related to sick building syndrome (SBS). Herein, we discuss the implications of quarantine measures on eye health, in particular on DED associated with SBS, and introduce some potential preventive strategies for lockdown-related ocular surface disorders. Several risk factors are implicated in their pathogenesis, including environmental changes (eg, air quality) and modifications in personal behaviors (eg, the abuse of digital devices, malnutrition, and sleep/psychiatric disorders). Considering a number of predisposing factors for DED, it is possible to state that patients under lockdown are at risk of ocular surface alterations. Accordingly, the COVID-19 pandemic era is expected to determine an increase in dry eye patients all around the world (a new phenomenon that we propose to name the "quarantine dry eye") in the event that the restrictive measures will be recursively extended over time.

Postmortem Ocular Findings in the Optical Coherence Tomography Era: A Proof of Concept Study Based on Six Forensic Cases.

Postmortem analysis of the ocular globe is an important topic for forensic pathology and transplantology. Although crucial elements may be gathered from examining cadaveric eyes, the latter do not routinely undergo in-depth analysis. The paucity of quantitative and objective data that are obtainable using current, invasive necroscopic techniques is the main reason for the limited interest in this highly specialized procedure. The aim of the current study is to describe and to object for the first time the postmortem ocular changes by mean of portable optical coherence tomography for evaluating ocular tissues postmortem. The design involved the postmortem analysis (in situ, and without enucleation) of 12 eyes by portable spectral-domain Optical Coherence Tomography. The scans were performed, in corneal, retinal and angle modality at different intervals: <6 h, 6th, 12th, and 24th hour and after autopsy (25th-72nd hour). The morphological changes in the cornea, sclera, vitreous humor and aqueous humor were easy to explore and objectify in these tissues in first 72 h postmortem. On the other hand, the "in situ" observation of the retina was difficult due to the opacification of the lenses in the first 24 h after death.

The architecture of corneal stromal striae on optical coherence tomography and histology in an animal model and in humans.

The purpose of this study was to use a portable optical coherence tomography (OCT) for characterization of corneal stromal striae (CSS) in an ovine animal model and human corneas with histological correlation, in order to evaluate their architectural pattern by image analysis. Forty-six eyes from female adult sheep (older than 2 years), and 12 human corneas, were included in our study. The eyes were examined in situ by a portable OCT, without enucleation. All OCT scans were performed immediately after death, and then the eyes were delivered to a qualified histology laboratory. In the ovine animal model, CSS were detected with OCT in 89.1% (41/46) of individual scans and in 93.4% (43/46) of histological slices. In human corneas, CSS were found in 58.3% (7/12) of cases. In both corneal types, CSS appeared as "V"- or "X"-shaped structures, with very similar angle values of 70.8° ± 4° on OCT images and 71° ± 4° on histological slices (p ≤ 0.01). Data analysis demonstrated an excellent degree of reproducibility and inter-rater reliability of measurements (p < 0.001). The present study demonstrated that by using a portable OCT device, CSS can be visualized in ovine and human corneas. This finding suggests their generalized presence in various mammals. The frequent observation, close to 60%, of such collagen texture in the corneal stroma, similar to a 'truss bridge' design, permits to presume that it plays an important structural role, aimed to distribute tensile and compressive forces in various directions, conferring resilience properties to the cornea.

Repeatability and reproducibility of post-mortem central corneal thickness measurements using a portable optical coherence tomography system in humans: a prospective multicenter study.

To assess the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements made by the portable iVue spectra-domain (SD) optical coherence tomography OCT (Optovue Inc, Fremont, CA) system in humans, and to prospectively establish the time-course of CCT after death. In a prospective multicenter setting, CCT measurements were obtained from 58 human eyes at the following 16 time-points after death: immediately (within 2 h), and at each hour by the next 17 h. The range of CCT values for each subject was determined and longitudinal data were used to illustrate the variation in open and close eye mode. All measurements were made by two independent and well-trained examiners for session. Main outcome measures were intraclass correlation coefficients (ICC), repeatability and reproducibility coefficients, and coefficients of variation of the average central (0-2 mm). Overall, a total of 5,568 OCT measurements were performed by examiners. The repeatability coefficient varied from 0.3 to 1.7% and the reproducibility coefficient varied from 0.3 to 1.6% throughout the entire experimental time frame. Furthermore, the values of the different ICCs were also high during the different postmortem intervals, thus demonstrating the excellent repeatability and reproducibility of the present OCT approach. When CCT measurements were analyzed longitudinally, corneal thickness showed different behavior based on the open or close eye mode. The present study demonstrates that portable OCT imaging can be reliably used for corneal pachymetric measurements in supine subjects and during the post mortem period, i.e. without visual fixation and normal physiology/architecture of examined tissues.

A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic Medications from the Drug Repurposing Approach during and after the Coronavirus Disease 2019 Era.

The coronavirus disease 2019 (COVID-19) represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its clinical manifestations are characterized by a heterogeneous group of symptoms and pictures (ranging from asymptomatic to lethal courses). The prevalence of conjunctivitis in patients with COVID-19 is at present controversial. Although it has been reported that only 0.9% developed signs of conjunctivitis, other report indicates that up to 31.6% of hospitalized patients had conjunctivitis. Considering the widespread use of topical ophthalmic medications (e.g., eye drops) by the general population, for various reasons (e.g., artificial tears, anti-glaucoma medications, topical antibiotics, etc.), the existence of their side effects as antiviral action should be investigated in-depth because it could possibly explain the aforementioned controversial data and represent a potential antiviral treatment for SARS-CoV-2 replication/diffusion on the ocular surface. Here, we discuss and elucidate the antiviral side effect of many eye drops and ophthalmic ointments commonly used for others purposes, thus showing that these secondary effects (not to be confused with the 'adverse effects') might be of primary importance in a number of viral infections (e.g., those for which there is no validated treatment protocol), according to a drug repurposing approach. Some active ingredients or excipients described here have activity against other types of viruses, thus suggesting potential broad-spectrum applications.

Optical coherence tomography angiography in multiple sclerosis: A cross-sectional study.

OBJECTIVES: To evaluate retinal axonal density and retinal capillary flow density (CFD) variations in patients affected by multiple sclerosis (MS) as documented by Optical Coherence Tomography Angiography (OCT-A). MATERIAL AND METHODS: A cross-sectional study was performed in a tertiary university eye hospital on 94 eyes from 48 MS patients compared to 37 eyes from 23 matched controls. MS patients were divided in two groups: those with previous episodes of optic neuritis (MS ON+, 71.4%) and those without any previous visual complaint (no optic neuritis group, MS ON, 28.6%). Patients underwent macular and optic nerve head OCT-A with Optovue XR Avanti (Optovue, Freemont, California) after that preliminary evaluation of the ganglion cell complex (GCC) and of the retinal nerve fiber layer (RNFL) was achieved for each single eye by SD-OCT. CFD was evaluated in three different retinal layers of MS patients and controls: superficial capillary plexus (SCP), deep capillary plexus (DCP) and the choriocapillaris layer (CL). Each layer was analyzed in 18 preset subregions automatically detected by the system. CFD values were then correlated to the RNFL thickness and GCC thickness in the groups: p values were computed by t-tests between each group of MS patients and controls. A p-value of <0.05 was considered significant. RESULTS: A significant difference in the overall CFD values was found between ON+ and ON- patients when compared to controls in 18 subregions of SCP. Furthermore, a significant difference was found between MS patients and controls in 16 subregions analyzed corresponding to the CL layer without difference between the two MS subgroups (ON+ and ON-). CONCLUSIONS: OCT-A when performed at the optic nerve head level and at the macular region is characterized by a reduction of retinal perfusion in a significant portion of MS patients independently if they had a previous history of optic nerve inflammation or not.

Safety Recommendations and Medical Liability in Ocular Surgery during the COVID-19 Pandemic: An Unsolved Dilemma.

Ocular surgery is one of the most performed medical procedures in the world. Its limitation or suspension, recursively extended over time, could be associated with a significant increase in the number of blind people worldwide. Indeed, cataract causes more than half of all cases of visual impairment in those countries with limited availability of means for performing eye operations (e.g., Africa or India). In this scenario, the pandemic of coronavirus disease 2019 (COVID-19) quickly resulted in the suspension or sharp reduction of various ophthalmic activities considered non-urgent, including lens replacement surgery or some intraocular injections. Despite the imperative need to continuously practice eye operations to avoid the abovementioned problems, there are currently little-shared and vague recommendations among the various countries on safety in operating rooms (for health care workers and patients) and poor legal protection for surgeons (potentially transmitting the COVID-19 infectious agent). Herein, we individuated and discussed some critical points in safety recommendations and medical liability. A paradigm shift for ocular surgery during the COVID-19 era is now mandatory. While telemedicine has been able to solve some problems in clinical ophthalmology, the lack of adequate health and legal protection for surgeons and patients may result in an excessive reduction in the volume of surgical interventions during a pandemic era and the immediately following period, thus determining inability to ensure health care to all patients.

The Ocular Surface and the Coronavirus Disease 2019: Does a Dual 'Ocular Route' Exist?

Coronavirus disease 2019 (COVID-19) is an important health problem that was defined as a pandemic by the World Health Organization on 11 March 2020. Although great concern has been expressed about COVID-19 infection acquired through ocular transmission, its underlying mechanism has not currently been clarified. In the current work, we analyzed and elucidated the two main elements that should be taken into account to understand the "ocular route", both from a clinical and molecular point of view. They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein. Although it seems, at the moment, that there is a low risk of coronavirus spreading through tears, it may survive for a long time or replicate in the conjunctiva, even in absence of conjunctivitis signs, indicating that eye protection (e.g., protective goggles alone or in association with face shield) is advisable to prevent contamination from external droplets and aerosol.

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Fourier-Domain OCT Imaging of the Ocular Surface and Tear Film Dynamics: A Review of the State of the Art and an Integrative Model of the Tear Behavior During the Inter-Blink Period and Visual Fixation.

In the last few decades, the ocular surface and the tear film have been noninvasively investigated in vivo, in a three-dimensional, high resolution, and real-time mode, by optical coherence tomography (OCT). Recently, OCT technology has made great strides in improving the acquisition speed and image resolution, thus increasing its impact in daily clinical practice and in the research setting. All these results have been achieved because of a transition from traditional time-domain (TD) to Fourier-domain (FD) technology. FD-OCT devices include a spectrometer in the receiver that analyzes the spectrum of reflected light on the retina or ocular surface and transforms it into information about the depth of the structures according to the Fourier principle. In this review, we summarize and provide the state-of-the-art in FD-OCT imaging of the ocular surface system, addressing specific aspects such as tear film dynamics and epithelial changes under physiologic and pathologic conditions. A theory on the dynamic nature of the tear film has been developed to explain the variations within the individual compartments. Moreover, an integrative model of tear film behavior during the inter-blink period and visual fixation is proposed.