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

PRCIS: This study showed that the XEN patency should be verified by OCT imaging in cases of encapsulated blebs. Although fibrosis plays the principal role, humor aqueous flow reduction could affect the "spacer" effect that inhibits the fibroblast attachments. PURPOSE: To evaluate the application of the anterior segment optical coherence tomography (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 3 eyes presenting a cystic bleb after an XEN63 implantation for uncontrolled intraocular pressure (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 mm Hg. 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 to the ostium, was performed 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 mm Hg, 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.

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.

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.

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.

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.

Global Spread of Coronavirus Disease 2019 and Malaria: An Epidemiological Paradox in the Early Stage of A Pandemic.

In the current work, we discovered and analyzed the epidemiological paradox between coronavirus disease 2019 (COVID-19) and malaria in the initial phase of the ongoing pandemic. From the analysis of distribution data, the endemic presence of malaria seems to protect some populations from COVID-19 outbreak, particularly in the least developed countries. In this sense, molecular and genetic variations associated with malaria (e.g., in ACE2) might play a protective role against coronavirus infection. Moreover, the mechanism of action of some antimalarial drugs, e.g., the antiviral function, suggests their potential role in the chemoprophylaxis of coronavirus epidemics, despite possible adverse effects (e.g., retinal toxicity). All these data provide important insights to understand the spreading mechanisms of COVID-19, and to direct scientific research toward the study of some currently available medications.

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.

Anxiety, Prenatal Attachment, and Depressive Symptoms in Women with Diabetes in Pregnancy.

The purpose of this study was to evaluate the relationship between anxiety, prenatal attachment, and depressive symptoms among women with diabetes in pregnancy. Participants were 131 consecutive pregnant women between the ages of 20 and 45 with a diagnosis of gestational or pregestational type 1 or type 2 diabetes. Data on previous psychiatric symptoms were obtained from the Anamnestic and Social Questionnaire and the Mini-International Neuropsychiatric Interview (MINI). Information on prenatal attachment was collected using The Prenatal Attachment Inventory (PAI), and The Edinburgh Postnatal Depression Scale (EPDS) assessed depressive symptoms in the third trimester of pregnancy (at a mean of 25 weeks). Results demonstrated that in women affected by diabetes in pregnancy, two facets of prenatal attachment (anticipation, interaction) were negatively correlated with depressive symptoms, and a history of anxiety, assessed with the MINI, moderated the relation between the prenatal attachment interaction factor and depressive symptoms during pregnancy.

COVID-19 and Italian Healthcare Workers From the Initial Sacrifice to the mRNA Vaccine: Pandemic Chrono-History, Epidemiological Data, Ethical Dilemmas, and Future Challenges.

On March 11, 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a pandemic. Simultaneously, in Italy, in which the first case had occurred on February 18, the rigid phase of the lockdown began. The country has attracted worldwide attention, becoming at the same time a field of study both concerning the spread of the pandemic and advanced assessments of the effectiveness of political, public health, and therapeutic measures. The protagonists of the Italian crisis were the healthcare workers (HCWs) who were exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without having any perception of what they were facing, courageously contributing to the containment of the epidemic to be defined by the media as "heroes." However, in the first phase of the pandemic (March-May 2020), the price that the Italian Public Health System had to pay both in terms of the number of positive virus cases and deaths among the HCWs was beyond and represented a peculiarity compared to what happened in other countries. In the current study, after a summary of the evolution of the pandemic in Italy, we offer an analysis of the statistical data concerning contagions and deaths among healthcare workers (physicians in particular). In conclusion, we describe the critical issues that still need to be resolved and the future challenges facing healthcare workers and the general population.

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

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

Optical coherence tomography in forensic sciences: a review of the literature.

Optical coherence tomography (OCT) is an interferometric imaging technique that has revolutionized clinical ophthalmology since the first half of the 1990's. Despite this approach being successfully employed in ophthalmology and having great potential in forensic cases, its use in different forensic fields appears to be quite limited. In this review we reviewed the scientific literature regarding the application of OCT in forensic science and legal medicine from 1995 to 2019. Our research showed the usefulness of this approach for the study of coronary injuries, postmortem ocular changes, forensic entomology, and several other applications of specific forensic interest (the study of blood stains, fingerprints, and hair bulbs for personal identification, as well as the study of materials found in the crime scene for comparation, or anti-fraud investigation). The creation of specific 'ad hoc' devices and a better knowledge of this type of technology by pathologists will be a fundamental step to continue to develop the use of OCT forensic fields.