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Pietro Emanuele Napoli,1,* Matteo Nioi,2 Maurizio Fossarello1,3,* 1Department of Surgical Science, University of Cagliari, Eye Clinic, Cagliari, Italy; 2Department of Clinical Sciences and Public Health, University of Cagliari, Forensic Medicine Unit, Cagliari, Italy; 3Clinica Oculistica, San Giovanni di Dio Hospital, Azienda Ospedaliera Universitaria di Cagliari, Cagliari, Italy*These authors contributed equally to this work.Correspondence: Pietro Emanuele Napoli Email pietronapoli@ymail.comAbstract: 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.Keywords: COVID-19, dry eye diseases, sick building syndrome, ocular surface, coronavirus, SARS-CoV-2, tear film, lockdown, quarantine, display device

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. Cho- roidal 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 mm2 vs. 0.491 ± 0.132, P = 0.006; 0.263 ± 0.152 mm2 vs. 0.340 ± 0.094, P = 0.002; 185.2 ± 79.8 mm vs. 216.8 ± 58.8 mm, P = 0.036, respectively). Best-corrected visual acuity was significantly correlated only with choroidal thickness (R = 20.509; P = 0.002). During the follow-up period in patients with GA, sub- foveal choroidal thickness decreased from 185.2 ± 79.8 to 152.2 ± 73.1 (P = 0.001), stromal area increased from 0.138 ± 0.090 mm2 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.

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.

Pietro Emanuele Napoli1,* Mirco Braghiroli,1,* Claudio Iovino,1 Giuseppe Demarinis,1 Maurizio Fossarello1,21Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy; 2Clinica Oculistica, San Giovanni di Dio Hospital, Azienda Ospedaliera Universitaria di Cagliari, Cagliari, Italy*These authors contributed equally to this work Background: Effective and tolerable therapeutic strategies for patients with refractory persistent epithelial defects (PEDs) are limited and generally provide poor outcomes. This retrospective case review describes four refractory cases of PEDs associated with recurrent corneal erosions (RCEs) and dry eye disease (DED), which were successfully treated with cyclosporine eye drops.Methods: Patients were treated with cyclosporine A 0.05% eye drops twice a day for at least 12 months. At enrolling time, each patient was asked to suspend topical steroids or other eye drops used for ocular surface abnormalities with the exception of lubricants and eye washing. A complete evaluation of ocular surface symptoms was performed including the McMonnies Dry Eye Questionnaire, Ocular Surface Disease Index, slit-lamp biomicroscopy, fluorescein break-up time, the fluorescein staining of the cornea and conjunctiva (according to the Oxford grading system), the Schirmer I test, and the meibomian secretion after digital pressure application on the lids. This set of exams was carried out at baseline and repeated at all follow-up assessments.Results: All participants that did not benefit from previous therapies, including corticosteroids tapering schedule, showed an important improvement in the clinical picture after two months with topical cyclosporine medication. Moreover, after 12 months of continuous therapy, all patients showed a clinical improvement in DED signs and symptoms, related to the absence of new RCE episodes. The treatment was well tolerated, and no adverse effects were reported.Conclusion: Although a small number of cases were available of our analysis, the treatment with cyclosporine eye drops represents a promising approach in the management of refractory PEDs with associated ocular comorbidities, since it may reduce the RCE episodes and improve the tear film stability, in absence of systemic or local side effects.Keywords: dry eye disease, persistent epithelial defects, cyclosporine eye drops, recurrentcorneal erosion, corneal adhesion

Objectives: The aim of the current work was to evaluate the frequency and the type of cases of medical liability from a single center in the first ten months of the pandemic as well as to identify critical issues associated with the organization of public health during the coronavirus disease 2019 pandemic. Methods: We compared 130 cases evaluated for medical liability from March 2020 to January 2021 and compared with 159 cases from March 2019 to January 2020. The cases were divided in four pre-established groups: surgical error, diagnostic/therapeutic errors and nosocomial diseases, delays, and problems related to assistance. Results: Analysis showed a significant increase in cases due to delay in treat-ment/hospitalization and shortages in health care of non-autonomous patients [χ2 (1, N = 289) = 5.6746, p = 0.02]. Conclusions: The work showed an increase in medical/legal cases regarding non-COVID-19 emergencies in which the outcome is related to the time of treatment and/or arrival at the hospital. There was also a rise in complaints of deficits in supervision and care for non-autonomous patients. Despite the persistence of preventive measures for the current pandemic, measures should be taken to improve health care in these categories of patients.

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.

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.

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 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 resilience properties to the cornea.

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.

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.

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.

In the current work, we discovered and analyzed the epidemiological paradox between coronavirus disease 2019 (COVID-19) and malaria. 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. Molecular and genetic variations associated with malaria (i.e. ACE2) may play a protective effect against coronavirus infection. Of note, the mechanism of action of some antimalarial drugs (e.g. antiviral function) suggests their potential role in the chemoprophylaxis of the epidemic. All these data provide important suggestions and insights on the possible prevention and management of the pathology.

Purpose To describe an unusual case of unilateral, chronic symptoms and signs of dry eye, and recurrent episodes of ocular irritation related to pinguecula, which were refractory to prior medical treatments, successfully treated with argon laser photocoagulation. Methods A 36-year-old man presented with an elevated yellowish mass on his conjunctiva in his left eye, which was associated with dry eye symptoms and general discomfort, such as "tightening sensation" and "stiffness". On clinical assessment, the left eye revealed a mild conjunctival injection, a fluorescein break-up time (FBUT) of 3.5 s, an abnormal fluorescein staining, and a Schirmer I test of 5 mm. Optical coherence tomography (OCT) imaging evidenced a height at the most elevated point of the pinguecula of 740 µm. The patient underwent argon-laser photocoagulation. Results After 2 weeks postoperatively, no residual of pinguecula or focal injection of the conjunctiva was detected by slit-lamp biomicroscopy and there was a significant improvement of clinical symptoms and signs: Schirmer I test and FBUT increased to 12 mm and >10 s, respectively, and fluorescein staining was absent. OCT imaging revealed a smooth structure of conjunctival contour, with a height of 404 µm. According to an ex juvantibus line of reasoning, definitive diagnosis was pinguecula-related dry eye disease. Conclusion Based on the concept that tear film instability and inflammation are two key components of the pathogenesis of dry eye, we coined the term "pinguecula-related dry eye disease," which can be successfully treated by a complete, accurate removal of the lesion with argon laser photocoagulation.

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.

The estimation of the time since death, or post-mortem interval (PMI), still remains a main conundrum in forensic science. Several approaches have been so far proposed from either a qualitative or a quantitative point of view, but they still lack reliability and robustness. Recently, metabolomics has shown to be a potential tool to investigate the time-related post-mortem metabolite modifications in animal models. Here we propose, for the first time, the use of a 1H NMR metabolomic approach for the estimation of PMI from aqueous humour (AH) in an ovine model. AH samples were collected at different times after death (from 118 to 1429 min). 1H NMR experiments were performed and spectral data analysed by multivariate statistical tools. A multivariate calibration model was built to estimate PMI on the basis of the metabolite content of the samples. The model was validated with an independent test set, obtaining a prediction error of 59 min for PMI 1000 min. Moreover, the metabolomic approach suggested a picture of the mechanisms underlying the post-mortem biological modifications, highlighting the role played by taurine, choline, and succinate. The time-related modifications of the 1H NMR AH metabolomic profile seem to be encouraging in addressing the issue of a reproducible and robust model to be employed for the estimation of the time since death.

The aim of the study was to define and characterize the optical behavior of the tear film during visual fixation in humans on en-face optical coherence tomography (OCT). We included 20 healthy participants, 60% female, aged from 25 to 42 years (33.05 ± 4.97 [mean ± SD]) and ten patients with severe dry eye, 50% female, aged from 26 to 42 years (33.7 ± 5.31). To perform high-resolution tear film imaging, participants were asked to gaze at the internal fixation point in the spectral-domain anterior segment OCT device, and meanwhile scanning session was executed at the following time-points after blinking: at the 2nd, 3rd, 4th, 5th, and 6th second. After one hour, OCT imaging was repeated (second session) by a different operator masked to the study to verify the reliability of results. During each measuring session, a pulse oximetry was used for continuously measuring the heart rate and oxygen saturation (SpO2%). A preliminary experiment was also performed to test the absence of geometric patterns from the anterior surface of a motionless artificial eye. OCT imaging showed a motionless, stable anterior surface of the artificial eye and in dry eye patients. Conversely, in the healthy participants of the study, a bull’s eye pattern of the tear film was detected by OCT at the 2nd, 3rd, 4th, 5th, and 6th second after blinking, respectively, in 45%, 60%, 45%, 60%, and 40% of OCT scans during the first session, and in 35%, 65%, 65%, 60%, and 35% of cases in the second session. Overall, a total of 200 OCT scans were performed in normal human population. A significant correlation was found between the novel tear film pattern and heart rate during the first and the second session (p

The estimation of the time since death, or post-mortem interval (PMI), still remains a main conundrum in forensic science. Several approaches have been so far proposed from either a qualitative or a quantitative point of view, but they still lack reliability and robustness. Recently, metabolomics has shown to be a potential tool to investigate the time-related post-mortem metabolite modifications in animal models.Here we propose, for the first time, the use of aAH samples were collected at different times after death (from 118 to 1429 min).A multivariate calibration model was built to estimate PMI on the basis of the metabolite content of the samples. The model was validated with an independent test set, obtaining a prediction error of 59 min for PMI 500 min, 104 min for PMI from 500 to 1000 min, and 118 min for PMI 1000 min. Moreover, the metabolomic approach suggested a picture of the mechanisms underlying the post-mortem biological modifications, highlighting the role played by taurine, choline, and succinate.The time-related modifications of the

Purpose. To compare and evaluate images of macular cysts with different degrees of reflectivity (from gray to black signal) as observed in B scan spectral domain OCT (SDOCT) and EnFace OCT with decorrelation signal obtained with OCT-angiography (OCTA) in eyes with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) and retinal vein occlusion (RVO). Methods. Images from 3033 patients affected by CME secondary to diabetes or RVO examined OCTA (Optovue XR Avanti, Optovue, USA) at the University Eye Clinic of Créteil, Hôpital Intercommunal, France, and at the University Eye Clinic of Cagliari, “San Giovanni di Dio” Hospital, Italy, were retrospectively examined. The deep capillary plexus OCTA images and the corresponding EnFace OCT images, both acquired with the same automatic segmentation, had been overlapped to compose RGB color images as red and green channels, respectively, using ImageJ software (National Institutes of Health, Bethesda, MD). Afterward, linear regions of interest were traced on the color images to obtain the profiles of OCTA and EnFace gray values. Number of pixels, mean gray value and standard deviation of the area traced in OCT-A, and EnFace image were analyzed and statistically correlated. Data were exported to Excel to create the plots. Results. 94 patients with DME and 27 patients with RVO showed intraretinal macular cystoid spaces with similar homogeneous, gray-looking content; 73 patients with DME and 113 patients with RVO showed macular cystoid spaces with homogeneous, black-looking content, as observed at SD-OCT, EnFace and OCTA scans. Interestingly, the limits of macular cystoid spaces were clearly detectable with OCTA. The analysis of red and green profiles demonstrated a clearly visible overlap between average OCTA and EnFace signal observed around cystoid spaces that could be attributed to a relationship between the dynamic vascularization and the structural density of the tissue. Conclusions. This is the first investigation that characterizes and correlates OCTA and EnFace signals on images of macular cystoid spaces in DR and RVO. The low intensity OCTA signals observed inside cystoid spaces raise a relevant question about their nature, as to whether they are due to the presence of corpusculated material pouring out from bloodocular-barrier or they should be considered OCTA artifacts.

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

Maria Silvana Galantuomo,1,* Maurizio Fossarello,1 Alberto Cuccu,1 Roberta Farci,1 Markus N Preising,2 Birgit Lorenz,2 Pietro Emanuele Napoli1,* 1Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy; 2Department of Ophthalmology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany *These authors contributed equally to this work Background: Juvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments. Purpose: The purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT). Methods: Eleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications. Results: Sequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect. Conclusion: This study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation. Keywords: juvenile X-linked retinoschisis, oral acetazolamide, topical dorzolamide, cystoid macular edema, macular schisis, foveal zone thickness

BACKGROUND Cilioretinal artery (CRA) occlusions are rare in young patients. In these cases, the most commonly associated causes are considered to be the same as those implicated in central retina artery occlusions, such as vasculitic processes, migraine, cardiac disorder, and coagulation abnormality. The aim of this article was to report for the first time the medical records and investigational results of an unusual case of simultaneous occlusion of three CRAs after scleral buckling surgery under local anesthesia. METHODS A complete ophthalmic examination, including color fundus image, fundus fluorescein angiography, optical coherence tomography, visual field, as well as systemic and laboratory assessments, was performed. RESULTS A case of contemporaneous blockage of three CRAs after ab externo surgery for retinal detachment in a 29-year-old Caucasian woman was reported. The interdisciplinary approach and the imaging results have allowed us the clinical definition of such a very rare case. CONCLUSION Here, we reported that optical coherence tomography is an indispensable tool to better delineate the pathological process and follow atrophic changes in the macula, especially in cases in which fundus fluorescein angiography and systemic tests may be poorly informative.

To describe a case of acute angle-closure glaucoma secondary to intermittent mydriasis related to Pourfour du Petit Syndrome caused by tracheal deviation.A 70-year-old Caucasian woman visited the Emergency Room of the University Eye Clinic complaining of blurring of vision and difficulty to move superior eyelid in her right eye. Examination revealed reactive mydriasis, and upper lid retraction on the right side. The rest of the ophthalmological examination was normal, and a cranial computed tomography (CT) did not identify any abnormalities. A cervical CT showed the presence of an accentuated lateral right convex deviation of the trachea, attributable to a fibrothorax. A right Pourfour du Petit syndrome was suspected. Although the mydriasis had in the meantime vanished, the patient was admitted to the Neurological Clinic.Five days later she suffered acute pain in her right eye. Ophthalmological examination of the right eye revealed conjunctival hyperemia, marked corneal edema, reduced depth of anterior chamber, permanent mydriasis. As assessed by Goldmann applanation tonometry, intraocular pressure (IOP) was 48 mm Hg. Fundus examination was normal in both eyes. Gonioscopy revealed angle closure in all quadrants. Slit lamp examination of the contralateral eye was normal; IOP was 10 mm Hg. After hypotensive medical therapy, iridotomy with YAG laser was performed. Thereafter, IOP stabilized at 12 mm Hg.This is the first report in the literature of a case of acute angle-closure glaucoma secondary to mydriasis related to Pourfour du Petit Syndrome caused by tracheal deviation.

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.

PURPOSE: The aim of this study was to describe by means of a portable Optical Coherence Tomography (OCT) the postmortem ocular findings in two cases of forensic interest. CASE 1. A 41-year-old Caucasian man, dead from a gunshot in the head, was found inside his car. Time of death was precisely assessed from the testimony of eye witnesses. The body was transported at the Morgue of Medico-Legal Institute at the University of Cagliari for autopsy. OCT scans of cornea, anterior chamber and retina were performed at the 6th, 12th and 24th hour postmortem without change eyelid opening status. Corneal examination showed a progressive tendency of tissue to thickening. From a morphological point of view, we also observed a progressive formation of waves in the posterior stroma and in the endothelium [we decided to call this phenomenon, described by our group for first time, Nioi-Napoli sign (NN sign)]. An ongoing modification in reflectivity between anterior (hyperreflective) and posterior (hypo-reflective) segment of the corneal stroma was detecetd and a progressive decrease in amplitude of anterior chamber, mainly related to changes in tissue curvature. The retinal tissue showed since the first scan an increasing trend of retinal oedema togheter with a diffuse vasal depletion. It was also detachable the formation of a scleral tache noir. CASE 2. A 42-year-old woman, dead from myocardial infarction, underwent an autopsy at the Medico-Legal Institute at University of Cagliari (as suspected case of medical malpractice). Exact time of death was deduced by certificate of death drawn up by the emergency medical team. Scans of cornea, retina and anterior chamber were executed at the 24th, 36th and 48th hour postmortem. From the first scan an enhancement of corneal thickness, if compared to the physiological in vivo ranges, was detected; a change in corneal curvature was observed while no images form the retinal tissue was achieved. Late scans evidenced a progressive corneal endothelial exfoliation, and an enhancement of posterior stroma waving. CONCLUSION Portable OCT may be an useful device to observe and to record postmortem ocular changes. 1,2,3 Its use could represent an important tool to study the early and the late modification of ocular tissues, with a special interest in the forensic scenario as post mortem interval estimation (PMI estimation) and in ophthalmology (viability of cornea for transplantation purposes).

PurposeTo evaluate the feasibility of 3D anterior segment optical coherence tomography (AS-OCT) for the detection of corneal endothelial features in patients with Fuchs' Endothelial Corneal Dystrophy (FECD).MethodsTwenty patients with clinical diagnosis of FECD (group A), and 20 control subjects (group B) were enrolled. In all patients a complete ophthalmological examination was performed, including best corrected visual acuity (BCVA), slit lamp examination for subjective grading of FECD and corneal endothelial specular microscopy. A 512x128 AS-OCT cube centered on the corneal apex was performed, and then the inner surface of the cornea was visualized and analyzed individually.ResultsOverall, the study participants were adults (mean age was 57.35 ± 8.45 years [mean ± SD] 80% female) with a BCVA ranged from 1.3 to 0 LogMAR. The OCT analysis disclosed three different patterns of the corneal endothelium (1, 2, 3) according to the signal distribution and the level of reflectivity: a homogenous, hypo-reflective surface (pattern 1); the presence of hyper-reflective orange-yellowish points (pattern 2); and a mottled appearance with a variable number of hyper-reflective areas (pattern 3). The distributions of these morphological models in the two populations were as follows: patterns 1, 2 and 3 were observed respectively in 0%, 80%, and 20% of patients in group A, and in 80%, 20% and 0% of subjects in group B. Correlation analysis unveiled a positive relationship between OCT corneal endothelium reflectivity and the clinical severity score (assessed with biomicroscopy), as well as an inverse relationship between the OCT pattern and the integrity of corneal endothelium.Conclusion3D AS-OCT is a useful tool in investigation of endothelial features and therefore may represent a valuable support in the setting of FECD diagnosis and staging.

Objective To provide a qualitative and quantitative analysis of filtering blebs with optical coherence tomography (OCT) in patients after primary trabeculectomy. Design Evaluation of diagnostic technology. Participants We retrospectively studied 20 eyes of 20 patients who had a fornix-based flap in primary trabeculectomy: 14 with mitomycin C (MMC) and 6 without MMC. Methods Filtering blebs were examined using 2 types of OCTs working at a wavelength of 840 and 1310 nm. In this study, we analyzed both the OCT morphologic pattern and the internal structures of blebs, including bleb wall thickness, scleral flap thickness, and the route under the scleral flap, and quantified the reflectivity of the intrableb area. Results Blebs were classified according to the Hirooka scheme in 3 OCT morphologic patterns: cystoid, diffuse, and layer type. The MMC was associated with the surgical success (100%). A significant association was found between good functionality and cystoid type with both devices: 840-nm OCT ( p = 0.02) and 1310-nm OCT ( p = 0.04). A significant difference in morphologic patterns was found using the 2 OCTs. There were no significant differences between successful and unsuccessful filtering surgery for intrableb structures. The reflectivity of filtering blebs correlated very well to the postoperative intraocular pressure (IOP; R 2 = 0.90; p R 2 = 0.58; p = 0.001). Our method to quantify the reflectivity showed a significant degree of intergrader consensus (intraclass correlation coefficient=0.99; p Conclusions Although 840-nm OCT was not developed to assess the anterior segment, it may be considered a useful tool to evaluate the functionality of blebs in the postoperative period.

The purpose of this study was to determine the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements by using a real-time, portable optical coherence tomography (OCT) system on an animal model and to prospectively evaluate the time-course of post-mortem changes in CCT. Forty-six ocular globes of sheep (Ovis aries) were analyzed with a portable spectral-domain OCT device by two operators at different postmortem intervals (PMIs) as follows: immediately (i.e. within 10 minutes), at the 30th minute, at the 1st, 6th, 12th, 24th and 48th hour and later (up to the 96th hour). The coefficient of repeatability ranged from 0.3% to 3.5% and coefficients of reproducibility ranged from 0.2% to 3.7% in the central region of the cornea. The intraclass correlation coefficients were particularly high at different PMIs, thus confirming good measurement reliability with the portable OCT. The average CCT decreased immediately and then increased thereafter, with two peaks at 6 and 24 hours after death. Our results suggest that portable OCT is a reliable tool for monitoring CCT variations after death and may be useful in characterizing corneas before explantation, detecting quantitative variations during post-mortem corneal degeneration or assessing changes in CCT for forensic implications.

Purpose To compare a novel spectral-domain optical coherence tomography (SD-OCT) technique with traditional lid transillumination for evaluation of meibomian glands (MGs) and to assess the relation of MG morphologic changes to the glandular atrophy. Design Evaluation of diagnostic technology. Participants Sixty-one patients with obstructive MGD (30 men, 31 women; age [mean ± standard deviation] 45.1 ± 12.1 years), and 75 control subjects (32 men, 43 women; 44.1 ± 12.5 years) were recruited in order to have a balanced distribution of glandular features. Methods Agreement between SD-OCT and lid transillumination examination for the detection of drop-out (partial or complete loss of MGs) and microscopic changes (i.e. shortening, distortion, segmentation and entanglement), as well as the relationship between morphological features and MG atrophy were evaluated. Main Outcome Measures Agreement between the two meibographic techniques, bias in symmetry of classification, and association analysis between microscopic changes and MG dropout. Results Overall agreement for all morphological features was substantial (Cohen kappa coefficient = 0.77; p

Objective The aim was to determine the influence of meibomian gland dysfunction (MGD) and aqueous tear deficiency dry eye (ADDE) on the adhesive properties of the central cornea by means of optical coherence tomography (OCT), and to investigate the relationship between corneal adhesiveness and classical tear tests, as well as the reliability of results, in these lacrimal functional unit disorders. Design Prospective, case-control study. Methods Twenty-eight patients with MGD and 27 patients with ADDE were studied. A group of 32 healthy subjects of similar age and gender distribution served as a control group. The adhesive properties of the anterior corneal surface were measured by OCT, based on the retention time of adhesion marker above it, in all participants. Results An excellent (≥5 minutes), borderline (within 3–5 minutes), fair (within 1–3 minutes) and poor (

PURPOSE. The purpose of this work was to gather preliminary data on tear film stability, and the adhesive properties of the corneal surface in dry eye patients and control group subjects, using a new, minimally invasive optical coherence tomography (OCT) imaging method. METHODS. We screened 85 human subjects for dry eye and classified them in two groups, as dry eye or normal patients. Sodium carboxymethylcellulose (NaCMC) adhesiveness over the central cornea was measured using Fourier domain anterior segment OCT. The corneal adhesiveness for NaCMC was compared between the two groups, correlated with classical tests, and analyzed for diagnostic validity and repeatability. RESULTS. The corneal adhesiveness for NaCMC median and mode values was fair (between 1 and 3 minutes) for dry eye subjects (n ¼ 36) and borderline (between 3 and 5 minutes) for control group subjects (n ¼ 49), and was significantly different between the two groups (P < 0.001). Significant correlations were observed between the corneal adhesiveness measures and dry eye patients’ symptoms (P < 0.001), Schirmer I test (P < 0.001), ocular surface staining (P < 0.001), and, particularly, fluorescein break-up time (P < 0.001). The area under the receiver operating characteristic curve was 0.94 (P < 0.001), suggesting reliable sensitivity and specificity of OCT imaging. A statistically significant intraclass correlation (ICC) value of 0.99 was found for measurements of corneal adhesiveness on two subsequent days at the same time (P < 0.001). CONCLUSIONS. This minimally invasive, novel technique of OCT imaging of the corneal surface following NaCMC drop instillation provides a measure of corneal adhesiveness. This technique may improve the clinician’s ability in the understanding and diagnosis of the dry eye syndrome.

PURPOSE: To analyze in vivo the dynamic changes induced by different artificial tears (ATs) in the precorneal tear film (PCTF) and lower tear meniscus (LTM) by using spectral-domain (SD) anterior segment optical coherence tomography (OCT). METHODS: We prospectively examined 42 normal human eyes by using SD-OCT imaging. On the day before OCT imaging, all enrolled subjects were evaluated for abnormalities of ocular surface. All tear film images were obtained before and after instillation of three different types of ATs (mucomimetic, lipid-based, and saline) in five serial scans: immediately (within 30 seconds), at the first, fifth, 10th, and 20th minute. Subjects received a drop of 35 μL in one randomly selected eye. All examinations were conducted in the same conditions of temperature, brightness, humidity, and time of day. RESULTS: Changes in the morphological pattern of both LTM and PCTF were associated with the type of artificial tear instilled on the ocular surface. Similarly, the radius of curvature (rc), the height (h), and the depth (d) showed dynamic variations depending on treatment. Although by the 20th minute, both h and d returned to baseline values in all groups, a significant difference in rc (compared with baseline) was detected for mucomimetic ATs (P = 0.04) and lipid ATs (P = 0.02). CONCLUSIONS: Spectral-domain OCT imaging has preliminarily proved to be a noninvasive tool to evaluate, in real time, the different changes induced by ATs instillation. An important stride in understanding the clinical response to various tear substitutes can be achieved by this objective and quantitative approach.