Clinical and Diagnostic Findings of Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy in the COVID-19 Era.

BACKGROUND: Growing evidence suggests an association between the infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and eye disorders. The aim of this review was to analyze the clinical presentation and diagnostic features of acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM) associated with COVID-19 infection. The features are then compared with previous reports regarding these retinal disorders, to recognize possible specific characteristics and to assess the role of multimodal ophthalmic imaging. SUMMARY: A literature search was performed by consulting PubMed, Scopus, and Embase. The following terms were searched: "(COVID-19 OR SARS-CoV-2 OR coronavirus) AND ([acute macular neuroretinopathy] OR [paracentral acute middle maculopathy])." Inclusion criteria were as follows: (1) publication date from January 31, 2020 to January 31, 2022; (2) English language; (3) original research or case report; (4) free full-text availability.Optical coherence tomography (OCT) findings in AMN patients were hyper-reflectivity (HR) of the outer plexiform layer, of the outer nuclear layer, and ellipsoid or interdigitation zones (EZ and IZ, respectively) disruption. In most cases, the presence of HR and EZ/IZ abnormalities resulted combined. When performed, OCT angiography (OCTA) identified attenuation of signal of the deep capillary plexus (DCP). The most common OCT finding in PAMM was an alteration of the inner nuclear layer, associated with other areas of HR, while no signs of EZ/IZ disruption were detected. When performed, OCTA showed the attenuation of signal of both the DCP and the superficial capillary plexus. KEY MESSAGES: In this review, we reported a case series of AMN and PAMM in patients with a previous or concomitant infection from SARS-CoV-2. The microvascular changes in these cases are highlighted by the OCTA scans. Even if we are far from the determination of a direct link between COVID-19 and these retinal disorders, we could hypothesize that the vascular alterations associated with SARS-CoV-2 infection could be a possible risk factor for both AMN and PAMM.

The morphology of choroidal neovascularization in chronic central serous chorioretinopathy presenting with flat, irregular pigment epithelium detachment.

PURPOSE: To evaluate morphological characteristics of choroidal neovascularization in chronic central serous chorioretinopathy (CSC) presenting with flat and irregular pigment epithelium detachment (FIPED) by means of innovative multimodal imaging. METHODS: In this observational cross-sectional study, we examined 10 consecutive patients affected by chronic CSC and FIPED using fluorescein angiography (FA), indocyanine-green angiography (ICGA) and optical coherence tomography angiography (OCTA). A qualitative analysis of the nature and characteristics of neovascular membrane was performed, combining available multimodal imaging and literature data. RESULTS: Multiple areas of retinal pigment epithelium alterations, macular hypo- and hyperpigmentation and atrophic areas were identified. Spectral domain OCT (SD-OCT) showed subretinal fluid in 80% of eyes and the 'double layer sign' in all patients. Late FA phases showed staining areas without leakage in all eyes; ICGA showed a hyperfluorescent plaque with surrounding hypofluorescence in 80% of patients. OCTA detected characteristic neovascular networks in the outer retina within the FIPEDs, classified as filamentous vessels with a pruned tree-like pattern in five eyes and a tangled pattern in three eyes. The choriocapillaris network showed dark areas in 80% of eyes and diffuse dark spots in all eyes. CONCLUSION: Multimodal imaging completes clinical characterization of FIPEDs in chronic CSC. This study using OCTA technology describes the phenotype of hidden neovascular lesions in shape and morphology.

OCULAR HYPERTENSION AND GLAUCOMA FOLLOWING VITRECTOMY: A Systematic Review.

PURPOSE: Pars plana vitrectomy has been reported to increase the risk of ocular hypertension and open-angle glaucoma. The authors conducted a systematic review of randomized and nonrandomized studies to compare the incidence of open-angle glaucoma and ocular hypertension in vitrectomized versus nonvitrectomized eyes. METHODS: A literature search was performed using MEDLINE and EMBASE until August 2016. Data on ocular hypertension and open-angle glaucoma incidence and mean intraocular pressure after at least 1 year were pooled using random-effects metaanalysis models. Because only nonrandomized studies were retrieved, ROBINS-I tool was used to assess risk of bias in the review. RESULTS: Seven included studies had a paired design to compare the outcomes of vitrectomized versus fellow eyes, with mean follow-up of least 12 months. Four studies (851 patients) provided data on open-angle glaucoma: incidence in vitrectomized versus non-vitrectomized eyes was 7.8% and 4.8%, respectively, yielding a metaanalytic odds ratio of 1.67 (95% CI: 1.08-2.57). Six studies (1,060 patients) reported on the occurrence of ocular hypertension, which was 5.8% in vitrectomized eyes versus 3.1% in fellow eyes (odds ratio: 2.03, 95% CI: 0.97-4.22), without significant differences in the mean postoperative intraocular pressure (mean difference 0.31 mmHg, 95% CI: -0.26 to 0.89). CONCLUSION: Although the review found increased risk of open-angle glaucoma with pars plana vitrectomy, the studies were heterogenous or inconsistent regarding ocular hypertension and intraocular pressure increase. Larger studies should be conducted in homogenous cohorts of patients undergoing macular surgery, excluding complex conditions such as retinal detachment or diabetic retinopathy.

Heavy and standard silicone oil: intraocular inflammation.

PURPOSE: Proliferative vitreoretinopathy in the inferior retina remains clinically challenging. Heavier-than-water intraocular tamponades have been developed to improve inferior tamponading properties, and their chemical compositions have been substantially improved over the years, in parallel with developments in vitrectomy instrumentation and surgical techniques. Herein we present an updated review of the clinical use of standard formulations and HSO, focusing on analysis of the intraocular inflammation associated with endotamponade agents, and comparison of the adverse effects of these agents on the physical and biological properties of the eye. METHODS: A detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Fifty-eight articles matched our inclusion criteria that were included in this systematic review. RESULTS: Perfluorocarbon liquids and partially fluorinated alkanes are associated with tamponade emulsification, intraocular inflammation, and rises in intraocular pressure, but these associations are not as strong when these substances are mixed with a heavy silicone oil (HSO). Two recently approved heavy silicone oil tamponades, Oxane HD and Densiron 68, are now available for use in clinical practice. While the complication spectrum of the new generation of these HSOs seems to be similar to that of conventional silicone oil tamponades, they provide better support for the inferior retina and the posterior pole. CONCLUSION: Both regular and heavy silicone oils usually yield good success rates in cases of complicated retinal detachment. Decisions as to whether to utilize heavy or regular silicone oil should be made on a case-by-case basis.

Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes.

PURPOSE: To report initial clinical results of transepithelial corneal collagen cross-linking with iontophoresis (I-CXL). METHODS: Twenty eyes of 20 patients diagnosed as having progressive keratoconus who underwent I-CXL were included in this prospective non-randomized clinical study. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, various corneal topography and Scheimpflug tomography parameters, aberrometry, anterior segment optical coherence tomography, and endothelial cell count were assessed at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: CDVA improved significantly at 3, 6, and 12 months postoperatively (logMAR difference of -0.07 ± 0.01, -0.09 ± 0.03, and -0.12 ± 0.06, respectively; P < .05). Aberrometry remained stable during follow-up and a trend toward improvement was noted. All topographic parameters (including maximum keratometry) were stable during the follow-up, but exhibited a positive non-significant trend toward improvement. Minimum corneal thickness values were stable for up to 12 months postoperatively. None of the patients showed a progression of keratoconus. Endothelial cell counts did not change significantly (P > .05). CONCLUSIONS: Preliminary results up to 1 year postoperatively indicate the efficacy of I-CXL in stabilizing the progression of this degenerative disease combined with significant improvement of CDVA. I-CXL, which spares the corneal epithelium, has the potential to become a valid alternative for halting the progression of keratoconus while reducing postoperative patient pain, risk of infection, and treatment time in select patients; however, the relative efficacy of this technique compared to standard epithelium-off techniques remains to be determined.

Ten Years of Experience With a Telemedicine Platform Dedicated to Health Care Personnel: Implementation Report.

BACKGROUND: Telemedicine, a term that encompasses several applications and tasks, generally involves the remote management and treatment of patients by physicians. It is known as transversal telemedicine when practiced among health care professionals (HCPs). OBJECTIVE: We describe the experience of implementing our telemedicine Eumeda platform for HCPs over the last 10 years. METHODS: A web-based informatics platform was developed that had continuously updated hypertext created using advanced technology and the following features: security, data insertion, dedicated software for image analysis, and the ability to export data for statistical surveys. Customizable files called "modules" were designed and built for different fields of medicine, mainly in the ophthalmology subspecialty. Each module was used by HCPs with different authorization profiles. IMPLEMENTATION (RESULTS): Twelve representative modules for different projects are presented in this manuscript. These modules evolved over time, with varying degrees of interconnectivity, including the participation of a number of centers in 19 cities across Italy. The number of HCP operators involved in each single module ranged from 6 to 114 (average 21.8, SD 28.5). Data related to 2574 participants were inserted across all the modules. The average percentage of completed text/image fields in the 12 modules was 65.7%. All modules were evaluated in terms of access, acceptability, and medical efficacy. In their final evaluation, the participants judged the modules to be useful and efficient for clinical use. CONCLUSIONS: Our results demonstrate the usefulness of the telemedicine platform for HCPs in terms of improved knowledge in medicine, patient care, scientific research, teaching, and the choice of therapies. It would be useful to start similar projects across various health care fields, considering that in the near future medicine as we know it will completely change.

Corneal cross-linking as a treatment for keratoconus: four-year morphologic and clinical outcomes with respect to patient age.

PURPOSE: To report the 4-year outcomes of corneal cross-linking (CXL) for progressive keratoconus in a population of different age groups. DESIGN: Retrospective, single-center, nonrandomized clinical study. PARTICIPANTS: Four hundred consecutive eyes treated with corneal CXL for progressive keratoconus from April 2006 through April 2010. INTERVENTION: After removal of the epithelium, the cornea was irrigated for 30 minutes with a solution of 0.1% riboflavin and 20% dextran, followed by irradiation with an ultraviolet A light of 3 mW/cm(2) for 30 minutes. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), sphere and cylinder refraction, corneal topography, Scheimpflug tomography, and aberrometry were assessed at baseline and at 1, 6, 12, 24, 36, and 48 months after corneal CXL treatment. The compiled data were stratified according to age (group A, younger than 18 years; group B, 18-29 years; group C, 30-39 years; and group D, older than 40 years). RESULTS: Comparative analysis included 400 eyes of 301 patients. Functional results showed a significant increase in BCVA in group A by a mean reduction of -0.11 logarithm of the minimum angle of resolution (logMAR) after 12 months, in group B by a mean reduction of -0.31 logMAR after 36 months, in group C by a mean reduction of -0.33 logMAR after 36 months, and in group D by a mean reduction of -0.26 logMAR after 36 months. Morphologic results showed an analogous regularization of corneal shape with a significant reduction of opposite sector index by a mean value of -0.53 at 12 months in group A, -1.14 at 36 months in group B, -1.10 at 36 months in group C, and -0.55 at 12 months for group D. Optical quality improvement was demonstrated by a mean significant reduction of coma -1.52 µm after 12 months in group A, -1.58 µm after 24 months in group B, -2.57 µm after 36 months for group C, and -0.25 µm after 36 months in group D. CONCLUSIONS: Outcomes stratified by age indicate the efficacy of corneal CXL in stabilizing the progression of ectatic disease in all age groups and improving the functional and morphologic parameters in select groups. Results indicated better functional and morphologic results in the population between 18 and 39 years of age. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy.

INTRODUCTION: Proliferative vitreoretinopathy (PVR) is a severe inflammatory complication of retinal detachment. Pathological epiretinal membranes grow on the retina surface leading to contraction, and surgery fails in 5% to 10% of the cases. We evaluated the expression of VEGF-A, Otx1, Otx2, Otx3, and p53 family members from PVR specimens to correlate their role in inducing or preventing the pathology. METHODS: Twelve retinal samples were taken from patients affected by PVR during therapeutic retinectomies in vitreoretinal surgery. Gene expression was evaluated using quantitative real-time reverse transcriptase PCR analysis and immunohistochemistry, using four healthy human retinae as control. RESULT: Controls showed basal expression of all genes. PVR samples showed little or no expression of Otx1 and variable expression of VEGF-A, Otx2, Otx3, p53, and p63 genes. Significant correlation was found among VEGF-A, Otx2, p53, and p63 and between Otx1 and Otx3. CONCLUSIONS: Otx homeobox, p53 family, and VEGF-A genes are expressed in PVR human retina. We individuated two possible pathways (VEGF-A, Otx2, p53, p63 and Otx1 and Otx3) involved in PVR progression that could influence in different manners the course of the pathology. Individuating the genetic pathways of PVR represents a novel approach to PVR therapies.

COVID-19 pandemic and ophthalmological emergencies: a case-control analysis of the impact of lockdowns in a University Hospital in Lombardy region, Italy.

PURPOSE: To evaluate the incidence of ocular pathologies seen at the ophthalmological emergency department (OED) during the national lockdown in 2020 due to the COVID-19 pandemic and compare it to the corresponding period in 2019. METHODS: Electronic records of patients who presented at the OED of our University Hospital in Varese, Italy during the COVID-19 lockdown were compared with that from the corresponding period in 2019. Records from the spring (2020A) and winter (2020B) lockdowns were compared with each other and with the same periods in 2019 (2019A and 2019B). Statistical analyses were performed by unpaired Student's t-tests, Poisson's regression and Chi-square test. RESULTS: The number of consultations at the OED significantly decreased during the COVID-19 lockdown (p value <.0001). The largest decreases were observed in the youngest (age <15 years: -77.3%) and oldest (age >61 years, -68.5%) age groups. The proportion of men who consulted increased significantly from 61.76% in 2019A to 67.63% in 2020A, and from 54.56% in 2019B to 62.79% in 2020B. A significant reduction in deferrable consultations was also reported (from 943 in 2019 to 335 in 2020; p value <.0001). A statistically significant decrease in the number of consultations involving ocular trauma was also reported despite an increase in its proportion among all consultations for ocular pathologies in 2020. CONCLUSIONS: Our evaluation showed a significant reduction in the number of OED consultations in all deferrable pathologies. Although the incidence of conditions that affect visual function was lower, these were more frequent in the lockdown period. The significant reduction in the number of deferrable consultations highlights the misuse of the OED.

Macular Holes: Main Clinical Presentations, Diagnosis, and Therapies.

Macular holes are a spectrum of retinal diseases that comprehends full-thickness macular holes (FTMHs), refractory/recurrent macular holes, lamellar macular holes (LMHs), myopic macular holes (MMHs), traumatic macular holes, and macular holes secondary to other retinal pathologies or injuries. There are various classifications of the subtypes of macular hole, and only in recent times researchers defined a common nomenclature, especially thanks to the evolution in retinal imaging, offered by new instruments like the swept-source OCT. The proposed therapies for macular holes are different and range from a "wait-and-see" approach to the vitrectomy, with different results in each subtype of macular hole. This narrative review has the purpose to investigate the available evidence in literature to give a summary of the knowledge about these retinal pathologies.

Glaucoma and Driving License: How to Identify Patients at Risk of Revocation.

Aim: To identify clinical criteria that are easily achievable with follow-up tests and can identify subjects not suitable for driving. Patients and methods: We recruited 194 subjects with a clear diagnosis of glaucoma, with no other conditions that could affect the visual field (VF), and who performed a reliable VF examination. All patients underwent a full ophthalmologic evaluation and a questionnaire considering driving habits. An integrated visual field (IVF) was built using both monocular VF charts; the number of missed points (NoMP) within the central 20°, the average sensitivity (AS), and the better eye mean deviation (BEMD) were evaluated. Results: A total of 128 subjects showed a valid driving license (DL); 61.7% of drivers did not show missed points within the central 20° of the IVF, 27.4% presented one to three missed points, and 10.9% had four or more missed points. Best corrected visual acuity (BCVA) was highly above the legal criteria.Stratifying drivers by their BEMD (-7, -10, and -14 dB), we confirmed that the BEMD decrease corresponds to an increased NoMP and a decreased AS. Conclusion: Better eye mean deviation can be useful in clinical practice to identify patients at increased risk of being unsuitable for driving. Nevertheless, it is important to set specific cut-offs based on on-road driving performance. IVF evaluation may also be implemented in perimeter analysis software so that the composition of IVF, the BEMD, and the AS could directly describe the patient's binocular VF, excluding recourse to the Esterman visual field test (EVFT). Clinical significance: This new methodology will allow every physician-not just ophthalmologists-even if not an expert in evaluating a VF test, in assessing the ability to drive of glaucomatous patients. How to cite this article: Landini L, Donati S, Digiuni M, et al. Glaucoma and Driving License: How to Identify Patients at Risk of Revocation. J Curr Glaucoma Pract 2022;16(2):117-123.

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study.

Purpose: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. Methods: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. Results: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of -0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles. Conclusions: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.

Myopic Simple Hemorrhage Presenting as Radial Hemorrhage in Henle's Fiber Layer.

This case report describes a simple hemorrhage (SH) presenting as radial hemorrhage in Henle's fiber layer (HFL) in a patient with high myopia. A 26-year-old girl with high myopia was referred to our center for sudden onset of decreased vision and a central scotoma in the right eye (OD). Best corrected visual acuity (BCVA) was 20/100 OD. Fundus examination showed a stellate intraretinal hemorrhage in the fovea of the OD. The hemorrhage was organized in a peculiar petaloid pattern with feathery distal edges, suggesting localization within the radially oriented HFL. The presence of both choroidal neovascularization and microvascular abnormalities consistent with macular telangiectasia type 2 (MacTel 2) were excluded. Based on these findings, a diagnosis of myopic SH was made. At 4-month follow-up BCVA OD spontaneously improved to 20/40, without any treatment been ever administered to the patient. Spectral-domain optical coherence tomography OD showed reabsorption of the hemorrhage and almost complete restoration of the foveal architecture. The intraretinal location and spread of the hemorrhage into the HFL in our patient are an unusual presentation of SH, which vividly highlights the anatomy of the fovea. Since fibers in HFL are quite delicate and loosely arranged, this layer is very susceptible to deposition of transudates, exudates, hemorrhage, and other products. Radial hemorrhage in HFL has been originally reported in 4 patients as complication of MacTel 2. It has been previously postulated that it may represent a characteristic finding in MacTel 2 that may develop as a result of microvascular abnormalities of the deep retinal capillary plexus. On the contrary, our data suggest that radial hemorrhage in the HFL does not represent a characteristic finding of MacTel 2, but must rather be considered a non-specific sign with multiple possible etiologies.

OCT Biomarkers in Neovascular Age-Related Macular Degeneration: A Narrative Review.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly people. Neovascular AMD (nAMD) is responsible for the majority of cases of severe visual loss in eyes with AMD. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow-up of nAMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response. The aim of this review is to describe and analyze various structural OCT-based biomarkers, which have practical value during both initial assessment and treatment follow-up of nAMD patients. While central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management. The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid) will be discussed firstly. In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analyzed in detail. The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub-RPE hyperreflective columns, prechoroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with nAMD progression. OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. This up-to-date review article provides a comprehensive description on how structural OCT-based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in nAMD patients. Thus, in this perspective, clinicians will be able to allocate hospital resources in the best possible way and tailor treatment to the individual patient's needs.

Optical coherence tomography angiography and arterial hypertension: A role in identifying subclinical microvascular damage?

INTRODUCTION: To evaluate retinal microvasculature modifications by means of optical coherence tomography angiography in human subjects diagnosed with arterial hypertension and to assess potential clinical relevance for early diagnosis. METHODS: A cross-sectional study of 30 subjects affected by arterial hypertension compared to a matched cohort of healthy patients was conducted. Patients were evaluated by the Outpatient Clinic for Hypertension and the Retina Center, University of Insubria, Varese, Italy. Patients were divided into three groups: Group 1-healthy subjects, Group 2-patients first diagnosed with hypertension, and Group 3-patients with treated hypertension. Optical coherence tomography angiography was performed applying different analysis protocols for macula and optic disk, using an AngioVue OCTA System on an Optovue device. Morphological data were compared to and correlated with clinical vascular parameters, to evaluate preclinical microvascular damage. RESULTS: A significant reduction in deep vascular layer density (Group 1: 59.2% ± 1.5% standard deviation; Group 2: 59.2% ± 2.2% standard deviation; Group 3: 57.8% ± 2.6% standard deviation; p < 0.05) as well as an enlargement of the deep foveal avascular zone area (Group 1: 0.34 ± 0.09 mm2; Group 2: 0.36 ± 0.07 mm2; Group 3: 0.39 ± 0.1 mm2; p < 0.05) was measured in patients with first diagnosed hypertension and in treated patients compared to healthy subjects. We also observed a significant decrease in mean foveal choroidal thickness in affected patients compared to controls (Group 1: 319.68 ± 61.72 µm standard deviation; Group 2: 251.04 ± 63.1 µm standard deviation; Group 3: 262.65 ± 51.08 µm standard deviation; p < 0.05). Our preliminary data did not show a significant correlation with microalbuminuria levels. DISCUSSION: Retinal vascular density showed pathological modifications between healthy subjects and hypertensive patients. These preliminary findings suggest that optical coherence tomography angiography may identify pathological markers of an early hypertensive damage and help monitor disease progression with potential therapeutic advantages.

Expression of Otx Genes in Müller Cells Using an In Vitro Experimental Model of Retinal Hypoxia.

INTRODUCTION: Müller glial cells typically activate to react to hypoxic tissue damage in several retinal diseases. We evaluated the in vitro response to a hypoxia-mimicking stimulus on the expression of a set of genes, known to contribute to eye morphogenesis and cell differentiation. MATERIALS AND METHODS: A MIO-M1 Müller cell line was cultured in a hypoxia-mimicking environment by the addition of cobalt chloride to the culture medium, followed by a recovery time in which we mimic restoration from the hypoxic insult. The HIF-1α protein and VEGF-A gene expression were quantified to verify the induction of a hypoxia-like state. RESULTS: Among the genes under study, we did not observe any difference in the expression levels of Otx1 and Otx2 during treatment; conversely, Otx1 was overexpressed during recovery steps. The VEGF-A gene was strongly upregulated at both the CoCl2 and recovery time points. The transactivated isoform (TA) of the TP73 gene showed an overexpression in long-term exposure to the hypoxic stimulus with a further increase after recovery. Discussion. Our molecular analysis is able to describe the activation of a set of genes, never before described, that can drive the response to a hypoxia-like status. The improved comprehension of these cellular events will be useful for designing new therapeutical approaches for retinal pathologies.

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy.

Importance: Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears. Objectives: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions. Design, Setting, and Participants: Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test. Exposure: SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs. Main Outcomes and Measures: Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data. Results: A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus. Conclusions and Relevance: In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

Novel treatment modalities for Graves' orbitopathy.

Non-surgical treatments for moderate to severe and active Graves' orbitopathy (systemic glucocorticoids with or without orbital radiotherapy) have limited effects on the underlying autoimmune process causing the disease. Although the clinical responses to treatment are often good, at least one third of patients with Graves' orbitopathy are eventually dissatisfied with the treatment outcome. Progress in our understanding of the autoimmune basis of Graves' orbitopathy (although still incomplete) made it possible, similar to other autoimmune disorders, to envision the use of novel immunomodulating drugs. Among the currently available biologic agents, the CD20+ B cell-depleting agent, rituximab, and tumor necrosis factor-alpha inhibitors are presently the drugs that have the best chance of being employed in the future for the treatment of Graves' orbitopathy. However, randomized, controlled clinical trials to support their use are warranted.

Lamellar Macular Holes: The Role of Microperimetry in Functional Assessment.

INTRODUCTION: The aim of our observational cross-sectional study was to evaluate the association between visual function and anatomical characteristics of LMH, considering in particular different subtypes of LMH and their features. MATERIALS AND METHODS: This observational clinical study has been conducted in the Ophthalmology Clinic, ASST-Sette Laghi, University of Insubria of Varese-Como, Italy. Included patients underwent a complete ophthalmological examination, as well as MP1 microperimetry evaluation and optical coherence tomography (OCT). Two experienced masked observers evaluated OCT imaging in order to assess the integrity of the photoreceptor layer (interdigitation zone and ellipsoid zone: IZ/EZ) and the external limiting membrane (ELM). RESULTS: Twenty-five patients affected by an LMH were evaluated. Eighteen eyes of 18 patients met the study criteria and were included. Based on morphological and functional data, LMHs were divided into two subgroups: tractional (tLMH) and degenerative (dLMH). We identified 11 tLMHs and seven dLMHs. Functional parameters showed a significative difference in visual acuity and retinal sensitivity between the two groups, respectively: (sample median and the interquartile range) 0.0 (0.0; 0.09) LogMAR vs 0.15 (0.09; 0.52) LogMAR and 16.2 (14.2; 17.7) dB vs 10.0 (7.5; 11.8) dB (p < 0.05). Fixation was predominantly central in 90.9% of tLMH vs 71.4% of dLMH and stable in 81.8% tLMH vs 42.9% dLMH, but the differences were not statistically significant. Tractional and degenerative LMHs showed no significant differences in central foveal thickness. Conversely, LMH depth and horizontal diameters appeared different between the two groups. Tractional LMH showed a greater depth 257 (205; 278) µm vs 190 (169; 249) µm, whereas degenerative LMH showed a greater horizontal diameter 653 (455; 750) µm vs 429 (314; 620) µm (p < 0.05). IZ/EZ line was unaffected in 81.8% of tLMHs eyes versus 14.3% of dLMHs eyes (p < 0.05). Visual acuity and retinal sensitivity were higher in eyes with integrity of both IZ/EZ and ELM compared to those with a disruption of one or both layers (p < 0.05). CONCLUSION: Two different subtypes of LMH showed peculiar functional aspects due to their morphological features. Tractional LMHs revealed higher visual acuity and retinal sensibility due to the relative preservation of the outer retinal layers compared to degenerative LMHs. Moreover, we underlined the importance of microperimetry to better identify functional defects in macular degenerative pathologies.

Endoscopic Transnasal Cryo-Assisted Removal of Orbital Cavernous Hemangiomas: Case Report and Technical Hints.

BACKGROUND: Cryoprobe devices are used by ophthalmic and orbital surgeons for extraction of fluid-filled intraorbital lesions. No series has described cryodissection via an exclusively transnasal approach. We describe 2 cases of purely endoscopic transnasal removal of intraconal orbital hemangiomas with the aid of a dedicated cryoprobe. METHODS: All transnasal endoscopic intraorbital procedures were collected and analyzed. In cases in which intraorbital dissection was performed with the use of an Optikon Cryo-line probe, clinical features, histology, size and location of the lesion, early and late complications, surgical procedure time, and hospital length of stay were analyzed. Patient follow-up included endoscopic endonasal evaluations performed at 2, 4, and 8 weeks after surgery and ophthalmologic and orthoptic evaluations performed 2 days and 2 months after surgery. RESULTS: Two transnasal intraorbital endoscopic procedures with the aid of the dedicated Cryo-line probe were collected. Lesions were located in the intraconal space, medial to the optic nerve. In both patients, the histologic evaluation was compatible with cavernous hemangioma, and complete resection was obtained. Mean hospital stay was 5.5 days. Postoperative ophthalmologic and orthoptic evaluations performed 2 months postoperatively revealed complete resolution of preoperative symptoms. CONCLUSIONS: Cryoprobes represent an adjunctive tool in the orbital surgeon's armamentarium useful in the extraction of fluid-filled intraorbital lesions. This preliminary experience suggests that their use can ease the removal of intraconal hemangiomas with an exclusively transnasal approach. The analysis of further cases is necessary to confirm safety and efficacy.