Postmortem Ultrastructural Analysis of the Retina from COVID-19 Deceased Patients.

PURPOSE: COVID-19 (coronavirus disease 2019) is an infectious disease caused by SARS-CoV-2, first reported in 2019 in Wuhan, China. Among the common complications is a pro-inflammatory and hypercoagulative response that compromises the vasculature among various organs. METHODS: In this report, we present the postmortem retinal findings of five patients observed by means of optical microscopy and transmission and scanning electron microscopy techniques. RESULTS: Clinical manifestations such as retinal hemorrhages and exacerbated inflammatory infiltrate, altered ultra structure with swollen mitochondria and pyknotic cells in both layers of the retina were observed in all analyzed eyes. CONCLUSION: Our data point to the fragility of this tissue in cases of severe COVID-19.

Presumed SARS-CoV-2 Viral Particles in the Human Retina of Patients With COVID-19.

Importance: The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunological changes. Objective: To demonstrate the presence of presumed SARS-CoV-2 viral particles and its relevant proteins in the eyes of patients with COVID-19. Design, Setting, and Participants: The retina from enucleated eyes of patients with confirmed COVID-19 infection were submitted to immunofluorescence and transmission electron microscopy processing at a hospital in São Paulo, Brazil, from June 23 to July 2, 2020. After obtaining written consent from the patients' families, enucleation was performed in patients deceased with confirmed SARS-CoV-2 infection. All patients were in the intensive care unit, received mechanical ventilation, and had severe pulmonary involvement by COVID-19. Main Outcomes and Measures: Presence of presumed SARS-CoV-2 viral particles by immunofluorescence and transmission electron microscopy processing. Results: Three patients who died of COVID-19 were analyzed. Two patients were men, and 1 was a woman. The age at death ranged from 69 to 78 years. Presumed S and N COVID-19 proteins were seen by immunofluorescence microscopy within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. At the perinuclear region of these cells, it was possible to observe by transmission electron microscopy double-membrane vacuoles that are consistent with the virus, presumably containing COVID-19 viral particles. Conclusions and Relevance: The present observations show presumed SARS-CoV-2 viral particles in various layers of the human retina, suggesting that they may be involved in some of the infection's ocular clinical manifestations.

Translaminar Pressure Difference and Ocular Perfusion Pressure in Glaucomatous Eyes with Different Optic Disc Sizes.

PURPOSE: Intracranial pressure (ICP) and ocular perfusion pressure (OPP) are both involved with the pathogenesis of glaucoma. The orbital ICP determines a retrolaminar counter pressure that is antagonistic to the intraocular pressure (IOP). The purpose of this study is to evaluate whether the translaminar pressure difference (TLPD) and the OPP varies in glaucoma patients with different optic disc sizes. METHODS: In this university hospital-based, observational, cross-sectional clinical study, all patients underwent an ophthalmic evaluation. Blood pressure, height, weight, and the results of retinal nerve fiber layer examination with optical coherence tomography examination were recorded. TLPD and OPP were calculated for each patient using proxy algorithms to attain indirect surrogate parameter values. Patients' eyes were stratified into three quantiles according to optic disc sizes and the differences compared. Data from both eyes were used after using the appropriate correction for inter-eye dependency. RESULTS: The sample consisted of 140 eyes of 73 patients with primary open-angle glaucoma and suspects. Patients with large disc size presented with higher TLPD as compared to those with average and small-sized discs (2.4 ± 4.5, 2.8 ± 3.8, and 3.7 ± 4.7 mmHg for first, second, and third tertile, respectively (P < 0.000). OPP did not vary according to the optic disc size. CONCLUSION: Glaucoma patients with larger optic discs have higher TLPD. The pathological significance of this finding warrants further investigation.

COVID-19 Retinal Findings in Patients Admitted to Intensive Care Units and Wards.

The main purpose of this study was to investigate ocular clinical findings in patients with confirmed COVID-19 infection, of various levels of disease severity, who required mechanical ventilation and admission to intensive care units or specialized wards. Longitudinal, observational study conducted from March 2020 to June 2020. Color fundus and red-free photography were performed in both eyes following pupillary dilation. 104 participants were recruited from 2 different centers: 60 (58%) from the Hospital Municipal de Barueri intensive care unit (ICU) and 44 (42%) from specialized wards for patients with COVID-19 at the Hospital São Paulo. 21.9% presented with eye lesions, in 3% these lesions were vision compromising. Our results have shown similar rate of intraocular lesions in patients in both the ward or intensive care unit, regardless of medication use, including anticoagulant drugs.

Correlation between ocular perfusion pressure and translaminar pressure difference in glaucoma: Evidence for a three-pressure disease?

AIM: To evaluate the correlation between the translaminar pressure difference (TLPD) and the ocular perfusion pressure (OPP) in glaucoma patients. METHODS: This was a cross-sectional study. Primary open-angle glaucoma (POAG) patients and normal individuals underwent an ophthalmic evaluation as well as blood pressure, height, and weight measurements. Intracranial pressure (ICP) and OPP were calculated using proxy mathematical formulas to attain indirect surrogate parameter values. The TLPD was calculated as intraocular pressure minus ICP. The association between the variables was evaluated using linear and non-linear regression analysis and the correlation estimated with Pearson's correlation coefficient. RESULTS: The sample included 50 POAG patients and 25 normal subjects. The mean OPP for all 75 subjects (75 eyes) was 53.1 ± 9.3 mmHg and the calculated TLPG was 3.1 ± 4.2 mmHg. TLPG showed a negative correlation with OPP (r = -0.580; 95% CI, -0.690 to -0.366; p < 0.0001). CONCLUSION: The negative correlation between OPP and TLPD observed in the study substantiates the concept of glaucoma as a three-pressure disease.

Reproducibility of laser in situ keratomileusis flap thickness using a new multifunctional femtosecond laser platform and correlation with clinical preoperative measurements.

PURPOSE: To analyze the reproducibility of laser in situ keratomileusis (LASIK) flap thickness (target 120 µm) using the multifunctional femtosecond laser (Lensx) and correlate postsurgical measurements with preoperative factors. SETTING: Hospital Oftalmológico Visão Laser, Santos, São Paulo, Brazil. DESIGN: Prospective case series. METHODS: Patients with stable refraction for over a year were evaluated. Patients who submitted to refractive surgery with -1.25 to -6.00 diopters (D), with or without astigmatism up to -4.00 D, and corneal curvature of 40.00 to 47.00 D were included. At 100 days postoperatively, an independent examiner performed 4 high-resolution tomographic sections of the cornea for each eye at 45- to 225-degree, 90- to 270-degree, 135- to 315-degree, and 0- to 180-degree meridians. Two masked experienced observers analyzed each section using measuring points located at the center of the cornea (0.0 mm), 2.0 mm to the left and to the right of the center, and 4.0 mm to the left and to the right of the center. RESULTS: The study comprised 33 patients (63 eyes), aged 21 to 50 years. A significant difference from the target flap thickness (120 µm) was found in 2 of 20 measurements; however, the actual difference was approximately 2.2 µm. Interrater reliability was excellent (ICC > 0.75), with an interrater bias close to 0. Clinical measurements were not predictive of the set of 20 postoperative measurements. CONCLUSION: Reproducibility of the multifunctional femtosecond laser was good for LASIK flap creation and no predictive correlation was found with preoperative clinical factors.

Validation of an Equation Model to Predict Intracranial Pressure in Clinical Studies.

Objective: There has been an interest regarding the possible role intracranial pressure (ICP) plays in the pathogenesis of the glaucoma optic neuropathy. A major impediment to the understanding of the possible role of ICP on glaucoma is the reliance on alternative noninvasive methods to measure the ICP. A formula was developed to estimate the ICP for the Chinese population. This was cross-sectional, observational study aimed to compare the predicted ICP with the real ICP measured with an aneroid manometer through lumbar puncture in a cohort of 39 subjects. Main points of discussion: The Bland-Altman plot of the differences between the two techniques against their averages revealed that most data points were sited between the two limits of agreement. Conclusion: The results of this study favor the use of the equation as a proxy method to predict ICP and it could be used in clinical studies.