Search

An 89-year-old man with multiple episodes of inferior corneal oedema and low-grade anterior segment inflammation over 18 months was diagnosed and managed as viral keratitis; however, the episodes kept recurring every time treatment, vis-à-vis topical steroids, were tapered or stopped. History of cataract surgery few months prior to onset of the symptoms, lack of other features of viral keratitis, such as keratic precipitates and inferior corneal oedema in the presence of slight pupillary peaking led to the suspicion of either a retained lens fragment (RLF) or other possible iatrogenic insult. This was confirmed by anterior segment optical coherence tomogram, which revealed the RLF in inferior angle; this was removed surgically as an emergency procedure. This resulted in significant improvement in the corneal oedema, as well as marked symptomatic relief confirmed by the patient.

A transocular infection has been proved as one of the main approaches that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the body, and angiotensin-converting enzyme 2 (ACE2) plays a key role in this procedure. Dynamic and quantitative details on virus distribution are lacking for virus prevention and drug design. In this study, a radiotraceable pseudovirus packed with an enhanced green fluorescent protein (EGFP) gene

Cytomegalovirus (CMV) can cause recalcitrant recurrent keratouveitis and secondary glaucoma. We report a case of chronic recurrent anterior uveitis with secondary glaucoma presenting with acute visual loss and interface fluid 9 years after laser in situ keratomileusis. Based on clinical presentation, a viral aetiology was suspected. Aqueous tap was positive for CMV-DNA by real-time quantitative PCR of the aqueous humour. The patient was treated with systemic antivirals, topical corticosteroids and antiglaucoma medications. The interface fluid resorbed rapidly. The intraocular pressure (IOP) was controlled by trabeculectomy. There was no further corneal deterioration at 7-month follow-up and the IOP had also stabilised. We believe this is only the third reported case of CMV-related interface fluid syndrome. This case highlights the role of quantitative PCR analysis for establishing viral aetiology in recurrent unilateral hypertensive anterior uveitis and reports the unusual finding of interface fluid which resolved after starting systemic antiviral therapy.

A 27-year-old immunocompetent woman presented to our clinic with redness, mild pain and blurring of vision in her left eye (LE) for 3 weeks with no preceding history of injury or contact lens wear. At presentation, her visual acuity was 20/20 and 20/60 in the right eye and LE, respectively. Slit

Aims / background Rubella virus-associated uveitis (RVAU) classically presents with the clinical features of Fuchs uveitis syndrome (FUS). We report a series RVAU, and discuss the relevance of available diagnostic strategies, and how vaccination could potentially prevent disease. Methods We retrospectively included patients with RV-positive aqueous humor (AH) with RT-PCR and/or intraocular RV-IgG production, between January 2014 and December 2019. RV-IgG titers from AH and serum were compared with other virus-specific IgG titers (VZV and/or CMV and/or HSV-1), to determine the derived Goldmann-Witmer coefficient (GWC’). Clinical findings at presentation and during follow-up are reported, as well as the anti-RV vaccination status. Results All 13 included patients demonstrated intraocular synthesis of RV-IgG (median GWC’: 9.5; 3.2–100). RV-RNA was detected in one patient while PCR results were negative for other HSV1, VZV and CMV. The mean delay in diagnosis was 13 ± 12.6 years, with an initial presentation of FUS in only 3 patients (23%). Only four patients had been vaccinated, but all after the recommended age. Conclusion As RVAU is a pleiomorphic entity, virological analysis (RV RT-PCR and GWC’) of aqueous humor is essential to improve the diagnosis and management of this entity. Improper vaccination against RV appears to be implicated in RVAU.

Since the initial outbreak of coronavirus disease 2019 (COVID-19), extensive research has emerged from across the globe to understand the pathophysiology of this novel coronavirus. Transmission of this virus is a subject of particular interest as researchers work to understand which protective and preventative measures are most effective. Despite the well understood model of aerosol-respiratory mediated transmission, the exact mechanism underlying the inoculation, infection and spread of COVID-19 is currently unknown. Given anatomical positioning and near constant exposure to aerosolized pathogens, the eye may be a possible gateway for COVID-19 infection. This critical review explores the possibility of an ocular-systemic or ocular-nasal-pulmonic pathway of COVID-19 infection and includes novel insights into the possible immunological mechanisms leading to cytokine surge.

This study attempts to review whether the coronavirus disease-2019 (COVID-19) is transmitted through the ocular surface and examine the symptoms and signs of ocular disease. Considering that COVID-19 is transmitted by airborne droplets and close contact with infected individuals, we will also review the conditions to which eye clinics and ophthalmologists should pay attention to prevent the transmission of the disease. Although some researchers have argued that COVID-19 transmission cannot occur through the ocular surface, most of them are of the opinion that the ocular surface is a potential pathway of transmission. Until date, ocular signs and symptoms have been rarely reported in the COVID-19 patients. However, there are case reports of conjunctivitis as the first, and rarely, the only clinical symptom of the disease. In addition, low coronavirus RNA positivity can be detected in the ocular surface samples. Further laboratory and clinical investigations are needed to ascertain whether the ocular surface is one of the potential transmission pathways through which severe acute respiratory syndrome-coronavirus 2 can gain entry into the human body.

Purpose To determine classification criteria for varicella zoster virus (VZV) anterior uveitis DESIGN: Machine learning of cases with VZV anterior uveitis and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 123 cases of VZV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for VZV anterior uveitis included unilateral anterior uveitis with either 1) positive aqueous humor polymerase chain reaction assay for VZV; 2) sectoral iris atrophy in a patient ≥60 years of age; or 3) concurrent or recent dermatomal herpes zoster. The misclassification rates for VZV anterior uveitis were 0.9% in the training set and 0% in the validation set, respectively. Conclusions The criteria for VZV anterior uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

PURPOSE: To determine classification criteria for cytomegalovirus (CMV) retinitis. DESIGN: Machine learning of cases with CMV retinitis and 4 other infectious posterior/panuveitides. METHODS: Cases of infectious posterior/panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. RESULTS: Eight hundred three cases of infectious posterior/panuveitides, including 211 cases of CMV retinitis, were evaluated by machine learning. Key criteria for CMV retinitis included: 1) necrotizing retinitis with indistinct borders due to numerous small satellites; 2) evidence of immune compromise; and either 3) a characteristic clinical appearance or 4) positive polymerase chain assay for CMV from an intraocular specimen. Characteristic appearances for CMV retinitis included: 1) wedge-shaped area of retinitis; 2) hemorrhagic retinitis; or 3) granular retinitis. Overall accuracy for infectious posterior/panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for CMV retinitis were 6.9% in the training set and 6.3% in the validation set. CONCLUSIONS: The criteria for CMV retinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

In this cross-sectional study, we investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 Ribonucleic Acid (SARS-CoV-2 RNA) in the tears of hospitalized COVID-19 patients. After laboratory confirmation of SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) analysis, tear samples from both eyes of each patient were collected using conjunctival swab for RT-PCR. Detailed demographic profile, systemic and ocular symptoms, comorbidities, clinical, ancillary, and ocular manifestations were evaluated. Of the 83 patients enrolled in the study, 7 (8.43%) had SARS-CoV-2 RNA detected in the tear samples. Neutrophils’ count, C-reactive protein, and D-dimer were higher in patients with SARS-CoV-2 detected in tears than in patients without virus in ocular surface samples. One patient with SARS-CoV-2 in tears showed mild ocular eyelid edema, hyperemia, and chemosis. No relevant ocular manifestations were detected in the other patients. Although the levels of viral RNA on ocular surface samples were low for most patients (5/7), with positivity only for gene N and CT higher than 30, two patients were positive for all viral targets tested ( N, E, and RpRd), with viral load near 1 × 105 ePFU/mL, indicating that the ocular transmission of SARS-CoV-2 is a possibility that needs to be considered, especially in the hospital environment. Further studies need to be conducted to demonstrate whether infective viral particles could be isolated from tears.

Background and Objectives: A cross-sectional single-center study was conducted to investigate the etiology in hypertensive anterior uveitis whose clinical features are not fully distinctive from cytomegalovirus or from rubella virus and to demonstrate the possible coexistence of both these viruses in causing anterior uveitis. Materials and Methods: The clinical charts of a cohort of patients with hypertensive viral anterior uveitis of uncertain origin consecutively seen in a single center from 2019 to 2022 were retrospectively reviewed; data on the clinical features, aqueous polymerase chain reaction, and antibody response to cytomegalovirus and rubella virus were collected. Results: Forty-three eyes of as many subjects with viral anterior uveitis of uncertain origin were included. Thirty-two patients had an aqueous polymerase chain reaction or antibody index positive to cytomegalovirus only, while 11 cases had an aqueous antibody response to both cytomegalovirus and rubella virus. This latter overlapping group had a statistically significant higher rate of hypochromia and anterior vitritis (p-value: 0.02 and < 0.001, respectively). Conclusions: The simultaneous presence of intraocular antibodies against cytomegalovirus and rubella virus could redefine the differential diagnosis of hypertensive viral anterior uveitis, demonstrating a possible “converged” immune pathway consisting in a variety of stimuli.

The aim of this study was to evaluate the relationship between clinical findings and viral load in adenoviral keratoconjunctivitis (Ad-Kc). In this cross-sectional study, 30 eyes of 30 patients with Ad-Kc were assessed. Real-time polymerase chain reaction was performed to detect and quantify adenovirus in all samples. Patients were divided into three subgroups according to baseline viral load (10

OBJECTIVES: To observe the changes of viral load in aqueous humour samples and visual outcomes in varicella zoster virus (VZV)-induced acute retinal necrosis (ARN). METHODS: Observational retrospective study. Medical records and viral load measured by real-time quantitative polymerase chain reaction (qPCR) of 20 eyes with VZV-induced ARN were reviewed. RESULTS: The mean viral load at presentation was 5.7 × 10(7) ± 9.7 × 10(7) copies/mL. An initial plateau phase for viral load lasting up to 2 weeks occurred in most eyes (18 eyes, 90%). In the following logarithmic reduction phase, the mean slope of the decline in viral load was −0.103 ± 0.029 log/day, and the expected time for half reduction of the initial viral load was 3.2 ± 1.0 days. At the end of the first 8-week’s antiviral treatment, the viral load was below detection threshold in all 20 eyes (100.0%). The mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 1.1 ± 0.7 (Snellen equivalent 20/250) to 0.7 ± 0.6 (Snellen equivalent 20/100) after a follow-up of 8.6 ± 2.0 months. Thirteen of the 20 eyes (65.0%) suffered retinal detachment and underwent vitrectomy. The initial viral load was the independent predictive factor of logMAR BCVA at the last follow-up (β = 0.745, P

Significance The effectiveness of masking is rarely evaluated or reported in single- or double-masked clinical trials. Knowledge of treatment assignment by participants and clinicians can bias the assessment of treatment efficacy. Purpose This study aimed to evaluate the effectiveness of masking in a double-masked trial of 5% povidone-iodine for the treatment of adenoviral conjunctivitis. Methods The Reducing Adenoviral Patient Infected Days study is a double-masked, randomized trial comparing a one-time, in-office administration of 5% povidone-iodine with artificial tears for the treatment of adenoviral conjunctivitis. Masking was assessed by asking participants and masked clinicians at designated time points if they believed the treatment administered was povidone-iodine or artificial tears, or if they were unsure. Adequacy of masking was quantified using a modified Bang Blinding Index. Results Immediately after treatment, 34% of participants who received povidone-iodine and 69% of those who received artificial tears guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.31 and -0.38, respectively). On day 4, 38% of the povidone-iodine participants and 52% of the artificial tear participants guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.24 and -0.05, respectively), indicating adequate and ideal masking. On days 1, 4, 7, 14, and 21, masked clinicians guessed incorrectly or were unsure of treatment in 53%, 50%, 40%, 39%, and 42% among povidone-iodine participants compared with 44%, 35%, 38%, 35%, and 39% among artificial tears participants, respectively. The modified Bang Indices for clinician masking in the povidone-iodine group ranged from -0.05 to 0.25 and from 0.13 to 0.29 in the artificial tears group. Conclusions Masking of participants and clinicians was adequate. Successful masking increases confidence that subjective measurements are not biased. We recommend quantitative assessment and reporting the effectiveness of masking in ophthalmic clinical trials.

Purpose: To evaluate the results of conjunctival and nasopharyngeal swab tests in patients with confirmed COVID-19. Methods: This prospective study included 45 patients who were hospitalized for confirmed COVID-19. Nasopharyngeal swab samples were obtained from the patients before hospitalization. Only one eye of each patient was randomly selected for-conjunctival sampling. All participants underwent a complete slit- lamp examination. Conjunctival and nasopharyngeal swab samples were analyzed by reversetranscriptase-polymerase-chain reaction (RT-PCR). Results: Twenty seven (60%) of the patients were male and 18 (40%) were female. Conjunctival swab was positive in only one (2.22%) patient. None of the COVID-19 patients showed ocular changes and symptoms. There were no abnormalities of the ocular surface, anterior chamber or posterior segment at slit-lamp examination. Conclusions: The RT-PCR was not high positive in the conjunctiva as in nasopharyngeal swabs. Ocular changes were not common in COVID-19 patients.

Purpose Determine the efficacy of combination intravitreal and systemic antiviral therapy for the treatment of acute retinal necrosis (ARN) and risk factors impacting visual acuity (VA) and retinal detachment (RD) outcomes. Design Single-center retrospective case series. Participants Patients with an ARN diagnosis based on clinical features and polymerase chain reaction confirmation who were treated at a tertiary referral, university-based academic practice. Methods Patient records were reviewed for demographic information including age and gender. Snellen VA, disease findings including RD outcomes, optic nerve involvement, and treatments were recorded. Incidence rates of major VA and RD outcomes were calculated based on the number of events and exposure times. Cox proportional hazards regression modeling and survival analyses were used to identify factors related to VA and RD outcomes over time. Main Outcome Measures Logarithm of the minimal angle of resolution VA, 2-line or more VA gain, severe vision loss (SVL) of 20/200 or worse, RD development, and fellow eye involvement. Results Twenty-three eyes of 21 patients (11 male, 10 female) were reviewed. Thirteen patients (62%) had herpes simplex virus and 8 patients (38%) had varicella zoster virus. The event rate for 2-line or more VA gain was 0.49 events/eye-year (95% confidence interval [CI], 0.26–0.86 events/eye-year), whereas the rate of SVL was 0.61 events/eye-year (95% CI, 0.34–1.02 events/eye-year). Retinal detachment development was observed at a rate of 0.59 events/eye-year (95% CI, 0.33–1.00 events/eye-year). Thirteen of 23 eyes (57%) demonstrated RD with a mean time of 120 days after ARN diagnosis. With each additional quadrant of retina involved, a greater risk of RD development over time was observed (hazard ratio, 2.21; 95% CI, 1.12–4.35). Nine percent of eyes progressed with additional quadrantic involvement, despite combination systemic and intravitreal antiviral therapy; however, none of the 19 patients demonstrating unilateral ARN showed fellow-eye involvement after initiation of therapy. Conclusions Combination intravitreal and systemic antiviral therapy for ARN can be effective in improving VA and limiting retinitis progression. Each additional quadrant of retina involved was associated with a 2.2-fold greater risk of RD, which may impact monitoring, timing of intervention, and patient counseling.

Purpose To characterize corneal subbasal nerve plexus features of normal and simian immunodeficiency virus (SIV)-infected macaques by combining in vivo corneal confocal microscopy (IVCM) with automated assessments using deep learning-based methods customized for macaques. Methods IVCM images were collected from both male and female age-matched rhesus and pigtailed macaques housed at the Johns Hopkins University breeding colony using the Heidelberg HRTIII with Rostock Corneal Module. We also obtained repeat IVCM images of 12 SIV-infected animals including preinfection and 10-day post-SIV infection time points. All IVCM images were analyzed using a deep convolutional neural network architecture developed specifically for macaque studies. Results Deep learning-based segmentation of subbasal nerves in IVCM images from macaques demonstrated that corneal nerve fiber length and fractal dimension measurements did not differ between species, but pigtailed macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques (P = 0.005). Neither sex nor age of macaques was associated with differences in any of the assessed corneal subbasal nerve parameters. In the SIV/macaque model of human immunodeficiency virus, acute SIV infection induced significant decreases in both corneal nerve fiber length and fractal dimension (P = 0.01 and P = 0.008, respectively). Conclusions The combination of IVCM and robust objective deep learning analysis is a powerful tool to track sensory nerve damage, enabling early detection of neuropathy. Adapting deep learning analyses to clinical corneal nerve assessments will improve monitoring of small sensory nerve fiber damage in numerous clinical settings including human immunodeficiency virus.

Aim The current world has changed in all shapes since the emergence of the novel coronavirus (nCoV-2) also known as COVID-19. Among the extra-pulmonary manifestations of nCoV-2, ophthalmic symptoms have less been systematically studied. The so far existing body of evidence indicates that nCoV-2 has the potential to affect both anterior and posterior chambers of the eye. Albeit, the exact mechanisms which underlie ophthalmic manifestations of nCoV-2 are yet to be elucidated. Methods The present brief review is an attempt to put together and highlight the significant yet limited number of studies which have spotlighted ophthalmic issues in nCoV-2 patients using a systematic literature search strategy. Results All case series or reports (including both published and preprint articles) which described ocular manifestations of patients with COVID-19 and/or documented testing of SARS-COV-2 in ocular secretions via various sampling or detection methods were sought to be included. Conclusion The ophthalmic presentations in SARS-COV-2 are often found to be salient. Raising awareness in this respect may help defining evidencebased protective measures in today’s practice of ophthalmology and allied disciplines.

The aim of this study is to evaluate the usefulness of specular microscopy as an alternative diagnostic tool for cytomegalovirus (CMV) corneal endotheliitis.A retrospective study.One hundred and four patients with clinical manifestations of infectious corneal endotheliitis, iridocyclitis, and retinitis were included in this study. The presence of CMV deoxyribonucleic acid (DNA) was confirmed by multiplex polymerase chain reaction (PCR). Viral load was measured using real-time PCR. Corneal endothelium was observed by specular microscopy. The medical records and clinical manifestations of the patients were retrospectively reviewed and linked with the PCR results.Seventeen of 104 cases were CMV endotheliitis and/or iridocyclitis and had no history of intraocular surgery or corneal transplantation. There was a negative correlation between viral load and corneal endothelial cell counts. In 14 of 17 cases, owl's eye cells were observed by specular microscopy. The corneal endothelial cell counts were significantly reduced in the cases in which owl's eye cells were observed.In CMV endotheliitis, owl's eye cells were observed by specular microscopy with high probability (82%). Corneal endothelial cells significantly decreased when owl's eye cells were observed by specular microscopy. Specular microscopy represents a useful noninvasive auxiliary tool for diagnosing and monitoring CMV corneal endotheliitis.

Neovascular complications from cytomegalovirus necrotizing retinopathy developed in 5.1%/cases and 3.4%/eyes in patients after haploidentical stem cell transplantation. Immune-mediated cytomegalovirus vasculitis could be an isolated manifestation in patients with a minimal immune deviation, which could only be found on fluorescein angiography and warrants the needs for long-term follow-up., Purpose: To report the incidence and clinical features of neovascular complications from cytomegalovirus (CMV) necrotizing retinopathy in patients after haploidentical hematopoietic stem cell transplantation. Methods: Thirty-nine patients (58 eyes) of CMV necrotizing retinopathy after haploidentical hematopoietic stem cell transplantation in our institute between January 2018 and June 2020 were retrospectively reviewed, and cases that developed neovascular complications during follow-up were identified and described. Results: Two (2 eyes) cases that developed neovascular glaucoma from CMV necrotizing retinopathy were identified. Both of them manifested as granular peripheral retinitis, panretinal occlusive vasculitis, and some degree of intraocular inflammation, which were consistent with chronic retinal necrosis. Insidious progression of isolated immune-mediated occlusive vasculitis that could only be observed on fundus fluorescein angiography without active retinitis or intraocular inflammation was recognized to be the cause in one of two cases. Conclusion: Neovascular glaucoma developed in 5.1%/cases and 3.4%/eyes complicated by CMV chronic retinal necrosis and vasculitis in patients after haploidentical hematopoietic stem cell transplantation, which warrants the needs for long-term follow-up. Immune-mediated CMV vasculitis could be an isolated manifestation in patients with a minimal immune deviation and may only be found on fundus fluorescein angiography, which emphasizes the importance of fundus fluorescein angiography on a regular basis during follow-up.

Aims: Cases of infectious uveitis in immunodeficient patients may present with atypical clinical features because the clinical course of disease is usually affected by the compromised immune system. Therefore, it is sometimes difficult to determine the correct diagnosis. The aim of this study was to evaluate a prevalence of immunodeficient HIV-negative individuals among patients with infectious uveitis and to assess diagnostic and therapeutic approaches. Methods: A retrospective study. Results: In years 2003-2017, we diagnosed 594 patients with infectious uveitis. In 35 of them, infectious uveitis occurred on the basis of immunodeficiency (malignancy, immunosuppressive therapy etc.). The most common infectious uveitis was cytomegalovirus retinitis, followed by acute retinal necrosis, herpetic anterior uveitis, endogenous fungal endophthalmitis, toxoplasmic retinochoroiditis, progressive outer retinal necrosis and syphilis. In indicated cases, intraocular fluid examination was a valuable diagnostic tool. After initiation of treatment, improvement of BCVA was observed in 13 eyes, stabilization in 13 eyes and deterioration in 11 eyes. In some patients who experienced adverse effects of medication, the recommended doses were decreased. Conclusion: Our experience shows that patients with diagnoses of acute retinal necrosis or progressive outer retinal necrosis have a poor visual prognosis. The occurrence of cytomegalovirus retinitis signifies a very unfavorable survival prognosis in patients who underwent hematopoietic stem cell transplantation; the patients in our study died within 1 year from cytomegalovirus retinitis diagnosis.

Cytomegalovirus (CMV)-related corneal endotheliitis is an inflammation of the corneal endothelium caused by CMV. It may occur de novo or after ocular surgery in otherwise healthy individuals. In patients who have undergone keratoplasty, the differential diagnosis of viral endotheliitis and immune-related graft rejection is challenging due to the similar clinical findings. Here we report a patient who underwent penetrating keratoplasty and was using local and systemic immunosuppressive agents due to previous history of graft rejection. At postoperative year 4, ophthalmologic examination revealed localized corneal edema, coin-shaped keratic precipitates, and increased intraocular pressure, consistent with viral endotheliitis. Polymerase chain reaction revealed CMV-DNA amplification in the aqueous humor sample. Valganciclovir treatment was started and the symptoms improved in 2 months. It should be kept in mind that local or systemic immunosuppressants used after keratoplasty may trigger CMV reactivation. Anti-CMV treatment should be initiated immediately in patients with coin-shaped keratic precipitates.

Background: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 10 (SARS-CoV-2). Recent studies demonstrated not only retinal impairments but also detected SARS-CoV-2 in the retina of patients with COVID-19. Purpose: This letter discusses the retinal tropism of SARS-CoV-2, describing possible routes for this coronavirus to reach the retina and cellular mechanisms involved in the retinal cell infection. Conclusions: Determining how SARS-CoV-2 can affect the retinal tissue is essential for the development of new therapeutic strategies and preventive measures, as well as for understanding the possible relationship between COVID-19 damage to the retina and to the brain.

The recently identified novel coronavirus (CoV), the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes the coronavirus disease 2019 (COVID-19). While published data about other highly infectious human COVs [that is, the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV)] provide helpful information about the infectivity of SARS-CoV-2, there is limited understanding surrounding knowledge of ocular manifestation of the virus. This paper reviews published data which reveal the presence of SARS-CoV-2 RNA in tears and conjunctival scrappings of some COVID-19 patients by real-time-polymerase chain reaction assay, although the detection rate is low compared to samples from respiratory sites. Nevertheless, the ocular complications from SARS-CoV-2 infection are uncommon. The evidence partly supports the eye as a portal of entry for SARS-CoV-2 to infect respiratory cells or viral shedding from respiratory cells via the nasolacrimal duct unto the ocular surface. The possibility of ocular secretions as source for SARS-CoV-2 to spread externally has substantial public health implications.

Since December 2019, the novel COVID-19 outbreak has spread rapidly around the globe and infected millions of people. Although the major transmission route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to be airborne droplets and close contact, the ocular transmission route has been reported with great concern. The current work summarises the characteristics of SARS-CoV-2, the ocular distribution of the major SARS-CoV-2 binding protein, and the experimental and clinical evidence of the ocular transmission route. Although it seems that the likelihood of the ocular surface being an infection gateway is low, SARS-CoV-2 infection or transmission via the ocular surface may cause conjunctivitis and other ocular discomfort. Therefore, good eye protection is an essential safeguard procedure, especially for medical staff.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus causing an ongoing pandemic in 2020. Although the symptomatic patients infected by SARS-CoV-2 generally show respiratory distress, atypical manifestations such as conjunctivitis are also observed. A series of cases are reported in which reverse transcriptase polymerase chain reaction (RT-PCR) testing on tears had demonstrated the presence of the virus. However, the transmission of the virus through ocular fluids remains unknown. Case description: In this case report, the development of conjunctivitis is presented as the sole symptom of a new coronavirus disease 2019 (COVID-19) in an emergency health care worker. The patient’s first application was to the ophthalmology clinic due to redness, stinging, tearing, and photophobia for one day in the right eye. The patient had no symptoms of fever, cough, shortness of breath, or fatigue. Two days later, the RT-PCR test, blood analysis, and chest computed tomography (CT) were applied to the patient for being in contact with a COVID positive patient. Conjunctival swabs did not identify SARS-CoV-2 by RT-PCR. However, nasopharyngeal swab and blood test confirmed the diagnosis of COVID-19. Chest CT did not show pneumonia. Conclusion: This phenomenon shows that conjunctivitis may occur as a sole manifestation of COVID-19 which needs to be carefully evaluated by health care workers and eye care professionals during the pandemic.

Herpes simplex keratitis, caused primarily by human herpes simplex virus type 1 (HSV-1), remains the most common infectious cause of unilateral blindness and vision impairment in the industrialized world. Major advances in the care of HSV keratitis have been driven in large part by the landmark Herpetic Eye Disease Study randomized clinical trials, which were among the first in ophthalmology to reflect emerging trial conventions, including multicenter subject enrollment, double-masking, placebo controls, and a priori sample size determinations. The results of these trials now form much of the evidence basis for the management of this disease. However, management patterns in clinical practice often deviate from evidence-based care. These perceived quality gaps have given rise to the evolving field of implementation science, which is concerned with the methods of promoting the application of evidence-based medicine within routine care. To overcome variations in the quality and consistency of care for HSV keratitis, a range of clinical- and technology-based innovations are proposed. The most pressing needs include the following: a rational and tractable disease classification scheme that provides an immediate link between the anatomical localization of disease (corneal epithelial, stromal, or endothelial) and the appropriate treatment, and the actualization of an electronic medical record system capable of providing evidence-based treatment algorithms at relevant points of care. The latter would also input data to population-wide disease registries to identify implementation-rich targets for quality improvement, education, and research. These innovations may allow us to reduce the human and economic burdens of this highly morbid, and often blinding, disease.

To investigate the possibility of ocular involvement in the 2019-novel coronavirus infectious (2019-nCoV) and vital preventive measures in the field of ophthalmology.All the studies that were most relevant to the 2019-nCoV ocular involvement and routes of transmission, especially in the field of ophthalmology, thoroughly reviewed.From the ocular perspective, conjunctivitis may be the first presenting symptom of 2019-nCoV, so, we as ophthalmologists are at the forefront of exposure with newly infected patients. Although transconjunctival aerosol is a suspected but, the main route of transmission is the known respiratory droplets which will be more significant due to close contact in the field of ophthalmology. This review advise a set of recommendation for preventive care to minimize cross-infection of 2019-nCoV.Ophthalmologists have an essential role in guiding cross-infection control measures between patients and staff. Until a vaccine is created, public health strategies are likely the best weapons against this invisible enemy.

Purpose: To present a patient with bilateral conjunctivitis, testing positive for viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both nasopharyngeal and conjunctival samples. Methods: A 40-year-old man with bilateral acute conjunctivitis and suspicious signs of coronavirus disease 2019 (COVID-19) presented to the hospital. A detailed ophthalmic examination was performed. Samples obtained from conjunctival and nasopharyngeal swabs were tested by reverse transcription PCR (RT-PCR) for the detection of SARS-CoV-2 virus. Ocular findings and duration of the presence of viral RNA in the conjunctival specimens were evaluated at follow-up visits. Results: Slit-lamp biomicroscopy revealed bilateral acute follicular conjunctivitis. The RT-PCR assay demonstrated the presence of viral RNA in the nasopharyngeal and conjunctival specimens at the initial visit and at the 4-day follow-up. Conjunctivitis findings were decreased after 4 days and recovered completely without any sequelae within10 days. The PCR results of both nasopharyngeal and conjunctiva specimens were negative for the viral RNA at 10 days. Conclusions: Bilateral conjunctivitis is rare in patients infected with COVID-19. Although it is difficult to detect viral RNA from conjunctival swabs, conjunctival secretions may be a source of contamination, and protective measures must be taken.

The study objective was to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in conjunctival swabs from patients with confirmed SARS-CoV-2 infection.Forty patients who tested positive by real-time reverse transcription (rRT)-polymerase chain reaction (PCR) of nasopharyngeal and oropharyngeal swabs were enrolled. Conjunctival swabbing was used to collect the tear and conjunctival secretions of patients.Conjunctival swab rRT-PCR was positive for three patients and negative for 37 patients. Ten of the patients (25%) were diagnosed with conjunctivitis during the ophthalmic examination. Of these patients, one was found positive by conjunctival swab rRT-PCR, and nine were found negative. The difference between patients who tested positive or negative using conjunctival swab rRT-PCR was without statistical significance in terms of the presence of conjunctivitis (The rate of positivity from conjunctival swab rRT-PCR was 7.5% in patients with confirmed SARS-CoV-2 infection.

To evaluate ocular findings in patients with Coronavirus Disease 2019 (COVID-19) in the Northeast of Iran.In a cross-sectional, observational study all consecutive patients with confirmed COVID-19 diagnosis at the central referral center of these patients in northeast of Iran were included. Ocular examinations (external and slit) were randomly performed for the patients who were admitted to the Intensive Care Unit (ICU) and six COVID wards of the hospital. Moreover, Chart records and serum chemistry results were collected.A total of 142 patients with the mean age of 62.6 ± 15 years (range: 23-96 years) and almost equal gender distribution (male: N = 77, 54.2%) were included in the study. During the initial external examination by the ophthalmologist, 44 (31%) patients were found to have conjunctival hyperemia and 22 (15.5%) patients had chemosis. Consecutive slit examination showed 41 (28.9%) conjunctival hyperemia, 22 (15.5%) chemosis, 11 (7.7%) cataract, and 9 (6.3%) diabetic retinopathy. The patients with at least one ocular manifestation had significantly higher blood urea levels at the time of admission compared to those with no obvious ocular involvement (median: 41.5, IQR: 28-66.3 vs. median: 33, IQR: 23.8-51.8,Ocular manifestation was observed in more than half of our COVID-19 patients. Hence, it seems important to involve ophthalmologist in the diagnosis and management of these patients.

Purpose Coronavirus disease 2019 (COVID-19) is an ongoing global public health problem, and most of the COVID-19 research is focused mainly on the respiratory system because of life-threatening results. However, manifestations in other organs should not be ignored since they can also be a mode of transmission. We sought to describe the ocular manifestations of COVID-19 and investigate the association between ocular involvement and clinical presentation and laboratory outcomes. Methods This cross-sectional study was conducted between March 1, 2020, and April 30, 2020. Ninety-three sequentially hospitalized and clinically confirmed COVID-19 patients were included in the study. The systemic and ocular symptoms, clinical findings, and laboratory outcomes were recorded. Results Of the 93 COVID-19 patients, 54 (58.1%) were male, and 39 (41.9%) were female. Mean age of the patients was 39.4 ± 21.9 (min 7, max 88) years. Twenty patients (n 21.5%) had at least one ocular abnormality. Most common findings included hyperemia (n = 20), epiphora (n = 9), increased secretion (n = 6), chemosis (n = 3), follicular conjunctivitis (n = 2), and episcleritis (n = 2). The most common symptom was photophobia (n 15). Patients with ocular involvement were more likely to have higher neutrophil counts (p = 0.001), and increased CRP (p < 0.001), PCT (p = 0.001), and ESR levels (p < 0.001). Mean lymphocyte count was statistically lower in patients with ocular manifestations (p = 0.001). Mean age and number of patients with fever over 37.3 °C in the ocular involvement group was found to be higher (p < 0.001, p = 0.006, respectively). Conclusion Older age, high fever, increased neutrophil/lymphocyte ratio, and high levels of acute phase reactants seemed to be risk factors for ocular involvement.

The COVID-19 pandemic has brought with it the huge burden of mortality and morbidity across the world and the added effects of the mandatory lockdown measures to try and control the spread. A number of aspects of healthcare including eye donation and eye collection require adequate safety precautions in place to keep both the involved healthcare workers and patients safe. This paper highlights the consensus-based guidelines by an expert panel on how to restart eye banking and eye collection services and carry out emergency corneal surgeries during this COVID-19 time. These guidelines will be applicable to all eye banks across the country and should help ophthalmologists and eye banking staff to restart eye banking while safeguarding themselves and their patients.

Background The current outbreak of COVID‐19 has spread rapidly all over the world. Respiratory droplets and contaction with infected patients are the two major transmission routes. However, the value of tear virus nucleic acid is still not clear. We dynamic detected the SARS‐CoV‐2 in eye sample of one COVID‐19 patient with obstruction of common lacrimal ducts. Methods Besides the routine examination, nasopharyngeal and eye swab were continuously measured by polymerase chain reaction assay and next‐generation sequencing (NGS). Gene detection was performed for drug use guidance, and flow cytometry was performed to analyse the lymphocyte subsets. Results Nasopharyngeal swabs were positive for 22 days, but eye swabs were still continuously positive for 2 weeks after nasopharyngeal swabs turned negative. The low level of lymphocyte and the high level IL‐6 lasted for almost 4 weeks, then became near normal. Next‐generation sequencing (NGS) confirmed the existing of SARS‐CoV‐2, HSV1 and HHV6B virus nucleic acid. The gene detection for drug use guidance showed the genetic locus ABCB1 (3435T>C) rs1045642 belonged to type CC and it mean the efficiency of lopinavir–ritonavir would be significantly decreased. The flow cytometry of lymphocyte subsets showed PD‐1+ CD95+ cells was accounting for 94.8% in CD3+ CD8+ T subset and for 94.8% in CD3+ TCRγδ+ T subset. Conclusions As obstruction of common lacrimal duct, positively detection in one eye for 2 weeks more after nasopharyngeal swab became negative. More eye swabs should be collected from COVID‐19 patients, especially from those immunocompromised, those with eye symptoms and those had a history of ocular diseases.

In December 2019, a novel coronavirus (CoV) epidemic, caused by the severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) emerged from China. This virus causes the coronavirus disease 2019 (COVID-19). Since then, there have been anecdotal reports of ocular infection. The ocular implications of human CoV infections have not been widely studied. However, CoVs have been known to cause various ocular infections in animals. Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models. In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed. The review article will also highlight animal CoVs and their associated ocular infections. We hope that this article will serve as a start for further research into the ocular implications of human CoV infections.

Viral anterior uveitis (VAU) needs to be suspected in anterior uveitis (AU) associated with elevated intraocular pressure, corneal involvement, and iris atrophic changes. Common etiologies of VAU include herpes simplex, varicella-zoster, cytomegalovirus, and rubella virus. Clinical presentations can vary from granulomatous AU with corneal involvement, Posner-Schlossman syndrome, Fuchs uveitis syndrome, and endothelitis. Due to overlapping clinical manifestations between the different viruses, diagnostic tests like polymerase chain reaction and Goldmann-Witmer coefficient analysis on the aqueous humor may help in identifying etiology to plan and monitor treatment.

Herpes stromal keratitis (HSK) represents a spectrum of pathologies which is caused by herpes simplex virus type 1 (HSV-1) infection and is considered a leading cause of infectious blindness. HSV-1 infects corneal sensory nerves and establishes latency in the trigeminal ganglion (TG). Recently, retraction of sensory nerves and replacement with "unsensing" sympathetic nerves was identified as a critical contributor of HSK in a mouse model where corneal pathology is caused by primary infection. This resulted in the loss of blink reflex, corneal desiccation, and exacerbation of inflammation leading to corneal opacity. Despite this, it was unclear whether inflammation associated with viral reactivation was sufficient to initiate this cascade of events.We examined viral reactivation and corneal pathology in a mouse model with recurrent HSK by infecting the cornea with HSV-1 (McKrae) and transferring (intravenous [IV]) human sera to establish primary infection without discernible disease and then exposed the cornea to UV-B light to induce viral reactivation.UV-B light induced viral reactivation from latency in 100% of mice as measured by HSV-1 antigen deposition in the cornea. Further, unlike conventional HSK models, viral reactivation resulted in focal retraction of sensory nerves and corneal opacity. Dependent on CD4+ T cells, inflammation foci were innervated by sympathetic nerves.Collectively, our data reveal that sectoral corneal sensory nerve retraction and replacement of sympathetic nerves were involved in the progressive pathology that is dependent on CD4+ T cells after viral reactivation from HSV-1 latency in the UV-B induced recurrent HSK mouse model.

Purpose: To examine subbasal corneal nerve changes in patients with bacterial infectious keratitis using in vivo confocal microscopy. Methods: Thirteen patients (13 eyes) with unilateral bacterial keratitis and 12 healthy controls were prospectively enrolled in the study. In vivo confocal microscopy was performed in all the patients at 2 time points, in the acute phase of infectious keratitis and at 28 ± 0.6 months after resolution of the infection. Results: The subbasal nerve length was 5.15 ± 1.03 mm/mm2 during the acute phase of bacterial keratitis (compared with that of the controls: 19.02 ± 1.78 mm/mm2, p

Purpose The purpose of this study was to report 2 patients with anterior scleritis manifesting after coronavirus disease 2019 (COVID-19). Methods The patients with confirmed COVID-19 developed anterior scleritis after their systemic symptoms were markedly improved. A thorough systemic workup identified no underlying autoimmune diseases. Ocular characteristics and safety and efficacy of systemic immunosuppressive therapy were evaluated. Results Case 1 was a 67-year-old woman who presented with necrotizing anterior scleritis in both eyes 3 weeks after the onset of COVID-19. One-week treatment with topical betamethasone and oral prednisolone (65 mg daily) did not result in improvement, so she was started on intravenous cyclophosphamide and subcutaneous adalimumab in addition to oral prednisolone. Necrotizing scleritis was gradually improved over 3 months. Case 2 was a 33-year-old man who presented with sectoral anterior scleritis in his right eye 2 weeks after the onset of COVID-19. He was started on topical betamethasone and oral prednisolone (85 mg daily). One week later, all signs and symptoms disappeared, and topical and oral corticosteroids were gradually tapered off over 2 weeks. There was no recurrence of respiratory symptoms or active scleritis in any cases after discontinuation of treatment. Conclusions These cases suggest that COVID-19 can be associated with anterior scleritis, which responds to immunosuppressive and biologic agents. Ophthalmologists should consider anterior scleritis in patients with COVID-19 who present with ocular pain and redness during the convalescent phase of the illness.

Purpose Considering the difficulty of obtaining adequate biological tissue in clinical practice, we established an animal model of cytomegalovirus (CMV) keratouveitis in rats and investigated the viral infection sites and corresponding imaging and histopathological features. Methods Subconjunctival injection and topical use of dexamethasone were used to induce ocular immunosuppression in rats followed by intracameral inoculation of murine cytomegalovirus (MCMV). The clinical manifestations, intraocular pressure (IOP) and imaging changes were observed. Infected eyes were further examined by immunofluorescence, light microscopy, and electron microscopy. MCMV RNA was detected by reverse transcription-polymerase chain reaction. Results Typical keratouveitis occurred in the experimental rats and was characterized by corneal edema, keratic precipitates, and iridocyclitis with increased IOP. Corneal endothelial lesions displayed as "black holes," enlarged intercellular gaps, and high-intensity cellular infiltration by confocal microscopy, consistent with the pathological changes of "ballooning degeneration," endothelial cell detachment, and inflammatory cell infiltration. Mitochondrial edema was the most prominent organelle lesion in endothelial cells. Trabeculitis, mechanical obstruction of Schlemm's canal, and anterior chamber angle stenosis accounted for elevated IOP. Inflammation of the iris and ciliary body tended to transform into a chronic form. Immunofluorescence revealed that corneal endothelial cells, iris cells, trabecular meshwork cells, and monocytes could be infected by MCMV. MCMV RNA was found in the anterior segments after infection. Conclusions CMV can widely infect anterior segment tissue, including the corneal endothelium, iris, and trabecular meshwork, in vivo, inducing the corresponding clinical manifestations. Corneal endotheliitis and hypertensive anterior uveitis could be the specific stage of anterior segment infection of CMV.