Herpetic Keratitis Research Articles

Prevalence and characteristics of ocular diseases in Sphynx cats: A retrospective assessment (2012-2021) and comparison with non-Sphynx cats.

To describe the prevalence of ocular diseases in Sphynx cats, and compare disease characteristics with other feline breeds. Medical records of Sphynx cats presented to an ophthalmology referral center between 1/2012 and 4/2021 were examined. Cats of other breeds examined during the same period served as controls. One hundred ten Sphynx cats were examined during the study period, diagnosed with corneal sequestrum (n= 42 cats), lower eyelid entropion (n= 25), presumed herpetic keratoconjunctivitis (n= 19), conjunctivitis (n= 7), corneal ulcers (n= 6), nasolacrimal duct atresia/obstruction (n= 6), corneal dystrophy (n= 3), eosinophilic keratitis (n= 2), uveitis (n= 2), non-ulcerative keratitis (n= 1), and cataract (n= 1). Corneal sequestrum was significantly more common in Sphynx versus non-Sphynx cats (odds ratio=8.0, 95% CI=5.3-12.2, p< .001), and age of diagnosis was significantly younger in Sphynx cats (2.0± 1.5 years vs. 5.9± 4.0 years, p< .001). Corneal sequestrum recurrence was noted in 19.4% Sphynx eyes and 6.4% non-Sphynx eyes undergoing surgery (p= .015). Lower eyelid entropion-most often bilateral (80%)-was significantly more common in Sphynx versus non-Sphynx cats (odds ratio=4.1, 95% CI=2.3-7.1, p< .001), and age of diagnosis was significantly younger in Sphynx cats (0.9± 1.4 years vs. 3.5± 3.3 years, p< .005). Corneal sequestrum and entropion were overrepresented and diagnosed at an earlier age in Sphynx cats when compared with the general feline population. Given the high prevalence, early age of onset, and relatively high recurrence of corneal sequestrum in Sphynx cats, further studies are warranted to better understand etiopathogenesis and preferred therapies.

Analyse vectorielle de la correction de l’astigmatisme par incisions arciformes au laser femtoseconde dans les astigmatismes géants post-kératoplastie transfixiante

To study the results of femtosecond laser-assisted arcuate keratotomy in extreme astigmatism after penetrating keratoplasty, using a Ziemer LDVZ6 with a modified Lindstrom nomogram. Case series, retrospective study. Consecutive eyes that underwent femtosecond laser-assisted arcuate keratotomy between 2014 and 2019 in the Nantes University Hospital for extreme astigmatism after penetrating keratoplasty were included. Twenty-four eyes of 24 patients were included. The mean age was 53.3±12.2 years at the time of the arcuate keratotomies. Indications for penetrating keratoplasty were keratoconus in 66.7% of cases, herpes keratitis in 16.7% of cases, and corneal dystrophy in 16.7% of cases. The mean initial best corrected visual acuity was 0.36±0.23 logMar versus 0.26±0.15 logMar at the 3-month postoperative visit (P=0.04). At the postoperative visit, 54% (13/24) of eyes had improved best corrected visual acuity (BCVA), and 25% had no change in BCVA, with a mean cylinder reduction of 3.3 diopters. The mean preoperative topographic cylinder was 9.5±3.2 diopters versus 6.2±2.8 diopters postoperatively (absolute values; P<0.001), i.e. a 34.7% reduction in astigmatism. At the 3-month postoperative visit, 20.8% of eyes (5/24) had topographic astigmatism less than 3 diopters with a mean astigmatism reduction of 97±55% (range: 17; 201) using the Alpins method. No suppurative keratitis or endophthalmitis were observed. Twenty-one percent of patients underwent a second arcuate keratotomy after 3 to 6 months due to insufficient refractive results. Development of new nomograms designed for extreme astigmatism after penetrating keratoplasty would enhance the precision and reproducibility of femtosecond laser-assisted arcuate keratotomy in these cases.

Initial TK-deficient HSV-1 infection in the lip alters contralateral lip challenge immune dynamics

Primary infection with herpes simplex type 1 (HSV-1) occurring around the mouth and nose switches rapidly to lifelong latent infection in sensitive trigeminal ganglia (TG) neurons. Sporadic reactivation of these latent reservoirs later in life is the cause of acute infections of the corneal epithelium, which can cause potentially blinding herpes simplex keratitis (HSK). There is no effective vaccine to protect against HSK, and antiviral drugs provide only partial protection against recurrences. We previously engendered an acute disease-free, non-reactivating latent state in mice when challenged with virulent HSV-1 in orofacial mucosa, by priming with non-neurovirulent HSV-1 (TKdel) before the challenge. Herein, we define the local immune infiltration and inflammatory chemokine production changes after virulent HSV-1 challenge, which were elicited by TKdel prime. Heightened immunosurveillance before virulent challenge, and early enhanced lymphocyte-enriched infiltration of the challenged lip were induced, which corresponded to attenuation of inflammation in the TG and enhanced viral control. Furthermore, classical latent-phase T cell persistence around latent HSV-1 reservoirs were severely reduced. These findings identify the immune processes that are likely to be responsible for establishing non-reactivating latent HSV-1 reservoirs. Stopping reactivation is essential for development of efficient vaccine strategies against HSV-1.

MO230: De Novo Double Glomerulopathy (Membranous Nephropathy, Mn and Collapsing Focal Segmental Glomerulosclerosis, CFSGS) Associated to Positive Myeloperoxidase-O (MPO) Antibody Following Pfizer-Biontech MRNA Vaccination Covid 19

Abstract BACKGROUND AND AIMS In the COVID 19 pandemic era, anti SARS-CoV-2 vaccination showed high efficacy at preventing the infection and its most severe complications. The aim of this report is to describe an unusual double glomerulopathy related to anti SARS-CoV-2 vaccination and the good results obtained with the immunosoppressive treatment. METHOD An 80-year-old caucasian woman developed a nephrotic syndrome, progressive renal insufficiency and microhematuria. The patient presented a medical history of thrombocytopenic purpura treated and resolved by steroids in 2013, hypothyroidism, hypertension, ischaemic heart disease treated with surgical bypass in 2019 and pacemaker in 2020 for atrial ventricular block. Due to pandemic COVID 19 status, she received two doses of the Pfizer BioNTech mRNA COVID-19 vaccine in March 2021. Two weeks after the second dose her weight increased of 23 kg. The family physician added furosemide to her therapy for generalized edema with no diuretic effect. In April, creatinine was 1.38 mg/dL (versus 0.8 mg/dL 1 year before); urinalysis showed proteinuria (300 mg/dL) and microscopic hematuria; serum total cholesterol level was 218 mg/dL and triglycerides 178 mg/dL; then it was suggested to increase the doses of furosemide. In May 2021, creatinine resulted 2 mg/dL, serum albumin 2 g/dL, and urinalysis confirmed proteinuria and microscopic hematuria; proteinuria was 10 g/day. Abdomen ultrasound showed normal liver, kidneys and spleen, not ascites. Lower limb eco-Doppler showed right superficial femoral artery stenosis of 60% and absence of venous thrombosis. The physical examination evidenced anasarca. The patients were admitted to the nephrology unit; hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antigen and antibody were negative. Both complement C3 and C4 levels resulted within the normal range. Cryoglobulins were absent. Urinary Bence Jones, antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double stranded DNA (nDNA) antibodies were negative. Antineutrophil cytoplasm antibodies (ANCA) were 1:2560 with Perinuclear pattern and anti-MPO positivity (716 UA/mL); anti-proteinase-3 antibodies (PR3) were negative. Anti-phosholipase A2 receptor antibody (PLA2R Ab) was positive with high titre. A kidney biopsy was performed showing a double nephropathy: a focal segmental glomerulosclerosis (FSGS) with some collapsing features, superimposed on membranous glomerulonephritis (Fig. 1). RESULTS We started the Ponticelli regimen (alternate months steroids and cyclophosphamide). After the first month of therapy, blood tests revealed creatinine 1.7 mg/dL, haemoglobin 11.7 g/dL; serum albumin 2.7 g/dL and urinalysis without microscopic haematuria. At the third month of therapy, the patient developed atrial fibrillation and started anticoagulation; blood tests were as follows: creatinine 1.1 mg/dL, serum albumin 3.0 g/dL, Ab anti-MPO 7 UA/mL and PLA2R Ab was absent. A left ocular, frontal and parietal herpes zoster induced a short discontinuation of therapy and responded well to Acyclovir; then we concluded the fourth month of therapy. At the fifth month, a SARS CoV 2 RT PCR unexpectedly resulted positive; the patient remained asymptomatic, but we stopped definitively the therapy. One month later, blood tests showed: creatinine 1 mg/dL, serum albumin 4 g/dL, proteinuria 0.7 g/die, MPO 2 UA/mL and PLA2R Ab absent. CONCLUSION To our knowledge, this is the first case of nephrotic sindrome secondary to a de novo MN and FSGS, associated with positive MPO antibody, following Pfizer–BioNTech mRNA vaccination COVID 19; the patient responded well to immunosoppression going in remission and regaining renal function.

Clinical efficacy and anti-recurrence effect of isatis root eye drops combined with ganciclovir eye drops in the treatment of Herpes simplex keratitis; a case report

Purpose: The rate of gastrointestinal adenomatous polyps, often regarded as precancerous lesions, developing into cancer is 40 – 70 %. Endoscopic resection has been the preferred method for treating gastric polyps since the late 1960s. Surgical removal of polyps continues to play an important role in the treatment of polyps; however, the efficacy of such treatment cannot be guaranteed, and polyps may recur.Case presentation: Here, we report a 44-year-old man suffering from gastrointestinal polyps who refused surgical treatment and instead was treated with traditional Chinese herbal medicine (TCHM) for approximately 1 year. The patient was diagnosed with “qi deficiency and dampness syndrome” based on traditional Chinese medicine theory and was treated with the TCHM “strengthen qi and remove dampness formula”, referred to as the shen-ling-bai-zhu powder/decoction.Conclusion: This case suggests that TCHM may play an important role in the treatment of gastrointestinal polyps. Relevant data are, however, limited and a randomized controlled trial is needed to confirm TCHM efficacy in a larger population.

A proof-of-concept study for the efficacy of dispirotripiperazine PDSTP in a rabbit model of herpes simplex epithelial keratitis

Herpes simplex keratitis is an important infectious cause of blindness worldwide. The mainstay of antiviral therapy is treatment with long-established nucleoside analogues orally or topically. However, the emergence of resistant strains may become a major health concern in the future. Therefore, the development of backup antiherpetic medicines is urgently needed. Small molecule PDSTP is known to be active against herpes simplex type 1 strains in vitro, affecting early host-pathogen interactions. Here, we evaluated its preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. The mean course of keratitis and the corneal lesions in the 1.0% PDSTP gel group was statistically significantly less than in the negative control group and was comparable to that in the aciclovir group. These findings open up new opportunities for the development of antiherpetic drugs with an original mechanism of action.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

Combinatorial Herpes Simplex Vaccine Strategies: From Bedside to Bench and Back.

The development of vaccines against herpes simplex virus type 1 and type 2 (HSV1 and HSV-2) is an important goal for global health. In this review we reexamined (i) the status of ocular herpes vaccines in clinical trials; and (ii) discusses the recent scientific advances in the understanding of differential immune response between HSV infected asymptomatic and symptomatic individuals that form the basis for the new combinatorial vaccine strategies targeting HSV; and (iii) shed light on our novel “asymptomatic” herpes approach based on protective immune mechanisms in seropositive asymptomatic individuals who are “naturally” protected from recurrent herpetic diseases. We previously reported that phenotypically and functionally distinct HSV-specific memory CD8+ T cell subsets in asymptomatic and symptomatic HSV-infected individuals. Moreover, a better protection induced following a prime/pull vaccine approach that consists of first priming anti-viral effector memory T cells systemically and then pulling them to the sites of virus reactivation (e.g., sensory ganglia) and replication (e.g., eyes and vaginal mucosa), following mucosal administration of vectors expressing T cell-attracting chemokines. In addition, we reported that a combination of prime/pull vaccine approach with approaches to reverse T cell exhaustion led to even better protection against herpes infection and disease. Blocking PD-1, LAG-3, TIGIT and/or TIM-3 immune checkpoint pathways helped in restoring the function of antiviral HSV-specific CD8+ T cells in latently infected ganglia and increased efficacy and longevity of the prime/pull herpes vaccine. We discussed that a prime/pull vaccine strategy that use of asymptomatic epitopes, combined with immune checkpoint blockade would prove to be a successful herpes vaccine approach.

Manifestation of Herpetic Eye Disease after COVID-19 Vaccine: A UK Case Series

ABSTRACT Purpose To highlight the potential risk of herpetic eye disease (HED) reactivation following COVID-19 vaccine. Methods Retrospective analysis of all patients who presented with HED within 28 days post-first dose COVID-19 vaccination. Results Eleven eyes (n = 10 patients) were included. The mean interval between COVID-19 vaccination and ocular symptoms/signs was 12.3 ± 10.3 days. Four (40%) patients presented with HSV keratitis, and six (60%) patients presented with VZV keratitis (five had concurrent other signs of herpes zoster ophthalmicus). Common ocular signs included multiple scattered dendritic/pseudodendritic corneal epitheliopathy (90.9%), anterior uveitis (63.6%), and endothelitis (27.3%). All cases were successfully treated with topical and systemic antiviral treatment and/or topical corticosteroids (mean healing time = 3.9 ± 1.6 weeks). Conclusions Our case series highlights the potential temporal association between HED and COVID-19 vaccine. Prophylactic antiviral treatment is recommended in patients with a history of HED prior to COVID-19 vaccination.

Neurotrophic Keratitis. Etiology, Pathogenesis, Clinical Manifestations. Review. Part 1

Neurotrophic keratitis (also called neurotrophic keratopathy) (NTK) is a degenerative disease of the cornea, accompanied with neurogenic inflammation. It caused by a sensitive innervation loss of the trigeminal nerve and characterized by reduced sensitivity of the cornea and a retardation of its healing process. NTC-causing damage to the trigeminal nerve can occur at different levels-from the nucleus to the terminals located in the cornea, and can be caused by ocular and systemic diseases both. The most common causes include herpetic keratitis, diabetes, chemical burns and iatrogenic injuries during ophthalmic operations, intracranial neoplasms, disorders of cerebral circulation and neurosurgical interventions. Corneal changes include epitheliopathy (grade I), persistent erosion (grade II), ulcer and its complications (grade III). The determining diagnostic sign of NTK is a decrease or loss of corneal sensitivity. The morphological characteristics of the corneal nerves can be studied using confocal microscopy.

Chlorhexidine in the treatment of microsporidial stromal keratitis and the effect of host immunity: A case series and literature review.

Microsporidial stromal keratitis is an increasingly well-known vision-threatening disease. A large proportion of cases are initially misdiagnosed as herpes simplex keratitis and treated with topical steroids. In most of such cases, medical treatment failed, and corneal transplantation was required. This study reported the results of 0.02% topical chlorhexidine used to treat three cases of microsporidial stromal keratitis and reviewed the literature on the outcomes of microsporidial stromal keratitis treatment. In the first case, histopathology of a specimen from penetrating keratoplasty (PK) revealed severe chronic inflammation involving the entire stromal layer but no microorganism activity after the application of topical chlorhexidine for 10 months. The second case exhibited complete resolution of keratitis after topical chlorhexidine. The patient in the third case did not respond to medical treatment, and therapeutic PK was performed. Histopathological examination revealed numerous microsporidial spores that had colonized in the mid and deep stroma, where few inflammatory cells were observed. These findings explain the variable microsporidial susceptibility to chlorhexidine, suggesting the crucial role of host immunity. In cases of host immunity, topical chlorhexidine may represent a promising option for the treatment of microsporidial stromal keratitis.

Herpes Simplex Virus-1 Induced Serotonin-Associated Metabolic Pathways Correlate With Severity of Virus- and Inflammation-Associated Ocular Disease.

Herpes simplex virus-associated diseases are a complex interaction between cytolytic viral replication and inflammation. Within the normally avascular and immunoprivileged cornea, HSV ocular infection can result in vision-threatening immune-mediated herpetic keratitis, the leading infectious cause of corneal blindness in the industrialized world. Viral replicative processes are entirely dependent upon numerous cellular biosynthetic and metabolic pathways. Consistent with this premise, HSV infection was shown to profoundly alter gene expression associated with cellular amino acid biosynthetic pathways, including key tryptophan metabolism genes. The essential amino acid tryptophan is crucial for pathogen replication, the generation of host immune responses, and the synthesis of neurotransmitters, such as serotonin. Intriguingly, Tryptophan hydroxylase 2 (TPH2), the neuronal specific rate-limiting enzyme for serotonin synthesis, was the most significantly upregulated gene by HSV in an amino acid metabolism PCR array. Despite the well-defined effects of serotonin in the nervous system, the association of peripheral serotonin in disease-promoting inflammation has only recently begun to be elucidated. Likewise, the impact of serotonin on viral replication and ocular disease is also largely unknown. We therefore examined the effect of HSV-induced serotonin-associated synthesis and transport pathways on HSV-1 replication, as well as the correlation between HSV-induced ocular serotonin levels and disease severity. HSV infection induced expression of the critical serotonin synthesis enzymes TPH-1, TPH-2, and DOPA decarboxylase (DDC), as well as the serotonin transporter, SERT. Concordantly, HSV-infected cells upregulated serotonin synthesis and its intracellular uptake. Increased serotonin synthesis and uptake was shown to influence HSV replication. Exogenous addition of serotonin increased HSV-1 yield, while both TPH-1/2 and SERT pharmacological inhibition reduced viral yield. Congruent with these in vitro findings, rabbits intraocularly infected with HSV-1 exhibited significantly higher aqueous humor serotonin concentrations that positively and strongly correlated with viral load and ocular disease severity. Collectively, our findings indicate that HSV-1 promotes serotonin synthesis and cellular uptake to facilitate viral replication and consequently, serotonin’s proinflammatory effects may enhance the development of ocular disease.

Evidence in the prevention of the recurrence of herpes simplex and herpes zoster keratitis after eye surgery

Herpetic keratitis, either due to herpes simplex keratitis (HSK) or herpes zoster ophthalmicus (HZO), can recur after eye surgery.º Prophylaxis is postulated as necessary to avoid it. The objective of this study was to review the scientific evidence on the preventive methods used in the perioperative period in patients previously affected by HSK/HZO.An exhaustive search was carried out in the PubMed and Web of Science databases to identify relevant articles on prophylaxis and risk of recurrence of HSK/HZO in patients undergoing eye surgery up to 31 December 2019.There is strong evidence that oral prophylaxis should be recommended after penetrating keratoplasty in patients who have previously had HSK/HZO. For other types of surgery, the evidence is less compelling. However, a latent period of inactivity should be considered between disease and oral prophylaxis.Penetrating and lamellar keratoplasty, corneal crosslinking, cataract surgery, and photorefractive and phototherapeutic surgery cause an alteration of the subbasal nerve plexus of the cornea. Due to surgical trauma, as well as the modulation of the ocular immune response caused by steroids applied in the postoperative period, it is possible to induce the reactivation of HSK/HZO, which is common in some cases. Within this article, we discuss the available evidence for HSK/HZO prophylaxis in eye surgery. Further studies are necessary to define the real risk of HSK/HZO recurrence after ocular surgeries, particularly in cataract surgery, and to confirm the efficacy of perioperative prophylaxis with anti-HSK/HZO antivirals.

Nectin-1 and Non-muscle Myosin Heavy Chain-IIB: Major Mediators of Herpes Simplex Virus-1 Entry Into Corneal Nerves.

Herpes Simplex Virus 1 (HSV-1) invades corneal nerves upon its infection of the cornea and then establishes latency in the trigeminal ganglion (TG). The latent virus in TG is often reactivated and travels back to the cornea, causing recurrent herpes simplex keratitis (HSK). The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence. Several gD and gB receptors have been identified, including nectin-1, herpes virus entry medium (HVEM) and 3-O-sulfated heparan sulfate (3-OS-HS) as gD receptors, and non-muscle myosin heavy chain IIA (NMHC-IIA), NMHC-IIB and myelin-associated glycoprotein (MAG) as gB receptors. However, which receptors contribute to the entry of HSV-1 into corneal nerves are yet to be determined. This study observed that receptors nectin-1, HVEM, 3-OS-HS, NMHC-IIA, and NMHC-IIB, not MAG, were expressed in healthy corneal nerves. Further, we cultured TG neurons extracted from mice in vitro to screen for functional gD/gB receptors. Both in vitro siRNA knockdown and in vivo antibody blocking of either nectin-1 or NMHC-IIB reduced the entry and the replication of HSV-1 as shown by qPCR analysis and immunofluorescence measure, respectively. Also, we observed that the re-localization and the upregulation expression of NMHC-IIB after HSV-1 exposure were inhibited when gD receptor nectin-1 was knocked down. These data suggest that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.

Targeting NECTIN-1 Based on CRISPR/Cas9 System Attenuated the Herpes Simplex Virus Infection in Human Corneal Epithelial Cells In Vitro.

PurposeViral keratitis caused by herpes simplex virus 1 (HSV-1) is a lifelong recurring disease and an unignored cause of blindness worldwide. Current antiviral therapy cannot eliminate the transcriptionally silent HSV-1 in latently infected patients. With the explosive applications of the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease (Cas) 9 gene-editing system in recent years, we aim to develop a CRISPR/Cas9 system targeting down the major HSV receptor, NECTIN-1 on human corneal epithelial cells (HCECs), to provide a novel strategy for herpes simplex keratitis (HSK) treatment.MethodsThe selected single guide RNAs (sgRNAs) targeting human nectin cell adhesion molecule 1 (NECTIN-1), together with Cas-9, were assembled into lentivirus. HCECs were infected with Lenti-Cas9-gRNAs to establish NECTIN-1 knockdown cells. Following HSV–green fluorescent protein (GFP) infection, cell survival and virus infection were determined by fluorescence microscopy and flow cytometry. Relative HSV DNA amount was also compared through quantitative reverse transcriptase–polymerase chain reaction.ResultsLentivirus packaged with the CRISPR/Cas9 system and the two selected sgRNAs both successfully edited down the protein levels of NECTIN-1 of HCECs. After HSV-GFP infection, the infection rate of HCECs in knockdown groups dramatically decreased, especially in the NECTIN-1 knockdown group 1. In addition, the relative HSV DNA amount of both knockdown groups was only 30% when compared with the control group.ConclusionsWe successfully knocked down the NECTIN-1 expression in vitro by the CRISPR/Cas9 system, which alleviated the HSV infection in HCECs.Translational RelevanceThis study offered a promising target for the cure of HSK.

Optical coherence tomography angiography in herpetic leucoma

BackgroundHerpes simplex virus (HSV) keratitis remains a leading infectious cause of blindness worldwide. Although all forms of HSV keratitis are commonly recurrent, the risk is greatest in stromal keratitis, which is the most likely to result in corneal scarring, thinning, and neovascularization. Recent studies showed the ability of Optical Coherence Tomography Angiography (OCTA) to detect and study vascular abnormalities in the anterior segment, including abnormal corneal vessels. This study intends to investigate the potential of OCTA device to image and describe quantitatively the vascularization in eyes diagnosed with herpetic leucoma and to discuss and review the usefulness of this technique in this pathology.MethodsA Cross-sectional study was made, including 17 eyes of 15 patients with leucoma secondary to herpetic keratitis. All eyes underwent anterior segment Slit-Lamp photography (SLP), and OCTA with en-face, b-scans and c-scans imaging. The vessel density (VD) was analyzed in the inferior, nasal and temporal corneal margin in all patients, and in the central area, in eyes with central corneal neovascularization (CoNV). The measurements were calculated after binarization with ImageJ software, using OCTA scans with 6 × 6 mm in a depth of 800 μm.ResultsPatients included had a mean age 53.267 ± 21.542 (years ± SD). The mean total vessel area was 50.907% ± 3.435%. VD was higher in the nasal quadrant (51.156% ± 4.276%) but there were no significant differences between the three analyzed areas (p = 0.940). OCTA was able to identify abnormal vessels when SLP apparently showed no abnormal vessels; OCTA was able to distinguish between larger and smaller vessels even in central cornea; OCTA scans allowed the investigation of several corneal planes and the relation of them with clinical findings.ConclusionsOCTA can be useful in both qualitative and quantitative follow-up of patients and may become a non-invasive alternative to objectively monitor treatment response in eyes with corneal vascularization due to herpetic infection.

Host Molecules That Promote Pathophysiology of Ocular Herpes.

Herpes simplex virus type-1 (HSV-1) is a human virus that causes lifelong infections in a large population worldwide. Recurrence of HSV-1 from latency in trigeminal ganglion (TG) is the trigger of the morbidities seen with this virus. In addition to causing fever blisters and cold sores, occasionally the virus can also cause corneal lesions resulting in blindness in untreated individuals. Several host cell proteins play important roles in HSV-1 infection of the eye. HSV-1 enters into the corneal epithelial cells via its interactions with cell surface receptors. In parallel, the Toll-like receptors sense viral invasion and activate defense mechanisms to fight the infection. New data shows that Optineurin, a host autophagy receptor is also activated to degrade viral particles. In contrast, activation of heparanase, a host enzyme, induces an immune-inflammatory response, which triggers pro-inflammatory and pro-angiogenic environment and ultimately results in many of the clinical features seen with HSV-1 infection of the cornea. Rarely, HSV-1 can also spread to the central nervous system causing serious diseases. In this review, we summarize the latest knowledge on host molecules that promote pathophysiological aspects of ocular herpes.

Activation of the STAT5 Signaling Pathway by Yiqi Jiedu Formula Induces Regulatory T Cell-Mediated Alleviation of Corneal Immunopathological Damage in Mice With Recurrent Herpes Simplex Keratitis.

This study aimed to investigate the effect of Yiqi Jiedu (YQJD) formula on the repair of corneal lesions in mice with recurrent herpes simplex virus keratitis (HSK). Sixty female BALB/c mice were randomly divided into three groups: a normal control group (Naive), a recurrence model group (Re), and a YQJD group. After inducing recurrence by ultraviolet irradiation, the ocular surfaces of different groups of mice were observed using a slit lamp and photographed, and ocular surface scores were calculated. The abundance of CD4+CD25+Foxp3+ regulatory T (Treg) cells was determined by flow cytometry in peripheral blood and spleen cells. The CD4+Foxp3+ Tregs were assessed by immunofluorescence in the cornea. The levels of the cytokines IL-10 and TGF-β in serum and splenocyte culture supernatants were detected by enzyme-linked immunosorbent assay. Furthermore, the activation status of the STAT5 signaling pathway was examined by protein blotting, and the effect of YQJD on Treg cells through inhibition of the STAT5 pathway was observed in vitro. YQJD alleviated corneal inflammation by enhancing the STAT5 signaling pathway, thereby promoting the differentiation of CD4+CD25+Foxp3+ Treg cells, increasing the levels of anti-inflammatory cytokines such as IL-10 and TGF-β, and maintaining immune tolerance. YQJD increased the proportion of CD4+Foxp3+ Treg cells; also, in the cornea, YQJD inhibited the aggregation of macrophages and CD4+ cells and reduced the proportion of Th17 cells and other pro-inflammatory cells. Moreover, YQJD promoted the secretion of IL-4 to protect the cornea, leading to the mitigation of corneal immunopathological damage. YQJD reduced corneal lesions in recurrent HSK mice by stimulating Treg cells, inducing immune tolerance, and inhibiting corneal immunopathological responses via modulation of the STAT5 signaling pathway.

Corneal endothelial regeneration in human eyes using endothelium-free grafts

BackgroundTo report on corneal endothelial regeneration, graft clarity, and vision recovery when using endothelium-free grafts.MethodsWe evaluated the donor’s cell viability using trypan blue staining and dual staining with calcein acetoxy methyl ester and ethidium homodimer-1. To preserve eyeball integrity, we performed therapeutic penetrating keratoplasty using cryopreserved donor tissue without endothelium on 195 consecutive patients who suffered from corneal perforation due to progressive primary corneal disease such as herpes simplex keratitis, fungal keratitis, ocular thermal burns, keratoconus, and phlyctenular keratoconjunctivitis. Of these, 18 eyes recovered corneal graft clarity and underwent periodic slit-lamp microscopy, A-scan pachymetry, and in vivo confocal microscopy to observe the clinical manifestations, variations in corneal thickness, and repopulation of the corneal endothelial cells on the donor grafts.ResultsNo viable cells were detected in the cryopreserved corneas. After the therapeutic penetrating keratoplasty, notable corneal graft edema was observed in all 18 eyes for 1–4 months, and no corneal endothelial cells were detected on the grafts during this period. Thereafter, we observed gradual and progressive regression and final resolution of the stromal edema, with complete recovery of corneal graft clarity. Through periodic confocal microscopy, we observed the corneal endothelium’s regenerating process, along with single cells bearing multiple nuclei and cell division-like morphology. The regenerated endothelium on the grafts reached a mean cell density of 991 cells/mm2. Remarkable vision rehabilitation was achieved in all 18 patients.ConclusionsWe obtained conclusive evidence that host-derived endothelial cells can regenerate a new endothelium over the endothelium-free graft, which possesses normal functions for corneal clarity and vision recovery.