Herpetic Keratitis Research Articles

Nanoparticle ocular immunotherapy for herpesvirus surface eye infections evaluated in cat infection model.

Ocular herpes simplex type 1 (HSV-1) infections can trigger conjunctivitis, keratitis, uveitis, and occasionally retinitis, and is a major cause of blindness worldwide. The infections are lifelong and can often recrudesce during periods of stress or immune suppression. Currently HSV-1 infections of the eye are managed primarily with anti-viral eye drops, which require frequent administration, can cause irritation, and may take weeks for full resolution of symptoms. We therefore evaluated the effectiveness of an ocular immune activating nanoparticle eye drop as a novel approach to treating HSV-1 infection, using a cat feline herpesvirus -1 (FHV-1) ocular infection model. In vitro studies demonstrated significant induction of both type I and II interferon responses by the liposome-dual TLR 3/9 agonist nanoparticles, along with suppression of FHV-1 replication. In cats with naturally occurring eye infections either proven or suspected to involve FHV-1, ocular nanoparticle treated animals experienced resolution of signs within several days of treatment, including resolution of keratitis and corneal ulcers. In a cat model of recrudescent FHV-1 infection, cats treated twice daily with immune nanoparticle eye drops experienced significant lessening of ocular signs of infection and significantly fewer episodes of viral shedding compared to control cats. Treatment was well-tolerated by all cats, without signs of drug-induced ocular irritation. We concluded therefore that non-specific ocular immunotherapy offers significant promise as a novel approach to treatment of HSV-1 and FHV-1 ocular infections.

Prolonged Herpetic Keratitis in Chronic Sinusitis and Tonsillitis: Experience of Practical Solutions

Aim: to describe the experience of practical solutions for herpetic keratitis of a protracted course with latent chronic sinusitis and tonsillitis.Material and methods. We observed 111 patients with various forms of prolonged herpetic keratitis and inflammatory ENT pathology. All patients underwent a study of biological secretions (tear, saliva, blood and urine) for the presence of DNA of herpetic viruses by PCR, systemic antiviral therapy was prescribed. All patients underwent a standard otorhinolaryngological examination, СТ scan of the paranasal sinuses (if necessary), microbiological study of nasopharynx swabs. Local therapy of herpetic keratitis included anti-inflammatory and antibacterial components.Results and discussion. Isolated sinus inflammation occurred in 59 % of cases (65 patients), in 38 % of cases (42 patients) there were variants of combinations of sinus inflammation (sinusitis, sphenoethmoiditis, pansinusitis). In 24 % of those included in the study (n = 27), during examination, in addition to the presence or absence of sinusitis, chronic tonsillitis was determined. In 30 % of cases (more often than in other secrets), herpetic viruses were detected in saliva, coccal flora dominated in swabs from the nasopharynx. A marked reduction in ophthalmological symptoms correlated with start of ENT therapy.Conclusions. This clinical and laboratory study has showed a close pathogenetic relationship of anterior ophthalmic herpes and concomitant inflammatory pathology of the paranasal sinuses and oropharynx. Active ethiotropic therapy of sinusitis and tonsillitis promotes short-term reduction of ophthalmic symptoms.

Experience in the Use and Evaluation of the Therapeutic Efficacy of a Drug Based on Para-Aminobenzoic Acid in the Complex Therapy of Herpesvirus Conjunctivitis and Keratitis

According to statistics, infectious and inflammatory eye diseases of various etiologies are widespread in the world (about 18 million cases per year). In some cases, they are severe and can lead to a decrease in acuity and even loss of vision. About 12 million in the structure of infectious and inflammatory diseases of the eye are conjunctivitis, which may be accompanied by inflammation of the edges of the eyelids (blepharoconjunctivitis) and / or the cornea (keratoconjunctivitis). A viral infection is one of the common causes of inflammation of the mucous membrane of the eyes. In the routine practice of ophthalmologists, adeno- and herpesvirus lesions of the organ of vision are most often diagnosed. Eye diseases of herpetic etiology are among the most common infections. Herpetic conjunctivitis usually develops as a result of an initial attack by Herpes simplex virus type 1 (HSV-1) in early childhood. But there is reason to believe that in adults they are no less common than herpetic keratitis, however, the diagnosis of isolated herpetic conjunctivitis is extremely rare, since, unlike herpetic keratitis or creatoconjunctivitis, the clinic is less pronounced, not always confirmed by laboratory, which leads to underdiagnosis. During the treatment of ophthalmic herpes, one should rely not only on the antiviral effect of drugs, but also on the presence of immunomodulators (interferons or inducers of endogenous interferonogenesis) in the complex therapy, which contribute to faster recovery with fewer relapses.The aim of this study was to evaluate the effectiveness of the use of the drug OCTALMOL in the treatment of 34 patients with conjunctivitis and keratitis of herpesvirus etiology. The drug contributed to the relief of clinical symptoms of inflammation and a reduction in the duration of therapy in 89 % of patients, while the average duration of treatment was 10.7 ± 0.3 days. The therapeutic effect in the group where OCTALMOL was included in the basic therapy was statistically higher than in the control group.

Herpes simplex viral keratitis - A mixed bag of challenging case scenarios

Herpes simplex virus (HSV) keratitis is a potentially blinding condition of the eyes. HSV can afflict any of the anatomical layers of the cornea, sometimes more than one layer at one time, and presents with a spectrum of clinical manifestations. Recalcitrant course, recurrences, and variable response to therapy can make managing these patients a true challenge, particularly in the pediatric age group and recipients of corneal transplants. Here, we report a series of five cases of HSV keratitis from our practice that presented with diagnostic and management dilemmas and were successfully managed with a combination of medical and surgical treatment.

Triple trouble

A middle-aged female with previous history of being treated as herpes keratitis, presented with a central deep stromal ulceration and overlying neurotrophic epithelium. On re-scraping, the culture grew Pseudomonas aeruginosa and Aspergillus flavus. Due to the aggressive nature of the organisms, during follow up, a central perforation was noted, for which emergency therapeutic keratoplasty was done and post-operatively medicated with topical eye drops as per culture and sensitivity. Hence, we are presenting this rare case report of Pseudomonas aeruginosa in a non-contact lens user, along with a co-infection of Aspergillus flavus in a previously compromised cornea with herpetic keratitis.

Scientific legacy of Professor A.A. Kasparov. Inductor of endogenous interferon Poludan in the treatment of ocular herpes and other corneal diseases

This article presents a retrospective analysis of the research findings by professor A.A. Kasparov, who developed and implemented a novel approach to treating ocular herpes. The treatment system is fundamentally different from the conventional chemotherapeutic approach and revolves around non-specific immunotherapy using an endogenous interferon inducer - a biosynthetic complex of polyriboadenylic and polyribouridylic acids, known as Poludan. This approach also incorporates personalized cell therapy based on Poludan, along with herpes vaccine aimed at preventing recurrence. The regenerative and antiviral properties of this approach have proven successful in treating other corneal conditions such as adenovirus infections, early postoperative bullous keratopathy, as well as in stimulation of epithelialization after refractive surgeries (photorefractive keratectomy, phototherapeutic keratectomy).

Infekcije kože uzrokovane Herpes simpleks virusom

Infections caused by the Herpes simplex virus belong to highly contagious diseases, where humans are the reservoir of this virus, and the infection is transmitted through direct contact with an infected person. Human Herpes simplex (HS) virus comprises two types of virus, Herpes simplex 1 (HSV-1) and Herpes simplex 2 (HSV-2), which cause numerous primary and recurrent infections of the skin and mucous membranes. Commonly HSV-1 causes Herpes labialis, herpetic stomatitis and keratitis. HSV-2 usually causes genital herpes, and is transmitted primarily through direct sexual contact with the lesions of an infected person. However, it is estimated that most genital herpes infections are transmitted by individuals who are asymptomatic at the time of transmission. The disease is one of the most common viral infections in humans, and Herpes simplex virus infection can be a significant clinical problem in infants, the elderly, and immunocompromised patients. Timely antiviral therapy leads to adequate rehabilitation and prevention of complications caused by the Herpes simplex virus. The paper presents the most important information about the causative agent of the infection, the mechanism of origin and manifestation of the disease, diagnosis and timely application of antiviral therapy that will prevent possible complications caused by the herpes simplex virus.

Combined versus sequential penetrating keratoplasty and cataract surgery for herpes simplex keratitis: a retrospective study.

To compare the surgical outcomes of combined penetrating keratoplasty (PK) and cataract surgery with those of sequential surgery (cataract surgery after PK) for herpes simplex keratitis (HSK). The medical records of consecutive patients diagnosed with HSK who underwent combined or sequential PK and cataract surgery in active and stable stages between June 2015 and June 2022 were reviewed retrospectively. Complications, graft survival, endothelial cell density (ECD), and final BCVA were compared and analyzed between both surgical methods in each stage. A total of 171 eyes of 171 patients were enrolled, including active stage (69 combined, 46 sequential) and stable stage (34 combined, 22 sequential). The average follow up was 24.2 ± 15.8 months (range, 3 months - 48 months). The final BCVA had obvious improvement and the postoperative ECD was not different in combined and sequential groups of each stage. In sequential group of active stage, 66.7% of persistent epithelial defects and 50% of HSK recurrence occurred within 3 months after cataract surgery; nevertheless, compared to that in sequential group, capsular rupture (p = 0.021), persistent epithelial defects (p = 0.027), and HSK recurrence (p = 0.035) occurred more frequently in combined group, leading to a lower graft survival rate (p = 0.045); at the last visit, 46.4 and 67.4% of grafts remained clear in combined and sequential groups, respectively. By contrary, 82.4 and 50.0% of grafts remained clear in stable stages of combined and sequential groups at the last visit, respectively, and a higher graft survival rate was observed in combined group (p = 0.030). Although the postoperative ECD is not different between two surgical groups in each stage, sequential surgery in active stage of HSK seems to have advantages in less complications and higher graft survival rate, whereas combined surgery in stable stage has a better outcome than that in sequential surgery.

Herpes Zoster Dermatitis after Corneal Collagen Cross-Linking with Riboflavin: A Case Report

A middle-aged female presented with complaints of decreased vision in both eyes OD (right eye) > OS (left eye), since 6 months, and eye rubbing. Due to steep keratometry readings on an automated keratometer, pentacam was done, and the findings were suggestive of keratoconus in OD and formefruste keratoconus in OS. As best corrected visual acuity (BCVA) decreased only since 6 months and pentacam readings were suggestive of keratoconus, the patient was treated with corneal collagen cross-linking with riboflavin (C3R) in OD, to halt the progression. On post-op day 5, the patient presented with erythema, small papulovesicular lesions over the right half of the face and forehead, suggestive of herpetic skin lesions. She was prescribed topical eye drops for post-C3R haze and oral acyclovir for skin lesions, which were regressed within 1 week. Early diagnosis and appropriate treatment of herpes zoster dermatitis prevent worsening of signs and decrease further risk of herpetic keratitis and associated complications. Thus in this case, ultraviolet (UV)-A irradiation acted as a trigger for herpes zoster virus reactivation.

Prevalence of Herpesvirus DNA in Corneal Transplant Recipients

Purpose: Graft failure after penetrating keratoplasty (PK) is a serious complication, especially in eyes with herpetic keratitis (HK). This study evaluated the prevalence and graft survival of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) DNA in recipient corneas during PK. Methods: The retrospective study was performed at the Department of Ophthalmology at University Hospital in Mainz, Germany. We analyzed data from every patient who underwent PK between January 2020 and June 2021. According to our clinical routine, we performed HSV-1 and VZV polymerase chain reaction (PCR) on all excised corneal buttons regardless of the primary clinical diagnosis. Results: We included 112 eyes of 112 consecutive patients who underwent PK. At the time of PK, 91 (81.25%) patients had no history of HK and 21 (18.75%) patients did. The recipient corneas of 91 patients without a history of HK tested positive for HSV-1 DNA in 12 (13.2%) eyes, for VZV DNA in 3 (3.3%) eyes, and for HSV-1 and VZV DNA simultaneously in 2 (2.2%) eyes. The recipient corneas of 21 patients with a preoperative history of HK tested positive for HSV-1 DNA in 13 (61.9%) eyes and VZV DNA in 1 (4.8%) eye. All patients with positive herpes DNA and no history of HK prior to PK received antiherpetic treatment and had a 100% graft survival rate after 1 year. Conclusions: We found herpesvirus DNA in 18.7% of recipient corneas without clinical suspicion or history of herpes keratitis. This suggests the need of routine HSV-1 and VZV PCR testing in all explanted corneas regardless of clinical suspicion, to detect, treat and prevent possible recurrence of herpes infection in corneal grafts and support graft survival.

Incidence of Complications Related to Corneal Graft in a Group of 758 Patients.

Purpose: this study aimed to assess the frequency of complications related to corneal grafts, including epithelialization disorders, wound dehiscence, infectious keratitis, recurrence of herpetic keratitis, graft rejection, late graft failure, and infectious and noninfectious corneal melting, while also considering risk factors, particularly indications. Methods: this retrospective analysis of corneal graft failure included a chart review of the hospital records of patients who underwent penetrating keratoplasty (PK) between January 2016 and December 2020 at the Department of Ophthalmology of the District Railway Hospital, Katowice, Poland. Results: Between 2016 and 2020, a total of 758 PK procedures were carried out at the ophthalmology department. Bullous keratopathy (20.58%), keratoconus (18.07%), and corneal perforation (13.32%) were the primary indications for keratoplasty. Secondary glaucoma was diagnosed in 99 patients (13.06%). The success rate of PK was 72.43% (494). The most frequent treatment complication was secondary glaucoma (13.06%), followed by late endothelial failure, perforation (4.1%), and bacterial keratitis (3.23%). Patients in the high-risk group were 4.65 times more likely to develop complications than those in the low-risk group. Multivariate regression analysis showed that concomitant ophthalmic diseases (odds ratio (OR): 3.12, confidence interval (CI): 1.60−6.08, p = 0.00) and connective tissue diseases (OR: 7.76, CI: 2.40−25.05, p = 0.00) were significant factors associated with the occurrence of complications. Diabetes, dermatological diseases, primary glaucoma, and sex were not associated with corneal graft failure (p > 0.05). Conclusion: Chronic loss of the endothelium was the primary cause of graft failure in individuals who underwent PK. The high-risk transplant has up to 4.65 times higher risk of complications compared to the indications with a good prognosis.

Overweight and Obesity as Risk Factors for Recurrent Herpetic Stromal Keratitis during Long-Term Antiviral Prophylaxis.

Although past research has shown an association between obesity and herpes simplex virus infection, the relationship between body mass index (BMI) and herpetic stromal keratitis (HSK) recurrence has never been investigated. In this study, we included HSK patients who received oral valacyclovir as prophylactic treatment between January 2016 and January 2021. Recurrence, possible risk factors, and the time to recurrence were recorded during follow-ups. Among the 56 patients included in this study, recurrence was reported in 21 (37.5%) patients. The age at disease onset and mean follow-up time were not significantly different in the recurrence and non-recurrence groups. However, in the Cox regression analysis, BMI ≥ 24 kg/m2 was noted as the variable having significant correlation with recurrence (p = 0.01 in univariate analysis and p = 0.001 in multivariate analysis). In conclusion, overweight and obesity were revealed as risk factors for HSK recurrence in patients receiving long-term antiviral prophylaxis. Further studies are needed to determine the appropriate acyclovir concentrations in the blood or aqueous humour in order to achieve desirable prophylactic effects, especially in the overweight and obese patients.

En Bloc Keratolimbal Allograft and Central Penetrating Keratoplasty: A Novel Surgical Technique in Severe Limbal Stem Cell Deficiency.

The purpose of this study was to present a novel surgical technique combining 360-degree keratolimbal allograft (KLAL) and simultaneous central keratoplasty termed en bloc KLAL with the central penetrating keratoplasty (PKP) performed in those cases with total limbal stem cell deficiency (LSCD) and corneal scars. Nine eyes of 9 patients underwent en bloc KLAL and central PKP between 2014 and 2016. All patients had bilateral total LSCD with total corneal opacity due to different etiologies. The exclusion criteria were previous limbal stem cell transplantation and the presence of active and uncontrolled ocular surface inflammation. The same donor globe was used for harvesting 360-degree KLAL and central PKP. The 1-piece integrity of the KLAL and PKP graft was preserved during the described technique. All patients received modified immunosuppressive regimens compatible with the Cincinnati solid organ transplantation protocol. The average age of patients was 58.6 ± 18.6 years. The diagnosis was mustard gas keratopathy in 6, herpes simplex keratitis in 1, and severe acid chemical burn in 2 patients. Seven patients were male. An integrated ocular surface without epitheliopathy and a clear cornea was achieved in 8 patients (88.8%) with an average of 6.5 years in follow-up. The average best-corrected visual acuity was 1.89 ± 0.18 (20/1600) preoperatively which improved to 1.02 ± 0.64 (20/200) logMAR in the postoperative period. Endothelial immune rejection episodes were observed in 3 patients. KLAL rejection was not observed in any patient. One patient required repeat PKP due to corneal graft failure. En bloc 360-degree KLAL and central PKP could simultaneously be performed in patients with total LSCD and corneal opacification.

Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice

The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICESaCas9+Ab system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection.

PKHB1 peptide induces antiviral effects through induction of immunogenic cell death in herpes simplex keratitis.

Herpes simplex keratitis (HSK) is a severe, infectious corneal disease caused by herpes simplex virus type 1 (HSV-1) infection. The increasing prevalence of acyclovir resistance, the side effects of hormonal drugs, and the ease of recurrence after surgery have made it crucial to develop new methods of treating HSK. HSV-1 evades the host immune response through various mechanisms. Therefore, we explored the role of the immunogenic cell death inducer PKHB1 peptide in HSK. After subconjunctival injection of PKHB1 peptide, we observed the ocular surface lesions and survival of HSK mice and detected the virus levels in tear fluid, corneas, and trigeminal ganglions. We found that PKHB1 peptide reduced HSV-1 levels in the eye and alleviated the severity of HSK. Moreover, it increased the number of corneal infiltrating antigen-presenting cells (APCs), such as macrophages and dendritic cells, and CD8+ T cells in ocular draining lymph nodes. We further observed that PKHB1 peptide promoted the exposure of calreticulin, as well as the release of ATP and high-mobility group box 1 in HSV-1-infected cells in vitro. Our findings suggested that PKHB1 peptide promoted the recruitment and maturation of APCs by inducing the release of large amounts of damage-associated molecular patterns from infected cells. APCs then phagocytized antigenic materials and translocated to the lymph nodes, triggering a cytotoxic T lymphocyte-dependent immune response that ultimately alleviated HSK.

Keratitis fugax hereditaria ‐ useful to consider when you have a child with non‐specific corneal findings and symptoms

AbstractPurpose: To report clinical findings in children diagnosed with the autosomal dominant periodic corneal autoinflammation, keratitis fugax hereditaria (KFH, MIM 148200), and to highlight its geographical distribution.Methods: Patients were clinically examined in the Helsinki University Hospital between February 4, 2006, and December 31, 2021, and genetically verified to be carriers of the c.61G > C (rs200154873) variant in NLRP3 by Sanger sequencing. Variant allele frequencies were determined from Genome Aggregation Database (gnomAD) version 2.1.1.Results: The data consist of 10 children from 8 families; 6 boys and 4 girls. Age of onset varied from 3 to 14 (median, 8) years. Patients had typical KFH symptoms: eye pain, photophobia, conjunctival injection, and foreign body sensation. Five patients had corneal oval opacities, and 3 had a mild anterior chamber reaction. Seven were correctly diagnosed at the first visit based on family history. The remaining three children were diagnosed 1, 3, and 8 years after the first visit. Initial diagnoses were anterior uveitis, corneal erosion, and herpetic keratitis. Additionally, epithelial recurrent erosion dystrophy (ERED) or subepithelial mucinous corneal dystrophy (SMCD) had been suspected. Geographically, KFH concentrates to the bilingual Swedish‐speaking coastal areas of Finland. Allele frequencies are 0.014% in Finland, and 0.011% in Sweden, based on gnomAD.Conclusions: Scandinavian ophthalmologists should be aware of the possibility of KFH in case of suspected anterior uveitis, herpetic keratitis, or recurrent corneal erosion in children. Symptoms of paediatric KFH patients are equal to those in adults, but the typical corneal opacity still might recover between the attacks.

Antiviral Activity of Oridonin Against Herpes Simplex Virus Type 1.

In search of new potent treatment of herpes simplex keratitis (HSK), inhibitory effect of oridonin (Ori) on herpes simplex virus type 1 (HSV-1) was validated by experiments. For evaluating inhibitory effect of oridonin on herpes simplex virus type 1, a series of in-vivo and in-vitro studies were carried out. Mouse HSV-1 infection model was used in the in-vivo experiments. Experimental mice were classified infivedifferentgroups: Mock (mock-infected), HSV-1+ DMSO, HSV-1+ Ori, HSV-1+ ACV, combined Ori and ACV+HSV-1. Corneas of Mock, HSV-1+ DMSO, HSV-1+ Ori group were sent formRNA-sequencing after 3 days post infection (dpi). The expression of virus and host-related genes was evaluated by quantitative real-time polymerase chain reaction (qPCR). Vero cells HSV-1 infection models were used in the in-vitro experiments. The application of ACV, Oridonin alone or a combination of both could alleviate HSV-1 severity and inhibit HSV-1 virus replication in C57BL/6 mice models. qPCR showed that compared with mock group, the expression of interleukin-6 (il-6), interleukin-1α (il-1α), and Tumor-necrosis factor-alpha (tnf-α) was up-regulated in DMSO+HSV-1 group and suppressed in other three group. Moreover, the expression of nod-like receptor protein (nlrp3), caspase 1 and interleukin-1β (il-1β) were depressed in the oridonin-treated group. Oridonin significantly inhibits HSV-1 replication, HSV-1 related gene expression, and the production of progeny HSV-1 viruses in vitro. Besides, oridonin affect the replication phase but not HSV-1 entry or penetration and cannot inactivate HSV-1. Oridonin alleviates herpes simplex keratitis infection in mouse, which may be attributed to inhibition of the NLRP3-inflammasome-IL-1β pathway. Our study illustrates that Oridonin has potential promise for application in treating HSK and other diseases caused by HSV-1 infection.

The use of anterior segment optical coherence tomography in infectious keratitis

AbstractPurpose: To describe the anterior segment optical coherence tomography (AS OCT) findings in infectious keratitis.Methods: Forty‐five patients with confirmed microbial keratitis were included in this prospective, observational case series study. All subjects underwent ophthalmologic examination. AS OCT scanning was performed on presentation and at follow‐up.Results: 25 patients (55%) had microbial keratitis, 18 patients (40%) had herpetic keratitis and Two patients (4%) had Fungal keratitis. Twelve different patterns were identified. Thirty‐two of the 45 eyes (71%) had epithelial defect associated with sub‐epithelial infiltrates in twenty cases (44%). In 13 of these cases, hydropic changes were observed. Thirty‐six eyes (80%) showed stromal involvement. Stromal infiltrates were also seen, in twenty cases, as a diffuse or local hyper‐reflective area. Five cases (11%) were associated with uveitis: Retrocorneal hyperreflective deposits, thick inflammatory plaque attached to the endothelium and anterior chamber inflammatory cells were imaged.Conclusions: Infectious keratitis has characteristic features on AS‐OCT images. These patterns are not specific and do not orient towards the nature of the microorganisms but AS‐OCT imaging may provide useful supplementary information for diagnosing and monitoring infectious keratitis.

Corneal fine‐needle diathermy with intrastromal and subconjunctival injection of bevacizumab in a child with corneal neovascularization of herpetic origin

AbstractPurpose: Corneal neovascularization (CNV) in the paediatric population has a variety of etiologies including bacterial ulcers, herpes keratitis, exposure keratopathy, blepharokeratoconjunctivitis and corneal anaesthesia. Monotherapy with antiangiogenic agents or corneal fine‐needle diathermy (FND) alone do not completely resolve CNV; however, the combined treatment of these two seems to offer better results.Methods: We present the results of FND with adjuvant injection of intrastromal and subconjunctival Bevacizumab in a child with CNV of herpetic origin.Results: A 3‐year‐old patient who has been treated in our hospital for corneal involvement in the left eye (LE) due to herpetic keratitis of weeks of evolution comes to our consultation. Examination under general anaesthesia reveals in LE an inferior paracentral corneal leukoma with partial involvement of the visual axis and CNV that enters through the limbus from 5 to 8 h and begins to involve corneal stroma; no epithelial lesions, no corneal oedema or inflammatory activity in the anterior segment. After not improvement, it was decided to perform FND of lower CNV in conjunction with an intrastromal injection and another subconjunctival injection of Bevacizumab. Subsequently, it remains stable with topical and oral antiherpetic treatment, and topical corticosteroid therapy. At 3 months, the CNV reactivated, for which FND + intrastromal and subconjunctival bevacizumab was performed again. Finally, at 2 months, the patient is asymptomatic with VA LE of 1.0, with 2 corneal leukomas without CNV or epithelial lesions, and continues to be treated with oral acyclovir at prophylactic doses.Conclusions: FND of CNV together with adjuvant treatment with intrastromal and subconjunctival Bevacizumab is a good choice in children to treat those active corneal neovascularizations that do not respond to corticosteroid.

Current landscape in antiviral drug development against herpes simplex virus infections.

Herpes simplex viruses (HSV) are common human pathogens with a combined global seroprevalence of 90% in the adult population. HSV-1 causes orofacial herpes but can cause severe diseases, such as the potentially fatal herpes encephalitis and herpes keratitis, a prevalent cause of infectious blindness. The hallmark of HSV is lifelong latent infections and viral reactivations, leading to recurrent lesions or asymptomatic shedding. HSV-1 and HSV-2 can cause recurrent, painful, and socially limiting genital lesions, which predispose to human immunodeficiency virus infections, and can lead to neonatal herpes infections, a life-threatening condition for the newborn. Despite massive efforts, there is no vaccine against HSV, as both viruses share the capability to evade the antiviral defenses of human and to establish lifelong latency. Recurrent and primary HSV infections are treated with nucleoside analogs, but the treatments do not completely eliminate viral shedding and transmission. Drug-resistant HSV strains can emerge in relation to long-term prophylactic treatment. Such strains are likely to be resistant to other chemotherapies, justifying the development of novel antiviral treatments. The importance of developing new therapies against HSV has been recognized by the World Health Organization. In this review, we discuss the current approaches for developing novel antiviral therapies against HSV, such as small molecule inhibitors, biopharmaceuticals, natural products, gene editing, and oligonucleotide-based therapies. These approaches may have potential in the future to answer the unmet medical need. Furthermore, novel approaches are presented for potential eradication of latent HSV.