Impact of the use of anti-glaucoma medications on the risk of herpetic keratitis recurrence.

PURPOSE: Numerous case reports have associated anti-glaucoma medications with recurrence of herpes simplex virus (HSV) and herpes zoster virus (HZV) keratitis. The aim of our study was to determine whether different anti-glaucoma agents are associated with recurrence of herpetic keratitis. METHODS: This was a retrospective cohort study using health databases from a Canadian province from January 2001 to December 2012. A new cohort of users on topical prostaglandins (PGs), beta blockers (BBs), alpha-2 agonists (AAs) and carbonic anhydrase inhibitors (CAIs) was created. The date of the third anti-glaucoma drug dispensation within 90 days was deemed the index date of the case. Herpetic keratitis events, as defined by an ICD-9/10 code for HSV or HZV keratitis, or the dispensation of an anti-viral medication by either an ophthalmologist or an optometrist, were examined prior to and following the index date. Risk ratios (RRs) were computed to compare the risk of HSV/HZV keratitis among the PG, BB, AA, and CAI groups individually and collectively while adjusting for age and sex. RESULTS: Among 19,986 users of glaucoma medications identified, there were 684 cases of HSV/HZV keratitis. There was no increased risk of HSV/HZV keratitis recurrence for any of the four glaucoma medications classes individually or collectively when adjusted for age and sex. There was also no increased risk for redeveloping either HSV keratitis only or HZV keratitis only amongst all anti-glaucoma users. CONCLUSION: There is no association between the use of topical ocular hypotensive therapies and HSV/HZV keratitis recurrence. Further studies are needed to confirm these findings.

[Ocular manifestations of herpes simplex viruses]. / Atteintes oculaires liées aux virus herpes simplex.

Ocular manifestations of herpes simplex virus are mostly caused by herpes simplex (HSV-1), and are the second most frequent clinical manifestation of HSV-1 after cold sore. Corneal involvement, known as herpetic keratitis is by far the most frequent: in France, it affects 90,000 people with nearly 20,000 attacks each year. Herpes keratitis is considered to be the leading cause of infectious blindness in industrialized countries. In addition to its visual consequences, this recurrent disease may severely impact the quality of life. This review will first focus on current pathophysiological concepts and epidemiological data, then detail clinical forms and their treatment and finish with new therapeutic challenges and developing therapeutic strategies.

The Role of C21orf91 in Herpes Simplex Virus Keratitis.

Background and Objectives: This paper aims to describe the single nucleotide polymorphisms (SNPs) of C21orf91 rs1062202 and rs10446073 in patients with herpetic keratitis by evaluating corneal sub-basal nerves, as well as the density of Langerhans cells (LC) and endothelium cells (EC) during the acute phase of the disease. Materials and Methods: A prospective clinical study included 260 subjects: 70 with herpetic eye disease, 101 with previous history of herpes labialis-but no history of herpetic eye disease-and 89 with no history of any herpes simplex virus (HSV) diseases. All subjects underwent a complete ophthalmological examination including in vivo laser scanning confocal microscopy (LSCM) of the central cornea. C21orf91 rs1062202 and rs10446073 were genotyped using the real-time polymerase chain reaction (PCR) method with the Rotor-Gene Q real-time PCR quantification system. SNPs were determined using TaqMan genotyping assay, according to the manufacturer's manual. Results: The C21orf91 rs10446073 genotype GT was more frequent in the HSV keratitis group, compared with healthy controls (20.0% vs. 7.9%), OR 2.929[1.11-7.716] (p <0.05). The rs10446073 genotype TT was more frequent in healthy controls (12.4% vs. 1.4%), OR 22.0[2.344-260.48] (p <0.05). The rs10446073 genotype GT increased the risk of EC density being less than 2551.5 cell/mm2, OR 2.852[1.248-6.515] (p <0.05). None of the SNPs and their genotypes influenced the LC density and corneal sub-basal nerve parameters (p >0.05). Conclusions: Our study reports a new association between herpetic keratitis and human gene C21orf91, with the rs10446073 genotype GT being more common in herpetic keratitis patients and increasing the risk for the disease by a factor of 2.9.

Appearance of herpes simplex keratitis on anterior segment optical coherence tomography.

PURPOSE: To describe the anterior segment AS-OCT findings of herpetic simplex keratitis. METHODS: Forty-two eyes of 42 patients with proven herpetic keratitis of varying severity were included in this prospective, observational, non-comparative case series study. All subjects underwent ophthalmologic examination and AS-OCT imaging. RESULTS: Twenty-five of the 42 eyes (59.5%) had sub-epithelial infiltrates. In 11 of these cases, the overlying epithelium appeared intact, but in 14 cases, hydropic changes, heaping, and defects were observed. Seventeen eyes (40.5%) showed stromal involvement: six cases with scar at presentation and one case associated with uveitis. Stromal infiltrates were also seen, in ten cases, as a diffuse or local lentiform or spindle-shaped hyper-reflective area in the stroma. CONCLUSION: Herpetic keratouveitis has characteristic features on AS-OCT images. This study demonstrates that herpetic keratitis also has characteristic AS-OCT features, including sub-epithelial infiltration and specific stromal hyper-reflective patterns. These features are not unique to herpetic keratitis, but AS-OCT imaging may provide useful supplementary information for diagnosing and monitoring herpetic keratitis.

[The role of infection foci in the onset and sustenance of inflammatory diseases of the eye]. / Rol' fokal'nykh ochagov infektsii v vozniknovenii i podderzhanii vospalitel'nykh zabolevanii glaz.

Numerous clinical observations indicate the importance of the role of 'focal sepsis' in the development and facilitation of inflammation in the anterior eye segment. The article describes possible routes of infection spread from various local foci to the eye. Studying the connection between local infection foci and inflammatory eye diseases will give ophthalmologists more opportunities for effective treatment and prevention of disease recurrences.

[The linkage of oral infection foci and inflammatory diseases of the eye]. / Vzaimosviaz' fokal'nykh odontogennykh ochagov infektsii i vospalitel'nykh zabolevanii glaza.

The paper presents a review of numerous clinical observations that indicate an important role of 'focal sepsis' in the development and persistence of the anterior eye segment inflammation. Possible routes of infection spread from local dental infectious foci to the eye are discussed.

Could polymerase chain reaction tests on conjunctival swabs be useful to diagnose herpetic keratitis?

INTRODUCTION: Diagnosis of HSV-1 keratitis (HK) is frequently based on clinical findings. Invasive specimens (corneal scrapings, biopsies) are required for microbiological diagnosis. METHODS: Corneal scrapings and conjunctival swabs were collected on patients with/without clinical suspicion of HK from 2007 to 2012. RESULTS: The sensitivity, specificity, positive and negative predictive values for conjunctival swabs by PCR was 77.8, 92.1, 84.4 and 88.3, respectively. DISCUSSION: Conjunctival swabs by PCR may help in the diagnosis of HK, despite the limited sensitivity.

Herpetic Keratitis Following Treatment of Acute Antibody-Mediated Rejection in a Renal Transplantation Recipient.

We report an incident case of herpetic keratitis in a renal transplant recipient treated for acute renal allograft rejection. A lady in her forties, a renal transplant recipient on treatment for allograft rejection, was referred with mild ocular symptoms in the right eye for two days. On evaluation, she had mild conjunctival hyperemia and extensive herpetic epithelial keratitis involving the limbal and central corneas. The patient healed without sequelae from the antivirals and lubricants. Viral keratitis in immunosuppressed patients should be suspected, even in patients with mild symptoms, as early initiation of treatment can prevent rapid stromal involvement and scarring.

Chronic inflammation as a proposed risk factor for ocular surface squamous neoplasia.

PURPOSE: Chronic inflammation is a predisposing factor for metaplastic changes and ultimately dysplasia. We describe cases of OSSN occurring in the setting of chronic ocular surface inflammation. METHODS: Sixteen eyes from 14 individuals were included from one ocular oncology clinic between 2010 and 2023. Patients presented with ocular surface squamous neoplasia (OSSN) in the setting of chronic inflammation. The diagnosis of OSSN was made using anterior segment high-resolution optical coherence tomography (HR-OCT) and confirmed by histopathological analysis in all cases. RESULTS: Median age on presentation was 61 [IQR 47.5-69.2] years. Eleven (86%) individuals were male and five (36%) identified as White Hispanic. Ten eyes were referred with ocular surface diagnoses including pannus (n = 4), scarring (n = 3), pterygium (n = 2), and herpetic keratitis (n = 1). Only six eyes were referred as possible neoplasia. All individuals had a history of ocular surface inflammation. The most common inflammatory conditions were ocular rosacea (seven individuals) and atopic keratoconjunctivitis (AKC) (five individuals). Two individuals were found to have bilateral OSSN, one in the setting of ocular rosacea and the other in the setting of AKC. All 16 eyes from 14 individuals were suspected to have OSSN based on HR-OCT findings which guided the location of the incisional biopsies that subsequently confirmed histopathological diagnosis in all cases. CONCLUSION: OSSN may arise in the setting of chronic inflammation on the ocular surface. Identification of the tumor can be challenging in these cases, and HR-OCT can be a key diagnostic tool in detecting OSSN.

Neurotrophic Keratopathy and Topical Insulin Therapy: A Case Report.

Neurotrophic keratopathy is a rare disorder caused by the loss of corneal sensation. It is characterized by persistent epithelial defects, corneal ulceration, and, ultimately, corneal perforation if not managed in a timely manner. The management includes aggressive lubrication, prophylactic topical antibiotics, therapeutic contact lenses, tarsorrhaphy, and amniotic membrane transplantation. Some novel therapeutic options are also available, one of which is topical insulin therapy. We report the clinical course of a patient with neurotrophic keratopathy that was successfully treated with topical insulin. A 64-year-old male presented to our outpatient department with a three-month history of painless blurring of vision following prior episodes of herpetic keratitis. Ocular examination showed a bilateral reduction in corneal sensations, bilateral corneal opacities, and a corneal ulcer in the left eye. He was diagnosed as a case of neurotrophic keratopathy secondary to prior herpetic keratitis. He was then treated with topical and oral acyclovir along with topical insulin drops. There was a remarkable improvement in his condition after a month with a reduction in the size of the ulcer and, after two months, the ulcer was completely re-epithelialized. This case report illustrates the use of topical insulin in the initial management of neurotrophic keratopathy as opposed to its conventional use in refractory neurotrophic corneal ulcers.

Clinical Characterization and Outcomes of Culture- and Polymerase Chain Reaction-Negative Cases of Infectious Keratitis.

PURPOSE: To examine the clinical presentation, management, and outcomes of culture and polymerase chain reaction (PCR) negative cases of infectious keratitis. METHODS: In this retrospective case series, we evaluated the laboratory and medical records of culture- and PCR-negative cases (2016-2020) reported to a tertiary care center, which were presumed to be infectious keratitis on the basis of clinical history and presentation. RESULTS: A total of 121 cases with culture-negative keratitis were included in this study. The mean age of the patients was 48.42 ± 1.89 years, and 53.72% were female. At presentation, the presumed etiology was viral in 38.01%, bacterial in 27.27%, fungal in 8.26%, Acanthamoeba in 6.61%, and unlisted in 28.92% of cases. The most common risk factors were a previous history of ocular surface diseases (96.69%) and contact lens use (37.19%). In total, 61.98% of the patients were already on antimicrobial medication at presentation. The initial management was altered in 79 cases (65.29%) during the treatment course. Average presenting and final (post-treatment) visual acuities (VA) were 0.98 ± 0.04 (LogMAR) and 0.42 ± 0.03 (LogMAR), respectively. A significantly higher frequency of patients with a final VA worse than 20/40 (Snellen) had worse VA at initial presentation (p < 0.0001). A history of ocular surface disease, cold sores, and recurrent infection (p < 0.05) were more commonly associated with a presumed diagnosis of viral keratitis. The patients with presumed bacterial etiology were younger and had a history of poor contact lens hygiene (p < 0.05). CONCLUSIONS: We observed a distinct difference in clinical features among patients with culture-negative and PCR-negative keratitis managed for presumed viral and bacterial infections. Although there was significant variability in presentation and management duration in this cohort, the visual outcomes were generally favorable.

Frequency and visual outcomes of herpes simplex keratitis in a Kuwaiti tertiary referral center.

Background: Herpes simplex virus (HSV), a cause of many ocular pathologies, may affect the corneal epithelium, stroma, or endothelium, with the epithelium as the most frequently affected location. We aimed to determine the frequency and visual outcomes of HSV keratitis over a 1-year period at Farwaniya Hospital, Kuwait. Methods: This prospective observational case series included patients diagnosed with HSV keratitis who presented to the outpatient or eye casualty department between September 2022 and September 2023. Full history, demographic profile, detailed ocular and slit-lamp examinations, and visual acuity assessments were recorded prior to and after treatment. Baseline corneal sensation was assessed in the four corneal quadrants using the cotton wisp test. Results: Of the 227 patients who presented with infectious keratitis, 72 (31.7%) were diagnosed with HSV keratitis. The mean (SD) age was 45.86 (16.06) years, and 48 (66.7%) patients were male. The subtypes of HSV keratitis were endotheliitis in 27 (37.5%) patients, dendritic ulcer in 22 (30.6%), stromal keratitis with ulceration in 9 (12.5%) and without ulceration in 8 (11.1%), and geographic ulcer in 6 (8.3%). The mean baseline best-corrected distance visual acuity (BCDVA) differed significantly between the HSV keratitis subtypes (P < 0.001). Most patients (n = 70, 97.2%) had unilateral eye involvement, were treated within 1 - 2 weeks, and demonstrated improved BCDVA. Despite the improvement in BCDVA in all HSV keratitis subtypes, a significant difference in the median BCDVA remained after treatment (P < 0.001). Pairwise comparisons revealed a significantly better BCDVA after treatment in eyes with dendritic epithelial ulcers than in eyes with HSV stromal keratitis with ulceration (P = 0.003) or geographic epithelial ulcers (P = 0.005). After treatment, corneal haze and neovascularization were detected in 54 (75.0%) and 24 (33.3%) patients, respectively. Conclusions: We detected a substantial frequency of HSV keratitis in one of the governorates of Kuwait, with endotheliitis as the most common manifestation. Timely standard treatment interventions based on valid guidelines resulted in BCDVA improvement in all subtypes of HSV keratitis in our series, indicating the importance of early treatment. However, the BCDVA in eyes with dendritic epithelial ulcers remained substantially better than that in eyes with geographic epithelial ulcers or HSV stromal keratitis with ulceration, signifying the effect of the initial HSV keratitis subtype on visual outcomes. To our knowledge, this is the first study to highlight the frequency of HSV keratitis in a Kuwaiti hospital, and larger-scale research in this region is needed to further understand and manage the condition.

Putting drug resistant epithelial herpes keratitis in the spotlight: A case series.

PURPOSE: To strengthen the sparse evidence on acyclovir (ACV) resistance, especially in recalcitrant herpetic keratitis (HK), by describing the clinical course of 3 genotypically proven ACV resistant HK cases. An overview of mechanisms of resistance and therapeutic options currently available to ophthalmologists is provided based upon recent literature search. OBSERVATIONS: Resistance to ACV due to known mutations in the gene encoding the viral thymidine kinase was confirmed in 2 cases, and a novel mutation in the UL23 gene (N202K) conferring phenotypical resistance to ACV was discovered in 1 case. Three unique therapeutic strategies finally led to epithelial closure. CONCLUSIONS: The novel thymidine kinase mutation (N202K) should be considered to infer resistance to all molecules requiring activation by the viral thymidine kinase. Current topical alternatives in the ophthalmologist's armamentarium include trifluridine 1%, foscarnet 1,2%-1,4% or cidofovir 0,2-0,5%. Epithelial debridement, high-frequency dosing and reduction of immunosuppression are useful adjuncts. IMPORTANCE: Clinicians should perform epithelial debridement in recalcitrant HK, allowing geno- and phenotypically guided therapy, even without a history of long-term anti-viral prophylaxis or recurrent HK. This report provides mandatory knowledge allowing the reader to comprehend how therapy should be altered based upon these results. To the best of our knowledge, successful treatment of proven ACV resistant HK with topical foscarnet has not yet previously been published.Furthermore, this paper highlights a lack of controlled studies investigating alternative topical treatments in case of viral resistance, offering opportunities for future research.

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.

Herpetic endotheliitis and stromal keratitis following inactivated COVID-19 vaccination.

Given the scarcity of data regarding ocular complications following COVID-19 vaccination, the approach toward patients with suggestive symptoms and established clinical practice is lacking. Herein, we report the first case of herpetic endotheliithis and secondary stromal keratitis following inactivated COVID-19 vaccination who experienced a relapse due to poor adherence.

A Case of Herpetic Keratitis in an Orthokeratology Contact Lens Wearer.

We report a case of herpetic keratitis in an orthokeratology lens wearer. A 17-year-old man who wore an overnight orthokeratology lens for correction of myopia presented to our hospital with pain, lacrimation, and blurred vision affecting the left eye. His corrected visual acuity decreased to 18/20, and he showed dendrites and decreased corneal sensitivity in the left eye. The herpes simplex virus (HSV) immunochromatographic assay kit for the diagnosis of herpes epithelial keratitis was positive. As these findings were suggestive of HSV keratitis, topical acyclovir ointment was administered five times daily. All findings disappeared and visual acuity recovered to 20/20 at 14 days after the first visit. Herpetic keratitis rarely develops in orthokeratology lens wearers as well as contact lens (CL) wearers, although Acanthamoeba keratitis is sometimes erroneously diagnosed as herpetic keratitis in CL wearers with dendrites.

Herpes simplex virus PCR in 2230 explanted corneal buttons.

PURPOSE: To determine herpes simplex virus (HSV) DNA prevalence and mean cycle threshold of polymerase chain reaction (PCR) in corneal tissue of patients with penetrating keratoplasty (PKP), with (HSK+) and without (HSK-) previous clinical herpetic keratitis history. METHODS: Retrospective review of recipient corneal buttons which were explanted through PKP between March 2010 and September 2018 at the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar, Germany. Corneal tissue samples were analysed by real-time PCR for the presence of HSV DNA. For each subject, clinical data, including patients' demographics and clinical diagnoses, were collected. RESULTS: In total, 2230 corneal samples (age at the time of the surgery 57.3 ± 19.2 years) of 1860 patients were analysed. HSV PCR was positive in 137 (6.1%) corneal samples, with a 30.57 ± 6.01 (range 14-39) mean cycle threshold (Ct) value. Two hundred ninety-eight (13.4%) corneas of 266 patients were clinically HSK+, and 1932 (86.6%) corneas of 1600 patients were clinically HSK-. HSV DNA was detected significantly more frequently (p < 0.0001) in HSK+ corneal samples (108 corneal samples; 36.2%), than in HSK- corneal samples (29 corneal samples; 1.5%). Ct value was significantly lower in HSK+ than in HSK- corneal samples (29.8 ± 5.8 versus 32.6 ± 5.9; p = 0.008). CONCLUSION: Our data demonstrate that a positive clinical history of HSK is related to HSV PCR positivity in about every 2.8th patient. In addition, about every 66th explanted corneal tissue is HSV PCR-positive despite the lack of clinical suspicion. These patients may need additional local/systemic antiviral treatment to avoid newly acquired HSK following penetrating keratoplasty.

Is COVID-19 Infection a Trigger for Herpetic Stromal Keratitis?

In June 2020, a 28-year-old female patient was admitted to our clinic with reduced vision in the left eye. She had systemic COVID-19 infection in May 2020 and during her treatment course, her visual complaints had begun approximately 1 week after the beginning of the COVID-19. Previously, the patient had bilateral femtosecond assisted - Laser in situ Keratomileusis in our clinic in 2018. There was no previous history of herpetic eye involvement. In her examination, the uncorrected visual acuity was 20/20 in the right and 20/32 in her left eye. Slit-lamp examination revealed interlamellar infiltration at the flap interface in the left eye. Considering herpetic activation, ganciclovir ointment 5 × 1, valacyclovir tablet 2 × 1, and prednisolone acetate 1.0% eye drops 5 times a day and artificial tear 5 × 1 were started. Two weeks later, the infiltration completely resolved and the uncorrected visual acuity increased to 20/20.

Herpetic Keratitis Following Corneal Crosslinking for Keratoconus: A Case Series.

Background: Corneal crosslinking is widely applied to enhance corneal biomechanical properties and delay the progression of keratoconus. The surgical procedure and application of ultraviolet A irradiation (UVA) during corneal crosslinking have been recognized to induce the reactivation of simplex herpes virus (HSV) but are rarely reported and poorly analyzed. Case Presentation: We report the first case series of herpetic keratitis in 4 keratoconus patients undertaking corneal crosslinking, who were all clinically diagnosed at routine follow-up visits 3 days to 1 month after the surgery. Different from the typical new onset of secondary herpetic keratitis that mainly presents with epithelial lesions and severe eye pain, these patients all presented with stromal infiltrates and were generally asymptomatic except for vision blurring in 2 patients. All patients responded well to antiviral therapy, topical steroids, and epithelial nourishment medication, leaving corneal macula or nebula at the last follow-up visit. Conclusion: Close follow-up is essential and the most effective way to diagnose herpetic keratitis after corneal crosslinking due to the lack of subjective symptoms. The prophylactic use of antiviral therapy on asymptomatic patients is controversial and should be evaluated based on long-term prognosis.