Search Results (32)

Background and Clinical Significance: Acanthamoeba keratitis (AK) is a rare but serious corneal infection that can lead to severe visual impairment or blindness if not promptly treated. The condition is primarily associated with contact lens use but can also occur due to ocular trauma or environmental contamination. The most frequently used treatment options include biguanides and diamidines, though dosing protocols remain empirical and vary widely among clinicians. Recent research has explored a new standardized protocol with 0.08% polihexanide (polyhexamethylene biguanide, PHMB) as a monotherapy for AK, offering improved efficacy and better corneal penetration. Case Presentation: This case report describes a 35-year-old female contact lens wearer who presented with redness, pain, photophobia, and vision loss in her right eye. Upon referral, a slit-lamp examination revealed stromal infiltrates and perineural involvement, with in vivo confocal microscopy (IVCM) confirming Acanthamoeba cysts. The patient was treated with a new standardized intensive regimen of polihexanide 0.08% monotherapy, leading to rapid clinical improvement. Corneal infiltrates were significantly reduced, and the best-corrected visual acuity (BCVA) improved from 0.4 logMAR to 0.15 logMAR. Resolution with only discrete stromal haze was achieved over the following months, without recurrence. Conclusions: This case highlights the potential of polihexanide 0.08% monotherapy as an effective treatment for AK in a new standardized treatment protocol. Full article

(1) Introduction: The main way of spreading the herpes simplex virus 1 (HSV-1) is through direct contact, as the virus enters the host via mucous membranes. Ocular infection can occur as a primary infection or as a recurrent one. The movement of HSV-1 along the ophthalmic branch of the fifth cranial nerve from its latency phase in the trigeminal ganglion and its activation represent a process influenced by various symbiotic factors, such as environmental conditions and the host’s genetic characteristics. The aim of this study was to assess the frequency of IL28 (rs12980275) and (rs8099917) in recurrent ocular HSV infections. (2) Materials and methods: The study included 60 patients aged over 18, of both sexes, all of whom had a history of herpes simplex labialis (HSL). Patients were tested for HSV-1-specific IgG antibodies, and seropositive individuals were genotyped for single nucleotide polymorphisms (SNPs) rs12980275 and rs8099917. A total of 57 seropositive patients were included in the study. (3) Results: A statistically significant association was found between recurrent HSV keratitis (HSK) and heterozygous GT rs8099917 and homozygous TT rs8099917, as well as heterozygous AG rs12980275 and homozygous AA rs12980275 (p < 0.01). Interestingly, patients with homozygous GG polymorphism for both genotypes GG rs8099917 and GG rs12980275 did not develop recurrent HSV keratitis. (4) Conclusion: The most frequent SNP variations in patients with recurrent HSV disease were heterozygous AG rs12980275 (61.40%) and heterozygous GT rs8099917 (52.63%). Patients with recurrent HSV keratitis lacked the homozygous GG polymorphism in both GG rs8099917 and GG rs12980275 genotypes, suggesting that HSV-seropositive individuals expressing these genotypes may have lower predisposition to develop recurrent stromal HSV keratitis. Full article

Objectives: Anterior Segment Optical coherence tomography (AS–OCT) can help in the diagnosis and treatment of infectious keratitis, but it has not been studied in cases occurring after corneal refractive surgery procedures such as femtosecond laser in situ keratomileusis (FS–LASIK) and keratorefractive lenticule extraction (KLEx). In these procedures, a surgical interface is created, where infections usually start, thus determining a different AS–OCT pattern compared to non–surgical infections, which begin on the corneal surface. Methods: We retrospectively reviewed 22,756 eyes of 13,564 patients who underwent FS–LASIK and KLEx at our surgical center. Results: Four cases of post–refractive surgery infectious keratitis were included (two after FS–LASIK and two after KLEx), in which the AS–OCT identified an initial infiltrate in the interface, followed by interface inflammation. In one case, after FS–LASIK, interface fluid accumulation occurred. In one case, after KLEx, diffuse interface inflammation led to stromal reabsorption, later compensated by stromal reformation and epithelial hyperplasia, well documented by OCT. Conclusions: AS–OCT represents a useful tool for assessing corneal infections after refractive surgery, guiding the treatment, and evaluating the healing process and residual corneal scarring. Full article

Purpose: To review the clinical features, risk factors, microbiological profile, and treatment regimens of fungal keratitis in Galicia, a region in Northwestern Spain with temperate humid weather. Patients and methods: A retrospective case series was employed, including patients with fungal keratitis from nine hospitals within the region of Galicia, Spain, between 2010 and 2020. Data obtained from clinical records were analysed. Results: Out of 654 cases of infectious keratitis, 77 cases (9.9%) were identified as fungal keratitis. The median age of affected patients was 68.0 years, with a higher incidence in rural areas (62.3%). Candida spp. infections were the most frequent type (55.8%) and were associated with a higher median age than were the non-dermatophyte mould infections. The primary risk factors included steroid eyedrop use (29.9%), recent keratoplasty (18.2%), ocular trauma (19.5%), and contact with vegetable matter (11.7%). Most ulcers displayed stromal involvement, and 37.7% presented corneal thinning. The median duration of infection was longer in fungal than in bacterial keratitis, and surgical intervention was required in 48.1% of cases. Conclusions: Fungal keratitis, mainly involving Candida spp., accounted for 9.9% of microbial keratitis cases in Galicia, Spain, with significant risk factors being topical steroid use, ocular trauma, and contact with vegetable matter. Delayed diagnosis often resulted in poor outcomes, highlighting the need for early detection through awareness and new technologies to improve prognosis. Full article

Background: Mooren’s ulcer (MU) is a rare and debilitating form of peripheral ulcerative keratitis (PUK), characterized by a crescent-shaped ulcer with a distinctive overhanging edge at the corneal periphery. If left untreated, MU can lead to severe complications such as corneal perforation and blindness. Despite various treatment approaches, including anti-inflammatory and cytotoxic drugs, as well as surgical interventions, there is no clear evidence of the most effective treatment due to the lack of randomized controlled trials. AS-OCT is a non-invasive imaging technique that provides high-resolution cross-sectional images of the anterior segment, allowing for accurate evaluation of corneal ulcer characteristics, including depth, extent, and disease progression. Methods: We present the case of a 20-year-old male patient with MU managed using a stepladder approach, which included local and systemic corticosteroids, limbal conjunctival resection, and Cyclosporine A 1% eye drops. The patient underwent consecutive AS-OCT examinations and strict follow-up to tailor systemic and topical therapy. Results: Complete healing of the corneal ulcer with resolution of the inflammatory process was achieved. There was no recurrence of the disease at the 7-month follow-up. AS-OCT demonstrated progressive reorganization and thickening of the stromal tissue until the complete recovery of stromal thickness. Conclusions: The AS-OCT imaging modality allowed for the accurate evaluation of corneal ulcer characteristics, facilitating informed decision-making regarding the use of systemic immunosuppression, surgical interventions, and local immunomodulation and providing detailed and precise assessment of disease progression. This approach enabled a tailored and effective treatment strategy for the patient and played a critical role in guiding the therapeutic approach. Full article

Herpes simplex virus (HSV) is one of the most common etiologic agents of corneal disease and a significant cause of corneal blindness worldwide. Although most cases can be successfully managed with medical therapy, HSV keratitis associated with visually significant stromal scarring often requires corneal transplantation for visual rehabilitation. While penetrating keratoplasty (PK) represented the traditional keratoplasty technique, the past few decades have seen a shift towards lamellar keratoplasty procedures, including deep anterior lamellar keratoplasty and mushroom keratoplasty. This paper describes the current surgical techniques and perioperative antiviral prophylaxis regimen for herpetic keratitis and reviews their postoperative clinical outcomes. Full article

CD80 is the best-known costimulatory molecule for effective T cell functions. Many different reports have summarized the role of CD80 in HSV-1 and its functions in maintaining adaptive immunity, which is the main player in causing herpes stromal keratitis (HSK). To determine the effects of absence or overexpression of CD80 in HSV-1 infection, we infected CD80^-/- and WT mice with a recombinant HSV-1 expressing murine CD80 (HSV-CD80) in place of the latency associated transcript (LAT). Parental dLAT2903 virus lacking LAT was used as a control. After infection, critical components of infection like virus replication, eye disease, early cellular infiltrates into the corneas and trigeminal ganglia (TG), latency-reactivation in the infected mice were determined. Our findings reveal that the absence of CD80 in the CD80^-/- mice infected with both viruses did not affect the viral titers in the mice eyes or eye disease, but it played a significant role in critical components of HSV-induced immunopathology. The WT mice infected with dLAT2903 virus had significantly higher levels of latency compared with the CD80^-/- mice infected with dLAT2903 virus, while levels of latency as determined by gB DNA expression were similar between the WT and CD80^-/- mice infected with HSV-CD80 virus. In contrast to the differences in the levels of latency between the infected groups, the absence of CD80 expression in the CD80^-/- mice or its overexpression by HSV-CD80 virus did not have any effect on the time of reactivation. Furthermore, the absence of CD80 expression contributed to more inflammation in the CD80^-/--infected mice. Overall, this study suggests that in the absence of CD80, inflammation increases, latency is reduced, but reactivation is not affected. Altogether, our study suggests that reduced latency correlated with reduced levels of inflammatory molecules and blocking or reducing expression of CD80 could be used to mitigate the immune responses, therefore controlling HSV-induced infection. Full article

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20–25% for the general adult population. The infections caused by these viruses remain difficult to study because a large proportion of infected individuals are asymptomatic. Furthermore, given the neurotropic characteristics of the virus, studies aimed at understanding the complex pathogenesis in humans is difficult. As a result, animal models have been developed to understand several characteristics of HSV biology, pathogenesis, disease and host responses to infection. These models are also commonly used as the first evaluation of new drugs and vaccines. There are several well-established animal models to study infection with HSV, including mice, guinea pigs and rabbits. Variables within the animal models depend on the species of animal, route of infection, viral strain, dosage, etc. This review aims at summarizing the most commonly used animal models to study HSV pathogenesis and therapies. Full article

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon^® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon^® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans. Full article

Background and Objectives: Herpes simplex keratitis (HSK) is the leading infectious cause of corneal damage and associated loss of visual acuity. Because of its frequent recurrence, it represents a major health problem; thus, timely and accurate diagnosis is the key to successful treatment. To enable this, we aimed to determine HSK patients’ demographic and clinical features. Materials and Methods: This prospective study included 55 patients diagnosed with HSK between March 2019 and August 2022 at the Department of Ophthalmology, Clinical Hospital Rijeka. Results: We found that HSK is most prevalent in the elderly, with 72.73% of patients older than 60. The most common HSK types were dendritic (HSK-D; 43.64%) and stromal with epithelial ulceration (HSK-SEU 23.64%). HSK recurrences occurred in 65.45% of patients, with most having two to five recurrences (55.56%). Visual acuity at presentation (65.5%) and after treatment (50.9%) was mostly in the 20/50 range. The longest period until the disease symptoms were resolved was in the group with stromal HSK without epithelial ulceration (HSK-SnEU), for which symptoms lasted more than 11 weeks in 87.5% of patients. The overall incidence of HSK-related complications was high (85.45%), with 76.4% of patients having corneal scarring. The average time from symptom to treatment was 15.78 days. Interestingly, we observed a strong seasonality in the incidence of HSK, which was most prevalent in the colder months, with 63.6% of cases occurring between October and March. Conclusions: To the best of our knowledge, this is the first prospective study in Croatia, and one of the few in Europe, to describe the demographic and clinical features of HSK patients. We found that HSK is most common in the elderly population, with its dendritic form as a clinical presentation. We have shown that HSK is prone to recurrence and secondary complications, with a worryingly long time between symptom and treatment, indicating the need for diagnostic testing in routine practice. Full article

Background: Beauveria bassiana is a filamentous fungus commonly used as an insecticide that rarely causes keratitis. Methods: Patients affected by Beauveria bassiana keratitis were retrospectively recruited at San Raffaele Hospital (Milan, Italy) between 2020 and 2022. All subjects underwent comprehensive ophthalmic evaluation, including in vivo confocal microscopy (IVCM) and microbiologic examination of corneal scrapings. Beauveria bassiana was identified using 18S rDNA targeted PCR. Results: Four eyes of four patients (51 ± 8.8 years old) were evaluated. The main risk factors were soft contact lens wear (75%) and trauma with vegetative matter (50%). A superficial infiltrate was displayed in the majority of patients. Three cases (75%) showed hyphae on IVCM. All patients showed clinical improvement after topical antifungal therapy, although mostly through a combination of two antifungals (75%). One patient with a deeper infection required a systemic antifungal agent after one month of topical therapy. All cases required debridement to reduce the microbial load and enhance drug penetration. All patients experienced keratitis resolution following medical treatment (average: 3.3 months). Conclusions: The identification of risk factors and the early diagnosis of Beauveria bassiana keratitis are fundamental in order to avoid its penetration in the deeper corneal stromal layers. Topical antifungal drugs, possibly accompanied by ulcer debridement, may be a successful treatment if instilled from the early phases of the disease. Full article

Purpose: The purpose of this paper is to report the clinical manifestations, diagnostic evaluation, management and outcomes of microsporidial keratitis in post-keratoplasty eyes. Methods: This is a retrospective review of three patients diagnosed with microsporidial stromal keratitis in post-keratoplasty eyes between January 2012 and December 2021 at a tertiary referral center (Ospedali Privati Forlì “Villa Igea”, Forlì, Italy). Results: All patients presented with fine multifocal granular infiltrates following keratoplasty for a presumed herpetic keratitis. No microorganisms were isolated from the corneal scrapings and no clinical response was observed with broad-spectrum antimicrobial therapy. In all cases, confocal microscopy demonstrated spore-like structures. The histopathologic examination of the excised corneal buttons confirmed the diagnosis of microsporidial stromal keratitis. Following therapeutic keratoplasty and treatment with an initial high dose and extended taper of topical fumagillin, clinical resolution was achieved in all eyes. The Snellen visual acuities at the final follow-up were 20/50, 20/63 and 20/32. Conclusions: Prior to definitive surgery, confocal microscopy can be employed for the in vivo detection of pathogenic microorganisms such as Microsporidium. In post-keratoplasty eyes, therapeutic keratoplasty and an initial high dose of topical fumagillin with extended taper can allow the resolution of microsporidial stromal keratitis with a satisfactory visual prognosis. Full article

Infectious keratitis is a major global cause of vision loss and blindness. Prompt diagnosis and targeted antibiotic treatment are crucial for managing the condition. Topical antimicrobials are the most effective therapy for bacterial keratitis, but they can lead to unsatisfactory results due to ocular perforation, scarring, and melting. Intrastromal injection is a newer technique for delivering antimicrobials directly to the site of infection and has been successful in treating severe, treatment-resistant infectious keratitis, especially when surgery is not recommended. In cases where deep stromal disease is resistant to topical treatment, intrastromal antimicrobial injections may be necessary to achieve higher drug concentration at the infection site. However, the use of intrastromal antibiotics is limited, as topical antibacterial agents have better penetration than antifungal agents. Bacterial and fungal keratitis have been extensively researched for intrastromal medication injections, while there is limited evidence for viral keratitis. This review emphasizes the potential of intrastromal antimicrobial injections as an alternative for managing severe refractory infectious keratitis. The technique offers direct targeting of the infection site and faster resolution in some cases compared to topical therapy. However, further research is needed to determine the safest antimicrobials options, minimal effective doses, and concentrations for various pathogens. Intrastromal injections may serve as a non-surgical treatment option in high-risk cases, with benefits including direct drug delivery and reduced epithelial toxicity. Despite promising findings, more studies are required to confirm the safety and efficacy of this approach. Full article

The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 °C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased significantly by the value of 0.3% compared to previous weeks. In all of the cases, the TPU/PLA doped with 12 mg of the CsA platform effectively reduced the clinical symptoms of keratitis, leading to the complete remission of the corneal opacity and infiltration four weeks post-injection. The results from this study showed that the PLDLA/TPU matrix enriched with the CsA platform was well tolerated by the equine model and effective in treating superficial and mid-stromal IMMK. Full article

Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host’s life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host’s innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/β) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses. Full article