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Herpetic keratitis (HK) is characterized by a wide spectrum of corneal lesions, ranging from superficial epithelial to deep endothelial and stromal involvement. Each lesion type correlates with distinct pathogenetic mechanisms involving viral replication, inflammatory responses, and immune dysregulation.

1. Epithelial Keratitis: Role of Viral Replication

Epithelial keratitis is the earliest and most common corneal involvement in herpetic infection, caused by active replication of herpes simplex virus within epithelial cells.

Pathogenesis:

1. Viral Entry:

– HSV infects the corneal epithelium by binding to cellular receptors such as nectin-1 and HVEM (herpesvirus entry mediator). Upon entry, viral DNA is released into the host cell nucleus where active replication begins.

2. Cellular Destruction:

– Viral replication leads to accumulation of viral particles intracellularly followed by cell lysis.

– Characteristic dendritic or geographic ulcers form, visualized with fluorescein staining.

3. Inflammatory Response:

– Innate immunity is triggered, leading to secretion of interferons (IFN-α, IFN-β) and recruitment of neutrophils.

– Local inflammation limits viral replication but may also cause additional epithelial cell damage.

Clinical Manifestations

• Typical symptoms include pain, photophobia, foreign body sensation, tearing, and decreased vision.

• Biomicroscopic examination reveals branch-like dendritic lesions with blister-like edges filled with viral particles.

Treatment Features

• The primary approach involves antiviral therapy (e.g., topical acyclovir or ganciclovir препараты).

• Avoidance of corticosteroids at this stage is crucial, as they can enhance viral replication.

2. Stromal Keratitis: Autoimmune Reactions and Fibrosis

Stromal keratitis occurs with involvement of the deeper layers of the cornea, often as a result of viral reactivation or autoimmune dysregulation. It is the most destructive form of herpetic keratitis, capable of causing irreversible structural changes in the cornea.

Pathogenesis:

1. Initiation of Inflammation:

• Stromal keratitis is not always associated with active viral replication; instead, immune mechanisms initiated by viral antigens are at the core.

• Expression of viral proteins in stromal cells provokes an inflammatory response, attracting T cells and macrophages.

2. Autoimmune Component:

• Reactive T cells (especially TH1 and TH17) attack stromal tissues, perceiving them as foreign.

• Secretion of cytokines such as IFN-γ and IL-17 enhances inflammation and causes degradation of the extracellular matrix.

3. Fibrosis:

• Chronic inflammation stimulates fibroblasts to produce excess collagen, leading to scar tissue formation.

• Neovascularization of the cornea, driven by inflammation, impairs transparency.

Clinical Manifestations

• Patients complain of progressive visual acuity reduction, photophobia, and pain.

• Biomicroscopy reveals stromal edema, infiltrates, and scarring.

Treatment Features

• Combined therapy with antiviral agents and topical corticosteroids (to control inflammation).

• Immunosuppressants such as cyclosporine may be used for severe forms.

3. Endothelial Keratitis: Endothelial Dysfunction

Endothelial keratitis (disciform keratitis) is a deep corneal lesion characterized by inflammation of the endothelium and stroma, leading to marked impairment of its transparency.

Pathogenesis:

1. Viral Reactivation in the Endothelium:

• Viral antigens or particles activate localized inflammation in endothelial cells.

• Direct viral infection of the endothelium is rarer; damage is more commonly immune-mediated.

2. Immune Inflammation:

• Circulating T cells and monocytes infiltrate the endothelium, provoking dysfunction.

• Release of proinflammatory cytokines (e.g., TNF-α, IL-6) causes corneal and stromal edema.

3. Endothelial Dysfunction:

• The endothelium loses its ability to effectively regulate corneal hydration.

• Pronounced stromal edema develops, significantly reducing corneal transparency and visual acuity.

Clinical Manifestations

• Patients report rapid vision deterioration associated with corneal edema.

• Biomicroscopy reveals disc-shaped edema and endothelial precipitates.

Treatment Features

• Antiviral drugs combined with corticosteroids are used to control inflammation.

• In cases of refractory edema, hyperosmotic agents (e.g., sodium chloride solutions) may be required.

General Remarks on Lesion Types

• Progression Between Forms: Corneal lesions may progress from epithelial to stromal and endothelial keratitis, necessitating timely intervention.

• Chronic Changes: Stromal fibrosis and neovascularization are irreversible, emphasizing the importance of early diagnosis and treatment.

• Immunomodulation: Modern therapeutic approaches include immunotherapy aimed at reducing autoimmune damage without compromising antiviral defense.

Characteristics of pathogenesis, clinical manifestations, and treatment of various herpetic keratitis forms are summarized in Table 1.

Conclusion:

The types of corneal lesions in herpetic keratitis illustrate the complex interplay between viral and immune factors. Effective treatment requires an individualized approach based on disease stage and the predominant pathogenetic mechanism.