Herpetic keratitis: from symptoms to recovery

Herpetic keratitis (HSV keratitis) displays a variety of clinical forms that differ in the depth of corneal involvement, pathogenetic mechanisms, and prognosis. The classification includes epithelial, stromal (necrotic and interstitial), endothelial, and metaherpetic keratitis. Each form has distinct clinical and diagnostic features important for timely diagnosis and treatment.

1. Epithelial Herpetic Keratitis

Clinical Manifestations:

• Patients complain of acute decrease in visual acuity, foreign body sensation, photophobia, tearing, and mild pain.

• Typical lesions include:

– Dendritic ulcers: branching linear lesions of the corneal epithelium with typical bulbous endings.

– Geographic ulcers: larger, irregularly shaped lesions formed by coalescing dendritic patches.

Pathogenesis:

• Associated with active HSV replication in epithelial cells leading to their destruction and inflammation.

• The viral component predominates, with minimal immune response at this stage.

Diagnostic Features:

– Biomicroscopy with fluorescein staining reveals ulcers with bright fluorescence.

– Confocal microscopy shows the presence of viral particles and inflammatory cells.

Prognosis and Complications:

• With timely therapy, the process usually remains confined to the corneal surface without deep tissue damage.

• Without treatment, progression to stromal keratitis may occur.

2. Stromal Herpetic Keratitis

Classification:

• Necrotizing Stromal Keratitis:

– Less common, characterized by direct viral infection of stromal cells with massive inflammation.

– Accompanied by pronounced corneal tissue necrosis, neutrophilic infiltration, and edema.

– Frequently leads to scar formation, corneal thinning, and perforation.

• Interstitial Stromal Keratitis:

– Immune-mediated lesion without active viral replication.

– Driven by immune reactions against viral antigens or autoantigens.

– Characterized by chronic stromal inflammation with infiltration of lymphocytes, plasma cells, and macrophages.

Clinical Manifestations:

• Visual acuity reduction, pain, photophobia.

• Biomicroscopy reveals infiltration foci, stromal edema, and corneal haze.

• Corneal neovascularization may occur.

Prognosis:

– Stromal scarring and neovascularization often lead to irreversible loss of corneal transparency and necessitate corneal transplantation.

3. Endothelial Herpetic Keratitis (Disciform Keratitis)

Clinical Manifestations:

• Patients experience a gradual decrease in vision due to corneal edema.

• Biomicroscopy reveals:

– Localized disc-shaped edema.

– Cellular precipitates on the endothelium.

– No significant changes in the epithelium or stroma.

Pathogenesis:

• Occurs due to inflammation associated with immune-mediated attack on endothelial cells.

• Immune complexes and cytokines disrupt the endothelial barrier function leading to impaired corneal hydration.

Prognosis:

• With adequate treatment using anti-inflammatory drugs (corticosteroids) and antiviral therapy, improvement is often observed.

• Chronic forms can lead to persistent corneal opacity.

4. Metaherpetic (Trophic) Keratitis

Clinical Manifestations:

• Characterized by a chronic epithelial defect that fails to heal over a prolonged period despite resolution of active viral infection.

• Patients report persistent vision decrease, photophobia, pain, and tearing.

Pathogenesis:

• Results from impaired epithelial regeneration and altered corneal trophic support.

Main Mechanisms:

• Damage to the basal membrane and limbal stem cells.

• Decreased corneal sensitivity (neuropathic epitheliopathy).

• Chronic inflammation hindering tissue repair.

Clinical Features:

• Extensive epithelial defects with irregular edges.

• Development of vascularization, thinning, and scarring of the cornea.

Prognosis:

• This keratitis form is difficult to treat and often requires surgical intervention, including corneal transplantation.

Key Diagnostic Aspects of HSV Keratitis Forms

• Visualization: Biomicroscopy using fluorescein or rose bengal staining to detect superficial defects.

• Confocal Microscopy: Identification of deep lesions such as endothelial precipitates and stromal infiltrates.

• Laboratory Diagnostics: Polymerase chain reaction (PCR) for viral DNA identification; cytology for detecting giant cells using the Тцанка method.

Conclusion:

Classification of HSV keratitis forms highlights the diversity of lesions from superficial epithelial to deep structural changes. Early diagnosis and accurate determination of the disease form are key to successful treatment and prevention of irreversible complications.

Characteristic Signs of HSV Keratitis

Patient Complaints

Clinical presentation varies with corneal lesion depth and disease form, but some typical complaints can guide diagnosis:

1. Photophobia:

• Caused by receptor irritation in the cornea and increased sensitivity of inflamed tissues to light.

• Patients report discomfort even under moderate lighting.

2. Visual acuity reduction:

• Linked to corneal optical changes including epithelial defects, stromal edema, infiltrates, and scarring.

• Severity depends on lesion location and extent.

3. Ocular pain:

• Ranges from mild to severe depending on disease form.

• Usually caused by superficial corneal inflammation, intensifying with deeper involvement.

4. Foreign body sensation:

• Related to epithelial defects and nerve ending irritation in the cornea.

• Can be accompanied by excessive blinking and reflex tearing.

5. Tearing and Discharge:

• Patients often report clear ocular discharge.

• In bacterial superinfection, discharge may become mucopurulent.

Objective Findings

Using slit-lamp biomicroscopy, key signs of HSV keratitis can be identified that aid in differentiating disease forms:

1. Epithelial Signs:

• Dendritic ulcers:

– The most characteristic feature of epithelial keratitis.

– Branching shape with thickened ends often containing active viral particles.

– Well visualized with fluorescein staining (fluorescence) or rose bengal.

• Geographic ulcers:

– Larger, irregularly shaped defects resulting from coalescence of dendritic ulcers.

– Indicative of progression of epithelial damage.

2. Subepithelial Infiltrates:

• Located beneath the superficial corneal layer and associated with immune response to viral antigens.

• Common in stromal and mixed keratitis types.

• Appear as corneal opacities with localized loss of transparency.

3. Keratoprecipitates (KP):

• Small inflammatory cell deposits on the corneal endothelium.

• Indicative of deep corneal involvement (endothelial keratitis).

• Color and structure vary:

• Fresh KP are small, white, and soft.

• Chronic KP are larger, pigmented, and dense.

4. Corneal Edema:

• Can be localized (in endothelial keratitis) or diffuse (in severe forms).

• Associated with reduced transparency and increased corneal thickness measured by pachymetry.

5. Vascular Invasion (Neovascularization):

• Common in chronic stromal keratitis.

• New vessels invade the corneal stroma disrupting its transparency.

6. Thinning and Scarring:

• Typical of severe and recurrent forms.

• Leads to structural deformities such as keratoconus or perforation.

Additional Objective Signs in Complications

1. Reduced Corneal Sensitivity:

– Often observed in chronic forms.

– Diagnosed with esthesiometry.

– Linked to nerve ending damage caused by HSV neurotrophic effects.

2. Chronic Limbal Inflammation:

– Indicates involvement of corneal epithelial stem cells in the pathological process.

– Manifests as hyperemia and tissue infiltration around the limbus.

Differential Signs

1. Epithelial Keratitis:

– Predominantly viral component.

– Characterized by dendritic or geographic ulcers.

2. Stromal Keratitis:

– Immune-mediated lesion with stromal infiltrates.

– Often associated with neovascularization.

3. Endothelial Keratitis:

– Localized corneal edema and presence of keratoprecipitates on the endothelium.

– Minimal epithelial changes.

4. Metaherpetic Keratitis:

– Presence of chronic epithelial defect with reduced regeneration and corneal vascularization.

Practical Significance

Accurate interpretation of symptoms and objective findings allows rapid diagnosis of HSV keratitis and determination of its form. This is critical for therapy selection, as different clinical manifestations require varied treatment approaches.

Differential Diagnosis of HSV Keratitis

Differential diagnosis plays a crucial role in timely application of appropriate treatment strategies, as several infectious agents may present with similar clinical signs. The main tasks are distinguishing HSV keratitis from other viral, bacterial, fungal infections, and autoimmune diseases.

1. HSV Keratitis vs. VZV Keratitis

Varicella-Zoster Virus (VZV), the cause of chickenpox and shingles, is also a herpesvirus but induces clinically distinct keratitis forms compared with HSV. Differentiating these infections requires thorough clinical assessment and laboratory data.

Clinical Differences:

1. Lesion Localization:

• HSV can affect one or both eyes, most commonly involving central and peripheral cornea.

• VZV primarily causes unilateral involvement, often affecting lateral corneal areas. VZV keratitis is frequently associated with herpetic dermatitis presenting as vesicles, often in the region of the ophthalmic nerve.

2. Lesion Character:

• HSV typically features dendritic or geographic ulcers and subepithelial infiltrates.

• VZV shows more pronounced stromal infiltrates which may be necrotic and often accompanied by marked neovascularization.

3. Associated Symptoms:

• HSV lacks significant cutaneous inflammation and skin vesicles; patients may not exhibit skin manifestations in herpes recurrence.

• VZV keratitis commonly co-occurs with herpetic dermatitis characterized by vesicular eruptions in the orbital region.