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Herpetic keratitis (Herpes Simplex Virus keratitis) remains one of the most significant causes of infectious blindness worldwide despite advances in modern medicine. Its recurrent nature, complex diagnosis, and need for prolonged treatment make this disease an important topic for ophthalmologists.

Herpetic Keratitis as a Leading Cause of Infectious Blindness

Herpetic keratitis (HK) holds a leading position among infectious causes of vision loss, surpassing bacterial, fungal, and parasitic keratitis. Mechanisms of blindness include:

• Damage to the corneal epithelium and stroma with formation of irreversible scarring.

• Chronic inflammation leading to corneal neovascularization.

• Development of secondary complications such as glaucoma or dry eye syndrome.

1. Statistics:

• According to the World Health Organization (WHO), herpetic keratitis affects more than 1.5 million people globally each year, with approximately 40,000 losing vision in one or both eyes. See Appendix (QR code for Source No. 1)

• In 25% of cases, this disease leads to keratoplasty.

2. Epidemiology: Global Prevalence and Risk Groups

The global prevalence of herpetic keratitis varies depending on the region, healthcare level, and climatic conditions. General indicators:

• HSV-1 infection prevalence among the population reaches up to 90% in some regions, creating a high likelihood of ophthalmic manifestation of the disease.

• Recurrence frequency: more than 25% of patients who experienced the first episode of HK suffer recurrences within the first year, and 50% within 5 years. See Appendix (QR code for Source No. 2)

Risk groups:

• Patients with immunodeficiency conditions (e.g., HIV infection, long-term immunosuppressive therapy, organ transplantation).

– Elderly individuals with reduced regenerative capabilities of corneal tissues.

• Children and young people with a high risk of primary infection.

• Residents of regions with high levels of ultraviolet radiation, as UV exposure activates the virus. See Appendix (QR code for Source No. 3)

Climatic factor:

• Tropical and subtropical countries show a higher frequency of cases associated with viral activation by sunlight.

3. Economic and Social Burden of the Disease

Direct Medical Costs:

Treatment of herpetic keratitis requires substantial resources including:

• Prolonged therapy with antiviral drugs and immunomodulators.

• Repeated physician visits for monitoring.

• Possible surgical intervention (e.g., keratoplasty).

Recent studies indicate the annual direct treatment cost for herpetic keratitis in the United States is approximately $17.7 million, substantially lower than previous estimates. This figure refers specifically to herpetic keratitis and does not include the broader spectrum of herpetic eye disease. See Appendix (QR code for Source No.4)

Indirect Costs:

• Loss of patients’ working capacity, especially during recurrences.

• Work absenteeism and reduced productivity due to the need for regular treatment.

• Social costs including psychological stress related to the chronic nature of the disease.

Quality of Life:

Vision impairment and frequent exacerbations of HK considerably reduce patients’ quality of life, including:

• Limitation of daily activities.

• Fear of vision loss due to recurrences.

•Depression and anxiety disorders associated with prolonged treatment.

Economic burden of herpes:

According to WHO, 2024:

• Annual economic losses from herpes are estimated at $35 billion.

• Genital herpes causes significant healthcare expenses and reduced labor productivity. See Appendix (QR code for Source No. 5)

Conclusion:

Herpetic keratitis is not only a medical but also a socio-economic problem that requires an interdisciplinary approach to treatment and prevention. Its global significance dictates the need to develop new diagnostic, therapeutic, and preventive methods that will reduce disease prevalence and its severe consequences.

Brief Overview of Herpes Simplex Virus (HSV)

Human herpesvirus (Herpes Simplex Virus, HSV) is a widespread DNA-containing virus belonging to the Herpesviridae family. Its unique feature is the ability of latent persistence in the body and reactivation under the influence of external and internal factors. In ophthalmology, two types of the virus play a key role: HSV-1 and HSV-2.

1. Types HSV-1 and HSV-2

HSV-1 and HSV-2 share a similar genetic structure but differ in preferred transmission routes, tissue tropism, and disease spectrum.

HSV-1 (Herpes Simplex Virus Type 1):

Main clinical manifestations:

• Leading cause of ophthalmic herpes: causes epithelial, stromal, and endothelial keratitis, keratouveitis, and recurrent eyelid lesions (herpetic blepharitis).

• Also associated with oral herpes and encephalitis.

Transmission routes:

• Contact: through saliva, skin, mucous membranes.

• Possible transfer to the cornea through contaminated hands or objects (e.g., contact lenses).

Epidemiological significance:

• Over 60% of the adult population worldwide is infected with HSV-1.

• Predominates in countries with temperate and cold climates.

HSV-2 (Herpes Simplex Virus Type 2):

Main clinical manifestations:

• More commonly causes genital herpes but can affect the eyes (e.g., keratoconjunctivitis) in neonatal herpes.

• Less frequently involved in ophthalmic pathology in adults.

Transmission routes:

• Sexual: main mode among adults.

• Vertical: from mother to newborn during childbirth.

Epidemiological significance:

• Occurs in 10—20% of the population depending on the region, more frequent in countries with high HIV prevalence. See Appendix (QR code for Source No. 6)

Comparison of Types:

HSV-1 is more tropic to the trigeminal nerve ganglia and ocular region, whereas HSV-2 mainly affects sacral ganglia. However, both types can affect the eyes and other organs.

2. Mechanisms of Infectivity and Viral Persistence

One of the key features of HSV is its ability for lifelong persistence and periodic reactivation. These properties are explained by unique mechanisms of interaction between the virus and host cells as well as the immune system.

Stages of the Infectious Cycle:

1. Entry into the Epithelium:

– HSV binds to receptors on the surface of epithelial cells, including heparan sulfate proteoglycans (HSPG) and nectin-1 protein.

– The viral capsid is delivered into the nucleus of the cell, where viral DNA is released.

2. Replication and Assembly of Viral Particles:

– The viral genome replicates using host cell enzymes.

– Early and late viral proteins necessary for the assembly of new virions are synthesized.

3. Cytotoxic Effect:

– Lysis of the host cell leads to inflammation and localized tissue destruction, for example, of the corneal epithelium.

Mechanisms of Persistence:

Following primary infection, the virus migrates via sensory nerves to neuronal ganglia, where it can persist in a latent form:

• In the latent phase:

– Viral DNA is maintained in the nucleus of neurons as an episome (circular form, not integrated into host DNA).

– Viral protein synthesis is minimal, rendering the virus “invisible” to the immune system.

• Upon Reactivation:

– Trigger factors (such as ultraviolet radiation, stress, immunosuppression) induce active viral replication and migration back along the nerve pathways to the original site of infection.

3. Zone of Viral Latency in the Trigeminal Nerve

The trigeminal nerve (n. trigeminus) is the key structure where HSV-1 persists in latent form.

• Location: The Gasserian ganglion (ganglion trigeminale) serves as the principal viral reservoir, where the virus resides in a dormant state between recurrences.

• Mechanism of Latency:

– Viral genetic activity remains minimal due to epigenetic control.

– Latency Associated Transcripts (LAT-RNA), which are non-coding RNAs, play a crucial role in suppressing viral replication and maintaining neuronal viability.

• Viral Activation:

– Under the influence of triggers, epigenetic control diminishes, allowing viral replication and migration back to the cornea.

– Repeated activations lead to chronic inflammation and irreversible corneal damage.

4. Modern Aspects of HSV Study

Contemporary research focuses on the latent phase of HSV, prevention of reactivation, and reduction of inflammation-induced damage:

• Molecular Inhibitors:

– New drugs targeted at inhibiting specific viral proteins involved in activation are under development.

• Genome Editing Technologies:

– Use of CRISPR/Cas9 to disrupt the viral genome during latency is being explored.

• Immune Approaches:

– Vaccines capable of eliciting durable cellular immunity against HSV are being investigated.

Conclusion

HSV is a unique pathogen that combines high infectivity, latent persistence, and a recurrent nature.

For ophthalmologists, understanding the mechanisms of infection, latency, and reactivation is essential to selecting optimal strategies for treatment and prevention of herpetic keratitis.

The features of the mechanism of action of herpes simplex virus in the human body are illustrated in Scheme 1.