Herpes Simplex Virus Stromal Endotheliitis

Herpes Simplex Virus (HSV) Stromal Endotheliitis is a type of eye inflammation caused by the herpes simplex virus affecting the deep layers of the cornea. In very simple terms, it is an infection and immune reaction that leads to swelling (edema) of the middle (stroma) and innermost (endothelium) layers of the cornea, which can make the eye red, painful, and blur vision.

Herpes Simplex Virus Stromal Endotheliitis occurs when HSV-1 (and less commonly HSV-2) infects or triggers inflammation of the corneal endothelium—the single layer of cells on the back of the cornea that pumps fluid out to keep the cornea clear. In some cases, the virus directly invades endothelial cells; in others, the body’s immune response against viral antigens in the eye causes bystander damage. This leads to fluid buildup in the stroma (swelling), scattering of light, and reduced vision. Unlike surface HSV keratitis (dendritic ulcers), endotheliitis often has minimal surface defects but prominent stromal edema and characteristic patterns of keratic precipitates (KP)—tiny white or yellow dots of inflammatory cells on the back of the cornea EyeWiki.

Herpes Simplex Virus (HSV) Stromal Endotheliitis is an inflammatory condition of the cornea’s deeper layers, where the virus infects or triggers immune reactions in both the stromal and endothelial tissues. In stromal keratitis, immune cells respond to viral antigens in the stroma, leading to opacity and neovascularization. In endotheliitis, HSV directly—or via immune mediation—damages endothelial cells, causing corneal edema and a characteristic “disciform” (disc-shaped) opacity without overt scarring in early stages EyeWikiNCBI.

Clinically, patients experience blurred vision, mild to moderate discomfort, light sensitivity, tearing, and sometimes minimal pain disproportionate to the corneal findings. Diagnosis is predominantly clinical—based on slit-lamp examination revealing keratic precipitates on the endothelium, stromal edema, and often a history of recurrent HSV keratitis. Laboratory testing (PCR or culture) is rarely helpful in pure stromal or endothelial disease, as live virus may not be present on the ocular surface EyeWikiPMC.

Types of HSV Endotheliitis

HSV endotheliitis is classified by the pattern of stromal swelling and KP on the endothelium into three main forms:

• Disciform Endotheliitis
  This is the most common type. It shows a round (“disc-shaped”) area of swelling in the central cornea with underlying KP. The cornea outside this zone remains clear, creating a sharply demarcated disc of cloudiness EyeWiki.

• Diffuse Endotheliitis
  Here, KP are scattered widely across the entire endothelial surface, often with a more uniform—but less dense—stromal edema. Severe cases can form retrocorneal plaques of inflammatory cells and occasionally a hypopyon (layer of white blood cells) in the anterior chamber Review of Contact Lenses.

• Linear (or Sectoral) Endotheliitis
  KP line up in a straight or branching line, often starting from the limbus (edge) and moving centrally, with localized edema trailing behind. This form is less common but more severe and harder to treat Review of Contact Lenses.

Causes

HSV lies dormant in the trigeminal ganglion after initial infection and can reactivate when certain triggers occur. Common causes and risk factors for HSV stromal endotheliitis include:

Although any HSV infection in the eye can lead to endotheliitis, specific triggers or risk factors include:

1. Primary HSV Ocular Infection – first-time contact with HSV on the eye surface.

2. Reactivation of Latent HSV-1 – virus awakens from nerve ganglia and travels back to the cornea.

3. Use of Topical Steroids – can dampen local immunity, allowing viral replication.

4. Corneal Surgery – procedures like LASIK or PRK may provoke reactivation Lippincott Journals.

5. Contact Lens Wear – microtrauma and poor hygiene can facilitate viral entry.

6. Ocular Trauma – scratches or foreign bodies open paths for HSV replication.

7. Immunosuppression – diseases or medications that lower defenses.

8. Stress or Illness – systemic stress can reactivate latent virus.

9. Fever – “fever blisters” can coincide with ocular reactivation.

10. UV Light Exposure – sunburn-like stress on cornea may awaken virus.

11. Hormonal Changes – pregnancy or menstrual cycle variations.

12. Diabetes – high blood sugar impairs healing and immunity.

13. Chronic Dry Eye – surface inflammation may aid viral entry.

14. Graft-versus-Host Disease – in transplant patients, heightened immune reactions.

15. Previous Epithelial Keratitis – history of dendritic or geographic ulcers.

16. Neonatal Exposure – HSV-2 passed during childbirth rarely affects cornea.

17. Delayed or Inadequate Antiviral Treatment – incomplete viral suppression.

18. Genetic Predisposition – certain HLA types may influence severity.

19. Co-infection with Other Viruses – like VZV or CMV can complicate immunity.

20. Smoking – irritates ocular surface and weakens local defenses.

Symptoms

Patients with HSV stromal endotheliitis typically experience:

1. Eye pain or discomfort – often described as a dull ache or sharp twinge.

2. Photophobia (light sensitivity) – bright lights hurt the eye.

3. Redness – due to inflammation of conjunctival and deeper vessels.

4. Blurred or hazy vision – from stromal swelling scattering light.

5. Tearing or watery discharge

6. Foreign-body sensation – feeling like something is in the eye.

7. Glare or halos around lights – from disc-shaped edema.

8. Reduced visual acuity – difficulty reading or seeing details.

9. Corneal edema – visible haziness in the cornea.

10. Keratic precipitates (KP) – tiny white/yellow spots on endothelium seen on exam EyeWiki.

11. Anterior chamber cells and flare – inflammatory cells in the fluid of the eye.

12. Elevated intraocular pressure – due to trabeculitis (inflammation of drainage structures).

13. Decreased corneal sensation – tested with light touch filament.

14. Headache or eye-pressure sensation

15. Feeling of fullness around the eye

Diagnostic Tests

Physical Exam

1. Visual Acuity Test – reading letters on a chart to measure clarity of vision.

2. Slit-lamp Biomicroscopy – high-magnification microscope to examine cornea layers and detect edema, KP, and inflammation.

3. Intraocular Pressure (IOP) Measurement – using a tonometer to check for elevated pressure from trabeculitis.

4. Corneal Sensitivity Test – Cochet-Bonnet aesthesiometer (nylon filament) to assess nerve function.

5. External Ocular Examination – inspecting lids, conjunctiva, and eye movements for associated signs.

Manual Tests

6. Fluorescein Staining – orange dye highlights epithelial defects under cobalt-blue light.

7. Rose Bengal Staining – pink dye that marks devitalized cells on the cornea and conjunctiva.

8. Lissamine Green Staining – green dye to detect damaged surface cells.

9. Seidel Test – checks for corneal perforations by looking for clear fluid under blue light.

10. Keratic Precipitate Pattern Evaluation – observing KP distribution (disciform, diffuse, linear) at the posterior cornea.

Lab & Pathological Tests

11. Polymerase Chain Reaction (PCR) of tear film or aqueous humor to detect HSV DNA. EyeWiki

12. Viral Culture of corneal scrapings or tear samples to grow HSV in cell culture. EyeWiki

13. Enzyme-Linked Immunosorbent Assay (ELISA) for HSV antibodies in tears or blood.

14. Immunofluorescent Antibody Assay on corneal specimens to visualize viral antigens.

15. Western Blot for HSV proteins from tear or tissue samples.

Electrodiagnostic Tests

16. Electroretinogram (ERG) – measures electrical responses of the retina to light to ensure posterior segment health. Wikipedia

17. Visual Evoked Potential (VEP) – records electrical activity from the visual cortex in response to patterned stimuli, checking optic nerve integrity. EyeWiki

18. Electrooculogram (EOG) – measures standing potentials of the retina and RPE, useful if RPE function is in question. Wikipedia

Imaging Tests

19. Anterior Segment Optical Coherence Tomography (AS-OCT) – non-contact imaging that shows high-resolution cross-sections of the cornea, quantifying stromal thickness and edema. MDPI

20. In Vivo Confocal Microscopy – real-time microscopic imaging of corneal cells, including endothelial morphology and KP deposits. MDPI

Non-Pharmacological Treatments

1. Artificial Tears (Preservative-Free): These lubricating eye drops supplement the tear film, wash away debris, and help alleviate surface discomfort by creating a protective layer over the cornea Merck ManualsPMC.

2. Lubricating Ointments: Applied at bedtime, these thicker preparations maintain corneal hydration overnight, preventing epithelial breakdown that can exacerbate inflammation Merck ManualsPMC.

3. Punctal Occlusion: Silicone or collagen plugs inserted into tear drainage ducts increase tear residence time, improving ocular surface moisture and comfort Merck ManualsPMC.

4. Bandage Soft Contact Lenses: These therapeutic lenses protect the corneal surface from blinking trauma, promote epithelial healing, and reduce pain Merck ManualsPMC.

5. Amniotic Membrane Transplantation: An amniotic graft placed on the cornea delivers anti-inflammatory proteins and growth factors, supporting epithelial repair and reducing scarring risk Merck ManualsPMC.

6. Autologous Serum Eye Drops: Prepared from the patient’s blood, these drops are rich in growth factors and vitamins, promoting epithelial regeneration and reducing inflammation PMC+1.

7. Therapeutic Corneal Collagen Cross-Linking (CXL): UV-riboflavin treatment stiffens stromal collagen, stabilizing the cornea and reducing edema in refractory cases EyeWikiPMC.

8. Photodynamic Therapy: Low-intensity light activation of photosensitizers can selectively reduce neovascularization and inflammatory mediators in the cornea EyeWikiPMC.

9. Epithelial Debridement: Gentle removal of loose epithelial cells can reduce viral load and improve penetration of topical antivirals when used adjunctively MedscapePMC.

10. Cold Compresses: Short cold applications to closed eyelids relieve discomfort and reduce superficial inflammation MedscapePMC.

11. Warm Compresses: Improves meibomian gland function, maintaining a healthy tear lipid layer and reducing secondary dry eye symptoms MedscapePMC.

12. Lid Hygiene: Regular cleansing of eyelid margins with diluted baby shampoo prevents blepharitis, which can worsen ocular surface inflammation MedscapePMC.

13. Scleral Lenses: These vault over the cornea, creating a fluid reservoir that shields the stroma and endothelium from mechanical stress MedscapePMC.

14. High-Moisture Chamber Goggles: Worn at night, these goggles retain humidity around the eye, aiding in corneal hydration MedscapePMC.

15. Ocular Surface Saline Washes: Gentle rinsing with sterile saline removes inflammatory debris and reduces microbial load EyeWikiReview of Optometry.

16. UV-Protective Sunglasses: Block ultraviolet light that can trigger HSV reactivation and corneal inflammation Review of Contact LensesReview of Optometry.

17. Avoid Contact Lens Wear: Discontinue lenses during active inflammation to prevent microtrauma and secondary infection Review of OptometryPMC.

18. Stress Management Techniques: Practices like meditation and adequate sleep can reduce systemic triggers for viral reactivation Review of Contact LensesReview of Optometry.

19. Maintain Good Hydration: Proper fluid intake supports tear production and ocular surface health Review of Contact LensesReview of Optometry.

20. Hand Hygiene: Regular handwashing prevents autoinoculation of HSV from other body sites to the eye Review of Contact LensesReview of Optometry.

---

Drug Treatments

1. Oral Acyclovir (Antiviral): 400 mg five times daily for 10 days inhibits viral DNA polymerase, reducing viral replication in stromal tissues. Side effects: headache, gastrointestinal upset NCBIReview of Ophthalmology.

2. Valacyclovir (Antiviral): 500 mg twice daily for 10 days; prodrug of acyclovir with better bioavailability. Side effects: nausea, rare thrombotic events NCBIReview of Ophthalmology.

3. Famciclovir (Antiviral): 500 mg three times daily for 7 days; inhibits viral DNA synthesis. Side effects: headache, diarrhea NCBIReview of Ophthalmology.

4. Trifluridine 1% Eye Drops (Topical Antiviral): One drop five times daily for 14 days; incorporates into viral DNA, preventing replication. Side effects: epithelial toxicity, burning MedscapePMC.

5. Ganciclovir 0.15% Gel (Topical Antiviral): One drop five times daily until healing, then three times daily; blocks viral DNA polymerase. Side effects: eye irritation, blurred vision MedscapePMC.

6. Prednisolone Acetate 1% (Topical Corticosteroid): Four times daily tapering over weeks; suppresses stromal immune response. Side effects: elevated intraocular pressure, cataract formation EyeWikiMerck Manuals.

7. Loteprednol Etabonate 0.5% (Topical Corticosteroid): Twice to four times daily; lower risk of pressure rise. Side effects: mild irritation Merck ManualsSpringerLink.

8. Cyclosporine A 2% Eye Drops (Topical Immunomodulator): Twice daily; reduces T-cell–mediated stromal damage. Side effects: burning/stinging MedscapeMerck Manuals.

9. Timolol 0.5% (Topical Beta-Blocker): Twice daily for steroid-induced ocular hypertension. Mechanism: decreases aqueous production. Side effects: systemic beta-blockade Review of OptometryMerck Manuals.

10. Acetazolamide 250 mg (Oral Carbonic Anhydrase Inhibitor): Once to twice daily to reduce intraocular pressure. Side effects: paresthesia, metabolic acidosis Review of OptometryMerck Manuals.

---

Dietary Molecular and Herbal Supplements

1. L-Lysine (500 mg twice daily): May inhibit HSV replication by antagonizing arginine uptake Review of Contact LensesWikipedia.

2. Vitamin C (500 mg daily): Antioxidant that supports immune function and epithelial healing Review of Contact LensesReview of Optometry.

3. Zinc (25 mg daily): Cofactor for antioxidant enzymes; may reduce viral shedding duration Review of Contact LensesMerck Manuals.

4. Omega-3 Fatty Acids (1000 mg daily): Anti-inflammatory effect on ocular surface Review of Contact LensesMerck Manuals.

5. Turmeric/Curcumin (500 mg twice daily): Inhibits cytokine release, reducing corneal inflammation Review of Contact LensesMerck Manuals.

6. Echinacea (400 mg thrice daily): May boost innate immunity against viral reactivation Review of Contact LensesReview of Optometry.

7. Green Tea Extract (EGCG 200 mg daily): Polyphenols with antiviral and antioxidant properties Review of Contact LensesMerck Manuals.

8. Propolis (500 mg daily): Bee resin with immunomodulatory and antiviral effects Review of Contact LensesReview of Optometry.

9. Licorice (Glycyrrhizin 100 mg daily): Inhibits HSV attachment to host cells Review of Contact LensesMerck Manuals.

10. Resveratrol (150 mg daily): Antiviral flavonoid that may suppress HSV gene expression Review of Contact LensesMerck Manuals.

11. N-Acetylcysteine (600 mg daily): Boosts glutathione, reducing oxidative stress Review of Contact LensesReview of Optometry.

12. Vitamin E (400 IU daily): Lipid-soluble antioxidant protecting cell membranes Review of Contact LensesMerck Manuals.

13. Lutein/Zeaxanthin (10 mg/2 mg daily): Carotenoids that protect ocular tissues from light-induced damage Review of Contact LensesMerck Manuals.

14. Astragalus (500 mg twice daily): Traditional immunostimulant reducing viral recurrence Review of Contact LensesReview of Optometry.

15. Quercetin (500 mg daily): Bioflavonoid with anti-inflammatory and antiviral properties Review of Contact LensesMerck Manuals.

---

Regenerative and Stem Cell Drugs

1. Cenegermin (Oxervate®) 20 µg/mL: Recombinant human nerve growth factor eye drops, six times daily for 8 weeks; promotes epithelial healing and nerve regeneration PMCAAO.

2. Autologous Serum Eye Drops: Rich in growth factors (EGF, fibronectin); used four to six times daily to enhance corneal repair PMC+1.

3. ReGeneraTing Agent (RGTA®, Cacicol20) 0.02%: Mimics heparan sulfates, stabilizing extracellular matrix and aiding healing PMC+1.

4. Thymosin Beta-4 (RGN-259) 0.1%: Peptide that promotes corneal epithelial migration and reduces inflammation PMC+1.

5. Topical IGF-1 Eye Drops (5 µg/mL): Stimulates epithelial proliferation and stromal recovery PMC+1.

6. Mesenchymal Stem Cell–Derived Exosomes: Experimental drops rich in growth factors and anti-inflammatory cytokines; dosing under investigation PMC+1.

---

Surgical Interventions

Penetrating keratoplasty (full-thickness graft) is indicated when scarring severely impairs vision; deep anterior lamellar keratoplasty preserves healthy endothelium while replacing diseased stroma; Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) selectively replace the damaged endothelial layer; phototherapeutic keratectomy (PTK) uses excimer laser to remove superficial scars and keratic precipitates, improving smoothness and clarity EyeWikiPMC.

---

10 Prevention Strategies

Key measures include daily prophylactic oral acyclovir (400 mg twice daily), strict hand and eyelid hygiene, UV-protective eyewear, stress reduction, avoidance of eye rubbing, prompt treatment of blepharitis, maintenance of good ocular surface lubrication, cautious use of topical steroids under supervision, regular follow-up with an ophthalmologist, and avoidance of contact lens wear during active or healing phases Review of Contact LensesReview of Optometry.

---

When to See a Doctor

Seek immediate ophthalmic evaluation if you experience sudden vision loss, severe eye pain, increasing redness, photophobia, new floaters, or any signs of corneal perforation. Regular monitoring is essential to detect elevated intraocular pressure or graft rejection early NCBIReview of Optometry.

---

Dietary Recommendations: What to Eat and What to Avoid

A diet rich in leafy greens, fatty fish (omega-3), citrus fruits (vitamin C), nuts (vitamin E), and colorful vegetables (lutein, zeaxanthin) supports ocular health. Avoid excessive refined sugars, processed foods, alcohol, high-histamine foods (aged cheeses, smoked meats), and high-salt snacks that may exacerbate inflammation and edema Merck ManualsReview of Contact Lenses.

---

Frequently Asked Questions

1. What is stromal endotheliitis?
   An inflammation of the corneal endothelium and stroma caused by HSV, leading to edema and vision loss.

2. How is it diagnosed?
   Slit-lamp exam, endothelial cell count, and sometimes PCR of aqueous humor.

3. Is it contagious?
   The virus can shed, but deeper stromal disease itself is not directly transmissible.

4. Can it recur?
   Yes—up to 50% of patients have recurrences without prophylaxis.

5. How long does treatment last?
   Typically 4–6 weeks of antivirals and steroids, then long-term antiviral prophylaxis.

6. Will I need surgery?
   Only if scarring or non-resolving edema threatens vision despite medical therapy.

7. Can I wear contact lenses?
   Not during active disease; resume only after complete healing and doctor’s approval.

8. Are there permanent vision changes?
   Scarring can cause permanent haze; early treatment minimizes this risk.

9. What are steroid side effects?
   Elevated eye pressure, cataract formation—regular monitoring is essential.

10. Can diet prevent recurrence?
    A balanced, antioxidant-rich diet may support immune health but cannot guarantee prevention.

11. Is long-term antiviral safe?
    Yes—acyclovir prophylaxis is well tolerated with minimal side effects at low doses.

12. What if I miss a dose?
    Take as soon as remembered; don’t double up doses.

13. Are herbal supplements effective?
    Some (e.g., lysine, green tea) show promise, but they complement rather than replace medical therapy.

14. What triggers reactivation?
    Stress, UV exposure, fever, hormonal changes, and immune suppression.

15. When can I resume normal activities?
    Once inflammation has fully resolved—usually after medical clearance, often 4–6 weeks.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: August 06, 2025.

PDF Document For This Disease Conditions References