What is Herpes Simplex Keratitis?
Herpes simplex keratitis is a common, potentially sight-threatening condition that stems from repeated corneal infections with the herpes simplex virus (HSV). It’s the top infectious reason for corneal ulcers and blindness across the globe. HSV has two common types: HSV-1 and HSV-2, both of which only affect humans. HSV-1 typically causes infections in the mouth, lips, and eyes, while HSV-2 usually causes sores in the genital area. However, these patterns are shifting. Initial infection with HSV happens when the mucous membranes or skin come into contact with the virus, often without the person even realizing it. After first infection, the virus goes dormant, hiding in the nerve cells of the spine and staying there throughout a person’s life. Further infections occur when the virus reactivates in particular areas of the nervous system.
Herpes simplex keratitis can occur with the first eye-area HSV infection or with later infections. After the first infection, the virus moves to a group of nerve cells found on the side of the face called the trigeminal ganglion. When the virus gets reactivated, it travels back to the cornea, causing inflammation. The outer layer of the eyeball, the cornea, along with the iris, lens, vitreous and retina can be affected. The reappearance of HSV within the cornea results in herpes simplex keratitis. The disease can show up in a number of ways such as herpetic dendrites, geographical ulcers, stromal keratitis, disciform keratitis, and neurotrophic keratopathy, with herpetic stromal keratitis being the most common. Inflammation of the cornea can lead to a decrease in corneal sensation, scarring, and blindness. Additionally, an HSV infection can potentially cause anterior uveitis, iridocyclitis, complicated cataracts, vitritis, and retinal detachment, which, if not addressed promptly, can rapidly lead to corneal tearing or blindness.
Initially, doctors diagnose herpes simplex keratitis based on clinical symptoms, including a detailed examination with a piece of equipment known as a slit lamp. Other tests like PCR, ELISA, and immunofluorescent antibody lab tests may be performed to confirm the diagnosis, but a viral culture test is the most trusted method. The treatment for herpes simplex keratitis includes topical antibiotic eye drops, anti-viral medications, and systemic antivirals. These treatments aim to limit the virus’s ability to reproduce, lessen the severity of sores, and prevent further spread.
What Causes Herpes Simplex Keratitis?
Herpes simplex keratitis is a common and potentially severe eye condition resulting from recurring herpes simplex virus (HSV) infections in the cornea – the clear, front part of the eye. There are two types of this virus, HSV-1 and HSV-2, both of which can affect humans. Once this virus gets into our system, it stays for life.
Traditionally, HSV-1 usually affected the face and upper body, while HSV-2 was common in the genital and lower body area. However, these days, either type can affect either region. Sometimes, transmission might occur from an infected mother to her baby during childbirth, leading to an eye condition in the newborn known as neonatal conjunctivitis.
Initial infection mostly happens in childhood and can result from droplet transmission or direct contact. These primary infections often go undetected and might manifest as a mild fever, malaise, or an upper respiratory tract infection. Although infections during the first six months of life are rare due to protection from maternal antibodies, severe illness can happen in newborns, needing quick diagnosis, careful intervention, and certain medications.
Transmission of HSV is more likely in crowded and unsanitary conditions. After the initial infection, the virus exists in a hidden or dormant (latent) state within the person’s body. It can flare up later in life due to various triggers such as fever, trauma, immune suppression, hormonal changes, radiation, or exposure to ultraviolet light.
Primary infection with HSV in the eye usually doesn’t show noticeable symptoms. However, once apparent, it can lead to conditions like blepharitis (inflammation of the eyelids) or follicular conjunctivitis (inflammation of the eye surface), which then can lead to keratitis (inflammation of the cornea).
Following the initial infection, HSV stays latent in the facial nerve ganglion, but travels back to the cornea and causes inflammation when reactivated. The main complication of HSV recurrence in the eye is keratitis, which can take on various forms. This condition can also affect other parts of the eye, like the iris and retina. Different manifestations of herpes simplex keratitis include herpetic dendrites, geographical ulcers, stromal keratitis, disciform keratitis, and neurotrophic keratopathy, with stromal keratitis being the most common.
Risk Factors and Frequency for Herpes Simplex Keratitis
Herpetic eye disease is the leading cause of blindness in the cornea due to infection in developed nations. In the United States, more than half the population carries HSV-1, and over 15% of sexually active people carry HSV-2. Around the globe, HSV-1 has infected nearly 4.85 billion people, and around 836 million people above the age of 15 have HSV-2. The rates vary from region to region; it’s most prevalent in Africa according to the World Health Organization, and least prevalent in the Americas.
According to 2016 data, 64% of people aged between 0 and 49 had oral HSV-1 infection, while 13% of people aged between 15 and 49 had HSV-2.
It was estimated in 2012 that globally, there were 1.5 million new cases of herpetic keratitis, and 40,000 new cases of vision impairment in one eye every year. In developing countries, herpes simplex virus is responsible for as many as 60% of corneal ulcers. It’s estimated that herpes simplex virus might be affecting up to 10 million people’s eyes worldwide. The average age for the first eye infection with HSV-1 is 37.4 years in the US and 25 years in Britain.
The frequency of recurrences is directly related to the number of previous outbreaks. After the primary infection, the virus moves to the sensory ganglia of the dermatome, where it stays inactive. The reported reactivation rate for ocular herpes after the primary infection is about 10% in the first year and 50% at 10 years.
Types of recurring infections include dendritic keratitis (56.3%), stromal keratitis (29.5%), and geographical lesions (9.8%). Recurrences can also be influenced by other factors such as immune stressors, and usually occur in a specific pattern causing reactivation of cell responses and production of antibodies.
- Risk factors for severe disease including frequently recurring infections, atopic eye disease, age (children are at higher risk), immunodeficiency or suppression, malnourishment, alcoholism, fever, stress, malaria, and inappropriate use of topical steroids leading to geographical ulceration.
Signs and Symptoms of Herpes Simplex Keratitis
Herpes simplex keratitis is a condition that should come to mind when people experience sudden one-sided eye pain, sensitivity to light, blurred vision, and watery discharge from the eye. Previous episodes of herpes, especially around the mouth, face, or eye areas, increase the likelihood of this condition. Contributing factors can include wearing contact lenses, history of scratched corneas, exposure to certain light therapies, or use of corticosteroid medications.
A primary infection of herpes simplex keratitis doesn’t always show symptoms. But if it does, it might present as gentle inflammation of the eyelids and conjunctiva (the membrane covering the eye) with sores or blisters on the corneal surface. Patients might also experience fever, fatigue or symptoms of a cold. When the disease recurs, people often describe feelings of pain, like there’s something in the eye, along with light sensitivity, redness, blurred vision, and decreased corneal sensation. The variety of symptoms differs based on the type of keratitis and requires a special type of eye exam called a slit-lamp examination to identify and evaluate any lesions.
- Underactive immune system (which might result from illness or medications)
- Eyelid disorders
- Wearing contact lenses
- Burns or other injury to the cornea
- Exposure to certain light therapies
- Use of corticosteroid medications.
Further analysis helps to pinpoint the specific type of herpes simplex keratitis. Symptoms can range from discomfort, pain, redness, light sensitivity, to watering and blurred vision. Changes to the cornea might take the form of swollen cells, centrally located branching ulcers, and ultimately growing ulcerations that resemble an amoeba. Eye pressure can rise, vision can decrease, and after healing, there might be mild scarring or a foggy stain on the cornea.
Stromal keratitis and endothelial disease happen due to an active herpes simplex virus infection or an adverse immune response to the viral antigens in the cornea. This can lead to blurred vision, reduced corneal sensations, discomfort, and redness – though less severe than the epithelial disease. Eventually, a faint stromal and subepithelial scar may become worse, leading to the formation of superficial or deep blood vessels in the recurrent disciform keratitis.
In some cases, a persistent corneal defect and even perforation might follow prolonged topical medication, mostly due to reduced corneal sensation and medication toxicity. Another rare condition, necrotizing stromal keratitis, takes place as a result of active virus replication within the corneal tissue due to immune-mediated inflammation. Symptoms may include stromal necrosis with profound interstitial opacification and other features.
Iridocyclitis, or inflammation of the iris and ciliary body in the eye, might also result from viral replication. Increased intraocular pressure is common in this instance, believed to be caused by inflammation of the trabecular meshwork or as a side-effect of corticosteroid usage. Diagnosis requires a thorough eye examination.
Testing for Herpes Simplex Keratitis
If you have herpes simplex keratitis, a type of eye infection, your doctor will use a mix of physical examination and laboratory tests to diagnose the condition, define the kind of herpes simplex virus you have, and figure out how extensive the infection is. While the primary diagnosis is based on symptoms, laboratory tests can definitively confirm the infection.
Lab tests are key to confirming if you have an HSV cornea infection. There are several ways to do this, including:
Polymerase chain reaction (PCR) is the top choice for lab diagnosis because it’s accurate at spotting HSV DNA in samples from your eye. It’s thought of as the best standard for diagnosing viral eye infections, including herpes simplex keratitis. Other methods like viral culture and direct fluorescent antibody testing also offer useful info, but their use is less common compared to PCR.
In a viral culture, the sample from your eye is planted onto cell cultures which HSV can infect. If HSV infection signs appear, the virus is present. This test is less sensitive and can take longer than PCR, so is less useful for a quick diagnosis.
Direct fluorescent antibody testing uses special antibodies that bind to HSV antigens in eye samples. This method is quicker and more specific than viral culture, but less sensitive than PCR, and needs viable cells, so how the sample is handled is vital.
Immunohistochemistry involves staining parts of eye tissue with HSV antigen-targeting antibodies which are then looked at under a microscope. This is useful for detecting viral antigens in biopsy samples, but is typically used for research or when other diagnostic techniques are not conclusive.
Serological tests don’t usually diagnose active herpes simplex keratitis because they can’t differentiate between past exposure and active eye infection. HSV antibodies are common in the general population thanks to widespread HSV exposure. Even so, they are useful to detect past or recent infections.
How samples are collected and handled is crucial for an accurate diagnosis. An experienced eye doctor should collect any scrapings from your cornea to make sure enough material for analysis is obtained without causing further damage to your eye.
Tear analysis can be particularly revealing, but is not often used. It involves taking tear fluid from patients suspected of having an HSV infection and analyzing it for viral DNA. This technique’s advantage is its non-invasive nature and potential for early virus detection, especially in cases where corneal scraping is not advisable or the specimen is insufficient. However, tear analysis might be less sensitive than that of direct corneal samples due to the diluted nature of tears.
Aqueous humor sampling from the front of the eye for PCR testing is used mainly when HSV endotheliitis is suspected or the diagnosis remains uncertain. However, it’s a more invasive procedure that needs careful handling to avoid complications.
Other evaluations include: In vivo confocal microscopy – a revolutionary, non-invasive imaging method that provides high-resolution, real-time images of the corneal layers, helping identify microstructural changes in the cornea, including nerve fiber alterations, that are indicative of herpes simplex keratitis. It also helps in distinguishing herpes simplex keratitis from other types of keratitis. Corneal sensitivity testing – This simple, non-invasive procedure assesses the cornea’s ability to perceive tactile stimuli, offering valuable information on the functional status of the corneal nerves. Lower than normal corneal sensitivity supports the diagnosis of neurotrophic keratitis and can provide insight into the extent of nerve damage in the cornea.
Treatment Options for Herpes Simplex Keratitis
Treatment for herpes simplex keratitis, an eye condition, primarily uses nucleoside analog medications that interfere with the viral DNA. Although some types of ulcers may heal on their own, they can lead to significant scarring and formation of new blood vessels.
Treating Epithelial Keratitis
Epithelial keratitis is usually treated with eye drops or ointments like acyclovir or ganciclovir, which are applied five times a day. Trifluridine is another option, which can be used up to nine times a day. Almost all cases will clear up within two weeks with these treatments. After a week of treatment, the dosage of trifluridine can be reduced. Other older drugs, idoxuridine and vidarabine, may be less effective and cause more side effects. If these treatments are not effective, a medical procedure called debridement might be required. Here, the surface of the cornea is anaesthetised and wiped clean to eliminate the virus. For those with weaker immune systems or who don’t respond well to topical treatments, oral antivirals like acyclovir may be beneficial. However, if treatment is delayed or healing is slow and recurrences are frequent, it might suggest the presence of a resistant strain of the virus, and a combination of treatments might be needed.
Caution needs to be exercised while using certain drugs as they can worsen the condition. Drugs that dilate the pupil or promote breakdown of a protein should be avoided as they can increase the activity of the virus and cause inflammation. Instead, antiglaucoma drugs can be used to control glaucoma caused by inflammation of the eye’s drainage system.
Treating Disciform Keratitis
Disciform keratitis treatment involves the use of steroid and antiviral eye drops, which should be gradually reduced over a month as the condition improves. Steroid eye drops should only be used minimally when there’s active epithelial disease, and antiviral treatment should be increased. In severe cases, oral steroid treatment might be needed. Topical cyclosporin may also be helpful.
Treating Neurotrophic Keratitis and Necrotizing Stromal Keratitis
Neurotrophic keratitis is typically treated with the same regimen used for persistent epithelial defects. Necrotizing stromal keratitis treatment is similar to that for disciform keratitis, but with more intensive antiviral treatment. Both conditions require careful management to prevent further damage to the cornea.
Keratoplasty Therapy
In extreme cases where the disease has caused irreversible damage to the cornea, a cornea transplant (keratoplasty) may be needed. However, this is considered a last resort due to the risk of recurrence and rejection of the graft. Prior to surgery, a trial of rigid contact lenses should be attempted, and post-surgery patients should be given oral acyclovir to increase graft survival.
Preventative Measures
For patients who experience frequent recurrences or have the disease in both eyes, prophylactic medication can be considered to prevent future outbreaks. Oral antivirals such as aciclovir, valaciclovir or famciclovir can be used, though kidney function needs to be monitored during long-term treatment. These drugs are usually well tolerated and can reduce the recurrence rate of the disease by about 50%. Currently, a vaccination strategy is being studied for the prevention of ocular disease.
What else can Herpes Simplex Keratitis be?
When checking for herpes simplex keratitis, which is an eye infection caused by the herpes virus, doctors will also need to consider other conditions that may cause similar eye problems. These include:
- Herpes zoster keratitis (another type of herpes eye infection)
- Psuedodendrite (a mark left on the cornea when it is healing from an injury)
- Recurrent corneal erosion (when the cornea’s outermost layer repeatedly breaks down)
- Acanthamoeba keratitis (an eye infection caused by a type of amoeba)
- Vaccinia keratitis (an eye infection resulting from a smallpox vaccine)
- Epithelial rejection in a corneal graft (rejection of a transplanted cornea)
- Tyrosinaemia type 2 (a rare genetic disorder)
- Effects or impressions from long-term soft contact lens use
- Toxic keratopathy (damage to the cornea caused by eye medication)
- Preservative-induced keratopathy (damage to the cornea caused by preservatives in eye drops)
Your doctor will need to consider these possibilities and perform the right tests to make sure they make an accurate diagnosis.
What to expect with Herpes Simplex Keratitis
The outlook for people with HSV keratitis, a kind of eye infection, is generally positive with treatment. Most cases of dendritic ulcers, which are a specific kind of eye sore, get better on their own without needing any treatment. Mild to moderate cases usually get better with 2 weeks of topical treatment like ointments or eye drops, and sometimes an additional small surgical procedure might be needed.
However, if the epithelial or disciform keratitis—the formal terms for more serious eye inflammation—lasts for a long time, it might cause scarring and unwanted blood vessels. This could potentially lead to a loss in the quality of vision.
Possible Complications When Diagnosed with Herpes Simplex Keratitis
After getting herpes simplex keratitis, it’s important to watch out for some potential complications. For instance, additional infections can happen, the most common being bacterial keratitis. Here’s a list of other complications:
- Secondary glaucoma, which could be due to inflammation or constant use of steroids
- Complicated cataract, which might occur from inflammation or long-term use of steroids
- Iris atrophy, which is a result of kerato-uveitis
- Thinning of the cornea
- Corneal perforation
- Scarring of the cornea
- Hypopyon, or pus in the eye
- Spillover intermediate or posterior uveitis, which are inflammations of certain parts of the eye
- Panuveitis, which is inflammation that affects all parts of the uvea
- Macular edema, or swelling in the macula (the area of the retina that gives us sharp, clear vision)
- Progressive outer retinal necrosis, which is a damaging eye condition that can lead to severe vision loss or blindness
Recovery from Herpes Simplex Keratitis
Patients who have undergone a keratoplasty, or cornea transplant, need extensive aftercare and rehabilitation. To ensure the best recovery, patients generally need to begin using topical antibiotics, oral antivirals, and extra supportive drugs, especially in therapeutic and tectonic keratoplasty cases. In situations where a patient has had an optical penetrating keratoplasty, they should start using topical steroids along with oral antiviral medications and extra supportive drugs. These steroids are usually applied every hour or every two hours for the first two days, before being slowly decreased over a span of three months.
Eye drops containing antibiotics are usually recommended six times a day for half a month and adjusted based on how well the patient responds. Additionally, patients will require the use of supportive medications such as homatropine eye drops twice a day and timolol eye drops twice a day, to prevent inflammation and secondary glaucoma respectively.
After the surgery, it’s crucial for the patients to have follow-up appointments on specific days: day 1, day 5, day 14, and day 28, then once a month for three months, and finally every two months following surgery. Patients are strongly advised to stick to this schedule to ensure the transplant is successful.
Education is a vital part of this process. Patients should be guided clearly about the importance of regular drug application and about the signs that could indicate graft rejection. The persistent importance of follow-ups for graft management and survival should be stressed to the patients.
Preventing Herpes Simplex Keratitis
The herpes simplex virus is extremely common. People who have this virus should avoid close contact with others if they have recurring outbreaks of herpes simplex virus lesions on any part of their body. To help prevent spreading this virus to others, it’s crucial to maintain good hand and general hygiene.
As much as possible, try not to touch your eyes with dirty hands, because this can spread the virus. Keeping hands clean through regular handwashing is important. If a person is infected, it’s best to keep them separate to reduce the risk of spreading the virus to people they live with or their other contacts.
Once a person has been diagnosed with herpes simplex keratitis, an eye condition caused by the virus, it’s crucial for them to be aware of recurring outbreaks. Any delay in dealing with these recurrences could result in severe consequences. Therefore, it’s crucial that they seek medical attention promptly to ensure they receive the right care and treatment. Using preventive treatment might also be necessary to reduce the likelihood of future outbreaks.
