What is Persistent Epithelial Defect?
The cornea, the clear front surface of the eye, has an outer layer known as the corneal epithelium. This layer helps create a clear optical surface for vision, acts as a protective barrier against infections and damage, and is the eye’s first line of defense against harmful particles. If this layer gets disturbed or damaged, it can leave the eye vulnerable to infections, ulcers (sores), or even a hole or tear in the eye, known as a perforation.
Most of the time, when the corneal epithelium gets scratched or abraded, it heals quickly and without complications. However, in the presence of certain risk factors, these scratches or ‘corneal abrasions’ might take longer to heal. If these abrasions don’t recover after about two weeks of regular treatment, they are referred to as ‘persistent epithelial defects’ (PEDs).
PEDs aren’t very common, but they are difficult to manage because they don’t respond well to standard treatments and often need to be monitored for a long time. If not treated correctly, they can lead to serious problems like scarring, infection, blood vessel growth in the cornea (vascularization), and even vision loss. This is why it’s important to understand how they develop, what factors increase the risk, how to diagnose them, and what are the current and upcoming treatment options.
What Causes Persistent Epithelial Defect?
The healing process of the cornea, the clear front surface of the eye, can be harmed by various factors. These could generally fall into the following categories:
Defective Epithelial Adhesion: Sometimes, the top layer of cells on the cornea doesn’t stick properly to the lower layer. This could be because the bottom layer is abnormal, there’s too much of something called ‘Matrix metalloproteinases’ (which are involved in breaking down tissues), or the cells that are supposed to fix the top layer are disrupted. This can happen in conditions like recurrent corneal erosions (scratchy surface of the cornea), band-shaped keratopathy (cloudy areas on the cornea), and Salzmann nodular degeneration (small bumps on the cornea).
Limbal Stem Cell Deficiency: The healing of the cornea can be deficient if its replenishing stockpile of special cells known as ‘limbal stem cells’ are lacking. This can occur in conditions like limbal stem cell deficiency (an eye disorder), and as a result of chemical injury and trauma.
Inflammation: Overactive inflammatory markers, excessively produced chemotactic factors, growth factors, and proteases can cause overgrowth and movement of fixing cells, and even melting of the cornea. These could be present in autoimmune diseases, keratoconjunctivitis sicca (dry eyes), rosacea, Sjogren syndrome (an autoimmune disorder that affects moisture-producing glands), peripheral ulcerative keratitis, Mooren ulcer, Steven-Johnson syndrome, and graft-versus-host disease.
Neurotrophic: The cornea’s nerves can be disrupted. This may occur in diabetes mellitus, herpetic keratitis (a viral infection of the cornea), misuse of local anaesthetics, severe dry eyes, or after nerve damage from an injury.
Surface Trauma: If the surface of the eye is hurt repeatedly, the loss of cells may exceed their regeneration capacity. This could happen in the presence of entropion (eyelids that fold inward), ectropion (eyelids that turn outward), lagophthalmos (inability to close the eyes completely), trachoma (an infectious eye disorder), severe dry eye, and corneal injuries due to chemical or thermal burns.
Hereditary: Some people may inherit not enough limbal stem cells or an irregular lower layer of cells on the cornea. This can be seen in conditions like aniridia (absence of the iris), and cell and lower layer disorders on the cornea.
Risk Factors and Frequency for Persistent Epithelial Defect
The exact number of people suffering from PED, also known as an orphan disease, is not clear. Studies estimate that less than 200,000 people in the U.S. are diagnosed with this condition each year. This estimate is based on the number of related illnesses that happen in a given year. Some have also observed PED in certain circumstances such as among 7558 patients who received a corneal transplant and between 2,480 to 5,257 people who had surgery for a diabetic eye condition known as vitrectomy. If you have diabetes, and especially if you suffer from diabetic keratopathy (a problem that affects the surface of your eye and is present in 47% to 64% of patients with diabetes), you’re at an increased risk of developing PED.
- Men aged over 60 are more susceptible to PED after undergoing penetrating keratoplasty for infectious keratitis.
- The risk of PED also goes up if the size of the graft is more than 9 mm or if the cause of the keratitis was a bacterial or viral infection.
- PED is common in people with related health problems like rheumatic disease, and in those undergoing chemotherapy.
- PED has been reported in higher numbers in patients who have undergone a type of eye surgery known as pars plana vitrectomy.
- Children on mechanical ventilation are also more likely to develop PED, which highlights the need for immediate intervention and extra care.
Signs and Symptoms of Persistent Epithelial Defect
People with a condition known as PED often complain of eye discomfort, including pain, watering, and a feeling like there’s something in the eye. However, these symptoms might not always be present for neurotrophic PEDs. In some cases, blurred vision, redness, sensitivity to light, pain during blinking, or while moving the eyes might occur. If not addressed properly, PED could result in issues concerning the cornea, the front surface of the eye. These issues could result in inflammation, infection, ulcers, scarring, melting, or even punctures, as the protective layers of the cornea are compromised.
The best way to make a diagnosis and implement an effective treatment plan in these cases requires a detailed review of the patient’s history. This includes understanding how long they’ve had the condition, if there was any trauma that led to it, what treatments have been attempted before, and if there were any surgeries. Also, other relevant factors such as other eye and general health conditions, family history, and the person’s immune status, should be considered. Part of this process includes distinguishing between an epithelial defect and a PED, based on how long it takes for an injury to fully heal. In the case of an epithelial defect, recovery is usually seen within 7 to 10 days, whereas a PED will not show improvement even after two weeks, and standard treatments typically do not work.
Testing for Persistent Epithelial Defect
Determining the cause of an eye condition is very important and requires a comprehensive examination of the eyes, their surrounding structures (adnexa), as well as a general health assessment. An eye exam may involve the use of a special dye called fluorescein, which helps your eye doctor take clear pictures of your eye for closer examination.
When examining the defect, the doctor might notice deeper defects with a grayish-white edge and possibly piled up eye tissue (epithelium). Other signs of infection, such as underlying haze and white blood cells (infiltrates) in the front chamber of your eye, may also be noticed. A wide range of conditions may be associated with these defects, such as dry eyes, allergic conjunctivitis, and foreign bodies in the eye. The doctor will also examine the area around your eyes for signs of abnormalities such as blepharitis, an inflammation of the eyelids, and for signs related to conditions such as facial nerve palsy. Checking corneal sensations is also important to rule out neurological factors contributing to the condition.
The diagnosis of certain eye conditions, like Persistent Epithelial Defects (PED), mainly rely on clinical symptoms. This is further supported by investigations that help to track the progress of the lesion. A non-invasive technique called AS-OCT is used for monitoring the epithelium’s thickness and loss over time. Confocal microscopy is another method employed to image thin layers of the cornea’s structural cells.
When suspected defects are connected to systemic diseases, additional investigations should be conducted. For example, if diabetes is suspected, blood sugar levels and Hb1AC values are tested. Similarly, an underactive immune system can be detected by testing antibodies such as Rheumatoid factor and anti-double-stranded DNA to rule out conditions like rheumatoid arthritis and systemic lupus erythematosus (SLE) respectively.
Treatment Options for Persistent Epithelial Defect
The main goal of treatment is to create a healing environment within the eye for new cells to grow and spread. The choice of treatment depends on many things such as other health issues, the overall health of the body, previous medication used, and how the patient is responding to the treatment. If there is an infection apparent under the surface of the eye, it is crucial to treat it promptly to prevent it from spreading or causing damage to the cornea, the clear front surface of the eye.
Certain eye drops can harm the cornea and slow down healing. For example, gentamicin and tobramycin, which are aminoglycoside antibiotics, can harm the cornea and delay its healing. Benzalkonium chloride, a preservative found in many eye drops, can also irritate the eye. To help the cornea heal, it may be necessary to change the patient’s medications. Regular check-ups are required to ensure that the treatment is working.
A step-by-step approach is taken to manage these eye conditions. After identifying the cause, the main condition must be treated, which can include taking nerve growth factor for neurotrophic keratopathy, improving blood sugar control in diabetic keratopathy, stopping specific medication in drug-induced causes, or doing a limbal stem cell transplant for limbal stem cell deficiency.
The typical treatment begins with the use of preservative-free artificial tears and sterile eye ointments to keep the eye lubricated. This enables the epithelium, or surface of the cornea, to rebuild its structure and function. All other medications which might delay recovery should be stopped.
The next step involves using punctal plugs that block one’s tear ducts, hence retaining more moisture in the eyes, which aids the healing process of the cornea. Moreover, harmful eye medication should be stopped before using these plugs.
Soft contact lenses can help shield the damaged corneal layer from further damage due to blinking, thereby aiding in recovery. To prevent additional infections, topical broad-spectrum antibiotics might be used alongside preservative-free artificial tears, specifically for conditions like neurotrophic keratitis.
Other treatments include oral tetracyclines due to their healing properties, and suggestive use of topical corticosteroids, depending on the case. If medical methods are unsuccessful, surgical interventions such as debridement and tarsorrhaphy, procedures to clean and protect the eye, may be recommended. If standard treatments do not work, amniotic membrane grafting or transplant, autologous serum eye drops, scleral contact lenses, among others, might be used.
New treatments are continuously being developed, which work by promoting healing through various mechanisms. Topical fibronectin may help, however, mixed results have limited its use. Other treatments involve manipulating growth factors which oversee the healing process of the corneal epithelium. Examples of these include topical epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), human growth hormone, among others.
What else can Persistent Epithelial Defect be?
Diagnosing a skin issue (an ‘epithelial defect’) is a straightforward task, but it’s crucial to determine if it’s a persistent defect, as this helps in early treatment and avoiding worsening conditions. A regular skin defect should fully heal within 7 to 10 days. However, a persistent defect won’t even heal in two weeks. Knowing the cause behind the skin defect is important to provide the right treatment.
What to expect with Persistent Epithelial Defect
Even though there are various treatments for PED (a condition affecting the eyes), the speed of recovery can vary. Some patients may see quick improvements with just one treatment, while others might take weeks to get better, requiring multiple forms of treatment. The best chance for a good recovery comes from finding and treating the problem early, as this allows the healing process to start faster, leading to quicker and more complete recovery. That’s why the main goal is to begin treatment as soon as possible, to help the damaged cells in the eye repair quickly and prevent further complications.
Possible Complications When Diagnosed with Persistent Epithelial Defect
- Infection
- Sores or Ulcers
- Scarring in connective tissues
- Softening or Dissolving (Melting)
- Holes or Tears (Perforation)
Preventing Persistent Epithelial Defect
Managing Posterior Epithelial Defects (PED) requires careful and consistent monitoring with regular check-ups, sometimes even daily, until the condition improves. It’s essential for patients to understand the importance of sticking to their treatment plan and not missing any follow-up visits. Because the success of the treatment hinges greatly on the proper delivery of medications, it is key that the correct method of drug administration is shown to the patient. Once the condition is fully resolved, doctors should offer clear explanations on preventative steps that the patient can take to avoid the issue recurring.
