What is Epithelial Downgrowth?
Epithelial downgrowth is a rare eye condition that can threat your vision. It often occurs after an injury to the eye or as a complication of eye surgery. In this condition, epithelial cells, which are usually found on your skin, enter the front part of your eye (the anterior chamber) and start to grow into various parts of your eye. Though normally, these type of cells are not supposed to be in the interior of our eyes, they can grow in almost any part of the eye when this condition happens. This growth can take three forms: pearls, cysts, or sheets.
The form that spreads out like a sheet is the most common and aggressive type. It frequently leads to complications like secondary glaucoma, which is a serious condition affecting the eye’s pressure. The cystic form is less severe but all types of epithelial downgrowth can lead to serious outcomes. This could lead to extensive invasion by these cells, causing inflammation, secondary glaucoma, bleeding in the eye, and eventually permanent loss of vision or even the loss of the eye itself.
This article briefly explains the cause, how the condition develops, and risk factors for epithelial downgrowth. It also gives a detailed discussion of numerous ways to diagnose and treat this condition, discussing both pros and cons of each method. It’s important to note that the terms “epithelial downgrowth” and “epithelial ingrowth” might be used to mean the same thing in some resources. However, in this article, we’re not discussing epithelial ingrowth that happens after certain types of eye surgery like LASIK, where cells grow into the cornea.
Lastly, it’s key to separate epithelial downgrowth from fibrous downgrowth. Both conditions have similar causes, risks, and complications and are usually managed similarly. But, they do have vital differences which will be discussed more in the ‘Differential Diagnosis’ section.
What Causes Epithelial Downgrowth?
The condition known as epithelial invasion was first identified in 1832 by Dr. William Mackenzie. He described it as a kind of see-through cyst located in the front chamber of a patient’s eye, which happened after an injury that pierced the eye. Since then, there has been a recognition of epithelial invasion, also called epithelial downgrowth, mostly after eye injuries and cataract surgeries. However, this condition has also been linked with other eye procedures like penetrating keratoplasty (which is a corneal graft procedure), pterygium excision (removal of non-cancerous growths in the clear, thin tissue of the eye), aqueous aspiration (removal of fluid from the eye), and surgery for retinal detachment.
Although contemporary surgical techniques have lessened the risk of this condition, it has still been reported after other surgical procedures. These include clear cornea phacoemulsification (a modern, stitch-less cataract removal surgery), Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK, which is a partial cornea transplant), Descemet’s Membrane Endothelial Keratoplasty (DMEK, which is another type of cornea transplant), glaucoma implant surgery (where a small device is placed in the eye to help drain fluid), and type 1 Boston Keratoprosthesis (KPro), which is a cornea replacement procedure.
Risk Factors and Frequency for Epithelial Downgrowth
Epithelial downgrowth, which mainly occurs post-cataract surgery, is commonly caused by both intracapsular and extracapsular processes. The rate at which this happens is relatively low, roughly between 0.076% to 0.12%. However, some reports mention occurrences ranging from 0% to 1.1%. Furthermore, after a specific eye procedure known as penetrating keratoplasty, the occurrence of this condition has been marked at 0.25%. Generally, most people experience epithelial downgrowth within a year after having intraocular surgery. Yet, it’s worth noting that there have also been instances where this condition appeared many years after surgery or eye trauma.
Signs and Symptoms of Epithelial Downgrowth
Epithelial downgrowth, a condition that can affect your eyes, usually shows up within a year of an incident that causes it. Signs can vary but generally include several symptoms, such as decreased clarity of vision, redness, eye pain, tearing, and sensitivity to light. Some people may notice intensified inflammation and pain. However, diagnosing epithelial downgrowth can be tough since these symptoms can point to multiple eye conditions.
Regular eye exams are crucial and may help with detection. During an eye exam, the doctor may use a slit-lamp, which is a special microscope that allows a detailed look at the structures of your eye. Findings might include a see-through growth with an irregular, scalloped edge on the back surface of the cornea (the clear front part of your eye) or the front part of the iris (the colored part of your eye). Additionally, an abnormal sac or cyst may be seen originating from a wound site.
Another technique called gonioscopy may show abnormal tissues covering the iris and drainage angle of your eye, which might lead to a condition called glaucoma. However, keep in mind that eye pressure is different for everyone and can often remain normal, especially in instances where there is a small channel, or fistula, present.
Testing for Epithelial Downgrowth
Doctors can use several tools to spot a condition called epithelial downgrowth, where unwanted cells grow where they aren’t supposed to be. Depending on what symptoms you have, some methods might be more helpful than others. A test called a Seidel can find abnormal tunnels (known as fistulas), a common cause for this growth.
If there’s a suspicion that the growth is involving your iris (the colored part of your eye), then a process called argon laser photocoagulation might help. It uses light to detect these extra cells. Typically, when your normal iris is exposed to this procedure, it turns dark. But, if there are extra cells present, they’ll show up as a fluffy white reaction. However, bear in mind this only helps to diagnose if your iris is involved.
There’s also cytology, which means looking at cells under a microscope. In case of observable free-floating cells in the anterior chamber (front part of the eye), this method can be used. The cells can be stained to reveal if they originate from epithelium (skin-like tissue).
A couple of pretty techy-sounding tests can also be used. One of these is Specular Microscopy. It’s a non-intrusive test that looks for a defined border between your normal cells (endothelium) and any other new growth. However, this might not work well if your cornea (the clear front of your eye) is swollen.
Then there’s Confocal Microscopy, a superior version of the previous test. It can examine living tissue at a higher resolution and isn’t affected by a swollen cornea. With this, you can spot characteristic round, shiny nuclei suggestive of epithelium invasion. It can differentiate between fibrous and epithelium growth and may prove useful for tracking the progression of the epithelium downgrowth, spotting any changes after treatment.
Doctors could also use Anterior Segment Optical Coherence Tomography (AS-OCT). This test helps in detecting epithelium downgrowth as a reflective layer. It’s another non-intrusive test used after certain eye surgeries.
Histopathologic analysis is a kind of tissue analysis that’s considered the gold standard to confirm epithelial downgrowth. It relies on finding specific characteristics in the eye. Yet, this method can reveal the source of the unwanted cells too. If there are cells called goblet cells, it indicates the growth has come from the conjunctiva (the membrane lining the eye) rather than the cornea.
Immunohistochemistry is another method. It locates cells by uncovering targeted antibodies called AE1/AE3 common in most epithelia – the type of tissue where epithelial downgrowth originates. However, it’s tricky to tell apart thin squamous epithelium and a layer of corneal endothelium using this method alone. Due to limited evidence, this option isn’t regularly used.
Treatment Options for Epithelial Downgrowth
Epithelial downgrowth is a condition that was traditionally treated with a wide variety of methods, including surgeries such as removal of a section of the iris (iridectomy), removal of the vitreous humor in the eye (vitrectomy), burning a part of the body to remove or close off a part of it (cautery), corneal transplant surgery (penetrating keratoplasty), freezing (cryotherapy), burning the retina with a focused beam of light (photocoagulation), and mechanical removal of tissues. Medical treatments historically included radiation, alcohol, steroids, and antibiotics. However, many of these methods are no longer used due to complications or a high rate of the condition reoccurring. Today, the treatment of epithelial downgrowth can vary depending on the severity of the condition and whether it is in the cystic or diffuse form.
Cryotherapy is a technique that can be used to remove epithelium if localized to the back of the cornea, drainage angle, or ciliary body. This approach can be combined with other surgical techniques to restore clarity and vision, but can sometimes result in loss of cells lining the inner surface of the cornea, possibly requiring corneal transplantation later.
Transcorneal photocoagulation is another treatment option typically used for the cystic form of epithelial downgrowth. It is less invasive than cryotherapy, however, it may require multiple sessions and potentially lead to a rise in pressure within the eye. Complete treatment particularly in cases of corneal clouding can be achieved using endoscopic photocoagulation with a diode laser.
Intracameral injections, an option instead of more aggressive surgical management, are when medications are injected into the chamber of the eye. Two specific medications, 5-fluorouracil (5-FU) and Mitomycin-C (MMC), have been reported as potentially effective treatments for epithelial downgrowth. These are intended to inhibit cell growth and may alter the appearance of epithelial cells. Intraocular injections, however, do run the risk of side effects including epithelial defect and corneal decompensation.
Using MMC for treatment in the cystic form of epithelial downgrowth is considered since it damages the epithelial cells that secrete cyst fluid leading to the regression of the cyst. If it leaks into the anterior chamber of the eye, MMC can have devastating effects and this procedure must be performed carefully.
Intravitreal Methotrexate is another treatment option for epithelial downgrowth. It involves injecting medication into the clear jelly part of the eye and has been successful in treating cases that are resistant to other treatments.
In severe cases, aggressive surgical procedures are required and their success rates vary greatly. They could involve complete excision of cysts along with affected intraocular structures with full-thickness corneoscleral grafting. Even these procedures run the risk of reoccurrence or converting a cyst into the diffuse form, and may cause damage to ocular structures.
Lastly, preventing epithelial downgrowth is critical. This involves careful suturing of wounds and care of incisions during and after surgery. Any leakage from wounds should also be evaluated and repaired as necessary.
What else can Epithelial Downgrowth be?
The term “retrocorneal membrane” includes both epithelial downgrowth and fibrous downgrowth, which can result from trauma or eye surgery. For instance, fibrous downgrowth has been reported after cataract surgery, rigid Schreck anterior chamber lens implantation, intraocular telescope implantation, and traumatic corneoscleral wound dehiscence. Common risk factors include persistent inflammation, wound reopening, and delayed wound closure. Both conditions have non-specific symptoms and appear as see-through retrocorneal membranes.
Fibrous downgrowth can lead to complications similar to epithelial downgrowth, such as glaucoma. Still, there are a few differences. The membrane in fibrous downgrowth is predominantly fibrous rather than cellular and may be vascular. Fibrous downgrowth is also seen more often than epithelial downgrowth and tends to progress more slowly. Tests to confirm fibrous downgrowth are few, but certain staining techniques can help point towards this diagnosis.
The main treatments for both types of downgrowth include photocoagulation, surgical removal, and intracameral metabolites—substances involved in metabolism. Bevacizumab is flagged as a potential unique treatment for fibrous downgrowth with documented use in reducing vascularization within the fibrous membrane to lower intraocular bleeding.
In another condition known as pseudophakic bullous keratopathy (PBK), there is an irreversible swelling of the cornea after cataract surgery and postoperative inflammation. This is due to the loss of corneal endothelial cells secondary to surgical injury. PBK can have symptoms similar to epithelial downgrowth, including reduced vision, tearing, and pain. However, PBK can be differentiated by presenting stromal swelling and subepithelial fluid-filled blisters. When a patient is thought to have PBK and undergoes transplant surgery for the cornea, the presence of epithelial downgrowth should be considered and could be confirmed with certain tests.
Secondary endothelial proliferation typically follows ischemia and can also occur after multiple intraocular surgeries. The endothelial cells can proliferate in the eye’s angle and the iris’s front surface. This condition can be a precursor to neovascularization of the iris, potentially leading to neovascular glaucoma. It can clinically present as new blood vessel formation in the iris, but can be histologically differentiated from epithelial downgrowth due to an absence of layering.
What to expect with Epithelial Downgrowth
Visual results after being diagnosed with a condition called epithelial downgrowth tend to be poor due to issues such as reoccurrence, hard-to-control eye pressure (or glaucoma), and a condition known as corneal decompensation. The prognosis is typically worse if the downgrowth appears in a widespread, sheet-like form because it’s harder to identify and needs more complicated surgery.
Historically, many cases end with the removal of the eye, referred to as enucleation. This result is most often due to serious secondary glaucoma. According to a look back at cases from 1953 to 1983, 52% of patients who had surgery and 95% of those who didn’t have surgery ended up needing their eye removed.
In a different study including 52 patients from 1980 to 1996, doctors used a method called the en bloc excision and corneoscleral grafting. With this approach, the average vision clarity score was 20/100 for cases with a cystic-type downgrowth and 20/200 for those with a diffuse-type. Interestingly, there were no reported cases of reoccurrence or removal of the eye.
While many cases do need early and aggressive treatment to avoid permanent vision loss, there are a few occasional reports of epithelial downgrowth getting better on its own.
Possible Complications When Diagnosed with Epithelial Downgrowth
Possible complications from a condition called “epithelial downgrowth” can be chronic inflammation, secondary glaucoma, corneal decompensation, and in severe cases, a condition called phthisis bulbi. Secondary glaucoma is common and happens when the substance that normally drains from the eye (part of the trabecular meshwork) gets blocked. The blockage can be caused either by the epithelium directly sticking to it, or through extra mucin from tiny cells in the eye.
This inflammation can also cause some parts of the eye to stick together (peripheral anterior synechiae) and further worsens normal fluid drainage from the eye. This type of glaucoma often doesn’t respond well to medication and is a leading cause of irreversible vision loss.
Typically, management of this condition revolves around using eye drops to lower intraocular pressure (pressure inside the eye) along with a glaucoma drainage device. Doctors might also recommend freezing procedures (cryoablation). In some cases, the epithelium can also progress to the back of the eye due to other injuries or conditions which can cause it to proliferate onto the inner part of the retina. This can lead to a condition where the retina of your eye detaches and the formation of membranes on the retina (epiretinal membranes).
Common Complications:
- Chronic inflammation
- Secondary glaucoma
- Corneal decompensation
- Phthisis bulbi in severe cases
- Peripheral anterior synechiae
- Trabeculitis, an inflammation of the trabecular meshwork in the eye
- Irreversible vision loss
- Tractional retinal detachment and epiretinal membranes
Typical Management Process:
- Topical intraocular pressure–lowering medications
- Glaucoma drainage device
- Cryoablation procedures (freezing procedures)
Preventing Epithelial Downgrowth
Patients should be made aware of the available treatment choices for epithelial downgrowth, a condition in which cells grow in unintended areas of the eye. It’s important to understand that this condition often comes back, even after treatment. Depending on how severe the condition is, the aim of treatment might not always be to fully restore your vision and eye function. Instead, we might focus on stabilizing the condition and ensuring you’re comfortable.
If surgery becomes a necessary part of your treatment plan, it’s crucial to follow all safety guidelines provided after your operation. Doing so can greatly help improve your recovery and the overall success of the surgery.
