corneal Ulcer

Corneal Ulcer (Introduction)
The eye is one of the vital organs in a human being. As seen on figure 1, the eye is composed of many different parts and function. The cornea is a clear covering over the colored iris and the pupil of the eye. The function of cornea is to help focus light on the retina and protect the iris, lens, etc. so that the eye can see. The cornea is best to compare with a standard contact lens. Although, the function of a cornea is to protect from harmful microorganisms, it is also vulnerable to those same unicellular organisms.
One of the major diseases affecting the cornea is a corneal ulcer. A corneal ulcer is an non-penetrating erosion, or open sore in the outer layer of the cornea, the transparent area at the front of the eyeball (Medlineplus). Corneal Ulcer has many different names, depending on the microorganism that causes the ulcer. Some of the major diseases include Bacterial Keratitis, Fungal Keratitis, Acanthamoeba Keratitis, and Herpes Simplex Keratitis. Bacteria, fungi, amoebae, and viruses are the prime cause for these diseases. These microorganisms settle in the cornea, grow, and feed on the cornea. This process causes a corneal ulceration. Contact lenses are the leading way these microorganisms enter the cornea (discussed later).
There contains multiple symptoms in order to identify corneal ulceration. Some of these symptoms include the following: eye redness, tearing increases, vision impairs, eye burning, itching, and photophobia (sensitive to light) start to develop (Medlineplus).
Many different methods of detecting corneal ulcer are present at the doctors office. Visual acuity test, Slit-lamp test, and Shirmers (tear) test are some of the tests that a doctor conducts during eye examination. Visual acuity test allows the doctor to measure a persons vision by reading the eye chart (figure 6). A Slit-lamp is a specialized magnifying microscope in which a doctor could examine the cornea, iris, and retina. Its use is to look in the interior of the eye with the built-in laser and a camera (figure 7). Shirmers test determines whether or not there is enough tears to keep the eye moist. Another methods of detecting for corneal ulcer are Keratometry (measurement of the cornea) and scraping of the ulcer for analysis (Medlineplus).
There are many different ways to treat corneal ulcer. Many times, corneal ulcer is treated in the doctors office using eye drops. The eye drops are used to treat minor corneal ulcers. Depending on the microorganism that causes that corneal ulcer, many different varieties of eye drops can be used. If the ulcer is very severe, a particular surgery needs to take place. Either cornea transplant or Amniotic Membrane Transplant (AMT) needs to take place (Medlineplus). The treatments are thoroughly stated later.
Bacterial Keratitis (Figure 3)
Bacterial keratitis is caused by a variety of bacteria, and it is one of the most virulent forms of corneal ulcer. It rapidly grows on the cornea, and some bacteria destroy a cornea in 24-48 hours. Some of the most common bacterial species associates with bacterial keratitis are the following: Streptococcus, Pseudomonas, Enterobacteriaceae (including Klebsiella, Enterobacter, Serratia, and Proteus), and Staphylococcus (Murillo-Lopez).
Many species of bacteria often enter the cornea because of an abnormal tear in the corneal epithelium tissue (Murillo-Lopez).Many bacteria have structure that aids them to take control of the host cell. In the initial stage, the invasion of the bacteria causes inflammation in the infected area. As it progresses, necrosis starts to develop. Necrosis is a death of a tissue in response to a disease or an injury (Medical Dictionary). The inflammatory products (pus) diffuse and cause hypopyon. Hypopyon is accumulation of pus that appears gray fluid between the cornea and the iris (Medical Dictionary). Different bacteria also produce several enzymes, such as elastase and alkaline protease. They excrete the enzymes and cause harm to the cornea (Murillo-Lopez).

Bacterial keratitis causes other major problems to also occur in the cornea. Such problems can lead to major complications and even loss of vision. Corneal leukoma, irregular astigmatism, and corneal perforation are three of the major complications that occur during bacterial keratitis. Corneal leukoma is when scar tissue starts to form over the infected area at the end of bacterial keratitis. It can be managed through surgery such as phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PK). These surgeries are done in extreme cases and will be discussed later. Irregular astigmatism is another complication that takes place when the healing is uneven. Astigmatism occurs when the light rays are focused in more than one place in the retina (Medical Dictionary). It can be resolved through contact lens, glasses, or surgery. Corneal perforation is the most dangerous complication because it threatens the loss of an eye. These three complications can occur even after bacterial keratitis begins to heal (Murillo-Lopez).

Bacterial keratitis can be caused by many different factors. By far, contact lens users are the number one cause for bacterial keratitis or any other forms of corneal ulcer. 8,000 cases per year relate contacts to bacterial keratitis. The second main cause is the lack of immunologic defenses. This lack is the secondary effect of alcoholism, malnutrition, and diabetes (Murillo-Lopez). Previous injuries or diseases in the eye play a major role in causing bacterial keratitis. In few cases the position and alteration of the eyelids also plays an important role in causing bacterial keratitis. These alterations may cause irritation in the cornea and even rupture it. Once the cornea ruptures bacteria starts to invade and cause bacterial keratitis.

A corneal specialist does many lab studies and imaging studies to find out information on the particular corneal disease. They may scrape the corneal ulcer and send it in for a culture to find out which microorganism is causing the ulcer. They use microscope slides and use Gram or Giemsa stains in order to classify the particular bacteria causing the keratitis. Doctors often take samples of eyelids, contact lens, or lens solutions to also find the origin of the keratitis. In imaging studying, doctors often use a slit-lamp or B-scan ultrasound. Slit-lamp photography is very useful in examining the progress of the keratitis (figure 7). To examine the regions that are not clearly visible, the doctor often uses B-scan ultrasound system. These studies give a better view of the factors that causes bacterial keratitis (Murillo-Lopez).

Bacterial keratitis is often treated with many different antibiotics. If the condition is very severe, it may be treated with surgery. Different species of bacteria needs different antibiotics as a cure. Bacteria are often classified as either gram positive bacteria or gram negative bacteria. Gram positive bacteria are the ones that are dyed in violet in Grams method. Gram negative bacteria are the ones that are dyed in pink in Grams method. They are dyed only as a way for classification. Certain antibiotics work on Gram positive and certain work only on Gram negative bacteria. Figure 8 shows how sensitive and resistance to antibiotics the different bacteria really are. They are categorized into Gram positive and negative bacteria and determine their resistance (Schaefer).
Antibiotics such as Cephalosporins, Chloramphenicol, Macrolides, Glycopeptides, and Fluoroquinolones are found to work in many cases dealing with bacterial keratitis (Murillo-Lopez). Of all the antibiotics, Fluoroquinolones are found the best choice in dealing with bacterial keratitis (Schaefer). A clinical and microbiological study shows that Fluoroquinolones is very effective therapy in treating bacterial keratitis. It is effective because it penetrates through the cornea without any damage and destroys both Gram positive and Gram negative bacteria. Fluoroquinolones affect the bacteria through gyrating the bacterial DNA and destroying it. Fluoroquinolones is therefore the best tool against bacterial keratitis (Schaefer).

Fungal Keratitis (Figure 4)
Fungal keratitis is a subdivision of corneal ulcer and is the number one challenge to the doctors. It is very difficult to isolate the fungi and study it. It mostly shows in people with outdoor activities, especially agriculture. The fungi that cause fungal keratitis are in the following groups: Moniliaceae (nonpigmented filamentary fungi, including Fusarium and Aspergillus species), Dematiaceae (pigmented filamentary fungi, including Curvularia and Lasiodiplodia species), and yeasts (including Candida species) (Alexandrakis). These organisms penetrate the cornea and release enzymes such as mycotoxins and proteolytic to damage the tissue (Alexandrakis).

The major symptoms that deal with fungal keratitis are the following: increase eye pain, visual acuity, and hypersensitivity to light (photophobia). Most of the fungal keratitis is related to outdoor activities. Another major cause for fungal keratitis is any previous corneal surgeries (Alexandrakis). Fungal keratitis is very common in agricultural countries such as China than in more industrialized countries (Dong). In industrialized countries, there are more people with bacterial keratitis than fungal keratitis. Fungal keratitis presents a rare chance in industrialized countries (Murray).

There are many studies done on patients to determine if the cause is a fungus. Tests, such as corneal scrapings and Gram stains are very common with any corneal ulcers. Doctors culture and classify the microorganisms and then treat it the right antibiotic. Other tests include electron microscopy, immunoflourescence staining, and polymerase chain reaction (PCR). Electron microscopy allows the doctor to look at the microorganisms even closer than regular microscopes, and it is very useful in classifying the microorganisms. Immunoflourescence staining is very similar to gram staining. It also helps in identifying the correct microorganisms. PCR is very effective in diagnosing fungal keratitis because it has greater sensitivity and less recognition time. PCR provides patients with faster diagnosis and therefore less suffering (Alexandrakis).
Although fungal keratitis is mostly treated with antibiotics, it is sometimes very ineffective. Antibiotics such as Amphotericin B and oral fluconazole and ketocanazole are often in use at early stages. Amphotericin B is an effective drug against fungal keratitis that is caused by yeast. Oral fluconazole and ketocanazole are very effective in managing deep fungal keratitis. These treatments are often very ineffective and raise concerns. Corneal surgery and PK are very effective in treating fungal keratitis and other corneal ulcers. They are discussed later in General Treatments.

Acanthamoeba Keratitis (Figure5)
Acanthamoeba Keratitis is another subdivision of corneal ulcer and it occurs in every part of the world. It is one of the most-feared and visual threatening that an Ophthalmologist will face. The cause of Acanthamoeba keratitis is a protozoan that is found in air and land but also in main water supplies. Their living conditions make them very resistance to many anti-microorganism agents. Ninety-three percent of all the cases of Acanthamoeba keratitis cause from contact lenses (Radford). Another main cause of this keratitis is any corneal trauma. Although this is less frequent, it still presents some threat (Wongseworaset).

The main cause for acanthamoeba keratitis is the use of contact lenses and solutions to clean contact lenses (Seal). The protozoan causes this diseases to occur. It penetrates through the cornea and starts its destruction just like bacteria. It is the prime factor for this for acanthamoeba keratitis.

Drug combinations are used in treating many different acanthamoeba keratitis. Patients are treated with intense topical propamidine and neomycin to treat the keratitis. These two drugs prove to be very effective against keratitis. Doctors try to use other methods such as PK to treat patients. Against acanthamoeba keratitis, PK proves to be a failure. It is more effective against fungi keratitis. The new protozoan feeds on the new cornea if PK is done. A continuing process is very much unsuccessful (Chynn).
Herpes Simplex Keratitis (Figure 6)
Herpes simplex virus (HSV) keratitis is one caused by a virus. HSV is a DNA based virus that normally affects humans. HSV type 1 is the virus that affects the ocular region. The type one virus is one that affects the nerve. After penetrating through epithelium, the virus heads for the nerve cell. The virus enters the nerve end and travels through the cell. The virus genome enters the nucleus of the neuron. The virus causes the nerve to produce lytic infection in the ocular tissues (Wang).
A person may have herpes simplex keratitis if they have the following symptoms: Pain in the eye, photophobia, blurred vision, tearing, and redness in the eye. Herpes simplex divides into four main categories: infectious epithelial keratitis, neurotrophic keratopathy, stromal keratitis, and endotheliitis (Wang). Infectious keratitis is very noticeable because the corneal vesicles and geographic ulcer (figure 6). A sign of infectious keratitis is small, raised and clear vesicles. Neurotrophic keratopathy only develops if the patient has any previous contact with HSV disease. It is not infectious but it comes from previously decreased corneal tears. Corneal stromal keratitis associates as a secondary condition infectious keratitis, neurotrophic keratopathy, and endotheliitis. Corneal stromal keratitis has two main forms: Necrotizing stromal keratitis, and ISK. Necrotizing stromal keratitis leads to thinning and perforation of cornea. ISK causes ghost vessels to appear in any part of the cornea (Wang). Endotheliitis may cause inflammation in the cornea of the eye (Wang).

The causes for the herpes simplex keratitis result from viral infection. Infectious epithelium keratitis causes from viral replication in the corneal epithelium tissue. Neurotrophic Keratopathy results from a tear done by any of the previous viral infections. Necrotizing stromal keratitis causes directly from corneal stroma. Endotheliitis is a reaction to an antigen, but it does harm than good.

The lab studies are the same as bacterial keratitis and fungal keratitis. Doctors often use corneal scraping to culture, examine, and identify the virus. They stain the culture using Gram dye. Viral cultures are about 70% sensitive and can identify all the subdivision of herpes simplex virus. PCR is used in both fungi keratitis and herpes simplex keratitis. It is a form of detecting and examining viruses (Wang).

Many different antiviral medications are present at this time, but it may not have a lasting effect. Drugs such as Trifluridine, Idoxuridine, Vidarabine (Vira-A), Acyclovir, and Famciclovir. All these drug perform similar functions. They have no means of destroying the virus. These drugs merely suppress the symptoms. These drugs are false enzymes that suppress all the symptoms. Corneal surgery is an option but the symptoms will return and cause same problems.
Contact Lenses
Contact Lenses has been identified as the main cause for corneal ulcer. It is the prime source for different microorganisms to grow and develop. The microorganisms trapped inside the contact lenses eventually start to grow on the cornea if the lenses are not cleaned properly. The microorganisms start to grow on the cornea and eventually cause an ulcer and ruin the vision.
On April 1991, the Food and Drug Administration (FDA) conducts a survey on different types of contact lenses and its effect on corneal ulcer. The studies involve 22,739 people in 48 groups wearing different types of contact lenses. The studies take place for eight years and the 48 groups are studied for that much time. The studies determine which brand and type of contact lenses causes corneal ulcer or other types of corneal diseases. The different contact lenses are the following: daily soft, daily rigid with gas permeable, extended soft, extended rigid with gas permeable, and aphakic extended soft.
Table one displays all the different studies and number of people in each studies. All the studies did not have equal number of people, but the average is around 500 to 700 people. Table 2 states the duration of the studies done on all the people. There are about 1,568 people with corneal ulcer in the extended wear rigid gas permeable group. This number is considering very minuscule in comparison with other contact lenses. Extended wear soft contact lenses have the biggest number of corneal ulcer. It is three and half times more than daily wear contact lenses. Extended wear soft contact lenses causes more complications than any other groups of contact lenses (MacRae).

Bacterial Keratitis, Fungal Keratitis, and Acanthaamoeba Keratitis are mainly caused by contacts lens users. Many people do not clean their contacts properly and contaminate their eyes. Bacterial keratitis is many times caused through Gram negative bacteria in soft contact lenses (Dart). In industrialized countries, fungal keratitis can only occur from contact lenses (Murray). Protozoan, which can survive in air, land, and water, causes acanthamoeba keratitis. Protozoas presence in pipe water makes it possible for protozoan to enter the contacts. They then pass on to the cornea and do some damages (seal). Contact lenses are classified to be the biggest threat in destruction of cornea.

General Treatments
There are many different treatments used for different types of keratitis. Many different generalized treatments are used in these keratitis. In the initial stages, doctors most often use antibiotics to treat these keratitis. If the condition is too severe, doctors prefer different surgeries than any other forms of treatment. Treatment such as AMT, PTK, and are used all the severe conditions.

Amniotic Membrane Transplants (AMT) is a very new way of treating severe keratitis. Keratitis is caused by bacteria, fungi, protozoan, or virus, and is very dangerous and sight threatening. The cornea becomes thin or even deteriorates. In severe conditions, the cornea is in very poor conditions and AMT is necessary. Amniotic membrane is the innermost layer of the placenta (Quinn). Amniotic membrane transplant helps suppress inflammation and allow the cornea to heal properly. First, the surgeon removes the contaminated corneal tissue. Then, the amniotic membrane is placed over the defected cornea. Then, a very soft contact lens is put in place for the cornea to heal. Depending on the condition of the cornea, the doctor may choose to continue with the antibiotics. In Germany, this process works on ninety percent of the patients. AMT is a great surgical treatment for the future (Quinn).

Phototherapeutic Keratectomy (PTK) is another treatment that is used in many complications. PTK uses a broadband laser to correct the cornea and several corneal tissues. It is used in corneal irregularity and other corneal problems. It gets rid of scars caused by trauma and different keratitis. It also improves vision by improving the cornea. PTK is done when the condition is not that severe. It improves the cornea and the visual (Karpecki).
Penetrating Keratoplasty (PKP) is mainly used in treating fungal keratitis. It is an effective treatment when the antibiotics do not work. This procedure requires a donor to donate the cornea. The defective cornea is completely removed. The surgeon then takes the donated cornea and places it on the patient. The cornea should be the same size in diameter and thickness. The cornea becomes part of the recipient. This technique is found very effective in fungal keratitis but not in acanthamoeba keratitis. In acanthamoeba keratitis, the protozoan still remains and affects the new cornea, creating an endless cycle (Xie).
Corneal Ulcer rages anywhere from a mild antibiotic to getting corneal transplants. It can be a vision threatening disease. It affects a very large number of populations in America and at international level. Corneal Ulcer is divided among four main groups: Bacterial Keratitis, Fungal Keratitis, Acanthamoeba Keratitis, and Herpes Simplex Keratitis. The main causes for all these groups are contact lenses. Antibiotics as well as surgeries can be performed to treat these diseases.
Bacterial keratitis is a form of corneal ulcer that is caused by bacteria. It is very harmful and even vision threatening because of its short time infection. It can infect the whole cornea in 24-48 hours. The bacteria in contact lenses mainly cause it. They penetrate the cornea and start to multiply and infect. Lab studies such as corneal scraping help identify the bacteria so that it can be treated. Bacteria keratitis is normally treated with an antibiotic in the doctors office. Severe condition may lead the doctor to perform a corneal surgery.

Fungal keratitis is a form of corneal ulcer caused by Fungi. It occurs mostly in agriculture-based countries. It is also a vision threatening disease because of harmful destruction of the cornea. Fungal keratitis is mostly caused from people working outdoors in farms. The fungi enter the eye from dust and penetrate the cornea. The only successful known treatment for fungal keratitis is PKP.
Acanthamoeba keratitis causes from a harmful protozoan. The protozoan can live in air, water, and land, and therefore it is resistant to many form of antibiotic. The protozoan can enter contact lenses from water and infect the cornea. PKP is proven very ineffective to treat this disease. This disease is often treated with combination of different antibiotics.
Herpes Simplex Keratitis is one cause from a virus. The virus enters the cornea and into the nerve cells. It then changes the nerve cell and infects internally. It takes the hosts nerve cell and manipulates it to infect the host itself. Clear vesicles on the cornea make it possible to identify the virus and treat it. There are many antibiotics but most of them treat only the symptoms and not the virus. A lot more research is being done to treat herpes simplex keratitis.

Contact lenses are the biggest threat in the development of corneal ulcer. It contains microorganisms that live on the lenses and later penetrate through the cornea. It multiplies and feed on corneal tissue. The normal symptoms are generally loss of vision and noticeable scars on the cornea. If the condition is severe, doctors often do AMT, PTK, or PKP. In AMT, the doctor transplants an amniotic membrane and seals it with a soft contact lens. It is suppose to act as a new cornea for the patient. In PTK, the doctor uses a broadband laser to correct the cornea and to get better vision. In PKP, the doctor transplants an entire cornea from a donor to the recipient. These three surgeries are very effective in treating the severe corneal ulcer.

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