Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
The underlying cause must be treated as soon as possible to stop the disease process. Corticosteroid drop can be used to minimize the scarring on the cornea along with antibiotic cover. However, residual scarring cannot be avoided which can result in long term visual impairment and corneal transplantation is not suitable due to high rejection rate from the corneal vascularization.
During an acute flare-up, therapy is targeted at reducing the inflammation present, and dilating the pupil. Mydriasis is important, as pupillary constriction is the primary reason for pain. Anti-inflammatory therapy is usually given both systemically, often in the form of flunixin meglumine, and topically, as prednisolone acetate. The mydriatic of choice is atropine. In the periods between acute attacks, no therapy has been shown to be beneficial.
Reduction of neovascularization has been achieved in rats by the topical instillation of commercially available triamcinolone and doxycycline.
Some evidence exists to suggest that the Angiotensin II receptor blocker drug telmisartan will prevent corneal neovascularization.
Recent treatment developments include topical application of bevacizumab, an anti-VEGF.
Proper diagnosis is essential for optimal treatment. Bacterial corneal ulcer require intensive fortified antibiotic therapy to treat the infection. Fungal corneal ulcers require intensive application of topical anti-fungal agents. Viral corneal ulceration caused by herpes virus may respond to antivirals like topical acyclovir ointment instilled at least five times a day. Alongside, supportive therapy like pain medications are given, including topical cycloplegics like atropine or homatropine to dilate the pupil and thereby stop spasms of the ciliary muscle. Superficial ulcers may heal in less than a week. Deep ulcers and descemetoceles may require conjunctival grafts or conjunctival flaps, soft contact lenses, or corneal transplant. Proper nutrition, including protein intake and Vitamin C are usually advised. In cases of Keratomalacia, where the corneal ulceration is due to a deficiency of Vitamin A, supplementation of the Vitamin A by oral or intramuscular route is given. Drugs that are usually contraindicated in corneal ulcer are topical corticosteroids and anesthetics - these should not be used on any type of corneal ulcer because they prevent healing, may lead to superinfection with fungi and other bacteria and will often make the condition much worse.
Herpetic stromal keratitis is treated initially with prednisolone drops every 2 hours
accompanied by a prophylactic antiviral drug: either topical antiviral or an oral agent such as acyclovir or valacyclovir. The prednisolone drops are tapered every 1–2 weeks depending on the degree of clinical improvement. Topical antiviral medications are not absorbed by the cornea through an intact epithelium, but orally administered acyclovir penetrates an intact cornea and anterior chamber. In this context, oral acyclovir might benefit the deep corneal inflammation of disciform keratitis.
Treatments for corneal neovascularization are predominately off-lab with a multitude of complications as a result. The desired results from medical therapy may not always occur, ergo an invasive procedure may be needed to prevent further decrease in corneal avascularity.
For contact lenses related hypoxia, ceasing the use of contact lenses is the first step until corneal neovascularization is addressed by a physician. Modern rigid gas permeable and silicon hydrogel contact lenses have a much higher level of oxygen transmissibility, making them effective alternatives to help prevent corneal neovascularization.
Topical administration of steroids and non-steroid anti-inflammatory drugs are first-line treatment for individuals with CNV. The administration of steroids can increase the risk of infection, glaucoma, cataracts, herpes simplex recurrence. The anti-inflammatory drugs, however, increase the risk of corneal ulceration and melting.
Since VEGF plays an important role in vasculogenesis and pathologic neovascularization associated with eye diseases, a potential treatment for CNV is to inhibit VEGF activity by competing the binding of VEGF with specific neutralizing anti-VEGF antibody. VEGF inhibitors include pegatanib sodium, ranibizumab, and off-label bevacizumab are currently used for treatment of various retinal disease. Anti-VEGF antibodies such as the application of ranibizumab or bevacizumab have has been shown to reduce corneal neovascularization. Both ranibizumab and bevacizumab uses the same mechanism and inhibits all iso-forms of VEGF. The significant reduction in invasion of in-growth blood vessels in terms of neovascular area and vessel caliber suggests that treatment with ranibizumab induces thinning of the blood vessels, however, there's no significant change of the blood vessel's length. Using anti-VEGF antibodies to treat CNV has some limitations such as it is not a cure and may require repeated treatments to maintain positive effects over time. Topical and/or subconjunctival administration of bevaicizumab or ranibizumab have demonstrated short-term safety and efficacy, however long term effects have not been documented. Anti-VEGF therapy is currently an experimental treatment.
If the cornea is inflamed via corneal neovascularization, the suppression of enzymes can block CNV by compromising with corneal structural integrity. Corneal neovascularization can be suppressed with a combination of orally administration of doxycycline and with topical corticosteroid.
Surgical Options
Invasive solutions for corneal neovascularization are reserved when the medical therapies do not provide the desired results.
Invading blood tissues and ablating tissues in the cornea can be obstructed by the use of laser treatments such as Argon and s. Irradiation and/or damages to adjacent tissues caused by the procedure can result in corneal hemorrhage and corneal thinning. Obstruction of the blood vessels can be unsuccessful due to the depth, size, and, high blood flow rate of the vessels. In conjunction, thermal damage from the lasers can trigger inflammatory response which can exaggerate the neovascularization.
An effective treatment is photodynamic therapy, however, this treatment has limited clinical acceptance due to high costs and many potential complications involved that are also related to laser ablation. Complications can include irradiation from previously injected photosensitive dye inducing apoptosis and necrosis of the endothelium and basement membrane.
Diathermy and cautery is a treatment where an electrolysis needle is inserted into the feeder vessels in the limbus. The vessels are obstructed by a coagulating current through the use of unipolar diathermy unit or by thermal cautery.
Epithelial keratitis is treated with topical antivirals, which are very effective with low incidence of resistance. Treatment of the disease with topical antivirals generally should be continued for 10–14 days. Aciclovir ophthalmic ointment and Trifluridine eye drops have similar effectiveness but are more effective than Idoxuridine and Vidarabine eye drops. Oral acyclovir is as effective as topical antivirals for treating epithelial keratitis, and it has the advantage of no eye surface toxicity. For this reason, oral therapy is preferred by some ophthalmologists.
Ganciclovir and brivudine treatments were found to be equally as effective as acyclovir in a systematic review.
Valacyclovir, a pro-drug of acyclovir likely to be just as effective for ocular disease, can cause thrombotic thrombocytopenic purpura/Hemolytic-uremic syndrome in severely immunocompromised patients such as those with AIDS; thus, it must be used with caution if the immune status is unknown.
Topical corticosteroids are contraindicated in the presence of active herpetic epithelial keratitis; patients with this disease who are using systemic corticosteroids for other indications should be treated aggressively with systemic antiviral therapy.
The effect of interferon with an antiviral agent or an antiviral agent with debridement needs further assessment.
There are a number of different treatments to deal with TSPK. Symptoms may disappear if untreated, but treatment may decrease both the healing time and the chances of remission.
- PRK laser eye surgery may cure this disease (NOTE: A full clinical study has not been done, but a case study of one person was reported in 2002 PRK-pTK as a treatment).
- Artificial tear eye-drops or ointments may be a suitable treatment for mild cases.
- Low-dosage steroidal eye-drops, such as prednisone, fluorometholone, loteprednol (Lotemax 0.5%) or rimexolone. Steroidal drops should be used with caution and the eye pressure should be regularly checked during treatment.
- Soft contact lenses.
- Ciclosporin is an experimental treatment for TSPK. It is usually used during transplants as it reduces the immune system response.
- Tacrolimus (Protopic 0.03% ointment) is also an experimental treatment.
- Laser eye treatment.
- Amniotic membrane (Case Study)
Early diagnosis, targeted treatment according to the severity of the disease, and regular monitoring of patients with neurotrophic keratitis are critical to prevent damage progression and the occurrence of corneal ulcers, especially considering that the deterioration of the condition is often poorly symptomatic.
The purpose of treatment is to prevent the progression of corneal damage and promote healing of the corneal epithelium. The treatment should always be personalized according to the severity of the disease. Conservative treatment is typically the best option.
In stage I, the least serious, treatment consists of the administration of preservative-free artificial tears several times a day in order to lubricate and protect the ocular surface, improving the quality of the epithelium and preventing the possible loss of transparency of the cornea.
In stage II, treatment should be aimed at preventing the development of corneal ulcers and promoting the healing of epithelial lesions. In addition to artificial tears, topical antibiotics may also be prescribed to prevent possible infections. Patients should be monitored very carefully since, being the disease poorly symptomatic, the corneal damage may progress without the patient noticing any worsening of the symptoms. Corneal contact lenses can also be used in this stage of the disease, for their protective action to improve corneal healing.
In the most severe forms (stage III), it is necessary to stop the progression towards corneal perforation: in these cases, a possible surgical treatment option is tarsorrhaphy, i.e. the temporary or permanent closure of the eyelids by means of sutures or botulinum toxin injection. This protects the cornea, although the aesthetic result of these procedures may be difficult to accept for patients. Similarly, a procedure that entails the creation of a conjunctival flap has been shown to be effective in the treatment of chronic corneal ulcers with or without corneal perforation. In addition, another viable therapeutic option is amniotic membrane graft, which has recently been shown to play a role in stimulating corneal epithelium healing and in reducing vascularisation and inflammation of the ocular surface . Other approaches used in severe forms include the administration of autologous serum eye drops.
Research studies have focused on developing novel treatments for neurotrophic keratitis, and several polypeptides, growth factors and neuromediators have been proposed[25]. Studies were conducted on topical treatment with Substance P and IGF-1 (insulin-like growth factor-1), demonstrating an effect on epithelial healing[26]. Nerve Growth Factor (NGF) play a role in the epithelial proliferation and differentiation and in the survival of corneal sensory nerves. Topical treatment with murine NGF showed to promote recovery of epithelial integrity and corneal sensitivity in NK patients[27]. Recently, a recombinant human nerve growth factor eye drop formulation has been developed for clinical use[28].
Cenegermin, a recombinant form of human NGF, has recently been approved in Europe in an eye drop formulation for neurotrophic keratitis.
One treatment used is polyhexamethylene biguanide, PHMB.
Propamidine isethionate has also shown some effectiveness.
Another possible agent is chlorhexidine.
Keratoplasty may sometimes be required.
A combined regimen of propamidine, miconazole nitrate, and neomycin has also been suggested.
A recent Cochrane review found one study that compared the effectiveness of chlorhexidine eye drops against PHMB eye drops, for eyes with "Acanthamoeba" keratitis. The differences between treatments were not statistically significant; the review found that 86% of eyes treated with chlorhexidine eye drops reported a resolution of infection, compared to 78% of eyes treated with PHMB eye drops. The study also found that 71% of eyes treated with chlorhexidine eye drops reported improved visual acuity after treatment, compared to 57% of eyes in the PMGB group; these results were also not significant.
Depending on severity, therapies may range from topical or oral anti-inflammatories to irrigation and surgical repair.
Topical antibiotics are used at hourly intervals to treat infectious corneal ulcers. Cycloplegic eye drops are applied to give rest to the eye. Pain medications are given as needed. Loose epithelium and ulcer base can be scraped off and sent for culture sensitivity studies to find out the pathogenic organism. This helps in choosing appropriate antibiotics. Complete healing takes anywhere from about a few weeks to several months.
Refractory corneal ulcers can take a long time to heal, sometimes months. In case of progressive or non-healing ulcers, surgical intervention by an ophthalmologist with corneal transplantation may be required to save the eye. In all corneal ulcers it is important to rule out predisposing factors like diabetes mellitus and immunodeficiency.
Previous long-standing eye infection which possibly during childhood time recalled as being treated with antibiotic and/or hospitalized over long period of time.
Horses that suffer from this disease can never be considered cured, although they can be managed by careful use of the therapy described above, and fast detection of new flare-ups. If the disease is not properly treated, it will eventually lead to blindness.
Topical antibiotics may be reasonable.
One review has found that eye drops to numb the surface of the eye such as tetracaine improve pain; however, their safety is unclear. Another review did not find evidence of benefit and concluded there was not enough data on safety.
NSAID eye drops are also useful. A 2000 review found no good evidence to support medications that paralyze the iris. A 2017 review did not find evidence to suggest that topical NSAIDs would significantly reduce pain over standard-of-care treatments, but did find that NSAIDs could be associated with people using fewer pain medications by mouth.
A presumptive diagnosis of fungal keratitis requires immediate empirical therapy. Natamycin ophthalmic suspension is the drug of choice for filamentous fungal infection. Fluconazole ophthalmic solution is recommended for Candida infection of the cornea. Amphotericin B eye drops may be required for non-responding cases, but can be quite toxic and requires expert pharmacist for preparation. Other medications have also been tried with moderate success. Consult your eye care professional in any case as they will have the best treatment.
There is not good evidence for the treatment of recurrent disease. Special content lenses do not appear very useful.
For the allergic type, cool water poured over the face with the head inclined downward constricts capillaries, and artificial tears sometimes relieve discomfort in mild cases. In more severe cases, nonsteroidal anti-inflammatory medications and antihistamines may be prescribed. Persistent allergic conjunctivitis may also require topical steroid drops.
Treatment depends on the cause of the keratitis. Infectious keratitis can progress rapidly, and generally requires urgent antibacterial, antifungal, or antiviral therapy to eliminate the pathogen. Antibacterial solutions include levofloxacin, gatifloxacin, moxifloxacin, ofloxacin. It is unclear if steroid eye drops are useful or not.
In addition, contact lens wearers are typically advised to discontinue contact lens wear and replace contaminated contact lenses and contact lens cases. (Contaminated lenses and cases should not be discarded as cultures from these can be used to identify the pathogen).
Aciclovir is the mainstay of treatment for HSV keratitis and steroids should be avoided at all costs in this condition. Application of steroids to a dendritic ulcer caused by HSV will result in rapid and significant worsening of the ulcer to form an 'amoeboid' or 'geographic' ulcer, so named because of the ulcer's map like shape.
The infection typically takes a long time to heal, since the fungus itself is slow growing. Corneal perforation can occur in patients with untreated or partially treated infectious keratitis and requires surgical intervention in the form of corneal transplantation.
Viral conjunctivitis usually resolves on its own and does not require any specific treatment. Antihistamines (e.g., diphenhydramine) or mast cell stabilizers (e.g., cromolyn) may be used to help with the symptoms. Povidone iodine has been suggested as a treatment, but as of 2008 evidence to support it was poor.
According to the American Optometric Association, the following steps can be taken to prevent "Acanthamoeba" keratitis:
- Always wash and dry your hands before handling contact lenses, ordinary water should never come in contact with your lenses.
- Rub and rinse the surface of the contact lens before storing.
- Use only sterile products recommended by your optometrist to clean and disinfect your lenses. Saline solution and rewetting drops are not designed to disinfect lenses.
- Avoid using tap water to wash or store contact lenses.
- Contact lens solution must be discarded upon opening the case, and fresh solution used each time the lens is placed in the case.
- Replace lenses using your doctor’s prescribed schedule.
- Do not sleep in contact lenses unless prescribed by your doctor and never after swimming.
- Never swap lenses with someone else.
- Never put contact lenses in your mouth.
- See your optometrist regularly for contact lens evaluation.
Due to the different underlying causes, proper diagnosis, treatment, and prognosis can only be determined by an eye care professional. Punctate epithelial erosions may be treated with artificial tears. In some disorders, topical antibiotic is added to the treatment. Patients should discontinue contact lens wear until recovery.
Some infections may scar the cornea to limit vision. Others may result in perforation of the cornea, (an infection inside the eye), or even loss of the eye. With proper medical attention, infections can usually be successfully treated without long-term visual loss.
Some of the adverse outcomes associated with intra-operative injuries include:
- Increased length of stay. This is due to ophthalmology consults required, associated infections and treatment.
- Increased costs. This is due to increased length of stay, cost of treating the complications.
- Pain and discomfort for the patient. Corneal abrasions are extremely painful for the patient and the treatment consists of drops and ointments applied in the eye which may cause further discomfort for the patient.