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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 meta-analysis found evidence that does not support the use of patching.
Treatment can occur in two ways: treating symptoms and treating the deficiency. Treatment of symptoms usually includes the use of artificial tears in the form of eye drops, increasing the humidity of the environment with humidifiers, and wearing wraparound glasses when outdoors. Treatment of the deficiency can be accomplished with a Vitamin A or multivitamin supplement or by eating foods rich in Vitamin A. Treatment with supplements and/or diet can be successful until the disease progresses as far as corneal ulceration, at which point only an extreme surgery can offer a chance of returning sight.
A punctal plug may be inserted into the tear duct by an optometrist or ophthalmologist, decreasing the removal of natural tears from the affected eye.
The use of contact lenses may help prevent the abrasion during blinking lifting off the surface layer and uses thin lenses that are gas permeable to minimise reduced oxygenation. However they need to be used for between 8–26 weeks and such persistent use both incurs frequent follow-up visits and may increase the risk of infections.
Alternatively, under local anaesthetic, the corneal layer may be gently removed with a fine needle, cauterised (heat or laser) or 'spot welding' attempted (again with lasers). The procedures are not guaranteed to work, and in a minority may exacerbate the problem.
Anterior Stromal Puncture with a 20-25 gauge needle is an effective and simple treatment.
An option for minimally invasive and long-term effective therapy is laser phototherapeutic keratectomy. Laser PTK involves the surgical laser treatment of the cornea to selectively ablate cells on the surface layer of the cornea. It is thought that the natural regrowth of cells in the following days are better able to attach to the basement membrane to prevent recurrence of the condition. Laser PTK has been found to be most effective after epithelial debridement for the partial ablation of Bowman's lamella, which performed prior to PTK in the surgical procedure. This is meant to smoothen out the corneal area that the laser PTK will then treat. In some cases, small-spot PTK, which only treats certain areas of the cornea may also be an acceptable alternative.
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.
People with recalcitrant recurrent corneal erosions often show increased levels of matrix metalloproteinase (MMP) enzymes.
These enzymes dissolve the basement membrane and fibrils of the hemidesmosomes, which can lead to the separation of the epithelial layer. Treatment with oral tetracycline antibiotics (such as doxycycline or oxytetracycline) together with a topical corticosteroid (such as prednisolone), reduce MMP activity and may rapidly resolve and prevent further episodes in cases unresponsive to conventional therapies. Some have now proposed this as the first line therapy after lubricants have failed.
Treatment options include contact lenses, intrastromal corneal ring segments, corneal collagen cross-linking, or corneal transplant.
When cross-linking is performed only after the cornea becomes distorted, vision remains blurry even though the disease is stabilised. As a result, combining corneal collagen cross-linking with LASIK ('LASIK Xtra') aims to strengthen the cornea at the point of surgery and may be useful in cases where a very thin cornea is expected after the LASIK procedure. This would include cases of high spectacle power and people with thin corneas before surgery. Definitive evidence that the procedure can reduce the risk of corneal ectasia will only become available a number of years later as corneal ectasia, if it happens, usually occurs in the late post-operative period. Some study show that combining LASIK with cross-linking adds refractive stability to hyperopic treatments and may also do the same for very high myopic treatments.
In 2016, the FDA approved the KXL system and two photoenhancers for the treatment of corneal ectasia following refractive surgery.
Non-surgical treatments of FCED may be used to treat symptoms of early disease. Medical management includes topical hypertonic saline, the use of a hairdryer to dehydrate the precorneal tear film, and therapeutic soft contact lenses. Hypertonic saline draws water out of the cornea through osmosis. When using a hairdryer, the patient is instructed to hold it at an arm's length or directed across the face on a cold setting, to dry out the epithelial blisters. This can be done two or three times a day. Definitive treatment, however, (especially with increased corneal edema) is surgical in the form of corneal transplantation. The most common types of surgery for FCED are Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK), which account for over half of corneal transplants in the United States.
More speculative future directions in the treatment of FED include in-vitro expansion of human corneal endothelial cells for transplantation, artificial corneas (keratoprosthesis) and genetic modification. Surgery where the central diseased endothelium is stripped off but not replaced with donor tissue, with subsequent Rho-Associated Kinase (ROCK) inhibition of endothelial cell division may offer a viable medical treatment.
A greater understanding of FED pathophysiology may assist in the future with the development of treatments to prevent progression of disease. Although much progress has been made in the research and treatment of FED, many questions remain to be answered. The exact causes of illness, the prediction of disease progression and delivery of an accurate prognosis, methods of prevention and effective nonsurgical treatment are all the subject of inquiries that necessitate an answer.
Increased attention must be given to research that can address the most basic questions of how the disease develops: what are the biomolecular pathways implicated in disease, and what genetic or environmental factors contribute to its progression? In addition to shaping our understanding of FED, identification of these factors would be essential for the prevention and management of this condition.
Corneal collagen cross-linking is a developing treatment which aims to strengthen the cornea, however, according to a 2015 Cochrane review, there is insufficient evidence to determine if it is useful in keratoconus.
In 2016, the US Food and Drug Administration approved riboflavin ophthalmic solution and KXL system for crosslinking based on three 12-month clinical trials.
Amniotic membrane transplantation is an effective and safe procedure for pterygium removal. Amniotic membrane transplantation offers practical alternative to conjunctival auto graft transplantation for extensive pterygium removal. Amniotic membrane transplantation is tissue that is acquired from the innermost layer of the human placenta and has been used to replace and heal damaged mucosal surfaces including successful reconstruction of the ocular surface. It has been used as a surgical material since the 1940s, and has been shown to have a strong anti-adhesive effect.
Using an amniotic graft facilitates epithelialization, and has anti-inflammatory as well as surface rejuvenation properties. Amniotic membrane transplantation can also be fixated to the sclera using sutures, or glue adhesive. Amniotic membrane by itself does not provide an acceptable recurrence rate.
In early stages of keratoconus, glasses or soft contact lenses can suffice to correct for the mild astigmatism. As the condition progresses, these may no longer provide the person with a satisfactory degree of visual acuity, and most practitioners will move to manage the condition with rigid contact lenses, known as rigid, gas-permeable, (RGP) lenses. RGP lenses provide a good level of visual correction, but do not arrest progression of the condition.
In people with keratoconus, rigid contact lenses improve vision by means of tear fluid filling the gap between the irregular corneal surface and the smooth regular inner surface of the lens, thereby creating the effect of a smoother cornea. Many specialized types of contact lenses have been developed for keratoconus, and affected people may seek out both doctors specialized in conditions of the cornea, and contact lens fitters who have experience managing people with keratoconus. The irregular cone presents a challenge and the fitter will endeavor to produce a lens with the optimal contact, stability and steepness. Some trial-and-error fitting may prove necessary.
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.
Prophylaxis consists of periodic administration of Vitamin A supplements. WHO recommended schedule, which is universally recommended is as follows:
- Infants 6–12 months old and any older children weighing less than 8 kg - 100,000 IU orally every 3–6 months
- Children over 1 year and under 6 years of age - 200,000 IU orally every 6 months
- Infants less than 6 months old, who are not being breastfed - 50,000 IU orally should be given before they attain the age of 6 months
Most patients can be treated non-surgically with eyeglasses, or contact lenses.
There is evidence suggesting corneal collagen cross-linking may be beneficial for patients with pellucid marginal degeneration. Research shows some promising results by combining collagen cross linking with photorefractive keratectomy, or with topography-guided transepithelial surface ablation.
Conjunctival auto-grafting is a surgical technique that is an effective and safe procedure for pterygium removal. When the pterygium is removed, the tissue that covers the sclera known as the Tenons layer is also removed. Auto-grafting covers the bare sclera with conjunctival tissue that is surgically removed from an area of healthy conjunctiva. That “self-tissue” is then transplanted to the bare sclera and is fixated using sutures or tissue adhesive.
The treatment of corneal perforation depends on the location, severity and the cause of damage
- Tissue adhesive can be used to seal small perforation, but this method cannot be used to treat perforations larger than 1 mm.
- Non infected corneal perforation generally heals when a pressure bandage is used.
- For certain types of corneal perforations, lamellar keratoplasty is used as treatment.
In case of corneal erosion, a doctor may prescribe eye drops and ointments to reduce the friction on the eroded cornea. In some cases, an eye patch may be used to immobilize the eyelids. With effective care, these erosions usually heal within three to seven days, although occasional sensations of pain may occur for the next six-to-eight weeks. As patients with LCD suffer with dry eyes as a result of erosion, a new technique involving the insertion of punctal plugs (both upper and lower) can reduce the amount of drops used a day, aiding ocular stability.
By about age 40, some people with lattice dystrophy will have scarring under the epithelium, resulting in a haze on the cornea that can greatly obscure vision. In this case, a corneal transplantation may be needed. There have been many cases in which teenage patients have had the procedure, which accounts for the change in severity of the condition from person to person.
Although people with lattice dystrophy have an excellent chance for a successful corneal transplantation, the disease may also arise in the donor cornea in as little as three years. In one study, about half of the transplant patients with lattice dystrophy had a recurrence of the disease between two and 26 years after the operation. Of these, 15 percent required a second corneal transplant. Early lattice and recurrent lattice arising in the donor cornea responds well to treatment with the excimer laser.
Phototherapeutic keratectomy (PTK) using [Excimer laser] can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies.
Treatment is aimed at managing the symptoms of the disease. A form of laser eye surgery named keratectomy may help with the superficial corneal scarring. In more severe cases, a partial or complete corneal transplantation may be considered. However, it is common for the dystrophy to recur within the grafted tissue.
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.
The effect is normally temporary and after a period of six to eight weeks, the cornea usually returns to its former transparency. The recovery can be aided nonsurgically by bandaging with an osmotic saline solution. Non-steroidal anti-inflammatory topical may be used to reduce the pain and inflammation.
Early stages may be asymptomatic and may not require any intervention. Initial treatment may include hypertonic eyedrops and ointment to reduce the corneal edema and may offer symptomatic improvement prior to surgical intervention.
Suboptimal vision caused by corneal dystrophy usually requires surgical intervention in the form of corneal transplantation. Penetrating keratoplasty, a common type of corneal transplantation, is commonly performed for extensive corneal dystrophy.
With penetrating keratoplasty (corneal transplant), the long-term results are good to excellent. Recent surgical improvements have been made which have increased the success rate for this procedure. However, recurrence of the disease in the donor graft may happen. Superficial corneal dystrophies do not need a penetrating keratoplasty as the deeper corneal tissue is unaffected, therefore a lamellar keratoplasty may be used instead.
Phototherapeutic keratectomy (PTK) can be used to excise or ablate the abnormal corneal tissue. Patients with superficial corneal opacities are suitable candidates for a this procedure.
The preferred treatment of congenital glaucoma is surgical not medical. The initial procedures of choice are goniotomy or trabeculotomy if the cornea is clear, and trabeculectomy ab externo if the cornea is hazy. The success rates are similar for both procedures in patients with clear corneas. Trabeculectomy and shunt procedures should be reserved for those cases in which goniotomy or trabeculotomy has failed. Cyclophotocoagulation is necessary in some intractable cases but should be avoided whenever possible because of its potential adverse
effects on the lens and the retina.
Low order aberrations (hyperopia, Myopia and regular astigmatism), are correctable by eyeglasses, soft contact lenses and refractive surgery. Neither spectacles nor soft contact lenses nor routine keratorefractive surgery adequately corrects high order aberrations. Significant high order aberration usually requires a rigid gas-permeable contact lens for optimal visual rehabilitation.
Customized Wavefront-guided refractive corneal laser treatments are designed to reduce existing aberrations and to help prevent the creation of new aberrations. The wavefront map of the eye may be transferred to a Lasik system and enable the surgeon to treat the aberration. Perfect alignment of the treatment and the pupil on which the Wavefront is measured is required, which is usually achieved through iris feature detection. An efficient eye tracking system and small spot size laser is necessary for treatment . Wavefront customization of ablation increases the depth of ablation because additional corneal tissue must be ablated to compensate for the high order aberrations. Actual results with Wavefront guided LASIK showed that not only it cannot remove HOA but also the optical aberrations are increased. However, the amount of increase in aberrations are less than conventional Lasik. Corneal optical aberrations after photorefractive keratectomy with a larger ablation zone and a transition zone are less pronounced and more physiologic than those associated with first-generation (5 mm) ablations with no transition zone. An upcoming systematic review will seek to compare the safety and effectiveness of wavefront excimer laser refractive surgery with conventional excimer laser refractive surgery, and will measure differences in residual higher order aberrations between the two procedures.
Aspherical intraocular lenses (IOLs) have been used clinically to compensate for positive corneal spherical aberrations. Although Aspherical IOLs may give better contrast sensitivity, it is doubtful, whether they have a beneficial effect on distance visual acuity. Conventional (not Aspherical) IOLs give better depth of focus and better near vision. The reason for improved depth of focus in conventional lenses is linked to residual spherical aberration. The small improvement in depth of focus with the conventional IOLs enhances uncorrected near vision and contribute to reading ability.
Wavefront customized lenses can be used in eyeglasses. Based on Wavefront map of the eye and with the use of laser a lens is shaped to compensate for the aberrations of the eye and then put in the eyeglasses. Ultraviolet Laser can alter the refractive index of curtain lens materials such as epoxy polymer on a point by point basis in order to generate the desired refractive profile.
Wavefront customized contact lenses can theoretically correct HOA. The rotation and decentration reduces the predictability of this method.
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.