Enfermedad corneal

Inherited corneal dystrophies are caused by mutations (changes) in specific genes. The TGFBI gene on chromosome 5 is responsible for several common dystrophies, including lattice and granular types. Fuchs dystrophy in most patients of European ancestry is linked to a gene called TCF4. Macular dystrophy is caused by mutations in a gene called CHST6. More than 70 different genes have been identified across the full range of corneal dystrophies.

With age, the cells of the corneal endothelium (inner layer) gradually decline in number. In Fuchs dystrophy, this process accelerates due to genetic susceptibility and oxidative stress—damage from unstable molecules called free radicals. Long-term exposure to ultraviolet (UV) radiation from the sun contributes to pterygia, corneal lipid deposits, and other degenerative changes.

In autoimmune conditions such as rheumatoid arthritis, lupus, and Sjögren’s syndrome, the immune system attacks the body’s own tissues. At the cornea, this triggers inflammation, releases enzymes that break down tissue, and can lead to thinning and ulceration. In dry eye disease, an imbalance in the tear film triggers a cycle of inflammation on the corneal surface, driven by immune cells and proteins called cytokines.

The cornea is one of the most densely innervated (nerve-rich) surfaces in the body. When the trigeminal nerve—the nerve that supplies sensation to the cornea—is damaged by herpes infection, diabetes, tumor surgery, or radiation, the cornea loses its ability to sense injury and signal for healing. Without normal nerve input, the corneal surface breaks down progressively.

Several systemic health conditions can affect the cornea. Diabetes mellitus alters the corneal nerves and slows healing of the surface layer. Wilson disease causes copper to deposit at the corneal edge. Rare metabolic disorders such as cystinosis lead to crystal deposits throughout the corneal tissue.

• Contact lens wear: the single most important risk factor for infectious keratitis in developed countries. Contact lens wearers have more than nine times the infection risk of non-wearers. Poor lens hygiene, sleeping in lenses, and wearing lenses while swimming dramatically increase risk.
• Eye injury: especially injuries involving plant material, soil, or contaminated objects. This is the leading risk factor for fungal keratitis in tropical and agricultural settings.
• Prior eye surgery: This disrupts the corneal surface and can allow bacteria and fungi to enter.
• Topical steroid eye drops: Steroids suppress the eye’s immune defenses and increase the risk of secondary infections.
• Diabetes: It impairs corneal healing and reduces the eye’s ability to fight infection.
• Existing eye surface disease: Dry eye, blepharitis (eyelid inflammation), and other surface problems weaken the cornea’s natural defenses.

• Older age: Prevalence rises steadily with age, from 2.7% in adults aged 18 to 34, to 18.6% in adults aged 75 and older.
• Female sex: Women are affected nearly twice as often as men (8.8% versus 4.5%).
• Postmenopausal status: Hormonal changes after menopause contribute to reduced tear production.
• Autoimmune disease: Sjögren’s syndrome is a leading cause of severe aqueous-deficient dry eye.
• Prolonged screen use: This reduces blink rate, accelerating tear evaporation.
• Certain medications: Antihistamines, antidepressants, and blood pressure medications can reduce tear production.
• Low-humidity environments: Air conditioning, heating, and dry climates accelerate evaporation.

• Older age: Symptoms most often appear after age 50, though the underlying cell loss begins earlier.
• Female sex: Women develop Fuchs dystrophy three to four times more often than men.
• Family history: The TCF4 gene variation associated with Fuchs dystrophy can be inherited.

Most corneal diseases are detected during a comprehensive eye exam. Adults should have dilated eye exams regularly—at least every one to two years—and more often if they have risk factors such as contact lens wear, a family history of corneal dystrophy, diabetes, or autoimmune disease. Several specialized tests are used to screen for specific conditions.

• Slit-lamp biomicroscopy: A microscope with a bright, narrow beam of light allows the doctor to examine all layers of the cornea in detail. This is the primary tool used to identify infections, dystrophies, and surface disease.
• Corneal topography and tomography: Computerized maps of the corneal surface detect early keratoconus, irregular astigmatism, and structural thinning. Scheimpflug imaging (using a device called a Pentacam®) provides both front and back surface maps and is the gold standard before any refractive surgery.
• Specular microscopy: A non-contact camera counts and evaluates the cells of the corneal endothelium. It is used to screen for and monitor Fuchs dystrophy and to plan surgery.
• Schirmer test and tear break-up time: Two simple in-office tests measure how much tears the eye produces and how quickly the tear film breaks down. Results guide dry eye diagnosis and treatment.
• Corneal esthesiometry: A thin nylon filament gently touches the corneal surface to measure sensation. Reduced or absent sensation can diagnose neurotrophic keratopathy.
• Corneal culture: When an infection is suspected, a small sample is taken from the corneal surface and sent to a laboratory to identify the specific organism and determine which medicines will kill it.
• Genetic testing: This is available for families with a known hereditary corneal dystrophy to confirm the diagnosis and identify family members at risk.

• Blurry, hazy, or distorted vision: Objects may appear unclear, foggy, or wavy.
• Eye pain or aching: This can range from mild discomfort or grittiness to severe, sharp pain.
• Redness: The white of the eye appears pink or red due to increased blood flow from irritation or infection.
• Light sensitivity (photophobia): Bright lights cause significant discomfort or pain.
• Excessive tearing: The eye produces more tears than usual in response to irritation.
• Foreign body sensation: This may be a feeling that something is caught in the eye, even when nothing is there.
• Decreased visual sharpness: Objects are harder to see clearly, even with glasses.

Infectious keratitis (corneal infection):

• Sudden onset of severe eye pain, redness, and light sensitivity
• Pus-like discharge from the eye, especially with bacterial infections
• A white or gray spot visible on the colored part of the eye where the infection is located
• Rapid worsening of vision over hours to days

Dry eye disease:

• Burning, stinging, or a gritty sensation, as though sand is in the eye
• Vision that blurs intermittently and clears temporarily when blinking
• Eye fatigue and discomfort with prolonged reading, driving, or screen use
• Stringy or sticky mucus in or around the eyes

Keratoconus:

• Progressively worsening vision and distortion, often worse in one eye at first
• Frequent changes in glasses or contact lens prescription
• Ghost images or double vision in one eye (called monocular diplopia)
• Difficulty seeing at night and increased sensitivity to glare
• In advanced disease, a V-shaped indentation of the lower eyelid when looking downward (called Munson’s sign)

Fuchs endothelial corneal dystrophy:

• Morning vision blurriness that gradually improves over the first few hours of the day—caused by fluid that accumulates in the cornea overnight and evaporates during waking hours. This is an early and characteristic sign of Fuchs dystrophy.
• Glare and halos around lights
• In advanced stages, painful blisters (called epithelial bullae) on the surface of the eye

Stromal corneal dystrophies (such as lattice or granular):

• Recurrent corneal erosions—sudden, sharp eye pain often upon waking, with tearing and light sensitivity
• Gradual, progressive haziness in central vision

Neurotrophic keratopathy:

• Paradoxically, little or no pain, even when the cornea is severely damaged—because the nerves that would signal pain are no longer functioning
• Redness and tearing without the pain one would expect
• Non-healing sores (epithelial defects) on the corneal surface visible during an eye exam

• Slit-lamp biomicroscopy: This is the essential examination tool for all corneal diseases. A bright, narrow beam of light is focused through a microscope onto the eye, giving the doctor a magnified, cross-sectional view of each corneal layer. This can reveal infiltrates, ulcers, edema (swelling), deposits, thinning, and endothelial changes.
• Visual acuity testing: An eye chart test measures how sharp a patient’s vision is at a standard distance. It establishes a baseline and tracks how vision changes over time.
• Fluorescein staining: A small amount of orange dye is placed in the eye. Viewed under a special blue light, the dye highlights any breaks in the corneal surface, including ulcers, erosions, and the characteristic tree branch-shaped sores (dendrites) of herpes simplex keratitis.
• Rose bengal or lissamine green staining: These dyes highlight damaged or dead cells on the corneal surface. They are especially useful for assessing dry eye disease and the degree of surface cell injury.

• Corneal topography: a computerized map of the front surface of the cornea. It detects irregular shapes, uneven curvature, and the characteristic cone pattern of keratoconus.
• Corneal tomography (Scheimpflug imaging): a more advanced imaging system that maps both the front and back of the cornea, measures corneal thickness throughout, and calculates total optical power. It is the gold standard tool for detecting early keratoconus and planning surgery.
• Anterior segment optical coherence tomography (AS-OCT): uses light waves to produce high-resolution cross-sectional images of all corneal layers. It can measure the thickness of individual layers and assess the position of a transplanted graft.
• Specular microscopy: a non-contact camera photographs the innermost layer of cells in the cornea (the endothelium) and automatically counts them. This is essential for monitoring Fuchs dystrophy progression and evaluating whether a patient is a good candidate for surgery.
• In vivo confocal microscopy: provides cellular-level photographs of any layer of the cornea. It can detect Acanthamoeba cysts, fungal threads (hyphae), and inflammatory cells that are invisible on standard imaging.

• Corneal scraping with culture: a small sample of cells is taken from the infected corneal surface and sent to a microbiology laboratory. Bacteria, fungi, and parasites are grown in culture to identify the specific organism. Sensitivity testing determines which antibiotics or antifungals will be most effective. This is the gold standard test for infectious keratitis.
• Polymerase chain reaction (PCR): a molecular test that can rapidly identify the genetic material of viruses such as herpes simplex and varicella-zoster, as well as Acanthamoeba. It is more sensitive than culture for viral and parasitic infections.
• Corneal biopsy: In rare cases where culture is negative and infections do not respond to empiric (best-guess) treatment, a small tissue sample is taken for more detailed analysis.

• Corneal pachymetry: measures the thickness of the cornea at multiple points. A thin cornea suggests keratoconus or other ectatic disease; a thicker-than-normal cornea suggests swelling (edema) from endothelial failure.
• Corneal esthesiometry: A filament of known length is used to gently touch the corneal surface. The doctor measures the shortest filament length the patient can feel. Reduced or absent sensation confirms neurotrophic keratopathy.
• Schirmer test: A strip of filter paper is placed in the lower eyelid. After five minutes, the amount of moisture on the paper is measured. Less than 5 mm of wetting suggests inadequate tear production.
• Tear break-up time (TBUT): After placing fluorescein dye in the eye, the doctor uses a slit lamp to time how long it takes for dry spots to appear on the tear film. Less than 10 seconds indicates an unstable tear film.
• Tear osmolarity: A small tear sample is tested for salt concentration. High osmolarity (above 308 mOsm/L) is a biomarker for dry eye disease.

Anti-infective medications for corneal infections:

• Fluoroquinolone antibiotic eye drops (such as moxifloxacin and gatifloxacin): the first-line treatment for bacterial keratitis. These broad-spectrum antibiotics are applied frequently (sometimes every hour initially) to kill the infection and prevent scarring.
• Fortified antibiotics (such as cefazolin combined with tobramycin): These are used for severe or aggressive bacterial ulcers that need stronger coverage than standard drops can provide.
• Natamycin 5% eye drops (Natacyn®): the only U.S. Food and Drug Administration (FDA)-approved topical antifungal for the eye. It is the first-line treatment for filamentous fungal keratitis caused by organisms like Fusarium and Aspergillus.
• Ganciclovir 0.15% ophthalmic gel (Zirgan®): This is FDA-approved for herpes simplex keratitis affecting the surface layer (dendritic ulcers).
• Trifluridine 1% eye drops (Viroptic®): This is an older antiviral used for HSV surface infections.
• Oral antiviral medicines (valacyclovir or acyclovir): These are used for deeper herpes infections affecting the stroma or endothelium, and for long-term suppression in people with frequent herpes keratitis flares.
• Polyhexamethylene biguanide (PHMB) and chlorhexidine eye drops: compounded (specially prepared) topical medicines that are the primary treatment for Acanthamoeba keratitis. Treatment typically lasts several months.

Medications for dry eye disease:

• Cyclosporine 0.05% (Restasis®): FDA-approved in 2002. It works by reducing T-cell-mediated inflammation on the ocular surface. Used twice daily as long-term maintenance therapy.
• Lifitegrast 5% (Xiidra®): FDA-approved in 2016. It blocks a specific immune pathway (LFA-1/ICAM-1) that drives ocular surface inflammation. Used twice daily.
• Cyclosporine 0.09% (Cequa®): This is a newer, higher-concentration cyclosporine formulation using a nanomicellar (nanoscale particle) delivery system for better penetration. FDA-approved in 2018.
• Varenicline nasal spray 0.03 mg (Tyrvaya®): FDA-approved in 2021. A nasal spray that stimulates the eye’s natural tear production through the trigeminal parasympathetic nerve pathway. Used twice daily.
• Miebo® (perfluorohexyloctane eye drops): FDA-approved in 2023. The first prescription treatment specifically targeting evaporative dry eye. It forms a thin protective layer on the tear film to slow evaporation. Used four times daily.

Anti-inflammatory medications:

• Prednisolone acetate 1% eye drops: a topical corticosteroid (steroid) used for immune-mediated stromal keratitis and to treat corneal transplant rejection episodes. Must be used with caution because prolonged use can increase eye pressure and promote secondary infections.
• Loteprednol etabonate 0.5%: This is a lower-risk topical steroid used for mild surface inflammation and postoperative care.
• Cenegermin eye drops 0.002% (Oxervate®): FDA-approved in 2018 for neurotrophic keratitis at all stages. It is a laboratory-made version of nerve growth factor (NGF), a protein that promotes nerve regrowth and corneal healing. Applied six times daily for eight weeks.

Corneal transplantation (keratoplasty):

Corneal transplant surgery replaces damaged corneal tissue with healthy donor tissue. Modern surgical techniques allow surgeons to replace only the diseased layer rather than the entire cornea when possible. This leads to faster recovery, better vision, and lower rates of rejection.

• Penetrating keratoplasty (PK): full-thickness replacement of the entire cornea. Used when all layers are affected—for example, with full-thickness scars or failed previous grafts. Visual recovery is slower (often more than a year to full correction), but the procedure is well established with a 10-year graft survival rate of 72–92%.
• Deep anterior lamellar keratoplasty (DALK): replaces the stroma and front layers while preserving the patient’s own endothelium (inner cell layer). Used for keratoconus and stromal scars when the endothelium is healthy. Has a lower rejection rate than full-thickness transplant because the patient’s own endothelium is retained.
• Descemet stripping automated endothelial keratoplasty (DSAEK): replaces only the diseased endothelium plus a thin layer of stroma. Used for Fuchs dystrophy and other endothelial diseases. Most patients achieve good vision within about a year.
• Descemet membrane endothelial keratoplasty (DMEK): the thinnest, most precise endothelial transplant, replacing only the Descemet membrane and endothelium. This is the preferred procedure for Fuchs dystrophy at many centers. It offers the fastest visual recovery—93% of patients achieve good vision within five years—and the lowest rejection rate of all transplant types.

Corneal collagen cross-linking (CXL):

Cross-linking is currently the only treatment proven to halt the progression of keratoconus. It is FDA-approved (under the brand names Photrexa® Viscous and Photrexa®, used with the KXL® UVA system). The procedure involves removing the outermost corneal layer, applying riboflavin (vitamin B2) drops for 30 minutes to saturate the cornea, then exposing the eye to controlled UVA light for 30 minutes. The UV light activates the riboflavin to create new bonds between the collagen fibers in the stroma, stiffening the cornea and stopping further thinning and bulging. Cross-linking does not reverse existing damage—it prevents future progression.

Other surgical interventions:

• Phototherapeutic keratectomy (PTK): An excimer laser (the same type used in LASIK) is used to precisely remove diseased or scarred tissue from the front layers of the cornea. It is highly effective for recurrent erosions, superficial corneal scars, and anterior dystrophies.
• Intracorneal ring segments (ICRS, also called Intacs): Thin, curved plastic arcs are implanted into the stroma of the cornea to flatten its central shape and improve vision in keratoconus. They do not stop progression but can improve functional vision, often enough to allow comfortable contact lens wear.
• Amniotic membrane transplantation: A biological tissue graft from donated placental membrane is placed over the corneal surface. It promotes healing, reduces inflammation, and prevents scarring. Used for persistent non-healing ulcers, chemical burns, and neurotrophic disease.
• Boston keratoprosthesis (artificial cornea): For patients who have failed multiple corneal transplants or are not candidates for donor grafts, an artificial cornea device (called a Boston Keratoprosthesis—KPro) can be implanted to restore functional vision.
• Conjunctival autograft: Tissue from the patient’s own eye (conjunctiva) is used to cover the site after pterygium removal. This is the gold standard surgical technique for pterygium because it significantly lowers the chance that the growth will return.

• Artificial tears and lubricating eye drops: the first-line treatment for dry eye disease. Preservative-free formulations are preferred for frequent use (more than four times per day) to avoid chemical irritation.
• Punctal plugs: tiny silicone or collagen plugs inserted into the small drainage openings at the inner corner of the eyelids to slow tear drainage and keep more moisture on the eye. Used for moderate to severe dry eye.
• Autologous serum eye drops: eye drops made from the patient’s own blood serum (the liquid part of blood after cells are removed). They contain growth factors and nutrients that support corneal healing. Used for severe dry eye, neurotrophic keratopathy, and persistent non-healing surface wounds.
• Scleral contact lenses: Large-diameter rigid gas-permeable contact lenses that vault completely over the cornea and rest on the white part of the eye (sclera). They create a fluid-filled reservoir between the lens and the corneal surface. Used for irregular corneas from keratoconus, post-transplant irregularity, and severe dry eye, where conventional lenses are not tolerated.
• Bandage soft contact lenses: soft lenses worn not for vision correction but to protect the healing corneal surface after surgery or injury. They reduce friction between the eyelid and the cornea.
• Warm compresses and lid hygiene: a standard recommendation for meibomian gland dysfunction and evaporative dry eye. Warming the eyelid margins softens the oil in the meibomian glands so it flows more easily onto the tear film.

• Omega-3 fatty acid supplements: Some evidence suggests that omega-3 supplements have anti-inflammatory effects that may benefit dry eye disease. The National Institutes of Health (NIH)-funded DREAM study found mixed results. These supplements are not FDA-approved as a treatment for corneal disease but may be discussed with your doctor as a complementary option.
• Acupuncture: Limited evidence exists for symptom relief in dry eye disease. It is not FDA-approved for any corneal condition.