Keratoconus
Introduction
Introduction to keratoconus Keratoconus (keratoconus) is a primary corneal degenerative disease characterized by corneal dilation, which causes the central part of the cornea to bulge forward and produce highly irregular myopic astigmatism and different visual impairment. It can be an independent The disease can also be part of multiple syndromes. It occurs mostly before and after puberty without inflammation. Acute corneal edema occurs in the late stage, which forms scars and severely impaired vision. The generalized keratoconus includes two types: the anterior keratoconus and the posterior keratoconus, which in turn can be divided into completeness and limitation. The narrow keratoconus generally refers only to the anterior keratoconus. basic knowledge The proportion of illness: 0.003% Susceptible people: no special people Mode of infection: non-infectious Complications: retinal detachment, keratopathy
Cause
Keratoconus etiology
(1) Causes of the disease
The exact cause is unclear and may be caused by multiple factors, such as genetic factors and endocrine factors.
(two) pathogenesis
1. Genetics: Ammon (1830), Jaensch (1929), Anelsdorst (1930) and others believe that keratoconus is a recessive inheritance, but in some cases there may be symptoms for two or three consecutive generations. For such cases, consideration should be given to Regular or irregular dominant inheritance.
Advocates of this theory suggest that keratoconus often incorporates other congenital anomalies, and this disease is accompanied by genetic factors such as retinitis pigmentosa, blue sclera, no iris, iris fissure, Marfan syndrome, anterior pole. Cataract, corneal dystrophy, congenital stupidity, etc.
More scholars believe that the disease is autosomal recessive. For example, Ammon (1830) reported that there were irregular cases in six families. Gaoqiao reported that three people in a compatriot were suffering from the disease. They also found that the relatives of these cases often had close relatives. History, but some cases can occur for 2 or 3 consecutive generations, sometimes interrupted, suggesting that the manifestation is incomplete, these should be considered as regular or irregular dominant inheritance, autosomal dominant keratoconus disease gene located in the chromosome 16q22 and 3q23, in some hereditary diseases such as retinitis pigmentosa, Downs syndrome, blue sclera and Marfan syndrome, may be combined with keratoconus.
2. Developmental Disorders: Collins et al (1925) and (1960) suggest that the disease is caused by a decrease in the central part of the cornea, a tough stenosis, and is incapable of resisting normal intraocular pressure. Mihalyhegy (1954) found that The keratoconus not only changes the curvature of the cornea, but also the obvious changes in the sclera. Therefore, he suggested that the cause of the keratoconus should be found from the interstitial hypoplasia.
3. Endocrine Disorder Theory: Siegrist (1912), Knapp (1929) and Stitcherska (1932) all believe that hypothyroidism has an important relationship with the occurrence of this disease. Siegrist (1912) suggested that hypothyroidism is an important factor in the occurrence of keratoconus. This statement was also praised by Knapp (1929) and Stitcherska (1932), and Hippel (1913) specifically emphasized the role of the thymus in the development of keratoconus.
4. Metabolic Disorder Theory: Myuhnk (1959) found that the basal metabolic rate of patients with this disease was significantly reduced. Tntapeho (1978) reported that zinc in the blood of patients with this disease, nickel content decreased significantly, titanium, lead and aluminum increased, while manganese The content is normal, so it is believed that the changes in these trace elements have a certain impact on the occurrence of this disease, Yukobckaa et al (1979) reported that the activity of glucose-6-phosphate dehydrogenase was significantly decreased in the blood and aqueous humor of patients with this disease.
5. Allergic theory: keratoconus often occurs simultaneously with allergic diseases such as catarrhal keratoconjunctivitis in the spring, which is characterized by decreased IgA response, increased IgE response, and defective cellular immunity. Boland (1963) statistics, patients with this disease 32.6% had hay fever and 33.3% had asthma. Ruedeman reported that 86% of the patients had a history of allergic reactions.
6. Wearing a contact lens can induce keratoconus: Hartstein (1968) reported that 4 cases of keratoconus after contact lens wear, think that wearing contact lenses may induce this disease, eye and corneal hardness may be reduced after wearing contact lens Risk factors for the disease.
7. PRK, LASIK and other excimer laser keratectomy secondary to keratoconus.
8. Chronic ocular dryness lesions and lack of tears will make the lower cornea steep and produce high corneal astigmatism, forming a secondary keratoconus.
Prevention
Keratoconus prevention
The keratoconus is a developmental corneal abnormality, which often causes visual loss in puberty. Occasionally, blunt contusion induces acute keratoconus formation. Late general glasses cannot be corrected. No matter what degree of keratoconus, drug treatment can not cure. In the medium term, contact lenses can be worn to improve vision. In the advanced stage, corneal transplantation should be preferred, with a success rate of 90%.
Complication
Keratoconus complication Complications, retinal detachment, keratopathy
Can be complicated by lens dislocation or retinal detachment, etc., can cause chronic keratopathy.
Symptom
Keratoconus symptoms common symptoms large corneal photophobia tears myopic astigmatism conjunctival edema and corneal ulcer conjunctival hyperemia retinal detachment
Symptoms and signs
(1) anterior keratoconus: clinically more common, divided into 4 phases according to the clinical process:
1 incubation period: there is no symptom in this period, it is difficult to diagnose clinically. If the disease has been diagnosed at one glance, the retinoscopy is used to detect the abnormality of the retinal (the phenomenon of shearing red light is reflected), and the confirmed case Those who have abnormal retinoscopy in their relatives should consider the possibility of this disease.
2 Initial stage: The clinical manifestations of this period are mainly refractive error, and the visual acuity of the naked eye is decreased. However, the eyesight can be corrected by glasses or contact lens. At the beginning, only simple myopia may appear, and gradually develop to regular or irregular astigmatism, so it is always Showing myopic astigmatism, the cornea gradually bulges forward, and its morphology can be examined by a variety of methods. For example, using the Placido disk for qualitative analysis, the corneal image of the Placido disk in this period will appear to be concentric with the concentric ring and the axis, ie above the cornea or The ring on the nasal side is wider, and the ring in the lower part of the ankle is narrowed. The ring in the center of the cornea is irregularly imaged and deformed in the horizontal axis, that is, the image is pear-shaped. Note that the disk should be aligned with the center of the cornea and not tilted. Otherwise, the results will be biased. When the keratometer is used for examination, regular astigmatism can be found, the corneal refractive power increases, and the radius of curvature becomes smaller. This instrument is not suitable for detecting irregular astigmatism. Photokeratoscope is used to record corneal morphology. In one method, the slanted part of the cornea shows a close concentric circle in the photo. This method can improve the initial diagnosis rate. The computer-assisted corneal topographic analysis system can qualitatively and quantitatively detect corneal morphological changes. The early corrected visual acuity of the keratoconus can be normal. The slit lamp and the Placido disk can be found without abnormal findings, but with corneal topography. Graph examination can detect early lesions. Some people have summarized three characteristics of early keratoconus with corneal topography:
A. The cornea becomes steeper under the iliac crest, the refractive power increases, and the radius of curvature becomes smaller.
B. The refractive power in the central region of the cornea is unevenly symmetric.
C. The difference in refractive power between the center and the periphery of the cornea is significantly increased from normal 2 to 3D to more than 10D. Usually the cornea under the quadrant becomes steeper first. As the disease progresses, the cornea becomes steep and extends to the lower nasal quadrant. It is the upper quadrant, but rarely affects the nasal upper quadrant. In this period of retinal retinoscopy, the pupil light band is open mouth opening and closing, that is, shearing shadow, and the corneal epithelium and the front elastic membrane can be seen when the slit lamp is examined. Increased reflection and weaker reflection of the stromal layer can be used for early diagnosis of keratoconus using the Orbscan corneal topography system.
3 Completion period: typical keratoconus symptoms, that is, visual acuity decreased significantly. Except for wearing contact lenses, general glasses can not correct vision. As the disease progresses, the sensitivity of the early corneal center becomes sensitive, which makes the period become dull. Known as Axenfeld sign, some chronic keratopathy, even long-term contact lens can also appear this sign, the corneal center is significantly thinner and conical when examined, when the downward gaze, the cone presses down the rim, making the next A bend appears in the rim of the rim, called the Munson sign.
Under the slit lamp, the optical cut surface is a special circular or elliptical cone. The top of the cone is located at the lower side of the cornea. The thinner the cornea is, the thinner, sometimes only 1/5 to 1/2 of the normal corneal thickness. During the development of the lesion, a number of thin lines about 2 mm long and parallel to each other are formed in the stromal layer. The thin line gradually becomes thicker and thicker like a fence, and the thick view is straight. The keratoconus line, also known as the Vogt stripe, is actually a vertical pressure line caused by an increase in wrinkles in the matrix layer. When pressure is applied to the eyeball, it can disappear, sometimes under the epithelium near the base of the cone. A yellow-brown ring with a width of about 0.5 mm has a diameter of 5 to 6 mm, which may be a complete ring shape or an incomplete ring or a semi-ring shape. After expansion, it is very conspicuous under the cobalt blue light line. It is caused by epithelial or anterior elastic membrane. The iron is thought to come from tears. Its typical distribution is caused by tear-impregnated cone bottom. This ring is called Fleischer ring and its appearance rate is about 50%. Young patient, corneal stroma The nerve fibers are clearly visible, sometimes in the form of a gray line, sometimes in the form of a grid. Punctiform epithelial exfoliation can occur near the top of the cone, and the epithelium can be a bit turbid, with new blood vessels growing near the limbus.
With a direct fundus microscope 10 to 30 cm away from the affected eye, a circular hazel shadow can be seen through the +5D lens, but this can also be seen in the early changes in the refractive index of the lens or in the early stage of nuclear cataract. The cornea should be examined in detail. The lens is distinguished, and the fundus image is not clear due to the obvious deformation of the cornea.
4 degeneration period: glassy degeneration under the epithelium of the cornea of the lesion, scar formation at the conical surface and neovascularization into the superficial cornea, the visual acuity of the patient is significantly reduced in this period, can not be corrected with glasses or contact lenses, sometimes can occur Acute post-elastic membrane rupture, called "acute stage keratoconus" or "acute keratoconus edema", at this time the patient complained of pain, photophobia, tearing and other serious irritation and visual acuity, the conjunctival hyperemia, cornea Acute edema of the stroma and epithelial layer, opacity, edema turbidity often indicates the size of the elastic membrane rupture, the larger the rupture, the wider the edema turbidity, the shape of the rupture often sickle-shaped or crescent-shaped, after several weeks, the rupture The nearby endothelial cells gradually become larger, migrate and cover the regenerated post-elastic membrane, and the corneal edema gradually subsides, forming a misty scar, which makes the cornea of the lesion appear translucent. If the scar involves the visual field, the visual acuity is significantly impaired. If it is not in the visual field, the scar of the stromal layer will flatten the cornea, the myopia and astigmatism will be reduced, the vision will be improved, and it is suitable for wearing. Vision correction contact lens, Descemet's membrane rupture acute lesions typically found in the latter part, occasionally seen in early, Bowman's membrane rupture may also occur, but more common in the early rupture repair of connective tissue, leaving a linear scar.
Clinical grading (Robertson, 1989):
Level 0: no cone.
Grade I: There is no obvious cone under the slit lamp, but it can be found by retinoscopy and keratometer.
Grade II: The concavity of the inner surface of the cornea increased, and the Vogt stripe appeared in the corneal stroma, but no scar appeared.
Grade III: The corneal stroma has a Vogt stripe line with a scar in the center of the cornea and a thinner tip at the tip of the cone.
Grade IV: Penetrating keratoplasty has been performed.
(2) posterior keratoconus: less common in clinical practice, most people think it is congenital abnormality, more common in women, often single eye disease, mainly as the posterior surface of the cornea, because the curvature of the anterior surface is normal, vision It is less damaged than the anterior keratoconus. The degree of visual acuity reduction depends on the location and size of the posterior cone. The posterior conical protrusion can be seen in the posterior elastic layer and the endothelium defect, accompanied by thinning of the stromal layer and scarring opacity. According to the range of the cone on the posterior surface of the cornea, it is further divided into 2 types:
Type 1 is a complete type: also known as a static type, showing a different degree of curvature increase on the posterior surface of the entire cornea, and even a hemispherical depression in the central portion, the stromal layer in the depressed area is significantly thinner, but the curvature of the anterior surface of the cornea It is always normal, and its cause may be congenital dysplasia, often accompanied by other congenital anomalies in the eye, such as anterior pyramidal lens, congenital aniridia or iris atrophy, pupillary ectopic and congenital angle abnormalities.
Type 2 is limited: it shows localized thinning and depression on the posterior surface of the cornea. The anterior surface is completely normal. This type is more common than the complete type. Most people think that it may be caused by localized elastic layer and endothelial damage. The type is only female, often with single eye involvement. When examined, the posterior corneal surface has an increased curvature and even a conical shape. The tip is often off center, and the curvature of the anterior surface is always normal. The elastic membrane often occurs during the development of the lesion. It is ruptured and there is acute corneal edema, which usually does not appear in the Fleischer ring. Scintiform motion often occurs in retinoscopy.
In women only, lesions are often monocular (61%).
The curvature of the posterior surface is increased and conical, the tip of the posterior surface is often off center, and the curvature of the anterior surface of the cornea is normal.
The rear elastic membrane ruptured more, there was no Fleischer's ring, and when it was examined with a plane mirror, a "scissor-like" shadow appeared.
The main pathological changes are thinning and prominent at the center of the cornea, rupture of the basement membrane in the epithelium, thickening of the anterior elastic membrane and degeneration of the fibrils. The anterior elastic membrane is wavy and has many fissures. The above defects are filled or grown by connective tissue. The epithelium, the posterior elastic membrane and the nearby matrix have a lot of wrinkles and curvature, and only 12.3% of the cases have rupture of the elastic membrane.
Under the electron microscope, the elastic membrane is broken before the early stage of the disease, and the corneal epithelium (basal cells) in contact with it is denatured, and the cells become flat, which seems to communicate with the corneal intrinsic cells below the rupture of the anterior elastic membrane, and the intrinsic cells contain a large amount. The proliferating substance and endoplasmic reticulum are negatively stained by PAS, surrounded by collagen III with different periodicity of mature collagen, and the central area of the cornea becomes thinner, but the number of collagen plates in the stromal layer is similar to that of normal cornea, indicating collagen. The reason for the change is not large, the thinning is caused by the decrease of the interstitial space between the small plates. In the late stage of the lesion, the fracture of the posterior elastic layer is cracked, and the aqueous humor penetrates into the corneal stroma through the fissure hole, causing corneal edema.
Early diagnosis of posterior keratoconus often requires Orbean examination. This device is a new type of optical interferometer that can simultaneously detect corneal anterior and posterior curvature, corneal thickness and anterior chamber depth.
Early diagnosis, in addition to symptoms, mainly rely on objective signs, the application of slit lamp microscope, retinoscopy, Placido disk, keratometer examination, diagnosis is not difficult to determine, corneal photography can record the shape of the cone, size and relationship with the surrounding If conditions permit, the corneal topography can be used to qualitatively and quantitatively diagnose the disease. The early diagnosis of posterior keratoconus can be performed by Orbcan. The identification of the anterior keratoconus depends mainly on the different symptoms, morphology and Special signs.
The diseases associated with keratoconus are commonly found in the following categories:
1.Down syndrome
Also known as congenital stupid type (ie, three-body chromosome 21 syndrome), it is the most common chromosomal abnormality disease associated with this disease, its incidence rate is about 7%, the incidence rate increases after adulthood, and more often appears acute keratoconus edema .
2. Allergic diseases
The keratoconus often combined with keratoconjunctivitis in the spring is often associated with allergic diseases such as hay fever and asthma. It is characterized by decreased IgA response, increased IgE response, and defective cellular immunity.
3. Systemic connective tissue disease
A variety of diseases are associated with interstitial dysplasia, collagen fragility, such as Ehlers-Danlos syndrome, due to lysine hydroxylase deficiency, in addition to Marfan syndrome, Liffle disease and Noonan syndrome, etc. In addition to the keratoconus, there may be lens dislocation or retinal detachment.
4. Systemic diseases
It has been found that hypothyroidism and mitral valve prolapse are associated with the onset of keratoconus.
5. Eye diseases
The ocular diseases associated with keratoconus include blue sclera, small cornea, no iris, retinitis pigmentosa, orbital sagging syndrome, and Leber congenital dark retinitis pigmentosa.
Examine
Keratoconus examination
Genetic examination
Related tests for thyroid and thymic function, biochemical examination of blood and aqueous humor.
2. Pathological examination
According to the keratoconus tissue specimens removed during penetrating keratoplasty, the most significant pathological change under light microscopy is that the central corneal stromal layer is significantly thinner than the peripheral part, with the conical top being the thinnest and the epithelial cells damaged early. It is characterized by cell edema and nuclear pyknosis. The cytoplasmic organelles are destroyed to varying degrees. In the late stage, the basal cells disappear, leaving only 1 or 2 flat cells. Around the bottom of the cone, iron is found in the layers of the epithelial cells. In the elastic membrane, the front elastic membrane is thickened and fibrotic. Under the phase contrast microscope, the membrane loses its normal homogeneity, is wavy, and has a fracture. The crack can be filled by the matrix collagen bulge or epithelial cells under it. This rupture is more likely to occur in an elliptical cone than a circular cone. The stromal layer can undergo collagen fiber degeneration and can be extensively destroyed. It is replaced by a new array of irregular connective tissue, and the late matrix is significantly thinner. Some collagen sheets are separated from other layers and the front elastic membrane, slipping off to make the cornea thin, not true collagen dissolution, some people in electron microscopy It was found that the number of collagen platelets in the stromal layer was similar to that of the normal cornea. It was considered that the collagen platelets themselves did not change much. The reason for the thinning was the decrease in the interstitial space between the small plates. It was reported that the elastic membrane ruptured after 12.3% of the cases occurred, and soon The rupture edge curls toward the anterior matrix, and then the adjacent endothelial cells cover the rupture zone by their own area enlargement and sliding movement. The new post-elastic membrane gradually flattens, the stromal layer edema gradually subsides, and the scar connective tissue is formed. Endothelial cells are still normal, and can be flattened in the late stage and undergo nuclear separation.
3. Orbcan examination: the corneal anterior and posterior curvature, corneal thickness and anterior chamber depth can be detected simultaneously.
4. Apply Placido's disc, retinoscopy, slit lamp microscope and keratometer for examination, often used for early diagnosis.
Diagnosis
Keratoconus diagnosis
The posterior keratoconus is distinguished from the anterior type in that the curvature of the posterior surface of the posterior cornea is increased, the curvature of the anterior surface is normal, and the curvature of the anterior and posterior corneas is varied.
The spherical cornea is a congenital corneal abnormality with a large range of involvement, which can invade the whole cornea. It is characterized by uniform thinning of the corneal stroma and peripheral parts, which is only about 1/5 of the normal corneal thickness. In some cases, even the surrounding area can be seen. The part is thinner than the central part. It is prone to corneal perforation under the impact of external force. The histological examination of the corneal layers is available. The etiology and pathogenesis are unknown. It may be the same type of disease as the keratoconus. Some reports have been reported. One case was a keratoconus and the other was a spherical cornea.
