| disease | Keratoconus |
| alias | Keratoconus |
The earliest report on keratoconus was by Mauchart (1748). Nottingham provided a detailed discussion of it in 1854 and distinguished it from other corneal expansions. In China, Luo Zongshen first reported the disease in 1933, and later, several other authors also described the condition.
bubble_chart Etiology
The exact cause of the disease is unknown, and the following theories currently exist:
1. Genetic Theory Ammon (1830), Jaensch (1929), Anelsdorst (1930), and others believe that keratoconus is a recessive hereditary condition. However, some cases exhibit symptoms across two or three consecutive generations. For such cases, consideration should be given to whether it follows a regular or irregular dominant inheritance pattern.
Supporters of this theory propose that keratoconus is often associated with other congenital abnormalities, which serves as additional evidence for the involvement of genetic factors. Examples include retinitis pigmentosa, blue sclera, aniridia, iris coloboma, Marfan syndrome, anterior polar cataract, corneal dystrophy, and Down syndrome.
2. Mesodermal Dysplasia Theory Collins et al. (1925) and δарьелъ (1960) suggested that this disease results from reduced resistance and poor toughness in the central part of the cornea, making it unable to withstand normal intraocular pressure. Mihalyhegy (1954) observed that keratoconus not only alters the curvature of the cornea but also causes significant changes in the sclera. Therefore, he proposed that the cause of keratoconus should also be sought in mesodermal hypoplasia.
3. Endocrine Disorder Theory Siegrist (1912) proposed that hypothyroidism is a significant factor in the development of keratoconus. This view was also supported by Knapp (1929) and Stitcherska (1932). Hippel (1913) particularly emphasized the role of the thymus in the onset of keratoconus.
4. Metabolic Disorder Theory Мучник (1956) found that the basal metabolic rate was significantly reduced in keratoconus patients. Титаренко (1978) used direct spectral analysis to examine changes in trace elements in the blood of keratoconus patients and discovered a significant decrease in nickel levels, an increase in titanium, aluminum, and lead levels, and no change in manganese levels. He believed that these alterations in trace elements play a role in the disease's development. Пучковская (1979) further observed a decrease in the activity of glucose-6-phosphate dehydrogenase in the blood and aqueous humor of keratoconus patients. Clearly, this reduction in enzyme activity could impair glutathione's antioxidant function, leading to the accumulation of peroxides in the body, which may be the factor damaging the cornea.5. Allergic Reaction Theory Boland (1963) conducted a statistical study showing that among keratoconus patients, 32.6% had hay fever and 33.3% had asthma, whereas the incidence of asthma in the general population was only 0.59%. Ruedemann reported similar findings: 86% of keratoconus patients had a history of allergic reactions.
bubble_chart Pathological Changes
The main pathological changes include thinning and protrusion of the central part of the corneal membrane, rupture of the epithelial basement membrane, thickening and fibrillar degeneration of the anterior elastic membrane. The anterior elastic membrane appears wavy with numerous fissures, and the aforementioned defects are filled or invaded by connective tissue. The posterior elastic membrane and adjacent stroma exhibit extensive folds and bends, with only 12.3% of cases showing rupture of the posterior elastic membrane.
bubble_chart Clinical Manifestations
This disease commonly occurs in young people aged 16 to 20, with a higher incidence in females. It typically starts in one eye, followed by the other, and the prognosis for the latter is better than the former.
1. Classification Duke-Elder (1946) and Barriel (1960) classified keratoconus into:
⑴ Anterior keratoconus
⑵ Posterior keratoconus, which is further divided into complete and localized types.
Takayuki Momose et al. (1978) identified an intermediate type between anterior and posterior keratoconus. Corneal ectasia caused by certain eye diseases, which resembles keratoconus in appearance, is referred to as pseudokeratoconus.
2. Symptoms and Signs
① Latent stage: Keratoconus is difficult to diagnose at this stage. If one eye has already been confirmed with keratoconus, the possibility of keratoconus should be considered if refractive errors appear in the other eye.
② Initial stage [first stage]: The main clinical manifestation is refractive errors, which can be fully corrected with glasses at this stage. It may start as myopia and gradually progress to astigmatism and irregular astigmatism.
Examination with Placido’s disk shows distortion in the concentric rings and axis of the corneal reflection.
During retinoscopy with a plane mirror, the pupillary light reflex may appear as an "open mouth" movement.
Slit-lamp microscopy reveals enhanced reflection from the corneal epithelium and Bowman’s membrane, with disordered and unclear reflections from the stromal layers.
Keratometry detects irregular astigmatism.
③ Advanced stage: Typical symptoms of keratoconus appear, including decreased vision that cannot be corrected with regular glasses and requires contact lenses.
As the condition progresses, the apex of the cone becomes translucent. In the initial stage, this area is sensitive, but in the advanced stage, sensitivity decreases, known as Axenfeld’s sign. This sign is not exclusive to keratoconus; it can also occur in chronic corneal diseases or even in long-term contact lens wearers.
When the patient looks downward, the corneal cone presses against the lower eyelid margin, causing a curvature known as Munson’s sign, though this is not specific to keratoconus.
Slit-lamp microscopy findings: The corneal cone is usually confined to the central cornea, with the apex often located slightly inferonasal to the center. This area becomes protruded and thinned, with a thickness only 1/5 to 1/2 of normal.
Fleischer’s ring: This ring surrounds the keratoconus, measuring 5–6 mm in diameter. It may be a complete or partial ring, 0.3–0.5 mm wide, with a sharp inner border and a blurred outer border, appearing yellowish or brownish-green. It is caused by hemosiderin deposition in Bowman’s membrane and is better visualized with cobalt-blue light. This ring is present in about 50% of keratoconus cases.
Keratoconus striae: Located in the corneal stroma at the apex, these are vertical, parallel lines about 2 mm long. As the disease progresses, they widen, resembling a palisade. Upon close inspection, they appear slightly curved rather than straight. This is not an organic change but results from pressure exerted by the upper and lower eyelids on the corneal limbus, with greater pressure vertically than horizontally.
Corneal stromal nerve fibers become more prominent, sometimes appearing as gray lines or a network. Punctate opacities develop beneath the corneal epithelium. Epithelial erosion resembling keratitis may occur near the cone apex. New blood vessels may invade the corneal limbus.
Fundus examination findings: Using a direct ophthalmoscope at 5–33 cm from the affected eye and focusing on the central cornea with a +5D lens, a round, faint reddish-brown shadow may be seen. However, this is not exclusive to keratoconus; it can also occur with changes in the lens refractive index or in early nuclear cataracts. To avoid confusion, the examiner should inspect the cornea from the temporal side to differentiate between corneal changes and lens abnormalities.
④ Degenerative stage: Degeneration occurs beneath the corneal membrane epithelium, primarily characterized by hyaline degeneration.
A scar forms at the apex of the conical cornea. Due to its central location, visual acuity sharply declines and can no longer be corrected with contact lenses.
New blood vessels grow into the superficial layer of the corneal membrane.
The Descemet's membrane ruptures in a sickle or crescent shape. The rupture often occurs suddenly, with edema and opacity appearing at the center of the cornea. The extent of the edema usually indicates the size of the Descemet's membrane tear—the larger the tear, the broader the edema area. Within 1–2 months, it is repaired by endothelial and connective tissues, becoming translucent. This typically occurs in the late stage (third stage) of the disease but is occasionally seen in early cases.
Rupture of Bowman's membrane is more common in the early stages of the disease. The ruptured area is filled with connective tissue, leaving linear scars that result in permanent visual impairment.
(2) Posterior keratoconus Posterior keratoconus is relatively rare and is clinically divided into two types: The first type is the complete form, also known as the stationary form. The curvature of the entire posterior corneal surface is increased to varying degrees, while the curvature of the anterior surface remains normal, possibly due to congenital abnormalities. The second type is the localized form, where the posterior corneal surface shows localized thinning while the anterior surface remains entirely normal. This type is more commonly encountered and may result from damage to the Descemet's membrane and endothelium. Its typical symptoms include:
It occurs exclusively in females, and the condition is usually unilateral (61%).
The curvature of the posterior surface increases, forming a cone shape, with the apex often deviating from the center, while the curvature of the anterior corneal surface remains normal.
Ruptures of the Descemet's membrane are more frequent. There is no Fleischer ring. "Scissor reflex" shadows appear during retinoscopy with a plane mirror.
In addition to relying on the patient's symptoms, the diagnosis primarily depends on objective signs. Examinations using Placido's disk, retinoscopy, slit-lamp microscopy, and a corneal gauge are often helpful for early diagnosis. When the disease progresses to the completion and degenerative stages, both symptoms and signs become evident. Beyond the aforementioned examinations, it is essential to perform photographic diagnosis using a fundus camera with a +16D lens or a Polaroid camera. The photographs can clearly reveal the size, location, and relationship of the cone to its surroundings.
The key distinction between posterior keratoconus and anterior keratoconus lies in the fact that the posterior type shows increased curvature of the posterior corneal surface while the anterior surface remains normal, whereas in the anterior type, the curvature of both the anterior and posterior corneal surfaces is altered.
bubble_chart Treatment Measures
Keratoconus is a challenging condition to treat, and numerous methods have been proposed, broadly categorized into pharmacological, optical correction, and surgical treatments. Depending on the progression of the disease, in its early stages, simple eyeglasses can correct the vision. When the corneal surface becomes irregularly astigmatic, contact lenses should be prescribed. Further progression may require keratoplasty or corneal transplantation (Figure 1).
Figure 1 Treatment principles for various stages of keratoconus
1. Pharmacological Treatment
(1) Topical application of pilocarpine eye drops; nighttime use of pressure bandages. The former can improve vision by constricting the pupil, while the latter may inhibit the progression of keratoconus. This method has limited efficacy but is simple and easy to implement.
(2) For patients with endocrine dysfunction, cautious use of appropriate doses of thyroid hormone or thymus extract (Тимус) may be considered.
(3) Antioxidant therapy: Such as tocopherol and vitamin P.
(4) Anterior chamber autologous blood injection: Suitable for the acute stage when Descemet's membrane ruptures and the endothelium is incomplete. The clotting effect of the blood helps seal these defects, achieving a "biological filling" effect. As the blood clot is gradually absorbed, a grayish-white, fine membranous scar forms in the original area.
2. Optical Correction
(1) Regular eyeglasses: In the early stages of keratoconus, myopia can be satisfactorily corrected with regular eyeglasses.
(2) Corneal contact lenses
① Rigid corneal contact lenses: When irregular astigmatism occurs, regular eyeglasses can no longer improve vision, and suitable contact lenses should be selected. For highly irregular astigmatism caused by keratoconus, corneoscleral contact lenses are appropriate. However, these lenses have several drawbacks: they are relatively bulky and inconvenient to wear; the corneal fluid cannot be frequently replaced, significantly affecting corneal oxidative metabolism and causing corneal epithelial edema, making them difficult for patients to tolerate. Gasset (1976) proposed a method of wearing contact lenses where the weight is evenly distributed between two areas: the apex of the cone and the upper edge of the cornea. This method was more satisfactory for patients. However, in 1978, he found that wearing corneal contact lenses could induce or accelerate keratoconus progression.
② Soft corneal contact lenses: In 1972, Tragakis reported good results in 17 cases of keratoconus with high or irregular astigmatism by using soft corneal contact lenses followed by regular eyeglasses to correct residual astigmatism. However, there are drawbacks: due to the softness of the lenses, their curvature tends to conform to the corneal surface, often resulting in suboptimal vision improvement for high astigmatism caused by keratoconus.
③ Hybrid (soft-hard) corneal contact lenses: Some keratoconus patients cannot tolerate rigid corneal contact lenses or struggle with proper centering. While soft corneal contact lenses are tolerable, they often fail to provide the best vision. However, sometimes combining soft and rigid contact lenses can yield better vision, temporarily avoiding surgical intervention.
This hybrid lens consists of a larger soft contact lens (13.5–15 mm in diameter, with a curvature radius of 8–8.5 mm) with a central depression to hold a rigid lens (8.2–8.5 mm in diameter, 0.2 mm deep).
This combination leverages the advantages of both soft and rigid lenses. Patients find it more comfortable than rigid lenses, and vision correction is better than with soft lenses alone. However, fitting is more challenging, and corneal epithelial edema may still occur.
3. Surgical Treatment: Various surgical methods exist, such as:
(1) Improving vision by removing the lens or displacing the pupil.
(2) Reducing intraocular pressure through anterior chamber paracentesis or sclerotomy to slow the progression of corneal coning.
⑶ Apply silver nitrate cauterization, direct cauterization, and electro-cauterization to create scars at the apex of the corneal cone, halting the progression of the lesion.
To improve vision, Knapp (1929) also performed tattooing and optical iridectomy on the scar at the center of the corneal membrane.
However, the above methods were not effective. In recent years, in addition to the use of corneal contact lenses, two surgical procedures have emerged: corneal thermokeratoplasty and corneal transplantation.
⑷ Corneal Thermokeratoplasty Since Gasset and his colleagues introduced corneal thermokeratoplasty in 1973, it has achieved excellent clinical results. According to Gasset's follow-up of 59 cases over two years post-operation, central vision often improved to 0.6 or better. The indications include:
① The apex of the corneal cone has no scarring and retains at least 0.5 of the normal corneal thickness.
② Poor correction with contact lenses or inability to wear them long-term.
③ Rapidly progressing keratoconus with a tendency for rupture of the anterior or posterior elastic membrane after wearing corneal contact lenses.
④ Mild central scarring in keratoconus with at least 0.5 of normal corneal thickness. Thermokeratoplasty can be attempted first; if unsuccessful, penetrating keratoplasty may follow.
⑤ Large corneal edema due to a giant tear in the posterior elastic membrane, making corneal transplantation difficult. Thermokeratoplasty can close the tear and reduce edema, facilitating subsequent transplantation.
⑥ Cases where corneal transplantation or post-operative care is challenging due to mental conditions (e.g., Down syndrome).
Corneal thermokeratoplasty is a novel reconstructive technique using heat. Heating the corneal surface causes collagen fibers to contract, reducing refractive error and astigmatism, and normalizing corneal curvature. Its greatest advantage is minimal complications, and even if it fails, corneal transplantation can still be performed without affecting prognosis.
⑸ Corneal Transplantation
① Lamellar Keratoplasty This can be performed for cases requiring penetrating keratoplasty or after failed thermokeratoplasty. Recent advancements in microsurgery and the use of full-thickness corneal flaps without endothelium have improved post-operative vision.
In 1977, Puchkovskaya et al. proposed a new technique for acute keratoconus. They first scraped off the corneal epithelium, made a small paracentral puncture to drain aqueous humor, flattening the cornea. A lamellar corneal graft with multiple tongue-shaped scleral flaps from a donor was transplanted and secured with "U" sutures, then covered with conjunctiva. Post-operatively, grade I corneal edema resolved quickly, restoring normal curvature.
② Penetrating Keratoplasty For late-stage (third-stage) keratoconus, penetrating keratoplasty is recommended. Grafts of 7.5–8.5 mm diameter are commonly used. Larger grafts reduce immune rejection and complications, while smaller ones may fail to correct the cone.
According to Keates et al. (1972), penetrating keratoplasty was performed on 25 cases (27 eyes) of keratoconus, aged 15–58. Twenty eyes received 8.0 mm grafts, and seven received 7 mm grafts. Post-operatively, 22 eyes achieved corrected vision of 0.5–0.6, and five eyes reached 0.3–0.4.
