Zonular Diseases - Associated Conditions and Their Manifestations

Introduction

Zonules are small, thread-like structures in the eye. These fibrous structures are arranged in a ring-like fashion anchoring the ciliary body (part of the middle layer of the eye made up of muscles) with the eye's lens. This structure is also known as the zonule of Zinn, named after Johann Zinn, who described this structure for the first time in 1755. These are also known as suspensory ligaments of the lens. These fibers originated from the basal laminae of the ciliary body's non-pigmented epithelium and got into the lens capsule at the equatorial region. The function of these structures is to hold the lens in place and to anchor the muscles. These fibers help to transmit the forces to the lens, helping to change its shape.

Thus these structures play a vital role in focusing the objects. The diseases associated with the ciliary zonule (thread-like structure present in the eye) or zonular layer can lead to serious vision disorders. Not only that, if they remain undiagnosed, but these pathological entities may also lead to post-operative complications. Therefore understanding the pathophysiology of zonular diseases is important.

What Are Zonular Diseases?

Zonular diseases are not single pathological entities. They are systemic disorders associated with decreased support from the zonular layer and malpositioning of the lens. These conditions are often termed coagulopathy or zonular dehiscence, or zonular dialysis. The conditions which are associated with zonular diseases are

• Marfan syndrome.

• Pseudoexfoliation syndrome.

• Homocystinuria.

• Weil-Marchesani syndrome.

• Ehlers–Danlos syndrome.

What Is Marfan syndrome?

Marfan syndrome is a hereditary connective tissue disorder caused by the mutation FBN1 Gene. This syndrome is related to an abnormality of the fibrillin molecules. These elastic fibers serve as bundle block molecules for muscles, tendons, and bones. Degradation of fibrillin molecules occurs due to the upregulation of matrix metalloproteinases 1 and 3. Qualitative and quantitative fibrillin deficiency is observed in zonal fibers ( band of fibers in zonular layer). This causes zonular stretching. The stretching leads to asymmetrical laxity of zonular fibers. As a result of this malpositioning of the lens, dislocation or notching of the lens happen.

The systemic manifestations are:

• Long, slender arms and toes.

• Excessive height.

• Scoliosis (abnormal curvature of the spine).

• Thoracic lordosis.

• Fatigue, shortness of breath, heart palpitation.

• Abnormal heart murmur and ECG (electrocardiogram) reading.

Ocular manifestations are

• Ectopia Lentis: This is characterized by dislocation or malposting of the lens.

• Myopia: This is the second most common complication of Marfan syndrome. The stretching of zonular fibers leads to the abnormal thickening of the lens, which causes an increase in the refractive power (ability to reflect light) of the lens.

• Glaucoma: Several types of glaucoma (groups of disorder that damage the optic nerve), like primary open-angle glaucoma, secondary angle-closure glaucoma, and pupillary block glaucoma, may be caused by this condition. The displacement of the Schlemm’s canal causes primary open-angle glaucoma due to the stretching of the zonular fibers. Forward displacement of the lens causes angular malformations and leads to secondary angle-closure glaucoma. Anterior subluxation of the lens causes primary open-angle glaucoma.

What Is Pseudoexfoliation Syndrome?

This is an age-related systemic disorder mainly seen in Scandinavian people. The deposition of microscopic granules of amyloid-like protein fibers characterizes this. Though the exact cause of this disease is not known association of several genetic factors like the LOXL1 gene, CLU gene, and CNTNAP2 gene have been observed over the years. Abnormal accumulation of fibrillin-1 microfibers causes unusual deposition of protein-like substances. Transforming growth factor-beta 1 (a chemical mediator regulating various cellular activities) is one of the key factors associated with accumulating these substances.

The ocular manifestations are

• On the Slit-lamp examination, a white dandruff-like deposition is present along the pupillary margin and anterior lens capsule.

• Continuous deposition of protein-like materials reduces the ability of the lens to change its geometry. This condition leads to changes in the shape of the lens. The altered shape of the lens and deposition of protein-like substances cause lysis of the zonular fibers.

• Loss of elasticity and atrophy of the dilator muscles can be observed.

• Degradation of the corneal endothelium (monolayer of cells present in posterior corneal surface).

• Occlusion of central retinal veins and optic neuropathy (damage of the optic nerve).

What Is Weil-Marchesani Syndrome?

This is a hereditary connective tissue disorder known as spherophakia-brachymorphia syndrome and mesodermal dysmorphodystrophy. This can be both autosomal dominant and recessive type. A mutation of the FBN-1 gene causes the autosomal dominant form, and DAMTS10, ADAMTS17, and LTPBP2 genes cause the autosomal recessive form. Mutation of these genes causes impairment in forming extracellular matrix proteins such as fibrillin. The ocular manifestations of these syndromes are

• Microspherophakia: small spherical lens.

• Lens dislocation and abnormally shaped lens.

• Increased corneal thickness.

• Patients may develop myopia (a condition in which close objects appear clearly, but far ones are not visible) and secondary glaucoma.

• Narrowing of the anterior chamber with the absence of myopic retinopathy ( damage of the retina and optic disc in myopia).

Extraocular manifestations are

• Progressive stiffness of the joints.

• The excessive thickness of the skin.

• Brachydactyly (short fingers and toes).

Cardiac complications present in such cases are - patent ductus arteriosis (opening between two major blood vessels), pulmonic stenosis (narrowing cardiac valves located between right ventricular and lungs), thoracic aortic aneurysm (wall of the aorta is weak), cervical artery dissection (tear in the walls the blood vessels).

What Is Ehlers–Danlos Syndrome ?

This combines several hereditary disorders affecting collagen formation. The mutation of COL5A1 and COL1A1 genes causes this autosomal dominant disorder. Collagen synthesis and processing are disrupted in this condition, resulting in the fragility of the connective tissues.

The clinical manifestations of these disorders are the following:

• Hyperextensibility (excessive movement in the joints) of the joints.

• The smooth and velvet-like texture of the skin.

• Delayed and poor wound healing.

• Subluxation (displacement of a bone from a joint) and dislocations of the joints.

• Joint pain and osteoarthritis (wearing off the protective cartilage of bone).

• Delayed teeth eruption and dentin dysplasia (abnormal dentin formation).

The ocular complications are as follows.

• Nonspecific irritation and foreign body sensation in the eye.

• Dryness of the eyes, blurred vision, and diplopia or double vision.

• Abnormal corneal thicking and curvature of the cornea. Keratoconus or cone-shaped bulging of the cornea can be seen.

• Telecanthus ( increased distance between the inner corners of the eye).

• Blue sclera: Underlying uvea can be seen due to the thinness and transparency of collagen fibers.

• Malposition of the lens with thinning of the zonular layer.

What Is Homocystinuria?

It is an inherited disorder of amino acid metabolism. A deficiency of the cystathionine beta-synthase enzyme causes it. The systemic manifestations are

• Kock knees.

• High-arched feet.

• Tall and thin build.

• Pectus excavatum: the abnormal chest and rib cage shape.

The ocular symptoms are similar to Marfan syndrome.

• Ectopia Lentis: unlike Marfan syndrome, the dislocation of the lens, in this case, is in a downward direction.

• Retinal detachment is seen.

• Secondary glaucoma and myopia are observed.

Conclusion

Systemic disorders cause serious complications of the suspensory ligaments of the lens. The pathological changes cause serious complications like myopia and glaucoma. As conditions associated with zonular diseases are inherited in nature, the treatment of such cases is difficult. Different intra-ocular lenses, like a scleral-sutured lens and an iris-sutured lens, can be placed in such conditions.