Spheroidal Degeneration : Introduction, Symptoms, Causes, Diagnosis, Management and Prevention - www.genericdrugscan.com

Spheroidal Degeneration : Information

Spheroidal degeneration (climatic droplet keratopathy, Biettis band-shaped nodular dystrophy, chronic actinic keratopathy or Labrador keratopathy) is a nonhereditary acquired degenerative condition of the eye. Spheroidal degeneration is characterised by sub-epithelial accumulation of spherical opalescent droplets that coalesce to form bands or nodules with elevated corneal epithelium. The degenerative process is mainly seen in the inter-palpebral part of the cornea.

Spheroidal degeneration may have a distribution in the cornea similar to that of band shaped keratopathy, and it also occurs in the conjunctiva.

Bietti et al in 1955, made his initial clinical observation of an unusual degenerative corneal condition characterised by deposition of yellowish globules in the superficial layers of the cornea. Biettis description of corneal degeneration, although it has been described by various names, is most commonly referred to as spheroidal degeneration. Fraunfelder and colleagues divided this condition into three basic forms viz.

• Type I or Primary corneal type occurring bilaterally associated with increasing age and without any prior ocular (eye) disease.
• Type II or Secondary corneal type associated with pre-existing ocular pathology or trauma.
• Type III or Conjunctival type wherein conjunctival deposits are prominent with or without corneal involvement. Conjunctival form is found more commonly after the age of sixty years and may be associated with pinguecula.

Frequency of spheroidal degeneration varies with geographic location and increases with age. It occurs most often in areas that have high sunlight exposure and sunlight reflection off snow or sand, in combination with wind-driven corneal damage by snow and sand. Probably it is caused due to micro-trauma from wind and sand or by solar radiations. This degenerative disease occurs due to excessive exposure to ultraviolet (UV) light. Males are more prone to develop spheroidal degeneration, especially those working outdoors, as compared to females.

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Spheroidal degeneration is asymptomatic in majority of the cases. Visual acuity may be affected if the deposits extend towards the center of the cornea, thereby, blocking the visual axis.

Ocular (eye) symptoms in advanced cases may be:

• Irritation.
• Discomfort.
• Foreign body sensation.
• Diminution of vision.]

The exact cause of spheroidal degeneration is not known. It is hypothesized to be due to:

• Drying of the cornea.
• Repeated corneal trauma.
• Wind driven corneal damage by snow (e.g. Arctic or Labrador region in Canada) and sand (e.g. in deserts). The specialised type of trauma related to ice and sand produces band shaped corneal spheroids arranged across the horizontal meridian.
• Ultraviolet light exposure (confirmed also in the welding population). It may also be associated with blue light exposure. It occurs most often in areas that have high sunlight exposure and sunlight reflection off snow or sand.
• Low humidity.
• Spontaneous in the conjunctiva and cornea of the aged.
• Associated ocular conditions viz.

- Traumatic corneal scars.

- Herpetic keratitis.

- Chronic corneal oedema.

- Lattice corneal dystrophy.

- Glaucoma.

- Pinguecula.

- Pterygium.

Although no definitive gene defect or inheritance pattern is established, it is thought that genetic predisposition to this condition, may play a role in its development along with environmental factors. Familial occurrence is very rare.

Although spheroidal degeneration is classically associated with ageing and ultraviolet exposure, it has also been described in childhood with much less frequency.

Diagnosis depends upon:

Clinical features:

Since spheroidal degeneration is associated with UV light exposure, patients may have other systemic findings of exposure to the elements such as history of skin cancer, pigmentary changes, or other actinic disorders.

Examination should be carried out under slit lamp (bio-microscopy) by an eye specialist.

Spheroidal degeneration is characterised by:

• Fine droplets or globules: The presence of fine droplets or globules, yellow or golden in colour, beneath the conjunctival or corneal epithelium. The globules appear oily, although they are not of lipid origin. These may be clear but often become cloudy or opaque over the time. The accumulation of the globules primarily involves Bowman s layer, however, it may occur in the sub-epithelial area and superficial layers of the stroma once Bowman s layer is disrupted. The deposits in the epithelium may damage the corneal epithelium and the band-shaped configuration may extend to the center, leading to decrease in vision. The deposition of slight golden-yellow globules is variable from few globules to aggregate or diffuse globules occupying central portion of the cornea.
• Lattice lines: Lattice lines may be seen in some patients. Lattice lines are short, fine, discrete, and measure about 1-3 mm in length. These appear clinically exactly like lattice lines in lattice corneal dystrophy. Some of the lattice lines are even seen deep in the corneal stroma. The lattice lines may be central, peripheral or bilateral. Lattice lines are seen among elderly patients and are observed in both primary and secondary corneal type. Lattice lines, unlike lines in lattice corneal dystrophy, occur late in life in the absence of family history and may be superficial and deep in the cornea. The lattice lines are usually non-arborising and lack orientation. The lines are thin, glossy and randomly placed, generally occupying the superficial layers of the cornea and close to the spherules. The lattice lines are not associated with painful recurrent corneal erosions and do not interfere with vision in patients with primary corneal type.
• Fine greyish fleck like opacities: Fine greyish fleck like opacities are sometimes dispersed in between the lattice lines and beside the globules.
• Amyloidosis: Amyloidosis of the cornea in spheroidal degeneration may be non-specific and is not well understood. It is believed that a decrease in the serum amyloid degrading activity may precede the accumulation of amyloid in the tissues. Amyloidosis of the cornea may be the result of multiple micro-traumas by sand, dust, UV rays and other factors.
• Cataract and pseudo-exfoliation of lens: Cataract and pseudo-exfoliation of lens are common among patients of spheroidal degeneration.
• Iris atrophy: Iris atrophy has also been observed.
• Decrease in corneal sensitivity: Decrease in corneal sensitivity or hypoesthesia has been noted in one study.

A clear zone may exist early on between peripheral edge of lesion and limbus, but is lost later on.

Type I or Primary corneal type: Primary type is characterised by corneal lesions that occur without other ocular or corneal disorders. The lesions are usually symmetrical and bilateral. In the primary form, degeneration begins peripherally and advances toward the center in the palpebral fissure area. As the condition advances, the droplets become larger and more nodular and lift the central corneal epithelium. The conjunctiva may be involved in patients with primary degeneration, especially nasally.

There are three grades of severity of primary form:

• Grade 1: Mild spherule deposition near the limbus. Fine shiny droplets are present peripherally only, without producing any symptoms.
• Grade 2: Moderate spherule deposition with band shaped haziness. The central part of cornea is involved with some diminution of vision.
• Grade 3: Large yellow aggregates of sub-epithelial droplets spherules reaching the central part of the cornea. There are large corneal nodules and vision is no better than 6/60 on Snellen s vision test types. Disease may be rapidly progressive, followed by ulceration of involved areas of cornea, with secondary bacterial infection.

Alternative grading of the condition depending on the severity is:

• Trace: Trace is characterised by small number of deposits in one eye, or only at the end of the interpalpebral strip in each eye (if bilateral).
• Grade 1: In grade 1, there is sparing of central cornea with involvement of medial and lateral interpalpebral strips.
• Grade 2: Grade 2 affects central cornea but there is no effect on visual acuity.
• Grade 3: In grade 3, central cornea is affected with reduced vision.
• Grade 4: Grade 4 shows elevated nodules in addition to the findings of Grade 3.

Type II or Secondary corneal type: Secondary corneal type is associated with other ocular disorders, corneal vascularisation and scarring. Secondary corneal type may occur along the edge of corneal scars.

Secondary corneal type is characterised by the presence of corneal scars and vascularisation with large and small yellow globules invading the epithelium, basement membrane, Bowman s layer and superficial stroma. There may be scarring within the adjacent layers of the cornea. The location of the globules depends on the degree of Bowman s layer disruption and the location of the corneal scars. Scars may be peripheral or central. The deposition is not always in a band-shaped configuration and can occupy the areas of the corneal scar. The disease may be either unilateral or bilateral. In cases with unilateral vascularized corneal scars, the degeneration occurs in the eye with corneal scars and may not occur in the other eye with clear cornea.

Recurrence of degeneration may occur in patients undergoing penetrating keratoplasty. Globular aggregates may occur in the corneal graft and usually in the center of the graft.

Type III or Conjunctival type: Conjunctival type may also show similar deposits on conjunctiva as are seen in corneal type. The conjunctival lesions may have engorged blood vessels.

Histopathology and Electron microscopy:

Staining properties:

Primary spheroidal degeneration:

• Unstained sections: Unstained sections reveal auto-fluorescence in superficial stromal deposits under ultraviolet illumination.
• Haematoxylin and Eosin (H&E) stained sections: Haematoxylin and Eosin (H&E) stained sections of the cornea show evidence of homogeneous proteinaceous globular deposits of variable sizes in the superficial layers. The globules are mainly seen along Bowman s layer which may show disintegration being produced by the globular deposits. The spherules are then seen in the sub-epithelial space disrupting the basement membrane and the superficial stroma. The sub-epithelial aggregates of spherules may cause elevation and thinning of the corneal epithelium.
• Masson trichrome stain: Masson trichrome stain reveals reddish-grey colour of spherules.
• Verhoeff Van Gieson stain: Most aggregates of spherules stain positively with Verhoeff Van Gieson stain for elastic tissue.
• Congo red stain: Congo red stain is positive in the areas of amyloid deposits which show birefringence with polarising light in some specimens with degeneration.

Staining for fat with oil red O and for calcium with Von Kossa stain is usually negative. Von Kossa stain may show positive staining for calcium in any associated calcification, but is rare.

Secondary spheroidal degeneration:

Haematoxylin and Eosin (H&E) stained sections of cornea: Haematoxylin and Eosin (H&E) stained sections of cornea show evidence of corneal scarring and vascularisation with homogeneous sub-epithelial globular deposits of variable sizes. Spherules may reach the superficial and even deeper layers of the stroma.

Electron microscopic study:

Electron microscopic study of the globules in patients with spheroidal degeneration reveals aggregates of extracellular electron dense round to oval globules among the collagen fibrils of the superficial stroma. The globules are of different sizes and cause disruption of Bowman s layer and the basement membrane of the epithelium.

Proteomic analysis and Pathogenesis:

Approximately 105 different proteins have been identified using proteomic analysis. Primary degeneration shows irregular collagen from abnormal fibroblasts. Secondary degeneration shows protein deposits from the interaction of UV light and plasma proteins (diffusing through the cornea from limbal vessels under normal conditions).

Spheroidal degeneration may be caused by an aggregation of advanced glycation end products (AGEs) and modified proteins resulting from UV radiation and ageing.

Corneal globular deposits show protein deposits having amino acids such as tryptophan, tyrosine, cysteine and cystine, which are not normally found in the corneal stroma.

Matrix metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPs): One study detected an up-regulation and increase in the level of MMP-9 and MMP-2 in the tear fluids in patients with spheroidal degeneration. TIMPs (inhibitors of MMP), where found as part of complexes in the TIMP-1, were significantly lower in patients. This study demonstrated that MMP-2 and MMP-9 tear levels were significantly elevated and may have resulted in delay in corneal re-epithelialisation and corneal scarring. The reduced expression of TIMP-1 in spheroidal degeneration, such as deficient anti-proteolytic shield, which may lead to rendering the corneas of patients vulnerable to enhanced MMP activity.

Annexin and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH): Annexin and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) are the proteins identified in patients with spheroidal degeneration using monoclonal antibodies. Annexin is found in the periphery but not in the center of cornea, while in spheroidal degeneration, it is found in abundance in the central portion of the cornea. Annexin and GAPDH are known for membrane fusion and allows cells to adhere to the collagen. The increased accumulation of Annexin and GAPDH in spheroidal degeneration as compared to normal cornea requires further investigation.

Spheroidal degeneration may be differentiated from:

There do not appear to be other corneal conditions that resemble spheroidal degeneration of the cornea. However, conditions which may be considered are:

• Band shaped keratopathy: Band shaped keratopathy shows deposition of calcium with Swiss cheese appearance.
• Pseudo-entrapment of eye ointment: Post-operative entrapment of eye ointment in the stroma of the cornea does not occur unless the material is forced under pressure. These resulting droplets are not characteristic of spheroidal degeneration. The droplets do not autofluoresce under ultraviolet illumination and they are easily identified without the use of a slit lamp. The eye ointment cannot be trapped in the crevice of a wound for long unless a pressure dressing is applied. Once the pressure dressing is removed the pseudo-entrapment of ointment disappears.
• Changes in the conjunctiva: Changes in the conjunctiva such as cysts, lymphangiectasis, xanthomatous patches or the presumed forward migration of fat cells to the episclera from the orbital fat pads, are quite different from the spheroids of the conjunctiva.]

Management should be carried out under medical supervision.

The majority of patients of spheroidal degeneration are asymptomatic.

Management of patients with spheroidal degeneration is mainly symptomatic. There is no specific treatment available for the resolution of spherules.

Most of the time, spheroidal degeneration pathology is located nasally and temporally, and observation alone is required.

General medical therapy:

• Ultraviolet light protection: Patients with spheroidal degeneration should have protection against ultraviolet light damage with sunglasses, to avoid further damage due to exposure.
• Topical artificial tears: Patients with mild degeneration may require lubrication with topical artificial tears. Lubrication can slow the process, if the tear film is decreased.

Surgical therapy:

Patients with corneal scarring and globules involving anterior central part of cornea compromising vision, or causing pain, may require surgical intervention.

• Excimer laser assisted phototherapeutic keratectomy (PTK): Phototherapeutic keratectomy with excimer laser may be used to gain useful vision. PTK may also be required for patients undergoing cataract surgery to improve visualisation.
• Lamellar or penetrating keratoplasty: Lamellar or penetrating keratoplasty may be used in patients with irregular corneal surface.

The spheroidal degeneration recurs after conjunctival resection.

Prognosis:

Long standing keratopathy may lead to visual impairment caused by involvement of visual axis due to secondary scarring.

Spheroidal degeneration may be prevented by:

• Ultraviolet light (UV) blocking sunglasses: UV light blocking sunglasses in areas of sand and dust. Side protectors of the sunglasses may be placed to prevent exposure to environmental irritants.
• Avoiding solar irradiation: Avoiding solar irradiation and repeated micro-trauma of the cornea may also prevent the formation of spheroidal degeneration.]