Keratoglobus : Symptoms, Causes, Diagnosis, Management and Complications

Keratoglobus : Symptoms, Causes, Diagnosis, Management and Complications

Keratoglobus is a rare non-inflammatory corneal thinning disorder characterised by generalised thinning and globular ectasis (protrusion) of the cornea. The non-inflammatory corneal ectasias are a group of disorders characterised by corneal thinning, protrusion, and scarring. Keratoglobus forms a rarer subset of this group.

Keratoglobus was first described as a separate clinical entity by Verrey in 1947, through detailed descriptions of his patients. In the past, it was considered synonymous with megalocornea and congenital glaucoma.

The exact genetics and pathogenesis of this disorder is still not clear. There are similarities with other non-inflammatory thinning disorder like keratoconus, which gave rise to hypothesis about the aetiopathogenesis.

Keratoglobus and keratoconus are both non-inflammatory ectatic disorders of the cornea. Cavara in 1950 made distinction between keratoglobus and keratoconus. The cornea in keratoglobus is diffusely thinned, often more markedly in the peripheral cornea, whereas in keratoconus the thinning is most prominent in the central cornea. The histopathological changes seen in keratoglobus, including disruption of Bowman’s layer and Descemet’s membrane breaks, are very similar to those seen in advanced keratoconus. These similarities have brought about confusion as to whether the disorders comprising this group are separate clinical disorders, or rather a spectrum of the same disease process.  In fact, the histological similarities have led to the speculation that keratoglobus may be an end-stage manifestation of advanced keratoconus.

Clinical presentation is characterised by progressive diminution of vision resulting from irregular corneal topography with increased corneal fragility due to extreme thinning. Conservative and surgical management for visual rehabilitation and improved tectonic (structural) stability have been described, but are challenging. In the absence of a definitive standard procedure for management of this disorder, various surgical procedures have been attempted in order to overcome the difficulties.

Both congenital and acquired forms have been shown to occur, and may be associated with various other ocular and systemic syndromes including the connective tissue disorders.

Congenital form is present at birth and is associated with:

  • Ehlers- Danlos syndrome type VI.
  • Blue sclera syndrome.
  • Leber’s congenital amaurosis.

Acquired form presents in adulthood and may evolve from pre-existing cases of keratoconus or pellucid marginal degeneration. It is associated with:

  • Chronic marginal blepharitis.
  • Dysthyroid ophthalmopathy.
  • Vernal keratoconjunctivitis.

 

Symptoms

Patients are generally asymptomatic.

Symptoms include:

  • Poor vision.
  • Suboptimal visual acuity with spectacle correction.
  • Poor fit, associated pain or suboptimal visual acuity with use of contact lenses.

Patient developing acute hydrops may present with:

  • Pain.
  • Watering.
  • Photophobia.
  • Sudden diminution of vision.

Due to extreme thinning and fragility of cornea, patients may present with:

  • Corneal perforation.

 

Causes

Causes of Keratoglobus may be:

  • Congenital: Keratoglobus is primarily considered a congenital disorder present since birth. The congenital form of the disorder is always bilateral. The exact genetics of the disorder have not been studied in detail and no definite inheritance pattern has been described. It is assumed to be autosomal recessive.

It has also been associated with:

– Ehlers–Danlos syndrome type VI: Ehlers–Danlos syndrome type VI is distinct for its ocular manifestations. These include corneal abnormalities of cornea plana, keratoconus and keratoglobus, blue sclera, and ocular fragility. Other systemic features in this type are the presence of hypermobile joints, skeletal abnormalities like scoliosis, pectus excavatum, a marfanoid habitus, and hearing loss. Skin laxity and fragility is not a characteristic finding, unlike in other types of Ehlers–Danlos syndromes, and lysyl hydroxylase activity may be normal.

– Marfan syndrome.

– Rubinstein–Taybi syndrome.

– Blue sclera syndromes: Blue sclera syndromes may be the manifestation of syndromes like Ehlers–Danlos syndrome type VI or osteogenesis imperfecta.

– Leber’s congenital amaurosis.

 

  • Acquired: In recent years, there have been reports of acquired forms of keratoglobus. It has been associated with disorders such as:

– Vernal keratoconjunctivitis.

– Chronic marginal blepharitis.

– Dysthyroid ophthalmopathy.

– Idiopathic orbital inflammation.

Case reports of keratoglobus being associated with syphilis, trauma and posterior polymorphous dystrophy have also been reported in the literature.

There are reports of keratoconus and keratoglobus, as well as pellucid marginal corneal degeneration and keratoglobus being clinically documented in the same patient over time. Overlaps in aetiological factors between keratoconus, pellucid marginal degeneration, and keratoglobus, such as their manifestations in connective tissue disorders and various acquired forms leads to speculation about their being different spectrums of the same disease. However, a constant association and progression between these ectatic disorders has not been described to validate the hypothesis.

 

Diagnosis

The diagnosis of keratoglobus is essentially clinical, owing to the characteristic clinical findings. In less severe cases, there may be difficulty in differentiating the condition from other ectatic conditions.

Keratoglobus, a bilateral ectatic disorder of the cornea, is characterised by a globular protrusion of the cornea associated with diffuse thinning from limbus to limbus. The age of onset is at birth.

Patients usually present with stable or worsening bilateral visual impairment which may not be corrected with spectacles or contact lenses. Rarely, patient may present with acute pain in eyes due to acute hydrops.

Clinical diagnosis is made by slit lamp examination (bio-microscopy) of the eye.

Clinical features:

  • Irregular retinoscopic reflex.
  • Myopia or high myopia.
  • Irregular astigmatism.
  • Globular protrusion of cornea.
  • Diffuse corneal thinning, most severe in peripheral part and may be up to one- fifth of the normal corneal thickness.
  • Folds, breaks, or thickening of Descemet’s membrane.
  • Spontaneous rupture or tear of Descemet’s membrane.
  • Clear cornea unless there are episodes of acute hydrops and scarring.
  • Normal corneal diameter, which distinguishes it from buphthalmos.
  • Vogt striae and Fleischer’s rings are not associated, unlike keratoconus.

Investigational procedures:

  • Corneal topography or videokeratography: Corneal topography or videokeratography show diffuse thinning.
  • Ultrasonic pachymetry: Ultrasonic pachymetry shows reduced corneal thickness.
  • Anterior segment optical coherence tomography (AS- OCT).
  • Scheimpflug analysis: A Scheimpflug system images the anterior segment by creating an optical section of the cornea. Topography and pachymetry of the cornea is calculated and displayed which shows generalised thinning.

Systemic examination may show features of blue sclera, skeletal abnormalities, hyper-mobility of joints, hearing loss, abnormal dentition or high-arched palate. There may be features specific to each syndrome. It has been seen in few cases that keratoglobus in association with blue sclera syndromes is more probable to undergo spontaneous perforation or after minimal trauma, and hence the name ‘brittle cornea’ is used.

Histopathology:

There are frequent disruptions or complete absence of Bowman’s layer, stromal thinning and disorganisation, and breaks or thickening of Descemet’s membrane. Acquired type of keratoglobus is characterised by an essentially normal Bowman’s layer that undergoes focal breaks with superficial stromal ectasia secondary to other corneal pathology.

Immunohistochemical studies: There are limited immunohistochemical studies in cases of keratoglobus. Meghpara et al. (2009) found decreased expression of proteinase inhibitor alpha-1-PI, and increased expression of the transcription factor Sp1 in the corneal epithelial cells. They found increased expression of matrix metalloproteinases (MMPs) 1, 2, and 3 within the epithelial cells. The MMPs are responsible for degradation of some component of the extracellular matrix. Increased Sp1 and MMP 1, 2, and 3 was found diffusely throughout the cornea, but maximally at the mid-periphery and corresponded to areas of underlying Bowman’s layer disruptions. The increased expression of pro-degradation products and decreased expression of inhibitory substances is most probably a key pathogenic factor in causing ectasia.

Differential diagnosis:

  • Keratoconus: Keratoconus develops around puberty and may progress until 40–50 years of age, whereas keratoglobus presents at birth. Keratoglobus is considered a non-progressive or minimally progressive disorder. The corneal thinning in keratoconus is most commonly seen in the inferior paracentral aspect of the cornea. The protrusion is commonly described as conical in shape, with maximal thinning at the apex. Keratoglobus presents with diffuse thinning and a globular protrusion. Keratoconus shows scarring, Vogt’s striae and Fleischer’s ring.
  • Pellucid marginal degeneration: Pellucid marginal degeneration presents around 20–40 years of age. Thinning involves the inferior aspect of cornea, as a band of 1–2 mm width and extending from 4 to 8 o’clock position. Protrusion occur superior to this area of thinning, leading to characteristic topographical patterns. Scarring and hydrops may also occur as well.
  • Congenital glaucoma: Congenital glaucoma may show moderate protrusion of the cornea, hydrops, and mild astigmatism with myopia. Hallmark of Congenital glaucoma is raised intraocular pressure and possible glaucomatous optic nerve changes that would be absent in the case of keratoglobus. There is no corneal thinning and corneal diameters may be increased. In congenital glaucoma, the myopia would result primarily from the increased anterior and posterior axial length, whereas in keratoglobus it would be mainly because of the increased corneal curvature.
  • Megalocornea: In megalocornea, the main differentiating feature is the increased corneal diameter (usually over 12.5 mm) with absence of any corneal thinning. This is in contrast to keratoglobus where corneal diameters are normal and there is profound, diffuse thinning. There is therefore an absence of any corneal protrusion, astigmatism, hydrops, or scarring in cases of megalocornea.

Management

Management should be carried out under medical supervision.

Conservative therapy:

  • Protective eye wear: Patients should use protective eye wear and avoid contact sports owing to the high risk of perforation. Enforcement of use of protective glasses is difficult in children, making them susceptible to injury.

Medical therapy:

  • Spectacle correction: High myopia may be corrected with spectacles, but is limited by high irregular astigmatism.
  • Contact lenses: Use of contact lenses is still a matter of debate because of the theoretical risk of perforation on contact lens insertion and removal over corneas that are known to perforate on even trivial trauma. The extreme protrusion and irregularity makes fitting complicated, with a need for balance between optical improvement and lens stability. Customised fitting of scleral lenses, small diameter rigid gas permeable (RGP) lenses, reverse geometry hydrogel lenses, as well as large diameter inverse geometry RGP lenses have been described for corneal ectasias.

Conventional treatment of acute hydrops is nonspecific, and involves the use of patching, bandage contact lens, topical hypertonic saline, and cycloplegics to reduce the oedema. In recent years intra-cameral (in anterior chamber of eye) gas has been tried for acute hydrops.

Surgical therapy:

Surgically, there is no known standard procedure for management of the condition owing to its rarity. Individual procedures have their own advantages and disadvantages.

  • Repair of perforations: Repair of perforations commonly resulted in poor outcomes because of the nature of the perforations that are usually large, and owing to the fragility of the thinned cornea that prevented stable placement of sutures that would cut through or ‘cheese-wire’.
  • Penetrating keratoplasty: Penetrating keratoplasty in keratoglobus is also not possible because of the thinned cornea and peripheral graft–host thickness disparity that prevents adequate wound closure. Patients also are left with extreme irregular astigmatism and ultimately poor visual outcome. Large limbus to limbus donor corneal grafts have been tried to avoid placement of the graft–host junction at the thinned mid-periphery, thereby creating better stability.
  • Pentacam- based deep anterior lamellar keratoplasty (DALK): In deep anterior lamellar keratoplasty (DALK), the anterior third to two-thirds of the cornea is replaced with donor tissue. Use of pentacam provides a three-dimensional image or thickness profile of the entire cornea preoperatively.
  • Corneoscleroplasty:  Corneoscleroplasty involves a central full thickness penetrating keratoplasty with a lamellar peripheral corneoscleral dissection from the edge of the full thickness keratoplasty.
  • Epikeratoplasty: Epikeratoplasty is a rare form of surgery. This is a type of on-lay lamellar keratoplasty in which a lens made of human corneal tissue is sutured onto the anterior surface of the cornea to change its anterior curvature and refraction.
  • ‘Tuck-in’ lamellar keratoplasty: ‘Tuck-in’ lamellar keratoplasty refers to a central lamellar keratoplasty with intrastromal tucking of the peripheral flange.
  • Corneoscleral rim: Corneoscleral rim is a temporary measure to provide tectonic stability over thinned corneal periphery. It slows progression of mid- peripheral thinning and delays further surgical intervention.

Prognosis:

The prognosis for keratoglobus is poor. Spectacle correction often results in sub-optimal ‘best corrected visual acuity’ (BCVA).

Surgical correction may be associated with complications.

 

Complications

Complications of keratoglobus may be:

  • Acute corneal hydrops: Advanced keratoglobus rarely may progress to acute corneal hydrops due to breaks in Descemet’s membrane, leading to corneal oedema.
  • Corneal perforation: Corneal perforation may occur either spontaneously or following minor trauma.

 

References :

http://www.nature.com/eye/journal/v27/n9/full/eye2013130a.html

http://eyewiki.aao.org/Keratoglobus

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821018

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