Keratoglobus

From EyeWiki
Original article contributed by: Carlton R. Fenzl, MD
All contributors: Carlton R. Fenzl, MD and Linda Rose, MD, PhD
Assigned editor: Linda Rose, MD, PhD
Review: Assigned status Update Pending by Linda Rose, MD, PhD on August 28, 2015.



Keratoglobus
Classification and external resources
ICD-10 H18.70
DiseasesDB 32591


Keratoglobus is a rare, noninflammatory corneal ectasia characterized by diffuse protrusion and thinning of the cornea.[1]

Disease Entity

Disease

Two forms of keratoglobus exist. The congenital form is present at birth and is associated with Ehler-Danlos type VI, Leber congenital amaurosis, and the blue sclera syndrome. The acquired form presents in adulthood and may evolve from preexisting cases of pellucid marginal degeneration or keratoconus.[2][3] It is associated with vernal keratoconjunctivitis, dysthyroid ophthalmopathy, and chronic marginal blepharitis.[4]

Etiology

The etiology is unknown. However, associations between keratoglobus and disorders such as Ehlers-Danlos type VI, Marfan syndrome, and the blue sclera syndrome indicate that the etiology may result from defects in collagen synthesis.[4]

Risk Factors

No risk factors have been identified. Unlike other noninflammatory corneal ectasias such as keratoconus, eye rubbing has not been designated a risk factor.

General Pathology

Histology

Keratoglobus characteristically exhibits diffuse stromal thinning as well as focal disruptions in Bowman's layer which are most severe in the peripheral cornea. Despite this thinning, stromal lamellar organization remains unchanged from its normal configuration.[1][4] Additional findings include central epithelial hyperplasia, neovascularization and scarring of the stroma, disruptions in Descemet's membrane, as well as thickening of Descemet's membrane.[4]

Immunohistochemistry

 In an attempt to uncover the mechanism behind the noninflammatory corneal ectasias, specific gene products have been investigated. Various publications have demonstrated decreased levels of alpha1-proteinase inhibitor (a1-PI) within the stroma of keratoconus patients. [5] Sp1, a transcription facter known to suppress a1-PI promoter activity, has been found to be elevated in these same patients. Meghpara et al found similar alterations in expression of Sp1 and a1-PI in patients with keratoglobus. This leads us to believe that the underlying cause of corneal thinning in noninflammatory corneal ectasias may be due to alterations in the stromal degradation.

Pathophysiology

The pathophysiologic mechanism is unknown.

Primary prevention

An effective means of prevention has not been discovered.

Diagnosis

History

Patients usually present with a stable or worsening bilateral visual impairment that cannot be properly corrected with spectacles or contact lenses. Rarely, they may present with an episode of severe eye pain due to corneal hydrops or corneal rupture.[6]

Physical examination

Physical examination begins with an assessment of visual acuity followed by retinoscopy and refraction. Measurements of pupillary reaction, ocular motility and alignment, as well as intraocular pressures should be documented. Gross examination followed by slit lamp biomicroscopy should then be performed to evaluate the anterior segment. Finally, evaluation of the optic disc, macula, retinal vessels, and peripheral retina should be completed after pupillary dilation.

Signs

  • Myopia or high myopia
  • Irregular astigmatism
  • Irregular retinoscopic reflex
  • Globular protrusion of the cornea
  • Diffuse corneal thinning most severe peripherally
  • Folds, breaks, or thickening of Descemet's membrane
  • Spontaneous rupture/tear of Descemet's membrane
  • Acute hydrops
  • Scarring or neovascularization of the stroma

Symptoms

  • Decreased visual acuity
  • Suboptimal visual acuity with spectacle correction
  • Poor fit, pain, or suboptimal visual acuity with contact lens use
  • A single or multiple episodes of eye pain followed by resolution and decreased visual acuity

Clinical diagnosis

A clinical diagnosis is made using slit lamp biomicroscopy. Necessary findings include globular protrusion of the cornea and diffuse corneal thinning most severe peripherally.

Diagnostic procedures

  • Ultrasonic pachymetry of the cornea
  • Corneal Topography
  • Anterior segment optical coherence tomography (OCT)

Laboratory test

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Differential diagnosis

  • Keratoconus
  • Pellucid marginal degeneration
  • Corneal ectasia following refractive surgery

Management

General treatment

Management begins with spectacle correction. A steep corneal curvature with keratometric readings as high as 50-60 diopters is present in some patients with keratoglobus. Spectacle correction of high myopia with or without astigmatism may significantly improve visual acuity. In addition, spectacles can provide ocular protection. Their diffusely thin stroma puts keratoglobus patients at a much greater risk of corneal rupture after minor ocular trauma.[1] Polycarbonate lenses are optimal in these patients because of inherent properties that allow them to flex and deform rather than shatter.[6][7] Opinions are mixed as to whether contact lenses are safe and effective as a second line therapy. Supporters advocate lenses that provide the most ideal combination of visual acuity improvement and fit.[1][8] As in other corneal ectasias, patients should begin with soft contact lenses and move to rigid gas permeable, hybrid, or scleral lenses. Particular attention is required for fitting rigid contact lenses because of complications associated with their use. Rigid lenses that are excessively flat may cause epitheliopathy or thinning at the corneal apex. Overly steep lenses may worsen or complicate the preexisting ectasia.[9] These risks in conjunction with the dramatically increased potential for corneal rupture secondary to minimal trauma lead some experts to discourage contact lens wear altogether.[10]

Medical therapy

No medical therapy has been discovered to treat the underlying pathology. Instead, attention is focused on complications such as acute hydrops. Hypertonic saline, cycloplegia, and bandage soft contact lenses are the mainstay of treatment. Aqueous suppressants have also been proposed to decrease stromal uptake of fluid.[1][11]

Medical follow up

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Surgery

Surgical management of keratoglobus is an extremely difficult task. Various techniques have been proposed, but there has yet to emerge a gold standard. Traditional penetrating keratoplasty (PK) was one of the first surgical procedures attempted. It has the advantage of being less technically difficult than other surgical options. However, midperipheral suture fixation approximates a normal thickness graft to extremely thin recipient tissue. Significant postoperative astigmatism is likely and results in poor visual outcomes.[10][12] Large diameter PK has also been utilized. Disadvantages include higher risk of graft rejection, delayed re-epithelialization, and postoperative glaucoma due to the proximity of the graft to limbal stem cells, limbal vasculature, as well as the trabecular meshwork. Eccentric PK has been proposed as a way to circumvent the disadvantages of both traditional and large diameter PKs. The initial case report resulted in a visual acuity of 20/50 without the previously described complications.[10]


Lamellar keratoplasty is another viable option. Several variations have been proposed involving trephination of the host cornea followed by lamellar dissection at different depths. The dissection is extended centrifugally posterior to the limbus. The donor tissue is then tucked beneath the limbus within the plane of the lamellar dissection and sutured in place. This technique provides structural support, improves corneal irregularities, and preserves limbal stem cells.[6][12] In cases where there is significantly opacified host tissue or host-donor interface abnormality a two-step procedure can be performed. Six months after the previously described lamellar graft transplantation, a penetrating keratoplasty is undergone. This allows for improved visual potential in selected patients with residual corneal opacification.[13]


Surgical management of acute hydrops resulting from Descemet's membrane tears is another complicated topic. Traditionally, acute hydrops associated with conditions such as keratoconus and keratoglobus was managed medically with hypertonic agents, contact lenses, and patching. Recent research has documented accelerated resolution of corneal edema in keratoconus patients who were treated with intracameral gas. A significant result was not found in keratoglobus patients receiving the same therapy.[11][14] This is likely due to the large size of tears upon presentation. A second surgical option involves the use of DSAEK donor tissue to patch the host endothelium. Palioura et al has documented the successful use of a DSAEK graft secured by a combination of 10-0 nylon sutures and intracameral air to recreate the endothelial barrier.

Surgical follow up

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Complications

  • Graft rejection
  • Epithelial nonhealing
  • Epithelial downgrowth
  • Intrastromal epithelial cyst
  • Neurotrophic ulcer
  • Interface neovascularization
  • Corneal infection involving donor epithelium, donor stroma, or host-donor interface
  • Endophthalmitis[6]

Prognosis

The prognosis for keratoglobus is poor. Spectacle correction often results in suboptimal BCVA. In addition, surgical correction is difficult and associated with complications.

Additional Resources

References

  1. 1.0 1.1 1.2 1.3 1.4 External Disease and Cornea. Basic and Clinical Science Course, Section 8. American Academy of Ophthalmology; 2011:302-3.
  2. Karabatsas CH, Cook SD. Topographic Analysis in Pellucid Marginal Corneal Degeneration and Keratoglobus. Eye(Lond). 1996;10(Pt4):451-5.
  3. Rumelt S, Rehany U. Surgically induced keratoglobus in pellucid marginal degeneration. Eye(Lond). 1998;12(Pt1):156-8.
  4. 4.0 4.1 4.2 4.3 Meghpara B, Nakamura H, Vemuganti G, et al. Histopathologic and Immunohistochemical Studies of Keratoglobus. Arch Ophthalmol. 2009 Aug; 127(8): 1029-35.
  5. Shen X, Park JS, Qiu Y, et al. Effects of Sp1 overexpression on cultured human corneal stromal cells. Genes Cells. 2009 Oct;14(10):1133-9.
  6. 6.0 6.1 6.2 6.3 Javadi MA, Kanavi MR, Ahmadi M, Yazdani S. Outcomes of epikeratoplasty for advanced keratoglobus. Cornea. 2007 Feb;26(2):154-7.
  7. Diallo ML, Simonet P, Frenette B, Sanschagrin B. Resistance of plastic ophthalmic lenses: the effect of base curve on different materials during static load testing. Optom Vis Sci. 2001 Jul;78(7):518-24.
  8. Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984 Jan-Feb;28(4):293-322.
  9. McMonnies CW. The biomechanics of keratoconus and rigid contact lenses. Eye Contact Lens. 2005 Mar;31(2):80-92.
  10. 10.0 10.1 10.2 Kodjikian L, Baillif S, Burillon C, Grange JD, Garweg JG. Keratoglobus surgery: penetrating keratoplasty redux. Acta Ophthalmol Scand. 2004 Oct;82(5):625-7.
  11. 11.0 11.1 Basu S, Vaddavalli PK, Ramappa M, Shah S, Murthy S, Sangwan VS. Intracameral Perfluoropropane Gas in the Treatment of Acute Corneal Hydrops. Ophthalmology. 2011 May;118(5):934-9.
  12. 12.0 12.1 Vajpayee RB, Bhartiya P, Sharma N. Central Lamellar Keratoplasty With Peripheral Intralamellar Tuck. Cornea. 2002 Oct;21(7):657-60.
  13. Jones DH, Kirkness CM. A New Surgical Technique for Keratoglobus-Tectonic Lamellar Keratoplasty Followed by Secondary Penetrating Keratoplasty. Cornea. 2001 Nov;20(8):885-7.
  14. Palioura S, Chodosh J, Pineda R. A Novel Approach to the Management of a Progressive Descemet Membrane Tear in a Patient With Keratoglobus and Acute Hydrops. Cornea. 2012 Aug 13. [Epub ahead of print]