Pellucid marginal degeneration (PMD) is a bilateral (may be asymmetric), progressive, inferior crescentic peripheral thinning of the cornea. There is no vascularisation, infiltration or scarring in the area of involved cornea. Band of thinning measures about 1 to 2mm in width and extends from 4 to 8 o’clock position (about 6 to 8mm), leaving a normal band of 1 to 2mm from the limbus. The condition affects both men and women between 20 to 40 years of age. The condition results in high irregular astigmatism and rarely may develop acute hydrops (stromal oedema due to leakage of aqueous humour through breaks in Descemet’s membrane) or even perforation. It differs from keratoconus in that it has no iron ring, its thinning is in inferior part without a cone; and the corneal protrusion is located above (rather than) in the area of thinning. Pellucid marginal degeneration and keratoconus may exist in the same eye and in different eyes of the same patient. This association in the same patient suggests that pellucid marginal degeneration, keratoconus and keratoglobus (generalised thinning and globular protrusion of the cornea) may be varying spectrum of the same pathophysiology rather than separate disease processes. The central cornea is usually of normal thickness, and the epithelium overlying the area of thinning is intact. Rarely, it may involve superior part of cornea.
Schalaeppi (1957), coined the term pellucid marginal degeneration to describe a progressive and non-inflammatory peripheral corneal thinning disorder. The word ‘pellucid’, meaning clear, was used to denote the clarity of the cornea in this condition despite the presence of ectasia.
The cause of pellucid marginal degeneration is not clearly established, but collagen abnormalities such as that occur in keratoconus have been reported. The condition is rare, but there may be a considerable underestimation of the incidence because these patients are often misdiagnosed as having keratoconus. Early cases of pellucid marginal degeneration may be diagnosed with corneal topography/videokeratography (maps the surface curvature of the cornea) only.
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Pellucid marginal degeneration is usually asymptomatic except for visual deterioration.
Symptoms may be:
Gradual progressive deterioration in vision.
Longstanding poor vision.
Rarer symptoms are:
Sudden scleral injection.
Sudden reduction in vision and photophobia (due to acute hydrops and/or spontaneous corneal perforation).
The exact cause of pellucid marginal degeneration is not clear and it is not known whether PMD, keratoconus, and keratoglobus are distinct diseases or phenotypic variations of the same disorder. Due to the concomitant presence of PMD with keratoconus in the same eye, many have proposed that PMD is a peripheral form of keratoconus.
To date, there is no evidence that PMD is genetically inherited.
Several conditions have been reported in patients with PMD, but none of them show an obvious pathogenic association.
Chronic open angle glaucoma.
Retinal lattice degeneration.
The exact pathophysiology of PMD has not been ascertained, but it is thought to be secondary to collagen abnormalities of cornea, similar to keratoconus.
Diagnosis depends upon history, slit-lamp examination, pachymetry (measures thickness of the cornea) and corneal topography.
Patients with PMD typically present with progressive reduction in vision or longstanding poor vision, resulting from large magnitude of irregular, against-the-rule astigmatism. Against-the-rule astigmatism is the condition in which horizontal meridian is steepest and it can be corrected by a minus cylinder in the vertical axis or the plus cylinder in the horizontal axis. There may be sudden reduction in vision and photophobia due to acute hydrops, being produced by breaks in Descemet’s membrane.
PMD is a bilateral condition but unilateral cases have also been described. This condition most commonly involves inferior cornea, but involvement of superior, nasal and temporal quadrants of cornea has been reported as well.
Clinical signs of PMD:
Refraction and keratometry: Refraction and keratometry shows against-the-rule astigmatism.
PMD features: PMD is characterised by a typical narrow, clear band of corneal thinning about 1 to 2mm in width which extends from 4-o’clock position to 8-o’clock position (6 to 8mm in size). The degree of thinning is usually severe and may cause up to 80% loss of stromal tissue. Between limbus and thinned band-like region there is typically a 1 to 2mm wide region of uninvolved normal cornea which is usually clear. The corneal protrusion is most marked just superior to the area of thinning and usually with normal thickness of the central cornea. Descemet’s folds, usually concentric with the inferior limbus, may develop which disappear with pressure on the cornea.
Unlike keratoconus, PMD usually does not show signs of Fleischer’s ring, corneal infiltration, vascularisation, scarring or lipid deposition. Since there is no obvious cone, cornea does not exhibit Munson’s sign (a V-shaped deformation of the lower eyelid when the eye turns downward) or Rizutti’s sign (a sharply focussed beam of light near nasal limbus produced by lateral illumination of the temporal limbus).
Corneal topography or videokeratography: Corneal topography is the gold standard in detecting corneal ectasia. The use of topography allows the detection of early and subclinical ectasia which is important in diagnosis as well as in pre-operative corneal laser refractive surgery assessment. Videokeratography shows low corneal power along the central vertical axis which increases as the inferior cornea is approached, and high corneal power along the inferior oblique meridians. There are various topography devices like TMS-1 which uses pacido rings method, Orbscan II utilises slit-scanning and Placido ring reflection, Oculus Pentacam uses Scheimpflug photography for topography with pachymetry, and Visante Omni combines Placido ring and optical coherence tomography (OCT) for topography with pachymetry. The hallmark of corneal topography in PMD is an obvious flattening of the cornea along the vertical meridian. Inferior-central cornea in PMD shows a ‘beer-belly’ appearance when viewed from the side. Topography shows that this inferior peripheral steepening extends into the mid-peripheral, inferior oblique corneal meridians in a classic ‘crab-claw’, ‘butterfly’ or ‘kissing doves’ appearance.
Classification or stages of PMD:
Being a rare disorder no clearly defined, guidelines have been proposed to categorise the severity of the condition. However, the ectatic process advances over time and it is suggested to have three stages:
Light microscopy may show irregularity in epithelium with oedema, increase in stromal mucopolysaccharides as well as an irregular Bowman’s membrane with ruptures at places. There may be folds in Descemet’s membrane and stromal thinning.
Electron microscopy may show breaks in Bowman’s layer, irregular arrangement of stroma with the presence of extracellular, granular electron-dense deposits. There is absence of inflammatory cells.
Scanning electron microscopy may reveal unusual electron-dense areas of fibrous long-spacing collagen in the peripheral thinned areas, scattered amongst regions of mostly normal collagen.
PMD is most frequently misdiagnosed as the more common corneal ectatic condition of keratoconus.
Keratoconus: Keratoconus is characterised by para-central corneal thinning and ectasia so that the cornea takes the shape of a cone. Pellucid marginal degeneration may be differentiated from keratoconus in most cases by the inferior band like location of the thinning on slit lamp (bio-microscopy) examination and by the classic butterfly pattern on videokeratography. In contrast to keratoconus, patients with pellucid marginal degeneration have no iron ring, no Vogt striae, and no central corneal thinning or scarring of the protruding cornea, and corneal protrusion is located above rather than in the area of thinning.
Keratoglobus: Keratolobus causes circumferential 360˚ thinning of the cornea, more marked at the limbus, and the entire cornea protrudes compared with regional thinning in keratoconus and inferior paralimbal thinning in pellucid marginal degeneration. Corneas with keratoglobus usually show diffuse thinning, varying from one-third to one-fifth of the normal corneal thickness at the mid-peripheral area. Vogt’s striae, sub-epithelial scarring, Fleischer’s ring, lipid deposition and corneal vascularisation are rarely found in the corneas with keratoglobus. The cornea can also become opaque and oedematous from breaks in Descemet’s membrane.
Terrien’s marginal degeneration: Terrien’s marginal degeneration is a non-inflammatory condition characterised by slowly progressive, bilateral, marginal corneal ectasia typically beginning superiorly which can then progress circumferentially. Terrien’s marginal degeneration most commonly affects males in their mid-twenties. Early signs on slit lamp examination include marginal opacification with peripheral vascularisation. Marginal thinning then begins parallel to the limbus, forming a ‘gutter-like furrow’ in the clear gap between opacification and limbus. Epithelium remains intact and does not ulcerate over the furrow and lipid deposition occurs as the furrow deepens. Pseudo-pterygium may develop near the furrowed area. As the disease continues, the thinning may extend to the inferior cornea, sparing the interpalpebral periphery. There is relative steepening of interpalpebral peripheral cornea, resulting in against-the-rule or oblique astigmatism. Terrien’s marginal degeneration progresses very slowly, frequently taking several years. Vast majority of patients with Terrien’s marginal degeneration complain of mild, intermittent ocular irritation only. Very rarely does it causes acute ocular inflammation with pain.
Furrow degeneration: Furrow degeneration, like pellucid marginal degeneration has an intact epithelium and the area of corneal thinning is not vascularised, at least in the acute phase. The area of thinning in furrow degeneration is much closer to the limbus with virtually no intervening zone of normal cornea. Furrow degeneration may on occasion involve superior part of cornea, and there may be an associated adjacent area of scleritis. The edges of the furrow are steeper than the gradual attenuation seen in pellucid marginal degeneration, and there may be a corneal infiltrate adjacent to the area of thinning. Furrow degeneration may have strong association with rheumatoid arthritis.
Mooren’s ulcer: Mooren’s ulcer, an idiopathic peripheral corneal melting disorder, is characterised by associated severe pain and may be accompanied by an epithelial defect over the area of thinning. It may be accompanied by corneal vascularisation adjacent to the area of thinning in the acute phase. Usually the site of involvement is the inferior limbus, with the ulceration then spreading circumlimbally and then centrally, eventually involving the entire cornea. At the end stages of Mooren’s ulcer, there is vascularisation and scarring of cornea with stromal thinning to less than half of the original corneal thickness.
Rheumatologic disorder affecting cornea: Rheumatologic disorder affecting cornea is also a peripheral melting disorder. It is characterised by pain and may be accompanied by an epithelial defect over the area of thinning. It may also be accompanied by corneal vascularisation adjacent to the area of thinning in the acute phase.
Contact lens-induced warping of cornea: Contact lens-induced warping of cornea may mimic the appearance of pellucid marginal degeneration on corneal topography.
Management should be carried out under medical supervision.
Vast majority of patients with PMD are managed by medical therapy.
Management of PMD is dependent on the severity of the disease.
Spectacle correction: To begin with in the early mild stages of the disease, spectacle correction is prescribed. Patients with high astigmatism may be prescribed with high refractive index sphero-cylindrical glasses.
Soft (hydro gel) toric contact lenses: Soft toric (lenses for astigmatism) contact lenses may be useful in the early mild stages of the condition only, usually before the progression of irregular astigmatism. Hybrid (rigid gas permeable and hydro gel combined) contact lenses viz. Saturn II lenses, SoftPerm lenses and SynergEyes lenses have also been used.
Rigid gas permeable (RGP) contact lenses: Rigid gas permeable (RGP) contact lenses may be required for moderate cases of PMD. Large amount of irregular against-the-rule astigmatism results in unstable lens centration and excessive inferior edge stand-off. Therefore, larger-diameter RGP lenses may provide satisfactory lens stability and tolerance with good visual acuity. ‘Bi-toric’ RGP contact lenses have also been used successfully. Specialised back surface design lenses may correct large amounts of corneal astigmatism and may provide good visual acuity. RGP and soft contact lens with ‘sector management control’ allow peripheral lens geometry to be customised to complement the anterior surface of the ectatic cornea.
Rigid gas permeable (RGP) scleral contact lenses: In advanced stages, adequate RGP lens centration may be difficult to achieve as additional corneal steepening increases the possibility of lens dislocation with blinking. Rigid gas permeable (RGP) scleral contact lenses have certain advantages.
Advantages of scleral contact lenses are:
- They are supported by the sclera thus reducing lid sensation.
- They provide good centration, thus high-powered lenses remain static.
- They are unlikely to dislodge upon blinking.
- They vault the area of the cornea affected by the disease making irregular topography less of a problem to fit.
- There is less risk of foreign body entrapment.
Disadvantages of scleral contact lenses are:
- Poor oxygen transfer to cornea.
- Difficulties in application as compared to corneal RGP lenses.
- Complicated manufacturing processes.
- Relatively few practitioners are experienced in fitting such lenses.
Keratoplasty: Keratoplasty is considered for patients with PMD whose vision is inadequate with contact lenses or for patients who are intolerant to lens.
Penetrating keratoplasty: In general, patients with PMD are usually poor candidates for penetrating keratoplasty as the corneal thinning occurs close to the limbus. As a result, large eccentric grafts are required and must be positioned very close to the limbus thus increasing the chances of graft rejection, suture-induced complications and corneal neovascularisation. Penetrating keratoplasty also induces large amounts of post-operative astigmatism which may be difficult to correct due to variation in the graft-host thickness.
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.
Lamellar crescentic keratoplasty: In lamellar crescentic keratoplasty, crescent-shaped donor lamellar cornea is used. Lamellar crescentic keratoplasty was used earlier to treat PMD.
Lamellar thermo- keratoplasty (LTK): Lamellar thermo-keratoplasty (LTK) is an adaptation of lamellar crescentic keratoplasty. This involves thermal shrinkage of the host lamellar bed, prior to the placement and suturing of the crescent-shaped donor lamellar cornea.
Lamellar crescentic resection (LCR): Lamellar crescentic resection (LCR) involves excision of the abnormally thinned stroma and then re-approximation of the near-normal thickness edges. The major advantage is that no donor tissue is required.
Corneal wedge excision/resection: Corneal wedge excision/resection is similar to lamellar crescentic resection, except that it involves full thickness corneal tissue removal followed by re-apposition of the remaining normal thickness cornea using sutures.
Epikeratoplasty: Epikeratoplasty is a rare form of surgery used for PMD. 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.
Intra-stromal corneal ring segment inserts (INTACS): Intrastromal corneal ring segment inserts (INTACS) helps in reducing the myopia and astigmatism and improving spectacle- corrected visual acuity. Intrastromal corneal ring segment inserts (INTACS) involves incorporation of two semi-circular plastic rings into the peripheral corneal stroma. In PMD, the ectatic corneal tissue has a thinner structure and is potentially more easily flattened as compared to normal eyes.
Combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking: Combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking consists of photo-polymerisation of corneal stroma by combining vitamin B2 (photosensitising substance) with UVA. This process increases rigidity of corneal collagen and thus reduces the likelihood of further ectasia.
Toric phakic intraocular lens (TPIOL): The use of toric phakic intraocular lens (TPIOL) has also been reported.
PMD patients presenting with acute hydrops or corneal perforation may be treated with glue tissue adhesive, bandage soft contact lenses, crescentic lamellar keratoplasty, penetrating keratoplasty or deep anterior lamellar keratoplasty.
Pellucid marginal degeneration progresses slowly over the years and may result in severe visual deterioration. Being rare, no large scale longitudinal studies are reported.
Since pellucid marginal degeneration affects corneal periphery, contact lens fitting and surgical correction is more difficult as compared to keratoconus.
Complications of PMD may be:
Acute corneal hydrops: PMD rarely may lead to acute corneal hydrops due to breaks in Descemet’s membrane, leading to corneal oedema. During recovery from acute hydrops, corneal vascularisation and scarring may occur.