Contact Lens & Anterior Eye Pellucid Corneal Marginal Degeneration: A

Contact Lens & Anterior Eye 34 (2011) 56–63

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Review Pellucid corneal marginal degeneration: A review

Amit Jinabhai, Hema Radhakrishnan, Clare O’Donnell ∗

The University of Manchester, England, UK article info abstract

Keywords: Pellucid marginal corneal degeneration (PMD) is a rare ectatic disorder which typically affects the inferior PMD peripheral cornea in a crescentic fashion. The condition is most commonly found in males and usually Clinical features appears between the 2nd and 5th decades of life affecting all ethnicities. The prevalence and aetiology Histopathology of this disorder remain unknown. Ocular signs and symptoms of patients with PMD differ depending Differential diagnosis on the severity of the condition. Unless corneal topography is evaluated, early forms of PMD may often Management be undetected however, in the later stages PMD can often be misdiagnosed as keratoconus. Visual signs and symptoms include longstanding reduced visual acuity or increasing against-the-rule irregular astigmatism leading to a slow reduction in visual acuity. In rare cases, patients may present with a sudden loss of vision and excruciating ocular pain due to corneal hydrops or spontaneous perforation. The vast majority of PMD patients are managed using spectacles and contact lenses. Several surgical procedures have been used in an attempt to improve visual acuity when spectacles and contact lenses do not provide adequate vision correction. Since patients with PMD make poor candidates for laser vision correction, an awareness of the topographical and slit-lamp features of PMD will be useful to clinicians screening for signs of corneal abnormality before corneal refractive surgery. This review describes the clinical features of PMD, its differential diagnosis and various management strategies presently available. © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

1. Introduction peripheral form of keratoconus. In agreement with this sugges- tion, other studies have reported the occurrence of keratoconus 1.1. Definition with PMD [11–13]. Kayazawa et al. [13] report that 17 out of 20 patients with PMD also showed concomitant keratoconus in the Pellucid marginal corneal degeneration (PMD) is a rare idio- same eye. Varley et al. [12] describe that 8 out of 12 patients with pathic, thinning disorder of the peripheral cornea most usually PMD also displayed corneal features suggestive of keratoconus. affecting the inferior quadrant in a crescentic fashion. The word Finally Sridhar et al. [11] report that PMD was associated with ker- ‘pellucid’, meaning clear, was first used by Schlaeppi [1] to denote atoconus in 12 out of 166 eyes evaluated. In agreement with the the clarity of the cornea in this condition despite the presence of findings of Karabatsas and Cook [14], Sridhar et al. [11] also reveal ectasia. The condition may also have been previously identified in that PMD was associated with keratoglobus in 15 out of 155 eyes early European studies under several other names such as pellucid investigated. marginal degeneration [2–4] or pellucid marginal dystrophy [1,5]. Fogla and colleagues [15] have discovered induced PMD in two This review describes the clinical features of PMD, its differential subjects who had undergone laser in situ keratomileusis (LASIK). diagnosis and the options for management. The authors discuss that an inherent weakness in the biome- chanical properties of the cornea is most likely in PMD and that performing LASIK in eyes with any topographical signs of corneal 1.2. Aetiology abnormality may inadvertently induce this form of keratectasia. This in agreement with other reports [16–18]. At present, the exact aetiology of PMD is unclear and it is not known whether PMD, keratoconus, and keratoglobus are distinct diseases or phenotypic variations of the same disorder [6–8]. Nev- 1.3. Epidemiology ertheless, several authors [2,3,9,10] have proposed that PMD is a To date, no bio-statistical studies have evaluated either the incidence or prevalence of PMD; however, the general consensus in the ∗ literature is that PMD is a rare condition, less common than other Corresponding author at: The University of Manchester, Faculty of Life Sciences, Manchester M60 1QD, UK. Tel.: +44 161 306 3872; fax: +44 161 306 3969. ectatic diseases such as keratoconus [6–8], but more common than E-mail address: Clare.O’[email protected] (C. O’Donnell). either keratoglobus [19] or posterior keratoconus [19].

1367-0484/$ – see front matter © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.clae.2010.11.007 A. Jinabhai et al. / Contact Lens & Anterior Eye 34 (2011) 56–63 57

Sridhar and collaborators’ [11] study is the largest investigation superior to the area of thinning, where the thickness of the central of PMD to date, the authors evaluated 116 eyes from 58 patients and corneal is usually normal [6–8,11,34]. found a higher incidence of PMD in males (77.6% of their subjects). The gold standard in detecting corneal ectasia is undoubtedly These findings are in agreement with an early study by Kompella corneal topography. The very first computer-based topographers, et al. [20], who found that 12 out of 15 patients examined with such as the TMS-1 device (Tomey Technology, Waltham, MA, US), PMD were male. Most recently, Tzelikis et al. [21] found that 30 out used the Placido rings method. More recently, the Orbscan II of the 45 patients they evaluated with PMD were male. However, (Bausch & Lomb, Rochester, NY, US) has been developed which prior to these three studies the literature had reported no gender utilises both slit-scanning (stereo-triangulation) and Placido rings predilection [6–8,22]. reflection to capture topographical and corneal thickness data. Krachmer et al. [6] explain that PMD is a slowly progressive con- Alternatively, the Pentacam device (OCULUS, Wetzlar, Germany) dition, classically discovered between the second and fifth decades uses Scheimpflug photography to determine corneal topogra- of life. Sridhar and co-workers’ [11] study concurs with Krachmer phy and pachymetry. Recent instrumentation such as the Visante et al.’s [6] report and shows that the average age for presentation Omni (Carl Zeiss Meditec, Dublin California, USA), combines both with PMD was 34 ± 15 years. Similarly, Kompella et al. [20] report Placido ring and optical coherence tomography techniques to the average age of presentation with the condition as 39 ± 14 years. derive corneal topography and thickness information in addition to On the other hand, Tzelikis et al. [21] report a still higher average providing highly detailed images of the anterior segment. The use age for presentation of 48 ± 12 years. The current literature sug- of such instruments allows the detection of early and subclinical gests that PMD affects all ethnicities and shows no geographical ectasia which is essential in pre-operative corneal laser refractive predisposition [6–8,19,22]. surgery assessment, because performing these procedures in early or known PMD [15] or keratoconus [35] patients can exacerbate 1.4. Heredity the progression of these conditions. The hallmarks of PMD are corneal topographical abnormali- To date, there is no evidence that PMD is genetically inherited. ties above the thinned zone which show an obvious flattening Only Santo and Kara-Jose [23] describe topographical evidence of of the cornea along the vertical meridian and “against-the-rule” corneal ectasia in asymptomatic family members of a patient with astigmatism [6–8]. When viewed from the side, several authors classic PMD. Unilateral cases however, usually manifest topograph- classically describe that the inferior-central cornea in PMD appears ical evidence of PMD in the contralateral eye or reveal the presence to show the side-profile contour of a “beer-belly” [36–38], as shown of other ectatic disorders [14]. Other authors have revealed mod- in Fig. 1(B). Although not diagnostic of any given ectatic condi- erate to high astigmatism in asymptomatic family members of tion, the corneal side-profile appearance may be used alongside patients with PMD [4,24,25]. corneal topography, central thickness measurements and corneal slit-section observations in the differentiation of PMD from keratoconus and keratoglobus. In advanced cases of PMD, Krachmer 2. Clinical features [7] reports that the ectatic zone steepens abruptly (from the centre downwards towards the periphery) with increases in curvature Both Sridhar et al. [11] and Krachmer et al. [6] agree that PMD is of as much as 20 D. Topographical investigations have shown that a bilateral condition, whereas other authors have also described this inferior peripheral steepening extends into the mid-peripheral, the occurrence of unilateral cases [26–29]. The condition most inferior oblique corneal meridians in a classic “crab-claw”, “but- commonly involves the inferior cornea [6–8,11,22] however, other terfly” or “kissing doves” appearance [11,14,34,39–41] as shown reports have shown that the site of involvement can also include in Fig. 2(B). However, Lee et al. [42] have discussed that a “claw- the superior [11,25,30–33], nasal [30] and temporal [30] quadrants shaped” pattern on corneal topography is not diagnostic of PMD and of the cornea. Classically, PMD is characterised by a typical nar- that such patterns may also be found in keratoconus. The authors row, clear band of corneal thinning around 1 or 2 mm in width suggest that slit-lamp signs as well as pachymetry maps must be which extends from the 4-o’clock position to the 8-o’clock position considered in conjunction with corneal topography for a reliable [7,8,11]. Robin et al. [8] explain that the degree of thinning is usu- diagnosis. ally severe, resulting in up to 80% stromal tissue loss. Between the As summarised in Table 1, corneas with PMD usually show no thinned band-like region and the limbus there is typically a 1–2- signs of Fleischer’s ring, corneal infiltration, scarring or vascularisa- mm wide region of uninvolved, normal cornea which is usually tion [6]. No obvious cone can be recognised and there are no signs clear [8,10,22]. The corneal protrusion in PMD is most marked just of lipid deposition [8]. In addition, these corneas do not exhibit

Fig. 1. The corneal side-proﬁle appearance of early-stage (A) and more advanced pellucid marginal corneal degeneration (B). When comparing the inferior and superior limbus in either image, the inferior peripheral cornea shows a protruding appearance. This classic “beer-belly” contour is more pronounced in image B than in image A, and gives some indication of how pellucid marginal corneal degeneration may progress over time. 58 A. Jinabhai et al. / Contact Lens & Anterior Eye 34 (2011) 56–63

Fig. 2. The corneal topography of a normal eye (A), an eye with pellucid marginal corneal degeneration (B) and an eye with moderate keratoconus (C). Note the classic “kissing doves” appearance in image B. The scale bar values are in mm, the red colours represent steeper corneal curvatures whereas the green/blue colours represent ﬂatter corneal curvatures. All three images were captured using the Medmont E300 corneal topographer (Medmont, Camberwell, Victoria, Australia). (For interpretation of the references to colour in this ﬁgure legend, the reader is referred to the web version of the article.)

Munson’s sign (a V-shaped deformation of the lower eyelid when membrane. The occurrence of corneal hydrops reflects a corneal the eye is looking downwards) or Rizutti’s phenomenon (a sharply response to progressive thinning. Sridhar et al. [11] evaluated 7 focussed beam of light near the nasal limbus produced by lateral eyes with hydrops due to PMD and reported that the sites of the illumination of the temporal limbus) [42]. Descemet’s folds may breaks in Descemet’s membrane were all above the area of thinning. develop and are usually found to be concentric with the inferior In patients with superior PMD, Taglia and Sugar [25] and Lucarelli limbus; such folds disappear when pressure is applied to the cornea et al. [47] describe corneal perforation at the inferior crescent. Dur- [6,43]. ing the recovery from acute hydrops, corneal vascularisation and Patients presenting with PMD most typically complain of a grad- scarring has been found to occur in patients with PMD [7,22]. ual, progressive reduction in vision or longstanding poor visual acuity; both symptoms most commonly result from large magnitudes of irregular, against-the-rule astigmatism [7,22]. Rarer 3. Classification symptoms experienced in PMD include sudden scleral injection, acute pain, a sudden reduction in vision and photophobia as a Owing to the rarity of the disorder, no clearly defined guidelines result of acute hydrops and/or spontaneous corneal perforation have been proposed to help categorise the severity of the condi- [7,25,44–55]. Corneal hydrops is also found in patients with ker- tion. However, the literature reports that early [37,56,57], moderate atoconus; similarly, the presenting signs for patients with PMD [28,58,59] and advanced [11,60,61] stages of the condition exist and are corneal oedema with an identifiable break in Descemet’s that the ectatic process advances over time [7].

Table 1 A summary of the differences in clinical signs between pellucid marginal corneal degeneration and keratoconus.

Feature Keratoconus Pellucid marginal corneal degeneration (PMD)

Best corrected spectacle visual acuity Becomes reduced even at the mild stage Generally only becomes signiﬁcantly reduced in the advanced stage ‘Scissors’ retinoscopic reﬂex Present in all severities Usually only seen in advanced cases Position of maximum protrusion Equivalent to the area of thinning Typically – superior to the thinned zone [6–8,11,22] Atypically – inferior to the thinned zone [11,25,30–33] Location of corneal thinning Can be centrally or just inferior to the visual axis Typically – in a narrow band of approximately 1–2 mm, located around 1.5 mm above the inferior limbus; the band is concentric to the limbus in a crescent-like shape, extending from the 4 o’clock to the 8 o’clock position [6–8,11,22] Atypically – in a narrow band of approximately 1–2 mm, located around 1.5 mm below the superior limbus; the band is concentric to the limbus in a crescent-like shape, extending from the 10 o’clock to the 2 o’clock position [11,25,30–33] Video-keratography appearance (A) An increased area of corneal power surrounded by Classic “kissing doves” or “crab-claw” pattern concentric areas of decreasing power demonstrating irregular, against-the-rule astigmatism (B) Inferior–superior power asymmetry (C) Skewing of the steepest radial axes above and below the horizontal meridian Central corneal thickness Reduced compared to normal Usually normal Fleischer’s ring Usually present around the base of the cone Absent Apical corneal scarring Usually present in the moderate and severe stages Absent Rizutti’s phenomenon Usually present in the moderate and severe stages Absent Munson’s sign Usually present in the moderate and severe stages Absent A. Jinabhai et al. / Contact Lens & Anterior Eye 34 (2011) 56–63 59

4. Histopathology is more prominent temporally. Lee et al. [42] have also advocated the use of pachymetry maps to make the most reliable identifica- Zucchini [2] carried out the first histopathological study of tion. A differential diagnosis of PMD from keratoconus is desirable PMD and found that even though Bowman’s layer was absent, since the prognosis and management can vary between the two the epithelium was normal. In addition, Zucchini reports an conditions [75]. increase in the stromal mucopolysaccharides. No abnormalities The differential diagnosis of PMD also includes the rare, bilateral of Descemet’s layer or the endothelium were noted in this ectatic condition keratoglobus. Keratoglobus is typically charac- investigation. Francois et al. [3] performed further detailed light- terised by limbus-to-limbus thinning causing the cornea to assume microscopy investigations and also discovered an increase in a globular profile [76], where keratometry measurements can stromal mucopolysaccharides as well as an irregular Bowman’s often be as high as 60–70 D [77]. As opposed to in keratoconus, layer with ruptures in places. Interestingly, Francois et al. also corneas with keratoglobus are usually diffusely thinned (to approx- describe epithelial oedema and irregularity, folds in Descemet’s imately one-third to one-fifth of the normal thickness [77])atthe layer and stromal thinning in their study. Pouliquen et al. [9] mid-peripheral cornea [78,79]. Vogt’s striae, sub-epithelial scar- conducted the first electron microscopy study of PMD and also ring, Fleischer’s ring, lipid deposition and corneal vascularisation revealed breaks in Bowman’s layer, an irregular arrangement of the are rarely found in corneas with keratoglobus [77,78]. However, stroma with the presence of extracellular, granular electron-dense the cornea can become opaque and oedematous from breaks in deposits. Zucchini [2], Francois et al. [3] and Pouliquen et al. [9] all Descemet’s membrane [19]. note the absence of inflammatory cells in their studies. Rodrigues Other peripheral corneal thinning disorders misdiagnosed with et al. [10] used scanning electron microscopy to evaluate corneas PMD include Mooren’s ulcer and Terrien’s marginal degeneration. with PMD and revealed unusual electron-dense areas of fibrous Mooren’s ulcer is an idiopathic condition characterised by either long-spacing (FLS) collagen with a periodicity of 100–110 nm in the unilateral or bilateral painful, inflammatory thinning and ectasia of peripherally thinned areas, scattered in amongst regions of mostly the peripheral cornea [8]. Slit-lamp examination signs of Mooren’s normal collagen which had a periodicity of 60–64 nm. Rodrigues ulcer classically include perilimbal corneal infiltrates, epithelial et al. [10] report that they had observed such FLS collagen in cases defects within the ulcerated region and finally the development of advanced keratoconus with scarring. of a shallow furrow at the edge of the ulcer [80]. Usually the site Other conditions reported in patients with PMD include chronic of involvement is the inferior limbus, with the ulceration then open-angle glaucoma [62], retinitis pigmentosa [20], retinal lat- spreading circumlimbally and then centrally, eventually involving tice degeneration [20] scleroderma (a progressive, multi-system the entire cornea. Vascularisation occurs during the healing pro- connective tissue disorder) [39], kerato-conjunctivitis [63], eczema cess which can last up to 12–18 months [81]. Chow and Foster [81] [3,5] and hyperthyroidism [1,64]; however, none of these condi- report that at the end-stages of Mooren’s ulcer, a scarred and vascu- tions have been proven to show an obvious pathogenic association larised cornea is typically found with stromal thinning to less than with PMD. half of the original corneal thickness. Terrien’s marginal degeneration is a non-inflammatory condition characterised by slowly progressive, bilateral, marginal corneal 5. Differential diagnosis of PMD ectasia typically beginning superiorly which can then progress circumferentially [8]. Terrien’s marginal degeneration most com- PMD is most frequently misdiagnosed as the more common monly affects males in their mid-twenties [82]. Forstot [82] reports corneal ectatic disorder keratoconus [19,42]. Keratoconus, is the that early slit-lamp examination signs include marginal opacifica- term used to describe the condition where the cornea takes on tion with peripheral vascularisation. Marginal thinning then begins a steepened, conical profile at the same position as the maximal to occur parallel to the limbus, forming a “gutter-like furrow” in the stromal thinning [6,65]. The disease process of keratoconus is non- clear gap between the opacification and the limbus. This furrow inflammatory, showing no signs of either vascularisation or cellular does not ulcerate and the epithelium remains fully intact how- infiltration [6]. The condition is usually bilateral and involves the ever, lipid deposition occurs as the furrow deepens [8]. Goldman central two-thirds of the cornea, with the cone apex most usually and Kaufman [83] have previously reported that pseudo-pterygia displaced inferior to the visual axis [66]. Keratoconus classically may develop near the furrowed area. As the process continues causes mild to marked impairment of visual function [19]. Typical the thinning may extend to the inferior cornea, sparing the inter- signs of keratoconus include a “scissors” retinoscopic reflex, an “oil- palpebral periphery [8]. Very few cases of central ectasia have drop” ophthalmoscopic reflex, Fleischer’s ring [67], Vogt’s striae been reported in association with Terrien’s marginal degeneration [68] and stromal tissue thinning with conical protrusion [69,70]. [84,85]. The corneal topography of Terrien’s disease is characterised Later signs of keratoconus include Munson’s sign, Rizutti’s phe- by corneal flattening over the areas of peripheral thinning pro- nomenon and apical corneal scarring [71,72]. duced by the disorder [86,87]. When the thinning is restricted to In moderate cases, Rabinowitz [66] explains that PMD can be the superior and/or inferior areas of the peripheral cornea only, a distinguished from keratoconus by slit-lamp biomicroscopic exam- relative steepening of the inter-palpebral peripheral cornea can be ination, due to the classic location of the region of corneal thinning. found, resulting in large magnitudes of against-the-rule or oblique However, in early cases of PMD the cornea may look relatively astigmatism [86]. Perforation of the ectatic regions may occur with normal, and in severe cases PMD may be difficult to differenti- ocular trauma or even spontaneously [8]. Terrien’s marginal degen- ate from keratoconus because the corneal thinning may involve eration progresses very slowly, frequently taking several years. the majority, if not all of the inferior cornea [8]. In both these Increases in irregular astigmatism cause a subsequent diminution cases corneal topography is most valuable in order to differentiate of best-corrected visual acuity. Very rarely does Terrien’s marginal between the two conditions, as they generally show distinctly dif- degeneration cause acute ocular inflammation with pain [88,89], ferent topographic patterns [14,34,73], as highlighted in Fig. 2(C). with the vast majority of patients complaining of mild, intermittent This example of a moderately keratoconic cornea shows a classi- ocular irritation [82]. cal inferior-central cone where the steepening extends towards Both Rabinowitz [66] and Robin et al. [8] propose that PMD the inferior limbus [73]. Rabinowitz and McDonnell [74] have also can be differentiated from Mooren’s ulcer and Terrien’s marginal reported that keratoconic corneas characteristically show steepen- degeneration because the area of thinning in PMD is always epithe- ing of the inferior cornea compared with the superior cornea, which lialised, without lipid deposition, remaining avascular and clear. 60 A. Jinabhai et al. / Contact Lens & Anterior Eye 34 (2011) 56–63

Table 1 summarises the subtle differences in clinical signs patients, in general, only show negative eccentricities in the infe- between PMD and keratoconus which could allow clinicians to rior quadrant of the cornea [40]. Therefore reverse-geometry lenses differentiate between the two conditions. could potentially cause superior lens binding, resulting in inadequate tear exchange and persistent epithelial damage. Modern day RGP and soft contact lens materials can be specif- 6. Management ically manufactured to offer “sector management control”; such designs allow the peripheral lens geometry to be customised to 6.1. Non-surgical methods complement the anterior surface of the ectatic cornea. White [103] has reported that these bespoke designs have been useful with soft Management of PMD is dependant on the severity of the disease. lens materials for keratoconic patients and has suggested that this In the early stages of the condition, PMD is most commonly man- technology may also be helpful for PMD patients. aged using spectacles [21,28,75]. Biswas et al. [28] achieved good As PMD progresses further to the advanced stages, adequate RGP visual acuity in PMD patients with high astigmatism after prescrib- lens centration can become very difficult to achieve as additional ing appropriate sphero-cylindrical spectacles with high refractive corneal steepening increases the possibility of lens dislocation with index lenses. Kompella et al. [20], Mahadevan et al. [90] and Srid- blinking. Several authors propose that RGP scleral contact lenses har et al. [11] all suggest that soft toric contact lenses can be useful, may be of use in such situations [28,104–107]. Scleral lenses are but usually only before the progression of irregular astigmatism advantageous in that they are supported by the sclera thus reduc- occurs. Other authors describe the successful use of hybrid contact ing lid sensation; they can vault the area of the cornea affected lenses for patients with PMD, including Saturn II lenses (Pilkington by the disease making the irregular topography less of a problem Barnes-Hind Inc., Sunnyvale, CA, US) [91]; SoftPerm lenses (Pilk- to fit; they provide good centration meaning high-powered lenses ington Barnes-Hind Inc., Sunnyvale, CA, US) [92,93] and SynergEyes remain static; they are unlikely to dislodge upon blinking and lenses (SynergEyes Inc., Carlsbad CA, US) [94,95]. However, Saturn II finally there is less risk of foreign body entrapment. Scleral lenses lenses tended to tighten with time [96] and had low oxygen perme- can have several disadvantages such as poorer oxygen transmission −11 2 ability (Dk = 14 × 10 (cm /s) (ml O2/ml × mmHg)) resulting in to the cornea; complicated manufacturing processes; difficulties corneal oedema and neovascularisation as common complications with application compared to corneal RGP lenses and lastly that [97]. SoftPerm lenses were manufactured with the same materials relatively few practitioners are experienced in fitting such lenses. as the Saturn II lenses, but used a larger diameter with a modi- The literature reviewed indicates that the vast majority of fied edge design to allow better tear circulation. Despite showing patients with PMD are managed using non-surgical methods fewer complications, both Maguen et al. [98] and Chung et al. [99] [20,21]. Both Kompella et al. [20] and Tzelikis et al. [21] report that found that SoftPerm lenses ripped easily between the RGP and soft approximately 88% of their participants successfully used either lens junction during lens handling. Both authors also reported a spectacles or contact lenses to correct their visual difficulties, with high rate of giant papillary conjunctivitis (GPC) in patients wearing around 12% of patients opting for surgical intervention. The differ- SoftPerm lenses. ent surgical strategies used for PMD will now be discussed. Compared to Saturn II (1st-generation) and SoftPerm (2nd- generation) hybrid lenses, SynergEyes lenses provide the benefits of a stronger RGP-hydrogel junction as well as higher oxygen per- 6.2. Surgical methods 2 meability (Dk = 100 (cm /s) (ml O2/ml × mmHg)). Nonetheless, Nau [95] found lens tightness and removal problems in patients using Penetrating keratoplasty (PK) is considered for patients with SynergEyes lenses, whilst Abdalla et al. [94] report the occurrence PMD whose vision is inadequate with contact lenses or for patients of GPC and allergies. who are lens intolerant [12,28,108]. In general however, patients Moderate cases of PMD usually require fitting with rigid gas per- with PMD are usually poor candidates for PK as the corneal thin- meable (RGP) contact lenses. In these patients, a common problem ning occurs close to the limbus. As a result large eccentric grafts with standard-diameter, spherical RGP lens use is excessive inferior are required and must be positioned very close to the limbus edge stand-off. This is primarily due to large amounts of irregular thus increasing the chances of graft rejection, suture-induced com- against-the-rule astigmatism resulting in unstable lens centra- plications and corneal neovascularisation [7,11,66]. In addition, tion. Consequently, many authors have fitted larger-diameter RGP PK typically induces large amounts of post-operative astigmatism lenses with successful results [20,21,28,100]. In these studies large which may be difficult to correct due to variation in the graft-host diameter RGP lenses were found to provide satisfactory lens stabil- thickness [66]. Biswas et al. [28] found that 66 months after surgery isation and lens tolerance with good visual acuity [20,21,28,100]. an average residual cylinder of 4.63 D still remained giving an aver- In addition, Raizada and Sridhar [60] and Mahadevan et al. [90] age best-corrected acuity of 6/15 in 3 eyes with PMD. On the other have described step-by-step methods to help practitioners obtain hand, in deep anterior lamellar keratoplasty (DALK), the anterior a good fit with large diameter spherical RGP lenses using a minimal third (to two thirds) of the cornea is replaced with donor tissue number of trial lenses. [50]. To date, only Millar and Maloof [50] have described the suc- ‘Bi-toric’ RGP contact lenses have also been shown to be successful use of DALK in a PMD patient presenting with a sudden loss cessful in managing patients with PMD. Dominguez et al. [101], of vision due to spontaneous corneal perforation. The authors found Kastl and Kirby [102] and Gruenauer-Kloevekorn et al. [40] have that post-operative visual acuity remained stable at 6/6-2 even one described the successful correction of large amounts of corneal year after surgery. astigmatism using specialised back surface design lenses leading to Earlier techniques used in treating PMD include lamellar cres- good visual acuity. These authors all report satisfactory contact lens centic keratoplasty [109,110]. Biswas et al. [28] have also reported comfort and tolerance in patients wearing these specialised lenses, conducting lamellar thermo-keratoplasty (LTK), an adaptation of however no evaluation of the average or maximum wearing times the surgical technique described by Schanzlin et al. [109], for one was made in any of the three studies. eye with PMD. This procedure involved thermal shrinkage of the Liu et al. [64] describe the use of reverse-geometry lenses in host lamellar bed, prior to the placement and suturing of the a patient with early PMD to allow better peripheral lens align- crescent-shaped donor lamellar cornea. Biswas et al. [28] recorded ment where the cornea is steepest. However, such lenses may be a best-corrected visual acuity of 6/6 one year after surgery in spite most useful in patients with negative corneal eccentricities. PMD of6Dofresidual astigmatism. A. Jinabhai et al. / Contact Lens & Anterior Eye 34 (2011) 56–63 61

Table 2 A summary of the non-surgical and surgical methods used to manage pellucid marginal corneal degeneration.

Non-surgical methods Surgical methods

Spectacles [21,28,75] Penetrating keratoplasty [12,28,108] Soft lenses [11,20,90,103] Deep anterior lamellar keratoplasty [50] Large diameter RGP lenses [20,21,28,60,90,100] Lamellar crescentic keratoplasty [109,110] Hybrid lenses [91–95] Lamellar thermo-keratoplasty [28] Bi-toric RGP lenses [40,101,102] Lamellar crescentic resection [59,112,113] Scleral lenses [28,104–107] Corneal wedge excision [114–116] Epikeratoplasty [117] Tuck-in lamellar keratoplasty [118] Intra-stromal corneal segment rings [36,56,58,119,120,124–126] Collagen cross-linking [121,122] Toric phakic intra-ocular lens [129]

Kremer et al. [111] had previously suggested a two-staged sur- the treatment by utilising a single INTACS insert. Ertan and Bahadir gical procedure which firstly involves lamellar grafting followed by [33] used this method to treat a 26-year old patient with superior a smaller penetrating graft, with a view to avoid the complications PMD. associated with large eccentric grafts and to achieve a topograph- The technique of corneal collagen cross-linking consists of ically satisfactory corneal surface. Rasheed and Rabinowitz [61] the photo-polymerisation of the stromal collagen fibres by the describe using additional astigmatic keratotomy for some of their combined action of a photosensitising substance (riboflavin, vita- patients in order to reduce large amounts of residual astigmatism min B2) and ultra-violet light from a solid-state UVA source during the post-surgical follow-up period. [127]. Photo-polymerisation essentially increases the rigidity of Lamellar crescentic resection (LCR) has also been carried out for the corneal collagen and its resistance to ectasia. The procedure patients with PMD [59,112,113]. The primary aim of LCR is the exci- involves epithelial debridement using a blunt spatula, followed sion of the abnormally thinned stroma and then re-approximation by the application of topical riboflavin drops before beginning of the near-normal thickness edges. The major advantage to this 30 min of constant UVA irradiation. During the irradiation step, procedure is that no donor tissue is required. riboflavin drops are applied every 5 min. Spadea [121] and Kymio- Corneal wedge excision (also referred to as corneal wedge resec- nis et al. [122] have each described a case resulting in the successful tion) is similar to LCR except it involves full corneal thickness tissue improvement of best-corrected visual acuity in a patient with early removal followed by re-apposition of the remaining normal thick- PMD. Both groups of authors discuss that longer post-operative ness cornea using sutures [114–116]. Busin et al. [115] coupled follow-up is required to better understand the efficacy of CXL in corneal wedge resection with two bevelled, sutureless, penetrat- patients with PMD. At present the use of CXL has been studied in ing relaxing incisions (at the 3 o’clock and 9 o’clock positions) to more depth in patients with keratoconus [128]. improve long-term astigmatic stability in 10 eyes of 10 patients De Vries et al. [129] have reported the use of toric phakic intra- with PMD. ocular lens (TPIOL) implants in a patient with bilateral early-stage Other rarer forms of surgery indicated in PMD are epikerato- PMD which was less pronounced in the left eye. The TPIOL implants plasty. This is a form of on-lay lamellar keratoplasty in which a lens were fixed onto the anterior iris (at the 3 and 9 o’clock positions) made of human corneal tissue is sutured onto the anterior sur- through a superior corneo-scleral incision. The authors elected to face of the cornea to change its anterior curvature and refractive use this treatment as they could not rule out future increases in properties [117]. astigmatism owing to the progressive nature of the condition; the More recent and novel surgical techniques used to treat PMD implants used were removable should the patient’s prescription include “tuck-in” lamellar keratoplasty (TILK) [118], intra-stromal increase dramatically over time. These results suggest that TPIOL corneal segment ring (INTACS) inserts [36,56,58,119,120], and implantation can provide good acuity in the early stages of PMD. collagen cross-linking with riboflavin and UVA irradiation (CXL) The authors discuss that due to the reversible nature of this surgery [121,122]. patients may prefer to elect for this treatment over more perma- The procedure for INTACS implantation involves the incorpora- nent procedures such as a graft. tion of two semi-circular plastic rings into the peripheral corneal Table 2 summarises the non-surgical and surgical methods stroma through a small radial incision. INTACS essentially flatten available to manage PMD. the centre of the cornea from within the stroma using an “arc shortening” effect [123]. The procedure for placement of INTACS 6.3. Acute management inserts is performed outside the central visual axis, and INTACS inserts can be removed or replaced if the required outcome is not As mentioned earlier, acute hydrops with corneal oedema may achieved. In PMD, the ectatic corneal tissue has a thinner struc- develop in patients with PMD [43]. As in keratoconus [130], the ture and is potentially more easily flattened compared to in normal main cause of such an episode is a rupture in Descemet’s mem- eyes. INTACS inserts are useful in managing contact lens–intolerant brane [43,44], which may occur as the disease progresses. PMD patients with clear corneas and central thicknesses above 400 ␮m patients presenting with acute hydrops or corneal perforation as an attempt to delay or perhaps avoid corneal transplantation. may be treated using a number of strategies which include the Several authors have revealed successful outcomes after surgery application of glue tissue adhesive [51–54], bandage soft contact [36,56,58,119,120]. Mularoni et al. [58] carried out INTACS inser- lenses [48], crescentic lamellar keratoplasty [54], penetrating ker- tion in 8 eyes of 8 patients with varying degrees of PMD. The authors atoplasty [47,51] and finally deep anterior lamellar keratoplasty evaluated their patients for a minimum of 12 months after treat- [50]. ment and report an improvement in the average best-corrected visual acuity from 6/15 to 6/9 after surgery. Successful results have 7. Conclusion also been described by Akaishi et al. [124], Barbara et al. [125], Ertan and Bahadir [126] and Pinero et al. [120]. 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