Recurrent Corneal Erosion Syndrome

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<p>SURVEY OF OPHTHALMOLOGY</p> <p>VOLUME 53 NUMBER 1 JANUARYFEBRUARY 2008</p> <p>MAJOR REVIEW</p> <p>Recurrent Corneal Erosion SyndromeSujata Das, MS, FRCS (Glasg.),1 and Berthold Seitz, MD, FEBO21</p> <p>Bhubaneswar Eye Institute, Bhubaneswar, Orissa, India; and 2Universita tsklinikum des Saarlandes, Klinik fu r Augenheilkunde, Homburg/Saar, GermanyAbstract. Recurrent corneal erosion syndrome is a chronic relapsing disease of the corneal epithelium characterized by repeated episodes of sudden onset of pain usually at night or upon rst awakening, accompanied by redness, photophobia, and watering of the eyes. Individual episodes may vary in severity and duration. These symptoms are related to corneal deepithelialization in an area in which the epithelium is weakly adhered. It is a frustrating disorder for both the patient and the physician. In the majority of cases, the acute episode is managed by patching, and cycloplegic and topical antibiotic ointment, with prophylactic application of gels during daytime and ointment at night to prevent further erosion. In a minority of cases these measures are insufcient and may need alternative treatment modalities including therapeutic contact lens wear, anterior stromal puncture, supercial keratectomy, Nd:YAG, and most effectively, excimer laser therapy (phototherapeutic keratectomy). (Surv Ophthalmol 53:3--15, 2008. 2008 Elsevier Inc. All rights reserved.) Key words. anterior stromal puncture excimer laser ablation keratectomy recurrent corneal erosion supercial keratectomy</p> <p>phototherapeutic</p> <p>I. HistoryRecurrent corneal erosion syndrome (RCES) has been recognized as a disease entity for over 100 years. It is a chronic relapsing disease of the corneal epithelium characterized by repeated episodes of sudden onset of pain usually at night or upon rst awakening, accompanied by redness, photophobia and watering of the eyes. The rst report was published in 1872 by Hansen.36 He termed the disease as intermittent neuralgic vesicular keratitis. Von Arlt published about the same phenomenon two years later.99 Both recognized antecedent trauma. Szili in 1900 reported epithelial irregularities and gray dots associated with recurrent erosion.91 Vogt in 1921 described ne white dots on Bowmans layer, uorescein staining lines, and an irregular epithelial surface with localised edema using a slit-lamp.98 Stood in 1901 suggested that3 2008 by Elsevier Inc. All rights reserved.</p> <p>trauma to the corneal epithelium and anterior stroma resulted in an inability of the new epithelium to form normal attachments to the injured anterior Bowmans layer.87</p> <p>II. Epidemiology and Clinical FeaturesBrown and Bron published a case series of 80 patients with RCES in an age range of 24--73 years (highest prevalence between the third and fourth decade).7 Mean age at the time of presentation was 42 years with a slight male predominance (56%). Microform erosions were seen in 56% of cases. The female patients with history of trauma were mostly due to scratches from a babys nger. They found that microform erosions were most common in the spontaneous cases, whereas macroform and combined microform and macroform variants were most</p> <p>0039-6257/08/$--see front matter doi:10.1016/j.survophthal.2007.10.011</p> <p>4</p> <p>Surv Ophthalmol 53 (1) January--February 2008</p> <p>DAS AND SEITZ</p> <p>commonly of traumatic origin. The interval between rst recurrence and initial abrasion varied from 2 days to 16 years. Family history suggesting dominant inheritance was found only in 3% of cases. In 10% of cases the disease appeared bilaterally. The frequency of recurrences varied considerably and ranged from minor recurrences each morning to major recurrences separated by months. Recurrences lasted from one to four hours in microform lesions and from 1--21 days in macroform lesions. Pain was the most common symptom followed by watering of the eye and blurred vision. Common site of erosion was central just below the pupil. Supercial corneal dystrophy was found in 78% of patients between 51 and 60 years of age. Intraepithelial microcysts were a common nding in healed corneas being present in 59% of eyes. Franceschetti described a familial type of recurrent erosion with an autosomal dominant inheritance pattern.25 Laibson and Krachmer reported familial occurrence of recurrent erosion associated with dot-map ngerprint dystrophy of the cornea.55 Wood has included 25 eyes of 22 patients with RCES for microdiathermy treatment.104 There were 16 women and 6 men with an age range between 26 and 66 years and a mean age of 44 years. History of injury was present in 18 eyes. Fingernail injury was common. Ten eyes with injury developed RCES within six months and the residual eight eyes developed RCES between 1 and 15 years after trauma. Hope-Ross et al had evaluated 30 patients with recalcitrant corneal erosion with an age range of 27 to 77 years, and a mean age of 45 years.43 Women were more (57%) commonly involved than men (43%). Combinations of macro- and microform erosion were most common (77%). Fingernail injury was the most common cause (16%) of initial corneal abrasion. Positive family history was present in two patients. Tiredness, menopause, menstruation, and alcohol were recognized to be aggravating factors. Of the 17 women in the study, 41% identied hormonal events such as menstruation, pregnancy, and menopause. Tear lm debris and reduced tear break-up time were found in all cases. Microcysts were the most common abnormality in patients. Fifty-six percent of patients suffered sharp pain accompanied by lacrimation on waking up. Seventeen percent of patients suffered only during night-time and awoke from sleep due to pain in the eye. Hykin et al presented a series of 117 patients with a history of RCES with a mean age of 38 years (range 14 to 80 years).44 Seventy-ve cases had a history of shallow corneal injury, 23 cases had epithelial basement membrane dystrophy (EBMD), and eight</p> <p>had both. They concluded patients with EBMD or a trauma-related focal epithelial basement membrane abnormality were more likely to present with chronic recurrent symptoms than trauma-related cases with no abnormality. Heyworth et al did a fouryear review for the same cohort of patients and found traumatic etiology to be less likely to suffer chronic recurrent erosion syndrome than those with EBMD.38 Riedy et al did a retrospective review of 104 patients (68 women, 36 men) with a mean age of 43 years.77 History of trauma was present in 45% of patients, 29% had EBMD, and 17% had both. More than 87% of erosions occurred in the inferior third of the cornea. Williams and Buckley found that 35% cases with RCES due to map-dot-nger print dystrophy had a Hudson-Sta hli line in the affected segment. In contrast, RCES of traumatic origin did not demonstrate such a predominant localisation.100</p> <p>III. Etiology and PathogenesisCogan believed that in his patients with bullous keratopathy, hypotonicity of the tears allowed the corneal epithelium to become more edematous at nights, causing it to worsen.12 Chandler also thought that this mechanism would explain the predominant occurrence of erosions in the morning.11 Recurrent corneal erosion syndrome may be either primary or secondary, depending on whether the defect in the epithelial basement membrane is intrinsic or acquired (Table 1). In the majority of patients with RCES, trauma is the initiating factor, especially trauma from a scratch that damages or destroys the corneal basement membrane. Primary dystrophic disorder is further classied according to the predominant location of the dystrophy within the cornea. EBMD is a frequent cause of RCES. Epithelial basement membrane dystrophy includes entities such as Cogans microcystic dystrophy (map-dot ngerprint dystrophy) and so-called nontraumatic recurrent erosion.105 The other causes may be due to Reis-Bu cklers, lattice, as well as macular and granular dystrophy. Secondary causes that may lead to RCES include chemical and thermal injuries, previous herpetic keratitis, meibomian gland dysfunction,43 ocular rosacea,1 diabetes mellitus, Salzmanns nodular degeneration,103 band keratopathy, previous bacterial ulceration, keratoconjuctivitis sicca, and epidermolysis bullosa. Typically microform erosions occur with spontaneous attacks associated with EBMD whereas macroform erosions are associated with traumatic etiology. Some individuals in families with lattice dystrophy</p> <p>RECURRENT CORNEAL EROSION SYNDROME TABLE 1</p> <p>5</p> <p>Classication of Etiology of RCES(A) PRIMARY (1) Epithelial basement membrane dystrophy (i) Cogans microcystic (map-dot-nger) dystrophy (2) Dystrophy involving Bowmans layer (i) Reis-Bu cklers dystrophy (ii) Thiel-Behnke dystrophy (3) Stromal dystrophy (i) Lattice dystrophy (ii) Macular dystrophy (iii) Granular dystrophy (4) Endothelial dystrophy (B) SECONDARY (1) Degeneration (i) Band keratopathy (ii) Salzmanns nodular degeneration (2) Trauma (i) Traumatic epithelial abrasions (ii) Chemical and thermal injury (3) Eyelid pathology (i) Entropion (ii) Ectropion (iii) Floppy eyelid (iv) Lagophthalmus (v) Meibomian gland dysfunction (vi) Blepharitis (4) Following ocular infection (i) Bacterial keratitis (ii) Viral keratitis (5) Following refractive surgery (i) Laser in situ keratomileusis (ii) Photo-refractive keratectomy (RCES rare) (6) Systemic causes (i) Diabetes mellitus (ii) Epidermolysis bullosa (iii) Juvenile X-linked Alports syndrome (7) Miscellaneous (i) Keratoconjuctivitis sicca (ii) Bullous keratopathy (iii) Idiopathic (iv) Mu nchhausen syndrome</p> <p>manifest recurrent epithelial erosions without clinically identiable stromal involvement. In the absence of epithelial erosions, the dystrophic lesions affect vision minimally. Nocturnal lagophthalmos has been reported to be associated with RCES.88 It is believed that damage to supercial squamous cells of the epithelium due to corneal exposure is responsible for RCES. It is hypothesized that saccades during early morning REM (rapid eye movement) sleep phase intensify the condition of nutritionally decient cornea during night, especially in the case of previously damaged corneal epithelium in conjunction with corneal dystrophy or microtraumas.40 Association of RCES with juvenile X-linked Alport syndrome has been reported. A survey among 39 patients with Alport syndrome revealed that six of</p> <p>them had suffered from RCES.84 One case of RCES was reported to be due to self-inicted injury (Mu nchhausen syndrome).92 Removal of corneal epithelium during vitrectomy is one of the causes of RCES. Recurrent corneal erosion syndrome has been reported after laser refractive surgery. It may rarely occur after photorefractive keratectomy (PRK)75 and following laser in situ keratomileusis (LASIK). Typically, after PRK, as after phototherapeutic keratectomy (PTK), the epithelium adheres even stronger than before the laser treatment. After LASIK RCES may be due to corneal neuropathy that occurs after cutting the ap in addition to the epithelial manipulation at the edge of the ap. Sometimes undiagnosed EBMD may have been present before LASIK. LASIK can induce or precipitate RCES;95 thus, it seems to be important to minimize epithelial damage during LASIK to prevent RCES afterwards. The ultrastructural changes which reduce adhesion of the corneal epithelium include a decient epithelial basement membrane, the absence and abnormality of hemidesmosome, and the loss of anchoring brils. The importance of the anchoring system in maintaining epithelial adhesion has long been established and a defective anchoring system has been incriminated in recurrent corneal erosion and other anterior basement membrane disorders.53 The anomalous production of basement membrane and connective tissue material within and under the corneal epithelium can disrupt the attachment. Abnormal deposition of normal basement membrane is believed to be one of the pathogenetic roles of RCES. A possible cause for the pathologic changes observed in RCES is degradation of the epithelial attachment complexes by matrix degrading enzymes. Increased level or activity of several members of the matrix metalloproteinase (MMP) enzyme family, including MMP-2 and MMP-9 have been reported in patients with recurrent erosion.1,29 MMP-2 expression is upregulated in human epithelium with RCES compared to normal control samples. Immunolocalization studies suggest that MMP-2 is concentrated in basal epithelial cells where it may play an important role in degradation of the epithelial anchoring system and recurrent epithelial slippage and erosion.29 The apparent cause of RCES is failure of epithelial cells to regain tight adhesive contacts to the underlying corneal stroma after trauma in EBMD; it is the failure of the epithelial cells to maintain tight adhesion to a defective basement membrane. Cell adhesion molecules of the integrin family are in large part responsible for the adhesion of the corneal epithelium to the stroma. A mouse</p> <p>6</p> <p>Surv Ophthalmol 53 (1) January--February 2008</p> <p>DAS AND SEITZ</p> <p>model for the study of RCES has implicated role of a-9 b-1 integrin in progression of the disease.74</p> <p>of the epithelial cell membrane. Normal and degenerated polymorphonuclear leucocytes were found within and between the epithelial cells and within the anchoring layer.</p> <p>IV. HistopathologyGoldman et al described the rst electron microscopic study of post traumatic recurrent erosion.34 In this study, segmental absence of hemidesmosomes and basement membrane was demonstrated. The normal columnar basal epithelial cells were attened adjacent to the defective basement membrane. Intercellular edema was seen at all levels of the epithelium. Tripathy and Bron found that the epithelium was extremely thickened and pale, secondary to intercellular and intracellular edema using light and electron microscopy in a case of bilateral socalled nontraumatic recurrent erosion.96 Electron microscopic examination of the pale cells demonstrated desmosomal attachments with decreased intercellular digitations and intercellular clefts. In addition, hemidesmosomes were reduced or absent in the area of pale epithelial cells. Fogle et al found subepithelial brocytic cells and brillogranular material in so-called nontraumatic recurrent erosion.21 They also demonstrated intraepithelial extension of redundant basement membrane. Basement membrane complexes were frequently discontinuous and a decreased number of anchoring brils was noted. Kenyon et al described three categories of ultrastructural abnormalities in eyes with RCES52 (Kenyon et al, Invest Ophthalmol Vis Sci [Suppl] 21:39, 1981). First, in diabetic patients and patients with map-dot-ngerprint changes, multilaminar basement membranes were found attached to the basal epithelial cells. Secondly, posttraumatic recurrent erosion was characterized by basal cell rupture, absence of basement membrane adherent to the epithelium, and segmental appearance of new baseme...</p>