Essential iris atrophy, Chandler's syndrome, and Cogan-Reese syndrome have in common a primary disorder of the corneal endothelium and together represent the iridocorneal endothelial (ICE) syndrome.1 The basic defect is a cellular proliferation of the endothelium which leads to an extension of a membrane across portions of the anterior chamber angle and anterior surface of the iris.1,2 Broad peripheral anterior synechiae often progress circumferentially and anterior to Senwalbe's line onto the periphery of the cornea.3
In essential iris atrophy, iris features predominate with marked correctopia, ectropion uvea, and slowly progressive atrophy leading to iris holes, nearly always associated with glaucoma.4·5 In the early stages, there is thinning of the iris stroma in the mid-periphery and eccentricity of the pupil progressing to full -thickness hole formation. Some holes may be caused by traction while others are thought to be ischemic in nature.6
Chandler's syndrome, a variant of essential iris atrophy, is characterized by the frequent presence of corneal endothelial cell decompensation which takes on a hammered silver appearance similar to Fuchs' dystrophy,7 In addition, corneal edema often occurs early and at pressures normal or only slightly elevated. Peripheral anterior synechiae are not as diffuse and do not extend as far anteriorly in Chandler's syndrome as in essential iris atrophy. The most significant factor distinguishing Chandler's syndrome from essential iris atrophy is the lack of iris hole formation and the absent or minimal iris distortion.7
Cogan-Reese syndrome is similar to essential iris atrophy although differentiated by pigmented lesions on the iris8 which often grow more numerous and darker with time.6 One type has characteristic fine, pedunculated nodules on the anterior surface of the iris, often occurring late in the course of the disease.9 The second type of iris lesion is a diffuse process which creates a matted appearance on the stroma of the iris with velvety, superficial whorl-like patterns and loss of iris crypts.10
In a series of 82 eyes with ICE syndrome, 44% required some type of surgery either for control of glaucoma, corneal edema, or both.11 As corneal edema and bullous keratopathy often occur early and at normal pressures in Chandler's syndrome patients, the eyes of these patients are most likely to initially require penetrating keratoplasty. Results of penetrating keratoplasty in ICE syndrome have been considered favorable based upon a study by Buxton and Lash in 1984. 12 They reported successful penetrating keratoplasty in five of five eyes with ICE with no evidence of recurrence of the corneal abnormalities. They concluded that penetrating keratoplasty is a relatively safe and effective procedure for eyes with diminished visual acuity secondary to corneal abnormalities in the ICE syndrome. The patients included in their study were four with Chandler's syndrome and one with essential iris atrophy.12 A study by Chang et al assessing the prognosis of corneal transplantation in ICE syndrome found the overall prognosis good with 75% of eyes achieving 20/40 visual acuity or better, although one corneal graft failed after immune rejection. Their 12 cases included 11 eyes with Chandler's and one with iris nevus; none had essential iris atrophy.13 A third study by Crawford et al found favorable clinical outcomes in six eyes with Chandler's syndrome and three eyes with essential iris atrophy.14 These past studies provide favorable results in penetrating keratoplasty in eyes with primarily the Chandler's syndrome variant of ICE syndrome, The three subcategories of ICE syndrome, however, progress in different ways and should be analyzed separately in terms of surgical results.
One notable characteristic that appears to be more prominent with essential iris atrophy than the other ICE syndrome variants is the presence of iridocyclitis. The presence of anterior uveitis11 and posterior uveitis10 has been described in patients with ICE syndrome. Harms, in his original description of ICE syndrome in 1913, raised the possibility of an inflammatory etiology for the endothelial abnormalities.15 Eagle et al described the presence of mild chronic iridocyclitis in 10 of 16 patients specifically with essential iris atrophy.1 More recently, Al varado et al evaluated eight keratoplasty specimens by electron microscopy and morphometry methods and found evidence for the presence of low-grade, long-standing chronic inflammation.16 In six of eight corneal buttons, an endotheliitis involving lymphocytes was present and it was determined that the endothelium tended to be most affected in eyes with essential iris atrophy.16
This increased tendency for inflammation in eyes with essential iris atrophy may have an impact on postoperative results, especially after penetrating keratoplasty. Anterior chamber inflammation which occurs after penetrating keratoplasty can be detrimental to graft survival. Documented results of penetrating keratoplasty in eyes specifically with essential iris atrophy are lacking, with only one study evaluating more than one case of this entity. We now provide a retrospective review of eyes with essential iris atrophy that underwent penetrating keratoplasty for corneal decompensation.
MATERIALS AND METHODS
All patients seen at the Eye and Ear Institute and the University of Pittsburgh with the diagnosis of ICE syndrome over the past 21 years (1971-1992) were reviewed. A total of six eyes with the diagnosis of essential iris atrophy had undergone penetrating keratoplasty for corneal decompensation. Classification of essential iris atrophy by Chandler and Grant includes 1) distortion and atrophy of the iris, 2) corneal edema caused by dystrophy of the corneal endothelium, and 3) peripheral anterior synechiae of the iris to the cornea at Schwalbe's line or anterior to Schwalbe's line.17 Standards adopted by Shields et al were that the eyes must have two of the three above criteria to be given the diagnosis of essential iris atrophy.11 All eyes included in this study adhered to the classification scheme set up by Shields et al and also were nonfamilial, unilateral, progressive, and had no history of trauma to the involved eye. In addition to better differentiate eyes with essential iris atrophy from Chandler's syndrome, all eyes included in this study were required to have a history of marked iris distortion and in fact all six eyes eventually developed full thickness iris hole formation.
Because the cases spanned a period of 21 years, the operative and postoperative regimen was not uniform for all eyes. The usual postoperative corticosteroid course involved topical corticosteroid drops initially every 1 hour while awake tapered to four times a day by 2 weeks postoperatively and then a gradual taper to once a day by 3 to 4 months postoperatively.
Case 1. A 60-year-old white female with essential iris atrophy in the left eye, diagnosed in 1966, was referred for evaluation of bullous keratopathy in the left eye in December 1985. She had a history of cyclocry other apy in the left eye in 1974 and since this time, intraocular pressures (IOPs) have been stable in the mid-teens. On examination, her visual acuity was 20/20 in the right eye and count fingers in the left eye. The left cornea had diffuse scarring and bullous keratopathy. There was endothelial pigment, iris atrophy, and trace nuclear sclerosis in the left eye. IOP by applanation tonometry was 15 mm Hg in the right eye and 6 mm Hg in the left eye. A penetrating keratoplasty in the left eye was performed in May 1986. Three months later, she developed severe iritis in the left eye with keratoprecipitates. Despite aggressive oral and topical corticosteroids, a Khodadoust line developed and she went on to graft failure by September 1986. A repeat penetrating keratoplasty in the left eye was performed in January 1987. Seven months later, an anterior uveitis and graft reaction were controlled with topical corticosteroids. She had an extracapsular cataract extraction in the left eye with posterior chamber intraocular lens implantation in February 1988. A persistent low grade anterior uveitis occurred postoperatively. Graft reactions occurred in the left eye in June 1990 and December 1990 with continued recalcitrant iritis in the left eye. This second graft failed by February 1991.
Case 2. A 78-year-old female was diagnosed with essential iris atrophy in the left eye after presenting with pupillary distortion and iris atrophy in 1983. Corneal decompensation and recurrent erosions in the left eye occurred in July 1988. On examination, her visual acuity was 20/30 in the right eye and 20/400 in the left eye. Examination of the right eye was unremarkable. The leñ cornea had an irregular epithelium with multiple bullae present, a ground glass appearance to the stroma, and multiple Descemets folds. There were multiple broad peripheral anterior synechiae present. The iris was atrophic with multiple holes, and the pupil was irregular, displaced, and peaked superiorly. The lens had 2 + nuclear sclerosis and there were rare cells in the anterior chamber of the left eye. IOP by applanation tonometry was 20 mm Hg in both eyes. In November 1988, the patient had a penetrating keratoplasty, extracapsular cataract extraction, and insertion of posterior chamber intraocular lens in the left eye. Until December 1990, the graft remained thin and clear. At this time, however, persistent low grade cell and flare of the left anterior chamber were present and a graft reaction occurred in May 1991. By June 1991, there had been no evidence of rejection.
Case 3. A 56-year-old male presented, who first noticed an abnormal pupil of his right eye in 1966. He was diagnosed with essential iris atrophy in the left eye in 1976. IOP was elevated in 1981 as high as 40 mm Hg despite maximal medications. He underwent a trabeculectomy in the left eye in February 1981. In 1983, he had cataract extraction in the left eye without intraocular lens implantation. The patient was referred to the cornea service at the Eye and Ear Institute in February 1986. On examination, his visual acuity was count fingers at one foot inthe right eye and 20/20 -1 in the left eye. The right conjunctiva was 3-4+ injected. There was a flat bleb superiorly in the right eye. Diffuse corneal stromal and epithelial edema was present with multiple bullae in the right eye. The right pupil was eccentric with pseudopolycoria present. Iris atrophy was present in the right eye. Broad iridocorneal peripheral anterior synechiae were present. The left eye was normal. IOP was controlled in low teens in the right eye medically. He underwent penetrating keratoplasty and anterior vitrectomy for aphakic bullous keratopathy in May 1986. Six months later, his best visual acuity on pinhole examination was 20/200. Shortly thereafter, his IOP increased to approximately 30 mm Hg in the right eye on maximal medications, with progressive synechiae formation. He underwent cyclocryotherapy to the right ciliary body in January 1987. Subsequently, he had persistent moderate iritis in the right eye and slow failure of his graft. He underwent repeat penetrating keratoplasty in the right eye in November 1987. Three months later, he was refracted to 20/60 in the right eye and his IOP was well controlled in the teens. Continued anterior chamber flare was present in the right eye. The patient was last seen in April 1989, doing well, without signs of graft reaction.
Case 4. A 59-year-old female presented, who was found to have an IOP of 58 in the left eye on routine exam in October 1980. She was referred to the glaucoma service at the Eye and Ear Institute for elevated IOP in the left eye despite maximal medical therapy. On examination, she had extensive peripheral anterior synechiae in the left eye. Her left iris was remarkable for anterior stromal atrophy, two iris holes, and an irregular pupil with correctopia. The cornea had diffuse bullous keratopathy. IOP by applanation tonometry was 17 mm Hg in the left eye and 54 mm Hg in the right eye. She was diagnosed with essential iris atrophy in the left eye. Control of IOP necessitated a trabeculectomy in the left eye in 1981 and a trephine procedure in the left eye 1 year later. Iris hole formation continued to progress in the left eye. In April 1989, she underwent a penetrating keratoplasty by her local ophthalmologist and initially had a clear graft postoperatively. She was later referred to the cornea service at the Eye and Ear Institute in September 1990 for graft reaction. On examination, her visual acuity was hand motion in the left eye and her IOP in the left eye was 40 mm Hg. Her left cornea was hazy and edematous with pigmented cells on the endothelial surface and a corneal thickness by pachometry of 0.79 centrally. There was a Khodadoust line present inferiorly. Her anterior chamber was quiet. In October 1990, she had diffuse microcystic edema of the cornea in the left eye.
Case 5. A 56-year-old male was referred to the corneal service in October 1986 for evaluation of left iris atrophy and corneal decompensation. On examination, his visual acuity was 20/25 in the right eye and 20/200 in the left eye with improvement to 20/50 + 1 on pinhole examination. The right eye was within normal limits. The left eye had a large iris hole nasally and multiple areas of iris atrophy. The pupil was distorted and displaced temporally. Broad peripheral anterior synechiae and cystic corneal epithelial edema were present in the left eye. IOP by applanation tonometry was 14 mm Hg in the right eye and 13 mm Hg in the left eye. He was given a diagnosis of essential iris atrophy. He underwent penetrating keratoplasty in the left eye in October 1987 for corneal decompensation. His visual acuity at the time was count fingers at 2 to 3 feet in the left eye. Two weeks after penetrating keratoplasty, he had a best spectacle-corrected visual acuity of 20/ 100. He had a persistent low grade inflammation in his anterior chamber in the left eye after penetrating keratoplasty. In October 1988, he developed a graft reaction in the left eye. This was treated aggressively with topical corticosteroids and resolved in November 1988. In January 1989, he underwent extracapsular cataract extraction with posterior chamber intraocular lens placement in the left eye. In February 1989, his left corneal graft failed. In May 1989, he underwent repeat penetrating keratoplasty in the left eye with iridoplasty. His visual acuity subsequently improved to 20/100. In November 1989, a graft reaction occurred in the left eye and despite aggressive treatment, the graft failed in January 1991. During this period, his IOP remained in the mid-upper teens with medical treatment.
Case 6. A 78-year-old male with a diagnosis of essential iris atrophy and secondary glaucoma of his right eye since 1981 underwent a trabeculectomy in the right eye in 1983 to control elevated IOP. In April 1986, he had an extracapsular cataract extraction with posterior chamber intraocular lens placement in the right eye. In March 1988, he had a vitrectomy and anterior chamber tap in the right eye for presumed endophthalmitis; however, the cultures were sterile. He was referred to the cornea service in April 1988 for bullous keratopathy in the right eye. On examination, his visual acuity was count fingers at 6 inches in the right eye and 20/20 in the left eye. Corneal epithelial and stromal edema with bullous changes were present in the right eye. Broad peripheral anterior synechiae anterior to Schwalbe's line were present in the right eye. The right iris had numerous holes. The left eye was unremarkable. Secondary to elevated IOP in the right eye despite maximal medical therapy in May 1988, he had YAG laser cyclodestruction treatment to his ciliary body in the right eye. In September 1988, his visual acuity was count fingers at one foot in the right eye and he underwent penetrating keratoplasty for corneal decompensation in the right eye. Postoperatively, his best achieved visual acuity was 20/80 +2 in the right eye in January 1989. Persistent low grade cell and flare was present. Graft rejection was first noted in October 1989 and the graft failed by April 1990. During this period, his IOP was well controlled in the 8 to 22 mm Hg range.
All six eyes with essential iris atrophy had evidence of persistent low grade to moderate anterior uveitis with one or more episodes of graft reaction after penetrating keratoplasty. In fact, five of the six eyes ultimately went on to graft failure. In the one case that had not rejected, there had been episodes of graft reaction. Two of the six eyes rejected grafts on two separate occasions. In most of the eyes, the persistent anterior uveitis was resistant to intense topical, periocular, and oral corticosteroid treatment.
This iridocyclitis which was found to be prominent postoperatively has been described to be associated with eyes with the ICE syndrome.10-11-15,16 It has been postulated that the inflammatory reaction may be secondary to an autoimmune response, a reaction specific to corneal endothelium, a response to viral antigen, or a nonspecific inflammatory response.16-18 It is well known that an inflammatory process can lead to decompensation of graft endothelium19 and this detrimental effect of ocular inflammation on graft endothelium has been demonstrated experimentally by Polack on homologous corneal transplants in rabbits.20 In addition to the directly detrimental effect of iridocyclitis to the corneal endothelium, there is an increased chance of immune rejection. Primary immunogenic uveitis has been shown to induce expression of class II alloantigen on rabbit corneal endothelium which may predispose the graft to immunogenic rejection or may amplify a rejection episode.21,22
One limitation of this study is its retrospective nature. Due to the relatively low incidence of essential iris atrophy, a prospective study would be difficult if not impossible. Another limitation of this study is the inability to confirm that the anterior chamber cellular reaction observed postoperatively represented a true iridocyclitis rather than simply a pigment dispersion syndrome. Pigmentary cells that are released during intraocular surgery, however, often decrease to preoperative levels by 2 weeks postoperatively as demonstrated by the fiare celi meter.23 The fact that cells were present for extended periods and were accompanied by anterior chamber flare in all six eyes leads to the conclusion that a true inflammatory reaction was observed rather than uveal release of pigment.
Past studies have demonstrated that mild chronic iridocyclitis is a feature in ICE syndrome and particularly with essential iris atrophy. Iridocyclitis is known to be detrimental to graft survival after penetrating keratoplasty. Indeed in this retrospective study, we have found an increased incidence of chronic low grade iridocyclitis after penetrating keratoplasty in eyes with essential iris atrophy and a corresponding high rate of graft rejection.
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