Alex P. Hunyor, MB,
B.S. Franzco, FRACS,
C. Davis Belcher III, MD
Contents
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Epithelial Invasion |
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CHAPTER HIGHLIGHTS |
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Options in managing epithelial cysts and sheets
Epithelial and fibrous invasions into the anterior chamber have long been recognized as complications of cataract surgery, other anterior segment surgery, and trauma. These conditions, particularly the former, continue to pose a significant diagnostic and management problem for ophthalmic surgeons, despite their decreasing incidence resulting from advances in surgical technique.
Epithelial invasion
Historical perspective
In 1830 Mackenzie[1] described the occurrence of a posttraumatic iris inclusion cyst. Rothmund[2] in 1872 reported a study of 37 cases of epithelial cysts of the anterior chamber, with two occurring after cataract extraction and the remainder following trauma. He proposed that these cysts resulted from implantation of epithelium at the time of trauma or surgery. Collins and Cross[3] in 1892 demonstrated histopathologically the presence of epithelium in the anterior chamber in two cases of epithelial implantation cyst after cataract extraction. The work of Guaita[4] and Meller[5] emphasized poor wound healing in allowing entry of epithelial cells. Perera[6] in 1937 reviewed numerous reports, differentiating cystic epithelial lesions from sheetlike epithelial ingrowth, noting the importance of incarceration of iris or lens capsule and of hypotony in favoring epithelial invasion. He proposed a classification of epithelial invasion into (1) “pearl” tumors of the iris, (2) epithelial (inclusion) cysts of the iris, and (3) epithelialization (also referred to as epithelial ingrowth or downgrowth) of the anterior chamber. This classification remains useful in differentiating these three entities with related etiologies but clearly different clinical course, treatment and outcome.
Pearl tumors
Pearl tumors (pearl cysts) are rare, opaque, cystic or solid “pearly” lesions that usually occur after trauma but have been described after intraocular surgery.[7] They result from traumatic implantation of skin or hair follicles into the anterior chamber and usually form a small, circumscribed lesion that is not connected with the entry site and confined to the iris (Figure 53-1). These lesions grow slowly and rarely exceed 2–3mm in diameter. Histologically, they are encapsulated structures of cuboidal or stratified epithelial cells with a central mass of keratinized cells, cholesterol crystals, and necrotic debris; hair follicles and foreign bodies have also been found. In the uncommon instances that these cysts significantly enlarge or cause iridocyclitis, en bloc excision usually yields good results.
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Figure 53-1 “Pearl” tumor of the iris. |
Epithelial inclusion cysts
Of the two major forms of epithelial invasion resulting from implantation of surface epithelium into the anterior chamber, epithelial inclusion (or implantation) cysts tend to follow a more benign, although quite variable, clinical course.
Incidence
There are no figures for the incidence of epithelial cyst as a separate entity. The overall incidence of cystic and sheetlike epithelial invasion after accidental and surgical penetration of the anterior segment has been estimated in early studies[8,][9] at 0.06–0.11%, and cysts are considered the more common form.
Predisposing factors and pathogenesis
Epithelial inclusion cysts have been reported after cataract extraction, penetrating keratoplasty, and other forms of surgery and trauma to the anterior segment, as summarized by Farmer and Kalina.[10] In cases following cataract surgery, there is usually evidence of poor wound closure, often with incarcerated iris, lens matter, or vitreous. Rarely, cysts are discontinuous with the wound from their onset and are presumably due to implantation of surface epithelium by intraocular instruments, as discussed by Ferry.[11] Experimental evidence[12,][13] points to contact with the iris and exposure to plasmoid aqueous (containing proliferative factors) as determinants of the development and size of epithelial cysts.
The factors regulating development of implanted or ingrowing epithelial cells into cysts, as opposed to sheetlike ingrowths, are unclear. The number of cells, initial morphology of the ingrowth (a bilayer or loop as opposed to a single layer), degree of attachment to iris and angle structures, vascular supply, and duration of exposure to plasmoid aqueous (a longer exposure favoring progressive sheetlike ingrowth) may all play a role. As discussed later on, in some cases epithelial cysts may be converted into sheetlike downgrowth if treated with surgery or laser.
Presentation, clinical features, and diagnosis
Cysts may remain quiescent for many years before enlarging and/or causing symptoms. Patients may seek treatment because of recognition or noticeable enlargement of an otherwise asymptomatic lesion, visual symptoms caused by extension into the visual axis, or symptoms of intraocular inflammation and secondary glaucoma that may accompany periods of cyst growth.
Epithelial inclusion cysts are typically translucent or gray in appearance and usually are associated with the anterior surface of the peripheral iris. There may be displacement of an iris pillar or distortion of the pupil (Figure 53-2). Cysts may grow through an iridotomy or peripheral iridectomy into the posterior chamber and appear to arise from the iris itself. For a review of the differential diagnosis of cystic lesions of the iris, see Shields, Sanborn, and Augsburger.[14] Signs of anterior uveitis, sometimes with secondary glaucoma, may be present. Sympathetic ophthalmia associated with secondary glaucoma from cystic epithelial invasion of the anterior chamber has been reported,[15] as has mucogenic open-angle glaucoma resulting from a goblet cell cyst of the anterior chamber.[16] Subluxation of an anterior chamber intraocular lens (IOL) by a large epithelial cyst has also been noted.[17]Massive enlargement of cysts may cause corneal decompensation by extensive contact with the corneal endothelium.
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Figure 53-2 Epithelial inclusion cyst of the anterior chamber. |
The diagnosis of epithelial inclusion cyst is suggested by the history or signs of surgery or trauma; contact with the surgical or traumatic wound; characteristics of cystic lesions such as transillumination, occasionally mobility, and tremulousness; scant pigmentation; lack of vascularity; superficial relationship to the iris; and signs of associated uveitis.
Histopathologic features
Cysts are typically thin-walled structures lined with squamous or cuboidal epithelium, sometimes including goblet cells (Figure 53-3). Electron microscopic studies[18] demonstrate epithelial cells with a thin basal lamina, desmosomal junctions, cytoplasmic filaments, scant mitochondria, terminal bars, and apical microvilli, characteristic of ocular surface epithelium, most likely conjunctival. They contain straw-colored, turbid, or mucinous fluid. There may be pigmentation, particularly of the posterior portion of the cyst. Often there is evidence of contact between the cyst and the traumatic or surgical wound, which may be lost later in its development.
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Figure 53-3 Light microscopy of an epithelial inclusion cyst, showing a clear lumen lined by nonkeratinized squamous epithelium. (Hematoxylin and eosin stain; ×40.) |
Management
Although some authors have advocated early surgical intervention for epithelial cysts, they follow a highly variable clinical course (from spontaneous regression[19] to rapid growth), and there is a well-established risk of conversion to sheetlike epithelial downgrowth after surgery and laser treatment. There is general agreement that the most appropriate management includes periodic observation at 3–4-month intervals with serial anterior segment photography and prompt intervention in cases in which vision is impaired by encroachment on the visual axis, uveitis, glaucoma, or corneal edema.
Various treatment modalities have been employed, including needle aspiration, injection with radioactive and sclerosing substances, diathermy, cryotherapy, electrolysis, radiotherapy, photocoagulation, numerous surgical approaches, and combinations of the preceding methods. In the absence of any large series, comparison of the efficacy of these techniques is difficult. The management of epithelial cysts of the anterior chamber remains a difficult balance between the need for elimination of the cyst with low risk of recurrence and minimization of complications of the treatment itself. As yet, no single treatment modality has provided this combination.
Radiotherapy, despite the initial enthusiasm of Perera[6] and others, has been abandoned because of variable results and lack of safety. Diathermy coagulation[20,][21] has largely been supplanted by laser photocoagulation.
Ferry and Naghdi[22] successfully treated a large cyst by insertion of a cryostylet into the cyst (via a needle puncture), freezing it to −10° to 0 ° F for 15s, and exteriorization and excision of the cyst and adherent iris tissue. Cyst aspirations with injection of astatine,[23] iodine,[24] and other sclerosing agents have also been reported, with varying degrees of success and safety. Cyst aspiration with laser photocoagulation and/or cryotherapy, and surgical techniques, are the mainstay of current therapy and will be discussed in more detail.
Current techniques
For small unpigmented cysts, aspiration followed by cryotherapy to the collapsed cyst is the authors' preferred treatment. For unpigmented cysts too large for cryotherapy and for all pigmented cysts, aspiration followed by argon laser photocoagulation is favored. Large unpigmented cysts, if fully aspirated and collapsed against the iris with the technique to be described, are usually successfully photocoagulated using the heat sink effect of the underlying iris pigment.
Aspiration and photocoagulation
Meyer-Schwickerath,[25] Okun and Mandell,[26] and others have described treatment of epithelial cysts with xenon arc photocoagulation. Multiple treatments were required, and cysts were collapsed and fibrosed, preventing further growth. In 1975 L'Esperance and James[27] first described successful treatment of epithelial cysts by argon laser photocoagulation. The authors' preferred method of treatment for pigmented epithelial inclusion cysts and larger unpigmented cysts is argon laser photocoagulation, with a technique similar to that described by Thomas, Lederer, and Simmons,[28] as outlined next.
In a minor operating room under topical anesthesia (or peribulbar anesthesia in less cooperative patients), the affected eye is prepared as for cataract surgery with skin sterilization and draping, and a lid speculum is inserted. A first paracentesis through clear cornea is performed well away from the cyst with an angled 15° disposable blade (Figure 53-4). The second paracentesis is made into the cyst at its base, via its attachment to the anterior chamber angle where present (Figure 53-5), avoiding cyst puncture within the anterior chamber, which can potentially increase the risk of conversion to sheetlike ingrowth.
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Figure 53-4 Initial anterior chamber paracentesis is performed well away from the cyst. |
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Figure 53-5 Second paracentesis enters the base of the cyst, avoiding cyst puncture that communicates with the anterior chamber. |
A 27-gauge intraocular cannula attached to a syringe is inserted into the cyst cavity via the second paracentesis, and the cyst contents are aspirated to collapse the cyst (Figure 53-6). Cytologic examination of the aspirated fluid (for epithelial cells) may be performed. The anterior chamber is re-formed with air, which promotes the collapse of the cyst against its posterior wall (Figure 53-7). Blunt dissection of the anterior cyst wall from the posterior cornea, with a spatula inserted via the first paracentesis, may also be required (Figure 53-8). Physiologic saline solution is then exchanged for the air in the anterior chamber. Routine postoperative topical antibiotics are instilled in the eye.
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Figure 53-6 Cyst contents are aspirated with a 27-gauge intraocular cannula. |
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Figure 53-7 Anterior chamber is re-formed with air, promoting cyst collapse against the iris. |
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Figure 53-8 Blunt dissection of the cyst wall from the posterior cornea may be performed via the first paracentesis. |
The patient is then taken to the argon laser, and with a sterile Goldmann 3-mirror contact lens the cyst is treated with a spot size of 200μm, duration of 0.2s, and power increasing from 200–1000mW, as high as required to photocoagulate all visible epithelial tissue. Cyst epithelium extending into the angle of the anterior chamber should also be eradicated using the semicircular mirror of the Goldmann lens. Cycloplegic drops are instilled postoperatively, but topical steroids are generally avoided because the ensuing inflammatory response assists in fibrosis and contraction of cyst remnants. Further photocoagulation may be required if follow-up examination shows significant residual epithelial tissue. Cryotherapy to angle structures can also be used as an adjunct to photocoagulation. Figure 53-9 shows the appearance of the inclusion cyst in Figure 53-2 following the photocoagulation treatment described.
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Figure 53-9 Appearance of the cyst from Figure 53-2 following aspiration and photocoagulation. |
L'Esperance and James[27] reported shrinkage and disappearance of four cysts over a 6-week period following argon laser photocoagulation (without prior aspiration). Scholz and Kelly[29] and Sugar, Jampol, and Goldberg[30] reported successful eradication of epithelial cysts with the same technique. The authors prefer the technique outlined earlier, with aspiration before photocoagulation, because it facilitates more complete photocoagulation and theoretically reduces the likelihood of leaving a free epithelial edge, which may progress to sheetlike epithelial ingrowth. Honrubia, Brito, and Grijalbo[31] reported elimination of several epithelial cysts, with no recurrence or significant complications, using this technique.
The complications of photocoagulation include iritis, which may be marked; a transient rise in intraocular pressure resulting from outflow obstruction by protein and cellular debris, which usually responds to medical treatment and resolves within 2 weeks; corneal opacity from photocoagulation of cyst material adjacent or adherent to the posterior cornea (largely avoidable by posterior displacement of the cyst and angling of the laser beam); hemorrhage from iris vessels (rarely, hemorrhage into a cyst may facilitate argon laser absorption); cataract induction in the phakic eye; and conversion to sheetlike epithelial ingrowth.[32] Treatment of epithelial implantation cysts with the Nd:YAG laser is not recommended because without accompanying cryotherapy or photocoagulation to ensure fibrosis of cyst remnants, the risk of sheetlike ingrowth with such a procedure seems high. Recurrence of such cysts after Nd:YAG treatment is also likely.[33]
Surgery
Surgery for epithelial inclusion cysts has ranged from excision by iridectomy[10] following cryotherapy[22] or aspiration, including debridement or alcohol swabbing of the involved cornea,[34] to block excision with cryotherapy (with or without vitrectomy)[35] and more radical excision including lamellar corneal excision[36] or corneal and corneoscleral grafting.[37] A summary of surgical techniques is given in Table 53-1. Some authors still advocate en bloc excision as the treatment of choice for epithelial inclusion cysts. Surgical approaches, particularly more extensive procedures, carry considerable risks of complications, such as conversion to sheetlike ingrowth, glaucoma, corneal edema, vitreous loss and hemorrhage, and cystoid macular edema. Such procedures may often be avoided by thorough treatment with aspiration followed by cryotherapy with or without photocoagulation, depending on cyst size.
Table 53-1 -- Chronology of surgical techniques for epithelial inclusion cyst[†]
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Year |
Author(s) |
Technique/Comments |
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1955 |
Maumenee, Shannon[34] |
Eleven cases; subtotal/total cyst removal, large iridectomies, denudation of involved posterior cornea; no recurrence, complications, downgrowth |
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1955 |
Rizzuti[39] |
Aspiration-excision by iridectomy-iridodialysis; postoperative VA, 20/30 |
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1962 |
Sugar, Willenz[36] |
Excision of cyst, involved iris, posterior corneoscleral lamella; VA 20/25 |
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1974 |
Harbin, Maumenee[40] |
Reported 6 cases of conversion to epithelial downgrowth after cyst excision; urged conservative management (cyst aspiration with cryotherapy to angle and photocoagulation to cyst remnants on iris) |
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1981 |
Bruner et al[35] |
Closed-eye approach in aphakic patients: cyst aspiration/cryotherapy. Open-sky cyst excision/transscleral cryotherapy in phakic patients. Seven cases: 4 uncomplicated, 2 persistent CME, 1 sheetlike ingrowth, 1 persistent corneal edema; VA better than 20/60 in 43% |
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1981 |
Eiferman, Rodrigues[18] |
Iridocyclectomy/penetrating keratoplasty; wound dehiscence and graft failure from unrelated cause (no recurrence) |
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1981 |
Farmer, Kalina[10] |
Excision by iridectomy-iridodialysis; postoperative VA 20/20 |
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1992, 1996 |
Naumann, Rummelt[37,][38] |
Forty-five cases; block excision by sector iridectomy with excision of cornea, sclera and ciliary body and tectonic corneoscleral grafting; 28% vitreous hemorrhage; 22% corneal decompensation; VA 20/60 or better in 43%; no recurrences; no conversion to sheetlike ingrowth |
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CME, Cystoid macular edema; PPV, pars plana vitrectomy; VA, visual acuity (postoperative). |
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* |
This table is a summary only. The reader should consult the appropriate sources as referenced. |
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† |
Single case reports unless otherwise indicated. |
Regardless of technique, the aim of treatment should be complete eradication of the epithelial cells, as incomplete treatment carries a significant risk of conversion to sheetlike epithelial ingrowth. Early detection of treatment failures with more conservative techniques should allow consideration of more aggressive surgery, such as block excision, before ingrowth is too advanced. Long-term follow-up is required in all cases, as recurrences or conversion to sheetlike epithelial ingrowth may be detected years after initial apparently successful treatment.
Prognosis
The long-term outlook for eyes with epithelial inclusion cysts is far better than for sheetlike ingrowth; however, the visual results from published cases of surgical treatment of such cysts are generally poor. There is clearly considerable bias toward a poorer prognosis group in such reports, as the large numbers of epithelial cysts that require no intervention have not been included. Those eyes that develop complications of treatment (particularly sheetlike epithelial ingrowth and cystoid macular edema) and those with pre-existing poor visual acuity make up the majority of those with poor visual outcome. Corneal decompensation from causes other than sheetlike ingrowth is usually successfully treated with penetrating keratoplasty. Ideally, a large prospective study of such cysts, both treated and untreated, would give a more accurate assessment of the optimal treatment modality and overall prognosis.
Epithelial ingrowth
Since the 1800s, the grim visual prognosis of eyes with epithelial ingrowth, which almost always invariably progressed to intractable glaucoma and blindness, was recognized. This condition is also referred to as epithelial downgrowth, epithelialization of the anterior chamber, and diffuse or sheetlike epithelial ingrowth (to distinguish it from the cystic form described earlier). It may be difficult to diagnose, and despite the use of multiple therapies, including aggressive surgical approaches, its treatment remains challenging, and good visual outcomes are few.
Incidence
The quoted clinical incidence of epithelial ingrowth has long been accepted as an underestimate, owing to lack of recognition and the difficulty of making the diagnosis on clinical, rather than pathologic, grounds. As mentioned earlier, the overall incidence of cystic and sheetlike epithelial invasion of the anterior segment after trauma and surgery in earlier studies[8,][9] was 0.06% to 0.11% (up to 1.1% in one study[41]), and in a clinicopathologic review by Weiner et al.,[42] the incidence after cataract surgery was 0.12% overall from 1953 to 1983, dropping to 0.076% in the period 1973–1983.
More important than the incidence of this condition is its occurrence in eyes enucleated after cataract surgery – an average of 16% and 17%, respectively, in the large series compiled by Maumenee[43] and Jaffe et al.[44] A review of eyes enucleated more recently (1962–1976) by Merenmies and Tarkkanen[45] demonstrated epithelial ingrowth in 10.6% of eyes enucleated following cataract surgery; they noted that all cases of ingrowth occurred before 1969.
The decreasing incidence of epithelial ingrowth has been attributed to the use of the operating microscope; improvements in surgical technique (modern extracapsular and phacoemulsification surgery, with smaller incisions); and the use of finer, higher quality suture material. There are now several reports of epithelial ingrowth following sutureless small-incision cataract surgery, both with scleral tunnel and clear corneal incisions.[46–49] Despite the impression of a decreasing incidence of epithelial ingrowth, it is of significant concern that the proportion of cases that are clinically unrecognized appears to be increasing, which suggests a lower awareness by clinicians of this potentially devastating condition.[50]
Predisposing factors and pathogenesis
Epithelial ingrowth has most commonly been reported following intracapsular and extracapsular cataract surgery (with or without IOL implantation), trauma, and penetrating keratoplasty. In a series by Weiner et al.,[42] 15% of cases followed trauma, and 85% followed surgery (86% cataract surgery, 12% penetrating keratoplasty, 2% other). In a series of 207 histopathologically proven cases of epithelial ingrowth, Kuchle and Green found cataract surgery was the cause in 59.4% of cases.[50] Ingrowth has also been described after surgery for epithelial inclusion cyst (as discussed earlier), Nd:YAG laser treatment of inclusion cyst,[32] pterygium excision,[42] glaucoma filtration procedure,[9] transcorneal (McCannel) suture,[50] discission of posterior capsule,[51] and aspiration of aqueous.[52]
Predisposing factors
Factors predisposing to the development of epithelial ingrowth include technically difficult or complicated surgery (particularly with capsular rupture and vitreous loss); incomplete or delayed wound healing; hypotony; wound fistula; inadvertent filtering bleb; chronic inflammation; and incarceration of iris, vitreous, or lens remnants in the wound. Paufique and Hervouët[53] found that young, highly myopic or diabetic patients were at higher risk of developing ingrowth – the known poor wound healing of diabetics and the relative thinness of ocular tissues in young and highly myopic patients may account for these findings.
There is experimental evidence[54,][55] that anticoagulants inhibit the formation of the usual fibrinous barrier to epithelial migration, and five of Weiner's 124 cases were in anticoagulated patients; however, the significance of these findings is unclear. No other medications have been proposed to influence ingrowth. Previous assertions that epithelial ingrowth was less likely with a limbus-based than a fornix-based flap, not supported in larger series,[42,][56] are largely inconsequential in view of modern wound closure techniques. Similarly, corneoscleral sutures per se have been dismissed as a potential cause,[57] and catgut and silk sutures in cataract incisions (previously implicated in epithelial ingrowth) are essentially obsolete. In a considerable number of cases of epithelial ingrowth, surgery and the postoperative period appeared uneventful and no predisposing factors were identified.
Pathogenesis
Most attempts to further understand the pathogenesis of epithelial ingrowth, by the use of animal experimental models, have met with little success. For a review of experimental work in this area, which is beyond the scope of this chapter, see Burris, Nordquist, and Rowsey[58] and Regan.[13] Burris, Nordquist, and Rowsey[58–60] developed a cat model of epithelial ingrowth that correlates well both clinically and histologically with the features of the human condition. Despite its potential for evaluation of treatment modalities for epithelial ingrowth, we could find no reports of its use after 1986.[61]
It has generally been accepted that epithelial ingrowth largely results from suboptimal surgical technique, allowing a free edge of surface epithelium to proliferate into the anterior chamber. It is equally clear that implantation of epithelial cells alone will not produce ingrowth. The following factors are recognized as being significant in the pathogenesis of epithelial ingrowth; however, none are invariably present in cases of ingrowth, and, conversely, they may be present in the absence of ingrowth.
Poor wound healing, with or without a clinically evident fistula, may result from poor incision or suturing technique or incarceration of iris, vitreous, or lens remnants. Persistence of plasmoid or secondary aqueous, which contains proliferative factors not found in normal aqueous (which may not sustain the invading epithelium, let alone allow proliferation), appears important in establishing and maintaining ingrowth – its persistence may be due to hypotony or chronic inflammation. Approximation of iris tissue to the wound (even without incarceration) is frequently seen and provides a rich vascular bed for the epithelium. Damage to the underlying corneal endothelium may in part be a prerequisite for migration of the epithelial membrane (by loss of the usual cell contact inhibition) and to a larger extent may represent a cytotoxic effect of the extension of pseudopodia by the epithelial cells, causing disruption of the endothelial plasma membrane.[51,][59]
Many features of the pathogenesis of epithelial ingrowth remain unclear, particularly how in some eyes there can be relentless progression of the epithelial membrane in the absence of a fistula, hypotony, or signs of inflammation.
Presentation, clinical features, and diagnosis
Patients often present within weeks to months after surgery or trauma, but there are reports of presentations as early as 4 days[5] and as late as 38 years[50] following surgery. Weiner et al.[42] found the most common symptoms (in decreasing order of frequency) to be decreasing visual acuity, red eye, painful eye, tearing, photophobia, and foreign body sensation. Patients may have been labeled as having “uveitis” that failed to respond to topical corticosteroids.
The clinical signs at first presentation of epithelial ingrowth may individually be nonspecific (particularly in the absence of an obvious retrocorneal membrane), and a high index of suspicion is required to make an early diagnosis. A gaping wound, inadvertent filtering bleb, or an obvious wound fistula should arouse such suspicions.
The epithelial sheet (shown in Figure 53-10A) is most often seen as a retrocorneal membrane with a “gray line” at the leading edge (Figure 53-10B), sometimes with focal “pearl-like” regions resulting from clustering of epithelial cells. These features are best appreciated with retroillumination (Figure 53-11). The involved cornea is frequently clear, although there may be epithelial edema or prominent corneal vascularization. There is clinical evidence of stromal vascularization in approximately half of cases (which Calhoun[62] equated with more rapid progression of ingrowth) and histopathologic evidence in almost all (see further on). Burris, Nordquist, and Rowsey[58] identified pre-Descemet's vascularization as “a harbinger of occult epithelial downgrowth” in their cat model. Descemet's folds may be evident in hypotonous eyes, particularly those with corneal edema. Less common corneal findings include bullous keratopathy, band keratopathy, and a variable level of reduction in corneal sensation.
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Figure 53-10 A, Ingrowing epithelial membrane on the posterior corneal surface. B, Ingrowing epithelial membrane. Arrow indicates the leading edge of the epithelium. |
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Figure 53-11 Retroillumination appearance of the epithelial sheet on the posterior corneal surface, with thickened and irregular leading edge (arrow). |
There may be signs of iridocyclitis, and the membrane may be visible on the surface of the iris. Often iris involvement is manifest as loss of the usual iris contour and mobility or pupillary distortion. Advancement of epithelial ingrowth is usually more rapid over the richly vascular iris than the posterior cornea, and thus progression or otherwise of the retrocorneal membrane is not a reliable indicator. Gonioscopy (Figure 53-12) often reveals peripheral anterior synechiae, a degree of epithelialization of the angle, or incarcerated iris, lens remnants, or vitreous. An epithelialized communication with a fistula or bleb may also be evident.
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Figure 53-12 Gonioscopic view of the superior angle of the left eye, showing the ingrowing membrane throughout the entire view. A large strand of vitreous extends into the cataract incision at 12 o'clock. |
Intraocular pressure is abnormal in the majority of affected eyes, partly depending on the extent of disease on presentation. Hypotony is documented in up to one-third of cases and is highly suggestive of a wound fistula. A significant number of patients with a clinically demonstrable fistula have normal intraocular pressures. Glaucoma is present in approximately half of cases and is almost invariably present in advanced epithelial ingrowth.
The epithelial membrane may extend over the pupil, vitreous face, ciliary body, and retina and may cause retinal detachment. Epithelial ingrowth has been reported, primarily involving the anterior and posterior lens capsule,[63] and proliferating over the surface of an IOL.[64–66] Cystoid macular edema may be present, particularly in eyes with long-standing inflammation. The use of topical steroid medications may temporarily ameliorate some of the symptoms and signs associated with epithelial ingrowth, sometimes delaying the diagnosis.
Diagnostic adjuncts
The diagnosis of epithelial ingrowth requires a combination of awareness of the condition, history and thorough examination for the clinical signs outlined earlier, and the use of additional diagnostic procedures.
Noninvasive procedures
Seidel's test
To perform Seidel's test, 2% fluorescein drops are instilled into the eye, and gentle pressure is applied to the globe. Using the slit lamp with the cobalt blue filter, aqueous flowing from a fistula appears as a lighter stream of fluid in the pool of green fluorescein. Up to one-third of eyes have a fistula demonstrable in this fashion on presentation, although presumably all have a fistula at some stage in the development of ingrowth.
Specular and confocal microscopy
At the level of the endothelium, a sharply defined border may be seen between areas of normal endothelium and the epithelial membrane[51,][67] (Figure 53-13), and there is usually evidence of endothelial cell loss, reflected in the large size of the remaining endothelial cells, which also appear morphologically abnormal.[68] Confocal microscopy has also been used to identify epithelial ingrowth on the corneal endothelium.[69]
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Figure 53-13 A, Specular microscopy of epithelial ingrowth (×400). Top, Specular micrograph of inferior central (clear) part of corneal endothelium. Cells are grossly enlarged and distorted, and nuclei are prominent. Cell count is 600 per mm[2]. Bottom, Specular micrograph of leading edge of epithelial ingrowth. The membrane edge is sharp, and individual epithelial cells cannot be delineated in the area of epithelial ingrowth (EP). With careful focusing, individual enlarged, distorted corneal endothelial (CE) cells can be visualized. |
Argon laser photocoagulation
Application of a 500μm spot size, 100–300mW intensity burn for 0.1s will produce a characteristic white fluffy appearance if invading epithelium is present on the iris, and a slight focal burn on normal iris (Figure 53-14).
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Figure 53-14 A, Argon laser photocoagulation produces characteristic fluffing of iris involved with epithelial ingrowth and a slight focal burn on normal iris. B, Argon laser photocoagulation of iris involved in epithelial ingrowth. |
Invasive procedures
Iris biopsy
First advocated by Verhoeff,[70] full-thickness biopsy of iris adjacent to the wound, which is invariably involved in ingrowth if present, may be performed to confirm the diagnosis.
Curettage of the posterior corneal surface
Calhoun[71] described curettage of the posterior corneal surface in a region of suspected downgrowth. He used a 1mm serrated curette to procure a specimen for microscopy, which can easily differentiate between regular, evenly spaced endothelial cells and epithelial cells that are closely packed, spindled, and less regular and have denser cytoplasm. This technique is used infrequently.
Anterior chamber paracentesis
This technique[72] along with cytologic examination of aqueous for epithelial cells has been used, but has a relatively poor yield, and it is unhelpful if negative.
Differential diagnosis
As outlined by Maumenee,[43] the differential diagnosis of epithelial ingrowth includes:
|
1. |
Reduplication of Descemet's membrane, which appears as a glassy membrane on the posterior cornea, anterior iris, and angle. This usually occurs in eyes with chronic iridocyclitis and is the condition most likely to resemble epithelialization, but photocoagulation does not produce the appearance described earlier. |
|
|
2. |
Fibrous ingrowth, which may have a similar retrocorneal membrane but tends to be slower growing and display more prominent vascularity. |
|
|
3. |
Vitreocorneal adhesions, which may appear grayish and may cause corneal edema; however, their slit-lamp appearance is characteristic, and they and do not progress in the same fashion as ingrowth. |
|
|
4. |
Anterior shelved clear corneal or scleral tunnel incision. |
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|
5. |
Detachment of Descemet's membrane. |
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|
6. |
Peripheral corneal edema. |
Histopathologic features
Microscopic examination of tissue involved in epithelial ingrowth typically reveals 1 to 12 layers of irregularly arranged, stratified squamous ocular surface epithelium.[50] Goblet cells are sometimes seen, and even in their absence, the electron microscopic characteristics of the epithelium suggest conjunctiva rather than cornea as the source in many cases.[51,][59,][60,][73]
The epithelium is usually present as a membrane of one to three cell layers over the posterior cornea, almost invariably with evidence of stromal vascularization, particularly along the tract of the wound or incision.[74] Weiner et al.[42] found concomitant stromal (fibrous) ingrowth in 55% of postsurgical cases of epithelial ingrowth. The “gray line” that may be seen clinically corresponds to heaped up epithelial cells at the margin of the epithelial sheet. At the leading edge there is a sloping appearance, as observed in epithelial wound healing[75](Figure 53-15). The irregular arrangement of epithelial cells at the margin gives rise to the scalloped edge seen on slit-lamp examination.
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Figure 53-15 Light microscopy of ingrowing epithelium on the posterior corneal surface (corneal endothelium [CE]), with a tapered leading edge. The most superficial ingrowing cells are edematous and vacuolated. Descemet's membrane (DM) and the corneal stroma (CS) appear unaffected. (Basic fuchsin stain, ×400.) |
In the majority of cases, there is extension of the membrane as a “more luxuriant” growth averaging three to five cell layers[42] on the anterior surface of the iris and angle (or false angle created by peripheral anterior synechiae). The membrane may extend over the posterior iris, anterior vitreous face, ciliary body, and retina. Fibrous contraction resulting from concomitant rubeosis may cause ectropion uveae. Ocular surface epithelium usually extends well into the surgical or traumatic wound, and fine sectioning of enucleated specimens often reveals continuity of the epithelial lining of the anterior chamber with the surface epithelium. There is often incarceration of iris, lens remnants, or vitreous in the wound.
The mechanisms of glaucoma in epithelial ingrowth, as discussed by Smith et al.,[76] include secondary angle closure by contraction of the epithelial and fibrous tissue lining the false angle; obstruction of outflow by epithelium lining the entire angle; pupillary block from occlusion by the epithelial sheet; obstruction of the trabecular meshwork by macrophages and desquamating epithelial cells; chronic uveal inflammation, leading to trabeculitis and decreased outflow; and the rare mucogenic glaucoma resulting from goblet cell secretion.[77] An infiltrate of chronic inflammatory cells is commonly seen in the ciliary body, iris, and episclera. Cystoid macular edema may also be present in eyes with long-term inflammation.
Management
Although surgical eradication of epithelial ingrowth is the only widely accepted therapeutic modality capable of curing this condition, the results are modest even in the most experienced of hands. A chronologic summary of surgical techniques used in the management of epithelial ingrowth is given in Table 53-2.
Table 53-2 -- Chronology of surgical techniques for epithelial ingrowth*
|
Year |
Author(s) |
Technique/Comments |
|
1957 |
Maumenee[82] |
Single case; alcohol/curettage of epithelium from posterior cornea; iridectomy/anterior vitrectomy; VA 20/20 at 21/2 years, no recurrence |
|
1958 |
Sullivan[81] |
Four cases; corneoscleral excision/grafting; membrane excised from iris, ciliary body, vitreous; 1 enucleation; VA, 2 count fingers, one 20/100 |
|
1964 |
Maumenee[43] |
Conjunctival flap; identify/excise any fistula; excision of all involved iris; involved posterior cornea curetted, debrided, swabbed with 70% alcohol; 26 cases; 3 enucleations, 3 RD, 13 CO, 6 VA 20/50 or better (23%) |
|
1970 |
Maumenee et al[56] |
Preceding technique with excision/cryotherapy of involved ciliary body, anterior vitrectomy, either cryotherapy/curettng or alcohol to involved cornea; 40 cases; 5 enucleations, 20 CE, 17 glaucoma, 5 hypotony (3 phthisis), 1 RD, 11 successes (27.5%) |
|
1973 |
Brown[83] |
Three cases (advanced ingrowth); modification of Maumenees technique, with deep lamellar scleral/angle excision; cryotherapy to involved cornea; 1 subsequent PK; no recurrences; all 3 had postoperative (controlled) glaucoma; all achieved ambulatory vision (best 20/80) |
|
1977 |
Friedman[84] |
Three cases; en bloc excision of cornea, sclera, iris, ciliary body, vitreous; repair with corneoscleral graft; VAs 20/50, 20/60, 20/100; no recurrence |
|
1978 |
Stark et al[85] |
Ten cases; argon laser to define iris involvement; surgical technique as described in text; 4 PKs; VA improved in 8/10; 4 successes[†] (40%) |
|
1979 |
Brown[64] |
Fourteen cases of advanced ingrowth; 9 cases, technique as preceding (1973); 4 PKs; 3 recurrences, 1 success[†]; 5 cases, cornea debrided (not cryotherapy); 2 PKs; 1 recurrence, 1 success[†]; 6 required cyclocryotherapy for glaucoma (not caused by recurrence) |
|
1992 |
Naumann, Rummelt[37] |
Four cases; excision cornea, sclera, iris, ciliary body; anterior vitrectomy; tectonic corneoscleral grafting; complications: VH, CE, glaucoma; VA, 2 patients 20/100, 2 patients LP |
|
2002 |
Lai, Haller[88] |
Fluid-gas exchange with intraocular 5-FU; 2 treatments; VA 20/200 with no recurrence at 8 months |
|
2002 |
Shaikh et al[89] |
Intraocular 5-FU mixed with sodium hyaluronate–viscodissection of retrocorneal epithelial membrane; no recurrence at 14 months |
|
* |
This table is a summary only. Please consult the appropriate sources as referenced. |
|
† |
Defined as VA 20/50 or better, normal intraocular pressure on topical or no medication, no recurrence. CE, Corneal edema; CO, corneal opacification; 5-FU, 5-fluorouracil; LP, light perception; PK, penetrating keratoplasty; RD, retinal detachment; SO, sympathetic ophthalmia; VA, visual acuity (postoperative); VH, vitreous hemorrhage. |
Radiotherapy was first used in 1924[78] but was abandoned by the late 1960s because of questionable efficacy, unclear guidelines regarding dosage, and its high potential for damage to ocular structures. Reports of success with radiotherapy were also criticized for the lack of a tissue diagnosis in many cases. Early experience with surgery was so discouraging that it was considered to accelerate the progression of the disease,[79] which (treated or untreated) resulted in blindness and often in enucleation.
There was renewed interest in surgical treatment of epithelial ingrowth in the 1950s[80–82] (see Table 53-2), and Maumenee[43] in 1964 was the first to publish a large series (26 cases) of surgically treated ingrowths. His technique involved identification and excision of any fistula; wide excision of all involved iris tissue; and treatment of the involved area of posterior cornea with curettage, debridement, or swabbing with 70% alcohol. Subsequent modifications to this technique by Maumenee and co-workers have resulted in the currently accepted surgical approach, as outlined here.
In his 1970 series of 40 cases, Maumenee established stringent criteria for success in treating epithelial ingrowth:[56] postoperative visual acuity 20/50 or better, no recurrence of ingrowth, and intraocular pressure controlled on topical or no medication. Limited anterior vitrectomy was added to excision of involved iris and ciliary body, with cryotherapy to the involved posterior corneal surface becoming preferred to other methods of epithelial eradication. Success was achieved in 27.5% of cases, enucleation was required in 12.5%, and complications included corneal edema, hypotony, glaucoma, vitreous opacity, and retinal detachment.
Alterations to Maumenee's technique (see Table 53-2) have included deep lamellar excision of sclera and angle structures,[83] cryotherapy to suspected areas of angle/ciliary body involvement,[64] corneoscleral excision and grafting,[39,][81,][84] and the modifications of Stark et al.[85] (see further on). The more surgically destructive approaches, in an attempt to more thoroughly eradicate invading epithelium, have not achieved any higher success rates; however, they have included small numbers of patients or, in the case of Brown's series, involved more advanced cases of ingrowth (involving at least 50% of the cornea, iris, or both).
Current techniques
The most widely accepted surgical approach is the modification of Maumenee's technique by Stark et al.[85] Preoperative argon laser photocoagulation is used to delineate the extent of iris involvement. This is best performed within 24h of surgery, as this degree of photocoagulation usually results in significant anterior-chamber inflammation.
Rectus muscle traction sutures are placed transconjunctivally after conjunctival peritomy. A limbal or fornix-based conjunctival flap is dissected to expose the superior corneoscleral limbus. A careful search for aqueous leakage from a fistula (which may not have been evident with Seidel's test at the slit-lamp examination) is performed, using 2% fluorescein and external pressure on the globe. If a fistula is found, it is excised and closed with sutures; or a scleral flap, hinged anteriorly, is prepared for later closure of larger fistulae. The leading edge of the epithelial sheet on the posterior surface of the cornea may be marked with a blade.
In cases where a pars plana vitrectomy approach is used, sclerotomies are performed 3–4mm posterior to the limbus, and the vitrectomy instrument is used to excise involved iris and vitreous. Bleeding is controlled with bipolar diathermy or by transiently increasing intraocular pressure. Excised tissue is studied cytologically to confirm the diagnosis of epithelial ingrowth. As complete a vitrectomy as possible should be performed, to allow space for fluid–air exchange to enhance the effects of cryotherapy, and minimise the risk of vitreous prolapse or incarceration.
If a large fistula is present, its site is sealed by suturing the previously prepared scleral flap to the peripheral cornea. Indirect ophthalmoscopy with scleral indentation is performed, and any retinal tears are treated with cryotherapy, laser, and/or scleral buckling as required. After fluid–air exchange, transcorneal and transscleral cryotherapy is then performed to eliminate residual epithelium on the posterior cornea, angle, and ciliary body (Figure 53-16). Stark et al.[85] recommend that a single freeze is adequate if air insulation is used. Unless required for tamponade of retinal breaks, the air bubble is replaced with physiologic saline solution. Frequent topical corticosteroid drops are used postoperatively. The treated epithelium on the cornea usually sloughs after a few days.
|
Figure 53-16 Transcorneal and transscleral cryotherapy is used to eliminate residual ingrowing epithelium. |
Stark et al.[85] achieved impressive results in their report of 10 consecutive patients treated with this technique (average 23 months' follow-up), with improvement in visual acuity in 8 of 10 cases and four eyes with 20/40 or better vision. Four eyes required penetrating keratoplasty: one eye had residual epithelial cells on examination of the corneal button, and all grafts remained clear during the follow-up period. Brown,[64] who used a similar technique with more extensive excision of angle structures, also reported favorable results from keratoplasty in eyes treated for ingrowth. As emphasized by previous authors, patients with epithelial ingrowth must be observed for some years after treatment before recurrence can be ruled out.
Most contemporary cases of epithelial ingrowth that we have seen as a complication of cataract surgery have involved aphakic eyes with secondary anterior chamber IOLs. The IOL is usually removed as part of the surgical management of this condition, although there are no data to suggest the optimal surgical management in these circumstances. Experience with posterior-chamber IOLs is limited.
In eyes with extensive involvement from epithelial ingrowth not amenable to curative surgery, particularly in very elderly patients, it is reasonable to aim for control of intraocular pressure, preservation of some functional vision, and avoidance of enucleation. Fish et al.[86] reported nine cases in which Molteno implants were used for intractable secondary glaucoma caused by epithelial ingrowth, achieving control of intraocular pressure in seven, comfort in six, and maintenance of formed vision (at least 1/200) in five patients. The use of a Krupin-Denver valve for control of glaucoma in this condition has also been described.[87] Closure of a fistula is contraindicated if curative surgery is not possible because intraocular pressure will almost certainly become uncontrollable.
The most promising recent advance in the treatment of diffuse epithelial ingrowth is the use of intraocular 5-fluorouracil (5-FU).[88,][89] Loane and Weinreb[90] reported the use of subconjunctival 5-FU, but this had only a temporary effect in halting the progress of the epithelial membrane, and the eye was ultimately enucleated. Lai and Haller[88] treated an aphakic patient with fluid-gas exchange and 500 μg of 5-FU injected into the anterior chamber, followed by face-down positioning to concentrate the 5-FU in the retrocorneal space. After a second injection of 5-FU, the epithelial membrane was no longer visible. There was no recurrence at 8 months' follow-up. Shaikh et al.[89] used 1mg of 5-FU mixed with sodium hyaluronate to viscodissect an epithelial ingrowth membrane from the posterior corneal surface. Repeat penetrating keratoplasty was required for graft failure, but no recurrence was observed at 14 months' follow-up.
The use of 5-FU (and possibly other antimetabolites) may offer a less invasive approach, or act as a useful adjunct to surgical intervention, for management of these challenging cases. Even if corneal endothelial toxicity and corneal decompensation occurs, penetrating keratoplasty has a reasonable chance of success if the ingrowth has been eliminated. Further experience and long-term follow-up are required to establish the role of this treatment modality.
Prognosis
Even if clinically recognized and surgically treated, epithelial ingrowth carries a poor prognosis. Patients with fistulae were recognized by Maumenee[43] as having a worse outcome. Even in patients with ultimately poor visual acuity, surgery improves outcome in terms of comfort and avoidance of enucleation, compared with medical management (topical antibiotics and steroids) or no treatment. In the series by Weiner et al.,[42] 52% of patients with epithelial ingrowth after surgery eventually required enucleation; only 19% of patients treated with iridectomy and surgical excision had enucleations, compared with all patients treated medically and 95% of those not treated.
Fibrous ingrowth
In contrast to epithelial ingrowth, there has been relatively little attention given to fibrous ingrowth in the ophthalmic literature. It is often an incidental pathologic finding and infrequently behaves in the aggressive, almost malignant fashion of epithelial ingrowth. Alternative expressions for fibrous ingrowth include fibrous overgrowth, fibrous metaplasia, fibrocytic ingrowth, fibroblastic ingrowth, stromal ingrowth, and stromal overgrowth. Some authors also use the term retrocorneal membrane interchangeably with fibrous ingrowth, particularly in cases following penetrating keratoplasty.
Historical perspective
Early in the twentieth century, fibrous ingrowth was included in discussions of the complications of cataract surgery, with Henderson[91] emphasizing the role of incarceration of iris, lens capsule, or lens debris in allowing entry of connective tissue to the anterior chamber, paralleling epithelial invasion, and Collins[92] asserting that fibrous ingrowth was invariably a result of infection. In 1947, Levkoieva[93] highlighted the incidence of fibrous ingrowth in eyes enucleated after penetrating injury. He and others have debated the likely source of the ingrowing fibrous tissue (see Predisposing Factors and Pathogenesis)
Incidence
Fibrous ingrowth is usually diagnosed on pathologic grounds, and estimates of its clinical incidence have not been reported. Its incidence in enucleated eyes after cataract surgery is as high as 36% in some series[94] and has generally been found to be more common than epithelial ingrowth. Despite this, fibrous ingrowth is a less frequent cause of enucleation than is epithelial ingrowth. Weiner et al.[42] found concomitant fibrous ingrowth in 55% of cases of epithelial ingrowth following cataract surgery.
Predisposing factors and pathogenesis
Similar factors predispose to fibrous ingrowth as those discussed earlier under epithelial ingrowth, namely technically difficult or complicated surgery (particularly with capsular rupture and vitreous loss); incomplete or delayed wound healing; hypotony; uveitis; and incarceration of iris, vitreous, or lens remnants in the wound. Swan[95] emphasizes recurrent hemorrhage as a predisposing factor to fibrous ingrowth and states that more posterior incisions, which may damage the deep scleral plexus, are more likely to cause hemorrhage. The importance of incarceration of material in the cataract wound was emphasized by findings of McDonnell, de la Cruz, and Green:[96] 84% of cases with vitreous incarceration after cataract surgery studied histopathologically showed evidence of fibrous ingrowth. Swan[95] noted that ingrowth along incarcerated tissue is unlikely if the outer wound edges are in good apposition.
The exact source of fibroblasts in fibrous ingrowth remains a contentious issue. Swan[95] confirmed the observations of Henderson[91] that subepithelial connective tissue is most likely the major source of fibroblasts that invade the anterior chamber in fibrous ingrowth (rather than being overgrowth of corneal, scleral, or limbal stroma, as is often stated). He also observed that the usual physiologic degree of fibroblastic ingrowth, as part of wound healing, may extend further than usual if the endothelium (which usually bridges the inner wound margin) has been damaged. This is supported by the studies of Brown and Kitano[97] in rabbits. The degree of perforation of Descemet's membrane (which may determine the likelihood of invasion of fibrous tissue) has been highlighted by some authors[98,][99] as an important pathogenetic factor.
Blood-derived mononuclear cells[95] and metaplastic endothelial cells have also been proposed as sources of fibroblasts. Retrocorneal/posterior corneal membranes resulting from fibrous metaplasia of endothelial cells, such as those following penetrating keratoplasty and clear corneal cataract incisions, differ in histologic appearance to those of fibrous ingrowth from limbal incisions and should be considered separately. One report[100] describes a “double membrane” composed of an anterior, vascularized fibrous ingrowth, apparently arising from subepithelial connective tissue, and a posterior, relatively amorphous and acellular layer, which appeared to arise from fibroblastic transformation of endothelial cells. Production of extracellular matrix by endothelial cells in response to disease and injury is well established and has been discussed in detail by Waring et al.[101–103] Their classification of abnormal collagenous tissue in the region of the posterior cornea into three types of “posterior collagenous layer of the cornea” is a useful and more accurate method of describing this fibrous tissue, regardless of its cell(s) of origin.
Presentation, clinical features, and diagnosis
Fibrous ingrowth has been observed following penetrating anterior segment trauma, cataract surgery, glaucoma filtering surgery, and penetrating keratoplasty. It has some features in common with epithelial ingrowth, but as a rule runs a self-limiting course, and the ingrowing membrane has a different appearance (Figure 53-17).
|
Figure 53-17 A, Marked corneal opacity resulting from fibrous ingrowth. B, Magnified view demonstrating the irregular serrated margin of the fibrous membrane. |
The clinical course of fibrous ingrowth is highly variable and depends on extent of the factors promoting ingrowth. Frequently, it runs an insidious course with little discomfort, and if the condition is diagnosed clinically, the membrane is often noted as an incidental finding. Less commonly, patients present with decreased visual acuity caused by the fibrous membrane or symptoms related to uveitis, glaucoma, or (rarely) retinal detachment.
Typically, the membrane of fibrous ingrowth is gray or white and has a less well-defined border than that of epithelial ingrowth. It is well described by Swan[104] as an interlacing meshwork of fine fibers, with the appearance of woven cloth, and fine tonguelike strands of fibrous tissue extending from the leading edge. Any extension over the angle, iris, and vitreous is usually identifiable as a thick fibrous membrane. It may also appear as a fine gray sheet over the vitreous face, resembling the membrane associated with postoperative iridocyclitis or hyphema. In cases associated with recurrent hyphema, the membrane may be straw colored as a result of blood pigment deposition. The membrane on the posterior cornea may also be translucent, with a relatively well-defined margin and a similar appearance to the membrane of epithelial ingrowth, especially in regions of stripping of Descemet's membrane, or vitreous touch.
There is usually corneal edema overlying the affected area of cornea, and bullous keratopathy is also common. An updrawn pupil resulting from contraction of fibrous tissue may be evident. Glaucoma is a frequent finding and may be due to overgrowth of the anterior chamber angle or peripheral anterior synechiae associated with chronic inflammation. The degree of inflammation tends to parallel the behavior of the fibrous proliferation, from self-limited fibrous ingrowth with minimal inflammation to extensive proliferation of fibrous tissue, which may be accompanied by marked uveitis. As noted by Duke-Elder,[105] there may be an absence of marked inflammatory changes if the uveal structures are enveloped in fibrous tissue. Subsequent contraction of this tissue may result in retinal detachment, hypotony, and phthisis bulbi. Conversely, fibrous ingrowth is a common finding in phthisical eyes enucleated after cataract surgery.[99]
The diagnosis of fibrous ingrowth should be made on the basis of the preceding clinical features and awareness of the factors predisposing to the development of fibrous ingrowth in the setting of previous anterior segment surgery or trauma. There are no specific recommended diagnostic adjuncts, although if there is sufficient suspicion of epithelial ingrowth on clinical grounds, the further tests recommended earlier may be useful. The differential diagnosis of fibrous ingrowth corresponds to that of epithelial ingrowth, as detailed earlier. Clearly, if surgery is performed for one of the complications mentioned previously, a histopathologic diagnosis should be made on examination of the excised tissue.
Histopathologic features
Externally there may be evidence of poor apposition of wound edges. Similar inadequate apposition internally is reflected in a larger gap between the cut edges of Descemet's membrane, filled with advancing fibrous tissue. The source of this fibrous tissue (subepithelial connective tissue, corneal/limbal stroma, or metaplastic endothelium) is usually not apparent. The corneal stroma may show deep vascularization and a chronic inflammatory cell infiltrate. There may be evidence of suture-related inflammation, and poorly placed or improperly tensioned sutures, resulting in poor wound coaptation, may be seen.
There is usually damage to the endothelium and stripping of Descemet's membrane adjacent to the wound. The anterior chamber angle may be closed by peripheral anterior synechiae or a fibrocellular sheet; the trabecular meshwork in eyes with long-standing fibrous ingrowth appears atrophic or sclerotic. There may be incarceration of iris, lens capsule, lens cortical remnants, or vitreous, as discussed earlier. A pupillary membrane may be present, and contraction of fibrous tissue may lead to pupillary distortion, or, in cases of extensive ingrowth, retinal detachment (Figure 53-18). Wound fistulae appear less common in cases of fibrous ingrowth (without concomitant epithelial ingrowth) than in epithelial ingrowth alone.
|
Figure 53-18 Light microscopy of massive fibrous ingrowth through a cataract incision forming a dense secondary membrane and causing retinal detachment. (Hematoxylin and eosin stain; ×10.) |
Management
As for epithelial ingrowth, modern surgical technique has led to a reduction in the risk factors for development of fibrous ingrowth. Prevention of these conditions is far more effective than attempts at cure. Treatment of the underlying ingrowth itself is not nearly so important in fibrous as in epithelial ingrowth; as many eyes remain stable or progress little over the years, treatment is usually confined to managing specific sequelae of ingrowth. This may include treatment for corneal edema or uveitis (although it is generally accepted that topical steroids will not halt progression of membrane itself); retrocorneal membrane excision with or without penetrating keratoplasty; surgical or Nd:YAG cutting of pupillary membranes; release of vitreous and retinal traction, which may require vitrectomy and scleral buckling; and management of secondary glaucoma. Viscoelastic displacement of a retrocorneal membrane due to fibrous ingrowth has also been recently described.[106] Although Friedman and Henkind[107] proposed radiotherapy in progressive fibrous ingrowth, there are no clinical reports of its use.
Prognosis
In the absence of any large clinical series of cases of fibrous ingrowth, the prognosis of this condition is based largely on anecdotal experience. The overall outlook is considerably better than that of epithelial ingrowth, because many cases of fibrous ingrowth are self-limited. Eyes with more extensive or progressive forms of fibrous ingrowth have a poor prognosis, similar to that of epithelial ingrowth, and surgery may be of benefit in treatment of specific complications, although results are modest at best.
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