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Sequential Sectoral Conjunctival Epitheliectomy (SSCE)
Harminder S. Dua
Introduction
The limbal epithelium, with its repository of stem cells, acts as a barrier that exerts an inhibitory growth pressure, preventing the migration of conjunctival epithelial cells onto the cornea.1 When an ocular surface epithelial defect involves the cornea and limbus, this barrier is lifted and conjunctival epithelium often migrates across the denuded limbus to cover the corneal surface. The participation of conjunctival epithelium in the healing of corneal epithelial wounds has been known for a long time.2 It was believed that conjunctival epithelium covering the cornea undergoes a slow transformation to assume characteristics resembling corneal epithelium, a process referred to as conjunctival transdifferentia- tion.3–8 However, several investigators are of the opinion that complete conjunctival transdifferentiation probably does not occur. The consensus from most animal studies is that, although morphological transdifferentiation is possible, biochemically and functionally it is far from satisfactory.1,9–11 Moreover, it has also been suggested that, in animal studies supporting conjunctival transdifferentiation, transdifferentiation could have occurred due to incomplete removal of limbal basal epithelium.12 This incomplete removal would explain how regenerated epithelium could demonstrate both corneal and conjunctival features without one actually changing into the other. Long-term follow-up of conjunctivalized corneas in humans has revealed that clinical transdifferentiation of the conjunctival epithelial phenotype into corneal epithelial phenotype does not occur.13 Impression cytology studies have revealed persistence of goblet cells in areas of conjunctivalization.
The corneal surface covered by conjunctival epithelium is characterized by the presence of goblet cells and is usually vascularized.14 It appears thin, irregular, and is prone to recurrent erosions.15 When it covers the pupillary area, vision can be significantly impaired.
It therefore follows that, in ocular surface defects, conjunctival epithelium should be prevented from covering the corneal surface, or if unavoidable or already established at the time of presentation, it should be removed at a later date to facilitate corneal epithelial cover for the cornea. Removal of conjunctival epithelium may have to be staged or repeated until the desired end point is attained. Sequential sector conjunctival epitheliectomy (SSCE) describes the above procedure, wherein conjunctival epithelium, covering a sector of the cornea and limbus, or adjacent bulbar conjunctiva, is removed and prevented from crossing the limbus until the denuded surface is covered by corneal epithelium derived cells.13
Indications for SSCE
Following are the indications for SSCE:
1.During the healing of acute ocular surface defects involving the cornea and limbus to prevent conjunctivalization of the cornea.
2.In patients with partial limbal stem cell deficiency with established conjunctivalization of the cornea.
3.In patients undergoing limbal allografts (including living-related tissue) and limbal autografts for total stem cell deficiency.
4.Following excision of limbal lesions.
It is well established that large ocular surface epithelial defects, involving the cornea, limbus, and adjoining conjunctiva heal by centripetal migration of epithelial cells from the remaining intact corneal and conjunctival epithelium, and by circumferential migration of limbal epithelial cells along the limbus, arising from the two ends of the remaining intact limbal epithelium.16 The circumferentially migrating limbal epithelial sheets meet to reestablish the limbal epithelial
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Figure 14.1. Diagrammatic representation of the healing of an ocular surface defect involving the limbus. (A) Arrowheads indicate the formation of tongue-shaped epithelial sheets, from the remaining intact epithelium, at either end of the limbal defect (hatched area represents fluorescein staining). (B) Arrows indicate the circumferential migration of tongue-shaped sheets along the limbus. (C) Limbal cover is always re-established before the central defect heals. (D) Conjunctival epithelium (solid black) may extend across the limbus to cover the cornea and inhibit further migration of the limbal epithelial sheets. (E and F) Area covered by limbal epithelium is sharply demarcated from normal corneal epithelium, is thin, irregular, and attracts new blood vessels. (Dua HS et al. Brit J Ophthalmol 1994; 78:402. Reproduced with permission from the BMJ Publishing Group.)
barrier (Figure 14.1). It has been postulated that this preferential circumferential migration along the limbus may represent a repopulation of the limbus with stem cells.15,16 Centripetal migration also occurs from this newly established limbal epithelium to eventually close the central corneal epithelial defect, following a pattern similar to that occurring in patients with a central corneal epithelial defect and an intact limbus.17 Often, however, the centripetally migrating healing conjunctival epithelium reaches the limbus and crosses it to cover the cornea to a variable extent. This conjunctival epithelial sheet contact inhibits the circumferentially migrating limbal epithelium, and the area of limbus covered by it remains “conjunctivalized” and devoid of limbal stem cells.16
The same migration patterns are seen following limbal alloand autografts used in the management of total stem cell deficiency. Cells derived from the limbal explants following autologous and living-related donor transplants migrate centripetally and circumferentially along the limbus. Here too, despite peritomy and conjunctival recession, conjunctival epithelium often reaches the limbus and encroaches on the corneal surface.18,19 The conjunctival encroachment results in an admixture of limbal explant-derived corneal cells and conjunctival cells. When cadaveric donor limbal tissue
is used, the transplanted limbal tissue is more complete through 360 degrees of the recipient eye, and centripetal migration is predominantly observed. However, depending on the technique used, gaps may exist and provide an avenue for conjunctival cells to reach the limbus and encroach on the cornea.
In the circumstances described above, SSCE is performed to prevent conjunctival epithelium from reaching the limbus. It is effectively held back until repopulation of the limbus from surviving limbal cells or donor limbus is achieved. Similarly, if conjunctivalization has already occurred, the epithelium over the affected area of the cornea and limbus is removed to allow healing from healthy limbus-derived cells.
The same principles will apply following resection of limbal lesions and other surgical procedures performed during ocular surface reconstruction.
Contraindications for SSCE
Following are the contraindications for SSCE:
1.Total limbal involvement.
2.Dense fibrovascular pannus.
3.Thin underlying stroma.
4.Very dry eye.
5.Anaesthetic cornea.
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Total limbal involvement with conjunctivalization of the cornea is a definite contraindication for SSCE. Removal of conjunctival epithelium from the cornea will only result in more conjunctival cells coming in, since there is no surviving limbus to provide corneal epithelial cells. In such situations, a limbal transplant procedure is the primary intervention.
The presence of a dense fibrovascular pannus with partial stem cell deficiency is a relative contraindication. A fibrovascular pannus requires excision. The underlying stromal bed, if healthy, may support epithelialization from limbus-derived corneal epithelial cells. If not it may result in a persistent epithelial defect with exposed stromal collagen. In such instances, an amniotic membrane transplant may need to be combined with SSCE.20 In patients in whom the ocular surface is very dry, the corneal stroma under the fibrovascular pannus is very thin. If corneal sensation is markedly reduced, removal of an established cover, albeit abnormal, can lead to a persistent defect, exposure, and stromal melt risking perforation.
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It is important to determine the clock hours of surviving limbus. If less than 3 clock hours of limbus survive, the strategy of SSCE may need to be modified such that it aims to achieve only visual axis cover with normal epithelium, rather than trying to establish normal cover for the entire cornea. There is a theoretical risk of “stretching the surviving limbus too far.” Extensive SSCE may provide a good result in the short term, but eventually could lead to stem cell exhaustion.
Involvement of the visual axis invariably affects vision, and SSCE is certainly an option to be considered. If, however, the visual axis is not involved and vision is reasonable, one may consider no intervention, only observation over the long term. Studies have shown that corneal and conjunctival epithelial phenotypes can coexist on the corneal surface over prolonged periods of time.13 At times, however, the patient’s symptoms may dictate intervention. Recurrent erosions and filamentary keratitis are the common associations when SSCE may be considered, even if the visual axis is not involved.
Preoperative Considerations
The preoperative workup of a patient for SSCE involves asking the following questions:
1.What is the extent of conjunctivalization of the cornea?
2.How many clock hours of the limbus are involved?
3.Is the visual axis covered with abnormal epithelium?
4.Is the patient symptomatic?
Examination to determine the tear function, corneal sensation, and thickness of the underlying stroma should also be carried out.
The extent of conjunctivalization of the cornea is determined by clinical examination. Instillation of a drop of 2% fluorescein will highlight the abnormal epithelium with a green fluorescence in blue light. The abnormal epithelium shows a stippled staining pattern and may also show filaments and small erosions. Another key clinical sign is late fluorescein staining of abnormal epithelium. This dull green appearance occurs a few minutes after instillation and is to be differentiated from the immediate bright green positive stain of an epithelial defect. The demarcation between abnormal and normal (limbus derived) epithelium is readily identified by the presence of tiny “protrusions” or “buds” of corneal epithelium all along the line of contact of the two epithelial phenotypes. Pooling of dye is also seen along this line of contact, since the abnormal epithelial sheet is thinner than the adjacent healthy normal corneal epithelium (Figures 14.2 and 14.3). Impression cytology helps to identify goblet cells, and confirm the conjunctival nature of the abnormal epithelium.
Surgical Technique
The surgical technique is a superficial mechanical debridement of the abnormal epithelium maintaining, as far as possible, the integrity of the underlying stroma.13 When describing the procedure to the patient, the word “scraping” should be avoided. The alternative of “brushing off” the abnormal cells is more acceptable. Patients should be forewarned about the pain that may be experienced in the first 24 to 48 hours postoperatively.
The eye is first anaesthetized with a topical anaesthetic agent. A drop of 2% fluorescein is instilled immediately before the procedure. At the slit-lamp, the abnormal epithelium is gently brushed or peeled off using a surgical blade or crescent knife. An assistant may be required to hold the lids apart, or a wire speculum may be inserted. Usually, however, the surgeon can manage alone. In established cases of conjunctivalization of the cornea, it is important to include the edge of the existing corneal epithelial sheet, i.e., the removal should extend a millimeter beyond the contact line into normal corneal epithelium (Figure 14.4). After initial removal of the bulk of the epithelium with a surgical instrument, the denuded surface is wiped firmly with a dry absorbent surgical sponge. When more than 3 clock hours of normal limbus are preserved, the entire corneal area with abnormal epithelium, the corresponding limbus, and the adjacent conjunctiva for approximately 3 to 5 mm, are denuded. When less than 3 clock hours of limbus is present, only an area corresponding to the pupillary aperture, to include the visual axis, is denuded.
When SSCE is used as a preventive measure, as after limbal transplantation, denudation of conjunctival epithelium is carried out when it approaches to within a
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Figure 14.2. Slit-lamp diffuse view of a fluorescein-stained cornea of a patient with a corneal graft showing a clear demarcation between corneal and conjunctival epithelial phenotypes. The conjunctival epithelium shows light staining with fluorescein and blood vessels can be seen extending on the conjunctivalized epithelium. Tiny “buds” of corneal epithelium can be seen along the line of contact between corneal and conjunctival epithelium (arrowheads). The pupillary area is covered by corneal epithelium with is “sustained” by 2 clock hours of intact limbus (between large arrows). The best corrected visual acuity was 6/12. SSCE is not usually necessary in such cases (where visual axis is not involved) ( 10). (Dua HS Brit J Ophthalmol 1998; 82:1408. Reproduced with permission from the BMJ Publishing Group.)
Figure 14.3. Slit-lamp diffuse view of a fluorescein-stained cornea of a patient with a corneal graft showing a clear demarcation between corneal and conjunctival epithelial phenotypes. The pupillary area is covered by conjunctival epithelium. Tiny “buds” of corneal epithelium can be seen along the line of contact between corneal and conjunctival epithelium (arrowheads) ( 10). In such cases, visual acuity is impaired and SSCE is beneficial. (Dua HS
Brit J Ophthalmol 1998; 82:1407. Reproduced with permission from the BMJ Publishing Group.)
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Figure 14.4. (A). Photograph of fluorescein-stained cornea of a patient who had presented several months after a chemical injury, showing a clear demarcation between corneal and conjunctival epithelial phenotypes (arrowheads). The pupillary area is almost entirely covered by conjunctival epithelium. Tiny “buds” of corneal epithelium can be seen along the line of contact between corneal and conjunctival epithelium. The patient’s vision was 3/18 ( 10). (B) The eye after SSCE. All conjunctival epithelium from the corneal surface and limbus was removed ( 10). (C) The eye on day 3 following SSCE. The corneal sheet has covered the pupillary area, but the conjunctival epithelium has encroached on the cornea along the temporal limbus ( 10).
(D) The eye after complete healing. A new line of contact is established between corneal and conjunctival epithelial phenotypes (arrowheads), but the pupillary area is covered by healthy corneal epithelium. The patient’s vision improved to 6/9 ( 10). (Dua HS Brit J Ophthalmol 1998; 82:1410. Reproduced with permission from the BMJ Publishing Group.)
couple of millimeters of the healing corneal epithelium (Figures 14.5 and 14.6). In all cases, a bandage contact lens is inserted after the procedure. In individuals who are apprehensive about the procedure at the slit-lamp, it can be performed under the operating microscope with the patient lying down.
Postoperative Management
Immediately following the procedure, the eye is treated with preservative-free drops of antibiotics, a corticosteroid such as prednisolone acetate 0.5%, and nonsteroidal anti-inflammatory drugs (ketorolac tromethamine 0.5%) as prophylaxis against infection, inflammation, and pain. When more than 50% of the corneal surface is denuded, autologous serum drops may provide added benefit. Nonsteroidal anti-inflammatory drops are discontinued after 2 to 3 days, and the remaining medications are continued until epithelial healing is complete.
Close monitoring of the healing epithelium with regular follow-up every 24 to 48 hours is the key to the success of SSCE. Migration of conjunctival epithelium to-
ward or onto the limbus can be anticipated by close observation of the healing ocular surface and can be prevented by repeating the procedure when required, until corneal epithelial cover for the cornea is reestablished. As mentioned previously, it is not always necessary to aim for coverage of the entire cornea with phenotypic corneal cells. SSCE can be terminated as soon as a reasonable proportion of the cornea, including the visual axis, is covered by corneal epithelial cells.21
SSCE and the principle of preventing conjunctival epithelium from encroaching on the corneal surface is essential in establishing appropriate epithelial cover for the corneal surface during epithelial wound healing, and particularly following limbal transplantation. It must be remembered, however, that conjunctival epithelial cover is better than no epithelial cover. Hence, in severe ocular surface injury, when the entire limbus is affected or involved, it is prudent to allow the conjunctival epithelium to cover the cornea. This situation can be maintained until the acute phase settles and appropriate surgical intervention can be undertaken with an enhanced chance of success.
Figure 14.5. Photographs of fluorescein-stained ocular surface of recipient eye that had undergone conjunctival limbal autograft. On day 2 following surgery, donor epithelial cells can be seen migrating onto the recipient surface from the explants placed at the 6 o’clock (A) and 12 o’clock (B) positions. Arrows indicate the anterior edge of the explants. On day 4 following surgery, host conjunctival epithelial cells can be seen migrating from the edge (arrows) of the recessed conjunctiva on both the temporal (C) and nasal (D) sides. SSCE of the advancing conjunctival epithelial sheets was carried out with a surgical blade (E), leaving behind the limbal-explant derived expanding corneal epithelial cells (arrows). (F). The circumferentially migrating lim- bal-explant derived corneal epithelial cells have met temporally and nasally. The large corneal epithelial defect healed with corneal cells and the small nasal conjunctival defect healed with conjunctival cells. Healing was complete by day 8. (Dua HS and Azuara-Blanco A Brit J Ophthalmol 2000; 84:275. Reproduced with permission from the BMJ Publishing Group.)
A B
Figure 14.6. (A) Clinical slit-lamp diffuse photograph of eye of patient described in Figure 14.5. The photograph illustrates the large persistent epithelial defect following alkali burn. (B) The same eye following autolimbal transplant and SSCE. The corneal surface is completely derived from (auto)limbal explant corneal epithelial cells. (Dua HS and Azuara-Blanco A Brit J Ophthalmol 2000; 84:276. Reproduced with permission from the BMJ Publishing Group.)
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