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PURPOSE: The conjunctival epithelium performs an important role in the homeostasis and integrity of the eye. To protect the integrity of the ocular surface, these cells must be replaced from locally concentrated or randomly distributed foci of stem cells. These slow-cycling stem cells produce transient amplifying cells that undergo further divisions before becoming mature conjunctival epithelial cells. In the current study, the source of palpebral conjunctival cells was determined. METHODS: Adult rabbits were injected intraperitoneally with bromodeoxyuridine (BrdU) at a dose of 50 mg/kg body weight and killed after 1, 3, 5, and 7 days and 2 months. The orbital contents and eyelids were exenterated en bloc, frozen to maintain the orientation between the eyelids and globe, and sectioned in a parasagittal plane. Random midglobe sections were stained for the presence of proliferating cell nuclear antigen (PCNA). Additional sections were immunostained to detect BrdU-labeled conjunctival epithelial cells. BrdU-positive cells were counted in a series of 0.4-mm zones from the mucocutaneous junction of the eyelid, through the fornix and bulbar conjunctiva. A second set of rabbits received daily injections of BrdU for 2 or 4 weeks followed by a 2-month BrdU-free period before death and processing. RESULTS: In all eyelid sections examined, there was a focus of PCNA-positive cells in the mucocutaneous junction and a few scattered PCNA-positive cells along the length of the palpebral conjunctiva toward the fornix. In both the upper and lower eyelids, the peak concentration of BrdU-labeled cells/0.4-mm zone was located at progressively greater distances from the mucocutaneous junction in the animals killed at 1, 3, and 5 days respectively and was unidentifiable by 7 days. A focus of BrdU-labeled conjunctival cells remained within 1 to 2 mm of the mucocutaneous junction at all postinjection intervals. These were always found within one cell height of the basement membrane in the basal layer of the epithelium. In the long-term studies, BrdU-labeled nuclei were retained at the mucocutaneous junction. CONCLUSIONS: The mucocutaneous junction of the conjunctival epithelium is a source of actively dividing transient amplifying cells that migrate toward the fornix at a rate of approximately 1.7 mm/d with a transit time of approximately 6 days. Long-term retention of label at the mucocutaneous junction indicates that slow-cycling stem cells are present at this location. It appears that most palpebral conjunctival epithelial stem cells are located near the mucocutaneous junction. These results are not necessarily at variance with previous studies, but they diminish the relative importance of the forniceal region in palpebral conjunctival homeostasis. The mucocutaneous junction may provide a therapeutically significant source of replacement conjunctival cells.

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PURPOSE: The conjunctival epithelium performs an important role in the homeostasis and integrity of the eye. These cells need to be replaced in order to protect the integrity of the ocular surface. Epithelial cells are replaced from slow cycling stem cells which in turn produce transient amplifying cells that undergo further divisions before becoming mature conjunctival epithelial cells. The natural history of the bulbar palpebral conjunctival cells has not been previously described. METHODS: A single injection of bromodeoxyuridine (brdU), a thymidine analogue, was administered intraperitoneally to adult rabbits at a concentration of 50 mg/kg body weight. The rabbits were sacrificed at 1, 3, 5, and 7 days following the injections. The orbital contents including the eyelids were exenerated en bloc, frozen in a manner that maintained the orientation and continuity between the eyelids and globe and sectioned in a parasagittal plane. The tissue was stained immunohistochemically to detect brdU labeled conjunctival epithelial cells. The brdU-positive epithelial cells were counted in a series of 0.4 mm zones starting at the mucocutaneous junction of the eyelid and progressing through the fornix and bulbar conjunctiva. Rabbit eyelids and human eyelid surgical specimens were stained for cyclin D1, a marker for cells that are in the G1 phase of the cell cycle. RESULTS: In both the upper and lower eyelids, the peak number of brdU labeled cells/0.4 mm zone was located at progressively greater distances from the mucocutaneous junction in the animals sacrificed at 1, 3 and 5 days respectively, and gone by 7 days. A focus of brdU-labeled conjunctival cells remained within 1-2 mm of the mucocutaneous junction at all post-injection intervals. Foci of cyclin 1-positive cells were found almost exclusively near the mucocutaneous junction, but not in the fornix. CONCLUSIONS: The mucocutaneous junction of the conjunctival epithelium is a source of actively dividing transient amplifying cells that migrate toward the fornix at a rate of about 1.7 mm/day as replacement conjunctiva so that at least some conjunctival epithelial stem cells must be located near the mucocutaneous junction. The presence of cyclin D1 staining cells at the mucocutaneous junction supports this view. These results are not necessarily at variance with previous studies, but they do diminish the relative importance assigned the forniceal region in palpabral conjunctival homeostasis. Moreover, the mucocutaneous junction might provide a therapeutically significant source of replacement conjunctival cells. The transit time of conjunctival epithelial cells is about 6 days.

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Topical cyclosporin A was used in the management of 43 patients with a variety of anterior segment inflammatory disorders that had failed corticosteroid treatment. Treatment with topical cyclosporin A ranged from 1 week to 43 months, with a mean treatment period of 13 months. Thirty-five patients (81%) with disorders including high-risk keratoplasty, atopic and vernal keratoconjunctivitis, ligneous conjunctivitis, ulcerative keratitis, and Mooren's ulcer had a beneficial result, with resolution, reduction, or prevention of inflammation. Six patients (14%) with scleritis, ocular cicatricial pemphigoid, or endothelitis showed no clinical improvement. Two patients (5%) had significant ocular discomfort, and the drug had to be discontinued in them. None of the other patients developed local side effects. Twenty-seven of these patients were followed with serial cyclosporin A blood levels and serum creatinine. None of these patients developed measurable drug blood levels or renal toxicity.

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We reviewed the pattern of astigmatism after penetrating keratoplasty and transsclerally sutured posterior chamber lens (TSPCL) placement in 73 patients. Thirty-five patients (48%) had an axis of astigmatism oriented perpendicularly to the haptics of the TSPCL. Twenty-seven patients (37%) had an orientation of astigmatism that was in the same meridian of the haptics of the TSPCL. Eleven patients (15%) had an axis of astigmatism oriented obliquely to the meridian of the haptics of the TSPCL. The distance the haptic fixation sutures were placed behind the limbus appeared to be correlated with the orientation of astigmatism. Patients having the lens fixated within 0.75 mm of the limbus were more likely to have astigmatism oriented perpendicular to the meridian of the haptics of the posterior chamber lens in the early postoperative period. Patients having the lens fixated 2-3 mm posterior to the limbus were more likely to have astigmatism oriented in the same meridian as the haptics of the posterior chamber lens in the early postoperative period. In an eye bank model of TSPCLs during penetrating keratoplasty, the placement of a posterior chamber lens with haptics fixated within 0.75 mm of the limbus significantly widens the recipient bed an average of 0.3 mm in the meridian of the haptics of lens placement (p = 0.02). When the posterior chamber lens haptics were fixated 3 mm posterior to the limbus, the recipient bed was significantly narrowed in the meridian of lens placement an average of 0.2 mm (p = 0.02). It appears that the TSPCLs may have an effect on early postkeratoplasty astigmatism by distorting the corneal wound at the time of keratoplasty.

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Cells and tissues of the anterior uvea and aqueous humor express activities which inhibit immune responses. These activities include soluble factors such as TGF-beta and uncharacterized cell surface interactions. Relatively little is known regarding the immunologic activities of corneal endothelium, despite its potentially important role in contributing to the immune privilege of the anterior chamber and the high success rate of corneal transplantation. In this report, in vitro studies of cultured rat corneal endothelial (CE) cells were done using S-antigen-specific LEW rat T cell lines, or S-antigen-specific T cell hybridomas, to examine the immunologic capabilities of CE cells. Monolayers of LEW rat CE cells were unable to present antigen or a mitogen, Con A, to T cell lines or hybridomas as assessed by the lack of a proliferative response or IL-2 secretion. Furthermore, the CE cells exerted a potent inhibitory effect when added to in vitro proliferation assays of T cell lines stimulated with antigen or Con A. When T cells were preactivated on conventional antigen presenting cells and then transferred to wells containing CE cells, their proliferation was not inhibited. Although CE cells inhibited activation of T cell lines and hybridomas, they did not inhibit the growth of T cell hybridomas or CTLL cells, nor did the CE cells adversely affect the viability of resting T cells cultured on CE monolayers. The inhibitory effect was reversible as preincubation of T cells on CE cells for up to 6 days followed by washes restored T cell responsiveness when assayed on splenocytes. The inability to stimulate proliferative responses was not affected by preincubation of the CE cells with lymphokines which increase MHC antigen expression. The inhibition observed in these assays was not MHC-restricted as CE cells from both LEW and BN rats were equally inhibitory. CE cells from rabbits and cats were also potent inhibitors of T cell activation, suggesting that the mechanism is evolutionarily conserved. The mechanism of inhibition of CE cells is unknown at this time.

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We reviewed the outcome in 115 patients who underwent penetrating keratoplasty and transscleral fixation of a posterior chamber lens. One patient died soon after surgical procedures, and nine patients were lost to follow-up, leaving a cohort of 105 patients. Mean follow-up time was 26.8 months (range, six to 43 months). Visual acuity of 20/40 or better was found in 29 patients (27.6%) and 20/50 to 20/200 in 37 patients (35.2%). Reasons for poor visual outcome included cystoid macular edema in ten patients (9.5%), age-related macular degeneration in six patients (5.7%), and retinal detachment in four patients (3.8%). None of the patients developed lens decentration. There were no instances of hyphema and only one patient had a perioperative limited suprachoroidal hemorrhage. New-onset increase in intraocular pressure developed in 20 of 66 patients (30.3%). Analysis of the 39 patients with preoperative increase in intraocular pressure that required medical treatment demonstrated an improvement in 13 patients (33.3%), worsening in 12 patients (30.8%), and unchanged status in 14 patients (35.9%). The exposed haptic suture was covered by using one of the following three alternative methods: a conjunctival flap, a scleral flap, or a corneal tissue button. Exposure of the haptic suture through the conjunctiva was a complication in 21 patients (20%). Of these 16 (76.1%) occurred in the group with a conjunctival covering, five (23.8%) occurred in the group with a scleral flap, and none occurred in the corneal tissue button group. This study demonstrated that transscleral fixation of a posterior chamber lens is a viable option in the treatment of patients undergoing penetrating keratoplasty and intraocular lens implantation with absent capsular support.

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