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Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva.

Superior limbic keratoconjunctivitis (SLK) is a chronic and recurrent inflammatory disease of the superior tarsal, bulbar and limbal conjunctiva that often responds to topical treatment with silver nitrate. As an alternative treatment in 11 patients (13 eyes), we applied thermal cautery to the inflamed superior bulbar conjunctiva following subconjunctival injection of 2% xylocaine. The overall positive response rate to thermocautery was 73% (8 patients). Of the positive responders, 63% (5 patients) had been considered silver nitrate treatment failures. Keratitis sicca was additionally noted in 55% of the patients studied. Impression cytology of involved superior bulbar conjunctiva was nearly devoid of goblet cells during the acute stage of the disorder. Following successful cauterization, goblet cells returned. Thus, thermocauterization of the superior bulbar conjunctiva appears to be a safe and effective mode of therapy for SLK.

Adult↗

Ocular penetration and bioconversion of prostaglandin F2alpha prodrugs in rabbit cornea and conjunctiva.

The objective of this study was to identify prostaglandin F2alpha (PGF2alpha) prodrugs that have an optimal ocular absorption profile and therefore could be potentially useful for the treatment of glaucoma. Rabbit cornea, conjunctiva, and iris/ciliary body were mounted in a flow-through chamber to evaluate the permeability and bioconversion of PGF2alpha and its prodrugs. The prodrugs tested were PGF2alpha 1-isopropyl, 1,11-lactone, 15-acetyl, 15-pivaloyl, 15-valeryl, and 11,15-dipivaloyl esters. After 4 h in the donor or acceptor compartments, the products and formation of PGF2alpha were analyzed by HPLC. Effects on intraocular pressure and ocular surface hyperemia were also determined. All prodrugs penetrated the rabbit cornea faster than PGF2alpha by 4- to 83-fold. All prodrugs penetrated conjunctiva faster than PGF2alpha, except the 15-acetyl ester prodrug, which was equally permeable. No direct correlation between drug lipophilicity and permeability across the cornea or conjunctiva was apparent. The most metabolically stable prodrug was the 1,11-lactone, followed by the 11,15-dipivaloyl, 15-pivaloyl, 15-acetyl, 1-isopropyl, and the 15-valeryl esters, the latter of which was extensively converted to PGF2alpha. A separation index for various prodrugs was calculated from the ratio of the bioavailable PGF2alpha for ocular hypotension to the bioavailable PGF2alpha for hyperemia. The highest separation index was observed for the 1,11-lactone prodrug (2.33), followed by the 11,15-dipivaloyl ester prodrug (1.80). Thus the 1,11-lactone and 11,15-dipivaloyl ester prodrugs appeared to be superior to the others in providing bioavailable PGF2alpha for ocular hypotension, while minimizing hyperemia. The favorable separation index for these compounds appeared to be due to their metabolic stability at the corneal surface and conjunctiva combined with sufficient bioavailability for ocular hypotension.

Absorption↗

Presence and possible significance of immunohistochemically demonstrable metallothionein expression in pterygium versus pinguecula and normal conjunctiva.

PURPOSE: To investigate metallothionein (MT) expression in pterygium, pinguecula and normal conjunctiva and define its possible significance in this area of the eye. In order to further elucidate the mechanism of MT expression we correlated it with lymphocyte subpopulations (T4, T8), macrophages (CD68), Langerhans' cells (S100) and the proliferation-associated indices (PCNA, Ki67). METHODS: Eighty-five surgically excised pterygia, 15 pingueculae and 20 normal conjunctivae were immunohistochemically studied by the avidin-biotin (ABC) method. A monoclonal antibody (E9) against a conserved epitope of I and II isoforms of MT was used on formalin-fixed, paraffin-embedded tissues. Statistical analysis was performed using the SPSS statistical package. RESULTS: Epithelial MT expression was detected in all 120 cases examined and in most of them both nuclear and cytoplasmic immunoreactivity was present. Nevertheless no statistically significant difference of MT expression was found between the three types of tissue. A statistically significant positive correlation between MT expression and lymphocyte subsets, macrophages and Langerhans' cells was found in pterygium. On the contrary, we did not find any statistical correlation in pinguecula and normal conjunctiva. In all three types of tissues MT expression was also positively correlated with the proliferation-associated indices. CONCLUSION: The data suggest that there is immunohistochemically demonstrable MT expression in the epithelium of pterygium, but also of normal conjunctiva and pinguecula. MT may serve a photoprotective role in this region. In pterygium in particular, the biochemical pathway of MT synthesis seems interestingly to cross the pathways of cell proliferation, inflammation and immune activation.

Adult↗

[Long-term results of autologous conjunctiva-limbus transplantation in pterygium].

BACKGROUND: Conjunctiva-limbus autografting is known as a safe surgical technique for the removal of pterygia, with a low rate of recurrence. However, the long-term effect of this surgical maneuver is not clear. This study now investigates the long-term efficacy of conjunctiva-limbus autografts to prevent pterygium recurrence. METHODS: Conjunctiva-limbus transplants for primary (n = 62) or recurrent (n = 8) pterygia were reevaluated 11 to 83 months after surgery (mean: 44.97 months). Slit-lamp appearance and photomicrographs were studied with respect to the configuration of the transplant and the recurrence of the fibrovascular tissue typical of pterygia. RESULTS: Corneal pterygium recurrence has been observed in 2 cases. Fibrovascular tissue was found at the peripheral transplant-margin in 15 cases, and transplant compression towards the limbal margins were detected in further 7 patients. These conjunctival changes have not been observed during the first postoperative months. CONCLUSIONS: Conjunctiva-limbus autografts in pterygia have excellent efficacy against recurrence within the first few years. The transplant compression and fibrovascular changes within the peripheral conjuctiva seen in this study suggest that recurrencies might, however, develop on the long-term.

Adult↗

[1991 new developments regarding the conjunctiva].

Publications on the subject of conjunctiva in 1991 have been reviewed. Clinical relevant topics have been stressed. In the field of conjunctival affections caused by microorganisms a spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16 were first documented. Chlamydial antibodies cause proliferation of lymphocytes. The peripheral lymphocyte proliferative response to whole chlamydial elementary bodies seems to have a strong correlation between the responses to the Chlamydia trachomatis serotypes B and L1. In the field of impression cytology of the conjunctiva the topographical distribution of ocular surface cells was described. In patients with glaucoma using long-term topical medication, there seem to be significant degrees of conjunctival metaplasia associated with the number of glaucoma medications. These changes in the conjunctival surface may be related to the preservatives in the preparations (benzalkonium compounds). An ultrastructural defect in conjunctiva in recessive dystrophic epidermolysis bullosa may increase the susceptibility of the conjunctiva to minor mechanical trauma. Thus resulting in the bullous and cicatrical changes seen clinically.

Adrenergic beta-Antagonists↗

Cidofovir transport in the pigmented rabbit conjunctiva.

PURPOSE: To characterize cidofovir (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine) transport in the pigmented rabbit conjunctiva and to evaluate the formulation influence on its transport. METHODS: The excised pigmented rabbit conjunctiva was mounted in the modified Ussing chamber. Cidofovir transport was initiated by applying 3H-cidofovir to the donor compartment and assayed by measuring the radioactivity accumulated in the receiver fluid over 180 min. RESULTS: Cidofovir flux in the mucosal-to-serosal direction increased proportionally with drug concentration over the 0.01 to 1 mM range. Cidofovir transport (0.01 mM) at 37 degrees C in the mucosal-to-serosal direction was not significantly different from that in the opposite direction or from that at 4 degrees C. Hypotonicity (80 mOsm/kg), 0.5% EDTA, and 0.0125% benzalkonium chloride increased the apparent permeability coefficient of cidofovir 3, 21, and 49 times, respectively. This was accompanied by a corresponding 43%, 86%, and 96% reduction in the transconjunctival electrical resistance over 180 min. The reduction in transepithelial electrical resistance elicited by hypotonicity was reversible. There was a good correlation between apparent permeability coefficient and the transconjunctival conductance, suggesting that cidofovir may undergo paracellular passive diffusion in the conjunctiva. CONCLUSION: Cidofovir transport in the rabbit conjunctiva may be via paracellular passive diffusion. Formulation changes may improve cidofovir absorption from the conjunctival route.

Animals↗

The conjunctiva and nictitating membrane of the eyelids in some reptilian species: a SEM overview.

The conjunctiva and nictitating membrane of reptilian eyelids have been studied by means of SEM. The whole surface pattern of the eyelids can be subdivided into the centrally positioned A-zone near the rims and the surrounding B-zone, including the fornix conjunctivae. The A-zone is characterized by the presence of epithelial lamellae or similar arranged cellular protrusions. All conjunctival epithelial cells demonstrate protrusions of extent morphological variety. Numerous goblet-cells occur in the B-zone and progressively increase in density in the direction of the fornix conjunctivae and the epithelial cells exhibit decreasing protrusions. The lower eyelid incorporates the discus conjunctivae, a platelike formation. It consists of dense connective tissue in which the collagen fibres stretch out orthogonally in a plywood-like manner. The nictitating membrane can be considered as a conjunctival fold near the rostral angle of the eyelids. Its bulbar surface folds in a perpendicular direction.

Animals↗

Analysis of Ag-presenting cells in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis.

PURPOSE: The aim of this study was to investigate the phenotypes of antigen (Ag) presenting cells (APCs) in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis (EC), which serves as a model for investigation of severe types of human allergic conjunctivitis. METHODS: Brown Norway rats treated by ovalbumin (OVA) were used in this study. To confirm the restriction of MHC class II by OVA-specific T cells, monoclonal Abs against MHC class II were added to the conventional proliferation assay. To evaluate the MHC class II expression in the conjunctiva during the development of EC, an immunohistochemical analysis, either as the single or double staining, was performed. Conjunctival fibroblast cell lines were established from naive rats and the MHC class II expression was evaluated by flow cytometric analysis. To examine the roles of costimulatory molecules, OVA-specific T cells were stimulated with anti-TcR Ab and anti-CD28 Ab and then subjected for Western blotting to evaluate the ERK phosphorylation. Finally, in vivo expression of B7 molecules was examined immunohistochemically. RESULTS: OVA-specific T cells recognized OVA in the context of MHC class II. MHC class II was expressed in conjunctival macrophages but not in fibroblasts. EC induction was accompanied by abundant infiltration of macrophages positive for MHC class II. MHC class II was also expressed in conjunctival epithelial cells by EC induction. Stimulation from CD28 was necessary for ERK phosphorylation. B7-2, but not B7-1, was expressed in the conjunctiva. CONCLUSION: Conjunctival macrophages may represent a major source of APCs for the induction of EC in the conjunctiva.

Animals↗

Non-invasive detection of multinucleated giant cells in the conjunctiva of patients with sarcoidosis by in-vivo confocal microscopy.

AIM: To explore the use of in-vivo confocal microscopy (IVCM) as a potential non-invasive adjunctive tool for diagnosing sarcoidosis. METHODS: Conjunctivae were imaged using confocal microscopy in 10 patients with sarcoidosis and 27 control subjects. We utilized the ASL-1000 Scanning Confocal Microscope (Advanced Scanning Ltd., New Orleans, LA) and the Confoscan 3 (Nidek Co. Ltd., Gamagori, Japan). Two masked observers reviewed the in-vivo confocal images of the conjunctivae in these subjects. One masked observer was experienced in reviewing confocal images. The most striking and obvious feature seen in granulomatous inflammation on confocal microscopy is the presence of multinucleated giant cells (MGCs). RESULTS: Unmasked observation of the scans revealed MGCs in six of the 10 sarcoid patients and no MGCs in the controls. One experienced masked observer found MGCs in five of the 10 patients with sarcoidosis and had no false-positive results (Fisher's exact test, p = 0.001; specificity = 1; sensitivity = 50% for the diagnosis of sarcoidosis and 83% compared to the unmasked observer). The second less-experienced masked observer detected MGCs in three of the 10 patients and three of the 27 controls (11.1% of the controls) (p = 0.186; specificity = 0.89; sensitivity = 30% of all patients with sarcoidosis and 50% compared to the unmasked observer). CONCLUSIONS: The utilization of IVCM to visualize the basic histology and pathology in sarcoidosis of the conjunctiva is novel. Initial results indicate that trained observers can detect MGCs in granulomatous inflammation. The ASL-1000 microscope tends to have better resolution and deeper penetration of the conjunctiva compared with the Confoscan 3.

Adult↗

Metabolism of [des-Gly10, D-Trp6]LHRH ethylamide in the rabbit conjunctiva.

It was the objective of this study to determine whether [des-Gly10, D-Trp6]LHRH ethylamide, an LHRH agonist known as deslorelin, is degraded by the rabbit conjunctiva. Intact conjunctiva was incubated with deslorelin either alone or in the presence of 0.1 mM ouabain, 0.1% 2,4-dinitrophenol, 0.1 mM phosphoramidon, 0.1 mM N-tosyl-L-phenylalanine chloromethylketone (TPCK), 2% EDTA, 1% ZnCl2, 0.1% dithiothreitol (DTT), or 0.1% N-ethylmaleimide (NEM) at 37 degrees C. Furthermore, deslorelin alone was incubated with conjunctiva at 4 degrees C. All incubation solutions were made isotonic, and the pH was adjusted to 5.0. A reversed-phase HPLC was used to analyze supernatants collected at the end of 90 min. Deslorelin metabolism was inhibited at low temperature, as suggested by the disappearance of metabolite peaks at low temperature. Both ouabain and dinitrophenol failed to alter the intact drug remaining in the supernatant, indicating that energy-dependent cellular uptake of deslorelin is unlikely in the conjunctiva. Phosphoramidon- and TPCK- sensitive endopeptidases did not contribute to the observed metabolism, as suggested by the lack of effect of phosphoramidon and TPCK on deslorelin levels. DTT and NEM also failed to affect deslorelin levels. On the other hand, EDTA and ZnCl2 significantly elevated the intact deslorelin levels by 61 and 53%, respectively, and almost completely abolished the metabolite peaks, indicating a possible role for either metaldependent peptidases or metallo-peptidases in the conjunctival metabolism of deslorelin.

2,4-Dinitrophenol↗

Expression of p63 in pterygium and normal conjunctiva.

PURPOSE: The p63 gene has been identified as a marker of epithelial stem cells. Because pterygium may arise through an expansion of the proliferative capacity of the conjunctiva, we sought to document the expression of p63 in normal conjunctiva and pterygium specimens. METHODS: Immunostaining for p63 expression was performed on 10 pairs of pterygium and normal conjunctiva using a monoclonal antibody directed against human p63. RESULTS: Immunopositive reactions were seen in all samples. Levels of p63-positive cells were not statistically different between pterygium and normal conjunctivae (P = 0.7). CONCLUSION: These results strongly support previous studies that indicate that pterygium arises as a result of incorrect control of cellular apoptosis rather than from an increase in proliferative capacity.

Antibodies, Monoclonal↗

In vivo confocal microscopy of normal conjunctiva and conjunctivitis.

PURPOSE: To analyze the appearance of normal conjunctiva and conjunctival inflammation by in vivo confocal microscopy. METHODS: Conjunctiva of 15 normal patients and 21 patients with conjunctivitis including bacterial, papillary, follicular, granulomatous, and cicatrizing disease were analyzed by the Heidelberg retina tomograph (HRTII)/Rostock cornea modul (RCM). RESULTS: Scans of normal bulbar and tarsal conjunctiva corresponded well to the established anatomy except for a prominent, thickened epithelial basement membrane observed by in vivo microscopy. Presumed goblet cells were visible throughout the conjunctival epithelium. Adenoid structures and hair follicles were discernible in the tarsal conjunctiva in vivo. Conjunctival perfusion could be observed directly. Acute and chronic inflammatory cells, conjunctival papillary, and follicular reactions, as well as conjunctival cicatrization, could be discriminated. In a patient with conjunctival granuloma, in vivo confocal microscopy disclosed suture material inside the lesion. CONCLUSION: Confocal microscopy using near-infrared laser light is a useful new tool in the analysis of conjunctival tissue in vivo. It is a valuable aid in the differential diagnosis of conjunctival inflammation and thus may guide therapeutical decisions.

Adult↗

Fibrin sealant for Müller muscle-conjunctiva resection ptosis repair.

PURPOSE: To determine the safety and efficacy of fibrin sealant for use in Müller muscle-conjunctiva resection ptosis repair. METHODS: This was a retrospective review of a consecutive case series. All patients underwent Müller muscle-conjunctiva resection ptosis repair with fibrin sealant used for wound closure. Surgery was performed in a manner similar to a previously described technique, using fibrin tissue sealant rather that suture for wound closure. Postoperative symmetry was defined as MRD1 of each eyelid within 0.5 mm. RESULTS: Müller muscle-conjunctiva resection ptosis repair with fibrin sealant used for wound closure was performed on 53 eyelids of 33 patients. There were 27 female patients and 6 male patients. Twenty patients underwent bilateral ptosis repair and 13 patients underwent unilateral ptosis repair. Average follow-up was 17 weeks (range, 3 to 45 weeks). Mean preoperative MRD1 was 1.22 mm (range, -1.5 to 2.5 mm) in the right upper eyelid and 1.50 mm (range, 0 to 2 mm) in the left upper eyelid. Mean postoperative MRD1 was 3.11 mm (range, 2 to 4.5 mm) in the right upper eyelid and 3.12 mm (range, 1 to 4.5 mm) in the left upper eyelid. Postoperative symmetry was found in 32 of 33 patients (97%). We found no evidence of keratopathy or other complications attributable to the fibrin sealant. CONCLUSIONS: Müller muscle-conjunctiva resection ptosis repair with fibrin sealant used for wound closure may allow for predictable results with few complications and appears to be an acceptable alternative to traditional suture techniques.

Blepharoptosis↗

The lupus band test in oral mucosa, conjunctiva and skin.

The prevalence and clinical significance of subepithelial immunoglobulin and complement deposition (the lupus band) were examined in the uninvolved sun-protected skin of the forearm, the uninvolved sun-protected lip mucosa and sun-protected bulbar conjunctival mucosa in systemic lupus erythematosus (SLE) and chronic cutaneous lupus erythematosus (CCLE). In SLE, linear deposition of an immunoreactant at the BMZ was detected in 32% (6/19) of skin biopsies; 21% (4/19) of lip mucosal biopsies and 42% (5/12) of conjunctival biopsies. There was no significant difference in the sensitivity of the test at different sites in SLE and no correlation between a positive test in skin, lip or conjunctiva and clinical mucosal involvement. In CCLE, linear deposition of an immunoreactant at the BMZ was found in 3% (1/32) of skin biopsies; 3% (1/29) of lip mucosal biopsies and 50% (10/20) of conjunctiva and clinical mucosal involvement. In the conjunctiva, IgG was present in all but one of the biopsies and was the only immunoreactant in 90% (9/10) of positive CCLE biopsies and 60% (3/5) of positive SLE biopsies. In lupus erythematosus immunoreactants may be deposited in the basement membrane zone beneath non-keratinizing mucosal surfaces of the lip and the eye as well as the skin. In CCLE, the test may be positive in conjunctiva when skin and lip are negative.

Adolescent↗

Diffuse reflectance spectra of the palpebral conjunctiva and its utility as a noninvasive indicator of total hemoglobin.

The palpebral conjunctiva is an attractive location to qualitatively examine for the presence of anemia; however, this method of diagnosis has not been shown to be accurate. A spectroscopic examination of the palpebral conjunctiva enables the use of a quantitative parameter as a basis for diagnoses. Visible range diffuse reflectance spectra from the palpebral conjunctiva are examined from 30 patients and hemoglobin levels are extracted from these signatures using both a partial least-squares (PLS) multivariate regression model and a discrete spectral region model. Hemoglobin concentration derived from both these models is compared to an in vitro measurement of hemoglobin. Root mean squared errors of cross validation for the two analytical methods are 0.67 g/dL and 1.07 g/dL, respectively. Conjunctival reflectance spectra coupled with a PLS analysis achieve an enhanced specificity and sensitivity for anemia diagnoses over reported observational studies using the palpebral conjunctiva and achieve improved accuracy to other reported methods of noninvasive hemoglobin measurement.

Anemia↗

Staining of the conjunctiva and conjunctival tear film.

Both the distribution of tear fluid over the conjunctiva and any injury to the conjunctival epithelium can be made visible by instilling a fluorescent solution into the eye and observing with an appropriate combination of excitation and barrier filters. Sulphorhodamine B, which has an orange fluorescence that can be separated from the green natural fluorescence of the ocular tissues, gives a greater contrast than fluorescein. The tear film is seen to cover the surface of the conjunctiva and to be concentrated in its folds. Small circular areas of thin tear film appear transiently in the neighbourhood of the limbus after a blink. Occasional cells stain on the normal conjunctiva, particularly in the interpalpebral area. The density of the staining increases in dry eye conditions. Conjunctival trauma is sensitively revealed by the method, and its healing can be followed. Hard contact lenses are seen to traumatize continually the inferior limbal conjunctiva in symptomless wearers.

Conjunctiva↗

Diquafosol elicits increases in net Cl- transport through P2Y2 receptor stimulation in rabbit conjunctiva.

The purpose of the present study was to understand the mechanisms of action of diquafosol, a stable derivative of uridine 5'-triphosphate, on Cl(-) transport across the isolated rabbit conjunctiva. Rabbit conjunctivas were isolated and mounted in a modified Ussing chamber. Under short-circuit conditions, the effects were determined of mucosal (tear) side diquafosol application on the short-circuit current (Isc). Diquafosol rapidly and dose-dependently increased the Isc at concentrations ranging from 0.1 to 968 microM when added to the mucosal side of the conjunctiva. In the absence of the serosal Cl(-), the Isc induced by 10 microM diquafosol was substantially reduced. On the contrary, in the absence of mucosal side Na(+), the diquafosol-induced increases in Isc were unchanged. Following 45-min preincubation, the P2Y(2) antagonist suramin inhibited the diquafosol-induced increases in the Isc whereas the P2Y(1) antagonist pyridoxal-phosphate-6-azophenyl-2'4'-disulfonic acid had no effect. These studies suggest that diquafosol stimulates net Cl(-) secretion from the serosal to the mucosal side via stimulation of P2Y(2) receptors in the rabbit conjunctiva.

Animals↗

Molluscum contagiosum of the palpebral conjunctiva. Report of a case.

A molluscum contagiosum nodule, situated at the palpebral conjunctiva of the left lower eyelid at the level of the marginal and tarsal conjunctiva, was observed in a 53-year-old male. A mild follicular conjunctivitis was present, except in a zone immediately below the molluscum. On the corresponding site of this molluscum at the bulbar conjunctiva, the limbus and the cornea, no follicles, epithelial keratitis nor erosions were seen. Clinical diagnosis in atypically situated mollusca can be difficult. Cytological studies in these cases are very helpful. Alcohol-carbowax fixated and Papanicolau stained preparations proved to be very satisfactory for cytological examination. It has never been reported that a molluscum, situated in the palpebral conjunctiva, disappeared spontaneously.

Conjunctiva↗