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PubMed1997

Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera.

PURPOSE: To characterize quantitatively the paracellular permeation routes in rabbit cornea, conjunctiva, and sclera using polyethylene glycol (PEG) oligomers. METHODS: Corneal, conjunctival, and scleral tissues from New Zealand white rabbits were tested individually in a modified two-chamber Ussing apparatus with the mixture of PEGs with mean molecular weights 200, 400, 600, and 1000 in glutathione bicarbonated Ringer's solution buffer on the donor side of the chamber. The samples and standards were analyzed with high-performance liquid chromatography-thermospray mass spectrometry method. The pore sizes and the pore densities of the corneal and conjunctival epithelia were calculated using an effusion-like approach. RESULTS: The conjunctival and scleral tissues were 15 to 25 times more permeable than the cornea and the molecular size affected the conjunctival permeability less than that of the cornea. The palpebral and bulbar conjunctivas had equal permeabilities. The scleral permeability was approximately half of that in the conjunctiva and approximately 10 times more than in the cornea. The conjunctival epithelia had 2 times larger pores and 16 times higher pore density than the cornea. The total paracellular space in the conjunctiva was estimated to be 230 times greater than that in the cornea. CONCLUSIONS: The conjunctival epithelium, due to its higher membrane permeability and larger absorptive and intercellular space surface areas, is the most viable route for ocular delivery of peptides and oligonucleotides.

Absorption↗
PubMed1984

Mucoepidermoid carcinoma of the conjunctiva.

A 73-year-old man had a limbal nodule that, on histopathologic examination, proved to be mucoepidermoid carcinoma of the conjunctiva. Despite radiation therapy and extensive corneoscleral lamellar resection, widespread invasion of the lids and orbit ultimately led to exenteration. Although mucoepidermoid carcinoma of the conjunctiva resembles squamous cell carcinoma clinically and histopathologically, it pursues a more rapid and destructive clinical course. Intraepithelial invasion often leads to tumor involvement of conjunctiva and skin that seem normal on clinical examination. Special stains and a high level of suspicion are required for diagnosis of mucoepidermoid carcinoma of the conjunctiva, and proper initial management demands more aggressive surgical resection than is usually indicated for squamous cell carcinoma.

Aged↗
PubMed2005

The immunization protocol determines whether endogenous interferon-gamma suppresses the infiltration of eosinophils into the conjunctiva.

BACKGROUND: Studies with interferon-gamma knockout (GKO) mice showed that endogenous IFN-gamma suppresses the infiltration of inflammatory cells into the conjunctiva. To examine whether this phenomenon is universally true, we induced conjunctival inflammation by four different immunization protocols. METHODS: Both wild type (WT) and GKO mice (C57BL/6 background) were immunized with ragweed (RW) in aluminum hydroxide (alum). Two different immunization protocols were used: either the emulsion was injected into only the left hind footpad or it was also injected into the tail base (50 microg RW in 2mg alum per injection site). In addition, to compare the effects of the immunization dose of RW and the immunization site, 100 microg RW in 2mg alum was injected into only the left hind footpad and 25 microg RW in 2mg alum per injection site was injected into both the left hind footpad and the tail base. Ten days later, the mice were challenged with 2mg RW in 10 microl PBS. Twenty-four hours later, the conjunctivas were analyzed histologically, and the cellular and humoral immune responses in the spleens and sera were determined, respectively. RESULTS: Similar to a previous report, GKO mice showed significant eosinophilic infiltration into the conjunctiva after the footpad only injection of 50 microg RW. However, injection of 50 microg RW per injection site into the footpad plus the tail base resulted in comparable levels of eosinophilic infiltration in WT and GKO mice. On the contrary, either immunization of 100 microg RW in 2mg alum into only the left hind footpad or that of 25 microg RW in 2mg alum into both the left hind footpad and the tail base induced significant infiltration of eosinophils into the conjunctiva of GKO mice, compared to WT mice. CONCLUSIONS: These results show that the immunization protocol employed has a marked effect on the severity of eosinophilic infiltration. These observations indicate that in interpreting experimental results in the study of EC, the immunization protocol employed must be considered.

Allergens↗
PubMedDate not supplied

Detection of specific Mycoplasma conjunctivae antibodies in the sera of sheep with infectious keratoconjunctivitis.

The serological cross reactions between Mycoplasma conjunctivae, the etiological agent of infectious keratoconjunctivitis (IKC), and the antigenetically and phylogenetically closely related Mycoplasma ovipneumoniae, which is often found in sheep, were analysed. Cross reacting antigens were identified using sera from sheep with IKC and from sheep of herds known to be free of IKC, as well as rabbit hyperimmune serum specific to the two Mycoplasma species. Cross reactions were predominantly due to the strongly antigenic proteins of 42 kDa and 83 kDa. Serospecific antigens of M. conjunctivae could be separated from cross-reacting antigens by the extraction of Tween 20-soluble membrane proteins. The Tween 20-extracted proteins of the M. conjunctivae strain HRC/581T were used for the development of an indirect ELISA test. This ELISA test was shown to be a useful serological method for the diagnosis of M. conjunctivae infections and to identify infected sheep herds.

Animals↗
PubMed1995

[Lymphatic congestion of the conjunctiva after pre-auricular lymph node excision].

PATIENT: A 68-year-old woman presented with massive congestion of lymphatic vessels of temporal inferior conjunctiva two months after extirpation of the parotic gland for an aciniform epithelioma on the same side. Clinical findings of the right and left eye were unremarkable otherwise. The congestion resolved spontaneously. METHODS: Patent Blue 2.5% was injected into the subconjunctiva in 5 mm distance of the limbus. The superior conjunctiva revealed a normal circular pattern of lymphatic vessels. In the temporal inferior conjunctiva massively congested lymphtic vessels could be demonstrated. This area is normally drained by the regional lymphnodes now interrupted by the surgery. CONCLUSION: The individual anatomy of the lymphatic vessels may be of significance also in filtering surgery. Especially radial conjunctival cuts may interrupt the lymphatic vessels. The regional lymphatic drainage from the temporal inferior conjunctiva is blocked by massive surgery of the parotic gland.

Aged↗
PubMed1988

The occurrence of Mycoplasma conjunctivae in The Netherlands and its association with infectious keratoconjunctivitis in sheep and goats.

The occurrence of Mycoplasma conjunctivae in the Netherlands is reported for the first time. M. conjunctivae was detected in all five sheep flocks examined with clinical signs of infectious keratoconjunctivitis (IKC) and in none of five sheep flocks without these clinical signs. These observations suggest a primary aetiological role of this organism in IKC in the Netherlands. M. conjunctivae was also detected on a goat farm with clinical signs of IKC. Experiences in culturing this organism are reported. From each sheep flock at least one strain was isolated and characterised in more detail. All Dutch strains, including two strains of M. conjunctivae isolated from sheep milk, as well as type strain HRC 581, formed film and spots which is in contrast with the description of the type strain. All strains, including the type strain, failed to grow in an anaerobic atmosphere generated by GasPak anaerobic system (BBL). Moraxella ovis was detected in nearly all flocks and was apparently not associated with IKC. Mycoplasma arginini was also isolated from ovine eyes.

Animals↗
PubMed2006

Conjunctival malignant melanoma-associated pseudomelanoma of the apposing tarsal conjunctiva.

PURPOSE: To describe a case of conjunctival malignant melanoma associated with pseudomelanomatous alteration of the apposing tarsal conjunctiva. METHODS: A 93-year-old woman presented with an elevated, pigmented mass on her superior bulbar conjunctiva. The tumor was associated with increased pigmentation of the apposing superior tarsal conjunctiva. An excisional biopsy of the epibulbar melanoma and pigmented tarsal conjunctiva was performed. RESULTS: Histopathologic evaluation of the epibulbar tumor revealed epithelioid melanocytes diagnostic of malignant melanoma. Histopathologic evaluation of the pigmented tarsal lesion showed large areas of ulceration and foci of granulation tissue composed of neovascular sprouts arising in the background of a loose connective tissue, with a moderate chronic inflammatory infiltrate. The infiltrate was composed of mature lymphocytes, plasma cells, and scattered histiocytes. Densely packed intracytoplasmic, brown pigment granules that stained positive with HMB 45 were found, attesting to adjacent melanocytes' releasing melanin-laden granules. There was no evidence of malignancy in the pigmented tarsal specimen. CONCLUSION: Noncontiguous pigmented conjunctival tumor can be found in apposition to an epibulbar melanoma. Although a limited biopsy could be considered, only a complete resection and histopathologic evaluation can determine whether the entire lesion is free of malignant melanoma.

Aged, 80 and over↗
PubMed2003

Characterization of LppS, an adhesin of Mycoplasma conjunctivae.

A serine-rich membrane protein named LppS from Mycoplasma conjunctivae, the aetiological agent of infectious keratoconjunctivitis (IKC) of domestic and wild Caprinae, was characterized. Gene cloning and sequence analysis of the lppS gene revealed that it encoded a membrane protein precursor. The protein had a typical signal sequence and a signal peptidase II cleavage site followed by a cysteine residue representing a potential acylation site. The mature LppS protein had an apparent molecular mass of 150 kDa and was found in the detergent-associated fraction of Tween 20 extracted M. conjunctivae proteins. It possessed a serine-rich domain of 41 aa with 37 (90.2 %) serine residues. Twenty-seven of these serine residues were contiguous. The protein adhered to lamb joint synovial cells. Using an in vitro adhesion model, Fab fragments from IgG directed against recombinant purified LppS were shown to specifically inhibit adhesion of M. conjunctivae to lamb cells. Thus, LppS is likely to be an adhesin of M. conjunctivae that may play an important role in the pathogenesis of IKC.

Adhesins, Bacterial↗
PubMed1997

Adenoid squamous carcinoma of the conjunctiva--a clinicopathological study of 14 cases.

AIMS: In order to determine the clinicopathological features and optimum management of a series of patients with adenoid squamous cell carcinoma of the conjunctiva, all cases of squamous cell carcinoma (SCC) of the conjunctiva and cornea on file in the registry of the ophthalmic pathology at the Armed Forces Institute of Pathology were reviewed. METHODS: On histopathological examination, a predominant adenoid or pseudoglandular pattern due to islands of neoplastic squamous or epidermoid cells surrounded by acantholytic cells was necessary for inclusion in the study. Histochemical and transmission electron microscopic studies (TEM) were performed. Clinical features of all the patients were extracted from the charts. RESULTS: The anatomical location of the 14 tumours was corneoscleral limbus (seven patients) and bulbar conjunctiva (seven patients). Eight patients presented with inflammatory signs and irritation (red eye, tearing, foreign body sensation), while six patients developed a slowly growing, painless mass. Histochemical and TEM studies showed extracellular hyaluronic acid and no intracellular mucin. Of the two patients initially treated by enucleation, one was free of disease after 2 years while the second patient had recurrence in the socket and died of brain metastases despite wide orbital excision and radiotherapy. All five patients with recurrent tumours initially had irritated red eyes and two required enucleation. One such patient, after orbital exenteration and radiotherapy, died of unrelated disease. CONCLUSION: The study demonstrates that adenoid SCC of the conjunctiva often presents with inflammatory signs. The tumour is locally aggressive and may metastasize and should, therefore, be histopathologically differentiated from the less aggressive conventional squamous cell carcinoma. Optimum treatment includes wide excision with documented histological clear margins of resection on permanent sections and frequent follow up.

Adult↗
PubMed2001

Malignant melanoma of the palpebral conjunctiva in a captive fallow deer.

A case of malignant melanoma in the conjunctiva of the eyelid of a captive 13-yr-old female fallow deer (Dama dama) was studied. The black tumor that protruded to the palpebral conjunctiva of the right lower eyelid consisted of an infiltrative growth of melanin-containing neoplastic cells with marked cytological atypia. The tumor involved the conjunctiva of the right lower eyelid and infiltrated to the conjunctival epithelial layer, but did not reach the palpebral skin. Numerous mitotic figures and lymphatic invasions were observed. This is a very rare case of a malignant melanoma arising from the palpebral conjunctiva in a wild ruminant.

Animals↗
PubMed1999

[Prognostic factors in malignant melanoma of the conjunctiva. An anatomo-clinical study of 56 patients].

UNLABELLED: We have reviewed a serie of 56 patients treated in our Institute for malignant melanoma of the conjunctiva between 1980 and 1992. We selected cases where histology had been reviewed. PATIENTS AND METHOD: The median follow up is 96 months. The age varies from 13 to 88 years with a mean age of 56 years. There were 22 men and 34 females. In 29 cases (51%) the melanoma appeared de novo, ten cases (17%) it derived from a naevus and in 14 cases (25%) on a precancerous melanosis. The tumour was localized at the limbus and bulbar conjunctiva in 57% of cases. The mean diameter was 6.1 mm and the mean thickness was 2.3 mm. The treatment consisted in surgical excision of the tumour followed by external beam radiothérapy in 49 cases. Histological examination showed invasion of the chorion in 44 cases (78%) and of the sclera in 6 cases (1%). RESULTS: 38 patients are alive and 29 without disease. 2 with disease, 7 lost follow-up. 18 patients died (32%) and among them 14 (25%) died of metastatic disease. 22 patients (39%) have presented local recurrence and among them 10 have had multiple recurrences. The mean delay for recurrence was 56 months. The overall survival was 77% at 5 years and 64% at 10 years. Tumours appeared de novo have a worse prognosis. If we consider the localization tumour located at the limbus or on bulbar conjunctiva have less metastasis. CONCLUSION: Malignant melanoma of conjunctiva is a tumour that can frequently recur. Metastasis are not infrequent and follow up must be prolonged.

Adolescent↗
PubMed1999

[Squamous metaplasia of bulbar conjunctiva in the course of long-term topical antiglaucoma therapy].

PURPOSE: The aim of this study was to determine how long-term topical antiglaucoma treatment affects the bulbar conjunctiva. MATERIAL AND METHODS: 59 glaucoma patients and 30 healthy people were examined by the use of impression cytology for changes in bulbar conjunctiva. Patients with glaucoma were on stable regimen of one or two antiglaucoma drugs for a minimum 1 year. RESULTS: Squamous metaplasia of bulbar conjunctiva was found in 26.6% of patients treated with beta-blocker alone for 1-2 years and in 42.8% of patients treated with this drug for longer than 2 years. Similar changes were found in patients treated with beta-blocker with miotic--in 60% people who were on stable regimen for 1-2 years and in 70% treated longer than 2 years. No conjunctival changes were observed in healthy people. CONCLUSIONS: Long-term topical antiglaucoma medication may produce squamous metaplasia of bulbar conjunctiva.

Administration, Topical↗
PubMed2002

Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine.

OBJECTIVES: To compare conjunctival goblet cell numbers as well as epithelial turnover in patients with non-Sjögren syndrome--associated keratoconjunctivitis sicca (NSS-KCS) and those with SS-KCS before and after 6 months of treatment with topical cyclosporine A (CsA) ophthalmic emulsion. METHODS: Conjunctival biopsy specimens from 16 patients with NSS-KCS and 12 with SS-KCS were obtained at baseline and after 6 months' therapy with CsA or vehicle alone. Conjunctival biopsy specimens were also obtained from 11 normal subjects. Periodic acid--Schiff staining determined the number of goblet cells present. Immunofluorescence microscopy for Ki-67 localization was used to evaluate the number of actively cycling cells. RESULTS: Periodic acid--Schiff staining showed fewer goblet cells at baseline in both dry eye populations when compared with normal subjects (P<.001). After 6 months of CsA treatment, conjunctival biopsy specimens of both NSS-KCS and SS-KCS groups revealed an increase in goblet cells compared with baseline (P<.05). More Ki-67--positive cells were observed in NSS-KCS conjunctiva at baseline than in normal conjunctiva (P<.05) whereas numbers of these cells in SS-KCS conjunctiva were similar to normal at baseline. After 6 months of CsA treatment, conjunctival biopsy specimens of NSS-KCS revealed a decrease in Ki-67--labeled cells compared with baseline (P<.001). In contrast, no substantial change was observed for CsA treatment in patients with SS-KCS. CONCLUSIONS: Treatment of dry eye syndrome for 6 months with topical CsA resulted in an increase in goblet cell numbers in patients with NSS-KCS and SS-KCS and a decrease in epithelial turnover in those with NSS-KCS. Reducing ocular surface inflammation might have an effect on the proliferative activity of the epithelium.

Aged↗
PubMed1992

The effect of indomethacin on prostaglandin E2 in human cornea and conjunctiva.

We studied the inhibitory effect of topical 1% indomethacin aqueous suspension on prostaglandin E2 in 20 conjunctivae extracted during cataract surgery and 16 corneas extracted during penetrating keratoplasty. Thirty minutes before each surgical procedure, indomethacin or placebo (0.9% sodium chloride solution) was instilled into the eye to be operated on in a masked fashion for conjunctiva and selectively for cornea. The excised corneal buttons and conjunctival tissue were homogenized and assayed for prostaglandin E2 concentration using radioimmunoassay. The levels of prostaglandin E2 in the conjunctiva significantly decreased (P less than .0033) after administration of indomethacin (203.7 +/- 219.5 pg/mg) compared with the placebo-treated tissues (849.8 +/- 564.1 pg/mg). The levels of prostaglandin E2 in the corneas significantly decreased (P less than .0157) after administration of indomethacin (522.5 +/- 570.2 pg in the cornea) compared with the placebo-treated tissues (1636.3 +/- 1344.1 pg in the cornea). Indomethacin may serve as a potent anti-inflammatory agent in conjunctival and corneal inflammatory disorders.

Adolescent↗
PubMed1996

Reversal of topical antiglaucoma medication effects on the conjunctiva.

OBJECTIVE: To determine whether the adverse effects of antiglaucoma medications could be reversed before filtration surgery, potentially reducing the risk of subsequent failure. METHODS: One month before surgery, 30 patients who were receiving multiple antiglaucoma medications underwent an inferior bulbar conjunctival biopsy, ceased using sympathomimetic drops, and began treatment with topical corticosteroid, (1% fluorometholone four times daily). At the time of surgery two conjunctival biopsy specimens were obtained, one from the operation site (superior bulbar region), and one from the inferior bulbar region. The biopsy specimens were quantitatively analyzed by light microscopy. In addition, the outcome of first trabeculectomy for 16 of these patients was compared with that of 16 matched patients who had not undergone an altered preoperative regimen of topical therapy. RESULTS: During a 1-month period a notable decrease occurred in the number of fibroblasts and inflammatory cells throughout the conjunctiva. Inferior bulbar conjunctiva was found to be representative of superior bulbar conjunctiva with respect to these changes. Furthermore, evidence comparing the matched patients suggested that the altered preoperative regimen may have improved the success rate of trabeculectomy. CONCLUSIONS: The preoperative regimen used reversed the adverse conjunctival effect of topical medication. The regimen may be of clinical benefit in improving the success rate of trabeculectomy.

Administration, Topical↗
PubMed1976

Mucoepidermoid carcinoma of the conjunctiva: a clinicopathologic study of five cases.

Five patients with mucoepidermoid carcinoma of the conjunctiva were studied. The tumors were located close to the limbus in three patients, in the bulbar conjunctiva in one, and in the lower cul-de-sac in the remaining patient. Histopathologically, they exhibited lobules of tumor cells showing an admixture of epidermoid and mucus-secreting cells. Histochemical stains for mucin were most useful in arriving at a correct diagnosis. Follow-up information revealed that all five tumors recurred rapidly, invading the corneal stroma, intraocular structures, and orbit. Biologically, these tumors appear to be locally aggressive and should be differentiated histopathologically from the conventional squamous cell carcinoma of the conjunctiva, which carries a better prognosis. They should be managed by wide local excision, and the margins should be carefully examined for residual tumor. Frequent follow-up is recommended to detect early recurrence.

Aged↗
PubMed1987

Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea.

This investigation examined some of the barrier properties of the conjunctival, scleral, and corneal membranes. The diffusion of nadolol, timolol, propranolol, penbutolol, sucrose, and inulin was measured across the isolated corneal and scleral membranes of the rabbit using a two-chamber glass diffusion cell. Drug absorption across the cornea and the conjunctiva was studied in vivo by measuring precorneal drug clearance. The drug samples were analyzed either by HPLC or liquid scintillation counting (LSC). For all the compounds tested, the scleral permeability was significantly higher than the respective corneal permeability. The permeability coefficients of the beta-blockers varied in the following manner: propranolol > penbutolol > timolol > nadolol for the cornea, and penbutolol > propranolol > timolol > nadolol for the sclera. The cornea offered substantially more resistance to inulin, a polar, macromolecular substance, than did the conjunctiva. However, the cornea and conjunctiva offered comparable resistance to the smaller and less polar drug timolol. This information may serve as a basis for optimizing the intraocular delivery of drugs that are poorly absorbed across the cornea due to their physicochemical properties.

Animals↗
PubMed1994

Mucosa-associated lymphoid tissue (MALT) in the human conjunctiva.

The recent description of conjunctival lymphomas with features of lymphomas that arise in mucosa-associated lymphoid tissue (MALT) infers the presence of MALT in the human conjunctiva. Some authors suggest that organized MALT is found in the normal human conjunctiva, but others disagree. In order to resolve this problem, we have examined the conjunctival fornix from unselected autopsies with no prior history of conjunctival or ocular disease for the presence of organized MALT. In only 31 per cent of cases was organized lymphoid tissue found with the morphological and immunophenotypic features of MALT. This finding suggests that MALT is not found in the normal human conjunctiva but is acquired during life in a proportion of apparently asymptomatic individuals.

Adolescent↗