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Polar solute transport across the pigmented rabbit conjunctiva: size dependence and the influence of 8-bromo cyclic adenosine monophosphate.

PURPOSE: To characterize the conjunctival permeability to polar solutes ranging from 182 to 167,000 daltons in molecular weight (m.w.). METHODS: Solute transport across the excised pigmented rabbit conjunctiva with a baseline transepithelial electrical resistance (TEER) of 1,285 +/- 46 ohm.cm2 was evaluated in the modified Ussing chamber under open-circuit conditions. The model solutes were mannitol (m.w. 182), 6-carboxyfluorescein (m.w. 376), and fluorescein isothiocyanate-labeled dextrans (FD4, m.w. 4,400-FD150, m.w. 167,000). RESULTS: For a given solute, the apparent permeability coefficient (Papp) was independent of solute concentration and direction of transport. As expected, the Papp decreased with solute size, from 27.7 x 10(-8) cm/sec for mannitol to 0.31 x 10(-8) cm/sec for FD150. When the experimental temperature was lowered from 37 degrees C to 4 degrees C. Papp decreased by approximately 50% for FD4 through FD40 and by > 80% for both FD70 and FD150. Equivalent pore analysis, assuming restricted solute diffusion via cylindrical, water-filled pores across the isolated tissue, revealed a radius of 5.5 nm at a pore density of 1.9 x 10(8) pores per cm2. The addition of 1 mM 8-bromo cyclic adenosine monophosphate (8-BrcAMP), known to stimulate Cl- secretion and decrease TEER, to the mucosal side of the conjunctiva increased the transport of mannitol, FD4, and FD40 by 28%, while not affecting FD150 transport. CONCLUSIONS: Our findings suggest that polar solutes up to FD40 traverse the conjunctival epithelial barrier primarily by restricted diffusion through equivalent pores of 5.5 nm radius and that solute movement is affected by reduction of TEER. On the other hand, polar solutes of the FD70 or larger may cross the barrier primarily via non-diffusional pathways such as non-specific endocytosis.

Animals↗

Visualisation of "Marx's line" along the marginal eyelid conjunctiva of human subjects with lissamine green dye.

PURPOSE: To qualitatively assess the frequency and intensity of the staining of Marx's line with lissamine green dye. METHODS: Eighty-five non-contact lens wearers, aged 18-78 years and of white (European) or Arabic origin, were assessed. The subjects had no major eye disease, although some had mild-to-moderate congestion of the main tarsal (Meibomian) glands and/or anterior blepharitis. Lissamine green dye strips were used to stain the marginal zone of the palpebral conjunctiva, and then high magnification photo slitlamp images were taken. RESULTS: A lissamine green staining line was unmistakable in 83 of the subjects, and just evident in the other two. The line extends along the entire length of the upper and lower lid margins, and the staining broadens and extends over the puncta. In most subjects, the lissamine green-stained line was posterior to the main tarsal gland orifices, but in five subjects it was distinctly anterior to the orifices. In over two-thirds of the subjects, the width of line was much less than the distance between the gland orifices, and was at a similar distance to its width from the orifices. However, in one-third of the subjects, the width of the line was around half that of the distance between the orifices or slightly greater (i.e. approximately 0.5 mm), and this feature was more commonly present in those of non-European origin. CONCLUSION: Lissamine green dye highlights a very distinct line of cells along the marginal zone, and should be a useful tool to visualise this feature. This line of cells is thought to be the natural site of contact between the eyelid margin and the surfaces of the bulbar conjunctiva and cornea.

Adolescent↗

[Fornicate structure of blind saccular lymph vessel segments in the conjunctiva--scanning electron microscopy studies].

BACKGROUND: The accepted fundamental element of the initial lymphatic system is a tubular structure (lymphatic capillary), which is present either in the form of a finger-shaped blind-ending protuberance, or in the nature of a plexiform composite arrangement. We were able to demonstrate experimentally that the finger-shaped protuberances, which are known as "initial segments" are in fact temporary filling states. As the filling process continues, these vascular elements become intermediate segments, via which other parts of the vascular network take up the dye. To date there have been no investigations of the internal structure of these apparently blind-ending vessel segments. In this study, lymphographically represented "terminal segments" should be cut away for the purpose of examining the fornix by scanning electron microscopy. Is the internal surface of the fornix regular and unbroken, or are there fissure-like structures which could explain the observed filling processes? MATERIAL AND METHODS: In conjunctiva of bovine eyes (n = 80), interstitial double-contrast lymphography (Berlinblue solution/air) under a slit-lamp microscope was used specifically to search for finger-shaped terminal segments. The conjunctivae had previously been prepared by fixing in polymeric resins. A proportion (n = 21) of the specimens were amenable to examination under the scanning electron microscope. RESULTS: Notwithstanding the observed great variation in the shape of the lymphographically obtained blind-ending structures-in the form of terminations shaped variously like fingers, balloons, domes, pistons or pyramids, terminations with two humps, and terminations shaped like spear heads-scanning electron microscopy revealed within the fornices many relatively uniformly shaped structures in the form of fissures, configured with lips and saw-tooth edges, rather like zip fasteners. These findings are suggestive of preformed connections to neighbouring segments. This appears to be another element, in addition to the familiar flap-like structures, for controlling the circulation of lymph. Does the "initial part" of the lymphatic system now have to be redefined?

Animals↗

[Oncocytoma of the conjunctiva].

A 72-year-old woman presented with a lesion in her right eye, which had developed over 2 years. The cherry red lesion was located in the bulbar conjunctiva in the area of the plica semilunaris. Ophthalmologic examination was otherwise normal. Differential diagnosis included a pyogenic granuloma and a hemangioma. Excision of the tumor was performed. Histological examination revealed solid nests and cords of polyhedral cells exhibiting abundant, finely granular acidophilic cytoplasm and round to oval paracentral nuclei usually containing a single prominent nucleolus. The diagnosis of oncocytoma was established. Ocular oncocytomas are rare neoplasms and are mostly found in the caruncle. A location in the bulbar conjunctiva is extremely rare and only two reports are found in the literature with both of these located in the plica semilunaris.

Adenoma, Oxyphilic↗

[Static and dynamic infrared thermometry and thermography in malignant melanoma of the uvea and conjunctiva].

BACKGROUND: Thermometry and -graphy prove asymmetries of the circulation. Contact-free thermometry of the cornea is applied to find out whether this method can contribute to differential diagnosis of ocular melanomas. MATERIALS AND METHODS: Under standardized conditions the temperature of the cornea was measured in 30 patients with malignant melanoma of the choroid and the conjunctiva and 35 healthy subjects. The instruments were a handpyrometer (HPM, Messgerätewerk, Magdeburg) and the thermovision camera of AGA Infrared System, Sweden, with dynamic recording in colour. RESULTS: In healthy subjects there are no significant asymmetries in temperature under standardized conditions. The temperature of the cornea is elevated in both malignant melanomas of the choroid and the conjunctiva. CONCLUSIONS: Thermometry and -graphy of the cornea can contribute to the differentiation of malignant ocular melanomas from other ophthalmological diseases. They are also suited in long term observation of the course of the melanomas.

Body Temperature Regulation↗

[Distribution of melanoma-associated antigens (HMB 45 and S 100) in benign and malignant melanocytic tumors of the conjunctiva].

The reactivity of the monoclonal antibody HMB 45 was evaluated in melanocytic tumors of the conjunctiva. Among these are 10 acquired melanoses, 19 nevi and 34 melanomas. Results were compared with the presence of the S 100 antigen. Especially the intraepithelial and junctional components of primarily benign lesions were stained with HMB 45. Within malignant melanoma this antibody reacts with melanocytes in the epithelial, junctional and subepithelial areas. The polyclonal antibody S 100 stains all melanocytes in pigmented lesions of the conjunctiva. Intraepithelial or subepithelial malignant infiltrating tumor cells show very intense staining with HMB 45. HMB 45 has therefore high specificity for stimulated melanocytes, but it does not distinguish benign and malignant proliferating melanocytic cells.

Antibodies, Monoclonal↗

[Bacterial pathogen and resistance spectrum of the non-irritated conjunctiva. 7,845 preoperative smears at the ophthalmologic clinic of the Erlangen university].

The type and extent of bacterial colonization of the conjunctiva at the time of an intraocular operation may have a major influence on the risk of post-operative endophthalmitis. Between March 1986 and December 1988 a total of 7845 preoperative conjunctival smears were therefore examined by culture of Erlangen University Eye Hospital, in cooperation with the Department of Clinical Microbiology. Altogether, 1221 (15.6%) of the smears were classified as positive. Surgery on the patients concerned was postponed and gentamicin eye drops were administered for decontamination of their conjunctivae until the smears were negative. From the positive smears 1393 strains were cultured, identified, and submitted to a resistance test. The present paper reports the frequency distribution of the species of bacteria isolated and their resistance behavior, and compares the results with those of other authors. The value of preoperative cultures in the prevention of postoperative endophthalmitis and the importance of resistance tests in the context of topical application of antibiotics are discussed.

Bacteria↗

[S-100 protein in non-pigmented melanocytic and neuro-ectodermal tumors of the conjunctiva].

Using an immunoperoxidase method, S-100 protein was localized in 51 nonpigmented or slightly pigmented nevi, eight malignant melanomas, three neurofibromas, and one neurilemmoma of the conjunctiva. Clinico-immunohistochemical correlations are presented. Cells of these neuroectodermal tumors contain S-100 protein. Epithelial invaginations arising from the conjunctival surface and lying between melanocytes are S-100 protein-negative. This facilitates the differential diagnosis of particularly amelanotic lesions of the conjunctiva. Immunohistochemical identification of the S-100 protein represents an improvement in current histochemical differential diagnosis of these tumors.

Conjunctiva↗

[Lymph drainage of the cornea, limbus and conjunctiva].

Air (n = 30), patent blue (n = 30), Berlin blue (n = 30), Berlin blue and air (n = 30), and Berlin blue and Mercox (n = 30) were injected into the corneas and conjunctivas of 150 enucleated cattle eyes. Using air for injection, so-called Bowman "corneal tubes" form in the cornea, which can easily be filled with pigment (patent blue, Berlin blue). In some cases (n = 3) the conjunctival lymphatics were filled with air during injection into the cornea. Besides the "corneal tubes", larger vessel-like structures can be demonstrated, which seem to be connected to corneal nerves. The significance of these structures as prelymphatics and their importance in the lymph drainage of the cornea are discussed. The injection of patent blue and Berlin blue into the limbus leads to the formation of a delicate network of arch-shaped lymphatics, from which larger lymphatics take their color. In the case of Berlin blue and Mercox, and Berlin blue and air injection, sections of lymphatic vessels in the shape of pointed arches form at the edges of the segments. It can be shown stereomicroscopically that these are not valves or invaginations, but only hump-shaped diverticula of the vessels. Annular constrictions of the lymphatic vessels were found, rather than bicuspid valves. The valveless pump mechanism described by Liebau is discussed as a possible means of lymph transport in the conjunctiva.

Animals↗

Eicosapentaenoic acid metabolism in cynomolgus and rhesus conjunctiva and eyelid.

We have demonstrated that cynomolgus and rhesus monkey ocular tissues such as conjunctiva and eyelids have the capacity to synthesize cyclo-oxygenase and lipoxygenase products from arachidonic acid (AA). In the present study, we demonstrate that another fatty acid, eicosapentaenoic acid (C20:5), which is found mainly in marine diets, can be converted by cynomolgus and rhesus monkey conjunctiva and eyelids into cyclo-oxygenase (3-series) and lipoxygenase (5-series) products. EPA-lipoxygenase activity (ranging from 6.5% to 10.4%) was greater than EPA-cyclo-oxygenase activity (ranging from 1.5% to 3.5%) in these tissues. Furthermore, BW755, a cyclo-oxygenase and lipoxygenase inhibitor, inhibited the synthesis of EPA-derived cyclo-oxygenase and lipoxygenase product synthesis, indicating the enzymatic nature of EPA metabolism.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

The pruritogenic and inflammatory effects of prostanoids in the conjunctiva.

The therapeutic utility of cyclooxygenase (CO) inhibitors, such as ketorolac, in reducing the inflammatory events associated with allergic conjunctivitis is not unexpected since prostanoids (PG) elicit conjunctival redness (PGD2, PGE2, PGF2 alpha), edema (PGD2, TxA2), eosinophil infiltration (PGD2, PGJ2) and mucous cell discharge (PGD2, PGJ2, TxA2). Recently, topically administered ketorolac has also been reported to alleviate the itching associated with allergic conjunctivitis. This was viewed as intriguing since CO inhibitors are not regarded as useful for treating itching dermatoses and PGs do not elicit itching when applied to the skin. In order to investigate the antipruritic activity of ketorolac, we developed a model for reproducibly measuring ocular surface itch responses. The model involves itch-scratch responses to pruritogens applied locally to the ocular surface. Painful and foreign body stimuli do not produce an itch-scratch response. Unlike reported skin studies, PGE2 was a potent itch-producing substances in the conjunctiva. PGD2 was weakly pruritogenic but PGF2 alpha and the TxA2-mimetic U-46619 were inactive. The PG precursor arachidonic acid was also a potent pruritogen and its effects were inhibited by ketorolac pretreatment. Ketorolac also dose-dependently inhibited the itching associated with experimental allergic conjunctivitis. It appears that PGs are potent itch-producing substances in the conjunctiva and the anti-itch efficacy of ketorolac in allergic conjunctivitis appears to involve inhibition of conjunctival PG biosynthesis from arachidonic acid.

Animals↗

N-linked glycoside and glucuronide conjugates of the retinoid, acitretin, are biologically active in cornea and conjunctiva.

The purpose of this study was to test two water-soluble, synthetic retinoids, glucoseamido acitretin and glucuronamido acitretin, for biological activity in cells of the cornea and conjunctiva. Vitamin A-deficient, xerophthalmic rats were treated topically with these retinoids, and corneas were examined histologically for effects on epithelial keratinization. The effect of these retinoids on the proliferation of rabbit conjunctival fibroblasts in culture was also investigated. Glucoseamido acitretin treatment restored a normal cornea after eight to nine days of treatment, while no improvement was observed in the vehicle-treated corneas. Likewise, glucuronamido acitretin application restored a normal corneal surface and reversed keratinization after eight to ten days of treatment. These retinoids caused no irritation of the eye or ocular adnexa. In culture, exposure of conjunctival fibroblasts to glucoseamide acitretin inhibited cell proliferation. Cultures exposed to glucoseamido acitretin at 10(-8) M or 10(-6) M had cell densities 77.3% and 51.9% of control, respectively, after seven days. Glucuronamido acitretin also inhibited cell proliferation. Cultures exposed to glucuronamido acitretin at 10(-8) M had a cell density of 69.2% of control at day seven, while at 10(-6) M this retinoid completely inhibited cell proliferation. These results show that glucoseamide acitretin and glucuronamido acitretin are biologically active in the cornea and conjunctiva, and may be considered for ophthalmic use in diseases involving abnormalities of ocular surface cell differentiation or hyperproliferation of fibroblasts.

Acitretin↗

Lymphoid infiltrates of the orbit and conjunctiva. A morphologic and immunophenotypic study of 99 cases.

Most of the earlier clinicopathologic studies of orbital and conjunctival lymphoid infiltrates were done before the development of immunohistologic methods. In this study, we have examined 99 lymphoid infiltrates of the orbit and conjunctiva immunohistologically and correlated clinical and histologic features with immunophenotype. Sixty-six infiltrates expressed monotypic immunoglobulin; one case was immunoglobulin-negative, B-lineage; and 32 infiltrates expressed polytypic immunoglobulin. Using histologic criteria, 36 cases were malignant (35 monotypic; one immunoglobulin-negative, B-lineage), 44 were indeterminate (31 monotypic, 13 polytypic), and 19 were benign (all polytypic). Combining histologic and immunophenotypic criteria, 67 cases were diagnosed as malignant lymphoma. Seventy-six percent of the lymphomas were classified as low-grade according to the Working Formulation; small lymphocytic lymphoma (45%) was the most common histologic subtype. Cytologic atypia (p less than .0001) and Dutcher bodies (p less than .05) were found only in lymphomas. Similarly, bilateral involvement (p less than .05) and dissemination at time of presentation (p less than .001) occurred only in lymphomas. No other histologic or clinical features reliably distinguished lymphomas from benign orbital and conjunctival lymphoid infiltrates. Nineteen patients had a prior history of extraorbital malignant lymphoma, and eight patients had a history of pseudolymphoma. Patients with a history of malignant lymphoma more often presented with dissemination (p less than .001) and less often had the small lymphocytic subtype (p = .07) than patients without a history of lymphoma. However, not all patients with a history of extraorbital lymphoma had monotypic orbital and conjunctival infiltrates, and the incidence of monotypic orbital and conjunctival lesions in these patients was similar to that of the patients without a history of lymphoma. Patients with a history of pseudolymphoma always presented with localized disease (p less than .01) and more often had benign lesions (p = .08) as compared with patients without a history of pseudolymphoma. We conclude that the presence of either cytologic atypia or Dutcher bodies is a reliable criterion of malignant lymphoma in the orbit and conjunctiva. However, for one-third of the cases in this study, immunohistologic studies were the only means of distinguishing malignant from benign lymphoid infiltrates.

Conjunctiva↗

Clinical grading of the upper palpebral conjunctiva of non-contact lens wearers.

PURPOSE: To categorize the appearance of the normal upper palpebral conjunctiva using a grading scale and to investigate interobserver agreement with a grading scale modified to include decimal increments. METHODS: Upper palpebral conjunctival appearance of 96 non-contact lens wearing subjects aged 18 to 75 years was assessed using a photographic grading scale that has a generic (zero to four) scale to score redness and roughness of the palpebral conjunctiva. RESULTS: Median redness and roughness was about 1.25 units. About 5% of subjects had redness or roughness >2.0 units. Interobserver agreement improved during the study. By the end of the study, the standard deviation of the discrepancy scores was 0.12 to 0.19 units. CONCLUSIONS: Upper palpebral conjunctival redness or roughness >2.0 units are unusual. The grading scale can be used successfully with decimal rather than integer scale increments. For experienced clinicians, a change in grade of > or =0.5 units may be significant.

Adolescent↗

Bacillary angiomatosis with cytomegaloviral and mycobacterial infections of the palpebral conjunctiva in a patient with AIDS.

We report the clinical and histopathologic findings of bacillary angiomatosis involving the palpebral conjunctiva with concomitant infection by cytomegalovirus and Mycobacterium species in a patient with acquired immune deficiency syndrome. After debulking, the conjunctival tissue was studied with the use of light and electron microscopy; stains for bacteria, acid-fast bacilli, and Bartonella species; and immunohistochemical studies for cytomegalovirus and herpes simplex virus. We observed the typical histopathologic findings of bacillary angiomatosis, the presence of bacilli stained by the Steiner and Steiner method, and the electron microscopic demonstration of bacilli consistent with Bartonella species. Immunohistochemistry confirmed infection with cytomegalovirus, which had been suggested by characteristic cytologic abnormalities. Acid-fast bacilli were also found in the excised tissue. Patients with bacillary angiomatosis of the conjunctiva may have infections with multiple additional microorganisms.

AIDS-Related Opportunistic Infections↗

Secondary orbital implants after evisceration: a new conjunctiva-sparing technique.

PURPOSE: To describe a new conjunctiva-sparing technique for secondary orbital implantation after evisceration. METHODS: Two patients with conjunctival cicatrization and a volume-deficient anophthalmic socket had implantation of an intraconal biointegratable implant. This was placed through a lateral canthal approach, after temporary disinsertion of the lateral rectus, thereby avoiding further injury to the conjunctiva. RESULTS: A good surgical outcome was achieved in both patients. There were no intraoperative or postoperative complications, and both have remained stable for nearly 2 years. CONCLUSIONS: Secondary intraconal implantation through the lateral canthal approach is safe and effective and suitable for patients in whom it is desirable to avoid a conjunctival incision.

Adult↗

Orbital reconstruction after eyelid- and conjunctiva-sparing orbital exenteration.

PURPOSE: To describe the technique and results of eyelid- and conjunctiva-sparing orbital exenteration with temporalis transfer and dermis-fat graft. METHODS: Five patients who underwent this procedure were studied, based on retrospective chart review. Schematic drawings were produced to illustrate the surgical technique. RESULTS: The study included three female and two male patients with an age range of 7 to 76 years. Two patients required surgery for invasive optic nerve sheath meningioma, one for hemangiopericytoma, and the fourth for mesenchymal chondrosarcoma. The last patient had eyelid-sparing exenteration performed more than 20 years earlier for retinoblastoma and underwent a similar reconstruction. One case was complicated by infection and graft atrophy. The remaining four cases retained orbital volume and eyelid structures with a reasonable cosmetic outcome. Average follow-up period was 21 months, during which one patient had development of intracranial meningioma at the proximal end of the optic canal. CONCLUSIONS: Eyelid- and conjunctiva-sparing orbital exenteration with temporalis transfer and dermis-fat graft is a useful technique that minimizes the usual deformity and achieves good results. Case selection is emphasized, as this technique is mainly reserved for histopathologically benign orbital lesions that exhibit local aggressive behavior and for malignant lesions only if there is no eyelid, lacrimal gland, or orbital fissure involvement nor significant conjunctival or deep extension of an intraocular tumor.

Adult↗

Isolation of Mycoplasma conjunctivae from conjunctival swabs of Alpine ibex (Capra ibex ibex) affected with infectious keratoconjunctivitis.

Mycoplasma conjunctivae was isolated four times from the eyes of nine Alpine ibex (Capra ibex ibex) suffering from keratoconjunctivitis. The animals examined were affected in two different outbreaks in the Swiss Alps. Parasitological and bacteriological studies, including investigations for chlamydia and mycoplasmas, were performed. The results indicate that M. conjunctivae is the primary pathogenic agent causing infectious keratoconjunctivitis in this species.

Animals↗