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Topical 5-fluorouracil in treating epithelial neoplasia of the conjunctiva and cornea.

PURPOSES: To evaluate the efficacy of topical 5-fluorouracil (5-FU) in treating conjunctival and corneal epithelial neoplasia. METHODS: Three patients underwent surgical excision of bulky disease followed by topical 1% 5-FU in artificial tear base for 2 to 3 weeks or until epithelial separation occurred. An additional three patients underwent treatment with topical 1% 5-FU alone. RESULTS: Minimum follow-up was 6 months. In one patient with conjunctival in situ carcinoma and no detectable normal conjunctiva, who had normal findings on conjunctival histologic examination after application of topical 5-FU, a focus of invasive disease requiring orbital exenteration. One patient had a favorable response to 5-FU therapy but required a repeat excision for control of bulky disease. Four patients have remained disease-free for 10, 13, 18, and 30 months after topical 5-FU therapy. CONCLUSION: With its potential selective toxicity on dysplastic epithelium, topical 5-FU shows promise as an adjunctive treatment for managing conjunctival and corneal epithelial neoplasia.

Administration, Topical↗

Pneumocystis carinii infection of the conjunctiva in a patient with acquired immune deficiency syndrome.

BACKGROUND: Ocular disease, especially the development of choroidal lesions, is a known extrapulmonary manifestation of Pneumocystis carinii infection in the acquired immune deficiency syndrome (AIDS). To our knowledge, conjunctival involvement due to P. carinii has not been described previously. METHODS: The authors describe a 33-year-old homosexual male with AIDS in whom a large placoid, white lesion developed involving the tarsal conjunctiva of the right upper lid. Conjunctival malignancy was suspected and biopsies and swabs were taken. At this time, the patient had been receiving monthly aerosolized pentamidine prophylaxis for 18 months, and there was neither a history of pneumonia nor any clinical signs of disseminated infection due to P. carinii. RESULTS: Histopathologic examination results of the conjunctival biopsy specimen showed a necrotic, frothy tissue surrounded by activated fibroblasts. Within this material, Gomori methenamine silver stains showed numerous round and cup-like cysts of P. carinii, confirming the diagnosis that had already been obtained by an indirect fluorescent-antibody stain of a conjunctival smear specimen. CONCLUSIONS: The presence of white placoid conjunctival lesions in a patient with AIDS may indicate an infection due to P. carinii. Conjunctival disease due to P. carinii widens the spectrum of AIDS-associated ophthalmic pneumocystosis.

AIDS-Related Opportunistic Infections↗

Cytologic changes in the conjunctiva mimicking malignancy after topical mitomycin C chemotherapy.

PURPOSE: To describe the epithelial changes observed in the conjunctiva secondary to the use of topical mitomycin C (MMC) for treatment of primary acquired melanosis with atypia. DESIGN: Retrospective comparative case series. PARTICIPANTS AND CONTROLS: Conjunctival biopsy specimens (18) were taken during the follow-up of ten patients treated with MMC drops (0.02% or 0.04%) during 14 or 21 days for primary acquired melanosis with atypia. An equal number of age- and sex-matched patients with normal conjunctival biopsy findings were included for control. Conjunctival biopsy specimens from patients treated with MMC were compared with the morphologic changes already described in the urothelium following the use of the same chemotherapeutic agent. METHODS: Hematoxylin and eosin-stained biopsy samples were evaluated for recurrent neoplasm and chemotherapeutic effect in the epithelium using the following criteria: nuclear enlargement, nuclear hyperchromasia, smudging of the chromatin, presence of nucleoli, cytoplasmic eosinophilia, and individual cell necrosis. MAIN OUTCOME MEASURES: The presence or absence of morphologic changes in the conjunctival epithelium related to the use of MMC. RESULTS: Morphologic features consistent with chemotherapy effect were seen in the biopsy specimens of nine patients. Nuclear enlargement and chromatin smudging-hyperchromasia localized in the superficial layers of the epithelium were the main features observed (9 patients). Cytoplasmic eosinophilia, single cell necrosis, and occasionally subepithelial chronic inflammation were also seen. CONCLUSIONS: Secondary changes with the topical use of MMC are seen in the conjunctival epithelium and are similar to the changes described in the urothelium. These changes are important to recognize and to differentiate from recurrent neoplasm. The localization of the described features in the superficial layers of the conjunctival epithelium is the key feature in the differential diagnosis.

Administration, Topical↗

The effect of transdermal estradiol on the conjunctiva in postmenopausal women.

OBJECTIVE: To evaluate the effect of hormonal replacement therapy on the conjunctiva in postmenopausal women. STUDY DESIGN: A prospective clinical study in the setting of a tertiary-care university hospital. Eleven postmenopausal women received hormonal replacement therapy (transdermal estradiol or transdermal estradiol plus medroxyprogesterone acetate) for 4 months. Serum estradiol levels as well as vaginal and conjunctival maturation value (a cytological parameter) were measured before and after the treatment. Data were analysed using the Wilcoxon matched pairs signed-Rank test. RESULTS: A significant increase of serum estradiol levels (P < 0.01) and of vaginal maturation value (P < 0.01) were found. Cytological maturation changes in conjunctival epithelium were also observed. These changes, although mild, were statistically significant (P < 0.01). CONCLUSION: These data support the view that the hormonal replacement therapy induces cytological maturation changes in conjunctival epithelium in postmenopausal women.

Administration, Cutaneous↗

Clonality of benign lymphoid hyperplasia in orbit and conjunctiva.

In order to thoroughly characterize the clonal population of lymphoid hyperplasia of the orbit and conjunctiva, we investigated six cases which were histologically proven to be benign lymphoid hyperplasia. We analyzed the clonal rearrangements of the antigen receptors and bcl-2 gene, Epstein-Barr virus (EBV), and human T-cell leukemia virus type 1 (HTLV-I) by Southern blot and/or polymerase chain reaction (PCR), and performed in situ hybridization for mRNA of kappa and lambda immunoglobulin. Five cases showed rearrangements of immunoglobulin heavy chain gene (JH) and/or light chain gene (J kappa), and the monoclonal V-J recombination of JH in PCR. However, the rearranged bands were much more faint than was the germ-line band. We considered the monoclonal population of B cells small. Two of the five cases recurred locally after four and nine years respectively. Because benign lymphoid hyperplasias frequently contain an occult monoclonal B-cell population, a follow-up should be conducted. The remaining case in our investigation showed a rearrangement of the T-cell-receptor gene and proviral DNA of HTLV-I, and it showed rapid progress to adult T-cell leukemia after the biopsy. EBV and bcl-2 gene rearrangements were not observed in any of the six cases we studied.

Adult↗

A comparison of the iodine and fluorescent antibody methods for staining trachoma inclusions in the conjunctiva.

In terms of the rate of positive diagnoses the indirect fluorescent antibody (FA) test was rather more effective than iodine for demonstrating trachoma (TRIC) inclusions in conjunctival scrapings, but the degree of advantage was not statistically significant. In duplicate scrapings stained at random by one or the other method, FA staining yielded the higher inclusion count significantly more often than did iodine. Some inclusions that failed to stain with FA were found on subsequent staining with Giemsa. A method is described for improving the post-FA Giemsa staining of conjunctival smears stored at subzero temperatures. Given adequate facilities, the FA stain is preferable to iodine for demonstrating TRIC inclusions in the conjunctiva; but the iodine method, properly used, holds advantages for field use.

Child, Preschool↗

Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye.

The objective of this study was to collect a comprehensive database of ocular tissue permeability measurements found in a review of the literature to guide models for drug transport in the eye. Well over 300 permeability measurements of cornea, sclera, and conjunctiva, as well as corneal epithelium, stroma, and endothelium, were obtained for almost 150 different compounds from more than 40 different studies. In agreement with previous work, the corneal epithelium was shown generally to control transcorneal transport, where corneal stroma and endothelium contribute significantly only to the barrier for small, lipophilic compounds. In addition, other quantitative comparisons between ocular tissues are presented. This study provides an extensive database of ocular tissue permeabilities, which should be useful for future development and validation of models to predict rates of drug delivery to the eye.

Animals↗

Open sky Müller's muscle-conjunctiva resection for ptosis surgery.

PURPOSE: We describe a surgical technique for ptosis correction in moderate to good levator function involving resection of Müller's muscle of the upper eyelid. This is a substantial modification of the technique described by Putterman. We then present our experience of and the results from this method. METHODS: A subtotal resection of Müller's muscle plus underlying conjunctiva is performed under direct visualisation. The muscle stump is reattached to the tarsus and the sutures passed through to the skin crease. In those cases where the phenylephrine test was positive to a level less than the desired lid height, a 1 mm of strip of tarsus is included in the tissue resection. The sutures are removed between 5 days and 3 weeks postoperatively allowing control over lid height and contour. A total of 61 eyes of 48 patients underwent this procedure. RESULTS: Of 61 eyelids, 56 undergoing this procedure were within 0.5 mm of the desired end point, giving a success rate of 92%. Of 61 eyelids, 60 were within 1 mm of the desired height. Preoperative phenylephrine 10% was highly predictive of postoperative lid height (58/61). An excellent lid contour was noted in all cases (61/61). CONCLUSIONS: We present a new approach to ptosis correction using Müller's muscle. It has a high success rate and good cosmetic outcome. It is technically straightforward and easy to learn.

Adolescent↗

Effect of topical dexamethasone and ciprofloxacin on bacterial flora of healthy conjunctiva.

PURPOSE: To investigate the effects of topical dexamethasone and ciprofloxacin, alone and in combination, on the colony counts of conjunctival bacterial flora of healthy subjects. METHODS: A total of 100 healthy subjects were randomly divided into four groups, consisting of 25 subjects each. Group 1 was treated with dexamethasone phosphate 0.1% (Maxidex). Group 2 was treated with ciprofloxacin 0.3% (Ciloxan) and Group 3 with a combination of these drugs. Group 4 received artificial tear solution (Tears Naturale) and served as control. The drops were administered one drop every 1 min. A pretreatment culture and recultures at 30, 90, and 180 min after application of final drops were performed on all subjects. The bacterial growth was evaluated in a quantitative manner. All cultures were performed in a double-masked fashion. ANOVA test was used for statistical analyses. RESULTS: While there was no significant difference among mean number of pretreatment colonies between the groups (P=0.85); the differences at 30, 90, and 180 min were statistically significant (P<0.001). During the study there was no statistically significant change in colony counts in Groups 1 and 4 (P=0.66 and 0.55, respectively). The colony count numbers decreased significantly at 30 and 90 min in Group 2 (P<0.001 and P=0.004) and at 30 min in Group 3 (P=0.002). CONCLUSION: Topically applied dexamethasone did not cause a significant change in colony counts of the healthy conjunctiva. Both ciprofloxacin and a combination of ciprofloxacin and dexamethasone were effective in the reduction of bacterial ocular flora.

Administration, Topical↗

Detection of oestrogen receptors (ER) alpha and beta in conjunctiva, lacrimal gland, and tarsal plates.

PURPOSE: Lack of Oestrogen and androgen may be of importance in the pathogenesis of keratoconjunctivitis sicca (KCS). The signal of Oestrogens is transmitted via specific Oestrogen receptors (ER). It was the purpose of this study to evaluate the expression of ER alpha and ER beta in tear-producing tissues. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR, ER alpha + beta) and immunohistochemical evaluation (ER alpha only) were performed for ER detection and localization in tissue samples of bulbar conjunctiva (20 samples of 20 patients undergoing cataract surgery), tarsal plates (14 samples of 12 patients undergoing eye lid surgery), and lacrimal glands (20 samples of 13 cornea donors). RESULTS: Messenger RNA ER alpha was identified via RT-PCR in all tissue samples with variable expression, ER beta predominantly in lacrimal gland tissue. Immunohistochemical staining for ER alpha was negative in most cases, probably due to the thermolability of ERs and very small sample sizes. CONCLUSIONS: The detection of ER alpha and ER beta mRNA expression supports the concept of a receptor-based effect of Oestrogen in these tissues contributing to KCS. This may encourage therapeutical efforts including topical Oestrogen administration.

Adult↗

Continuous oxygen monitoring of the conjunctiva in neonates.

OBJECTIVE: To report the first use of a noninvasive conjunctival oxygen monitor in neonates. We wished to investigate if measuring the partial pressure of oxygen directly from the conjunctiva could track hyperoxia and hypoxia as well as, or better than, pulse oximetry. This has the potential to reflect brain oxygenation while yielding important systemic information. STUDY DESIGN: Criteria standard. SETTING: Tertiary care hospital neonatal intensive care unit. PATIENTS: Ten newborns monitored with pulse oximetry. INTERVENTION: The conjunctival oxygen monitor was studied for effectiveness and safety and compared to pulse oximetry. RESULTS: The device remained on the eyes up to 120 minutes. The correlation coefficient between conjunctival oxygen tension and pulse oximetry was significant for all readings (p<0.001) and for pulse oximetry measurements below 100% (p=0.024). One infant developed eyelid edema, which subsided when the device was removed and one sustained a small corneal abrasion that healed overnight. CONCLUSION: This initial pilot report suggests that the conjunctival oxygen monitor is effective and relatively safe in neonates. The device holds promise to indicate a tissue oxygen reading, which may provide neonatologists with more information about systemic oxygenation.

Conjunctiva↗

Blockage of complement regulators in the conjunctiva and within the eye leads to massive inflammation and iritis.

The open environment of the eye is continuously subject to an influx of foreign agents that can activate complement. Decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 are regulators that protect self-cells from autologous complement activation on their surfaces. They are expressed in the eye at unusually high levels but their physiological importance in this site is unstudied. In the rat, a structural analogue termed 5I2 antigen (5I2 Ag) has actions overlapping DAF and MCP. In this investigation, we injected F(ab')2 fragments of 5I2 mAb into the conjunctiva and aqueous humor, in the latter case with and without concomitant blockage of CD59. Massive neutrophilic infiltration of the stroma and iris resulted upon blocking 5I2 Ag activity. Frank necrosis of the iris occurred upon concomitant intraocular blockage of CD59. C3b was identified immunohistochemically, and minimal effects were seen in complement-depleted animals and in those treated with non-relevant antibody. The finding that blockage of 5I2 Ag function in periocular tissues and within the eye causes intense conjunctival inflammation and iritis demonstrates the importance of intrinsic complement regulators in protecting ocular tissues from spontaneous or bystander attack by autologous complement.

Animals↗

["Masquerade foreign body" of the conjunctiva].

CASE REPORT: An eight months old child presented with a "red eye" and a corneal erosion since a week. The parents reported on a "hair" which was invisible most of the time but appeared intermittently at the lid margin. The medical history was otherwise unremarkable. In general anaesthesia, a long structure could be easily extracted. The tapering structure disclosed several tiny hair-like filaments sprouting from the thickened end. This end was embedded within a fold of conjunctiva, thus giving the impression of a hair sheath. Clinically, an ectopic "giant hair" was supposed. Histology, however, revealed plants cells and a birefringence too high for a hair so that a diagnosis of a plant foreign body was established. CONCLUSION: Conjunctival foreign bodies may be overlooked especially in young children with no history of foreign body acquisition. They may occur as a "masquerade foreign body".

Conjunctiva↗

[Non-Hodgkin lymphoma of the conjunctiva (MALT lymphoma)--clinical and pathological markers].

BACKGROUND: Lymphoid tumors of the conjunctiva are extremely rare. Primarily such tumors can appear as isolated neoplasm or secondarily within a systemic disease. PATIENTS: The difficulties relating to dignity of the clinical diagnosis and the histological examination of the biopsies are presented. Both patients received orbital radiation therapy. RESULTS: The therapeutically success and clinical course are reported.

Adult↗

[Lymphangioma of the conjunctiva].

A 23-year-old female presented with a yellow-brownish, asymptomatic tumour of the bulbar conjunctiva in her left eye. The lesion had been detected 5 years previously and had grown since then. Prior to presentation there were 2 episodes of intratumoral hemorrhage. Funduscopy revealed tortuous vessels on the left. Complete tumour excision was performed. Histology showed numerous channels lined by a flat endothelium, and inflammatory cells in the fibrous septae. A diagnosis of a conjunctival lymphangioma was established. The tortuosity of the retinal vessels was probably associated by chance or caused by an undetected orbital lymphangioma.

Adult↗

[Allergic granuloma of the conjunctiva (Splendore-Hoeppli phenomenon)].

A 35-year-old woman from Georgia presented with multiple bilateral yellow nodules of the upper bulbar conjunctiva, accompanied by a severe injection of conjunctival vessels. The histologic examination of excisional biopsies showed the characteristic morphology of the Splendore-Hoeppli-phenomenon, which describes granulomas with a necrotized eosinophilic center, surrounded by a ring of epitheloid cells, giant cells and eosinophils. Although nematodes could be identified in only a few lesions, they should always be kept in mind as the causing agent of this condition. No cause of the lesions was found in our patient. The nodules may regress spontaneously. Topical application of corticosteroid eye drops, however, may give relief of symptoms, and sometimes excision of the granulomas will be necessary.

Adult↗

[Blue nevi of the conjunctiva].

PATIENT AND METHODS: A 54-year-old man presented with multifocal pigmentations of the left bulbar and palpebral conjunctiva. He had first noticed these changes 5 years ago without any evidence of progression. The pigmented lesions were located in the plica, caruncle, the lower fornix and the mucocutaneous junction of the lower lid. The right cornea showed a focal superficial scar paracentrally due to a herpes simplex keratitis in 1970. Visual acuity was 20/20, otherwise the eyes were unremarkable. Biopsies were performed in all areas. One year after surgery, there was no recurrence of the lesions. MICROSCOPY: Histopathologically, the conjunctival epithelium is essentially unremarkable. The substantia propria display mostly uniformly pigmented spindle-shaped melanocytic cells. Many cells contain coarsely clumped melanin granules. Other areas reveal poorly pigmented to unpigmented melanocytic cells, some of them with Schwannian features. Intranuclear vacuoles are commonly present. The tumor cells are often located in stromal areas displaying increased amounts of collagen. A few polyhydral melanophages are present within the lesion. DIAGNOSIS: Biopsy A (plica)--blue nevus with areas of cellular blue nevus. Biopsy B (caruncle)--cellular blue nevus. Biopsy C (lower fornix)--cellular blue nevus. Biopsy D (mucocutaneous junction of left lower lid)--Blue nevus.

Biopsy↗

[Normal flora of the human conjunctiva: examination of 135 persons of various ages].

PURPOSE OF THE STUDY: Conjunctival flora is a prime suspect in searching for the cause of post-traumatic or post-operative ocular infections. Better information on its individual composition is therefore desirable. METHODS: 135 persons (66 women, 69 men) were examined during a period of 1 1/2 years. The youngest patient was 3 years old, the oldest 90. Both eyes of all patients were examined. RESULTS: Megasphaera elsdenii, Bacteroides ureolyticus, Bacteroides pneumosintes, Stomatococcus mucilaginosus, and group ANF Corynebacterium were isolated for the first time in the eye by this study. The latter was found so often that it can be ascribed the role of an aerobic indicator organism. Characteristic changes appear in the conjunctival flora at different stages of life. In particular, for example, the species spectrum of aerobic bacteria broadens with advancing age, and the population of aerobic bacteria increases in density. CONCLUSIONS: With increasing age aerobic cocci are found less frequently in favor of the Corynebacteria. The proportion of anaerobic cocci increases among the anaerobes, while Propionibacteria are demonstrated less frequently. The significance of the organisms found in conjunctiva by this study for the first time is still unclear. No qualitative or quantitative sex-specific influence on the development of conjunctival flora was found.

Adolescent↗