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Biomedical subjects

S C Pflugfelder

Publications and source records attributed to S C Pflugfelder.

At least 37 records · Page 2Linked to original sources
PubMed2000

[The abnormal expression of epidermal growth factor receptor family in pterygium].

OBJECTIVE: To evaluate the expression of type 1 growth factor receptor family [epidermal growth factor receptor (EGFR), ErbB2 and ErbB3] by the epithelium in pterygium so as to understand the pathogenesis of this disorder. METHODS: The immunofluorescent staining and Western blotting were performed in 15 patients with primary pterygium, compared to normal conjunctival epithelium, to determine the expression of EGFR, ErbB2 and ErbB3 proteins. RESULTS: The EGFR was present at the basal cells while the ErbB2 and ErbB3 were expressed by the superficial cells in normal conjunctival epithelium in immunofluorescent staining. Of 15 pterygia, 11 pterygia expressed the stains of EGFR, ErbB2 and ErbB3 in the full thickness of epithelium and with stronger staining compared to the control group, 4 of them showed the same staining pattern as that in the normal conjunctiva. Compared to normal conjunctiva, the stronger density of protein bands of EGFR, ErbB2 and ErbB3 was also demonstrated by western blotting in 11 pterygia with strong staining of these antibodies. CONCLUSIONS: The expression of EGFR, ErbB2 and ErbB3 is increased in pterygium, showing that the pterygium is a disorder with proliferation. The abnormal expression of EGFR, ErbB2 and ErbB3 by epithelium and their communicating with cytokines at stroma in pterygium may be one of the key pathogenetic factors in this disorder.

Adult↗
PubMed1999

Corneal surface regularity and the effect of artificial tears in aqueous tear deficiency.

PURPOSE: To evaluate corneal surface regularity and the effect of artificial tears on the regularity of the corneal surface in dry eye. DESIGN: A prospective, clinic-based, case-control study. PARTICIPANTS: A total of 64 eyes of 33 normal subjects and 42 eyes of 22 patients with aqueous tear deficiency were evaluated. METHODS: Indices of the TMS-1 corneal topography instrument (Tomey Technology, Cambridge, MA) were used to evaluate corneal surface regularity and potential visual acuity (PVA) in patients with aqueous tear deficiency dry eye before and after the instillation of artificial tears and in normal subjects. The TMS-1 topographic maps were classified into round, oval, symmetric bow-tie, asymmetric bow-tie, and irregular patterns. MAIN OUTCOME MEASURES: The surface regularity index (SRI), surface asymmetry index (SAI), PVA index, and topographic pattern of the TMS-1 were compared between normal and dry eyes and in dry eyes before and after the instillation of artificial tears. RESULTS: The SRI and SAI were significantly elevated and the PVA was significantly reduced in dry eye patients compared with normal subjects: 0.31+/-0.22, 0.30+/-0.16, and 20/17.89+/-20/3.04, respectively, in normal subjects and 1.28+/-0.73, 1.05+/-1.17, and 20/33.45+/-20/13.99, respectively, in patients with dry eye (P<0.001 for all indices). The average amount of astigmatism was also increased in dry eyes (2.10+/-1.96 prism diopters) compared with normal eyes (1.13+/-0.53 prism diopters, P = 0.02). In dry eyes, the SRI and SAI were positively correlated with corneal fluorescein staining scores (P = 0.005 for SRI and P = 0.016 for SAI). The mean PVA was not significantly different from the mean actual corrected visual acuity. The dry eyes had a significantly lower percentage of symmetric bow-tie patterns and a greater percentage of irregular patterns on topographic maps than normal eyes. After the instillation of artificial tears, the SRI, SAI, and mean astigmatism all decreased significantly (P<0.001 for SRI, P<0.002 for SAI, P = 0.04 for astigmatism) and the PVA improved (P<0.001) in dry eyes. An irregular topographic pattern was observed in 45.24% of dry eyes, and this decreased to 30.95% after the instillation of artificial tears (P<0.005). CONCLUSIONS: Patients with aqueous deficiency have an irregular corneal surface that may contribute to their visual difficulties. The SRI and SAI could be used as objective diagnostic indices for dry eye as well as for evaluating the severity of this disease and the effect of artificial tears. Artificial tears have the secondary benefit of smoothing the corneal surface in dry eye.

Aged↗
PubMed1999

Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms.

OBJECTIVE: To correlate and compare the Schirmer 1 test and a new method of measuring tear fluorescein clearance with the CytoFluor II fluorometer with the severity of ocular irritation symptoms, clinical signs of meibomian gland disease, corneal fluorescein staining scores, and corneal and conjunctival sensitivity. DESIGN: Case-control study. PARTICIPANTS: Forty patients presenting with a chief complaint of ocular irritation, and 40 asymptomatic control subjects of similar age distribution. INTERVENTION: All subjects completed a symptom questionnaire, a baseline ocular examination, fluorescein clearance test (FCT), and Schirmer 1 test. MAIN OUTCOME MEASURES: The FCT was performed with a CytoFluor II fluorophotometer by measuring the fluorescein concentration in minimally stimulated tear samples collected from the inferior tear meniscus 15 minutes after instillation of 5 microl of 2% sodium fluorescein. Severity of ocular irritation was assessed with a symptom questionnaire. Schirmer 1 test, biomicroscopic meibomian gland evaluation, corneal fluorescein staining score, and corneal and conjunctival sensation scores were assessed with the Cachet-Bonnet anesthesiometer in all subjects. RESULTS: Irritation symptoms correlated with higher log tear fluorescein concentration (symptomatic 3.08 +/- 0.62 units/,microl, normal control 1.89 +/- 0.7 units/microl, P < 0.005) and lower Schirmer 1 test scores (symptomatic 12.6 mm, normal control 22.3 mm, P < 0.005). The FCT showed greater predictive value for identifying ocular irritation than the Schirmer 1 test. A fluorescein concentration of 274 units//microl eliminated 80% of the normal subjects (specificity) and identified 85% of the abnormal subjects (sensitivity). Log of tear fluorescein concentration and the Schirmer 1 test correlated with meibomian gland orifice metaplasia (2.81 +/- 0.78 units/microl and 14.47 +/- 9.53 mm in those with metaplasia vs. 1.83 +/- 0.71 units/microl and 23.14 +/- 7.67 mm in those without metaplasia, P < 0.001) and with the percentage of acinar dropout. Both log of tear fluorescein concentration and the Schirmer 1 test correlated with corneal fluorescein staining (Pearson correlation of 0.394 P < 0.0001 for Schirmer 1 test and 0.312 P < 0.005 for log of tear fluorescein). In addition, log of tear fluorescein and Schirmer 1 test scores correlated with corneal and conjunctival sensation scores (Spearman's rho for corneal sensation: log of tear fluorescein -0.38, P < 0.003, Schirmer 1 test -0.39, P < 0.002, and for conjunctival sensation: log of tear fluorescein -0.391, P < 0.001, Schirmer 1 test -0.23, P < 0.061). CONCLUSIONS: The FCT shows a greater predictive value for ocular irritation than the Schirmer 1 test. It correlates better with age, meibomian gland dysfunction, and decreased corneal and conjunctival sensation. Decreased tear clearance was identified as a risk factor for ocular irritation, even in subjects with normal Schirmer scores. This simple technique may provide new clues into the mechanism and therapy of ocular irritation.

Adult↗
PubMed1999

Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren syndrome.

OBJECTIVE: To review the efficacy and side effects of topical nonpreserved corticosteroid therapy for treatment of severe keratoconjunctivitis associated with Sjögren syndrome. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-one patients with Sjögren syndrome-associated keratoconjunctivitis sicca and annoying ocular irritation. INTERVENTION: Treatment with topical nonpreserved methylprednisolone sodium succinate. MAIN OUTCOME MEASURES: Symptom severity, frequency of instillation of artificial tears, corneal fluorescein staining scores, resolution of filamentary keratitis, steroid-related side effects. RESULTS: Before starting methylprednisolone therapy, all patients were experiencing moderate-to-severe eye irritation despite prior punctal occlusion in most cases and frequent use of nonpreserved artificial tears by all. After 2 weeks of topical application, three to four times per day, moderate (43%) or complete (57%) relief of irritation symptoms was experienced by all patients and no complications were observed. An average decrease in corneal fluorescein scores of 2.6 +/- 0.5 points (on a 12-point scale) was observed, and filamentary keratitis resolved in all ten eyes with this condition. Therapy was stopped after 2 weeks in eight patients, and six of these patients reported that their symptoms remained at a tolerable level for weeks to months. Lower dose steroid therapy was continued in the remaining patients, whose symptoms worsened after attempted weaning. Complications of corticosteroid therapy in patients receiving prolonged therapy included increased intraocular pressure in one patient at 3 months, worsening of pre-existing posterior subcapsular cataracts in one patient at 6 months, and formation of posterior subcapsular cataracts in another patient at 6 months. CONCLUSIONS: These findings indicate that topical nonpreserved methylprednisolone is an effective treatment option for patients suffering from severe keratoconjunctivitis sicca who continue to experience bothersome eye irritation despite maximum aqueous enhancement therapies. They also suggest that inflammation is a key pathogenic factor in this condition. Careful monitoring is essential in dry eye patients treated with corticosteroids for more than 2 weeks because steroid-related complications (increased intraocular pressure and cataract formation) were observed after several months of therapy in this series. Because of the chronic nature of this disease and the likelihood of patients developing steroid-related complications with their long-term use, topical nonpreserved methylprednisolone therapy appears to be most appropriate for short-term "pulse" treatment of exacerbations of keratoconjunctivitis sicca.

Administration, Topical↗
PubMed1999

Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca.

PURPOSE: To compare epidermal growth factor (EGF) concentration in tear fluid and levels of inflammatory cytokines in the conjunctival epithelium of patients with Sjögren's syndrome keratoconjunctivitis sicca with those of normal controls. METHODS: Schirmer 1 tear testing, corneal fluorescein staining and conjunctival impression cytology for quantitation of goblet cell density were performed in ten patients with Sjögren's syndrome-associated keratoconjunctivitis sicca and ten asymptomatic normal controls. ELISA was used to detect the concentration of EGF in tear fluid and interleukin 6 in lysates of conjunctival cytology specimens obtained from all subjects. The levels of RNA transcripts encoding inflammatory cytokines [interleukin 1alpha_(IL-1alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha_(TNF-alpha), and transforming growth factor beta1 (TGF-beta1)] as well as a housekeeping gene (G3PDH) were evaluated in conjunctival cytology specimens taken from all subjects by semiquantitative competitive reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Decreased tear fluid EGF concentration was noted in Sjögren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts were found in the conjunctival epithelium of Sjögren's syndrome patients compared to controls (P < 0.05), while the level of G3PDH was similar in both groups. The concentration of IL-6 protein was significantly higher in Sjögren's syndrome conjunctiva samples (P = 0.012). Tear EGF concentration correlated with Schirmer 1 scores (rho 0.767, P < 0.001), corneal fluorescein staining scores (rho -0.562, P = 0.01), conjunctival goblet cell density (rho 0.661, P = 0.001) and the levels of IL-1alpha_and IL-8 RNA in the conjunctival epithelium (rho -0.677 and -0.747, respectively, P = 0.001). Both IL-1alpha_and IL-8 RNA in the conjunctival epithelium increased as Schirmer 1 scores decreased (P </= 0.001). IL-8 RNA level correlated with corneal fluorescein staining (rho 0.690, P = 0.001) and conjunctival goblet cell density (rho -0.767, P < 0.001). A significant decrease in IL-8 RNA level, corresponding to improvement in irritation symptoms and ocular surface disease, was observed in six eyes after two weeks of topical corticosteroid therapy. CONCLUSIONS: The balance of cytokines in the tear fluid and conjunctival epithelium is altered in Sjögren's syndrome. The severity of keratoconjunctivitis sicca in this condition increases as tear fluid EGF concentration decreases and levels of inflammatory cytokines in the conjunctival epithelium increase. These findings provide new insight into the pathogenesis of keratoconjunctivitis and provide potential targets for therapy.

Adult↗
PubMed1999

Corneal thickness is reduced in dry eye.

PURPOSE: To evaluate and compare corneal thickness in normal and dry eyes. METHODS: The Orbscan corneal topography system was used to measure the corneal thickness at nine locations in the central and peripheral (superior, superonasal, nasal, inferonasal, inferior, inferotemporal, temporal, superotemporal) cornea in 38 eyes of 21 patients with aqueous tear deficiency dry eye and 34 eyes of 21 normal subjects. RESULTS: The average thickness of nine sites in the central and midperipheral cornea was significantly decreased in dry eyes compared with that of normal eyes. The superior cornea was found to be the thickest area in both groups, measuring 0.629 +/- 0.030 mm in normal eyes and 0.589 +/- 0.031 mm in dry eyes. The center of the cornea was noted to be the thinnest in both groups, measuring 0.571 +/- 0.028 mm and 0.534 +/- 0.034 mm in normal and dry eyes, respectively. In color-coded pachymetry maps, the oval pattern was observed in 67.6% of normal corneas and 39.5% of dry eyes, while the decentered oval pattern was noted in 2.9% and 31.6% of normal and dry eyes, respectively (p < 0.025 for oval pattern and p < 0.005 for decentered oval map). The mean astigmatism was 0.99 +/- 0.43 diopter (D) in normal corneas and 1.42 +/- 0.92 D in dry eyes (p = 0.015). In the anterior elevation maps, the island pattern was the most commonly observed pattern in both groups, 88.3% in normal corneas and 60.5% in dry eyes (p < 0.01). No significant difference in the patterns of posterior corneal elevation maps and axial power maps of the anterior corneal surface was noted between groups. CONCLUSION: The corneal thickness of the central and midperipheral cornea was significantly decreased in the dry eyes. It is possible that the chronic state of desiccation and immune activation in dry eye may contribute to the observed corneal thinning. Perhaps the frank corneal ulceration that occurs in some dry eyes is a more severe manifestation of this phenomenon.

Adult↗
PubMed1999

Evaluation of corneal thickness and topography in normal eyes using the Orbscan corneal topography system.

AIMS: To map the thickness, elevation (anterior and posterior corneal surface), and axial curvature of the cornea in normal eyes with the Orbscan corneal topography system. METHODS: 94 eyes of 51 normal subjects were investigated using the Orbscan corneal topography system. The anterior and posterior corneal elevation maps were classified into regular ridge, irregular ridge, incomplete ridge, island, and unclassified patterns, and the axial power maps were grouped into round, oval, symmetric bow tie, asymmetric bow tie, and irregular patterns. The pachymetry patterns were designated as round, oval, decentred round, and decentred oval. RESULTS: The thinnest point on the cornea was located at an average of 0.90 (SD 0. 51) mm from visual axis and had an average thickness of 0.55 (0.03) mm. In 69.57% of eyes, this point was located in the inferotemporal quadrant, followed by the superotemporal quadrant in 23.91%, the inferonasal quadrant in 4.35%, and the superonasal quadrant in 2.17%. Among the nine regions of the cornea evaluated (central, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal, and superior) the central cornea had the lowest average thickness (0.56 (0.03) mm) and the superior cornea had the greatest average thickness (0.64 (0.03) mm). The mean simulated keratometry (SimK) was 44.24 (1.61)/43.31 (1.66) dioptres (D) and the mean astigmatism was 0.90 (0.41) D. Island (71.74%) was the most common elevation pattern observed in the anterior corneal surface, followed by incomplete ridge (19.57%), regular ridge (4.34%), irregular ridge (2.17%), and unclassified (2.17%). Island (32.61%) was the most common topographic pattern in the posterior corneal surface, following by regular ridge (30.43%), incomplete ridge (23. 91%), and irregular ridge (13.04%) patterns. Symmetric bow tie was the most common axial power pattern in the anterior cornea (39.13%), followed by oval (26.07%), asymmetric bow tie (23.91%), round (6. 52%), and irregular (4.53%) patterns. In the pachymetry maps, 47.83% of eyes had an oval pattern, and round, decentred oval, and decentred round were observed in 41.30%, 8.70%, and 2.18% of eyes, respectively. CONCLUSION: The information on regional corneal thickness, corneal elevation and axial corneal curvature obtained with the Orbscan corneal topography system from normal eyes provides a reference for comparison with diseased corneas. The Orbscan corneal topography system is a useful tool to evaluate both corneal topography and corneal thickness.

Adult↗
PubMed1999

Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea.

PURPOSE: To correlate tear fluorescein clearance with interleukin-1alpha (IL-1alpha) concentration and gelatinase B (matrix metalloproteinase [MMP]-9) activity in the tear fluid of patients with ocular rosacea and normal control subjects. METHODS: Gelatinase activity was evaluated by gelatin zymography in tear fluid obtained from 13 patients with ocular rosacea (including 1 patient with recurrent epithelial erosion, 2 with recurrent peripheral corneal infiltrates and vascularization, and 2 patients with epithelial basement membrane dystrophy) and 13 normal subjects with normal aqueous tear production and no irritation symptoms. Tear fluorescein clearance was evaluated by measuring fluorescence in tear fluid collected from the inferior meniscus 15 minutes after instillation of 5 microl of 2% Na-fluorescein with a CytoFluor II fluorometer. Pro-MMP-9 and IL-1alpha concentrations in the tear fluid were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with normal control subjects, patients with ocular rosacea had a greater delay of tear fluorescein clearance (P < 0.001), a higher tear IL-1alpha concentration (P < 0.001), and a greater pro-gelatinase B (92 kDa) activity (P < 0.001) in their tear fluid. The 84-kDa active form of gelatinase B was observed in 46% of the rosacea tear samples and none of the controls. The zymographic results were confirmed by ELISA that showed a significantly greater concentration of pro-MMP-9 (92 kDa) in the tear fluid of rosacea patients than controls. Delayed tear clearance was correlated with elevated tear IL-1alpha concentration (p=0.67, P < 0.001) and increased tear gelatinase B activity (p=0.84, P < 0.001). Tear IL-1alpha concentration was correlated with tear gelatinase B activity (p=0.58, P < 0.002). CONCLUSIONS: Gelatinase B (MMP-9) activity is greater in patients with ocular rosacea than in normal eyes. The majority of this activity is due to 92-kDa proform of this enzyme. This activity is correlated with delayed tear clearance and tear fluid concentration of interleukin-1alpha, a proinflammatory cytokine that has been reported to stimulate gelatinase B production. Elevated gelatinase B activity in ocular rosacea may be involved in the pathogenesis of the irritation symptoms, recurrent epithelial erosions, vascularization, and epithelial basement membrane dystrophy that develops in the corneas of patients with this condition.

Adult↗
PubMed1998

Cytokines and tear function in ocular surface disease.

In summary, tear EGF levels correlate most strongly with tear production in normals, and it is likely that some form of homeostatic mechanism exists to provide a constant supply to the ocular surface. Commercial ELISA kits appear to measure EGF in tears with good consistency and may be useful in the future to improve comparability of data from different studies. In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there is a differential increase in the level of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this elevation appears to be the result of reduced tear turnover, which may form an important positive feedback mechanism encouraging tear stagnation and the perpetuation of ocular surface inflammation.

Adult↗
PubMed1998

Alterations of ocular surface gene expression in Sjögren's syndrome.

We have demonstrated that conjunctival epithelium of SS patients displays increased numbers of S-phase cells compared with non-dry eye controls. Moreover, in SS patients, these S-phase cells are distributed throughout all strata of the epithelium. The expression of MUC-1, a cell surface marker indicative of terminally differentiated epithelium, is localized to the conjunctival epithelial surface in SS and control patients. However, MUC-1 surface immunoreactivity appears to be reduced in SS epithelium, suggesting disruption of normal epithelial differentiation. A MUC-1 epitope exposed by pretreatment with neuraminidase is expressed in the basal and suprabasal layers of both patient populations. This antigen likely represents nascent, partially processed MUC-1(6) and may serve as a marker of the preterminally differentiated epithelial phenotype. Messenger RNA encoding several different inflammatory cytokines, including TNF-alpha, IL-1 alpha and beta, IL-6, IL-8, IL-10, and TGF-beta 1, is expressed at elevated levels within the conjunctival epithelium of SS patients compared with non-dry eye controls. Based on these observations, we have formulated a model to explain the ocular surface pathology of Sjögren's syndrome. We hypothesize that mechanical abrasion secondary to aqueous tear deficiency creates an inflammatory environment where conjunctival epithelial cells and lymphocytes are stimulated to produce and secrete various cytokines (i.e., IL-1, TNF-alpha, IL-6, IL-8, etc.) into the tear film. Elevated cytokine levels within the tear film, perhaps combined with reduced concentrations of essential lacrimal gland-derived factors (i.e., EGF, retinol), create an environment in which terminal differentiation of the ocular surface epithelium is impaired. As a consequence, the epithelium becomes hyperplastic, displaying increased mitotic activity, and loses the ability to express mature protective surface molecules including the membrane-bound mucin, MUC-1. This would imply that anti-inflammatory medications (i.e., corticosteroids or cyclosporine) that suppress the inflammatory component of this cascade may ameliorate the ocular surface disease and discomfort experienced by SS patients.

Cell Cycle↗
PubMed1998

A unified theory of the role of the ocular surface in dry eye.

It is our belief that the pathology of dry eye occurs when systemic androgen levels fall below the threshold necessary for support of secretory function and generation of an anti-inflammatory environment (Fig. 3). When this occurs, both the lacrimal gland and the ocular surface become irritated and inflamed, and they secrete cytokines that interfere with the normal neural connections that drive the tearing reflex. This leaves the lacrimal gland in an isolated condition, perhaps exacerbating atrophic alterations of the glandular tissue. These changes allow for antigen presentation at the surface of the lacrimal acinar cells and increase lymphocytic infiltration of the gland. A similar series of events may be occurring on the ocular surface. From this hypothesis we conclude: 1. The ocular surface, lacrimal gland, and interconnecting innervation act as an integrated servo-mechanism. 2. Once the lacrimal gland loses its androgen support, it is subject to immune/neurally mediated dysfunction. 3. The ocular surface is an appropriate target for dry eye therapeutics.

Animals↗
PubMed1998

Nontuberculous mycobacterial keratitis in south Florida.

OBJECTIVE: This study aimed to review the clinical features, therapeutic response, and histopathology of cases of nontuberculous mycobacterial keratitis at the Bascom Palmer Eye Institute. DESIGN AND PARTICIPANTS: Retrospective review of medical records, clinical photographs, histopathology, and microbiology of 24 cases of nontuberculous acid-fast keratitis over the past 15 years. RESULTS: Causal organisms included Mycobacterium chelonae (16), M. fortuitum (3), M. avium-intracellulare (2), M. nonchromogenicum (1), M. triviale (1), and M. asiaticum (1). Clinically, the keratitis had a superficial location except in those patients with a history of surgery. Amikacin was the most commonly used antibiotic (63%). Three patients were treated with Clarithromycin. In one patient, it was stopped because of toxicity; the other two had resolution of their infiltrates. Fifty-five percent did not respond to topical antimicrobial therapy. The organisms as a group were sensitive to amikacin and Clarithromycin and resistant to the fluoroquinolones. Sixty-four percent of the group that failed to respond to medical treatment were treated with steroids after the diagnosis was known, in comparison to 44% of the group treated successfully with medications. The histopathology of the patients treated with steroids showed minimal inflammation despite a large number of organisms, in contrast to the dense infiltrates seen in the specimens from patients not treated with topical steroids. CONCLUSION: Nontuberculous mycobacterial keratitis is a chronic insidious infection that is often unresponsive to medical therapy. The authors recommend that steroids be withheld. Based on the authors' experience of three patients, topical Clarithromycin may hold promise as a therapeutic agent. Lamellar keratectomy or penetrating keratoplasty should be considered in those patients who do not respond to medical therapy or those who have recurrent exacerbations on attempted weaning of topical antibiotic therapy.

Adult↗
PubMed1998

Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation.

PURPOSE: To determine which subjective assessments and objective tests have clinical utility as diagnostic tools in ocular irritation associated with Sjögren's syndrome-related aqueous tear deficiency (ATD), non-Sjögren ATD, inflammatory meibomian gland disease (MGD) associated with rosacea, and atrophic MGD. METHODS: Forty adults with ocular irritation and 10 with normal ocular surfaces were enrolled in a nonrandomized, nonblinded clinical trial. Symptoms were evaluated. Tests included biomicroscopy; evaluation of tear-film integrity, production, and clearance; fluorescein and rose bengal staining; and serum autoantibody screening. RESULTS: Symptoms were similar among groups and most severe in the Sjögren's group. Fluorescein tear break-up time was significantly faster in the ATD and MGD groups than that in controls. Schirmer scores were significantly lower in the ATD group than those in MGD and control groups. Tear clearance was delayed in the ATD and atrophic MGD groups. Xeroscope grid distortion was noted only with ATD. The Sjögren's group had greater loss of naso-lacrimal reflex, slower fluorescein clearance, and greater ocular-surface fluorescein and rose bengal staining than did the others. More MGD subjects had meibomian gland orifice metaplasia and acinar dropout than did those with Sjögren-related ATD and controls. Schirmer scores correlated inversely with rose bengal staining, corneal fluorescein staining, and grid distortion. Rose bengal staining correlated with grid distortion and loss of nasal-lacrimal reflex, but not with MGD. CONCLUSION: Subjective assessments and objective diagnostic tests have clinical utility as diagnostic tools in tear-film disorders. ATD is correlated with ocular-surface disease. An algorithm summarizing the diagnostic utility of these tests is included.

Adolescent↗
PubMed1998

Topographic pattern and apex location of keratoconus on elevation topography maps.

PURPOSE: To compare topography pattern and apex location in elevation and axial curvature topographic maps of keratoconic corneas. METHODS: We prospectively evaluated 72 corneas of 42 patients who had one or more corneal findings of keratoconus with the elevation and axial curvature displays of the PAR Corneal Topography System (PAR-CTS) and 66 of these corneas with the axial curvature display of the Tomey Topographic Modeling System (TMS-1). Topography maps were evaluated for topography pattern and location of the cone apex. RESULTS: Axial curvature displays of the PAR-CTS and the TMS-1 showed good concordance in terms of topographic patterns (96% for right, 86% for left corneas) and apex locations of cones (92% for right, 80% for left corneas). On the other hand, low concordances were noted when comparing topographic patterns (35.3% for right, 36.8% for left corneas) and apex locations (47% for right, 38% for left corneas) on curvature and elevation mode displays of PAR-CTS. Apices were found in the inferotemporal quadrant in 65% of corneas evaluated with the PAR-CTS. This distribution is significantly different from the apex location in axial curvature maps (p < 0.04). Twenty-nine percent of corneas that showed an apex on the axial curvature mode of the PAR-CTS had a normal pattern, without a detectable cone apex, on the elevation mode display. CONCLUSIONS: The results of this study clearly show the difference between elevation and curvature-based corneal topographic evaluation of keratoconus. Unlike axial curvature maps, the majority of apices on elevation maps are clustered in the inferotemporal quadrant. This new information about apex location in keratoconic corneas provided by elevation topography may have better diagnostic specificity than regional differences of curvature on axial curvature maps. Because elevation mapping shows the physical location of the cone, it may improve results of contact lens fitting and surgical management.

Cornea↗
PubMed1998

The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.

BACKGROUND: Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female. HYPOTHESIS: Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye. THERAPY: Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic. CONCLUSION: Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.

Animals↗
PubMed1998

Advances in the diagnosis and management of keratoconjunctivitis sicca.

Keratoconjunctivitis sicca is a common ocular surface disease that develops in patients with aqueous tear deficiency. Recent advances have been made in diagnosis, pathogenesis, and therapy of this condition. Advances in diagnosis include improved understanding of the specificity of the tests used for diagnosis, elucidation of the mechanism of the ocular surface rose bengal and fluorescein staining that occurs in this condition, and the expanded use of impression cytology. Advances in pathogenesis include the concept that keratoconjunctivitis sicca is a condition of abnormal growth and differentiation and immune activation of the ocular surface epithelium. These findings indicate that keratoconjunctivitis sicca may represent a chronic wound-healing response to a poorly lubricated and inflamed ocular surface. Advances in therapy include improved nonpreserved artificial tears and therapies targeted at decreasing ocular surface inflammation.

Animals↗
PubMed1997

Inflammatory cytokines in the tears of patients with ocular rosacea.

OBJECTIVE: The purpose of the study is to compare tear fluid concentrations of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF) in ocular rosacea with those in control subjects and to examine the relation between tear functions, such as production and clearance rate, and the concentrations of cytokines in tear fluid. PARTICIPANTS AND INTERVENTION: Fourteen patients with severe meibomian gland disease, facial rosacea, and symptoms of ocular irritation were examined for ocular surface disease, tear production, and tear clearance rate (TCR). Twelve control subjects, frequency-matched for age, and 15 ideal normal subjects with no ocular symptoms and normal tear function were assessed using the same parameters. Minimally stimulated tear samples (20 microl) were drawn from each subject and analyzed using a sandwich enzyme-linked immunosorbent assay to detect IL-1alpha, TNF-alpha, and EGF. RESULTS: Tear IL-1alpha concentration was significantly higher in patients with rosacea than in age-matched (P = 0.003) and ideal control subjects (P < 0.001). Tumor necrosis factor-alpha was not detected in patients or control subjects, indicating levels of less than 10 pg/ml. Epidermal growth factor was not significantly higher in patients with rosacea than in age-matched control subjects. Tear turnover LN(TCR) was lower in patients with rosacea than in both age-matched (P = 0.048) and ideal control subjects (P = 0.002). Schirmer I scores were statistically lower in patients with rosacea than in ideal control subjects (P = 0.013), but not age-matched control subjects. Interleukin-1alpha was correlated inversely with LN(TCR) (r= -0.58, P < 0.0001) and Schirmer I (r = -0.39, P = 0.012). CONCLUSIONS: Concentrations of IL-1alpha are present in normal tears but are elevated in ocular rosacea, whereas TNF-alpha is not present in either case. The reduced tear turnover, LN(TCR), its inverse correlation with IL-1alpha, and the absence of TNF-alpha in the tears of these patients suggest that the increased concentration of IL-1alpha observed may be largely because of clearance failure of cytokine normally produced at the ocular surface.

Adult↗