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At least 73 records · Page 4Linked to original sources

Normal protein and glycoprotein profiles of reflex tears and trace element composition of basal tears from heavy and slight deposits on soft contact lenses.

We investigated the hypothesis that lacrimal component accumulation on soft contact lenses (SCL) may be induced by an abnormal protein, glycoprotein, or trace element composition of the tear fluid. Individual tear samples were collected from healthy non-SCL wearers (normal patients) and SCL wearers grouped as either "slight-depositor" or "heavy-depositor" following SCL spoilage rate and frequency. The reflex tear proteins were analyzed by three electrophoretic procedures: sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on minigels, isoelectric focusing (IEF) on immobilized pH gradients (IPG 4-7), and two-dimensional separation combining IEF in the first dimension to orthogonal SDS-PAGE. After separation, the proteins were detected by silver staining and identified by immunologic probes. The reflex tear glycoproteins were analyzed by lectin affinity associated electrotransfer of SDS-PAGE with a panel of five biotinylated lectin probes: Canavalia ensiformis (Con A), Artocarpus integrifolia (Jacalin), glycine max (SBA), Ulex europaeus (UEA 1), and Triticum vulgaris (WGA) agglutinins. The basal tear trace elements were analyzed by Synchrotron Radiation X-ray Fluorescence. Despite the highly sensitive techniques used in the study, the profiles of reflex tear proteins, glycoproteins, and trace elements appeared to vary slightly among individuals. No evident qualitative difference in reflex tear fluid related to SCL wear or deposit formation susceptibility was found. The presence or absence of a particular protein, glycoprotein, or trace element could not be correlated with a different reactivity to SCL. However, potassium and carbohydrate residues having affinity with Jacalin and WGA presented little but not significant variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Correlation between secretion rate and electrolyte concentration of human tears, and classification of patients with decrease in basal tear secretion].

We have reported that [K+] of human reflex tears is significantly higher than that of the basal tears, as reported in the rabbit. We investigated further the relation between secretion rate and parameters of pH, time-dependent change (delta pH1), [Na+], and [K+], to analyse the functional details of tear secretion. We reconfirmed elevation of [K+] of the tears at a high secretion rate, and noted a similar increase in delta pH1. In addition, we found a positive correlation between the tear secretion rate and delta pH1 and [K+]. In accordance with these results, we speculated that there were K(+)- and HCO3(-)-dependent secretory mechanisms in the lacrimal acinal cells and that the lacrimal secretion was maintained with these parallel mechanisms. Based on these results, we tried further to classify patients with decrease in basal tear secretion using the parameters of delta pH1 and [K+]. As a result we could classify patients on the basis of decrease in basal tear secretion.

Adult↗

Radial tears associated with cleavage tears of the medial meniscus in athletes.

PURPOSE: To evaluate the significance of a small radial tear in the root of the posterior horn of the medial meniscus in an otherwise normal-looking meniscus in individuals who play vigorous sports. TYPE OF STUDY: Retrospective review. METHODS: Arthroscopy was performed in 1,270 patients; 11 patients (0.86%) had a small radial tear in the root of the medial meniscus. Trimming of the tear revealed a large horizontal cleavage tear of the posterior horn and body of the meniscus. The average age of the affected patients was 29.6 years (range, 21 to 45 years), and all were active in sports. Magnetic resonance imaging was of dubious diagnostic value. Three patients had undergone previous arthroscopy at which time the small radial root tear had been noted but was not thought to warrant treatment. RESULTS: All 11 patients returned to their former levels of activity after adequate surgery. CONCLUSIONS: When a radial root tear in the medial meniscus is found in an athletic patient, the edges of the tear should be trimmed, the root of the medial meniscus examined, and any additional torn cartilage resected.

Adult↗

Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy.

BACKGROUND: The aim of this study was to evaluate the effect of linoleic acid (LA) and gamma-linolenic acid (GLA), both precursors of PGE(1), on tear production, tear fluorescein clearance and on the ocular surface after photorefractive keratectomy (PRK). METHODS: Sixty subjects (age 25+/-10 years; refractive error -3+/-2 diopters (spherical equivalent), mean +/- standard deviation) undergoing PRK were enrolled. The inclusion criteria were: Schirmer 1 test >10 mm/5 min, no corneal fluorescein staining, low irritation symptoms (questionnaire score <5), standardised visual scale (to evaluate tear fluorescein clearance) score <3. Patients were randomly divided into two groups. One group of 31 subjects was treated once daily orally with tablets containing LA (28.5 mg) and GLA (15.1 mg) (from 3 days before PRK to 1 month after PRK). The control group (29 subjects) underwent PRK and received no treatment with LA and GLA. A symptoms questionnaire, Schirmer 1 test and fluorescein clearance test (FCT) using the standardised visual scale were performed before starting therapy (T(0)) and 30 days after PRK (T(1)). RESULTS: All patients completed the study. The Schirmer 1 test varied from 16.3+/-6.9 (T(0)) to 17.6+/-7.2 (T(1)) for the treated group and from 18.3+/-6.2 (T(0)) to 15.7+/-7.4 (T(1)) for the untreated group ( P<0.0001, two-tailed unpaired t-test). FCT was 1.9+/-0.6 at T(0) and 1.6+/-0.8 at T(1) for the treated group and 1.7+/-0.7 at T(0) and 2.0+/-0.9 at T(1) for the untreated group ( P<0.0001). The symptoms score was 4.7+/-1.9 at T(0) and 7.6+/-7.2 at T(1) for the treated group and 4.2+/-2.0 at T(0) and 10.1+/-7.6 at T(1) for the untreated group ( P<0.05). CONCLUSION: Reduced corneal sensitivity has already been proved after PRK. This could be the main reason for a decrease in tear production and for a reduced blinking rate leading to delayed tear clearance. The oral precursors of PGE(1), LA and GLA, could be helpful in increasing tear production and clearance after PRK.

Adult↗

Tear evaporimeter for measuring water evaporation rate from the tear film under controlled conditions in humans.

The rate of water evaporation from the tear film depends on the conditions under which it is determined. If measured in a controlled and easily reproducible setting, tear evaporation rate could serve as a useful diagnostic and research tool. We have developed a tear evaporimeter that provides a non-invasive method for evaluating water evaporation rate in eyes with normal or pathologic tear films. The subject is fitted with a pair of swimmer's goggles modified so that the air over the test eye is conditioned to a desired baseline of relative humidity (29.5%) and temperature (23 +/- 1 degree C). To eliminate other sources of water, the lids and skin under the goggles are covered with petroleum jelly. The subject is asked to keep his/her eye open and to avoid blinking during the 1-min test. The increase in relative humidity due to water evaporation from the tears is then determined. The surface area of the eye exposed to evaporation is calculated from the lid aperture. We measured the water evaporation rate in 52 normal eyes (average = 4.07 X 10(-7) +/- 0.40 X 10(-7) g/cm2/sec) and compared the results with values obtained in 52 eyes with various tear-film abnormalities (average = 8.17 X 10(-7) +/- 2.65 X 10(-7) g/cm2/sec). The difference between the two groups is statistically significant (P less than 0.01). In normal eyes, after the instillation of one drop of 0.5% proparacaine, the increase in evaporation rate was statistically significant.

Adult↗

Evaluation of the tear film stability after laser in situ keratomileusis using the tear film stability analysis system.

PURPOSE: To evaluate the tear film stability of patients before and after laser in situ keratomileusis (LASIK) using the tear film stability analysis system (TSAS). DESIGN: Prospective observational case series. METHODS: New videokeratography software for a topographic modeling system (TMS-2N) was developed that can automatically capture consecutive corneal surface images every second for 10 seconds. Thirty-four subjects (64 eyes) who underwent myopia LASIK were enrolled in this study. All subjects were examined with the new system before LASIK and at 1 week, 1 month, 3 months, and 6 months after the surgery. Corneal topographs were analyzed for tear breakup time (TMS breakup time) and breakup area (TMS breakup area). Based on pre-LASIK TSAS analysis, subjects were separated into normal and abnormal TSAS value groups. The criteria for the normal group were either TMS breakup time more than 5 seconds or TMS breakup area less than 0.2. The percentage of the occurrence of superficial punctuate keratitis was compared between the two groups with regard to subject's dry eye signs and symptoms. RESULTS: Tear film stability decreased significantly during the early period after LASIK, as indexed by decreased TMS breakup time and increased TMS breakup area. Tear film instability resolved at 6 months after surgery. Before LASIK, 22 subjects (43 eyes) had normal TSAS evaluation and 12 subjects (21 eyes) were abnormal. After LASIK, among normal TSAS value eyes, 8 of 43 (18.6%) eyes developed superficial punctuate keratitis. In sharp contrast, 14 of 21 (66.7%) eyes in the abnormal group displayed superficial punctuate keratitis, correlating well with the patients' dry eye symptoms. The difference in the presence of superficial punctuate keratitis after LASIK between normal and abnormal TSAS value groups was statistically significant (P <.001). Subjects with abnormal TSAS evaluation also displayed resistance to dry eye treatment and had extended period of recovery. CONCLUSIONS: Tear film stability analysis can be a useful means for screening LASIK candidates before surgery and for prognosticating dry eye symptoms thereafter.

Adult↗

Quantification of tear interference image: tear fluid surface nanotechnology.

PURPOSE: To review the literature on lipid supplementation therapy for dry eye and on image analysis using tear interference images from the specific tear lipid layer interference camera DR-1. METHODS: Systematic literature review of lipid supplementation therapy for lipid tear deficiency dry eye, kinetic analysis of tear interference images using DR-1 camera, and computer-synthesized interference color chart for DR-1 camera. CONCLUSION: To establish lipid supplementation therapy, a quantification system of tear lipid layer is required. Tear lipid thickness could be quantified using a computer-synthesized interference color chart system.

Castor Oil↗

Effect of topical tropicamide on tear production as measured by Schirmer's tear test in normal dogs and cats.

OBJECTIVE: To evaluate the effect of a single dose of topical 1% tropicamide on tear production as measured by the Schirmer tear test (STT) in the normal dog and cat. MATERIAL AND METHODS: Twenty-eight dogs and 32 cats received 50 micro l : l of 1% tropicamide in one eye and the opposite eye served as the control. STTs were performed immediately before instillation of tropicamide and then at 1, 4, 8 and 24 h post drug instillation. STT results were compared between the control and treated eyes at the different times. RESULTS: Aqueous tear production in dogs, measured by STT, was not significantly reduced. The mean +/- SEM STTs for the baseline time for control and tropicamide-treated eyes were 19.9 +/- 0.8 and 20.3 +/- 0.8 mm wetting/min, respectively. For the control eyes, the subsequent mean +/- SEM STT levels were 20.3 +/- 0.9 (1 h), 21.1 +/- 0.8 (4 h), 20.1 +/- 0.9 (8 h), and 18.7 +/- 0.7 (24 h). For the tropicamide-treated eyes, the subsequent mean +/- SEM STT levels were 19.4 +/- 0.9 (1 h), 19.3 +/- 0.9 (4 h), 20.0 +/- 0.9 (8 h), and 18.4 +/- 0.8 (24 h). Aqueous tear production of both eyes was significantly reduced in cats at 1 h but returned to baseline by 4 h post tropicamide instillation. The mean +/- SEM STT levels for the baseline time in cats for control and tropicamide-treated eyes were 14.9 +/- 0.8 and 14.7 +/- 0.8 mm wetting/min, respectively. Subsequent mean +/- SEM STT levels for the control eyes were 6.4 +/- 1.1 (1 h), 11.9 +/- 1.0 (4 h), 13.9 +/- 0.8 (8 h), and 16.4 +/- 1.0 (24 h). For the tropicamide-treated eyes, the subsequent mean +/- SEM STT levels were 5.3 +/- 0.8 (1 h), 10.2 +/- 0.8 (4 h), 14.7 +/- 1.0 (8 h), and 16.6 +/- 1.0 (24 h). CONCLUSION: Single dose 1% tropicamide does not significantly lower tear production rates, as measured by the STT, in normal dogs. However, in normal cats single doses of 1% tropicamide in one eye cause significant reductions in tear production of both eyes at 1 h that recovered to baseline levels by 4 h.

Administration, Topical↗

Outflow of tears and its influence on tear secretion and break up time (B.U.T.).

Schirmer's test shows that a retarded outflow of tears causes reduction of the tear secretion. The B.U.T. is independent of the outflow of tears in patients with epiphora (119 eyes with mechanical obstruction, functional obstruction, or normal passage). Mucomimetics prolong the B.U.T. and retard the outflow of tears, whereas ointments reduce both the B.U.T. and the outflow (74 eyes). The B.U.T. becomes reduced when tears are absorbed by filter paper in Schirmer's test, but remains uninfluenced by filter paper inserted in the fornix. The B.U.T. is a valuable clinical test. It is the resultant of many different factors (tear volume, mucus, fat, etc.).

Humans↗

Biomicroscopy of the tear film: aqueous and lipid tear substitutes in the normal and abnormal eye.

Polarised light biomicroscopy was used to assess the behaviour and interactions of two polymer-containing preparations of artificial tears, and two lipid-containing ointments, with the normal and abnormal pre-corneal tear film. The preparations were used topically in six normal dogs, and three dogs with keratoconjunctivitis sicca. A transient morphological alteration of the surface lipid layer of the tear film was commonly observed after the use of polymer solutions. The ointments spread as a continuous or semi-continuous layer over the normal, or polymer-supplemented, aqueous tears. Further applications of artificial tears produced only a temporary disruption of this layer. In dogs with keratoconjunctivitis sicca, thickening of the lipid layer of the tear film was observed for over 20 hours after the administration of ointment. These observations are discussed in relation to the prospects for the improved medical treatment of keratoconjunctivitis sicca by the use of polymer-containing solutions and ointments in combination.

Animals↗

[The change of tear secretion and tear film stability in castrated male rabbits].

OBJECTIVE: To evaluate the effect of androgen on tear secretion and tear film stability by observing the changes of ocular surface and tear film in the castrated male rabbit. METHODS: Sixteen male rabbits were selected and randomly divided into the normal control group (8 rabbits) and the castrated group (8 rabbits). Schirmer's tests, tear film break-up time (BUT) and rose bangle (rb) staining were performed on the eyes of two groups at 1, 2, 3, 4 weeks, 2 and 3 months. The Chiron Diagnostics ACS: 180 Automato Chemilluminescence Systems was used to determine the two groups' testosterone level in serum at pre-castrate and post-castrate. Results were analyzed statistically. Lacrimal gland, Harder's gland, conjunctiva, cornea and limbus were removed for observation histopathologically after three months. RESULTS: Both Schirmer's test and break-up time scores were significantly lower in the castrated group compared with the control group. The difference became more and more prominent in the course of observation. Rose bangle staining was positive in the castrated group. Testosterone level in serum was significantly lower in the post-castrate than that in the pre-cartrate. Histopathological observation showed that lacrimal glandular epithelial cells were atrophic and flat, the lumen of gland was enlarged and vesicular mucous in acinus cells disappeared. PAS positive material and conjunctival globlet cells were significantly decreased in the castrated group. Compared with the control group there were no significant morphologic changes in the corneal epithelium and limbal stem cells. CONCLUSIONS: The low level of testosterone in castrated rabbit may contribute to the atrophy and applanation of lacrimal glandular epithelium, disappearance of vesicular mucous in acinar cells and the significant decrease of the number of conjunctival globlet cells. All these can lead to decrease of both the quantity and quality of tear secretion and thus cause the instability of tear film.

Androgens↗

[Fluorophotometric measurement of tear volume and tear turnover rate in human eyes].

Tear volume and turnover rate were measured in 31 normal eyes using a newly designed objective fluorophotometer. After instillation of 1 microliter of 50,000 ng/ml fluorescein solution, its concentration in the lower marginal strip was measured every minute for 10 minutes after instillation. The tear volume and the tear turnover rate were determined using the method of Mishima et al. (Invest. Ophthalmol. Vis. Sci., 1966). The tear volume in this study was 12.4 +/- 6.2 microliters, initial turnover rate was 31.5 +/- 14.4%/min., and basal turnover rate was 24.0 +/- 14.2%/min. (Mean +/- SD). There were no significant differences in sex, age or use of contact lens. We also measured the tear volume and turnover rate using 5 microliters of 10,000 ng/ml fluorescein solution in the same way. The result turned out to be significantly higher, suggesting that minimal irritation is required for evaluating the tear flow.

Adult↗

Determination of the incidence and clinical characteristics of subsequent retinal tears following treatment of the acute posterior vitreous detachment-related initial retinal tears.

PURPOSE: To determine the incidence of subsequent retinal tears (SRT) in patients who were previously treated for acute posterior vitreous detachment (PVD)-related retinal tears. DESIGN: Retrospective chart review. METHODS: A retrospective chart review of 155 eyes of 137 consecutive patients treated for acute PVD-related retinal tears was performed. RESULTS: During a median follow-up of 13 months (range 3 to 157 months) after treatment, SRT developed in 19 (12.2%) of 155 treated eyes. Most of the SRT occurred during the first 6 months (12 of 19 eyes) after initial treatment. Subsequent vetinal tears developed within the first 12 months in 15 of 19 treated eyes, however only six of 15 of these eyes were symptomatic. Of those patients who developed SRT after 12 months, all had new visual symptoms. CONCLUSION: Patients who present with acute PVD-related retinal tears are at a low but significant risk for developing SRT. A significant number of patients treated for PVD-associated retinal tears present within 1 year with SRT without symptoms.

Acute Disease↗

Acute rotator cuff tear: do we miss the early diagnosis? A prospective study showing a high incidence of rotator cuff tears after shoulder trauma.

The aim of this study was to evaluate the epidemiologic data of patients with an acute soft-tissue injury to the shoulder, with an emphasis on improving the early diagnosis of acute rotator cuff tears. This study included 104 patients, with a median age of 49 years (range, 19-75 years). The patients were evaluated clinically and with ultrasonography at a median of 13 days (range, 3-49 days) after the injury. A total of 60 patients (58%) had some degree of cuff lesion on the ultrasonographic examination. Of these patients, 33 (32%) had a full-thickness rotator cuff tear, 14 (13%) had a partial-thickness cuff tear in the tendon substance, and 13 (13%) had a partial cuff tear at the insertion site on the major tubercle. The injury mechanism or activity at the moment of injury did not correlate with the presence of a rotator cuff lesion, but we found a strong age correlation, with a prevalence of any rotator cuff tear, above 50%, for patients aged above 50 years and with a prevalence of full-thickness tears of 50% in the groups aged 50 to 59 years and aged 60 to 69 years. In conclusion, this study found a high incidence of rotator cuff lesions by further evaluation of patients undergoing consultation at the emergency department, with an inability to perform active abduction above 90 degrees and normal radiographs, after an acute shoulder trauma.

Adult↗

Ascending aorta replacement and local repair of tear site in type A aortic dissection with arch tear.

BACKGROUND: Transaortic repair of the tear was previously proposed as a compromise alternative to total arch replacement for acute type A aortic dissection with an arch tear. However, there are no data about long-term prognosis and radiologic findings after this procedure. METHODS: We reviewed the postoperative course and computed tomographic findings of 13 patients who underwent replacement of the ascending aorta and transaortic repair of an arch tear for acute type A aortic dissection. RESULTS: There were no early or late deaths during a mean follow-up period of 36.8 months. Computed tomographic follow-up showed complete thrombosis with or without later regression of the false lumen in the descending thoracic aorta in 9 patients (69.2%). Thrombosis of the false lumen usually occurred within 3 months postoperatively. Repair techniques incorporating the full thickness of the aortic wall in closure of the tear resulted in higher rate of success than approximation of the intima only (7 of 8 versus 2 of 5 patients, p < 0.05). CONCLUSIONS: Transaortic repair of the arch tear with replacement of the ascending aorta can be an option in selected patients who have a small intimal tear in the aortic arch. This option would be more viable for less experienced surgeons who would hesitate to replace the total arch.

Acute Disease↗

[Comparative study of treatment of the dry eye syndrome due to disturbances of the tear film lipid layer with lipid-containing tear substitutes].

BACKGROUND: A deficiency in the tear film lipid layer is aetiological in about 80 % of the patients suffering from dry eye, which results in excessive evaporation (so-called hyperevaporative dry eye). The treatment with conventional artificial tears did not prove to be successful here. In this study the treatment with two tear substitutes containing lipids were set in contrast with each other. MATERIAL AND METHODS: The randomised, controlled, multicentre cross-over study included 74 patients suffering from dry eye caused by a deficiency of the tear film lipid layer, which were organised into two groups. Group A (n = 38) was treated for the first 6 weeks with a liposomal eye spray (Tears Again), while the patients of the group of B (n = 36) were treated with an eye gel containing triglycerides (Liposic) in the same period. After 6 weeks the crossover was performed. The patients were treated in the following 6 weeks with the product which was not used before. Control examinations by masked examiners took place at the beginning of the study as well as after 6 and 12 weeks, considering the following parameters: eyelid edge-parallel conjunctival folds (LIPCOF), BREAK UP time (BUT), Schimer-I test, measurement of the tear meniscus, investigation of the edges of eyelid and visual acuity. In addition. the subjective feelings of the patients were also determined by means of questionnaires. RESULTS: At the beginning of the study the two groups did not differ significantly with respect to the initial values. After the first treatment period the improvement of the examined parameters LIPCOF, BUT, Schirmer, visual acuity and inflammation of the lid margin in group A (eye spray) proved to be significantly superior in comparison to group B (eye gel). The results of the second treatment period after the crossover were similar and showed an analogous supremacy of the liposomal eye spray. The interviews with the patients revealed that the subjective evaluation concerning efficacy and compatibility of the eye spray turned out to be explicitly more favourable than that concerning the eye gel. 74.6 % of the patients favoured the application as an eye spray onto the closed eyelids over the eye gel into the conjunctival sac. 62.5 % of the patients rated the liposomal eye spray to be better all in all, 12.5 % rated that both preparations are equal and 25 % favoured the eye gel. CONCLUSIONS: The treatment with phospholipids liposomes shows statistically significant clinical advantages and proves to be favourably and explicitly superior compared to the conventional standard treatment all in all.

Adult↗

Posterior tibialis tendon tears: comparison of the diagnostic efficacy of magnetic resonance imaging and ultrasonography for the detection of surgically created longitudinal tears in cadavers.

RATIONALE AND OBJECTIVES: The optimal advanced imaging method for detection and characterization of posterior tibialis tendon (PTT) tears is unclear. The purpose of this study was to investigate the utility of ultrasonography (US) and MR imaging in the detection of surgically created PTT tears in cadavers. MATERIALS AND METHODS: This was a prospective blinded study in which 16 fresh cadaveric foot and ankle specimens (3 men, 13 women; average age at death 83.9 years; age range 71-96 years) were scanned with both US and MR imaging before and after the surgical creation of 64 variable length longitudinal tears of the PTT. Ultrasonography was performed with a 12 MHz linear transducer with independent interpretations of static and dynamic studies separately by two blinded and experienced musculoskeletal radiologists. MR imaging was performed at 1.5 T with a standard transmit-receive extremity coil using axial, sagittal, coronal T1-weighted (TR 600, TE 20), and axial fast spin echo proton density and T2-weighted (TR 3000, TE 161/20, ETL 12) images. MR images were reviewed independently by two experienced musculoskeletal radiologists who were blinded to the status of the PTT. RESULTS: Sensitivity, specificity, and accuracy of MR imaging in the diagnosis of PTT tears were 73%, 69%, and 72%, respectively. Dynamic US interpretation yielded values of 69% sensitivity, 81% specificity, and 72% accuracy. Static US interpretation was less reliable than dynamic interpretation, and the only significance of static imaging was a high specificity (94%) for detection of longitudinal tears. The positive predictive value (PPV) for MR imaging and US was 88% and 92% respectively, and the negative predictive value (NPV) was 46% for both MR imaging and US. CONCLUSION: Our results suggest that US and MR imaging perform at the same level for the detection of surgically created longitudinal PTT tears in a cadaveric model. US has a higher specificity compared with MR imaging.

Aged↗

Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear production and tear stability and reduced immunopathology in rabbits with induced autoimmune dacryoadenitis.

BACKGROUND: The most common cause of ocular morbidity in developed countries is dry eye, many cases of which are due to lacrimal insufficiency. Dry eye affects approximately 10 million in the United States, most of whom are women. In the U.S. alone, an estimated 2 million Sjögren's syndrome patients have dysfunctional lacrimal glands and severe dry eye, and there is no satisfactory treatment. These patients would benefit if their lacrimal tissue function could be restored. METHODS: The effect of adenovirus-mediated transfer of tumor necrosis factor (TNF)-alpha inhibitor gene on induced autoimmune dacryoadenitis was evaluated in a rabbit model. Soluble transgene protein was detected in tears by ELISA for 7 days following transduction. RESULTS: Two weeks after induction of disease with activated lymphocytes, tear production, as determined by Schirmer testing, was reduced by about 40%, while tear film stability, as measured by tear breakup time (BUT), declined by 43%. Adenovirus-mediated gene therapy using AdTNFRp55-Ig given 2 weeks after disease induction, resulted in the return of tear production to normal levels by week 4. In the treated disease group, tear BUT improved significantly by week 4. Rose bengal scores, an indicator of corneal surface defects, increased after disease induction and declined after gene therapy. In the lacrimal gland, the CD4 to CD8 T cell ratio was 4:1 in the disease group compared to 1:2 in the treated group. Infiltration of T cells and CD18+ cells was reduced approximately 50% after gene therapy. CONCLUSION: We concluded that therapeutic levels of soluble TNF inhibitor were achieved in the lacrimal gland and on the corneal surface. Anti-inflammatory cytokine gene expression might offer a potential therapeutic modality for the treatment of autoimmune dacryoadenitis, once suitable vectors become available.

Journal Article↗