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A novel class of neurons at the trigeminal subnucleus interpolaris/caudalis transition region monitors ocular surface fluid status and modulates tear production.

Reflex tears are produced by many conditions, one of which is drying of the ocular surface. Although peripheral neural control of the lacrimal gland is well established, the afferent pathways and properties of central premotor neurons necessary for this reflex are not known. Male rats under barbiturate anesthesia were used to determine whether neurons at the ventral trigeminal subnucleus interpolaris- caudalis (Vi/Vc) transition or the trigeminal subnucleus caudalis-cervical cord (Vc/C1) junction region in the lower brainstem were necessary for tears evoked by noxious chemical stimulation (CO2 pulses) or drying of the ocular surface. Both the Vi/Vc transition and Vc/C1 junction regions receive a dense direct projection from corneal nociceptors. Synaptic blockade of the Vi/Vc transition, but not the Vc/C1 junction, by the GABA(A) receptor agonist muscimol inhibited CO2-evoked tears. Glutamate excitation of the Vi/Vc transition, but not the Vc/C1 junction, increased tear volume. Single units recorded at the Vi/Vc transition, but not at the Vc/C1 junction, were inhibited by wetting and excited by drying the ocular surface. Nearly all moisture-sensitive Vi/Vc units displayed an initial inhibitory phase to noxious concentrations of CO2 followed by delayed excitation and displayed an inhibitory surround receptive field from periorbital facial skin. Drying of the ocular surface produced many Fos-positive neurons at the Vi/Vc transition, but not at the Vc/C1 junction. This is the first report of a unique class of moisture-sensitive neurons that exist only at the ventral Vi/Vc transition, and not at more caudal portions of Vc, that may underlie fluid homeostasis of the ocular surface.

Action Potentials↗

Amniotic membrane transplantation in ocular surface disorders.

In this prospective study, 81 eyes of 70 patients diagnosed with various ocular surface disorders were enrolled to document the use of amniotic membrane transplantation in various ocular surface disorders. Detailed history and ocular examination was done. Ocular photographs and consent from all patients were taken. Fluorescein staining and impression cytology was done preoperatively and postoperatively in selected cases. Amniotic membrane was prepared from the placenta of a donor (consent taken and negative for infectious disorders), after separating amnion from chorion. It was washed with antibiotic solutions, transferred over nitrocellulose paper and stored in Dulbecco's modified Eagle's minimum essential medium at -80 degrees C. Recipient bed was prepared by removing the fibrovascular pannus and necrosed conjunctiva. Amniotic membrane was transplanted with the epithelial side up and sutured. Sixty-four eyes had good result by clinical evaluation or impression cytology findings, 5 eyes later required limbal stem cell culture and transplantation. All the 3 eyes had failure of the fornix reconstruction and 5 eyes had recurrence of the pterygium. Amniotic membrane provides lower recurrence rate in cases of recurrent pterygium. Alkali injuries are more dangerous but showed good response to amniotic membrane transplantation combined with limbal autografting or ex-vivo expansion and later transfer. Initial proper assessment of limbal involvement, conjunctival necrosis and corneal involvement is the key to the management of acute cases. Contracted sockets showed no improvement. Shield ulcers and persistent epithelial defect and ocular surface defects secondary to tumour excision showed excellent results.

Amnion↗

Ocular surface changes after excimer laser phototherapeutic keratectomy.

PURPOSE: To study the ocular surface disorder in patients with Avellino, granular, and lattice dystrophy, band keratopathy, and corneal leukoma before and after excimer laser phototherapeutic keratectomy. DESIGN: A prospective case-controlled study. PARTICIPANTS: A total of 45 eyes of 33 patients with superficial corneal opacities seen at Kobe Kaisei Hospital, Department of Ophthalmology, and 40 eyes of 20 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film break up time (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival impression cytology. MAIN OUTCOME MEASURES: The patients and the control subjects were compared for prephototherapeutic keratectomy (PTK) tear function parameters, tear film lipid layer interferometry grade, goblet cell density, and conjunctival squamous metaplasia grade. Alterations of these parameters within 3 months after PTK were also looked for. RESULTS: The average pre-PTK corneal sensitivity and tear film break up time were lower in patients compared with control subjects before PTK. Tear film lipid layer interferometry grade and conjunctival squamous metaplasia grades were higher in the patients than the controls before PTK. All these parameters improved gradually and significantly after PTK. Goblet cell density was significantly lower in the patients compared with controls before PTK. Schirmer test results and goblet cell density did not show any significant alterations after PTK. CONCLUSIONS: Concurrent improvements in corneal sensitivity, tear film break up time, lipid layer interference grades, and conjunctival squamous metaplasia grades all point to the favorable effects of PTK on the ocular surface by improving the stability of the tear film and ocular surface health through attainment of a regular corneal surface and probably inducing qualitatively/quantitatively better mucin production by a healthier epithelium after PTK.

Adult↗

[In vivo confocal microscopy and ocular surface diseases: anatomical-clinical correlations].

PURPOSE: To describe corneal and conjunctival epithelial changes in various ocular surface disorders with a new in vivo confocal microscope (Corneal HRT II module) and to compare these results with those obtained by immunohistology on impression cytology specimens. METHODS: In this study, we investigated 36 eyes of 18 patients with ocular surface diseases such as corneal epitheliopathy induced by ocular rosacea (five patients), keratoconjunctivitis sicca related to tear evaporative condition in Meibomian gland dysfunction (eight patients), or tear-deficient dry eye in Sjögren's syndrome (five patients). In vivo confocal microscopy imaging (Heidelberg Retina Tomograph II Rostock Cornea Module) and impression cytology of the cornea and/or conjunctiva were performed. The images were analyzed for epithelial cell morphology at nuclear and cytoplasmic levels, in the cornea and the conjunctiva, number of goblet cells and their possible presence within the corneal epithelium, corneoconjunctival junction at the limbus, and density and presence of inflammatory cells within both epithelia. RESULTS: Images obtained consisted of two-dimensional 400x400 microm optical sections oriented parallel to the surface of the eye and compared with impression cytology. Conjunctival and corneal epithelia showed dramatic changes in ocular surface disease. In keratoconjunctivitis sicca, we found squamous metaplasia, inflammatory cell infiltration, goblet cell depletion, as well as a nuclear snake-like chromatin pattern. In rosacea associated with corneal epitheliopathy, a corneal conjunctivalization (goblet cells together with conjunctival epithelial cells within the corneal epithelium layer) was found. The images provided by this technique are in excellent correlation with the findings using impression cytology. CONCLUSION: The HRT II in vivo confocal microscope facilitates the study of both central and peripheral ocular surface epithelia compared to first-generation confocal microscopy devices. In vivo confocal microscopy, showing corneal and conjunctival epithelial structures in the live eye at the cellular level, is likely to open up a new promising way to investigate ocular surface involvement in complex diseases, providing a new insight on corneal and conjunctival disorders in the future.

Conjunctiva↗

Clinical impact of conjunctivochalasis on the ocular surface.

PURPOSE: To report the clinical impact of conjunctivochalasis on the ocular surface by evaluating the effect of a new concept of conjunctivochalasis operation on the resolution of patients' symptoms and corneal epithelial damage. Also, the association of inflammation with conjunctivochalasis is examined. PATIENTS AND METHODS: A total of 168 eyes of 131 conjunctivochalasis patients with (50 eyes) or without (118 eyes) dry eye who received the newly designed conjunctivochalasis operation were enrolled. All patients had prominent conjunctivochalasis at the lower tear meniscus and their ocular symptoms were not sufficiently controlled by the usual eyedrop therapy. Subjective symptoms of patients were assessed before and after the operation by questionnaires. Scores of corneal fluorescein staining were evaluated before and after the operation in patients with dry eye. Four samples of the lower part of conjunctiva from non-dry eye conjunctivochalasis patients were investigated by immunostaining and compared with samples from 4 normal conjunctiva and 3 conjunctiva showing inflammation due to Mooren ulcer, ocular cicatricial pemphigoid, and alkali burn. RESULTS: The most frequent chief subjective symptoms before the operation were irritation (51.7%) and lacrimation (31.4%) in conjunctivochalasis patients without dry eye and irritation (80.0%) in those with dry eye. Improvement of the chief symptoms was obtained in 88.2% and 78.0% of these 2 patient groups, respectively. Furthermore, in patients with dry eye, corneal fluorescein staining scores (mean+/-SD) were significantly improved after the operation compared with before the operation: A (area), 0.6+/-0.7 and D (density), 0.8+/-0.9 versus A, 1.3+/-0.5 and D, 1.9+/-0.9; P<0.0001. Based on the immunostaining study, conjunctival samples from eyes with conjunctivochalasis and normal eyes showed negligible inflammation compared with those from inflamed conjunctiva. CONCLUSIONS: This study suggests that conjunctivochalasis has a great clinical impact on the ocular surface, and the newly developed operation is very effective in resolving patient complaints and also ocular surface damage in conjunctivochalasis with dry eye. It may also be suggested that the conjunctivochalasis has a negligible association with conjunctival inflammation.

Aged↗

Gelatinase expression in ocular surface disorders.

PURPOSE: To determine the expression of gelatinase A [matrix metalloproteinase (MMP)-2] and gelatinase B (MMP-9) in ocular surface disorders, we carried out examinations of the eyes of patients with such disorders. METHODS: The cases consisted of a normal group comprising three eyes as the control and a patient group comprising six eyes of patients with ocular surface disorders. These groups underwent the following examinations. (1) Gelatin zymography: Tear samples taken by using the Schirmer I test were eluted and analyzed by gelatin zymography. (2) Immunohistochemical study: By using the alkaline phosphate-anti-alkaline phosphatase or avidin-biotin complex method, corneal or conjunctival tissue was examined for the presence of MMP-2, MMP-9, and membrane type 1 (MT1)-MMP, which activates MMP-2. (3) Reverse transcription-polymerase chain reaction (RT-PCR): Total RNA was eluted from the specimens, and the expression patterns of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed. RESULTS: (1) Gelatin zymography: Only the proforms of MMP-2 and MMP-9 were detected in the normal group. Both active MMP-2 and active MMP-9 were detected in all studied cases in the patient group. (2) Immunohistochemical study: In the normal group, only MMP-2-positive cells were present in conjunctival epithelium. In the patient group, cells positive for MMP-2, MMP-9 and MT1-MMP were present in the epithelium of the conjunctiva or cornea except in one thermal burn case. (3) RT-PCR: In the normal group, only MMP-2 expression was observed. MMP-2, MMP-9, and MT1-MMP mRNA expression was observed in three cases in the patient group. CONCLUSIONS: MMP-2, MMP-9, and MT1-MMP, which activates MMP-2, were expressed in the patients with various ocular surface disorders. In ocular surface disorders, therefore, the expression of gelatinases is upgraded.

Conjunctival Diseases↗

In vivo confocal microscopy of the ocular surface.

Over the past two decades, the applications of in vivo confocal microscopy to the investigation of ocular surface diseases in the living eye have been greatly extended. Confocal microscopy enables detailed investigation of tarsal and palpebral conjunctiva, central and peripheral cornea, tear film, and lids, and it allows evaluation of the ocular surface at the cellular level. High-quality imaging in both contact and noncontact modes has allowed new understanding of the functions of the ocular surface system, and in the coming years, such knowledge will become increasingly comprehensive and specific. Confocal microscopy may provide a link between well-established ex vivo histology and in vivo study of ocular pathology, not only in clinical science but also in clinical practice. The purpose of this review is to summarize the current knowledge about in vivo confocal microscopy of the ocular surface.

Conjunctiva↗

Identification of insulin in the tear film and insulin receptor and IGF-1 receptor on the human ocular surface.

PURPOSE: Insulin produces pleiotropic effects on sensitive tissues, including the ocular surface, through the tyrosine kinase insulin receptor. Cerebrospinal fluid and secreted fluids, such as milk and saliva, have been reported to contain insulin. In the present study, the presence of insulin was examined in tear film, and the expression of insulin and insulin-like growth factor (IGF)-1 receptor was examined in the human cornea and conjunctiva. METHODS: Stimulated tear samples collected from 33 volunteers (17 men, 16 women), aged 23 to 51 years, who were fed or fasted for 12 hours, were assayed for total protein and insulin content by the biuret dye test and a radioimmunoassay, respectively. Frozen sections of human cornea (n = 4) and conjunctiva (n = 3) were incubated with anti-insulin receptor and anti-IGF-1 receptor antibodies and developed with a secondary antibody-peroxidase conjugate. RESULTS: Insulin was detected in all tear samples analyzed, the mean concentration being 0.404 +/- 0.129 ng/mL. There were no gender-related differences. In fed subjects, tears tended toward a higher insulin content than those in fasted individuals. There was no linear correlation between insulin and total protein content (mean, 4.61 +/- 0.79 mg/mL) in the tear film. Insulin and IGF-1 receptors were detected in the plasma membrane and cytoplasm of corneal and conjunctival epithelial cells. CONCLUSIONS: To the best of the authors' knowledge, this study represents the first demonstration of insulin in human tear film and the presence of insulin and IGF-1 receptor on the human ocular surface. These results suggest that the pancreatic hormone may play a metabolic and/or mitogenic role on the ocular surface.

Adolescent↗

Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease.

AIMS: To evaluate the efficacy of 50% autologous serum drops against conventional treatment in ocular surface disorders refractory to normal treatments in a prospective randomised crossover trial. METHOD: Patients fulfilling ophthalmological and haematological entry criteria were randomised to either 3 months of autologous serum 50% followed by 3 months of their conventional treatment, or 3 months of conventional treatment, followed by 3 months of autologous serum. Clinical assessments, including Schirmer's test, rose Bengal, and fluorescein staining, were carried out on entry and at monthly intervals. Impression cytology was performed at entry, 3 and 6 months. Grading was carried out on degrees of squamous metaplasia and goblet cell density. Subjective comfort was recorded daily using the "faces" scale. These categorical scores were converted to linear measurement using Rasch analysis. Statistical analysis was carried out using Wilcoxon's signed rank test and ANOVA. RESULTS: 16 patients were recruited with 31 eyes studied. The ocular surface diseases chiefly included Sjögren's syndrome (n = 6) and keratoconjunctivitis sicca (n = 5). Impression cytology available in 25 of 31 eyes showed significant improvement on serum treatment, p<0.02. Rasch weighted faces scores were statistically significantly better with serum, p<0.01. CONCLUSION: The results of this randomised study provide further evidence of the beneficial effects of autologous serum in severe ocular surface disorders. For most of these patients, autologous serum was superior to conventional treatment for improving ocular surface health and subjective comfort.

Adult↗

Long-term outcomes of keratolimbal allograft for the treatment of severe ocular surface disorders.

PURPOSE: To investigate the long-term outcome of keratolimbal allograft (KLAL) for the treatment of severe ocular surface disorders. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty patients (23 eyes) with severe ocular surface disorders. INTERVENTION: Thirty-three KLAL procedures were performed. Ten patients (10 eyes) underwent KLAL in combination with other surgical procedures. Oral or topical cyclosporine or both were used after surgery in 15 patients to prevent allograft rejection. MAIN OUTCOME MEASURES: Reconstruction of the ocular surface with restoration of phenotypic corneal epithelium, reduction of corneal vascularization and conjunctivalization, decreased pain, and visual improvement. RESULTS: The mean follow-up was 60 months (range, 15-96 months). Eight eyes (24.2%) never reepithelialized and were considered primary failures. The remaining 25 grafts initially restored a phenotypic corneal epithelium, but at last follow-up only 7 (21.2%) were stable. Graft survival rate was 54.4% at 1 year, 33.3% at 2 years, and 27.3% at 3 years. Visual acuity improved or was unchanged in 19 eyes (82.6%) and decreased in 4 eyes (17.4%). Seventeen corneal transplantations (3 lamellar keratoplasties and 14 penetrating keratoplasties) were performed either in combination with or after a KLAL. All three lamellar keratoplasties were successful, whereas 13 of the 14 penetrating keratoplasties failed. Cyclosporine was used initially in high-risk recipients and later in all recipients. Allograft rejection episodes occurred in 13 KLAL procedures of 11 eyes (39.4%) and were more common in patients treated with cyclosporine compared with the untreated group (87.5% vs. 22.2%). Graft survival was longer in the cyclosporine-treated group compared with the untreated group. CONCLUSIONS: Keratolimbal allograft is useful in ocular surface reconstruction and restores phenotypic corneal epithelium. Graft survival rate, however, decreases dramatically over a 2-year period. Long-term use of cyclosporine appears to prolong graft survival but does not prevent acute allograft rejections.

Administration, Oral↗

Inherent risks associated with manufacture of bioengineered ocular surface tissue.

OBJECTIVE: To review the potential health risks associated with bioengineered ocular surface tissue, which serves as a bellwether for other tissues. METHODS: All clinical trials using bioengineered ocular surface tissue published between July 1, 1996, and June 30, 2005, were reviewed with respect to materials used and statements of risk assessment, risk remediation, adverse events, manufacturing standards, and regulatory oversight. RESULTS: Ninety-five percent of investigational protocols used 1 or more animal-derived products and an overlapping 95% used 1 or more donor human tissues. Consideration of risks reveals a very low probability of potential harm but a significant risk of disability or death if such an event were to occur. Details of ethics approval, patient consent, and donor serologic test results were not consistently provided. No references were made to risk assessment or to codes of manufacturing and clinical practice. CONCLUSION: While a degree of risk is associated with bioengineered ocular surface tissue, investigational reports of this new technology have yet to address issues of risk management and regulatory oversight. CLINICAL RELEVANCE: Attention to risk and codes of manufacturing and clinical practice will be required for advancement of the technology. We suggest the adoption of international standards to address these issues.

Cell Culture Techniques↗

[Study of ocular surface involvement in diabetic patients].

INTRODUCTION: Diabetes mellitus leads to microvascular complications and altered basement membranes, which are partly responsible for ocular complications. Corneal nerve impairment is involved in ocular surface disease as well. We examined the possible relation between ocular surface signs and retinal or neuronal degenerative complications due to diabetes. PATIENTS AND METHODS: Diabetics and control subjects were compared for corneal sensitivity and tear function parameters such as the Schirmer test, tear film break-up time (BUT), and fluorescein and lissamine green stainings. The relation of the duration of the disease, the stage of retinopathy, metabolic control (HbA1c), and diabetic peripheral neuropathy with ocular surface disorders were noted. RESULTS: Twelve healthy patients were compared to 48 diabetics. The Schirmer test value, BUT, and fluorescein and lissamine green impregnations were significantly modified in diabetics compared to controls (p<0.0001), with no relation to the duration of the disease or metabolic control. The mean corneal sensitivity was significantly lower in diabetic patients (p<0.01), diabetics with peripheral neuropathy (p=0.00008), and diabetics with preproliferative retinopathy (p=0.0003). Tear function parameters were more frequently altered in patients presenting preproliferative retinopathy and peripheral neuropathy (p<0.001). CONCLUSIONS: Diabetes can lead to ocular surface impairments with qualitative and quantitative tear disorders, all of which seem to evolve in close relation with retinopathy and peripheral neuropathy. These lacrymal and corneoconjunctival abnormalities, even if not currently mentioned by diabetic patients, can result in severe neurotrophic complications.

Basement Membrane↗

Autologous serum-derived cultivated oral epithelial transplants for severe ocular surface disease.

OBJECTIVE: To evaluate the use of autologous serum (AS)-derived cultivated oral epithelial transplants for the treatment of severe ocular surface disease. METHODS: We used AS from 10 patients with severe ocular surface disease and total limbal stem cell deficiency to develop autologous cultivated oral epithelial equivalents. These were compared with epithelial equivalents derived from conventional fetal bovine serum-supplemented medium. Surgery involved removal of the corneal pannus and surrounding diseased tissue and transplantation of the AS-derived epithelial equivalents. The oral equivalents were analyzed by review of histologic and immunohistochemical findings. RESULTS: Oral epithelial sheets cultivated in AS- and fetal bovine serum-supplemented media were similar in morphology, and both formed basement membrane assembly proteins important for maintaining graft integrity. Complete corneal epithelialization was achieved within 2 to 5 days postoperatively. The ocular surface remained stable without major complications in all eyes during a mean +/- SD follow-up of 12.6 +/- 3.9 months. The visual acuity improved by more than 2 lines in 9 of 10 eyes, with transplanted oral epithelium surviving up to 19 months. CONCLUSION: The successful use of an AS-derived oral epithelial equivalent to treat severe ocular surface disease represents an important advance in the pursuit of completely autologous xenobiotic-free bioengineered ocular equivalents for clinical transplantation.

Adult↗

Mucin gene expression is not regulated by estrogen and/or progesterone in the ocular surface epithelia of mice.

PURPOSE: Dry eye syndrome is prevalent in post-menopausal women, and post-menopausal women secrete less mucus in their reproductive tracts. Using a mouse model, the purpose of this study was to determine if estrogen and/or progesterone regulates Muc4 and Muc5AC gene expression in the ocular surface epithelia, as the hormones do in reproductive tract epithelia. METHODS: Adult C57BL/6 mice were ovariectomized, and 19 days later, pellets containing estrogen, progesterone, or a combination were inserted subcutaneously. Ocular surface and reproductive tract tissues were harvested following seven days of hormone treatment. A control group consisted of ovariectomized mice that received no hormone treatment. Real-time reverse transcription-polymerase chain reaction was used to determine the tissue expression levels of mucin mRNA of each treatment group relative to the control. Muc4 mRNA expression levels were determined for the reproductive tract, and both Muc4 and Muc5AC expression levels were determined for the ocular surface epithelia. Muc4 and Muc5AC gene expression in ocular surface and Muc4 in reproductive tract epithelia was demonstrated by In Situ hybridization, and Muc4 and Muc5AC protein was demonstrated in the epithelia of animals in the experimental groups. RESULTS: The mRNA expression levels of Muc4 and Muc5AC and the immunofluorescence localization pattern in the ocular surface epithelia were not significantly different in any hormone treatment group when compared to the control ovariectomized group. By comparison, mice that were administered estrogen had a significant increase of Muc4 mRNA in the reproductive tract epithelia, progesterone given in combination with estrogen antagonized the upregulatory effects of estrogen in the reproductive tract, and the amount of Muc4 mRNA in the reproductive tract of progesterone-treated animals was not different from ovariectomized controls. Immunofluorescence localization of Muc4 in the reproductive tract epithelia of the experimental groups correlated to message levels, with lack of Muc4 protein detected in the control and progesterone groups. CONCLUSION: In comparison to reproductive tract epithelia, Muc4 and Muc5AC are not hormonally regulated by estrogen or progesterone in the ocular surface epithelia of mice. These data demonstrate that regulation of epithelial mucin genes is tissue specific.

Animals↗

Defensins and other antimicrobial peptides at the ocular surface.

Although constantly exposed to the environment and "foreign bodies" such as contact lenses and unwashed fingertips, the ocular surface succumbs to infection relatively infrequently. This is, in large part, due to a very active and robust innate immune response mounted at the ocular surface. Studies over the past 20 years have revealed that small peptides with antimicrobial activity are a major component of the human innate immune response system. The ocular surface is no exception, with peptides of the defensin and cathelicidin families being detected in the tear film and secreted by corneal and conjunctival epithelial cells. There is also much evidence to suggest that the role of some antimicrobial peptides is not restricted to direct killing of pathogens, but, rather, that they function in various aspects of the immune response, including recruitment of immune cells, and through actions on dendritic cells provide a link to adaptive immunity. A role in wound healing is also supported. In this article, the properties, mechanisms of actions and functional roles of antimicrobial peptides are reviewed, with particular emphasis on the potential multifunctional roles of defensins and LL-37 (the only known human cathelicidin) at the ocular surface.

Journal Article↗

Human uroplakin Ib in ocular surface epithelium.

PURPOSE: To investigate the expression and localization of the human gene encoding uroplakin Ib in ocular surface epithelium. METHODS: The full-length cDNA of human uroplakin Ib was isolated from a cDNA library of human corneal epithelium, and the expression of uroplakin Ib in various tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR). In cornea and conjunctiva, the expressions of uroplakin Ia, II, and III were also examined by RT-PCR. Finally, the localization of uroplakin Ib in the ocular surface was analyzed by immunofluorescence confocal microscopy, by using an antiserum against a synthetic peptide. RESULTS: Two mRNA isoforms, arising through two polyadenylation sites, were isolated. RT-PCR detected uroplakin Ib in cornea, conjunctiva, bladder, placenta, and kidney. Among other uroplakins, uroplakin II was also faintly detected in cornea and conjunctiva. Immunofluorescence confocal microscopy documented uroplakin Ib protein in the cell membranes of superficial and wing cells in the corneal epithelium. It was not found, however, in the most apical corneal epithelial cells. In limbus and conjunctiva, uroplakin Ib was also localized in the cell membranes of all epithelial layers, apart from the most apical cells. CONCLUSIONS: Uroplakin Ib is highly expressed in ocular surface epithelia. As in bladder epithelium, uroplakin Ib may protect the ocular surface from bacterial infection.

Amino Acid Sequence↗

Ocular surface reconstruction for thermal burns caused by fireworks.

PURPOSE: To describe 6 eyes with severe firework-related ocular surface injuries that were treated by limbal stem cell transplantation combined with amniotic membrane transplantation (AMT). METHODS: Six eyes of 6 patients with firework-related ocular injuries were retrospectively studied. All subjects were men, with age ranging from 9 to 26 years. All patients were in chronic stage of thermal injury, and all had total limbal stem cell dysfunction and subsequent conjunctival fibrosis. They had limbal stem cell transplantation (1 had an allograft and 5 had autograft transplantation) combined with AMT to restore vision. Mitomycin C was used in 1 eye intraoperatively. RESULTS: After ocular surface reconstruction using limbal stem cell transplantation combined with AMT, corneal epithelialization was achieved in 4 eyes after a mean duration of 20.8 +/- 12.2 days (range, 4-33 days). After a mean follow-up period of 36 months (range, 5-87 months), marked reduction of fibrosis was noted in all eyes. At last examination, the corneal surface was covered by corneal-phenotype epithelium in 4 eyes, and the remaining 2 eyes had conjunctivalization. The cornea was optically clear in 3 eyes, with corrected visual acuity of 20/100 in these 3 eyes. Both eyes that developed conjunctivalization had massive fibrosis preoperatively and severe eyelid deformities. CONCLUSION: Although severe firework-related ocular surface injuries were difficult to treat, limbal stem cell transplantation combined with AMT enable some success in cosmetic and visual outcome. Management of eyelid abnormalities and ocular surface fibrosis seemed to be a key to success in visual rehabilitation.

Adolescent↗

Video-assessment of tear meniscus height in elderly Caucasians and its relationship to the exposed ocular surface.

PURPOSE: An adequate volume of tears is considered essential to prevent desiccation of the exposed ocular surface, especially in elderly individuals. Few assessments of tear meniscus height (TMH) have however been reported for elderly individuals. METHODS: Close-up images of the lower marginal tear strip were obtained by videography over about 30 s in 56 elderly individuals (38 women, 18 men; 71 +/- 5 years of age) without significant eye disease and having a functional lacrimal system (Schirmer test). From such an "en face" view, the vertical height of the tear meniscus (TMH) at the lower eyelid was measured from stopped video frames. Firstly, TMH was assessed at the mid-point of the eyelid from five frames separated by 5 s; these values were averaged to give a time-averaged assessment of TMH (a tTMH value). Secondly, a position-averaged method (pTMH) was used in which TMH was assessed at 5 locations along the eyelid margin from a single frame that included several mm of marginal tear strip, and an average value calculated. The videographs were also used to assess palpebral aperture and the exposed ocular surface, a 1 min Schirmer test measure (closed eye) was also made, and keratometry data was available for most subjects. RESULTS: A wide range of average values was encountered for both tTMH (range 0.057 to 0.271 mm) and pTMH (0.031 mm to 0.325 mm). The group-averaged tTMH value was 0.172 +/- 0.047 mm (median 0.164 mm) while the group-averaged pTMH value was 0.171 +/- 0.058 mm (median 0.168 mm), with no difference being found between the two methods (p = 0.84, paired t-test). With either method, the apparent TMH value was greater when the exposed ocular surface value (average 1.68 +/- 0.51 cm(2)) was lower and vice versa, and was statistically-significant for the tTMH measures (p = 0.02, r = 0.32), but not the pTMH measures (p = 0.18, r = 0.18). Neither TMH measure was related to the Schirmer test values or to central corneal curvature. CONCLUSIONS: The results indicate that healthy elderly individuals can be expected to have a measurable lower marginal tear strip, and that objective assessment of this may be a useful alternative to the Schirmer test. A possible association was found between the measures of TMH and the palpebral aperture height (and thus the exposed ocular surface), and so might need to be considered when TMH is assessed.

Aged↗