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Tear film osmolarity and ocular surface disease in two rabbit models for keratoconjunctivitis sicca.

We report the natural history of keratoconjunctivitis sicca (KCS) in two rabbit models. The first one (full KCS model) was created by closing the lacrimal gland excretory duct, and removing the nictitating membrane and harderian gland. We created the second one (lacrimal gland duct only [LGDO]-KCS model) by closing the lacrimal gland excretory duct. Although tear film osmolarity was abnormally high in both models, it was higher in the full KCS model. Decreases in corneal epithelial glycogen and in conjunctival goblet cell density, and morphological abnormalities of the conjunctiva correlated with increases in tear film osmolarity and duration of disease.

Animals↗

Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in Sjögren's syndrome.

BACKGROUND: Previous studies have shown a poor correlation between dry eye symptoms and objective clinical signs in patients with Sjögren's syndrome. We examined the hypothesis that reduced corneal sensitivity is associated with increased ocular surface disease and reduced symptoms in patients with Sjögren's syndrome. METHODS: Eighteen subjects with a diagnosis of Sjögren's syndrome attending a Sjögren's clinic participated in the study. All participants completed the Ocular Surface Disease Index (OSDI) and the Symptom Severity of Discomfort (SSD) scale and answered a question regarding overall severity of dry eye symptoms. The subjects underwent measurement of best-corrected Snellen visual acuity, corneal sensitivity testing with the Cochet-Bonnet esthesiometer, fluorescein and lissamine green staining of the cornea, Schirmer's test I and determination of the tear film break-up time. The results were analysed using Pearson correlational analysis. RESULTS: Both fluorescein and lissamine green staining of the cornea correlated negatively with central corneal sensation (r = -0.3542, p = 0.034, and r = -0.3748, p = 0.029 respectively), indicating that corneal sensation was reduced with increased ocular surface disease. The overall symptom severity correlated negatively with lissamine green staining of the cornea (r = -0.4310, p = 0.011), suggesting reduced symptoms with increased corneal disease. INTERPRETATION: Reduced corneal sensation correlated with increased ocular surface disease. Ocular surface disease similarly demonstrated a reciprocal relation with patients' dry eye symptoms. Consequently, we found that patients with Sjogren's syndrome with advanced corneal staining tended to have fewer dry eye symptoms than patients with less corneal staining.

Adult↗

Oculoplastic technique of connecting a glaucoma valve shunt to extraorbital locations in cases of severe glaucoma.

PURPOSE: To describe a technique for inserting glaucoma shunts to the sinuses or the lacrimal sac as a means of lowering intraocular pressure in patients with refractory glaucoma associated with severe ocular surface disease. METHODS: Nineteen patients with severe ocular surface disease necessitating a keratoprosthesis and with intractable glaucoma underwent placement of a modified Ahmed shunt to direct aqueous in the maxillary or ethmoid sinus or lacrimal sac. RESULTS: Intraocular pressure is presently well controlled without glaucoma medications in two thirds of patients. None of the patients had endophthalmitis. CONCLUSIONS: Established oculoplastic surgery techniques may be used to redirect aqueous to extraorbital locations and effectively lower intraocular pressure in patients with severe ocular surface disease and refractory glaucoma. This procedure has not been associated with endophthalmitis.

Cornea↗

Limbal stem cell transplantation in chronic inflammatory eye disease.

OBJECTIVE: The goal of this study was to describe the outcome of limbal stem cell transplantation (LSCT) in patients with severe ocular surface disease caused by underlying chronic inflammatory eye disease. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Nine patients with limbal stem cell deficiency caused by an underlying ocular inflammatory disease who underwent LSCT. METHODS: The authors reviewed the records of 11 eyes of 9 patients with immunologically mediated ocular surface disease that underwent LSCT. MAIN OUTCOME MEASURES: The main outcome measures were reepithelialization of the corneal surface, restoration of corneal surface, and improvement in visual acuity. RESULTS: A total of 11 eyes underwent either autologous (n = 1) or HLA-matched living related donor (n = 10) LSCT for ocular surface disease secondary to inflammatory disease. Reepithelialization of the corneal surface in the immediate postoperative period occurred in 10 eyes (91%) within an average of 10 days (range, 3-21 days). Long-term restoration of the corneal surface was achieved in six (55%) eyes. Visual acuity improved in six eyes (55%). Reasons for poor outcomes included microbial infection, limbal stem cell graft rejection, and corneal ulceration. No donor eyes had complications. CONCLUSIONS: Patients with underlying immunologically mediated diseases, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or ocular cicatricial pemphigoid, who undergo LSCT have lower success rates than do those patients with noninflammatory ocular surface diseases.

Adult↗

Regulation of MMP-9 production by human corneal epithelial cells.

The matrix metalloproteinases, MMP-2 and MMP-9, are known to be critical extracellular-remodeling enzymes in wound healing and other diseases of the ocular surface. This study investigated the regulation of MMP-2 and MMP-9 in human corneal epithelial cells by growth factors and pro-inflammatory cytokines (IL-1beta and TNF-alpha) they are exposed to, and by doxycycline, a medication used to treat ocular surface disease. Primary human corneal epithelial cell cultures were treated with one of the following cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha) or growth factors (EGF, HGF, KGF, PDGF-BB, TGF-alpha, TGF-beta), with or without their corresponding inhibitors. The conditioned media were collected after 24 hr for gelatin zymography and MMP-9 activity assay. Total RNA was extracted from the cells treated for 6 hr and was subjected to RT-PCR and Northern hybridization. Between the two gelatinases, MMP-2 and MMP-9, detected by zymography, the 92 kDa MMP-9 in the conditioned medium was markedly up-regulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. The MMP-9 protein and activity were dose-dependently stimulated by IL-1beta or TNF-alpha at 0.1, 1.0 and 10 ng ml(-1). This up-regulation was nearly abolished by neutralizing antibodies (IL-1beta and TNF-alpha) and by IL-1 receptor antagonist. Semi-quantitative RT-PCR and Northern hybridization disclosed that the MMP-9 transcript was also markedly up-regulated in a dose-dependent manner by IL-1beta and TNF-alpha. Doxycycline (10 microg ml(-1)) suppressed MMP-9 protein level and activity, but not its mRNA, that was stimulated by IL-1beta and TNF-alpha (1 ng ml(-1)). In contrast, the 72 kDa MMP-2 was not significantly modulated by any of these cytokines. In conclusion, production of MMP-9 is stimulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. These factors may play a role in the pathogenesis of MMP-9 mediated corneal matrix degradation. The efficacy of doxycycline in treating ocular surface diseases may be related to its ability to suppress MMP-9 production in the corneal epithelium.

Cell Culture Techniques↗

Cellulose acetate impressions of the ocular surface. Dry eye states.

Cellulose acetate impressions of the ocular surface were obtained for normal eyes, eyes with blepharoconjunctivitis, eyes with keratoconjunctivitis sicca, and eyes with primary ocular surface disease. Normal eyes and eyes with blepharoconjunctivitis had morphologically normal epithelium and goblet cells on the bulbar and palpebral ocular surfaces. Eyes with primary ocular surface disease had abnormal ocular surface impressions (decreased, abnormal, or absent goblet cells with abnormal epithelial cells) on both the bulbar and palpebral ocular surfaces. Conversely, eyes with keratoconjunctivitis sicca had substantial abnormalities of the epithelium and goblet cells only on the bulbar ocular surface, suggesting an environmental role in this disease process.

Adult↗

[The study of the therapeutic application of PV contact lens].

PURPOSE: To evaluate the indications and effects of continuously wearing the Bausch & Lomb Pure-Vision (PV)Contact Lens. METHOD: Twenty-nine patients (31 eyes) who required therapeutic contact lens wear were selected non-randomly from Zhongshan Ophthalmic Center for wearing (Pure Vision, PV) contact lens. Therapeutic indications included pain and irritation relief, corneal protection, and enhancement of corneal wound healing. Simultaneously antibiotics and artificial tears were used according to the ocular diseases. And then, the effect of treatment, anterior segment of eyes, contact lens fitting characteristics, lens deposits and the presence of contact lens-relative complications were evaluated. RESULTS: The duration of PV contact lens wear on 31 eyes were 3-57 days, averagely 20.9 days. Patients included bullous keratopathy (6 cases, 6 eyes), keratitis incorporated with descemetocele (5 cases, 5 eyes), chemical burns with epithelial abrasions (6 cases, 7 eyes), post-keratoplasty (3 cases, 3 eyes), filamentary keratitis (3 cases, 3 eyes), corneal epithelial erosion syndrome (2 cases, 3 eyes), repetitive corneal epithelial stripping syndrome (1 case, 1 eye), corneal lamellar laceration and epithelial coloboma (1 case, 1 eye), post-extraction of traumatic cataract with durative corneal ulcer (1 case, 1 eye), post-limbal & amnia transplantation (1 case, 1 eye). For the treatment of pain and irritation relief (21 patients, 22 eyes), all patients had complete or partial relief. For corneal healing (20 patients, 22 eyes), full healing was noted in 15 patients (16 eyes) (72.7%), partial healing occurred in 4 patients (5 eyes) (22.7%). For corneal protection (21 patients, 23 eyes), lens wear was fully protective in all cases, except one case of loosely fitting. Our result shows that PV Contact Lens exhibits prominent efficiency in CONCLUSION: treating corneal diseases and ocular surface diseases, as well as corneal protection, corneal healing and pain relief. The lens has increased oxygen transmissibility and good anti-deposit quality, reducing the risk of ocular complications. As a result of these, PV Contact Lens is the ideal bandage therapeutic lens.

Adolescent↗

Dry eye signs and symptoms in women with premature ovarian failure.

OBJECTIVE: To examine whether women with premature ovarian failure (POF) have abnormal findings in ocular surface or tear parameters and whether they report symptoms of ocular discomfort compared with age-matched controls. METHODS: Sixty-five patients with POF and 36 age-matched healthy controls were examined for signs and symptoms of dry eye. The Ocular Surface Disease Index questionnaire and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) were administered to the participants. Assessments of ocular surface damage (Oxford and van Bijsterveld scores of vital dye staining) and tear status (Schirmer tests 1 [without anesthesia] and 2 [with anesthesia] and tear breakup time) were performed. RESULTS: Women with POF scored significantly worse than controls on all ocular surface damage parameters: Oxford score (3.2 vs 1.7; P =.001), conjunctival lissamine green (2.1 vs 1.3; P =.02), corneal fluorescein staining (1.2 vs 0.4; P =.005), and van Bijsterveld score (2.1 vs 1.3; P =.02). Further, the proportion of patients with POF meeting the dry eye diagnostic criterion of a van Bijsterveld score greater than or equal to 4 was significantly greater among women with POF than among controls (20% vs 3%; P =.02). The POF group also tended to have worse scores than controls on self-reported symptoms, as measured by the overall Ocular Surface Disease Index (12.5 vs 2.1; P<.001) and the overall NEI-VFQ (94 vs 98; P =.001) after adjustment for age and race. Schirmer test scores and tear breakup time did not differ. CONCLUSIONS: Women with POF were more likely to exhibit ocular surface damage and symptoms of dry eye than age-matched controls. They were not, however, more likely to have reduced tear production. To our knowledge, this association between ocular surface disease and POF has not been previously reported. These data provide further evidence of the multifaceted role of sex hormones in the health and disease of the ocular surface.

Adolescent↗

Combined penetrating keratoplasty and limbal allograft transplantation for severe corneal burns.

The management of ocular surface disease presents a significant challenge to ophthalmologists. Recent advances in the etiology and pathophysiology of ocular surface diseases, such as chemical and thermal burns or Stevens-Johnson syndrome, include the concept of the limbal stem cell. Limbal stem cell theory suggests that the corneal limbus contains epithelial stem cells that are responsible for a continuous supply of corneal epithelial cells, which not only migrate from the deep to superficial epithelial layers, but also progress in a centripetal direction, inward from the limbus. Support for this concept is provided indirectly by the relatively poor prognosis for penetrating keratoplasty for these types of ocular surface diseases. In such cases, it is suggested that limbal damage and depletion is present and is a significant factor in loss of integrity of the ocular surface; therefore, conventional penetrating keratoplasty, which does not include limbal tissue, does not have a high success rate.

Adult↗

Survival of rabbit limbal stem cell allografts.

Failure of a specialized population of corneal epithelial stem cells found in the peripheral cornea and limbus results in ocular surface disease, which may be amenable to treatment by transplantation of limbal tissue. This study was designed to investigate donor limbal stem cell allograft survival in rabbits with ocular surface disease. Rabbits underwent corneal epithelial debridement and limbal ablation to induce ocular surface disease and were then treated by limbal stem cell allotransplantation, by allotransplantation plus topical steroid, or by topical steroid only (n = 7 for each group). Donors and recipients were sex mismatched. Recipients were followed for up to 5 months. Outcome was assessed by daily slit-lamp examination, weekly impression cytology and photographic record, end-point sex chromatin and fluorescent cell tracer analyses, histology, and immunohistochemistry. In no case was a completely normal ocular surface regained, but some animals that received grafts plus corticosteroids fared best by all criteria used. In the absence of immunosuppression, graft hemorrhagia (believed to be a manifestation of graft rejection) occurred within the first month, the cornea became resurfaced with conjunctiva-derived cells, and no donor cells survived centrally in the long term. Topical corticosteroids reduced the number and severity of these episodes significantly, and were associated with survival of some donor-derived cells in the central cornea of some grafted animals. Thus, rabbit limbal stem cell allografts appeared to undergo rejection, which could be modified by immunosuppression, but useful regeneration of the ocular surface occurred only where rejection was circumvented.

Animals↗

Antimicrobial management of presumed microbial keratitis: guidelines for treatment of central and peripheral ulcers.

AIMS: To determine the quantitative relation between the major risk factors for microbial keratitis of previous ocular surface disease and contact lens wear and central and peripheral infiltration, often associated with ulceration, in order to establish a rational chemotherapeutic management algorithm. METHODS: Data from 55 patients were collected over a 10 month period. All cases of presumed microbial keratitis where corneal scrapes had been subjected to microbiological examination were included. Risk factor data and laboratory outcome were recorded. Antimicrobial regimens used to treat each patient were documented. RESULTS: 57 episodes of presumed microbial keratitis were identified from 55 patients, 24 male and 31 female. There were 30 central infiltrates and 27 peripheral infiltrates of which 28 were culture positive (73% of central infiltrates, 22% of peripheral infiltrates). 26 patients had worn contact lenses of whom 12 had culture positive scrapes (9/14 for central infiltrates, 3/12 for peripheral infiltrates). 31 patients had an ocular surface disease of whom five previous herpes simplex virus keratitis patients developed secondary bacterial infection. Anterior chamber activity and an infiltrate size > or = 4 mm2 were more common with culture positive central infiltrates than peripheral infiltrates (chi 2 test = 11.98, p < 0.001). CONCLUSIONS: Predisposing factors for "presumed" microbial keratitis, either central or peripheral, were: ocular surface disease (26/57 = 45.6%), contact lens wear (26/57 = 45.6%), and previous trauma (5/57 = 8.8%). Larger ulceration (> or = 4 mm2) with inflammation was more often associated with positive culture results for central infiltration. None of these four variables (contact lens wear, ocular surface disease, ulcer size, anterior chamber activity) were of intrinsic value in predicting if a peripheral infiltrate would yield identifiable micro-organisms. Successful management of presumed microbial keratitis is aided by a logical approach to therapy, with the use of a defined algorithm of first and second line broad spectrum antimicrobials, for application at each stage of the investigative and treatment process considering central and peripheral infiltration separately.

Acanthamoeba Keratitis↗

The influence of gender on the ocular surface.

PURPOSE: Dry eye is more prevalent among women than men. To examine whether gender influences the ocular surface, conjunctival goblet-cell density was monitored for a 30-day period. Changes in goblet-cell density are a sensitive marker for ocular surface disease. METHODS: Six men and twelve women who were free from ocular surface disease were sampled by impression cytology on the inferior bulbar conjunctiva every other day for 30 days. Samples were analyzed for goblet-cell content. The mean age of the subjects was 24 years for the men and 25.4 years for the women. A minimum of 200 epithelial cells were scored per microscopic field examined. RESULTS: There is a statistically significant difference in goblet-cell count between men and women over the 30-day test period. The mean goblet-cell count measured for men was 3.75% +/- 1.04%, while the mean count for women was 2.545% +/- 0.8%. When the data on women were replotted with reference to the menstrual cycle, the largest and longest depression of goblet-cell count occurs midcycle, around the time of ovulation. A significant difference in goblet-cell count was also noted when subjects using oral contraceptives (3.065% +/- 0.98%) are compared with those not using oral contraceptives (2.28% +/- 0.92%). CONCLUSION: It appears there may be a reproductive hormonal influence on conjunctival goblet-cell count.

Adult↗

[Autologous serum-eye-drops for ocular surface disorders. A literature review and recommendations for their application].

The natural tear film has mechanical, optical, antimicrobial and nutritional properties. Tear film components, such as EGF, fibronectin and vitamin A, play a vital role in the proliferation, migration and differentiation of the corneal and conjunctival epithelium. In ocular surface disease, such as severe dry eye, the epithelia may be depleted of these nutritional factors. Replacing the aqueous component of tears alone,by using pharmaceutical tear substitutes,often has little effect on the ocular surface.Eye-drops prepared from autologous serum are a new treatment option for severe ocular surface disease. They can be produced according to the regulations on drug use as an unpreserved blood preparation. Autologous serum eye-drops are non-allergenic and their biomechanical and biochemical properties are similar to normal tears. In cell culture experiments, serum was found to be superior to preserved or unpreserved pharmaceutical products in the maintenance of human keratinocyte morphology and function. It supports the migration of corneal epithelial cells and the differentiation of conjunctival epithelial cells. The first clinical cohort studies report its successful use for severe dry eyes and persistent epithelial defects. In these studies, however, varying methods for the preparation and different concentrations of autologous serum eye-drops were used. These methodological variations determine the biochemical properties and thus the epitheliotrophic effect of serum eye-drops. In this review we summarise the currently available clinical evidence, discuss relevant legislatory restrictions and describe a standard operating protocol for the use of serum eye drops. This has to be evaluated and optimised in more detail before any meaningful, randomised, controlled trial can attempt to establish the role of serum eye-drops in the management of severe ocular surface disease.

Blood Proteins↗