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PubMed2006

Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion.

BACKGROUND: Dry eye syndrome is a highly prevalent, yet largely under diagnosed, condition that can substantially affect quality of life. Left untreated, dry eye is associated with chronic eye pain and increased risk of ocular surface disease. Current demographic changes and lifestyle factors indicate that the dry eye syndrome patient population will increase significantly, ensuring that general practitioners and ophthalmic clinicians alike will experience more patients presenting with dry eye symptoms. Greater public and practitioner awareness of emerging research, technologies, and therapies is crucial to ensuring appropriate interventions to meet specific patient needs and result in clinically favorable outcomes. ROUNDTABLE ASSEMBLY: In August 2005, a team of ocular surface experts convened for a 1-day roundtable session to discuss the latest information on diagnosing and treating dry eye syndrome and real-world issues in artificial tear therapy, including preservative use. ROUNDTABLE DISCUSSION: The discussion centered on the mild to moderate dry eye patient and critical features of the ideal artificial tear, which are preservative-free formulation, protection from microbial contamination, cost-effective, non-blurring, and easy to use. Products that match this profile have the advantage of being able to benefit the myriad of patients who comprise the dry eye syndrome population. Ocular surface health should always remain a top priority. Preferred Practice Pattern Dry Eye Syndrome Medical Treatment guidelines should be modified to recommend the use of preservative-free formula artificial tear products for all levels of dry eye conditions in consideration of the medical benefit they offer to dry eye syndrome sufferers. CONCLUSION: The growing prevalence of dry eye syndrome demands increased attention. Further research, enhanced diagnostic tests, increased use of preservative-free artificial tear formulations as first-line therapy, greater patient-practitioner interaction, and patient education are warranted.

Cost-Benefit Analysis↗

PubMed2003

Management of the late ocular sequelae of Stevens-Johnson syndrome.

The acute conjunctivitis seen initially in Stevens-Johnson syndrome is followed by a cicatricial phase, which often leads to severe ocular surface disease and visual morbidity. Manifestations include keratinization of the conjunctiva, lid margins, and lacrimal and meibomian ducts, resulting in an unstable tear film and mechanical trauma to the conjunctiva and cornea with blinking. Limbal stem cell deficiency is the most vision-threatening sequela of Stevens-Johnson syndrome, as it causes corneal neovascularization, chronic corneal inflammation, and an irregular corneal epithelium. Management of late sequelae often requires a multipronged approach, including strategies for ocular surface protection, ocular surface support, and ocular surface reconstruction. In this review, established therapies, as well as new experimental therapies, are discussed.

Journal Article↗

PubMed1991

Ocular disease leads to decreased concentrations of epidermal growth factor in the tear fluid.

The concentration of epidermal growth factor (EGF) in tear fluid (TF) was recently shown to decrease with increasing tear fluid flow (TFF). The purpose of the present study was to clarify the effects of ocular surface disease on the TF EGF concentrations. Tear fluid samples (n = 243) were collected from diseased eyes by means of blunted glass capillaries. The time of collection was measured for each sample, and the tear fluid flow in the capillaries (TFFc) was calculated. The concentration of human EGF (hEGF) was determined using a time-resolved immunofluorometric assay (TR-IFMA). For statistical analysis diagnosis-dependent multigrouping was performed and the data of the patient groups were compared to the data for a control group. The control material consisted of 271 TF samples collected from healthy eyes before (n = 59) and after stimulation of reflex tearing (n = 212). It was shown that TF specimens of patients (n = 243) contained significantly (p less than 0.001) less EGF (mean 952 pg/ml) than the TF of healthy control individuals before (n = 59 samples; mean 6589 pg/ml) or after stimulation of reflex tearing (n = 212 samples; mean 2762 pg/ml). The EGF concentration of every patient group was significantly lower than that found in the TF of control individuals both before and during reflex tearing (p less than 0.001). The rate of EGF released with TF during collection did not differ significantly between the various groups of patients or from that released with the TF of normal individuals before induction of reflex tearing.(ABSTRACT TRUNCATED AT 250 WORDS)

Corneal Diseases↗

PubMed2004

Changes in the tear film and ocular surface from dry eye syndrome.

Dry eye syndrome (DES) refers to a spectrum of ocular surface diseases with diverse and frequently multiple aetiologies. The common feature of the various manifestations of DES is an abnormal tear film. Tear film abnormalities associated with DES are tear deficiency, owing to insufficient supply or excessive loss, and anomalous tear composition. These categorizations are artificial, as in reality both often coexist. DES disrupts the homeostasis of the tear film with its adjacent structures, and adversely affects its ability to perform essential functions such as supporting the ocular surface epithelium and preventing microbial invasion. In addition, whatever the initial trigger, moderate and severe DES is characterized by ocular surface inflammation, which in turn becomes the cause and consequence of cell damage, creating a self-perpetuating cycle of deterioration. Progress has been made in our understanding of the aetiology and pathogenesis of DES, and these advances have encouraged a proliferation of therapeutic options. This article aims to amalgamate prevailing ideas of DES development, and to assist in that, relevant aspects of the structure, function, and production of the tear film are reviewed. Additionally, a synopsis of therapeutic strategies for DES is presented, detailing treatments currently available, and those in development.

Animals↗

PubMed2005

Amniotic membrane use in ophthalmology.

PURPOSE OF REVIEW: The purpose of this review is to describe the most recent and relevant clinical and experimental data about the use of amniotic membrane in ophthalmology. RECENT FINDINGS: The amniotic membrane is a biologic tissue that has been used as a graft for corneal and conjunctival reconstruction in a variety of ocular surface diseases. It is avascular and possesses anti-angiogenetic, anti-scarring and antiinflammatory properties. It is not a substitute but rather a substrate upon which cells can migrate and regenerate, forming new and healthy tissue. The amniotic membrane can also be used as a biologic patch, as a bandage, to treat acute inflammatory disorders. With the development of cell therapy, amniotic membrane can be also used as a carrier of limbal stem cells or their progeny, cultivated in vitro. SUMMARY: Amniotic membrane use in ophthalmic surgery has been shown to provide an alternative for corneal and conjunctival reconstruction in many clinically challenging situations; however, there is still a lack of scientific evidence based on randomized comparative studies to prove that its use is better than other alternative therapies for ocular surface reconstruction.

Amnion↗

PubMed1990

Qualitative tear film disease.

Abnormalities of the lipid and mucin components of the preocular tear film may result from diseases of the eyelid margins and conjunctiva. Chronic keratoconjunctivitis with epithelial edema and superficial corneal neovascularization, with or without ulceration, characterizes qualitative tear diseases. Tear components other than lipid and mucin that carry probable clinical significance include tear proteins, all-trans retinal, cholesterol, glucose, and electrolytes. Although less common than quantitative or aqueous deficiencies, qualitative abnormalities are recognized as primary or secondary causes of ocular surface disease in companion animals.

Animals↗

PubMed1999

Survival of rabbit limbal stem cell allografts after administration of cyclosporin A.

OBJECTIVES: To evaluate the efficacy of systemic or topical administration of cyclosporin A (CsA) after limbal transplantation of stem cell allografts in rabbits. METHODS: Thirty-six rabbits underwent corneal epithelial debridement and limbal ablation to induce ocular surface disease and were then treated by limbal allograft transplantation. Animals received either systemic CsA (10 mg/kg per day, intramuscularly), 1% CsA eyedrops, or vehicle eyedrops immediately after transplantation and 28 days thereafter. Concentration of CsA in plasma and aqueous humor was determined by fluorescence polarization immunoassay after 4 weeks of therapy. Graft survival was inspected clinically. RESULTS: Both systemic and topical administration of CsA resulted in a significant prolongation of graft survival. In addition, one of seven of the limbal allografts in either group of systemic and topical CsA survived >60 days on cessation of CsA. There was no significant difference in mean survival time between systemic and topical application, although plasma levels of CsA were significantly higher after systemic administration. However, a significant higher aqueous concentration was found in topical treatment. CONCLUSIONS: Limbal allografts were stable in maintaining the reconstructed ocular surface under attentive postoperative immunosuppression. Topically administered CsA was as effective as systemic use.

Animals↗

PubMed1985

Topical retinoid treatment for various dry-eye disorders.

We evaluated the clinical efficacy of treating various dry-eye disorders using 0.01% and 0.1% (weight/weight) topical all-trans retinoic acid ointment. Twenty-two patients were selected and classified into four major groups: keratoconjunctivitis sicca (6 patients; 11 eyes), Stevens-Johnson syndrome (9 patients; 17 eyes), ocular pemphigoid or drug-induced pseudopemphigoid (3 patients; 6 eyes), and surgery or radiation-induced dry eye (4 patients; 4 eyes), based on the criterion that they remained symptomatic even under maximum tolerable conventional medical and/or surgical therapies. The results indicated that squamous metaplasia with mucin deficiency secondary to goblet cell loss and keratinization may be the basis for the development of clinical symptoms and morbidities, as these epithelial abnormalities were invariably present before treatment. After treatment, all patients demonstrated clinical improvements in symptoms, visual acuity, rose Bengal staining, or Schirmer test. Most importantly, this topical vitamin A treatment caused the reversal of squamous metaplasia as evidenced by impression cytology. Therefore, this treatment may represent the first nonsurgical attempt to treat these disorders by reversing diseased ocular surface epithelium.

Administration, Topical↗

PubMed2000

Management and outcome of cataract surgery in ocular cicatricial pemphigoid.

BACKGROUND: Patients with ocular cicatricial pemphigoid (OCP) lose vision due to corneal disease or cataract, which may be senile, drug induced or complex. The success of cataract surgery in these patients may be limited by an increased risk of surgical complications due to difficult access and visualisation, exacerbation of the cicatrising disease following surgery or later progression of the corneal disease. We report our experience on cataract surgery in OCP. METHODS: Cataract surgery was performed on 15 eyes of 13 patients. In the pre- and postoperative examinations the stage of the condition (according Foster's classification), the degree of conjunctival hyperaemia and the visual acuity (VA) were evaluated and topical and systemic medication recorded. All procedures used a corneal incision. The technique was intracapsular (ICCE) in 1, extracapsular (ECCE) in 4 and phacoemulsification in 10 eyes. In 13 of 15 cases an intraocular lens was implanted. The unoperated fellow eyes constituted a control group. Duration of postoperative follow-up was 35.8+/-39.1 months. RESULTS: 10 of 15 eyes had stage III disease or worse before surgery. Two eyes following ECCE showed early postoperative progression of the disease. Postoperative visual acuity improved in 14 eyes by 2 or more lines. Preoperatively 5 eyes met the criteria for blind registration, whereas postoperatively all eyes achieved a VA of at least 0.1. In 6 eyes the VA was sufficient to allow driving. However, by the 22nd postoperative month progressive cicatricial and ocular surface disease resulted in a regression of the achieved visual rehabilitation in 8 eyes. CONCLUSION: OCP does not prevent successful cataract surgery if appropriate techniques are used and precautions taken. Systemic perioperative immunosuppression is necessary in patients with active conjunctival inflammation. The use of small clear corneal incision surgery is recommended to reduce the risk of an acute exacerbation of conjunctival inflammation. Although visual rehabilitation may be only temporary due to progression of the conjunctival or corneal disease in OCP, cataract surgery can provide some benefit, in severely disabled patients, without precipitating an acute exacerbation of OCP.

Aged↗

PubMed1994

The effects of daily wear contact lenses on goblet cell density.

BACKGROUND: Some patients can wear contact lenses with a low tear breakup time while others with an identical tear breakup time cannot wear lenses. This suggests the current method of tear film assessment is inadequate at differentiating between these two types of patients. The study attempts to expand our knowledge of the tear film with special attention directed to a critical yet little studied component: mucin. Mucin is vital to maintenance of the tear film and functions as a tear film stabilizer. The condition of the precorneal tear film is a major determinant in the success of contact lens wear. METHODS: Eighteen subjects free of ocular surface disease who had never worn contact lenses had the goblet cell density of their inferior bulbar conjunctiva determined by impression cytology. The subjects were then fit in a 38 percent water polymacon lens and their goblet cell density determined on a monthly basis for 6 months. RESULTS: Nearly a 2-fold increase in goblet cell density was observed in 88 percent of the subjects over the 6-month period. The first statistically significant increase occurred 5 months after the initiation of lens wear when the goblet cell density rose from 4.19-7.84 percent. CONCLUSIONS: We speculate the increase in goblet cells is an adaptive response of the ocular surface to a coated daily wear contact lens.

Adolescent↗

PubMed2000

Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group.

OBJECTIVE: To compare the efficacy and safety of cyclosporin A ([CsA] 0.05% and 0.1% ophthalmic emulsions) to vehicle in patients with moderate to severe dry eye disease. DESIGN: Multicenter, randomized, double-masked, parallel-group, 6-month, vehicle-controlled. PARTICIPANTS: A total of 877 patients with defined moderate to severe dry eye disease (292 to 293 in each treatment group). METHODS: Two identical clinical trials; patients were treated twice daily with either CsA, 0.05% or 0.1%, or vehicle. The results of these two trials were combined for analysis. MAIN OUTCOME MEASURES EFFICACY: corneal and interpalpebral dye staining, Schirmer tear test (with and without anesthesia), tear break-up time, Ocular Surface Disease Index (OSDI), facial expression, patient subjective rating scale, symptoms of dry eye, investigator's evaluation of global response to treatment, treatment success, and daily use of artificial tears. SAFETY: occurrence of adverse events, best-corrected visual acuity, intraocular pressure, biomicroscopy, and blood trough CsA concentrations. RESULTS: Treatment with CsA, 0.05% or 0.1%, gave significantly (P < or = 0.05) greater improvements than vehicle in two objective signs of dry eye disease (corneal staining and categorized Schirmer values). CsA 0.05% treatment also gave significantly greater improvements (P < 0.05) in three subjective measures of dry eye disease (blurred vision, need for concomitant artificial tears, and the physician's evaluation of global response to treatment). There was no dose-response effect. Both CsA treatments exhibited an excellent safety profile, and there were no significant topical or systemic adverse safety findings. CONCLUSIONS: The novel ophthalmic formulations CsA 0.05% and 0.1% were safe and effective in the treatment of moderate to severe dry eye disease yielding improvements in both objective and subjective measures. Topical CsA represents a new pharmacologically based treatment for dry eye disease that may provide significant patient benefits.

Cornea↗

PubMed2000

Eye care for the critically ill.

PURPOSE: To evaluate the effectiveness and efficiency of an algorithm in the prevention of ocular surface disease in sedated and unconscious patients in the intensive care unit (ICU). METHODS: The eyes of all sedated and unconscious patients admitted to an ICU between September and December 1998 were managed according to an eye care algorithm. The applications of the preventive measures were assessed by a single observer twice weekly. The lid position, the presence and degree of keratopathy, sedation score, and the treatment received were documented at every assessment. RESULTS: Thirty-four patients were recruited for management according to the eye care algorithm over a period ranging from 1 to 28 days. Four patients were excluded because of failure by staff to adhere to the protocol. In 18 patients no active treatment was required. Out of six patients who had conjunctival exposure and were given ocular lubricants, four maintained clear corneas. No corneal or conjunctival staining was noted in two of the four patients whose lids required closure with Micropore tape for corneal exposure. Use of lid taping and lubricants prevented corneal abrasion in two patients who were prone ventilated. The prevalence of ocular surface abnormalities was 8.7 % where the algorithm was properly followed (23 patients). CONCLUSION: The proposed eye care algorithm appears to be effective in preventing ocular surface abnormalities in the sedated and unconscious patients in the ICU, and efficient in that it may reduce the workload required for critically ill patients.

Adult↗

PubMed2006

Legeais BioKpro III keratoprosthesis implantation: long term results in seven patients.

AIMS: The long term results of the Legeais BioKpro III keratoprosthesis are presented for seven patients with severe corneal scarring. METHODS: The study took place at Moorfields Eye Hospital, London. Patients had either end stage ocular surface disease or corneal opacification after multiple failed graft surgery, with the potential for significant visual improvement. After insertion the device was covered with a conjunctival flap or buccal mucous membrane graft, which was later opened to expose the optic. The outcome measures were vision, complications, and retention of the device. RESULTS: The BioKpro III was inserted into seven patients with severe corneal scarring: ocular cicatricial pemphigoid, measles keratitis, thermal injury, Stevens-Johnson syndrome, aniridia, chemical injury, and congenital rubella. The follow up was 18-48 months. The keratoprosthesis failed in six, because of extrusion occurring 2-28 months postoperatively. Retroprosthetic membranes occurred in three patients, and endophthalmitis in one. Vision improved from hand movements to 6/12 in the only patient who retained the KPro; however he was troubled by mucus accumulation on the optic. CONCLUSIONS: The one success has been in a patient with thermal burns. The remaining results have been poor, with the KPro extruding in six of the seven patients.

Adult↗

PubMed1999

Limbal allografting from related live donors for corneal surface reconstruction.

OBJECTIVE: To report the results of limbal allograft transplantation, from human leukocyte antigen (HLA)-matched and -unmatched related live donors, in patients with ocular surface disease due to chemical burns and Stevens-Johnson syndrome. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eight patients (nine eyes) with severe chemical burns (n = 7 eyes) and Stevens-Johnson syndrome (n = 2 eyes). INTERVENTION: Recipient eyes were treated with excision of cicatricial tissues. Transplantation of superior and inferior limbal grafts was performed from related live HLA-matched (n = 7) and -unmatched donors (n = 2). Systemic cyclosporine was not used in any of the recipients. MAIN OUTCOME MEASURES: Reconstruction of corneal surface epithelium, restoration of avascularity, increase in ocular comfort, and improvement in visual acuity. RESULTS: With a mean observation period of 17.2 months, phenotypically corneal epithelium, decreased vascularization of the corneal surface, and improved ocular comfort were seen in seven (77.8%) eyes. In all seven eyes, gradual recurrence of peripheral corneal vascularization occurred during the follow-up period. Features of graft rejection developed in three (42.9%) of these seven eyes. In two eyes, limbal transplantation from HLA-unmatched donors failed to reconstitute the corneal surface. Limbal allograft transplantation resulted in visual acuity of 20/400 or greater in only two (22.2%) eyes at last follow-up. Corneal grafts performed 7 and 16 months after successful limbal transplantation in two eyes developed recurrent epithelial breakdown and superficial corneal scarring. None of the donor eyes in this study had any complication. CONCLUSION: Transplantation of limbal tissue from related live donors successfully reconstructs the corneal surface in HLA-matched recipients. Recurrence of vascularization on long-term follow-up probably results from inadequate stem cell transfer, immune-mediated stem cell damage, or both. Limbal allografting is best performed by transplanting the entire limbus from a cadaveric donor eye with systemic immunosuppression of the recipient, even if the donor is HLA-compatible.

Adolescent↗

PubMed1997

Storage, surgery, outcome, complications, and new developments in corneal and conjunctival grafts.

This review covers last year's literature on corneal, limbal, and conjunctival transplantation including tissue storage and eye banking. In this area, the main themes were related to a better evaluation of tissue viability and the exclusion of disease transmission. An analysis of the changing indications for penetrating keratoplasty shows the differences between American and European series. Most efforts in relation to surgical techniques are oriented toward obtaining better refractive results, whereas the study of large series sheds new light on the risk factors for graft failure and other complications. Limbal transplants have acquired the status of a new field in the surgical treatment of ocular surface disease, particularly in relation to corneal stem cell deficiencies.

Conjunctiva↗

PubMed2004

Ocular surface stem cells and disease: current concepts and clinical applications.

Corneal and conjunctival epithelial stem cells are responsible for the homeostasis and regeneration of the ocular surface epithelium. Corneal epithelial stem cells reside in the basal region of the limbus, while the conjunctival forniceal region appears to be the site that is enriched in conjunctival stem cells. Ocular surface disease arising from limbal stem cell deficiency is characterised by persistent epithelial defects, corneal vascularisation, chronic inflammation, scarring and conjunctivalisation, resulting in visual loss. Limbal stem cell transplantation replaces the corneal stem cell population in these eyes with the hope of restoring vision. More recently, the use of bioengineered ocular surface tissue-equivalents has had promising results, and may represent the future for replacement and regeneration of ocular tissues in various ocular disorders.

Biomedical Engineering↗

PubMed2006

Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dry-eye patients having laser in situ keratomileusis.

PURPOSE: To evaluate dry-eye signs, symptoms, and refractive outcomes in patients with dry-eye disease having laser in situ keratomileusis (LASIK). METHODS: In this randomized parallel double-masked prospective clinical trial, 42 eyes of 21 myopic patients (mean spherical equivalent -4.3 diopters [D], range -1.00 to -10.63 D) with dry-eye disease were treated with unpreserved artificial tears or cyclosporine 0.05% ophthalmic emulsion twice a day beginning 1 month before LASIK. Treatment with the study drug was discontinued for 48 hours post surgery and then resumed for 3 additional months. Both groups used additional artificial tears as needed. Study visits occurred pretreatment (baseline), before surgery, and at 1 week and 1, 3, 6, and 12 months after surgery. RESULTS: Statistically significant increases from baseline were found in Schirmer scores for artificial tears at 1 month (P = .036) and for cyclosporine 0.05% before surgery and 1 week, 1 month, and 6 months after surgery (P<.018). There were no significant differences from baseline or between groups in responses to the Ocular Surface Disease Index questionnaire or best corrected visual acuity (BCVA), nor were there significant between-group differences in superficial punctate keratitis or uncorrected visual acuity. Mean refractive spherical equivalent in cyclosporine-treated eyes was significantly closer to the intended target at 3 and 6 months after surgery than in artificial-tears-treated eyes (P = .007). A greater percentage of cyclosporine eyes was within +/-0.5 D of the refractive target 3 months after surgery than artificial tears eyes (P = .015). CONCLUSION: Successful outcomes after LASIK were achieved for dry-eye disease patients. Treatment with cyclosporine 0.05% provided greater refractive predictability 3 and 6 months after surgery than unpreserved artificial tears.

Administration, Topical↗

PubMed2006

Flow cytometrical analysis of adhesion molecules, T-lymphocyte subpopulations and inflammatory markers in pterygium.

BACKGROUND/AIM: Pterygium is a relatively frequent ocular surface disease with an unexplained etiopathogenesis. Our study was carried out with the aim to identify the presence of inflammatory cells and mediators such as T-lymphocyte subgroups (CD4 and CD8), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and human leukocyte antigen-DR (HLA-DR) in pterygium tissue. METHODS: Pterygium tissue, obtained from 24 patients, and normal conjunctival tissue, from the nasal bulbar conjunctiva obtained from 14 patients operated for ocular perforations or vitrectomy, were separated into epithelial and stromal components under the microscope and suspended with phosphate-buffered saline solution to form a suspension. Cell suspensions were treated with specific antibodies for ICAM-1, VCAM-1, and HLA-DR and T-lymphocyte subgroups and evaluated with flow cytometry. The obtained data were compared statistically. RESULTS: When compared to the control tissue samples, higher rates of ICAM-1-positive cells, VCAM-1-positive cells and HLA-DR-positive cells were recorded in pterygium tissue samples. CD4 and CD8 lymphocytes were also found to be at higher levels when compared to the control group. There was a statistically significant difference between the two groups. CONCLUSION: When compared with normal conjunctival tissue, pterygium tissue had increased levels of T-lymphocyte infiltration and inflammatory markers demonstrating the possible contribution of cellular immunity to the pathogenesis.

Adult↗