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Gary N Foulks

Publications and source records attributed to Gary N Foulks.

17 recordsLinked to original sources
PubMed2006

MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls.

Mucins are highly glycosylated proteins that are vital to the maintenance of healthy epithelial surfaces including the ocular surface. Mucins act as lubricants, protectants, and mediators of signal transduction. The majority of the O-glycosylation sites on the transmembrane mucin MUC1 are found in a highly polymorphic core region containing a variable number of tandem repeats (VNTR). MUC1 alleles can be divided into size classes that contain small (30-45) or large (60-90) numbers of repeats. Although at least 12 splice variants of MUC1 have been found in other tissues, no splice variants have been reported in human ocular surface tissues. We have used RT-PCR to identify MUC1 splice variants that were then confirmed by sequencing. We here report the presence in some samples of human cornea, conjunctiva, and lacrimal gland of MUC1/B which features canonical splicing between exons 1 and 2 and MUC1/A, a transcript that retains 27bp from the 3' end of intron 1 and is predicted to add 9 amino acids to the MUC1 sequence upstream of the tandem repeat region. Cornea and conjunctiva both contain the MUC1/SEC splice variant that lacks the transmembrane domain and, therefore, results in a soluble, secreted form of MUC1. Cornea and conjunctiva also contain MUC1/Y and MUC1/Z(X) variants that lack the tandem repeat region. Cornea, conjunctiva, and lacrimal gland also contain a previously undescribed MUC1 variant transcript, termed MUC1/YI, that retains 99bp from the 5' end and 27bp from the 3' end of the first intron, resulting in a frame shift and premature stop codon. This transcript is predicted to produce a novel 27 amino acid peptide after signal peptidase cleavage. Analysis of brush cytology samples revealed that the percentage of dry eye patients expressing the MUC1/A variant in the conjunctival epithelium is lower than in normal control donors. Western blotting confirmed that MUC1/A is associated with alleles containing the large size class of tandem repeats. Therefore, we propose that one factor in susceptibility to dry eye disease may be the lengths of the MUC1 VNTR in conjunctival epithelium based on the rationale that longer VNTR provide better lubrication and greater protection of the ocular surface against inflammation.

Alternative Splicing↗
PubMed2006

Prolonging contact lens wear and making contact lens wear safer.

PURPOSE: To summarize the present status of safety and efficacy of contact lens wear. DESIGN: Literature review. METHODS: Ovid Medline searches were performed on records from 1966 through 2005 using keywords: keratitis, contact lens complications, extended-wear contact lenses, and silicone-hydrogel contact lenses. RESULTS: Patients desire comfort, clarity of vision, and prolonged contact lens wear when contact lenses are used to correct refractive error. Practitioners desire patient satisfaction but also require maintenance of the integrity of the eye and no complications that jeopardize vision or health of the eye. Improvements in the oxygen permeability of the contact lens materials, design of the contact lens and its surface, and solutions for the maintenance of the lens have reduced but not eliminated the risks of infection, inflammation, and conjunctival papillary reaction associated with contact lens wear. The lessons of past and recent history suggest that patient education and practitioner participation in the management of contact lens wear continue to be critical factors for patient satisfaction and safety in the extended wear of contact lenses. CONCLUSIONS: The availability of highly oxygen permeable contact lenses has increased the tolerance and safety of extended contact lens wear, but patient instruction and education in proper use and care of lenses is required and caution is advised.

Contact Lenses↗
PubMed2006

Expression in human ocular surface tissues of the GalNAc-transferases that initiate mucin-type O-glycosylation.

PURPOSE: Mucins are highly glycosylated proteins that act as lubricants, protectants, and mediators of signal transduction. The UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGaNTase) family members initiate mucin-type O-glycosylation. Because O-glycosylation provides mucins with the viscoelastic properties required for proper mucin function, ppGaNTase expression is vital to the maintenance of healthy epithelial surfaces including the ocular surface. Differences of expression of ppGaNTase isoforms might be factors influencing susceptibility to dry eye disease. Therefore, we determined the expression of the ppGaNTase isoforms in normal human ocular surface tissues and the conjunctival epithelium from patients with aqueous-deficient dry eye. METHODS: Expression of ppGaNTase isoforms was quantitated by real-time reverse transcriptase polymerase chain rection (RT-PCR). RESULTS: Conjunctiva and cornea expressed multiple ppGaNTase isoforms, with isoforms T12 and T4 being the most strongly expressed in conjunctiva and T12 and T3 in the cornea. In contrast, lacrimal gland expressed fewer isoforms and had lower total ppGaNTase expression. Brush cytology was found to be superior to impression cytology for harvesting conjunctival epithelium in terms of ease of use, safety, and reproducibility of results. Similar to whole conjunctiva, the strongest isoforms in conjunctival epithelial cells were T12 and T4, followed by T3, T1, T5, and T2. No significant differences of ppGaNTase expression were found between the conjunctival epithelium of dry eye and normal control groups. CONCLUSION: Human ocular surface tissues express multiple ppGaNTase isoforms, suggesting a requirement for glycosylating diverse mucin-type substrates. However, there is no evidence to date to suggest that differences of ppGaNTase expression levels might contribute to susceptibility to dry eye disease.

Conjunctiva↗
PubMed2006

Glycoprotein 340 in normal human ocular surface tissues and tear film.

The tear film is a complex mixture of secreted fluid, ions, proteins, glycoproteins, and lipids that lubricates and protects the ocular surface. Recently, several antimicrobial peptides have been described in the tear fluid. In this study, we describe the presence of the large secreted glycoprotein gp340 in the tear film. Western blot analysis showed that gp340 is abundant in secreted tears and in the lacrimal glands. Lesser amounts of gp340 were detected in the cornea and conjunctiva. Consistent with Western blot data, reverse transcription-PCR and real-time quantitative PCR showed that gp340 transcripts were abundant in lacrimal gland tissue and were also present in the cornea and conjunctiva. Immunohistochemistry localized gp340 to the acinar cells of the lacrimal gland and the deeper layers of the conjunctival epithelium. gp340 was not detected in conjunctival goblet cells. In the cornea, gp340 was present only in a peripheral band of basal epithelial cells, suggesting that gp340 may play a role in the cycle of corneal epithelial renewal. To determine if tear film gp340 may function as a bacterial agglutinin as it does in saliva, tears were incubated with streptococcal cells and the formation of bacterial aggregates was monitored. Addition of tears to late-exponential-phase Streptococcus mutans cells resulted in time- and dose-dependent aggregation of the bacteria. Furthermore, Western blot analysis confirmed the presence of cell-associated gp340 in isolated bacterial aggregates. The ocular pathogen Staphylococcus aureus, but not Pseudomonas aeruginosa, also aggregated when incubated with tears. These results suggest that gp340 is a normal component of the tear film and that the glycoprotein may function as a bacterial agglutinin.

Adult↗
PubMed2005

Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years.

OBJECTIVE: To evaluate cyclosporine 0.1% ophthalmic emulsion over a 1- to 3-year period in moderate to severe dry eye disease patients. DESIGN: Nonrandomized, multicenter, open-label clinical trial extending 2 ophthalmic cyclosporine phase III clinical trials. PARTICIPANTS: Four hundred twelve patients previously dosed for 6 to 12 months with cyclosporine 0.05% or 0.1% in prior phase III trials. INTERVENTION: Patients instilled ophthalmic cyclosporine 0.1% twice daily into both eyes for up to 3 consecutive 12-month extension periods. MAIN OUTCOME MEASURES: Corneal staining, Schirmer tests, and symptom severity assessments were conducted during the first 12-month extension, with a patient survey during the second 12-month extension. Biomicroscopy and visual acuity (VA) examinations, intraocular pressure (IOP) measurements, and adverse effects queries occurred at 6-month intervals. RESULTS: Mean duration of treatment was 19.8 months. Improvements in objective and subjective measures of dry eye disease were modest, probably because of prior treatment with cyclosporine. Most survey respondents said their symptoms began to resolve in the first 3 months of cyclosporine treatment during the previous phase III clinical trials. At study exit, VA decreased in 12.6% (93/738) and increased in 5.4% (40/738) of eyes by > or =2 lines; severity of biomicroscopy findings increased in 3.4% (chemosis; 26/760), 7.2% (conjunctival hyperemia; 55/760), or 8.5% (tear film debris; 64/756) of eyes; and mean IOP increased 0.18 mmHg relative to baseline. The most common treatment-related adverse events were burning (10.9% of patients [45/412]), stinging (3.9% [16/412]), and conjunctival hyperemia (3.4% [14/412]). No serious treatment-related adverse events occurred. Most patients (95.2% [140/147]) said they would continue cyclosporine therapy; 97.9% (143/146) would recommend it to other dry eye patients. CONCLUSIONS: Therapy of chronic dry eye disease with cyclosporine 0.1% ophthalmic emulsion for 1 to 3 years was safe, well tolerated, and not associated with systemic side effects. The results supplement the safety record of the commercially available cyclosporine 0.05% ophthalmic emulsion.

Adult↗
PubMed2003

The evolution in therapeutic contact lenses.

Therapeutic soft contact lenses were first approved in the 1970s, but the variety of available materials and parameters continues to evolve. Currently, the armamentarium of therapeutic contact lenses allows the clinician to select lenses that not only protect the corneal surface but also assist in modulation of the healing process. This article summarizes the available contact lenses, the conditions most amenable to treatment, and the decision-making process that allows optimal selection of a therapeutic contact lens for a specific patient. Many of the hydrophilic soft contact lenses used for cosmetic correction are not approved for therapeutic use but have been used in an off-label manner as therapeutic lenses. Communicating with the patient is important when recommending the use of a therapeutic contact lens, explaining the goals of therapy, warning about the risks contingent upon contact lens use, and determining whether the lens is being used in an off-label fashion. The advances in contact lens technology have opened new options for use of therapeutic contact lenses. With a new generation of high-Dk lenses whose makers promise fewer limiting problems of vascularization and infection, the utility of the older, traditional therapeutic lenses can be enhanced and the more selective application of individual lenses can be permitted. By considering the healing objectives of the particular treatment plan for a specific patient, greater control of the endpoint and timeframe of therapy is now possible.

Contact Lenses, Hydrophilic↗
PubMed2003

The evolving treatment of dry eye.

Palliative treatments that historically have been the mainstay of therapy for dry eye continue to improve and are still appropriate therapy while we await new advances to control the underlying cause of dry eye disease. The approach of tear supplementation and tear preservation continues to be useful. The goal of tear stimulation or enhancement is elusive, but it may be nearer with the advent of P2Y2 agonists. The recognized importance of inflammation in producing dry eye through lacrimal gland and ocular surface damage is leading us to novel strategies to immunomodulate the disease and to restore hormonal balance to the ocular surface-lacrimal gland homeostatic cycle. It has taken 20 years of investigation to reach this threshold. The next 3 years should see promising treatments approved for dry eye disease.

Dry Eye Syndromes↗
PubMed2003

Therapy for meibomian gland disease.

Great advances have been made in the past half-century in our understanding of meibomian gland function and of the many inflammatory, hormonal, and infectious processes leading to its dysfunction. These advances have led to an exploration of exciting new avenues for treatment of this common but frustrating disease entity.

Eyelid Diseases↗
PubMed2003

Therapeutic contact lenses: the role of high-Dk lenses.

Currently, the armamentarium of contact lenses that can be used for therapeutic effect provides a wider selection of lenses than ever before. If the therapeutic goal is protection and healing of the corneal epithelium, epithelial or stromal edema is best avoided, and the selection of a high-Dk silicone hydrogel (balafilcon A, lotrafilcon A) lens or a very thin membrane-type lens (crofilcon) is the best choice. If the goal is surface protection as well as stimulation of stromal wound vascularization, selection of a low-water content, thick, hydrophilic lens is the better option. If the patient is prone to lens loss or requires frequent replacement of the therapeutic lens, a prudent economic decision is to select a daily disposable moderate-water content lens. Specific circumstances may mandate the selection of a specific therapeutic lens. Patients with a prior history of active giant papillary conjunctivitis may be better served by the use of a crofilcon glyceryl methacrylate lens, which has a lower incidence of this complication. Patients who have dry eye may benefit from a higher-water content lens if adequate unpreserved tear supplementation is provided with or without punctal occlusion. The options when selecting a therapeutic contact lens are wider than ever before. Although the new generation of high-Dk lenses promises fewer limiting problems of vascularization and infection, one can use the older traditional therapeutic lenses when induced vascularization of the cornea is needed or when an economic necessity exists. Not all of the available lenses are FDA approved for therapeutic use, and such wear is an off-label use. The patient should be informed of the goal of therapy as well as the benefits and risks of therapeutic contact lenses.

Contact Lenses↗
PubMed2003

Challenges and pitfalls in clinical trials of treatments for dry eye.

Clinical trials to evaluate the effectiveness of therapy for dry eye disease are challenging because of the nature of the disease, the multiple palliative methods used by patients to control their symptoms, and the potential limitations of the techniques available to evaluate therapeutic outcomes. This review identifies some of the pitfalls encountered in recent clinical trials in dry eye disease. The peculiarities of dry eye disease with respect to symptoms, signs, and patho- physiological changes are discussed. Potential problems that apply to all clinical trials, including patient selection, randomization in small populations, and assessment of the placebo effect, are presented with respect to dry eye clinical trials. Considerations regarding study design address inclusion/exclusion criteria and selection of outcome measures. Special attention is given to methods of symptom analysis, techniques of staining of the ocular surface, and grading systems for surface staining. Alternative methods to the standard clinical trial are mentioned to place them in perspective for overall evaluation of dry eye disease therapy. Finally, caveats are provided to encourage investigators to vigorously conduct future clinical trials in dry eye therapy.

Journal Article↗
PubMed2003

Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading.

Although meibomian gland disease (MGD) is one of the most common disorders encountered in ophthalmic practice, there has been no descriptive system consistently accepted to clinically characterize the anatomical and correlative biochemical alterations that occur in this condition. The purpose of this review is to synthesize a clinical description of meibomian gland disease and to provide a scheme for diagnosis, classification, and quantification that will be of value in the clinical setting and in the conduct of clinical trials.

Journal Article↗
PubMed2003

What is dry eye and what does it mean to the contact lens wearer?

PURPOSE: To define dry eye disease and describe the evolution of our understanding of the clinical expression and pathophysiology of dry eye. To relate tear function to contact lens wear and review the problems dry eye causes with contact lens tolerance and performance. METHODS: Review of literature. RESULTS: The rudimentary definition of dry eye as a lack of tears is expanded through an increased understanding of the clinical presentations of dry eye. The classification of dry eye is historically reviewed. The pathophysiology is related to the evolution of therapy for dry eye disorders. The function of the tear film is related to contact lens wear and the problems induced by dry eye correlated with contact lens intolerance. CONCLUSION: The tear film is critical to successful contact lens wear. Disturbances of the quantity or quality of the tear film, whether because of aqueous deficiency or evaporative tear problems, results in intolerance of contact lens wear and damage to the ocular surface.

Contact Lenses↗
PubMed2002

Amniotic membrane in the surgical management of acute toxic epidermal necrolysis.

OBJECTIVE: To report a new surgical technique to manage severe acute toxic epidermal necrolysis. DESIGN: Two interventional case reports. PARTICIPANTS: Two patients. Case 1: A 6-year-old boy had severe toxic epidermal necrolysis develop after being treated with trimethoprim and sulfamethoxazole for chronic otitis media. Both eyes and eyelids were affected. He underwent bilateral lysis of symblepharon and all adhesions and bilateral amniotic membrane transplantation to the entire ocular surface except the cornea. Loss of eyelid skin required transplantation of amniotic membrane to all four eyelids and strips of amniotic membrane at the eyelid margins. Case 2: An 8-year-old girl with severe toxic epidermal necrolysis associated with mycoplasma pneumonia had bilateral, diffuse keratoconjunctivitis, diffuse corneal epithelial defects, and bilateral symblepharon. Amniotic membrane transplantation was performed bilaterally, using a symblepharon ring in the left eye. INTERVENTION: Amniotic membrane transplantation. MAIN OUTCOME MEASURES: Preservation of normal ocular and eyelid surfaces and prevention of blindness. RESULTS: Case 1: Thirty-six months after bilateral ocular surgery, there is no symblepharon, good ocular surface wetting, and an uncorrected bilateral vision of 20/20. Case 2: Amniotic membrane transplantation protected both ocular surfaces and prevented conjunctival contracture without adhesion of the eyelids to the ocular surface. The central vision was preserved. There was minimal peripheral corneal vascularization and mild conjunctival scarring of the tarsal conjunctival surface 34 months postoperatively. CONCLUSIONS: These are the first cases of acute toxic epidermal necrolysis treated with amniotic membrane transplantation and the first use of the procedure on external eyelid surfaces with good healing of the eyelids. This new treatment for acute toxic epidermal necrolysis preserves normal ocular and eyelid surfaces and may prevent blindness.

Acute Disease↗
PubMed2002

Removal of INTACS for myopia.

OBJECTIVE: To evaluate the safety and efficacy of the removal of INTACS. DESIGN: Subgroup analysis from a nonrandomized comparative interventional trial. PARTICIPANTS: Four hundred fifty-two patients with best spectacle-corrected visual acuity of 20/20 or better and myopia (1.0-3.5 diopters [D]) were enrolled in the U.S. Food and Drug Administration clinical trials of INTACS. Forty-six eyes among a total of 684 underwent INTACS removal. INTERVENTION: INTACS removal. METHODS: Safety and efficacy of INTACS removal was assessed by comparison of results from preoperative and 3-month postremoval visits. Safety was assessed by maintenance of preoperative best spectacle-corrected acuity and induction of astigmatism (measured by manifest refraction). Efficacy was assessed by comparison of mean spherical equivalent measured by both manifest and cycloplegic refraction, as well as percentage of eyes within +/- 0.5 D and +/- 1.0 D of baseline values. A subset of 27 patients completed a prospective questionnaire assessing the frequency of six visual symptoms (glare, halos, double vision, photophobia, night vision difficulties, and fluctuating vision). MAIN OUTCOMES MEASURES: Best spectacle-corrected visual acuity, manifest refraction, and cycloplegic refraction. RESULTS: Forty-one of 46 patients' eyes that had undergone INTACS removal had reached the 3-month postremoval visit. Of these eyes, 73% (30 of 41) had returned to within +/- 0.5 D and 97% (40 of 41) to within +/- 1.0 D of baseline spherical equivalent as measured by manifest refraction. With respect to astigmatism, 88% (36 of 41) had returned to within +/- 0.5 D and 100% (41 of 41) to within +/- 1.0 D of preoperative value. No patient had a loss of best spectacle-corrected acuity of more than 2 lines, with equal numbers of eyes having a loss or gain of 1 line (nine eyes) and 2 lines (one eye). For most eyes, INTACS removal was associated with a substantial reduction in the six types of visual symptoms; however, in some eyes (up to 15%) symptoms that had not been detected preoperatively were noted after INTACS removal. CONCLUSIONS: INTACS removal was not associated with a loss (> 2 lines) of best spectacle-corrected visual acuity or induction (> 1 D) of astigmatism or myopia. INTACS removal was associated with a reversal to preoperative values in most cases.

Adult↗