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Significance: Optometry is desperately needed to combat the increasing rate of avoidable visual impairment that goes undiagnosed largely owing to the lack of integration of eye care services with primary care medicine. Government leaders are actively discussing substantive changes to health care legislation that will impact optometrists and their patients. The importance of a regular eye examination for disease prevention has long been undervalued in the setting of primary care. Consequently, many serious and potentially treatable ocular and systemic diseases go undiagnosed. Despite clear indicators that vision impairment increases the risk of morbidity and mortality from chronic systemic disease and decreases quality of life, vision health remains among the greatest unmet health care needs in the United States. To improve vision care services for all Americans, we must focus our attention on two central themes. First, we must educate the public, health care professionals, and policymakers on the importance of routine eye care as a preventive measure in the setting of primary care. Next, we need to recognize that optometrists, through their geographic distribution and advanced training, are in a strategic position to deliver integrated, comprehensive, cost-effective eye care services for individuals most in need. In this perspective, we discuss a model for integrating optometric services with the practice of primary care medicine to facilitate early detection of both eye and systemic disease while reducing serious and preventable health-related consequences.

Purpose: Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye., Methods: We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye., Results: Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1., Conclusions: Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.

The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms.

Purpose: To explore non-invasive, protein-based, membrane array technology as a means to evaluate the global immune and angiogenic profile of tear proteins in patients with active ocular cicatricial pemphigoid (OCP)., Methods: Forty-three proteins consisting of cytokines, angiogenic/growth factors, and immunoinflammatory modulators were measured by membrane array in tear samples of four control patients and four OCP patients during active disease and after treatment., Results: Signals for several distinct and consistent molecular entities were upregulated in all four active OCP tear samples relative to controls. In particular, interleukin-8 and matrix metalloproteinase-9 were elevated during active disease and decreased after systemic immunomodulatory therapy., Conclusions: Protein array analysis may provide a well-tolerated assay to monitor levels of inflammatory markers in the tears of OCP patients in response to therapy.

A devastating consequence of autoimmune-mediated, aqueous tear deficiency is pathological keratinization of the ocular surface. It is setoff by an aberrant immune response that promotes a program of altered mucosal epithelial cell differentiation. The management of keratinizing ocular surface disease is challenging. Topical therapies are largely inadequate for acute exacerbations, and progressive disease often requires systemic immunosuppression. A combination of translational and basic science research is necessary to understand the link between aberrant immunity and pathological keratinization. I review recent research and future directions aimed to develop targeted therapies that control or prevent ocular surface keratinization.

Purpose: Many bioactive proteins including cytokines are reported to increase in dry eye disease although the specific profile and concentration of inflammatory mediators varies considerably from study to study. In part, this variability results from inherent difficulties in quantifying low abundance proteins in a limited sample volume using relatively low sensitivity dot ELISA methods. Additional complexity comes with the use of pooled samples collected using a variety of techniques and intrinsic variation in the diurnal pattern of individual tear proteins. The current study describes a recent advance in the area of proteomics that has allowed the identification of dozens of low abundance proteins in human tear samples., Methods: Commercially available stationary phase antibody protein arrays were adapted to improve suitability for use in small volume biological fluid analysis with particular emphasis on tear film proteomics. Arrays were adapted to allow simultaneous screening for a panel of inflammatory cytokines in low volume tear samples collected from individual eyes., Results: A preliminary study comparing tear array results in a small population of Sjögren's syndrome patients was conducted. The multiplex microplate array assays of cytokines in tear fluid present an unanticipated challenge due to the unique nature of tear fluid. The presence of factors that exhibit an affinity for plastic, capture antibodies and IgG and create a complex series of matrix effects profoundly impacting the reliability of dot ELISA, including with elevated levels of background reactivity and reduction in capacity to bind targeted protein., Conclusions: Preliminary results using tears collected from patients with Sjögren's syndrome reveal methodological advantages of protein array technology and support the concept that autoimmune-mediated dry eye disease has an inflammatory component. They also emphasize the inherent difficulties one can face when interpreting the results of micro-well arrays that result from blooming effects, matrix effects, image saturation and cross-talk between capture and probe antibodies that can greatly reduce signal-to-noise and limit the ability to obtain meaningful results.

Background: Fluorophotometry can be used to quantify changes in epithelial permeability (Pdc), corneal pH, and tear exchange (T95; time to deplete 95% of a fluorescent dye from beneath a contact lens) associated with contact lens wear. Using fluorometric procedures, we present previously reported data in order to review the effects of contact lens wear on Pdc and pH. We also introduce a new method for measuring tear exchange beneath a soft contact lens and present preliminary data., Methods: Pdc was assessed on 32 subjects after 1 h of closed-eye soft contact lens wear. Stromal pH was assessed on 21 subjects wearing lenses with a range of different oxygen transmissibilities (Dk/L). T95 was assessed on 7 subjects who wore disposable lenses. Pdc estimates were derived by measuring the rate at which topically applied fluorescein crossed the epithelial barrier from the tears; corneal pH was quantified by alternately exciting a fluorescein-loaded cornea with two wavelengths of blue light and calculating the fluorescence intensity ratio (490/450 nm), which is pH-sensitive; and the T95 was estimated by applying 2 microliters of FITC-Dextran to the posterior surface of a soft contact lens and the monitoring the exponential decay of dye under the lens., Results: On average, 1 h of closed-eye contact lens wear caused a 41% increase in Pdc compared to the control eye. Corneal pH varied directly with a decrease in Dk/L. On average the T95 under contact lenses (mean = 29 min) was slow compared to normal rates with no lens (approximately 5 min)., Conclusions: Fluorophotometry can be used to quantify some interesting effects associated with contact lens wear, and the use of these techniques may provide new information about the impact of contact lens wear on corneal structure and function.