Lifetime Corneal Edema Load Model.

Purpose: To highlight the potential benefits for long-term use of silicone hydrogels daily disposable (DD) contact lenses, particularly with patients who are noncompliant, sleeping or napping while wearing their lenses, or those who have higher oxygen demands and wear this modality for decades. Methods: Published data for corneal swelling with lenses and no lens wear were used to develop a nonlinear least squares model. The edema load experienced with a range of oxygen transmissibilities (Dk/t) and wear compliance (sleep and napping) was determined. A mixed-effects linear regression model was used to compare the edema load for high and average corneal swellers. Results: The edema load generated demonstrates that a high Dk/t silicone hydrogel lens results in edema levels close to that with no lens wear. In comparison, hydrogels with a Dk/t of 27 (× 10-9 [cm mL{O2}][s mL mm Hg]), worn on a daily wear schedule will result in 1.5 times more edema and up to two times more if the patient is noncompliant over each decade of wear. High swellers after four decades of wear will have an edema load 10 to 17 times greater than average swellers depending on Dk/t and their degree of noncompliance with the daily wear modality. Conclusions: Prescribing silicone hydrogel DD lenses, particularly with higher DK/t, may help to maintain the long-term ocular health of patients, when they wear their lenses fulltime for many decades. Translational Relevance: Illustrates the importance of Dk/t for any CL wear modality where patients nap or sleep in lenses or have high oxygen needs.

Interpreting the corneal response to oxygen: Is there a basis for re-evaluating data from gas-goggle studies?

When anoxia (0% oxygen) is created within a gas-tight goggle, ocular physiological responses, including corneal swelling, limbal hyperaemia and pH change, are known to vary, depending on the presence or absence of a low, oxygen transmissibility contact lens. A new theory is proposed to account for this discrepancy based on the concept of lid derived oxygen, whereby oxygen originating from the vascular plexus of the palpebral conjunctiva supplements that available to the ocular surface in an open, normally blinking eye, even when the surrounding gaseous atmosphere is anoxic. The effect of a lid derived contribution to corneal oxygenation was assessed by using existing experimental data to model open-eye, corneal swelling behavior as a function of atmospheric oxygen content, both with and without the presence of a contact lens. These models predict that under atmospheric anoxia, contact lens wear results in 13.2% corneal swelling compared with only 5.4% when the lens was absent. Lid derived oxygen acts to provide the ocular surface in the non-contact lens wearing, normally blinking, open-eye with up to 4.7% equivalent oxygen concentration, even within the anoxic environment of a nitrogen filled goggle. Correcting for lid derived oxygen eliminates previously observed discrepancies in corneal swelling behavior and harmonizes the models for the contact lens wearing and gas-goggle cases. On this basis it is proposed that true anoxia at the ocular surface cannot be achieved by atmospheric manipulation (i.e. a gas-goggle) alone but requires an additional presence, e.g. a low, oxygen transmissibility contact lens, to prevent access to oxygen from the eyelids. Data from previously conducted experiments in which the gas-goggle paradigm was used, may have been founded on underestimates of the real oxygen concentration acting on the ocular surface at the time and if so, will require re-interpretation. Future work in this area should consider if a correction for lid derived oxygen is necessary.

Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding.

PURPOSE: This study investigated ocular surface components that contribute to matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal epithelial wounding. METHODS: Laboratory short-haired cats underwent corneal epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were collected at baseline and during various healing stages. Procedural control eyes (identical experimental protocol as wounded eyes except for wounding, n = 5) served as controls for tear analysis. MMP activity was analyzed in tears using gelatin zymography. MMP staining patterns were evaluated in ocular tissues using immunohistochemistry and used to determine MMP expression sites responsible for tear-derived MMPs. RESULTS: The proMMP-2 and proMMP-9 activity in tears was highest in wounded and procedural control eyes during epithelial migration (8 to 36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in tears only during and after epithelial restratification (day 3 to 4 and day 7 to 28 post-wounding, respectively) as compared to procedural controls (p<0.05). Tears from wounded and procedural control eyes showed no statistical differences for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and MMP-9 expression in the cornea during epithelial migration and wound closure. The conjunctival epithelium exhibited highest levels of both MMPs during wound closure, while MMP-9 expression was reduced in conjunctival goblet cells during corneal epithelial migration followed by complete absence of the cells during wound closure. The immunostaining for both MMPs was elevated in the lacrimal gland during corneal healing, with little/no change in the meibomian glands. Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP-9 staining. CONCLUSIONS: Following wounding, migrating corneal epithelium contributed little to the observed MMP levels in tears. The major sources assessed in the present study for tear-derived MMP-2 and MMP-9 following corneal wounding are the lacrimal gland and CALT. Other sources included stromal keratocytes and conjunctiva with goblet cells.

Tear film stability: a review.

Tear film stability can be assessed via a number of tools designed for clinical as well as research purposes. These techniques can give us insights into the tear film, and allow assessment of conditions that can lead to dry eye symptoms, and in severe cases, to significant ocular surface damage and deterioration of vision. Understanding what drives tear film instability and its assessment is also crucial for evaluating existing and new therapies. This review examines various techniques that are used to assess tear film instability: evaluation of tear break-up time and non-invasive break-time; topographic and interferometric techniques; confocal microscopic methods; aberrometry; and visual function tests. It also describes possible contributions of different tear film components; namely meibomian lipids, ocular mucins and proteins, and factors such as age, contact lens wear, ocular surgery and environmental stimuli, that may influence tear film instability.

Have silicone hydrogel lenses eliminated hypoxia?

OBJECTIVE: The purpose of this article is to review the literature to date to determine if silicone hydrogel lenses have eliminated corneal hypoxia. METHODS: Results from clinical studies, including short-term laboratory studies and retrospective and prospective clinical trials that have assessed the cornea's response to silicone hydrogels, will be evaluated. RESULTS: Silicone hydrogels have eliminated the physiologic signs associated with lens-induced hypoxia including ocular and limbal redness, neovascularization, epithelial microcysts, and endothelial responses. Responses to these markers are similar to those observed with nonlens wearers. Although, for most patients, the oxygen transmissibility of silicone hydrogels is enough to eliminate corneal edema, some patients with high oxygen needs and/or with high refractive errors will still demonstrate significant edema after overnight wear. CONCLUSIONS: The range of silicone hydrogels available today, regardless of wearing modality, have effectively eliminated hypoxia for most patients.

A preliminary study of changes in tear film proteins in the feline eye following nictitating membrane removal.

OBJECTIVE: To investigate the influence of nictitating membrane (third eyelid) removal on selected proteins in feline tears. ANIMAL STUDIED: Domestic short-haired cats (7-17 months; 2.6-5.2 kg) were used. PROCEDURES: Eye-flush tears were collected periodically for up to 18 weeks from both eyes of animals with nictitating membranes removed, but nictitating gland left intact, (n = 4) or with nictitating membranes intact (n = 4). Tear comparisons were based on total protein content (TPC) using micro bicinchoninic acid assay, immunoglobulin A (IgA), and matrix-metalloproteinase (MMP)-9 measurements using sandwich enzyme-linked immunosorbent assay (ELISA) and tear gelatinase activity using gelatin zymography. Expression of MMP-2 and -9 in nictitating membranes removed at baseline (week 0) and eyes collected at 18 weeks were also investigated in histological sections using immunoperoxidase for visualization. RESULTS: Nictitating membrane removal did not significantly change TPC and MMP-9 in tears within the first 4 weeks. MMP-9 was not detected by ELISA in tears from eyes without nictitating membranes from week 5 onwards. IgA (%IgA of TPC) data varied between animals. Gelatin zymography showed increased MMP-2 and -9 activity in tears from eyes without nictitating membranes at week 1 and a decrease following week 2 post-surgery. MMP-2 and -9 were immunolocalised to conjunctival goblet cells of removed nictitating membranes and to the conjunctival epithelium, respectively. After 18 weeks, the distribution of MMPs in tissue was comparable between eyes with and without nictitating membranes. CONCLUSIONS: Based on this preliminary study, nictitating membrane removal appeared to cause long-term changes in expression of tear proteins, including reduced MMP-9 expression.

The influence of surface topography of a porous perfluoropolyether polymer on corneal epithelial tissue growth and adhesion.

Design principles for corneal implants are challenging and include permeability which inherently involves pore openings on the polymer surface. These topographical cues can be significant to a successful clinical outcome where a stratified epithelium is needed over the device surface, such as with a corneal onlay or corneal repair material. The impact of polymer surface topography on the growth and adhesion of corneal epithelial tissue was assessed using porous perfluoropolyether membranes with a range of surface topography. Surfaces were characterised by AFM and XPS, and the permeability and water content of membranes was measured. Biological testing of membranes involved a 21-day in vitro tissue assay to evaluate migration, stratification and adhesion of corneal epithelium. Similar parameters were monitored in vivo by surgically implanting membranes into feline corneas for up to 5 months. Data showed optimal growth and adhesion of epithelial tissue in vitro when polymer surface features were below a 150 nm RMS value. Normal processes of tissue growth and adhesion were disrupted when RMS values approached 300 nm. Data from the in vivo study confirmed these findings. Together, outcomes demonstrated the importance of surface topography in the design of implantable devices that depend on functional epithelial cover.

A perfluoropolyether corneal inlay for the correction of refractive error.

This study assessed the long-term biological response of a perfluoropolyether-based polymer developed as a corneal inlay to correct refractive error. The polymer formulation met chemical and physical specifications and was non-cytotoxic when tested using standard in vitro techniques. It was cast into small microporous membranes that were implanted as inlays into corneas of rabbits (n = 5) and unsighted humans (n = 5 + 1 surgical control) which were monitored for up to 23 and 48 months respectively. Overall, the inlays were well tolerated during study period with the corneas remaining clear and holding a normal tear film and with no increased vascularisation or redness recorded. Inlays in three human corneas continued past 48 months without sequelae. Inlays in two human corneas were removed early due to small, focal erosions developing 5 and 24 months post-implantation. Polymer inlays maintained their integrity and corneal position for the study duration although the optical clarity of the inlays reduced slowly with time. Inlays induced corneal curvature changes in human subjects that showed stability with time and the refractive effect was reversed when the inlay was removed. Outcomes showed the potential of a perfluoropolyether inlay as a biologically acceptable corneal implant with which to provide stable correction of refractive error.

A comparison of basal and eye-flush tears for the analysis of cat tear proteins.

PURPOSE: To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. METHODS: Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 µl) were collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. RESULTS: Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. CONCLUSIONS: Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding.

Clinical observations of biofouling on PEO coated silicone hydrogel contact lenses.

Silicone hydrogel contact lenses, which have been a major advance in the field of vision correction, require surface modification or coatings for comfort and biocompatibility. While current coatings show adequate clinical performance, advanced coatings may improve the biocompatibility of contact lenses further by reducing biofouling and related adverse clinical events. Here, we have produced coatings on Lotrafilcon A contact lenses by deposition of a thin film of allylamine plasma polymer (ALAPP) as a reactive interlayer for the high density grafting of poly(ethylene oxide) dialdehyde (PEO(ALD)(2)), which had previously shown complete resistance to protein adsorption in vitro. The performance of these contact lenses was evaluated in a controlled clinical study over 6h using Focus Night and Day (also known as Air Optix Night & Day) contact lenses as control lenses. Surface modified lenses were characterised by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) before and after wear. Clinical data showed a high level of biocompatibility of the PEO coated lenses equivalent to control lenses. Surface analysis of worn contact lenses demonstrated that the high density PEO coating is effective in reducing biofouling in vivo compared to control lenses, however small amounts of protein deposits were still detected on all worn contact lenses. This study highlights that elimination of biofouling in vivo can be much more demanding than in vitro and discusses issues that are important for the analysis of worn contact lenses as well as the design of improved contact lenses.

Synthetic corneal inlays.

This review is based on the activities of the Vision Cooperative Research Centre (previously Cooperative Research Centre for Eye Research and Technology) Corneal Implant team from 1991 to 2007. The development of a synthetic polymer of perfluoropolyether (PFPE), meeting essential physical and biological requirements, for use as a corneal inlay is presented. Each inlay was placed in a corneal flap created with a microkeratome and monitored over a two-year period in a rabbit model. The results indicate that the PFPE implant shows excellent biocompatibility and biostability. As a result, a Phase 1 clinical trial is being conducted. Three years post-implantation, the PFPE inlays are exhibiting continued excellent biocompatibility. Corneal inlays made from PFPE are biocompatible with corneal tissue in the long term and offer a safe and biologically-acceptable alternative to other forms of refractive surgery.

Are inflammatory events a marker for an increased risk of microbial keratitis?

PURPOSE: To consider whether inflammatory events, such as contact lens-induced peripheral ulcers, contact lens-induced acute red eye, and infiltrative keratitis are a marker for an increased risk for the occurrence of microbial keratitis. METHODS: A review of relevant studies was undertaken with the view to answering two questions: 1) Do inflammatory events associated with contact lens wear progress to infection or microbial keratitis; and 2) Do episodes of inflammatory events predispose a patient to having an event of microbial keratitis? RESULTS: The large body of laboratory work, along with the epidemiologic data on incidence rates and clinical data with regard to differences between the nature of inflammatory events and infection, supports the supposition that inflammatory events are not a marker for increased risk of microbial keratitis. CONCLUSIONS: Inflammatory events are not a marker for increased risk of microbial keratitis, nor will they progress to infection because they are separate disease entities.

Accommodative facility in eyes with and without myopia.

PURPOSE: To compare accommodative facility in eyes with myopia to that in eyes with emmetropia or hyperopia and to determine whether accommodative facility can be used to predict an association with myopia. METHODS: In the Sydney Myopia Study, year-1 school children (6.7 +/- 0.4 years) were assessed for accommodative facility at distance (3 m) and near (33 cm) with semiautomated flippers. Spherical equivalent refractive error (RE) was defined as myopia (< or = -0.50 D), emmetropia (> -0.50 D, but < +1.50 D), and hyperopia (> or = +1.50 D) based on postcycloplegia readings. Only right eye data were considered. Differences between groups were analyzed with the Brown-Forsythe F test after adjustment for age and gender. Multiple comparisons were adjusted with the by the Games-Howell RESULTS: Of the 1328 right eyes assessed, 20 (1.5%) eyes were myopic, 977 (73.6%) were emmetropic, and 331 (24.9%) were hyperopic. At distance, mean facility was less for myopic eyes at 5.5 +/- 2.0 cycles per minute (cpm) in comparison to 6.9 +/- 1.7 cpm for eyes with emmetropia or hyperopia (P = 0.005). Myopic eyes recorded greater positive and negative accommodative response times than did emmetropic or hyperopic eyes (P < 0.05). There were no differences among the groups in near facility. The area under the receiver operating characteristic (ROC) curve for distance facility was 0.692 (P = 0.003, 95% CI, 0.580-0.805). CONCLUSIONS: Myopic eyes have reduced accommodative facility at distance, and accommodative responsiveness to both positive and negative defocus is slow. However, accommodative facility as a test does not have sufficient power to discriminate eyes with myopia from other refractive errors.

Silicone hydrogel contact lenses and the ocular surface.

For 30 years, contact lens research focused on the need for highly oxygen-permeable (Dk) soft lens materials. High Dk silicone hydrogel contact lenses, made available in 1999, met this need. The purpose of this review is to examine how silicone hydrogel lens wear affects the ocular surfaces and to highlight areas in which further research is needed to improve biocompatibility. Silicone hydrogel lenses have eliminated lens-induced hypoxia for the majority of wearers and have a less pronounced effect on corneal homeostasis compared to other lens types; however, mechanical interaction with ocular tissue and the effects on tear film structure and physiology are similar to that found with soft lens wear in general. Although the ocular health benefits of silicone hydrogel lenses have increased the length of time lenses can be worn overnight, the risk of infection is similar to that found with other soft lens types, and overnight wear remains a higher risk factor for infection than daily wear, regardless of lens material. Future contact lens research will focus on gaining a better understanding of the way in which contact lenses interact with the corneal surface, upper eyelid, and the tear film, and the lens-related factors contributing to infection and inflammatory responses.

The Max Schapero Memorial Award Lecture 2004: contact lenses on and in the cornea, what the eye needs.

PURPOSE: The aim of this study is to review the advances made in understanding the needs of the cornea and the way in which it responds to contact lens wear and corneal implants. METHODS: The review is based on personal knowledge and involvement of the author and colleagues from the 1970s to 2005. RESULTS: Development of silicone hydrogel contact lenses is presented as well as development of synthetic materials for implantation on the corneal surface (corneal onlay). CONCLUSIONS: The future of vision correction involves developing highly porous and biocompatible lens materials. For contact lenses, a better understanding of the effects of contact lens wear on the ocular surfaces, including the tear film, and development of lens materials with greater bacterial resistance are required. For those who require new solutions to permanent vision correction, corneal onlays (implantable contact lenses) are a minimally invasive and totally reversible procedure that can be removed or replaced as visual needs change over time.

Two-year preclinical testing of perfluoropolyether polymer as a corneal inlay.

PURPOSE: To assess the long-term biocompatibility and optical clarity of a perfluoropolyether (PFPE) polymer as a corneal inlay. METHODS: A 4-mm-diameter PFPE inlay was implanted under a microkeratome flap in the corneas of rabbits (n = 16) and maintained for predetermined time points of 6, 12, or 24 months. These were compared with normal (n = 3) and time-matched sham-wounded rabbit corneas (n = 8). All corneas were monitored clinically with a slit lamp. Histology was performed on all eyes on termination to assess the tissue response. RESULTS: Some sham and implanted animals were discontinued from study 1 to 2 days after surgery because of flap dislodgement. Ten animals with PFPE inlays remained in the study, and 7 of these were maintained to their predetermined time point for up to 2 years (3 were discontinued because of peripheral corneal defects). The corneas of these 7 animals remained clear and healthy, tear film remained normal, and there were no signs of inflammation, neovascularization, or increased conjunctival redness. All inlays remained centered and optically clear (clarity 85% or greater). Histology showed PFPE was biostable. The epithelia of operated corneas were stratified but slightly thinned compared with those of normal corneas. Stromal tissue anterior and posterior to each inlay appeared normal. Keratocytes in the vicinity of the inlay were normal in distribution but showed increased vacuolation, indicating tissue repair after the surgery. CONCLUSIONS: The PFPE polymer maintained a high level of optical clarity and showed long-term biocompatibility for up to 2 years when implanted as an inlay in the rabbit cornea.

Two presentations of contact lens-induced papillary conjunctivitis (CLPC) in hydrogel lens wear: local and general.

PURPOSE: The purpose of this study was to confirm that two distinct clinical presentations of contact lens-induced papillary conjunctivitis (CLPC), local and general, occur in hydrogel lens wear. METHODS: Retrospective analyses of 124 CLPC events were identified. The classification of CLPC was based on location and extent of papillae. CLPC was classified as local if papillae were present in one to two areas of the tarsal conjunctiva and general if papillae occurred in three or more areas. The CLPC events were compared with an asymptomatic control group in prospective clinical trials conducted from 1993 until 2003 at two clinical sites, Australia and India. Two hundred sixteen subjects from Australia and 914 subjects from India wore either high Dk silicone hydrogel or low Dk hydrogel lenses on a 6-night (6N) or 30-night extended-wear (EW) schedule. The physiological responses of the ocular surface, including tarsal conjunctiva redness and roughness, number of papillae present, lens fit and performance, and subjective patient symptoms, were measured during each visit at each site. These variables listed were compared between local CLPC groups and asymptomatic controls and general CLPC groups and asymptomatic controls. RESULTS: Two types of CLPC in hydrogel lens wearers have been confirmed. Of the 124 CLPC events, there were 61 local and 63 general events. Local and general CLPC cases reported significantly greater frequency of symptoms compared with the asymptomatic controls, in particular itching, lens awareness, secretion, and blurred vision (p < 0.1). CONCLUSIONS: The classification of CLPC into two types, local and general, in hydrogel lens wear was confirmed based on presentations at both sites. This distribution of papillae between local and general CLPC may indicate separate etiologies involved in the pathogenesis of the condition.

Microbial keratitis in prospective studies of extended wear with disposable hydrogel contact lenses.

PURPOSE: To report the annualized incidence of microbial keratitis with extended wear of low oxygen transmissible (Dk/t) disposable soft contact lenses from prospective postmarket clinical trials. METHODS: Seven hundred ninety subjects were enrolled at the L.V. Prasad Eye Institute (LVPEI), Hyderabad, India from March 1993 to March 2000, resulting in 1231 patient eye years, and 167 subjects were enrolled at the Cornea and the Contact Lens Research Unit (CCLRU), Sydney, Australia from July 1987 to December 1999, resulting in 842 patient eye years. RESULTS: The annualized incidence of microbial keratitis per 10,000 eyes per year of lens wear was 32.5 (95% CI 8.9 to 83.2) for LVPEI, 23.8 (95% CI=2.9 to 85.8) for CCLRU; when data are combined across both centers, the incidence was 28.9 (95% CI=10.6 to 63) per 10,000 eyes per year of lens wear. This equates to 57.0 per 10,000 wearers or 1 in 173 wearers per year of lens wear. All events were rated as slight to moderate in severity and did not result in visual loss. Two events were described to highlight the challenges in diagnosis and treatment of microbial keratitis. CONCLUSIONS: The incidence of microbial keratitis with extended wear of low-Dk/t disposable lenses was higher in these prospective studies (1 in 210 wearers per year at CCLRU and 1 in 154 wearers per year at LVPEI) than that seen in retrospective population-based surveillance studies (1 in 500 wearers per year). Practitioners and patients should always be alert to signs and symptoms, and practitioners should adopt conservative strategies for diagnosis and management of contact lens-related adverse events.

Comparison of the performance of 6- or 30-night extended wear schedules with silicone hydrogel lenses over 3 years.

AIM: To compare the clinical performance of silicone hydrogel lenses worn for 6- or 30-nights, with monthly replacement, for 3 years. METHODS: In this 3-year prospective clinical trial, 161 subjects were enrolled and 154 commenced extended wear. Clinical performance was assessed by comparing discontinuations and lens surface characteristics (front surface deposits, lens wettability, number of mucin balls), lens fitting performance (primary gaze movement, lens tightness), and physiologic parameters (limbal and bulbar redness, corneal and conjunctival staining, microcysts) and subjective parameters (ratings of comfort and vision) between groups. RESULTS: Eighty-eight subjects remained in the study after 36 months. There were no differences in the probability of subjects surviving in either group, and the major cause of lens-related discontinuation in both groups was contact lens-induced papillary conjunctivitis. There were no clinically important differences in performance between wear schedules. CONCLUSION: The long-term clinical performance of silicone hydrogels worn for 6- or 30-nights continuously was similar. Clinical markers of hypoxia were low in both groups, and the 6-night wear schedule was not superior to the 30-night wear schedule with regard to preventing lens spoilage, improving corneal physiology, or subjective symptoms of comfort and vision.