Recombinant Human Clusterin Seals Damage to the Ocular Surface Barrier in a Mouse Model of Ophthalmic Preservative-Induced Epitheliopathy.

There is a significant unmet need for therapeutics to treat ocular surface barrier damage, also called epitheliopathy, due to dry eye and related diseases. We recently reported that the natural tear glycoprotein CLU (clusterin), a molecular chaperone and matrix metalloproteinase inhibitor, seals and heals epitheliopathy in mice subjected to desiccating stress in a model of aqueous-deficient/evaporative dry eye. Here we investigated CLU sealing using a second model with features of ophthalmic preservative-induced dry eye. The ocular surface was stressed by topical application of the ophthalmic preservative benzalkonium chloride (BAC). Then eyes were treated with CLU and sealing was evaluated immediately by quantification of clinical dye uptake. A commercial recombinant form of human CLU (rhCLU), as well as an rhCLU form produced in our laboratory, designed to be compatible with U.S. Food and Drug Administration guidelines on current Good Manufacturing Practices (cGMP), were as effective as natural plasma-derived human CLU (pCLU) in sealing the damaged ocular surface barrier. In contrast, two other proteins found in tears: TIMP1 and LCN1 (tear lipocalin), exhibited no sealing activity. The efficacy and selectivity of rhCLU for sealing of the damaged ocular surface epithelial barrier suggests that it could be of therapeutic value in treating BAC-induced epitheliopathy and related diseases.

Changes in Symptoms of Midday Fogging with a Novel Scleral Contact Lens Filling Solution.

SIGNIFICANCE: Midday fogging of scleral contact lenses requires frequent lens removal and reapplication for a large portion of lens wearers. Using a lens filling solution that mimics the composition of tears is hypothesized to have an impact on the production of material trapped under a scleral lens. PURPOSE: The purposes of this open-label study were to assess the safety of a scleral lens filling solution, which closely approximates the ionic concentration and pH of human tears, and to assess signs and symptoms of midday fogging with this formulation and with subjects' habitual sodium chloride solutions. METHODS: Existing scleral lens wearers with midday fogging (N = 22) were examined and completed surveys of symptoms. Subjects filled the concavity of their current lenses with test solution and were assessed immediately and approximately 4 hours later for safety monitoring. Test solution was dispensed and used for 5 to 9 days when subjects were reexamined and repeated the surveys. Biomicroscopy and anterior optical coherence tomography images were used to assess midday fogging objectively. RESULTS: The median (interquartile range) Ocular Surface Disease Index score decreased from 27.1 (21.7) U when using habitual filling solution to 9.1 (20.1) U when using the test solution (P = .006). Current Symptoms Survey findings with the test solution compared with habitual solution resulted in statistically significant decreases in burning/stinging (P = .04), grittiness/foreign body sensation (P = .01), dryness (P = .002), blurry/fluctuating vision (P = .002), and overall pain/discomfort (P = .006). Objective assessment of corneal staining and fogging revealed decreases that were not statistically significant in this small sample size. CONCLUSIONS: This study establishes the safety and subject tolerance of a scleral lens filling solution that mimics the ionic composition of human tears. Significant improvements in subjective ratings, although likely biased in this unmasked trial, suggest that further studies of the effectiveness of this solution in reducing midday fogging are warranted.

Changes in Tear Lipid Layer Thickness and Symptoms Following the Use of Artificial Tears with and Without Omega-3 Fatty Acids: A Randomized, Double-Masked, Crossover Study.

PURPOSE: To determine if an eye drop containing omega-3 fatty acids (Refresh Optive MEGA-3®, Allergan plc, Dublin, Ireland) increases the lipid layer thickness (LLT) of the tear film versus a non-emollient eye drop (Refresh Optive, Allergan plc). METHODS: Patients (≥30 years) with baseline LLT ≤75 nm completed the Current Symptoms Survey (CSS - a visual analog survey of dry eye symptoms), and LLT was measured pre- and post-instillation (15 and 60 mins) of their randomly assigned treatment. After washout, patients were tested with the other treatment. Primary endpoint: change in LLT from baseline. Secondary endpoint: CSS results. RESULTS: Of 21 patients enrolled, 19 completed the study. With the omega-3-containing eye drop, the mean (standard deviation) LLT increase from baseline at 15 mins was statistically significant in the overall field (8.8 [11.5] nm; P<0.001), and in each individual zone (superior, central, and inferior). At 1 hr, the LLT change from baseline was statistically significant overall (4.4 [9.7] nm; P<0.02) and in the inferior and central zones. With the aqueous eye drop, LLT change from baseline was only significant at 15 mins in the inferior field. The CSS analysis revealed a ≥8.68-unit decrease in mean average dryness score from baseline at 15 and 60 mins post-instillation of the lipid-based treatment (P≤0.03). CONCLUSION: The eye drop containing omega-3 fatty acids increased LLT at 15 mins, maintaining it at 1 hr post-instillation. Dryness symptoms also improved and maintained improved levels 1 hr after instillation, indicating that the product may benefit symptomatic patients with evaporative dry eye.

Dynasore protects the ocular surface against damaging oxidative stress.

Water soluble "vital" dyes are commonly used clinically to evaluate health of the ocular surface; however, staining mechanisms remain poorly understood. Recent evidence suggests that sublethal damage stimulates vital dye uptake by individual living cells. Since cell damage can also stimulate reparative plasma membrane remodeling, we hypothesized that dye uptake occurs via endocytic vesicles. In support of this idea, we show here that application of oxidative stress to relatively undifferentiated monolayer cultures of human corneal epithelial cells stimulates both dye uptake and endocytosis, and that dye uptake is blocked by co-treatment with three different endocytosis inhibitors. Stress application to stratified and differentiated corneal epithelial cell cultures, which are a better model of the ocular surface, also stimulated dye uptake; however, endocytosis was not stimulated, and two of the endocytosis inhibitors did not block dye uptake. The exception was Dynasore and its more potent analogue Dyngo-4a, both small molecules developed to target dynamin family GTPases, but also having off-target effects on the plasma membrane. Significantly, while Dynasore blocked stress-stimulated dye uptake at the ocular surface of ex vivo mouse eyes when treatment was performed at the same time as eyes were stressed, it had no effect when used after stress was applied and the ocular surface was already damaged. Thus, Dynasore could not be working by inhibiting endocytosis. Employing cytotoxicity and western blotting assays, we went on to demonstrate an alternative mechanism. We show that Dynasore is remarkably protective of cells and their surface glycocalyx, preventing damage due to stress, and thus precluding dye entry. These unexpected and novel findings provide greater insight into the mechanisms of vital dye uptake and point the direction for future study. Significantly, they also suggest that Dynasore and its analogues might be used therapeutically to protect the ocular surface and to treat ocular surface disease.

Clusterin from human clinical tear samples: Positive correlation between tear concentration and Schirmer strip test results.

PURPOSE: To investigate the relationship between tear concentration of the homeostatic protein clusterin (CLU) and dry eye signs and symptoms, and to characterize tear CLU protein. METHODS: Two independent studies were conducted, one in Tucson (44 subjects), the other in Los Angeles (52 subjects). A cohort study design was employed to enroll patients without regard to dry eye diagnosis. Dry eye signs and symptoms were assessed using clinical tests. Tear samples were collected by Schirmer strip, and also by micropipette at slit lamp when possible. CLU from both sample types was quantified by immunoassay. The relationship between CLU concentration and clinical test scores was determined by Pearson's correlation coefficient (for individual eyes) and multiple linear regression analysis (including both eyes). CLU was also evaluated biochemically by western blotting. RESULTS: In the Tucson cohort, a positive correlation was observed between tear CLU concentration and results of the Schirmer strip test, a measure of tear flow (p = 0.021 includes both eyes). This result was corroborated in the Los Angeles cohort (p = 0.013). The mean tear CLU concentration was 31 ±â€¯14 µg/mL (n = 18 subjects, 33 eyes; range = 7-48 µg/mL). CLU from clinical tear samples appeared biochemically similar to CLU from a non-clinical tear sample and from blood plasma. CONCLUSIONS: Results support the hypothesis that an optimal concentration of tear CLU is important for ocular surface health, and that this drops below the effective threshold in dry eye. Tear CLU measurement might identify patients that could benefit from supplementation. Information about concentration will aid development of therapeutic dosage parameters.

Eye wash water flow direction study: an evaluation of the effectiveness of eye wash devices with opposite directional water flow.

INTRODUCTION: New designs of eye wash stations have been developed in which the direction of water flow from the fountain has been reversed, with two water streams originating nasally in both eyes and flowing toward the temporal side of each eye. No study has been done to determine the ideal direction of water flow coming from the eye wash in relation to the eye. MATERIALS AND METHODS: Ophthalmic eye examinations were conducted before and after the use of two eye wash stations with opposite water flow directionality. Fluorescein was instilled in both eyes before using an eye wash to measure the effectiveness of the water flow. Subjects were surveyed upon their experiences using the eye washes. CONCLUSION: Ophthalmic examination found no significant difference in the efficacy of the eye washes with nasal-to-temporal water flow when compared to temporal-to-nasal water flow direction.

Scleral Lenses in the Management of Corneal Irregularity and Ocular Surface Disease.

PURPOSE: To describe current practice patterns regarding the use of scleral lens therapy in the management of corneal irregularity and ocular surface disease among eye care providers who fit scleral lenses. METHODS: The Scleral Lenses in Current Ophthalmic Practice: an Evaluation (SCOPE) study group conducted an electronic survey of eye care providers from January 15 to March 31, 2015. Respondents ranked management options for corneal irregularity in the order in which they would generally consider their use. Respondents also ranked options for the management of ocular surface disease in the order in which they would use each of the treatments. Results for each option were analyzed as percentage first-place ranking; percentage first-, second-, or third-place ranking; and mean rank score. RESULTS: Survey responses were obtained from 723 providers who had fit 5 or more scleral lenses. Of these respondents, 629 ranked options for management of corneal irregularity and 612 ranked options for management of ocular surface disease. Corneal rigid gas-permeable lenses were the first option for management of corneal irregularity for 44% of respondents, and scleral lenses were the first option for 34% of respondents. Lubricant drops were the first therapeutic recommendation for ocular surface disease for 84% of respondents, and scleral lenses were ranked first by 6% of respondents. CONCLUSION: Scleral lenses rank second only to corneal rigid gas-permeable lenses for management of corneal irregularity. Scleral lenses are generally considered after other medical intervention and before surgery for the management of ocular surface disease.

Corneal epithelial bullae after short-term wear of small diameter scleral lenses.

Complications of scleral lens wear are not well documented or understood. While multiple studies focus on oxygen transmission during scleral lens wear and associated corneal swelling, little is known about the effects of varying scleral lens fitting relationships, especially when there is corneal interaction. Scleral lenses, by convention, are designed to completely clear the corneal surface and rest on the conjunctival and scleral tissue. However, some designs maximize oxygen transmission by reducing the lens diameter, thickness, and recommended corneal clearance.While the modifications increase oxygen transmission in any scleral lens design, they also distribute the lens mass closer to the limbus and make visualization of corneal clearance, especially narrow in the limbal region, more difficult. The sequelae from mechanical interaction between scleral lenses and the ocular surface, in particular the cornea, remain uncertain. This case series will describe corneal epithelial bullae, molding, and epithelial erosions as unintended scleral lens complications. These corneal changes corresponded to areas of contact lens-corneal bearing confirmed utilizing a combined scanning laser ophthalmoscopy (SLO) and anterior segment OCT. This case series will discuss epithelial bullae detection, their etiology, and suggestions for application of this information into scleral lens fitting protocols.

Tear lipid layer thickness with eye drops in meibomian gland dysfunction.

PURPOSE: The aim of this study was to evaluate the efficacy of a lipid containing emollient eye drop, Soothe XP, which was reformulated in 2014 with a more stable preservative and buffer system, compared to a control, non-emollient, eye drop (Systane Ultra) in improving lipid layer thickness (LLT) in subjects with dry eye due to meibomian gland dysfunction (MGD). PATIENTS AND METHODS: This prospective single-center, open-label, cross-over, examiner masked-study enrolled subjects aged 30-75 years with lipid-deficient dry eye and a clinical diagnosis of MGD as determined by a slit lamp examination, an evaluation of meibomian gland drop out with meibography, and a standard patient evaluation of eye dryness questionnaire of >5. Eligibility was then determined by a LLT of <75 nm at baseline and the inability to increase LLT ≥15 nm with three blinks, as determined by interferometric methods. Subjects were randomized to receive a single emollient or non-emollient eye drop at Visit 1 and were crossed over for the alternate treatment at Visit 2. At each visit, LLT was measured prior to and 15 minutes following the instillation of the assigned eye drop. The primary endpoint was the change in LLT from baseline. RESULTS: Subjects (n=40) were enrolled and 35 completed the two study arms. Mean (±SD) patient age was 55.7 years (10.9) and 69% were female. Mean (±SD) LLT at baseline was 49.5 nm (9.2). Instillation of Soothe XP resulted in an increase in LLT to 77.5 nm (29.3) 15 minutes following drop instillation, which is an increase of 28.0 nm (27.4) (P<0.001). In contrast, LLT 15 minutes after the instillation of Systane Ultra was 50.8 nm (14.1), which was not statistically significant when compared to the baseline LLT. CONCLUSION: In this study of subjects with MGD, the emollient, or lipid containing eye drop, increased the LLT of tears when measured 15 minutes after instilling a single eye drop.

A meta-analysis of studies on cosmetically tinted soft contact lenses.

BACKGROUND: Concerns regarding the safety of cosmetically tinted contact lenses have been reported in the literature. The purpose of this paper is to evaluate the safety of cosmetically tinted contact lenses in a large number of patients across six clinical trials that varied from 1 week to 3 months in duration. METHODS: LENSES TESTED INCLUDED: Naturelle limbal ring daily disposable, Lacelle limbal ring daily disposable, Lacelle colored cosmetic daily disposable, Lacelle limbal ring planned replacement at 2 weeks, and Alamode traditional/annual colored cosmetic lens. The primary safety outcome was slit-lamp examination, including epithelial edema, epithelial microcysts, corneal staining, bulbar injection, limbal injection, upper lid tarsal conjunctival abnormalities, corneal neovascularization, and corneal infiltrates. High contrast logMAR visual acuity with lenses, and lens wearing time, movement, and centration, are also presented. RESULTS: A total of 871 subjects (1,742 eyes) and 23 clinical investigators participated in the six studies, with an average completion rate of 96.4% across all studies. The mean age of the patients was 26.8 ± 6.6 years, and 86.7% of participants were female. The total number of slit-lamp examinations across the six studies was 2,456 visits by eye (1,228 visits by patient). There were no slit-lamp signs > grade 2 for any finding, with the exception of corneal staining in one study. In this study, grade 3 corneal staining was noted in one eye (0.1%) at follow-up visit 1 and four (0.6%) of all eligible dispensed eyes at follow-up visit 2, with no eyes requiring medical treatment. No adverse events were reported during any of the trials. CONCLUSION: The cosmetically tinted lenses evaluated in this meta-analysis appear to be safe when properly prescribed by an eye care professional and used in a compliant manner.

Tear cytokine response to multipurpose solutions for contact lenses.

PURPOSE: An increased risk of corneal infiltrative events has been noted with the use of certain contact lenses and multipurpose solutions (MPS). This study was designed to evaluate tear cytokine assay as a sensitive, objective, and quantitative measure of the ocular surface response to contact lens/MPS and to consider the assay's clinical relevance in the context of other measures of ocular surface response. METHODS: Two MPS, ReNu® Fresh™ (RNF) and Opti-Free® RepleniSH (OFR), were used with daily wear silicone hydrogel contact lenses in a randomized, prospective crossover study involving 26 subjects. Clinical data collection (conjunctival hyperemia, ocular surface sensitivity, solution induced corneal staining (SICS) test score, and subjective responses) and tear cytokine assays were conducted masked. Responses were tracked as change from baseline throughout the experimental schedule. RESULTS: SIMILAR RESPONSE PATTERNS FOR SEVERAL INFLAMMATORY CYTOKINES WERE SEEN THROUGHOUT BOTH PHASES: subjects who received OFR in Phase I had mean tear concentrations that were generally higher than those of the RNF Phase I group. OFR Phase I subjects had significant (P < 0.01) increases over baseline at day 1 and/or following washout for 13 cytokines (cc chemokine ligands [CCL] 3, CCL5, CCL11, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [INF]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-13, IL-15, IL-17, tumor necrosis factor [TNF]-α). These changes were not observed in RNF Phase I subjects, even though SICS test scores increased. Phase I OFR subjects also had increased dryness, while RNF Phase I subjects had decreased bulbar hyperemia. No changes were detected with respect to limbal hyperemia or surface sensitivity thresholds. CONCLUSION: The tear cytokine assay can detect and differentiate contact lens/MPS induced increases in inflammatory cytokines. Changes in cytokine levels were consistent with measurement of hyperemia and dryness but not with SICS scores, thereby suggesting a proinflammatory response to OFR compared to RNF that is not related to SICS test score. Tear cytokine profiles may be useful for reconciling clinical relevance of test results and in revealing signaling involved in the development of corneal infiltrative events.

Myopia progression during three years of soft contact lens wear.

PURPOSE: To analyze the effect of lens material alone on myopia progression in a multi-center non-randomized prospective study of daily wear hydrogel and continuous wear silicone hydrogel contact lenses. METHODS: Refractive error data from completing subjects were collected during a 3-year study of 54 subjects wearing low-Dk/t hydrogel contact lenses for daily wear and 230 wearing silicone hydrogel contact lenses for up to 30 nights continuous wear. Univariate analysis of refractive error changes was first conducted on factors of lens type, age at baseline, and baseline refractive error. Multivariate analysis was then performed to control for potential confounders of age (categorical by decade and continuous), and baseline refractive error. RESULTS: Multivariate analysis showed that refractive error changes were significantly affected by lens type (F = 78.2, p < 0.001, R = 0.218) and subject age (F = 131.2, p < 0.001, R = 0.319) but not baseline refractive error (F = 2.56, p = 0.11, R = 0.009). The model's overall R value is 0.376; the age-adjusted refractive error changes are +0.02 D for the silicone hydrogel contact lens wearers and -0.41 D for the hydrogel contact lenses for the 3-year follow-up period. CONCLUSIONS: Subject age and lens type significantly influenced the degree of myopic progression, with younger subjects and low-Dk/t hydrogel contact lens wearers increasing more during the study. The Lotrafilcon A silicone hydrogel lens material may contribute to less myopia progression in adult contact lens wearers.

Higher-order aberrations when wearing sphere and toric soft contact lenses.

PURPOSE: To determine the on-eye effect of spherical and toric contact lens design on higher-order aberrations (HOA). METHODS: Thirty eyes (15 subjects) entered a masked, randomized, cross-over study. Each eye was fitted with the spherical and toric lens of the following brands in random order: Acuvue Advance, Biomedics 55, Frequency 55, and SofLens 66. HOAs were measured using the Zywave II Aberrometer over a 6-mm aperture up to fifth order. A linear model accounting for the fixed effect of lens type and random effects of subject and eye was created. Paired t-tests were completed between lens brands within the spherical and toric lenses and between the spherical and toric lens within each brand. Best-corrected visual acuity (VA) was measured and compared. RESULTS: No clinically meaningful differences in total HOAs were found between brands or between the spherical and toric lens within a brand. Positive spherical aberration (SA) was reduced by all spherical and toric lenses compared to wearing no lens by 0.07 to 0.23 microm (p < 0.0001). Frequency toric induced the greatest change in SA. The thin-zone design lens (Acuvue Advance for Astigmatism) had a statistically different amount of vertical coma (-0.04 microm) than the three prism-balast toric lenses (0.11 to 0.23 microm; p < 0.0001). SofLens toric had the greatest amount of vertical coma, but better VA than Acuvue Advance for Astigmatism and Frequency toric. With the exception of Acuvue Advance for Astigmatism, toric lenses had greater absolute magnitude of vertical coma than their sphere counterparts (all p < 0.002). No other significant HOA differences were observed. CONCLUSIONS: Toric contact lenses with prism-ballast designs demonstrated more vertical coma, but better VA. Positive SA was reduced by spherical and toric contact lenses. The visual quality effect of lens design and material on induced HOAs warrants further investigation.

Fluorescein pattern interpretation in keratoconus.

PURPOSE: The purpose of this study is to assess the effect of disease severity on how accurately contact lens fluorescein patterns can be interpreted in keratoconus by clinician assessment. METHODS: Two clinicians evaluated fluorescein patterns on 111 eyes of 60 patients with mild (<45 D, 14 eyes), moderate (45 D to 52 D, 61 eyes,) and severe (>52 D, 36 eyes) keratoconus. The masked clinicians were given six contact lenses in random order, the lens that just cleared the corneal apex (the first definite apical clearance lens), three lenses flatter (in 0.1 mm increments), and two lenses steeper (in 0.1 mm increments) than the first definite apical clearance lens. They ranked the lenses from flattest to steepest, based on the fluorescein patterns. The percentage of lenses correctly ranked was determined using (1) exact match with actual; (2) within 0.1 mm of actual; and (3) within 0.2 mm of actual. Accuracy was assessed as the sum of the squared differences between the actual base curve value and each clinician's ranking. Comparison of the mean percentage correctly ranked and accuracy for each keratoconus severity groups was performed using a mixed linear model. RESULTS: Neither percentage correctly ranked (using any of the three protocols) nor accuracy was found to be related to severity of keratoconus (p > 0.15 for all comparisons). CONCLUSIONS: Accuracy of ranking contact lenses in order of base curve radius based on fluorescein pattern assessment by clinicians does not seem to be related to severity of keratoconus. Many factors influence interpretation of fluorescein patterns including all components of the system, fluorescein, tears, cornea, contact lens, external forces, and technique.

Visual acuity with spherical and toric soft contact lenses in low- to moderate-astigmatic eyes.

PURPOSE: To evaluate the visual acuity of myopic, astigmatic eyes, with spherical and toric soft contact lenses. METHODS: A randomized, masked, cross-over study was conducted to compare acuity with soft spherical and toric contact lenses on patients with between -0.75 and -2.00 D of refractive astigmatism. A total of 15 patients (30 eyes) were fitted with four brands of spherical and toric lenses (Acuvue Advance, Biomedics 55, Frequency 55, and SofLens 66), in random order. An initial visit was conducted to fit the lenses and an over-refraction (OR) was performed to determine the best prescription. At the measurement visit, patients' pupils were dilated with 1.0% tropicamide and 2.5% phenylephrine to allow wavefront aberration measurements, and a final OR was performed. A 6-mm aperture was held in front of the eye to measure visual acuity through just the contact lens and the contact lens with the final OR. Acuity was measured monocularly, under photopic and mesopic conditions with high- and low-contrast logMAR charts at distance. Differences in acuity were analyzed using repeated measures analysis of variance. RESULTS: Visual acuity with soft spherical contact lenses was not significantly different between lens brands. For toric contact lenses, acuity was significantly better with Biomedics 55 and SofLens 66 than with Acuvue Advance; and acuity with SofLens 66 was significantly better than with Frequency 55. Low-astigmatic eyes gained between 3 and 5.5 letters of acuity with toric contact lenses vs. spherical lenses; and moderate-astigmatic eyes gained between 8 and 12.5 letters. CONCLUSIONS: Both low- and moderate-astigmatic eyes showed improvements in acuity with toric contact lenses. Lens brand had a measurable effect on acuity for toric contact lenses. Further investigation of aberrations induced by contact lens design is warranted to explain the observed differences in visual performance.

Inflammatory and mechanical complications associated with 3 years of up to 30 nights of continuous wear of lotrafilcon A silicone hydrogel lenses.

PURPOSE: To report the ocular complications occurring during a 3-year clinical trial of subjects wearing lotrafilcon A silicone hydrogel lenses for up to 30 nights of continuous wear. METHODS: Nineteen sites enrolled 317 subjects (286 current wearers and 31 new wearers), who were dispensed lotrafilcon A lenses with 3 years of follow-up. RESULTS: By the 1-month visit, continuous wear of up to 30 nights was recommended for 87% of subjects. The 27 lens-related adverse events included 15 (2.4%) eyes in year 1, seven (1.3%) eyes in year 2, and five (0.8%) eyes in year 3. Lens-related inflammatory events involved 12 (1.9%) eyes in year 1 and five (0.8%) eyes each in years 2 and 3. One third of the inflammatory events occurred in the first 3 months. Mechanical events included two superior epithelial arcuate lesions and one case of bilateral contact lens papillary conjunctivitis in years 1 and 2. No subjects experienced microbial keratitis during the 3-year trial. Two subjects with events discontinued from the trial. CONCLUSIONS: These results show that the rate of contact lens adverse events occurring with lotrafilcon A is low in this cohort, with the highest likelihood occurring during the first 3 months of the study. There was a decrease in the rate of events during the later years of the study. Although clinicians should understand the likelihood of adverse inflammatory and mechanical events and their possible recurrence, the rate of these events may be lower in practice than previously reported.

Long-term clinical results: 3 years of up to 30-night continuous wear of lotrafilcon A silicone hydrogel and daily wear of low-Dk/t hydrogel lenses.

PURPOSE: To summarize results of a 3-year clinical trial assessing subjective and objective experience with lotrafilcon A silicone hydrogel (SH) lenses for up to 30 nights of continuous wear or low-Dk/t daily-wear (LDW) hydrogel lenses. METHODS: Nineteen sites dispensed SH lenses to 317 subjects (286 current wearers and 31 new wearers) and 2-week replacement LDW lenses to 81 new wearers in a 3-year study. RESULTS: For the SH cohort, limbal redness, conjunctival redness, and corneal neovascularization improved among 23%, 21%, and 13% of eyes, respectively (P<0.001), with no signs increasing significantly. For the LDW cohort, limbal redness, papillary conjunctivitis, and corneal staining increased among 11%, 21%, and 13% of eyes, respectively (P<0.02), with no signs improving significantly. The change in average spherical equivalent power was -0.03 diopters for the age-matched SH cohort and -0.40 diopters for the LDW cohort (P=0.007). During the 3 years, the SH group reported significantly less frequent dryness during and at the end of the day, redness, photophobia, lens awareness, and blurred vision. Significantly more LDW lens wearers reported frequent during-the-day and end-of-day dryness and blurred vision. CONCLUSIONS: During the 3 years, lotrafilcon A lens wearers who wore their lenses continuously for up to 30 nights showed stable, long-term improvements in many signs of corneal health and symptoms along with less myopic progression versus daily wearers of low-Dk/t hydrogel lenses. Many biomicroscopy signs and symptoms worsened among neophytes wearing daily-wear low-Dk/t hydrogel lenses. The use of lotrafilcon A lenses may minimize many ocular changes from soft contact lens wear.

A new method for grading the severity of keratoconus: the Keratoconus Severity Score (KSS).

PURPOSE: To define a new method for grading severity of keratoconus, the Keratoconus Severity Score (KSS). METHODS: A rationale for grading keratoconus severity was developed using common clinical markers plus 2 corneal topographic indices, creating a 0 to 5 severity score. An initial test set of 1012 eyes, including normal eyes, eyes with abnormal corneal and topographic findings but not keratoconus, and eyes with keratoconus having a wide range of severity, was used to determine cutpoints for the KSS. Validation set 1, comprising data from 128 eyes, was assigned a KSS and compared with a clinician's ranking of severity termed the "gold standard" to determine if the scale fairly represented how a clinician would grade disease severity. kappa statistics, sensitivity, and specificity were calculated. A program was developed to automate the determination of the score. This was tested against a manual assignment of KSS in 2121 (validation set 2) eyes from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study, as well as normal eyes and abnormal eyes without keratoconus. Ten percent of eyes underwent repeat manual assignment of KSS to determine the variability of manual assignment of a score. RESULTS: From initial assessments, the KSS used 2 corneal topography indices: average corneal power and root mean square (RMS) error for higher-order Zernike terms derived from the first corneal surface wavefront. Clinical signs including Vogt striae, Fleischer rings, and corneal scarring were also included. Last, a manual interpretation of the map pattern was included. Validation set 1 yielded a kappa statistic of 0.904, with sensitivities ranging from 0.64 to 1.00 and specificities ranging from 0.93 to 0.98. The sensitivity and specificity for determining nonkeratoconus from keratoconus were both 1.00. Validation set 2 showed kappa statistics of 0.94 and 0.95 for right and left eyes, respectively. Test-retest analysis yielded kappa statistics of 0.84 and 0.83 for right and left eyes, respectively. CONCLUSION: A simple and reliable grading system for keratoconus was developed that can be largely automated. Such a grading scheme could be useful in genetic studies for a complex trait such as keratoconus requiring a quantitative measure of disease presence and severity.

The effect of overnight contact lens corneal reshaping on refractive error-specific quality of life.

PURPOSE: The purpose of this study is to determine the effect of corneal refractive therapy (CRT) on refractive error-specific quality of life. METHODS: The National Eye Institute Refractive Error Quality of Life Instrument (NEI RQL-42) was administered to 20 myopic patients (mean spherical equivalent -3.11 D +/- 0.96 D) between the ages of 21 and 37 years both before and 1 month after being successfully fit with Paragon CRT lenses. High- and low-contrast best-corrected visual acuity (BCVA) and higher-order aberrations were also measured. Scores for the 13 NEI RQL-42 subscales were calculated and a Wilcoxon sign rank test was used to determine whether there was a significant change in each of the subscale scores. Post hoc power analyses were also performed. RESULTS: Statistically significant changes were found in three of the 13 NEI RQL-42 subscales. Significant improvements in subscale score were found for the symptoms (mean +/- standard deviation, 10.18 +/- 10.57, p = 0.0007) and dependence on correction (43.13 +/- 27.42, p < 0.0001) subscales. A significant reduction was found in the glare subscale (-32.50 +/- 35.22, p = 0.001). No significant changes were found in the clarity of vision, expectations, near vision, far vision, diurnal fluctuations, activity limitations, worry, suboptimal correction, appearance, or satisfaction with correction subscales. CONCLUSIONS: CRT may improve a patient's perception of their visual independence, decrease the amount of ocular symptoms they report, and increase symptoms of glare. A larger, well-controlled clinical trial is necessary to verify these results. An increase in patient-reported glare is likely the result of measured increases in higher-order aberrations after CRT, especially spherical aberration under mesopic and scotopic conditions.