Development and evaluation of the MiCheck® Prostate test for clinically significant prostate cancer.

BACKGROUND: There is a clinical need to identify patients with an elevated PSA who would benefit from prostate biopsy due to the presence of clinically significant prostate cancer (CSCaP). We have previously reported the development of the MiCheck® Test for clinically significant prostate cancer. Here, we report MiCheck's further development and incorporation of the Roche Cobas standard clinical chemistry analyzer. OBJECTIVES: To further develop and adapt the MiCheck® Prostate test so it can be performed using a standard clinical chemistry analyzer and characterize its performance using the MiCheck-01 clinical trial sample set. DESIGN, SETTINGS, AND PARTICIPANTS: About 358 patient samples from the MiCheck-01 US clinical trial were used for the development of the MiCheck® Prostate test. These consisted of 46 controls, 137 non-CaP, 62 non-CSCaP, and 113 CSCaP. METHODS: Serum analyte concentrations for cellular growth factors were determined using custom-made Luminex-based R&D Systems multi-analyte kits. Analytes that can also be measured using standard chemistry analyzers were examined for their ability to contribute to an algorithm with high sensitivity for the detection of clinically significant prostate cancer. Samples were then re-measured using a Roche Cobas analyzer for development of the final algorithm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression modeling with Monte Carlo cross-validation was used to identify Human Epidydimal Protein 4 (HE4) as an analyte able to significantly improve the algorithm specificity at 95% sensitivity. A final model was developed using analyte measurements from the Cobas analzyer. RESULTS: The MiCheck® logistic regression model was developed and consisted of PSA, %free PSA, DRE, and HE4. The model differentiated clinically significant cancer from no cancer or not-clinically significant cancer with AUC of 0.85, sensitivity of 95%, and specificity of 50%. Applying the MiCheck® test to all evaluable 358 patients from the MiCheck-01 study demonstrated that up to 50% of unnecessary biopsies could be avoided while delaying diagnosis of only 5.3% of Gleason Score (GS) ≥3+4 cancers, 1.8% of GS≥4+3 cancers and no cancers of GS 8 to 10. CONCLUSIONS: The MiCheck® Prostate test identifies clinically significant prostate cancer with high sensitivity and negative predictive value (NPV). It can be performed in a clinical laboratory using a Roche Cobas clinical chemistry analyzer. The MiCheck® Prostate test could assist in reducing unnecessary prostate biopsies with a marginal number of patients experiencing a delayed diagnosis.

Prevalence and Patterns of Refractive Errors in Children and Young Adults in an Urban Region in South India: the Hyderabad Eye Study.

PURPOSE: To determine the prevalence of refractive error (RE) and associated risk factors for myopic refractive errors in children and young adults from the urban region of Hyderabad, South India. METHODS: Four thousand sixty-five (4,065) participants aged 6-22 years were enrolled and examined in this cross-sectional study conducted from October 2013 to January 2015. Participants were enrolled from a random sample of schools and universities in regions representative of urban Hyderabad. RE was determined using cycloplegic autorefraction. The association of demographic factors such as age, gender, and socio-economic category (SEC) (low/mid/high) with myopia was explored with logistic regression with robust standard error. RESULTS: Of the total participants, 2,259 were children aged 6-15 years and 1,806 were adolescents and young adults aged 16-22 years. Overall prevalence of myopia, high myopia (≤ -5.00D and ≤ -6.00 D), hyperopia, emmetropia, and astigmatism was 29.8% (95% CI: 26.0% to 33.6%, n = 1,216), 2.9% (95% CI: 1.9% to 3.9%, n = 120), 1.1% (95%CI: 0.7% to 1.5%, n = 46), 14.7% (95% CI: 12.4% to 17.0%, n = 599), 46.9% (95% CI: 43.7% to 50.1%, n = 1913) and 8.6% (95% CI: 7.4% to 9.9%, n = 352) respectively. A strong correlation existed between age and prevalence of myopia (R2 = 0.88, p < .001) and high myopia (R2 = 0.71, p < .001). Children from schools of low SEC (34.7%) had higher prevalence of myopia compared to the mid SEC (16.8%) (p = .043). CONCLUSION: Myopia was the most prevalent refractive error and increased with age in this urban population. More myopia was observed in schools of low SEC.

The effect of hydroxypropyl-guar nanoemulsion on signs and symptoms of dry eye.

PURPOSE: To examine the effect of hydroxypropyl-guar nanoemulsion (HP-Guar nanoemulsion, Alcon Laboratories Ltd, Fort Worth, TX, USA) versus saline (0.9% sodium chloride; Pfizer Inc., Bentley WA Australia) on the comfort and tear film properties of people with dry eye disease both in the short-term (up to 2 h post-drop instillation) and longer-term (after 4 weeks of 4-times daily use), and to examine the effect on tear inflammatory markers after 4 weeks. METHODS: This was a prospective, investigator-masked, randomised, cross-over dispensing study. Twenty participants with dry eye disease (5 males: 15 females) with average age 46.9 ± 14.4 (range 26 to 70) years were randomized to either HP-Guar nanoemulsion, or saline eye drops. Ocular symptoms, lipid layer thickness, tear evaporation, tear osmolarity and non-invasive break-up time were measured pre-drop instillation, 1 h and 2 h post-eye drop instillation, and after 4-weeks of 4-times daily drop use. Tear inflammatory mediators were measured pre-drop instillation and after 4-weeks. After 4-weeks, patients had a 4-week washout period and then crossed over to the alternate drop. RESULTS: With HP-Guar nanoemulsion, participants reported less grittiness/burning/stinging 1 h post eye drop instillation compared to baseline (79.5 ± 23.3 vs. 66.8 ± 27.7, p = 0.02); less dryness 1 h and 2 h post eye drop instillation compared to baseline (77.8 ± 23.0 and 76.2 ± 23.7 vs. 61.0 ± 27.1 respectively, p < 0.01 for both); and greater overall satisfaction 1 h post drop instillation and after 4 weeks of daily use compared to baseline (80.4 ± 21.6 and 83.4 ± 16.6 vs. 68.6 ± 26.0 respectively, p ≤ 0.011 for both). With saline, participants reported less dryness after 4 weeks of daily use compared to baseline (74.2 ± 23.8 vs. 60.2 ± 24.0, p < 0.01). For HP-Guar nanoemulsion, average lipid layer thickness was significantly thicker 2 h post drop-instillation (79.5 ± 21.7 nm) compared to baseline (63.7 ± 18.9 nm) and the 4-week assessment (62.4 ± 23.1 nm, p < 0.01 for both). For saline, average lipid layer thickness was significantly thicker at 1 h and 2 h post eye drop instillation (76.0 ± 23.8 nm and 80.4 ± 24.8 nm) compared to baseline (61.0 ± 15.6 nm, p < 0.01 for both). There was no difference in inflammatory mediators or other tear variables between drops or visits. CONCLUSION: HP-Guar nanoemulsion was more effective for improving a range of subjective dry eye symptoms both in the short and long-term compared to saline. Both HP-Guar nanoemulsion and saline transiently increased lipid layer thickness.

Subjective Responses to Various Filling Solutions in the Posterior Fluid Reservoir of Miniscleral Lenses at Application.

PURPOSE: To compare the effect of the use of different lubrication eye drops and nonpreserved saline for the application of miniscleral contact lenses (CLs) on subjective experience during 6 hr of lens wear. METHODS: Experienced soft CL wearers aged 18 to 45 years (inclusive) were enrolled in this prospective, randomized, double-masked, three arm comparison cross-over study. Subjects were custom fitted with KATT 16.5 mm diameter miniscleral lenses, ordered to their prescription. Subjects attended visits on three separate days and were randomized to receive instillation of an HP-guar/nanoemulsion drop or an HP-guar/sodium hyaluronate (HA) eye drop into the miniscleral lens before filling with saline or filling with saline alone (control). Subjective responses were collected up to 6 hr postapplication. Generalized linear mixed models with multinomial distribution and cumulative logit link were used to compare the rate at which responses improved post-CL application for the different treatments. RESULTS: Twenty-four participants completed the study. Dryness symptoms were more likely to improve at a slower rate postlens application with saline alone compared with the addition of HP-guar/nanoemulsion (P=0.005) or HP-guar/HA (P=0.049) before lens application. Furthermore, the addition of HP-guar/nanoemulsion was more effective than saline alone in improving symptoms of fluctuating vision (P=0.011), grittiness/burning/stinging (P=0.001), and foreign body sensation (P=0.006) more quickly. CONCLUSIONS: The use of postlens lubrication may be useful in enhancing adaptation to miniscleral lenses.

Factors Affecting Microbial Contamination on the Back Surface of Worn Soft Contact Lenses.

SIGNIFICANCE: The results of this study demonstrate that Smart Touch Technology packaging, which is designed to reduce and simplify contact lens handling before insertion, is effective in reducing the frequency of bacterial contamination of the back surface of contact lenses after short-term wear. PURPOSE: The purpose of this study was to investigate the effect of lens packaging type, chelating agent, and finger contamination on microbial contamination on the back surface of worn soft contact lenses. METHODS: Twenty-five subjects completed each contralateral lens wear comparison in this randomized study: Smart Touch Technology versus conventional blister packaging for (1) silicone hydrogel lenses with ethylenediaminetetraacetic acid (EDTA) and (2) hydrogel lenses without EDTA in the packaging, and (3) silicone hydrogel lenses without EDTA versus hydrogel lenses with EDTA both in Smart Touch Technology packaging. Participants washed hands, underwent finger swabs, and inserted the lenses. After 45 minutes, lenses were removed aseptically and the posterior lens surfaces cultured. RESULTS: Thirty-eight subjects (average age, 30.9 ± 12.5 years) participated in this study. Overall, the level of back surface contamination was low for both lens materials, ranging from 0 to 43 colony-forming unit (CFU)/lens for the silicone hydrogel and 0 to 17 CFU/lens for the hydrogel lenses. The proportion of lenses with zero back surface contamination ranged from 16 to 64% for silicone hydrogel lenses and 28 to 64% for hydrogel lenses. Contact lenses from conventional packaging containing EDTA had 3.38 times increased risk (95% confidence interval [CI], 1.02 to 11.11; P = .05) of contamination being present compared with lenses from Smart Touch packaging with EDTA. Contact lenses from conventional packaging without EDTA had 3.4 times increased risk (95% CI, 1.02 to 11.36; P = .05) of contamination being present compared with Smart Touch packaging without EDTA, and silicone hydrogel lenses had a 6.28 times increased risk (95% CI, 1.65 to 23.81; P = .007) of contamination being present compared with hydrogels. The median (interquartile range) number of bacteria isolated from fingers used to perform lens insertion after handwashing but before lens insertion was not significantly different between the silicone hydrogel and hydrogel lenses (63.7 [204.2] vs. 59 [84.5], P = .09). Finger contamination was not significantly associated with lens contamination in the presence or absence of EDTA. CONCLUSIONS: Smart Touch Technology packaging was effective in reducing the proportion of contaminated lenses. Although silicone hydrogel lenses were more likely to be contaminated, the presence of EDTA ameliorated this effect. Finger contamination was not associated with lens contamination.

CLEAR - Anatomy and physiology of the anterior eye.

A key element of contact lens practice involves clinical evaluation of anterior eye health, including the cornea and limbus, conjunctiva and sclera, eyelids and eyelashes, lacrimal system and tear film. This report reviews the fundamental anatomy and physiology of these structures, including the vascular supply, venous drainage, lymphatic drainage, sensory innervation, physiology and function. This is the foundation for considering the potential interactions with, and effects of, contact lens wear on the anterior eye. This information is not consistently published as academic research and this report provides a synthesis from all available sources. With respect to terminology, the report aims to promote the consistent use of nomenclature in the field, and generally adopts anatomical terms recommended by the Federative Committee for Anatomical Terminology. Techniques for the examination of the ocular surface are also discussed.

Effect of Eyelid Treatments on Bacterial Load and Lipase Activity in Relation to Contact Lens Discomfort.

OBJECTIVES: To evaluate the effect of microblepharon exfoliation on the number of eyelid bacteria and their lipase activity and the relationship of these to contact lens discomfort. METHODS: Thirty experienced contact lens wearers had their eyelid margin physiology, tear properties, and comfort scores assessed. The number, type, and frequency of lower eyelid margin bacteria, and their lipase activity, were measured. Eyelids were treated with a foam cleanser or microblepharon exfoliation. Clinical and microbiological tests were repeated at each visit. Changes and correlations were examined. RESULTS: Symptomatic lens wearers had a higher ratio for the number and frequency of gram-positive rods and cocci. Microblepharon exfoliation reduced the number and ratio of gram-positive rods to cocci from baseline for symptomatic wearers that lasted 7 to 10 days after treatment (P<0.05). Numbers of bacteria, the ratio of rods to cocci, and lipase activity correlated with lash contamination (r≥0.385; P≤0.046) and anterior blepharitis (r≥0.359; P≤0.048). Bacterial lipase correlated with meibomian gland secretions (r=0.422; P=0.038) and the tear evaporation rate (r=0.479; P=0.022). Microblepharon exfoliation produced a significant reduction in CLDEQ-8 scores and converted 10 symptomatic into asymptomatic lens wearers. CONCLUSIONS: There was dysbiosis in the lid microbiome of symptomatic lens wearers. Microblepharon exfoliation reduced the number, frequency of isolation, and ratio of gram-positive rods and cocci. Bacterial numbers and their lipase production correlated with changes to clinical signs and symptoms. Symptomatic lens wearers could be converted to asymptomatic lens wearers after microblepharon exfoliation.

The Effect of Microblepharon Exfoliation on Clinical Correlates of Contact Lens Discomfort.

SIGNIFICANCE: Microblepharon exfoliation improved eyelid signs and tear film characteristics after a single in-office treatment in symptomatic contact lens wearers. PURPOSE: The purpose of this study was to assess the effect of two eyelid hygiene treatments-microblepharon exfoliation and a hypoallergenic foam cleanser (LidHygenix)-on clinical signs of the eyelids, meibomian glands, and tear film in contact lens discomfort. METHODS: A randomized, interventional, unmasked, crossover trial was conducted on 30 experienced daily-wear soft contact lens wearers. Assessment of clinical signs of the eyelid margin, meibomian gland morphology and secretion, and tear film biophysical properties was performed (baseline 1), and participants were randomly assigned to receive one of the two treatments (microblepharon exfoliation or foam cleansing using LidHygenix) as a single in-office procedure. Symptoms were evaluated using the Contact Lens Dry Eye Questionnaire-8 immediately after treatment, and assessment of all the study variables was repeated at the follow-up visit 7 to 10 days after treatment. After 28 to 30 days of washout, participants returned for reassessment of the study variables (baseline 2) and were crossed over to receive the alternate treatment. Follow-up was repeated 7 to 10 days after the second treatment. RESULTS: Seven to 10 days after treatment with microblepharon exfoliation, symptomatic wearers showed significant improvement in anterior blepharitis (mean difference, 0.60; P = .04), lid wiper staining (0.50; P = .06), and lid-parallel conjunctival folds (0.68, P = .02) along with orifice capping (median difference, 0.65; P < .001), foam (0.90; P < .001), secretion volume (0.69; P < .001), quality (0.74; P < .001), and expressibility (0.49; P = .002), which were also clinically significant changes. However, in tear properties, significant improvements were observed in tear volume (LidHygenix, -1.25 mm; microblepharon exfoliation, -1.62 mm), break-up time (-0.14 seconds; -0.14 seconds), tear evaporation rate without contact lenses (21.52 g m h; 45.43 g m h), and lipid layer thickness (-20.61 nm; -25.13 nm) after both treatments but in symptomatic lens wearers only (P < .05). CONCLUSIONS: Microblepharon exfoliation improved eyelid signs and tear film characteristics in symptomatic contact lens wearers after a single in-office treatment.

Predictive Potential of Eyelids and Tear Film in Determining Symptoms in Contact Lens Wearers.

SIGNIFICANCE: Early diagnosis of clinical markers of contact lens discomfort can help clinicians set realistic expectations and monitor and provide prophylactic management for contact lens wearers. PURPOSE: The purpose of this study was to evaluate the potential of eyelid- and tear film-related clinical markers to be used as predictive factors for diagnosing discomfort in contact lens wearers. METHODS: A cross-sectional study was performed on 30 contact lens wearers (6 male, 24 female) with median age of 23 years (range, 18 to 41 years). Eyelid signs and tear film characteristics were evaluated during a single visit, and subjects completed the Contact Lens Dry Eye Questionnaire to evaluate ocular discomfort. Area under the curve (AUC) statistics and sensitivity and specificity values from receiver operating characteristic curves were analyzed to evaluate the predictive potential of clinical signs in discriminating symptoms of contact lens discomfort. RESULTS: The presence of foam at meibomian gland orifices (AUC, 0.944; P < .05; sensitivity >0.7), meibomian gland secretion volume (AUC, 0.935; P < .05; sensitivity >0.7), quality (AUC, 0.969; P < .05; sensitivity >0.7), and expressibility (AUC, 0.933; P < .05; sensitivity >0.7) were significant and strong predictors of discomfort in lens wear. Tear evaporation rates with (AUC, 0.779; P < .05; sensitivity >0.7) or without contact lenses (AUC, 0.788; P < .05; sensitivity >0.7), palpebral conjunctival roughness (AUC, 0.859; P < .05; sensitivity >0.7), palpebral conjunctival staining (AUC, 0.817; P < .05; sensitivity >0.7), palpebral conjunctival hyperemia (AUC, 0.746; P < .05; sensitivity >0.7), meibomian gland orifice capping (AUC, 0.873; P < .05; sensitivity >0.7), pouting (AUC, 0.891; P < .05; sensitivity >0.7), and lid-parallel conjunctival folds (AUC, 0.770; P < .05; sensitivity >0.7) were other acceptable discriminators of symptoms of discomfort during contact lens wear. An equation was developed to identify symptomatic from asymptomatic lens wearers based on the significant predictors: Symptom discriminant function score = 3.378 (meibomian gland secretion grade) + 0.224 (meibomian gland morphology grade) + 0.61 (tear evaporation rate without contact lenses) + 0.439 (lid-parallel conjunctival folds grade) - 0.346 (palpebral conjunctival health grade) - 4.625. CONCLUSIONS: This study demonstrated that clinical signs related to meibomian gland secretions and morphology, tear evaporation, lid-parallel conjunctival folds, and palpebral conjunctival health may successfully predict symptoms of discomfort in contact lens wearers.

The eyelids and tear film in contact lens discomfort.

PURPOSE: To investigate characteristics of the eyelid margins, meibomian glands and the tear film of contact lens wearers, and to determine whether these characteristics were related to symptoms of contact lens discomfort. METHODS: A cross sectional study was performed on thirty existing daily wear soft contact lens wearers (6 male; 24 female) with median age of 23 years (range 18-41). Eyelid signs and tear film characteristics were evaluated during a single visit and subjects completed the contact lens and dry eye questionnaire (CLDEQ-8) to evaluate ocular discomfort. RESULTS: Based on the CLDEQ-8 responses, subjects were classified as symptomatic (n = 17) or asymptomatic (n = 13). Grades of foam at meibomian gland orifices (3 ±â€¯1), expressibility (2 ±â€¯1) and quality of secretions (2 ±â€¯1), tear evaporation rate with (112 ±â€¯54 g/m2/h) or without (88 ±â€¯45 g/m2/h) contact lens wear, fluorescein tear breakup time (8 ±â€¯2 seconds) and tear lipid layer thickness (45 ±â€¯17 nm) were significantly associated with symptoms of discomfort in symptomatic lens wearers only (r2 > 0.45; p value < 0.05). Upper lid-wiper epitheliopathy, meibomian gland acini reflectivity and tear meniscus height showed significant correlations with comfort scores in both symptomatic and asymptomatic contact lens wearers (p < 0.05). A greater number of Demodex mites was also observed in the upper eyelid of symptomatic lens wearers (2 ±â€¯1) compared to asymptomatic lens wearers (0 ±â€¯0; p value = 0.042). CONCLUSIONS: Morphological irregularities of the meibomian glands and alterations to tear film secretions that affect tear evaporative dynamics were associated with symptoms of discomfort amongst the symptomatic lens wearers.

Comparison of conventional method of contact lens fitting and software based contact lens fitting with Medmont corneal topographer in eyes with corneal scar.

PURPOSE: To compare conventional method of contact lens fitting with software based contact lens fitting using Medmont corneal topographer in eyes with nebular and macular corneal scars. METHODS: Fifteen participants who were diagnosed with nebular and macular scars were fitted with rigid gas permeable lenses using conventional method of contact lens fitting. During the lens dispensing visit, participants underwent Medmont corneal topography. Agreement between the two methods of contact lens fitting was studied. RESULTS: Parameters of contact lenses which were concluded using conventional method was compared to that of software based fitting. Mean difference in base curve of contact lens between the two methods was 0.094 mm±0.147 mm (95% CI: +0.383 to -0.194). Mean difference in diameter of contact lens between the two methods was 0.16 mm±0.172 mm (95% CI: +0.497 to -0.177). Contact lens parameters that were achieved using two different methods of fitting showed good correlation. Correlation coefficients, as comparison of two methods in base curve and diameter were 0.96 (P<0.05) and 0.94 (P<0.05), respectively. CONCLUSION: Software based contact lens fitting would be useful for contact lens practitioners to predict initial base curve of contact lens in corneal scars.