Development of a Novel Assay for the Detection of Active Neutrophil Elastase in Patients with Chronic Obstructive Pulmonary Disease

Neutrophil elastase (NE), a biomarker of infection and inflammation, correlates with the severity of several respiratory diseases including chronic obstructive pulmonary disease (COPD). However, it’s detection and quantification in biological samples is confounded by a lack of reliable and robust methodologies. Standard assays using chromogenic or fluorogenic substrates are not specific when added to complex clinical samples containing multiple proteolytic and hydrolytic enzymes which have the ability to hydrolyse the substrate, thereby resulting in an over-estimation of the target protease. Furthermore, ELISA systems measure total protease levels which can be a mixture of latent, active and protease-inhibitor complexes. Therefore, we have developed a novel immunoassay (ProteaseTag™ Active NE Immunoassay) which is selective and specific for the capture of active NE in sputum and Bronchoalveolar Lavage (BAL) in patients with COPD. The objective of this study was to clinically validate ProteaseTag™ Active NE Ultra Immunoassay for the detection of NE in sputum from COPD patients. 20 matched sputum sol samples were collected from 10 COPD patients (M=6, F=4; 73 ± 6 years) during stable and exacerbation phases. Samples were assayed for NE activity utilising both ProteaseTag™ Active NE Ultra Immunoassay and a fluorogenic substrate-based kinetic activity assay. Both assays detected elevated levels of NE in the majority of patients (n=7) during an exacerbation (mean=217.2 μg/ml ±296.6) compared to their stable phase (mean=92.37 μg/ml ±259.8). However, statistical analysis did not show this difference to be significant (p=0.07, ProteaseTag™ Active NE Ultra Immunoassay; p=0.06 kinetic assay), most likely due to the low study number. A highly significant correlation was found between the 2 assay types (p≤0.0001, r=0.996). NE as a primary efficacy endpoint in clinical trials or as a marker of inflammation within the clinic has been hampered by the lack of a robust and simple to use assay. ProteaseTag™ Active NE Immunoassay specifically measures only active NE in clinical samples, is quick and easy to use (< 3 hours) and has no dependency on a kinetic readout. ProteaseTag™ technology is currently being transferred to a lateral flow device for use at Point of Care.

Utilisation of a novel ProteaseTag™ activity immunoassay for the specific measurement of neutrophil elastase in BAL from children with cystic fibrosis

Introduction: Neutrophil elastase (NE) is a serine protease implicated in the pathogenesis of several respiratory diseases including cystic fibrosis (CF). The presence of free NE in BAL is a predictor of subsequent bronchiectasis in children with CF (Sly et al, 2013, NEJM 368: 1963-1970). Furthermore, children with higher levels of sputum NE activity (NEa) tend to experience a more rapid decline in FEV1 over time even after adjusting for age, gender and baseline FEV1 (Sagel et al, 2012, AJRCCM 186: 857-865). Its detection and quantification in biological samples is however confounded by a lack of robust methodologies. Standard assays using chromogenic or fluorogenic substrates are not specific when added to complex samples containing multiple proteolytic and hydrolytic enzymes. ELISA systems measure total protein levels which can be a mixture of latent, active and protease-inhibitor complexes. We have therefore developed a novel assay (ProteaseTag™ Active NE Immunoassay), which couples an activity dependent NE-Tag with a specific antibody step, resulting in an assay which is both selective and specific for NEa. Aims: To clinically validate ProteaseTag™ Active NE for the detection of free NEa in BAL from children with CF. Methods: A total of 95 paediatric BAL samples [CF (n=76; 44M, 32F) non-CF (n=19; 12M, 7F)] collected through the Study of Host Immunity and Early Lung Disease in CF (SHIELD CF) were analysed for NEa using ProteaseTag™ Active NE (ProAxsis Ltd) and a fluorogenic substrate-based assay utilising Suc-AAPV-AMC (Sigma). IL-8 was measured by ELISA (R&D Systems). Results were analysed to show comparisons in free NEa between CF and non-CF samples alongside correlations with a range of clinical parameters. Results: NEa measured by ProteaseTag™ Active NE correlated significantly with age (r=0.3, p=0.01) and highly significantly with both IL-8 (r=0.4, p=<0.0001) and the absolute neutrophil count (ANC) (r=0.4, p=<0.0001). These correlations were not observed when NEa was measured by the substrate assay even though a significant correlation was found between the two assays (r=0.8, p<0.0001). A trend towards significance was found between NEa in the CF and non-CF groups when measured by ProteaseTag™ Active NE (p=0.07). Highly significant differences were found with the other inflammatory parameters between the 2 groups (IL-8: p=0.0002 and ANC: p=0.006). Conclusion: NEa as a primary efficacy endpoint in clinical trials or as a marker of inflammation within the clinic has been hampered by the lack of a robust and simple to use assay. ProteaseTag™ Active NE has been shown to be a specific and superior tool in the measurement of NEa in paediatric CF BAL samples (supporting data from previous studies using adult CF expectorated samples). The technology is currently being transferred to a lateral flow device for use at Point of Care. Acknowledgements: This work was supported by the National Children’s Research Centre, Dublin (SHIELD CF) and grants from the Medical Research Council and Cystic Fibrosis Foundation Therapeutics.

Nifedipine-induced gingival hyperplasia

This case study reports on the management of a woman suffering from thrombocytopenic purpura who was referred to the periodontal clinic with gingival swelling and bleeding. This condition was related to nifedipine therapy for hypertension.

Establishing the Evidence Bar for Molecular Diagnostics in Personalised Cancer Care

While personalised cancer medicine holds great promise, targeting therapies to the biological characteristics of patients is limited by the number of validated biomarkers currently available. The implementation of biomarkers has undergone many challenges with few biomarkers reaching cancer patients in the clinic. There have been many biomarkers that have been published and claimed to be therapeutically useful, but few become part of the clinical decision-making process due to technical, validation and market access issues. To reduce this attrition rate, there is a significant need for policy makers and reimbursement agencies to define specific evidence requirements for the introduction of biomarkers into clinical practice. Once these requirements are more clearly defined, in an analogous manner to pharmaceuticals, researchers and diagnostic companies can better focus their biomarker research and development on meeting these specific requirements, which should lead to the more rapid introduction of new molecular oncology tests for patient benefit.

The Impact of Multimedia Education on Uptake of Comprehensive Eye Examinations in Rural China: A Randomized, Controlled Trial

PURPOSE: To study the effect of multimedia education on acceptance of comprehensive eye examinations (CEEs), critical for detecting glaucoma and diabetic eye disease, among rural Chinese patients using a randomized, controlled design.
METHODS: Patients aged ≥40 years were recruited from 52 routine clinic sessions (26 intervention, 26 control) conducted at seven rural hospitals in Guangdong, China. Subjects answered demographic questionnaires, were tested on knowledge about CEEs and chronic eye disease, and were told the cost of examination (range US$0-8). At intervention sessions, subjects were cluster-randomized to view a 10-minute video on the value of CEEs and retested. Control subjects were not retested. Trial outcomes were acceptance of CEEs (primary outcome) and final knowledge scores (secondary outcome).
RESULTS: At baseline, >70% (p = 0.70) of both intervention (n = 241, 61.2 ± 12.3 years) and control (n = 218, 58.4 ± 11.7 years) subjects answered no knowledge questions correctly, but mean scores on the test (maximum 5 points) increased by 1.39 (standard deviation 0.12) points (p < 0.001) after viewing the video. Intervention (73.0%) and control (72.9%) subjects did not differ in acceptance of CEEs (p > 0.50). In mixed-effect logistic regression models, acceptance of CEEs was associated with availability of free CEEs (odds ratio 18.3, 95% confidence interval 1.32-253.0), but not group assignment or knowledge score. Acceptance was 97.5% (79/81) when free exams were offered.
CONCLUSIONS: Education increased knowledge about but not acceptance of CEEs, which was generally high. Making CEEs free could further increase acceptance.

Factors influencing the output of rural cataract surgical facilities in China: the SHARP study

Purpose: To identify factors associated prospectively with increased cataract surgical rate (CSR) in rural Chinese hospitals.

Methods: Annual cataract surgical output was obtained at baseline and 24 months later from operating room records at 42 rural, county-level hospitals. Total local CSR (cases/million population/y), and proportion of CSR from hospital and local competitors were calculated from government records. Hospital administrators completed questionnaires providing demographic and professional information, and annual clinic and outreach screening volume. Independent cataract surgeons provided clinical information and videotapes of cases for grading by two masked experts using the Ophthalmology Surgical Competency Assessment Rubric (OSCAR). Uncorrected vision was recorded for 10 consecutive cataract cases at each facility, and 10 randomly-identified patients completed hospital satisfaction questionnaires. Total value of international nongovernmental development organization (INGDO) investment in the previous three years and demographic information on hospital catchment areas were obtained. Main outcome was 2-year percentage change in hospital CSR.

Results: Among the 42 hospitals (median catchment population 530,000, median hospital CSR 643), 78.6% (33/42) were receiving INGDO support. Median change in hospital CSR (interquartile range) was 33.3% (-6.25%, 72.3%). Predictors of greater increase in CSR included higher INGDO investment (P = 0.02, simple model), reducing patient dissatisfaction (P = 0.03, simple model), and more outreach patient screening (P = 0.002, simple and multiple model).

Conclusions: Outreach cataract screening was the strongest predictor of increased surgical output. Government and INGDO investment in screening may be most likely to enhance output of county hospitals, a major goal of China's Blindness Prevention Plan.

Assessment of cataract surgical outcomes in settings where follow-up is poor:PRECOG, a multicentre observational study

Background: Poor follow-up after cataract surgery in developing countries makes assessment of operative quality uncertain. We aimed to assess two strategies to measure visual outcome: recording the visual acuity of all patients 3 or fewer days postoperatively (early postoperative assessment), and recording that of only those patients who returned for the final follow-up examination after 40 or more days without additional prompting. Methods: Each of 40 centres in ten countries in Asia, Africa, and Latin America recruited 40-120 consecutive surgical cataract patients. Operative-eye best-corrected visual acuity and uncorrected visual acuity were recorded before surgery, 3 or fewer days postoperatively, and 40 or more days postoperatively. Clinics logged whether each patient had returned for the final follow-up examination without additional prompting, had to be actively encouraged to return, or had to be examined at home. Visual outcome for each centre was defined as the proportion of patients with uncorrected visual acuity of 6/18 or better minus the proportion with uncorrected visual acuity of 6/60 or worse, and was calculated for each participating hospital with results from the early assessment of all patients and the late assessment of only those returning unprompted, with results from the final follow-up assessment for all patients used as the standard. Findings: Of 3708 participants, 3441 (93%) had final follow-up vision data recorded 40 or more days after surgery, 1831 of whom (51% of the 3581 total participants for whom mode of follow-up was recorded) had returned to the clinic without additional prompting. Visual outcome by hospital from early postoperative and final follow-up assessment for all patients were highly correlated (Spearman's r_s=0·74, p<0·0001). Visual outcome from final follow-up assessment for all patients and for only those who returned without additional prompting were also highly correlated (r_s=0·86, p<0·0001), even for the 17 hospitals with unprompted return rates of less than 50% (r_s=0·71, p=0·002). When we divided hospitals into top 25%, middle 50%, and bottom 25% by visual outcome, classification based on final follow-up assessment for all patients was the same as that based on early postoperative assessment for 27 (68%) of 40 centres, and the same as that based on data from patients who returned without additional prompting in 31 (84%) of 37 centres. Use of glasses to optimise vision at the time of the early and late examinations did not further improve the correlations. Interpretation: Early vision assessment for all patients and follow-up assessment only for patients who return to the clinic without prompting are valid measures of operative quality in settings where follow-up is poor. Funding: ORBIS International, Fred Hollows Foundation, Helen Keller International, International Association for the Prevention of Blindness Latin American Office, Aravind Eye Care System. © 2013 Congdon et al. Open Access article distributed under the terms of CC BY.

Prevalence of corneal astigmatism before cataract surgery in Chinese patients

Purpose: To assess the demographics and distribution of corneal astigmatism before cataract surgery in Chinese patients. Setting: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Design: Clinic-based cross-sectional study. Methods: From July 2009 to May 2011, preoperative bilateral partial coherence interferometry (IOLMaster) was performed in consecutive patients having cataract surgery. Patient demographics and keratometric data were recorded. Results: The mean age of the 2849 patients (4831 eyes) was 70.56 years ± 9.55 (SD); there was a predominance of women patients (64.0%). The mean axial length was 23.58 ± 1.13 mm. The mean corneal astigmatism in this cohort was 1.01 D (range 0.05 to 6.59 D). Corneal astigmatism was between 0.25 D and 1.25 D in 67.7% of eyes, 1.25 D or higher in 27.5% eyes, and less than 0.25 D in 4.8% of eyes. Astigmatism was with the rule in 25.1% of eyes, against the rule (ATR) in 58.2% of eyes, and oblique in 16.7% of eyes. The mean steep keratometry measurement was 44.76 ± 1.56 D. Against-the-rule astigmatism increased significantly with older age. Conclusions: Corneal astigmatism largely fell between 0.25 D and 1.25 D in these predominantly elderly female Chinese patients, and ATR astigmatism increased with age. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS.

Impact of age, various forms of cataract, and visual acuity on whole-field scotopic sensitivity screening for glaucoma in rural Taiwan.

OBJECTIVE: To evaluate the impact of age, various forms of cataract, and visual acuity on whole-field scotopic sensitivity screening for glaucoma in a rural population. DESIGN: Clinic-based study with population-based recruitment. SETTING: Jin Shan Township near Taipei, Taiwan. SUBJECTS: Three hundred forty-six residents (ages, > or = 40 years) of Jin Shan Township. INTERVENTIONS: Whole-field scotopic testing, ophthalmoscopy with dilation of the pupils, cataract grading against photographic standards, and screening visual field testing in a random one-third subsample. MAIN OUTCOME MEASURES: Whole-field scotopic sensitivity (in decibels) and diagnostic status as a case of glaucoma, glaucoma suspect, or normal. RESULTS: Participants in Jin Shan Township did not differ significantly in the rate of blindness, low visual acuity, or family history of glaucoma from a random sample of nonrespondents. Scotopic sensitivity testing detected 100% (6/6) of subjects with open-angle glaucoma at a specificity of 80.2%. The mean +/- SE scotopic sensitivity for six subjects with open-angle glaucoma (32.78 +/- 1.51 dB) differed significantly from that of 315 normal individuals (38.51 +/- 0.22 dB), when adjusted for age and visual acuity (P = .05, t test). With linear regression modeling, factors that correlated significantly with scotopic sensitivity were intraocular pressure, screening visual field, best corrected visual acuity, presence of cortical cataract, and increasing age. CONCLUSIONS: Although cataract affects the whole-field scotopic threshold, it appears that scotopic testing may be of value in field-based screening for glaucoma.

A proposed simple method for measurement in the anterior chamber angle: biometric gonioscopy

OBJECTIVE:

To design a system of gonioscopy that will allow greater interobserver reliability and more clearly defined screening cutoffs for angle closure than current systems while being simple to teach and technologically appropriate for use in rural Asia, where the prevalence of angle-closure glaucoma is highest.

DESIGN:

Clinic-based validation and interobserver reliability trial.

PARTICIPANTS:

Study 1: 21 patients 18 years of age and older recruited from a university-based specialty glaucoma clinic; study 2: 32 patients 18 years of age and older recruited from the same clinic.

INTERVENTION:

In study 1, all participants underwent conventional gonioscopy by an experienced observer (GLS) using the Spaeth system and in the same eye also underwent Scheimpflug photography, ultrasonographic measurement of anterior chamber depth and axial length, automatic refraction, and biometric gonioscopy with measurement of the distance from iris insertion to Schwalbe's line using a reticule based in the slit-lamp ocular. In study 2, all participants underwent both conventional gonioscopy and biometric gonioscopy by an experienced gonioscopist (NGC) and a medical student with no previous training in gonioscopy (JK).

MAIN OUTCOME MEASURES:

Study 1: The association between biometric gonioscopy and conventional gonioscopy, Scheimpflug photography, and other factors known to correlate with the configuration of the angle. Study 2: Interobserver agreement using biometric gonioscopy compared to that obtained with conventional gonioscopy.

RESULTS:

In study 1, there was an independent, monotonic, statistically significant relationship between biometric gonioscopy and both Spaeth angle (P = 0.001, t test) and Spaeth insertion (P = 0.008, t test) grades. Biometric gonioscopy correctly identified six of six patients with occludable angles according to Spaeth criteria. Biometric gonioscopic grade was also significantly associated with the anterior chamber angle as measured by Scheimpflug photography (P = 0.005, t test). In study 2, the intraclass correlation coefficient between graders for biometric gonioscopy (0.97) was higher than for Spaeth angle grade (0.72) or Spaeth insertion grade (0.84).

CONCLUSION:

Biometric gonioscopy correlates well with other measures of the anterior chamber angle, shows a higher degree of interobserver reliability than conventional gonioscopy, and can readily be learned by an inexperienced observer.

Cataract surgery and subtype in a defined, older population: the SEECAT Project

AIM:

To describe the distribution of cataract subtypes present before surgery among a defined population of older, bilaterally pseudophakic individuals.

METHODS:

This was a cohort study of bilaterally pseudophakic individuals participating in the Salisbury Eye Evaluation (SEE), and their locally resident siblings. Subjects underwent slit lamp and retroillumination photography and grading using the Wilmer Cataract Grading System. For all individuals determined to be bilaterally pseudophakic, an attempt was made to determine for each eye the type(s) of cataract present before surgery, based on previous SEE photographs (for SEE participants) and/or medical records obtained from the operating ophthalmologist (for both SEE participants and their siblings).

RESULTS:

The mean age of 223 participants providing data in this study was 78.7 (SD 5.2) years, 19.3% of subjects were black and 60.1% female. The most common surgically removed cataract subtype in this population was pure nuclear (43.5%), followed by nuclear combined with posterior subcapsular cataract (PSC) (20.6%), and nuclear combined with cortical (13.9%); less common types were pure cortical (4.9%), pure PSC (4.5%), and PSC combined with cortical (2.7%). Factors such as sex and source of lens data (study photograph versus clinical record) did not significantly affect the distribution of lens opacity types, while PSC was significantly (p = 0.01) more common among younger people and nuclear cataract was significantly (p = 0.001) more common among white compared to black people.

CONCLUSION:

Epidemiological studies have suggested that the different subtypes of cataract are associated with different risk factors. As studies begin to identify new prevention strategies for cataract, it would appear likely that different strategies will be efficacious against different types of cataract. In this setting, it will be helpful to know which cataract types are most frequently associated with surgery. Among this older, majority white population, nuclear cataract showed a clear predominance among individuals having undergone surgery in both eyes. This may be contrasted with both clinic and population based studies of younger people, which have generally found PSC cataract to predominate.

Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure.

PURPOSE: To estimate the relationships between ocular parameters and tonometrically measured intraocular pressure (IOP), to determine the influence of ocular parameters on different instrument measurements of IOP, and to evaluate the association of ocular parameters with a parameter called hysteresis. METHODS: Patients presenting at a glaucoma clinic were recruited for this study. Subjects underwent IOP measurement with the Goldmann applanation tonometer (GAT), the TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements of central corneal thickness (CCT), axial length, corneal curvature, corneal astigmatism, central visual acuity, and refractive error. Chart information was reviewed to determine glaucoma treatment history. The ORA instrument provided a measurement called corneal hysteresis. The association between measured IOP and the other ocular characteristics was estimated using generalized estimating equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read lowest, and ORA read highest, and GAT measurements were closest to the mean IOP of the 3 instruments. In a multiple regression model adjusting for age, sex, race, and other ocular characteristics, a 10 microm increase in CCT was associated with an increase of 0.79 mm Hg measured IOP in untreated eyes (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10 mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related to measured IOP, features in addition to CCT, such as hysteresis and corneal curvature, may also be important. Tonometric instruments seem to be affected differently by various physiologic characteristics.

Impact of cataract screening outreach in rural China.

PURPOSE: To examine differences between patients with cataract detected during screening and presenting to clinic in rural China. METHODS: Subjects were recruited from 27 screenings and an eye clinic in the same town. All had pinhole-corrected vision < or =6/18 in > or =1 eye due to ophthalmologist-diagnosed cataract. Subjects were administered a previously validated questionnaire on barriers to surgery in four areas: knowledge (K), perceptions of quality (Q), transportation (T), and cost (C). RESULTS: Screening group (SG; n = 120) and clinic group (CG; n = 120) participants did not differ from eligible, examined screening and clinic patients respectively in age, gender, or vision. SG participants were significantly more likely to be female (P = 0.002) and had a smaller housing area and less education (P < 0.001 for both) than those in the CG. Those in the CG were more likely to be blind (habitual VA < or = 6/60) in the better-seeing eye (P = 0.05) and more willing to undergo and pay for cataract surgery (P < 0.001 for both) than SG. In logistic regression models, SG subjects had significantly lower quality scores (P < 0.001) and better habitual vision (P = 0.02) than did CG participants, and SG subjects who agreed to cataract surgery (78.3%) had significantly higher knowledge scores (P < 0.001) than those who refused. DISCUSSION: Screening outreach has the potential to ameliorate disparities in access to cataract surgery in rural China, as it appears more likely to detect patients with cataract with gender-related, economic, educational, and attitudinal barriers to surgery. However, education may be needed to convince screening subjects to undergo surgery.

Use of eye care services among diabetic patients in urban and rural China.

OBJECTIVE: To assess the use of eye care and its predictors among diabetic patients in China. DESIGN: Cross-sectional, clinic-based study. PARTICIPANTS: Diabetic patients 18 years of age or older were recruited consecutively from an urban tertiary and community hospitals and from a rural clinic in Guangdong, China. METHODS: Information obtained by questionnaire and chart review included: demographic and socioeconomic status, knowledge about diabetic retinopathy (DR), and ocular and medical history. MAIN OUTCOME MEASURES: Self-reported or chart history of an eye examination ever or within the preceding 12 months. RESULTS: The participation rate among 889 eligible subjects was 92.7%. Among 824 participants (mean age, 62.6+/-12.9 years; 58.8% female), 550 (66.7%) had not been examined in the last year as recommended by the American Academy of Ophthalmology, and 356 (43.2%) had never been examined. For the rural hospital, these figures were 81.1% and 68.7%, respectively. In regression analyses, factors associated with having an eye examination in the last year were: attendance at urban hospitals (odds ratio [OR], 3.46 [P<0.001] and 1.76 [P = 0.021] for the tertiary and community hospitals, respectively, compared with the rural clinic), higher DR knowledge score (OR, 1.24; P = 0.001), greater concern about vision loss (OR, 1.22; P = 0.007), and recommendation of regular eye examinations by the provider (OR, 2.36; P = 0.011). Predictors of ever having an eye examination were similar. Monthly income and health insurance status were not predictive of being examined. CONCLUSIONS: These results suggest that the low proportion of diabetic receiving recommended annual eye examinations in China may be improved through patient and physician education. Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Determinants of postoperative corneal edema and impact on goldmann intraocular pressure.

PURPOSE: Recent studies report that increased corneal edema because of contact lens wear under closed lids is associated with elevated Goldmann intraocular pressure (GAT IOP). We sought to assess whether the impact of postoperative corneal edema on GAT IOP would be similar and to determine the differential effect of different amounts of edema. METHODS: The setting is a tertiary level cataract clinic in Shantou, China. Pre- and postoperative (day 1) GAT IOP, central corneal thickness (CCT), corneal hysteresis, corneal resistance factor, and radius of corneal curvature were measured for consecutive patients undergoing phacoemulsification surgery by 2 experienced surgeons. Corneal edema was calculated as the percentage increase in CCT. RESULTS: Among 136 subjects (mean age, 62.5 ± 15.4 years; 53.7% women), the mean increase in CCT was 10.3% postoperatively. Greater corneal edema was associated with lower GAT IOP in unadjusted analyses (P < 0.03) and in linear regression models (P < 0.01). In the model, higher corneal resistance factor (P < 0.001), lower corneal hysteresis (P < 0.001), and steeper radius of corneal curvature (P < 0.001) were associated with higher GAT IOP. Among subjects with edema < the median, edema was associated with lower GAT IOP (P = 0.004), whereas among those with edema ≥ the median, edema was not associated with GAT IOP. An increase in CCT of 7% was associated with an 8 mm Hg underestimation of GAT IOP in our models. CONCLUSIONS: The effect of postoperative edema on GAT IOP seems to be the opposite of contact lens-induced edema. The magnitude of the effect is potentially relevant to patient management.