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Noncontact optical coherence tomography for measurement of corneal flap and residual stromal bed thickness after laser in situ keratomileusis.

PURPOSE: Studies show significant variability in the thickness of laser in situ keratomileusis (LASIK) corneal flaps cut by various microkeratomes. Most studies of corneal flap thickness are based on contact ultrasonic pachymetry measurements taken during the surgical procedure. This study reports a technique to obtain reproducible corneal flap thickness and residual stromal bed thickness measurements using noncontact optical coherence tomography (OCT) following LASIK. METHODS: The corneal flap thicknesses of 26 eyes of 15 patients were measured following LASIK in which the flap was created using the Amadeus microkeratome: 160-microm head, 9.5-mm ring, 4.0-mm/s translation speed, 8000 oscillations/m, and full vacuum. Zeiss Humphrey OCT-2 line scans were performed on postoperative days 1 and 7. The raw data from three scans for each eye and day were exported to Microsoft Excel for processing, averaging, and analysis. RESULTS: The OCT corneal flap thickness and residual stromal bed thickness measurements correlated well with ultrasonic pachymetry measurements performed during surgery (R2 = .92). The OCT technique yielded reproducible results, as the variance for repeated scans was only 2.5% of the variance between eyes. In bilateral cases a single blade was used for both eyes. The mean flap thickness of 15 first eyes was significantly greater than that of the 10 second eyes: 181 +/- 31 microm vs. 143 +/- 41 microm (P < .01). A positive correlation was found between the preoperative pachymetry and corneal flap thickness. CONCLUSIONS: The OCT scan averaging technique is a reproducible, noncontact postoperative method for measuring corneal flap and residual stromal bed thicknesses following LASIK.

Adult↗

Formulation of matrix solutions for use in matrix-assisted laser desorption/ionization of biomolecules.

We report a simple method for converting solid matrices into useful matrix solutions for matrix-assisted laser desorption/ionization (MALDI). This method is based on the dissolution of the solid matrix in a liquid support of low volatility such as glycerol. An appropriate solubilizing reagent was added to promote the dissolution of the matrix materials into the liquid support. Selection of the solubilizing reagent is empirically related to an acid-base relationship, i.e., an acidic solid matrix requires a basic organic compound to form a stable matrix solution in the liquid support and vice versa. A tenfold increase in the solubility can be obtained for many solid matrices when appropriate solubilizing reagents are added into the glycerol support. This solubility enhancement is tentatively attributed to the ion-pair formation in a polar nonvolatile liquid support. In addition, the hydrophobicity of the solid matrix seems to play an important role in the efficiency of the resulting matrix solution. By using glycerol as liquid support, a hydrophilic matrix, such as 2,5-dihydroxybenzoic acid (DHB), showed a substantial "peripheral effect," in which good analyte ion signals could only be recorded at the peripheral region of the sample droplet. More hydrophobic matrices, such as alpha-cyano-4-hydroxycinnamic acid (alpha-CCA), exhibit better and more homogeneous responses at different regions of the droplets. The performance of these matrix solutions was evaluated in terms of the durability, reproducibility, sensitivity, high mass capability, and generality. A typical sample droplet can afford more than an hour of repeated sampling with excellent shot-to-shot reproducibility. A low picomole sensitivity was demonstrated using a luteinizing hormone releasing hormone (LHRH) in a Fourier transform ion cyclotron resonance mass spectrometer with a homemade external MALDI ion source. By using a commercial MALDI time-of-flight mass spectrometer, proteins with masses as high as 66,000 Da were successfully analyzed by using these matrix solutions.

Cyclotrons↗

Multiplex ligation-dependent probe amplification for the detection of 1p and 19q chromosomal loss in oligodendroglial tumors.

Multiplex ligation-dependent probe amplification (MLPA) is a new assay for the detection of multiple chromosomal deletions in tumor tissue in a single experiment. Since genotyping of gliomas with oligodendroglial features by the detection of 1p/19q chromosomal deletions became essential for treatment decisions, we developed and validated an MLPA-based assay to determine these losses in formalin fixed and paraffin embedded oligodendroglial tumors (OG). Nineteen OGs, and 10 control samples were analyzed by MLPA and the results were correlated with those obtained by fluorescent in situ hybridization (FISH). The MLPA results were reproducible in all samples in which repeated experiments were performed. In 18 of 19 OGs, MLPA and FISH were concordant for presence or absence of 1p deletion. In 3 OGs, MLPA detected a 19q deletion not shown by FISH. For the other 15 OGs, MLPA and FISH were concordant. In one sample with 50% to 75% of tumor, MLPA failed to detect the 1p/19q deletions revealed by FISH (though with borderline values of significance). We conclude that MLPA is a valid and reproducible method for the detection of 1p/19q chromosomal deletions in OGs stored on formalin fixed, paraffin embedded tissue.

Brain Neoplasms↗

Reproducibility of chronic and acute infarct size measurement by delayed enhancement-magnetic resonance imaging.

OBJECTIVES: The aim of this study was to evaluate the reproducibility of acute and chronic infarct size (IS) by delayed enhancement (DE) magnetic resonance imaging (MRI). BACKGROUND: Infarct size measurements can be used as surrogate end point to reduce the sample size in studies comparing different reperfusion strategies in myocardial infarction (MI). Delayed enhancement MRI is a rather new technique, and so far infarct IS reproducibility has not been established appropriately. METHODS: In 21 patients (10 acute MI and 11 chronic MI), IS was assessed repeatedly on consecutive days by DE-MRI. Reproducibility, interobserver, and intraobserver variabilities were assessed and compared by the Bland-Altman method. RESULTS: Acute and chronic IS were 17.1 +/- 19.6% (range 5.1% to 69.8%) of LV mass (%LV) and 16.9 +/- 9.9 %LV (range 2.0% to 36.0%), respectively. Infarct size difference (bias) between scan I and scan II was -0.5 %LV, and limits of agreement were +/-2.4 %LV. Mean bias (-0.7 %LV) and limits of agreement (+/-3.2%) were slightly higher for acute in comparison with chronic MI with -0.4 +/- 1.3 %LV. Intraobserver and interobserver variability was low with a mean bias of 0.3 %LV (limits of agreement +/- 1.7 %LV) and -0.7 %LV (limits of agreement +/- 2.2 %LV), respectively. CONCLUSIONS: Infarct size measurement by DE-MRI is an excellent tool for IS assessment, owing to its excellent repeatability in chronic and acute MI. It has therefore the potential to serve as a surrogate end point to uncover advantages of new reperfusion strategies.

Acute Disease↗

Induction of atrial fibrillation and flutter in dogs using methacholine.

Systemic infusion of methacholine has been used to facilitate induction of atrial fibrillation. However, the dose-response relationship, reproducibility and effect of anesthetic agents on induction are not well understood. The use of methacholine to facilitate electrical induction of sustained (>10 minutes duration) atrial fibrillation or flutter was examined. In 25 dogs induction of atrial arrhythmias was attempted using a series of ten 50 Hz trains of 10 seconds duration delivered via an endocardial catheter in the baseline anaesthetized state and subsequently in the presence of graded doses of intravenous methacholine (maximum 5 microg/kg/min). Studies were repeated in 13 dogs to assess reproducibility. Twelve dogs (48%) had inducible sustained atrial flutter or fibrillation lasting greater than 10 minutes in the baseline state. During infusion of methacholine the remaining 13 (52%) dogs also had inducible sustained atrial flutter or fibrillation (mean infusion rate 1.6 +/- 1.9 microg/kg/min). Induction of sustained atrial flutter or fibrillation was reproducible in all but one dog. The type of anesthetic did not significantly affect inducibility. Induction of prolonged atrial fibrillation or flutter is possible in the baseline anaesthetized state in approximately half of dogs using high frequency programmed electrical stimulation. The yield of inducible sustained atrial fibrillation or flutter with programmed stimulation during intravenous infusion of methacholine was increased to 100%. Induction of sustained atrial fibrillation or flutter was highly reproducible.

Anesthetics, Inhalation↗

Reliability and consistency of visual acuity and contrast sensitivity measures in advanced eye disease.

PURPOSE: The purpose of this article is to establish reliability of standard visual function measures in patients with severe vision loss. METHODS: Legally blind subjects were enrolled in a repeated-measures study to determine the reproducibility of a battery of psychophysical vision measures. Tests reported here include ETDRS visual acuity (VA) under regular and dim illumination and Pelli-Robson letter contrast sensitivity (CS) under regular, dim, and glare conditions. Two to five test repetitions were performed at monthly intervals. Subject groups included retinitis pigmentosa (RP) (n = 29), macular disease (MD) (n = 17), optic nerve disease (ON) (n = 4), diabetic retinopathy (DR) (n = 5), and other retinal diseases (OR) (n = 10). RESULTS: For most subject groups, VA measures had mean 95% coefficient of repeatability (CR.95) of 0.20 (group means between 0.13 and 0.36) log units, and CS measures had mean CR.95 of 0.35 (group means between 0.19 and 0.48) log units. CONCLUSIONS: The established reliability of VA and CS tests in subjects with severe visual impairments will allow investigators to determine whether a significant change in vision has occurred during future clinical trials to reverse, halt, or slow vision loss. The criterion for change needs to be larger than for normally sighted controls, i.e., approximately two to three lines for VA and between eight to 11 letters for CS.

Adult↗

The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress.

BACKGROUND: The clinical assessment and investigation of irritable bowel syndrome would be greatly facilitated by the introduction of a simple, easy to use severity scoring system. Such a system, developed in our department over a number of years, has been submitted to validation in a total of 141 patients and 40 healthy controls. METHODS: The system, incorporating pain, distension, bowel dysfunction and quality of life/global well-being, was assessed for its ability to reliably score patients previously classified as mild, moderate or severe. The reproducibility and sensitivity to change of the system was also assessed. RESULTS: The maximum achievable score was 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and > 300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission. There was a highly significant difference between controls and patients as a whole (P = 0.0001) as well as significant differences (P < 0.01) between all severity categories. Scores repeated within 24 h were very reproducible and sensitivity to change was also extremely good (P < 0.001) with a change of 50 reliably indicating improvement. CONCLUSION: These results suggest that this scoring system should prove to be a valuable instrument in helping to meet the many challenges offered by irritable bowel syndrome.

Adult↗

Ability to reproduce head position after whiplash injury.

STUDY DESIGN: A two-group design with repeated measures. OBJECTIVES: To determine if there is loss of the ability to reproduce target position of the cervical spine individuals who have sustained a whiplash injury. SUMMARY OF BACKGROUND DATA: The ability to sense position is a prerequisite for functional movement. Injury may have a deleterious effect on this ability, resulting in inaccurate positioning of the head and neck with respect to the body coordinates and to the environment. METHODS: Eleven subjects with history of whiplash injury (age, 42 +/- 8.7 years) and 11 age-matched asymptomatic subjects (age, 43 +/- 3.1 years) participated in the study. Effects of whiplash injury on the ability to replicate a target position of the head were assessed. Maximum rotation of the neck and ability to reproduce the target angle were measured using a standard cervical range-of-motion device. Subjects' perception of "neutral" position was also assessed. RESULTS: Analysis of variance indicated the whiplash subjects were less accurate in reproducing the target angle than were control subjects. These whiplash subjects tended to overshoot the target. In addition, the subjects in the whiplash group were often inaccurate in their assessment of neutral position. CONCLUSIONS: Subjects who have experienced a whiplash injury demonstrate a deficit in their ability to reproduce a target position of the neck. These data are consistent with the hypothesis that these subjects possess an inaccurate perception of head position secondary to their injury. This study has implications for the rehabilitation of individuals with whiplash injury.

Adult↗

Reproducibility of exercise-induced ventricular premature beats.

Repeated maximum exercise testing with an intertest interval of one hour is a valid model for testing drug efficacy and safety on ventricular arrhythmias occurring during exercise. In the two consecutive exercise tests the mean total number of VES was 182 and 184 respectively and the slope of the regression equation relating both tests was close to unity.

Adult↗

Reliability of manometric eustachian tube function tests in children.

OBJECTIVE: To assess the reliability of manometric eustachian tube function tests in children with ventilation tubes in situ. STUDY DESIGN: Repeated manometric eustachian tube function tests during one session. SETTING: The study took place at a secondary referral hospital and a tertiary referral hospital. PATIENTS: Ninety-nine children with ventilation tubes in situ because of persistent otitis media with effusion. MAIN OUTCOME MEASURES: Opening pressure (Po), closing pressure (Pc), and tubal function group. RESULTS: Analysis of Po and Pc showed a decrease with repeated measurement (p = 0.0001 and p = 0.001, respectively). The effect of repeated measurement on Po was more pronounced than the effect on Pc. The results of the first and second pressure equilibration tests showed 99% agreement. CONCLUSIONS: This study showed good reproducibility of the categorized results of the pressure equilibration test, whereas the results of the forced-response test seemed to be less reproducible and showed a downward shift with repeated measurement. A single measurement using wet swallowing and starting pressures of 100 and -100 daPa and the mean of the first three measurements of the Po and Pc are sufficient to determine tubal function. Further studies are needed to determine the discriminative power of these tests in children with different degrees of middle ear disease.

Child, Preschool↗

Noninvasive measurement of concurrent single-kidney perfusion, glomerular filtration, and tubular function.

To assess the reliability of electron beam computed tomography (EBCT), measurements of single-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and intratubular contrast medium concentration (ITC) of radiographic contrast media were quantified in anesthetized pigs before and after acetylcholine-induced vasodilation and diuresis. EBCT measurements were compared with those obtained with intravascular Doppler and inulin clearance. The capability of EBCT to detect chronic changes in single-kidney function was evaluated in pigs with unilateral renal artery stenosis, and their long-term reproducibility in normal pigs was studied repeatedly at 1-mo intervals. EBCT-RBF (ml/min) correlated with Doppler-RBF as RBF(EBCT) = 45 + 1.07 * RBF(Doppler), r = 0.81. EBCT-GFR (ml/min) correlated with inulin clearance as GFR(EBCT) = 11.7 + 1.02 * GFR(inulin), r = 0.80. During vasodilation, RBF and GFR increased, whereas ITC decreased along the nephron. In renal artery stenosis, single-kidney GFR decreased linearly with the degree of stenosis, and ITC increased along the nephron, indicating increased fluid reabsorption. EBCT-RBF, GFR, and ITC were similar among repeated measurements. This approach might be invaluable for simultaneous quantification of regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.

Animals↗

Determinants of reproducibility of lung function tests in children aged 7 to 10 years.

Lung function (LF) tests are part of many investigations in childhood lung disease. However, individual reproducibility of LF will confound between-subject differences. At the same time, increased LF variability has been linked to respiratory disease. In a sample of 598 children, two LF tests, separated by a 5-min interval, were recorded, and reliability (Rel) of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC (MEF50) was determined. Rel was also assessed in children trained and untrained in the performance of LF. To investigate determinants of reproducibility for FEV1, the absolute difference between two repeated tests was calculated. Whenever this difference was > 120 ml, a child was considered to demonstrate excessive variability (poor reproducibility) in FEV1. For volume parameters coefficients of reliability (Crel) were found to be better than for MEF50 (FEV1: 0.96; FVC: 0.94, MEF50: 0.91). In untrained children Crel for FEV1 was only 0.91, but it was increased in subsequent visits (0.98, 0.97, and 0.97 at the second, third, and fourth tests, respectively). Excessive variability in FEV1 was observed in 10% of children and was related to the presence of wheeze [odds ratio (OR) 6.31; 95% confidence interval (CI) 1.78-22.4), shortness of breath (OR 3.14; 95% CI 1.00-9.93), a diagnosis of asthma (OR 6.25; 95% CI 1.76-22.1), and bronchial hyperresponsiveness (OR 4.30; 95% CI 2.07-8.94). We conclude that increased variability of LF is likely to be present in young children not accustomed to the testing procedure and in children with respiratory symptoms. Therefore, before guidelines for LF testing are applied, children should be trained to perform the tests and we should be cautious in the interpretation of test results in children who present with symptoms.

Child↗

TNF and Plasmodium berghei ANKA-induced cerebral malaria.

The cerebral pathology observed in Plasmodium berghei ANKA-infected CBA mice has been attributed to overproduction of TNF, the mice in which this syndrome is seen being those with the highest serum TNF levels. To investigate this further, we injected recombinant human TNF into malaria-primed mice to see if we could reproduce the cerebral changes observed in P. berghei ANKA infections. A range of doses, administered as a single or repeated injections, or via osmotic pumps, failed to reproduce these changes, but did induce hypoglycaemia, midzonal liver necrosis and neutrophil adhesion in pulmonary vessels. This pathology is seen in terminal Plasmodium vinckei infections, but absent in terminal P. berghei ANKA. In addition, the permeability of the blood-brain barrier to Evan's blue, which is present in P. berghei ANKA but not in normal or P. vinckei-infected mice, was not induced by exogenous TNF. Serum levels of TNF were measured in an ELISA assay, and found to be consistently higher in P. vinckei rather than P. berghei ANKA terminal infections. This is consistent with the pathological changes we could reproduce by injecting TNF. For these reasons we suggest that the cerebral pathology seen in mice infected with P. berghei ANKA may be governed by TNF produced locally by monocytes sequestered within the cerebral blood vessels, not simply by systemic levels of this cytokine.

Animals↗

An overview of radiographic film holders.

OBJECTIVES: To provide an overview of radiographic film holders, from their inception in the early 1900s to present day. METHODS: A Medline literature search was conducted for dental studies that used keywords that pertain to radiographic film holders. Hand searches of the bibliographies were also conducted. Sixty articles (dating from 1896 to 1998) that describe new or improved film holders are reviewed here. RESULTS: From the earliest days of dental radiography, dentists attempted to standardize radiographic images and techniques. The focus of researchers in the 1950s to the 1970s was to develop a film holder that would hold the film and allow easy and predictable alignment of the X-ray tube. As research projects became more dependent on dental radiographic measurements, the focus shifted to producing reproducible radiographic images, from which highly repeatable measurements could be made. CONCLUSION: Existing devices have strengths and weaknesses. Readily available devices are adequate for routine clinical use; however, user-friendly and patient-friendly film-holding devices that result in highly reliable and accurate measurements have yet to be introduced.

Copying Processes↗

Effect of hyperventilation and mental stress on coronary blood flow in syndrome X.

OBJECTIVES: To assess the effect of hyperventilation and mental stress on coronary blood flow and symptom production in patients with syndrome X. DESIGN: A prospective study. Hyperventilation and mental stress tests were performed on the ward and were repeated in the cardiac catheter laboratory where coronary blood flow velocity was also measured with an intracoronary Doppler catheter in the left anterior descending coronary artery. Oesophageal manometry studies were also performed. PATIENTS: 29 patients with syndrome X (typical anginal chest pain, a positive exercise test, and normal coronary angiogram). SETTING: A regional cardiothoracic centre. RESULTS: Hyperventilation produced typical chest pain in 16 patients on the ward. 13 patients experienced their typical chest pain with mental stress test 5. Ten patients experienced chest pain with both hyperventilation and mental stress tests. This pattern was reproduced exactly when the tests were repeated in the cardiac catheter laboratory. Hyperventilation produced a significant increase in the rate-pressure product during ward and laboratory testing. There was, however, no significant change in the rate-pressure product on mental stress tests. The mean (SEM) coronary flow velocity decreased significantly on hyperventilation in the catheter laboratory from 10.0 (0.92) cm/s to 5.9 (0.72) cm/s (p < 0.001). There was also a significant reduction in the mean (SEM) coronary blood flow velocity on mental stress tests from 9.8 (0.86) cm/s to 7.4 (0.6) cm/s (p < 0.001). This reduction in flow velocity occurred in the absence of any changes in diameter of the left anterior descending artery. Further analysis showed that the coronary flow velocity was reduced significantly in only that group of patients in which hyperventilation and mental stress provoked chest pain. There was a significant increase in the arterial concentrations of noradrenaline on both hyperventilation and mental stress testing. Oesophageal manometry showed abnormalities in 17% of patients. CONCLUSIONS: Both hyperventilation and mental stress can produce chest pain in patients with syndrome X and this is associated with a reduction in coronary blood flow velocity. The results of this study suggests that this reduction in coronary flow occurs as a result of increased microvascular resistance.

Adult↗

Accuracy of results obtained by performing a second ligase chain reaction assay and PCR analysis on urine samples with positive or near-cutoff results in the LCx test for Chlamydia trachomatis.

Nucleic acid amplification assays such as the ligase chain reaction and PCR have encountered reproducibility problems. The initial extract and a newly extracted aliquot of urine specimens (n = 120) which had signal-to-cutoff (S/CO) ratios above 0.80 by the LCx Chlamydia assay were retested. Nucleic acid was extracted from an additional urine sample for testing by the AMPLICOR PCR Chlamydia assay. Fifteen percent (18 of 120) of the urine specimens were negative by all repeat tests (initial mean S/CO ratio by the LCx Chlamydia assay, 0.93; S/CO ratio range, 0.80 to 3.30). Repeat testing of the 102 specimens with possible positive results by the LCx Chlamydia assay by use of the initially extracted aliquot confirmed the results for 95 (93.1%) of the specimens; repeat testing of a newly extracted aliquot confirmed the results for 87 (85.3%) of the specimens. Twenty specimens had discordant results by the two repeat LCx Chlamydia assays. A total of 78 of 102 (76.5%) of the specimens were positive by the AMPLICOR PCR, and the AMPLICOR PCR confirmed the results for 82.1% (78 of 95) and 89.6% (78 of 87) of the specimens positive by the two repeat LCx Chlamydia assays, respectively. Some of the discrepancies observed by multiple repeat tests may have been due to specimen mislabeling or contamination during performance of the procedure rather than to the LCx Chlamydia assay. Both assays suffered from a lack of reproducibility on repeat testing with a small proportion of specimens, probably due to the presence of low levels of DNA, the presence of variable amounts of amplification inhibitors, and the loss of DNA during extraction.

Algorithms↗

Immediate reproducibility of the tilt-table test in adults with unexplained syncope.

There are few data regarding the immediate reproducibility of the tilt-table test (TTT). Therefore, the immediate reproducibility of the TTT was examined in 19 patients (11 men and 8 women; mean age 49 +/- 19 years) with syncope or presyncope. The mean number of episodes that patients had experienced was 14 +/- 25 (range 1 to 100). After baseline supine observation for 10 minutes, patients were placed in 80 degrees of head-up tilt until a positive response occurred or for a maximum of 10 minutes. Patients were then returned to the supine position for 5 minutes, followed by retilt for another 10 minutes. If the baseline tilt was negative, the study was repeated with intravenous isoproterenol, and immediate reproducibility was examined in the same manner. The 19 patients underwent a total of 31 TTTs (19 baseline and 12 follow-up on drug). The TTT was immediately reproducible in 24 of 31 tests performed (77%). Eight tests were reproducibly positive and 16 negative. The results of 7 TTTs (23%) (5 baseline and 2 follow-up on drug) were not reproducible. In 6 of these studies (86%), the positive result occurred first and the negative result second. The reproducibility of an initially negative TTT result (16 of 17; 94%) was much higher than that of an initially positive one (8 of 14; 57%). The immediate reproducibility of the TTT in adult patients with unexplained syncope is approximately 75%. In studies that are not reproducible, most (86%) are positive first and negative second. Therefore, in most patients it is not necessary to check immediate reproducibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Assessment of changes in eye redness by a photographic method and the relation to sensory eye irritation.

The purpose of the present study was to evaluate the relation between photographically assessed changes in eye redness and sensory eye irritation in 17 patients suffering from hayfever, provoked by increasing doses of birch pollen in the eye. Pre- and post-exposure diapositives were compared in a randomized and double blind design by a panel of five members. By evaluating the photographs we found a high reproducibility between panel members and for repeated evaluation by the individual panel member. Furthermore, we found that the photographic method was more sensitive for measurements of changes in eye redness than the observations normally performed during such conjunctival provocation tests. The correlations of the objective findings with the symptoms reported were good at high pollen doses, but at lower doses of birch pollen (about half the effective dose) a decreased eye redness was observed. We found that sensory irritation (often expressed as dryness) measured simultaneously by questionnaires, in general occurred before any increased eye redness. The study indicates that photographic measurement of eye redness is reproducible, sensitive, unbiased and therefore a useful tool in environmental studies. Furthermore we demonstrated that the relation between eye redness and eye irritation is interestingly biphasic and may need further clarification.

Conjunctivitis, Allergic↗