Evaluation of augmented reality training for a navigation device used for CT-guided needle placement.

PURPOSE: Numerous navigation devices for percutaneous, CT-guided interventions exist and are, due to their advantages, increasingly integrated into the clinical workflow. However, effective training methods to ensure safe usage are still lacking. This study compares the potential of an augmented reality (AR) training application with conventional instructions for the Cube Navigation System (CNS), hypothesizing enhanced training with AR, leading to safer clinical usage. METHODS: An AR-tablet app was developed to train users puncturing with CNS. In a study, 34 medical students were divided into two groups: One trained with the AR-app, while the other used conventional instructions. After training, each participant executed 6 punctures on a phantom (204 in total) following a standardized protocol to identify and measure two potential CNS procedural user errors: (1) missing the coordinates specified and (2) altering the needle trajectory during puncture. Training performance based on train time and occurrence of procedural errors, as well as scores of User Experience Questionnaire (UEQ) for both groups, was compared. RESULTS: Training duration was similar between the groups. However, the AR-trained participants showed a 55.1% reduced frequency of the first procedural error (p > 0.05) and a 35.1% reduced extent of the second procedural error (p < 0.01) compared to the conventionally trained participants. UEQ scores favored the AR-training in five of six categories (p < 0.05). CONCLUSION: The AR-app enhanced training performance and user experience over traditional methods. This suggests the potential of AR-training for navigation devices like the CNS, potentially increasing their safety, ultimately improving outcomes in percutaneous needle placements.

Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. METHOD: The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. RESULTS: The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001). CONCLUSIONS: Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Diurnal IOP control with bimatoprost versus latanoprost in exfoliative glaucoma: a crossover, observer-masked, three-centre study.

AIM: To evaluate the diurnal intraocular pressure (IOP) control and safety of bimatoprost versus latanoprost in exfoliative glaucoma (XFG). METHODS: One eye of 129 consecutive patients with XFG (mean (SD) age 66.5 (8.3) years) was included in this prospective, observer-masked, three-centre, crossover comparison. After a 4-6 week medicine-free period patients were randomised to bimatoprost or latanoprost monotherapy for 3 months. Patients were then switched to the opposite treatment for another 3 months. At the end of the washout and the treatment periods diurnal IOP was measured at 0800, 1300, and 1800. RESULTS: At baseline the IOP (mean (SD)) was 28.0 (4.0), 26.9 (3.6), and 25.9 (3.6) mm Hg, at the three time points, respectively. Both treatments significantly reduced mean diurnal IOP at month 3. Mean diurnal IOP was 26.9 (3.5) mm Hg at baseline, 17.6 (3.3) mm Hg with bimatoprost, and 18.6 (3.6) mm Hg with latanoprost (p<0.0001). Furthermore, lower IOP values were obtained with bimatoprost at all time points (17.9 (3.4), 17.3 (3.3), and 17.6 (3.5) mm Hg, respectively) compared with latanoprost (18.7 (3.6), 18.5 (3.6), and 18.6 (4.1) mm Hg, respectively). The corresponding mean differences (0.8, 1.1, and 1.0 mm Hg, respectively) were all significant (p<0.001 for each comparison). Significantly more patients with XFG obtained a target diurnal IOP <17 mm Hg with bimatoprost than with latanoprost, 55/123 (45%) v 34/123 (28%); (p = 0.001), and significantly fewer patients were non-responders with bimatoprost than with latanoprost (5 v 13, p = 0.021). More patients reported at least one adverse event with bimatoprost than with latanoprost (58 v 41 at 3 months; p = 0.0003). CONCLUSION: This crossover study suggests that better diurnal IOP control is obtained with bimatoprost than with latanoprost in patients with XFG.

A 1-year study to compare the efficacy and safety of once-daily travoprost 0.004%/timolol 0.5% to once-daily latanoprost 0.005%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: The objective of the study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004%/timolol 0.5% ophthalmic solution (Trav/Tim) to latanoprost 0.005%/timolol 0.5% ophthalmic solution (Lat/Tim), dosed once daily in the morning, in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS: This was a randomized, double-masked, multicenter, parallel group, active-controlled study conducted at 41 sites. At the eligibility visit the patients were randomized (1:1) to the assigned masked medication if they met inclusion/exclusion criteria, and the mean IOP values in the eligible eyes were > or =24 mmHg at 9 AM and > or =21 mmHg at 11 AM and 4 PM. Patients were excluded if the mean IOP in either eye was >36 mmHg. Patients were instructed to administer the assigned medication each morning at 9 AM. During the treatment phase of the study, IOP was measured at 9 AM at week 2, week 6, month 3, and month 9. At the month 6 and month 12 visits, IOP was measured at 9 AM, 11 AM, and 4 PM. Statistical methods included a repeated measures analysis of variance (ANOVA); to test for noninferiority, a 95% confidence interval for the treatment group difference was constructed based on the ANOVA results for each time point at month 12. RESULTS: Patients (n=408) with OAG or OH were enrolled at 41 sites. One patient withdrew prior to receiving medication so 207 in the Trav/Tim group and 200 in the Lat/Tim group were evaluable for safety. Baseline demographic characteristics as well as IOP values showed no statistical differences between the two groups. Trav/Tim provided lower mean IOP values than Lat/Tim that were statistically significant at the week 2 9 AM (p=0.0081), month 6 9 AM (p=0.0056), and month 6 11 AM (p=0.0128) time points and at 9 AM time point pooled across all visits (p=0.0235) when mean IOP was 0.6 mmHg lower in the Trav/Tim group. Treatment-related adverse events were mild in both groups. Although hyperemia was reported from a higher percentage of patients in Trav/Tim group, differences in average hyperemia scores between the two groups were not considered clinically relevant. CONCLUSIONS: Travoprost 0.004%/timolol 0.5% ophthalmic solution produced mean IOP levels that are statistically noninferior to latanoprost 0.005%/timolol 0.5% ophthalmic solution. Furthermore, at 9:00 AM, 24 hours after dosing, IOP was statistically lower for travoprost 0.004%/timolol 0.5% pooled across all visits. Travoprost 0.004%/timolol 0.5% fixed combination ophthalmic solution is an effective treatment for reducing IOP and it is safe and well-tolerated in patients with OAG or OH.

Increased erythropoiesis and subclinical inflammation as part of the metabolic syndrome.

Recent studies have suggested the insulin resistance might be accompanied by enhanced erythropoiesis. We have examined this association in individuals with the metabolic syndrome (MS) who in addition to insulin resistance harbor a chronic low grade inflammation. This study is relevant because chronic inflammation might have a suppressive effect on erythropoiesis. 280 and 554 non-smoking women and men with respective age of 46.4+/-9.3 (mean+/-S.D.) and 44.0+/-11.0 years are included. A significant correlation was noted between the numbers of the components of the MS and the inflammatory biomarkers including the white blood cell count, high sensitivity C-reactive protein, fibrinogen concentrations and the erythrocyte sedimentation rate. In addition, a significant correlation (r=0.157, p=0.008) was noted between the number of components of the MS and the number of red blood cells in the peripheral blood in women. The same was true for men (r=0.192, p<0.0005). We conclude that enhanced erythropoiesis could be a new, hitherto unrecognized component of the MS. The enhanced erythropoiesis could give an erroneous impression of general "good" health in these individuals.

Oral temperature in daily life. A new look in the era of microinflammation.

It has been repeatedly shown that apparently healthy individuals and those with atherothrombotic risk factors harbor a low grade subclinical internal inflammation (microinflammation). This low grade acute phase response is relevant for the presence of atherothrombosis and future vascular events. Since these events are associated with a febrile response, we thought that it is relevant to clarify whether the microinflammatory response has an influence on the oral temperature. Included were 2,340 men and 1,280 women in whom the white blood cell count (WBCC) and differential, as well as the erythrocyte sedimentation rate (ESR), quantitative fibrinogen and high sensitivity C-reactive protein (hs-CRP) were determined in addition to the oral temperature in quiescent conditions. There was no association between these inflammatory biomarkers, except from a weak association with the absolute number of polymorphonuclear leukocytes. This association could be, however, related to the stress of the examination itself. Thus, it is unlikely that the microinflammatory response in daily life is associated, to a significant degree, with an enhanced oral temperature. The results are relevant for the findings of elevated oral temperature during conditions of acute ischemia/infarction where the temperature is probably related to the event itself and not to the patient's background microinflammation.

The effect of continuous strenuous exercise on intraocular pressure.

The effect of a continuous 110-km march with a 20-kg backpack load on intraocular pressure (IOP), plasma osmolarity, blood lactate, pH, and other related laboratory parameters was studied in 22 healthy young volunteers. Intraocular pressure decreased significantly at all marching intervals and returned to baseline level 3 hr after the completion of marching. The maximal average reduction during marching was 4.1 mmHg, 26.5% below the baseline level. The IOP decreased again 48 hr after the march and returned to baseline level 48 hr later. There were two peaks of increased plasma osmolarity (one during the march and the other 48 hr after the march). There was no correlation between IOP changes and levels of pH, blood lactate, serum proteins, and electrolytes or hematologic parameters. These findings suggest that IOP reduction is related inversely to plasma osmolarity during and after strenuous exercise.

Anterior and posterior axial lens displacement and human aqueous outflow facility.

We studied the effect of anterior and posterior axial crystalline lens displacement (and thereby ciliary tone) on the aqueous humor outflow facility in enucleated human eyes. After attaching a reversible footplate plunger to the anterior lens capsule with cyanoacrylate, the lens was placed in one of three positions: "neutral baseline," posterior displacement (2.5 mm), or anterior displacement (2.0 mm). In seven pairs of eyes, the mean "neutral baseline" was not statistically different from the control eye, but anterior lens displacement decreased outflow facility "C" by 0.14 (36%) (P less than 0.0001), and posterior displacement increased "C" by 0.18 (50%) (P less than 0.01). Anterior or posterior lens displacement after complete ciliary body detachment produced no effect on outflow facility in two pairs. Histologic correlation studies demonstrated narrowing of the intertrabecular spaces and Schlemm's canal in the eyes fixed in anterior lens displacement, and widening of the same structures in the eyes fixed in posterior lens displacement. The lens-zonular-ciliotrabecular force vectors are responsible for the compression or decompression of the meshwork and Schlemm's canal in this model, with compression decreasing, and decompression increasing aqueous humor outflow facility.

Nonpeptidic analogues of the Arg-Gly-Asp (RGD) sequence specifically inhibit the adhesion of human tenon's capsule fibroblasts to fibronectin.

PURPOSE: Scar formation from the process of wound healing is mediated primarily by fibroblasts and is a major problem in ophthalmology in general and in glaucoma therapy in particular. Interactions between fibroblasts and glycoprotein components of the extracellular matrix (ECM) are among the major causes of scar formation. Recognition of ECM glycoproteins occurs via cell surface integrins that are specific for adhesion epitopes, such as the Arg-Gly-Asp (RGD-) containing amino acid sequence. The RGD sequence, which is present in several matrix and plasma proteins, including fibronectin (FN) and vitronectin, is involved in cell-ECM interactions that occur during inflammatory and homeostatic reactions. The present study was designed to examine the possibility of using RGD-mimetics as inhibitors of fibroblasts-FN interactions. METHODS: Two nonpeptidic mimetics of RGD were designed and constructed, and their inhibitory effect on the adhesion of human tenon's capsule fibroblasts to FN was examined. SF-6,5 consisting of the carboxylate group of Asp and the guanidinium group of Arg divided by a linear atom spacer and a newly designed mimetic, designated NS-11, were examined herein. RESULTS: The RGD mimetics, SF-6,5 and NS-11, but not an Arg-Gly-Glu (RGE) mimetic inhibited the adhesion of ocular fibroblasts to immobilized FN. SF-6,5 and NS-11 did not inhibit adhesion of the fibroblasts to laminin or spontaneous proliferation of fibroblasts. Trypsin pretreatment of the nonpeptidic RGD mimetics did not affect their ability to inhibit adhesion of the ocular fibroblasts to FN, whereas that of the RGD-containing peptide was abolished by the pretreatment. CONCLUSION: Nonpeptidic mimetics of RGD are attractive candidates for therapeutic agents to prevent the formation of scar tissue and related RGD-dependent pathologic events.

Fuch's heterochromic iridocyclitis: an electron microscopic study of the iris.

The irides of two patients with Fuch's heterochromic iridocyclitis were investigated by electron microscopy. The main findings were abnormal melanocytes with relatively few, small, and at times immature melanin granules, abundance of plasma cells, and membranous degeneration of nerve fibers. The defective melanin production may be due to abnormal adrenergic innervation, either primary or secondary to the inflammatory process. The cause for this inflammatory reaction was not evident in this study.

Healthy volunteer effect in industrial workers.

Volunteers for epidemiological research, have lower mortality rates than non-volunteers, thereby producing a bias referred to as the "healthy volunteer effect" (HVE). Occupationally active persons have been similarly shown to have a reduced mortality relatively to the general population (the "healthy worker effect"). To determine whether a HVE exists in occupationally active persons, we followed for 8 years a cohort of Israeli male industrial employees, of whom 71.6% agreed to participate in 1985 in screening examinations for cardiovascular disease. We calculated standardized mortality ratios (SMRs) of the entire cohort relative to the general population, and compared the mortality among participants with that of the non-participants. Over 8 years follow up, SMRs were 78% for the entire cohort, 71% for participants and 99% for non-participants. Participants were older than non-participants and worked more commonly in smaller factories. A proportional hazard model indicated that after adjusting for these variables, the all cause mortality hazard ratio among participants and non-participants was 0.69 (95% CI = 0.51-0.94). During the first and last two years of the 8-year follow-up there were 39.6 and 30.0 age-adjusted deaths per 10,000 person-years among participants, and 58.6 and 51.5 respectively among non-participants. We conclude that the HVE occurs in occupationally active persons, and that it may persist for up to 8 years follow-up.

Delayed response to argon laser trabeculoplasty in monkeys. Morphological and morphometric analysis.

In eight cynomolgus monkeys we performed argon laser trabeculoplasty and evaluated morphological changes in the trabecular meshwork (TM). Four weeks after laser treatment, the treated spots were detected as regions of flattened and collapsed beams covered by a cellular sheet extending from the corneal endothelium. The inner wall of Schlemm's canal beneath these regions was flat, with no vacuoles despite fixation with intraocular pressure maintained at 15 mm Hg. Adjacent nonlasered spots had wide open intertrabecular spaces with herniations of juxtacanalicular TM and of inner wall endothelium into and across the lumen of Schlemm's canal. The herniations contained chronic inflammatory cells and large vacuoles. Statistical morphometric analysis in three monkeys established that these herniations were significantly wider, more numerous, and contained more vacuoles than did control eyes. Our findings suggest that a biologic process is involved in these reactions to argon laser trabeculoplasty. Scarring is seen to obliterate TM in spots treated by the laser, and this apparently causes the flow of the aqueous humor to be diverted through adjacent nonlasered regions that become structurally altered to compensate for this overload of flow.

Short-term effect of argon laser trabeculoplasty in monkeys.

We performed argon laser trabeculoplasty (ALT) in four cynomolgus monkeys and evaluated the morphologic changes in the trabecular meshwork one hour and 14 hours following the laser treatment. One hour after ALT, disruption of the trabecular beams and coagulative necrosis of the tissue were evident. Fragmented cells and fibrillar tissue debris were found in the trabecular spaces, accumulating in the juxtacanalicular region. This might explain the elevation of intraocular pressure seen immediately following ALT in some glaucomatous patients. Also, many trabecular endothelial cells were rounded up, displaying different stages of leaving the beams; these cells were actively phagocytic. Such stimulation of trabecular meshwork cells with subsequent removal of tissue debris might explain the temporary nature of elevation of intraocular pressure following ALT.

Laser iridotomy in closed-angle glaucoma.

An argon laser iridotomy was performed on 53 eyes of 34 patients with closed-angle glaucoma. Technically, all of the iridotomies were successful. Blue irides were more resistant to treatment than brown irides. The iridotomies were performed with high energy of 2 W and a very short exposure time of 0.01 to 0.04 s, thus minimizing thermal damage to adjacent tissues. Patients with narrow angles who underwent preventive laser irodotomy benefited most from the procedure, and all the eyes of this group maintained a normal intraocular pressure (IOP) after the iridotomy. Of the 20 eyes with acute angle-closure glaucoma, 17 maintained a normal IOP after iridotomy, and only three were resistant to this treatment, calling for filtering operations later. The IOP of eyes with chronic closed-angle glaucoma did not change after the procedure, and the iridocorneal angles remained practically the same. Argon laser iridotomy by this technique is highly recommended as the procedure of choice for eyes with acute angle-closure glaucoma and for preventive iridotomy in the fellow eye. The procedure is simple, is performed in the outpatient clinic, and engenders no major complications.

Patterns of aqueous humor outflow in glaucomatous and nonglaucomatous human eyes. A tracer study using cationized ferritin.

We used cationized ferritin, which binds to negatively charged membrane surfaces, as a tracer to delineate the aqueous humor outflow pathway by perfusing it into the anterior chamber of 14 normal human eyes and five with primary open angle glaucoma. In the normal human eyes, diffuse labeling with cationized ferritin was evident throughout the outflow pathway, while in the glaucomatous eyes distinctly different staining patterns were noted. A decorating pattern similar to that seen in normal eyes was observed, as well as apparent areas of underperfusion, suggestive of possible segmental changes in aqueous outflow. These findings may support the hypothesis that primary open angle glaucoma is a segmental disease of the outflow system due to possible regional increases in resistance to aqueous outflow.

Q-switched neodymium-YAG laser trabeculopuncture in monkeys.

In nine cynomolgus monkeys, trabeculopuncture was performed with a Q-switched neodymium-YAG laser, using a pulse energy of 5 to 7 millijoules and an exposure time of 14 nanoseconds. A penetration into Schlemm's canal was successfully achieved with two to four pulses; this penetration was accompanied by intraocular pressure (IOP) reduction and blood reflux into the anterior chamber. However, after eight days, IOP returned to baseline level, while white tissue was observed gonioscopically to fill in the puncture sites. Histologically, one hour after laser treatment, a blasting effect on the trabecular meshwork was observed with no signs of necrosis. Ater eight days, a hypertrophic scar formed, with the corneal endothelium extending over the scarred surface. At eight weeks and at six months after laser treatment, further shrinkage of the scar and the formation of a membrane over it was evident. Attempts to control scar formation by preventing blood reflux or injecting fluorouracil subconjunctivally for two weeks were unsuccessful. Scar formation at the trabecular puncture site severely limits the applicability of this potentially simple glaucoma treatment.

Molteno implant surgery in refractory glaucoma.

In recent years aqueous drainage implants have become a useful adjuvant in the treatment of refractory glaucomas. The Molteno implant is one of the most widely used devices for providing a permanent channel of aqueous flow from the anterior chamber to a collecting reservoir in the posterior subconjunctival space. Recently, modifications in design and surgical technique of the Molteno implant have enhanced its success rate, with a reduction in complications such as prolonged hypotony, anterior chamber flattening, and tube-corneal touch. These modifications include intracamerally injecting hyaluronic acid, using a needle track to provide an opening into the anterior chamber for the tube, performing the operation in two stages, using a double plate, temporarily ligating the tube, using a donor scleral patch, and giving adjunctive antifibrotic therapy. The rationale for application of the Molteno implant, the indications, techniques, results, and complications are described.

Ongoing clinical assessment of the safety profile and efficacy of brimonidine compared with timolol: year-three results. Brimonidine Study Group II.

OBJECTIVE: We compared the safety profile and efficacy of brimonidine 0.2% BID with those of timolol 0.5% BID over 3 years in patients with ocular hypertension and glaucoma. METHODS: Ninety-four eligible patients from an ongoing multicenter, interventional, double-masked clinical trial were followed through year 3, 48 receiving brimonidine 0.2% and 46 receiving timolol 0.5%. Study visits occurred at months 24, 27, 30, 33, and 36. The primary efficacy variable was mean reduction from baseline intraocular pressure (IOP) at trough. Visual acuity, visual fields, and safety variables (adverse events, ocular symptoms, heart rate, blood pressure, and laboratory test results) were monitored throughout the study. RESULTS: The 2 treatment groups were well matched, with no significant differences in demographic or clinical characteristics. Both drug regimens caused significant mean reductions from baseline IOP at trough during year 3 (P < 0.001), with no significant differences between groups at any study visit. The overall mean reduction from baseline IOP at trough was 5.02 mm Hg with brimonidine and 5.57 mm Hg with timolol (P = 0.383). Brimonidine caused reductions in IOP at trough that were equivalent to those with timolol at months 30 and 36 (within the 95% CI). Visual fields were unchanged or improved in 95% of patients in both treatment groups. Both drug regimens appeared to be safe and were well tolerated. Ocular allergy occurred in 2 brimonidine-treated patients (4.2%). There were no statistically significant differences in adverse-event reports and no clinically significant effects on any ocular or systemic safety variable in either group. CONCLUSIONS: Brimonidine 0.2% BID continues to appear to be safe, well tolerated, and effective in the long-term management of ocular hypertension and glaucoma. Over 3 years, it provided sustained IOP-lowering efficacy and visual-field preservation equal to those with timolol 0.5% BID.

Usefulness of the protection motivation theory in explaining hearing protection device use among male industrial workers.

The present study examined the usefulness of personal variables: noise annoyance, and components of the protection motivation theory (R. W. Rogers, 1983) along with social-organizational factors in explaining hearing protection device (HPD) use among Israeli manufacturing workers. Participants were 281 men exposed to harmful noise levels for which routine HPD use is required by regulation. In practice, 3 HPD user groups were identified: nonusers (n = 38), occasional users (n = 125), and regular users (n = 118). HPD use was objectively verified. HPD use was primarily related to the personal variables but not to management pressure, coworker pressure, or family support. The most powerful predictors of HPD use were perceived self-efficacy (for long-term HPD use), perceived susceptibility (to hearing loss), and noise annoyance, together explaining 48% of the outcome variance. These findings have implications for interventions aimed at motivating workers to use HPDs regularly.

Adjunctive use of delayed and adjustable low-dose 5-fluorouracil in refractory glaucoma.

We used delayed 5-mg subconjunctival injections of 5-fluorouracil as an adjunct to filtering surgery in ten eyes with refractory glaucoma. The first 5-fluorouracil injection was made three to 15 days postoperatively and was used only when clinical signs suggested an impending bleb failure. These signs included flattening and localization of bleb, increased vascularity, early subconjunctival scarring, loss of microcystic conjunctival changes, and increased intraocular pressure. After a follow-up of ten to 17 months (mean, 13.7 months), an intraocular pressure of less than 21 mm Hg was attained in five eyes without medication and in four eyes with medication. The treatment failed in one eye. The average dose of 5-fluorouracil was 28 +/- 12 mg per eye. There were no conjunctival wound leaks. Six eyes developed transient corneal epithelial defects. The modified administration of 5-fluorouracil can result in fewer conjunctival wound leaks. Its use can be limited to those patients who show evidence of impending bleb failure.