Tube-Shunt Bleb Pathophysiology, the Cytokine Story.

PURPOSE: To define tube bleb-pathophysiology, outlining factors that may play a major role in the ultimate success or failure of the bleb. Methods that may be used to advance success of these blebs are discussed. MATERIALS AND METHODS: The study describes the importance of tube shunt bleb pathophysiology, including the role of cytokines, relating to bleb failure or success. Methods to influence these outcomes, are outlined. RESULTS: Understanding the various parameters involved with the pathophysiology of tube shunt blebs, especially intraocular pressure (IOP), and cytokine content of aqueous. The production of cytokines by tube shunt blebs, and the possible adverse results of this action on a second tube shunt in a different quadrant of the eye. CONCLUSIONS: Tube shunts are conduits transporting aqueous from within the eye to the subconjunctival space. The ultimate end result is to create a drainage bleb over the tube plate. The formation of the bleb is controlled by multifactorial components, including age of the patient, racial background, presurgical IOP, and thereby aqueous cytokine content, and patient's individual reaction to the presence of a foreign body beneath the conjunctiva. Prolonged IOP within the bleb results in cytokine production by the bleb lining. Occluding the tube of a failed implant can prevent damage to a new implant in a different eye quadrant.

Oral lichen planus pemphigoides: a series of four cases.

OBJECTIVE: Lichen planus pemphigoides (LPP), which is a rare autoimmune blistering mucocutaneous disease of the pemphigoid family of diseases, is characterized by the development of vesiculobullous lesions on or adjacent to the areas of lichen planus (LP). LPP primarily affects the skin, and oral involvement alone is rare. The objective of this case series was to report four new cases of oral LPP. STUDY DESIGN: We present four cases with clinical, histologic, and direct immunofluorescence (DIF) features characteristic of LPP, with three cases having oral involvement only. RESULTS: The four patients (including two males) were aged 49, 50, 51, and 61 years; only one patient had skin lesions. All patients had typical reticular, erythematous, or ulcerative oral LP involving the gingiva and the buccal mucosa. Mucosal biopsies showed features consistent with LP, mucous membrane pemphigoid (MMP), or a combination of both, and DIF studies in all 4 cases showed linear deposition of immunoglobulin G (IgG) and C3 at the interface. CONCLUSIONS: Correlation of clinical findings, routine histopathology, and DIF studies is essential for the diagnosis.

Long-term comparison using Ex-PRESS glaucoma shunt in black and white patients.

OBJECTIVE: To compare clinical outcomes, including patterns of failure, using the Ex-PRESS glaucoma shunt, in black and white patients with open-angle glaucoma. DESIGN: Retrospective comparative study. PARTICIPANTS: Sixty-three eyes of 50 black patients and 44 eyes of 34 white patients with open-angle glaucoma. METHODS: The Ex-PRESS shunt procedure was performed for uncontrolled glaucoma in a series of white and black patients with glaucoma. Success was defined as an intraocular pressure (IOP) between 5 and 18 mm Hg, 20% reduction from baseline, with or without suture lysis or adjuvant medication, but no additional glaucoma surgery. RESULTS: Mean length of follow-up was 29 months (range 12-81 months) for black patients and 25 months (range 12-66 months) for white patients. Mean preoperative IOP was 27 ± 7.2 and 30 ± 7.7 mm Hg for black and white patients, respectively. Mean postoperative IOP was 13 ± 3.6 and 12 ± 3.3 mm Hg for black and white patients, respectively. Using Kaplan-Meier survival curves, the success rates were 77.6% and 95% at 12 months for black and white patients, respectively. The log-rank test for comparison of survival curves indicated a significant difference between the 2 groups at 12 months (p = 0 .015) but revealed no difference at 2 years (p = 0.462). CONCLUSIONS: This study shows that patterns of failure between black and white patients treated with the Ex-PRESS glaucoma shunt change significantly with the passage of time. Black patients experience failure early, whereas white patients experience failure later at a greater pace resulting in a similar survival rate at 2 years.

Pro-inflammatory cytokines in glaucomatous aqueous and encysted Molteno implant blebs and their relationship to pressure.

PURPOSE: To ascertain the presence of additional pro-inflammatory cytokines in glaucomatous aqueous, and their relationship with IOP. METHODS: To quantify the levels of 23 pro-inflammatory cytokines, and correlate levels with IOP, aqueous humor samples were analyzed from 23 eyes with open angle glaucoma (OAG) undergoing glaucoma filtration procedures, and from 24 Molteno blebs during the hypertensive phase. Control aqueous was derived from 13 eyes without glaucoma undergoing cataract removal. RESULTS: A significant difference (P<0.05) was noted between hypertensive bleb aqueous and controls in the amount TGF-ß2, interleukins IL-6, IL-10, and chemokine (C-X-C motif) ligand 1 (CXCL1; GROα). The levels of these cytokines were higher in the glaucomatous aqueous, but not significantly so. A significant difference was noted in levels of chemokine (C-C motif) ligand 2 (CCL2; MCP-1, monocyte chemotactic protein-1) in the glaucoma eye and bleb aqueous compared with controls. Of the 23 cytokines tested for, 19 were found in the bleb group, 14 in the glaucoma group, and 16 in the control group. Compared with controls, all cytokines levels were higher in the glaucoma group and highest in the bleb group. CONCLUSIONS: The study confirms the well documented presence of TGF-ß2 in glaucomatous aqueous. The presence of significant levels of CCL2 in glaucomatous aqueous is a new finding. The finding of higher levels of all the cytokines in the aqueous from the encysted blebs, in which the IOP was the highest, suggests that their levels increase with an increase in IOP, as well as the possibility that encysted blebs form cytokines.

Supra-tenon capsule placement of original Molteno vs Molteno 3 tube implants in black patients with refractory glaucoma: a single-surgeon experience.

OBJECTIVE: To evaluate the efficacy of supra-Tenon capsule placement of original Molteno vs Molteno 3 tube implants (Molteno Ophthalmic, Dunedin, New Zealand) in black patients with refractory glaucoma. METHODS: A retrospective study comparing the efficacy of supra-Tenon capsule placement of the original Molteno tube implant (130-mm(2) plate size) with the newer Molteno 3 tube implant (175-mm(2) plate size). Original Molteno tube implants were placed into 17 eyes and Molteno 3 tube implants into 27 eyes. RESULTS: Success was defined as an intraocular pressure of 18 mm Hg or less with or without adjuvant medical therapy. The median follow-up periods were 24 months (range, 12-48 months) for the original Molteno-implanted group (hereafter referred to as the original Molteno group) and 18 months (range, 12-48 months) for the Molteno 3-implanted group (hereafter referred to as the Molteno 3 group). The median preoperative intraocular pressures were 30 mm Hg for the original Molteno group and 24 mm Hg for the Molteno 3 group. The median postoperative intraocular pressures were 13 mm Hg for the original Molteno group and 14 mm Hg for the Molteno 3 group. Using Kaplan-Meier analysis, survival percentages were 71% for the original Molteno group and 88% for the Molteno 3 group. Log-rank test for comparison of survival indicated no significant difference between the 2 groups (P > .25). CONCLUSIONS: Supra-Tenon capsule placement of single-plate Molteno tube implants of different sizes can adequately control intraocular pressure in a group of patients with refractory glaucoma. Tenon capsule elimination seems to negate the effect of plate size.

What is new after 40 years of glaucoma implants.

Forty years ago, Molteno introduced the prototype of the present day long tube implant. Since then, modifications in size and shape and introduction of valve system have taken place. Aqueous has been shown to contain proinflammatory substances that have been shown to influence the thickness of the bleb wall, and the hypertensive phase has been seen with the implants. The effect of the aqueous may be modified by the use of systemic antiinflammatory medication or by surgical modification, namely supra-Tenon insertion of the implant. Recent studies have shown that tube implantation is as efficacious as trabeculectomy in patients who were either pseudophakic or earlier had failed filters. Newer nontube implants, such as the Express shunt, have been introduced along with others, such as the gold micro shunt implant and the iStent, presently in clinical trials.

Cardiopulmonary bypass has minimal effects on the pharmacokinetics of fentanyl in adults.

BACKGROUND: Although fentanyl has been widely used in cardiac anesthesia, no complete pharmacokinetic model that has assessed the effect of cardiopulmonary bypass (CPB) and that has adequate predictive accuracy has been defined. The aims of this investigation were to determine whether CPB had a clinically significant impact on fentanyl pharmacokinetics and to determine the simplest model that accurately predicts fentanyl concentrations during cardiac surgery using CPB. METHODS: Population pharmacokinetic modeling was applied to concentration-versus-time data from 61 patients undergoing coronary artery bypass grafting using CPB. Predictive ability of models was assessed by calculating bias (prediction error), accuracy (absolute prediction error), and measured:predicted concentration ratios versus time. The predictive ability of a simple three-compartment model with no covariates was initially compared to models with premedication (lorazepam vs. clonidine), sex, or weight as covariates. This simple model was then compared to 18 CPB-adjusted models that allowed for step changes in pharmacokinetic parameters at the start and/or end of CPB. The predictive ability of the final model was assessed prospectively in a second group of 29 patients. RESULTS: None of the covariate (premedication, sex, weight) models nor any of the CPB-adjusted models significantly improved prediction error or absolute prediction error, compared to the simple three-compartment model. Thus, the simple three-compartment model was selected as the final model. Prospective assessment of this model yielded a median prediction error of +3.8%, with a median absolute prediction error of 15.8%. The model parameters were as follows: V1, 14.4 l; V2, 36.4 l; V3, 169 l; Cl1, 0.82 l. min-1; Cl2, 2.31 l x min-1; Cl3, 1.35 l x min-1. CONCLUSIONS: Compared to other factors that cause pharmacokinetic variability, the effect of CPB on fentanyl kinetics is clinically insignificant. A simple three-compartment model accurately predicts fentanyl concentrations throughout surgery using CPB.