Intra-operative mitomycin C for glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for glaucoma to lower the intraocular pressure (IOP). Mitomycin C (MMC) is an antimetabolite used during the initial stages of a trabeculectomy to prevent excessive postoperative scarring and thus reduce the risk of failure. OBJECTIVES: To assess the effects of intraoperative MMC compared to placebo in trabeculectomy. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1985 to 20 March 2005), SIGLE (1980 to December 2004), the National Research Register (Issue 1, 2005), LILACS (29 March 2005) and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised trials of intraoperative MMC compared to placebo in trabeculectomy surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted trial investigators for missing information. MAIN RESULTS: Eleven trials, involving a total of 698 participants, were included. The trials enrolled three types of participants (high risk of failure, trabeculectomy combined with cataract surgery, no previous surgical intervention). Mitomycin C appears to reduce the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean IOP was significantly reduced at 12 months in all three participant groups receiving MMC compared to placebo. No significant increase in permanent sight-threatening complications was detected. However, none of the trials were large enough or of sufficient duration to address the long-term risk of bleb infection and endophthalmitis which has been reported in observational studies. Some evidence exists that MMC increases the risk of cataract. AUTHORS' CONCLUSIONS: Intraoperative MMC reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean IOP at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following MMC, there was insufficient power to detect any increase in other serious side effects such as endophthalmitis.

Repeatability and reproducibility of upper eyelid measurements.

AIM: The aim of this study was to assess the repeatability and reproducibility by physicians of upper lid measurements and to investigate the influence of clinical experience on the learning curve effect. METHODS: Both eyes of 22 outpatients were assessed for three basic measures of ptosis: marginal reflex distance (MRD) for upper and lower lids, upper lid skin crease (SC), and levator function (LF). Patients with variable eyelid positions were excluded. The patients were measured twice by a consultant and once by each of a clinical fellow, a specialist registrar, and a senior house officer in random order. Each observer was masked to their colleagues' results and followed a standard measurement protocol. Data were analysed using Bland-Altman plots. RESULTS: Consultant repeatability was high and consistent, the median difference between measures being 0 for each of the four parameters. Clinically acceptable reproducibility was shown in all measurements for even the least experienced physician and was particularly consistent for extreme observations. There was evidence of a learning curve effect. CONCLUSIONS: These results suggest that interobserver and intraobserver variability in assessment of upper lid ptosis using a standard measurement protocol is low and clinically acceptable when the technique of assessment is standardised.

Intra-operative mitomycin C for glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intra-ocular pressure. Mitomycin C is an antimetabolite applied between the sclera and conjunctiva during the initial stages of a trabeculectomy to prevent excessive post-operative scarring and thus reduce the risk of failure. OBJECTIVES: The objective of this review is to assess the effects of intra-operative application of mitomycin C in eyes of people undergoing trabeculectomy. SEARCH STRATEGY: We searched the Cochrane Eyes and Vision Group specialised register, The Cochrane Controlled Trials Register - CENTRAL, MEDLINE, EMBASE and the reference lists of relevant articles. We used the Science Citation Index to search for articles that cited the included studies. We contacted investigators and experts for details of additional relevant trials. SELECTION CRITERIA: We included randomised trials of intra-operative mitomycin C compared to placebo in trabeculectomy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We contacted trial investigators for missing information. Data were summarised using relative risk, odds ratio and weighted mean difference. MAIN RESULTS: This review includes 11 trials involving a total of 698 participants. The trials included three types of participants (those at high risk of failure, those undergoing trabeculectomy combined with cataract surgery, and those with no previous surgical intervention). Mitomycin C appears to be effective in reducing the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean intra-ocular pressure was significantly reduced at 12 months in all three participant groups receiving mitomycin C compared to placebo. No significant increase in permanent sight threatening complications was detected. Some evidence exists that mitomycin C increases the risk of cataract. The quality of trial reporting is poor in eight trials. Repeat analysis with three trials rated as low risk of bias did not yield different results. REVIEWER'S CONCLUSIONS: Intra-operative mitomycin C reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean intra-ocular pressure at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following mitomycin C, no demonstrable significant increase in other side effects was detected.

Current concepts in immunotherapy for the treatment of colorectal cancer.

Immunotherapy could have a role in the therapy of colorectal cancer as there is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. The MAb 17-1A has been used in advanced and primary disease, along with newer agents such as anti-epidermal growth factor receptor (EGFR) antibody. Immunotherapy with autologous tumour cell vaccine, genetic modification of immunostimulatory cytokines, suicide genes and TAAs as discussed. The multiplicity of peptide and carbohydrate antigens which can be potential targets for immunotherapy are also discussed. These include MUC1, Thomsen-Friedenreich and Sialosyl-Tn antigens and HER2 / neu. Active specific immunotherapy with the anti-idiotypic antibodies CEAVac and 105AD7, along with DC vaccines, is being currently used in adjuvant clinical trials. 105AD7 has been shown to cause significantly greater apoptosis of tumour cells in colorectal cancer patients, while CEAVac generated T cell proliferative anti-CEA responses. Dendritic cells pulsed with tumour mRNA or TAAs currently are being assessed in clinical trials. The role of HSPs in the anti-tumour immune response is discussed. Non-specific immunotherapeutic agents used in clinical trials with chemotherapeutic regimens have not shown any definitive benefit. Tumour progression may occur as result of escape from the host anti-cancer immune response. Better understanding of mechanisms of tumour evasion could explain why immunotherapy trials in patients have not shown better results. These include down-regulation of immune responses by the tumour, altered expression of MHC and/or TAAs by tumour cells, altered expression of adhesion molecules by tumour and/or DCs and usurpation of the immune response to the advantage of the cancer.

Effect of treatment by medicine or surgery on intraocular pressure and pulsatile ocular blood flow in normal-pressure glaucoma.

PURPOSE: To study the effect of trabeculectomy and monotherapy with topical betaxolol, brimonidine and latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in patients with normal-pressure glaucoma (NPG). METHODS: In this retrospective study NPG patients attending the glaucoma research unit at Moorfields Eye Hospital were reviewed. Patients treated by surgery or topical medication (betaxolol, brimonidine or latanoprost) who had pre- and post-treatment IOP and POBF measurements were studied. For those patients who were having treatment to both eyes, one eye was selected at random for analysis. RESULTS: A total of 147 patients were reviewed. Forty-three eyes were receiving betaxolol 0.5%, 58 eyes latanoprost 0.005%, 23 eyes brimonidine 0.2% and 23 eyes had undergone trabeculectomy surgery. There were more female than male patients in all four groups, and the groups were similar with regards age. Pre-treatment IOP and POBF values were similar among the groups ( P=0.27, P=0.08 respectively). Post-treatment IOP values tended to be lower than pre-treatment values for all four groups. All groups had an increased POBF except for betaxolol, where POBF decreased. CONCLUSION: Patients treated by trabeculectomy and those receiving topical latanoprost and brimonidine had lower IOP and higher POBF following treatment. The betaxolol-treated group, despite a slight decrease in IOP, had a decreased POBF. Lowering IOP by treatment may not necessarily be associated with an increase in POBF.