An in vitro assessment of the thermoreversible PLGA-PEG-PLGA copolymer: Implications for Descemet's membrane endothelial keratoplasty.

BACKGROUND: To explore the use of a thermoreversible copolymer gel coating to prevent donor tissue scrolling in Descemet's membrane endothelial keratoplasty (DMEK). METHODS: PLGA-PEG-PLGA triblock copolymer was synthesised via ring opening polymerisation. Two formulations were fabricated and gelation properties characterised using rheological analyses. Endothelial cytotoxicity of the copolymer was assessed using a Trypan Blue exclusion assay. Thickness of the copolymer gel coating on the endothelial surface was analysed using anterior segment optical coherence tomography (OCT) (RTVue-100, Optovue Inc.). Gold nanoparticles were added to the copolymer to aid visualisation using OCT. Prevention of Descemet membrane donor scrolling was represented via a novel, in vitro, immersion of copolymer coated donor graft material. RESULTS: Two different formulations of PLGA-PEG-PLGA copolymer were successfully fabricated and the desired peak gelling temperature of 24°C was achieved by polymer blending. Application of 20%, 30% and 40% (wt/vol) polymer concentrations resulted in a statistically significant increase in polymer thickness on the endothelium (p < 0.001). There was no detectable endothelial cytotoxicity. The polymer was easy to apply to the endothelium and prevented scrolling of the DMEK graft. CONCLUSION: This PLGA-PEG-PLGA thermoreversible copolymer gel could be exploited as a therapeutic aid for preventing DMEK graft scrolling.

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1- and 3-year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re-transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic-type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.

Excimer laser refractive surgery versus phakic intraocular lenses for the correction of moderate to high myopia.

BACKGROUND: Myopia is a condition in which the focusing power (refraction) of the eye is greater than that required for clear distance vision. There are two main types of surgical correction for moderate to high myopia; excimer laser and phakic intraocular lenses (IOLs). Excimer laser refractive surgery for myopia works by removing corneal stroma to lessen the refractive power of the cornea and to bring the image of a viewed object into focus onto the retina rather than in front of it. Phakic IOLs for the treatment of myopia work by diverging light rays so that the image of a viewed object is brought into focus onto the retina rather than in front of the retina. They can be placed either in the anterior chamber of the eye in front of the iris or in the posterior chamber of the eye between the iris and the natural lens. OBJECTIVES: To compare excimer laser refractive surgery and phakic IOLs for the correction of moderate to high myopia by evaluating postoperative uncorrected visual acuity, refractive outcome, potential loss of best spectacle corrected visual acuity (BSCVA) and the incidence of adverse outcomes. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 February 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing excimer laser refractive surgery and phakic IOLs for the correction of myopia greater than 6.0 diopters (D) spherical equivalent. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We performed data analysis. We summarised data for outcomes using odds ratios. We used a fixed-effect model as only three trials were included in the review. MAIN RESULTS: This review included three RCTs with a total of 228 eyes. The range of myopia of included patients was -6.0 D to -20.0 D of myopia with up to 4.0 D of myopic astigmatism. The percentage of eyes with uncorrected visual acuity (UCVA) of 20/20 or better at 12 months postoperative was not significantly different between the two groups. Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12 months postoperatively. However there is a low risk of developing early cataract with phakic IOLs. Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL surgery also scored more highly on patient satisfaction/preference questionnaires. AUTHORS' CONCLUSIONS: The results of this review suggest that, at one year post surgery, phakic IOLs are safer than excimer laser surgical correction for moderate to high myopia in the range of -6.0 to -20.0 D and phakic IOLs are preferred by patients. While phakic IOLs might be accepted clinical practice for higher levels of myopia (greater than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism), it may be worth considering phakic IOL treatment over excimer laser correction for more moderate levels of myopia (less than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism). Further RCTs adequately powered for subgroup analysis are necessary to further elucidate the ideal range of myopia for phakic IOLs. This data should be considered alongside comparative data addressing long-term safety as it emerges.

Accommodative intraocular lens versus standard monofocal intraocular lens implantation in cataract surgery.

BACKGROUND: Following cataract surgery and intraocular lens (IOL) implantation, loss of accommodation or postoperative presbyopia occurs and remains a challenge. Standard monofocal IOLs correct only distance vision; patients require spectacles for near vision. Accommodative IOLs have been designed to overcome loss of accommodation after cataract surgery. OBJECTIVES: To define (a) the extent to which accommodative IOLs improve unaided near visual function, in comparison with monofocal IOLs; (b) the extent of compromise to unaided distance visual acuity; c) whether a higher rate of additional complications is associated the use of accommodative IOLs. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 9), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 October 2013. SELECTION CRITERIA: We include randomised controlled trials (RCTs) which compared implantation of accommodative IOLs to implantation of monofocal IOLs in cataract surgery. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, assessed risk of bias and extracted data. All included trials used the 1CU accommodative IOL (HumanOptics, Erlangen, Germany) for their intervention group. One trial had an additional arm with the AT-45 Crystalens accommodative IOL (Eyeonics Vision). We performed a separate analysis comparing 1CU and AT-45 IOL. MAIN RESULTS: We included four RCTs, including 229 participants (256 eyes), conducted in Germany, Italy and the UK. The age range of participants was 21 to 87 years. All studies included people who had bilateral cataracts with no pre-existing ocular pathologies. We judged all studies to be at high risk of performance bias. We graded two studies with high risk of detection bias and one study with high risk of selection bias.Participants who received the accommodative IOLs achieved better distance-corrected near visual acuity (DCNVA) at six months (mean difference (MD) -3.10 Jaeger units; 95% confidence intervals (CI) -3.36 to -2.83, 2 studies, 106 people, 136 eyes, moderate quality evidence). Better DCNVA was seen in the accommodative lens group at 12 to 18 months in the three trials that reported this time point but considerable heterogeneity of effect was seen, ranging from 1.3 (95% CI 0.98 to 1.68; 20 people, 40 eyes) to 6 (95% CI 4.15 to 7.85; 51 people, 51 eyes) Jaeger units and 0.12 (95% CI 0.05 to 0.19; 40 people, binocular) logMAR improvement (low quality evidence). The relative effect of the lenses on corrected distant visual acuity (CDVA) was less certain. At six months there was a standardised mean difference of -0.04 standard deviations (95% CI -0.37 to 0.30, 2 studies, 106 people, 136 eyes, low quality evidence). At long-term follow-up there was heterogeneity of effect with 18-month data in two studies showing that CDVA was better in the monofocal group (MD 0.12 logMAR; 95% CI 0.07 to 0.16, 2 studies, 70 people,100 eyes) and one study which reported data at 12 months finding similar CDVA in the two groups (-0.02 logMAR units, 95% CI -0.06 to 0.02, 51 people) (low quality evidence).The relative effect of the lenses on reading speed and spectacle independence was uncertain, The average reading speed was 11.6 words per minute more in the accommodative lens group but the 95% confidence intervals ranged from 12.2 words less to 35.4 words more (1 study, 40 people, low quality evidence). People with accommodative lenses were more likely to be spectacle-independent but the estimate was very uncertain (risk ratio (RR) 8.18; 95% CI 0.47 to 142.62, 1 study, 40 people, very low quality evidence).More cases of posterior capsule opacification (PCO) were seen in accommodative lenses but the effect of the lenses on PCO was uncertain (Peto odds ratio (OR) 2.12; 95% CI 0.45 to 10.02, 91 people, 2 studies, low quality evidence). People in the accommodative lens group were more likely to require laser capsulotomy (Peto OR 7.96; 95% CI 2.49 to 25.45, 2 studies, 60 people, 80 eyes, low quality evidence). Glare was reported less frequently with accommodative lenses but the relative effect of the lenses on glare was uncertain (RR any glare 0.78; 95% CI 0.32 to 1.90, 1 study, 40 people, and RR moderate/severe glare 0.45; 95% CI 0.04 to 4.60, low quality evidence). AUTHORS' CONCLUSIONS: There is moderate-quality evidence that study participants who received accommodative IOLs had a small gain in near visual acuity after six months. There is some evidence that distance visual acuity with accommodative lenses may be worse after 12 months but due to low quality of evidence and heterogeneity of effect, the evidence for this is not clear-cut. People receiving accommodative lenses had more PCO which may be associated with poorer distance vision. However, the effect of the lenses on PCO was uncertain.Further research is required to improve the understanding of how accommodative IOLs may affect near visual function, and whether they provide any durable gains. Additional trials, with longer follow-up, comparing different accommodative IOLs, multifocal IOLs and monofocal IOLs, would help map out their relative efficacy, and associated late complications. Research is needed on control over capsular fibrosis postimplantation.Risks of bias, heterogeneity of outcome measures and study designs used, and the dominance of one design of accommodative lens in existing trials (the HumanOptics 1CU) mean that these results should be interpreted with caution. They may not be applicable to other accommodative IOL designs.

Laser-assisted in-situ keratomileusis (LASIK) versus photorefractive keratectomy (PRK) for myopia.

BACKGROUND: Myopia (also known as short-sightedness or near-sightedness) is an ocular condition in which the refractive power of the eye is greater than is required, resulting in light from distant objects being focused in front of the retina instead of directly on it. The two most commonly used surgical techniques to permanently correct myopia are photorefractive keratectomy (PRK) and laser-assisted in-situ keratomileusis (LASIK). OBJECTIVES: To compare the effectiveness and safety of LASIK and PRK for correction of myopia by examining post-treatment uncorrected visual acuity, refractive outcome, loss of best spectacle-corrected visual acuity, pain scores, flap complications in LASIK, subepithelial haze, adverse events, quality of life indices and higher order aberrations. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2012), EMBASE (January 1980 to November 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 November 2012. We also searched the reference lists of the studies and the Science Citation Index. SELECTION CRITERIA: We included randomised controlled trials comparing LASIK and PRK for the correction of any degree of myopia. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We summarised data using the odds ratio and mean difference. We combined odds ratios using a random-effects model after testing for heterogeneity. MAIN RESULTS: We included 13 trials (1135 participants, 1923 eyes) in this review. Nine of these trials randomised eyes to treatment, two trials randomised people to treatment and treated both eyes, and two trials randomised people to treatment and treated one eye. None of the paired trials reported an appropriate paired analysis. We considered the overall quality of evidence to be low for most outcomes because of the risk of bias in the included trials. There was evidence that LASIK gives a faster visual recovery than PRK and is a less painful technique. Results at one year after surgery were comparable: most analyses favoured LASIK but they were not statistically significant. AUTHORS' CONCLUSIONS: LASIK gives a faster visual recovery and is a less painful technique than PRK. The two techniques appear to give similar outcomes one year after surgery. Further trials using contemporary techniques are required to determine whether LASIK and PRK as currently practised are equally safe. Randomising eyes to treatment is an efficient design, but only if analysed properly. In future trials, more efforts could be made to mask the assessment of outcome.

Excimer laser refractive surgery versus phakic intraocular lenses for the correction of moderate to high myopia.

BACKGROUND: Myopia is a condition in which the focusing power (refraction) of the eye is greater than that required for clear distance vision. There are two main types of surgical correction for moderate to high myopia; excimer laser and phakic intraocular lenses (IOLs). Excimer laser refractive surgery for myopia works by removing corneal stroma to lessen the refractive power of the cornea and to bring the image of a viewed object into focus onto the retina rather than in front of it. Phakic IOLs for the treatment of myopia work by diverging light rays so that the image of a viewed object is brought into focus onto the retina rather than in front of the retina. They can be placed either in the anterior chamber of the eye in front of the iris or in the posterior chamber of the eye between the iris and the natural lens. OBJECTIVES: The aim of this review is to compare the effect of excimer laser refractive surgery versus phakic IOLs for the correction of moderate to high myopia. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to November 2011), EMBASE (January 1980 to November 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 28 November 2011. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing excimer laser refractive surgery and phakic IOLs for the correction of myopia greater than 6.0 diopters (D) spherical equivalent. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We performed data analysis. We summarised data for outcomes using odds ratios. We used a fixed-effect model as only three trials were included in the review. MAIN RESULTS: This review included three RCTs with a total of 228 eyes. The range of myopia of included patients was -6.0 D to -20.0 D of myopia with up to 4.0 D of myopic astigmatism. The percentage of eyes with uncorrected visual acuity (UCVA) of 20/20 or better at 12 months postoperative was not significantly different between the two groups. Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12 months postoperatively. However there is a low risk of developing early cataract with phakic IOLs. Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL surgery also scored more highly on patient satisfaction/preference questionnaires. AUTHORS' CONCLUSIONS: The results of this review suggest that phakic IOLs are safer than excimer laser surgical correction for moderate to high myopia in the range of -6.0 to -20.0 D and phakic IOLs are preferred by patients. While phakic IOLs might be accepted clinical practice for higher levels of myopia (greater than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism), it may be worth considering phakic IOL treatment over excimer laser correction for more moderate levels of myopia (less than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism). Further RCTs adequately powered for subgroup analysis are necessary to further elucidate the ideal range of myopia for phakic IOLs.

Quality of life in high myopia before and after implantable Collamer lens implantation.

PURPOSE: To examine changes in vision-related quality of life after implantable Collamer lens (ICL) implantation for the correction of myopia. DESIGN: Prospective, interventional, consecutive case series. PARTICIPANTS: We included 34 consecutive patients (68% female; mean age, 37 years [range, 23-49]) with preoperative myopia (mean ± standard deviation [SD] refraction spherical equivalent, -11.0 ± 3.12). INTERVENTION: Bilateral ICL implantation. MAIN OUTCOME MEASURES: Quality of life Impact of Refractive Correction (QIRC) score. RESULTS: The median postoperative interval before questionnaire administration was 4 months (range, 3-7). The QIRC scores were significantly higher postoperatively (preoperative QIRC score [mean ± SD], 40.45 ± 4.83; postoperative QIRC score 53.79 ± 5.60; P < 0.001), with significant improvements (P<0.01) for 14 of 19 items. Nineteen (58%) patients reported a worsening in night vision symptoms (mostly nonspecific glare and halo or arc effects) after surgery, but overall levels of satisfaction were high; 88% were either satisfied or very satisfied with the results of surgery. No patients reported overall dissatisfaction. In free text responses, 11 patients (32%) described ICL implantation as life changing or wished that they had opted for the surgery sooner. CONCLUSIONS: Implantation of an ICL for myopia is associated with significant improvements in quality of life. Any dissatisfaction with the procedure largely relates to night vision symptoms, which are common in the early postoperative period.

Correcting post-keratoplasty anisometropia with the implantable collamer phakic intraocular lens.

BACKGROUND: We evaluate the Visian Implantable Collamer Lens (Staar, Monrovia, CA, USA) phakic intraocular lens for treating post-keratoplasty anisometropia. METHODS: Case series of three eyes (2 phakic and 1 pseudophakic). RESULTS: The mean age was 47.3 years (range 30-73 years), with a minimum of 3-month follow up. The mean preoperative spherical equivalent was -8.75 ± 5.17 D (-4.00 to -14.25 D) improving to -0.29 ± 1.21 D postoperatively (range 0.75 to -1.625 D). Mean logMAR uncorrected visual acuity improved from 1.66 ± 0.60 (6/240) preoperatively to 0.41 ± 0.52 (6/15(2) ). Mean logMAR best spectacle-corrected visual acuity improved from 0.32 ± 0.15 (6/12) preoperatively to 0.10 ± 0.11 (6/7.5). Anisometropia improved from a difference of 6.37 ± 2.59 D preoperatively to 2.09 ± 1.37 D postoperatively, and there were no complications. CONCLUSION: Our technique for this clinical indication shows that the Visian Implantable Collamer Lens is a safe and effective alternative for treating post-keratoplasty anisometropia.

Quality of life in high myopia: implantable Collamer lens implantation versus contact lens wear.

PURPOSE: To compare vision-related quality of life in implantable Collamer lens (ICL) recipients and successful contact lens (CL) wearers not seeking refractive surgery. DESIGN: A comparative cross-sectional study of consecutive cases. PARTICIPANTS: Forty-one consecutive cases of bilateral ICL implantation in Moorfields Eye Hospital, London, and a control group of 41 CL wearers with a similar starting level of myopia attending consecutively at 1 of 2 community optometric practices in the London area. INTERVENTION: Quality of Life Impact of Refractive Correction questionnaire administration in a semistructured interview. MAIN OUTCOME MEASURE: Quality of Life Impact of Refractive Correction score. RESULTS: Quality of Life Impact of Refractive Correction scores were significantly higher (P<0.001) in ICL recipients (53.67+/-4.50) than in CL wearers (44.42+/-5.07). Age (mean+/-standard deviation [SD], 37.7+/-7 vs. 37.5+/-7.3), gender distribution (% female, 90% vs. 74%; P = 0.295), and preoperative (ICL recipients) or uncorrected (CL wearers) refractive error (mean refractive spherical equivalent+/-SD, 11.0+/-2.7 vs. 11.3+/-3.5) were similar in ICL recipients and CL wearers, respectively. Postoperative uncorrected visual acuities in ICL recipients (0.04 [20/20]+/-0.18) and CL-corrected visual acuities in control patients (0.01 [20/20]+/-0.14) measured in the better eye in each group also were similar (P = 0.53). CONCLUSIONS: Implantable Collamer lens implantation may offer significant quality-of-life advantages over CL wear for patients with high myopia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Blow-back technique for confirmation of peripheral iridectomy patency.

We describe a simple blow-back technique that can be used to confirm the patency of a peripheral iridectomy. Flow reversal is used to flush the iridectomy specimen onto the corneal surface to look for the presence of iris pigment epithelium in small basal iridectomies fashioned using a vitrector.

Biometry and formula accuracy with intraocular lenses used for cataract surgery in extreme hyperopia.

PURPOSE: To audit intraocular lens (IOL) power predictions for cataract surgery in extreme hyperopia and to compare the accuracy across different biometry formulae and IOL types. DESIGN: A retrospective analysis of 76 eyes from 56 patients undergoing cataract surgery with IOLs ranging in power from 30 to 35 diopters (D). METHODS: Axial lengths, corneal powers and anterior chamber depths were measured with ultrasound or optical methods, and the IOLMaster (Carl Zeiss Meditech, Inc, Dublin, California, USA) software was used to predict the refractive outcome for each IOL used. Differences between the predicted and actual postoperative refraction were then analyzed for each formula. RESULTS: In practice, 55% of patients were within +/-1.0 D of the refraction predicted by their surgeon. In theory, the Haigis formula would have given the smallest mean refractive error (+0.51 +/- 0.12 D), followed by the Hoffer Q (-0.70 +/- 0.14 D), Holladay 1 (-1.11 +/- 0.13 D), and SRK/T formulae (-1.45 +/- 0.14 D). The Haigis formula overpredicted the lens power required, which would have generated a myopic result. The other formulae underpredicted the lens power required and would have generated a hyperopic result. There was a significant difference between lens designs: the Haigis was more accurate for open-loop, whereas the Hoffer Q was more accurate for plate-haptic lenses. The anterior chamber depth measurement could also be used to predict changes in intraocular pressure after surgery. CONCLUSION: This represents the largest published series to date of biometry predictions for cataract surgery in extreme hyperopia and confirms the Haigis formula to be the most accurate. A consistent difference between open-loop and plate-haptic lenses suggests that haptic design may influence the effective lens position in very small eyes. We further propose a simple formula to optimize the Haigis and Hoffer Q formulae in patients with extreme hyperopia.

Corneal transplant rejection rate and severity after endothelial keratoplasty.

PURPOSE: To examine the corneal transplant rejection rate and the rate of graft failure subsequent to rejection in the first 2 years after endothelial keratoplasty (EK) and to compare this to background data for similar cases of penetrating keratoplasty (PK). METHODS: Anonymized data from consecutive cases of EK [deep lamellar (DLEK) or Descemet stripping (DSEK)] for Fuchs corneal endothelial dystrophy or pseudophakic bullous keratopathy operated on before August 2004 were collected in 4 participating centers. The number and timing of rejection episodes and cases of subsequent graft failure were recorded, together with the time to cessation of topical steroid medication. Two-year postoperative findings were compared with background data for similar patients undergoing PK recorded in the Swedish Corneal Transplant Registry. RESULTS: Rejection episodes were less frequent after EK than PK (P = 0.035). Fifteen (7.5%) of 199 EK cases had a rejection episode in the first 2 years after surgery versus 92 (13%) of 708 PK cases. Graft failure after rejection in EK may have been less frequent than in PK (P = 0.063), with only 1 (6.7%) case of rejection after EK versus 26 (28.3%) cases of rejection after PK proceeding to graft failure. A strong trend toward continued use of low-dose topical steroid medication was observed in the EK group. Eighty percent of EK patients were still taking topical steroid medication 2 years after surgery, whereas topical steroid medication had been ceased within a year of surgery in almost all PK patients in the comparator group. CONCLUSIONS: Corneal transplant rejection is less frequent and may be less severe after EK than after PK. It is not yet clear whether these apparent differences are simply a product of relatively prolonged postoperative topical steroid cover in EK patients.

Evidence for superior efficacy and safety of LASIK over photorefractive keratectomy for correction of myopia.

PURPOSE: To examine possible differences in efficacy and safety between LASIK and photorefractive keratectomy (PRK) for correction of myopia. DESIGN: Meta-analysis/systematic review. PARTICIPANTS: Patient data from previously reported prospective randomized controlled trials (PRCTs) and a systematic review of prospective case series in the Food and Drug Administration (FDA) clinical trials database. METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify PRCTs comparing LASIK and PRK for correction of myopia. A meta-analysis was performed on the results of PRCTs. In parallel, a systematic review of prospective data from FDA case series of LASIK and PRK for correction of myopia was undertaken. MAIN OUTCOME MEASURES: Key efficacy outcomes (uncorrected visual acuity [UCVA] > or = 20/20, +/-0.50 diopters [D] of the target mean refractive spherical equivalent) and safety outcomes (loss of > or =2 lines of best spectacle-corrected visual acuity [BSCVA], final BSCVA > or = 20/40, and final BSCVA < 20/25 where preoperative BSCVA was > or =20/20). RESULTS: Seven PRCTs were identified comparing PRK (683 eyes) and LASIK (403 eyes) for correction of myopia. More LASIK patients achieved UCVA > or = 20/20 at 6 months (odds ratio, random effects model [95% confidence interval], 1.72 [1.14-2.58]; P = 0.009) and 12 months (1.78 [1.15-2.75], P = 0.01). Loss of > or =2 lines of BSCVA at 6 months was less frequent with LASIK (2.69 [1.01-7.18], P = 0.05). Data from 14 LASIK (7810 eyes) and 10 PRK (4414 eyes) FDA laser approval case series showed that more LASIK patients achieved UCVA of 20/20 or better at 12 months (1.15 [1.03-1.29], P = 0.01), significantly more LASIK patients were within +/-0.50 D of target refraction at 6 months (1.38 [1.26-1.50], P<0.00001) and 12 months (1.21 [1.08-1.36], P = 0.0009) after treatment, and loss of > or =2 lines of BSCVA at 6 months was less frequent with LASIK (2.91 [2.22-3.83], P<0.00001). CONCLUSIONS: LASIK appears to have efficacy and safety superior to those of PRK. However, the data examined are from studies conducted > or =5 years ago. It is therefore unclear how our findings relate to present-day methods and outcomes. Further trials comparing contemporary equipment and techniques are needed to reevaluate the relative merits of these procedures.

Interaction with collagen IV protects lens epithelial cells from Fas-dependent apoptosis by stimulating the production of soluble survival factors.

PURPOSE: To investigate the sensitivity of lens epithelial cells (LECs) to Fas-dependent apoptosis and to determine the role of interaction with the extracellular matrix (ECM) in the regulation of Fas-dependent apoptosis. METHODS: Sensitivity to Fas-mediated apoptosis of primary human LECs and HLE-B3 LECs cultured on different substrates was determined by Hoechst staining after incubation with Fas-stimulating or control IgM. Fas expression was determined by Western blot analysis. Effects of varied cell density and conditioned media from HLE-B3 cells cultured on different substrates on the Fas sensitivity of HLE-B3 cells cultured on tissue culture (TC) plastic were determined. RESULTS: Primary LECs cultured as free-floating anterior capsulotomy specimens were resistant to Fas-dependent apoptosis. The LE cell line, HLE-B3, was sensitive to Fas-dependent apoptosis when cultured on TC plastic but not on lens capsule. Culture on collagen IV, but not on laminin, rendered HLE-B3 cells resistant to Fas-dependent apoptosis, although Fas was still expressed. Primary LECs cultured on TC plastic after migration from lens capsule explants were resistant to Fas-dependent apoptosis if the lens capsule and attached cells were still present, but not if the lens capsule had been removed. Conditioned medium from LECs cultured on collagen IV, but not TC plastic, protected cells cultured on TC plastic from Fas-dependent apoptosis. The protective effect of culture on collagen IV diminished with decreasing cell density. CONCLUSIONS: LECs are protected from Fas-dependent apoptosis by interaction with collagen IV. Soluble factors released by the LECs cultured on collagen IV protect LECs from Fas-dependent apoptosis.

Improved safety in contemporary LASIK.

PURPOSE: To examine the risk of serious visual loss in contemporary LASIK. DESIGN: Retrospective, noncomparative, consecutive case series combined with a structured literature review and comparison with historical controls. PARTICIPANTS: One thousand consecutive cases of LASIK performed from January 2000 to January 2004 by 1 surgeon. One thousand nine hundred eighty-two cases with 6-month review data in postmillennial Food and Drug Administration (FDA) trials of LASIK for myopia and astigmatism and 5203 patients with 6 month review data in similar premillennial FDA trials. METHODS: LASIK was performed with the Hansatome microkeratome and a VISX Star (S2, S3, or S4) laser. There were 899 myopic treatments (spherical equivalent < or =-10.5 diopters [D]; average -4.2 D; standard deviations [SD] D = 1.9 D; astigmatism < or =4.75 D), 87 hyperopic treatments (spherical equivalent < or =+4.25 D; average +2.4 D; SD = 0.9 D; astigmatism < or =3.5 D), and 14 treatments for mixed astigmatism (< or =4.5 D). Outcome data were obtained from a review of case notes and compared with historical data from FDA trials. MAIN OUTCOME MEASURES: Best-spectacle corrected visual acuity (BSCVA) preoperatively and at final review was compared in our case series with reference to the United Kingdom driving standard (BSCVA> or =20/30). Subsidiary outcome measures included duration of follow-up, intraoperative, and postoperative complication rates. Six-month postoperative data on standard safety criteria (numbers of patients losing > or =2 lines BSCVA, BSCVA <20/40, and final BSCVA <20/25 for patients with preoperative BSCVA > or =20/20) were examined in FDA trials. RESULTS: In our clinical series, no case with a preoperative BSCVA of 20/20 or better had a final BSCVA of <20/30 at final review (97.5% confidence interval [CI], 0%-0.37%); 4 eyes had a BSCVA <20/25 (0.41%; 95%CI, 0.11%-1.02%). The median interval between surgery and final review was 2 months (range, 1-45 months). In FDA studies recruiting pre-2000, 1.4% of patients lost > or =2 lines of BSCVA versus 0.6% in postmillennial studies (P = 0.005); 0.45% of patients in premillennial studies lost BSCVA to <20/40 compared with no patients in postmillennial studies (P = 0.001); and 1.68% of patients in premillennial studies with a preoperative BSCVA > or =20/20 had a postoperative BSCVA <20/25 compared with 0.16% in postmillennial studies (P< or =0.001). CONCLUSIONS: Compared with premillennial results, the risk of visual loss is significantly reduced in contemporary LASIK.

Biometry accuracy using zero- and negative-powered intraocular lenses.

PURPOSE: To audit the accuracy of biometry using the SRK/T formula when negative- or zero-powered intraocular lenses (IOLs) are predicted and to compare the results between A-scan, B-scan, and optical methods of biometry. SETTING: Moorfields Eye Hospital, London, United Kingdom. METHODS: This retrospective analysis comprised 78 eyes of 54 patients having cataract surgery with zero- or negative-powered IOLs. Axial lengths were measured with A-scan, B-scan, applanation, or optical methods. Differences between SRK/T-predicted and actual postoperative refraction were analyzed for 75 eyes having cataract surgery. Ocular comorbidity, visual acuity, and biometry readings were also compared. RESULTS: Forty-one percent of 75 patients analyzed were within +/-1.00 diopter (D) of the predicted refraction, although there was a significant tendency toward a hyperopic overcorrection by 1.14 D (95% confidence interval, 0.89-1.39 D). This overcorrection error was consistent across all 3 biometry methods used to estimate axial length and increased with the use of stronger (more negative) IOLs. CONCLUSION: Surgeons should be aware of the tendency for negative-powered lenses to overcorrect and lead to a hyperopic outcome when using the SRK/T biometry formula in highly myopic eyes. A weaker-powered negative IOL is recommended to aim for a more myopic postoperative outcome by about 1.00 to 2.00 D.

Tacrolimus therapy for refractory acute renal allograft rejection: definition of the histologic response by protocol biopsies.

UNLABELLED: Protocol biopsies were performed to define the histologic response to tacrolimus therapy in patients with refractory acute renal allograft rejection. Renal allograft biopsies were performed at defined intervals after initiation of tacrolimus therapy. Protocol biopsies were performed before tacrolimus therapy (within 48 hr of initiation of therapy) and after 1 week of therapy. If the 1-week biopsy did not show rejection reversal, repeat protocol biopsies were obtained at 1- to 2-week intervals, until histologic reversal was observed. Additional biopsies were obtained at 4 weeks and at 8-12 weeks after initiation of tacrolimus therapy. Indicated biopsies were also performed to evaluate increases in serum creatinine. A total of 92 biopsies were performed in 23 patients (average 4.0 biopsies/ patient). Biopsies were performed in each patient immediately before starting tacrolimus therapy (23 biopsies), and 69 biopsies (3.0 biopsies/patient) were performed during tacrolimus therapy. Rejection diagnosis was based on strict Banff criteria. Pretacrolimus biopsies demonstrated mild acute rejection in 64% of patients and moderate acute rejection in 36%. One week after initiation of tacrolimus therapy, protocol biopsies revealed the following: no rejection (60%), improvement (13%), no change (20%), and worsening rejection (7%). Histologic changes at 1 week did not correlate with changes in renal function, as 63% of patients that showed histologic improvement or reversal during the first 2 weeks of therapy did not show improvement in serum creatinine. A lack of histologic improvement (or worsening) at 1 week was demonstrated in a significant proportion of patients (27%); increased tacrolimus dosing provided rejection reversal or improvement in 1-2 weeks in each of these patients. Recurrent rejection was diagnosed on eight biopsies in seven patients, however six episodes were diagnosed by protocol biopsies alone (i.e., in the absence of an elevation in serum creatinine). Delayed improvement in renal function, despite histologic reversal, was likely due to physiologic effects of tacrolimus (i.e., afferent arteriolar vasoconstriction), as histologic evidence of tacrolimus toxicity was not observed during the first 2 weeks of therapy. Histologic evidence of tacrolimus nephrotoxicity (nodular arteriolar hyalinosis) was found in 21% (15 of 69) of biopsies in 39% of patients (9 of 23) at a median time of 60 days (range 12-150 days). Tacrolimus dose and blood levels (by IMx assay) did not correlate with development of clinically silent or clinically evident nephrotoxicity. IN CONCLUSION: 1) protocol biopsies provide information that allows individualization of tacrolimus rejection therapy, 2) histologic resolution of rejection often precedes biochemical improvement, 3) histologic evidence of tacrolimus nephrotoxicity is seldom observed in the first 2 weeks of therapy, and 4) clinically silent recurrent rejection and clinically silent tacrolimus nephrotoxicity are observed with significant frequency during tacrolimus therapy for refractory renal allograft rejection.

Comparison of pancreas transplantation with portal venous and enteric exocrine drainage to the standard technique utilizing bladder drainage of exocrine secretions.

Although bladder drainage of pancreatic exocrine secretions has been reported to decrease morbidity and improve pancreas allograft survival, significant complications remain associated with this technique. Furthermore, this technique requires systemic venous drainage of pancreas allografts. Evidence suggests that portal venous drainage of pancreas grafts prevents hyperinsulinemia and improves lipoprotein composition. This report documents our initial experience with portal venous and enteric exocrine drainage of pancreas allografts (portal/enteric technique) and compares it with the standard technique of systemic venous and bladder exocrine drainage (systemic/bladder technique). Patient and allograft survival, as well as allograft function, were comparable for the two procedures. There were no significant technical complications in this pilot series. Enteric exocrine drainage was associated with a significant reduction in the incidence of acidosis and dehydration when compared with bladder drainage (P<0.005). The portal/enteric technique also avoided reoperation for enteric conversion, as was required by 33% of patients in the systemic/bladder group. The incidence and outcome of allograft rejection were similar for the two techniques. These data suggest that combined pancreas/kidney transplantation with portal venous and enteric exocrine drainage is safe and results in outcomes similar to the standard technique, while eliminating many complications of bladder drainage. These findings should encourage additional studies to determine the consequences of portal venous drainage.

Multicenter survey of daclizumab induction in simultaneous kidney-pancreas transplant recipients.

We report an experience with 71 simultaneous kidney-pancreas transplant (SKPT) recipients receiving daclizumab induction in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. The mean follow-up time was 5.9+/-2.5 (SD) months (range 0.5-11 months). The study population included 47 males (65%) and 24 females (35%) with a mean age of 40+/-8 years. The mean pretransplant duration of diabetes and dialysis were 25+/-8 and 1.5+/-0.9 years (34 hemodialysis, 16 peritoneal dialysis), respectively. Mean HLA match was 1.2+/-1.5, with one patient receiving a second transplant. The mean cold ischemic times for the kidney and the pancreas were 15+/-5 and 16+/-4 hr, respectively. Six-month patient, kidney, and pancreas graft survival and rejection rates were 97, 96, 93, and 35%, respectively. There were two deaths, one due to fungal infection and the other due to a cardiac event. There were three kidney graft losses, two immunological, and one death with function. Of the five pancreas graft losses, two were due to infection, one immunological, one thrombosis, and one death with function. The patient population was then stratified according to the number of daclizumab doses: 4-5 doses (n=45) or 1-3 doses (n=26). There were no differences in patient and kidney graft survival rates, 98 vs. 96%, and 92 vs. 92%, respectively. However, there was a trend toward improved pancreas graft survival in the group receiving 4-5 doses (96%) compared with 1-3 doses (85%), P=0.07. Although more patients receiving 1-3 doses had rejection (54%) than patients receiving 4-5 doses (24%), there was no dose response relationship between the total number of doses or the adjusted total mg/kg dose and time to rejection. All patients with functioning grafts have good renal and pancreas allograft function at 6 and 12 months. The overall incidence of major infection was 27% and there were no differences in the incidence of infection between the two groups. No major adverse events were attributed to daclizumab use. In conclusion, excellent short-term outcomes were noted in this retrospective, multicenter survey of initial experience with daclizumab induction in combination with TAC, MMF, and steroids in SKPT recipients. Optimal dosing strategies for SKPT recipients remain to be determined.

Portal vein thrombosis and stenosis in pediatric liver transplantation.

The aim of this study was to determine the outcome of venous conduits used in living donor liver transplantation (LDLT). We analyzed the portal vein complications in 66 LDLT recipients and 48 cadaveric reduced-size liver transplant (RLT) recipients performed from November 1989 through January 1995. Three different venous conduits were utilized in the LDLT recipients: Group 1, reconstructed vein from the living donor, n=18; Group 2, cadaveric cryopreserved iliac vein, n=37; and Group 3, cadaveric cryopreserved femoral vein, n=11. Overall, 47 percent of the patients were less than one year of age; the age distribution was not significantly different among the groups. The incidence of early thrombosis was significantly greater in LDLT Group 1, (33%) than any of the other groups (LDLT Group 2, 8%; LDLT Group 3, 9%; and RLT, 4%:P<0.0005 vs. reduced graft and < 0.03 vs. other LDLT groups). The incidence of late portal vein stenosis or thrombosis was significantly higher in the LDLT Group 2, (51%) than any of the other groups (LDLT 1, 16%; LDLT Group 3, 9%; RLT 4%;P<0.005 vs. cadaveric and < 0.02 vs. LDLT Group 1 and LDLT Group 3). Five year arterial graft and patient survival for patients who have experienced portal vein thrombosis or stenosis is 61% and 67%, respectively, versus 67% and 71% for those patients who have not experienced portal vein pathology, P=ns. Based on this experience, we recommend avoiding the use of cryopreserved iliac vein for portal vein reconstruction in liver transplantation. Every effort should be taken to eliminate the need for venous conduits in liver transplantation. If venous conduits must be utilized, cryopreserved femoral veins seem to provide superior patency rates. Careful clinical and ultrasonopraphic monitoring of patients at high risk for late venous thrombosis permits therapy with excellent graft and patient survival.