The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1.

PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Acanthamoeba Keratitis Risk Factors for Daily Wear Contact Lens Users: A Case-Control Study.

PURPOSE: This study was designed to establish risk factors for the development of Acanthamoeba keratitis (AK) for daily disposable (DD) contact lens (CL) users compared with daily wear (DW) reusable lens users and for risks unique to DD users. This is important because, in many major economies, CL use is the principal cause of microbial keratitis, of which AK accounts for approximately 50% of cases with sight loss. Determining these AK risks informs practitioner advice and consumer behavior. DESIGN: Case-control study. PARTICIPANTS: Cases and controls were recruited from an Accident and Emergency Department serving South-East England. Cases were new CL users with AK recruited retrospectively from January 2011 to February 2013 and prospectively thereafter until August 2014. Controls were recruited prospectively from February 2014 to June 2015. METHODS: Analysis of a self-administered questionnaire. MAIN OUTCOME MEASURES: Independent risk factors and population attributable risk percentage (PAR%) for AK. RESULTS: A total of 83 AK cases and 122 controls were recruited; DD use was reported by 20 (24%) cases and 66 (54%) controls. In multivariable analyses adjusted for potential confounders, the odds of AK was higher for DW reusable soft lenses (odds ratio [OR], 3.84; 95% confidence interval [CI], 1.75-8.43) and rigid lenses (OR, 4.56; 95% CI, 1.03-20.19) than for DD lenses. Within the DD-using subset, AK was associated with the following modifiable risk factors: less frequent professional follow-up visits (OR, 10.12; 95% CI, 5.01-20.46); showering in lenses (OR, 3.29, 95% CI, 1.17-9.23); lens reuse (OR, 5.41; 95% CI, 1.55-18.89); and overnight wear (OR, 3.93; 95% CI, 1.15-13.46). The PAR% estimated that 30% to 62% of cases could be prevented by switching from reusable soft lens to DD lens use. CONCLUSIONS: Acanthamoeba keratitis risks are increased > threefold in DW reusable lens users versus DD lens use. Acanthamoeba keratitis risks for DD lens users can be minimized by adherence to safe use guidelines (no reuse, overnight wear, or contamination by water). Safe CL use can be improved by increasing the prominence of risk avoidance information from manufacturers and regulators. Because AK accounts for half of severe keratitis in CL users, these measures can be expected to have public health benefits.

Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers.

BACKGROUND AND AIMS: Polyhexamethyl biguanide (PHMB), a widely used topical treatment for Acanthamoeba keratitis (AK), is unlicensed with no formal safety assessment. This study evaluated its safety and tolerability. METHODS: A prospective, randomised, double-masked controlled trial in 90 healthy volunteers. Subjects were treated with topical 0.04%, 0.06%, 0.08% PHMB or placebo (vehicle) 12× daily for 7 days, then 6× daily for 7 days. The rates of dose-limiting adverse events (DLAEs) leading to interruption of dosing, mild adverse events (AEs) (not dose limiting) and incidental AEs (unrelated to treatment) were compared. The primary outcome was the difference between treatments for DLAE rates. RESULTS: 5/90 subjects developed DLAE within <1-4 days of starting treatment; 2/5 using PHMB 0.06% and 3/5 PHMB 0.08%. These resolved within 1-15 days. There were no significant differences in DLAE between treatment groups. Mild AEs occurred in 48/90 subjects (including placebo). There was no trend for an increased incidence of any AE with increasing concentrations of PHMB, except for corneal punctate keratopathy with PHMB 0.08%, which fully resolved within 7-14 days. CONCLUSION: These findings are reassuring for PHMB 0.02% users. They also suggest that higher PHMB concentrations may show acceptable levels of tolerance and toxicity in AK subjects, whose susceptibility to AE may be greater than for the normal eyes in this study. Given the potential benefits of higher PHMB concentrations for treating deep stromal invasion in AK, we think that the use of PHMB 0.08% is justified in treatment trials. TRIAL REGISTRATION NUMBER: NCT02506257.

Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases.

AIMS: To test the hypothesis that Acanthamoeba keratitis (AK) outcomes differ for different topical antiamoebic therapies (AAT) and to provide the detailed patient outcome data. METHODS: A retrospective cohort study of 227 patients developing AK between 25 July 1991 and 10 August 2012. Inclusion criteria required a complete record of AAT treatment for both the primary outcome of a medical cure rate at 12 months and the secondary outcome of Snellen visual acuity ≤6/24 and/or surgical intervention. Analysis used multivariable regression to control for differences in baseline disease characteristics for both primary and secondary outcomes with unadjusted analyses for other outcomes. Subjects were categorised for analysis both by the AAT used at baseline and also by mutually exclusive AAT (patients exposed to all the drugs in each group, and no others, for some period). AAT categories were PHMB monotherapy, PHMB+diamidine, PHMB+chlorhexidine+diamidine, diamidine monotherapy and other AAT. RESULTS: Analysis by baseline AAT showed no notable difference between treatments for both a medical cure at 12 months in 60.79% (138/227) or for a poor outcome in 49.34% (112/227). When AATs were analysed by mutually exclusive groups, PHMB monotherapy provided the best outcomes. These findings are subject to bias requiring careful interpretation. Overall cure rates for the 214 subjects with resolved outcomes were 94.27% (214/227), median time to cure 5 months (IQR 3.25-9.00 months) and range 1-26.24 months. CONCLUSION: PHMB 0.02% monotherapy for the initial treatment of AK is as effective as biguanide+diamidine combination therapy. Chlorhexidine monotherapy was too infrequent for comparison. The outcome data are the most detailed available.

Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors.

BACKGROUND/AIMS: Acanthamoeba keratitis (AK) is a chronic debilitating corneal infection principally affecting contact lens (CL) users. Studies were designed to test claims that the UK incidence may have increased in 2012-2014 and to evaluate potential causes. METHODS: Annualised incidence data were collected from January 1984 to December 2016. Case-control study subjects were recruited between 14 April 2011 and 05 June 2017. Reusable CL users with AK were recruited retrospectively and prospectively. Controls were reusable CL users, recruited prospectively, with any disorder other than AK. Multivariable analysis of questionnaire data measured independent risk factors for AK. RESULTS: The current outbreak of AK started in 2010-2011 with an incidence threefold higher than in 2004-2009. Risk factors for AK were: Oxipol disinfection, CLs made of group IV CL materials, poor CL hygiene, deficient hand hygiene, use of CLs while swimming or bathing, being white British, and for those in social classes 4-9. CONCLUSION: AK is a largely preventable disease. The current outbreak is unlikely to be due to any one of the identified risk factors in isolation. Improving CL and hand hygiene, avoiding CLs contamination with water and use of effective CL disinfection solutions, or daily disposable CLs, will reduce the incidence of AK. In the longer-term, water avoidance publicity for CL users can be expected to reduce the incidence further. Ongoing surveillance of AK numbers will identify changes in incidence earlier. Evaluation of Acanthamoeba contamination in end-user drinking water would contribute to our understanding of regional variations in the risk of exposure.

Number of incident cases of the main eye diseases of ageing in the UK Biobank cohort, projected over a 25-year period from time of recruitment.

OBJECTIVES: To estimate the number of new cases of age-related macular degeneration, cataract and glaucoma accruing in the UK Biobank cohort, over a period of 25 years from time of recruitment. Our secondary objective was to assess the statistical power of nested case-control studies of these eye diseases. We aimed to provide quantitative information relevant to UK Biobank's eye disease case ascertainment efforts and to the potential for UK Biobank-based research into the causes of eye disease. METHODS: We constructed a Markov discrete-time state transition model to simulate the population dynamics of the eye disorders within the UK Biobank cohort, using prevalence data from population-based epidemiological studies to derive incidence, and Office for National Statistics data on mortality and migration overseas. RESULTS: By 2023, >900 new cases of each of 'wet' (neovascular) and 'dry' age-related macular degeneration, >1200 cases of primary open angle glaucoma and almost 15 000 cases of cataracts are expected to have accrued in the subcohort of 68 500 participants who had ocular assessment at baseline, with around seven times as many cases of each disease in the whole cohort of 500 000 participants. These predicted incident case numbers generate good or substantial statistical power for a range of nested case-control studies of potential genetic, lifestyle and environmental determinants of disease. CONCLUSIONS: Over the next few years, UK Biobank is expected to generate sufficient numbers of new cases for statistically well-powered studies of the determinants of the major causes of sight loss: age-related macular degeneration, vision-impairing cataract and glaucoma.

Acanthamoeba keratitis in 194 patients: risk factors for bad outcomes and severe inflammatory complications.

BACKGROUND/AIMS: To determine demographic and clinical features of patients with Acanthamoeba keratitis (AK) that are independent risk factors both for bad outcomes and for severe inflammatory complications (SIC). METHODS: A retrospective audit of medical records of AK cases at Moorfields Eye Hospital from July 2000 to April 2012, including 12 earlier surgical cases. Cases with a bad outcome were defined as those having one or more of the following: corneal perforation, keratoplasty, other surgery (except biopsy), duration of antiamoebic therapy (AAT) ≥10.5 months (the 75th percentile of the whole cohort) and final visual acuity ≤20/80. SICs were defined as having scleritis and/or a stromal ring infiltrate. Multivariable analysis was used to identify independent risk factors for both bad outcomes and SICs. RESULTS: Records of 194 eyes (194 patients) were included, having bad outcomes in 93 (48%). Bad outcomes were associated with the presence of SIC, aged >34 years, corticosteroids used before giving AAT and symptom duration >37 days before AAT. The development of SIC was independently associated with aged >34 years, corticosteroids used before giving AAT and herpes simplex virus (HSV) keratitis treatment before AAT. CONCLUSIONS: The prompt diagnosis of AK, avoidance of a misdiagnosis of HSV keratitis and corticosteroid use before the exclusion of AK as a potential cause of keratitis are essential to the provision of a good outcome for patients and for the avoidance of SIC. Older age is an unmodifiable risk factor that may reflect differences in the immune response to AK in this patient subset.

Mucous Membrane Pemphigoid with Ocular Involvement: The Clinical Phenotype and Its Relationship to Direct Immunofluorescence Findings.

PURPOSE: This study explored the validity of the First International Consensus on Mucous Membrane Pemphigoid (MMP) guidance, which recommends that clinically indistinguishable patients, who have direct immunofluorescence (DIF)-negative biopsies, be excluded from a diagnosis of MMP. Misdiagnosis, or delayed diagnosis, of MMP with ocular involvement leads to the inappropriate use of topical therapy, the standard of care for causes of cicatrising conjunctivitis other than MMP, rather than systemic immunomodulatory therapy, resulting in irreversible clinical deterioration in patients with MMP. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients meeting the clinical criteria of ocular MMP, including those with positive and negative DIF findings. METHODS: A case report form was used to collect the demographic details, the clinical history, and the results of a detailed clinical assessment by ophthalmologists, otolaryngologists, dermatologists, and oral medicine specialists. All anatomic sites potentially affected by MMP were examined apart from the esophagus (and larynx in a subset). The DIF results were recorded. MAIN OUTCOME MEASURES: Differences between DIF-positive and -negative patients in demography, sites of involvement, and disease severity as determined by the degree of conjunctival scarring (using Tauber staging), central corneal disease (vascularization, scarring, ulceration, and conjunctivalization), history of conjunctival or lid surgery, and requirement for systemic immunotherapy at the time of screening. RESULTS: A total of 73 patients with ocular MMP were recruited, of whom 20 of 73 (27.4%) had ocular-only disease. There was no significant demographic or clinical difference between patients with positive and negative DIF results. This finding included differences in disease severity for which the only significant difference was that of more severe central corneal disease in DIF-negative patients. Asymptomatic disease at different sites was frequent. CONCLUSIONS: These findings do not support the classification of DIF-negative patients, meeting the clinical criteria for ocular MMP, as having a different disease. This category of patients should be accepted as having DIF-negative MMP, for clinical management purposes, with patients having inflamed eyes being treated with systemic immunomodulatory therapy. The frequent finding of asymptomatic ocular, oral, and nasopharyngeal MMP is clinically significant and implies that these sites should be routinely screened in asymptomatic patients.

The Impact of Topical Corticosteroids Used in Conjunction with Antiamoebic Therapy on the Outcome of Acanthamoeba Keratitis.

PURPOSE: To examine the impact of topical corticosteroid use after the start of antiamoebic therapy (AAT) on the outcomes of Acanthamoeba keratitis (AK) therapy. DESIGN: Cohort study. PARTICIPANTS: A total of 196 patients diagnosed with AK at Moorfields Eye Hospital, London, between January 1991 and April 2012. In 13 patients with bilateral AK, 1 eye was randomly excluded from analysis. METHODS: Patient demographics and clinical examination findings were collected both at the start of AAT and subsequently at the time that topical corticosteroid therapy was initiated. Preliminary a priori investigations were used to identify effect modifiers/confounders and extreme associations requiring consideration in multivariate regression modeling. A multivariable logistic model, optimized for assessment of corticosteroid use after the start of AAT, was used to estimate the odds ratios (ORs) of a suboptimal outcome. MAIN OUTCOME MEASURES: Suboptimal outcome was defined as final visual acuity ≤20/80, corneal perforation, or the need for keratoplasty. RESULTS: In multivariable analysis, restricted to 129 eyes (1 eye per patient) free of scleritis and hypopyon at the start of AAT, topical corticosteroids were not associated with worse outcomes (OR, 1.08; 95% confidence interval [CI], 0.39-3.03), even when corticosteroids had been used before the start of AAT. Risk factors significantly associated with worse outcomes were topical corticosteroid use before the start of AAT (OR, 3.85; 95% CI, 1.35-11.03), a corneal ring infiltrate (together with at least 1 other feature of AK) present at the start of AAT (OR, 5.89; 95% CI, 1.17-29.67), and age ≥33 years at the start of AAT (OR, 4.02; 95% CI, 1.46-11.06). CONCLUSIONS: Many corneal specialists currently are uncertain about the risk benefit associated with the use of topical corticosteroids for the management of inflammatory complications of AK. The evidence from this study gives clinicians and patients reassurance that the potential benefits of topical corticosteroid therapy, for treating pain and discomfort, are not associated with worse outcomes when initiated after starting modern AAT. Other potential benefits, in terms of resolution of inflammatory complications, will not be demonstrated without a carefully designed randomized clinical trial.

Therapeutic and optical keratoplasty in the management of Acanthamoeba keratitis: risk factors, outcomes, and summary of the literature.

OBJECTIVE: To report the risk factors for and outcomes of therapeutic and optical keratoplasty in the management of Acanthamoeba keratitis (AK). DESIGN: Retrospective case series. PARTICIPANTS: A total of 50 eyes of 196 patients with retrievable medical records, diagnosed with AK at Moorfields Eye Hospital, London, underwent keratoplasty between January 1991 and April 2012. METHODS: Patient demographics, initial clinical examination findings, and management details were collected. The ophthalmic characteristics of patients who underwent keratoplasty for AK were compared with those who did not. Patients undergoing therapeutic keratoplasty were compared with those undergoing optical keratoplasty for baseline characteristics, management details, and visual outcomes. A multivariate logistic model was used to derive the odds ratios of a poor visual outcome in all keratoplasty patients. MAIN OUTCOME MEASURES: Poor visual outcome was defined as final visual acuity of 20/200 or worse. Secondary outcomes of interest included number of clinic visits and the need for additional intraocular surgery. RESULTS: Of the 196 AK patients, a total of 50 patients (25.5%) underwent penetrating or anterior lamellar keratoplasty, 10 of whom (20%) underwent repeat procedures. Of these 50 patients, 26 (52%) had therapeutic keratoplasty, predominantly for corneal perforation. The remaining 24 patients (48%) underwent optical keratoplasty for visual rehabilitation. Thirty-seven (80.4%) patients in the keratoplasty group initially were misdiagnosed as having herpes simplex keratitis versus 59 (41.8%) patients who did not require a keratoplasty (P < 0.001). Final visual outcomes were significantly better in the optical group compared with the therapeutic group, with 13 (54.2%) achieving visual acuity of 20/30 or better versus 7 (26.9%), respectively. On multivariate analysis, beginning therapy at a hospital other than Moorfields and undergoing a therapeutic, rather than an optical, keratoplasty were associated significantly with a poor visual outcome from keratoplasty. CONCLUSIONS: The prognosis of keratoplasty differs markedly when performed for therapeutic purposes compared with visual rehabilitation. Where possible, keratoplasty should be delayed until such time as the eye is uninflamed and medically cured of Acanthamoeba.

The impact of topical corticosteroid use before diagnosis on the outcome of Acanthamoeba keratitis.

OBJECTIVE: To examine the impact of topical corticosteroid use before the diagnosis of Acanthamoeba keratitis (AK) on final visual outcomes and to determine the prognostic factors predicting poorer outcomes. DESIGN: Cohort study. PARTICIPANTS: A total of 209 eyes of 196 patients with retrievable medical records, diagnosed with AK at Moorfields Eye Hospital, London, between January 1991 and April 2012. One eye was randomly excluded from analysis in the 13 cases of bilateral AK. METHODS: Patient demographic, initial clinical examination findings, and management details were collected. The outcomes of patients treated with topical corticosteroids before diagnosis of AK were compared with those not treated with topical corticosteroids before diagnosis. A multivariable logistic model, optimized for prior corticosteroid use, was used to derive the odds ratios (ORs) of a suboptimal visual outcome. MAIN OUTCOME MEASURES: Suboptimal visual outcome was defined as final visual acuity (VA) ≤ 20/80, corneal perforation, or need for keratoplasty. RESULTS: Acanthamoeba keratitis was diagnosed on microbiological culture in 94 eyes (48.0%), on histopathologic examination in 27 eyes (13.8%), on confocal microscopy in 38 eyes (19.4%), and on the basis of a typical clinical course and response to treatment in 37 eyes (18.9%). Final VA and prior corticosteroid use data were available for 174 eyes (88.8%). In multivariable analysis, corticosteroid use before diagnosis was associated with suboptimal visual outcome (OR, 3.90; 95% confidence interval [CI], 1.78-8.55), as were disease stage 3 at presentation (OR, 5.62; 95% CI, 1.59-19.80) and older age (60+ years) at diagnosis (OR, 8.97; 95% CI, 2.13-37.79). CONCLUSIONS: Corticosteroid use before diagnosis of AK is highly predictive of a poorer visual outcome. This is largely due to the initial misdiagnosis of AK as herpetic keratitis. It is important to include AK in the differential diagnosis of keratitis in all contact lens users with keratitis, particularly before making a diagnosis of herpes keratitis and before the use of topical corticosteroids in the therapy of any indolent keratitis.

Outcomes of pseudophakic retinal detachment.

PURPOSE: To provide data on the outcome of pseudophakic retinal detachment (PRD). METHODS: In a retrospective case-control study, we identified a consecutive series of 63 298 cataract extractions (45 520 patients) performed in a single institution between 1994 and 2003. We included 249 cases with PRD and 845 controls that had cataract surgery on the same day as cases but without PRD. Outcome measures were the risk of impaired vision (6/18-6/60) or blindness (<6/60). A multinomial logistic regression model evaluated risk factors for impaired vision or blindness, while multivariable regression models measured the relative risk of poor visual outcome for posterior capsule tear (PCT) and PRD. RESULTS: Primary pars plana vitrectomy was performed on 207 (84.5%) of the 245 cases treated with surgery, of which 175 (71.4%) needed one procedure. The final acuity was <6/60 in 62 cases (24.9%) and 34 controls (4.0%). After PRD, the relative risk for a final visual outcome <6/60 was 6.8 [95% confidence interval (CI) 4.3-10.6; p < 0.001], and we estimated that the proportion of blindness attributable to PRD was 1.1% (CI 0.7-1.9%). A PCT prior to a PRD was not associated with an increased risk of macular detachment (p = 0.165), but it did carry an increased risk of blindness [odds ratio 4.8 (CI 2.2-10.2; p < 0.001]. CONCLUSION: Although a PCT has an adverse effect on visual outcome after cataract surgery, a PRD is the foremost surgery-related risk for a poor visual outcome. Patient education of symptoms and prompt treatment may limit the visual consequences.

Modelling the prevalence of age-related macular degeneration (2010-2020) in the UK: expected impact of anti-vascular endothelial growth factor (VEGF) therapy.

AIMS: To project the number of cases with age-related macular degeneration (AMD) and the numbers with attributable sight loss in the UK in 2010-2020, taking into account the expected beneficial effect of the new anti-vascular endothelial growth factor (VEGF) therapies. METHODS: A 'system dynamics' approach was used in constructing the model to simulate the dynamics of the disease in large populations. The model computed the pool of affected cases over the simulation period, taking into account the expected demographic changes. Other determinants taken into account included: prevalence; incidence; mortality; and the expected efficacy and coverage of anti-VEGF treatment. RESULTS: In the UK, 608,213 persons in 2010 are estimated to have AMD, and this is expected to increase to 755,867 by the end of the decade. Numbers with sight loss from AMD are expected to rise from 223,224 in 2010 to 291,982 by 2020. Cases with sight loss due to neovascular AMD are expected to increase from 145,697 to 189,890 by the end of the decade. CONCLUSIONS: The model predicts that the beneficial effects of the treatment would be outweighed by the strong anticipated demographic 'ageing' effect. This reaffirms the importance of continuing efforts to develop more effective and more broadly applicable therapies for AMD.

Effect of cataract surgery on the corneal endothelium: modern phacoemulsification compared with extracapsular cataract surgery.

PURPOSE: To investigate whether modern phacoemulsification surgery results in more damage to the corneal endothelium than extracapsular cataract extraction (ECCE), and to examine which preoperative, operative, and postoperative factors influence the effect of cataract surgery on the endothelium. DESIGN: Randomized controlled trial. PARTICIPANTS: Five hundred patients 40 years or older were randomized into 2 groups (ECCE, 249; phacoemulsification, 251). METHODS: Central corneal endothelial cell counts, coefficient of variation of cell size, and hexagonality were assessed before surgery and up to 1 year postoperatively. MAIN OUTCOME MEASURE: Endothelial cell count. RESULTS: Four hundred thirty-three patients completed the trial. The initial preoperative mean cell count for the entire sample was 2481 (standard error [SE]: 18.6), reduced at 1 year postoperatively to 2239 (SE: 23.5). An average 10% reduction in cell count was recorded by 1 year postoperatively. There was no such change in hexagonality or in the coefficient of variation. There was no significant difference in overall percentage cell loss between the 2 treatment groups. Factors associated with excessive cell loss (> or =15% by 1 year) were a hard cataract (odds ratio [OR]: 2.1, 95% confidence limits: 1.1-4.1; P = 0.036), age (OR: 1.04, P = 0.005), and capsule or vitreous loss at surgery (OR: 2.38, P = 0.106). Phacoemulsification carried a significantly higher risk (OR: 3.7, P = 0.045) of severe cell loss in the 45 patients with hard cataracts relative to ECCE (52.6% vs. 23.1%; chi-square test, P = 0.041), with both procedures achieving similar postoperative visual acuity outcomes. CONCLUSIONS: No significant difference in overall corneal endothelial cell loss was found between these 2 operative techniques. The increased risk of severe cell loss with phacoemulsification in patients with hard cataracts suggests that phacoemulsification may not be the optimal procedure in these cases, and that ECCE should be preferred.

Retinal detachment in cytomegalovirus retinitis: intravenous versus intravitreal therapy.

PURPOSE: To compare the rate of retinal detachment in a group of patients treated with intravitreal ganciclovir to the rate of retinal detachment in a group of patients treated with systemic ganciclovir. METHODS: A retrospective non-randomized comparative case series was conducted. The participants were 186 consecutive patients with cytomegalovirus (CMV) retinitis treated at two centres over the period from June 1990 to May 1997. Of the 186, 133 patients had systemic therapy of whom 113 had intravenous ganciclovir or foscarnet and 20 had oral ganciclovir, and 53 patients had intravitreal induction and maintenance therapy. The main outcome measure was the rate of retinal detachment, which was calculated using person-months-at-risk denominators. The effect measure used in the main comparative analysis was the hazard ratio obtained from multiple regression using the Cox proportional hazards model. RESULTS: Retinal detachment occurred in three of 53 patients in the intravitreal therapy group, one of 20 patients receiving oral maintenance therapy and 21 of 113 patients receiving intravenous maintenance therapy. The risk of retinal detachment with systemic therapy was 14-fold higher than with intravitreal therapy (P < 0.001)and up to fourfold higher with oral maintenance therapy. CONCLUSIONS: Intravitreal therapy offers a significant advantage over systemic therapy in the treatment of CMV retinitis by substantially reducing the risk of CMV-related retinal detachment.

Refractive error and visual outcome after cataract extraction.

PURPOSE: To determine the range of biometry prediction error of the postoperative refraction and the visual outcome after cataract surgery. SETTING: Postgraduate teaching hospital. METHODS: Refraction and visual outcomes were recorded prospectively for a consecutive case series of 1817 cataract procedures. Complete preoperative and postoperative data were available for 1676 eyes (92.4%). The paired mean error of the difference between the predicted and achieved refraction, the percentages falling within +/-0.50 diopter (D), +/-1.00 D, and +/-2.00 D, and the values that contained 99% of data points were then calculated. The number that achieved a final Snellen visual acuity of 6/12 was determined in all eyes and in eyes without preoperative ocular comorbidity. This analysis was repeated in 1265 eyes that received a single intraocular lens (IOL) design (C10UB/C11UB) after phacoemulsification through a clear corneal incision. RESULTS: The paired mean error of the difference between the predicted and achieved postoperative refraction in all eyes was -0.32 D +/- 1.05 (SD); 72.3% of eyes were within +/-1.00 D of the planned refraction, with bounds of 99% of observation of +2.92 D and -3.98 D. In the single IOL group, the paired mean error was -0.32 +/- 0.94 D; 74.2% of eyes fell within +/-1.00 D of the planned refraction, with bounds of 99% of observation of +2.54 D and -3.81 D. Axial length did not determine the magnitude of the biometry prediction error. At discharge from the service, 86.9% of all eyes and 95.4% of eyes without preoperative ocular comorbidity achieved a final corrected Snellen acuity of 6/12. CONCLUSION: These data provide benchmark information that can be used to monitor clinical practice.