Predictive factors for postoperative visual acuity in idiopathic epiretinal membrane: a systematic review.

The aim of this study was to review the literature on predictive factors for postoperative visual acuity (VA) in surgery for idiopathic epiretinal membrane (ERM). A systematic review of the literature in the databases of PubMed and Embase was performed. The risk of bias was assessed based on predefined criteria and the results were summarized. In total, 1927 studies were retrieved of which 35 were potentially eligible. Nineteen studies were of adequate quality in terms of bias. Preoperative VA, central foveal thickness (CFT) and inner segment/outer segment (IS/OS) integrity on optical coherence tomography (OCT) were most extensively studied. Other preoperative factors studied were severity of metamorphopsia, several OCT parameters, fundus autofluorescence and multifocal electroretinogram. In the current literature, preoperative VA is the only variable consistently associated with postoperative VA. IS/OS integrity on OCT is probably associated, and the severity of metamorphopsia, cone outer segment tips integrity and fundus autofluorescence are possibly associated with postoperative VA. CFT is not associated with postoperative VA. Further studies with adequate methodological quality are needed to confirm these findings. Therefore, an overall prediction model, including different parameters, is still awaited.

Impact of duration of macula-off retinal detachment on visual outcome: a systematic review and meta-analysis of literature.

PURPOSE: To systematically review the influence of the lag time between macula-off retinal detachment and surgical intervention on postoperative visual acuity as main outcome measure. METHODS: Systematic review and meta-analysis of articles published from 1995 to October 2013 of patients with macula-off retinal detachment and treated with scleral buckling or pars plana vitrectomy. Eligible data were pooled in a meta-analysis, analyzing the odds ratio between different durations of ≤ 3, ≤ 4, ≤ 7, and ≤ 10 days, comparing a final visual acuity of ≤ 0.4 logMAR with >0.4 logMAR, using a random-effects model. Last, the number needed to treat was calculated. RESULTS: Fourteen articles were eligible, of which 9 studies contained data that were suitable for meta-analysis. Patients who were operated with scleral buckling (n = 602) within 3 days since macular detachment had a statistically significant better chance of reaching a final visual acuity of 0.4 logMAR or better compared with a longer duration of macular detachment, with an odds ratio for ≤ 3 days versus 4 days to 7 days of 2.86 (95% confidence interval, 1.37-5.99) and an odds ratio for ≤ 3 days versus >3 days of 3.09 (95% confidence interval, 1.56-6.12), and with a number needed to treat of 4. For pars plana vitrectomy, the limited amount of data precluded a meta-analysis with substantial results. CONCLUSION: This meta-analysis suggests that scleral buckling for macular detachment must preferably be performed within 3 days to optimize visual outcome.

Corneal cross-linking for treatment of progressive keratoconus in various age groups.

PURPOSE: To compare the effect of corneal cross-linking (CXL) for keratoconus in various age groups and to investigate the influence of the topographic cone location on the outcome of CXL. METHODS: This cohort study included 95 patients (119 eyes) diagnosed as having progressive keratoconus who underwent epithelium-off standard protocol CXL from January 2010 through May 2012. For statistical analysis, patients were divided into three age groups: pediatric patients (< 18 years), adolescent patients (18 to 26 years), and adults (> 26 years). Visual acuity and refraction, topography, intraocular pressure, and endothelial cell counts were recorded preoperatively and postoperatively. RESULTS: Topographic cones were located more centrally in pediatric corneas (0.85 ± 0.66 mm) compared to adolescent corneas (1.49 ± 0.76 mm, P = .002) and adult corneas (1.86 ± 0.99 mm, P < .001). Pediatric corneas flattened 1 year after CXL by a mean of 1.8 diopters (D), compared to 1.1 D in the other age groups. Central cones (0 to 1 mm) were steeper (62.3 ± 8.3 D) before treatment than peripheral cones (3 to 4 mm) (55.9 ± 8.9 D). One year after CXL, corrected distance visual acuity improved in all age groups, with the highest improvement in pediatric eyes (-0.23 ± 0.40 logMAR, P = .044). CONCLUSIONS: Before CXL, cones of pediatric keratoconic corneas were located more centrally than in the two older age groups. After CXL, pediatric corneas showed more corneal flattening and more corrected distance visual acuity improvement. Pediatric CXL was equally safe compared to adolescent and adult CXL.

Effect of the eyelid speculum on pachymetry during corneal collagen crosslinking in keratoconus patients.

PURPOSE: To compare central corneal thickness (CCT) with and without using an eyelid speculum during corneal collagen crosslinking (CXL). SETTING: University Medical Center Utrecht, Utrecht, the Netherlands. DESIGN: Prospective nonrandomized comparative study. METHODS: Eyes with progressive keratoconus were treated by CXL and consecutively divided into 2 groups. In Group A, an eyelid speculum remained in place throughout the entire CXL procedure. In Group B, the eyelids remained closed during the 30-minute riboflavin instillation. Intraoperative ultrasound pachymetry measurements were performed at different timepoints. The visual acuity, refraction, keratometry, pachymetry, and endothelium were evaluated 6 months after CXL. The main outcome measures were intraoperative CCT measurements and the clinical CXL effect after 6 months. RESULTS: Fifty-two eyes (50 patients) were treated. After riboflavin instillation, a statistically significant difference in CCT reduction was found between the 2 groups (P<.001), with a mean CCT decrease of 62 µm±53 (SD) (13%±11%) in Group A and 11±35 µm (2%±8%) in Group B. No statistically significant between-group differences were found after epithelial removal or ultraviolet-A (UVA) irradiation. Six months after CXL, no statistically significant between-group difference was found in the visual acuity, refraction, keratometry, pachymetry, or endothelium. CONCLUSIONS: Avoidance of an eyelid speculum during riboflavin instillation resulted in less CCT reduction during CXL. This finding could increase the chance of attaining the required pachymetry safety margin for applying UVA and thus decrease the chance of premature CXL treatment termination. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Effective corneal collagen crosslinking in advanced cases of progressive keratoconus.

PURPOSE: To evaluate the 1-year results of corneal collagen crosslinking (CXL) in mild to moderate cases and advanced cases of progressive keratoconus. SETTING: Department of Ophthalmology, University Medical Center Utrecht, the Netherlands. DESIGN: Retrospective cohort study. METHODS: Eyes with progressive keratoconus had CXL between January 2010 and April 2011. Patients were divided into 2 subgroups as follows: Group 1, mild to moderate keratoconus with a preoperative maximum keratometry (K) of less than 58.0 diopters (D), and Group 2, advanced keratoconus with a maximum K of 58.0 D or more. Visual acuity, refraction, and elevation-based topography were evaluated at baseline and 12 months after CXL. RESULTS: The study comprised 53 eyes of 42 patients. In the overall group, progression was halted in 48 eyes (91%). The CXL-induced corneal flattening occurred in 11 (42%) of 26 eyes in Group 1 and 20 (74%) of 27 eyes in Group 2. Five of 7 keratoconus indices improved 12 months after CXL. The failure rate was comparable in the subgroups (3 eyes in Group 1, 2 eyes in Group 2). No major complications occurred in either subgroup. CONCLUSIONS: Stabilization after CXL was achieved in mild to moderate cases and advanced cases of progressive keratoconus. The amount of failure was comparable in the 2 subgroups. The CXL-induced flattening was more pronounced in the advanced subgroup.

Corneal crosslinking for progressive keratoconus in four children.

The authors describe four children with progressive keratoconus treated by corneal crosslinking (CXL). The current CXL guidelines recommend treatment of patients 18 years and older. Nevertheless, keratoconus can rapidly progress in young teenagers. CXL could be a safe procedure to prevent a keratoplasty at a young age.

A network meta-analysis combined direct and indirect comparisons between glaucoma drugs to rank effectiveness in lowering intraocular pressure.

OBJECTIVE: It is difficult to rank treatments according to their effect size when several treatments are available and not all treatments have been compared directly. The purpose of this study was to show a new statistical technique (network meta-analysis) to address this problem and to rank glaucoma drugs according to their intraocular pressure (IOP)-reducing effect. STUDY DESIGN AND SETTING: Network meta-analysis of randomized controlled trials was used to combine direct and indirect estimates of the effect of eight drugs and placebo from 28 randomized controlled trials in patients with primary open-angle glaucoma or ocular hypertension patients, 6,841 for the peak effect and 6,953 patients for the trough effect. RESULTS: All drugs differ from placebo in lowering IOP. At the peak, the rank order from high to low in terms of the mean IOP reduction reached is bimatoprost, travoprost and latanoprost, brimonidine, timolol, dorzolamide, betaxolol, brinzolamide. At the trough, this rank order is bimatoprost, latanoprost, travoprost, timolol, betaxolol, dorzolamide, brinzolamide, brimonidine. The results based on direct or indirect estimates were similar. This ranking differed from the ranking based on the mean IOP change from baseline of all arms including the study drug from all randomized controlled trials. CONCLUSIONS: A network meta-analysis can be used to combine direct and indirect treatment effects in a formal way. Applied to glaucoma medications, it shows that there is a rank order in treatment effects on IOP.

Side effects of commonly used glaucoma medications: comparison of tolerability, chance of discontinuation, and patient satisfaction.

BACKGROUND: To compare the tolerability of commonly prescribed topical glaucoma medications by determining frequency and bother of side effects, patient satisfaction with their medication, and the chance of discontinuation of eye drops. METHODS: The tolerability of topical glaucoma medication was studied in glaucoma patients from nine hospitals. The frequency and severity of side effects was investigated together with patient satisfaction with the medication and the probability to change medication due to reported side effects. To register side effects of topical glaucoma medication, patients were requested to fill in a questionnaire based on "the Comparison of Ophthalmic Medications for Tolerability" (COMTOL) questionnaire supplemented with items based on the most frequently observed and severe side effects. RESULTS: The number of patients responding was 3,333 (87%). Most patients (79%) were satisfied with their eye medication. The median score for ocular side effects was 58 on a scale ranging from 0 to 320. The probability that medication would be changed by the ophthalmologist at the next visit due to reported side effects occurring since the patients' last or last but one visit to the ophthalmologist was 9%. The most frequently prescribed drugs were timolol, latanoprost, and the fixed combinations of dorzolamide/timolol (Cosopt) and latanoprost/timolol (Xalcom). Only small differences in tolerability were found between these drugs. CONCLUSIONS: The tolerability of timolol, latanoprost, and the fixed combinations of latanoprost/timolol (Xalcom) and dorzolamide/timolol (Cosopt) seem to be comparable. Patients are satisfied with their glaucoma medication and have a low chance of discontinuation of eye drops due to side effects.

Predicting intraocular pressure change before initiating therapy: timolol versus latanoprost.

PURPOSE: To study intraocular pressure (IOP) reductions with timolol and latanoprost reached in clinical practice, taking into account data that are routinely collected by the ophthalmologist; to predict IOP reduction from these variables. METHODS: A cohort of patients with primary open-angle glaucoma (suspect) or ocular hypertension was recruited from nine Dutch centres. Mean absolute and relative IOP reduction was calculated in order to compare timolol to latanoprost. IOP reduction was calculated by comparing patients with certain characteristics to those who had none. RESULTS: One hundred and fifty-six persons started on timolol and 76 started on latanoprost monotherapy. Mean [95% confidence interval (CI)] absolute reduction was 7.2 mmHg (7.9; 6.5) for timolol and 6.9 mmHg (8.0; 5.8) for latanoprost. Mean relative reduction (95% CI) was 27.2% (29.3; 25.1) for timolol and 26.6% (30.2; 22.9) for latanoprost. No significant difference in IOP reduction between timolol and latanoprost was found when adjusting for data that are routinely collected by the ophthalmologist. At the time of starting treatment, none of these items normally used for the management of glaucoma, except IOP at baseline, could predict change in IOP. CONCLUSION: In clinical practice, timolol and latanoprost achieve similar IOP reductions that are comparable to those achieved in randomized trials. No clinically relevant information for glaucoma management can be used to predict IOP reduction accurately.

Intraocular pressure-lowering effect of adding dorzolamide or latanoprost to timolol: a meta-analysis of randomized clinical trials.

OBJECTIVE: To estimate the intraocular pressure (IOP)-lowering effect of 2% dorzolamide or 0.005% latanoprost when added to 0.5% timolol. DESIGN: Meta-analysis of randomized clinical trials. PARTICIPANTS: Seventeen articles reporting on 19 study arms with 5 possible treatment combinations and 4 study arms serving as controls. METHODS: Articles written in English, German, French, or Dutch and published up to December 2004 were identified in Medline, Embase, the Cochrane Controlled Trials Register, and references from relevant articles. For the article to be considered, over 85% of the patients had to have primary open-angle glaucoma or ocular hypertension. The pooled 1- to 3-month additional IOP-lowering effect after a run-in phase on timolol was calculated by performing meta-analysis using the random effects model. MAIN OUTCOME MEASURES: Absolute and relative changes in IOP after run-in on timolol for peak moment, trough moment, or mean diurnal curve. RESULTS: The pooled change from baseline [mean (95% confidence interval)] for 0.5% timolol varied from -0.7 mmHg (-1.2 to -0.2, for the mean diurnal curve) to -2.0 mmHg (-1.3 to -2.7, at peak). Pooled changes for 2% dorzolamide in concomitant use with 0.5% timolol were -4.1 mmHg (-4.4 to -3.8) at trough and -4.9 mmHg (-5.3 to -4.5) at peak. The fixed 2% dorzolamide and 0.5% timolol combination resulted in a pooled change of -3.8 mmHg (-4.2 to -3.4) at trough and -4.9 mmHg (-5.3 to -4.5) at peak. The concomitant use of 0.005% latanoprost and 0.5% timolol gave a pooled change from baseline of -6.0 mmHg (-6.8 to -5.2) at the mean diurnal curve. The fixed combination of 0.005% latanoprost and 0.5% timolol resulted in a mean change of -3.0 mmHg (-3.8 to -2.2) at the mean diurnal curve. CONCLUSION: In this meta-analysis of clinical trials, the addition of dorzolamide or latanoprost further lowers IOP in eyes on timolol. This result may not be generalizable because these trials may have included nonresponders to timolol.

Changes in glaucoma treatment and achieved IOP after introduction of new glaucoma medication.

PURPOSE: To describe changes in glaucoma treatment and achieved IOP (intraocular pressure) over the period 1995-2002, 4 years before and 4 years after new glaucoma drugs had become available (January 1999). METHODS: An observational study was conducted in primary open-angle glaucoma (suspect), and ocular hypertension patients (n=1561) who had started medical treatment in 1995 or thereafter. The processes of starting, changing and intensifying medical treatment in general, and in patients with contraindications to beta-blockers before and after January 1999 were described. The change in mean IOP and the percentage of patients achieving an intraocular pressure below 18 or 22 mmHg were calculated. RESULTS: After January 1999, a shift from starting on betaxolol to hypotensive lipids took place. This shift was more pronounced in patients with respiratory comorbidity. The percentage of patients starting on timolol did not differ between both periods. After January 1999, therapy was changed more often in the first two visits compared with the period before January 1999 (38% versus 27%, P<0.0001). In more recent years, a larger percentage of glaucoma patients were treated with two or more drugs (34% in 2002 versus 13% in 1995). Over the period 1995-2002, baseline IOP did not change (P=0.85); for mean IOP at visit 4, a trend to lower IOPs was observed (P<0.0001). More patients achieved an IOP level under 22 and 18 mmHg after January 1999 than before, 85% versus 77%, and 46% versus 33%, respectively (P<0.0001). CONCLUSIONS: This study shows a change in process of glaucoma treatment and lower achieved IOP after new glaucoma drugs had become available.

Intraocular pressure-lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials.

OBJECTIVE: To estimate the intraocular pressure (IOP) reduction achieved by the most frequently prescribed glaucoma drugs and a placebo in a meta-analysis of randomized clinical trials. DESIGN: Meta-analysis of randomized clinical trials. PARTICIPANTS: Twenty-seven articles reporting on 28 randomized clinical trials. These articles reported 6953 participants for the trough and 6841 for the peak. METHODS: Articles published up to December 2003 were identified in the following data sources: Medline, Embase, and the Cochrane Controlled Trials Register, and references from relevant articles. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OH), and articles had to be written in English, German, French, or Dutch. Quality of trials was assessed by a Delphi list with additions. The pooled 1-month IOP-lowering effect from baseline at peak and trough was calculated by performing meta-analysis using the random effects model. MAIN OUTCOME MEASURES: Absolute and relative change in IOP from baseline, for peak and trough moments. RESULTS: Relative IOP reductions from baseline [mean (95% confidence interval)] were -23% (-25% to -22%) for a peak and -20% (-23% to -17%) for a trough for 0.5% betaxolol; peak, -27% (-29% to -25%), and trough, -26% (-28% to -25%), for 0.5% timolol; peak, -22% (-24% to -20%), and trough, -17% (-19% to -15%), for 2.0% dorzolamide; peak, -17% (-19% to -15%), and trough, -17% (-19% to -15%) for 1.0% brinzolamide; peak, -25% (-28% to -22%), and trough, -18% (-21% to -14%) for 0.2% brimonidine; peak, -31% (-33% to -29%), and trough, -28% (-30% to -26%) for 0.005% latanoprost; peak, -31% (-32% to -29%), and trough, -29% (-32% to -25%) for 0.004% travoprost; peak, -33% (-35% to -31%), and trough, -28% (-29% to -27%) for 0.03% bimatoprost; and peak, -5% (-9% to -1%), and trough, -5% (-10% to -0%) for the placebo. The difference in absolute IOP reduction from baseline between timolol and prostaglandin analogs or prostamide varied from -0.4 to 0.1 mmHg at trough and from 1.0 to 1.5 mmHg at peak. Quality scores of included studies were generally high, a mean of 14.2 on a scale from 0 to 20 (interquartile range, 13-16). CONCLUSION: This meta-analysis suggests that bimatoprost, travoprost, latanoprost, and timolol are the most effective intraocular pressure-reducing agents in POAG and OH patients.

The impact of a nationwide introduction of new drugs and a treatment protocol for glaucoma on the number of glaucoma surgeries.

PURPOSE: To study the trend in number of glaucoma surgeries, and the influence hereon of the introduction of new glaucoma medication, reimbursement of its costs, and the introduction of a treatment protocol. METHODS: Out of the Dutch Health Care Registration, all open angle glaucoma and ocular hypertension patients aged 20 years and older, who underwent glaucoma surgery were selected. Over the period 1995 until 2003 the trend in the number of monthly performed glaucoma surgeries was described by LOESS spline procedure. RESULTS: From 1995 until 2003, 15,888 surgeries were included. Overall mean age was 67.5 years (SD 13.0). Mean age declined by 0.29 year per year (95% CI, 0.21-0.37). In 1995 and 1996 the number of yearly performed glaucoma surgeries was approximately 2400. From 1997 onwards this number started to decrease, resulting in a 45% decrease in the year 2000. From 2000 on the number of surgeries stabilized at approximately 1350 per year. In 1999 the total number of prescriptions rose by 20% compared with 1998, and then stabilized. In 2002, 48% of the prescriptions were prescriptions for new medication. CONCLUSION: The number of glaucoma surgeries in the Netherlands almost halved over a 3.5-year period, most likely due to the introduction of new medications. In the remaining study period the number leveled off. From the present data a substitution effect and not merely a postponement of glaucoma surgeries may be suggested, providing additional evidence that a sustained reduction in the number of glaucoma surgeries was reached in the studied period.

Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial.

BACKGROUND: Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance. METHODS: In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat. FINDINGS: After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation. INTERPRETATION: Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.