Outcomes in randomised controlled trials of multifocal lenses in cataract surgery: the case for development of a core outcome set.

BACKGROUND/AIMS: To describe and summarise the outcomes reported in randomised controlled trials of multifocal versus monofocal intraocular lenses in cataract surgery. METHODS: We identified all randomised controlled trials of multifocal versus monofocal lenses in a Cochrane review (last search date June 2016). We extracted and summarised data on all outcomes reported using the framework of domain, measurement, metric and method of aggregation. RESULTS: All studies collected data on distance and near visual acuity but there was considerable variation in the measures used and whether these outcomes were unaided or best corrected. Most studies reported final value measurements, rather than change from baseline. Approximately half of the studies reported data as a continuous measure only, one-third reported both continuous and categorical measures and a minority reported categorical measures only. There was little consensus as to cut-points. Although a majority of studies included one or more patient-reported outcome measures, none of the studies reported patient involvement in the choice of outcomes. CONCLUSION: The collection and analysis of data on outcome measures in studies of multifocal intraocular lenses in cataract surgery are complicated. As a result, there is considerable heterogeneity in collection and reporting in the medical literature. This makes it difficult to synthesise such data to provide robust estimates of effect and is a potential source of research waste. Investigators in this field must produce a core outcome set that is informed by patients' views and we propose an initial set of outcomes on which these could be based.

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity (VA) is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: To assess the visual effects of multifocal IOLs in comparison with the current standard treatment of monofocal lens implantation. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), 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 13 June 2016. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. We also considered trials comparing multifocal IOLs with "monovision" whereby one eye is corrected for distance vision and one eye corrected for near vision. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed the 'certainty' of the evidence using GRADE. MAIN RESULTS: We found 20 eligible trials that enrolled 2230 people with data available on 2061 people (3194 eyes). These trials were conducted in Europe (13), China (three), USA (one), Middle East (one), India (one) and one multicentre study in Europe and the USA. Most of these trials compared multifocal with monofocal lenses; two trials compared multifocal lenses with monovision. There was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask participants and outcome assessors. It was also difficult to assess the role of reporting bias.There was moderate-certainty evidence that the distance acuity achieved with multifocal lenses was not different to that achieved with monofocal lenses (unaided VA worse than 6/6: pooled RR 0.96, 95% confidence interval (CI) 0.89 to 1.03; eyes = 682; studies = 8). People receiving multifocal lenses may achieve better near vision (RR for unaided near VA worse than J3/J4 was 0.20, 95% CI 0.07 to 0.58; eyes = 782; studies = 8). We judged this to be low-certainty evidence because of risk of bias in the included studies and high heterogeneity (I2 = 93%) although all included studies favoured multifocal lenses with respect to this outcome.People receiving multifocal lenses may be less spectacle dependent (RR 0.63, 95% CI 0.55 to 0.73; eyes = 1000; studies = 10). We judged this to be low-certainty evidence because of risk of bias and evidence of publication bias (skewed funnel plot). There was also high heterogeneity (I2 = 67%) but all studies favoured multifocal lenses. We did not additionally downgrade for this.Adverse subjective visual phenomena were more prevalent and more troublesome in participants with a multifocal IOL compared with monofocals (RR for glare 1.41, 95% CI 1.03 to 1.93; eyes = 544; studies = 7, low-certainty evidence and RR for haloes 3.58, 95% CI 1.99 to 6.46; eyes = 662; studies = 7; moderate-certainty evidence).Two studies compared multifocal lenses with monovision. There was no evidence for any important differences in distance VA between the groups (mean difference (MD) 0.02 logMAR, 95% CI -0.02 to 0.06; eyes = 186; studies = 1), unaided intermediate VA (MD 0.07 logMAR, 95% CI 0.04 to 0.10; eyes = 181; studies = 1) and unaided near VA (MD -0.04, 95% CI -0.08 to 0.00; eyes = 186; studies = 1) compared with people receiving monovision. People receiving multifocal lenses were less likely to be spectacle dependent (RR 0.40, 95% CI 0.30 to 0.53; eyes = 262; studies = 2) but more likely to report problems with glare (RR 1.41, 95% CI 1.14 to 1.73; eyes = 187; studies = 1) compared with people receiving monovision. In one study, the investigators noted that more people in the multifocal group underwent IOL exchange in the first year after surgery (6 participants with multifocal vs 0 participants with monovision). AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs although there is uncertainty as to the size of the effect. Whether that improvement outweighs the adverse effects of multifocal IOLs, such as glare and haloes, will vary between people. Motivation to achieve spectacle independence is likely to be the deciding factor.

Spontaneous regression of a conjunctival naevus.

Conjunctival naevi are one of the most common lesions affecting the conjunctiva. While benign in the vast majority of cases, the risk of malignant transformation necessitates regular follow-up. They are well known to increase in size; however, we present the first photo-documented case of spontaneous regression of conjunctival naevus. In most cases, surgical excision is performed due to the clinician's concerns over malignancy. However, a substantial proportion of patients request excision. Highlighting the potential for regression of the lesion is important to ensure patients make an informed decision when contemplating such surgery.

Multifocal versus monofocal intraocular lenses after cataract extraction

BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. METHODS: Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register), The Cochrane Library 2012, Issue 2, MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 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. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included ...

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register), The Cochrane Library 2012, Issue 2, MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 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. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal IOLs for information about additional published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial quality. Where possible, we pooled data from the individual studies using a random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen completed trials (1608 participants) and two ongoing trials were identified. All included trials compared multifocal and monofocal lenses but there was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask patients and outcome assessors. It was also difficult to assess the role of reporting bias. There was moderate quality evidence that similar distance acuity is achieved with both types of lenses (pooled risk ratio, RR for unaided visual acuity worse than 6/6: 0.98, 95% confidence interval, CI 0.91 to 1.05). There was also evidence that people with multifocal lenses had better near vision but methodological and statistical heterogeneity meant that we did not calculate a pooled estimate for effect on near vision. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse subjective visual phenomena, particularly haloes, or rings around lights, were more prevalent and more troublesome in participants with the multifocal IOL and there was evidence of reduced contrast sensitivity with the multifocal lenses.

Randomized Controlled Study of Ocular Lubrication Versus Bandage Contact Lens in the Primary Treatment of Recurrent Corneal Erosion Syndrome.

PURPOSE: To investigate the efficacy of bandage contact lenses (BCLs) in comparison with that of ocular lubricants (OLs) in the initial management of recurrent corneal erosion syndrome. METHODS: A randomized controlled trial of 29 patients with recurrent corneal erosion syndrome presenting to the ophthalmology departments of the Oxford Eye Hospital and the Royal Berkshire Hospital, United Kingdom. The patients were randomized to wear either BCLs (for a 3-month duration, replaced every 30 days) or use OLs (4 times a day, with Lacri-Lube ointment at night for 3 months). The patients were assessed monthly for 4 months, and their symptoms were graded by visual analog scores. The main outcome measure was the complete resolution of symptoms with no noticeable corneal surface abnormality. Patients with a complete resolution were followed up for another 3 months to check for recurrence. RESULTS: Fourteen patients were randomized to the BCL arm, and 15 were randomized to the OL arm. After 3 months, a complete resolution was achieved in 71% of the patients (10/14) with BCLs compared with that achieved in 73% of the patients (11/15) on OLs (P > 0.05). Partial resolution was noted in 7% of the patients with BCLs versus 13% of the patients on OLs. Twenty-one percent of the patients in the BCL group and 13% of the patients in the OL group failed to respond to the treatment. Patients on BCLs had earlier resolution of symptoms, with a mean time of 5 weeks compared with 9 weeks for OLs (P = 0.02). None of the patients with BCLs developed adverse side effects. CONCLUSIONS: BCLs do not increase the likelihood of complete resolution when compared with OLs in the initial management of RCES. However, BCL treatment seems safe, and some patients experience earlier relief from symptoms.

The secretome of alginate-encapsulated limbal epithelial stem cells modulates corneal epithelial cell proliferation.

Limbal epithelial stem cells may ameliorate limbal stem cell deficiency through secretion of therapeutic proteins, delivered to the cornea in a controlled manner using hydrogels. In the present study the secretome of alginate-encapsulated limbal epithelial stem cells is investigated. Conditioned medium was generated from limbal epithelial stem cells encapsulated in 1.2% (w/v) calcium alginate gels. Conditioned medium proteins separated by 1-D gel electrophoresis were visualized by silver staining. Proteins of interest including secreted protein acidic and rich in cysteine, profilin-1, and galectin-1 were identified by immunoblotting. The effect of conditioned medium (from alginate-encapsulated limbal epithelial stem cells) on corneal epithelial cell proliferation was quantified and shown to significantly inhibit (P≤0.05) their growth. As secreted protein acidic and rich in cysteine was previously reported to attenuate proliferation of epithelial cells, this protein may be responsible, at least in part, for inhibition of corneal epithelial cell proliferation. We conclude that limbal epithelial stem cells encapsulated in alginate gels may regulate corneal epithelialisation through secretion of inhibitory proteins.

PAX6 mutation in association with ptosis, cataract, iris hypoplasia, corneal opacification and diabetes: a new variant of familial aniridia?

BACKGROUND: We report a family with ptosis, cataract, iris hypoplasia and gradual corneal opacification occurring in association with a PAX6 mutation. DESIGN: Case-series. PARTICIPANTS: Fourteen family members - 8 affected, 6 unaffected controls. METHODS: All participants underwent ophthalmological assessment, including best-corrected visual acuity, slit-lamp-examination, pachymetry, endothelial cell-count, tonometry and dilated fundoscopy. All subjects underwent anthropometry and assessment of glycaemic status. Genetic analysis of the PAX6 gene was performed. MAIN OUTCOME MEASURES: Presence of ptosis, corneal, iris and lenticular changes, gycaemic and PAX6 status. RESULTS: All eight affected subjects had ptosis with reduced levator function, anterior polar cataracts, and corneal changes of variable severity - two patients had undergone penetrating keratoplasties, with graft histology revealing conjunctival cells on the cornea and severe fibroinflammatory change. Five patients had iris hypoplasia. One patient had aphakic glaucoma and another had hypoplastic optic discs. Four of the six controls had no ocular features of this syndrome, and two had isolated mild ptosis. There was no difference in height or body mass index between cases and family controls (p > 0.05), but Haemoglobin A1c was greater in the cases (median [interquartile range] 5.6(0.8) vs 5.1(0.3), p = 0.028). Genetic analysis confirmed a pathogenic PAX6 mutation in exon 12 (c1439delC) in all eight patients, but none of the controls. CONCLUSION: This is the first report of this particular constellation of ocular signs occurring in association with a PAX6 mutation. There was no association with anthropometric features, but affected subjects had worse glycaemia than controls, which may be related to the known role of PAX6 in development of the pancreas.

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 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. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal IOLs for information about additional published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial quality. Where possible, we pooled data from the individual studies using a random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen completed trials (1608 participants) and two ongoing trials were identified. All included trials compared multifocal and monofocal lenses but there was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask patients and outcome assessors. It was also difficult to assess the role of reporting bias. There was moderate quality evidence that similar distance acuity is achieved with both types of lenses (pooled risk ratio (RR) for unaided visual acuity worse than 6/6: 0.98, 95% confidence interval (CI) 0.91 to 1.05). There was also evidence that people with multifocal lenses had better near vision but methodological and statistical heterogeneity meant that we did not calculate a pooled estimate for effect on near vision. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse subjective visual phenomena, particularly haloes, or rings around lights, were more prevalent and more troublesome in participants with the multifocal IOL and there was evidence of reduced contrast sensitivity with the multifocal lenses. AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs. Whether that improvement outweighs the adverse effects of multifocal IOLs will vary between patients. Motivation to achieve spectacle independence is likely to be the deciding factor.

Enhanced viability of corneal epithelial cells for efficient transport/storage using a structurally modified calcium alginate hydrogel.

AIMS: Therapeutic limbal epithelial stem cells could be managed more efficiently if clinically validated batches were transported for 'on-demand' use. MATERIALS & METHODS: In this study, corneal epithelial cell viability in calcium alginate hydrogels was examined under cell culture, ambient and chilled conditions for up to 7 days. RESULTS: Cell viability improved as gel internal pore size increased, and was further enhanced with modification of the gel from a mass to a thin disc. Ambient storage conditions were optimal for supporting cell viability in gel discs. Cell viability in gel discs was significantly enhanced with increases in pore size mediated by hydroxyethyl cellulose. CONCLUSION: Our novel methodology of controlling alginate gel shape and pore size together provides a more practical and economical alternative to established corneal tissue/cell storage methods.

Multifocal versus monofocal intraocular lenses in cataract surgery: a systematic review.

OBJECTIVE: To assess the visual effects of multifocal intraocular lenses (IOLs) compared with the current standard treatment of monofocal IOL implantation. DESIGN: Systematic literature review and meta-analysis of randomized controlled trials. METHODS: The study was performed according to the Cochrane Collaboration methodology. Computer database and manual searches were made to identify all randomized trials comparing multifocal IOL implantation with a monofocal control group. Data were extracted using a standardized form and analyzed using Review Manager software. When study reporting allowed meaningful comparison, meta-analysis was performed. The chi-square test was used to examine heterogeneity between studies. Odds ratios were calculated for dichotomous outcomes and standardized mean differences for continuous variables. MAIN OUTCOME MEASURES: There is no single outcome measure that can be thought of as summarizing the efficacy of an IOL. A number of different outcomes had to be examined. The primary outcomes for this review were distance and near visual acuity (unaided and corrected) and spectacle dependence. The secondary outcomes for this review included depth of field, contrast sensitivity, glare, subjective assessment of quality of life or visual function, and surgical complications. RESULTS: Eight trials were identified. There was significant variability among the trials in the outcomes reported. Distance acuity was similar in multifocal and monofocal IOLs. Unaided near vision tended to improve with the multifocal IOL. This resulted in decreased spectacle dependence with use of the multifocal IOL. Adverse effects included reduced contrast sensitivity and the subjective experience of halos around lights. CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs. Whether that improvement outweighs the adverse effects of multifocal IOLs will vary between patients, with motivation to achieve spectacle independence likely to be the deciding factor.