Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older. OBJECTIVES: The objective of this review was to investigate the effects of anti-VEGF (vascular endothelial growth factor) modalities for treating neovascular AMD. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006, 2007 for ongoing trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We contacted trial authors for additional data. We summarized outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean differences. MAIN RESULTS: We included five RCTs of good methodological quality. All five trials were conducted by pharmaceutical companies. An intention-to-treat analysis using the last observation carried forward method was done in most trials. Two trials compared pegaptanib versus sham. One trial compared ranibizumab versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin PDT versus verteporfin PDT alone. Fewer patients treated with pegaptanib lost 15 or more letters of visual acuity at one year follow-up compared to sham (pooled relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for 1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13 (95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for 0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and 3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60). The NNT was 4.35 (95% CI 2.78 to 11.11). Pooled RR for gain of 15 or more letters visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab plus verteporfin PDT versus verteporfin PDT. Frequency of endophthalmitis in included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with pegaptanib. Improvement in vision-specific quality of life was reported for both treatments. AUTHORS' CONCLUSIONS: Pegaptanib and ranibizumab reduce the risk of visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in visual acuity in many eyes. Quality of life and cost will be important for treatment decisions. Other agents blocking VEGF are being tested in ongoing trials.

Surgical implantation of steroids with antiangiogenic characteristics for treating neovascular age-related macular degeneration.

BACKGROUND: Neovascular age-related macular degeneration (AMD) is associated with rapid vision loss due to choroidal neovascularization (CNV), leakage, and scarring. Steroids have gained attention in their role for the treatment of neovascular AMD for their antiangiogenic and anti-inflammatory properties. OBJECTIVES: This review aims to examine effects of steroids with antiangiogenic properties in the treatment of neovascular AMD. SEARCH STRATEGY: We searched for trials in CENTRAL, MEDLINE, EMBASE, and LILACS on 2 October 2006. SELECTION CRITERIA: We included randomised controlled clinical trials of intra- and peri-ocular steroids in people diagnosed with neovascular AMD. DATA COLLECTION AND ANALYSIS: Review authors extracted the data and assessed trial quality independently. We did not pool data since the included studies evaluated difference comparisons. MAIN RESULTS: We report the risk of losing three or more lines vision at 12 months - "vision loss". One trial (139 people randomized) reported that a single dose of intravitreal triamcinolone (n = 75) (4 mg) had no significant effect on the risk of vision loss compared to placebo (n = 76). (Risk ratio vision loss 0.97, 95% confidence interval (CI) 0.74 to 1.26). Eyes treated with triamcinolone were more likely to develop cataracts and experience increased intraocular pressure (IOP) compared to untreated eyes. One trial (128 people randomized) reported the effects of anecortave acetate (3 mg (n = 32), 15 mg (n = 33) or 30 mg (n = 33) single dose with retreatment every six months if indicated) compared to placebo (n = 30). Risk ratio vision loss 0.80 (95% CI 0.45 to 1.45) in the 3 mg group, 0.45 (95% CI 0.21 to 0.97) in the 15 mg group and 0.91 (95% CI 0.52 to 1.58) in the 30 mg group. Side effects were similar in all treatment groups with the anecortave group having a slightly higher incidence of foreign body sensation compared to placebo. There was a high loss to follow-up. The final analysis may have been subject to selection bias as participants who were not selected for retreatment, possibly with worsening disease, were excluded. There was also a possibility of type I error due to multiple statistical comparisons. The sample size was estimated on the basis of a single 2-way comparison but three 2-way comparisons were analysed and presented. One trial reported that anecortave acetate (n = 263) (15 mg administered at beginning of study and six months) gave similar results to photodynamic therapy (n = 267) (risk ratio vision loss 1.08, 95% CI 0.91 to 1.29). AUTHORS' CONCLUSIONS: Overall there is weak evidence as to the benefits and harms of steroids with antiangiogenic properties for treating neovascular AMD with only three published trials of variable quality. Intravitreal triamcinolone injection for neovascular AMD does not appear to prevent severe vision loss and is associated with increased IOP and higher risk of cataract formation. Anecortave acetate 15 mg may have a mild benefit in stabilizing vision, but further better quality evidence is needed. The role of steroids in combination with other treatment modalities is yet to be determined.

Topical corticosteroids as adjunctive therapy for bacterial keratitis.

BACKGROUND: Bacterial keratitis is a serious ocular infectious disease that can lead to severe visual disability. Risk factors for bacterial corneal infection include contact lens wear, ocular surface disease, corneal trauma and previous ocular or eyelid surgery. Topical antibiotics constitute the mainstay of treatment in cases of bacterial keratitis where as the use of topical corticosteroids remains controversial. Topical corticosteroids are usually used to control inflammation using the smallest amount of the drug. Their use requires optimal timing, concomitant antibiotics and careful follow up. OBJECTIVES: The objective of the review was to assess the clinical effectiveness and adverse effects of corticosteroids as adjunctive therapy for bacterial keratitis. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and LILACS up to 15 January 2007. We also searched the Science Citation Index to identify additional studies that had cited the included trial, an online database of ongoing trials (www.clinicaltrials.gov), reference lists of included trials, earlier reviews and the American Academy of Ophthalmology guidelines. We also contacted experts to identify any unpublished and ongoing randomized trials. SELECTION CRITERIA: We included randomized controlled trials evaluating adjunctive therapy with topical corticosteroids in people with bacterial keratitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all the retrieved articles. Methodological quality of the one included trial was assessed using forms developed using pre-specified criteria by at least two review authors. We planned to extract data on outcomes using forms developed for the purpose. We planned to report risk ratios for dichotomous outcomes and mean differences for continuous outcomes. MAIN RESULTS: A single trial was eligible for inclusion in the review. Participants in the trial were randomized using a random numbers table. Allocation concealment was not attempted. Masking of participants, and care-providers was also not attempted. Outcome assessment was conducted independently by two physicians. Neither was masked to the treatment allocation. The trial reported the healing rate of epithelial defects and improvement in visual acuity. AUTHORS' CONCLUSIONS: There are no good quality randomized trials evaluating the effects of adjunct use of topical corticosteroids in bacterial keratitis. The only randomized trial we identified in the literature suffered from major methodological inadequacies.

Corticosteroids for treating optic neuritis.

BACKGROUND: Optic neuritis is an inflammatory disease of the optic nerve. It occurs more commonly in women than in men. Usually presenting with an abrupt loss of vision, recovery of vision is almost never complete. Closely linked in pathogenesis to multiple sclerosis, it may be the initial manifestation for this condition. In certain patients, no underlying cause can be found. OBJECTIVES: To assess the effects of corticosteroids on visual recovery of patients with acute optic neuritis. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (issue 4, 2005), MEDLINE (1966 to December 2005), EMBASE (1980 to January 2006), NNR (issue 4, 2006), LILACS and reference lists of identified trial reports. SELECTION CRITERIA: We included randomized trials that evaluated corticosteroids, in any form, dose or route of administration, in people with acute optic neuritis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data on methodological quality and outcomes for analysis. MAIN RESULTS: We included five randomized trials which included a total of 729 participants. Two trials evaluated low dose oral corticosteroids and two trials evaluated a higher dose of intravenous corticosteroids. One three-arm trial evaluated low-dose oral corticosteroids and high-dose intravenous corticosteroids against placebo. Trials evaluating oral corticosteroids compared varying doses of corticosteroids with placebo. Hence, we did not conduct a meta-analysis of such trials. In a meta-analysis of trials evaluating corticosteroids with total dose greater than 3000 mg administered intravenously, the relative risk of normal visual acuity with intravenous corticosteroids compared with placebo was 1.06 (95% CI 0.89 to 1.27) at six months and 1.06 (95% CI 0.92 to 1.22) at one year. The risk ratio of normal contrast sensitivity for the same comparison was 1.10 (95% CI 0.92 to 1.32) at six months follow up. We did not conduct a meta-analysis for this outcome at one year follow up since there was substantial statistical heterogeneity. The risk ratio of normal visual field for this comparison was 1.08 (95% CI 0.96 to 1.22) at six months and 1.02 (95% CI 0.86 to 1.20) at one year. Quality of life was assessed and reported in one trial. AUTHORS' CONCLUSIONS: There is no conclusive evidence of benefit in terms of recovery to normal visual acuity, visual field or contrast sensitivity with either intravenous or oral corticosteroids at the doses evaluated in trials included in this review.

Interventions for stimulus deprivation amblyopia.

BACKGROUND: Stimulus deprivation amblyopia (SDA) develops due to an obstruction to the clear passage of light, preventing clear formation of an image on the retina for example, cataract, ptosis (droopy eyelid). It is particularly severe and can be resistant to treatment and the visual prognosis is often poor. Stimulus deprivation amblyopia is rare and precise estimates of prevalence difficult to come by; it probably constitutes less than 3% of all cases of amblyopia. In developed countries most patients present under the age of one; in less developed parts of the world presentation is likely to be significantly later than this.The mainstay of treatment is patching of the better-seeing eye but regimes vary, treatment is difficult to execute and results are often disappointing. OBJECTIVES: The objectives of this review were to evaluate the effectiveness of occlusion treatment for SDA, determine the optimum treatment regime and factors that may affect outcome. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (2006, Issue 1), MEDLINE (1996 to April 2006), EMBASE (1980 to April 2006) and LILACS (Latin American and Caribbean Literature on Health Sciences) (to November 2004). There were no date or language restrictions. SELECTION CRITERIA: We aimed to include randomised and quasi-randomised controlled trials of subjects with unilateral SDA defined as worse than 0.2 LogMAR or equivalent. There were no restrictions with respect to age, gender, ethnicity, co-morbidities, medication use, and the number of participants. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study abstracts identified by the electronic searches. MAIN RESULTS: No trials were identified that met the inclusion criteria. AUTHORS' CONCLUSIONS: It is not possible to conclude how effective treatment for SDA is or which treatment regime produces the best results. There is a need for further study in this area.

Lens extraction for chronic angle-closure glaucoma.

BACKGROUND: Angle-closure glaucoma is characterized by obstruction to the outflow of aqueous humor and consequent rise in intraocular pressure. The obstruction may result from an anatomical predisposition of the eye or may be due to pathophysiologic processes in any part of the eye. The former is considered the primary form and the latter a secondary form of angle closure. Relative pupillary block obstructing free flow of aqueous from the posterior chamber of the eye to the anterior chamber is considered to be the most common mechanism of angle closure. Crowding of the angle is another mechanism, which often coexists with pupillary block. This can result from an anterior placement of the lens due to an increase in the thickness of the lens (as occurs with aging), anterior displacement by a posterior force (for example choroidal effusion), or laxity of the zonules. OBJECTIVES: The objective of this review was to assess the effectiveness of lens extraction for chronic primary angle-closure glaucoma compared with other interventions for the condition in people without past history of acute-angle closure attacks. SEARCH STRATEGY: We searched CENTRAL (2005, Issue 3), MEDLINE (1950 to April 2006), EMBASE (1980 to April 2006), and LILACS (to August 2005). We searched the reference lists of included studies and used the Science Citation Index database. SELECTION CRITERIA: In the absence of any randomized trials we included non-randomized studies comparing lens extraction with other treatment modalities for chronic primary angle-closure glaucoma including, but not limited to, laser iridotomy, medications, and laser iridoplasty. We excluded studies with a case-series design. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on methodological quality of the included studies, outcomes for the review, and study characteristics including participant characteristics, interventions, and sources of funding. Differences were resolved through discussion. MAIN RESULTS: We found no randomized trials evaluating the effects of lens extraction as a treatment for chronic primary angle-closure glaucoma. Two non-randomized comparative studies included in the review have several methodological flaws including selection bias. While these studies and other non-comparative studies provide information on biological plausibility and treatment effect they do not provide proof of effectiveness. Also, they do not address the question of how primary lens extraction compares with other treatments for chronic primary angle-closure glaucoma. AUTHORS' CONCLUSIONS: There is no evidence from good quality randomized trials or non-randomized studies of the effectiveness of lens extraction for chronic primary angle-closure glaucoma.

Aqueous shunts for glaucoma.

BACKGROUND: Aqueous shunts are employed for intraocular pressure (IOP) control in primary and secondary glaucomas that fail medical, laser, and other surgical therapies. OBJECTIVES: This review compares aqueous shunts for IOP control and safety. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, EMBASE, NRR all in January 2006, LILACS to February 2004 and reference lists of included trials. SELECTION CRITERIA: We included all randomized and quasi-randomized trials in which one arm of the study involved shunts. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for included studies and a third adjudicated discrepancies. We contacted investigators for missing information. We used fixed-effect models and summarized continuous outcomes using mean differences. MAIN RESULTS: We included fifteen trials with a total of 1153 participants with mixed diagnoses. Five studies reported details sufficient to verify the method of randomization but only two had adequate allocation concealment. Data collection and follow-up times were variable.Meta-analysis of two trials comparing Ahmed implant with trabeculectomy found trabeculectomy resulted in lower mean IOPs 11 to 13 months later (mean difference 3.81 mm Hg, 95% CI 1.94 to 5.69 mm Hg). Meta-analysis of two trials comparing double-plate Molteno implant with the Schocket shunt was not done due to substantial heterogeneity. One study comparing ridged with standard double-plate Molteno implants found no clinically significant differences in outcome. Two trials investigating the effectiveness of adjunctive mitomycin (MMC) with the Molteno and Ahmed implants found no evidence of benefit with MMC. Two trials that investigated surgical technique variations with the Ahmed found no benefit with partial tube ligation or excision of Tenon's capsule. One study concluded there were outcome advantages with a double versus a single-plate Molteno implant and one trial comparing the 350 mm(2) and 500 mm(2) Baerveldt shunts found no clinically significant advantage of the larger device but neither of these trials included all patients randomized. One study suggested improved clinical outcome when MMC was employed with a newly described shunt including ultrasound supporting the conclusion. One small study did not demonstrate an outcome advantage to systemic steroid use postoperatively with single-plate Molteno shunts. One study comparing endocyclophotocoagulation (ECP) with Ahmed implant in complicated glaucomas found no evidence of better IOP control with Ahmed implant over ECP. AUTHORS' CONCLUSIONS: Relatively few randomized trials have been published on aqueous shunts and methodology and data quality among them is poor. To date there is no evidence of superiority of one shunt over another.