PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (635558)

Clipboard (0)
None

Related Articles

1.  Anti-vascular endothelial growth factor for neovascular age-related macular degeneration 
Background
Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision.
Objectives
To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens.
Search methods
We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014.
Selection criteria
We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year.
Data collection and analysis
Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We analyzed outcomes as risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by The Cochrane Collaboration.
Main results
We included 12 RCTs including a total of 5496 participants with neovascular AMD (the number of participants per trial ranged from 28 to 1208). One trial compared pegaptanib, three trials ranibizumab, and two trials bevacizumab versus controls; six trials compared bevacizumab with ranibizumab. Four trials were conducted by pharmaceutical companies; none of the eight studies which evaluated bevacizumab were funded by pharmaceutical companies. The trials were conducted at various centers across five continents (North and South America, Europe, Asia and Australia). The overall quality of the evidence was very good, with most trials having an overall low risk of bias.
When compared with control treatments, participants who received any of the three anti-VEGF agents were more likely to have gained 15 letters or more of visual acuity, lost fewer than 15 letters of visual acuity, and had vision 20/200 or better after one year of follow up. Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same regimens were compared in the same RCTs, despite the substantially lower cost for bevacizumab compared with ranibizumab. No trial directly compared pegaptanib with other anti-VEGF agents; however, when compared with controls, ranibizumab or bevacizumab yielded larger improvements in visual acuity outcomes than pegaptanib.
Participants treated with anti-VEGFs showed improvements in morphologic outcomes (e.g., size of CNV or central retinal thickness) compared with participants not treated with anti-VEGF agents. There was less reduction in central retinal thickness among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD −13.97 μm; 95% confidence interval (CI) −26.52 to −1.41); however, this difference is within the range of measurement error and we did not interpret it as being clinically meaningful.
Ocular inflammation and increased intraocular pressure after intravitreal injection were the most frequently reported serious ocular adverse events. Endophthalmitis was reported in fewer than 1% of anti-VEGF treated participants; no cases were reported in control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to detect a meaningful difference between groups. Data for visual function, quality of life, and economic outcomes were sparsely measured and reported.
Authors’ conclusions
The results of this review indicate the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; ranibizumab and bevacizumab were also shown to improve visual acuity. The information available on the adverse effects of each medication do not suggest a higher incidence of potentially vision-threatening complications with intravitreal injection compared with control interventions; however, clinical trial sample sizes may not have been sufficient to detect rare safety outcomes. Research evaluating variable dosing regimens with anti-VEGF agents, effects of long-term use, combination therapies (e.g., anti-VEGF treatment plus photodynamic therapy), and other methods of delivering the agents should be incorporated into future Cochrane reviews.
doi:10.1002/14651858.CD005139.pub3
PMCID: PMC4270425  PMID: 25170575
Angiogenesis Inhibitors [*therapeutic use]; Antibodies, Monoclonal [therapeutic use]; Antibodies, Monoclonal, Humanized, Aptamers, Nucleotide [therapeutic use]; Choroidal Neovascularization; Macular Degeneration [*drug therapy]; Porphyrins [therapeutic use]; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A [*antagonists & inhibitors]; Aged; Humans; Middle Aged
2.  Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial 
The British Journal of Ophthalmology  2008;92(12):1606-1611.
Aims:
To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD).
Methods:
Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3.
Results:
As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment.
Conclusion:
The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.
doi:10.1136/bjo.2007.132597
PMCID: PMC2584239  PMID: 18614570
3.  Pegaptanib sodium treatment in neovascular age-related macular degeneration: clinical experience in Germany 
Background
The VEGF Inhibition Study In Ocular Neovascularisation (VISION) reported the efficacy of intravitreal (ITV) vascular endothelial growth factor (VEGF) inhibition with pegaptanib sodium (Macugen®) for the treatment of neovascular age-related macular degeneration (AMD). This paper reports clinical experience with pegaptanib sodium for the treatment of occult or minimally classic choroidal neovascularization (CNV) due to AMD.
Material and methods
The study included 50 eyes (in 49 patients) with either occult CNV or minimally classic CNV secondary to neovascular AMD who were not eligible for photodynamic therapy (PDT). Study data were analyzed retrospectively. During the 6-month study, patients were administered an average 2.74 injections of 0.3 mg ITV pegaptanib sodium. Angiography and optical coherence tomography (OCT) examinations were carried out and intraocular pressure (IOP) and visual acuity (VA) were measured at baseline, at 3 months and at 6 months. An eye examination was performed and VA was measured the 2 days following treatment and then again at weeks 4–6, and at 3 and 6 months. OCT, VA, and IOP were also assessed at 1 month.
Results
ITV pegaptanib sodium was well tolerated and no treatment complications arose. Mean VA was measured as: 0.37 ± 0.24 at baseline; 0.37 ± 0.25 at 1 month; 0.37 ± 0.25 at 3 months and 0.40 ± 0.26 at 6 months. VA was stabilized in approximately 90% of eyes treated with pegaptanib sodium. OCT examination showed a minimal change in central retinal thickness (CRT) during the course of the study, from 251.19 μm at baseline to 251.63 μm at 6 months. No elevation in IOP was measured during treatment at 4–6 months in patients receiving pegaptanib sodium.
Conclusions
ITV therapy with pegaptanib sodium for occult and minimally classic CNV secondary to neovascular AMD offered good efficacy with a favorable adverse events profile. The majority of patients showed stabilization in all assessed parameters. In clinical practice, careful consideration should be given to the use of nonselective VEGF inhibition in patients with a high cardiovascular risk profile or in those with a history of thromboembolic events.
PMCID: PMC2693993  PMID: 19668713
Intravitreal (ITV) injection; age-related macular degeneration (AMD); choroidal neovascularization (CNV); anti-VEGF therapy; pegaptanib sodium
4.  Pegaptanib and ranibizumab for neovascular age‐related macular degeneration: a systematic review 
The British Journal of Ophthalmology  2007;91(9):1177-1182.
Aims
To assess the clinical effectiveness of pegaptanib sodium and ranibizumab for neovascular age‐related macular degeneration (AMD).
Methods
A systematic review of randomised controlled trials (RCTs) identified through searching 12 electronic databases, bibliographies and consultation with experts and manufacturers. RCTs were eligible if they assessed the effects of pegaptanib or ranibizumab with best supportive care, sham injection or photodynamic therapy (PDT) on patients with subfoveal choroidal neovascularisation associated with wet AMD and examined outcomes including visual acuity and adverse events.
Results
Three RCTs of ranibizumab (MARINA, ANCHOR, FOCUS) and two of pegaptanib (VISION study) met the inclusion criteria. The RCTs included patients with different lesion types. The studies showed statistically significant benefit on different measures of visual acuity for patients receiving pegaptanib, ranibizumab or ranibizumab with PDT compared to control (sham injection, PDT or sham injection with PDT) after 12 months. These differences appeared to be clinically significant. Although adverse events were common among those receiving pegaptanib or ranibizumab, they were considered mild to moderate in nature. Meta‐analysis of ranibizumab trials and indirect comparison of the two drugs were not possible due to differences in the study populations' lesion types. However, results from the RCTs of ranibizumab tended to show a greater effect on visual acuity than results from the RCT of pegaptanib.
Conclusions
Pegaptanib and ranibizumab appear to slow or stop the progression of neovascular AMD. Uncertainty remains over the relative benefits of pegaptanib compared with ranibizumab and other unlicensed drugs (eg, Avastin), due to the nature of the evidence. Head‐to‐head RCTs and economic evaluations comparing these alternatives are needed.
doi:10.1136/bjo.2007.118562
PMCID: PMC1954893  PMID: 17475698
5.  A protocol for the retina surgeon’s safe initial intravitreal injections 
Purpose
To determine the safety of a surgeon’s initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure.
Design
A retrospective chart review.
Participants
Fifty-nine patients (30 females, 29 males) received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections.
Methods
The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab) were reviewed. All injections were performed in an office-based setting. Povidone–iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection.
Main outcome measures
Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage.
Results
There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections.
Conclusion
The incidence of serious complications was very low for the intravitreal injections given. A surgeon’s initial intravitreal injections may be performed with a very high degree of safety using this protocol.
doi:10.2147/OPTH.S12846
PMCID: PMC2994216  PMID: 21139676
intravitreal injection; post injection complications; intraocular disease; age-related macular degeneration; bevacizumab; endophthalmitis; pegaptanib; ranibizumab
6.  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.
doi:10.1002/14651858.CD005139.pub2
PMCID: PMC4267250  PMID: 18425911
Angiogenesis Inhibitors [*therapeutic use]; Antibodies; Monoclonal [therapeutic use]; Aptamers; Nucleotide [therapeutic use]; Choroidal Neovascularization; Macular Degeneration [*drug therapy]; Porphyrins [therapeutic use]; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A [*antagonists & inhibitors]; Aged; Humans; Middle Aged
7.  Pegaptanib sodium for ocular vascular disease 
Indian Journal of Ophthalmology  2007;55(6):427-430.
Pegaptanib sodium (MacugenTM) is a selective RNA aptamer that inhibits vascular endothelial growth factor (VEGF) 165 , the VEGF isoform primarily responsible for pathologic ocular neovascularization and vascular permeability, while sparing the physiological isoform VEGF 121 . After more than 10 years in development and preclinical study, pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration. Its excellent ocular and systemic safety profile has also been confirmed in patients receiving up to three years of therapy. Early, well-controlled studies further suggest that pegaptanib may provide therapeutic benefit for patients with diabetic macular edema, proliferative diabetic retinopathy and retinal vein occlusion. Notably, pegaptanib was the first available aptamer approved for therapeutic use in humans and the first VEGF inhibitor available for the treatment of ocular vascular diseases.
PMCID: PMC2635976  PMID: 17951898
Age-related macular degeneration; aptamer; diabetic macular edema; pegaptanib; vascular endothelial growth factor
8.  Newly diagnosed exudative age-related macular degeneration treated with pegaptanib sodium monotherapy in US community-based practices: medical chart review study 
BMC Ophthalmology  2010;10:2.
Background
Studies have shown that early detection and treatment of neovascular age-related macular degeneration (NV-AMD) can delay vision loss and blindness. The objective of this study was to evaluate the efficacy/safety of intravitreal pegaptanib sodium monotherapy in treatment-naïve subjects with newly diagnosed NV-AMD and to gain insight into characteristics of lesions treated in community-based practices.
Methods
From seven private US practices, charts were retrospectively reviewed on 73 subjects with previously untreated subfoveal choroidal NV-AMD treated with their first dose of pegaptanib monotherapy on/after 4/1/2005 through 6/5/2006, receiving ≥4 treatments at 6-week intervals over 21 weeks. Primary endpoint: mean visual acuity (VA) change from baseline to month 6.
Results
75% of lesions were occult, and 82% were subfoveal. From baseline to month 6, mean VA change was -0.68 lines; 58% and 16% gained ≥0 and ≥3 lines of VA, and 70% were responders (<3 lines lost). In 35 subjects with early disease, 80% were responders with a mean gain of 0.46 lines.
Conclusion
Pegaptanib is effective in real-world patients with treatment-naïve NV-AMD in uncontrolled community-based retina practices.
doi:10.1186/1471-2415-10-2
PMCID: PMC2836307  PMID: 20144224
9.  Clinical experience with pegaptanib sodium 
Pegaptanib sodium (Macugen®) blocks the extracellular vascular endothelial growth factor (VEGF) isoform VEGF165, whose elevated levels are associated with the development of choroidal neovascularization (CNV). This selective inhibition prevents binding to the VEGF receptors and the development of the increased vascular permeability and the CNV associated with neovascular age-related degeneration (AMD). The VEGF Inhibition Study In Ocular Neovascularization (VISION) demonstrated that pegaptanib sodium confers clinically meaningful benefit in the treatment of all angiographic subtypes of neovascular AMD. It also has a favorable safety profile after 1 and 2 years of continuous treatment, and recent data suggest that the agent has a disease-modifying effect. Post hoc analysis of VISION suggests that treatment benefit may be greatest in patients with early lesions, in whom 80% achieved the primary endpoint of <15 letters lost, 47% maintained visual acuity (VA), and 20% gained ≥15 letters of vision. Similarly, our own clinical experience indicates that pegaptanib sodium achieves better outcomes in early lesions than in established lesions, particularly in patients with previously untreated minimally classic and occult lesions in whom VA improvement and lesion size stabilization has been recorded. Observations indicate that pegaptanib sodium has a slower mode of action than unselective VEGF inhibitors, resulting in an average of 3–4 injections being required to stabilize VA and lesion size. Pegaptanib sodium has good efficacy and safety profiles and represents a good treatment option for patients with early CNV membranes associated with neovascular AMD.
PMCID: PMC2694030  PMID: 19668746
vascular endothelial growth factor (VEGF); choroidal neovasularization (CNV); age-related macular degeneration (AMD); pegaptanib sodium; early lesions; visual acuity (VA)
10.  The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology 
Mayo Clinic Proceedings  2012;87(1):77-88.
Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.
doi:10.1016/j.mayocp.2011.10.001
PMCID: PMC3498409  PMID: 22212972
11.  Pegaptanib in the treatment of wet, age-related macular degeneration 
Age-related macular degeneration (AMD) is a major cause of severe visual loss worldwide. Neovascular (wet) AMD accounts for 90% of the visual loss associated with the disorder and vascular endothelial growth factor (VEGF) has been shown to play a major role in neovascularization and vascular permeability, the major causes of visual loss in AMD, making it an ideal target for therapeutic intervention. To utilize this strategy, pegaptanib, an aptamer that specifically binds to and blocks VEGF165, the VEGF isoform primarily responsible for abnormal vascular growth and permeability in AMD, was developed. Following encouraging preclinical trials, clinical trials showed that pegaptanib stabilized vision and reduced the risk of severe visual loss in the majority of patients with AMD, with some patients showing visual improvement. Pegaptanib has maintained a good safety profile with only occasional adverse effects. Even greater success was achieved when pegaptanib was used in combination with another therapeutic strategy, such as photodynamic therapy or bevacizumab, a pan isoform VEGF inhibitor. Further investigation of pegaptanib for the therapy of wet AMD, particularly in combination with other modes of therapy, should be encouraged.
PMCID: PMC2426796  PMID: 17717967
age-related macular degeneration; pegaptanib; vascular endothelial growth factor; choroidal neovascularization; macular edema
12.  An open-label, one-year, noncomparative study to evaluate the safety and tolerability of intravitreal pegaptanib sodium in patients with diabetic macular edema 
Background
The purpose of this study was to evaluate the safety and tolerability of pegaptanib in patients with diabetic macular edema.
Methods
An open-label, multicenter, noncomparative, one-year study of approximately 500 patients was planned. Recruitment was terminated after enrollment of 46 patients. Enrolled patients were fully informed and reconsented; 12 patients elected to complete the study. Patients received intravitreal injections of pegaptanib 0.3 mg once every 6 weeks or less frequently, as determined by the investigator. Clinical benefit was evaluated after the patient received two or more injections. Ocular and nonocular adverse events were closely monitored throughout the study.
Results
Compared with baseline, mean best-corrected visual acuity increased by week 6. Ten patients reported ocular-related adverse events, none of which were severe, and eight patients reported nonocular adverse events, two of which were severe but unrelated to study treatment. Three serious adverse events, unrelated to study treatment, were reported.
Conclusion
In this limited set of patients with diabetic macular edema, pegaptanib appeared to be well tolerated with evidence of efficacy.
doi:10.2147/OPTH.S68498
PMCID: PMC4149402  PMID: 25187694
pegaptanib; diabetic macular edema; safety; tolerability
13.  Diabetic retinopathy (treatment) 
Clinical Evidence  2011;2011:0702.
Introduction
Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia being most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with diabetic retinopathy? What are the effects of treatments for vitreous haemorrhage? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: peripheral retinal laser photocoagulation, focal and grid laser photocoagulation for maculopathy, corticosteroids for macular oedema, vascular endothelial growth factor inhibitors, and vitrectomy for vitreous haemorrhage.
Key Points
Diabetic retinopathy is the most common cause of blindness in the UK, with older people and those with worse diabetes control, hypertension, and hyperlipidaemia most at risk. Diabetic retinopathy can cause microaneurysms, haemorrhages, exudates, changes to blood vessels, and retinal thickening.
Peripheral retinal laser photocoagulation reduces the risk of severe visual loss compared with no treatment in people with preproliferative (moderate/severe non-proliferative) retinopathy and maculopathy. We don't know if any one type of laser treatment is superior to another.We don't know whether peripheral laser photocoagulation is effective in people with background or preproliferative (non-proliferative) retinopathy without maculopathy because we found no RCTs assessing it in this population.
The benefits of laser photocoagulation are more notable in people with proliferative retinopathy than in those with maculopathy. Focal macular laser photocoagulation reduces the risk of moderate visual loss in eyes with clinically significant macular oedema plus mild to moderate preproliferative (moderate/severe non-proliferative) diabetic retinopathy, compared with no treatment. Grid photocoagulation to zones of retinal thickening may improve visual acuity in eyes with diffuse maculopathy. Photocoagulation is unlikely to be beneficial in eyes with maculopathy but without clinically significant macular oedema.
Intravitreal triamcinolone acetonide improves visual acuity and reduces macular thickness in eyes with macular oedema refractory to previous macular laser photocoagulation, but repeated injections are needed to maintain benefit. Secondary ocular hypertension and progression of cataract are common complications with intravitreal triamcinolone; infectious endophthalmitis is rare.
Intravitreal vascular endothelial growth factor (VEGF) inhibitors pegaptanib and bevacizumab improve visual acuity and reduce macular thickness in eyes with centre-involving diabetic macular oedema and vision loss, but repeat intravitreal injections are needed to maintain benefit. Bevacizumab is not licensed for intraocular use.We don't know the long-term ocular and systemic safety of bevacizumab.We don't know if any one intravitreal VEGF inhibitor or treatment regimen is superior to another.We don't know whether combination treatment with VEGF inhibitor injection plus macular laser photocoagulation is effective as we found only one trial assessing ranibizumab as part of combined treatment.
Vitrectomy can reduce visual loss if performed early in people with vitreous haemorrhage, especially if they have severe proliferative retinopathy. We don't know whether vitrectomy is effective in people with vitreous haemorrhage plus maculopathy as we found no RCTs assessing it.
PMCID: PMC3217806  PMID: 21609511
14.  Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration 
American journal of ophthalmology  2011;152(2):266-272.
Purpose
To determine longitudinal rates of ocular complications after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD) in a nationally representative longitudinal sample.
Design
retrospective, longitudinal case-control study.
Methods
Using the Medicare 5% claims database, diagnoses of neovascular AMD and anti-VEGF injections of ranibizumab, bevacizumab, or pegaptanib were identified from International Classification of Diseases (ICD-9-CM) and Current Procedural Terminology (CPT) procedure codes. 6,154 individuals undergoing anti-VEGF treatment for neovascular AMD (total of 40,903 injections) were compared with 6,154 matched controls with neovascular AMD who did not undergo anti-VEGF treatment. Propensity score matching was used to match individuals receiving anti-VEGF injections with controls. Rates of post-injection adverse outcomes (endophthalmitis, rhegmatogenous retinal detachment, retinal tear, uveitis, and vitreous hemorrhage) were analyzed by cumulative incidence and Cox proportional hazards model to control for demographic factors and ocular comorbidities.
Results
At 2-year follow-up, the rates of endophthalmitis per injection (0.09%; p<0.01), uveitis (0.11%; p<0.01), and vitreous hemorrhage per injection (0.23%; p<0.01) were significantly higher in the anti-VEGF treatment group. With Cox proportional hazards modeling, the anti-VEGF treatment group had an 102% higher risk of severe ocular complications overall, and a 4% increased risk per injection, both of which were statistically significant (p<0.01)
Conclusions
Rates of endophthalmitis, uveitis, and vitreous hemorrhage were higher in the group treated with anti-VEGF injection than in the control group, though nevertheless rare in both groups. The overall risk of severe ocular complications was significantly higher in the anti-VEGF treatment group.
doi:10.1016/j.ajo.2011.01.053
PMCID: PMC3143287  PMID: 21664593
15.  Treatment of retinal pigment epithelial detachment with antiangiogenic therapy 
Purpose
Evaluate the efficacy of pegaptanib, a selective anti-vascular endothelial growth factor (VEGF) agent, and bevacizumab, a nonselective anti-VEGF agent, for retinal pigment epithelial detachment (PED) associated with occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
Methods
Prospective, comparative, nonrandomized pilot study included patients with PED comprising >50% of total lesion in subfoveal location with visual acuity (VA) 20/40–20/400 and lesions either previously untreated or treated only with photodynamic therapy/verteporfin. Seven patients received pegaptanib 0.3 mg intravitreally (IVT); eight received IVT bevacizumab 1.25 mg. Follow-up occurred every 4–6 weeks for 6 months. Reinjection of initial medication occurred if there was intra- or subretinal fluid observed by optical coherence tomography (OCT) or increased PED. Endpoints were mean changes from baseline to month 6 in VA (ETDRS) and foveal thickness.
Results
At baseline, mean VA was lower, and mean foveal thickness was greater in pegaptanib versus bevacizumab-treated patients (36.1 vs 49.5 letters; 470.4 vs 321.1 μm). Mean improvements to month 6 in VA and foveal thickness were greater for pegaptanib (VA: +9.1 vs +7.2 letters; foveal thickness: −88.2 vs −52.9 μm). On average, pegaptanib-treated patients had slower but more sustained improvement in VA and foveal thickness; bevacizumab-treated patients showed rapid improvement with a slow return towards baseline. Both agents were well tolerated.
Conclusion
Intravitreal injections of pegaptanib or bevacizumab are both efficacious and safe treatments for PED associated with occult CNV secondary to AMD.
PMCID: PMC2861946  PMID: 20463807
bevacizumab; pegaptanib; retinal pigment epithelial detachment
16.  Pegaptanib Sodium versus Pegaptanib Sodium Combined with Macular Laser Photocoagulation or Laser Alone for Diabetic Macular Edema 
Journal of Ophthalmology  2010;2009:672178.
Purpose. To report the outcomes after primary intravitreal pegaptanib sodium in patients with diabetic macular edema (DME). Methods. We conduced a retrospective analysis of eyes with DME treated with primary intravitreal pegaptanib sodium (Macugen) (intravitreal pegaptanib group). The results were compared with the ones of eyes treated with intravitreal pegaptanib sodium associated with macular laser photocoagulation (combined treatment group), and the ones of eyes treated with primary macular laser photocoagulation (macular laser photocoagulation group). Results. For the intravitreal pegaptanib group (13 eyes), we found significant changes in mean best-corrected visual acuity (BCVA) and reductions in mean central macular thickness (CMT) at the last follow-up visit (P = .0014 and P = .0001). For the macular laser photocoagulation group (15 eyes), we found no statistically significant changes in mean BCVA and CMT at the last follow-up visit (P > .05). For the combined treatment group (12 eyes), we found no significant changes in mean BCVA at the last follow-up visit (P > .05) despite significant reductions in mean CMT (P = .0188). Conclusion. Intravitreal pegaptanib treatment alone may be superior to macular laser photocoagulation alone and to combined intravitreal pegaptanib treatment associated with macular laser photocoagulation in patients with DME.
doi:10.1155/2009/672178
PMCID: PMC2836737  PMID: 20339449
17.  Current treatments in diabetic macular oedema: systematic review and meta-analysis 
BMJ Open  2013;3(3):e002269.
Objectives
The aim of this systematic review is to appraise the evidence for the use of anti-VEGF drugs and steroids in diabetic macular oedema (DMO) as assessed by change in best corrected visual acuity (BCVA), central macular thickness and adverse events
Data source
MEDLINE, EMBASE, Web of Science with Conference Proceedings and the Cochrane Library (inception to July 2012). Certain conference abstracts and drug regulatory web sites were also searched.
Study eligibility criteria, participants and interventions
Randomised controlled trials were used to assess clinical effectiveness and observational trials were used for safety. Trials which assessed triamcinolone, dexamethasone, fluocinolone, bevacizumab, ranibizumab, pegaptanib or aflibercept in patients with DMO were included.
Study appraisal and synthesis methods
Risk of bias was assessed using the Cochrane risk of bias tool. Study results are narratively described and, where appropriate, data were pooled using random effects meta-analysis.
Results
Anti-VEGF drugs are effective compared to both laser and placebo and seem to be more effective than steroids in improving BCVA. They have been shown to be safe in the short term but require frequent injections. Studies assessing steroids (triamcinolone, dexamethasone and fluocinolone) have reported mixed results when compared with laser or placebo. Steroids have been associated with increased incidence of cataracts and intraocular pressure rise but require fewer injections, especially when steroid implants are used.
Limitations
The quality of included studies varied considerably. Five of 14 meta-analyses had moderate or high statistical heterogeneity.
Conclusions and implications of key findings
The anti-VEGFs ranibizumab and bevacizumab have consistently shown good clinical effectiveness without major unwanted side effects. Steroid results have been mixed and are usually associated with cataract formation and  intraocular pressure increase. Despite the current wider spectrum of treatments for DMO, only a small proportion of patients recover good vision (≥20/40), and thus the search for new therapies needs to continue.
doi:10.1136/bmjopen-2012-002269
PMCID: PMC3612765  PMID: 23457327
Ophthalmology
18.  Bilateral same-session intravitreal injections of anti-vascular endothelial growth factors 
AIM
To document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.
METHODS
A retrospective case series study. Consecutive records of seventy four patients receiving simultaneous bilateral intravitreal injections of either ranibizumab or bevacizumab, between September 2010 and September 2013, were reviewed and the outcomes were assessed. Data collected included number of injections, indications for injections, pre-injection and post-injection visual acuity (VA), pre-injection and post-injection intraocular pressure and ocular and systemic complications/complaints after each injection.
RESULTS
A total of 342 injections were administered to 74 patients, with a mean of 4.62 injections per patient. Seventy-three patients received bevacizumab (Avastin; Genentech Inc., South San Francisco, California, USA) alone, and only one patient received both bevacizumab and ranibizumab (Lucentis; Genentech Inc.) distributed between the injections. Pre- and post-injection VA follow-up measurements were available for 65 patients. Mean follow up period was 22mo. The indications for initiating therapy were choroidal neovascular membrane from age-related macular degeneration (3 patients) and diabetic macular edema (71 patients). The mean Snellen VA before each injection was 6/22. The next post-injection follow-up mean Snellen VA was 6/20. One patient had a painful, culture-positive endophthalmitis in one eye 3d after bilateral bevacizumab. Another patient had a painless subconjunctival hemorrhage in one eye. No other ocular or systemic adverse side effects/complaints have been registered in this study group.
CONCLUSION
Bilateral same-session intravitreal injections using a separate povidone-iodine preparation, speculum, needle, and syringe for each eye are well-tolerated. None of the subjects in this study requested to switch to alternating unilateral injections. Proper patient counseling as to the risk of complications with this procedure is necessary.
doi:10.3980/j.issn.2222-3959.2014.06.20
PMCID: PMC4270969  PMID: 25540758
anti-vascular endothelial growth factor; diabetic macular edema; age-related macular degeneration; endophthalmitis; visual acuity
19.  Pegaptanib sodium for neovascular age-related macular degeneration: clinical experience in the UK 
The pathogenesis of age-related macular degeneration (AMD) is unclear, but it can take either a neovascular/exudative/wet form, characterized by choroidal neovascularization (CNV), or a dry form. No treatments are available for the dry form, but there are a number of pharmacological interventions that inhibit vascular endothelial growth factor (VEGF), which is central to the pathogenesis of CNV and neovascular AMD. Available anti-VEGF agents either target all active VEGF isoforms (eg, ranibizumab), or take a more selective approach and inhibit only VEGF165 (eg, pegaptantib sodium). Current guidance on their use is equivocal and restrictive at best, resulting in associated difficulties in securing adequate, timely funding for treatment. The Moorfields Eye Hospital undertook an audit of 70 patients receiving intravitreal (ITV) pegaptanib sodium on a pro re nata (prn) dosing schedule. Despite initial funding delays, the audit recorded superior treatment outcomes compared with those reported in the VISION trials at 12 weeks: 88% of audit patients maintained stable vision, 29% gained vision and 6% experienced severe vision loss compared with 70%, ≥6% and ≤10% of patients in VISION at 54 weeks, respectively. The audit indicates a positive correlation between patients with better baseline visual acuity (VA) and improved therapeutic benefits, including a greater likelihood of both vision gain and vision preservation. Experience at Moorfields also suggests that pegaptanib sodium is more useful in occult lesions than minimally classic lesions, and clinical experience suggests that combination therapies may offer the best approach with anti-VEGF therapies. Further randomized clinical trials will help better determine the optimal treatment strategies with pegaptanib sodium in neovascular AMD.
PMCID: PMC2693996  PMID: 19668726
age-related macular degeneration; choroidal neovascularization; vascular endothelial growth factor; pegaptanib sodium; visual outcomes; funding
20.  Role of pegaptanib sodium in the treatment of neovascular age-related macular degeneration 
Age-related macular degeneration (AMD) is responsible for more than half the blind registration in the United Kingdom. Retinal manifestations of AMD can be categorized as either atrophic or neovascular. The hallmark of AMD is the development of choroidal neovascularization (CNV). Until recently, there have been few, limited treatment modalities (eg, photodynamic therapy [PDT]) for this condition and the mainstay of treatment has comprised social and lifestyle support. However, increased understanding of the molecular processes at work in neovascular AMD and CNV in recent years has led to the introduction of new anti-angiogenic agents that target vascular endothelial growth factor (VEGF). These agents either inhibit a selected VEGF isoform (eg, VEGF165 inhibition by pegaptanib sodium) or inhibit all forms of the VEGF isoform (eg, non-selective VEGF blockade by ranibizumab). The trial data suggest that non-selective inhibition of VEGF offers better treatment outcomes in neovascular AMD. As a result, agents that inhibit all VEGF isoforms are now widely used as first-line therapy for this condition. However, it is known that VEGF plays an important role in maintaining the intergrity of the cardiovascular system and, particularly as the age of patients with AMD places them at an elevated risk of thromboembolic events, long-term post-marketing surveillance data are essential to determining whether non-selective VEGF blockade confers any increased risk. Theoretically, selective VEGF inhibition may reduce any risk associated with pan-VEGF blockade, yet on the basis of initial trials, their use remains more limited at this time. However, clinical practice suggests that initial trials may have under-estimated the efficacy of selective-VEGF inhibition. Observational studies also indicate that better treatment outcomes may be possible by combining VEGF inhibitors sequentially with each other, or with existing therapies (eg, photodynamic therapy [PDT]). The optimum role and indications of anti-VEGF agents will come through careful consideration of the available efficacy and safety data, from the outcomes of long-term follow-up studies, and through assessment of the relative merits of the two approaches to VEGF inhibition in clinical practice. At this time, further head-to-head trials, and economic evaluations, comparing the treatment alternatives are needed.
PMCID: PMC2693972  PMID: 19668725
age-related macular degeneration (AMD); choroidal neovascularization (CNV); vascular endothelial growth factor (VEGF); cardiovascular; ranibizumab; pegaptanib sodium
21.  Recombinant Human VEGF165b Inhibits Experimental Choroidal Neovascularization 
The alternative splice form of VEGF, VEGF-A165b, inhibits choroidal neovascularization at very low doses in mice, indicating that it may be an effective therapy for age-related macular degeneration, comparable with or better than existing anti-VEGF therapy.
Purpose.
Vascular endothelial growth factor (VEGF-A) is the principal stimulator of angiogenesis in wet age-related macular degeneration (AMD). However, VEGF-A is generated by alternate splicing into two families, the proangiogenic VEGF-Axxx family and the antiangiogenic VEGF-Axxxb family. It is the proangiogenic family that is responsible for the blood vessel growth seen in AMD.
Methods.
To determine the role of antiangiogenic isoforms of VEGF-A as inhibitors of choroidal neovascularization, the authors used a model of laser-induced choroidal neovascularization in the mouse eye and investigated VEGF-A165b effects on endothelial cells and VEGFRs in vitro.
Results.
VEGF-A165b inhibited VEGF-A165–mediated endothelial cell migration with a dose effect similar to that of ranibizumab and bevacizumab and 200-fold more potent than that of pegaptanib. VEGF-A165b bound both VEGFR1 and VEGFR2 with affinity similar to that of VEGF-A165. After laser injury, mice were injected either intraocularly or subcutaneously with recombinant human VEGF-A165b. Intraocular injection of rhVEGF-A165b gave a pronounced dose-dependent inhibition of fluorescein leakage, with an IC50 of 16 pg/eye, neovascularization (IC50, 0.8 pg/eye), and lesion as assessed by histologic staining (IC50, 8 pg/eye). Subcutaneous administration of 100 μg twice a week also inhibited fluorescein leakage and neovascularization and reduced lesion size.
Conclusions.
These results show that VEGF-A165b is a potent antiangiogenic agent in a mouse model of age-related macular degeneration and suggest that increasing the ratio of antiangiogenic-to-proangiogenic isoforms may be therapeutically effective in this condition.
doi:10.1167/iovs.09-4360
PMCID: PMC2910649  PMID: 20237252
22.  Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study 
The British Journal of Ophthalmology  2010;94(12):1611-1617.
Aim
To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy.
Methods
A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30–120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20–20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration.
Results
Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation).
Conclusions
An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.
doi:10.1136/bjo.2009.174946
PMCID: PMC2991041  PMID: 20472746
Macula; macular degeneration; pegaptanib sodium; vascular endothelial growth factor A
23.  Treatments for macular oedema following central retinal vein occlusion: systematic review 
BMJ Open  2014;4(2):e004120.
Objectives
To review systematically the randomised controlled trial (RCT) evidence for treatment of macular oedema due to central retinal vein occlusion (CRVO).
Data sources
MEDLINE, EMBASE, CDSR, DARE, HTA, NHSEED, CENTRAL and meeting abstracts (January 2005 to March 2013).
Study eligibility criteria, participants and interventions
RCTs with at least 12 months of follow-up assessing pharmacological treatments for CRVO were included with no language restrictions.
Study appraisal and synthesis methods
2 authors screened titles and abstracts and conducted data extracted and Cochrane risk of bias assessment. Meta-analysis was not possible due to lack of comparable studies.
Results
8 studies (35 articles, 1714 eyes) were included, assessing aflibercept (n=2), triamcinolone (n=2), bevacizumab (n=1), pegaptanib (n=1), dexamethasone (n=1) and ranibizumab (n=1). In general, bevacizumab, ranibizumab, aflibercept and triamcinolone resulted in clinically significant increases in the proportion of participants with an improvement in visual acuity of ≥15 letters, with 40–60% gaining ≥15 letters on active drugs, compared to 12–28% with sham. Results for pegaptanib and dexamethasone were mixed. Steroids were associated with cataract formation and increased intraocular pressure. No overall increase in adverse events was found with bevacizumab, ranibizumab, aflibercept or pegaptanib compared with control. Quality of life was poorly reported. All studies had a low or unclear risk of bias.
Limitations
All studies evaluated a relatively short primary follow-up (1 year or less). Most had an unmasked extension phase. There was no head-to-head evidence. The majority of participants included had non-ischaemic CRVO.
Conclusions and implications of key findings
Bevacizumab, ranibizumab, aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO. Long-term data on effectiveness and safety are needed. Head-to-head trials and research to identify ‘responders’ is needed to help clinicians make the right choices for their patients. Research aimed to improve sight in people with ischaemic CRVO is required.
doi:10.1136/bmjopen-2013-004120
PMCID: PMC3927713  PMID: 24513867
Systematic Review; Anti-VEGF; Central Retinal Vein Occlusion; Macular Oedema
24.  Age related macular degeneration 
Clinical Evidence  2007;2007:0701.
Introduction
Sight-threatening (late) age-related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early-stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression of early- or late-stage age-related macular degeneration; and exudative age-related macular degeneration? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiangiogenesis (using pegaptanib, ranibizumab, interferon alfa-2a, or anecortave acetate), antioxidant vitamins plus zinc, external beam radiation, laser treatment to drusen, photodynamic therapy with verteporfin, submacular surgery, thermal laser photocoagulation, transpupillary thermotherapy.
Key Points
Sight-threatening (late) age related macular degeneration (AMD) occurs in 2% of people aged over 50 years in industrialised countries, with prevalence increasing with age. Early stage disease is marked by normal vision, but retinal changes (drusen and pigment changes). Disease progression leads to worsening central vision, but peripheral vision is preserved.85% of cases are atrophic (dry) AMD, but exudative (wet) AMD, marked by choroidal neovascularisation, leads to a more rapid loss of sight.The main risk factor is age. Hypertension, smoking, and a family history of AMD are also risk factors.
High dose antioxidant vitamin and zinc supplementation may reduce progression of moderate AMD, but there is no evidence of benefit in people with no, or mild AMD, or those with established late AMD in both eyes.
CAUTION: Beta-carotene, an antioxidant vitamin used in AMD, has been linked to an increased risk of lung cancer in people at high risk of this disease.
Photodynamic treatment with verteporfin reduces the risk of developing moderate or severe loss of visual acuity and legal blindness in people with vision initially better than 20/100 or 20/200, compared with placebo. Photodynamic treatment is associated with an initial loss of vision and photosensitive reactions in a small proportion of people.
Thermal laser photocoagulation can reduce severe visual loss in people with exudative AMD. It is frequently associated with an immediate and permanent reduction in visual acuity if the lesion involves the central macula, but it remains a proven effective treatment for extrafoveal choroidal neovascularisation. About half of people treated with thermal lasers show recurrent choroidal neovascularisation within 3 years.We don't know whether laser treatment of drusen prevents progression of disease, and it may increase short term rates of choroidal neovascularisation.
Antiangiogenesis treatment using vascular endothelial growth factor (VEGF) inhibitors such as ranibizumab or pegaptanib reduces the risk of moderate vision loss, and may improve vision at 12 and 24 months. Antiangiogenesis treatment using anecortave acetate may be as effective as photodynamic therapy in reducing vision loss.
Studies investigating external beam radiotherapy have given contradictory results, and have failed to show an overall benefit in AMD.
Subcutaneous interferon alfa-2a and submacular surgery have not been shown to improve vision, and are associated with potentially severe adverse effects.
We found no RCT evidence on the effects of transpupillary thermotherapy.
PMCID: PMC2943806  PMID: 19454069
25.  Joint Assessment of Intended and Unintended Effects of Medications: An Example Using Vascular Endothelial Growth Factor Inhibitors for Neovascular Age-Related Macular Degeneration 
Journal of Ophthalmology  2010;2009:540431.
Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events) on quality-of-life among persons with neovascular age-related macular degeneration. Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY). Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects. Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration.
doi:10.1155/2009/540431
PMCID: PMC2836847  PMID: 20339464

Results 1-25 (635558)