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1.  Critical appraisal of ranibizumab in the treatment of diabetic macular edema 
Diabetic retinopathy is the leading cause of blindness among individuals of working age in industrialized nations, with most of the vision loss resulting from diabetic macular edema (DME). The formation of DME depends on the action of several growth factors and inflammatory mediators, but vascular endothelial growth factor (VEGF) appears to be critical for breaking down the blood-retinal barrier and promoting the accumulation of macular edema. Laser photocoagulation has been the standard-of-care for three decades, and although it stabilizes vision, significant gains in visual acuity after treatment are unusual. Several VEGF inhibitors (pegaptanib, aflibercept, and ranibizumab) have been initially developed and tested for the treatment of age-related macular degeneration and subsequently for DME. In Phase I, II, and III trials for DME, ranibizumab has been shown to be superior to macular laser photocoagulation and intraocular triamcinolone acetonide injections for improving visual acuity and drying the macula. As a result, ranibizumab is the only anti-VEGF drug that has been approved by the United States Food and Drug Administration for the treatment of DME. Most experts now consider intravitreal anti-VEGF therapy to be standard-of-care for DME involving the fovea.
PMCID: PMC3699322  PMID: 23836955
aflibercept; bevacizumab; diabetic macular edema; diabetic retinopathy; ranibizumab; vascular endothelial growth factor
3.  Aflibercept (VEGF Trap-eye): the newest anti-VEGF drug 
The British Journal of Ophthalmology  2012;96(9):1157-1158.
PMCID: PMC3432488  PMID: 22446028
Macula; retina; choroid; angiogenesis; drugs
4.  Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept 
Age-related macular degeneration (AMD) has become a major public health problem and a leading cause of blindness in industrialized nations. AMD results from the ageing eye’s inability to metabolize and dispose completely of photoreceptor outer segments and other waste products. As a result, lipids, particularly apolipoproteins, accumulate within Bruch’s membrane, leading to chronic ischemia and inflammation. The subsequent upregulation of inflammatory cytokines and growth factors, including vascular endothelial growth factor (VEGF), induces the growth of neovascular membranes from the choriocapillaris into the subretinal or subretinal pigment epithelium spaces. To counter this, intravitreally administered drugs (pegaptanib, bevacizumab, ranibizumab) that specifically target VEGF have become the standard treatment for exudative AMD. Aflibercept, a recently approved fusion protein, binds to all isoforms of both VEGF-A and placental growth factor with high affinity. Phase III trials showed that monthly or every other month injections of aflibercept prevent vision loss (fewer than 15 letters) in 95% of patients. Additionally, aflibercept injections every 4 or 8 weeks produce average vision gains of 6.9 letters to 10.9 letters, comparable with those achieved with monthly ranibizumab. After one year of regularly administered aflibercept injections, patients required an average of only 4.2 injections during the second year. Aflibercept promises to decrease the injection frequency required for many patients and appears to serve as an effective “salvage” therapy for patients who respond poorly to other anti-VEGF drugs.
PMCID: PMC3422153  PMID: 22973088
age-related macular degeneration; choroidal neovascularization; vascular endothelial growth factor; aflibercept; ranibizumab; bevacizumab; VEGF trap
5.  A retrospective cohort study of clinical outcomes for intravitreal crystalline retained lens fragments after age-related cataract surgery: a comparison of same-day versus delayed vitrectomy 
This analysis compared outcomes for same-day (under a no-move, no-wait policy) versus delayed vitrectomy for intravitreal crystalline retained lens fragments after surgery for age-related cataract.
This was a retrospective, nonrandomized treatment comparison cohort study with a consecutive series of 35 eyes (23 same-day, 12 delayed) receiving both cataract surgery and vitrectomy at the Mayo Clinic Florida between 1999 and 2010. Outcome measures included visual acuity (VA), glaucoma progression, visual utility, and complications. Several techniques (bootstrapping, robust confidence intervals, jackknifing, and a homogeneous sample) were used to reduce selection bias and increase confidence in our small sample’s results.
No significant baseline treatment group differences. Mean previtrectomy delay (12 eyes) was 40.9 days (median 29.5, range 1–166). Mean postvitrectomy follow-up (35 eyes) was 47.5 months (median 40.5, range 3.1–123.5). Same-day patients had significantly better final VA (adjusted for age [t = −2.14, P = 0.040] and precataract surgery VA [t = −2.98, P = 0.006]); a higher rate of good final VA (≥20/40), 78.3% (18/23) versus 58.3% (7/12); a lower rate of bad final VA (≤20/200), 4.3% (1/23) versus 25.0% (3/12); and fewer final retinal conditions, 4.3% (1/23) versus 50.0% (6/12). Same-day patients also had marginally significant better mean final VA in the operated eye (20/40 versus 20/90, Z = 1.51, P = 0.130) despite poorer initial VA (20/98 versus 20/75) and higher age (3+ years), better final visual utility, and longer survival times for better VA. Among patients with preexisting glaucoma, same-day patients experienced significantly less differential (operated versus nonoperated eye) glaucoma progression.
Results favored same-day patients, who experienced better final VA and visual utility, less differential glaucoma progression, and fewer complications. Results need confirmation with larger samples.
PMCID: PMC3413336  PMID: 22888212
intraoperative complications; retained lens fragments; visual acuity; glaucoma; evaluation studies; visual utility; statistics as topic; small nonrandomized sample analysis
6.  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.
PMCID: PMC3498409  PMID: 22212972
7.  Meta-analysis comparing same-day versus delayed vitrectomy clinical outcomes for intravitreal retained lens fragments after age-related cataract surgery 
We aimed to perform a systematic review and meta-analysis comparing the risk difference of clinical outcomes for same-day (SD) vs delayed (DEL) pars plana vitrectomy (PPV).
We searched MEDLINE (English; January 1, 1985 to July 16, 2013) and article reference lists, for patients with crystalline retained lens fragments and discussion of SD-PPV vs DEL-PPV. For the meta-analysis, articles needed the number of patients receiving SD-PPV and DEL-PPV, and the number, in each group, who experienced one or more of the outcomes: not good visual acuity (VA) (<20/40), bad VA (≤20/200), retinal detachment, increased intraocular pressure/glaucoma, intraocular infection/inflammation, cystoid macular edema, and corneal edema.
Of 304 articles identified, 23 provided data for the meta-analysis. Results were mixed, indicating 1) neither vitrectomy time produced better outcomes in all studies (not good VA risk difference =10.3% [positive numbers favored SD-PPV; negative numbers favored DEL-PPV], 95% confidence interval [CI] = [−0.4% to 21.0%], P=0.059; and bad VA risk difference =−0.3%, 95% CI = [−10.7% to 10.1%], P=0.953); 2) better outcomes with immediate SD-PPV compared with all DEL-PPV (not good VA risk difference =16.2%, 95% CI = [0.8% to 31.5%], P=0.039; and bad VA risk difference =8.5%; 95% CI = [0.8% to 16.2%], P=0.030); and 3) immediate SD-PPV and prompt DEL-PPV (3 to 14 days after cataract surgery) had no significant differences and so may produce similar outcomes (not good VA risk differences range = [−19.9% to 6.5%], 95% CI = [−59.9% to 36.4%]; and bad VA risk differences range = [−6.9% to 7.4%], 95% CI = [−33.1% to 31.8%]).
Perhaps SD-PPV should be limited to facilities at which a vitreoretinal surgeon is immediately available. Otherwise, these results support referring a patient with retained lens fragments promptly to a vitreoretinal surgeon but do not support interfacility transport for SD-PPV.
PMCID: PMC4242692  PMID: 25429196
retained lens fragments; vitrectomy; time factors; visual acuity; meta-analysis; systematic review
8.  Human immunodeficiency virus and its effects on the visual system 
Infectious Disease Reports  2012;4(1):e25.
During the first 15 years of the AIDS epidemic patients experienced a high incidence of blindness due to cytomegalovirus (CMV) retinitis and other severe ocular opportunistic infections. Highly active anti-retroviral therapy, introduced in 1996, dramatically decreased the incidence of CMV retinitis. Though CMV retinitis still causes 40% of vision loss in AIDS patients, other conditions such as immune reconstitution uveitis, cataracts, and a significant othercategory -which most investigators believe is directly due to HIV - comprise the majority of cases. HIV causes vascular abnormalities of the conjunctiva and retina in the majority of AIDS patients, as well as retinitis, anterior and posterior uveitis and vasculitis. HIV frequently causes an optic neuropathy and is responsible for the majority of eye movement disorders among HIV patients. Physicians need to be aware that these problems may be the initial manifestation of HIV infections or a sign of highly active anti-retroviral therapy (HAART) failure. Therefore, patients with identifiable risk factors for AIDS who present with ophthalmologic conditions of unknown etiology should be considered for HIV testing. Finally, anti-retroviral therapy has been reported to cause asymptomatic deposits as well as degenerative conditions of both the anterior and posterior segments of the eye.
PMCID: PMC3892652  PMID: 24470932
HIV; AIDS; vision; eye; retina.
9.  A 6-month, subject-masked, randomized controlled study to assess efficacy of dexamethasone as an adjunct to bevacizumab compared with bevacizumab alone in the treatment of patients with macular edema due to central or branch retinal vein occlusion 
To determine if intravitreal bevacizumab combined with the dexamethasone intravitreal implant 0.7 mg improves visual acuity and macular thickness more than bevacizumab monotherapy in eyes with macular edema due to branch and central retinal vein occlusions.
Thirty eyes were randomly assigned to receive either combination therapy or bevacizumab monotherapy. All patients received intravitreal bevacizumab at baseline, followed by dexamethasone implants or sham injections 1 week later. Monthly bevacizumab injections were given if the central subfield thickness (CST) was >250 μm, and the combined group received a second implant at month 4 or 5 if CST was >250 μm.
At 6 months, several secondary endpoints were met. Patients receiving combined therapy required fewer bevacizumab reinjections compared to those receiving monotherapy (two versus three; P=0.02), experienced greater mean reductions in CST from randomization (−56 μm versus +45 μm; P=0.01), and were more likely to have resolved all edema (CST <250 μm) (7/11 versus 2/14; P=0.02). The primary endpoint was not met since mean visual acuity changes from baseline were similar in the two groups (P=0.75).
In patients with macular edema due to vein occlusions, bevacizumab with dexamethasone implants produces greater improvements in macular thickness compared to bevacizumab monotherapy, despite fewer bevacizumab injections.
PMCID: PMC4051812  PMID: 24940042
dexamethasone implant; central retinal vein occlusion; branch retinal vein occlusion; vascular endothelial growth factor
10.  Optimal management of cytomegalovirus retinitis in patients with AIDS 
Cytomegalovirus (CMV) retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient’s immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post- HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.
PMCID: PMC2861935  PMID: 20463796
cytomegalovirus; AIDS; retinitis; immune recovery uveitis; retinal detachment; treatment

Results 1-10 (10)