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When the retina becomes ischemic, it releases a protein called Vascular Endothelial Growth Factor (VEGF).  The vascular endothelial growth factor (VEGF) causes abnormal blood vessels (neovascularization) to develop on the surface of the retina and on other parts of the inside of the eye such as the optic nerve and iris. Blindness may develop from massive proliferation of the neovascularization (aka abnormal blood vessels) causing either retinal detachment or, a rare type of painful glaucoma (neovascular glaucoma – NOT the regular glaucoma). So far, ischemia has caused vascular endothelial growth factor (VEGF) to be liberated.  The VEGF has caused neovascularization to develop. If we laser the peripheral retina, the portion of the retina away from the macula, we can stop the production of VEGF in most cases and arrest the proliferative phase of the diabetic retinopathy. Since the early 1970s, laser therapy has been used in the horse world for treating equine concerns and helping owners and trainers keep their horses in top shape. Age-related macular degeneration is the most common cause of vision loss in adult white Americans. The current therapeutic standard is consecutive monthly injections of ranibizumab (Lucentis, Genentech).
Furthermore, the additional potential benefit is an increase in visual acuity compared to the outcome produced with ranibizumab monotherapy, but with reduced need for retreatment at the same time.
This contribution will summarize highlights of combination therapy for patients with wet AMD reported in 2009.
In these two large, prospective trials, PDT is being combined with intravitreal injections of ranibizumab. In the first two DENALI treatment groups, ranibizumab is given at baseline, at months 1 and 2, and then as needed; in the third group, ranibizumab is administered monthly for the first year and as needed for the second year. Sayegh and colleagues reported outcomes in 375 eyes of 251 elderly patients (mean age of 82 years) with occult CNV lesions treated sequentially with dexamethasone, bevacizumab (Avastin, Genentech), and large-spot diode laser photocoagulation. A triple therapy consisting of PDT, bevacizumab and dexamethasone was administered to 146 patients (Figure 2). Patients randomly assigned to combination treatment groups received one initial treatment and those randomly assigned to ranibizumab monotherapy received three initial treatments (baseline and months 1 and 2).
In the multicenter CAVE Study, reduced-fluence PDT plus bevacizumab plus triamcinolone therapy was compared with bevacizumab monotherapy, as well as with PDT plus bevacizumab dual therapy. In treatment-naïve patients, Hughes and Sang administered reduced-duration photodynamic therapy plus dexamethasone plus ranibizumab and compared outcomes with monthly ranibizumab monotherapy (n=30 in each group). At one year, 19 (63%) of the triple therapy patients had received only one retreatment. Data on real world practice patterns regarding dual and triple therapies are also beginning to accrue.
Another potential therapeutic strategy involves blockade of VEGF effects by inhibiting the tyrosine kinase cascade downstream from the VEGF receptor; vatalanib and pazopanib are drugs in this class currently under exploration. QLT announces 12-month results from Novartis sponsored MONT BLANC study evaluating standard-fluence Visudyne® combination therapy. Brown D: One year results of a phase 2, randomized, controlled-dose and interval-ranging study of intravitreal VEGF Trap-Eye in patients with neovascular AMD.
Retinal Physician delivers in-depth coverage of the latest advances in AMD, diabetic retinopathy, macular edema, retinal vein occlusion as well as surgical intervention in posterior segment care.
Although controlling your glucose levels is important when you have diabetes, DME requires additional treatment. These newer, effective treatments target one or more of the proteins that stimulate growth of the leaky vessels in the eye. In addition to VEGF-A, anti-angiogenic treatments also block a protein called Placental Growth Factor (PIGF) that may play a role in DME.
To deliver the anti-angiogenic and anti-VEGF-A drugs into the eye, an eye or retina doctor first numbs the eye surface and then injects the medication using a short, thin needle. As the anti-angiogenic or anti-VEGF-A medication is absorbed into the tissues of the macula, it lowers the levels of VEGF-A that cause the leaky blood vessels. By lowering the levels of VEGF-A in the retina, the impact it has on retinal blood vessels is reduced, and leaking blood vessels diminish, begin to break down, and regress. Anti-VEGF-A therapy may reduce vascular permeability (a condition where molecules or even whole cells can pass in and out of the vessel), decrease thickening of the macula and retina, and improve visual acuity. The injection may be slightly uncomfortable for some people, and you may have to wear an eye patch for a few hours afterward to protect your eye(s). During laser photocoagulation, areas of leakage in the retina are exposed to small laser burns that decrease the amount of fluid and slow down leakage. Laser therapy stabilizes vision and can prevent vision loss caused by DME, but rarely improves visual acuity. This is a procedure in which the vitreous is replaced with a salt solution to improve visual acuity and maintain the anatomy of the eye.
These drugs work by targeting different mechanisms of the disease: inflammation, or swelling, and VEGF factors. Corticosteroids are anti-inflammatory and can interfere with the mechanisms that cause inflammation within blood vessels. Corticosteroids have greater short-term benefit than laser treatment but, after several months, their benefit declines.

If you are undergoing any of these treatments or plan on having these treatments, this discussion guide will help you with questions you may have for your doctor. Janelle and Bart describe some of the difficulties faced when travelling, and how, with Bart’s help, she overcomes these. Janelle Colquhoun is a successful opera singer, public speaker, writer and director of Salubrious Productions, an agency specializing in disabled artists. You can purchase audio books and magazines, talking watches, glucometers, and memo recorders. An additional protein, called Placental Growth -->Factor (PIGF), may play a role in DME, but anti-VEGF-A treatment does not target this protein. In addition to VEGF-A, anti-angiogenic treatments also block a protein called Placental Growth Factor (PIGF) that may play a role in diabetic macular edema (DME). As VEGF-A levels in the eye are reduced, the growth of the abnormal blood vessels is halted, and these vessels begin to break down and regress.
If you want to report an adverse side-effect or quality complaint, please contact your healthcare professional (e.g. PhysiciansJobsPlus allows you to post your resume, receive relevant ophthalmology open position alerts via email and apply for positions online.
The prevalence of AMD, based on data from population-based epidemiological studies, is assumed to be increasing in many countries worldwide, in part due to the increasing longevity of the population.
The licensed indication recommends monthly injections of ranibizumab on a continuing, indefinite basis.6 In most cases however, these monotherapies cannot fully address the multifactorial pathogenesis of wet AMD (Figure 1). Although the main emphasis will be triple therapies, we will begin with a brief summary of available findings from two major clinical trials of dual therapies.
MONT BLANC, a two-year, randomized, double-masked, European multicenter trial, is comparing PDT and ranibizumab with ranibizumab alone in 255 patients. Criteria for retreatment included presence of subretinal blood or fluid on clinical exam, significant macular thickening on OCT, VA decrease, late leakage on fluorescein angiogram, or occult plaque on indocyanine green. Mean VA improvement was three letters, with 12% having three lines of visual improvement. Early- and late-phase angiography and OCT of a minimally classic lesion and some fibrosis with a 14-month follow-up. Early- and late-phase angiography and OCT of a case who received a triple therapy (PDT, bevacizumab, dexamethasone) and four months later a second bevacizumab injection due to remaining edema and some metamorphopsia. RADICAL, a multicenter, randomized, single-masked trial is currently comparing PDT plus ranibizumab plus dexamethasone with ranibizumab monotherapy. There was less need for retreatment with combination therapy (three to four times) compared to monotherapy (five times), while no additional safety concerns occurred. Data from 103 patients were evaluated at one year.16 All patients were treated at baseline and returned for follow-up every six weeks, with retreatment as needed based on FA and OCT criteria.
No patient received more than two cycles of triple therapy or two additional ranibizumab injections.
The Visudyne registry database compiled data on treatment outcomes of over 1,600 patients, including VA assessments, results of ocular exams, serious adverse event reporting, and any additional treatments.
Small-interfering RNA (siRNA) technology-based therapies may be able to downregulate the production of VEGF or VEGF receptors by degrading specific messenger RNA.
Review of recent clinical evidence suggests that a combination approach may improve VA outcomes, reduce retreatment rates, and consequently result in larger treatment-free intervals. Augustin, PhD, are on the faculty in the Department of Ophthalmology at the Klinikum Karlsruhe in Germany.
Constitutive production and thrombin-induced release of vascular endothelial growth factor by human mega-karyocytes and platelets. Same-day triple therapy with photodynamic therapy, intravitreal dexamethasone, and bevacizumab in wet age-related macular degeneration.
Intravitreal VEGF values and inflammatory parameters — rationale and clinical results of an individualized combination treatment of wet AMD. RADICAL: Results of a randomized clinical trial of reduced fluence vPDT-anti-VEGF-dexamethasone in AMD.
Triple therapy (reduced duration PDT + same day dexamethasone and bevacizumab) as rescue treatment in patients with previously treated exudative AMD. It reaches both retinal specialists and general ophthalmologists with practical insight regarding current and future treatment strategies in medical and surgical retina care. These effects include improved healing time, pain reduction, increased circulation and decreased swelling.
These treatments have been shown to stop DME in many patients and, in some cases, reverse vision loss by reducing the growth of new blood vessels, decreasing leakage, and preventing bleeding. In diabetic macular edema (DME), VEGF-A is produced at higher than normal levels in the retina.
However, with anti-angiogenic and anti-VEGF-A treatments, it is possible to control angiogenesis as well as vascular hyperpermeability and the related swelling to gain or stabilize vision and prevent further damage to the macula. You will likely need someone to come with you to your appointment to help you get around for a few hours after the injection.

Safety issues include possible discomfort during the procedure and potential damage or scarring to the retina. They have also been shown to suppress VEGF, which may play an important role in the development of DME.
They may cause other eye complications, such as cataracts or an increase in intraocular pressure, which is a risk factor for glaucoma. Janelle was diagnosed with Type 1 diabetes as a child, and has suffered from many of the complications that are associated with the condition, one of which is Diabetic Eye Disease. Light is absorbed by the skin very efficiently and is quite safe to use to stimulate acupuncture points, trigger points and for the accelerated healing of wounds.
Thus, dual- and triple-combination therapies with a steroid, PDT or laser photocoagulation, and an anti-VEGF agent are now being intensely investigated.
Standard-fluence PDT (or sham) was administered at baseline and then at intervals of at least three months, as required based on predefined retreatment criteria. Monthly follow-up will consist of VA and optical coherence tomography assessments, and retreatment will be based on OCT findings. Group 1 consisted of 30 patients who did not have subretinal retinal pigment epithelium exudation.
Nine patients in group 2 had a complete collapse of the RPE detachment, and mean VA improvement was five letters. Results show that PDT plus an anti-VEGF agent plus a corticosteroid can improve VA (means of 5.7. RPE-derived factor-based therapies, nicotinic acetylcholine receptor antagonists, and integrin antagonists are other new drugs under investigation for use in treating wet AMD.
This research may lead to a lesser treatment burden for many patients and potentially a reduction of overall treatment costs. The most comprehensive retinal care journal, Retinal Physician puts into perspective what the scientific developments mean to today’s practice and discusses ramifications of new studies, treatments and patient management strategies. Laser Therapy has been widely utilized in Europe by physical therapists, nurses and doctors as far back as the 1970's. There are a few differences between anti-VEGF-A treatment and anti-angiogenic therapy, including how they work inside the eye. Lowering VEGF-A with anti-VEGF-A drugs reduces its effects on retinal blood vessels, prompting a reduction in macular edema without risk of developing major eye conditions. Your eye doctor can determine which treatment is best for you and how often it should be administered.
If you have diabetic macular edema (DME) in both eyes, your doctor will usually treat one eye at a time, with several weeks in between treatments.
Vitrectomy has been very successful with restoring sight by removing blood; however, vision recovery after retinal detachment repair is not guaranteed. These drugs can be delivered by intravitreal injection or by sustained release implants, which may require less frequent dosing than injections.
In the early 90s, Janelle underwent laser photocoagulation to prevent her vision declining. And, as on this Web site, some sites have the option to provide an audio presentation of content in addition to the text. The intent is to provide different and complementary mechanisms of action to decrease inflammation, destroy existing choroidal neovascularization, prevent the formation of new CNV, and inhibit further VEGF production.
Median time to first re-treatment was extended by approximately one month in the combination group (month 6) compared with the monotherapy group (month 5). Now, after FDA clearance in 2002, Laser Therapy is being used extensively in the United States. There also may be more or fewer injections required to impact your vision, depending on the treatment chosen by you and your retina specialist. Unfortunately this did little to help and caused extensive retinal scarring leading to extensive deterioration in Janellea€™s vision. Sealing ocular blood vessels by using laser photocoagulation is another option, with only a small minority of patients eligible for this treatment.
There were no unexpected safety findings, and the adverse event incidence was similar between groups.7 Final analysis will need to be made available in order to draw firm conclusions. Currently, none of the authors reports any financial interest in any products mentioned in this article.
Despite this, she has continued to lead a successful career with the help of her husband and carer, Bart Brameijer.

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