Eyes | July 8, 2014 | Author: The Super Pharmacist
Exudative macular degeneration is a condition caused by neovascularisation (abnormal blood vessel growth) in the choroid. This lies between the sclera (outer structure) and retina (which contains the cells that allow visual perception) of the human eye, and contains capillaries (small blood vessels) that supply nutrients to these structures.
Neovascularisation of these may damage the nearby macula, or the area within the eye where central vision is processed. This may occur through bleeding or scar tissue formation, which damages the layers of photoreceptors (light-processing molecules) in the macula, ultimately leading to specific types of vision loss.
Exudative macular degeneration is one of two main types of macular degeneration (MD), and is also known as 'wet' MD. Approximately 2.5 million people suffer from this variant of the condition.
Both types of macular degeneration are associated with many risk factors
The condition is associated with high levels of vascular epithelial growth factor (VEGF), a protein that plays a central role in blood vessel development.
Wet MD is characterised by certain signs and symptoms. These include:
There are a number of drugs in use to treat wet MD. These include:
Ranibizumab and aflibercept are particularly effective anti-VEGF drugs. These are similar in action, but have some differences which may affect the decision to use one or the other when addressing a case of wet MD.
Both aflibercept and ranibizumab inhibit VEGF by attaching themselves to the protein before it can bind to its receptor in the choroid. Therefore, the shape of VEGF is changed to such an extent that the receptor will no longer recognise it, and thus new vessel growth will be avoided.
Both drugs may significantly reduce or even halt the progressive vision loss associated with MD.
This type of drug action is particularly associated with specific molecules designed to identify and bind to corresponding proteins, known as monoclonal antibodies. Ranibizumab is one such antibody that has been developed to bind to the A subunit of VEGF (VEGF-A) with significant affinity.
Aflibercept is not an antibody, but rather recombinant (replicated in a lab) subunits of both subtypes (one of each) of the VEGF receptor itself, bound to a 'foundation' protein. Ranibizumab is partially synthetic (i.e. not found in humans) whereas aflibercept mimics aspects of both human VEGF receptor subtypes exactly. Therefore, the affinity of aflibercept may be superior to ranibizumab. Both ranibizumab and aflibercept are administered intra-vitreally, i.e. they must be administered by injection into the eye.
Ranibizumab is associated with significant VEGF binding and retention of visual ability. However, a seven-year multicentre study into the long-term outcomes of therapy with this drug showed that a third of patients documented had declines in visual acuity after treatment. On the other hand, more frequent injections of ranibizumab (i.e. 11 or more over a 3-4 year period compared to 7 or less) were associated with significant improvements.
Aflibercept, approved by the FDA in 2011, has demonstrated very similar efficacy and vision improvement profiles in comparison with ranibizumab. However, there is evidence to suggest that the newer drug maintains its effects for longer, indicating that it requires fewer injections per year than ranibizumab to achieve the same therapeutic gain. In other words, a monthly ranibizumab injection will be necessary to treat wet MD, in comparison with approximately four injections of aflibercept per year. Monthly treatments are required for both drugs in the first year of treatment, however.
The more common side-effects of ranibizumab include:
More serious and unusual adverse events include:
In contrast, aflibercept is not strongly associated with these severe side effects. However, this may be due to its status as a relatively new drug, and the concomitant lack of independent long-term studies on the outcomes and adverse reactions of aflibercept treatment. On the other hand, it is also associated with the typical side-effects of VEGF inhibition, such as ocular hypertension, eye pain and haemorrhaging. Both aflibercept and ranibizumab may also cause a dangerous increase in intraocular pressure, in rare cases.
Wet macular degeneration is a disease than can significantly affect the visual capacity of patients.
It is caused by abnormal blood vessel proliferation in the choroidal capillaries of the eye. If this impinges on the macula, it may result in the loss of central vision.
This condition is mainly associated with advancing age and genetic risk factors.
It is thought to be caused by high levels of VEGF in the affected eye(s). This is a protein known as a growth factor that contributes to blood vessel development.
Wet macular degeneration is treated by drugs that bind VEGF before it can bind to its receptor, which stimulates blood vessel growth.
Prominent VEGF inhibitors include ranibizumab, a monoclonal humanized antibody, and aflibercept, a recombinant human protein.
Comparative studies indicate that these drugs are equally effective, although aflibercept may have greater affinity to VEGF. However, ranibizumab may have a shorter duration of effect than aflibercept; in other words, treatment with this drug may require more frequent doses.
van Lookeren Campagne M, LeCouter J, Yaspan BL, Ye W. Mechanisms of age-related macular degeneration and therapeutic opportunities. The Journal of pathology.2014;232(2):151-164.
Maguire MG, Daniel E, Shah AR, et al. Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials. Ophthalmology.2013;120(10):2035-2041.
Chew EY, Clemons TE, Agron E, et al. Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report no. 36. JAMA ophthalmology.2014;132(3):272-277.
Semeraro F, Morescalchi F, Duse S, Parmeggiani F, Gambicorti E, Costagliola C. Aflibercept in wet AMD: specific role and optimal use. Drug design, development and therapy.2013;7:711-722.
Nano ME, Lansingh VC, Pighin MS, et al. Risk factors of age-related macular degeneration in Argentina. Arquivos brasileiros de oftalmologia.2013;76(2):80-84.
Liu Y, Hou S, Lang W, et al. Roles of three common VEGF polymorphisms in the risk of age-related macular degeneration. Genetic testing and molecular biomarkers.2014;18(4):245-252.
Huang C, Xu Y, Li X, Wang W. Vascular endothelial growth factor A polymorphisms and age-related macular degeneration: a systematic review and meta-analysis. Molecular vision.2013;19:1211-1221.
Lu Y, Shi Y, Xue C, Yin J, Huang Z. Pooled-analysis of the associations between three polymorphisms in the VEGF gene and age-related macular degeneration. Molecular biology reports.2012;39(6):6547-6553.
Finger RP, Wickremasinghe SS, Baird PN, Guymer RH. Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration. Survey of ophthalmology.2014;59(1):1-18.
Sakurada Y, Yoneyama S, Imasawa M, Iijima H. Systemic risk factors associated with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. Retina (Philadelphia, Pa.).2013;33(4):841-845.
Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study Report Number 3. Ophthalmology.2000;107(12):2224-2232.
de Jong PT. Age-related macular degeneration. The New England journal of medicine.2006;355(14):1474-1485.
Stewart MW. Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept. Clinical ophthalmology (Auckland, N.Z.).2012;6:1175-1186.
Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW. Aflibercept for age-related macular degeneration: a game-changer or quiet addition? American journal of ophthalmology.2012;154(2):222-226.
Marshall LL, Roach JM. Prevention and treatment of age-related macular degeneration: an update for pharmacists. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists.2013;28(11):723-737.
Frampton JE. Ranibizumab: a review of its use in the treatment of neovascular age-related macular degeneration. Drugs & aging.2013;30(5):331-358.
Ventrice P, Leporini C, Aloe JF, et al. Anti-vascular endothelial growth factor drugs safety and efficacy in ophthalmic diseases. Journal of pharmacology & pharmacotherapeutics.2013;4(Suppl 1):S38-42.
Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology.2013;120(11):2292-2299.
Nuzzi R, Tridico F. Local and Systemic Complications after Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Different Ocular Diseases: A Five-Year Retrospective Study. Seminars in ophthalmology.2013.
Tolentino M. Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease. Survey of ophthalmology.2011;56(2):95-113.
Sarraf D, Chan C, Rahimy E, Abraham P. Prospective evaluation of the incidence and risk factors for the development of RPE tears after high- and low-dose ranibizumab therapy. Retina (Philadelphia, Pa.).2013;33(8):1551-1557.
Guber J, Praveen A, Saeed MU. Retinal pigment epithelium rips after ranibizumab in neovascular age-related macular degeneration: incidence, risk factors and long-term outcome. Klinische Monatsblatter fur Augenheilkunde.2014;231(4):432-435.
Daniel E, Toth CA, Grunwald JE, et al. Risk of scar in the comparison of age-related macular degeneration treatments trials. Ophthalmology.2014;121(3):656-666.
Rasmussen A, Bloch SB, Fuchs J, et al. A 4-year longitudinal study of 555 patients treated with ranibizumab for neovascular age-related macular degeneration. Ophthalmology.2013;120(12):2630-2636.
Bressler NM, Boyer DS, Williams DF, et al. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials. Retina (Philadelphia, Pa.).2012;32(9):1821-1828.