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29 Jul 16
Qaisrah Khalid, Associate Analyst for GBI Research

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Ophthalmology: New Molecular Targets to Reshape the Clinical and Commercial Landscape

Written By Qaisrah Khalid, Associate Analyst for GBI Research

Ophthalmology is a therapy area that deals with the diagnosis, treatment and prevention of diseases associated with the eyes and visual system. Ophthalmic conditions are among the most common types of disorders worldwide, and approximately 3.4 million Americans aged 40 and older are either blind or visually impaired (CDC, 2015).

Most ophthalmologic disorders cannot currently be cured, and treatment is aimed at managing the disease indication in order to reduce the severity of symptoms and slow progression. If left untreated, serious long-term co-morbidities can arise, such as additional ophthalmic problems that can have an impact on both morbidity and vision leading to a lowered quality of life – particularly blindness. Cataracts are the leading cause of blindness globally (representing 47.9% of cases), followed by glaucoma (12.3%), age-related macular degeneration (AMD) (8.7%) and diabetic retinopathy (DR) (4.8%) (WHO, 2016).

AMD is one of the leading causes of vision loss among people aged 50 and over in the developed world.  It is characterized by the deterioration or breakdown of the macula, a small area of the central retina that is responsible for high-acuity vision, the ability to see fine details, and central vision. AMD can progress to one of two types: dry AMD (dAMD) and wet AMD (wAMD).

dAMD develops due to the breakdown of retinal pigment epithelial cells in the macula and the buildup of drusen deposits on the retina (light-sensitive tissue found at the back of the eye), beneath the macula. Although the causes are not fully understood, recent studies of the molecular composition of drusen have shown inflammation to play a key role in the pathogenesis of dAMD. This insight has opened up studies into the immunologic factors involved in dAMD, and a range of new potential molecular targets for drugs to treat the condition.

dAMD develops slowly, causing gradual vision loss that occurs over a number of years. This progression can be asymptomatic for many years. In most severe cases, dAMD causes a blank patch in the central vision of both eyes and can affect color perception. However, it does not affect peripheral vision, and therefore does not cause total blindness.

In contrast, wAMD develops when the macula stops functioning correctly and new blood vessels form to compensate for the issue. However, the blood vessels do not grow in the correct place and are leaky, causing swelling and bleeding beneath the macula. This neovascularization causes further damage to the macula, leading to scarring, and therefore a blank patch in the central vision of both eyes. Unlike dAMD, this condition is fast developing and can have serious consequences on central vision in a short period of time, with any sight loss being permanent. However, neither type of AMD leads to total blindness, as peripheral vision is not affected.

There is currently no cure for AMD, but studies have shown that diet and lifestyle changes play a role in slowing disease progression (Lawrenson and Evans, 2012). Therapeutic interventions focus exclusively on wAMD, due to its progressive and debilitating nature, and there are a number of therapeutic treatments available for the maintenance of good vision in patients with this condition. In contrast, no form of treatment can currently prevent vision loss in dAMD.

Studies on various cellular growth factors, including VEGF, in a variety of ocular neovascular processes have led to the development of VEGF inhibitors, VEGF antibodies and other antiangiogenic molecules that inhibit pro-angiogenic cytokines. Anti-VEGF treatments are available for wAMD, and work by restricting the neovascularization, therefore stopping any scarring from occurring.

Anti-angiogenesis drugs can be injected directly into the eye and work by blocking the activity of VEGF protein, preventing interaction with VEGF receptors on the surface of endothelial cells, thereby inhibiting the process of angiogenesis.

The introduction and widespread use of ocular anti-VEGF therapies for AMD has been successful due to the clinical efficacy demonstrated in numerous trials. Trials have shown therapies to reduce the growth of new blood vessels and the edema (swelling) they may cause, reducing the risk of scarring and damage to the retina caused by these new vessels. This in turn can help to avoid further sight loss, and lead to improved vision for some patients.

The clinical success of angiogenesis inhibitors has also been demonstrated commercially in the ophthalmology market, and such targeted therapies appear to be a promising treatment option for wAMD and other ophthalmological indications. Angiogenesis inhibitors are the most effective and most common therapies used in not just wAMD, but in a range of other ophthalmological indications, such as DR, macular edema and retinal vein occlusion. This class of compounds has been the most commercially successful in the past decade, with products such as Eylea and Lucentis generating strong annual revenues. Macugen was the first anti-VEGF agent used in ophthalmology, approved in 2004, but has largely been replaced with the development of Lucentis (Ferrara et al., 2006).

With 80–90% of AMD patients suffering from dAMD, there is a significant unmet need for safe and efficacious treatment options (Mogk, 2015). The ophthalmology market is set to be driven further by new approvals for drugs that will supplement current market leaders, such as Eylea, and offer a broader range therapeutic options, including products with novel mechanisms of action that do not target VEGF. Promising examples include Fovista, SPK-RPE65, Lampalizumab, Roclatan and Rhopressa, which are all expected to be approved between 2016 and 2022.

One of the most promising pipeline candidates is Ophthotech’s Fovista, which has shown promise in wAMD, and is anticipated to overtake sales for Lucentis, becoming a blockbuster drug in the process. Fovista is an aptamer molecule that inhibits PDGF-B and PDGF-2, and therefore has a new mechanism of action that offers an alternative to targeting VEGF.

Additionally, significant advancements are being made in dAMD, with the expected approval of Roche’s lampalizumab between 2016 and 2022. This anticipated approval is expected to address the pressing unmet need for a safe and effective drug for this therapy area. Clinical trials have shown lampalizumab to be effective in dAMD patients. For example, the MAHALO Phase II trials showed a reduction in dAMD lesion progression in patients treated with lampalizumab by 20%. These Phase II trials have progressed into the Phase III programs for further safety and efficacy evaluation, and these will include 936 patients in each study (Holz et al., 2014).

In addition to an increasingly growing and competitive therapeutic landscape in both wAMD and dAMD, there will be a steady rise in overall prevalence rates in the forecast period. Prevalence rates have been increasing gradually for a number of years, and this increase has been associated with multiple factors, including aging populations (owing to the proportionally high incidence of the disease in the elderly), continued improvements in diagnosis, and improvements in quality of life leading to an increase in the number of elderly people, owing to the development of novel and effective medicines.

With new therapies expected to enter the market, the number of patients who can be treated by pharmaceutical products is expected to increase dramatically, and they are expected to benefit from a reduced rate of disease progression. These factors will result in market growth, and the ophthalmology market is forecast to increase at a CAGR of 9.48% from $13.7 billion in 2015 to $26 billion in 2022.


CDC (2015). Vision Health Initiative (VHI) – National Data. Centers for Disease Control and Prevention. Available at: [Accessed July 28, 2016]

Ferrara N, et al. (2006). Development of ranibizumab: An anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina; 26: 859-870

Holz FG, et al. (2014). Recent developments in the treatment of age-related macular degeneration. Journal of Clinical Investigation; 124(4): 1430-1438

Lawrenson JG and Evans JR (2012). Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration. Cochrane Database of Systematic Reviews. Available at: [Accessed July 28, 2016]

Mogk LG (2015). The Difference Between Wet and Dry Age-Related Macular Degeneration. VisionAware. Available from: [Accessed February 29, 2016]

WHO (2016). Causes of blindness and visual impairment. World Health Organization. Available from: [Accessed July 28, 2016]


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