The retina is a thin layer of neural tissue lining the back inner surface of the eye. This layer mainly consists of five types of neurons: photoreceptors, i.e. cones and rods, horizontal cells, bipolar cells, amacrine cells, and ganglion cells. The macula is the small, central portion of the retina, which comprises cones only. Such a unique structure enables the macula to provide the clearest, most distinct vision. On the other hand, it makes the macula vulnerable to degeneration due to the lack of blood vessels in this little area.
Macular degeneration is categorized into three types: Age-related macular degeneration (AMD), Myopic Macular Degeneration (MMD), and Juvenile macular degeneration or Stargardt's disease.
AMD is the leading cause of vision impairment and blindness in the elderly over 50 years of age in developed countries. AMD usually occurs in people aged 50 and older and is the most common macular degeneration. MMD is associated with high myopia. Juvenile macular degeneration is a hereditary ocular disease affecting over 25,000 Americans, occurring in approximately one in 10,000 children.
Demographic changes in population and longer life expectancy in many countries are now causing a rapid increase in the number of AMD patients. AMD has a tremendous impact on the physical and mental health of the geriatric population and their families. The cost to society should not be ignored, either. A recent analysis of AMD in Australia predicts that the disease costs $2.6 billion per year. This is projected to grow to $6.5 billion by 2025, a total cost of $59 billion over the next 20 years. A treatment that reduces the progression by only 10% would save Australia $5.7 billion over that same period of time. Similar analyses for the United States are lacking, but given the demographics and higher costs of medical care in the US, the costs would be projected to as much as twenty-fold higher.
The pathogenesis of AMD has not been fully elucidated. While many unanswered questions remain, some contributing factors have been exposed including: aging; retinal ischemia or oxidative stress; long-term exposure to intense light especially blue light; toxification by cigarette smoke, possibly alcohol consumption and some medications; hypertension, high blood cholesterol and triglycerides, which may impede blood circulation; high blood fibrinogen which helps blood clotting; and supper oxidation.
AMD can be manifested in two forms: dry AMD and wet AMD. Dry AMD accounts for 90% of cases, and wet AMD, 10%. Severe vision loss is typically associated with wet AMD but up to 20% of legal blindness from AMD is due to the dry form.
1. The pathologic changes of dry AMD: (1) Apoptosis: this process is associated with neurodegeneration including macular degeneration, leading to cell shrinkage and death in the inner choroid, RPE, photoreceptors, bipolar cells, and amacrine cells. (2) Capillaries in choroid are thinned and sclerosed. (3) Nodular drusen, observed as yellowish white spots by ophthalmoscope, are possibly from the lipoidal degeneration of RPE cells. But inflammation may also be involved in their formation. (4) Scar formation: The spaces left by the dead cells seem to be filled by the enlarged adjacent cells or by scar tissue, which will cause the retinal surface to be uneven and further visual impairment when the scars contract. (5) Geographic atrophy is characterized by an area of well demarcated atrophy of RPE, representing the classic picture of end stage dry AMD.
2. The pathologic changes of wet AMD: (1) Choroidal neovascularization (CNV), the hallmark of the wet AMD, represents the new blood vessel formation from the choroid. CNV can extend from the choroid to the space under RPE and further to the space between the RPE and the retina. (2) Hemorrhage and exudates: Since the new blood vessels are leaky, as a result, the blood and liquid ooze out, forming serous or hemorrhagic detachment of the RPE. (3) Inflammation has been reported to exist in the wet AMD process. (4) Scar formation: This is the same as in dry AMD but the scars can be a lot more severe, forming a disciform scar, representing the end stage of the wet AMD.
Myopic macular degeneration (MMD), caused by high myopia, is more prevalent than AMD in China. MMD has been the first major cause of new blindness registered in 2001-2009 in Shanghai, China. The pathology of MMD are similar in many aspects with that of AMD. The changes are mostly atrophic in nature.                1) The choroid presents atrophic changes. The capillaries become thinned and sclerosed. There are less pigments and elastin.        2) Lacquer cracks: The Bruch's membrane—pigment epithelium-choroiocapilaris complex gets stretched and ruptured which is termed as lacquer cracks.        3) The RPE cells changed in shape and there is pigment proliferation, which forms black conglomerate masses in or around the macula called Fuch's spots.        4) Formation of CNV occurs in some MMD the same as in the wet AMD.        5) Leakage and hemorrhage may happen due to the CNV in some cases or due to the Lacquer cracks in other cases without CNV.        6) Rods and cones in the retina are atrophied.        
The treatment of macular degeneration has been an ongoing topic of ocular research studies in recent decades. Some important progress has been achieved in western medicinal treatments.    1. Laser photocoagulation was approved by the US FDA in 1991 for wet AMD. This treatment uses hot laser radiation to coagulate retinal new blood vessels around the macula (not for those in the center of the macula) and stops bleeding, but this procedure causes damage to the normal retina, leading to scar tissue and permanent visual impairment. Moreover, it does not prevent the new blood vessels from forming again.    2. Photodynamic therapy (PDT) was approved in 2000 by the US FDA for wet AMD, and employs cool (low energy) laser and a light-sensitive chemical-verteporfin (Visudyne®) to destroy choroidal new blood vessels without damaging normal tissue. The PDT not only limits vision loss in wet AMD but can also significantly improve vision for 5.6% of wet AMD cases (add 3 log lines or more). Using PDT as the first-line treatment has saved the vision of hundreds of thousands of people afflicted with wet AMD. Therefore, in 2002 Dr. David Dolphin, along with Julia Levy, was awarded the Prix Galien, the highest award the American Chemical Society gives to an industrial chemist, for the discovery, development, and commercialization of Visudyne®. Although the PDT therapy has been in recent years replaced by vascular epithelial growth factor (VEGF) inhibitors as the first-line treatment, it may still play a role in combination procedures.    3. VEGF inhibitors for wet AMD. Currently, there are mainly four anti-VEGF agents that are available for clinical use: Pegaptanib (brand name Macugen®, Eyetech Pharmaceuticals Inc., New York, USA), Ranibizumab (Lucentis®, Genentech Inc., California, USA), Bevacizumab (Avastin®, Genentech Inc., California, USA) and VEGF trap-eye (also known as Eylea®, Regeneron Pharmaceuticals, Inc. N.Y.)            1) Pegaptanib was approved by the US FDA in 2004, and is the first anti-VEGF agent for wet AMD. Its efficacy was demonstrated in the phase III clinical trial. Six percent of the patients in the treatment group gained 3 lines or more visual acuity (VA) as compared with two percent in the sham-injection group.        2) Ranibizumab was approved by the US FDA in 2006 and is the first treatment for neovascular AMD to improve vision for most patients. In the phase III clinical trial approximately 25-33% of the patients treated with ranibizumab gained 3 lines or more in visual acuity (VA), as compared with 5% or less in the sham injection group at 12 and 24 months.                    The serious ocular events, associated with either the drug or its intraocular injection procedures, included endophthalmitis, uveitis, retinal tear, rhegmatogenous retinal detachment, vitreous hemorrhage, and lens damage, with a total event number of 21 out of 477 patients (4.4%). The elevated postinjection intraocular pressure occurred at 15.9-20.5% in the Ranibizumab-treated group, as compared with 3.4% in the sham-injection group.                        2) Bevacizumab was approved by the US FDA in 2004 for colorectal cancer treatment. However, given its lower cost, it has been widely used off-label for wet AMD in many countries. Its effectiveness was shown to be similar to that of Ranibizumab while Bevacizumab was linked to a higher risk of adverse events.        3) VEGF trap-eye was approved by the US FDA in 2011 for wet AMD. The clinical trial results showed about 30% of the patients gained 3 lines or more in visual acuity during the study in both VEGF trap-eye group and the Ranibizumab group. Adverse effects also did not differ markedly between the two groups.        
Scientists and ophthalmologists believe that the introduction of anti-VEGF agents is a major advancement and a true revolution in the history of wet macular degeneration treatment. The leader of this revolution, Napoleone Ferrara, a scientist from Genentech Inc., won the 2010 Lasker award, one of the most respected science prizes in the world, for the discovery of VEGF and the development of anti-VEGF therapy for wet AMD.
Chinese herbal medicine treatment for vision problems has been used for more than 400 years in China. However, ancient traditional Chinese medicine (TCM) practitioners had no way to distinguish what herbs were effective for macular degeneration since there had been no concept of macula at that time. Modern TCM doctors, educated with basic western medicine knowledge as part of their curriculum, have been able to know the existence of edema, bleeding, etc. in the troubled macula. When prescribing herbs based on the TCM principles, they also add herbs against those pathologic changes to improve the outcome of the treatment. This kind of prescription, however, is highly individualized and, therefore, not many clinically tested formulas are available for general use on the market.
Accordingly, there is a need for new treatments for both dry and wet macular degeneration which have a higher efficacy and lower risks. Such need is met by the use of Chinese herb compositions of the present invention.