Improvement of Presbyopia Using a Mixture of Traditional Chinese Herbal Medicines, Including Cassiae Semen, Wolfberry, and Dendrobium huoshanense

1. Background

The prevalence of presbyopia in the population is gradually growing worldwide. Its prevalence was estimated to be at 1.7–2.0 billion people globally in 2015. A total of 826 million of those affected do not have sufficient vision correction. In China, ≥12% of patients with vision impairment are a result of uncorrected presbyopia [1]. Presbyopia typically affects people from the 4th decade of life; however, accommodation to it decreases with age, with it nearly finishing after age fifty and impacting almost 100% of people over the age of 65. It is worth noting that, in recent years, the overuse of smartphones and portable computers has led to the rapid progression and onset of presbyopia (around 35 years). The mechanisms of accommodation depend on the contraction of the ciliary muscle and iris; changes in the shape of the lens and convergence can show a variation in dioptric powers to enable people to see or work easily at near distances [2].

When people gaze at objects intently, the accommodation initiates a series of actions. Accommodation is the ability of the eye to change focus, and the amplitude of accommodation (AA) is the maximum potential increase in diopter that an eye can achieve in adjusting its focus. The accommodative system is controlled by acetylcholine (Ach) from the parasympathetic nerves. The change in biometry that diopters exert and increasing lenticular stiffness are responsible for presbyopia. AA should be measured corresponding to the acuity at the viewing distance. When a human wants to see objects about 40 cm in front of the eyes and the accommodation is functional, the ciliary muscles began to contract, anchor at the scleral spur, and the trabecular meshwork with peripheral cornea comes forward. Lastly, the thickness of the lens increases, and the person is able to view nearby objects. Presbyopia is a physiologic inevitability and aging is the primary etiology. With the development of society, the overuse of portable computers and smartphones has become an important cause of presbyopia [3, 4]. Geographic and sex factors have also been reported [5, 6]. In general, presbyopia manifests at 40–45 years of age due to the gradual loss of accommodation, necessitating the extra-additional (Add) power of reading spectacles. AA generally decreases at a rate of 0.3 D per year. The symptoms of presbyopia usually occur when the AA value decreases to below about 3–4 D. At this point, subjects with presbyopia suffer from blurred vision, asthenopia, ocular pain, and headaches after reading or working at close distances for prolonged periods. In our current understanding of the principles, the add diopter is about 0.097 to 0.105 D/year for presbyopia. When patients are 45 to 50 years of age, the decline in accommodation is around 3 D/year. By the fifth decade of life, there is an obvious reduction in AA. It is not surprising that this accommodation decreases to nearly zero at the age of 70 years [7].

Except for AA, presbyopia occurs due to changes in the chemical composition and physical structure of the lens [8]. There exists a close relationship between the biomechanics of the lens, accommodative system, and presbyopia. The thickness of the elastic capsule of the lens and the flexibility of zonular fibers change during adulthood may impact patients with presbyopia. An increase in the fibrillary materials of zonules reduces the compliance of the posterior insertion of the ciliary muscle. The deterioration of the elastic components of the ciliary body and choroid may result in a decline in AA. Furthermore, vitreous liquefaction occurs and the pressure between the anterior and posterior chamber may change with age [9]. The irregularity of the fibrous morphology of the lens is also noted when humans become older. These findings have been reported as the predisposing factors for presbyopia [10]. Hence, the loss of AA in individuals begins early in life at 40 to 50 years of age and rapidly progresses when people are around 55 years old.

Presbyopia is also believed to reflect a loss of accommodation due to cataract formation and the weakening of the ciliary muscles—the lens zonules apparatus.

Cassiae Semen is a well-known traditional medicine that has been used for improving eyesight, liver function, and various types of inflammation in China since ancient times. Of late, cassia seeds have been used to treat headaches, obesity, periocular pain, constipation, hypertension, hyperlipidemia, Alzheimer’s disease, ischemic stroke, and bronchospasm, as well as some ocular diseases such as dry eye and retinitis pigmentosa [58]. A total of 55 chemical compounds in Cassiae Semen were identified, including flavonoids, emodin, chrysophanol, physcion, obtusin, rhein, aurantio-obtusin, chryso-obtusin, and anthraquinones—which showed various pharmacological functions, including anticoagulant, antiangiogenic, antimicrobial, and antioxidant abilities. For example, physcion belongs to polyphenol, which has antioxidative and anti-inflammatory properties. Aloe-emodin regulates the apoptosis of retinal ganglion cells and prevents glaucoma. Besides this, obtusin and aurontio-obtusin may enhance vasodilation and diuresis. Chrysophanol and physcion were suggested to decrease IOP in our study in 2013 [19]. We know that shallow A/C and the elevation of IOP may be found during accommodation, resulting in periocular pain and even headaches. Therefore, the ability of cassia seeds to lower the IOP function could relieve the symptoms of presbyopia. Furthermore, obtusifolin and emodin are important in accommodation due to acetylcholinesterase (AChE) activity in the cholinergic nervous system through the activation of the muscarinic receptors [59]. We believed that the contractility of the ciliary muscle, relaxation of zonules, more curved lenses, mydriasis, increase in the thickness of the lens, and modification of the shape and position of the lens during accommodation due to parasympathetic functions may be due to the effects of cassia seed extracts. Hence, taking Cassiae Semen may help to obtain AA and good near vision. The real mechanisms behind accommodative pathways need to be investigated more exhaustively in the future.

The fruit of L. barbarum or goji berries has been used as an antiaging herb to maintain good health for a long time. Goji can also improve “Kidney Yang Deficiency Syndrome” and balance the “yin” and “yang” in the body. There are various primary extracts of goji berries, including carotenoids, phenolic acid, flavonoids, betaine, taurine, β-sitosterol, polysaccharides, scopoletin, and vitamins [60]. Goji berries exhibit cytoprotective, immunomodulatory, antifatigue, neuroprotective, anti-inflammatory, antiradiation, antiapoptotic, anticoagulant, antiplatelet, cardioprotective, antiproliferative, antimicrobial, and antioxidant effects. These berries can also improve arterial compliance, skeletal muscle power, renal function, and hemopoiesis and ameliorate anemia, asthma, metabolic syndrome, diabetes mellitus, various types of cancers, and Parkinson’s disease [61]. A recent study showed that the use of goji berries led to a change in serum metabolic profiles, including energy metabolism (lactic acid), lipid metabolism (cholesterol), and biosynthesis of catecholamine (norepinephrine). Furthermore, Guo et al. demonstrated that L. barbarum polysaccharides could increase the level of cortisol and epinephrine [62]. In the ophthalmic field, wolfberries are known to be beneficial for presbyopia-induced dry eye, blurred vision, ocular fatigue, age-related macular degeneration, diabetic retinopathy, UV light-induced retinal degeneration, retinitis pigmentosa, and even glaucoma [63].

Dendrobium, known as “Shihu,” is a Chinese traditional medicinal herb that belongs to the Orchidaceae family. The stem has been traditionally used for centuries for treating diseases such as throat inflammation and chronic superficial gastritis, strengthening the body, and prolonging life. Dendrobium is widely famous since ancient times for its medical value in treating cataracts. The ingredients extracted from DD are alkaloids, stilbenoids, anthracene, polysaccharides, fluorine, flavone, phenanthrene, and gigantol that have several pharmacological functions, including enhancing immune activities, controlling blood sugar, inhibiting tumor growth, and protecting the liver from oxidative stress [64]. DD is also used for several ophthalmic diseases, such as dry eye and diabetic and ischemic retinopathy. Accumulating evidence indicates that all improvements in ocular conditions are due to the plant’s anti-inflammatory and antioxidant abilities. DD also shows significant hypoglycemic and anticataract activities through its inhibition of nitric oxide (NO), aldose reductase, protein glycation, and advanced glycation end products (AGEs) [65]. During aging, the cortex thickens, the lens becomes more curved, and the nucleus becomes less deformed. The pharmacologic mechanisms of DD include the prevention of the development of cataracts and improvement in AA. Except for DD, cassia seeds and wolfberries also contribute to slowing down the formation of cataracts through their antioxidants. For example, cassia seeds contain polysaccharides, emodin, and flavonoids that may resist oxidase stress and decrease the maturation of cataracts. The anthraquinones have inhibitory activity in protein glycation and aldose reductase, preventing the formation of cataracts [66]. As for L. barbarum, it can induce the activation of suituin 1 and thereby decrease cataract formation [67]. The extracts from goji berries, including polysaccharides, phenolic acid, and flavonoids, can help in preventing free radicals from attacking the lens fibers. Therefore, goji berry and cassia seeds have a stronger antioxidant ability, which may retain lens clarity and prevent presbyopia.

In this study, we administered mixed herbal drugs to subjects aged 45 to 70 years for six months. The mean AA reached a maximum value of 2.1 D after the sixth month (P < 0.05), and this decreased to 2.0 D at the ninth month without herbal treatments (P < 0.05). This indicates that these drugs could still exert positive effects after taking them for six months and further for at least three months without drug intake. The outstanding pharmacologic effects are prolonged because of the increased AA gain. Besides this, pupil size and near vision reached their maximal levels (5.6 mm and J 1.5) in the sixth month. The effective ability of mydriasis and near vision (4.2 mm and J 2.5) was also noted after the ninth month. We suggest that the parasympathetic function is predominant even in the ninth month. The primary pharmacological effects of the improvement in near vision were due to accommodation rather than miosis. A smaller pupil-enhanced DoF (sympathetic function) and good accommodative ability may increase the AA more (parasympathetic function). Cassiae Semen could enhance the accommodation by the parasympathetic effects that obtain AA. Besides this, intake of cassia seeds leads to miosis, followed by the pinhole effect and DoF, and goji berries supply sympathetic effects for dilated pupils. It is interesting that cassia seeds have parasympathetic effects; however, L. barbarum in our herbal capsule showed sympathetic effects. We conducted several previous studies and found that the ideal ratio of cassia seeds and L. barbarum was 5 : 5, to affect the presbyopic participants to have the best near visual acuity, with dilated pupils. In other words, the parasympathetic function is predominant when taking the designed herbal capsules, while the ratio of cassia seeds and L. barbarum was 5 : 5 in our previous small sample of studies after many adjustments (not published yet). The partial ability of the sympathetic function of goji berries may be counteracted by the parasympathetic function from Cassiae Semen. However, just the combined concentrations of two herbal drugs could enhance the near vision at around J 1.5. DD has an anticataract ability. In this study, we used three herbal drugs to offset the decrease in AA in presbyopic subjects. According to past studies, the best-estimated ratio of cassia seeds and L. barbarum was 5 : 5. When we added DD, we found the golden ratio of cassia seeds, goji berries, and DD to be 5 : 5:1. The final weight was 200 mg of cassia seeds, 200 mg of goji berries, and 40 mg of DD in one capsule, which may aid in improved AA of the participants.

5. Conclusion

Presbyopia describes the progressive loss of accommodation, weakness of the contraction of the ciliary muscles, reduction in the elasticity of zonules and lens capsules, and increased stiffness of the lens. The mechanism of our designed treatment is based on enhancing the accommodative ability and pupil control. Besides this, ameliorating the developing cataract formation is also important.

In this study, we proposed a novel herbal combination including Cassiae Semen, wolfberry, and DD for use in presbyopia. The parasympathetic function of cassia seeds could enhance the accommodative system, and the goji berry could supply appropriate effects for the sympathetic nervous system and moisturizing effects for the presbyopic symptoms and associated dry eyes. DD diminishes the progression of cataracts through the inhibition of sorbitol and AGE accumulation, and Cassiae Semen and wolfberry exhibit strong antioxidant abilities. The success rate was approximately 95% after six months of therapy. Therefore, we suggest that herbal drug supplements may be another choice because of their convenience, safety, and persistence of their beneficial pharmacologic functions.

https://onlinelibrary.wiley.com/doi/10.1155/2021/9902211