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Review | DOI: https://doi.org/10.31579/2690-8794/233
Advisor doctor and expert trainer, The National Training and Development Center, Iran.
*Corresponding Author: Aamir Jalal Al-Mosawi, Advisor doctor and expert trainer, The National Training and Development Center, Iran.
Citation: Aamir Jalal Al-Mosawi, (2024), Presbyopia Cure Research progress: An Educational Article and expert Opinion, Clinical Medical Reviews and Reports, 6(8); DOI:10.31579/2690-8794/233
Copyright: © 2024, Aamir Jalal Al-Mosawi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 13 September 2024 | Accepted: 20 September 2024 | Published: 27 September 2024
Keywords: presbyopia; pilocarpine; topical agents; near vision improvement; pharmacologic treatments; ocular health; education article; expert opinion
Presbyopia, commonly known as "old man's eye disease," is a condition that leads to difficulty seeing near objects due to changes in the eye's lens. Historical explanations date back to Aristotle, with significant contributions from figures like René Descartes and Ernst Brücke, who helped identify the ciliary muscle's role in accommodation. Benjamin Franklin devised the first bifocals in the 1780s as a solution for presbyopia. In the 19th century, advancements included the development of eye charts by Heinrich Kuechler and Eduard Jaeger for assessing near vision. Hermann von Helmholtz later explained that presbyopia results from the loss of lens elasticity due to aging. Presbyopia, an age-related decline in near vision, has driven the search for effective and convenient pharmaceutical therapies. Topical parasympathomimetic agents, particularly pilocarpine, have emerged as promising treatments for this condition. The aim of this paper is to provide an understanding and an overview of presbyopia research progress. Pilocarpine has been shown to effectively improve near vision in presbyopic patients. Early studies demonstrated its potential for inducing accommodative changes in the lens. Subsequent research confirmed that pilocarpine combined with diclofenac or phenylephrine can enhance near vision while maintaining distance vision and minimizing side effects. More recent studies affirmed that pilocarpine 0.4% improves near vision with a good safety profile. Additionally, investigations into lipoic acid choline ester suggest new avenues for improving lens elasticity and treating presbyopia.
Conclusion: Topical pharmacologic treatments, especially those involving pilocarpine, represent a significant advancement in managing presbyopia. Current evidence supports the effectiveness of these therapies in improving near vision without severely affecting distance vision. The combination of pilocarpine with other agents like diclofenac or phenylephrine has demonstrated both efficacy and safety. Ongoing research into new compounds and formulations, such as lipoic acid, holds promise for future developments in presbyopia treatment. Further studies are needed to refine these therapies, address side effects, and optimize treatment protocols.
Presbyopia, or "old man's eye disease" (where "presbys" is a Greek word meaning "old man" and "ops" means "eye"), is the decreased ability of elderly people to clearly see near objects. Aristotle (384-322 BC) attempted to explain why elderly people do not see as well as younger individuals. Lucius Mestrius Plutarchus, around 100 AD, also tried to explain the occurrence of presbyopia in his book “Symposiacs” [1].
In 1677, René Descartes attributed the insufficiency of accommodation to changes in lens shape, suggesting that lens curvature increases to enable viewing near objects [2]. Descartes's notion was later supported by the recognition of the ciliary body (Figure-1) and the ciliary muscle, known as “Brücke’s muscle,” by Ernst Brücke (Figure 2A) in 1847. Brücke’s anatomical description of the eye remains valid to this day.
Figure-1: The ciliary body
Figure-2A: Ernst Wilhelm Ritter von Brücke (July 1819- January 1892), a German physician and physiologist
The ciliary muscle is a ring of smooth muscle in the uvea, the middle layer of the eye. It controls accommodation for seeing at various distances and changes the shape of the lens [3].
Most likely, during the 1780s, Benjamin Franklin (Figure-2B) devised the first pair of bifocals (eyeglasses), marking the first treatment for presbyopia [4].
Interestingly, in 1840, James Hunter from Edinburgh reported a case of sudden transient presbyopia in a young boy [5].
Figure-2B: Benjamin Franklin (1705-1790), an American scientist and inventor
In 1845, William White Cooper (Figure-2C) emphasized that between the ages of forty-five and fifty, it is very common for individuals to find that they can no longer see near objects with the same distinctness as before due to
changes in their eyes’ refractive powers resulting from diminished lens convexity. The rays from near objects are no longer focused on the retina. Cooper pointed out that double convex glasses were used at that time to treat presbyopia because they reduce the divergence of rays from near objects [6]
Figure-2C: William White Cooper (November 1816-June 1886), an English surgeon-oculist
In 1843, German physician Heinrich Kuechler (1811-1873) designed one of the earliest eye charts to test vision, which included one word per line, with the first word at the top being large and the size progressively decreasing with each line. Three different versions of the Kuechler chart were used to prevent patients from memorizing the words.
In 1854, Austrian ophthalmologist Eduard Jaeger (Figure-3A) devised an eye chart consisting of paragraphs of decreasing font sizes to test near vision acuity, which is more relevant to presbyopia. The Jaeger eye chart, also known as the Jaeger card, included text of gradually smaller size rather than a single word per line like Kuechler’s chart [7-9].
Figure-3A: Eduard Jäger von Jaxtthal (June 1818-July 1884), an Austrian ophthalmologist
The larger font size on a modern Jaeger chart is J10 (14-point in Times New Roman font), and the smallest is J1 (3-point type in Times New Roman). Some Jaeger charts also include J1+ text, which is even smaller.
In 1867, Hermann von Helmholtz (Figure-4) suggested that the lens becomes more convex with ciliary muscle contraction, contributing to lens elasticity. He proposed that presbyopia occurs due to loss of lens elasticity, a consequence of sclerotic changes associated with aging [10]
Figure-4: Hermann Ludwig Ferdinand von Helmholtz (August 1821-September 1894), a German physicist and physician
In 1976, Dr. J. George Rosenbaum (Figure-5) presented a card-sized vision screener at the American Academy of Ophthalmology, which has been increasingly used to test near vision [11].
Figure-5: Dr. J. George Rosenbaum
In 1976, Ian L. Bailey (Figure-6A) and Jan Lovie-Kitchin (Figure 6B) from the National Vision Research Institute of Australia designed the LogMAR
chart test, which can be used to measure distance and near vision acuity. Each line contains five letters, and each correctly read letter represents 0.02 logMAR, so a line read correctly receives 0.1 logMAR [12].
Figure-6A: Ian L. Bailey, an optometrist from Australia
Figure-6B: Jan Lovie-Kitchin, an optometrist from Australia
The increasing demand for convenient treatments for presbyopia has led to renewed interest in topical pharmacologic agents, particularly parasympathomimetic drugs such as pilocarpine. Historical and recent studies highlight various approaches to leveraging these treatments for managing presbyopia, a common age-related vision condition.
Pilocarpine was isolated from the bark and leaves of Pilocarpus jaborandi in 1874 by A.W. Gerrard (Figure-7), a pharmaceutical chemist from London, and by H. Hardy in France in 1877. It has been used to treat glaucoma for over 140 years. It is a lactone alkaloid and a cholinergic muscarinic receptor agonist that causes miosis and contraction of the ciliary muscle (accommodative spasm), resulting in lens thickening and forward movement, increasing depth of focus [13].
Figure-7: A.W. Gerrard, a pharmaceutical chemist from London
In 1882, Simeon Snell (1851-1909), an English ophthalmologist, reported the use of pilocarpine in a 70-year-old female patient with an attack of acute glaucoma seen in September 1880. The patient had reduced vision associated with severe pain. After declining treatment with iridectomy, the patient improved with pilocarpine treatment, resulting in complete restoration of vision [14].
The Pilocarpus jaborandi species was officially included as a drug in the British Pharmacopoeia in 1914.
In 1968, Lindstrom studied the effects of 2% pilocarpine eye drops on the visual performance of 20 normal individuals. They observed significant individual variability in response, with maximum effects on visual acuity, accommodation, and refraction noted in younger subjects. Older individuals experienced less change. The most significant change was an initial reduction in distance visual acuity. All individuals experienced characteristic miosis without considerable reduction in peripheral fields, with an average decrease in intraocular pressure of 1.7 mm Hg. All subjects showed some reduced dark-adaptive ability [15].
In 1973, David H. Abramson and colleagues reported a study involving presbyopic volunteers aged 60 to 80 years. They performed high-resolution ultrasonic biometry before and at 15-minute intervals after topical instillation of 2% pilocarpine hydrochloride. Pilocarpine had a measurable effect within 15 minutes, resulting in axial thickening of the lens (average 0.25 mm) and 85% of the eyes showing a shallowing of the anterior chamber (average 0.19 mm). The maximum effect of pilocarpine was observed 45 to 60 minutes after instillation [16].
2005 Study by Koeppl et al. demonstrated that pilocarpine induces a forward shift of the lens in presbyopic individuals, showing its effectiveness primarily in those with presbyopia rather than younger individuals.
Koeppl et al. reported a study involving 10 emmetropic young individuals aged 23 to 25 years and 11 emmetropic presbyopic individuals aged 51 to 62 years. They studied the effects of two drops of 2% pilocarpine, measuring anterior chamber depth and lens thickness using partial coherence interferometry. The application of pilocarpine eye drops mainly affected presbyopic individuals, inducing ciliary muscle contraction, which resulted in a significant forward shift of the anterior and posterior lens poles, leading to a translational forward lens shift of about 150 micrometers. This study showed that pilocarpine eye drops had primarily a physiological action in young phakic individuals but acted as a super-stimulus in presbyopic phakic individuals [17].
2012 Research by and colleagues investigated the use of 1% pilocarpine combined with 0.1% diclofenac, finding it improved near vision in presbyopic patients without affecting distance vision, with effects lasting up to five years.
Benozzi and colleagues from Argentina emphasized that presbyopia occurring after age 40 results from a progressive decline in accommodation,
which depends on the contraction of the ciliary muscle and iris, lens changes, and convergence. They suggested the possibility of correcting accommodation in emmetropic presbyopic patients and restoring near vision without affecting distance vision using topical cholinergic medication combined with non-steroidal anti-inflammatory drugs.
Benozzi and colleagues treated 100 patients aged between 45 and 50 who had presbyopia with a combination of 1% pilocarpine and 0.1% diclofenac eye drops given six-hourly. These patients initially had a near vision of Jaeger 1 (J1) and a far vision of 20/20. One percent of the patients experienced ocular burning and discomfort, leading them to stop treatment. Over the first year, treatment improved near vision without affecting distance vision, and the vision improvement was maintained for five years. Benozzi and colleagues concluded that a topical muscarinic cholinergic agonist combined with diclofenac can restore accommodation and near vision without affecting far vision [18].
In 2003, Rainer Schalnus from Germany noted that nonsteroidal anti-inflammatory drugs (NSAIDs) eye drops, including diclofenac, are increasingly used in ophthalmology to prevent and manage ocular inflammation and edema from various causes, as well as in the treatment of allergic conjunctivitis [19].
In 2010, Kim and colleagues reiterated the emerging uses of NSAID eye drops in reducing miosis and inflammation, treating scleritis, and preventing and treating cystoid macular edema, among others. They also pointed out that the simultaneous application of topical NSAIDs and pilocarpine can reduce ocular discomfort [20].
2015 Study by Abdelkader explored a combination of carbachol and brimonidine, showing improved near vision and high patient satisfaction.
Almamoun Abdelkader suggested the use of carbachol, a parasympathomimetic medication plus an alpha agonist (brimonidine) to induce optically beneficial miosis to improve near vision in presbyopia. They reported a placebo-controlled study which included emmetropic patients having presbyopia, aged between 43 to 56 years. Thirty patients were treated with single dose of 2.25
Recent studies confirm that topical agents like pilocarpine, often combined with non steroidal anti-inflammatory drugs or other drugs, offer effective treatments for presbyopia by enhancing near vision without severely compromising distance vision.
Pilocarpine's ability to induce ciliary muscle contraction and facilitate accommodation has been demonstrated across various studies and formulations, showing lasting benefits for presbyopic patients.
While pilocarpine combined with diclofenac or phenylephrine appears effective and generally safe, side effects such as ocular discomfort and headaches have been noted. Advances in treatment also include exploring new compounds like lipoic acid for improving lens elasticity.
Overall, the ongoing research supports the potential of topical pharmacologic therapies as a viable approach for managing presbyopia, although further studies are needed to refine these treatments and optimize their effectiveness and safety profiles.
Acknowledgement
The author has the copyright of all the sketches (Figures) included in this paper.
Conflict of interest: None.
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