The understanding of glaucoma has changed greatly from ancient times to the present. The ancient Greek term “glaukos” referred to a blue-green discoloration of the pupil, possibly originating from corneal edema seen in acute angle-closure glaucoma. At that time, it was not even distinguished from cataracts or keratitis.
After the early modern period, the association between eye hardness and visual dysfunction became clinically recognized1). In the 19th century, von Graefe’s tonometer and the Imbert-Fick applanation principle emerged, establishing the basis for objective measurement of intraocular pressure1). With the spread of the ophthalmoscope and the development of intraocular pressure measurement, a disease concept linking elevated intraocular pressure and optic disc cupping was formed1).
In the 20th century, the development of accurate tonometers (Friedenwald & Moses 1950, Goldmann 1954), the use of gonioscopy (Barkan 1954), and population-based epidemiological studies transformed the understanding of glaucoma2). Particularly important was the recognition that asymptomatic open-angle glaucoma (OAG) is a disease associated with various levels of intraocular pressure2). Before that, the term “glaucoma” referred only to angle-closure glaucoma or secondary glaucoma with extreme intraocular pressure elevation2).
QWhy is it important to know the history of glaucoma?
A
The concept of glaucoma has changed significantly over time. What was once a vague term referring to a change in pupil color is now precisely defined as a group of diseases characterized by optic neuropathy. Understanding the historical evolution helps grasp why current diagnostic criteria and treatment strategies were formed, and also provides insight into future research directions. Moreover, knowing how the old idea that “intraocular pressure above 21 mmHg is abnormal” has been revised is essential for understanding the modern concept of target intraocular pressure.
2. Recognition of Glaucoma in Ancient to Medieval Times
The ancient Greek word “glaukos” meant blue-green and referred to a pathological color change of the pupil. Hippocrates described “glaukosis” primarily as a disease of the elderly. He stated that when the pupil turned blue-green, silver, or blue, vision was lost. This description is thought to have included multiple diseases such as cataract, keratitis, and glaucoma.
In ancient India, the surgeon Sushruta (circa 800–700 BCE) described “Adhimantha” in the Sushruta Samhita. It was characterized by severe eye pain, marked inflammation, and rapid vision loss within 3 to 7 days, corresponding to today’s acute angle-closure glaucoma.
From the 8th century onward, Arab scholars translated Greek medical literature into Arabic. Hunayn ibn Ishaq translated “glaukos” as “zarqaa,” expressing both a light-colored iris and pathological discoloration. Avicenna described a hardened eye in which the lens became immobile due to thickening of the intraocular fluid. The method of diagnosing eye hardness by palpation was also established during this period.
In Europe, Arabic texts were translated into Latin, and the green discoloration of the pupil was called “viriditas.” During the Renaissance, advances in anatomy revealed that the pathology extended not only to the lens but to the entire eye.
Period
Key Figure
Contribution
Ancient Greece
Hippocrates
Description of glaukosis
Circa 800 BCE
Sushruta
Description of Adhimantha
8th century
Ibn Ishaq
Introduction of the concept of zarqaa
1622
Richard Banister
Association between ocular hardening and optic nerve damage
3. Establishment of Modern Ophthalmology (19th Century)
In the early 18th century, Michel Brisseau first clearly separated glaucoma and cataract as two distinct diseases. However, it took more than a century to understand the nature of glaucoma.
Invention of the Ophthalmoscope and Establishment of Glaucomatology
In 1851, Hermann von Helmholtz invented the ophthalmoscope. This allowed direct observation of the fundus, enabling for the first time the evaluation of optic disc changes in glaucoma.
Albrecht von Graefe graduated from medical school at age 19 and trained throughout Europe. In 1854, he founded the specialized ophthalmology journal Archiv für Ophthalmologie and is known as the “father of modern ophthalmology and glaucoma.” He hypothesized that chronic glaucoma is caused by elevated intraocular pressure and demonstrated in 1857 at the first International Congress of Ophthalmology that iridectomy is effective for glaucoma treatment.
Understanding the Angle and Development of the Tonometer
In 1861, Frans Donders and Jozef Haffmans introduced the concept of “glaucoma simplex,” which corresponds to current primary open-angle glaucoma.
Before the invention of the tonometer, intraocular pressure was assessed by palpation through the upper eyelid (digital tonometry). In 1862, von Graefe built an early tonometer, but it was placed on the eyelid due to the lack of ophthalmic anesthetics. In 1905, Hjalmar Schiotz invented the indentation tonometer, enabling consistent intraocular pressure measurement for the first time.
QHow did the invention of the ophthalmoscope contribute to the understanding of glaucoma?
A
Before 1851, the fundus could not be directly observed, and the pathology of glaucoma remained speculative. Some physicians, like Jules Sichel, argued that glaucoma was a choroidal disease. The ophthalmoscope allowed observation of optic disc cupping, establishing the understanding that glaucoma is a disease of the optic nerve. Furthermore, it enabled objective evaluation of treatment effects and monitoring of disease progression, forming the foundation of modern glaucomatology.
Calabar bean (1862): Sir Thomas Fraser introduced it as the first intraocular pressure-lowering drug. It is the source of the potent miotic physostigmine (eserine). Its ability to lower intraocular pressure was officially reported in 1876.
Pilocarpine: The second miotic drug introduced by Adolf Weber, a student of von Graefe. It was the mainstay of glaucoma treatment for many years.
Epinephrine (1901): Discovered accidentally by French physician Jean Darier while studying adrenal extracts. It became commercially available only in the 1950s.
Modern Pharmacotherapy (Late 20th Century)
Timolol (FDA approved 1978): A non-selective beta-blocker developed by Merck. It was used as the optimal first-line agent for 20 years.
Latanoprost (FDA approved 1996): Discovered accidentally by Lazlo Bito while studying ocular inflammatory mediators. Due to its high safety and efficacy, it is now the leading first-line agent.
Antiglaucoma drugs have been available since 1875, and various drug classes have been introduced over time 3). Drance initially popularized the concept that open-angle glaucoma occurring at normal intraocular pressure is essentially a different disease 2). However, subsequent randomized controlled trials showed that lowering intraocular pressure slows glaucoma progression regardless of whether baseline pressure is normal or elevated 2).
QWhy have prostaglandin analogs become first-line agents?
A
Prostaglandin analogs provide a powerful intraocular pressure-lowering effect (approximately 25–33%) with once-daily dosing. They have few systemic side effects and lack the cardiopulmonary effects associated with beta-blockers. They have a unique mechanism of action that enhances aqueous humor outflow through the uveoscleral pathway, and they are easily combined with other drug classes. Due to these advantages, they have established themselves as the first-line treatment for glaucoma worldwide since the late 1990s.
Iridectomy (1856): The first surgery established by von Graefe for glaucoma treatment.
Full-thickness fistulizing procedures (early 1900s): Aimed at increasing aqueous outflow but were associated with serious complications such as hypotony, flat anterior chamber, cataract, and infection.
Trabeculectomy (1968): Popularized by John Cairns. It involves removing a portion of the trabecular meshwork and Schlemm’s canal, with flow regulation via a scleral flap. In modern practice, outcomes have improved with the use of antifibrotic agents.
Tube Shunt to Minimally Invasive Glaucoma Surgery
Tube Shunt (1969): Anthony Molteno introduced a silicone tube drainage device. In 1993, Mateen Ahmed designed a pressure-sensitive valve, achieving controlled outflow.
iStent (FDA approved 2012): A trabecular bypass placed in Schlemm’s canal.
Hydrus Microstent (FDA approved 2018): A longer stent that scaffolds Schlemm’s canal to enhance outflow.
XEN Gel Stent (approved 2016): Creates a pathway from the intraocular space to the subconjunctival space.
Notable in the history of glaucoma surgery are the earliest attempts at drainage implants. In 1876, French surgeon Louis de Wecker placed a gold wire implant in a patient with absolute glaucoma. In 1925, Jon Stefansson reported outcomes of coiled gold wire implants in 25 glaucoma patients. These pioneering efforts led to the later Molteno tube shunt.
In the untreated group of the EMGT (Early Manifest Glaucoma Trial), the natural rate of visual field progression averaged 1.08 dB/year 3). It varied by type: 1.31 dB/year for high-tension glaucoma, 0.36 dB/year for normal-tension glaucoma, and 3.13 dB/year for pseudoexfoliation glaucoma3). The accumulation of such evidence has contributed to optimizing the timing and methods of treatment intervention.
With the rise of molecular genetics and gene therapy, new treatments for glaucoma are being developed.
Stem Cell Therapy: In animal models, bone marrow-derived mesenchymal stem cells have shown protective effects on retinal ganglion cells, suggesting potential for optic nerve regeneration. However, human trials have not confirmed visual improvement.
Gene Therapy: Research is underway using CRISPR-Cas9 to modify the expression of glaucoma-causing genes. Animal models have reported suppression of glaucomatous damage, but further studies are needed to confirm efficacy in humans.
Age and intraocular pressure remain the most important risk factors for glaucoma3). Non-white race (especially Black), family history of glaucoma, pseudoexfoliation, disc hemorrhage, thin cornea, and myopia are also reported as major risk factors 3).
Stamper RL. A history of intraocular pressure and its measurement. Optom Vis Sci. 2011;88(1):E16-E28. doi:10.1097/OPX.0b013e318205a4e7.
Quigley HA. Understanding glaucomatous optic neuropathy: the synergy between clinical observation and investigation. Annu Rev Vis Sci. 2016;2:235-254. doi:10.1146/annurev-vision-111815-114417.
European Glaucoma Society. European Glaucoma Society Terminology and Guidelines for Glaucoma, 6th Edition. Br J Ophthalmol. 2025.
Copy the article text and paste it into your preferred AI assistant.
Article copied to clipboard
Open an AI assistant below and paste the copied text into the chat box.
