Open-angle glaucoma

# Overview
Glaucoma not a single disease but a group of disorders characterized by a progressive optic neuropathy, leading to a characteristic appearance of the optic disc and a specific pattern of irreversible visual field defects that are associated frequently but not invariably with raised intraocular pressure. The normal range of eye pressure in general population is usually between 10-22 mmHg. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness.
Open Angle Glaucoma is typically a chronic, slowly progressive optic neuropathy
with characteristic patterns of optic nerve damage and visual field loss.
It can be Primary, i.e. without any known underlying etiology or secondary with known underlying etiologies.

# Historical Perspective
Glaucoma has been known in medicine since Antiquity.  In Greek 'glaukos' a word appearing in the works of Homer where it seems to mean a sparkling silver glare. Later the word was used for colours such as sky-blue or green.The word entered ophthalmology when Hippocrates, in his Aphorisms, lists among the infirmities of the aged a condition he called glaucosis which he associated with dimness of vision. The implied meaning is that of a clouded or blue-green hue of the cornea in end stage forms that may result in corneal edema and/or coinciding cataract. The Hippocratic writings make no clear distinction between cataract and glaucoma. Both Classical and Alexandrian Greeks did not recognize the specific disease which we now call glaucoma.
The definition of glaucoma has changed drastically since its introduction around the time of Hippocrates in approximately 400 BC. The first recognition of a disease associated with a rise in intraocular pressure and thus corresponding to what is now known as glaucoma occurred in the Arabian writings, Book of Hippocratic treatment, of At-Tabari (10th century). In European writings, it was Richard Bannister (1622), an English oculist and author of the first book of ophthalmology in English, who recognized glaucoma as a disease with four features: increased intraocular pressure, long duration of the disease, the absence of perception of light and the presence of a fixed pupil. However, throughout the 18th century the term glaucoma was still merely a label applied to an inflamed eye wherein the pupil appeared greenish-blue and the visual prognosis was bad, but the tension of the eye was not stressed.
It was only after the careful description by Antoine-Pierre Demours (1818) that the central concept of a rise in intraocular pressure became fully established. G.J. Guthrie (1823) and William McKenzie, a Scottish clinician (1835) confirmed these findings. Donders (1862) described an incapacitating increased eye tension occurring without any inflammatory symptoms as "simple glaucoma". In 1973 Drance provided for the first time the definition of glaucoma as an optic neuropathy caused by increased intraocular pressure and other associated risk factors.
The first patient in the United States federal government's Compassionate Investigational New Drug program, Robert Randall, was afflicted with glaucoma and had successfully fought charges of marijuana cultivation because it was deemed a medical necessity (U.S. v. Randall) in 1976.

# Classification

# Pathophysiology

# Causes

# Differentiating Any Disease from other Diseases

# Epidemiology and Demographics
Primary open-angle glaucoma (POAG) poses a significant public health problem. The estimated
prevalence of POAG in the United States in individuals older than 40 years is 1.86% (95% confidence
interval, 1.75%1.96%), based on a meta-analysis of population-based studies. Applied to data from
the 2000 US census, this percentage translates to nearly 2.22 million Americans affected. The number of POAG patients is estimated to increase by 50%, to 3.36 million in 2020.
The World Health Organization (WHO) undertook an analysis of the literature to estimate the
prevalence, incidence, and severity of the different types of glaucoma on a worldwide basis. The data collected predominantly in the late 1980s and early 1990s, it was estimated the global
population of persons with high IOP (>21 mm Hg) to be 104.5 million. The incidence of POAG was
estimated at 2.4 million persons per year. Blindness prevalence for all types of glaucoma was
estimated at more than 8 million persons, with 4 million cases caused by POAG. Glaucoma was
theoretically calculated to be responsible for 12.3% of blindness. This makes glaucoma the second
leading cause of blindness worldwide, following cataract.
The estimated prevalence varies
widely as per different studies population-based samples; the Rotterdam Study (northern European population)
showing a prevalence of 0.8% and the Barbados Eye Study (Caribbean population) showing a
prevalence of 7% in individuals older than 40 years. In these studies, there is an increase in the prevalence of glaucoma in older individuals, with estimates for persons in the 7th decade being generally 3 to 8 times higher than those for persons in their 4th decade.
Among whites aged 40 years and older, a prevalence of between 1.1% and 2.1% has been
reported based on population-based studies performed throughout the world. The prevalence among
black persons and Latino persons is up to 4 times higher compared to the prevalence among whites.
Black individuals are also at greater risk of blindness from POAG, and this risk increases with age: in
persons aged 4665 years, the likelihood of blindness from POAG is 15 times higher among blacks
than that among whites.

# Risk Factors
- Age : The risk increases with the increase in age.The visual field defects were 7 times more likely to progress in patients aged 60 years or older than in those younger than 40 years. Although increased lOP with age has been observed in many populations and may account for part of the relationship between age and glaucoma, studies in Japan have shown a relationship between glaucoma and age even with no increase in lOP in the population.
- Race : The prevalence of POAG is 3 to 4 times greater in black persons and Hispanic persons than in non-Hispanic white individuals. Blindness from glaucoma is at least 4 times more common in blacks than in whites. Glaucoma is more likely to be diagnosed at a younger age and likely to be at a more advanced stage at the time of diagnosis in black patients than in white patients.The Baltimore Eye Survey found that the prevalence of glaucoma increases dramatically with age, particularly among black persons, exceeding 11% in those aged 80 years or older.
- Family History: A positive family history is also a risk factor for POAG. The relative risk of POAG is increased approximately 3.7-fold for individuals who have a sibling with POAG.
- Myopia : The evidence supports an association between POAG and myopia.  The concurrence of POAG and myopia cause difficulty in diagnosis and management of POAG. There is an increased difficulty in evaluation of the optic disc is particularly complicated in highly myopic eyes that have tilted discs or posterior Staphyloma. The magnification of the disc due to the myopic refractive error interferes with optic disc evaluation. Myopia-related retinal abnormalities can cause visual field defects apart along with glaucoma. High refractive error may also make it difficult to perform accurate perimetric measurement and to interpret visual field abnormalities.
- Diabetes Mellitus : The role of diabetes mellitus in causing POAG is still controversial. Though some studies have found diabetes plays a significant role in the disease, other studies have not found diabetes to be major risk factor.
- Hypertension : The systemic hypertension is associated with a low risk of the presence of glaucoma in younger patients and with an increased risk in older (>65 years) patients. It is considered that with advancing age, the adverse effects of chronic hypertension on the optic nerve microcirculation may lead to  the nerve's susceptibility to the development of glaucomatous optic neuropathy.  Many studies demonstrate that lower ocular perfusion pressure is a strong risk factor for the development of glaucoma, independent of lOP alone. Some research groups define ocular perfusion pressure as blood pressure (systolic, diastolic, or mean arterial) minus lOP. The overtreatment of systemic hypertension may be a contributing factor to glaucoma progression in some cases and hence, should be avoided.
- Retinal vein occlusion : The patients with central retinal vein occlusion may lead to an elevated lOP and glaucoma. In some case, there may be presentation of preexisting POAG or other types of glaucoma. After CRVO, patients may develop angle-closure glaucoma or, at a later stage, neovascular glaucoma. The comorbidity is due to elevated lOP in susceptible individuals, thus are at risk of developing CRVO.
- Sleep apnea
- Thyroid disorders
- Hypercholesterolemia
- Migraine
- Raynaud Phenomenon

# Differential diagnosis
- Ocular hypertension - elevated IOP but no definite signs of glaucomatous optic neuropathy
- Normal tension glaucoma - all the features of POAG but IOP always measured within normal limits
- Primary angle closure glaucoma - narrow drainage angle on gonioscopy
- Pigment dispersion glaucoma - Krukenberg spindle, iris transillumination, heavily pigmented angle in all 360 degrees
- Pseudoexfoliation glaucoma - pseudoexfoliative material seen on pupil margin and lens
- Steroid-induced glaucoma - history of topical or systemic steroid usage
- Posner-Schlossman Syndrome - mild inflammation, unilateral
- Physiological cupping - normal large optic disc with large cup:disc ratio; should be symmetric
- Myopia - optic discs can be very difficult to assess, and may be associated visual field defects which are not generally progressive

# Natural History, Complications and Prognosis
The Collaborative Normal-Tension Glaucoma Study (CNTGS) reported that lowering IOP by at least
30% reduced the 5-year risk of visual field progression from 35% to 12%, confirming that IOP has a
clear role in this disease. However, because some patients did progress despite the reduction in IOP,
-ther factors may be operative as well. It should be noted that the protective effect of IOP reduction
was evident only after adjusting for the effect of cataracts, which were more frequent in the treated
group.
The treatment of normal-tension glaucoma is generally initiated
unless the optic neuropathy is determined to be stable. The CNTGS study demonstrated that in 65% patients the disease did not progress over the length of the study despite the lack of treatment, whereas in 12%, the disease progressed despite successful IOP reduction. The rate of visual
field progression was highly variable but slow in the majority of those with visual field progression.
Treatment benefit was lower among patients with a baseline history of disc hemorrhage. The potential
role of neuroprotective agents is experimental and remains under investigation.
The initial goal of therapy should be to use currently available treatments to achieve an IOP level
that is approximately 30% below a carefully determined baseline, with appropriate adjustments of the
target pressure that take into account the baseline severity of the optic nerve damage, the risks of
therapy, and other relevant factors, such as life expectancy and comorbid conditions. Target pressure
should be reassessed and adjusted as needed during follow-up visits in order to maintain visual
function.
As with POAG, topical medical therapy in the management
-f normal-tension glaucoma should be initiated as the first mode of intervention. 
In addition to their IOP-lowering effect, some glaucoma medications
may also have neuroprotective properties or may improve ocular circulation. 
Medications, laser trabeculoplasty, and glaucoma filtering surgery may be indicated in an attempt
to achieve the target IOP range. 
An antifibrotic agent, either mitomycin C or 5-fluorouracil, may be
used to improve the success rate of filtering surgery. In the EMGT, the combination of betaxolol and
argon laser trabeculoplasty (ALT) had little pressure-lowering effect on eyes with baseline IOPs of 15
mm Hg or lower, suggesting that in such eyes incisional surgery and medications other than -
blockers are more likely to be beneficial.

# Diagnosis
History and Symptoms | Ocular Examination

# Treatment
Medical Therapy | Surgery

# Case Studies
Case #1