Glaucoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

Glaucoma is one of the earliest recognized ocular diseases since Antiquity. In Greek language the word ‘glaukos’ appears in the works of Homer, where it means – “a sparkling silver glare.” The word entered ophthalmology when Hippocrates, in his “Aphorisms”, when he listed – “glaucosis”, among the other diseases of the aged; 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 have not clearly differentiated between cataract and glaucoma.

• The definition of glaucoma has changed drastically since its introduction around the time of Hippocrates in approximately 400 BC.^[1]
• 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).^[2]
• In European medicine, 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 primary 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 used for inflamed eye wherein the pupil appeared greenish-blue and the visual prognosis was bad, but the tension of the eye was not stressed.^[3]
• The first complete description came from Antoine-Pierre Demours (1818) after the concept of a rise in intraocular pressure became fully established. G.J. Guthrie and William McKenzie, a Scottish clinician confirmed these findings in 1823 and 1835, respectively.
• In 1862, Donders 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.^[3]
• 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.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

The glaucoma is typically classified is as open angle or closed angle and as primary or secondary. There have been multiple schemes proposed for the classification for glaucoma. However the classification of the glaucomas based on initial events and classification based on mechanisms of outflow obstruction are commonly used.

• Developmental glaucoma

• Primary congenital glaucoma
• Infantile glaucoma
• Glaucoma associated with hereditary of familial diseases

• Primary glaucoma

• Primary open-angle glaucoma, also known as chronic open-angle glaucoma, chronic simple glaucoma, glaucoma simplex
• Low-tension glaucoma
• Primary angle-closure glaucoma, also known as primary closed-angle glaucoma, narrow-angle glaucoma, iris– block glaucoma, acute congestive glaucoma

• Acute angle-closure glaucoma
• Chronic angle-closure glaucoma
• Intermittent angle-closure glaucoma
• Superimposed on chronic open-angle closure glaucoma (combined mechanism)

• Variants of primary glaucoma

• Pigmentary glaucoma
• Exfoliation glaucoma, also known as pseudoexfoliative glaucoma or glaucoma capsulare

• Secondary glaucoma

• Inflammatory glaucoma

• Uveitis of all types
• Fuchs heterochromic iridocyclitis

• Phacogenic glaucoma

• Angle-closure glaucoma with mature cataract
• Phacoanaphylactic glaucoma secondary to rupture of lens capsule
• Phacolytic glaucoma due to phacotoxic meshwork blockage
• Subluxation of lens

• Glaucoma secondary to intraocular hemorrhage

• Hyphema
• Hemolytic glaucoma, also known as erythroclastic glaucoma

• Traumatic glaucoma

• Angle recession glaucoma: Traumatic recession on anterior chamber angle
• Postsurgical glaucoma

• Aphakic pupillary block
• Ciliary block glaucoma

• Neovascular glaucoma
• Drug-induced glaucoma

• Corticosteroid induced glaucoma
• Alpha- chymotrypsin glaucoma. Postoperative ocular hypertension from use of alpha chymotrypsin.

• Glaucoma of miscellaneous origin

• Associated with intraocular tumors
• Associated with retinal detachments
• Secondary to severe chemical burns of the eye
• Associated with essential iris atrophy

• Absolute glaucoma

1. Pre-trabecular (membrane overgrowth)

   • Fibrovascular membrane (neovascular glaucoma)
   • Endothelial layer, often with Descemet-like membrane (iridocorneal endothelial syndrome, posterior polymorphous dystrophy, penetrating and non-penetrating trauma)
   • Epithelial downgrowth
   • Fibrous ingrowth
   • Inflammatory membrane (Fuchs heterochromic iridocyclitis,luetic interstitial keratitis)

2. Trabecular

   • Idiopathic (chronic open-angle glaucoma, juvenile open-angle glaucoma)
   • “Clogging” of trabecular meshwork

   • Red blood cells (hemorrhagic-, ghost cell-, sickled red blood cells)
   • Macrophages (hemolytic-, phacolytic-, melanomalytic-)
   • Neoplastic cells (primary ocular tumors, neoplastic tumors, juvenile xanthogranuloma)
   • Pigment particles (pigmentary-, exfoliation syndrome / glaucoma capsulare, malignant melanoma)
   • Protein (uveitis, lens-induced glaucoma)
   • Viscoelastic agents
   • α-chymotrypsin-induced glaucoma
   • Vitreous

   • Alterations of the trabecular meshwork

   • Steroid-induced glaucoma
   • Edema (uveitis, scleritis, episcleritis, alkali burns)
   • Trauma (angle recession)
   • Intraocular foreign bodies (hemosiderin, chalcosis)

3. Post-trabecular

   • Obstruction of Schlemm’s canal (e.g. collapse at canal)
   • Elevated episcleral venous pressure
   • Carotid cavernous fistula
   • Cavernous sinus thrombosis
   • Retrobulbar tumors
   • Thyroid ophthalmopathy
   • Superior vena cava obstruction
   • Mediastinal tumors
   • Sturge-Weber syndrome
   • Familial episcleral venous pressure elevation

1. Anterior (“pulling”)

   • Contracture of membranes

   • Neovascular glaucoma
   • Iridocorneal endothelial syndrome
   • Posterior polymorphous dystrophy
   • Penetrating and non-penetrating trauma

   • Consolidation of inflammatory products

2. Posterior (“pushing”)

   • With pupillary block

   • Pupillary block glaucoma
   • Lens-induced mechanisms (phacomorphic lens, ectopia lentis)
   • Posterior synechiae (iris-vitreous block, pseudophakia, uveitis)

   • Without pupillary block

   • Ciliary block (malignant) glaucoma
   • Lens-induced mechanisms (phacomorphic lens, ectopia lentis)
   • Following lens extraction (forward vitreous shift)
   • Anterior rotation of ciliary body (following scleral buckling or panretinal photocoagulation, central retinal vein occlusion)
   • Intraocular tumors (retinoblastoma, malignant melanoma)
   • Cysts of the iris and ciliary body
   • Retrolenticular tissue contracture (retinopathy of prematurity, persistent hyperplastic primary vitreous)

1. Incomplete development of trabecular meshwork / Schlemm’s canal

   • Congenital (infantile) glaucoma
   • Axenfeld-Rieger syndrome
   • Peter’s anomaly
   • Glaucomas associated with other developmental anomalies

2. Iridocorneal adhesions

   • Broad strands (Axenfeld-Rieger syndrome)
   • Fine strands that contract to close angle (aniridia)

1. Combination of two or more forms of glaucoma present either sequentially or simultaneously
2. IOP elevation can occur as a result of either or both of the following:

   • The intrinsic resistance of the trabecular meshwork to aqueous outflow in open-angle glaucoma
   • The direct anatomic obstruction of the filtering meshwork by synechiae in ACG

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

The four major types of glaucoma have their own unique causes. Open-angle glaucoma and congential tends to run in families and acute angle closure glaucoma occurs when the exit of the aqueous humor fluid is suddenly blocked and secondary glaucoma occurs as a result of complications of other medical conditions and/or procedures.

The four major types of glaucoma have their own unique causes. Specific causes by each major type of glaucoma are:

• The cause is unknown. An increase in eye pressure occurs slowly over time. The pressure pushes on the optic nerve and the retina at the back of the eye.
• Open-angle glaucoma tends to run in families. Your risk is higher if you have a parent or grandparent with open-angle glaucoma. People of African descent are at particularly high risk for this disease.

• It occurs when the exit of the aqueous humor fluid is suddenly blocked.
• Dilating eye drops and certain medications may trigger an acute glaucoma attack.
• Medication Side Effect- Lisinopril and Hydrochlorothiazide, Losartan potassium and Hydrochlorothiazide, Paroxetine

• It is present at birth and results from the abnormal development of the fluid outflow channels in the eye.
• It is often hereditary and tends to run in families.

• It is caused as complications of other medical conditions and/or procedures, including eye surgery, advanced cataracts, eye injuries, certain eye tumors, and uveitis.
• It can be caused by drugs such as corticosteroids, which are used to treat eye inflammations.
  • Pigmentary glaucoma is caused when pigment from the iris breaks off, thereby slowing the fluid drainage and blocking the meshwork.
  • Neovascular glaucoma is a severe form of secondary glaucoma that is linked to diabetes.

Common drugs causing glaucoma include:

• Carbinoxamine

• Difluprednate
• Dexamethasone
• Hydrochlorothiazide
• Medrysone
• Prednisolone
• Prednisone
• Rimexolone
• Scopolamine
• Umeclidinium

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

Glaucoma is the second leading cause of blindness worldwide. The global prevalence of glaucoma for population aged 40–80 years is 3.54%. The overall prevalence of OAG in the US population 40 years and older is estimated to be 1.86%, with 1.57 million white and 398,000 black persons affected. Acute angle-closure glaucoma has the highest incidence between the ages of 55 and 65 years, but it can also occur in young adults and has been reported in children as well.

• The global prevalence of glaucoma for population aged 40–80 years is 3.54%.
• The estimated number of people with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040.^[1]

• Glaucoma affects one in two hundred people aged fifty and younger and one in ten over the age of eighty.
• Worldwide, it is the second leading cause of blindness.^[2]

• The prevalence of POAG is highest in Africa – 4.20%.^[1]
• The overall prevalence of OAG in the US population 40 years and older is estimated to be 1.86%, with 1.57 million white and 398,000 black persons affected.
• After applying race, age, and gender-specific rates to the US population as determined as per the 2010 US census, it was estimated that OAG affects 5.47 million US citizens.
• Due to the rapidly increasing size of the geriatric population, the number with OAG will increase by 50% to 3.36 million by 2020.

^[3]

• The Rotterdam and Barbados study, recorded a significant increase in the prevalence of glaucoma in older individuals, with persons in their 70s being generally 3 to 8 times higher than those for persons in their 40s.
• Various multiple population-based surveys have demonstrated higher prevalence of glaucoma in specific ethnic groups.^[4][5]

Gender

• As per the Bayesian meta-regression model, men were more likely to have POAG than women, people of African ancestry were more likely to have POAG than people of European ancestry, and people living in urban areas were more likely to have POAG than those in rural areas.^[1]

• 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 46-65 years, the likelihood of blindness from POAG is 15 times higher among blacks than that among whites.

• The prevalence of PACG is highest in Asia – 1.09%^[3]

• The depth and volume of anterior chamber decrease with age.
• These changes predispose the eye to pupillary block and thus, the prevalence of angle-closure glaucoma with pupillary block increases with age.
• Acute angle-closure glaucoma has the highest incidence between the ages of 55 and 65 years, but it can also occur in young adults and has been reported in children as well.

• Acute angle-closure glaucoma has been reported more in women than in men, and several population-based surveys have shown that the women are at increased risk of angle-closure glaucoma.
• Studies of normal eyes have shown that women have shallower anterior chambers than men.

• The prevalence of primary angle-closure glaucoma (PACG) varies among different racial and ethnic groups.
• The prevalence is estimated at 0.1%, in Caucasian populations in the United States and Europe.
• The Inuit populations from the Arctic regions have the highest-known prevalence of PACG about 20 to 40 times higher than that for Caucasian.
• The available data suggests that for most Asian population groups, the prevalence of PACG is between that for Caucasian and Inuit populations.
• The studies have shown that the prevalence of PACG among blacks is similar to that among whites, with most cases among this group being chronic variety.

• PACG is typically associated with hyperopia, however, it may occur in eyes with any type of refractive error.
• The depth and volume of the anterior chamber are reduced in hyperopic eyes, thus predisposing them to PACG.

• The anatomical features of the eye that increase the risk to pupillary block.
• The lens position and lens thickness are hereditary traits.
• A more anterior position and greater lens thickness predispose a patient to glaucoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

Common risk factors include a positive family history, increased age, myopia, diabetes mellitus, hypertension, sleep apnea, thyroid disorders, hypercholesterolemia, migraine, raynaud phenomenon.

Common risk factors

• Age:
  • The risk increases with the increase in age.
  • The visual field defects are 7 times more likely to progress in patients above the age 60 years in comparison to those younger than 40 years.
  • Although an increase in lOP with age has been observed in many populations.
  • Several studies in Japan have shown a relationship between glaucoma and age even with no increase in lOP in the population.^[1]
• Race:
  • The prevalence of POAG is 3-4 times greater in black persons and Hispanic persons as compared to non-Hispanic Caucasian individuals.
  • The loss of vision as a consequence of glaucoma is at least 4 times more common in blacks than in Caucasian population.
  • 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.^[2]
• Family History:
  • A positive family history is a risk factor for POAG. The relative risk of POAG is increased by 3.7-fold for individuals who have a sibling with diagnosed POAG.^[3]
• 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.
  • Myopia-related retinal abnormalities can cause visual field defects along with glaucoma.
  • A 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 not clear.
  • Though some studies have found diabetes plays a significant role in the disease, other studies have not found any corelation.^[4]
• Hypertension:
  • The systemic hypertension is associated with a low risk of the presence of glaucoma in younger patients and with an increased risk in patients above 65 years of age.
  • 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.
  • Some studeis demonstrate that lower ocular perfusion pressure is a strong risk factor for the development of glaucoma, independent of lOP alone.
  • The overtreatment of systemic hypertension may be a contributing factor to glaucoma progression in some cases and hence, should be avoided.^[4]
• Retinal vein occlusion:
  • The patients with central retinal vein occlusion may lead to an elevated lOP and subsequentlu 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.
• Sleep apnea
• Thyroid disorders
• Hypercholesterolemia
• Migraine
• Raynaud Phenomenon

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

The purpose of glaucoma screening tests is to detect those with early stage disease, so that these patients can be treated to reduce the risk of visual field loss. The patients in the pre-perimetric stage of glaucoma, screening tests only evaluate the optic nerve and the NFL

• There has been emphasis on glaucoma screening, since usually there is an insidious start of the disease (with no clear start point, POAG), and progression in many cases is slow and unnoticed b the patient.
• Additionally, there is a recognized stage of the disease in which patients are apparently in a pre-perimetric (before loss of the visual field is present) stage, bringing a challenge to the diagnosis and screening techniques.
• The purpose of glaucoma screening tests is to detect those with early stage disease, so that these patients can be treated to reduce the risk of visual field loss.
• The patients in the pre-perimetric stage of glaucoma, screening tests only evaluate the optic nerve and the NFL.^[1]
• Optic nerve and retinal nerve fiber layer imaging is used to detect anatomic alterations.
• The OCT of the optic nerve; the new spectral domain OCT is now being used commonly to screen for loss of the retinal fiber layer in glaucoma. However clinical evaluation is paramount, the increase in vertical cup/disc ratio, the appearance of cup notching or hemorrhages in the disc are taken as a positive screening for glaucoma.^[2]
• It is recommended that stereoscopic pictures of the optic nerve be taken with some regularity, and is considered as the most sensitive early detection method.
• Caution must be taken due to the fact that there is certain variability between observers, and to the fact that there is no gold standard unique test for the diagnosis of glaucoma, but rather a set of factors that all together lead to the diagnosis.^[3]
• Every patient during a visit to an ophthalmologist is checked for visual acuity, intraocular pressure and cup/disc ratio as part of the optic nerve assessment.
• If any of those key points raises suspicion such as decreased visual acuity (with no other apparent cause), high or borderline intraocular pressure, or a characteristic glaucomatous vertical optic nerve excavation or disc hemorrhages studies are ordered for a more detailed evaluation of the optic nerve fibers and visual function.^[4]
• The rate of progression through at multiple time points should be recorded since it fundamental for diagnostic and treatment decisions.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]..

• The absence of symptoms in open angle glaucoma (OAG) causes delay in the timely detection and diagnosis of the disease.
• Usually before the patient presents with first symptoms, severe and irreversible damage has usually occurred to the visual field in one or both eyes.
• The rate of prognosis of the visual field defect varies from patient to patient, and treatment of the glaucoma does not completely halt the visual field loss and the deterioration in the visual field progresses despite aggressive therapy.^[1]
• The incidence of blindness 20 years after the initial diagnosis of OAG has been estimated at 27% for one eye and 9% for both eyes in a primarily Caucasian population.^[2]
• There are multiple studies covering people of various ethnicities that have found the mean change in visual field testing for European-derived, Hispanic, African-derived and Chinese was –1.12, –1.26, –1.33 and –1.56 dB/year, respectively.^[3]
• The Ocular Hypertension Treatment Study (OHTS) shows that the after 5 years of regular follow-up, progression of OAG from ocular hypertension was 4.4% in the treated group in comparison to 9.5% in the untreated group. However, over 90% of the untreated subjects did not develop visual field or disc changes consistent with OAG.^[4]
• The Collaborative Normal Tension Glaucoma Study (CNTGS) studied the natural course of untreated NTG.^[5]
• The study specifically focused on patients with glaucomatous optic nerve damage and visual field loss accompanied by IOP in the normal range.
• It is believed that NTG represents a distinct variety of glaucoma from primary OAG, the two represent a continuum of glaucomas.
• At 5–7 years of follow-up, the progression of the visual field defect increases to 60% of those individuals with untreated glaucoma with optic nerve damage, visual loss and IOP under 21 mmHg.
• The treatment targeting IOP lowering of >30% decreased the progression rate to 20%.
• Most cases progressed slowly, requiring several years to demonstrate progression; in other cases, deterioration manifested within 1 year.
• The mean estimated slope of the MD index deterioration for all untreated subjects was –0.41 dB/year. However, the MD index ranged from –0.2 dB/year to –2 dB or more/year.
• This 10-fold range reflects the broad range in the rates of deterioration.^[6]

• ACG is characterized by apposition of the peripheral iris against the trabecular meshwork, thus resulting in obstruction of the aqueous outflow.
• The main mechanisms of closure are pupillary block, plateau iris, lens-related and retrolenticular causes.
• ACG may be divided into acute, subacute and chronic ACG. All the three types have varied clinical manifestations, but they can still occur at different times in the same person.
  • In acute ACG, closure of the angle occurs suddenly, resulting in rapid rise in IOP. The affected person presents with dramatic symptoms i.e. severe ocular pain, nausea, vomiting, headache and blurred vision.
  • Subacute or intermittent ACG occurs when episodes of pupillary block resolve spontaneously and can recur repeatedly over time.
  • Chronic ACG develops when the angle narrows slowly and results in scarring between the peripheral iris and the trabecular meshwork.

• The natural history of ACG has been subdivided into three stages:

1. an anatomically narrow angle without elevated IOP, abnormal visual fields or peripheral anterior synechia.
2. development of peripheral anterior synechia or a closed angle with elevated IOP.
3. development of an anatomical angle closure with glaucomatous optic nerve and visual field changes, termed primary angle closure glaucoma.

• The prevalence and pattern of disease varies across different parts of the world. The majority of patients with ACG are Asian due to their anatomical predisposition.^[7]
• The first-line treatment of LPI relieves the relative pupillary block element.
• The response to LPI and the long-term course of PACG appears to vary by race.
• Studies found that LPI in Caucasian subjects with ACG were more likely to effectively prevent the subsequent need for surgical intervention than LPI in Asian subjects. Intraocular pressure was controlled with LPI alone in 65–76% of eyes, with only 0–13% of the eyes requiring subsequent filtering surgery.^[8]
• In comparison in Asian populations, the majority of eyes with established ACG required antiglaucoma medications or filtering surgery, despite undergoing treatment with LPI.
• The disease in Asians appears to be more aggressive.
• Even after laser iridotomy for eyes with narrow angles, the rates of progression to ACG can be significant.
• A decade after treatment for acute PAC, 47.8% of the patients developed glaucomatous optic neuropathy.^[9]
• Several years after the initial attack of acute angle closure in Asian subjects, 17.8% were blind in the affected eye and half had blindness caused by the advanced glaucoma.
• Thus, Asian patients are at a higher risk of further glaucomatous damage even after patent LPI and would benefit from long-term follow-up.^[10]

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