What is the definition of glaucoma?

Glaucoma is a type of optic neuropathy specifically of the optic nerve head (optic disc) which can lead to loss of vision. It is this damage to the optic nerve head that causes the increased cup to disc ratio seen on fundoscopy which is a characteristic sign of glaucoma.

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Glaucoma can be categorised into primary and secondary causes, primary being idiopathic and secondary caused by pre-existing medical conditions. The two most important subsets of glaucoma to understand are open angle glaucoma, and acute angle-closure glaucoma which are both primary diseases. Open angle is the most common, and acute angle-closure is a medical emergency and therefore should not be missed.

 

(Although a major risk factor of glaucoma is a raised intraocular pressure, this is not fundamental or necessary for it to be classed as glaucoma.)

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What types of glaucoma are there?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Above: Non-exhaustive list of some types of glaucoma categorised into primary and secondary causes.

 

Open angle and acute angle-closure glaucoma are the two subcategories to focus on.

 

What is some important anatomy know?

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Figure 1. Labeled Anatomy of the Eye (1, 2)

 

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What is some important physiology to know?

Aqueous humour is the clear fluid that occupies the anterior chamber of the eye from the lens to the cornea. It provides the transport of nutrients to the anterior tissues that do not have a direct vascular supply. It is produced in the posterior chamber of the eye by the ciliary processes, which are part of the ciliary body. It then flows through the pupil into the anterior chamber via both an active process and passive diffusion. Then the aqueous humour passes out of the eye via the trabecular meshwork through to the canal of Schlemm where it joins the venous system(3)(4)(5).

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There is a smaller amount of aqueous humour that passes out of the eye through the uveoscleral pathway. This is an indistinct route through the tissues to the space between the choroid and the sclera which ends in the lymphatic system. Any disturbance to this equilibrium of aqueous humour into and out of the eye changes the intraocular pressure (IOP)(4)(5).

 

 

 

 

 

 

 

 

 

 

 

 

 

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Figure 2. Diagram demonstrating the pathway that the aqueous humour takes from the ciliary processes in the posterior chamber of the eye, to the anterior chamber and into the canal of Schlemm.

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What is the relevant pathophysiology of Glaucoma?

In both open-angle glaucoma and acute angle-closure glaucoma the equilibrium of aqueous humour inflow and outflow is disrupted. The production of the aqueous humour continues; however, the drainage is obstructed. This causes an overall increase in pressure which creates a respective force on the posterior structures of the eye. The weakest structure at the back of the eye is the lamina cribrosa which is a mesh-like structure through which the nerve fibres that form the optic nerve and the accompanying blood vessels pass. Therefore, when the pressure rises in the eye, the lamina cribrosa is the structure that is compressed and deformed causing damage to the traversing nerve fibres or the blood vessels supplying the optic nerve head resulting in optic neuropathy(3)(4)(6).

 

In primary open-angle glaucoma, there is a gradual partial obstruction at the trabecular meshwork before the canal of Schlemm. This slowly increases the intraocular pressure over time resulting in damage to the optic nerve and progressive visual loss. It is currently unknown what obstructs the trabecular meshwork(3)(7)(6).

 

In acute angle-closure glaucoma, there is a suddenly decreased angle between the iris and the cornea which stops the aqueous humour from passing through to the trabecular meshwork. Several anatomical causes result in the iris being pulled forward towards the cornea or pushed from behind closing the angle. The most common cause is a thickening of the lens which closes the gap between the lens and the iris creating increased resistance through the pupil (also known as a pupillary block). The pressure then builds up in the posterior chamber pushing the iris anteriorly closing the drainage angle. Thickening of the lens is normally related to the normal ageing process(3)(4)(8).

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Figure 3. Diagram showing how equilibrium is disrupted when the outflow of aqueous humour is obstructed. The red arrows demonstrate the increased pressure in the anterior chamber which then increases the pressure in the posterior part of the eye.

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What are the risk factors associated with primary open angle glaucoma?

• Increasing age

• Ethnicity (African American, Afro-Caribbean, and West African patients have increased risk)

• Positive family history, there is some evidence of an autosomal dominant inheritance pattern, however this could be influenced by environmental factors.

• Certain genes have been isolated, mutations in the MYOC gene which codes for the protein myocilin has been isolated as a risk factor(3)(9).

• Increased IOP

• Myopia

• Previous use of anti-VEGF therapy

• Contraceptive pill

• Vascular Disease

• Diabetes

• Systemic Hypertension

• Anatomical variances (thinner central cornea or increased cup-to-disc ratio)

 

What are the risk factors associated with acute angle-closure glaucoma?

• Increasing age

• Female sex

• East Asian ethnicity

• Positive family history

• Hypermetropia

• Anatomical variances (shallow anterior chamber, small corneal diameter, or short axial length)

• Drug induced (mydriatics, previous surgical procedures on the eye)

 

What is the clinical presentation of primary open angle glaucoma?

Diagnosing primary open-angle glaucoma can be difficult as it is typically asymptomatic until the later stages of the disease. The rise of intraocular pressure is gradual and therefore takes a long time to elicit any symptoms. It is commonly an incidental finding in routine screening. However, in the later stages of the disease, there is a progressive loss of peripheral vision that can progress to central tunnel vision. Patients can experience other symptoms such as headaches, pain, blurring of vision, and halos appearing around light sources, although these are atypical(3)(5)(6).

 

What is the clinical presentation of acute angle-closure glaucoma?

Acute angle-closure glaucoma is an ophthalmological emergency, and it is therefore vital the diagnosis is not missed. Patients typically present with an acute onset of severe pain either associated with their eye or presenting as a headache. There are typically peripheral visual field changes starting with the nasal edge which progresses centrally. This can be accompanied by blurring of the vision and the appearance of coloured halos around bright light sources. Patients can also suffer systemic upset with nausea and vomiting. There can also be conjunctival injection, a mid-dilated fixed pupil, and a hazy iris/pupil from the fluid that has built up in the cornea(3)(5)(8)(10).

 

What investigations should be performed if suspecting glaucoma?

Investigations for glaucoma include an assessment of the IOP, the anterior chamber angle, the optic disc, and visual fields.

(Here is a nice video showing how you can use a Goldmann to measure IOP)

 

Gonioscopy

Using a gonioscope and a slit lamp allows visualisation of the anterior chamber of the eye and the angle between the cornea and the iris. This can allow for a definitive diagnosis of acute angle-closure glaucoma and differentiation from primary open-angle glaucoma, as it is possible to see where the peripheral iris obstructs the drainage through the trabecular meshwork. It can also be used to visualise any other pathology in the anterior eye. The assessment can be summarised using various angle grading and classification systems such as the Scheie system, the Shaffer system, or the Spaeth system. Although this is an excellent diagnostic tool it requires a specialist to use and may not be available outside of the ophthalmology department.

 

The alternative to gonioscopy is the van Herick method which is a technique using only a slit lamp. This is a great choice if the patient is unable to undergo gonioscopy. The van Herick method uses a slit beam directed at the temporal limbus at 60 degrees. It should be positioned so that the beam is perpendicular to the cornea. This beam produces a second beam of scattered light from the iris in parallel with the first. The thickness of the initial beam is then compared to the gap between the two beams of light, which represents the anterior chamber depth. The ratio is then graded according to the van Herick grading technique and can determine how likely it is that the angle is closed(3)(11).

 

Check out Gonioscopy.org for great videos on this topic (it can be quite tricky to visualise!)

 

Visual Field Assessment

An assessment of the visual fields is part of your ophthalmological examination and can be a crude way to test for those early changes in glaucoma especially if you do not have access to more advanced ophthalmological equipment.

It can also be assessed using the Humphrey visual field analyser which is a computerised system that can detect subtle early changes in glaucoma. However, this is highly dependent on the patient’s ability to interact with the programme as it requires prolonged concentration and understanding of how to use the system. The programme also has a high rate of producing artefacts.

 

Slit Lamp Assessment

The optic nerve should be assessed in glaucoma and the best way to visualise it is using a slit lamp. Although it can be assessed using an ophthalmoscope, a slit lamp allows for clearer inspection and quantitative documentation of accurate measurements.

In a slit lamp assessment for glaucoma, it is important to assess for optic disc cupping (increased cup-to-disk ratio), thinning of the neuroretinal rim and signs of haemorrhage around the optic disc. It can also be used to give an approximate measure of the anterior chamber depth, although this should not replace gonioscopy as it is less accurate. 

It is generally thought that the cup-to-disc ratio is not an accurate parameter for assessing glaucoma as there are huge variations between individuals. Changes to the neuroretinal rim are considered a more accurate sign of glaucoma. The neuroretinal rim is the margin between the central cup and the disc of the optic nerve head. It is typically uniform in width and therefore asymmetry of the rim can suggest glaucoma. The ‘ISNT’ rule is a way of assessing the neuroretinal rim. The Inferior neuroretinal rim should be the thickest in diameter, followed by the Superior rim, then the Nasal rim, and finally the Temporal rim. The first letter of each makes up the ‘ISNT’ acronym. This rule is not highly specific, however, is very sensitive(3)(12).

 

Tonometry

A Goldmann tonometer can be used to assess intraocular pressure which is a prime risk factor for glaucoma. Multiple measurements should be taken and if there are previous measurements available, they can be reviewed and compared. Normal intraocular pressures range from 12-21mmHg.

 

Optical Coherence Tomography

An imaging modality to visualise the anatomy of the eye. It is very useful to document to help identify future changes from the patient’s baseline.

 

What are the treatment options for primary open angle glaucoma?

Management is focused on slowing the progression of the disease down to prevent changes to the patient’s vision. Most of the pharmacological treatments work by bringing down the IOP.

Active management is typically started when measurements of the IOP are above 24mmHg or when the patient has evidence of optic nerve damage(6). However, these parameters are not rigid. It should be based on each patient; ensuring their risk factors and preferences are considered. If they do not meet these criteria a ‘watch and wait’ approach can be taken.

 

NICE recommend 360-degree selective laser trabeculoplasty for a new diagnosis of primary open-angle glaucoma. The laser is used to help remodel the trabecular meshwork and improve the drainage of aqueous humour into the canal of Schlemm(13)(14). This has a high success rate at 6 months and decreases the need for pharmacological management(15).

 

If this is not suitable or the patient declines, a generic prostaglandin analogue is used as first line pharmacological treatment(13)(6). An example is latanoprost 0.005% eye drops. This group of drugs increase the outflow of aqueous humour via the uveoscleral pathway and therefore decreases the overall IOP(16). Second line treatment is with beta blockers such as timolol, levobunolol or betaxolol. These work by decreasing the amount of aqueous humour produced.

Further pharmacological options are carbonic anhydrase inhibitors, miotics, or alpha agonists.

 

For those with advanced glaucoma or that have exhausted all the other options, surgical procedures can be performed(17). An extra pathway can be created in the sclera from the anterior chamber to the conjunctiva which allows aqueous humour to pass out and slowly dissipate through the bloodstream. This can be achieved with a trabeculectomy, a hole in the sclera, or a drainage shunt, a small flexible tube through the sclera(13)(6). Mitomycin C is given alongside surgery, it is an antiproliferative agent that stops scarring of the created hole and decreases failure rates(18).

 

What are the treatment options for acute angle-closure glaucoma?

If acute angle-closure glaucoma is suspected, it must be assessed and treated immediately as it can quickly progress to permanent loss of vision.

 

If immediate secondary care assessment is not possible some steps can be taken in primary care whilst organising the transfer. Ensure the patient is lying supine, without pillows to remove as much pressure on the eye. Then, if available, administer pilocarpine eye drops, a muscarinic receptor agonist that helps open the trabecular meshwork by making the ciliary muscles contract.

Oral acetazolamide, a carbonic anhydrase inhibitor, can be given as well to reduce the production of aqueous humour. Carbonic anhydrase is an enzyme found in the ciliary epithelia where aqueous humour is created. This enzyme mediates the transport of bicarbonate which influences the osmotic gradient and therefore, when inhibited, reduces the flow of fluid(19). Pain relief and antiemetics are also vital(10).

 

In secondary care further pharmacological management is continued with beta blockers, selective alpha agonists, and other carbonic anhydrase inhibitors(10)(20). For example: topical Dorzolamide/Timolol, Apraclonidine, or IV Acetazolamide(20)(21).

 

The definitive treatment, however, is iridotomy. Laser Iridotomy increases the flow from the posterior chamber into the anterior chamber by creating a hole in the iris. This helps push the iris back, increasing the angle between the iris and the cornea, and allowing for free drainage of the aqueous humour into the canal of Schlemm. This is then followed with steroids(8)(7). If this has no response or is not possible to carry out, alternatives are phacoemulsification or iridoplasty(20). Once the patient’s IOP is controlled, they are to be reviewed at 1 week, 1 month, then annually(21).
 

Bibliography

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2.        Drake RL, Vogl AW, Mitchell AWM. Gray’s Anatomy for Students. Second. Philadelphia, PA: Churchill Livingstone/Elsevier; 2010.

3.        Glaucoma. In: Basic and Clinical Science Course [Internet]. American Academy of Ophthalmology; 2019. Available from: https://www.ptonline.com/articles/how-to-get-better-mfi-results

4.        Dietze J, Blair K, Havens S. Glaucoma [Internet]. StatPearls Publishing. 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538217/

5.        Salmon JF. Kanski’s Clinical Ophthalmology. Ninth. Elsevier, editor. Elsevier; 2020.

6.        N M, LA F, K T. Open Angle Glaucoma [Internet]. StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441887/

7.        Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma: A Review. Journal of the American Medical Association. 2014;311(18):1901–11.

8.        Khazaeni B, Khazaeni L. Acute Closed Angle Glaucoma [Internet]. StatPearls Publishing. 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430857/

9.        Allingham RR, Liu Y, Rhee DJ. The genetics of primary open-angle glaucoma: A review. Experimental Eye Research. 2009;88(4):837–44.

10.      Scenario: acute angle closure and angle closure glaucoma [Internet]. NICE. 2022. Available from: https://cks.nice.org.uk/topics/glaucoma/management/acute-angle-closure-angle-closure-glaucoma/

11.      Bhartiya S, Shaarawy T. Evaluation of the Van Herick technique for screening for occludable angles in an African population. Journal of Current Glaucoma Practice. 2013;7(2):88–90.

12.      Harizman N, Oliveira C, Chiang A, Tello C, Marmor M, Ritch R, et al. The ISNT rule and differentiation of normal from glaucomatous eyes. Archives of Ophthalmology. 2006;124(11):1579–83.

13.      Management options for people with chronic open angle glaucoma [Internet]. NICE (National Institute for Health and Care Excellence); 2022. Available from: https://www.nice.org.uk/guidance/ng81

14.      Jones E, Gazzard G. Selective Laser Trabeculoplasty Patient Information. Moorfields Eye Hospital NHS Foundation Trust. 2020.

15.      De Keyser M, De Belder M, De Belder S, De Groot V. Where does selective laser trabeculoplasty stand now? A review. Eye and Vision [Internet]. 2016;3(10). Available from: http://dx.doi.org/10.1186/s40662-016-0041-y

16.      Hitchings A, Lonsdale D, Burrage D, Baker E. The Top 100 Drugs. Second. Elsevier; 2019. 192–193 p.

17.      Glaucoma: diagnosis and management [Internet]. NICE (National Institute for Health and Care Excellence); 2017. p. 1–37. Available from: https://www.nice.org.uk/guidance/ng81

18.      Al Habash A, Aljasim LA, Owaidhah O, Edward DP. A review of the efficacy of mitomycin C in glaucoma filtration surgery. Clinical Ophthalmology. 2015;9:1945–51.

19.      Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous Humor Dynamics: A Review. The Open Ophthalmology Journal. 2010;4(1):52–9.

20.      The Management Of Angle-Closure Glaucoma. The Royal College of Ophthalmologists; 2022.

21.      Jackson TL. Moorfields Manual of Ophthalmology. Second. JP Medical Ltd; 2014.