Secondary open-angle glaucoma

• Summary
• Classification
• Pseudoexfoliative glaucoma
• Pigment dispersion syndrome
• Neovascular glaucoma
• Uveitic glaucoma
• Lens related glaucoma (Phacolytic glaucoma)
• Traumatic glaucoma
• Iridocorneal Endothelial Syndrome
• Glaucoma secondary to epithelial ingrowth
• Iridocorneal dysgenesis
• References
• Author(s)

Summary

Secondary Open Angle Glaucoma is a glaucoma where the angle between iris and the cornea is in an ‘open’ configuration, and occurs as a result of another medical condition or trauma.

Classification

We can classify causes of secondary open angle glaucoma into three categories based on where the aqueous outflow obstruction is.

Pre-trabecular

Aqueous outflow is blocked by a membrane covering the trabecular meshwork. For example, fibrovascular tissue, such as in neovascular glaucoma, endothelial cell proliferation or epithelial cell proliferation.

Trabecular

This is where clogging of the meshwork itself prevents aqueous outflow. Examples, and the various materials that block the meshwork, are listed below:

• Pigmentary glaucoma – pigment particles
• Red cell glaucoma – red bloof cells
• Ghost cell glaucoma – degenerate red cells
• Phacolytic glaucoma – macrophages and lens proteins
• Hypertensive uveitis – proteins
• Psuedoexfoliative glaucoma – pseudoexfoliative material
• Trabecular glaucoma can also be caused by oedema (trabeculitis) or by any scarring (e.g. after post-traumatic angle recession)

Post trabecular

Here the trabecular meshwork is unaffected, however elevated episcleral venous pressure impedes aqueous outflow. Examples include carotid-cavernous fistula, Sturge-weber syndrome, or Superior vena cava obstruction.

Pseudoexfoliative glaucoma

Pathogenesis:

Pseudoexfoliative material (PXF) is a grey-white fibrillary material derived from abnormal extracellular matrix metabolism. This material is deposited on various ocular structures: the lens capsule, zonular fibres, iris, trabeculum and conjunctiva. Almost all patients with pseudoexfoliative syndrome have single nucleotide polymorphisms in the LOXL1 gene involved in elastin production, and 50% of patients go on to develop pseudoexfoliative glaucoma.

PXF and liberated iris pigment obstructs the trabecular meshwork and results in elevated IOP. However, it is important to note that glaucomatous optic neuropathy has been reported in eyes with visible PXF but normal IOP, and in the fellow normal eyes in individuals with the condition that have no visible PXF and normal IOP. It is the commonest cause of secondary open angle glaucoma.

Features:

Diagnosis is usually incidental, although vision loss can be a presenting symptom, and often begins unilaterally. PXFl can be seen deposited on the cornea (often a Krukenberg vertical spindle like we see in pigment dispersion syndrome), in the anterior chamber (seen as aqueous flare), and the iris (seen as pupillary ruff loss and patchy transillumination defects at the pupillary margin.) PXF angle deposits may be seen on gonioscopy.

Prognosis:

Often worse than POAG – IOP is often much higher, and severe damage can ensue rapidly.

Treatment:

Medical treatment is the same as with POAG. Laser trabeculoplasty is perhaps more effective than in POAG, however the trabecular pigmentation can lead to increased absorption of laser and hence gentle laser must be applied. Phacoemulsification can significantly lower IOP, especially with trabeculectomy.

Pigment dispersion syndrome

Pathogenesis:

This involves liberation of pigment granules from the iris pigment epithelium and their deposition throughout the anterior segment. In primary pigment dispersion syndrome, the posterior layer of the iris rubs against the zonule as a result of excessive bowing of the mid-peripheral portion of the iris. This reverse pupillary block results in an increase in anterior chamber pressure. Acute IOP elevation may occur when the trabeculum is obstructed by pigment, whereas a chronic elevation is caused by damage to the trabeculum. The resulting glaucoma is known as pigmentary glaucoma. A range of genetic loci have been linked and the condition is likely to have a multifactorial genetic basis. Myopia is a risk factor, with higher degrees of myopia associated with more severe glaucoma.

Features:

Often detected on routine eye examination. The classic triad consists of dense trabecular meshwork pigmentation, mid-peripheral iris transillumination defects, and pigment deposition on the posterior surface of the central cornea. Pigment is deposited on the corneal endothelium in a vertical spindle shape known as a Krukenberg spindle. The anterior chamber is typically deep, and melanin granules may be seen in the aqueous. Radial spoke-like transillumination defects may be seen in light coloured irides. On gonioscopy, one can sometimes see a characteristic mid peripheral iris concavity where the iris bows backwards. Pigment may also be seen on or anterior to Schwalbe’s line – this is known as a Sampaeolesi line. IOP may be volatile with patients experiencing higher levels and greater fluctuations than in POAG, however over time as the pigment liberation decreases IOP control may improve. In the posterior segment, lattice degeneration may be seen.

Treatment:

Avoidance of certain forms of exercise such as jogging and running up and down stairs. Medical treatment is similar to that of POAG – miotics facilitate aqueous outflow however may exacerbate myopia and also could precipitate retinal detachment in short sighted eyes. Laser trabeculoplasty is an option, and iridotomy is thought to slow pigment liberation.

Image demonstrating a Krukenberg spindle (a spindle-shaped vertical deposit of brown pigment in the cornea), indicated by the arrow, in a patient with pigment dispersion syndrome. Image courtesy of Bhallil et al.

Neovascular glaucoma

Pathogenesis:

Neovascular glaucoma occurs as a result of rubeosis iridis: iris neovascularisation, usually secondary to severe and chronic retinal ischaemia. Retinal ischemia triggers a cascade of events where inadequate oxygen supply to the retinal cells leads to release of angiogenic factors including VEGF and interleukin-6, resulting in retinal and anterior segment neovascularisaton. Anterior segment vascularisation then results in blockage of outflow in the presence of an open angle. Ischaemic CRVO accounts for 30%+ of cases, followed by diabetes mellitus.

Features:

Subtle vessels at the pupillary margin are often an early sign. New vessels grow radially over the surface of the iris towards the angle. On gonioscopy, angle neovascularisation may occur and neovascular tissue may proliferate across the face of the angle resulting in a membrane that might contract and close the angle.

Diagnosis:

Treatment:  Medical treatment as with POAG, however miotics should be avoided. Pan retinal photocoagulation is usually effective in inducing regression of neovascularization and if performed early, preventing progression to glaucoma. It will not reverse an established fibrovascular membrane however. Intraocular VEGF can also be an effective adjunct. Cyclocryotherapy can be considered if medical IOP control is not possible. If visual acuity is hand movement or better, filtration surgery (such as a glaucoma drainage device) is the preferred option.

Uveitic glaucoma

Pathogenesis:

Glaucoma following intraocular inflammation – commonly occurs in Fuch’s uveitis syndrome and chronic anterior uveitis with juvenile idiopathic arthritis. Posterior uveitis is less likely to affect the aqueous outflow pathway and is less likely to lead to IOP elevation. Aqueous outflow may be blocked by trabecular obstruction by inflammatory cells and debris, or acute trabeculitis resulting in oedema of the trabecular meshwork may occur. In chronic anterior uveitis, reduced outflow is due to trabecular scarring and sclerosis.

Treatment:

Uveitic glaucoma poses a therapeutic concern, particularly in cases which are steroid-induced. A beta blocker is usually the first line choice – steroids must be given with caution and prostaglandin derivatives may promote inflammation and macular oedema. Miotics are contraindicated as they increase vascular permeability and and miosis promotes the formation of posterior synechiae. Laser iridotomy and surgical options may work, however control of uveitis prior to this is essential.

Posner-Schlossman Syndrome:

This is a rare condition characterized by recurrent attacks of unilateral acute raised IOP associated with mild anterior uveitis. The mechanism is thought to be acute trabeculitis, and it is thought that CMV or H pylori may play a role. Males are more frequently affected.

Lens related glaucoma (Phacolytic glaucoma)

Pathogenesis:

Phacolytic glaucoma is a secondary open angle glaucoma that occurs due to a hypermature cataract. Trabecular obstruction is caused by lens proteins that leak through the intact capsule into the aqueous humour. Macrophages also contribute to this.

Features:

Pain with poor vision due to cataract. Slit lamp shows corneal oedema, a hypermature cataract and a deep anterior chamber. Gonioscopy would also show lens material in the angle.

Treatment:

After IOP is controlled medically, proteinaceous material is washed out from the anterior chamber and the cataract is removed.

See our secondary angle closure glaucoma article to learn more about phacolytic glaucoma – another lens related glaucoma.

Traumatic glaucoma

Pathophysiology:

IOP elevation may result from trabecular obstruction by red blood cells. The size of a hyphaemia is a useful indicator of prognosis and risk of complications – if the entire anterior chamber is filled with blood, then a good outcome is only achieved in 1/3 cases. IOP elevation may also occur through angle recession – this is when the face of the ciliary body ruptures (the portion between the iris root and scleral spur) due to blunt trauma, resulting in angle recession glaucoma).

Treatment:

Coagulation abnormalities should be excluded and any anticoagulants should be risk assessed. A beta blocker ad/or topical or systemic carbonic anhydrase inhibitor is often the best medical management. Laser photocoagulation of angle bleeding points may be helpful. Surgical evacuation of blood is required in 5% of cases, and may be required if IOP remains elevated for 5+ days. On discharge, the patient should be advised to avoid any activities that may lead to eye trauma. For angle recession glaucoma, medical management is similar to other types of secondary glaucoma, however usually the response not satisfactory.

Iridocorneal Endothelial Syndrome

Iridocorneal endothelial (ICE) syndrome typically affects one eye of a middle-aged woman. It consists of the following three clinical presentations: Chandler syndrome, progressive (also termed essential) iris atrophy and iris naevus (Cogan–Reese) syndrome. In all three conditions, an abnormal corneal endothelial cell layer proliferates and migrates across the anterior chamber angle and onto the surface of the iris occurs, resulting in glaucoma (in 50% of cases) and corneal decompensation. This condition can also present as a closed angle glaucoma - see our secondary closed angle glaucoma article!

Glaucoma secondary to epithelial ingrowth

This is a rare complication of anterior segment surgery or trauma, which might occur when conjunctival or corneal epithelial cells migrate through a wound and proliferate in the anterior segment. Raised IOP can be due to trabecular obstruction (secondary open angle glaucoma), but also synechial angle closure may occur (secondary angle closure glaucoma). The aim of treatment is the eradication of invading epithelium to avoid recurrence. Block excision (removing the defect and covering it with a corneoscleral graft) cryotherapy are treatment options.

Iridocorneal dysgenesis

The iridocorneal dysgeneses are a heterogeneous group of developmental disorders affecting the anterior segment of the eye. They are divided into subtypes including aniridia, Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon.

In Axenfeld anomaly, strands of iris tissue attach to the Schwalbe line; in Rieger anomaly, in addition to the attachment of iris tissue to the Schwalbe line there is also iris stromal atrophy with hole or pseudo-hole formation and corectopia. The conditions have a 50% chance of developing glaucoma.

Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea.

Check out our article on congenital glaucoma!

References

1. Salmon, John F., and Jack J. Kanski. Kanski’s Clinical Ophthalmology: A Systematic Approach. Ninth Edition, Elsevier, 2020.
2. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86(2):238-42.
3. Coats G., Further cases of thrombosis of the central vein. Roy Lond Ophthal Hosp Rep 1906; 16:516.
4. Irido-Corneo-Trabecular Dysgenesis (Concept Id: C0344559) - MedGen - NCBI. https://www.ncbi.nlm.nih.gov/medgen/91031. Accessed 10 Apr. 2023.
5. Bhallil, S., et al. ‘Pigment Dispersion Syndrome: An Atypical Presentation’. Oman Journal of Ophthalmology, vol. 3, no. 1, 2010, pp. 36–37. PubMed Central, https://doi.org/10.4103/0974-620X.60022.

Author(s)

Dr Sara Memon

Sara is the Co-Founder of Ophtnotes. She is a doctor who graduated from UCL Medical School in London. She won the Allen Goldsmith Prize in Ophthalmology. Sara is also the co-founder of PAMSA: an organisation linking doctors and medical students of Pakistani origin. She’s especially passionate about teaching and education, having presented a workshop she designed herself at the 2019 Annual GMC Conference.