Figure 1. Hypertensive acute anterior uveitis with mutton fat keratic precipitates. Note the area of iris hyperaemia (arrow) indicating herpetic iritis. Empirical treatment was commenced with oral antivirals and topical steroids.
Dr Ehud Zamir
McKinnon Eye Clinic, McKinnon VIC
For the purpose of this review we will assume that eggs come from chickens and that chickens come from the supermarket.
CASE REPORT 1
Let us start with a story
A middle-aged man with a lifelong hypermetropia of about +5.0 walks into his usual optometrist’s practice complaining of acute discomfort and visual symptoms in one eye. The eye is red and inflamed, and the pressure is over 50. There are cells floating in the anterior chamber.
A diagnosis of hypertensive uveitis (or uveitic glaucoma) is made and the patient is treated with topical steroids and atropine. While the redness and discomfort improve, the pressure two weeks later is still above 50, when he is noted to have shallow anterior chambers and full-on angle closure glaucoma in his symptomatic eye. The other eye has slit angles with imminent angle closure.
Both eyes then undergo laser iridotomies and are just fine the next morning. The patient goes on to have bilateral lens extraction and intraocular lenses for resolution of his angle closure glaucoma. In hindsight, his first presentation was merely acute, primary, pupillary block glaucoma, diagnosed as uveitis due to the presence of anterior chamber cells, which is one of the common features of acute angle closure glaucoma.
This case demonstrates that the combination of uveitis and high pressure can be tricky. We expect the pressure to drop in acute anterior uveitis, due to dysfunction of the ciliary body and increased uveoscleral outflow. However, when the pressure is high in this context, there could be many different reasons for it, all requiring different diagnostic and therapeutic steps. The clinician has to stop, think and decide:
1. Which is the ‘chicken’ and which is the ‘egg’ (uveitis vs high pressure)?
2. If indeed uveitis is the chicken, why is it causing high pressure?
3. If indeed uveitis is the chicken, is it really uveitis, or is it another problem that looks like uveitis? For example: acute glaucoma, pigment dispersion syndrome, lymphoma or haemorrhage.
It is conceptually easier to approach this diagnostic junction/tangle from the glaucoma side. This is because one can reliably walk down a concise algorithm in diagnosing acutely elevated intraocular pressure and reach a diagnosis. It is a mechanistic process with a more definite and simpler route to the diagnosis than the elusive and complex uveitis.
Understanding the mechanism of increased pressure can help us diagnose the uveitis correctly, too. Therefore, I will outline the main junctions in this algorithm here, and provide some detail on each of them, using questions that we should ask ourselves when approaching this problem.
The pressure is high and there are signs of uveitis
Is the angle open or closed?
This question, if it had been asked, would have averted the misdiagnosis described above. It is difficult to miss angle closure if you think about it. It is much easier to miss if you don’t.
Open angle (more common)
This scenario is more common than hypertensive uveitis with a closed angle. Possibilities include:
1. Trabeculitis (inflammation of the trabecular meshwork) usually seen in:
a. Viral anterior uveitis (most often HSV/VZV/CMV)
b. Posner Schlossman syndrome
c. Infectious posterior uveitis (toxoplasmosis, herpetic retinitis, endophthalmitis)
d. Autoimmune disease (sacroidosis)
Trabeculitis usually improves quickly with intensive topical steroid therapy. This is a helpful diagnostic feature, as patients whose intraocular pressure drops dramatically overnight with topical steroids alone (without anti-glaucoma therapy) probably have trabeculitis.
2. Steroid response, in patients who have already had previous attacks and are chronically treated with topical steroids.
3. Fuchs’ uveitis, mistakenly diagnosed as acute because of new symptoms.
4. Hyphaema mistaken for uveitis. This can happen especially with spontaneous, non-traumatic hyphaemas.
5. Brimonidine-induced uveitis1 tends to paradoxically worsen the glaucoma control, and present with small keratic precipitates and (only sometimes) a red eye, days to years after commencing treatment with brimonidine.
6. Phacolytic glaucoma should be considered if there is a dense, hypermature cataract with a hypopyon and high pressure (beware of endophthalmitis).
7. Pigment dispersion syndrome/glaucoma may be mistaken for uveitis, due to the presence of pigmented cells in the aqueous.
8. Intraocular lymphoma, which in this setting presents with multiple keratic precipitates and debris blocking the trabecular meshwork, usually with vitritis and/or signs of lymphoma in the retina and choroid.
9. Anterior uveal melanoma infiltrating the angle
Closed angle (less common)
Once we established that the angle is closed, we need to find out the mechanism of angle closure. Possibilities include:
1. Pupil block
a. Posterior synechiae, causing iris bombe
b. Fibrin ‘plug’ blocking the pupil
c. Primary angle closure glaucoma with a mid-dilated, non-reactive pupil and bilaterally narrow angles, as the case above demonstrated, where the ‘egg’ was confused with a ‘chicken’.
2. Forward pushing of the iris from behind:
a. Choroidal effusions, as may happen in some types of choroiditis or posterior scleritis
b. Uveal tumours such as malignant melanoma
c. Malignancy of the iris causing diffuse iris thickening, most commonly lymphoma.
3. Forward pulling of the iris from the front:
a. Anterior synechiae in chronic uveitis
b. Rubeosis of the iris from any cause.
Figure 2. Same eye as in Figure 1, two months later. Note resolution of uveitis, and appearance of typical iris atrophy and transillumination in the same area, confirming the original suspicion. Slitlamp photographs taken with a mobile phone camera.
CASE REPORT 2
Now that we have a list of possibilities, divided into mechanistic headings, let us look at another patient story.
A middle-aged man was seen by his optometrist for a painful loss of vision in one eye. The optometrist noted signs of severe anterior uveitis, deep anterior chamber and a high intraocular pressure of 40. A diagnosis of Posner Schlossman syndrome was made and the patient received a combination of topical dexamethasone, brimonidine and timolol, with partial reduction in the pressure and improvement of the uveitis.
The patient then complained of worsening vision three weeks later. Examination included pupil dilation this time, revealing a large toxoplasma retinitis lesion with a secondary macula off retinal detachment.
This case demonstrates an important principle: anterior uveitis is a diagnosis of exclusion; it can be called that only if we know for a fact the patient does not have posterior uveitis. If the fundus is not visualised (no attempt made/ hazy view), one cannot be sure that the source of this ‘anterior’ uveitis is not posterior infectious uveitis requiring urgent and specific treatment.
This treatment may need to be antiparasitic or antiviral therapy, either systemically or intraocularly, and in the case of endophthalmitis, vitrectomy, intraocular antibiotic treatment and systemic treatment of sepsis.
One of the most common scenarios is unilateral, hypertensive, truly anterior uveitis with mutton fat keratic precipitates. In this scenario, the most common culprit is a herpetic infection. One has to think about this possibility and look for supportive evidence.
1. Is there a vesicular (blistery) rash on the patient’s upper lid, forehead, brow, or scalp to indicate zoster?
2. Is there evidence of past or present herpetic keratitis?
3. Is there focal iris hyperaemia or swelling?
4. Is there iris atrophy and transillumination in a typical herpetic pattern?
If one or more of these features is present, I usually treat the patient with a combination of topical steroids and topical or even oral anti-herpetic therapy, in an attempt to reduce the risk of long-term complications of iris atrophy, atonic pupil et cetera. If I think it may be herpetic but cannot be sure, I sometimes perform a tap of the anterior chamber and send the aqueous for viral DNA testing.
Hypertensive uveitis is a tricky and potentially dangerous presentation. High intraocular pressure makes the aetiology of uveitis more likely to be infectious or even cancerous. The following key questions must be considered in such patients.
1. Which is the chicken (the cause) and which is the egg (the result): glaucoma vs uveitis.
2. Is the angle open or closed?
3. Could this be an intraocular infection?
4. Could this be something else, not uveitis (cancer, phacolysis or a bleed)?
Remember that the differential diagnosis is very wide and includes a few serious pitfalls of conditions that can blind or kill the patient if not diagnosed correctly and treated appropriately.
1.Beltz J, Zamir E. Brimonidine induced anterior uveitis. Ocul Immunol Inflamm 2015; 23: 1-6.
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