Case Example

A 60 year old woman presents to you for a routine review.

Past ocular history: Myopia

Past medical history: Migraines, Raynaud’s phenomenon

Medications: Aspirin

Family history: Mother had glaucoma

Examination:

VA with glasses

Right eye: 6/6 Left eye: 6/6

IOP 18 mmHg 15 mmHg

Ishihara colour plates 12/13 13/13

Pupils No RAPD

Gonioscopy d40r d40r

Central corneal thickness

493 497

Appearance of the optic nerves:

Figure 1a – Right optic nerve

Figure 1b – Left optic nerve

Figure 2a – Right visual field

Figure 2b – Left visual field

Figure 3 – RNFL thickness analysis

Question 1. What features of the examination make you suspicious for a glaucomatous optic neuropathy?

• Asymmetry of the optic nerves

The right optic disc is tilted with oblique entry of the retinal vessels. The neuroretinal rim is irregular with thinning/notching at the inferior and temporal regions as well as marked adjacent beta-zone parapapillary atrophy. The right optic disc is also cupped with a vertical cup-disc ratio of 0.80. There is a pigment crescent at the nasal border.

The left optic disc appears relatively normal with healthy, thick regular neuroretinal rim, a vertical cup-disc ratio of 0.40, and non-specific parapapillary pigment crescents.

• Visual field changes

Both visual fields are reliable

There is right a superior arcuate visual field defect

• Decreased RNFL thickness

There is thinning of the right RNFL (average thickness 74.76 microns) compared to the left RNFL (average thickness 89.81 microns). The inferior quadrant is particularly thinned, in keeping with the appearance of the optic nerves and the appearance of the visual fields.

Question 2: What are your differential diagnoses?

• Normal tension glaucoma • Vascular insult to the optic nerve such as NAION, GCA, shock optic

neuropathy o These tend to present with an acute change in vision, and late

stage cupping is often associated with pallor • Compressive optic neuropathy

o A disproportionately large decrease in colour vision, age less than 50, neuroretinal rim pallor, vertically aligned visual field defects and a visual acuity less than 6/12 should raise the suspicion for compressive optic neuropathy and patients should be considered for neuroimaging

• Congenital optic nerve defects

[1]

Question 3: At what level is a patient deemed to have ‘Normal Tension Glaucoma’?

Normal tension glaucoma is defined as a patient with glaucomatous optic neuropathy where the pre-treatment IOP never exceeds 21mmHg.

[2]

Question 4: How many patients with primary open angle glaucoma have NTG?

Worldwide the proportion of POAG which is NTG varies. Most western studies report that NTG represents 25-50% of all cases of POAG, however in one Japanese study NTG represented 92% of all POAG cases. [1]

Question 5: What aspects of this patients history makes them at risk for progression of NTG?

Our patient is at high risk of progression due to the following factors described by the Collaborative Normal Tension Glaucoma Study (CNTGS)

• Female sex • History of migraine • Family history of glaucoma

[2] Question 6: Are there any other risk factors for progression of NTG?

The other risk factor for progression of NTG identified by this study was disc haemorrhage at presentation Question 7: How quickly will you see progression of disease in a patient with NTG? The CNTGS found that the rate of visual field progression in patients is variable between patients. Although some cases showed progression within months, around half of the patients receiving no treatment had not worsened at the 5 year follow up. Hence careful clinical decisions should be made based on the severity of disease and the presence of risk factors. [3] Question 8: How is progression of glaucoma determined and how what did the results of the CNTGS show with regard to this? Progression of glaucoma is often based on worsening of HVF defects. However in patients with NTG receiving frequent HVF testing looking for subtle changes, there is a chance of falsely judging a worsening of visual fields. Hence the results of the CNTGS suggested that at least two VF showing progression were required for confirmation. [2] However progression should also be determined based on clinical correlation, IOP and optic disc changes. Question 9. What is the IOP goal for treatment of NTG, and what are risks and benefits of the treatment types? Again, the CNTGS found that lowering IOP by 30% slowed progression of visual field loss compared to those not treated. This was achieved by medical, laser, surgical or a combination of treatments. This 30% reduction could be achieved with medical therapy and laser trabeculoplasty in about half the patients. Surgical treatments produced the most cataracts. [3] Question 10: Why are beta-blockers and alpha agonists not considered first line therapy for NTG? As a vascular aetiology involving hypoperfusion of the optic nerve head is suspected in NTG. Theoretically, beta-blockers and alpha agonists could exacerbate this however there is no strong evidence to support this. In the CNTGS these two medical therapies were not included due to theoretical systemic effects. The low pressure glaucoma treatment study found that systemic beta-blockers were a risk factor for disc haemorrhage. Pre-test reading: 1. Mudumbai RC. Clinical update on normal tension glaucoma. Seminars in Ophthalmology. 2013; 28: p. 173-179. informahealthcare.com/doi/pdf/10.3109/08820538.2013.771202

2. Anderson, D. R. (2003). Collaborative normal tension glaucoma study. Current opinion in ophthalmology, 14(2), 86-90. Case 3 Exam: 1. Which of the following is not usually associated with a vascular insult to the optic nerve? A: NAION B: Leber Hereditary Optic Neuropathy C: GCA D: Shock optic neuropathy 2. Which of the following is most suggestive of a compressive optic neuropathy? A: Normal colour vision B: Visual acuity better than 6/12 C: Vertically aligned visual field defect D: Nasal visual field defect 3. Which of the following are a risk factor/factors for progression of NTG as identified by the CNTGS? A: Female sex B: History of migraines C: Disc haemorrhage at presentation D: All of the above 4. What is the common etiology that is thought to link Raynaud’s phenomenon and NTG? A: Vasospasm B: Peripheral inflammation C: Neurodegeneration D: Sympathetic overstimulation 5. NTG seems to make up a higher proportion of all glaucoma in Japan compared to most western countries. True or false? 6. After 5 years what proportion of patients with untreated NTG will show evidence of progression according to the CNTGS? A: 50% B: 60% C: 70% D: 80% 7. What was the target IOP reduction shown to be effective in slowing progression in the CNTGS? A: 10% B: 30% C: 3mmHg D: 10mmHg

8. Which of the following IOP lowering treatments is most likely to result in cataract formation? A: Selective laser trabeculoplasty B: Topical prostaglandin analogue C: Trabeculectomy D: Topical carbonic anhydrase inhibitor 9. Which of the following has been found to give patients an increased risk of disc haemorrhage? A: Topical carbonic anhydrase inhibitor B: Systemic carbonic anhydrase inhibitor C: Topical beta blocker D: Systemic beta blocker 10. Disc haemorrhage is more common in high tension glaucoma compared to normal tension glaucoma. True or false? 11. Which of the following is modifiable risk factor for NTG? A: History of Raynaud’s phenomenon B: Intraocular pressure C: History of migraines D: All of the above 12. Which of the following topical medical treatments were included in the treatment arm of the CNTGS? A: Alpha agonists B: Beta-blockers C: Prostaglandin analogues D: None of the above 13. Pallor of the neuroretinal rim is suggestive of? A: Compressive optic neuropathy B: NTG C: Congenital disc abnormality D: POAG 14. Which of the following is NOT a risk factor for progression of NTG as identified by the CNTGS? A: Male gender B: Family history of glaucoma C: Disc haemorrhage at presentation D: History of migraine 15. Lowering blood pressure is an effective tool for treating normal tension glaucoma. True or false? 16. Which of the following is NOT a risk factor for detection of disc haemorrhage in NTG as identified by the low pressure glaucoma study? A: Systemic beta blockers B: High systemic blood pressure

C: History of migraine D: All of the above 17. An acute change in vision as a presenting symptom is most suggestive of which diagnosis? A: NAION B: NTG C: Congenital disc abnormality D: Compressive optic neuropathy 18. Which of the following is NOT a requirement for a diagnosis of NTG? A: Pre-treatment IOP never exceeding 21mmHg B: Open angles to gonioscopy C: Evidence of glaucomatous disc damage D: Decreased colour vision 19. Which of the following support a vascular component to the aetiology of NTG? A: Increased rate of disc haemorrhages B: An association with migraines C: An association with Raynaud’s phenomenon D: All of the above 20. According to the CNTGS, visual field progression in NTG can be detected from a single visual field. True or false? 21. In the CNTGS approximately how many patients achieved a 30% reduction in baseline IOP with medical and laser therapy only? A: 10% B: 50% C: 90% D: All patients 22. A marked decrease in colour vision is most suggestive of which of the following diagnoses? A: NAION B: NTG C: Congenital disc abnormality D: Compressive optic neuropathy 23. Which of the following is the least likely to cause a visual field defect that respects the horizontal midline? A: Pituitary mass B: Occipital lobe infarct C: Glioblastoma involving the optic radiation D: NAION 24. Which of the following is suggestive of NAION rather than NTG? A: Segmental disc pallor B: Arcuate visual field defect

C: High cup to disc ratio D: All of the above 25. Medical and laser treatment alone will not be able to reduce IOP by 30% in NTG. True or false? References: 1. Mudumbai RC. Clinical update on normal tension glaucoma. Seminars in Ophthalmology. 2013; 28: p. 173-179. informahealthcare.com/doi/pdf/10.3109/08820538.2013.771202 3. Anderson, D. R. (2003). Collaborative normal tension glaucoma study. Current opinion in ophthalmology, 14(2), 86-90. 2. Drance S, Anderson DR, Schulzer M, for The Collaborative Normal Tension Glaucoma Study Group. Risk factors for progression of visual field abnormalities in normal tension glaucoma. Am J Ophthalmol 2001; 131: 699-708