What conditions, other than glaucoma, can cause an increase in the cup-disc ratio on a fundoscopic exam?

Non-Glaucomatous Causes of Increased Cup-Disc Ratio

While glaucoma is the most common cause of increased cup-disc ratio, several non-glaucomatous optic neuropathies can produce optic nerve cupping, including compressive optic neuropathies, arteritic anterior ischemic optic neuropathy (particularly from giant cell arteritis), hereditary optic neuropathies, optic neuritis, and non-arteritic anterior ischemic optic neuropathy. 1

Primary Non-Glaucomatous Causes

Compressive Optic Neuropathies

• Benign and malignant tumors compressing the optic nerve can cause pathological cupping 2
• These are potentially treatable conditions that must not be missed 2

Arteritic Anterior Ischemic Optic Neuropathy (AAION)

• Giant cell arteritis is the most common non-embolic vascular cause in patients over 50 and represents an ophthalmologic emergency 3
• GCA causes inflammatory disease of the proximal ocular artery with vessel wall thickening and occlusion, resulting in simultaneous ischemia of the optic disc 3
• Immediate high-dose systemic corticosteroid therapy is critical to prevent vision loss in the fellow eye 3

Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)

• Low ocular perfusion pressure contributes to inadequate blood flow to the optic nerve head 4
• Risk factors overlap significantly with glaucoma but require different management 4
• Previous NAION in one eye increases risk for the fellow eye 4

Hereditary Optic Neuropathies

• These conditions can produce cupping that mimics glaucomatous changes 1

Optic Neuritis

• Inflammatory optic nerve disease can result in subsequent cupping 1

Other Optic Atrophies

• Various causes of optic atrophy show a small but significant increase in cup-disc ratio compared to normal eyes 5

Key Differentiating Features

Clinical Characteristics That Suggest Non-Glaucomatous Cupping

Optic Disc Appearance:

• Pallor of the neuroretinal rim is the hallmark feature distinguishing non-glaucomatous from glaucomatous cupping 1
• In glaucoma, the neuroretinal rim maintains its color despite thinning 6

Pattern of Cupping:

• Glaucomatous cupping typically shows preferential inferior and superior pole damage (violating the ISNT rule) 6
• Non-glaucomatous cupping may show different patterns depending on the underlying cause 1

Associated Findings:

• Absence of disc hemorrhages (which are characteristic of glaucoma) 6
• Absence of beta-zone parapapillary atrophy (characteristic of glaucoma) 6
• Visual field defects that do not respect the horizontal midline (unlike glaucoma) 6

Anatomical Considerations

Two Components of Cupping:

• Prelaminar thinning: shallow cupping related to loss of retinal ganglion cells 1
• Laminar thinning: involves damage to the lamina cribrosa and peripapillary scleral connective tissue 1

Disc Size Matters:

• Small optic discs can have glaucomatous damage with misleadingly low cup-disc ratios 7
• In these cases, parapapillary changes may be more sensitive indicators than cup-disc ratio alone 7

Diagnostic Approach

Immediate Assessment Required

History:

• Age over 50 with acute vision loss suggests AAION requiring emergent evaluation 3
• Temporal headache, jaw claudication, or polymyalgia rheumatica symptoms suggest giant cell arteritis 3
• Family history of hereditary optic neuropathies 1

Visual Function Testing:

• Visual acuity assessment 1
• Color vision testing (often more severely affected in non-glaucomatous causes) 1
• Visual field testing to assess pattern of defects 1

Ocular Examination:

• Intraocular pressure measurement 8
• Gonioscopy to assess anterior chamber angle 8
• Magnified stereoscopic visualization through dilated pupil using slit-lamp biomicroscope 3
• Red-free illumination to evaluate retinal nerve fiber layer 3
• Assessment for disc hemorrhages 8

Ancillary Testing:

• Central corneal thickness measurement 8
• Optical coherence tomography of retinal nerve fiber layer and ganglion cell layer-inner plexiform layer 1

Emergency Evaluation When Indicated

For Suspected Giant Cell Arteritis:

• Check ESR/CRP immediately and initiate high-dose corticosteroids if suspected 3
• Do not delay treatment while awaiting temporal artery biopsy 3

For Retinal Artery Occlusions:

• Prompt referral to stroke center given high acute stroke risk 3

Common Pitfalls

Misdiagnosis Risk

• Up to 20% of patients may be misdiagnosed and treated for glaucoma due to misinterpretation of optic disc cupping 2
• The optic nerve should not be examined in isolation—always consider the complete clinical picture 1

Small Disc Caveat

• Glaucomatous eyes with small optic nerve heads can have misleadingly low cup-disc ratios 7
• In these cases, look for parapapillary chorioretinal atrophy and retinal nerve fiber layer defects 7

Risk Factor Overlap

• Risk factors for NAION overlap significantly with those for glaucoma, but management approaches differ 4
• Low ocular perfusion pressure is a risk factor for both conditions 4