What is the approach to investigating and managing preperimetric glaucoma?

Investigating and Managing Preperimetric Glaucoma

Preperimetric glaucoma requires comprehensive structural assessment of the optic nerve and retinal nerve fiber layer, as these changes often precede visual field defects, and early intervention with IOP-lowering therapy should be initiated in high-risk patients to prevent progression to perimetric glaucoma.

Definition and Diagnosis

Preperimetric glaucoma refers to the presence of glaucomatous optic nerve or retinal nerve fiber layer (RNFL) damage without detectable visual field defects on standard automated perimetry (SAP) 1.

Key Diagnostic Elements:

• Optic Nerve Head (ONH) Examination: Critical for identifying early structural changes 1

  • Vertical elongation of the optic cup with decreased neuroretinal rim width
  • Cup enlargement
  • Diffuse or focal narrowing of the neuroretinal rim (especially superior/inferior)
  • Optic disc hemorrhages (significant risk factor for progression)
  • Nasalization of central ONH vessels
  • Baring of circumlinear vessels
  • Absence of pallor in the neuroretinal rim
  • Violation of the ISNT rule (normally rim is widest inferiorly, then superiorly, nasally, and temporally) 1

• RNFL Assessment:

  • Diffuse or focal thinning of the RNFL
  • Beta-zone parapapillary atrophy 1

• Intraocular Pressure (IOP) Measurement:

  • Multiple measurements at different times of day to assess fluctuations
  • Document time of day for each measurement 1
  • Note that many preperimetric glaucoma patients may have normal IOP readings 1

• Gonioscopy: Essential to exclude angle closure or secondary causes of IOP elevation 1

Diagnostic Testing

• Central Corneal Thickness (CCT): Thinner corneas are associated with higher risk of progression 1

• Structural Imaging:

  • Stereoscopic optic disc photography (preferably through dilated pupil)
  • Red-free RNFL photography
  • Optical Coherence Tomography (OCT) of ONH, RNFL, and macular ganglion cell complex 1, 2
  • Note: In preperimetric glaucoma, ONH and RNFL parameters on OCT have better diagnostic ability than macular ganglion cell-inner plexiform layer (GCIPL) parameters 2

• Visual Field Testing:

  • Standard Automated Perimetry (SAP) (normal in preperimetric glaucoma by definition)
  • Consider Frequency Doubling Technology (FDT) perimetry which may detect damage earlier 3
  • Pulsar perimetry may also be useful for early detection 3

Risk Factors for Progression

The following factors increase the risk of progression from preperimetric to perimetric glaucoma:

• Disc hemorrhage: Strong predictor of progression 4, 5
• Insufficient IOP reduction: Less than 20% reduction from baseline 4, 5
• Older age at diagnosis 6
• Presence of temporal raphe sign (horizontal straight line on macular ganglion cell-inner plexiform layer thickness map) 6
• Lamina pore visibility 6
• Greater pattern standard deviation on visual field testing 6
• Thinner central corneal thickness 1

Management Approach

Initial Assessment:

• Complete history including:
  • Ocular history (refractive error, trauma, prior surgery)
  • Race/ethnicity (higher risk in African Americans and Hispanics)
  • Family history of glaucoma
  • Systemic conditions (asthma/COPD, migraine, vasospasm, diabetes, cardiovascular disease)
  • Current medications (especially corticosteroids) 1

Treatment Decision:

Treatment decisions should be based on risk assessment:

• High-risk patients (those with multiple risk factors such as disc hemorrhage, thin CCT, large cup-to-disc ratio, family history) should be considered for treatment 1

• IOP-lowering therapy:

  • Results from the Ocular Hypertension Treatment Study (OHTS) demonstrate that lowering elevated IOP reduces the risk of developing glaucomatous damage 1
  • Target a minimum of 20% IOP reduction from baseline 5
  • Latanoprost 0.005% once daily can reduce IOP by 6-8 mmHg in patients with baseline IOP of 24-25 mmHg 7

Follow-up Protocol:

• Untreated low-risk patients: Every 12 to 24 months 1
• Treated or high-risk patients: More frequent follow-up (every 3-6 months) until stable 1, 5
• At each follow-up visit:
  • Visual acuity measurement
  • Slit-lamp biomicroscopy
  • IOP measurement
  • Periodic ONH and RNFL evaluation 1

Progression Rates and Monitoring

• Structural progression:

  • Angular widening of localized RNFL defects occurs at approximately 1° per year 5
  • Average RNFL thinning rate in untreated preperimetric glaucoma is about -0.46 μm/year 6

• Functional progression:

  • Mean deviation change in untreated preperimetric glaucoma is approximately -0.03 dB/year 6
  • In treated preperimetric glaucoma that progresses to perimetric glaucoma, the rate is about -0.23 dB/year 5

• Progression probability:

  • In untreated young patients (under 40), the 5-year progression probability is 39% by structural criteria and 5% by functional criteria 6
  • Overall, about 57% of patients with preperimetric glaucoma show progression over a 6.8-year follow-up period despite treatment 5
  • Approximately 27% develop perimetric glaucoma over this timeframe 5

Clinical Pearls and Pitfalls

• Don't rely solely on IOP: Many preperimetric glaucoma patients have normal IOP readings 1
• Watch for disc hemorrhages: Their presence significantly increases progression risk 4, 5
• Document structural changes meticulously: Optic nerve damage often precedes visual field defects in 55% of cases 1
• Consider both structure and function: Some patients may show functional deficits before detectable structural changes 1
• Adjust treatment based on risk factors: More aggressive IOP lowering for patients with disc hemorrhages or other high-risk characteristics 4, 5