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LANDMARK GLAUCOMA STUDIES TARIQ ALASBALI WHICH PATIENTS ARE AT RISK FOR THE PROGRESSION?

TARIQ ALASBALI WHICH PATIENTS ARE AT RISK FOR THE PROGRESSION?

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LANDMARK GLAUCOMA STUDIES

TARIQ ALASBALI

WHICH PATIENTS ARE AT RISK FOR THE PROGRESSION?

``Doctor is my glaucoma likely to get worse?``

``Doctor will my eye condition get worse?``

What is the diagnosis (OHT vs NTG vs POAG early or late ?)

Does the patient have the published risk Factor for progression?

Risk of Progression

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

Ocular hypertension treatment study

Aim To determine if glaucoma drops delays

or prevents glaucoma in ocular hypertensives

Arch Ophthalmol 120: 701-713, 2002.

OHTS - methods

RCT of 1600 patients IOP 24-32mmHg in one eye and 21-

32 in other eye Normal discs and fields

Drops prescribed to achieve IOP of ≤24mmHg AND at least 20% drop from baseline

Results

At 5 years 4.4% of treated group had progressed to

POAG 9.5% of untreated

Risk of Progression

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

9.5 4.4

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

What are the risk factors for

progression with OHT?

OHTS study

OHTS conclusions

Factors associated with progression ``I treat if:``

Older age High CDR (vertical or horizontal) > 0.4 High PSD IOP Thinner cornea

CCT and Glaucoma Risk

What are the risk factors for

progression in NTG?

NTGS study

Risk of Progression

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

Normal tension glaucoma study

Aim To determine if IOP plays a part in NTG

NTGS - methods

239 patients recruited

Uni or bilateral NTG as defined by IOP <21 in 10 baseline measurements

AND Glaucomatous cupping Defined type and severity of field loss

NTGS - methods

Randomised immediately if VF defect threatening fixation Previously documented disease

progression

Others randomised when evidence of progression

NTGS

145 (of 239) patients randomised One eye randomised to

Treatment Drops, ALT or surgery to achieve 30%

reduction in IOP No treatment until evidence of

progression Other eye could be treated in this group

NTGS results

30% drop achieved in half without surgery

Once 30% drop achieved rate of progressive field loss was lower than group that did not receive treatment (after allowing for cataract effect which was higher in treated group)

NTGS results

Rate of progression in untreated NTG highly variable

Half did not progress on VF in 5 years Factors associated with progression

Female Migraine Disc haemorrhages on presentation

NTGS conclusions

Overall, lowering IOP in NTG slows progression.

However, over half of patients did not progress without treatment at 5 years.

Risk of Progression

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

60 20

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

What are the risk factors for

progression in NTG?

NTGS study

• Factors associated with progression• ``I am aggressive if:``–Female–Migraine–Disc haemorrhages on presentation

What are the risk factors for

progression in early glaucoma?

EMGS study

Risk of Progression

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

Early Manifest Glaucoma Trial•Compared immediate treatment

versus no (or delayed) treatment for patients with newly diagnosed POAG

•Diagnosis based on reproducible visual field defects

• Included NTG

EMGT

•255 patients•Randomised to ▫ ALT and betaxolol▫No treatment

• If IOP >25mmHg in treated (>35 untreated)→ Latanoprost added

• If remains high → individualised treatment

EMGT

End point Progression of field and/or disc

EMGT - results

Over 6 years 62% untreated versus 45% of treated

group progressed Median time to progression 66 months

treated versus 48 months untreated

Risk of Progression

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

62 45

Advanced POAG(AGIS-7 yrs)

What are the risk factors for

progression in early glaucoma?

EMGS study

Early POAG risk factors (EMGS)

Baseline factors Pseudoexfoliation Older age Higher IOP Worse mean

deviation

Follow up factors IOP

Each 1mmHg reduction from baseline reduced risk of progression by 10%

Disc haemorrhages

Early POAG risk factors (EMGS)

• Factors associated with progression• ``I am aggressive if:`` Pseudo exfoliation

Bilateral disease Older age Higher IOP Worse mean

deviation Disc hemorrhage

Risk of Progression-Advanced glaucoma

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

Advanced Glaucoma Intervention Study

Aim To assess the outcome of sequences of

laser and surgical interventions in eyes that have failed on medical treatment

AGIS

•POAG, uncontrolled with drops•Randomised to 2 groups

1. Trab → ALT → Trab2. ALT → Trab → ALT

Medical treatment as required789 patients followed up for at least 5

years

AGIS outcomes

Primary outcome Decreased vision (substantial VA or VF

decrease)

AGIS results

Vision better in blacks if had ALT first In whites

Vision better in laser group for first 4 years

Then better in surgery group

AGIS results

Side arm looked at IOP and VF loss

Divided into 2 groups IOP <18mmHg at 100% visits (mean =

12.3mmHg) = little VF deterioration IOP <18mmHg at <50% of study visits

(mean = 20.2mmHg) = significantly more VF deterioration

100% of visits < 18mmHg

50-75% of visits < 18mmHg

0% of visits < 18mmHg

75-100% of visits < 18mmHg

AGIS conclusions (1992)

Blacks should have laser first Whites should have trab first

AGIS conclusions

Relationship between low IOP and VF loss remains important finding

In advanced glaucoma, lowering IOP to low teens means most will not progress

Risk of Progression-Advanced glaucoma

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

NTG(CNTG study 6 yrs )

Early POAG(EMGS study 6 yrs )

Advanced POAG(AGIS-7 yrs)

Not Known 30 VA 14 VF(IOP <15mmhg)

Factors associated with progression ``I am aggressive if:``

Older age Lower education Good VA DM High IOP > 18 IOP fluctuation

AGIS conclusions

Collaborative Initial Glaucoma Treatment Study (CIGTS)

Does not provide direct evidence that IOP has an impact on glaucomatous progression, but you need to know about it…

AIM:to assess the effect on early-diagnosed OAG of initial Tx with either topical meds or trab

CIGTS - Methods

Prospective RCT OAG (POAG, Pigmentary, PEX) N=607 Randomized → Medical management

↘ Trabeculectomy IOP target customized for each

patient Primary End Point: progression of VF

loss

CIGTS – Results at 5yrs

Medical Treatment

Surgical Treatment

IOP reduction 28mmHg→17-18mmHg

27mmHg→14-15mmHg

Progression at 5 years

No progression No progression

• Surgical group is at increased risk of visual loss initially but by 4yrs both groups are comparable

CIGTS summary

Surgery resulted in Lower IOP More cataract More ocular side effects Initial ↓ vision Initial ↓ visual field

CIGTS conclusions

Results do not support altering current practice of medical treatment first

``Doctor is my glaucoma likely to get worse?``

Diagnosis Risk of progression with no Rx (%)

Risk of progression with Rx (%)

OHTOHT study 5 yrs

9.5 4.4

NTG(CNTG study 6 yrs )

60 20

Early POAG(EMGS study 6 yrs )

62 45

Advanced POAG(AGIS-7 yrs)

Not Known 30 VA14 VF(IOP <15mmhg)

RISK OF PROGRESSIONTHE BEST EVIDENCE SUMMARY

Risk Factors for Progression

Factors OH Glaucoma Glaucoma ProgressionHigher age OHTS AGIS, CIGTS, EMGT

CCT OHTS

C:D ratio OHTS

Diabetes mellitus OHTS AGIS, CIGTS

Disc hemorrhage EMGT , NTGS

IOP (higher) OHTS EMGT

IOP (over f/u) OHTS EMGT

Male OHTS AGIS

PXF EMGT

Race (non-white) OHTS CIGTS

Visual field OHTS EMGT

Glaucoma Risk Calculation Results

Patient Age - - - 65Corneal Thickness - - - 490 micronsIOP - - - 23PSD - - - 1.4Vertical Cup / Disk Ratio - - - 0.7

Risk of developing glaucoma within the next five years.Risk without treatment - - - 41.71 %Risk with treatment - - - 16.68 %

Patient Age - - - 65Corneal Thickness - - - 550 micronsIOP - - - 23PSD - - - 1.4Vertical Cup / Disk Ratio - - - 0.7

Glaucoma Risk Calculation Results

Risk of developing glaucoma within the next five years.Risk without treatment - - - 16.86%Risk with treatment - - - 6.74 %

My “take home messages”

1. Every mmHg helps (EMGT)2. If get IOP very low (12mmHg) most

patients will not progress (AGIS)3. NTG is a funny disease

- Many do not progress- If do – only proven treatment is reducing IOP

4. Not all OHT needs treated – assess risk on individual basis and discuss with patient