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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT 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: , 2002.

OHTS - methods  RCT of 1600 patients  IOP 24-32mmHg in one eye and 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT study 5 yrs 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT study 5 yrs NTG (CNTG study 6 yrs ) 6020 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT study 5 yrs NTG (CNTG study 6 yrs ) Early POAG (EMGS study 6 yrs ) 6245 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT 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 → Trab 2. ALT → Trab → ALT Medical treatment as required 789 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 % 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 DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT 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 TreatmentSurgical Treatment IOP reduction 28mmHg → 17-18mmHg27mmHg → 14-15mmHg Progression at 5 years 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?``

DiagnosisRisk of progression with no Rx (%) Risk of progression with Rx (%) OHT OHT study 5 yrs NTG (CNTG study 6 yrs ) 6020 Early POAG (EMGS study 6 yrs ) 6245 Advanced POAG (AGIS-7 yrs) Not Known30 VA 14 VF (IOP <15mmhg) RISK OF PROGRESSION THE BEST EVIDENCE SUMMARY

Risk Factors for ProgressionFactors OH  Glaucoma Glaucoma  Progression Higher age OHTS AGIS, CIGTS, EMGT CCTOHTS C:D ratio OHTS Diabetes mellitus OHTS AGIS, CIGTS Disc hemorrhage EMGT, NTGS IOP (higher) OHTSEMGT IOP (over f/u) OHTSEMGT MaleOHTSAGIS PXFEMGT Race (non-white) OHTSCIGTS Visual field OHTSEMGT

Glaucoma Risk Calculation Results Patient Age Corneal Thickness microns IOP PSD Vertical Cup / Disk Ratio Risk of developing glaucoma within the next five years. Risk without treatment % Risk with treatment %

Patient Age Corneal Thickness microns IOP PSD Vertical Cup / Disk Ratio Glaucoma Risk Calculation Results Risk of developing glaucoma within the next five years. Risk without treatment % Risk with treatment %

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