To establish your knowledge in glaucoma as evidence based !

1. Management of Primary
Open Angle Glaucoma:
Evidence Based Medicine
By
Hend M. Safwat
Asst. Lecturer of Ophthalmology
Al-Azhar University
2016
All Rights are Preserved

2.  Closed angle glaucoma usually manifests
at early stages of functional damage.
 Open angle glaucoma
usually not diagnosed
at early stages of
functional damage .

3.  Should we need a screening system ?!
 According to Preferred Practice Pattern of
American Academy of Ophthalmology
(2010):
(Population-based screening for glaucoma is
currently not cost-effective. Screening may
be more useful and cost-effective when it is
targeted at populations at high risk for
glaucoma, such as older adults, those with a
family history of glaucoma, and African
Americans and Hispanics.

4.  Screening for glaucoma could be included in
general screening for eye disease, especially
among older populations).
(American Academy of Ophthalmology Vision Rehabilitation Committee. Preferred Practice Pattern® Guidelines.
Primary Open Angle Glaucoma. San Francisco, CA: American Academy of Ophthalmology; 2010. Available at:
www.aao.org/ppp).
 We all are invited to catch the glaucoma as
early as possible !
 Clinical tips in taking history; Always ask
about family history of glaucoma, as you
routinely ask about HTN and DM.

5.  In examination, do not let normal IOP guide
you.
 Remember, IOP is corneal biomechanics
dependant, and risk factor rather than a
cornerstone in the diagnosis.

6.  The evaluation of ONH is by Volk 90 D with
(dilated) pupil; is recommend by AAO and
European glaucoma society.
 If you suspect in the disc, document it, and
follow up after 6 months.
 Documentation is by coloured
stereophtography, or computerized imaging
methods as cSLO/OCT.

7.  Practice
Von Herick’s
technique as
a routine
for angle
assessment
as the gonioscopy
is not a routine.

8.  Do not depend in one visual field in
conclusion of glaucoma diagnosis(OHTS
founded 86% of patients had normal field on
2nd repetition, learning curve effect).

9.  Your patient is either a suspect or newly
diagnosed glaucoma.
 What’s the border of the suspect?
 Open angle glaucoma suspect (OAGS) is
patient of one of the following:
1- Ocular hypertension
2- Suspect ONH; cupping, asymmetry, focal
notch, ….
3- Suspect perimetry as large PSD without
obvious scotoma, or abnormal FDT with
normal SAP.
(American Academy of Ophthalmology Vision Rehabilitation Committee. Preferred Practice Pattern® Guidelines.
Primary Open Angle Glaucoma Suspect. San Francisco, CA: American Academy of Ophthalmology; 2010.
Available at: www.aao.org/ppp).

11. Early Manifest GlaucomaTrial
(EMGT)
Purpose: comparing treatment (Betaxolol +
Argon laser trabeculoplasty, ALT) Vs. no
treatment in early diagnosed open angle
glaucoma. The 2ndry purpose is assessment of
risk factors for Progression.
Study Design: multicentre randomized
controlled clinical trial with 255 newly
diagnosed glaucoma (POAG, NTG, and PEX
glaucoma), from1993 to1997.

12. Assessment: guided by ONH changes and standard
automated perimetry.
Results:
• 25% decrease of IOP from the 1s visit baseline >>>
50 % decrease in progression.
• The less baseline IOP, the less rate of progression.
• Untreated group >>>> 62 % progression.
• Treated group >>>> 45 % progression
• IOP fluctuation is not risk factor for progression.

13. • Lens opacity increased in treated group vs.
untreated group.
• The risk factors for progression at base line
are:
1- higher baseline IOP
2- pseudoexfoliation
3- hypotension (in NTG)
4- lower central corneal thickness + high IOP
5- disc haemorrhage.

14. Clinical Applications:
 Early treatment is associated of no
progression; but not all untreated patients
are associated with progression !!!
 So, tailor the management for every
patient.
(Heijl A, Leske MC, Bengtsson B, et al, Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma
progression. Results from the Early Manifest GlaucomaTrial.Arch Ophthalmol 2002;120:1268-79.
Leske MC, Heijl A, Hussein M, et al, Early Manifest Glaucoma Trial Group. Factors for glaucoma progression and the effect of
treatment.The Early Manifest GlaucomaTrial.Arch Ophthalmol 2003;121:48-56.
Leske MC, Heijl A, Hyman L, et al, Early Manifest Glaucoma Trial Group. Predictors of long-term progression in the Early Manifest
GlaucomaTrial. Ophthalmology 2007;114:1965-72. )

15. Collaborative NormalTension
Glaucoma Study (CNTGS)
Purpose: comparing treatment vs. no
treatment in normotensive glaucoma.
Treatment aim was 30% reduction of baseline
IOP by drops (except beta blocker or alpha2
agonist),ALT, or surgery.
Study Design: randomized controlled trial
with 230 patients.

16. Assessment: Progression assessment was
either by field or coloured
stereophotography.
Results:
• 30 % reduction of IOP was associated with
12 % progression vs. 35% in untreated group
• Variable progression value means in
untreated group.
• Cataract increased with surgery.

17. • Risk factors associated with progression:
1- female sex
2- migraine
3- disc hge
Clinical Applications:
The variable rates of NTG make some patients
need no treatment ... and others may progress
till blindness ...............................................................
.........................................................................................

18. So, NTG are 2 types:
 progressive type.
 non progressive type
• If you diagnosed your patient as early NTG
>>>> close follow up >>> if progression
occurs >>>> start treatment.
• 30 % reduction of initial IOP is a must.
(Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with
normal-tension glaucoma and patients with therapeutically reduced intraocular pressures.Am J Ophthalmol 1998;126:487-97.
Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-
tension glaucoma.Am J Ophthalmol 1998;126:498-505. )

19. Ocular HypertensionTreatment
Study (OHTS)
Purpose: Compare effect of ocular
hypotensive drugs on ocular hypertension vs.
no treatment.
Study Design: multicentre randomized
prospective controlled clinical trial. It contains
1637 patients. It started 1994. It had 2 phases

22. Results:
• After 5 years (treated group vs. untreated
group):
 4.4% in treated group showed onset of
glaucoma; vs. 9% in untreated group; 50%
reduction of risk.
• After 13 years (treated group from start vs.
treated group from phase 2):
 16% converted to glaucoma from treated
group from the start; vs. 22% from the treated
group from phase 2.

23. • Risk factors for progression were: thinner
CCT (555 um or less), disc hge, higher IOP,
older age, enlarged vertical cup/disc ratio,
and larger PSD.
• Cataract was associated with treated
group.
• Disc hge missed from clinical examination,
but detectable in colored
stereophotography in 87%.

24. Clinical Applications:
 Ocular hypertensives are either high risk or
low risk.
 High risk group will have benefit from early
treatment.
 Measurement of CCT for all glaucoma
suspect.
(Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the
onset of primary open-angle glaucoma.Arch Ophthalmol 2002;120:714-20;discussion 829-30. )

25. European Glaucoma Prevention
Study (EGPS)
Purpose: comparing dorzolamide eye drops
vs. placebo in OHT to delay onset of
glaucoma.
Study Design: multicentre randomized
double-masked placebo-controlled trial. 1081
patients. Follow up for 55 months (4.6 years).
Assessment: visual field and optic disc
changes.

26. Results:
 After 6 months:
• Dorzolamide group >>> 15% IOP reduction.
• Placebo group >>> 9% IOP reduction.
 After 5 years
• Dorzolamide group >>> 22% IOP reduction.
• Placebo group >>> 19% reduction.
• The risk factors for progression were as in
OHTS results + diuretics use.

27. Clinical application:
No clinical significant difference between
dorzolamide and placebo in delaying the onset
of glaucoma.
(Miglior S, Zeyen T, Pfelffer N, et al. Results of the European Glaucoma Prevention Study. Ophthalmology 2005; 112(3):
366-75.)

28. Collaborative Initial Glaucoma
Treatment Study (CIGTS)
Purpose:
1- Comparing initial medical vs. surgical
(trabeculectomy with or without 5 FL)
treatment in newly diagnosed open angle
glaucoma (primary, PEX, and pigmentary).
2- Effect of treatment on quality of life (QoL).
Study Design: multicentre, randomized
study. 607 patients. 1993-1997.

29. Assessment: IOP reduction, field
progression, QoL, visual acuity, and cataract
formation.
Results:
• IOP reduction was 48% by surgical vs. 35%
by medical.
• After 5 years: no difference in field
progression in both groups.
• After 8 years: the stability of field was
better in surgical group (22% progression
vs. 25% progression in medical group).

30. • QoL was initially better with medical group.
• Cataract formation was twice in surgical
group.
• Initial visual loss was with surgical group; but
after 4 years, both groups are the same.
• The risk of endophthalmitis in surgical group
was 1.1%.
• The reversal of ONH cupping was in surgical
group

31. • The risk factors for progression are like
the other trials + higher baseline IOP,
worse initial field , and low educational
status.
• Diabetic patients shows more
progression if treated initially with
surgery.

32. Clinical Applications:
 Newly diagnosed open angle glaucoma +
early field changes = better initial medical
treatment.
 Newly diagnosed open angle glaucoma +
moderate or sever field changes = better
initial surgical treatment.
 OAG + DM >>> do not rush for surgery.
(Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing
initial treatment randomized to medications or surgery. Ophthalmology 2001;108:1943-53.
Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of
treatment and other baseline factors. Ophthalmology 2009;116:200-7.
Parrish RK II, Feuer WJ, Schiffman JC, et al. Five-year follow-up optic disc findings of the Collaborative Initial Glaucoma Treatment Study.
Am J Ophthalmol 2009;147:717-24. )

33. LowTension GlaucomaTreatment
Study (LoGTS)
Purpose: comparing twice timolol maleate
0.5% vs. brimonidine tartrate 0.2% in low
tension glaucoma, on IOP and stability of field.
Study Design: multicentre randomized
monotherapy eye double-masked clinical trial.
Assessment: field, IOP, and coloured
stereophotography every 4 months.

34. Results:
• IOP reduction was the same in 2 groups.
• Visual field progression was 9.1% in
brimonidine group vs. 39.2% in timolol group.
• Adherence to brimonidine was bad due to
local side effects.
Clinical Applications:
• Brimonidine is better than B blockers.
• Don’t forget check heart rate, Bl Pr, and
asking about systemic B blockers taking.
(Krupin T, Liebmann JM, Greenfield DS, Rosenberg LF, Ritch R, Yang JW. The Low-pressure Glaucoma Treatment Study (LoGTS) study
design and baseline characteristics of enrolled patients.Ophthalmology. 2005;112:376–85)

35. Advanced Glaucoma Intervention
Study (AGIS)
Purpose: comparing ATT (Argon, Trab., Trab)
vs. TAT (Trab, Argon, Trab) regimens in
advanced glaucoma.
Advanced glaucoma here is patient not controlled with
maximum tolerated topical drugs (> 18 mmHg) with MD
less than 16 dB.
Study Design: multicentre, prospective,
randomized study. 789 eyes.

36. Assessment: visual acuity, IOP, visual
progression, and cataract formation.
Results:
After 1.5 years (3 visits):
 less field progression if IOP < 14 mmHg.
 More field progression if IOP > 17.5 mmHg.
After 7 years:
 IOP reduction was grater with TAT protocol.
 ATT worked well in African while TAT worked
well in Caucasians.

37. • Risk factors for progression were: older age,
longer follow up, and increasing number of
glaucoma interventions.
• Both ALT and SST failed in younger patients
with higher IOP.
• Reporting IOP fluctuation as a risk factor for
progression was debatable in this study.

38. Clinical Applications:
• Keep race in your mind when choosing
therapy.
• Lower IOP was associated with less visual
field loss.
(The AGIS Investigators.The Advanced Glaucoma Intervention Study (AGIS): 7.The relationship between control of intraocular pressure
and visual field deterioration.Am J Ophthalmol 2000;130:429-40.
The AGIS Investigators.The Advanced Glaucoma Intervention Study (AGIS): 13. Comparison of treatment outcomes within race.Ten-year
results. Ophthalmology 2004;111:651-64. )

39. TubeVs.Trabeculectomy (TVT)
Purpose: to report 5 year treatment
outcomes in the tube vs. trab.
Study Design: multicenter randomized
clinical trial.
The tube-shunt surgery using the 350-mm²
Baerveldt implant.
The trab with mitomycin-C in patients with
previous cataract extraction and/or failed
trabeculectomy .

40. Assessment: IOP, visual acuity, visual fields,
surgical complications, glaucoma medications,
and treatment failure.
Results:
 Tube-shunt surgery had a higher success rate
than trab (85% vs. 69%) after 3 years of follow-
up (no success was defined as: loss of vision,
and/or IOP less than or equal to 5 mmHg or
greater than or equal to 21 mmHg).
 Both surgical procedures were associated with
similar IOP reduction and use of supplemental
medical therapy at 3 years.

41. • Postoperative complications occurred more
frequently after trab, compared with tube-
shunt surgery, but the rate of serious
complications associated with vision loss
and/or reoperation to manage the
complication was similar with both
procedures.
Clinical Applications:
•The TVT Study supports the expanding use
of tube shunts beyond the surgical
management of refractory glaucoma.

42. •Trabeculectomy is not without its travails. It
requires the surgeon to tailor the procedure
to each patient (i.e., number of scleral flap
sutures and dosage of an antifibrotic agent),
whereas tube-shunt surgery is a more
standardized procedure.
•Also, trabeculectomies require more frequent
and more postoperative care than tube shunts.
(Gedde SJ, Schiffman JC, Feuer WJ, et al, Tube Versus Trabeculectomy Study Group. Three-year follow-up of the Tube
VersusTrabeculectomy Study.Am J Ophthalmol 2009;148:670-84.)

43. MinorTrials Comparing Surgeries
• Randomized clinical trials comparing
viscocanalostomy with trab generally suggest
greater IOP reduction with trab, and more
complications with viscocanalostomy.
(Yalvac IS, Sahin M, Eksioglu U, et al. Primary viscocanalostomy versus trabeculectomy for primary open-angle glaucoma: three-year
prospective randomized clinical trial. J Cataract Refract Surg 2004;30:2050-7)
• One randomized clinical trial found that
trabeculectomy was more effective than non
penetrating deep sclerectomy at lowering IOP.
And several others found that the two
surgeries were equally effective.
(Chiselita D. Non-penetrating deep sclerectomy versus trabeculectomy in primary open-angle glaucoma surgery. Eye (Lond)
2001;15:197-201.
Cillino S, Di Pace F, Casuccio A, et al. Deep sclerectomy versus punch trabeculectomy with or without phacoemulsification: a randomized
clinical trial. J Glaucoma 2004;13:500-6).

44. Trials for Laser in Glaucoma
Glaucoma LaserTrial (GLT)
• Newly diagnosed POAG.
• Medical therapy vs. laser trabeculoplasty.
• Initial laser trabeculoplasty lowered IOP more (-9 mmHg)
than initial treatment with topical timolol maleate (-7
mmHg), over 2 years.
• Initial laser trabeculoplasty was at least as effective in
preserving visual field and optic disc status over 5.5 years.
(Glaucoma Laser Trial Research Group. The Glaucoma Laser Trial (GLT) and Glaucoma Laser Trial Follow-up Study: 7. Results. Am J
Ophthalmol 1995;120:718-31. )

45. Moorfields Primary TreatmentTrial 3
• Newly diagnosed POAG.
• Medical therapy vs. laser trabeculoplasty vs.
trabeculectomy .
• Trabeculectomy lowered IOP the most (-60%);
laser trabeculoplasty (-38%) and medical therapy
groups (-49%).
• Medical group had more deterioration in visual
fields than trabeculectomy group.
(Migdal C, Gregory W, Hitchings R. Long term functional outcome after early surgery compared with laser and medicine in open-angle
glaucoma. Ophthalmology 1994;101:1651-7. )

52. All algorithms and tables data are from the European Glaucoma Society.
Terminology and Guidelines for Glaucoma. 4th ed. Savona, Italy: Editrice Dogma
S.r.l.; 2014:127.Available at: www.eugs.org/eng/EGS_guidelines.asp.

54.  Prostaglandin analogues as 1st line of
treatment are based on some facts:
1- Some clinical trials (not multicentre)
2- Effective IOP lowering
3- Less systemic side effect
4- Adherence to therapy (once per day)
5- Introduction of preservative free (bimatoprost
(0.01%) and travoprost BAK-free).
6- Only10% non responders.

55.  No clear evidence against use of beta
blockers as 1st line of therapy; except its
side effects, and twice use per day.
 If you can achieve your patient IOP target
by use of beta blockers ........ Go.
 Remember; alpha2 agonist or topical
carbonic anhydrase as monotherapy; must
used triple per day to avoid diurnal or
nocturnal IOP fluctuations.

56.  Don’t start by combined therapy as 1st line.
 Again .... don’t start by combined therapy as
1st line of treatment.
 Unfortunately; adding another drug to PG
analogues don’t increasing its efficacy .... but
not vice versa.
(Higginbotham EJ, Feldman R, Stiles M, Dubiner H. Latanoprost and timolol combination therapy vs monotherapy:
one-year randomized trial.Arch Ophthalmol. 2002;120:915-922)

57. Anti Glaucoma during
Pregnancy
 All IOP lowering drugs are class C (human
risk cannot be ruled out), except
bromindine is class B (no risk evidence on
human; but animal risk may be evidenced)
 Laser therapy may be the
safest line for treatment
during pregnancy.

58. Glaucoma and Neuroprotection
 Neurodegeneration occurs at 3 sites; axon,
ganglion cell body (retina), and
synapses(brain).
 Primary site of damage is debatable (axon or
cell body).
 Acute high rise in IOP causes damage in cell
body ... to save it; you have 45-90 minutes to
interfere (like CRAO).
 Open angle glaucoma cause damage to axons
1st; so you have time to interfere.

59.  Drugs that emerged as neuroprotective is
based on interference with pathophysiology
(cannot be detailed here).
 The evidence gives the power to
bromindine drops more than any drug.
(Data from Low-pressure GlaucomaTreatment Study, LoGTS).

60.  PG analogues are still lacked clinical trials
evidence as neurorptective in glaucoma ....
 However, intravitreal administration of
latanoprost has
demonstrated an
increase in RGC
survival following
trans-section of
the optic nerve !!

61.  Memantine is NMDA receptor
antagonists tablets.
 NMDA receptors are activated by glutmate
and nitric oxide, upregulated in POAG, and
increase intracelullar influx of Ca & Na.

62.  The largest randomized, progressive, Phase
3 clinical trial on neuroprotection studying
the safety and efficacy of memantine for
open angle glaucoma has been completed,
but it disappointingly failed to meet its
primary endpoint.
(Osborne NN. Recent clinical findings with memantine should not mean that the idea of neuroprotection in
glaucoma is abandoned.Acta Ophthalmol. 2009;87:450–4)
 Antioxidants and vitamins E, C & B.
 Calcium channel blockers as like
nifedipine and verapamil may exert
neuroprotection by increasing blood flow
to the RGC.

63.  Brain derived neurotrophic factors
(BDNF) drugs also show some clinical
promising but not yet evidence.
 Others are still experimental as: anti
apoptotic, gene therapy, immunotherapy and
stem cell therapy.