1. Medical Management in PACG: Differences from POAG
Dr Parul Ichhpujani
MS, MBA(HA),
Fellow International Society of Spaeth Fellows,
Associate Professor
Glaucoma and Neuro ophthalmology Service
Department of Ophthalmology
Government Medical College and Hospital
Chandigarh

2. Management of PACG Vs. POAG
Differs because of the fundamentally different mechanisms of the two diseases
Unlike POAG, PACG to some extent is a preventable disease.
Common Goal: IOP lowering
Additional Goal: Protect the anterior chamber angle and keep its drainage function (Main strategy for PACG).
Medical treatment should not be used as a substitute for laser iridotomy or surgical iridectomy in patients with PAC or PACG.
Friedman et al. Clin Exp Ophthalmol. 2012; 40: 381-7

3. Choice of management: Dependent on the stage of the disease.
PACS and PAC:
Aim is to modify the anterior segment configuration preventing angle closure and IOP elevation.
PACG:
Aim is to protect those yet not closed angle, and to lower the IOP to prevent the worsening of glaucomatous optic neuropathy and visual field loss.

4. Drugs: PACG Versus POAG
Hyperosmotic agents: Mannitol, Glycerol
Use in PACG:
Mannitol, 1.5 to 2 g/kg/dose intravenously over 30 minutes
Raise blood osmolality; create an osmotic gradient
Required for IOP reduction in Acute attack of angle closure or used pre filtering surgery
Use in POAG:
Generally, not required for POAG
May be used pre-filtering surgery
Indian J Ophthalmol.2011; 59(Suppl1): S82–S87.

5. II. Beta Blockers: Timolol
Still in the Game!! Use in PACG:
In Acute ACG: Beta-blockers reduce IOP by around 20% to 30% within 1 hour of instillation.
First Rx line for residual angle closure after LPI; with elevated IOP
Timolol 0.5% eye drop Vs Timolol eye gel 0.1%: Equal efficacy
Timolol Vs. Latanoprost: Metanalysis; 7RCTs; Greater mean and peak IOP reductions with latanoprost
J Med Assoc Thai Apr;95 Suppl 4:S
PLoS One May 9;9(5):e96852.

6. Use in POAG:
Beta-blockers constitute as much as 90% of prescriptions for POAG in India.
Timolol Vs. Betaxolol/ Carteolol/ Levobunolol: Timolol better
Used as Monotherapy or as a fixed combination (highly efficacious both at trough and peak)
Indian J Pharmacol. 2013;45(2):117–20.
Am J Ophthalmol 1986; 101: 535–41.
Ophthalmology 1988; 95: 735–41.
Dorzolamide-Timolol Study Group. Ophthalmology. 1998;105(10):
Combigan Study Group. J Ocul Pharmacol Ther. 2005;21(4):

7. Comparative effectiveness of first line drugs for POAG:
Levobetaxolol, brinzolamide, dorzolamide, bimatoprost, latanoprost, travoprost, tafluprost, and unoprostone have been compared directly with timolol in 44 comparisons.
Comparative effectiveness of first line drugs for POAG:
114 RCTs; patients; 14 drugs
When a comparison-specific heterogeneity is assumed, PGs lowered IOP more than 3 mths; difference in IOP compared with timolol ranged from 0.30 to 2.08 mmHg.
Timolol ranked 6th in mean IOP 3 mths.
Ophthalmology Jan;123(1):129-40

8. III. Miotics: Pilocarpine
Use in PACG
Prior to laser therapy in AACG/PACS/PAC/PACG
In AACG, after IOP is controlled to allow for iris reperfusion
134 patients; Combination of intravenous acetazolamide followed by oral acetazolamide, as well as topical pilocarpine, timolol, and steroid drops.
Medical Rx resulted in resolution of AACG within 12 h in 76.2% of the subjects and within 24 h in 89.2% of the subjects
This success rate is lower at preceding time points: 21.5% at 3 hours, 44.6% at 6 hours. Given this slow rate of resolution, other techniques like anterior chamber paracentesis should be tried alongside Medical Rx.
Ramli N. Eye (Lond) Oct;24(10):

9. When to exercise caution with Pilocarpine in Angle closure
Young patients
Increased headache
Blurred vision secondary to fluctuating myopia
Inflammatory conditions
Increases flare in the AC
Myopic patients
More at risk for RD
Patients with central cataracts
Pupil constriction limits vision
Small pupil can complicate cataract extraction

10. When not to use Pilocarpine
In cases where it may exacerbate pupil block, i.e., where AC is secondary to lens-induced or retro-lenticular mechanisms.
Pseudoexfoliation
Phacomorphic glaucoma
Aqueous misdirection

11. Use in POAG

12. Revisiting MOA of Pilocarpine:
Pilo. 1% in healthy eyes; Pilo. 2% in POAG
EDI-OCT Nasal corneoscleral limbus; 1 hr after instillation
Expands Schlemm’s canal. No differences in the effect were identified between the 2 groups.
Whether this finding results from a direct effect of pilocarpine on the SC or secondarily from its effect on the ciliary musculature and/or trabecular aqueous outflow remains to be determined.
JAMA Ophthalmol Sep 1;134(9): .

13. IV. Alpha Agonists: Brimonidine
Dual action:
Decreases aqueous production
Increases outflow
Reduces iris thickness with an increase in posterior chamber depth but does not alter the thickness and position of the lens; does not facilitate pupil block.
RCT; Brimonidine and BTFC caused passive miosis; widening of most of the AC angle parameters without changing the AC depth, in both normals and POAG patients.
Effects of BTFC on the angle were likely to be greater than those resulting from the pilocarpine.
Journal Ocular Pharmacol Therapeutics. 1999;15(4):
No effect on accomodation; passie paralysis of iris dilator; inhibits aplha 1 receptors by modulating NE
Kim JM. Jpn J Ophthalmol.2011; 55:

14. Use in PACG
In Acute ACG: Alpha-agonists reduce IOP by around 26% within 2 hours post- dose.  
Brimonidine Vs. Apraclonidine in Angle closure:
Comparable efficacy in preventing post LPI IOP spikes.
Apraclonidine 1.0% tends to have a pupil dilating effect while brimonidine 0.2% tends to constrict the pupil.
Use in POAG:
Network meta-analysis of 28 RCTs; 8 different glaucoma drugs (brimonidine, bimatoprost, travoprost, latanoprost, timolol, dorzolamide, betaxolol
Brimonidine had the 4th highest drop in IOP at peak, but had the lowest IOP reduction of the 8 drugs investigated at trough.
Yuen NS. Jpn J Ophthalmol. 2005;49(2):89-92.
J Clin Epidemiol 2009;62(12):

15. V. Prostaglandins Use in PACG:
Effective at lowering IOP in chronic PACG
Mech. Of Action in ACG:
EXACT Study: Efficacy of Xalatan in Angle Closure Glaucoma therapy
Exact MOA not known.
Latanoprost enhanced aqueous access to the ciliary body by way of the still- open part of the AC angle or across the iris root.
Delayed onset of action precludes its use in acute angle closure.
Work even in eyes with no visible uveoscleral meshwork or ciliary face; PGs gains access through a yet unidentified pathway that possibly involves the iris, and that outflow of aqueous may involve something other than uveoscleral meshwork
Aung T et al. Ophthalmology,2000; 107:
Aung T et al. Ophthalmology. 2004;111(3):
J Ocul Pharmacol Ther Feb;21(1): 


16. Efficacy in angle closure?
No correlation was found between efficacy of PGs and the extent of synechial closed angle
Even in eyes with 360 degrees of PAS, Latanoprost is still effective.
Metanalysis: 17 studies; 807 patients: Latanoprost safe and efficacious in angle closure.
Aung T.Ophthalmology,2005; 112:
Kook MS et al. J Ocul Pharmacol Ther,2005; 21:75-84
J Glaucoma Mar;25(3):e

17. Which PG is better?
Travatan CACG Study Group: Travatan Better than Xalatan (p=0.162)
Metanalysis: Latanoprost Vs.Others
10 RCTs; 1039 patients; Travoprost and bimatoprost are superior in IOP control than latanoprost, but latanoprost is better tolerated in patients with CACG.
Asian J Ophthalmol. 2006;8:2-8
Eur J Ophthalmol. 2015;25(1):18-26.

18. Use in POAG: First Line therapy; Increase uveoscleral outflow
27-34% IOP reduction; Equivalent efficacy(Lat. Vs. Bimato. VS. Travop)
Ther Adv Chronic Dis. 2014;5(1):30-43.

19. VI. CAI’s Use in PACG: Decrease aqueous production
Oral CAIs: Acetazolamide
Can open the angle, perhaps by a reverse pupillary block effect.
Lowe RF. Aust J Ophthalmol. 1973;1:24–26.
Topical CAIs: Dorzolamide, Brinzolamide
Lack of clinical data on the use of topical CAIs in AACG.
In AAC patients who are already on systemic CAI, adding a topical CAI may not have additional benefits.
Can be used as Adjunctive therapy in chronic PACG.
Rapid reduction in aqueous production lowers pressure in the posterior chamber compared with the anterior chamber. The momentary reversal of pressure gradient between the anterior and posterior chamber results in a concave iris configuration
Rosenberg LF.Ophthalmology. 1998;105:88–92.

20. Use in POAG:
18-22% IOP reduction; Second/third line adjuncts; Monotherapy as well as Combination (BTFC/ DTFC)
DTFC Vs BTFC in OAG: Greater IOP reduction; patients were more likely to achieve lower target pressures with DT than with BT.
Indian J Ophthalmol Feb;64(2):

21. Medical management of the different clinical types of angle closure glaucoma
Acute attack of angle closure:
RPC Data: 24.7% Acute presentation
PGI data: 4.7% Acute presentation
Initial IOP reduction with Hyperosmotics + Oral CAIs
Topical Beta blockers followed by pilocarpine
Topical Steroids to control inflammation
Oral analgesics and antiemetics
Medical therapy resulted in resolution of APAC within 12 h in 76.2% of the subjects and within 24 h in 89.2% of the subjects.
Sihota et al. Indian J Ophthalmol. 1998;46:25–9.
Ichhpujani et al. Indian J Ophthalmol. 2010;58(3):
Eye (Lond) Oct;24(10):

22. Primary treatment is laser; LPI/ laser iridoplasty.
II. Plateau Iris
Primary treatment is laser; LPI/ laser iridoplasty.
Low dose pilocarpine has a role in opening the angle as an alternative to iridoplasty.
III. Phacomorphic glaucoma/Ectopia lentis
Miotic therapy may worsen the angle closure
IV. Malignant Glaucoma
Concurrent use of Atropine drops, beta-blockers , alpha2- agonists, CAIs and hyperosmotics in full dosage from the beginning.
Medical Rx is allowed time to work; if elevated IOP persists, go in for Surgery
Am J Ophthalmol Sep; 128(3):

23. Innovations in pipeline…......
Chitosan-g-poly(N-isopropylacrylamide) copolymers as delivery carriers for intracameral pilocarpine administration.
Effective IOP reduction and pupillary constriction noted in rabbits intracamerally treated with pilocarpine-loaded poly(ε-caprolactone) nanoparticles.
Collagen shields cross-linked with ZnO/PVP NPs release Pilocarpine HCl over a period of 14 days; offering a promising sustained release Rx option for glaucoma.
Eur J Pharm Biopharm. 2017;113:
Nanoscale. 2017;9(32):
Int J Pharm. 2016;501(1-2):

24. Take Home Message
Medical treatment should not be used as a substitute for LPI.
Treatment Options for Angle closure:
Acute Presentation
Oral CAIs and Hyperosmotic agents
Topical beta-blocker and/or topical alpha-2 agonist
Topical cholinergic agonists
LPI after acute attack resolved; may consider lens extraction after acute attack resolved
Ongoing or Chronic Angle-Closure Glaucoma
Topical PGAs and/or topical beta-blocker and/or topical alpha-2 agonist
CAIs
Lens extraction surgery
Trabeculectomy and/or tube shunt

25. Thanks for your kind attention!!