Comparison of Efficacy of Two Groups of Glaucoma Drops (Xalatan vs.Cosopt) in Reducing Eye Pressure Following Laser (SLT)Treatment in the Management of Glaucoma.

Introduction Selective Laser Trabeculoplasty has been shown as a relatively safe and
effective treatment modality for lowering IOP in various forms of open-angle glaucoma
(Latina et al). It lowers IOP by increasing aqueous outflow through its effect at cellular
level possibly either (1) through migration and phagocytosis of trabecular meshwork debris
by macrophages or (2) by stimulating the proliferation of healthy trabecular and endothelial
cells.

Cases who don’t achieve target IOP following SLT therapy need additional treatment in form
of topical medications. Conventionally common topical antiglaucoma medications to treat
glaucoma after SLT therapy either suppress aqueous secretion (B-blockers or carbonic
anhydrase inhibitors) or enhances uveoscleral aqueous outflow (Prostaglandin analogues).
Since Selective Laser Trabeculoplasty acts on outflow pathway, further additional IOP
reduction can be achieved more effectively by a class of drug which acts on different
pathway; on aqueous secretion by aqueous suppressants like Cosopt. In contrast drugs acting
on outflow pathway like prostaglandin analogue ( Xalatan etc) will possibly be less additive
in further reducing IOP after SLT since SLT also has effect on the same pathway- outflow
pathway.

Previous studies (Fechtner et al. J Ocul Pharmacol Ther. 2005 Jun;21(3):242-9 and Fechtner
et al. Acta Ophthalmol Scand. 2004 Feb;82(1):42-8.) have shown equal efficacy of Cosopt and
Latanoprost in reducing IOP in treatment of glaucoma. But to our knowledge, no long term
prospective study has evaluated aqueous suppressants (Cosopt) and prostaglandin analogues
with respect to their comparative efficacy in treatment of uncontrolled glaucoma status post
SLT therapy.

OBJECTIVE The primary objective of this study is to compare the IOP lowering efficacy of
aqueous suppressants (Cosopt) and prostaglandin analogues (Xalatan) when used status post
SLT in the management of Open Angle Glaucoma or Ocular Hypertension.

INCLUSION CRITERIA 1. Adult subjects of either sex, of any race, eighteen years of age or
older. 2 Diagnosis: Primary Open Angle Glaucoma, Pseudoexfoliation Glaucoma, Ocular
Hypertension.

3. Mild to moderate glaucoma only: Pattern standard deviation (PSD); more than 1DB and less
than 6 DB on Humphrey Visual Field.

3. Subject may be;

- A newly diagnosed glaucoma or

- A pre-existing glaucoma on not more than two topical antiglaucoma medications. 3 On no
systemic medications known to increase IOP (e.g. steroids) 4 Visual acuity equal or
better than 20/200 in the study eye 5. IOP less than 35 mm Hg in the study eye 6 No
previous intraocular surgery within last 6 months, except laser PI greater than 3
months ago.

EXCLUSION CRITERIA Pigmentary OAG, Proliferative diabetic retinopathy, History of chronic or
recurrent severe inflammatory eye disease (i.e. scleritis, uveitis, herpes keratitis), known
allergy to COSOPT or any of Prostaglandin Analogues, Chronic Obstructive Airways Disease
(COPD), sinus bradycardia (heart rate < 60 beats per minute), second or third-degree
atrioventricular block, overt cardiac failure. Pregnant and nursing mothers.

STUDY DESIGN: Single site, unmasked, prospective, randomized study STUDY PROCEDURE

Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Screening Phase SLT Treatment Phase Safety
check 2 weeks after SLT RANDOMIZATION 4 to 6 weeks after SLT Follow up visit, 6 weeks after
randomization Last Visit 3 months after randomization Determine eligibility by doing routine
eye exam including IOP check by Goldmann applanation tonometer, Gonioscopy, fundus exam,
Humphrey Visual Field (if HVF not done within last 6 months).

Subjects, who fulfill the eligibility criteria and give consent for participating in study,
will be scheduled for SLT. All eligible subjects will receive SLT. Pre-existing glaucoma
cases already on antiglaucoma medications will discontinue all the antiglaucoma medications
since the day of SLT treatment and will be off the drops for next 4 to 6 weeks. Similarly
newly diagnosed glaucoma will not be on any antiglaucoma medications. for next 4 to 6 weeks.
Each subject will have IOP check at 2 weeks after SLT treatment. It will be done to rule out
any unusual IOP spike following SLT. Each subject will have routine eye exam including IOP
check at this visit. The subjects with uncontrolled IOP despite SLT therapy will be
randomized to receive either COSOPT or Prostaglandin analogue (XALATAN). IOP check and
routine eye exam. IOP check, routine eye exam including fundus exam and Humphrey Visual
Field.

 If IOP is uncontrolled at the visit 5, a stepped drug therapy will be initiated based on
following protocol:

1. For patients who are in Cosopt group after randomization. Sequence of additional
medications will be following:

First Step: Alphagan (Brimonidine) Second Step: Prostaglandin Analogues

2. For patients who are in Xalatan group after randomization. Sequence of additional
medications will be following:

First Step: Alphagan (Brimonidine) Second Step: Dorzolamide (Trusopt)

Note: IOP will be measured using a Goldmann Applanation Tonometer at 8 AM and 10 AM at
visits: Visit I, Visit IV, Visit V and Visit VI. A ± 30 minute window will be allowed for
each measurement recording.

IOP measurement at Visit II (SLT treatment phase) and Visit III (safety check) can be done
at random time.

Duration of Study Participation; Subjects who are eligible to participate in the study shall
be enrolled for approximately 6 months. References; Fechtner RD, McCarroll KA, Lines CR,
Adamsons IA. Efficacy of the dorzolamide/timolol fixed combination versus latanoprost in the
treatment of ocular hypertension or glaucoma: combined analysis of pooled data from two
large randomized observer and patient-masked studies.J Ocul Pharmacol Ther. 2005
Jun;21(3):242-9 Fechtner RD, Airaksinen PJ, Getson AJ, Lines CR, Adamsons IA; COSOPT versus
XALATAN Study Groups.

Efficacy and tolerability of the dorzolamide 2%/timolol 0.5% combination (COSOPT) versus
0.005% (XALATAN) in the treatment of ocular hypertension or glaucoma: results from two
randomized clinical trials. Acta Ophthalmol Scand. 2004 Feb;82(1):42-8.

Latina MA, Tumbocon Ja. SLT: a new treatment option for open-angle glaucoma. Curr Opin
Ophthalmol 2002; 13:94-6

Inclusion Criteria:

1. Adult subjects of either sex, of any race, eighteen years of age or older.

2. Diagnosis: Primary Open Angle Glaucoma, Pseudoexfoliation Glaucoma, Ocular
Hypertension.

3. Mild to moderate glaucoma only: Pattern standard deviation (PSD); more than 1DB and
less than 6 DB on Humphrey Visual Field.

4. Subject may be:

- A newly diagnosed glaucoma or

- A pre-existing glaucoma on not more than two topical antiglaucoma medications.

5. On no systemic medications known to increase IOP (e.g. steroids)

6. Visual acuity equal or better than 20/200 in the study eye

7. IOP less than 35 mm Hg in the study eye

8. No previous intraocular surgery within last 6 months, except laser PI greater than 3
months ago.

Exclusion Criteria:

1. Pigmentary OAG,

2. Proliferative diabetic retinopathy,

3. History of chronic or recurrent severe inflammatory eye disease (i.e. scleritis,
uveitis, herpes keratitis),

4. Known allergy to COSOPT or any of Prostaglandin Analogues,

5. Chronic Obstructive Airways Disease (COPD),

6. Sinus bradycardia (heart rate < 60 beats per minute),

7. Second or third-degree atrioventricular block,

8. Overt cardiac failure.

9. Pregnant and nursing mothers.