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Open angle Glaucoma

 Open angle glaucoma, one of the major causes of impaired vision worldwide, is a condition characterized by damage to and loss of optic nerve axons, resulting most commonly in loss of peripheral aspect of the visual field, which may progress to loss of central vision.
Ref: Ophthalmology 1999; 106: 653 - 663

Open angle Glaucoma: Treatment
Methods to reduce IOP include:  Use of systemic or topical medications  Use of laser energy applied to the trabecular meshwork to improve aqueous outflow.  Use of filtration surgery to produce an alternate route for aqueous outflow.
Ref: Ophthalmology 1999; 106: 653 - 663

Open angle Glaucoma: Medical therapy
 The expanded pharmacologic armamentarium in the last decade has greatly increased the efficacy and tolerability of medical therapy.  Medical treatment is costly, lifelong and is a daily reminder for patients that they have potentially vision threating disorder.
Ref: Curr Opin Ophthalmol; 2003; 14: 106 - 111

Open angle Glaucoma: Surgical Option
 European Ophthalmology community has advocated early incision surgery and demonstrated better IOP control compared with patients treated with eye drops.  Retrospective study demonstrated that 60% of eyes initially treated with medications required surgical interventions.  Surgery can be more cost-effective than a lifetime of medications.  Less inconvenience, patients do not have the daily psychological burden of treating the disease.  Surgical side effects: ptosis, chronic dysesthesia, surgical related visual compromise and risk of blebitis. Ref: Current Opinion Ophthalmol, 2003; 14: 106 - 111

rather. these studies suggest more effective control of glaucomatous damage can be obtained by immediate filtration surgery. increased attention to the impact of therapy on health-related quality of life has added another consideration in deciding upon appropriate treatment of such patients. Ref: http://www/net.nih-gov . In addition.BACKGROUND Recent studies have challenged the conventional wisdom of treating all newly diagnosed openangle glaucoma with eye drops.

2003 .Study Title: The Collaborative Initial Glaucoma treatment study (CIGTS) Ref: Current Opinion in Ophthalmology. 14. 106 – 111.

Objective: CIGTS is a randomized. controlled clinical trial designed to determine whether patients with newly diagnosed POAG are better treated by initial treatment with medications or by immediate filtration surgery. .

..Study design and Methods Organization:  Randomized controlled clinical trial  Duration of the study: 5 years  14 clinical centers enrolled patients from October 1993 – April 1997.  Study’s protocol and informed consent were approved by human’s studies review boards at all participating centers.

visual field changes. One of three combinations of qualifying IOP. pseudoexfoliative. 2. .Study design and Methods Inclusion criteria: 1. and optic disc findings as follows: • IOP of 20 mm Hg or higher. or pigmentary glaucoma in one or both eyes. Diagnosis of primary open-angle. Humphrey 24-2 visual field result with 3 contiguous points on the total deviation plot at the less than 2% level and glaucoma hemifield test result that is “outside normal limits” and optic disc compatible with glaucoma.

Age between 25 and 75 years 5. Visual acuity equal to or better than 20/40 on ETDRS chart.IOP between 20-26 mm Hg or higher. • IOP greater than 26 mm Hg and glaucomatous optic disc damage 3. Written informed consent • . Ability to meet the follow-up requirements for a minimum of 5 years 6. Humphrey 24-2 visual field result with 2 contiguous points on the total deviation plot at the less than 2% level and glaucomatous optic disc damage. 4.

visual field testing  Diabetic retinopathy with more than 10 micro aneurysms  Previous ocular surgery  Significant cataract  Use of corticosteroids (oral or ophthalmic) .Study design and Methods Exclusion criteria:  Use of glaucoma medication for more than 14 days  Use of glaucoma medication within 3 weeks of baseline visit (washout from < 14 days of use was permitted)  CIGTS visual field score > 16  Ocular disease that might affect measurement of IOP.

Center – (14 sites) 3. Asian and other) 5.  Adaptive randomization used – resulted in optimal balance across 5 strata: 1. pigmentary and pseudoexfoliative forms of open angle glaucoma)  Patients were randomized into either the medical or surgical arm. 65 to 75 2. .Study design and Methods (contd. Gender – (male. Age – 25 to 54.) Enrollment and Randomization  After two baseline visits (which measured visual field and IOP taken at each visit).patients were randomized. Diagnosis – (Primary. female) 4. white. Race – (African-American. other eligibility criteria confirmed . 55 to 64.

CIGTS: Treatment Flow Sheet Medical therapy 1. Trabeculectomy (5 FU. alternative monotherapy. Medication (topical β-blocker. 6. 5.optional) ALT Medication Trabeculectomy with antimetabolite Medication Ophthalmologist’s discretion . dual. 3. 6. 4. 3. 2. 5. 4. triple and/or oral medications) ALT Trabeculectomy (5-FU optional) Medication Trabeculectomy with antimetabolite Medication Ophthalmologist’s discretion Surgical therapy 1. 7. 2.

CIGTS: Criteria for intervention failure  Criteria for intervention failure had to be met each time that a further treatment step was initiated.  Criteria include:  Failure to meet a target IOP that was established at the time of randomization  Evidence of progressive visual field loss  Or both .

CIGTS: Target IOP calculation  Based on the patient’s reference IOP (ie.. the mean of six separate IOP measurements taken in the course of the 2 baseline visits)  Reference visual field score (ie. the mean of at least 2 visual fields taken during 2 baseline visits)  Formula for target IOP = (1-[reference IOP + visual field score]xref.33) x 28 = 0.67 x 28 = 19 mm Hg .IOP) 100  For eg. VF score = 5 = (1 – 0. IOP = 28 mm Hg then target IOP = (1 – [28+5]) x 28 100 Ref. Ref..

CIGTS: Criteria for Intervention Failure  IOP related intervention failure: If on a follow-up visit. the IOP was > 1 mm Hg above the target IOP and this confirmed on another visit. .  Visual field related intervention: Visual field score failure was > 3 or more units above the reference visual field score on 3 consecutive tests performed at separate clinic visits.

CIGTS Study: Main outcome measures  Primary outcome variable: Progression in visual field score  Secondary outcome variable:  Health related quality of life  Visual acuity  Intraocular pressure .

005 level) IOP measured before Gonioscopy/ dilating agent: Goldmann Applanation tonometry Visual acuity: ETDRS protocol – Patients are tested at 4 m .CIGTS Study: Outcome Assessment Methods Progression in VF score: Increase in the VF score of 3 units or more from the patient’s reference VF score. Visual field score: Range from 0 (no defect) to 20 (all points showing a defect at the p<0.

Full 136 – item sickness impact profile 7. 4 questions – Adaptations and social support 3. 43 item symptom and health problem list 5. Questions on compliance and satisfaction with their treatment .CIGTS Study: Outcome Assessment Methods (contd.) Health related quality of life: An instrument was developed that incorporates designed questionnaire: 1. Questions on a no of possible co-morbidities 8. 16 questions – General health perceptions 2. 8-item center for Epidemiologic studies depression questionnaire 6. 33 item visual activities questionnaire 4.

.) The instrument is administered by telephone contact with the patient in his or her home at a pre arranged time and requires approximately 45 minutes to administer.CIGTS Study: Outcome Assessment Methods (contd.

.CIGTS Study: Follow-up Patients followed up: 3 months after treatment has begun. 6 months and then at 6 months intervalsafter treatment initiation. subsequent visits are conducted at 6 month interval. after a 6 month visit. Health related quality of life interviews: at 2 months.

CIGTS Study: Follow-up Table. Tests performed at Study Visits through Month 24 Assessment Visual field Refraction Visual acuity Slit-lamp examination IOP Gonioscopy Dilated lens examination Dilated funds examination Baseline Yes Yes Yes Yes Yes Yes Yes Yes Month 2 Month 3 Month 6 No No No No No No No No Yes Yes Yes Yes Yes Yes No Yes Yes No Yes Yes Yes Yes Yes Yes No No Yes Month 12 Yes Yes Yes Yes Yes No Yes Yes Yes Month 18 Yes Yes Yes Yes Yes Yes No No Yes Month 24 Yes Yes Yes Yes Yes No Yes Yes Yes QOL interview Yes .

to investigate VF loss and VA loss  SAS proc mixed and SAC Proc Genmod was used  Study: 90% power .  Repeated measures logistic regression.  Time specific comparisons on mean values were conducted using student’s t test.CIGTS Study: Statistical analysis  Treatment group comparisons followed the intent-totreat principle.

93 P value* Immediate family history of 99 (32%) glaucoma Hypertension Diabetes Smoking history: current Glaucoma type: POAG 122 (40%) 60 (20%) 62 (20%) 278 (91%) .63 0.Table 1. Demographics and Ophthalmic Status of Enrolled patients by treatment group Patient characteristic Categorical variables Gender female Race: white Medicine (n=307) N (%) 143 (47%) 167 (54%) Surgery (n=300) N (%) 130 (43%) 170 (57%) 102 (34%) 103 (34%) 42 (14%) 65 (22%) 272 (91%) 0.47 0.09 0.73 0.71 0.20 0.

VF=visual field .71 0. POAG=primary open-angle glaucoma. Immediate = parents. in years Qualifying IOP. SD=standard deviation. N=number.6) 27.5) 4.2) 0.0 (4.6 (5.15 0.7 (0.2) 85.5) 0. siblings.6 (4.6 (0. IOP=intraocular pressure.1 (10.8 (5.2) 0.62 0.2) 0.51 *P values result from either Yates corrected chi-square tests contrasting proportions or independent two-sided Student's tests contrasting means in the medical and surgical groups.70 0.19 0.3) 85. children CDR= Cup/disc ratio.6 (0.9 (11.) Patient characteristic Quantitative variables Age.6 (5.2) 27.9) 0.4 (5.Table 1.7 (0. in mmHg Reference VF score VA score Horizontal CDR Vertical CDR Medicine (n=307) Mean (SD) 56.7) 5. Demographics and Ophthalmic Status of Enrolled patients by treatment group (contd. VA=visual acuity.2) Surgery(n=300) P value* Mean (SD) 58.

RESULTS .

5% .7% .CIGTS Study: VF comparison  Clinically substantial VF loss: 10.36 unit worst VF score than initial medical treatment .surgically treated  Initial surgery resulted in 0.medically treated 13.

CIGTS Study: Results Collaborative Initial Glaucoma Treatment Study visual field score by time and treatment group 8 8 8 V is u a l fie ld s c o r e 8 8 8 8 8 M S e i c i n e r g e r y d u Patients in the medical arm initially had 8improvements in 8visual field 8 8 8 8 8 8 8 3 3 8 8 8 8 8 8 8 8 8 T i m e . but at 5 years both groups converged towards similar scores 8 . m scores .

71.07.65)  Initial surgery had a marginally positive association with the risk of VF loss (adjusted OR.34. 6. race. 4.07)  Diabetic patients had a 59% increased risk relative to non-diabetics (adjusted OR. 3.08.38)  Patients with cataract were at increased risk of vf loss(adjusted OR. 95% CI. 1. 2. 2. 3.59.34. 4.65) .71.50.CIGTS Study: Visual Field Loss  Logistic regression analysis revealed significant associations of a 3 unit or more VF score increase with age. 95% CI. 6.  Older age (every 10 yr increment in age increased the risk of VF loss by 40%)  Nonwhites had a 50% increased risk relative to whites (adjusted OR. 95% CI 1. 95 CI. history of diabetes and time in study. 1. 1.

CIGTS: VA comparison V u l a u b tim a d tre tm n g u is a c ity y e n a e t ro p 8 8 M e d ic in e S u r g e r y 8 8 V i s u a l A c u i ty 8 8 8 8 8 8 8 8 8 8 E r r o r b a r s a r e + / - s t a n d a r d e r r o r s 3 3 8 8 8 8 T i m em . 8 8 8 8 8 8 8 8 Surgery resulted in a 3 letter loss of VA (about ½ a line) evident at month 3 whereas in the medicine groups showed essentially .

2% of surgically treated patients.CIGTS: VA comparison  Clinically substantial VA loss (defined as < 15 letters in VA from baseline) during 5 years of follow-up in 3. .9% of medically treated patients and 7.

Surgery: Baseline – 27 mm Hg After 5 years – 17-18 mm Hg Medical: Baseline – 28 mm Hg After 5 years – 17-18 mm Hg .CIGTS: IOP Comparison  The decrease in IOP was significantly greater in the surgery group compared to medical group.

e 8 8 8 8 8 8 8 8 IOP reduction 48% in the surgical group compared to 35% in the medical group .CIGTS: IOP Comparison Intraocular 8 8 pressure by tim and treatm e ent group M e d ic in e S u r g e r y 8 8 8 8 8 8 8 8 8 8 8 8 3 3 3 3 8 8 8 8 T im m .

8 88 % 8. 8 88 % .CIGTS: Cataract Development  Initial surgical treatment resulted in the development of more cataracts than initial medical treatment. 8 88 % 88 % . 8 Surgical treatment Medical treatment 88 % . 8 88 % 8. 8 8. 8 88 % . % of patients underwent cataract surgery 8.

3. 6.5% . Incidence of complication occuring during the first postoperative month: Intraoperative bleeding – 13.5% Shallow or flat anterior chamber – 14. 4.3% Anterior chamber bleeding – 10.9% Ptosis – 11.2% Encapsulated bleb – 11.9% Serous choroidal detachment – 11. 525 trabeculectomies were performed in 300 patients randomized to the surgery arm. 2. 5.CIGTS: Surgical Complications   1.

6% of medicine group patients underwent ALT 11.80.8% of surgical group patients underwent ALT . P=0. Kaplan-Meier estimates show: 23.5%. surgical 8.CIGTS: Treatment Crossover  Treatment crossover in the medical group and surgical group was comparable (medical 8.3%. log rank test)  By 1 year after treatment initiation.

0 23.3 14.9 11.9 21.5 32.4 23.8 31.9 11.1 24.4 32.9 11.1 43.1 22.4 29.8 14. blurring Something in eye Red eye Excessive tearing Skin sensitivity around eye 43.4 13.9 17.1 27.9 17.6 13.9 18.CIGTS: Quality of life Comparison 2 months Medical n=280 % Visual Function Symptoms Blurred vision Difficulty w/ bright light Vision problems w/ steps Local Eye Symptoms Eye irritation.4 17.6 16.3 34.2 20.7 43.2 30.4 12.1 23.0 31.1 34.6 40.9 32.7 Surgical n=268 % 12 months Medical n=276 % Surgical n=269 % 60 months Medical n=201 % Surgical n=186 % .9 47.5 19.2 18.1 38.3 48.2 16.8 18.7 29.8 11.7 34.1 50.2 29.0 29.3 15.

CIGTS: Quality of life Comparison (contd.) .

1 5.1 15.0 22.9 4.6 4.9 3.2 0.4 25.1 9.1 2.0 1.5 25.5 15.9 10.1 4.3 14.CIGTS: Quality of life Comparison (contd.6 4.1 11.4 10.0 7.3 8.6 15.0 3.1 11.3 4.1 12 months 60 months Surgical Medical Surgical Medical Surgical n=268 % n=276 % n=269 % n=201 % n=186 % .7 3.2 4.1 13.2 33.2 13.3 26.3 20.3 10.7 6.3 3.1 25.) 2 months Medical n=280 % Systemic symptoms Drowsiness Headache/ browache Wheezing Weakness Nausea Altered tasteor smell Weight loss Dizziness 28.3 11.6 15.5 7.5 9.0 19.1 2.0 12.0 16.4 7.9 17.1 7.

5% higher scores for surgical group on VAQ Acuity subscale to approximately 22% higher scores on symptom impact glaucoma total score. .  Medically treated patients less likely to develop cataracts.  Pertaining to QOL.  Over 5 years.CIGTS: Discussion  Both medications and surgery significantly reduce IOP.  Medically treated patients were less likely to develop VF loss.  Local eye subscale higher with surgical group  Less impact on QOL with initial medical treatment than initial surgical treatment. both groups of patients had similar low rates of VF progression.  Target IOP achieved in > 90% of patients in both groups. suffer noncataract VA loss or complain of ocular side effects.

PG analogues.  Protocol allowed inclusion of new medications like topical CAIs.  Provides directly applicable and germane guidance to clinicians on how best to begin treating a patient who is diagnosed with open angle glaucoma.  First long term study involving a large number of patients. the CIGTS randomization unit was patient and not the eye.CIGTS Study: Strengths  Unlike other trials like AGIS.  Effective randomization to provide 90% power  Thorough assessment of the patient’s health related quality of life. .  To assess treatment effects in patients rather than eyes.

 Baseline demographics do not mention the no of patients with cataract. .CIGTS: Weakness  Laser trabeculoplasty as initial therapy not studied in CIGTS.  Cost accounting of the two forms of therapy not studied.

both initial medication or surgery were equally effective in minimizing visual field loss. This can be attributed to an aggressive IOP – lowering treatment approach.CIGTS: Conclusion Over the period to follow up to date. .

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