Surgical Idiopathic Intracranial Hypertension Treatment Trial

Inclusion Criteria:

• Subject Eligibility Criteria Inclusion Criteria

1. Diagnosis of IIH by modified Dandy criteria (Table 4)
2. Age 18 to <64 years at time of consent
3. Age 18 to <61 years at time of diagnosis (time of diagnosis is the time at whichthe patient meets the modified Dandy criteria, usually after the lumbar punctureresults are reviewed)
4. Presence of bilateral papilledema
5. Lumbar puncture within 6 weeks of screening visit or completed as part ofscreening: Opening CSF pressure >250 mmH2O or 200 to 250 mmH2O with at least oneof the following:

• Pulse synchronous tinnitus
• Cranial nerve VI palsy
• Echography for disc drusen negative and no other disc anomalies mimickingdisc edema present
• Magnetic Resonance Venography (MRV) with lateral sinus collapse/stenosis,partially empty sella turcica on coronal or sagittal views of MRI, and opticnerve sheaths with filled out CSF spaces next to the globe on T2 weightedaxial MRI scans If the patient was treated with intracranial pressurelowering agents (e.g., acetazolamide) prior to obtaining a lumbar puncture,the agent(s) must be discontinued for at least 24 hours prior to performingthe diagnostic lumbar puncture.

6. At least one eye meeting all eligible eye inclusion criteria and no exclusioncriteria.
7. Able to provide informed consent
8. Investigator believes participant is a good candidate for the study, includingthe probability of returning for follow-up.

• Eye-Level Eligibility Criteria Subjects must have at least one eye meeting all of theinclusion criteria and none of the exclusion criteria. If both eyes meet eligibility criteria at the baseline examination, both will be includedin the primary outcome analysis. Inclusion

1. Visual field loss meeting the following criteria based on two full threshold 24-2 sizeV tests reviewed by the VFRC:

• PMD from -6 decibel (dB) to -27 dB
• Reproducible visual loss present on automated perimetry including no more than 15% false positive response

2. Visual acuity better than 20/200 (39 or more letters correct)

Exclusion Criteria:

• Subject Exclusion Criteria Exclusion Criteria

1. Treatment of IIH within the past 3 months with either (1) the maximally tolerateddosage of acetazolamide for at least one week or (2) more than one month ofacetazolamide with a cumulative dosage of more than 45 grams 'Maximally-tolerateddose' is defined as dosage was reached where dosage could not be increasedfurther either because of side effects or because a daily total dosage of 4 gramsper day was reached. If individual discontinued acetazolamide in the past due to side effects,individual is only eligible if investigator believes that the individual islikely to tolerate acetazolamide, as it will be prescribed in the study.
2. Treatment of IIH within the past 3 months with either (1) the maximally tolerateddosage of methazolamide for at least one week or (2) more than one month ofmethazolamide with a cumulative dosage of more than 4.5 grams 'Maximally-tolerated dose' is defined as dosage was reached where dosage couldnot be increased further either because of side effects or because a daily totaldosage of 400 mg per day was reached.
3. Treatment with topiramate within two months and average cumulative dosage for thepreceding month of more than 700 mg per week
4. Previous surgery for IIH, including ONSF, CSF shunting, subtemporaldecompression, or venous sinus stenting; gastric surgery for obesity is allowed
5. Abnormalities on neurologic examination except for papilledema and its relatedvisual loss or cranial nerve VI to VII paresis; if other abnormalities arepresent, the patient will need to be discussed with the Study Director (SD) forstudy entry.
6. Abnormal CT or MRI scan (intracranial mass, hydrocephalus, dural sinus thrombus,or arteriovenous malformation) other than findings known to occur with increasedintracranial pressure. Abnormalities on MRI that are not known to cause increasedintracranial pressure are acceptable.
7. Abnormal CSF contents: increased cells: > 8 cells; elevated protein: > 45 mg%;low glucose: < 30 mg% (If the lumbar puncture produces a cell count compatiblewith a traumatic needle insertion, the patient does not need to be excluded ifthe CSF white blood cell count (WBC) after correction is 8 cells/mm3 or less -see Manual of Procedures (MOP) for calculation. If > 8 cells or > 45mg% in CSFprotein are documented in the CSF or calculated after conversion from a traumaticlumbar puncture, the patient can be discussed with the Study Director forpossible inclusion.)
8. Abnormal blood work-up indicating a medical or systemic condition associated withraised intracranial pressure
9. Diabetes mellitus with diabetic retinopathy
10. Ingestion of a drug or substance, or presence of a disorder, that has beenassociated with increased intracranial pressure within 2 months of diagnosis,such as lithium, vitamin A related products (e.g., Retin-A), or various cyclines (see MOP for conditions and drugs)
11. Laboratory test results showing severe anemia, leukopenia or thrombocytopenia,renal failure, or hepatic disease, based on the Site Investigator's judgment
12. Other condition requiring continued use of oral, I.V. or injectable steroids (nasal, inhaled, or topical steroids are allowed since the systemic effects aresmall). Patients with a condition that resulted in recent or current use ofsteroids but may be safely tapered off will be handled on a case-by-case basisafter discussion with Study Director/co-Director. See Manual of Procedures (MOP)for details.
13. Presence of a medical condition that would contraindicate use of acetazolamide orfurosemide or significantly increase surgical risk
14. Pregnancy or unwillingness for a subject of childbearing potential to usecontraception during the first 6 months of the study Women of childbearingpotential must use an acceptable form of birth control during the first 6 monthsof the study. Acceptable forms include oral contraceptives, transdermalcontraceptives, diaphragm, intrauterine devices (IUDs), condoms with spermicide,documented surgical sterilization of either the subject or their partner, orabstinence.
15. Presence of a physical, mental, or social condition likely to affect follow-up (drug addiction, terminal illness, no telephone, homeless)
16. Anticipation of a move from the site area within six months and unwillingness toreturn for follow-up at a SIGHT study site
17. Allergy to pupil dilating drops or narrow angles precluding safe dilation
18. Presence of a condition that contraindicates general anesthesia
19. Participation in an investigational trial within 30 days of enrollment thatinvolved treatment with any systemic drug therapy or therapy that affects theeligible eye(s)

• Eye Level Exclusion Criteria Exclusion

1. Intraocular pressure currently >28 mm Hg or >30 mm Hg at any time in the past
2. Refractive error of more than -6.00 or more than +6.00 sphere or more than 3.00cylinder with the following exceptions:

• Eyes with more than 6.00 D of myopia but less than 8.00 D of myopia areeligible if: 1) there are no abnormalities on ophthalmoscopy related tomyopia that are associated with visual loss (such as staphyloma, retinalthinning in the posterior pole, or more than mild optic disc tilt), and 2)the individual will wear a contact lens for all perimetry examinations withthe appropriate correction.
• Eyes with more than 6.00 D of hyperopia but less than 8.00 D of hyperopiaare eligible if: 1) there is an unambiguous characteristic halo ofperipapillary edema as opposed to features of a small crowded disc or otherhyperopic change related to visual loss determined by the Site Investigatoror the Photographic Reading Center (PRC) Director (or his designate), and 2)the individual will wear a contact lens for all perimetry examinations withthe appropriate correction (which can be corrected for perimetry or with thepatient's own contact lens with over correction by lens at the perimeter). Note: Refractive error exclusion and exceptions refer to sphere not sphericalequivalent, with cylinder expressed in plus format.

3. Other disorders causing visual loss except for refractive error and amblyopia,including cells in the vitreous or iritis
4. Large optic disc drusen on exam or known in previous history (small drusen of thedisc can occur with longstanding papilledema and are allowed if not so numerousthat investigator determines they are contributing to vision loss)