Clinical Trials

Subject Inclusion Criteria: 

• Diagnosis of IIH by modified Dandy criteria:
  • Signs and symptoms of increased intracranial pressure;
  • Absence of localizing findings on neurologic examination;
  • Absence of deformity, displacement, or obstruction of the ventricular system and otherwise normal neurodiagnostic studies, except for evidence of increased CSF pressure (> 200 mm water). Abnormal neuroimaging except for empty sella turcica, optic nerve sheath with filled out CSF spaces, and smooth-walled non flow-related venous sinus stenosis or collapse, should lead to another diagnosis;
  • Awake and alert;
  • No other cause of increased intracranial pressure present.
• Age 18 to < 61 years at time of diagnosis (time of diagnosis is the time at which the patient meets the modified Dandy criteria, usually after the lumbar puncture results are reviewed).
• Age 18 to < 64 years at time of consent.
• Presence of bilateral papilledema.
• Lumbar puncture within 6 weeks of screening visit or completed as part of screening: Opening CSF pressure >250 mmH2O or 200 to 250 mmH2O, with at least one of the following:
  • Pulse synchronous tinnitus;
  • Cranial nerve VI palsy;
  • Echography for drusen negative and no other disc anomalies mimicking disc edema present;
  • MRV with lateral sinus collapse/stenosis, partially empty sella turcica on coronal or sagittal views of MRI, and optic nerve sheaths with filled out CSF spaces next to the globe on T2 weighted axial MRI scans
• If the patient was treated with intracranial pressure lowering agents (e.g., acetazolamide) prior to obtaining a lumbar puncture, the agent(s) must be discontinued for at least 24 hours prior to performing the diagnostic lumbar puncture. 
• At least one eye meeting all eligible eye inclusion criteria and no exclusion criteria.
• Able to provide informed consent.
• Investigator believes the participant is a good candidate for the study, including the probability of returning for follow-up.

Subject Exclusion Criteria: 

• Treatment of IIH within the past 3 months with either (1) the maximally tolerated dosage of acetazolamide for at least one week or (2) more than one month of acetazolamide with a cumulative dosage of more than 30 grams.
  • ‘Maximally-tolerated dose’ is defined as dosage was reached where dosage could not beincreased further either because of side effects or because a daily total dosage of 4 grams  per day was reached.
  • If individual discontinued acetazolamide in the past due to side effects, individual is only eligible if investigator believes that the individual is likely to tolerate acetazolamide, as it will be prescribed in the study.
• Treatment of IIH within the past 3 months with either (1) the maximally tolerated dosage  of methazolamide for at least one week or (2) more than one month of methazolamide  with a cumulative dosage of more than 3 grams.
  • ‘Maximally-tolerated dose’ is defined as dosage was reached where dosage could not be increased further either because of side effects or because a daily total dosage of 400 mg  per day was reached.
• Treatment with topiramate within two months and average cumulative dosage for the  preceding month of more than 700 mg per week.
• Previous surgery for IIH, including ONSF, CSF shunting, subtemporal decompression, or venous sinus stenting; gastric surgery for obesity is allowed.
• Abnormalities on neurologic examination except for papilledema and its related visual  loss or cranial nerve VI or VII paresis; if other abnormalities are present, the patient will need to be discussed with the Study Director for study entry.
• Abnormal CT or MRI scan (intracranial mass, hydrocephalus, dural sinus thrombus, orarteriovenous malformation) other than findings known to occur with increasedintracranial pressure. Abnormalities on MRI that are not known to cause increased intracranial pressure are acceptable.
• Abnormal CSF contents: increased cells: > 8 cells; elevated protein: > 45 mg%; low glucose: < 30 mg% (If the lumbar puncture produces a cell count compatible with a traumatic needle insertion, the patient does not need to be excluded if the CSF WBC  after correction is 8 cells/mm3 or less - see MOP for calculation. If > 8 cells or > 45mg% in CSF protein are documented in the CSF or calculated after conversion from a traumatic lumbar puncture, the patient can be discussed with the Study Director for  possible inclusion).
• Abnormal blood work-up indicating a medical or systemic condition associated withraised intracranial pressure.
• Diabetes mellitus with diabetic retinopathy.
• Ingestion of a drug or substance, or presence of a disorder, that has been associated 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).
• Laboratory test results showing severe anemia, leukopenia or thrombocytopenia, renal failure, or hepatic disease, based on the Site Investigator’s judgment.
• Other condition requiring oral, I.V. or injectable steroids (nasal, inhaled, or topical  steroids are allowed since the systemic effects are small).
• Presence of a medical condition that would contraindicate use of acetazolamide or furosemide or significantly increase surgical risk.
• Pregnancy or unwillingness for a subject of childbearing potential to use contraception  during the first 6 months of the study.
• Women of childbearing potential must use an acceptable form of birth control during the first 6 months of the study. Acceptable forms include oral contraceptives, transdermal contraceptives, diaphragm, intrauterine devices, condoms with spermicide, documented surgical sterilization of either the subject or their partner, or abstinence. 
• Presence of a physical, mental, or social condition likely to affect follow-up (drug  addiction, terminal illness, no telephone, homeless).
• Anticipation of a move from the site area within six months and unwillingness to return  for follow-up at a SIGHT study site.
• Allergy to pupil dilating drops or narrow angles precluding safe dilation.
• Presence of a condition that contraindicates general anesthesia.
• Participation in an investigational trial within 30 days of enrollment that involved  treatment with any systemic drug therapy or therapy that affects the eligible eye(s).

Eye-Level Eligibility Criteria:

• To be eligible, an individual must have at least one eye meeting the following inclusion criteria and none of the exclusion criteria.
• If both eyes meet eligibility criteria, then both will be included in the primary outcome analysis.

Eye Level Inclusion Criteria:

• Visual field loss meeting the following criteria based on two full threshold 24-2 size V tests reviewed by the VFRC:
  • PMD from -6 dB to -27 dB;
  • Reproducible visual loss present on automated perimetry including no more than 15% false positives.
• Visual acuity better than 20/200 (39 or more letters correct).

Eye Level Exclusion Criteria:

• Intraocular pressure currently > 28 mm Hg or > 30 mm Hg at any time in the past.
• Refractive error of more than -6.00 or more than +6.00 sphere or more than 3.00 cylinder with the following exceptions:
  • Eyes with more than 6.00 D of myopia but less than 8.00 D of myopia are eligible if:
    • there are no abnormalities on ophthalmoscopy or fundus photos related to myopia that are associated with visual loss (such as staphyloma, retinal thinning in the posterior pole, or more than mild optic disc tilt); and 
    • the individual will wear a contact lens for all perimetry examinations with the appropriate correction.
  • Eyes with more than 6.00 D of hyperopia but less than 8.00 D of hyperopia areeligible if:
    • There is an unambiguous characteristic halo of peripapillary edema as opposed to features of a small crowded disc or other hyperopic change related to visual loss determined by the Site Investigator or the PRC Director (or his designate); and
    • The individual will wear a contact lens for all perimetry examinations with the appropriate correction (which can be corrected for perimetry or the patient’s own contact lens with over correction by lens at the perimeter).
      • Note: Refractive error exclusion and exceptions refer to sphere not spherical equivalent, with cylinder expressed in plus format.
    • Other disorders causing visual loss except for refractive error and amblyopia, includingcells in the vitreous or iritis;
    • Large optic disc drusen on exam or in previous history (small drusen of the disc can occur with longstanding papilledema and are allowed if not so numerous that investigator determines they are contributing to vision loss).