Visual Field Outcomes for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).

PURPOSE: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) showed that acetazolamide provided a modest, significant improvement in mean deviation (MD). Here, we further analyze visual field changes over the 6-month study period. METHODS: Of 165 subjects with mild visual loss in the IIHTT, 125 had perimetry at baseline and 6 months. We evaluated pointwise linear regression of visual sensitivity versus time to classify test locations in the worst MD (study) eye as improving or not; pointwise changes from baseline to month 6 in decibels; and clinical consensus of change from baseline to 6 months. RESULTS: The average study eye had 36 of 52 test locations with improving sensitivity over 6 months using pointwise linear regression, but differences between the acetazolamide and placebo groups were not significant. Pointwise results mostly improved in both treatment groups with the magnitude of the mean change within groups greatest and statistically significant around the blind spot and the nasal area, especially in the acetazolamide group. The consensus classification of visual field change from baseline to 6 months in the study eye yielded percentages (acetazolamide, placebo) of 7.2% and 17.5% worse, 35.1% and 31.7% with no change, and 56.1% and 50.8% improved; group differences were not statistically significant. CONCLUSIONS: In the IIHTT, compared to the placebo group, the acetazolamide group had a significant pointwise improvement in visual field function, particularly in the nasal and pericecal areas; the latter is likely due to reduction in blind spot size related to improvement in papilledema. (ClinicalTrials.gov number, NCT01003639.).

Factors Affecting Visual Field Outcomes in the Idiopathic Intracranial Hypertension Treatment Trial.

BACKGROUND: To determine the prevalence of visual field (VF) performance failures (PF) and treatment failures (TFs), and identify factors associated with PFs in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: A total of 165 participants from 38 sites with idiopathic intracranial hypertension (IIH) and mild visual loss were randomized to either acetazolamide-plus diet or placebo-plus diet. The IIHTT Visual Field Reading Center evaluated 2950 Swedish Interactive Threshold Algorithm Standard 24-2 VFs from the enrolled participants. A TF was defined when the participant's VF mean deviation (MD) worsened ≥2 to 3 dB from the average baseline MD (range of -2 to -7 dB) with a second retest confirming the visual deterioration. A PF was determined when the participant's: 1) VF results met TF criteria but were not confirmed on retest, 2) deterioration was confirmed on retest but the IIHTT Adjudication Committee concluded a TF was clinically unlikely. RESULTS: TF was detected in 7/165 (4%) of the participants and PF was detected in 35/165 (21%) of the participants on at least 1 examination. Four of the 35 PFs were adjudicated for TF, however based on clinical review by the adjudication committee and a third retest, they were judged as PFs. Of the 2,950 total IIHTT VF examinations, 2.7% met PF criteria. CONCLUSIONS: PF was confirmed in 21% of subjects and in 2.7% of the total number of VF examinations and was reversible on repeat testing. We recommend retesting when perimetric worsening occurs in otherwise clinically stable or improving IIH patients.

Baseline visual field findings in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).

PURPOSE: To characterize visual field (VF) loss at the baseline visit and to evaluate VF quality control (QC) procedures in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: The Visual Field Reading Center (VFRC) evaluated 660 baseline VFs (1320 hemifields) from 165 enrolled patients. Three readers independently classified each superior and inferior hemifield and identified any abnormalities. A subset (20%) of the hemifields was reread to evaluate within- and between-reader agreements. The QC system addressed test parameters, patient data, and shipment errors. RESULTS: The majority (60%) of the baseline hemifields consisted of localized nerve fiber bundle-type VF loss. Approximately one-third (31.5%) of all the classifications consisted of partial arcuate defects combined with an enlarged blind spot, making this the most common type of hemifield classification. Inferior hemifield loss was greater than superior loss for both study and nonstudy eyes. Reader agreements were >90% for both inferior and superior hemifields for two out of three readers. Test-retest reliability agreement for individual readers was 95% for both hemifields. There were few QC errors with only 5.48 error points per 100-point VF. CONCLUSIONS: The most common type of IIHTT baseline hemifield abnormality was a localized nerve fiber bundle-like defect. Localized inferior hemifield loss was more common than superior hemifield loss. Quality control and within- and between-reader agreement were excellent for the IIHTT (ClinicalTrials.gov number, NCT01003639).

Baseline retinal nerve fiber layer thickness and macular volume quantified by OCT in the North American phase 3 fingolimod trial for relapsing-remitting multiple sclerosis.

BACKGROUND: Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis. METHODS: The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as "reduced" or "not reduced" for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed "abnormal" if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation. RESULTS: The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning. CONCLUSION: RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS.

Stratus OCT Quality Control in Two Multi-Centre Multiple Sclerosis Clinical Trials.

The University of California (UC) Davis Reading Center evaluated 19,961 scans from 981 subjects in two multiple sclerosis therapeutic trials with the aim of determining the influence of optical coherence tomography quality control procedures on error rates. There was no optical coherence tomography technician certification in Trial 1, and technicians had very limited monitoring and feedback during the trial in view of the fact that data were received retrospectively. However, technicians were certified in Trial 2 and submitted data in accordance with the protocol. Trial 2 scans had higher signal strengths, fewer errors, and more useable data than the scans in Trial 1. Thus, certified technicians and prompt transmission of data for ongoing quality control monitoring provided higher quality data in multiple sclerosis trials.

Visual field profile of optic neuritis: a final follow-up report from the optic neuritis treatment trial from baseline through 15 years.

OBJECTIVE: To evaluate visual field abnormalities after an episode of optic neuritis among participants in the Optic Neuritis Treatment Trial. METHODS: Three readers independently evaluated 10 443 visual fields from 454 patients and classified visual field abnormalities into 21 different monocular categories representing 3 general types of visual loss: diffuse, localized, and artifactual. Classification frequency was determined and reader agreement was evaluated. The association of visual field abnormality classifications with mean deviation, pattern standard deviation, visual acuity, and foveal threshold was assessed. RESULTS: At baseline, diffuse loss accounted for 66.2% of the abnormalities in the affected eyes but only 6.2% of the abnormalities in the fellow eyes. During years 1 through 15, the affected and fellow eyes exhibited predominantly localized loss in the nerve fiber bundle region (partial arcuate, paracentral, and arcuate defects). At year 1, 35.7% of the abnormalities in the affected eyes and 34.4% in the fellow eyes consisted of localized defects. At year 15, 39.5% of abnormalities in the affected eyes and 26.3% in the fellow eyes consisted of localized defects. Foveal threshold was highly correlated with visual acuity and contrast sensitivity in the affected eye at baseline (-0.82 vs 0.79, respectively), 6 months (-0.84 vs 0.81), and 1 year (-0.84 vs 0.79). CONCLUSIONS: Diffuse and central loss were more predominant in the affected eye at baseline, and nerve fiber bundle defects (partial arcuate, paracentral, and arcuate) were the most predominant localized abnormalities in both the affected and fellow eyes during the study.

Visual field quality control in the Ocular Hypertension Treatment Study (OHTS).

OBJECTIVE: To report the impact of visual field quality control (QC) procedures on the rates of visual field unreliability, test parameter errors, and visual field defects attributed to testing artifacts in the Ocular Hypertension Treatment Study (OHTS). METHODS: OHTS technicians were certified for perimetry and were required to submit 2 sets of visual fields that met study criteria before testing study participants. The OHTS Visual Field Reading Center (VFRC) evaluated 46,777 visual fields completed by 1618 OHTS participants between February 1994 and December 2003. Visual field QC errors, rates of unreliability, and defects attributed to testing artifacts were assessed. The OHTS QC system addressed 3 areas of clinic performance: (1) test parameter errors, (2) patient data errors, and (3) shipment errors. A visual field was classified as unreliable if any of the reliability indices exceeded the 33% limit. Clinical sites were immediately contacted by the VFRC via fax, e-mail, and/or phone and instructed on how to prevent further testing errors on fields with defects attributed to testing artifacts. MAIN OUTCOME MEASURES: QC errors (test parameter errors) and unreliability rates. RESULTS: A total of 2.4% (1136/ 46,777) of the visual fields were unreliable and 0.23% (107/46,777) had incorrect test parameters. Visual field defects attributed to testing artifacts occurred in approximately 1% (483/46,777) of the visual fields. CONCLUSIONS: Prompt transmission of visual fields to the VFRC for ongoing and intensive QC monitoring and rapid feedback to technicians helps to reduce the frequency of unreliable visual fields and incorrect testing parameters. Visual field defects attributed to testing artifacts were infrequent in the OHTS.

The association between glaucomatous visual fields and optic nerve head features in the Ocular Hypertension Treatment Study.

PURPOSE: To determine the association between change from baseline in the optic nerve head (ONH) and the visual field (VF) during follow-up of ocular hypertension participants in the Ocular Hypertension Treatment Study. DESIGN: Longitudinal randomized clinical trial. PARTICIPANTS: One hundred sixty-eight eyes of 152 ocular hypertensive participants ages 40 to 80 years. METHODS: Cox hazard models were applied to 3232 eyes, which included 81 eyes that reached a study end point by developing a glaucomatous VF (VF end point) and 128 eyes that reached a study end point by developing an optic disc change (optic disc end point). MAIN OUTCOME MEASURES: Primary open-angle glaucoma end point as determined by changes in the VF or optic disc. RESULTS: Forty-one eyes reached an end point by both VF and optic disc criteria; 40 eyes reached only a VF end point, and 87 reached only an optic disc end point. Times to reach isolated disc or field end points were similar. Visual field end points were more likely (P<0.0001) in eyes that showed the following ONH features: an ONH hemorrhage, thinning of the optic disc rim, or enlargement of the horizontal cup-to-disc (C/D) ratio. Optic disc end points were more likely (P<0.0001) in eyes that showed the following VF features: some evidence of a nasal step or a partial arcuate VF defect, or an increase in the pattern standard deviation (PSD). CONCLUSIONS: Both the VF and the optic disc must be monitored with equal diligence, because either may show the first evidence of glaucomatous damage. Changes in the ONH based on stereophotographic observation (rim thinning, hemorrhage, or a slight increase in C/D ratio) and VF changes (evidence of a nasal step/partial arcuate defect or an increase in PSD) suggest that these cases have an increased risk of developing glaucoma. Confirmation of such subtle findings should be sought through repeat testing and correlation with other clinical results.

Normal visual field test results following glaucomatous visual field end points in the Ocular Hypertension Treatment Study.

OBJECTIVE: To compare the occurrence of normal visual field (VF) test results following 2 vs 3 consecutive, abnormal, reliable test results in the Ocular Hypertension Treatment Study. METHODS: The Ocular Hypertension Treatment Study is a prospective, multicenter follow-up study as part of a longitudinal randomized clinical trial. Sixty-four (68 eyes) of 1636 participants developed a VF primary open-angle glaucoma (POAG) end point. We compared the proportion of normal VF test results after a VF POAG end point among eyes whose VF abnormality was confirmed by 2 (n = 9 eyes) vs 3 (n = 59 eyes) consecutive, abnormal, reliable VF test results. RESULTS: The proportion of VF test results that were normal subsequent to a VF POAG end point in eyes whose abnormality was confirmed by 2 consecutive, abnormal, reliable test results was significantly higher (73 [66%] of 110) compared with eyes whose abnormality was confirmed by 3 consecutive, abnormal, reliable test results (46 [12%] of 381) (P = .01). CONCLUSIONS: A VF POAG end point confirmed by 3 consecutive, abnormal, reliable VF test results appears to have greater specificity and stability than either 1 or 2 consecutive, abnormal, reliable VF test results. However, some eyes whose VF POAG end point was confirmed by 3 consecutive, abnormal, reliable test results nonetheless had 1 or more normal test results on follow-up.

Classification of visual field abnormalities in the ocular hypertension treatment study.

OBJECTIVES: (1) To develop a classification system for visual field (VF) abnormalities, (2) to determine interreader and test-retest agreement, and (3) to determine the frequency of various VF defects in the Ocular Hypertension Treatment Study. METHODS: Follow-up VFs are performed every 6 months and are monitored for abnormality, indicated by a glaucoma hemifield test result or a corrected pattern SD outside the normal limits. As of January 1, 2002, 1636 patients had 2509 abnormal VFs. Three readers independently classified each hemifield using a classification system developed at the VF reading center. A subset (50%) of the abnormal VFs was reread to evaluate test-retest reader agreement. A mean deviation was calculated separately for the hemifields as an index to the severity of VF loss. MAIN OUTCOME MEASURES: A 97% interreader hemifield agreement. RESULTS: The average hemifield classification agreement (between any 2 of 3 readers) for 5018 hemifields was 97% and 88% for the 1266 abnormal VFs that were reread (agreement between the first and second classifications). Glaucomatous patterns of loss (partial arcuate, paracentral, and nasal step defects) composed the majority of VF defects. CONCLUSION: The Ocular Hypertension Treatment Study classification system has high reproducibility and provides a possible nomenclature for characterizing VF defects.

Baseline visual field characteristics in the ocular hypertension treatment study.

PURPOSE: The Ocular Hypertension Treatment Study (OHTS) seeks to evaluate the safety and efficacy of topical ocular hypotensive medication in preventing or delaying the onset of visual field loss and/or optic nerve damage in ocular hypertensive subjects at risk for developing primary open-angle glaucoma. This study evaluates the baseline visual field test characteristics (visual field status, reliability properties, etc.) of patients who underwent eligibility visual field testing for entry to the OHTS. DESIGN: Cross-sectional study of baseline data as part of a longitudinal randomized clinical trial. PARTICIPANTS: Two thousand eight hundred nineteen ocular hypertensive individuals, aged 40 to 80 (mean age, 55). METHODS: Subjects underwent at least two Humphrey Field Analyzer Program 30-2 Full Threshold visual field examinations in both eyes for study eligibility. A third examination was performed if a prior test was abnormal, questionable, or unreliable. For final eligibility, two sets of visual field examinations had to meet OHTS criteria for reliability and had to be classified as "normal." All OHTS visual field tests of potential subjects were submitted for eligibility assessment to the OHTS Visual Field Reading Center. MAIN OUTCOME MEASURES: The percentage of visual fields that were normal and reliable according to OHTS criteria. RESULTS: Of the subset of 2304 subjects who completed the eligibility assessments, 1828 (79%) were OHTS-eligible based on visual field test requirements. A third eligibility test was required for 11% of all eyes because of unreliable, questionable, or abnormal test results. With the 33% fixation loss cutoff in the OHTS, 97% of all eligibility visual field examinations were reliable and 3% were unreliable. The most frequent cause (69.5%) of unreliability was excessive fixation losses. CONCLUSIONS: Permitting one repeat test after an abnormal or unreliable test allowed an extra 560 patients to be "eligible" for the study based on visual field tests. A clinical screening review of otherwise normal and reliable tests was not restrictive. The adoption of a 33% fixation loss cutoff significantly reduced the number of required retests and prevented study rejection of 89 patients.