A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111

BCVA was assessed for both eyes using the ETDRS visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

IOP, the fluid pressure inside the eye was measured and reported in millimeters mercury (mmHg).

Slit lamp examinations of study eyes included examination of Cornea, Conjunctiva, Iris, Lens, and Anterior Segment.

Dilated Ophthalmoscopy examination of study eyes included examination of Vitreous, Macula, Peripheral retina, Choroid, and Optic nerve.

The following lens opacity grades are reported for categories 1-4: Nuclear Opalescence grade, Nuclear Color grade, Cortical Cataract grade, and Posterior Cataract grade. Opacification severity is graded on a decimal scale, scores can range from 0.1 (no opacity) to 6.9 (maximum opacity) for the Nuclear Opalescence and Nuclear Color grades; and scores can range from 0.1 (lens clear) to 5.9 (lens unclear) for the Cortical and Posterior Cataract grades. Category 1 includes values 1, 1.0 and 0.x, Category 2 includes values 2, 2.0 and 1.x, Category 3 includes values 3, 3.0 and 2.x, and Category 4 includes values 4, 4.0, 3.x and any values above 4. For each opacification type the higher grading scores indicate greater severity.

SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil.

SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil.

SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil.

SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil.

SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil.

SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil.

Fundus AF was used to assess the total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy.

Fundus AF was used to assess the square root of total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy.

Fundus AF was used to assess the distance from foveal center to nearest border of preserved AF.

Number of participants with RPE hyperplasia are reported for severity grades: mild, moderate, severe.

Number of participants with retinal arteriolar narrowing are reported for severity grades: mild, moderate, severe.

Number of participants with retinal vessel sheathing are reported for severity grades: mild, moderate, severe.

Number of participants with optic atrophy/pallor are reported for severity grades: mild, moderate, severe.

Number of participants with optic disc swelling are reported for severity grades: mild, moderate, severe.

Microperimetry was conducted to assess retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity.

Microperimetry was conducted to assess bivariate contour ellipse area 63%.

Microperimetry was conducted to assess bivariate contour ellipse area 95%.

Microperimetry was conducted to assess fixation losses (in percentage) which samples the optic nerve blind spot for positive responses.

An AE is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug/surgical procedure, whether or not related to the investigational product or with the surgical procedure. TEAEs are defined as AEs starting on or after the day of the first surgery.

Tears (for both eyes- oculus dexter [OD] and oculus sinister [OS]), blood, urine and saliva samples were collected and tested using an appropriate assay for evidence of vector shedding. Participants with positive result for vector shredding post treatment are reported.

Participants with antibodies to the REP-1 transgenic product are reported.

Change from baseline in Systolic and diastolic blood pressures (BP) (millimeters of mercury [mmHg]) were reported.

Change from baseline in pulse rate (beats per minute) were reported.

BCVA was assessed for both eyes using the ETDRS VA chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved.

Fundus AF was used to assess change in total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. Here negative values indicate decline in total area of preserved autofluoroscence.

Fundus AF was used to assess change in square root of total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy. Here negative values indicate decline in total area of preserved autofluoroscence.

Fundus Autofluoroscence was used to assess change in distance from foveal center to nearest border of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence.

SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in foveal subfield thickness.

SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in total macular volume.

SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in central horizontal ellipsoid width.

SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in central ellipsoid area.

SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in square root of central ellipsoid area.

SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in choroidal thickness.

Microperimetry was conducted to assess change in retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity. A negative change from baseline indicates decline in retinal sensitivity.

Microperimetry was conducted to assess change in bivariate contour ellipse area 63%. A negative change from baseline indicates decline in bivariate contour ellipse area 63%.

Microperimetry was conducted to assess change in bivariate contour ellipse area 95%. A negative change from baseline indicates decline in bivariate contour ellipse area 95%.

Microperimetry was conducted to assess change in fixation losses (in percentage) which samples the optic nerve blind spot for positive responses. A negative change from baseline indicates decline in fixation losses.