Laser Intervention in Early Age-Related Macular Degeneration Study

LEAD is a patient and assessor masked, multi-centre randomized controlled exploratory medical device clinical investigation of 240 participants (1:1 active to shame laser procedure) designed to assess the effectiveness of nanosecond laser treatment of patients with early high-risk AMD.

No less than 240 participants will be randomized into either active laser treatment or sham laser procedure groups at a ratio of 1:1. Patient eligibility based on ocular inclusion criteria will be evaluated using measures of vision, fundus photography, OCT imaging, and macular integrity (MAIA) performed during the qualifying period. Fundus images and MAIA results will be sent to a coordinating centre where these will be reviewed to confirm eligibility based on lesion attributes and the criteria specified in the protocol. Following confirmation of eligibility by the coordinating centre, participants whom satisfy all the inclusion and exclusion criteria can be randomized. Allocation to treatment group will be stratified by smoking status. All participants will receive either active laser treatment or sham laser procedure at the treatment visit and be assessed for retreatment on a semi-annual basis. All participants will be contacted by telephone at 1 week and present for clinical examination visits at 1, 6, 12, 18, 24, 30 and 36 months.

Inclusion criteria

• Males or females from 50 to 95 years of age at the time of consent
• Best corrected visual acuity (BCVA) of 6/12 (20/40) or better in each eye.
• Bilateral high-risk early AMD: At least one druse ≥125um within an inner macular zone (a circle with a radius of 1500 microns centred on the fovea) with or without pigment.
• A MAIA static threshold sensitivity less than 25 dB at any point, within a customized grid, as measured using a Macular Integrity Assessment (MAIA) device), at the same location of the one eye on two separate occasions.
• Pupil dilation of a least 5 mm in each eye
• Fundus photographs, optical coherence tomography (OCT) and fundus autofluorescence (FAF) images of adequate quality as assessed by the LEAD Image Reading Centre.
• Ability and willingness to consent, and be randomized, to the 2RT active or sham laser treatment, and all qualification and follow-up phases of the study.

Exclusion criteria

• Any evidence of definite geographic atrophy within the macula (a circle with a radius of 3000 microns centred on the fovea).
• Any black (hypofluorescent) area of FAF consistent with GA (roughly round or oval shape, sharp margins), and corroborated on colour photography as a patch of hypopigmentation.
• Any evidence of 'preclinical atrophy' as determined on OCT: loss of the outer retina (RPE and photoreceptors on the cube scan (Spectralis OCT) (49 horizontal B scans, 120 µm apart over a 20 x 20 degree scan). This covers approximately 6 x 6 mm in an emmetropic eye (N.B., peri-papillary atrophy (PPA) further than 1500 microns from the fovea is allowed).
• Current CNV, or past evidence of CNV in either eye.
• Any other experimental treatment for AMD, excluding dietary supplements, received in the past 12 months or thought likely to chronically change the course of the participant's retinal disease.
• Any OCT showing evidence of intraretinal fluid, or subretinal fluid for which CNV cannot be excluded as a cause.
• A subfoveal pigment epithelial detachment/drusenoid detachment greater than 1000 microns in diameter.
• Other macular disease with subretinal deposits not typical of AMD, e.g., Malattia Leventinese, Sorsby fundus dystrophy, Alports syndrome
• Ocular disease in either eye, other than AMD, which significantly compromises the ability to treat or visualize the fundus or would compromise the ability to assess any effect following laser application including;
• Known allergic hypersensitivity to fluorescein.
• Previous retinal or other ocular surgical procedures, the effects of which may now or in the future complicate assessment of the progression of AMD.
• Requirement for any systemic or ocular medication known to be toxic to the retina, such as: Deferoxamine, Chloroquine/Hydroxychloroquine (Plaquenil), Chlorpromazine, Phenothiazines, Ethambutol
• Any serious systemic disease that will preclude a 3 year survival and regular attendance for follow up.
• Sensitivity to contact lens application.
• Any condition that would make adherence to the examination schedule for 3 years difficult or unlikely.
• Any history of prior laser surgery to the retina.
• Intraocular pressures of 26mm Hg or higher or if there is some reason to believe the participant may have glaucoma
• Significant cataract: Nuclear cataract grade 2 or 3, cortical cataract Grade 2 or 3 or posterior subcapsular cataract Grade 2 or 3, by Simplified Cataract Grading System (WHO Cataract Grading Group).