Purpose: The purpose of this study is (1) to determine baseline characteristics and natural history of immature full-thickness macular holes, (2) to describe progression and resolution, and (3) to present new aspects of pathogenesis of idiopathic macular hole. Methods: The authors analyzed 41 eyes with stage 2 macular holes (37 patients) in a multicentered prospective randomized trial; 19 eyes were randomized to observation (versus surgery) and had more than 12 months of follow-up, allowing determination of the natural course. Baseline and subsequent examinations included best-refracted visual acuity (Early Treatment of Diabetic Retinopathy Study, potential acuity meter, Pelli-Robson contrast sensitivity, and Bailey-Lovie reading vision), of clinical examinations, photography, and fluorescein angiography. Result: Mean Snellen visual acuity was 20/66 at baseline. Centric holes usually had a small break (201 μm average mean diameter) with a dark yellow ring and without significant retinal elevation. Eccentric holes had a high maximum/minimum diameter ratio (mean, 1.88 ± 0.7) and an incomplete cuff of subretinal fluid or yellow ring. Posterior vitreous detachment prevalence was 32% (8/25) in the centric hole group and 0% (0/16) in the eccentric hole group (P < 0.05). For the 19 eyes with 12 months of follow-up, progression rate to stage 3 (or 4) was 74% (n = 14). The diameter of the stage 2 holes increased significantly between baseline and 12 months (P < 0.001). Progression rate to stage 3 was 100% (8/8) in the eyes with pericentral hyperfluorescence (PCH) and 55% (6/11) in eyes without PCH (P < 0.05). Enlargement occurred in 100% of eccentric holes and 60% of centric holes (P = 0.09). Different progression patterns in eccentric and centric holes suggest different mechanisms of pathogenesis. Conclusion: Eccentric and centric stage 2 macular holes may have a different pathogenesis. Most stage 2 macular holes, especially with PCH (P < 0.05) or eccentric holes, progressed to stage 3 or 4. In addition to purely tangential traction, some component of obliquely oriented anteroposterior vitreous traction component may be important for pathogenesis of senile macular holes, particularly eccentric stage 2 macular holes.
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