Both primary open-angle and normal-tension glaucoma belong to an identical spectrum of diseases. Clinical presentations of primary open-angle or high-tension glaucoma (POAG) and normal-tension glaucoma (NTG) were studied in an attempt to determine prognostic, clinical factors and define the appropriate management. Clinical data obtained from 826 primary open-angle and normal-tension glaucoma patients were analyzed. In addition, the results of laboratory studies, including the immunological assay of heat shock protein (hsp) and gene analyses which were undertaken to identify risk factors at the molecular level, are discussed. 1. The identified prognostic factors were disk hemorrhage, peripapillary chorioretinal atrophy (PPA), maximum intraocular pressure (IOP), the recovery rate of skin temperature after exposure to cold, family history of glaucoma, systemic systolic channel blood pressure, and oral administration of Ca(2+)-channel antagonists. 2. Disk hemorrhage was observed in 30.5% of NTG patients and 15.4% of POAG patients. Cumulative probability of hemorrhagic events was 16.9% in POAG and 38.4% in NTG patients at the end of a 14.8-year follow-up. 3. The hazard ratio of disk hemorrhage decreased with the increase of IOP(26%/5 mmHg) and was 1.46 times higher in females than in males. Disk hemorrhage was closely associated with PPA: PPA becomes greater in association with the progression of glaucomatous optic neuropathy in both POAG and NTG. No such correlation was noted in primary angle-closure glaucoma. 4. Color Doppler imaging analyses and the hourly determination of ocular perfusion pressure (OPP) indicated a difference in retrobulbar hemodynamics between OPP-mean deviation concordant and OPP-mean deviation discordant patients: a circulatory disturbance causally unrelated to OPP seems to be involved in the OPP-mean deviation discordant patients. 5. The oral administration of Ca(2+)-channel antagonists was shown to favorably influence retrobulbar hemodynamics in NTG patients. 6. Serum antigen titer to hsps(hsp 27, alpha B crystallin, human & bacterial hsp 60) was higher in both POAG and NTG patients than in normal subjects. None of the hsp-antigens was correlated to any morphometric parameters of the optic disk or any global indices of the visual field. 7. Myocilin mutation was noted in only 0.5% of POAG patients and 2.37% of NTG patients. The very low rate of occurrence precludes the value of mutation of the gene as a prognostic factor in open-angle glaucoma(OAG). 8. IOP reduction achieved by mitomycin-C trabeculectomy is effective in maintaining visual function in OAG eyes. 9. Brovincamine fumarate is effective in inhibiting the progression of glaucomatous field loss in NTG.