Fluorescein filling defects of the optic nerve head in normal tension glaucoma, primary open-angle glaucoma, ocular hypertension and healthy controls

BACKGROUND: To evaluate fluorescein filling defects of the optic nerve head in normal tension glaucoma (NTG), primary open-angle glaucoma (POAG), ocular hypertension (OHT) and controls. METHODS: Forty patients with NTG (mean age 55 +/- 10 years), 40 patients with POAG (mean age 55 +/- 11 years), 40 patients with OHT (mean age 53 +/- 13 years), and 40 age-matched controls (mean age 54 +/- 11 years) were included in a prospective study. Video fluorescein angiograms were performed by means of a scanning laser ophthalmoscope. The extent of absolute filling defects of the optic nerve head was assessed (as a percentage of the disc area) using digital image analysis. Visual fields were tested by automatic static perimetry (Humphrey Field Analyzer, programme 24-2). RESULTS: Absolute filling defects were significantly larger in patients with NTG (12.2 +/- 15.5%) and POAG (12.9 +/- 13.1%) compared to patients with OHT (1.2 +/- 3.6%) and healthy controls (0.1 +/- 0.5%) (p < 0.0001). The area under the receiver operating characteristic (ROC) curve was 0.806 for NTG vs healthy controls, and 0.812 for POAG vs OHT. Absolute filling defects are significantly correlated to the global indices mean deviation (r = -0.63, p < 0.0001), pattern standard deviation (r = 0.61, p < 0.0001), and corrected pattern standard deviation (r = 0.62, p < 0.0001) and significantly correlated to horizontal (r = 0.50, p < 0.0001) and vertical (r = 0.53, p < 0.0001) cup-to-disc-ratios. CONCLUSIONS: Fluorescein filling defects of the optic disc representing capillary dropout are present in NTG and POAG. The extent of these filling defects is correlated to visual field loss and morphological damage. Fluorescein angiography may be useful in the diagnosis and management of NTG and POAG.     

Fluorescein angiography of the optic disc in ocular hypertension and glaucoma (author's transl)]

A fluorescein angiography of the optic disc has been performed on 62 eyes in 41 patients suffering from ocular hypertension or glaucoma. The angiogram was abnormal in 32 eyes. 11 eyes showed an absolute hypofluorescence involving the whole optic disc. 15 eyes showed an absolute hypofluorescence limited to a part of the cup and the rim. 6 eyes showed a late hyperfluorescence of the fundus of the cup. Total hypofluorescence throughout all phases of fluorescein angiogram corresponds to filling defects. Absolute hypofluorescence involving the whole optic disc is associated with visual field loss in all cases. Absolute hypofluorescence involving only an area of the optic disc is associated with a normal visual field in a few cases. It is postulated that the limited filling defects without visual fields defects may be an indication of impending loss of the visual field. Therefore fluorescein angiography could be helpful in clinical assessment of visual prognosis of chronic ocular hypertension and glaucoma. Nevertheless wider experience and followup are necessary to confirm the value of the method.     

Nerve fiber layer and optic disc fluorescein defects in glaucoma and ocular hypertension

Photographs of the optic discs and fluorescein angiograms of 31 patients with open-angle glaucoma and 43 patients with ocular hypertension were evaluated for nerve fiber layer (NFL) defects and absolute fluorescein filling defects. All of the glaucomatous eyes showed both defects. Of the 43 ocular hypertensive eyes, in which both NFL and absolute fluorescein filling defects were evaluated, 9% had only NFL defects, 19% had only fluorescein filling defects, 14% had both defects, and 58% had neither defect. The percent area of fluorescein defect in the optic disc increased with severity of NFL defect in glaucoma and ocular hypertension. This study confirms the relationship of fluorescein filling defects and NFL defects to glaucomatous abnormalities and thus the association between vascular damage to the optic nerve and axon loss in glaucoma. The earliest objective evidence of glaucomatous damage can be detected with a combination of NFL evaluation and optic disc fluorescein angiography.     

Measurement of fluorescein angiograms of the optic disc and retina using computerized image analysis

Computerized image analysis was used to quantify objectively fluorescein angiograms of the optic disc, peripapillary choroid, and retina. Techniques were developed to measure fluorescein filling rates of the optic disc and the retinal vessels and the area of fluorescein filling defects within the optic disc. Two subjects, one with glaucoma and the other with ocular hypertension, showed increases of areas of fluorescein filling defects of the optic disc on follow-up and are presented here as examples of the application of these techniques. This methodology can be applied to the longitudinal follow-up of individual patients with glaucoma and retinal diseases, as well as to cross-sectional studies of patient populations.     

Topography and fluorescein angiography of the optic nerve head in primary open-angle and chronic primary angle closure glaucoma.

PURPOSE: The purpose of this study is to correlate optic nerve head topography with fluorescein angiography of the optic nerve head in patients with primary open-angle glaucoma (POAG), chronic primary angle closure glaucoma (CPACG), and normal controls. METHODS: This was an institution-based, cross-sectional, case-control study of 30 consecutive patients each with POAG or CPACG, which were compared with 30 age- and sex-matched controls. The fluorescein angiograms undertaken in one eye of each of the 90 subjects were then analyzed both qualitatively and quantitatively. RESULTS: The mean age of controls (group 1) was 51.73 +/- 9.6 years, patients with CPACG (group II) was 53.26 +/- 9.5 years, and patients with POAG (group III) was 54.5 +/- 10.4 years. The mean deviation and corrected pattern standard deviation on Humphrey visual field analyzer, respectively, were -1.51 +/- 2.01 dB and 2.09 +/- 1.04 dB the in control group, -9.4 +/- 9.3 dB and 5.32 +/- 4.02 dB in the CPACG group, and -11.27 +/- 7.7 dB and 7.57 +/- 5.34 dB in the POAG group. There was no significant difference in the disc areas between the three groups (analysis of variance [ANOVA], p = 0.157). All circulatory parameters were delayed in both glaucoma groups compared with controls with the disc filling time (ANOVA, p = 0.001) and the choroidal filling time being significantly delayed (ANOVA, p = 0.006). The Moorfield regression analysis showed good correlation with the pattern of disc fluorescence in all quadrants in cases of CPACG and POAG. CONCLUSION: The optic nerve head and choroidal circulation was delayed in both patients with POAG and those with CPACG, which correlates with loss of neuroretinal rim and retinal nerve fiber layer on the Heidelberg Retina Tomograph II (HRT). Patients with POAG showed diffuse damage with significant rim loss, whereas patients with CPACG showed marked sectorial abnormalities (superotemporal and the inferior-temporal) on fluorescein angiography and HRT. One possible reason for this discrepancy could be sectorial ischemia occurring in cases of CPACG as a result of a sudden rise of intraocular pressure causing disc and visual field damage.     

开角型青光眼与正常大陷凹眼中视乳头旁萎缩区的比较研究

目的研究原发性开角型青光眼(POAG)、正常眼压性青光眼(NTG)与正常大陷凹眼的视乳头旁脉络膜萎缩区(PPA)的差异及其与视野的关系。方法利用计算机图像分析系统对拍摄的视乳头立体图像进行测量,比较42例(42只眼)POAG、40例(40只眼)NTG与45例(45只眼)正常大陷凹眼之间PPA的发生率及大小差异,分析PPA的有关参数与视乳头结构指标、视野分级之间的相关性。所有入选患者的屈光度(等效球镜度数)均在+3.00~-3.00D之间。结果正常大陷凹组、POAG组及NTG组α区的出现率分别为85.4%、100.0%、95.0%,β区的出现率分别为19.1%、48.9%、37.5%,POAG组和NTG组的α区和β区的出现率均大于正常大陷凹组,差异均有统计学意义(P<0.05)。正常大陷凹组、POAG组及NTG组β区面积分别为(0.08±0.25)、(0.24±0.36)、(0.14±0.21)mm2,POAG组的β区面积大于正常大陷凹组,差异有统计学意义(P<0.05)。三组的α区面积差异无统计学意义(Chi-Square=4.534,P=0.104)。而POAG组与NTG组间上述各指标及α区和β区出现率的差异均无统计学意义(P>0.05)。青光眼患者视乳头结构指标与视野相关分析结果表明,杯/盘比值与视野受损分级之间有较强相关性(r=0.5624,P<0.01)。而α区面积、β区面积与视野受损分级之间均为低相关性(α区:r=0.246,P<0.01;β区:r=0.2302,P<0.01)。有无青光眼性视野缺损相关因素的Logistic回归分析结果显示,在包括年龄、性别、屈光度、杯/盘比值分级指标及α区面积和β区有无的多个因素中,仅年龄和杯/盘比值分级指标被证实为两个可能的影响因素。结论排除了-3.00D以上的中高度近视人群后,POAG和NTG患者的α区和β区出现率及β区面积虽与正常大陷凹者有所不同,但其与视野缺损程度的相关性较传统的视乳头结构指标低,在两组青光眼患者间也未见明显差异。由此认为PPA不能作为诊断POAG的独立指标,也不能作为POAG与NTG的鉴别诊断指标。     

应用海德堡视网膜断层扫描仪检测开角型青光眼的视盘改变

目的探讨海德堡视网膜断层扫描仪(Heidelberg retinal tomography,HRT)检测青光眼性视盘改变是否与视野损害的部位相一致,了解正常眼压性青光眼(normal tension glaucoma,NTG)与原发性开角型青光眼(primary open angle glaucoma,POAG)早或中期视盘形态是否异同.方法对64例(64只眼)仅有半侧视野异常的开角型青光眼(POAG27只眼、NTG37只眼)患者进行HRT检测,将Humphery视野与HRT的检测结果以0°～180°为界,分成上下两部分进行对应分析.结果与正常半侧视野对应的1/2视盘比较,显示异常半侧视野对应的1/2视盘HRT参数中,杯盘面积比、视杯形态测量值显著增大,而盘沿面积、视网膜神经纤维层厚度及视网膜神经纤维层横断面积值显著减少 (t=-2.625～3.025,P=0.003～0.05);NTG眼和POAG眼对应与异常半侧视野的HRT视盘参数差异无显著性(t=-0.98～1.511,P=0.14～0.97).结论 HRT参数能较准确反映与视野损害相一致的视盘变化,其中尤以杯盘面积比、盘沿面积、视杯形态测量、平均视网膜神经纤维厚度及视网膜神经纤维层横断面积测量值较为准确.NTG和POAG眼的视盘形态相似,可能具备某些相似的视神经损害发生机制.     

Optic disc excavation in the atrophic stage of Leber's hereditary optic neuropathy: comparison with normal tension glaucoma

BACKGROUND: Abnormal optic disc excavations are reportedly seen in patients with Leber's hereditary optic neuropathy (LHON), a mitochondrial dysfunction disease. We examined the disc morphology in the eyes of patients with LHON at the atrophic stage and compared it to that in eyes with normal-tension glaucoma (NTG). METHODS: We studied 15 LHON patients with the 11778 mutation, 15 patients with NTG, and 25 normal subjects. The optic disc morphology was analyzed by Heidelberg retinal tomography (HRT). Ten parameters of the optic disc obtained by HRT were evaluated, including the diagnostic classification of glaucoma. RESULTS: Six of the nine morphological HRT parameters of the LHON patients, the exceptions being disc area, mean cup depth, and maximum cup depth, differed significantly from those of the normals. NTG patients had a significantly greater mean and maximum cup depth than LHON patients. The HRT glaucoma diagnostic software classified 22 (73%) of the 30 optic discs in LHON patients as glaucomatous. CONCLUSION: The optic discs at the atrophic stage of LHON eyes have glaucoma-like morphological changes. However, the cups were significantly deeper in NTG than LHON. The similarity in the optic disc findings in LHON and NTG suggests that alterations in mitochondrial function may be related to optic disc excavations.     

Glaucoma in a rural population of southern India: the Aravind comprehensive eye survey

PURPOSE: To determine the prevalence of glaucoma and risk factors for primary open-angle glaucoma in a rural population of southern India. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 5150 subjects aged 40 years and older from 50 clusters representative of three southern districts of Tamil Nadu in southern India. METHODS: All participants had a comprehensive eye examination at the base hospital, including visual acuity using logarithm of the minimum angle of resolution illiterate E charts and refraction, slit-lamp biomicroscopy, gonioscopy, applanation tonometry, dilated fundus examinations, and automated central 24-2 full-threshold perimetry. MAIN OUTCOME MEASURES: Definite primary open-angle glaucoma (POAG) was defined as angles open on gonioscopy and glaucomatous optic disc changes with matching visual field defects, whereas ocular hypertension was defined as intraocular pressure (IOP) greater than 21 mmHg without glaucomatous optic disc damage and visual field defects in the presence of an open angle. Manifest primary angle-closure glaucoma (PACG) was defined as glaucomatous optic disc damage or glaucomatous visual field defects with the anterior chamber angle partly or totally closed, appositional angle closure or synechiae in the angle, and absence of signs of secondary angle closure. Secondary glaucoma was defined as glaucomatous optic nerve damage and/or visual field abnormalities suggestive of glaucoma with ocular disorders that contribute to a secondary elevation in IOP. RESULTS: The prevalence (95% confidence interval) of any glaucoma was 2.6% (2.2, 3.0), of POAG it was 1.7% (1.3, 2.1), and if PACG it was 0.5% (0.3, 0.7), and secondary glaucoma excluding pseudoexfoliation was 0.3% (0.2,0.5). On multivariate analysis, increasing age, male gender, myopia greater than 1 diopter, and pseudoexfoliation were significantly associated with POAG. After best correction, 18 persons (20.9%) with POAG were blind in either eye because of glaucoma, including 6 who were bilaterally blind and an additional 12 persons with unilateral blindness because of glaucomatous optic neuropathy in that eye. Of those identified with POAG, 93.0% had not been previously diagnosed with POAG. CONCLUSIONS: The prevalence of glaucoma in this population is not lower than that reported for white populations elsewhere. A large proportion of those with POAG had not been previously diagnosed. One fifth of those with POAG had blindness in one or both eyes from glaucoma. Early detection of glaucoma in this population will reduce the burden of blindness in India.     

Optic disc topography as measured by confocal scanning laser ophthalmoscopy and visual field loss in Japanese patients with primary open-angle or normal-tension glaucoma

PURPOSE: To determine whether differences in the optic disc topography and those in the relation between the optic disc topography and visual field indices exist between Japanese patients with primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). METHODS: The study included consecutive Japanese patients with POAG (n = 60) or NTG (n = 60). Using the Heidelberg Retina Tomograph (HRT), we measured disc area, cup area, cup-to-disc area ratio, rim area, cup volume, rim volume, cup shape measure, and height variation contour. Each HRT parameter was measured in the total optic disc and in its four 90 degree quadrants (superior, temporal, inferior, and nasal). The mean deviation for the entire field and the sum of the total deviation values corresponding to each optic disc quadrant were calculated using the Humphrey full-threshold 30-2 program. RESULTS: No significant differences were found between the POAG and NTG groups for any HRT parameter either globally or regionally. There were no significant differences between the two groups in the correlation coefficients between any HRT parameter and the corresponding visual field indices either globally or regionally. CONCLUSION: No significant differences were apparent between Japanese patients with POAG and NTG both in the optic disc parameters as measured by HRT and in the degree of correlation between HRT parameter and the corresponding visual field indices.     

正常眼压性青光眼患者视盘区血管密度与视野指数和视野损伤形态的关系

目的：研究正常眼压性青光眼(NTG)视盘区血管密度变化与青光眼视野指数(VFI)和视野损伤形态分期的关系。

方法：选取我院2018-12/2020-12 NTG患者106例106眼和原发性开角型青光眼(POAG)患者79例79眼进行横断面研究,其中双眼病变者采用随机数字表选取1眼为样本,同时选取我院健康体检者92名为对照组,三组均完成视盘血管密度、VFI检测和视野缺损形态分期,然后分析视盘血管密度与VFI和视野缺损形态分期的关系。

结果：POAG组眼压明显高于NTG组和对照组(P<0.05); NTG组和POAG组视盘区全区域血管密度、大血管密度和毛细血管密度均明显低于对照组(P<0.05),无血管区密度均明显高于对照组(P<0.05),且NTG组和POAG组各项指标比较有差异(P<0.05); NTG组和POAG组VFI均明显低于对照组(P<0.05),视野平均缺损(MD)明显高于对照组(P<0.05),且NTG组和POAG组VFI和MD比较无差异(P>0.05); 随着视野缺损形态分期增加,NTG患者视盘全区域血管密度和毛细血管密度呈明显降低趋势(P<0.05); NTG患者视盘全区域血管密度和毛细血管密度与VFI呈正相关性,与视野缺损形态分期呈负相关性,无血管区密度与VFI呈负相关性,与视野缺损形态分期呈正相关性(均P<0.05)。

结论：NTG患者视盘血管密度较POAG患者和正常人群明显降低,且与VFI和视野缺损形态分期存在明显相关性,其中以毛细血管密度相关程度最高,可见OCTA对NTG诊断、治疗和随访均具有重要临床意义。     

New directions in the treatment of normal tension glaucoma

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.     

Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients

PURPOSE: In a recent study, we found the presence of serum autoantibody against neuron-specific enolase (NSE) in glaucoma patients. The purpose of the present paper is to investigate further the clinical significance of the presence of the serum antibody against NSE in glaucoma patients. METHODS: Serum autoantibody against NSE was examined by Western blot analysis in 143 patients with glaucoma (normal tension glaucoma [NTG], 45 cases; primary open angle glaucoma [POAG] 98 cases). Clinical characteristics including visual acuity, visual field, intraocular pressure (IOP), and optic disc features were compared between the serum autoantibody-positive and the serum autoantibody-negative patients. RESULTS: Maximum IOP in the serum anti-NSE antibody-positive patients was significantly lower than that in the negative patients (P <.05). However, no statistical differences were observed in visual field loss, disc cupping, or other clinical factors. During the clinical course, rates of the presence of anti-NSE antibody were significantly higher in the early stages of POAG (P <.0001) with visual field deterioration than without it. Although it was not statistically significant, the positive rates of serum anti-NSE antibody were relatively higher in the later stages of POAG and NTG with visual field deterioration than without it. CONCLUSION: The present observations suggest that the presence of serum autoantibody against NSE may be clinically useful for predicting the progression of visual field loss in POAG patients.     

Retinal mean transit time in patients with primary open-angle glaucoma and normal-tension glaucoma

PURPOSE: To compare the mean transit time (MTT) of retinal circulation in eyes with primary open-angle glaucoma (POAG) and eyes with normal-tension glaucoma (NTG) and examine the possible relationship between MTT and visual field damage, expressed as mean deviation (MD). METHODS: Video fluorescein angiography was performed in 40 patients with POAG or NTG. Dye curves for fluorescein passing through the retinal arteries and veins were used to calculate MTT in each patient with a computer-assisted technique based on an impulse-response analysis (MTT(IR)). RESULTS: We were able to analyse MTT(IR) in all 40 angiograms. Mean (SD) MTT(IR) was 5.0 (1.5) seconds in eyes with POAG and 4.7 (1.4) seconds in eyes with NTG. The difference was not statistically significant. There was a weak but significant correlation between the MD and MTT(IR) (MTT(IR) = 4.12-0.08*MD; r = -0.49, p = 0.0013). CONCLUSIONS: The results demonstrate that loss of neuronal tissue in glaucoma is combined with an effect on the retinal circulation and that the effect is similar in eyes with NTG and eyes with POAG.     

Fluorescein fundus angiography of optic nerve head in primary open angle glaucoma and low tension glaucoma]

Fluorescein fundus angiography was performed at angle of 20 degrees in the 58 low tension glaucoma (LTG) eyes (30 cases) and 77 primary open angle glaucoma (POAG) eyes (41 cases) and the relation of the optic nerve head fluorescein changes to visual field disturbances (stage classification of Kosaki) was compared between POAG and LTG groups. The filling defect of fluorescein in the deep area and the decrease in number of superficial capillaries were observed in the optic nerve head. The filling defect area of fluorescein in the optic nerve head corresponding to Bjerrum scotoma was recognized even in the mild visual field disturbance cases of both LTG and POAG. The following findings were noted in both LTG and POAG cases; expansion of the filling defect area and the decrease in number of superficial capillaries in the same area with progression of visual field disturbances. Filling defect area of fluorescein of the optic nerve head accorded with visual field disturbance area in 19 LTG eyes (32.8%) and 61 POAG eyes (79.2%). On the contrary, the filling defect area of the optic nerve head was wider than the visual disturbance area in 37 LTG eyes (63.8%) and 16 POAG eyes (20.8%). These findings suggest that blood circulatory disorders of the optic nerve head occurred earlier in LTG than in POAG and that the development of LTG might be closely associated with the blood circulatory disorders.     

Optic neuropathies of different etiology and normal tension glaucoma: the point of differential diagnosis

62 patients (109 eyes) with glaucoma-like optic nerve head cupping and normal IOP indices (Po not more than 21 mm Hg) were examined to find the etiology of optic nerve changes. Regarding corneal biomechanics new-onset primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) were diagnosed in 27% and 3% of examined patients respectively. In 59% of patients optic neuropathy (ON) of different etiology was found to be the cause of glaucoma-like optic nerve changes including compression ON due to lesion of intracranial portion of optic nerve and chiasma in 6% of cases. In 11% physiologic large optic nerve head cupping with normal visual functions and absence of nerve fiber structural changes was found.     

Relationship between optic nerve head microcirculation and visual field loss in glaucoma

PURPOSE: To study the relationship between optic nerve head blood flow velocity and visual field loss in patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: This study included 44 eyes of 44 patients with POAG and 44 eyes of 44 patients with NTG. To evaluate optic nerve head blood flow velocity, the square blur rate (SBR) was measured by means of laser speckle flowgraphy. The correlation between SBR and Humphrey visual field indices was evaluated with linear regression analysis. RESULTS: In the NTG group, the average SBR at the superior and inferior temporal neuroretinal rim was positively correlated with mean deviation (MD) (r = 0.349, p = 0.020). The SBR at the superior or inferior temporal neuroretinal rim was positively correlated with the sum of the total deviations in the corresponding hemifields (r = 0.299, p = 0.049; r = 0.354, p = 0.019, respectively). The correlations between SBR and MD did not differ statistically between the NTG and POAG groups; however, no significant correlation between SBR and visual field indices was observed in the POAG group. CONCLUSION: These results suggested that the change in the circulation of the optic nerve head may be related to visual field damage in the NTG group but may be less involved in visual field damage in the POAG group.     

正常眼压性青光眼诊断中存在的问题

患者具有典型的青光眼视盘损害、视野缺损、前房角开放、眼压正常，并排除眼部或全身性疾病引起的视神经病变，即可诊断为正常眼压性青光眼。准确的眼压测量、两次以上24小时眼压曲线描记以及对眼部和全身可能原发疾病的排除在诊断过程中至关重要。     

Ranking of optic disc variables for detection of glaucomatous optic nerve damage

PURPOSE: To describe optic disc variables assessed by evaluation of clinical optic disc photographs and to compare sensitivity and specificity of these optic disc parameters in identifying patients with ocular hypertension who have nerve fiber layer defects and normal visual fields and patients with visual field defects. METHODS: The study included 500 normal subjects, 132 patients with ocular hypertension with retinal nerve fiber layer defects and normal visual fields (preperimetric glaucoma), and 840 patients with glaucomatous visual field defects. Color stereo optic disc photographs were morphometrically evaluated. RESULTS: Highest diagnostic power for the separation between the normal group and the preperimetric glaucoma group had the vertical cup-to-disc diameter ratio corrected for its dependence on the optic disc size, total neuroretinal rim area, rim-to-disc area ratio corrected for disc size, and cup-to-disc area ratio corrected for disc size. Diagnostic power was lower for rim area in the temporal inferior and temporal superior disc sector, cup area corrected for disc size, and horizontal cup-to-disc diameter ratio corrected for disc size. Less useful for the differentiation between the normal subjects and the preperimetric glaucoma group were size of zones alpha and beta of parapapillary chorioretinal atrophy, and ratios of neuroretinal rim width and rim area comparing various optic disc sectors with each other. CONCLUSIONS: In subjects with ocular hypertension with retinal nerve fiber layer defects and normal conventional achromatic visual fields, the vertical cup-to-disc diameter ratio corrected for optic disc size, total neuroretinal rim area, rim-to-disc area ratio, and cup-to-disc area ratio corrected for disc size are the most valuable optic disc variables for early detection of glaucomatous optic nerve damage. Correction for optic disc size is necessary for optic disc variables directly or indirectly derived from the optic cup. Parapapillary atrophy is less important in the early detection of glaucoma.