The Collaborative Normal-Tension Glaucoma Study (CNTGS) (1998) was a randomized trial of treatment comparing reduction of IOP by 30 % vs. observation in progressive NTG patients. It showed that aggressive IOP reduction could reduce progression of glaucomatous disease from 35 to 12 % during approximately 5 years of follow-up [5]. Also, we know that IOP fluctuates during the waking day (diurnal variation) and asleep at night (nocturnal variation) and from office visit to office visit (usually between 8 AM to 5 PM). So, is it possible that some patients with “apparent” NTG may have IOPs that are much higher outside clinic exam hours or have increased IOP in the supine position during sleep? These “high” IOPs that occur outside the office visit time frame need to be considered when deciding a patient meets the criteria for NTG vs. traditional HTG.

Several studies have demonstrated that IOP may peak when measured at times other than the usual time of office visits. Yamagami et al. showed in NTG patients that mean diurnal IOP variation was 4.9 mmHg and peak IOPs most often occurred at 10 AM, but that 55 % of peak IOPs occurred between 6 PM and 8 AM outside usual clinic hours [21]. In another study, however, these researchers found that peak 24-h IOPs could be predicted from an average of six clinic IOPs, suggesting that there may be value in checking the IOP in low-tension patients relatively often [22]. A third 24-h IOP study concluded that IOP variation in NTG patients was similar to normal subjects and that sleep had little influence on 24-h IOP variation [23]. Sequential, daylong, office IOP measurements have recently been shown useful to help identify selected NTG patients demonstrating visual field deterioration with supposedly “controlled” IOP. IOPs were all highest in the early morning hours in NTG, POAG, and glaucoma suspect patients. IOP variations >5 mmHg were seen in 35 % of subjects, and in the NTG group there was a significant correlation between visual field deterioration and IOP peak and range, suggesting the importance of these factors to predict progression in NTG [24]. Whether or not it is useful to check patients at night or in a recumbent position remains to be determined.

Patients with diurnal IOPs ≤15 mmHg have been more frequently associated with having retinal nerve fiber layer (RNFL) defects closer to fixation than in eyes with diurnal IOPs >15 mmHg [25]. The width of RNFL defects seen in this study, however, was not different between the two groups. These findings were interpreted by the authors to indirectly support an alternative pathogenesis for optic nerve damage other than direct IOP-related causation in NTG, such as optic nerve ischemia due to sectoral vascular insufficiency from small branches of the short posterior ciliary arteries supplying the laminar and prelaminar optic nerve.

Diurnal 24-h IOPs in NTG patients have also been observed to show a general decline overtime or in relation to patient age. In one prospective Japanese study, one-ninth of patients with NTG were observed to have declining untreated IOPs over 3 years [26]. Yet in another cross-sectional study of NTG patients after 4 weeks of medication washout, the mean, maximum, minimum, and IOP variation over 24 h did not differ between two patient groups divided by age <60 years vs. >60 years. But, 24-h IOP in this study correlated negatively with patient age >60 years [27].

A number of studies during the past 25 years have demonstrated asymmetric optic nerve and visual field damage in some NTG patients, that is, the most affected eye has a higher IOP [28–31]. Note, however, that 24-h IOP in HTG eyes showed striking concordance of IOP variation between fellow eyes of 1.6–2.0 mmHg and the estimated probability of a 2-mmHg difference was 68–90 % and a 3-mmHg difference was 78–95 % for all time intervals studied [32]. More recently, these same researchers looked at the diurnal IOP fluctuation in untreated glaucoma suspect (GS) and NTG eyes [33]. They took 6 IOP measurements from 7 AM to 10 PM to evaluate the concordance of IOP between fellow eyes. The mean absolute IOP difference between eyes was 1.4–1.9 mmHg in the GS eyes and 1.3–1.5 mmHg for the NTG eyes (correlation between fellow NTG eyes, r = 0.81). The probability that the difference in IOP between fellow NTG eyes ranged within 3 mmHg was 86–93 %. These more recent studies bring into question the likelihood that true 24-h IOP asymmetry, which was not measured in the early studies, was the cause of the observed inter-eye disease asymmetry. As a result, one might postulate non-IOP-related factors, which were incorrectly attributed to the difference in measured daytime IOPs, to explain the observed asymmetry between fellow eyes of those NTG patients studied earlier.

Nocturnal, supine IOP rise may play a significant role in optic nerve damage seen clinically as “daytime” NTG. Intraocular pressure in the recumbent position is frequently elevated compared to the upright position. Even though we may never practically know how much our individual patient’s IOPs may rise during sleep, we can and should lower their daytime office IOPs with the most effective agents or interventions. We now know that prostaglandin analogues, laser trabeculoplasty, and surgical IOP lowering are the most effective interventions to lower daytime IOP and reduce 24-h fluctuations in IOP measured in the laboratory setting (see sections below on medical, laser, and surgical therapy for details). We should choose the best IOP-lowering therapy for each patient individually based on the stage of disease, demonstrated rate of progression, life expectancy, and willingness of the patient to engage in joint management of his or her own disease.

A number of studies have confirmed a thinner CCT (measured in μm by ultrasonic pachymetry) in NTG eyes vs. normal eyes vs. HTG eyes vs. OHT eyes, respectively (see Table 13.2). Aghaian et al. [34] found that CCT did not differ in normal eyes of Chinese, Caucasian, Hispanic, and Filipino individuals (548–555 μm), yet CCT was thinner in normal Japanese eyes (531 μm), eyes of HTG and NTG patients (538 and 529 μm), and normal African-Americans (521 μm) [35]. African-American patients have similarly been found with relatively thin CCTs in other population studies. For example, investigators found a similar CCT in normal eyes of Caucasians, Asians, and Hispanics (~550 μm), but thinner corneas in African-Americans (535 μm) [36]. Finally, a recent study of 1,699 normal Latino eyes in Los Angeles found a normal CCT of 547 μm in the same range as normal Caucasian, Chinese, Hispanic, and Filipino eyes studied elsewhere [37].

Thin CCT was associated with localized retinal nerve fiber defects in NTG eyes [38], with increased visual field defects at initial diagnosis but not with progression in POAG eyes, with visual field progression in POAG eyes (529 vs. 547 μm for progressing vs. non-progressing eyes) [39], and with a smaller IOP reduction in response to topical ocular hypotensive medications in OHT eyes [40]. From all evidence, consideration of CCT and its role in the diagnosis and progression of glaucoma is very important, with a thin CCT definitely associated with glaucomatous optic nerve and visual field damage and even response to IOP-lowering therapy.

In summary, in my practice I measure CCT in all glaucoma suspects and patients. If CCT is very thin (e.g., less than 500 μm), with an IOP <22 mmHg after multiple office-hour IOP measurements, and I suspect or diagnose NTG based on disc damage and/or visual field defects, then I typically aim for a goal of at least a 30 % IOP lowering (as supported by the CNTGS findings) with perhaps 5–10 % more lowering tacked on as a clinical “safety factor” for the unknown underestimation of true IOP.

Much more work needs to be done to sort out the actual contribution of corneal factors as represented by CCT or eye tissue biomechanics to IOP estimation and optic nerve susceptibility to glaucoma damage.

To summarize the above studies:

Eyes with a thin CCT may have higher IOPs than presumed by GAT and not be true NTG eyes (but HTG eyes). It is also logically possible that a thin CCT represents an inherent structural abnormality associated with the damage seen in glaucomatous optic discs and reflects an underlying structural weakness of the supportive collagen in the lamina cribrosa. Thus, an inherent susceptibility to IOP-related damage occurs, even at normal IOP levels, which leads to loss of retinal ganglion cell axons over time. This of course then results in classic glaucomatous optic nerve cupping and visual field loss as seen in NTG [41, 42].

A number of devices have been developed as alternatives to the GAT (see Table 13.3) to attempt to measure IOP in settings of abnormal, irregular, scarred, pathologic, and postsurgical corneas (e.g., nystagmus, corneal edema, posttraumatic keratoconus, Fuchs endothelial dystrophy, after corneal transplant, post-PRK, or post-LASIK). A more detailed discussion of these newer IOP measuring devices is found elsewhere in this book. Briefly, Pascal dynamic contour tonometry (DCT) has generally been found to be less affected by CCT than GAT, although not in all studies, and tends to measure IOP slightly higher than GAT. IOP measurements by pneumatonometer, Tono-Pen, and non-contact tonometry (NCT) all appear to be dependent on CCT, with the NCT as most dependent and the Tono-Pen least dependent on CCT. The ocular response analyzer (ORA) seems to measure IOP independent of the effect of CCT and higher than GAT, while rebound tonometry (RBT) measurements correlate with GAT and appear to be affected by CCT. The pressure phosphene tonometer has a wide variability in its ability to measure IOP accurately due to its very subjective end point in IOP determination. For the time being, the GAT still remains the IOP measurement device standard, and it remains to be seen if future work may replace it with a newer device. As a practical matter, clinicians should check the calibration of their Goldmann tonometers monthly to avoid introducing additional measurement variability into inherent physiological variability of IOP [47, 48].

The recent popularity of corneal refractive surgery such as photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) has impacted the ophthalmologist caring for glaucoma patients. The corneal thinning resulting from these procedures results in underestimates of true, manometric IOP when using GAT. This may result in a generation of the overdiagnosis of NTG or underdiagnosis of true HTG in many patients if the examiner is either unaware of the corneal surgery or does not account for it when measuring IOP. Generally, IOP measurements by GAT and NCT [49] are 2–5 mmHg lower after PRK/LASIK, depending on the amount of refractive correction achieved [50–52]. IOPs measured by the Tono-Pen [53] and pneumatonometer [54, 55] appear less affected by refractive thinning. Measurement of IOP on the nasal, non-affected cornea has been advocated to lessen the measurement inaccuracy [56]. Recent studies have suggested that IOP readings by the Pascal DCT are not affected by PRK/LASIK corneal thinning [57–59]. However, IOP measurements by the ORA are significantly reduced, with associated decreases in corneal hysteresis and corneal resistance factor, suggesting that LASIK permanently alters the viscoelastic properties of the cornea [59]. Finally, several correction algorithms for IOP following LASIK have been derived. These formulas may be considered when preoperative information about an individual patient is missing [60–64].

In summary, the best and most pragmatic advice at this time is to obtain good baseline, office-hour IOP measurements before anticipated refractive surgery and then again, several months after surgery, when the patient is off all topical steroids. The difference in the average pre- and postoperative IOPs would be the patient’s individual IOP correction factor. In the absence of preoperative data, perhaps one of the previously cited correction algorithms could be utilized.

The optic nerve transmits to the brain the retinal ganglion cell axons gathered from a total retinal area of more than 1,000 mm² concentrated down into an area of 2–3 mm². Although anatomically small in size, the optic disc is the key intraocular structure we study to help discriminate normal from abnormal with respect to diagnosing and following glaucoma patients [65] (Fig. 13.1).The normal optic nerve has about 970,000 ± 240,000 axons with a normal rate of age-related loss of about 4,900 axons per year [66]. The number of axons in the optic nerve is fairly constant from person to person despite varying sizes of the scleral canal outlet. There is no significant correlation between axon count and size of the scleral canal, which ranges from 1.6 to 2.9 mm² in pathology specimens of normal eyes [67]. Clinically, optic disc area can range in extremes from 0.8 to 6 mm² [68]. Some have suggested that a larger optic disc is more susceptible to IOP-induced damage.

Are myopia and optic disc size associated with NTG? In 1972, Tomlinson and Leighton compared the eyes of 11 NTG patients matched with respect to sex, age, and refractive with non-glaucomatous persons and HTG patients [68]. They found NTG eyes to have a longer overall axial length, with an increased cup-to-disc ratio (C/D), compared to normal and HTG eyes, although axial lengths and C/Ds did not differ between groups. Tomita et al. used computerized image analysis to study the optic nerves in 26 NTG patients [69]. They found a larger optic disc area and a higher mean IOP, associated with greater visual field loss, in 8 of 22 patients with disc size and IOP asymmetry, suggesting a greater vulnerability to IOP in eyes with larger discs. However, in 1995, Jonas et al. did not find an association between disc size, measured by morphometry, and visual field loss in NTG patients but noted more cupping and visual field loss in eyes with the smaller disc, suggesting a selection bias in the earlier studies [70].

In his comprehensive article on NTG in 1980, Levene reviewed a total of 767 NTG cases [3]. He concluded that certain characteristics were more common in NTG than HTG. These features were:

Have these findings held up in studies subsequent to Levene’s review? The finding of greater disc cupping associated with less generalized loss of visual field mean sensitivity, but a deeper central visual field loss was confirmed by Gramer et al. [71]. but not by Lewis et al. [72]. Caprioli and Spaeth examined eyes with early to moderate visual field loss and found the optic disc rim in NTG eyes to be significantly thinner inferiorly and inferotemporally than in HTG eyes with an average IOP 15 mmHg higher than the NTG eyes [73]. But they did not find comparative differences in disc pallor, peripapillary atrophy, disc hemorrhage, nasal cupping vessel overpass, and baring of the circumlinear vessels between groups. Cup contour was judged to be more gradually sloped toward the rim in NTG than HTG eyes, but HTG eyes had a steeper cup wall farther from the disc edge than in NTG. They also found initial visual field defects to be closer to fixation in NTG and more peripheral, but progressing centrally, in HTG. They felt their findings implied a different pathogenesis of optic nerve damage in these two groups, with NTG eyes more susceptible to vascular optic nerve injury and HTG eyes more susceptible to barotrauma, rather than vascular injury. These findings were confirmed by Heidelberg retinal tomography (HRT) in a study by Eid et al. who found larger cup areas and C/D ratios, smaller inferior neuroretinal rim area, and a greater mean deviation of the superior rather than inferior arcuate visual field zone in NTG eyes, compared with HTG eyes [74]. They felt this indicated more vulnerability of the optic nerve to focal damage in NTG eyes. By contrast, Lester and Mikelberg [75] and Lester [76] did not find any differences in the optic nerve parameters measured by HRT between NTG and HTG eyes.

Others have compared the optic nerves of NTG and HTG patients. Tezel et al. found only increased disc hemorrhages and arteriolar narrowing in NTG eyes [77]. Wang et al. [78] found only an increase in peripapillary atrophy in NTG eyes with IOP ≤15 mmHg, while Miller and Quigley [79] found no differences between the two groups, except that an “hour glass appearance” of connective tissue bundles within the scleral lamina cribrosa was less common in NTG eyes. Miller and Quigley proposed that inherent, underlying differences in optic nerve head architecture of the lamina cribrosa that they observed might explain the variable sensitivity to IOP between HTG and NTG eyes.

Attempts have been made to discriminate NTG from HTG based on observed patterns of optic disc cupping (focal vs. diffuse enlargement), disc hemorrhage occurrence, pattern of loss of the neuroretinal rim, amount of peripapillary atrophy, amount and appearance of retinal nerve fiber layer atrophy (localized vs. diffuse), and myopic tilting of the nerve (Figs. 13.2, 13.3, 13.4, 13.5, and 13.6). Spaeth has written that “LTG is not a valid clinical entity, just as HTG is not a valid clinical entity. The two overlap. The factor distinguishing LTG from HTG appears to be, paradoxically, not IOP but disk resistance.” [80] Yet, he and others have studied the glaucomatous disc with a view toward disease classification in an attempt to explain the pathogenesis of glaucoma by the various appearances of the disc seen on clinical exam. These researchers have carefully evaluated many glaucomatous optic nerves and discriminated four types of disc appearance, although none is exclusively associated with NTG:

Spaeth first described “primary ischemic glaucoma,” later termed “focal ischemic glaucoma,” based on fluorescein angiography studies of the optic nerve in 16 patients with clinical NTG [82]. These eyes were characterized by inferotemporal disc hypofluorescence, shallow and eccentric disc cupping with more pallor than expected, associated disc hemorrhages, and dense, often absolute, superior, paracentral scotomas frequently noted by the patient. He did not comment on the amount of cupping compared to the visual field. In the NTG patients with this focally damaged disc appearance, he found a possible association with diabetes mellitus, syphilis, severe heart disease, “hemodynamic crises,” and platelet abnormalities, suggesting localized ischemia of the optic nerve head to explain the disc injury.

Subsequent studies [83–90] have all confirmed that the focal ischemic disc appearance, also termed “acquired pit of the optic nerve,” [85] is seen also in HTG but more frequently in NTG (~15 % vs. 75 %, respectively [85]). These studies have revealed a number of associations with the focal ischemic disc.

In particular, the development of the optic pit has been speculated to arise from an underlying “laminar insufficiency” [85] due to a primary weakness of the optic nerve, whether from structural, vascular, or other etiologies. This theory is supported by pathologic findings from work by Quigley and coworkers who found a number of structural differences in the lamina cribrosa of patients with NTG compared to HTG [91, 92].

Geijssen and Greve first described “senile sclerotic glaucoma” characterized by older age, relatively low IOP (or NTG), normal anterior chamber angles, “senile excavation” or a saucerized cup with gradual sloping of the optic nerve cup toward the rim, atrophy of the peripapillary retina, and choroidal sclerosis (also called “fundus tessellation”) giving the disc a “moth-eaten” appearance [81]. HTG eyes, by contrast, had younger age, high IOP, abnormal anterior chamber angles, deep and steep optic nerve excavation, little peripapillary atrophy, and no choroidal sclerosis. They found larger superior than inferior visual field defects in the NTG eyes compared with equal superior and inferior visual field defects in HTG eyes. They suggested a primary local vascular disease with chronic ischemia causing damage in these senile sclerotic discs, leading to the appearance of peripapillary atrophy and choroidal sclerosis, and a primary IOP mechanism for damage in the HTG eyes, with a secondary role of insufficient blood supply causing disc injury in HTG. Subsequent studies have also found similar and additional characteristics in patients with senile sclerotic discs [83, 87, 93, 94].

Geijssen first proposed that myopic eyes might represent a distinct group of NTG with a characteristic disc appearance when damaged by glaucoma, separate from damage due to pathologic myopia [84]. In her study, she observed disc tilting with oblique insertion, shallow cupping, temporal crescents or peripapillary atrophy, and typical glaucomatous thinning and excavation of the superior and inferior poles of the neuroretinal rim. Subsequent studies have confirmed these and other findings in this type of myopic glaucomatous disc damage [83, 87, 95, 96].

Spaeth first called this type of optic nerve damage “primary hyperbaric glaucoma” characterized by elevated IOP, a normal disc fluorescein pattern, more symmetric, round enlargement of the optic cup, and visual field loss more often peripheral than central [80]. He proposed that disc damage in this group of eyes was purely mechanical in etiology from the chronic effects of elevated IOP. Other studies have also found a number of characteristics in patients with generalized optic cup enlargement [83, 87, 95, 96].

In summary, while these four types of disc cupping are often typical of eyes with NTG, they are not generally predominant in this disease entity. However, their identification may help target disease management from an ocular (e.g., degree of necessary IOP lowering) and systemic (e.g., treatment of cardiovascular risk factors) point of view.

Jonas et al. examined the pressure dependence of NRR loss in patients with NTG [97]. They found that optic disc size actually decreased with decreasing maximal IOP in eyes with the focal ischemic disc appearance, suggesting a vasogenic reason for the nerve fiber loss. This finding was also suggested by another study that found an abnormal retrobulbar circulation in NTG eyes [98]. Yet, Jonas et al. also found a correlation between a smaller NRR area in eyes with a relatively higher IOP compared to eyes with a lower IOP in all three of the focal ischemic, senile sclerotic, and myopic glaucomatous disc types seen in the NTG eyes he studied [97]. This suggests a barotraumatic mechanism for damage in all these disc types characteristic of NTG.

Tan et al. utilized the HRT to study NRR loss in OHT, OHT converters, NTG suspects, and NTG eyes [99]. These researchers found reproducible loss of NRR primarily at the superior and inferior poles of the OHT groups, especially inferiorly, consistent with prior studies showing vertical cup elongation in early glaucoma. NRR loss was detected in 11 % of OHT suspects and in 90 % of OHT eyes converting to glaucoma. NRR loss was detected in 58 % of NTG suspects but in only 54 % of NTG eyes and in 3 of 5 NTG converters in whom visual field defects developed. Temporal rim loss in these eyes correlated with dense paracentral visual field defects, as seen in other studies previously mentioned.

Optic disc hemorrhages are a hallmark of progressive glaucomatous optic nerve damage. ODHs were characterized by Drance et al. in the 1970s as localized ischemic optic neuropathy, and they noted a 20 % prevalence in NTG patients [99–102]. Since then, many studies have examined patients with NTG and ODHs to elucidate their characteristics and associations and to correlate ODHs with disease state.

Optic disc hemorrhages may be linear, flame-shaped, splinter-shaped, or occasionally blot type and rounded. They usually are found in the prelaminar area of the optic nerve and peripapillary retina, and rarely in the depth of the optic disc cup. ODHs are found with a higher frequency (~3:1) in the inferior vs. the superior disc pole of the disc. ODHs in NTG eyes have recently been found to be associated with branch retinal vein occlusions in the contralateral eye, suggesting a possible common microvascular thrombotic mechanism [103, 104].

Jonas and Budde investigated glaucomatous eyes with very high IOP (juvenile open-angle glaucoma) and very low IOP (NTG), in order to increase the possibility to detect differences in optic nerve appearance between the groups. In contrast to earlier studies, these authors found that the optic nerves in these two groups were similar in number of detectable localized retinal nerve fiber layer defects (RNFLDs), size of peripapillary atrophy, optic cup depth, steepness of disc cupping, rim/disc area ratio, retinal arteriole diameter, and degree of focal arteriolar narrowing. However, NTG eyes did have broader localized RNFLDs, more frequent NRR notches, and more frequent and larger ODHs [105]. They speculated that the lower frequency of detected ODH and NRR notches in high-pressure JOAG eyes resulted directly from the larger transmural pressure gradient across the small vessels of the optic disc in NTG eyes. Therefore, a small vessel rupture on the optic nerve in eyes with NTG would lead to a larger disc hemorrhage that reabsorbed more slowly, and hence have a higher chance to be detected in disc photos than in eyes with HTG. An ODH due to a similar vessel rupture in an HTG eye would be smaller, more easily reabsorbed, more easily missed in a disc photo, and lead to a smaller resulting RNFLD seen on subsequent clinical exam. Thus, the relative paucity of ODH in HTG vs. NTG may be an artifact of the examination which may not reflect the true frequency of occurrence.

Based on their findings, these researchers further speculated that the pathogenic mechanisms of disc damage in NTG and HTG may rather be more similar than different. This conclusion also agrees with:

In summary, ODHs serve as an easily identifiable sign of disease progression and should always be carefully searched for on clinical exam and review of disc photos. Their occurrence should prompt more investigation within 2–6 weeks into the status of a patient’s disease state such as:

Peripapillary atrophy is separated into two zones: zone α, a peripheral zone with irregular hyper- and hypopigmentation from loss of the RPE, and zone β, a central, whitish zone with visible choroidal vessels and sclera due to loss of both RPE and photoreceptors (Figs. 13.6, 13.7, and 13.8). This atrophy is felt to develop due to loss of the peripapillary choroidal branches from the short posterior ciliary arteries, which penetrate centripetally into the prelaminar portion of the optic nerve head in a sectoral fashion. These branches supply the optic nerve axons and collagenous laminar beams with blood. Absence or dysfunction of these branches would cause segmental ischemia and damage to the optic nerve head leading to axonal loss, focal disc notching, cupping, and acquired pits of the optic nerve with associated PPA.

Anderson first suggested in 1983 that peripapillary halos or atrophy were more common in NTG than HTG eyes [106]. Geijssen and Greve in 1987 first described the association of PPA with larger superior than inferior visual field defects in the NTG senile sclerotic disc compared to little PPA and equal visual field defects in the superior and inferior regions in HTG discs [81]. They concluded that primary local optic disc microvascular insufficiency could explain the pathogenesis of disc damage in NTG eyes, while in HTG eyes elevated IOP played a primary role and vascular insufficiency a secondary role in the pathogenesis of disc damage. Their findings are similar to those by Kawano et al. in 2006, who found that only the inferior half of zone β PPA correlated with glaucomatous VF damage [107]. Further, inferior PPA also correlated with axial length, while superior PPA correlated only with axial length but not VF damage. They felt these findings suggested that the inferior region of the ONH is more vulnerable to damage in NTG than the superior region, and therefore, inferior PPA is more clinically significant in NTG than superior PPA.

Similarly, Buus and Anderson found the incidence of PPA to be 64 % in NTG discs and only 34 % in OHT discs [108]. This difference persisted even after exclusion of eyes with myopia greater than −4 diopters. Araie et al. also found that the extent of PPA in untreated NTG eyes correlated with VF progression [109]. But, Tezel et al. found that zone β PPA was detected more often in NTG than HTG eyes, presumably because the NTG eyes were seen at a more advanced stage of disease [77]. They felt that the final appearance of the optic nerve damage was similar in NTG and HTG eyes for the same degree of damage, regardless of the possible different mechanisms for the optic neuropathy observed in the two groups. This was confirmed by Jonas and Xu, who did not find larger areas of zone α or β PPA in NTG eyes compared to HTG eyes, after exclusion of eyes with myopia greater than -8 diopters, when eyes were matched for stage of disease by the amount of remaining NRR area and visual field loss [110].

In summary, β PPA is a sign associated with advancing glaucomatous optic neuropathy. Its presence should lead the clinician to look for other signs of related disc damage such as associated disc notching or rim thinning, disc hemorrhages, retinal nerve fiber layer loss, and prompt VF testing to detect possible early disease, where NTG has not necessarily been suspected previously.

As documented from review of the early classical literature on NTG and from his own retrospective case series, Levene [3] concluded that VFDs in NTG eyes tend to:

In a retrospective review of NTG patients in 1976, Chumbley and Brubaker noted a nerve fiber bundle pattern of Goldmann VFDs in all eyes that could be evaluated [111]. Superior arcuate scotomas were seen in 84 % and inferior arcuate scotomas in 58 %, and both defects in 41 % of eyes (Figs. 13.3, 13.4, 13.9, 13.10, 13.11, 13.12, and 13.13). Interestingly, VFDs involved the macula in 25 % of eyes either at initial exam or progressed to involve the macula on follow-up in their study group.