(fERG) for both lightand dark-adapted states [44]. Inasmuch as some components of the fERG originate in the photoreceptor layer, and others reflect the activity of neurons populating the inner retinal layer, any changes in this potential are likely associated with changes in choroidal and retinal blood flow. In contrast to these minimal changes in neural function secondary to hyperperfusion, there were more dramatic changes in retinal reactivity to hypoperfusion. Furthermore, it is noteworthy that the neural responsiveness of the retina to transient decreases in the OPP differs dramatically when the retina is switched from a lightto dark-adapted state. Perhaps the most significant and interesting finding concerning the relationship between neural function and blood flow was the heightened vulnerability of rod photoreceptors to transient decrements in the OPP. When the retina was light adapted, the photopic fERG was not affected by either a transient increase or decrease in the OPP. However, when the retina was dark adapted and the neural response of the retina to light was driven exclusively by rod photoreceptors, both the a-wave and b-wave components of the scotopic fERG were significantly attenuated by a progressive decrease in the OPP [44]. This observation may reflect a change in the topographic distribution of blood, blood volume, and oxygen available to rods [45] in dark adaptation.

The changes in scotopically matched red and blue fERGs during 10% step decrements in the OPP, and the recovery pattern at 1-min intervals are shown in Fig. 10.15. The biphasic shape of the scotopic red fERG reveals the early cone and slower rod contributions to the fERG b-wave, while the monophasic blue fERGs show the rod-isolated responses. The rod components of the scotopic fERGs were seen to decrease when the OPP was reduced by as little as 10%. Further reductions in the OPP caused a progressive reduction in the rod contribution while the cone contribution remained unchanged until the OPP was reduced by ~40%. Furthermore, the cone contribution to the scotopic red fERG was still visible when the rod contribution was extinguished by a 50% reduction in the resting

OPP. In addition, when the resting OPP was returned, cone recovery to resting values was more rapid than the rod recovery. Because increased scleral suction was used to reduce the OPP, the cause of the increased vulnerability of scotopic fERGs to decrements in the OPP may also have involved the concomitant increase in pressure of the vitreous against the retina as the IOP was elevated through scleral suction [44].

The increased susceptibility to ischemia of the inner retinal layers during retinal dark vs. light adaptation was also observed through measurements of scotopic vs. photopic oscillatory potentials (OPs), which reflect the functional status of the amacrine cells. During transient experimental increased OPP as large as 70%, amacrine cell function indexed by the amplitude of photopic OPs remained largely unchanged [46]. In darkness, however, a transient reduction in the OPP attenuated all components of the OP complex, while a transient increase in the OPP induced by body declination caused an increase in the amplitude of OP5 [30] (Fig. 10.14). While the physiological basis for this component-specific vulnerability of the scotopic OPs to variations in the resting OPP remains to be determined for the human eye, these findings nonetheless highlight a unique diagnostic capability of the scotopic OPs for increased or decreased blood flow in the inner retinal layers.

10.6Blood Gases

The inspired gas content can easily be modified to alter the concentration of naturally occurring gases in arterial blood. Several studies have used such provocations to alter the concentrations of oxygen (O2), carbon dioxide (CO2), or nitrogen content in blood to study the effect on blood flow regulation [47, 48]. The ability of a vascular bed to adjust its blood flow parameters during transient changes in O2 saturation (SaO2) and/or other metabolites to preserve normal physiological function is referred to as “metabolic regulation.” Metabolic regulation in other organs or tissues during a period of hyper/

Baseline

a-wave

R1

R2

R3

50 ms

hypoxia or/and hyper/hypocapnia may be reflected by the vasomotor changes in the retinal vasculature. Because retinal vessels comprise the only vasculature in the human body that can be seen directly using noninvasive procedures, it is worthwhile for future research to determine whether changes in retinal vasodynamics and/or structure can be used clinically to diagnose subclinical changes in the systemic vasculature pathognomonic of life-threatening cardiovascular disease.

This idea is realistic since it is well known that narrowing of retinal arterioles or abnormal arteriovenous crossings are clinical indices of systemic hypertension.

This section will present studies on the retinal vessel dynamics [49], ONH perfusion [50], and POBF [51] during inhalation of 100% O2, as well as the changes in POBF following inhalation of carbogen (5% CO2 in 95% O2) [51] and a hypoxic gas (12% O2 in 88% nitrogen) [52].

Fig. 10.16 Inhalation of 100% O2 induced vasoconstriction in both retinal arteries and veins. The reduction in vessel diameter was ~5% greater in veins than arteries, and recovery from O2 occurred at the same rate in both vessel types. This profile of change in vessel diameter during inhalation of O2 and the recovery phase was the same in the four retinal quadrants centered on the ONH. The vasoconstriction response to inhalation of 100% O2 is interpreted as a regulatory response of blood flow to maintain constant levels of oxygen tension

Percent vessel diameter

Time (min)

10.6.1 Hyperoxia and Blood Flow

Inhalation of 100% O2 caused a progressive monotonic constriction of retinal vessels that reached a plateau within 4 min. The data in Fig. 10.16 show that veins constricted about 5% more than arteries, but their overall response profiles were similar. The plateau of constriction was sustained throughout the remaining time of O2 inhalation. When room air was reintroduced, both arteries and veins redilated monotonically to within ~2% of baseline caliber during the recovery interval. This profile of retinal vessel reactivity to O2 inhalation was the same for vessels populating each of the principal fundus quadrants relative to the ONH. This O2-induced vasoconstriction was interpreted as evidence for a mechanism regulating blood flow presumably to maintain the level of O2 required for normal metabolism.

The reactivity of the blood vessels perfusing the ONH was also examined in a separate study involving inhalation of 100% O2 with perfusion monitored by the CP. Transient systemic hyperoxia increased the area of pallor in the ONH, suggesting vasoconstriction of superficial and deeper capillaries and decreased perfusion of the anterior portion of the optic nerve [50]. However, the choroidal flow as indexed by the POBF [51] or the ChBF [53] was not altered during systemic hyperoxia.

10.6.2Hypercapnia-Hyperoxia and Choroidal Blood Flow

Inhalation of carbogen (O2 + 5 to 7% CO2), a gas mixture with increased concentration of CO2, increases the POBF [51], and the subfoveal ChBF [54], as well as the fundus pulsation amplitude (FPA), an index of choroidal pulsatile flow, in the macula [55] in man. Inhalation of CO2 in air has also been shown to increase blood flow in the macula, as measured by FPA [56, 57]. Similar results indicating an increase in ChBF with increased CO2 (in air, or in O2) were reported in animal studies [58–60], although others have reported that CO2 did not increase ChBF [61].

10.6.3Hypoxia and Pulsatile Choroidal Blood Flow

Early studies into vascular regulation reported that systemic hypoxia caused an increase in both the perifoveal capillary blood flow [62] and retinal blood flow [63]. However, inhalation of 12% O2 in nitrogen [mean SaO2 = 89.0%] did not affect ChBF as indexed by measurements of the POBF [52]. The absence of changes in the POBF could be interpreted to indicate that the pulsatile component of ChBF is unaffected by transient mild