The light peak/dark trough ratio (L/D) (Arden ratio¹) is widely accepted as useful for evaluating retinal pigment epithelium (RPE) activity since the light peak and dark trough represent mainly the changes of the RPE membrane potentials. It also depends on the photoreceptor activity and RPE-receptor attachment, because the photoreceptors and their attachment with the RPE are essential for evoking the light peak. The L/D is also changed by occlusion of the central retinal artery, which nourishes the middle and inner layers of the retina. Therefore, abnormal L/D alone does not necessarily indicate RPE disorders. So far as a photic stimulus to the photoreceptors is used, the response obtained is not solely specific to the RPE.

The ocular standing potential, which mainly comes from the transepithelial potential (TEP) of the RPE, can be changed by nonphotic stimuli. For example, hyperosmolarity,^5,8,10 bicarbonate,^11,12 and acetazolamide³ (Diamox) decrease the TEP in vitro and the ocular standing potential in vivo. We call these responses the hyperosmolarity response, bicarbonate response, and Diamox response, respectively. The standing potential is changed by breathing a hypoxic mixture of oxygen and nitrogen.⁹ These responses are recordable by conventional electro-oculographic (EOG) technique in the dark.

Figure 41.1 shows these three responses in normal human subjects. The EOG amplitude is virtually stabilized (V₀) usually about in 30 minutes in the dark. Then, a hypertonic solution (e.g., 20% mannitol or Fructmanit, see legend for figure 41.1), 7% sodium bicarbonate solution (Meylon), or Diamox is given intravenously. These procedures decrease the EOG amplitude in the dark down to the minimum (V_min) approximately 8 to 20 minutes after the onset of administration. The amplitude of the response is defined as the percent amplitude change of the EOG:100 × (V₀ − V_min)/V₀. The distribution of the amplitudes of these responses in the normal subjects is approximated by the normal distribution. Thus, their normal range is the mean ± 2 SD of the amplitude in the normal subjects; 22.8% to 45.2% for the hyperosmolarity response, 15.2% to 28.6% for the bicarbonate response, and 32.1% to 52.9% for the Diamox response (the dose of each stimulant is described in the legend for figure 41.1).

Figure 41.1.  

Hyperosmolarity response (A), bicarbonate response (B), and Diamox response (C) in normal human subjects. The mean and standard deviation of the EOG amplitude as a percentage of the stabilized amplitude (so-called base value) after dark adaptation of 30 minutes are shown. The hyperosmolarity response was recorded in 50 eyes of 30 subjects, bicarbonate response in 70 eyes of 45 subjects, and Diamox response in 36 eyes of 24 subjects. To evoke the hyperosmolarity response, Fructmanit (10% fructose, 15% mannitol) was given intravenously. The solution was administered for 15 to 20 minutes at a rate of 11% of the subject's total blood volume per hour. The total blood volume (liters) was calculated by the following formulas: 0.168H³ + 0.05W + 0.444 in males or 0.25H³ + 0.063W − 0.662 in females, where H is the height in meters and W is weight in kilograms. To evoke the bicarbonate response, 0.83mL/kg of 7% sodium bicarbonate (Meylon) was intravenously given in 5 minutes. To evoke the Diamox response, 500mg of Diamox was given intravenously in 1 minute. No light was used except for two dim miniature lamps to alternatively fixate the eye for the conventional EOG procedure. The onset of stimulant application was at 0 minutes on the abscissa.

The amplitudes of the hyperosmolarity response and bicarbonate response are frequently decreased in retinitis pigmentosa,¹⁵ rhegmatogenous retinal detachment even in a localized area,² diabetic retinopathy⁴ (occasionally abnormal even in diabetics without visible retinopathy), angioid streaks, Stargardt's disease-fundus flavimaculatus,^14,16 vitelliform macular dystrophy (Best's disease¹³), Vogt-Harada-Koyanagi disease,⁷ and temporarily after cataract extraction⁶ (especially after intracapsular extraction) (Table 41.1). The hyperosmolarity response is more frequently abnormal than the L/D in the aforementioned diseases. The Diamox response remains within the normal range in most of the diseases described above and predominantly depends on the RPE in the posterior region of the ocular fundus since this response is suppressed in patients with severe macular atrophy (e.g., advanced stage in Stargardt's disease).¹⁴