February 2009
Volume 50, Issue 2
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Visual Neuroscience  |   February 2009
Rod and Rod-Driven Function in Achromatopsia and Blue Cone Monochromatism
Author Affiliations
  • Anne Moskowitz
    From the Department of Ophthalmology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
  • Ronald M. Hansen
    From the Department of Ophthalmology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
  • James D. Akula
    From the Department of Ophthalmology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
  • Susan E. Eklund
    From the Department of Ophthalmology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
  • Anne B. Fulton
    From the Department of Ophthalmology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts.
Investigative Ophthalmology & Visual Science February 2009, Vol.50, 950-958. doi:10.1167/iovs.08-2544
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      Anne Moskowitz, Ronald M. Hansen, James D. Akula, Susan E. Eklund, Anne B. Fulton; Rod and Rod-Driven Function in Achromatopsia and Blue Cone Monochromatism. Invest. Ophthalmol. Vis. Sci. 2009;50(2):950-958. doi: 10.1167/iovs.08-2544.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. To evaluate rod photoreceptor and postreceptor retinal function in pediatric patients with achromatopsia (ACHR) and blue cone monochromatism (BCM) using contemporary electroretinographic (ERG) procedures.

methods. Fifteen patients (age range, 1–20 years) with ACHR and six patients (age range, 4–22 years) with BCM were studied. ERG responses to full-field stimuli were obtained in scotopic and photopic conditions. Rod photoreceptor (S rod , R rod ) and rod-driven postreceptor (log σ, V max ) response parameters were calculated from the a-wave and b-wave. ERG records were digitally filtered to demonstrate the oscillatory potentials (OPs); a sensitivity parameter, log SOPA 1/2 , and an amplitude parameter, SOPA max , were used to characterize the OP response. Response parameters were compared with those of 12 healthy control subjects.

results. As expected, photopic responses were nondetectable in patients with ACHR and BCM. In addition, mean scotopic photoreceptor (R rod ) and postreceptor (V max and SOPA max ) amplitude parameters were significantly reduced compared with those in healthy controls. The flash intensity required to evoke a half-maximum b-wave amplitude (log σ) was significantly increased.

conclusions. Results of this study provide evidence that deficits in rod and rod-mediated function occur in the primary cone dysfunction syndromes ACHR and BCM.

Achromatopsia (ACHR) refers to a group of congenital, stationary retinal disorders in which there is an absence or a paucity of functioning cones. 1 2 3 Complete ACHR, also called rod monochromatism, is an autosomal recessive condition characterized by reduced visual acuity, photophobia, nystagmus, deficits in color discrimination, and paradoxical pupillary constriction to dark. 1 2 3 4 5 Hyperopia is common, 1 6 7 though a broad distribution of refractive errors has been reported. 8 Fundus appearance is typically normal, 1 2 3 4 5 but exceptions have been reported. 9 10 Blue cone monochromatism (BCM) is an X-linked condition that shares many of the characteristics of autosomal recessive ACHR, sometimes exhibited with reduced severity. 1 2 3 11 12 Refractive error, however, is typically myopic. 8 11 13 14 15 Clinically, Berson plates discriminate patients with BCM from patients with ACHR. 16 17 18  
In ACHR, rods are the only functional photoreceptor type, whereas in BCM, rods and short wavelength–sensitive cones are functional. 12 19 ACHR and BCM are typically regarded as stationary conditions, but in both there have been reports of adults with progressive retinal disease. 10 20 21 22 23 24 25 26  
ACHR is understood to be a channelopathy of the cone photoreceptors. The most common molecular causes are mutations in the cGMP-gated cation channel genes CNGA3 (Online Mendelian Inheritance in Man [OMIM]600053) and CNGB3 (OMIM605080). 7 27 28 29 30 31 Less frequently, a mutation in the transducin protein GNAT2 (OMIM139340) has been associated with ACHR. 32 33 The most common molecular causes of BCM are mutations in the opsin gene array of long wavelength– and medium wavelength–sensitive cone visual pigments located adjacently on the X-chromosome. (OMIM303700). 25 34  
In both ACHR and BCM, cone and cone-driven electroretinographic (ERG) responses to full-field stimuli are markedly attenuated or nondetectable, whereas rod and rod-driven responses are typically reported to be normal or near normal (Wiesen MH, et al. IOVS 2008;49:ARVO E-Abstract 1267). 4 6 8 9 21 26 27 35 36 37 38 39 Recently, however, abnormal rod-driven ERGs have been reported in some patients with CNGB3 ACHR 10 and BCM. 23  
Our own clinical observations also indicated abnormalities in rod and rod-driven electroretinograms in pediatric patients with ACHR and BCM. Therefore, we undertook an analysis of rod photoreceptor and postreceptor ERG components. Our goal was to identify possible mechanisms underlying the abnormalities. 
Methods
Subjects
Twenty-one patients (Table 1) , 15 with complete ACHR and six with BCM, who had been monitored by the Department of Ophthalmology, Children’s Hospital Boston, were studied retrospectively. ACHR patients exhibited typical features of ACHR, including low visual acuity, photophobia, paradoxical pupillary constriction to dark, and low-amplitude, high-frequency, “jelly-like” nystagmus. All patients had normal fundus appearance. ACHR patients 1 and 8 are siblings. Clinical presentations of the patients with BCM were similar, though photophobia often appeared less severe. All were male, and all passed the Berson test, 16 indicating that unlike patients with ACHR, they were able to distinguish a purple-blue (Munsell Color System 7.5 PB; dominant wavelength 468 nm) arrow from blue-green (5.0 BG; 491 nm) arrows. Two male patients who were classified as having ACHR (ACHR 4 and 7) were too young for color vision testing. Median ages at ERG were 2.7 years (range, 1–20 years) for the ACHR patients and 8 years (range, 4–22 years) for the BCM patients. 
Visual acuity was measured in dim room light using age-appropriate tests (Teller Acuity Cards, HOTV, Lea, Feinbloom, or ETDRS). Refractive error was measured using cycloplegic retinoscopy. 41 The most recent visual acuity and spherical equivalent values for each patient are reported in Table 1 . Acuity was below normal for age in all patients. Twelve of the 15 ACHR patients were hyperopic; nine were outside the 99% prediction limit of normal for age. 41 42 Two of the three myopic ACHRs were also outside the normal limit. All six BCM patients were myopic; four were outside the 99% prediction limit of normal for age. 
Dark-adapted, rod-mediated visual thresholds, obtained in 11 ACHR patients and five BCM patients, were normal 43 in all but one patient (ACHR 7), who showed a mild (1.18 log units) but statistically significant threshold elevation. Four patients had repeat measurements with 1.5-year (ACHR 5), 6.8 year (BCM 21), 7.8-year (ACHR 9), and 9-year (ACHR 12) intervals between tests, and none showed a change in threshold, suggesting a stationary condition. 
ERG responses in the patients with ACHR and BCM were compared with responses in 12 healthy control subjects (median age, 23 years; range, 8–41 years). ERG response parameters in healthy subjects at the ages of our patients with ACHR and BCM (range, 1–22 years) do not differ significantly from those in adults. 44 All control subjects had normal ocular structures and corrected visual acuity of 20/25 or better; median spherical equivalent was −0.50 D (range, −4.75 to +0.88 D). 
Patients had been referred for examination and testing so that their eye and vision problems could be diagnosed. Patient data were analyzed retrospectively with the approval of the Children’s Hospital Committee on Clinical Investigation (CCI). Written informed consent was obtained from the control subjects after explanation of the nature and possible consequences of the study. The control study conformed to the tenets of the Declaration of Helsinki and was approved by the Children’s Hospital CCI. 
Electroretinography
Pupils were dilated with 1% cyclopentolate hydrochloride, and the patient was dark adapted for 30 minutes. All 12 control subjects and seven patients (four ACHR, three BCM) were tested awake (Table 1) ; 14 patients (11 ACHR, three BCM) had ERG testing under light inhalation anesthesia which has no significant effect on the ERG parameters studied herein. 45 After dark adaptation, 0.5% proparacaine was instilled and, under dim red light, a bipolar Burian-Allen electrode (Hansen Ophthalmic Development Laboratory, Coralville, IA) was placed on the cornea. A ground electrode was placed on the skin over the mastoid. Responses were recorded from both eyes of the patients and from one eye of the control subjects. In patients, the eye with the larger scotopic amplitudes was selected for analysis. 
The study was conducted over a period of several years. Thirteen patients (10 ACHR, three BCM) and all 12 control subjects were tested using an older electrophysiological recording system (Compact 4; Nicolet, Madison, WI), and eight patients (five ACHR, three BCM) were tested using a new system (Espion; Diagnosys, Lowell, MA). Despite differences between the two recording systems in the spectral composition of the stimuli (described below) and in data acquisition (2564 Hz digitization rate for the Nicolet; 2000 Hz for the Espion), a previous comparison 46 of rod and cone photoresponse parameters in normal adult subjects obtained using the Espion system (N = 7) and obtained earlier using the Nicolet system (N = 13) 44 47 showed no significant differences. Therefore, the data obtained using the two systems have been combined. 
Responses were differentially amplified, displayed, digitized, and stored for analysis. A voltage window was used to reject responses contaminated by artifacts. Two to 16 responses were averaged in each stimulus condition. The interstimulus interval ranged from 2 to 60 seconds and was selected so that subsequent b-wave amplitudes were not attenuated. 47  
Full-field stimuli were presented in an integrating sphere. Stimulus intensity was measured using a calibrated photodiode (IL1700; International Light, Newburyport, MA) placed at the position of the subject’s cornea. The troland values of the stimuli were calculated by taking each subject’s pupillary diameter into account. To test rod function, after dark adaptation, responses to brief (<3 ms), short-wavelength stimuli ranging from those that evoked a small b-wave (<15 μV) to those saturating the a-wave were recorded. In the Nicolet system, a filter (Wratten 47B, λ < 510 nm) was used; in the Espion system, a 470-nm LED (half-bandwidth, 30 nm) was used. Flashes were presented over a >4 log unit range, starting with the dimmest and increasing in 0.3-log unit steps. The maximum intensity flash produced approximately 3.0 log scotopic troland seconds (scot td s) for an 8-mm pupil. 
To isolate rod function in control subjects, dark-adapted responses to photopically matched long-wavelength flashes (Wratten 29 filter, λ > 610 nm) were recorded and subtracted from the responses to the corresponding short-wavelength flashes. 48  
Cone function was tested using long-wavelength flashes. In the Nicolet system, a filter (Wratten 29, λ > 610 nm) was used; in the Espion system, a 630-nm LED (half-bandwidth, 30 nm) was used. A 1.8-log unit range of red flash intensities was presented on a steady, rod-saturating background (∼3 log photopic trolands). The maximum intensity flash produced approximately 3.2 log photopic troland seconds (phot td s) for an 8-mm pupil. Seventeen of the 21 patients were also tested with a 30-Hz flickering white stimulus (2.4 log phot td s). 
Rod photoresponse characteristics were estimated from the a-wave by means of the Hood and Birch formulation 49 of the Lamb and Pugh model 50 51 52 of the biochemical processes involved in the activation of rod phototransduction. A curve-fitting routine (f min subroutine; MATLAB; The MathWorks) was used to determine the best-fitting values of S rod [(scot td)−1 s−3], R rod (μV), and t d (a brief delay, seconds) in the following equation:  
\[\mathrm{P}_{3}(\mathrm{I,t}){=}{\{}1{-}\mathrm{exp}{[}{-}0.5\ \mathrm{I}\ S_{rod}(\mathrm{t}{-}t_{d})^{2}{]}{\}}R_{rod}\ \mathrm{for}\ \mathrm{t}{>}t_{d}\]
In this equation, I is the flash in scotopic troland seconds. Assuming that the number of isomerizations of rhodopsin produced by the stimulus is known, the term S rod is related to the amplification constant, A, in the molecular models. 50 51 52 53 In these models, A summarizes the kinetics of the series of processes, initiated by the photoisomerization of rhodopsin, that result in closure of the channels in the plasma membrane of the photoreceptor. R rod is an estimate of the amplitude of the saturated response. Fitting of the model was restricted to the leading edge of the a-wave or to a maximum of 20 ms after stimulus onset. 
The b-wave responses to short-wavelength flashes were also analyzed. The stimulus/response function  
\[\mathrm{V(I)}{=}V_{max}{[}\mathrm{I/(I}{+}{\sigma}){]}\]
was fit to the b-wave amplitudes of each subject. In this equation, V is the b-wave amplitude produced by flash intensity I, V max (μV) is the saturated amplitude, I is the stimulus in scot td s, and σ is the stimulus that evokes a half-maximum b-wave amplitude. The function was fit only up to those higher intensities at which substantial a-wave intrusion occurred (∼+1.0 log scot td s). 54  
As established by Granit, the ERG waveform represents the algebraic sum of photoreceptor and postreceptor retinal responses. 55 56 The isolated rod photoresponse, called P3, is modeled by equation 1 . To evaluate postreceptor function, designated P2, a putatively “pure” postreceptor response was isolated from the intact electroretinogram by digital subtraction of P3 from the record. P2 primarily represents the bipolar cell response. 57 58 59 60 61  
For P2, the relation between flash intensity and the elapsed time between stimulus presentation and the instant at which the response reaches an arbitrary criterion voltage will be linear on a log-log plot with slope −0.2 in normal retina, consistent with three stages of integration in the rod photoreceptor and three stages of integration in the rod bipolar cell. 59 Departures from this relation indicate dysfunction of the ON bipolar cell G-protein cascade. 59 60 We selected a 50-μV criterion and noted the latency at which the rising phase of P2 reached that criterion. For a family of P2 waves, we plotted the latency-versus-intensity relationship. To test for dysfunction, regression lines were fit, and the slope of the regression line (P2 slope) in patients was compared with that in control subjects. 
Oscillatory potentials (OPs) were extracted from the derived postreceptor response (P2), as described previously. 62 In brief, P2 was digitally filtered using a fifth-order Butterworth filter (butter subroutine; MATLAB; The MathWorks) with bandpass 75 to 300 Hz. 63 The amplitude (μV) of each OP wavelet was defined as the difference between the peak and the trough immediately preceding it. To characterize the OPs, the summed amplitude of the OPs (SOPA) at each intensity was plotted as a function of stimulus energy, and the Michaelis-Menton equation  
\[\mathrm{SOPA(I)}{=}SOPA_{max}{[}\mathrm{I}^{\mathrm{n}}/(\mathrm{I}^{\mathrm{n}}{+}SOPA_{\mathit{1/2}}^{\mathrm{n}}){]}\]
was fit to the data. In this equation, SOPA(I) is the summed amplitude (μV) of the OPs in the response to a flash of I intensity, SOPA max is the saturated amplitude (μV) of the OPs, and SOPA 1/2 is the intensity at which the summed amplitude of the OPs is half SOPA max
Statistical Analyses
Preliminary analyses showed no significant difference between ACHR and BCM patients on any of the ERG parameters (S rod , R rod , log σ, V max , log SOPA 1/2 , SOPA max , and P2 slope; t-tests: df = 19; P > 0.2 on all tests). Furthermore, for each parameter, the range of values for ACHR and BCM patients was similar. Therefore, data from the two patient groups were pooled, and individual, independent sample t-tests for each ERG parameter were used to detect differences between patients and control subjects. The significance level for all tests was P < 0.01. 
Results
In Figure 1 , sample ERG records from an ACHR patient obtained in scotopic (Fig. 1A)and photopic (Fig. 1B)conditions are shown. In all patients with ACHR or BCM, scotopic activity was observed over a ≥3-log unit range of intensities, whereas photopic activity was absent or markedly attenuated (<5% of normal mean amplitude). Figure 1Cshows sample fits of the model (equation 1)of the activation of rod phototransduction 49 50 51 52 to the a-wave. Figure 1Dshows the fit of equation 2for determining the postreceptor (b-wave) response parameters. Note that lower values of log σ indicate greater sensitivity; that is, lower intensity produces the half-maximum response. 
Figure 2shows P2 responses derived from the records in Figure 1Aand a plot of the latency-versus-intensity relationship. Scotopic OP records extracted from the P2 responses shown in Figure 2are displayed in Figure 3 ; OPs from a control subject are also shown. 
Rod photoreceptor and postreceptor response parameters for the patients with ACHR and BCM and for control subjects are summarized in Figure 4 . Amplitude parameters for rods, R rod (t = −7.484, df = 31, P < 0.001) and for postreceptor activity, V max (t = −6.821, df = 31, P < 0.001) and SOPA max (t = −10.755, df = 31, P < 0.001) were significantly lower in patients than in controls, with little overlap. For all sensitivity parameters (S rod , log σ, and log SOPA 1/2 ), there was substantial overlap between patients and controls. However, b-wave log σ in patients differed significantly from that in controls (t = 3.152, df = 31, P = 0.0036); in patients, higher intensity was needed to evoke a half-maximum response. In a previous study of young, healthy subjects with myopia (as high as −10 diopters), we found no differences in rod and rod-driven postreceptor response parameters between myopes and controls. 64  
The mean slope of regression lines fit to P2 latency versus intensity plots was −0.19 (SD = 0.04) in the 12 control subjects and −0.20 (SD = 0.04) in the ACHR and BCM patients. These values were not significantly different from each other or from the normal mean slope of −0.2. 59 60 65  
Discussion
In these young patients with ACHR and BCM, we have demonstrated significant deficits in rod and rod-driven function. Specifically, mean photoreceptor (R rod ) and postreceptor (V max and SOPA max ) amplitude parameters were reduced compared with those in normal controls (Fig. 4) . Sensitivity parameters (S rod , log σ, log SOPA 1/2 ) were less affected; only b-wave log σ differed significantly from normal. 
Although rod photoreceptors are not directly affected by the genetic mutations causing ACHR and BCM, it has been suggested that alterations in rod structure occur. High-resolution adaptive optics imaging of the photoreceptor mosaic in a subject with CNGB3 ACHR showed increased diameter of rod inner segments, possibly due to rods expanding into space that would normally be occupied by cones. 66 In this subject, the density of rods at 10° eccentricity was reduced by about one-third compared with normal. 66 67 Thus, the low values of R rod in our ACHR and BCM subjects may be attributed to a decrease in the total number of rods. Shorter rod outer segment length would also reduce R rod . To our knowledge, rod outer segment length has not been measured in ACHR or BCM. 
Only one other study 10 quantitatively investigated rod activation in patients with ACHR. Khan et al. 10 evaluated four adults with CNGB3 ACHR who showed macular atrophy in middle age. Their rod photoreceptor and postreceptor amplitude parameters fell within the range of values observed in our patients. Our patients were younger than theirs (Table 1) , yet most showed greater deficits. We observed neither fundus abnormalities nor progressive worsening in visual acuity or dark-adapted visual thresholds in our patients. We wonder, therefore, whether the alterations in rod and rod-driven function may indicate anomalies in rod pathway signaling rather than rod disease. Persons with ACHR and BCM prefer dim environments, which would increase the metabolic load placed on the rods. This, in turn, would result in more circulating current, which would require more energy with possible adverse long-term effects on rod function. Thus, the low calculated values of R rod could be due to fewer rods, shorter rod outer segments, or defective rod functioning. 
In addition to the significant deficit in rod photoresponse amplitude, we observed deficits in postreceptor response parameters (V max , log σ, and SOPA max ). According to an explicit model, changes in R rod are predicted to alter b-wave sensitivity (log σ) but to have little effect on V max . 58 68 In our patients, mean log σ and mean V max were both approximately half the values in controls. The low V max could be caused by too few rod-driven bipolar cells. Although we are unaware of any anatomic evidence that the number of rod bipolar cells is reduced in ACHR or BCM, the reduced rod density found in the subject with ACHR 66 may be accompanied by a proportionate reduction in rod bipolar cell density. In another system (immature simian central retina), the numbers of cones and cone bipolar cells are proportionately decreased. 69 Another possible explanation for the reduction in V max that is consistent with the explicit model 58 68 is a postreceptor change resulting from abnormal function of rod bipolar cells. However, the normal P2 latency versus intensity slope (Fig. 2)indicates that, at the least, the G-protein amplification cascade in the rod bipolar cell was operational. 
Our data do not allow us to exclude the possibility that there is some alteration of the rod-driven circuitry in ACHR and BCM. Reorganization of the postreceptor retina is a well-documented consequence in a number of photoreceptor disorders. 62 70 71 72 73 The normal scotopic pathway is dominated by the rod-specific hyperpolarizing bipolar cell. 74 In addition to this primary pathway, there are anatomic connections between rods and cones and some between rods and depolarizing cone bipolar cells. 75 76 77 78 79 80 81 We speculate that the latter contacts may be more numerous in cone-deficient ACHR and BCM retinas. This would allow substantial rod input to cone-depolarizing bipolar cells, with consequent reduction in the apparent postreceptor response from the primary rod pathway in ACHR and BCM. In a CNGA3−/− mouse model, anomalous synapses between rods and cone bipolar cells are documented. 82  
OPs are affected by inputs from both rods and cones. 83 84 In ACHR and BCM retinas, cone input is absent or greatly diminished, possibly accounting for the dramatic attenuation in SOPA max observed in our patients. 
Whatever the actual mechanisms, the ERG data reported herein add evidence that deficits in rod and rod-mediated function occur in the primary cone dysfunction syndromes ACHR and BCM. Although it is well established that cones are adversely affected in primary rod disorders, 82 85 86 87 88 89 90 91 there is less evidence that rods are affected in disorders with primary cone dysfunction. 10 23 92  
Each of the possible mechanisms for abnormal retinal function considered leads to hypotheses that can be tested by further ultra-high resolution imaging of persons with ACHR and BCM and by study of animal models. 82 92 93 94 The new knowledge obtained will bolster efforts to design and evaluate effective therapies for cone dysfunction syndromes. 95 96  
 
Table 1.
 
Characteristics of Achromatopsia and Blue Cone Monochromatism Patients
Table 1.
 
Characteristics of Achromatopsia and Blue Cone Monochromatism Patients
Patient Sex Age at ERG (y) Spherical Equivalent (D) Visual Acuity (most recent) Photo Phobia Nystagmus PPR*
ACHR
 1 F 1.0 +3.75, ‡ 20/190, § Yes Yes Yes
 2 F 1.1 +5.50, ‡ 20/960, § No Yes Yes
 3 F 1.2 +6.50, ‡ 20/250 Yes Yes No
 4 M 1.5, † +7.75, ‡ 20/500 Yes Yes No
 5 M 1.6 +0.25 20/125 Yes Yes Yes
 6 F 2.3 +4.00, ‡ 20/133, § Yes Yes Yes
 7 M 2.3 +8.50, ‡ 20/180, § Yes Yes No
 8 M 2.7 +2.00 20/400 Yes Yes Yes
 9 F 3.0 +4.25, ‡ 20/250 Yes Yes Yes
 10 F 3.9 +8.00, ‡ 20/300 Yes Yes Yes
 11 F 4.9 −3.00, ‡ 20/320 Yes Yes Yes
 12 M 6.2, † +3.75, ‡ 20/200 No Yes No
 13 M 7.0 +1.00 20/222 Yes Yes Yes
 14 M 7.7, † −4.75, ‡ 20/200 Yes Yes No
 15 F 20.2, † −1.50 20/125 Yes Yes Yes
BCM
 16 M 4.0 −2.88, ‡ 20/160 Mild Yes Yes
 17 M 6.8 −1.75, ‡ 20/209 No Yes Yes
 18 M 7.7 −6.13, ‡ 20/400 Yes Yes Yes
 19 M 8.3, † −1.63 20/160 Mild Yes No
 20 M 9.4, † −0.50 20/80 Mild Yes Yes
 21 M 22.1, † −10.25, ‡ 20/130 Mild Yes No
Figure 1.
 
Sample ERG results from patient ACHR 9 whose scotopic amplitudes were near the mean for patients. (A) Dark-adapted ERG responses to a series of short-wavelength flashes. For clarity, the stimulus intensity in log scot td s is shown only for every other trace. (B) Light-adapted ERG responses to two long-wavelength flash intensities, +3.2 and +2.4 log phot td s, and to 30-Hz flickering white light (+2.4 log phot td s). The calibration bar pertains to A and B. (C) The first 40 ms of the ERG (solid lines) and the fit of equation 1(dashed lines) to the leading edge of the a-wave. Parameters S rod and R rod for the model fit to the data are indicated. (D) b-Wave amplitude plotted as a function of stimulus intensity. Equation 2was fit up to ∼+1.0 log scot td s, indicated by the closed circles; parameters V max and log σ are indicated.
Figure 1.
 
Sample ERG results from patient ACHR 9 whose scotopic amplitudes were near the mean for patients. (A) Dark-adapted ERG responses to a series of short-wavelength flashes. For clarity, the stimulus intensity in log scot td s is shown only for every other trace. (B) Light-adapted ERG responses to two long-wavelength flash intensities, +3.2 and +2.4 log phot td s, and to 30-Hz flickering white light (+2.4 log phot td s). The calibration bar pertains to A and B. (C) The first 40 ms of the ERG (solid lines) and the fit of equation 1(dashed lines) to the leading edge of the a-wave. Parameters S rod and R rod for the model fit to the data are indicated. (D) b-Wave amplitude plotted as a function of stimulus intensity. Equation 2was fit up to ∼+1.0 log scot td s, indicated by the closed circles; parameters V max and log σ are indicated.
Figure 2.
 
(A) Sample P2 records from ACHR 9. Inset: derivation of P2. (B) Latency at the 50-μV criterion plotted as a function of log stimulus intensity. The regression line has a slope of −0.20.
Figure 2.
 
(A) Sample P2 records from ACHR 9. Inset: derivation of P2. (B) Latency at the 50-μV criterion plotted as a function of log stimulus intensity. The regression line has a slope of −0.20.
Figure 3.
 
Scotopic oscillatory potentials for a series of flash intensities from ACHR 9 (left) and for a control subject (right). For clarity, the stimulus intensity in log scot td s is shown only for every other trace. Note that ACHR patient records are plotted at twice the gain of control subject.
Figure 3.
 
Scotopic oscillatory potentials for a series of flash intensities from ACHR 9 (left) and for a control subject (right). For clarity, the stimulus intensity in log scot td s is shown only for every other trace. Note that ACHR patient records are plotted at twice the gain of control subject.
Figure 4.
 
Rod photoresponse parameters, S rod and R rod , and postreceptor parameters, log σ, V max , log SOPA 1/2 , and SOPA max . Top: amplitude parameters (R rod , V max , and SOPA max ). Bottom: sensitivity parameters (S rod , log σ, and log SOPA 1/2 ). Log values are plotted for all parameters. Data for control subjects (triangles), patients with ACHR (filled circles), and patients with BCM (open circles) are shown in each graph. Horizontal lines: mean for each group.
Figure 4.
 
Rod photoresponse parameters, S rod and R rod , and postreceptor parameters, log σ, V max , log SOPA 1/2 , and SOPA max . Top: amplitude parameters (R rod , V max , and SOPA max ). Bottom: sensitivity parameters (S rod , log σ, and log SOPA 1/2 ). Log values are plotted for all parameters. Data for control subjects (triangles), patients with ACHR (filled circles), and patients with BCM (open circles) are shown in each graph. Horizontal lines: mean for each group.
MichaelidesM, HolderG, MooreA. Inherited retinal dystrophies.TaylorD HoytC eds. Pediatric Ophthalmology and Strabismus. 2005; 3rd ed. 183–241.Elsevier Saunders New York.
MichaelidesM, HuntDM, MooreAT. The cone dysfunction syndromes. Br J Ophthalmol. 2004;88:291–297. [CrossRef] [PubMed]
PokornyJ, SmithVC, VerriestG. Congenital color defects.PokornyJ SmithV VerriestG PinckersA eds. Congenital and Acquired Color Vision Deficits. 1979;Grune & Stratton New York.
KrillAE. Congenital color vision defects.KrillAE eds. Hereditary Retinal and Choroidal Disease. 1977;11:335–390.Harper & Row London.
HansenE. Clinical aspects of achromatopsia.HessR SharpeL NordbyK eds. Night Vision: Basic, Clinical and Applied Aspects. 1990;316–334.Cambridge University Press Cambridge.
KellyJP, CrognaleMA, WeissAH. ERGs, cone-isolating VEPs and analytical techniques in children with cone dysfunction syndromes. Doc Ophthalmol. 2003;106:289–304. [CrossRef] [PubMed]
WissingerB, GamerD, JagleH, et al. CNGA3 mutations in hereditary cone photoreceptor disorders. Am J Hum Genet. 2001;69:722–737. [CrossRef] [PubMed]
Haegerstrom-PortnoyG, SchneckME, VerdonWA, HewlettSE. Clinical vision characteristics of the congenital achromatopsias, I: visual acuity, refractive error, and binocular status. Optom Vis Sci. 1996;73:446–456. [CrossRef] [PubMed]
GoodmanG, RippsH, SiegelIM. Cone dysfunction syndromes. Arch Ophthalmol. 1963;70:214–231. [CrossRef] [PubMed]
KhanNW, WissingerB, KohlS, SievingPA. CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function. Invest Ophthalmol Vis Sci. 2007;48:3864–3871. [CrossRef] [PubMed]
SpiveyBE. The X-linked recessive inheritance of atypical monochromatism. Arch Ophthalmol. 1965;74:327–333. [CrossRef] [PubMed]
BlackwellH, BlackwellO. Rod and cone receptor mechanisms in typical and atypical congenital achromatopsia. Vision Res. 1961;1:62–107. [CrossRef]
FrancoisJ, VerriestG, Matton-Van LeuvenT, De RouckA, ManavianD. Atypical achromatopia of sex-linked recessive inheritance. Am J Ophthalmol. 1966;61:1101–1108. [CrossRef] [PubMed]
WeleberR, EisnerA. Cone degeneration (“bull’s eye dystropies”) and colour vision defects.NewsomeD eds. Retinal Dystropies and Degenerations. 1988;223–256.Raven Press New York.
WeissAH, BiersdorfWR. Blue cone monochromatism. J Pediatr Ophthalmol Strabismus. 1989;26:218–223. [PubMed]
BersonEL, SandbergMA, RosnerB, SullivanPL. Color plates to help identify patients with blue cone monochromatism. Am J Ophthalmol. 1983;95:741–747. [CrossRef] [PubMed]
PinckersA. Berson test for blue cone monochromatism. Int Ophthalmol. 1992;16:185–186. [CrossRef] [PubMed]
Haegerstrom-PortnoyG, SchneckME, VerdonWA, HewlettSE. Clinical vision characteristics of the congenital achromatopsias, II: color vision. Optom Vis Sci. 1996;73:457–465. [CrossRef] [PubMed]
SharpeL, NordbyK. The photoreceptors in the achromat.HessR SharpeL NordbyK eds. Night Vision: Basic, Clinical and Applied Aspects. 1990;335–389.Cambridge University Press Cambridge.
AyyagariR, KakukLE, BinghamEL, et al. Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy. Hum Genet. 2000;107:75–82. [CrossRef] [PubMed]
AyyagariR, KakukLE, CoatsCL, et al. Bilateral macular atrophy in blue cone monochromacy (BCM) with loss of the locus control region (LCR) and part of the red pigment gene. Mol Vis. 1999;5:13. [PubMed]
FleischmanJA, O'DonnellFE, Jr. Congenital X-linked incomplete achromatopsia: evidence for slow progression, carrier fundus findings, and possible genetic linkage with glucose-6-phosphate dehydrogenase locus. Arch Ophthalmol. 1981;99:468–472. [CrossRef] [PubMed]
KellnerU, WissingerB, TippmannS, KohlS, KrausH, FoersterMH. Blue cone monochromatism: clinical findings in patients with mutations in the red/green opsin gene cluster. Graefes Arch Clin Exp Ophthalmol. 2004;242:729–735. [CrossRef] [PubMed]
MichaelidesM, JohnsonS, SimunovicMP, et al. Blue cone monochromatism: a phenotype and genotype assessment with evidence of progressive loss of cone function in older individuals. Eye. 2005;19:2–10. [CrossRef] [PubMed]
NathansJ, DavenportCM, MaumeneeIH, et al. Molecular genetics of human blue cone monochromacy. Science. 1989;245:831–838. [CrossRef] [PubMed]
EksandhL, KohlS, WissingerB. Clinical features of achromatopsia in Swedish patients with defined genotypes. Ophthal Genet. 2002;23:109–120. [CrossRef] [PubMed]
NishiguchiKM, SandbergMA, GorjiN, BersonEL, DryjaTP. Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum Mutat. 2005;25:248–258. [CrossRef] [PubMed]
KohlS, VarsanyiB, AntunesGA, et al. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet. 2005;13:302–308. [CrossRef] [PubMed]
KohlS, BaumannB, BroghammerM, et al. Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet. 2000;9:2107–2116. [CrossRef] [PubMed]
JohnsonS, MichaelidesM, AligianisIA, et al. Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J Med Genet. 2004;41:e20. [CrossRef] [PubMed]
SundinOH, YangJM, LiY, et al. Genetic basis of total colour blindness among the Pingelapese islanders. Nat Genet. 2000;25:289–293. [CrossRef] [PubMed]
KohlS, BaumannB, RosenbergT, et al. Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet. 2002;71:422–425. [CrossRef] [PubMed]
AligianisIA, ForshewT, JohnsonS, et al. Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the alpha subunit of cone transducin (GNAT2). J Med Genet. 2002;39:656–660. [CrossRef] [PubMed]
NathansJ, MaumeneeIH, ZrennerE, et al. Genetic heterogeneity among blue-cone monochromats. Am J Hum Genet. 1993;53:987–1000. [PubMed]
ThalerARG, LesselMR, HeiligP. Light-induced oscillations of the standing potential in achromatopsia. Doc Ophthalmol. 1986;63:333–336. [PubMed]
AndreassonS, TornqvistK. Electroretinograms in patients with achromatopsia. Acta Ophthalmol. 1991;69:711–716.
CrognaleMA, FryM, HighsmithJ, et al. Characterization of a novel form of X-linked incomplete achromatopsia. Vis Neurosci. 2004;21:197–203. [CrossRef] [PubMed]
Defoort-DhellemmesS, LebrunT, ArndtCF, et al. [Congenital achromatopsia: electroretinogram in early diagnosis]. J Fr Ophthalmol. 2004;27:143–148. [CrossRef]
MichaelidesM, AligianisIA, AinsworthJR, et al. Progressive cone dystrophy associated with mutation in CNGB3. Invest Ophthalmol Vis Sci. 2004;45:1975–1982. [CrossRef] [PubMed]
TellerDY, McDonaldMA, PrestonK, SebrisSL, DobsonV. Assessment of visual acuity in infants and children: the acuity card procedure. Dev Med Child Neurol. 1986;28:779–789. [PubMed]
MayerDL, HansenRM, MooreBD, KimS, FultonAB. Cycloplegic refractions in healthy children aged 1 through 48 months. Arch Ophthalmol. 2001;119:1625–1628. [CrossRef] [PubMed]
ZadnikK, MannyRE, YuJA, et al. Ocular component data in schoolchildren as a function of age and gender. Optom Vis Sci. 2003;80:226–236. [CrossRef] [PubMed]
HansenRM, FultonAB. Development of scotopic retinal sensitivity.SimonsK eds. Early Visual Development, Normal and Abnormal. 1993;130–142.Oxford University Press New York.
FultonAB, HansenRM. The development of scotopic sensitivity. Invest Ophthalmol Vis Sci. 2000;41:1588–1596. [PubMed]
WongpichedchaiS, HansenRM, KokaB, GudasVM, FultonAB. Effects of halothane on children’s electroretinograms. Ophthalmology. 1992;99:1309–1312. [CrossRef] [PubMed]
FultonAB, HansenRM, MoskowitzA. The cone electroretinogram in retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2008;49:814–819. [CrossRef] [PubMed]
HansenRM, FultonAB. Development of the cone ERG in infants. Invest Ophthalmol Vis Sci. 2005;46:3458–3462. [CrossRef] [PubMed]
BirchDG, FishGE. Rod ERGs in retinitis pigmentosa and cone-rod degeneration. Invest Ophthalmol Vis Sci. 1987;28:140–150. [PubMed]
HoodDC, BirchDG. Rod phototransduction in retinitis pigmentosa: estimation and interpretation of parameters derived from the rod a-wave. Invest Ophthalmol Vis Sci. 1994;35:2948–2961. [PubMed]
LambTD, PughENJ. Phototransduction in vertebrate rods and cones: molecular mechanisms of amplification, recovery and light adaptation.StavengaDG deGripW PughENJ eds. Handbook of Biological Physics. 2000;3:183–255.Elsevier Amsterdam.
LambTD, PughEN, Jr. A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. J Physiol. 1992;449:719–758. [CrossRef] [PubMed]
PughEN, Jr, LambTD. Amplification and kinetics of the activation steps in phototransduction. Biochim Biophys Acta. 1993;1141:111–149. [CrossRef] [PubMed]
CideciyanAV, JacobsonSG. An alternative phototransduction model for human rod and cone ERG a-waves: normal parameters and variation with age. Vision Res. 1996;36:2609–2621. [CrossRef] [PubMed]
PeacheyNS, AlexanderKR, FishmanGA. The luminance-response function of the dark-adapted human electroretinogram. Vision Res. 1989;29:263–270. [CrossRef] [PubMed]
GranitR. The components of the retinal action potential in mammals and their relation to the discharge in the optic nerve. J Physiol. 1933;77:207–239. [CrossRef] [PubMed]
GranitR. The components of the vertebrate electroretinogram. Sensory Mechanisms of the Retina. 1963;38–68.Hafner Publishing London.
AlemanT, LaVailMM, MontemayorR, et al. Augmented rod bipolar cell function in partial receptor loss: an ERG study in P23H rhodopsin transgenic and aging normal rats. Vision Res. 2001;41:2779–2797. [CrossRef] [PubMed]
HoodDC, BirchDG. A computational model of the amplitude and implicit time of the b-wave of the human ERG. Vis Neurosci. 1992;8:107–126. [CrossRef] [PubMed]
RobsonJG, FrishmanLJ. Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram. Vis Neurosci. 1995;12:837–850. [CrossRef] [PubMed]
RobsonJG, FrishmanLJ. Photoreceptor and bipolar cell contributions to the cat electroretinogram: a kinetic model for the early part of the flash response. J Opt Soc Am. 1996;13:613–622.
WurzigerK, LichtenbergerT, HanitzschR. On-bipolar cells and depolarising third order neurons as the origin of the ERG b-wave in the RCS rat. Vis Res. 2001;41:1091–1101. [CrossRef] [PubMed]
AkulaJD, MockoJA, MoskowitzA, HansenRM, FultonAB. The oscillatory potentials of the dark-adapted electroretinogram in retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2007;48:5788–5797. [CrossRef] [PubMed]
MarmorMF, HolderGE, SeeligerMW, YamamotoS. Standard for clinical electroretinography (2004 update). Doc Ophthalmol. 2004;108:107–114. [CrossRef] [PubMed]
MoskowitzA, HansenR, FultonA. Early ametropia and rod photoreceptor function in retinopathy of prematurity. Optom Vis Sci. 2005;82:307–317. [CrossRef] [PubMed]
CooperLL, HansenRM, DarrasBT, et al. Rod photoreceptor function in children with mitochondrial disorders. Arch Ophthalmol. 2002;120:1055–1062. [CrossRef] [PubMed]
CarrollJ, ChoiSS, WilliamsDR. In vivo imaging of the photoreceptor mosaic of a rod monochromat. Vis Res. 2008;48:2564–2568. [CrossRef] [PubMed]
CurcioCA, SloanKR, KalinaRE, HendricksonAE. Human photoreceptor topography. J Comp Neurol. 1990;292:497–523. [CrossRef] [PubMed]
HoodDC, BirchDG, BirchEE. Use of models to improve hypothesis delineation: a study of infant electroretinography.SimonsK eds. Early Visual Development, Normal and Abnormal. 1993;517–535.Oxford University Press New York.
ChanTL, MartinPR, ClunasN, GrunertU. Bipolar cell diversity in the primate retina: morphologic and immunocytochemical analysis of a new world monkey, the marmoset Callithrix jacchus. J Comp Neurol. 2001;437:219–239. [CrossRef] [PubMed]
JonesBW, MarcRE. Retinal remodeling during retinal degeneration. Exp Eye Res. 2005;81:123–137. [CrossRef] [PubMed]
JonesBW, WattCB, MarcRE. Retinal remodelling. Clin Exp Optom. 2005;88:282–291. [CrossRef] [PubMed]
MarcRE, JonesBW. Retinal remodeling in inherited photoreceptor degenerations. Mol Neurobiol. 2003;28:139–147. [CrossRef] [PubMed]
LuM, HansenRM, CunninghamMJ, EklundSE, FultonAB. Effects of desferoxamine on retinal and visual function. Arch Ophthalmol. 2007;125:1581–1582. [CrossRef] [PubMed]
KolbH. The architecture of functional neural circuits in the vertebrate retina: the Proctor Lecture (published correction appears in Invest Ophthalmol Vis Sci. 1994;35:3576). Invest Ophthalmol Vis Sci. 1994;35:2385–404. [PubMed]
RaviolaE, GilulaNB. Gap junctions between photoreceptor cells in the vertebrate retina. Proc Natl Acad Sci U S A. 1973;70:1677–1681. [CrossRef] [PubMed]
NelsonR. Cat cones have rod input: a comparison of the response properties of cones and horizontal cell bodies in the retina of the cat. J Comp Neurol. 1977;172:109–135. [CrossRef] [PubMed]
SmithRG, FreedMA, SterlingP. Microcircuitry of the dark-adapted cat retina: functional architecture of the rod-cone network. J Neurosci. 1986;6:3505–3517. [PubMed]
DawNW, JensenRJ, BrunkenWJ. Rod pathways in mammalian retinae. Trends Neurosci. 1990;13:110–115. [CrossRef] [PubMed]
SchneeweisDM, SchnapfJL. Photovoltage of rods and cones in the macaque retina. Science. 1995;268:1053–1056. [CrossRef] [PubMed]
SharpeLT, StockmanA. Rod pathways: the importance of seeing nothing. Trends Neurosci. 1999;22:497–504. [CrossRef] [PubMed]
BuckSL. Rod-cone interactions in human vision.ChapulaLM WernerJS eds. The Visual Neurosciences. 2003;863–878.MIT Press Cambridge, MA.
HaverkampS, MichalakisS, ClaesE, et al. Synaptic plasticity in CNGA3(−/−) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods. J Neurosci. 2006;26:5248–5255. [CrossRef] [PubMed]
WachtmeisterL. Oscillatory potentials in the retina: what do they reveal. Prog Retin Eye Res. 1998;17:485–521. [CrossRef] [PubMed]
PeacheyNS, AlexanderKR, FishmanGA. Rod and cone system contributions to oscillatory potentials: an explanation for the conditioning flash effect. Vis Res. 1987;27:859–866. [CrossRef] [PubMed]
KajiwaraK, BersonEL, DryjaTP. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science. 1994;264:1604–1608. [CrossRef] [PubMed]
Mohand-SaidS, HicksD, LeveillardT, PicaudS, PortoF, SahelJA. Rod-cone interactions: developmental and clinical significance. Prog Retin Eye Res. 2001;20:451–467. [CrossRef] [PubMed]
RippsH. Cell death in retinitis pigmentosa: gap junctions and the “bystander” effect. Exp Eye Res. 2002;74:327–336. [CrossRef] [PubMed]
PinillaI, LundRD, SauveY. Contribution of rod and cone pathways to the dark-adapted electroretinogram (ERG) b-wave following retinal degeneration in RCS rats. Vis Res. 2004;44:2467–2474. [CrossRef] [PubMed]
TodaK, BushRA, HumphriesP, SievingPA. The electroretinogram of the rhodopsin knockout mouse. Vis Neurosci. 1999;16:391–398. [PubMed]
UsukuraJ, KhooW, AbeT, BreitmanML, ShinoharaT. Cone cells fail to develop normally in transgenic mice showing ablation of rod photoreceptor cells. Cell Tissue Res. 1994;275:79–90. [CrossRef] [PubMed]
CideciyanAV, HoodDC, HuangY, et al. Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man. Proc Natl Acad Sci U S A. 1998;95:7103–7108. [CrossRef] [PubMed]
ChangB, DaceyMS, HawesNL, et al. Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2. Invest Ophthalmol Vis Sci. 2006;47:5017–5021. [CrossRef] [PubMed]
BielM, SeeligerM, PfeiferA, et al. Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc Natl Acad Sci U S A. 1999;96:7553–7557. [CrossRef] [PubMed]
SidjaninDJ, LoweJK, McElweeJL, et al. Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet. 2002;11:1823–1833. [CrossRef] [PubMed]
KomaromyAM, AlexanderJJ, CooperAE, et al. Targeting gene expression to cones with human cone opsin promoters in recombinant AAV. Gene Ther. 2008;15:1073. [CrossRef]
AlexanderJJ, UminoY, EverhartD, et al. Restoration of cone vision in a mouse model of achromatopsia. Nat Med. 2007;13:685–687. [CrossRef] [PubMed]
Figure 1.
 
Sample ERG results from patient ACHR 9 whose scotopic amplitudes were near the mean for patients. (A) Dark-adapted ERG responses to a series of short-wavelength flashes. For clarity, the stimulus intensity in log scot td s is shown only for every other trace. (B) Light-adapted ERG responses to two long-wavelength flash intensities, +3.2 and +2.4 log phot td s, and to 30-Hz flickering white light (+2.4 log phot td s). The calibration bar pertains to A and B. (C) The first 40 ms of the ERG (solid lines) and the fit of equation 1(dashed lines) to the leading edge of the a-wave. Parameters S rod and R rod for the model fit to the data are indicated. (D) b-Wave amplitude plotted as a function of stimulus intensity. Equation 2was fit up to ∼+1.0 log scot td s, indicated by the closed circles; parameters V max and log σ are indicated.
Figure 1.
 
Sample ERG results from patient ACHR 9 whose scotopic amplitudes were near the mean for patients. (A) Dark-adapted ERG responses to a series of short-wavelength flashes. For clarity, the stimulus intensity in log scot td s is shown only for every other trace. (B) Light-adapted ERG responses to two long-wavelength flash intensities, +3.2 and +2.4 log phot td s, and to 30-Hz flickering white light (+2.4 log phot td s). The calibration bar pertains to A and B. (C) The first 40 ms of the ERG (solid lines) and the fit of equation 1(dashed lines) to the leading edge of the a-wave. Parameters S rod and R rod for the model fit to the data are indicated. (D) b-Wave amplitude plotted as a function of stimulus intensity. Equation 2was fit up to ∼+1.0 log scot td s, indicated by the closed circles; parameters V max and log σ are indicated.
Figure 2.
 
(A) Sample P2 records from ACHR 9. Inset: derivation of P2. (B) Latency at the 50-μV criterion plotted as a function of log stimulus intensity. The regression line has a slope of −0.20.
Figure 2.
 
(A) Sample P2 records from ACHR 9. Inset: derivation of P2. (B) Latency at the 50-μV criterion plotted as a function of log stimulus intensity. The regression line has a slope of −0.20.
Figure 3.
 
Scotopic oscillatory potentials for a series of flash intensities from ACHR 9 (left) and for a control subject (right). For clarity, the stimulus intensity in log scot td s is shown only for every other trace. Note that ACHR patient records are plotted at twice the gain of control subject.
Figure 3.
 
Scotopic oscillatory potentials for a series of flash intensities from ACHR 9 (left) and for a control subject (right). For clarity, the stimulus intensity in log scot td s is shown only for every other trace. Note that ACHR patient records are plotted at twice the gain of control subject.
Figure 4.
 
Rod photoresponse parameters, S rod and R rod , and postreceptor parameters, log σ, V max , log SOPA 1/2 , and SOPA max . Top: amplitude parameters (R rod , V max , and SOPA max ). Bottom: sensitivity parameters (S rod , log σ, and log SOPA 1/2 ). Log values are plotted for all parameters. Data for control subjects (triangles), patients with ACHR (filled circles), and patients with BCM (open circles) are shown in each graph. Horizontal lines: mean for each group.
Figure 4.
 
Rod photoresponse parameters, S rod and R rod , and postreceptor parameters, log σ, V max , log SOPA 1/2 , and SOPA max . Top: amplitude parameters (R rod , V max , and SOPA max ). Bottom: sensitivity parameters (S rod , log σ, and log SOPA 1/2 ). Log values are plotted for all parameters. Data for control subjects (triangles), patients with ACHR (filled circles), and patients with BCM (open circles) are shown in each graph. Horizontal lines: mean for each group.
Table 1.
 
Characteristics of Achromatopsia and Blue Cone Monochromatism Patients
Table 1.
 
Characteristics of Achromatopsia and Blue Cone Monochromatism Patients
Patient Sex Age at ERG (y) Spherical Equivalent (D) Visual Acuity (most recent) Photo Phobia Nystagmus PPR*
ACHR
 1 F 1.0 +3.75, ‡ 20/190, § Yes Yes Yes
 2 F 1.1 +5.50, ‡ 20/960, § No Yes Yes
 3 F 1.2 +6.50, ‡ 20/250 Yes Yes No
 4 M 1.5, † +7.75, ‡ 20/500 Yes Yes No
 5 M 1.6 +0.25 20/125 Yes Yes Yes
 6 F 2.3 +4.00, ‡ 20/133, § Yes Yes Yes
 7 M 2.3 +8.50, ‡ 20/180, § Yes Yes No
 8 M 2.7 +2.00 20/400 Yes Yes Yes
 9 F 3.0 +4.25, ‡ 20/250 Yes Yes Yes
 10 F 3.9 +8.00, ‡ 20/300 Yes Yes Yes
 11 F 4.9 −3.00, ‡ 20/320 Yes Yes Yes
 12 M 6.2, † +3.75, ‡ 20/200 No Yes No
 13 M 7.0 +1.00 20/222 Yes Yes Yes
 14 M 7.7, † −4.75, ‡ 20/200 Yes Yes No
 15 F 20.2, † −1.50 20/125 Yes Yes Yes
BCM
 16 M 4.0 −2.88, ‡ 20/160 Mild Yes Yes
 17 M 6.8 −1.75, ‡ 20/209 No Yes Yes
 18 M 7.7 −6.13, ‡ 20/400 Yes Yes Yes
 19 M 8.3, † −1.63 20/160 Mild Yes No
 20 M 9.4, † −0.50 20/80 Mild Yes Yes
 21 M 22.1, † −10.25, ‡ 20/130 Mild Yes No
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