INDEX

Page numbers followed by f or t indicate figures or tables, respectively.

A

AAION. See Arteritic ischemic optic neuropathy ABCR (ABCA4) gene mutations, 727–732, 784 Abetalipoproteinemia, 803–804

Absorption filters, 271

ac (alternating current) amplifiers, 239, 245, 256–257 Accommodation

aging and, 366, 366f–367f drug-induced changes in, 661

Acetazolamide responses, 126, 128–130, 130f, 553, 554t, 555f, 562 Acetylcholine, 86

drug/toxic effects on, 657, 657f Achiasmat visual pathways, 369

Achromatopsia, 112–113, 795–796, 798t, 799–800 Activities of daily living, 542–543

Acute idiopathic enlarged blind spot syndrome, 334 Acute zonal occult outer retinopathy (AZOOR), 687, 688f

Adaptation effects, 593–596. See also Dark adaptation; Light adaptation

“Adaptation pool,” 406

ADC. See Analog-to-digital converter

Adenosine triphosphatase (ATPase) transporters, 39–40 Adhesion, and synapses, 97–105, 99f–100f Adjustment, method of, 400

Adrenaline, 88

Adrenergic responses, and light peak, 149, 149f

Adult-onset foveomacular vitelliform dystrophies/degeneration (AOFVD), 765, 765t

Age-related macular degeneration alcohol electro-oculogram in, 135, 135f color vision in, 608–610, 609f

drusen with, 717–718, 723 multifocal ERG in, 334

Sorsby’s fundus dystrophy and, 772 Aging, and visual evoked potentials, 361–367

accommodation changes with, 366, 366f–367f amplitude changes with, 361, 363f

contrast threshold changes with, 362–364, 365f gender differences in, 362, 364f

general changes with, 361–362

luminance threshold changes with, 364, 365f peak latency changes with, 361–362, 364f pupillary size and, 365

temporal frequency changes with, 362, 363f Agnosia, 116

apperceptive, 116 associative, 116 object, 116

pure visual, 116

AIPL-1 gene, and Leber congenital amaurosis, 750, 751f AIR. See Autoimmune retinopathy

Akinetopsia, 113, 113f

Åland Island eye disease (AIED), 810 Albinism

autosomal recessive, 373

brown oculocutaneous, 373 electrophysiological assessment of, 369–395 Forsius-Eriksson ocular, 810

foveal hypoplasia in, 369, 370f foveation period in, 378–382

functional magnetic resonance imaging in, 374 genetic forms of, 370–373

lateral geniculate nucleus in, 370, 372f

misrouted optic nerve fibers in, 369, 371f–372f, 514–515, 516f ocular motor disorders in, 377–382

assessment for, 377

concomitant VEP assessment in, 377–382 misalignments and instability, 377–378, 378f–380f

optic chiasm in, 369–370 phenotype of, 369, 370f tyrosinase-negative, 373 tyrosinase-positive, 373

visual evoked potentials in, 369, 373–395, 373f age and, 386–396, 390f–394f

averaging of, 380–382, 383f checkerboard stimulus for, 378–382 data analysis of, 375, 376f

genetic differences in, 386, 387f–389f

hemispheric asymmetry in, 375–377, 376f, 382–395, 385f, 387f–394f

latency of, 382, 384f methodology for, 375–377

misrouting test of, 369, 375–377, 514–515, 516f pattern onset/offset, 378–380, 381f–384f pattern reversal, 378–380, 381f

principal component analysis of, 373–374, 374f, 382–385 stimulus for, 375

topography of, versus normal controls, 382–395 visual pathway anomalies in, 369–374, 371f–372f X-linked, 373, 386, 387f–389f

Alcohol

electro-oculogram effects of, 126–127, 130–133, 131f–135f toxicity of, 659

Alexia, pure, 116–117, 117f Aliasing, 241, 241f, 258, 281, 281f Allesthesia, visual, 114–115, 115f Alpha, of Type I error, 433 Alpha rhythm, of EEG, 208, 209f

Alternating current amplifiers, 239, 245, 256–257 Amacrine cell(s), 49, 50f–51f

AII, 58, 60, 63f, 86, 93–95 dopaminergic, 60, 61f, 63f, 88 embryological origins of, 25 function of, 86

GABAergic, 58–60, 59f, 62f glycinergic, 58, 59f

image properties of, 55–56 neurotransmitters of, 86–88 ON/OFF, 58, 60f

oscillatory potentials from, 568 piggybacking by, 58, 60f postsynaptic responses of, 85–86, 87f starburst, 61f, 86

subtypes of, 85–86

Amacrine cell(s) (continued)

synapses of, 57–62, 59f–62f, 85–86

with bipolar cells, 58–60, 60f–61f, 63f, 86, 93–95, 95f Amantadine, for Parkinson’s disease, 879

Amblyopia, 643–647

hysterical, electrodiagnostic testing in, 637 neurophysiology of, 643–644

prevalence of, 643 screening for, 643 subcategories of, 643

visual evoked potentials in, 644–647 binocular, 646–647

binocular summation and facilitation of, 646 dichoptic stimulation of, 646–647 interocular differences in, 644

latent nystagmus and, 645, 645f patching and, 645, 645f pattern assessment of, 644–645 threshold measurements of, 646 Vernier acuity and, 646

Ametropia, minimal, spatial contrast loss in, 414, 415f 2-Amino-4-phosphonobutyric acid (APB)

and a-wave, 153–154, 153f and b-wave, 162, 163f and multifocal ERG, 332

and oscillatory potentials, 569–570, 570f and scotopic threshold response, 170

Amnesia, visual, 117

AMPA receptors, 51, 53f–54f Amplifiers, 238–239, 255–260, 275–278

alternating current (ac), 239, 245, 256–257 bias of, 257

characteristics of, 277–278

common mode rejection ratio of, 238, 257, 277, 559, 617–618 definition of, 275–276

differential, 238, 239f, 257, 275–276, 276f, 617–618, 617f direct current (dc), 238–239, 256–257, 559

dynamic range of, 257, 277 electrode impedance and, 277, 278f for ERG, ISCEV standard for, 292

filters for, 239–240, 257–258, 277, 277f frequency response function of, 257–258, 257f gain of, 257, 276

input and output impedance of, 257 instrumentation, 275–276

isolation, 255–256, 277–278 linearity of, 257

long-tailed pair design of, 276, 276f

for multifocal ERG, 311, 327–329, 330f offset of, 238–239, 257

operational design of, 276, 276f and patient safety, 255–256

for pattern ERG, 299, 341 and phase distortions, 260

phase-sensitive (lock-in), 241, 260–261 sample and hold, 241, 242f saturation of, and artifacts, 620

for special-purpose systems, 260–263 synchronous, 456–457, 457f–458f for VEP recording, 229, 304–305

Amplitude characteristic, 440, 441f Amplitude fluctuations, 456

Analog-to-digital converter (ADC), 240–241, 258–261, 559 aliasing error with, 241, 241f, 258

frequency of, 240–241 resolution of, 240–241

Analytical techniques, 439–457. See also specific types

Anesthetics, for animal electroretinogram, 923–924, 925t–926t, 927 Angiography, fluorescein. See Fluorescein angiography

Angiotensin II antagonist toxicity, 658

Animal testing. See also specific animals and disorders chicken, 916–919

dog, 911–916, 923–931 larger animal, 923–931

anesthetics for, 923–924, 925t–926t, 927 bilateral ERG in, 931, 931f ERG-clinical correlation in, 929–931

guidelines/protocols for, 927–929, 928f, 930f photoreceptor variations in, 923

specific procedures for, 924–927, 927f monkey, 935–941, 943–944

mouse, 899–907, 935–939, 941–944 multifocal ERG, 331–333

reverse correlation, 465–466, 466f–467f visual evoked potential, 935–944

Anomaloscope, 599 Anomia

color, 116–117 object, 116–117 Antibiotic toxicity, 657

Anticholinergic drugs, for Parkinson’s disease, 879 Anticonvulsant toxicity, 658

Antiepileptic drug toxicity, 658 Anton syndrome, 110–111, 861

APB. See 2-Amino-4-phosphonobutyric acid (APB) Aphasia, optic, 117

Apperceptive agnosia, 116 Apraxia, ocular motor, 113–114

Arginine restriction, for gyrate atrophy, 711 Aristotle’s color theory, 597

Arousal, and visual evoked potentials, 224–226 Arrestin, 68–69, 69f

migration/translocation of, 72–75, 74f in Oguchi’s disease, 836–837

Arterial occlusions, 681. See also Branch retinal artery occlusion (BRAO); Central retinal artery occlusion (CRAO)

Arteritic ischemic optic neuropathy (AAION), 699 clinical presentation of, 699

histology of, 699 treatment of, 699

Artifact(s), 278–282, 615–620 amplifier saturation and, 620 averaging and smoothing, 317, 620 common, 279–280, 279f

definition of, 278

electrode, 245, 278–279, 282, 618–619 frame pulse, 281, 281f

localization of, dummy patient for, 282, 282f, 618–619, 618f mains interference and, 615–618, 616f

in multifocal ERG, 311, 314, 316–317 in new clinic, 615

patient-related, 279, 619 photovoltaic effect and, 280 rejection of, 242, 261–262, 299, 311 sources of, 278

stroboscope, 619 weak signal, 316f, 317

Associative agnosia, 116 Ataxia, optic, 113–114 ATPase transporters, 39–40

Attention, and visual evoked potentials, 224–226 Autocorrelation, 451, 453f

Autoimmune retinopathy (AIR), 691–697 clinical presentation of, 691

diagnosis of, 695

electroretinogram in, 691, 692f–694f, 695 family histories in, 691–695

future diagnostic techniques in, 697 Average, statistical, 431

Averagers (equipment), 260 Averaging, 455–456

improving signal-to-noise ratio with, 455 ISCEV standards for, 294, 299, 304–305 practical considerations on, 456 response fluctuations and, 455–456 stimulus for, 455

Averaging artifacts, 317, 620 a-wave, 4–5, 557, 558f

abnormal maximal, 506–507

in central retinal artery occlusion, 681

in central retinal vein occlusion, 675–681, 676f–677f, 679f–680f

clinical assessment of, 497–500, 498f–499f

cone response in, 154–155, 154f, 156f, 487, 488f age and, 493, 494f

high-intensity stimulation of, 487–489 model of, 492, 493f

in retinal disease, 497, 497f

S and Rmax parameters of, 497, 497f simpler equation for, 492–493

current source density analysis of, 151, 152f dark-adapted, 150, 150f

depth profile of, 152f early studies of, 151–152

in juvenile X-linked retinoschisis, 824–825, 826f laminin defect and, 99

leading edge of, 151–152

photoreceptor health model of, 487–500 alternative models of, 493–494

fitting of, 489–495

goodness-of-fit measure of, 491–492

normative values and repeat reliability of, 493, 494f in retinal disease, 495–497, 496f–497f

light-adapted, 150, 150f, 593 mouse model of, 902–906, 902f myopia and, 631–632, 632f origins of, 149–156, 809

pharmacological dissection studies of, 152–155

postreceptoral contributions to, 152–155, 153f–155f, 491, 492f receptor photocurrent and, 151–152, 151f–152f

in retinitis pigmentosa, 506–507, 790f, 791

rod response in, 154–155, 154f–155f, 157f, 487–500, 488f, 809 age and, 493, 494f

alternative models of, 493–495, 495f high-intensity stimulation of, 487–489, 488f–490f model of, 489–491, 490f–492f

in retinal disease, 495–497, 496f

S and Rmax parameters of, 495–497, 496f

time course of photoreceptor response in, 155–156, 157f

B

Background illumination, for ERG, 292, 593–595, 594f, 595t Bálint syndrome, 113–114

Band-pass characteristic, 229 Band-pass filter, 257–258, 257f Band-reject filter, 257–258, 257f

Bandwidth restriction, of oscillatory potentials, 565, 566f, 575–576

Barium (Ba2+)

and b-wave, 159, 162f and M-wave, 167, 168f

and photopic negative response, 170 Basement membrane, 99, 100f

Basilar laminar drusen

fluorescein angiography in, 536, 538f hyperabnormal ERG responses in, 536, 538f

Bassen-Kornzweig syndrome, 803–804

Bassoon, in synaptic transmission, 100–103, 102f Batten-Mayou syndrome, 889

Batten’s disease, 890. See also Neuronal ceroid lipofuscinoses Bayesian approach, 544

BCD. See Bietti’s crystalline dystrophy

Becker muscular dystrophy, electroretinogram in, 816 Bessel filter, 239

Bestrophin, 765

Best’s disease. See Best vitelliform macular dystrophy Best vitelliform macular dystrophy, 763–765

c-wave in, 560f, 561

electro-oculogram in, 129f, 130, 134, 505–506, 623–624, 763–765

electroretinogram in, 763, 765 fundus findings in, 763, 764f genetics of, 765

histology of, 763 multifocal ERG in, 334 vitelliruptive stage of, 763

Beta, of Type II error, 434 Beta rhythm, of EEG, 208, 209f Bias, in therapeutic trials, 544 Bias, of amplifier, 257

Bicarbonate responses, 128–130, 553, 554t, 555f Bietti’s crystalline dystrophy, 735–742

clinical description of, 735–740 corneal lesions of, 740, 740f differential diagnosis of, 742 diffuse, 735, 736f–737f electro-oculogram in, 742

electroretinogram in, 740f, 741–742, 814 fluorescein angiogram of, 423, 424f, 735, 738f–739f fundus appearance of, 735, 736f, 738f–739f Goldman perimetric visual fields in, 737f–739f histopathology of, 741, 741f–742f

historical perspective on, 735 natural history of, 735–740 physiology of, 741

regional or localized, 735, 736f, 740f relevant testing and findings in, 741–742 stages of, 735–740

Biliary cirrhosis, vitamin A deficiency in, 803, 805f Binding hypothesis, of visual perception, 881 Bipolar cell(s), 49, 50f–51f

in b-wave generation, 83–84, 84f, 156, 159, 162f, 809 center surround organization of, 54–55, 55f, 80

in color vision, 56–57, 57f

in d-wave generation, 164–165 embryological origins of, 25 glutamate receptors of, 50–52, 53f–54f image properties of, 52–55

light adaptation in, 84–85, 85f light response of, 79–80, 80f neurotransmitters of, 85–88

ON/OFF, 51–57, 53f–54f, 57f, 80–82, 80f–81f oscillatory potentials from, 568

rod, cGMP cascade in, 82, 82f–83f

Bipolar cell(s) (continued )

in cone dystrophy with mild nyctalopia, 89f, 90–91 in inherited night blindness, 88

in melanoma-associated retinopathy, 88 signal pathways of, 85

synapses of, 50–52, 53f–54f, 57–58, 59f, 79–85, 93–95, 94f–95f with amacrine cells, 58–60, 60f–61f, 63f, 86, 93–95, 95f

flat contact, 96, 97f

with ganglion cells, 51–52, 54f, 56, 57f, 93–95, 95f in inner plexiform layer, 93–96, 94f–95f invaginating, 96, 97f

in outer plexiform layer, 94f rod versus cone, 96

synaptic gain in, 82

Birdshot chorioretinitis, 685, 687f, 818, 819f Black box, in linear systems, 439–440, 440f Blind infant, management of, 751–752 Blindness. See Cortical blindness; Night blindness Blindsight, 111

Blind spot, in multifocal ERG, 317

Blind spot syndrome, multifocal ERG in, 334 Blue cone monochromatism, 795–796, 800 Blue-sensitive cones, 48, 599, 599f

pathways/synapses of, 56–57, 57f Boyle, Robert, 599

BPAG1, in synaptic transmission, 103 Branch retinal artery occlusion (BRAO), 334 Branch retinal vein occlusion (BRVO), 680 BRAO (branch retinal artery occlusion), 334 Brodmann’s area 18, 19, 109

Bruch’s membrane, 27, 99, 100f

eosinophilic deposits on, 769. See also Sorsby’s fundus dystrophy

extracellular deposits on, 717. See also Drusen BRVO (branch retinal vein occlusion), 681 Bull’s-eye maculopathy (BEM), 511

Burian-Allen contact lens electrodes, 245–247, 246f Butterworth filter, 239

b-wave, 5, 557, 558f

abnormal rod-specific, 506–507 background illumination and, 593–595, 594f barium effects on, 159, 162f

bipolar cell generation of, 83–84, 84f, 156, 159, 162f in central retinal artery occlusion, 507, 681

in central retinal vein occlusion, 675–681, 676f–678f chromatic recordings of, 585, 603

cone-driven, 161–162, 603

in cone dystrophy, with mild nyctalopia, 88–90, 89f in congenital stationary night blindness, 507–510

current source density analysis of, 152f, 156–157, 159f dc component of, 162–163, 164f

depth profile of, 152f, 156, 158f dog model of, 912

in flicker ERG, 581, 582f–583f intracellular recordings of, 156–157

in juvenile X-linked retinoschisis, 824–825, 825f–826f laminin defect and, 99

light-adapted, 161–162, 163f, 593

light-evoked [K+]0 changes in, 157–159, 160f–161f mouse model of, 900, 901f, 903, 904f, 906f Müller cell hypothesis of, 156–157, 159f–160f myopia and, 631–632, 632f

origins of, 156–163, 809

oscillatory potential relationship with, 569–570 in post-phototransduction dysfunction, 507–510 postreceptoral response in, 475–476, 475f

in retinitis pigmentosa, 506–507, 506f scotopic (dark-adapted), 160–161, 163f

stimulus-response functions for, 473–476, 474f, 476f

C

Ca2+-ATPase transporter, 39 Cadherins, in synapses, 97–98, 100f Calcium

in light adaptation, 84–85, 85f in phototransduction, 71–72 as second messenger, 41f, 42

Calcium-ATPase transporter, 39 Calcium channel(s)

L-type, 38, 42 voltage-dependent, 38, 79

Calcium-dependent chloride channels, 38–39 Calcium-dependent potassium channels, 38 Calmodulin, in phototransduction, 72 Cancer-associated retinopathy (CAR), 691–697

antiretinal antibodies in, 695 electroretinogram in, 692f–693f

Canine. See Dog(s)

CAR. See Cancer-associated retinopathy Carbamazepine toxicity, 658

Carbon disulfide toxicity, 659

Carbon fiber electrodes, 248f, 249–250 CAR-like syndrome, 691, 694f

Cat(s)

electroretinogram in, 923–931

anesthetics for, 923–924, 925t–926t, 927 correlation with clinical findings, 929–931 specific procedures for, 924–927

photoreceptor diseases in, 923, 924t Cataract, spatial contrast loss with, 414, 415f Categorization, in Parkinson’s disease, 879–880 b-Catenin, in synapses, 97–98

Cathode-ray tubes (CRTs), 267–269, 267f–268f frame pulse artifact from, 281, 281f m-sequence control of, 321–322

for multifocal ERG, 321–322, 327

optimal trigger location and methodology for, 269 output spectra of, 270, 270f

phosphors for, 268, 268f pitfalls with, 268–269

Ceiling effect, 543

Cell-cell adhesion, and synapses, 97–105, 99f–100f Center surround organization, 54–55, 55f, 80

dopamine and, 869–870, 869f–871f Central disorders of vision, 109–117, 111t Central retinal artery occlusion (CRAO), 681

c-wave in, 561, 561f

electroretinogram in, 507, 681, 816–817 Central retinal vein occlusion (CRVO), 675–681

electroretinogram in, 675–681, 676f–680f, 816–818, 818f amplitudes in, 675–676, 676f–677f

intensity-response analysis in, 677–678, 680f temporal factors in, 676–677, 678f–679f

ischemic, 817, 818f multifocal ERG in, 677 nonischemic, 817

photoreceptor function in, 679–680, 680f Central serous chorioretinopathy, 683–685

diagnosis of, 683–685 electroretinogram in, 683–685 etiology of, 683

fluorescein angiography of, 683, 684f multifocal ERG in, 685, 686f

Central serous retinopathy, multifocal ERG in, 334 Central vision disorders, 109–117, 111t

Cerebral achromatopsia, 112–113 CEVNet, 251–252

C-glide electrode, 248f, 249–250

cGMP. See Cyclic guanosine monophosphate Chebyshev filter, 239

Checkerboard stimulus in albinism, 378–382

and Fourier analysis, 451, 452f

for pattern ERG, 186, 188f, 191–193, 193f, 298 for VEP stimulation, 17, 215–216, 220

Chiasmal dysfunction (lesions), 857–860 in albinism, 369–370

etiology of, 857 misdiagnosis of, 857 pattern ERG in, 860

visual evoked potentials in, 231, 307, 505, 514–515, 516f, 857–860, 858f–860f

crossed asymmetry in, 858, 858f

for intraoperative monitoring, 859–860 treatment effects on, 859

visual field defects in, 857 Chicken(s)

electroretinogram in, 916–919 anesthetics for, 926t

delayed basal hyperpolarization in, 148, 148f in disease, 917–918, 917f–919f

long-flash, 917, 917f methods of recording, 916 normal, 916–917, 917f

Leber congenital amaurosis in, 749 retina of, versus human retina, 916

Chievitz, layer of, 25 Chloride channel(s), 38–39

calcium-dependent, 38–39 CIC-2, 39

in electro-oculogram, 124–126 voltage-activated, 39

Chloride-HCO3- exchanger, 40 Chloroquine toxicity, 655–656 color vision in, 610, 610f

multifocal ERG in, 335

Chondroitin 6-sulfate, in cone matrix sheaths, 26–27, 28f Choriocapillaris, drug effects on, 655

Choriocapillaris atrophy, c-wave in, 560f, 561 Chorioretinopathy, central serous, 683–685

diagnosis of, 683–685 electroretinogram in, 683–685 etiology of, 683

fluorescein angiography of, 683, 684f multifocal ERG in, 685, 686f

Choroidal disorders, 683–687. See also specific types Choroidal fissure, development of, 23 Choroideremia, 777–779

clinical characteristics of, 777 differential diagnosis of, 777–779 electroretinogram in, 777 female carriers of, 777, 778f

fluorescein angiogram of, 423, 424f, 777, 778f fundus appearance of, 777, 778f

gene function in, 779

versus gyrate atrophy, 712–713, 779 versus retinitis pigmentosa, 777

suppressive rod-cone interaction in, 419 versus Usher syndrome, 779

Chromatic constancy, 112–113, 600

Chromatic responses, 597–610. See also Color vision early receptor potential in, 585, 589–591, 589f–590f ERG recordings of, 585–591, 603–604

pattern ERG recordings of, 604

in protan/deutan genetic carriers, 587f, 588–589, 588f–589f psychophysical tests of, 607–610

rapid off-response, 585–589, 586f–588f suppressive rod-cone interaction in, 419 VEP recordings of, 218, 604–607, 605f–607f

Chromatic stimuli, visual evoked potentials to, 224 CIC-2 channel, 39

Cilia, of photoreceptors, 65–66, 66f–67f Cinchonism. See Quinine retinopathy Cl−/HCO3- exchanger, 40

Clinical findings, correlation of test results with, 628–629, 628t Clinical trials. See Therapeutic trials

CMMR (common mode rejection ratio), 238, 257, 277, 559, 617–618

Coats’ reaction, 427, 428f

Codon 172 RDS-related drusen, 717, 720–721, 720f, 722f Collagen, in synaptic transmission, 99, 103

Color anomia, 116–117

Color center, human (area V4), 109, 110f, 112f, 600 damage to, syndromes caused by, 112–113

Color confusion line, 602 Color constancy, 112–113, 600

Color contrast, 602–603, 607–608 Color perception, 112, 598–599

Color selectivity, reverse correlation of, 469–470, 469f Color space modulation, for VEP stimulation, 218 Color triangle, 602

Color vision, 597–610

in age-related macular degeneration, 608–610, 609f Aristotle’s theory of, 597

color contrast test of, 602–603, 607–608 cone specialization for, 47–49, 599–600, 599f in congenital stationary night blindness, 834 defects or deficiency of

acquired, 600–603

early receptor potential in, 585, 589–591, 589f–590f electrophysiology of, 585–591, 603–607

genetic carriers of, 587f, 588–589, 588f–589f genetic mechanisms of, 599f, 600, 601f inherited, 599–600, 600t, 601f

in males versus females, 599f, 600, 600t psychophysical tests for, 607–610

rapid off-response in, 585–589, 586f–588f suppressive rod-cone interaction in, 419

in diabetic retinopathy, 603, 608, 608f drug/toxic effects on, 610, 610f, 660–661

early receptor potential in, 585, 589–591, 589f–590f ERG recordings of, 585–591, 603–604

in glaucoma, 608, 609f, 854–855 Goethe’s theory of, 597–598 historical perspective on, 597–600 Newton’s theory of, 597–598

in optic atrophy, 609–610, 610f in Parkinson’s disease, 872–873 pathways of, 56–57, 57f pattern ERG recordings of, 604

physiological aspect of, developing of, 597–599 Plato’s theory of, 597

Schopenhauer’s theory of, 597–599

Color vision (continued)

silent substitution test of, 602

in Sorsby’s fundus dystrophy, 769 Stiles two-color technique in, 602

visual evoked potentials in, 218, 604–607, 605f–607f Coma, visual evoked potentials in, 232

Common mode rejection ratio (CMRR), 238, 257, 277, 559, 617–618

Complex cells, 468

reverse-correlation analysis of, 467f, 468 Conditioning flash effect, and oscillatory potentials, 574 Cone(s)

biochemistry of, 29–30 blue-sensitive, 48, 599, 599f

pathways/synapses of, 56–57, 57f cell cytology of, 28–30

cilia of, 65–66, 66f–67f

color selectivity of, 469–470, 469f

in color vision, 47–49, 599–600, 599f currents of, and a-wave, 151–152, 151f–152f in daylight vision, 47–49, 49f

definition of, 47

disc membranes of, 29

in duplicity theory, 404–405 embryological development of, 25–27 functional organization of, 47–48 green-sensitive, 48, 599, 599f

pathways/synapses of, 56, 57f image properties of, 49–50

inner segments of, 24f, 25, 29, 65, 66f long-wavelength-sensitive (L), 405, 599, 599f microfilaments of, 65, 67f

microtubules of, 65, 67f middle-wavelength-sensitive (M), 405, 599, 599f morphology of, 28–30

neurotransmitter release from, 79 orientation selectivity of, 469–470, 469f

outer segments of, 24f, 25, 28–29, 28f, 47, 48f, 65, 66f phototransduction in, 72

physiology of, 65–75

protein migration/translocation in, 72–75, 74f red-sensitive, 48, 599, 599f

pathways/synapses of, 56–57, 57f responses of. See Cone response short-wavelength-sensitive (S), 405, 599, 599f

responses in normal and disease states, 603–604 spatial density of, 405

subclasses of, 29

suppressive interaction with rods, 417–420. See also Suppressive rod-cone interaction

synaptic transmission in, 79–91 types of, 48

Cone dystrophy (degeneration), 795–801 autosomal-dominant, 800–801 autosomal-recessive, 801

clinical features of, 795, 797–799, 797t congenital, 795–796, 798t

“cookie cutter” macula appearance in, 795, 797f crystalline deposits in, 795, 796f

diagnosis of, 795 electro-oculogram in, 624

electroretinogram in, 88–90, 89f, 507, 510f, 795–797, 799f, 813 fluorescein angiography in, 796f

foveal structure in, 801, 801f

fundus albipunctatus associated with, 835, 837f fundus findings in, 795, 796f–797f

hereditary, 795–796, 798t known forms of, 799–800

later onset forms of, 795–796, 798t management of, 801

optic nerve atrophy in, 795, 798f

oscillatory potentials in, 570, 571f, 576f, 577 partial, 800, 800f

signs and symptoms of, 795, 797t synaptic transmission in, 88–91 vascular abnormalities in, 795, 796f X-linked, 795, 796f, 800

Cone matrix sheaths, 26–27, 28f, 30–31, 31f Cone notches, 29

Cone response, 72, 73f–74f, 405. See also specific disorders/findings a-wave, 154–155, 154f, 156f, 487–499, 488f

age and, 493, 494f

high-intensity stimulation of, 487–489 model of, 492, 493f

in retinal disease, 497, 497f

S and Rmax parameters of, 497, 497f simpler equation for, 492–493

background illumination and, 593–595, 594f b-wave, 161–162, 603

clinical assessment of, 497–500, 498f dark-adapted, 405–409, 406f, 595 in early receptor potential, 549–551 in electroretinogram

ISCEV standard for, 293–294 isolation of, 7–8

in flicker ERG, 581, 582f–583f hyperpolarizing, 49, 52f, 79 light-adapted, 593

in mouse, 899–900, 901f, 906, 906f in multifocal ERG, 197

myopia and, 631, 634 receptive field of, 49, 52f

S-cone, in normal and disease states, 603–604 Cone-rod degeneration. See also Retinitis pigmentosa

electroretinogram in, 813

versus Stargardt disease, 727–732 Confidence interval, 432 Confidence limits, 432

Congenital nystagmus, in albinism, 377–378, 378f–380f Congenital stationary night blindness (CSNB), 829–837

color vision in, 834

complete, 510, 511f, 809, 811f, 829–834 dark adaptation in, 409, 409f, 829, 831f electro-oculogram in, 832

electroretinogram in, 507–510, 511f, 809–810, 811f, 829–832, 831f–832f

intensity series in, 832, 833f long-flash photopic, 832, 834f

genetics of, 809–810, 834, 835f incomplete, 510, 511f, 809, 811f, 829–834 initial patient complaints in, 829, 830t

versus melanoma-associated retinopathy, 696–697, 697f oscillatory potentials in, 570, 571f, 577, 577f pathogenesis of, 834

refractive error in, 829, 830f Schubert-Bornschein type of, 829 scotopic threshold response in, 832, 833f visual acuity in, 829, 830f

Constant stimuli, method of, 400, 401f

Contact lens electrodes, 6–7, 7f, 245–247, 246f, 252, 558–559, 559f Contrast

color, for color vision testing, 602–603

definition of, 413

drug/toxic effects on, 660–661 spatial, 414–415, 414f

loss of, 414, 415f testing of, 415–416

temporal, 413–414, 414f, 415 Contrast dynamics, 192–194

Contrast perimetry, in multiple sclerosis, 875–878 Contrast reversal, in evoked potential evaluation, 210, 220 Contrast sensitivity

in glaucoma, 854–855

in multiple sclerosis, 875–878, 876f–877f in neurodegenerative disease, 867 testing of, 415–416

clinical results of, 415–416

means of producing stimuli for, 415 methods of, 415

Contrast transfer function

of pattern ERG, 194, 194f

of visual evoked potential, 194, 194f Control condition, 432–433

Control software, 242

“Cookie cutter” macula, in cone dystrophy, 795, 797f Correlation techniques, 451–453

Cortex. See Visual cortex Cortical blindness

causes of, 651

clinical visual signs of, 651 definition of, 651

retrochiasmal dysfunction and, 861–863 visual evoked potentials in, 651–652

works reporting abnormal, 652 works reporting normal, 651–652 works reporting recovery of, 652

Cortical time, 15 Cortical visual areas, 109

CRAO. See Central retinal artery occlusion Crawford masking, 408

CRB-1 gene, and Leber congenital amaurosis, 750 Criterion free, 402

Crohn’s disease, vitamin A deficiency in, 803 Cross-correlation, 451, 454–455

in multifocal ERG, 322–324, 322f–324f CRTs. See Cathode-ray tubes

Crumbs (molecule), 100f, 105

CRVO. See Central retinal vein occlusion CRX gene

and Leber congenital amaurosis, 749–750 and retinitis pigmentosa, 781

Crystalline retinopathy, 735. See also Bietti’s crystalline dystrophy CSNB. See Congenital stationary night blindness

Current source density (CSD), 142 of a-wave, 151, 152f

of b-wave, 152f, 156–157, 159f of d-wave, 164–165

of pattern response, 189f

c-wave, 5, 11, 123, 143–144, 144f, 557, 558f, 560–561 normal, 560–561

“off,” 561, 562f

in pigment epithelium disease, 560f, 561, 561f second, 149

Cyclic guanosine monophosphate (cGMP) cascade in rod bipolar cell, 82, 82f–83f

in cone dystrophy with mild nyctalopia, 89f, 90–91 in inherited night blindness, 88

in melanoma-associated retinopathy, 88

in Leber congenital amaurosis, 748–749 in phototransduction, 67, 68f, 70, 71f, 519 in retinitis pigmentosa, 783–784

Cystic fibrosis, electro-oculogram in, 136 Cytostatic toxicity, 656

D

Dalton, John, 599

Dark adaptation, 405–409, 405f bleaching parameters and, 408 clinical evaluation of, 408–409 of cones, 405–409, 406f, 595

in congenital stationary night blindness, 409, 409f, 829, 831f defects in, treatment for, 409

drug/toxic effects on, 660–661 early, 408

factors affecting, 407–409

in fundus albipunctatus, 829, 831f, 834 in gyrate atrophy, 707, 710f mechanisms of, 406–407

in neuronal ceroid lipofuscinoses, 890

in Oguchi’s disease, 829, 831f, 836, 837f–838f of rods, 405–409, 406f, 520–521, 521f, 595–596f in Sorsby’s fundus dystrophy, 409, 769–771

test stimulus wavelength and, 407, 407f in vitamin A deficiency, 803, 805f

Dark-adapted a-wave, 150, 150f Dark-adapted b-wave, 160–161, 163f

stimulus-response functions for, 473–476, 474f, 476f Dark-adapted electro-oculogram, 128

Dark-adapted electroretinogram, 7–8, 8f, 139–140, 140f, 150, 150f, 292–293, 595–596, 596f

Dark-adapted flash response, 520–521, 521f Dark-adapted oscillatory potentials, 573–575, 573f Dark choroid effect, 423, 426, 427f

Data acquisition systems, 237–244 building your own, 244

commercially available systems for, 243–244, 243t components of, 237

overview of, 237, 238f, 261–262, 261f patient positioning for, 237–238 selection of, questions for, 262–263 special-purpose, 260–263

general characteristics of, 261–262, 261f Data analyses, 431–437

Daylight vision, cone specialization for, 47–49, 49f dc. See Direct current

Decimation, of m-sequence, 321, 322f Deconvolution analysis, 221

Delay, 440–442

Delayed basal hyperpolarization, 147–148, 148f Delayed rectifier ion channels, 37

Dependent variable, 436

Depth selectivity, reverse correlation of, 469–470 Descriptive statistics, 431–432

Desferrioxamine toxicity, electro-oculogram in, 135 Detection threshold, 400

Deuteranopes (deutans)

early receptor potential in, 585, 589–591, 589f–590f

genetic carriers, ERG responses in, 587f, 588–589, 588f–589f genetic development of, 600

rapid off-response in, 585–589, 586f–588f suppressive rod-cone interaction in, 419 visual evoked potentials in, 604–607

Deuteranopia, 599. See also Deuteranopes

Deuteranopic color confusion line, 602 Diabetic retinopathy

color vision in, 603, 608, 608f multifocal ERG in, 333–334 oscillatory potentials in, 569, 569f S-cone response in, 603

Diagnostic flowcharts, 515–517, 516f

Diamox (acetazolamide) responses, 126, 128–130, 130f, 553, 554t, 555f, 562

Dichromatism. See Deuteranopes; Protanopes Difference threshold, 400

Differential amplifiers, 238, 239f, 257, 275–276, 617–618, 617f Digitalis toxicity, 657

Digital light projection (DLP) system, 271 Digoxin toxicity, 657

Direct current amplifiers, 238–239, 256–257, 559 Direct current component, of b-wave, 162–163, 164f Direct current electroretinogram, 252, 557–563

clinical applications of, 560, 560f equipment and procedure for, 557–560

Direct current potential, 11, 123–124, 126 Direction selectivity, 465, 466f

Disc membranes, of photoreceptors, 29 Disconnection(s)

visual-limbic, 117 visual-verbal, 116–117 visual-visual, 116

Distal retina, ERG components arising in, 143–149 Distortion, 442–444

linear, 442–444, 444f nonlinear, 443

DNA, mitochondrial, 665. See also Mitochondrial disorders Dog(s)

electroretinogram in, 911–916, 923–931 analysis of, 912

anesthetics for, 923–924, 925t, 927 bilateral, 931, 931f

components of, 912, 913f

correlation with clinical findings, 929–931 guidelines/protocols for, 927–929, 928f, 930f long-flash, 912, 913f

maturation of, 912, 913f

methods of recording, 911–912, 927–929, 928f, 930f in retinal dystrophies, examples of, 912–913

Leber congenital amaurosis in, 745, 747–748, 915–916 phenotype diversity in, 912

photoreceptor diseases in, 923, 924t, 929–931 progressive retinal atrophies in, 913–915, 914f–915f, 923,

924t

progressive rod-cone degeneration (prcd) in, 32, 914–915, 915f

retina of, versus human retina, 911 Domains, in Fourier analysis, 447–448 Dominant drusen, 717–724

clinical range of, 717, 719f

codon 172 RDS-related, 717, 720–721, 720f, 722f definition of, 717

distribution of, 717, 718f EFEMP1-related, 717, 721–722, 722f–723f electro-oculogram findings with, 718 electroretinographic findings with, 718 functional changes with, 717–718

genetics of, 717–724

multifocal ERG findings with, 718 TIMP3-related, 717, 719–720

Dominant optic atrophy (DOA), pattern ERG in, 346–347, 348f

Dopamine, 88

in amacrine cells, 60, 61f, 63f, 88 drug/toxic effects on, 657–658, 657f in Parkinson’s disease, 868–873

and spatial processing, 869–870, 869f–871f Dorsal pathway, 109–110, 110f

neuroanatomy and neurophysiology of, 113 syndromes of, 113–115

Double-blind study, 433

Double magnetic induction (DMI), of ocular motor assessment, 377

Double-opponent cells, 469–470

Double-sided (differential) amplifiers, 238, 239f, 257, 275–276, 617–618, 617f

Doyne’s honeycomb dystrophy, 717, 719f, 721 Drug toxicities, 655–661. See also specific drugs

cell-specific functional alterations in, 655–660 central nervous system effects of, 659–660 color vision in, 609–610, 660–661 electroretinogram in, 819, 820f

ganglion cell changes in, 658–659 inner retina alterations in, 657–658 muscular effects of, 661

patient history in, 660 photoreceptor alterations in, 657

retinal pigment epithelium effects of, 655–657 special testing considerations in, 660–661 from symptoms to diagnosis of, 660–661

Drusen

basilar laminar

fluorescein angiography in, 536, 538f hyperabnormal ERG responses in, 536, 538f

definition of, 717 dominant, 717–724

clinical range of, 717, 719f

codon 172 RDS-related, 720–721, 720f, 722f definition of, 717

distribution of, 717, 718f EFEMP1-related, 721–722, 722f–723f electro-oculogram findings with, 718 electroretinographic findings with, 718 functional changes with, 717–718 genetics of, 717–724

multifocal ERG findings with, 718 TIMP3-related, 719–720

as hallmark of disease, 717 hard, 717

hereditary versus nonhereditary, 723 nature of, 717

soft, 717

DTL electrode, 248f, 250 DTL-Plus electrode, 250

Duchenne muscular dystrophy, electroretinogram in, 816

Dummy patient, 282, 282f, 618–619, 618f Duplex retina, 48

Duplicity theory, 404–405 d-wave

current source density analysis of, 164–165 depth profile of, 164, 164f

of electroretinogram, 151 origins of, 164–165

of squirrel, 165, 165f Dystonin, 103 Dystroglycan, 103–105

Dystrophins, 99–100, 103–105, 816

E

Early dark adaptation, 408

Early receptor potential (ERP), 549–551, 624–626 amplitude of, 549–550

chromatic recordings of, 585, 589–591, 589f–590f clinical application of, 549–551

discovery of, 549, 550f

in ocular siderosis, 550, 550f origins of, 549

polarity of, 549, 550f

R1 component of, 549, 550f

R2 component of, 549, 550f

rod versus cone contribution to, 549 spectral sensitivity of, 549

Early Treatment for Diabetic Retinopathy Study (ETDRS), 541 Eccentric fixation, in multifocal ERG, 315f, 317

EEG. See Electroencephalogram

EFEMP1 gene, and drusen, 717, 721–722, 722f–723f Electrical noise, in multifocal ERG, 314f, 316 Electrode(s), 238, 245–254

for electro-oculogram, 252

for electroretinogram, 245–254 carbon fiber, 248f, 249–250 cleaning of, 291

contact lens, 6–7, 7f, 245–247, 246f, 252, 558–559, 559f for dc recording, 252

development of, 5–8

in dogs, 911–912, 928–929, 928f DTL fiber, 248f, 250

gold foil, 247–249, 248f ground, 291

international use of, 251–252 ISCEV guidelines on, 291

in larger animals, 928–929, 928f lid-hook, 247–250, 248f

in mice, 900 placement of, 143, 143f

polymethylmethacrylate, 252, 558 polyvinyl gel, 249

recording, 291 reference, 291 skin, 248f, 250–251 skin reference, 291 stability of, 291

for multifocal ERG, 197, 198f, 249, 310, 312, 319 for multifocal VEP, 199–200, 203f

for pattern ERG, 298, 341 10/20 system for, 227, 228f

for visual evoked potentials, 207, 226–229, 252–253, 304 ISCEV guidelines for, 304

number of, 227–229

positioning of, 207, 226–227, 228f, 304, 304f problems with, 227

Electrode artifacts, 245, 278–279, 282, 618–619 Electrode impedance, and amplifiers, 277, 278f

Electrodiagnostic testing. See also Electroencephalogram; Electrooculogram; Electroretinogram; Visual evoked potentials

commercially available systems for, 243–244, 243t data acquisition systems for, 237–244

versus psychophysical approaches, 399 stimulators for, 265–275

Electroencephalogram (EEG) alternatives to, 214–215

contrast and pattern reversal in, 210 dipole production in, 210

electrode positioning for, 226–227, 228f electrode problems in, 227

evoked potentials in

cortical sources of, localization of, 211–213, 213f–215f origins of and transmission to scalp, 210–214

pattern appearance, 211, 212f

visual, 207–210. See also Visual evoked potentials flash response in, 208–210

history of, 208–210

in malingering and hysteria, 638 as mass phenomenon, 211, 211f

postsynaptic potentials in, 210–211, 212f rhythms of, 208, 209f

signals and noise in, 255, 256t spatial summation in, 210 temporal summation in, 210–211

Electronegative electroretinogram, 809–819 in acquired diseases of eye, 816–819

autosomal-dominant inheritance of phenotype for, 814 in clinical practice, 819

definition of, 809

disorders associated with, 809–819, 810t in neurodegenerative disorders, 815–819 origins of, 809

Electronic noise, 255, 256t Electronic visual acuity (EVA), 541

Electro-oculogram (EOG), 123–136, 623–624. See also specific disorders/findings

acetazolamide test in, 126, 128–130, 130f, 553, 554t, 555f, 562 alcohol test in, 130–133, 131f–135f

bicarbonate test in, 128–130, 553, 554t, 555f classic, description of, 128

clinical findings of interest, in last 10 years, 135–136 clinical tests utilizing, 127–128

clinical utility of, 134–135

comparison and combination with other tests, 626–627 correlation with clinical findings, 628–629, 628t current fields in, 123–124, 124f–125f

dark and light adaptation in, 128 electrodes of, 252

fast oscillation, description of, 128, 129f history of, 11

hyperosmolarity test in, 126, 128–130, 130f, 553, 554t, 555f, 561–562

ISCEV standard for, 287–289 light rise in, 11, 124, 126, 130f

abnormal, in RPE dysfunction, 505–506 localization of lesions in, 505–506, 623–624, 624t–625t membrane mechanisms of, 124–126

in mitochondrial disorders, 667 nonphotic responses in, 128–130 pharmacology of, 126–127 physiological characteristics of, 126–127 signals and noise in, 255, 256t steady-state, 128

technical details of, 127

technical difficulties with, 127–128 variants of, 128

Electroretinogram (ERG), 140f. See also specific components, tests, and disorders abnormal findings in

abnormal rod-specific b-wave, abnormal maximal ERG response a-wave, 506–507

abnormal rod-specific b-wave, (electro-) negative maximal ERG response, 507–510

normal maximal ERG response, abnormal cone ERG, 507 adaptation effects on, 593–596

Electroretinogram (ERG) (continued) amplification for, 292

averaging in, 294

a-wave of, 4–5, 149–156, 557, 558f. See also a-wave background illumination for, 292, 593–595, 594f, 595t b-wave of, 156–163, 557, 558f. See also b-wave chicken, 916–919

anesthetics for, 926t

delayed basal hyperpolarization in, 148, 148f in disease, 917–918, 917f–919f

long-flash, 917, 917f methods of recording, 916 normal, 916–917, 917f

chromatic recordings of, 585–591 chromatic (color) recordings of, 603–604 clinical, 6–8

comparison and combination with other tests, 626–627 components of, 4–5

distal, interaction of, 149 distal origins of, 143–149 modeling of, 143

correlation with clinical findings, 628–629, 628t correlation with single-cell recordings, 142

c-wave of, 143–144, 144f, 557, 558f, 560–561. See also c-wave dark-adapted (scotopic), 7–8, 8f, 139–140, 140f, 150, 150f,

292–293, 595–596, 596f data display and averaging in, 292

diagnostic flowcharts for, 515–517, 516f direct current (dc), 557–563

clinical applications of, 560, 560f equipment and procedure for, 557–560

dog, 911–916, 923–931 analysis of, 912

anesthetics for, 923–924, 925t, 927 bilateral, 931, 931f

components of, 912, 913f

correlation with clinical findings, 929–931 guidelines/protocols for, 927–929, 928f, 930f long-flash, 912, 913f

maturation of, 912, 913f

methods of recording, 927–929, 928f, 930f in retinal dystrophies, examples of, 912–913

d-wave of, 164–165. See also d-wave electrodes of, 245–254

carbon fiber, 248f, 249–250 cleaning of, 291

contact lens, 6–7, 7f, 245–247, 246f, 252, 558–559, 559f for dc recording, 252

development of, 5–8 DTL fiber, 248f, 250 gold foil, 247–249, 248f ground, 291

international use of, 251–252 ISCEV guidelines on, 291 lid-hook, 247–250, 248f placement of, 143, 143f polymethylmethacrylate, 252, 558 polyvinyl gel, 249

recording, 291 reference, 291 skin, 248f, 250–251 skin reference, 291 stability of, 291

electronegative, 809–819

in acquired diseases of eye, 816–819 autosomal-dominant inheritance of phenotype for, 814

in clinical practice, 819 definition of, 809

disorders associated with, 809–819, 810t in neurodegenerative disorders, 815–819 origins of, 809

on electronic recording equipment, 292 e-wave of, 166

excitatory, 5, 6f

extracellular flow in, pattern of, 139

fast oscillation of, 557, 558f, 561–562, 562f

fast oscillation trough of, 143, 144f, 146–148, 147f fixation in, 293

flicker, 581, 582f–583f

photopic fast, 165, 166f, 293–294 general principles of, 139

Granit’s model of, 487, 488f high-intensity, 293, 487–489, 488f–490f

need for, 487 protocols for, 487–489

history of, 3–8

early discoveries, 3 early recording, 3, 4f first published, 3–4, 4f

hyperabnormal responses in, 533–540 classification of, 533–536, 537f distribution by category, 536, 537t

fluorescein angiographic correlation of, 536, 538f, 538t, 539f illustrative case reports of, 536–539

in macular degeneration, 536, 538, 538f–539f, 540 in optic nerve dysfunction, 536–538, 539f, 540 pathologic process suggested by, 539–540

in Stargardt’s disease, 536, 538f in infants, 745–746

inhibitory, 5, 5f

intraretinal depth recordings in, 142 ISCEV standard for, 287–288, 290–295

on basic technology, 291–293

on clinical protocol, 292–293, 784–791 on light adjustment and calibration, 292

on measurements and recordings, 294–295, 294f i-wave of, 165

kernel analysis in, 483–484 larger animal, 923–931

anesthetics for, 923–924, 925t–926t, 927 bilateral, 931, 931f

correlation with clinical findings, 929–931 guidelines/protocols for, 927–929, 928f, 930f specific procedures for, 924–927, 927f

latency of, 442

light-adapted (photopic), 7–8, 8f, 139–140, 140f, 150, 150f, 292–293, 593

light diffusion in, 291

light-evoked potassium changes in, 157–159, 160f–161f, 167, 168f light peak of, 143, 144f, 557, 558f, 561–562, 562f

light sources in, 291–292, 559 local, 142

localization of lesions in, 505–511, 515–517, 624t–625t, 626–629 luminance versus pattern, 185–186, 187f

macaque monkey, 150, 150f

in mitochondrial disorders, 666–669, 666t, 668t–669t modeling of cellular responses in, 143

mouse, 899–907, 900f

a-wave analyses in, 902–906, 902f basic recording technique for, 900

b-wave analyses in, 900, 901f, 903, 904f, 906f cone-mediated responses in, 899–900, 901f, 906, 906f

factors affecting, 900–901 general testing protocol for, 903 interstrain differences in, 903–907

Naka-Rushton analysis of, 903, 904f oscillatory potentials in, 903, 905f phototransduction in, 902–903

rod-mediated responses in, 899–900, 901f, 903, 904f–905f rod- versus cone-mediated comparisons in, 906

specialized recording techniques for, 901 standard strains for, 903

Müller cell contribution in, 141, 141f, 144–146, 145f, 156–157, 160f multifocal. See Multifocal electroretinogram

M-wave of, 166–168, 167f–168f myopia and, 631–634, 632f

normal values in, 294, 533–536, 534t, 535f optic nerve stimulation in, 176

orientation of cells in, 139 origins of, 139–177, 487, 899

approaches for determining, 141–143

oscillatory potentials of, 173–176, 565–578, 566f. See also Oscillatory potentials

paired-flash analysis in, 791, 791f

concept and methodology of, 519–520, 520f of dark adaptation, 520–521, 521f

of light adaptation, 521–525, 523f–524f, 526f

of recovery following bright illumination, 525–530, 527f–530f of rod phototransduction and adaptation, 519–530

patient isolation for, 292

patient preparation for, 292–293, 558 pattern. See Pattern electroretinogram pharmacological dissection in, 142

photopic negative response in, 168–170, 169f pigment epithelial component of, 146

in post-phototransduction dysfunction, 507–510 in pressure-induced retinopathy, 515–517, 517f processes of (PI, PII, PII), 4–5, 5f, 142 proximal negative response in, 166, 167f–168f P-wave of, 176

recalibration of, 292

relative magnitude of signals in, factors determining, 139–140 reporting results of, 294–295

in retinitis pigmentosa, 506–507, 506f, 508f scotopic threshold response in, 170–173 signals and noise in, 255, 256t

single-flash cone, 293

site-specific lesions/pathology in, 142

slow oscillation of, 557, 558f, 561–562, 562f slow PIII of, 143–146, 144f–145f

spatial buffering of [K+]o in, 140–141, 141f, 146 spreading depression in, 177

standard combined, 293 stimulus-response functions of, 473 stimulus strength-standard flash in, 292 stimulus wavelength in, 292

targeted mutations in, 142

waveform changes in disease, 626–628, 627t EMMPIRN, 105

Emotion, and visual evoked potentials, 226

Enhanced S-cone syndrome (ESCS), 507, 508f–509f, 603–604 Environmental rotation, 115, 115f

EOG. See Electro-oculogram

Epinephrine, electro-oculogram effects of, 126 Epitaxial semiconductor junction diodes, 272 Equipment. See also specific types

amplifiers, 238, 255–260, 275–278 analog-to-digital converter, 240–241, 258–260

cathode-ray tubes, 267–269

commercially available systems, 243–244, 243t control software, 242

data acquisition systems, 237–244 electrodes, 238, 245–254

filters, 239–240, 257–260, 271 light-emitting diodes, 271–275 liquid crystal displays, 269–271 plasma displays, 271 stimulators, 265–275

Equivalent background, 407 ERG. See Electroretinogram

ERG-Jet contact lens electrodes, 246f, 247 ERP. See Early receptor potential

Errors, Type I and Type II, 433–434 Essential nonlinearity, 479 Ethambutol toxicity, 659

Ethanol toxicity, 659

Ethical issues, in therapeutic trials, 544

Ethyl alcohol, electro-oculogram effects of, 126–127, 130–133, 131f–135f

EVA (electronic visual acuity), 541 Event-related potentials

in multiple sclerosis, 881–882

in Parkinson’s disease, 878–881, 880f Evoked potential(s)

alternatives to, 214–215

cortical sources of, localization of, 211–213, 213f–215f definition of, 207

evaluation of

contrast and pattern reversal in, 210 flash response in, 208–210

origins of and transmission to scalp, 210–214 pattern appearance, 211, 212f

steady-state, 15

visual, 15–18, 207–232. See also Visual evoked potentials visual subcortical, 16–17

e-wave, origins of, 166 Excitatory ERG (E-ERG), 5, 6f

Excitatory postsynaptic potentials, in EEG, 210–211, 212f Expectancy, and visual evoked potentials, 224–226 Experimental design, 431–437

basic elements of, 432–433 Eye movement artifacts, 619

Eye position control, for VEP recording, 229

F

Familial optic atrophy, electroretinogram in, 814 Farnsworth-Munsell 100-hue test, 602, 607

Fast flicker ERG, photopic, 165, 166f, 293–294

Fast Fourier transform, in oscillatory potential analysis, 566, 567f, 575–576

Fast oscillation electro-oculogram, 128, 129f Fast oscillation ERG, 557, 558f, 561–562, 562f

Fast oscillation trough (FOT), 143, 144f, 146–148, 147f Fast retinal potential, 565. See also Oscillatory potentials Fatty acid disorders, 889–895

Field potentials, 139

Figure-ground segregation, and visual evoked potentials, 219–220, 219f

Filter(s), 239–240, 257–260 absorption, 271

analog, 258, 258t band-pass, 257–258, 257f band-reject, 257–258, 257f

Filter(s) (continued)

digital, 240, 258–260, 258t

high-pass, 239, 257–258, 257f, 277, 277f interference, 271

low-pass, 239, 240f, 257–258, 257f

for multifocal ERG, 311, 327–329, 330f notch or line frequency, 240, 257–258, 257f phase-free, 449, 450f

roll-off of, 239 types of, 239–240

Filtering, of visual evoked potentials, 229, 258, 259f, 260 First harmonic, 444

First-order kernels, 463, 464f, 468, 479–480 First-order receptive fields, 463

Fixation

eccentric, 315f, 317

in electroretinogram, 293

in multifocal ERG, 311, 313, 315f, 317 Flashed-on pattern, 17

Flash lamps, 265–266, 267f Flash response, in EEG, 208–210 Flash stimulus

for high-intensity ERG, 487–489, 488f–490f and oscillatory potentials, 573–575, 573f

and visual evoked potentials, 221, 222f, 232, 304, 306, 307f Flat contact synapses, 96, 97f

Flicker ERG, 581, 582f–583f chromatic recordings of, 585

fast photopic, 165, 166f, 293–294 Flicker stimulus, 413

for oscillatory potentials, 572–573, 573f

for suppressive rod-cone interaction, 417–418, 418f–419f Floor effect, 543

Flowcharts, diagnostic, 515–517, 516f Fluorescein angiography, 423–427

basic principles of, 423

of Bietti’s crystalline retinal dystrophy, 423, 424f, 735, 738f–739f of birdshot chorioretinitis, 685, 687f

of central serous chorioretinopathy, 683, 684f of choroideremia, 423, 424f, 777, 778f

of cone dystrophy, 796f

correlation of hyperabnormal ERG responses in, 536, 538f, 538t, 539f

dark choroid effect in, 423, 426, 427f of gyrate atrophy, 707, 711f

of hereditary retinal diseases, 423–427

of juvenile retinoschisis, 424, 425f, 823, 825f

of macular degeneration, 536, 538, 538f–539f, 540 of macular schisis versus edema, 423–425, 425f

of pattern dystrophies, 425, 757, 758f–759f of quinine retinopathy, 841

of retinitis pigmentosa, 425, 426f, 427, 428f of Stargardt disease, 426, 427f, 536, 538f of temporal optic atrophy, 427, 427f

of Usher’s syndrome, 424, 425f Fluphenazine toxicity, 658 Forced-choice procedure, 401–402, 401f Forsius-Eriksson ocular albinism, 810

Foster-Kennedy syndrome, 700–701, 701f

FOT (fast oscillation trough), 143, 144f, 146–148, 147f Fourier, Joseph, 444, 444f

Fourier analysis, 241–242, 444–451 checkerboards and, 451, 452f domains in, 447–448

linearity in, 449

of oscillatory potentials, 566, 567f, 575–576

periodic functions in, 444–447, 446f–447f, 449f practical considerations on using, 448 receptive fields and, 451

spatial, aspects of, 449–451 spatial frequency in, 450–451

standard periodic signals in, 445, 445f test signals in, 447

time versus space in, 449, 450f of visual evoked potential, 230

Fourier integral, 445–446 Fourier series, 446 Fourier theory, 444 Fovea

development of, 25, 26f ganglion cells of, 56, 57f

Foveal hypoplasia, in albinism, 369, 371f Foveation period, in albinism, 377–382 Frame pulse artifact, 281, 281f Frequency dependence, 440, 441f–442f

Frequency response function, of amplifier, 257–258, 257f Frontal eye fields, 113

disorders of, 113–115 Frontal motor areas, 113 Frumkes effect, 798

“Functional disorders,” visual evoked potentials in, 231–232 Functional magnetic resonance imaging (fMRI), 214–215, 216f–217f Fundamental harmonic, 444

Fundus albipunctatus, 409, 829, 834–836 associated with cone dystrophy, 835, 837f dark adaptation in, 829, 831f, 834 electroretinogram in, 813, 835, 837f fundus appearance of, 834–836

genetics of, 835–836 pathogenesis of, 836 typical, 835, 836f

Fundus photography (FP), 423

Fusion, in infant vision, 357–358, 357f–359f

G

Gamma aminobutyric acid (GABA), 86–88 and b-wave, 160–161, 163f

drug/toxic effects on, 657–658, 657f and oscillatory potentials, 174–175

Gamma aminobutyric acid receptors, in amacrine cells, 58–60, 59f, 62f

Gamma-band activity, 881 Gamma rhythms, 881 Ganglion cell(s), 49, 50f–51f

alpha (cat), 52 beta (cat), 52

center surround organization of, 80 dopamine and, 869–870, 869f–871f drug/toxic effects on, 658–659 dysfunction of

multifocal VEP in, 202–203

pattern ERG in, 189–196, 190f–192f, 345–347, 511–512, 514f embryological origins of, 25

of fovea, 56, 57f

in glaucoma, 851–855 image properties of, 55–56

low-spatial-frequency attenuation of, 192–193 M cells, 52, 55–56, 57f

neurotransmitters of, 86–88

ON/OFF, 51–52, 55–58, 56f–57f, 86, 87f, 95 in oscillatory potential generation, 175

P (midget), 52, 55–56, 57f postsynaptic responses of, 86, 87f receptive field of, 55, 56f, 57–58 sustained versus transient, 86

synapses of, 51–52, 54f, 56–58, 57f, 59f, 86, 93, 94f with amacrine cells, 58–60, 60f–61f, 63f

with bipolar cells, 51–52, 54f, 56, 57f, 93–95, 95f Ganglion cell layer, 93

Ganzfield stimulator, 265–267, 266f, 559, 560f Gaussian noise, 451–453

for kernel analysis, 482 Generalized object agnosia, 116

Giant cell arteritis, ischemic optic neuropathy with, 699 Gibbs’ phenomenon, 445

Glass contact lens electrodes, 246 Glaucoma

color vision in, 608, 609f, 854–855 contrast sensitivity in, 854–855 flash electroretinogram in, 851–852 mechanical theory of, 851 multifocal ERG in, 335

multifocal VEP in, 202, 335 pathogenesis of, 851

pattern ERG in, 851–855, 852t, 853f primary open angle (POAG), 851 psychophysical studies of, 854–855 vascular theory of, 851

visual evoked potentials in, 851–852 visual field defect of, 851, 852f

Glaucomatous optic neuropathy (GOND), 875 Glial cells, drug/toxic effects on, 659 Glutamate, 85–86

a-wave effects of, 152–154 b-wave effects of, 157–158 drug/toxic effects on, 657, 657f

Glutamate receptor(s), 50–52, 53f–54f, 58, 59f, 80–82 ionotropic, 51, 53f–54f, 59f, 80–82

metabotropic, 51, 53f–54f, 59f in Parkinson’s disease, 872

Glutamate transporters, 79 Glycine, 86–88

drug/toxic effects on, 657, 657f

and oscillatory potentials, 174, 569–570, 570f Glycine receptors, in amacrine cells, 58, 59f Goethe’s color theory, 597–598

Gold contact lens electrode, 245–247, 246f Gold foil electrode, 247–249, 248f Goldmann-Favre syndrome, 823

electroretinogram in, 507 fluorescein angiogram of, 424

Goldmann kinetic visual field testing, 541–542 Goldmann-Weekers Dark Adaptometer, 408 GOND (glaucomatous optic neuropathy), 875

G-protein-coupled receptors, in phototransduction, 67, 68f Granit’s model, of electroretinogram, 487, 488f

Granit’s PII. See b-wave

Granit’s PIII. See a-wave Grating stimulus, 413

for visual evoked potentials, 215–216, 219 Green-sensitive cones, 48, 599, 599f

pathways/synapses of, 56–57, 57f Ground loop, 616–617, 616f

Guanylate cyclase, in phototransduction, 71 Guanylate cyclase-activating proteins, 71–72

GUCY2D gene, and Leber congenital amaurosis, 748–749, 748f Guinea pig, anesthetics for, 926t

Gyrate atrophy, 705–715 biochemistry of, 708–712, 712f versus choroideremia, 712–713, 779 clinical description of, 707

dark adaptation in, 707, 710f differential diagnosis of, 712–713 electro-oculogram in, 705, 708f

electroretinogram in, 705, 706f–707f, 710f fluorescein angiography in, 707, 711f histopathology of, 708, 711f

historical perspective on, 705 molecular genetics of, 712 muscle biopsy in, 707, 711f natural history of, 707, 709f–711f night blindness in, 707, 710f

OAT-deficient, 705, 708–713, 712f physiology of, 708

pyridoxine-nonresponsive, 705, 706f–707f, 708–711, 709f–710f pyridoxine-responsive, 705, 706f–707f, 708–711, 708f, 711f relevant testing in, 712–713

treatment of, 711–712

visual field defect in, 707, 710f

H

Hagberg-Santavuori disease, 889 Haloperidol toxicity, 658 Haltia-Santavuori disease, 889 Harmonic(s)

first or fundamental, 444

in Fourier analysis, 444–445, 445f higher, 444

Harmonic frequency, 440, 442f Helmholtz’s rule, 444

Hemianopia, in chiasmal dysfunction, 857 Hemispatial (hemifield) neglect, 114

Hemispheric asymmetry, in albinism, 382–395, 385f, 387f–394f Henkes Lovac contact lens electrodes, 245–247, 246f

Henle’s layer, 25, 26f

Higher cortical function, disorders of, 109 Higher harmonics, 444

High-pass resolution perimetry, in multiple sclerosis, 877 HK-loop electrode, 248f, 250

Horizontal cell(s), 49, 50f–51f

center surround organization by, 54–55, 55f, 80 embryological origins of, 25

feedback to, 54–55

image properties of, 52–55 light response of, 79–80 neurotransmitters of, 86–88 receptive field of, 52–54, 55f, 79

in suppressive rod-cone interaction, 417 synapses of, 52–55, 79–82

type A, 79 type B, 79

Horse(s)

electroretinogram in, 923–931

anesthetics for, 923–924, 925t–926t, 927 specific procedures for, 924–927

photoreceptor diseases in, 923, 924t Humphrey Field Analyzer, 408, 542 Hum reduction, 617–618

“Hum tracer,” 615

Hutchinson-Tay choroiditis, drusen in, 717 Hyperabnormal ERG responses, 533–540

classification of, 533–536, 537f

Hyperabnormal ERG responses (continued) distribution by category, 536, 537t

fluorescein angiographic correlation of, 536, 538f, 538t, 539f illustrative case reports of, 536–539

in macular degeneration, 536, 538, 538f–539f in optic nerve dysfunction, 536–538, 539f, 540 pathologic process suggested by, 539–540

in Stargardt’s disease, 536, 538f Hyperbolic function, 473

Hyperosmolarity responses, 126, 128–130, 130f, 553, 554t, 555f, 561–562

Hypertension. See also Glaucoma pattern ERG in, 851–855, 854f psychophysical studies of, 854–855

Hypoemotionality, visual, 117 Hypothesis testing, 432–433

Hysteria, electrodiagnostic testing in, 637–640, 638f–639f

I

Ideal observer, 402 Incandescent lamps, 266–267 Independent group design, 433 Independent variables, 436 Indomethacin toxicity, 657 Infant(s), 353–359

blind, management of, 751–752 electroretinogram in, 745–746

fusion and stereopsis in, 357–358, 357f–359f preterm, vision in, 355–356, 356f

visual acuity testing in, 232, 353–359

visual evoked potentials in, 17, 232, 306, 353–359 multiple sweep paradigms for, 358

special considerations for, 358–359

sweep, reliability and validity of, 356–357, 357f waveform development in, 361, 362f

visual maturation in, 353–355, 355f

Infantile Refsum’s disease, electroretinogram in, 815–816, 817f Inhibitory ERG (I-ERG), 5, 5f

Inhibitory postsynaptic potentials, in EEG, 210–211, 212f Inner limiting membrane, 99, 100f

Inner nuclear layer, 93 Inner plexiform layer (IPL)

adhesion in, 98

drug/toxic effects on, 657–658 ON/OFF processing in, 95 organization of, 57–58

oscillatory potential generation in, 174–175 synaptic connections in, 57–62, 59f, 93–96, 94f–95f

Inner segment, of photoreceptors, 24f, 25, 29, 65, 66f Input impedance, of amplifier, 257

Instrumentation amplifiers, 275–276

Integrin, in synaptic transmission, 98–99, 100f, 103 Interference filters, 271

Interhemispheric asymmetry, in albinism, 375–377, 376f, 382–395, 385f, 387f–394f

Internal limiting membrane, electrode positioning in, 5–6 International Society for Clinical Electrophysiology of Vision

(ISCEV)

guidelines for multifocal ERG, 287–288, 309–317 standards of, 287–288

for electro-oculogram, 287–289

for electroretinogram, 287–288, 290–295, 784–791 for oscillatory potentials, 293

for pattern ERG, 287–288, 297–300, 341 for visual evoked potentials, 287–288, 303t

International Society for Veterinary Ophthalmology, 927 Interphotoreceptor matrix, 23, 24f

biochemistry of, 30–31 composition of, 23 embryological origins of, 23–25 function of, 30–31

insoluble components of, 30–31, 31f pathologies affecting, 31–32

soluble components of, 30–31 structure of, 30–31

Interphotoreceptor space, development of, 23, 25–27 Interplexiform cell(s)

neurotransmitters of, 88 oscillatory potentials from, 568

Interval estimate, 432

Intracellular signaling, calcium in, 41f, 42 Intraflagellar transport, 66

Intraocular pressure, elevated, 851–855. See also Glaucoma Intraretinal electroretinogram, 142

Inward rectifier ion channels, 37–38

Iodoacetic acid, and oscillatory potentials, 569–570, 570f ION. See Ischemic optic neuropathy

Ion channel(s), 37–40 calcium-dependent, 38 chloride, 38–39 delayed rectifier, 37

in electro-oculogram, 124–126 inward rectifier, 37–38 M-type, 38

nonspecific, 38 potassium, 37–38 voltage-activated, 39 voltage-dependent, 38, 79

Ion transport

membrane proteins involved in, 37–40 by retinal pigment epithelium, 37–42, 41f

Ion transporters, 39–40

IPL. See Inner plexiform layer

ISCEV. See International Society for Clinical Electrophysiology of Vision

Ischemic central retinal vein occlusion, 817 Ischemic optic neuritis, 699

Ischemic optic neuropathy (ION), 699–701 arteritic (AAION), 699

clinical presentation of, 699 histology of, 699

treatment of, 699 conditions associated with, 699

nonarteritic (NAION), 699–701 clinical presentation of, 699

versus Foster-Kennedy syndrome, 700–701, 701f pattern ERG in, 700

treatment of, 699

visual evoked potentials in, 699–701, 700f Ishihara plates, 599

Isolation amplifiers, 255–256, 277–278 i-wave, 165

in dogs, 912, 915f

J

Jansky-Bielschowsky disease, 889

Juvenile macular degeneration. See Stargardt disease Juvenile (X-linked) retinoschisis, 823–825

a-wave analysis in, 824–825, 826f b-wave analysis in, 824–825, 825f–826f

differential diagnosis of, 823 electro-oculogram in, 823–824

electroretinogram in, 810–812, 811f, 823–825, 825f–826f fluorescein angiogram of, 424, 425f, 823, 825f

fundus appearance of, 823, 824f gene identification in, 823

photoreceptor and inner retinal responses in, 824–825, 826f scotopic threshold response in, 824

suppressive rod-cone interaction in, 419

K

Kainate receptors, 51, 53f–54f

Kearns-Sayre syndrome (KSS), 665, 667–668 Kernel(s)

definition of, 479

first-order, 463, 464f, 479–480, 480f pattern-reversal stimulus for, 483 second-order, 479–482, 480f

reverse correlation of, 468 zero-order, 479

Kernel analysis, 479–484

binary sequence control sequence for, 482, 482t deconvolution errors in, avoidance of, 482

for multifocal techniques, 483–484 pseudorandom sequences for, 479, 482–483 stimuli for, 479, 480f, 482–484

Kinesin II, 65–66

Kjer-type dominant optic atrophy, pattern ERG in, 346–347 Kohlrausch knick, 406

Köllner’s rule, 609–610 Kufs’ disease, 889

Kynurenic acid, a-wave effects of, 153

L

Lactic acid transport, 40, 41f, 42

Laminins, in synaptic transmission, 99–103, 100f–101f, 104f Laplacian derivation, of visual evoked potentials, 230–231 Lapsing rate, 402

Larger animals electroretinogram in, 923–931

anesthetics for, 923–924, 925t–926t, 927 bilateral, 931, 931f

correlation with clinical findings, 929–931 guidelines/protocols for, 927–929, 928f, 930f specific procedures for, 924–927, 927f

photoreceptor variations in, 923 retina of, versus human retina, 923

Latency, 440–442, 464 Latency jitter, 456

Lateral geniculate nucleus (LGN), 109, 213 in albinism, 370, 372f

in monkey, 937, 937f in mouse, 937–938

Lateral inhibition, and pattern ERG, 191–193 Late receptor potential, 151, 585

Layer of Chievitz, 25

LCA. See Leber congenital amaurosis LCDs. See Liquid crystal displays

LCHAD. See Long-chain 2-hydroxyacyl CoA dehydrogenase Lead intoxication, 658

Leber, Theodor, 845

Leber congenital amaurosis (LCA), 745–752 AIPL-1 gene and, 750, 751f

blind infant with, management of, 751–752

chicken model of, 749 clinical variability of, 745 CRB-1 gene and, 750 CRX gene and, 749–750 definition of, 745

dog model of, 745, 747–748, 915–916 electroretinogram in, 745–746, 748, 748f, 749–750, 751f genetics of, 745–751, 746t

GUCY2D gene defects and, 748–749, 748f light adaptation in, 594–595, 595t molecular diagnosis of, 745

mouse model of, 747, 749, 900 prevalence of, 745

RDH12 gene and, 751

RPE65 gene defects and, 746–748 RPGRIP-1 gene and, 750–751 therapeutic studies of, 748

Leber’s hereditary optic neuropathy (LHON), 845–847 clinical course of, 845

electro-oculogram in, 845 electroretinogram in, 845–846 fundus appearance of, 845 genetics of, 845

pathogenesis of, 845 pattern ERG in, 346–347 treatment of, 845

visual evoked potentials in, 845–847, 846f–848f Leber’s optic atrophy, color vision in, 610f

LEDs. See Light-emitting diodes

Lesion localization, 505–517, 623–629, 624t–625t comparison and combination of tests for, 626–627, 628t definitive tests for, 628–629, 628t

electro-oculogram for, 505–506, 623–624

electroretinogram for, 505–511, 515–517, 624t–625t, 626–629 pattern ERG for, 505–517, 624t–625t

test result-clinical finding correlation for, 628–629, 628t visual evoked potentials for, 510–517, 624t–625t

Levodopa, visual effects of, 870–871, 872f, 879, 881 LGN. See Lateral geniculate nucleus

LHON. See Leber’s hereditary optic neuropathy Lid-hook electrodes, 247–250, 248f

Light adaptation

in bipolar cells, 84–85, 85f of cones, 593

in electro-oculogram, 128

of rods, 521–525, 523f–524f, 526f Light-adaptation effect, and oscillatory potentials, 572 Light-adapted a-wave, 150, 150f, 593

Light-adapted b-wave, 161–162, 163f, 593

Light-adapted electroretinogram, 7–8, 8f, 139–140, 140f, 150, 150f, 292–293, 593

fast flicker, 165, 166f, 293–294

Light-adapted oscillatory potentials, 173, 174f, 570–573, 571f–572f Light-emitting diodes (LEDs), 265, 267, 271–275, 559–560

applications of, 275

applied current and light output of, relationship between, 273, 273f

arrays of, 274–275, 275f in color vision testing, 602 defects affecting, 274 feedback loop of, 273, 274f linear control in, 272–274

for multifocal ERG, 327, 329f organic, 273

pulse density modulation of, 274 pulse width modulation of, 274

Light-emitting diodes (LEDs) (continued) spatial output of, 272, 272f

spectral output of, 271–272, 273f types of, 273

typical, construction of, 272, 272f voltage drive circuit of, 273, 273f white, 272–273, 273f

Light peak (EOG or ERG), 143, 144f, 148–149, 557, 558f, 561–562, 562f

Light peak/dark trough ratio (L/D), 553

Light rise, in electro-oculography, 11, 124, 126, 130f abnormal, in RPE dysfunction, 505–506

Limits, method of, 400

Linear approximation, of nonlinear system, 479, 481f Linear distortion, 442–444, 444f

Linearity, 439–440, 440f–441f Linear regression analysis, 436 Linear systems

cardinal property of, 439–440 definition of, 439

pattern response of, 480, 481f stimulus-response functions of, 473–476

Line frequency filter, 240 Line noise, 280

Liquid crystal displays (LCDs), 269–271, 269f for multifocal ERG, 327, 328f

output spectra of, 270, 270f problems with, 270

refresh rate of, 270

Local electroretinogram, 142

Localization of lesions, 505–517, 623–629, 624t–625t comparison and combination of tests for, 626–627, 628t definitive tests for, 628–629, 628t

electro-oculogram for, 505–506, 623–624

electroretinogram for, 505–511, 515–517, 624t–625t, 626–629 pattern ERG for, 505–517, 624t–625t

test result-clinical finding correlation for, 628–629, 628t visual evoked potentials for, 510–517, 624t–625t

Lock-in amplifier, 241, 260–261

Long-chain 2-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency, 889, 893–895

electroretinogram in, 893–895, 895f fundus appearance of, 893, 894f

Low-spatial-frequency attenuation (LSFA), of ganglion cells, and pattern ERG, 192–193

L-type calcium channels, 38, 42 Luminance, for VEP stimulation, 220

Luminance ERG, versus pattern ERG, 185–186, 187f Luminance noise, 603

M

MacAdam ellipse, 602 Macaque monkey. See Monkey(s)

Macular degeneration (dystrophy) age-related

alcohol electro-oculogram in, 135, 135f color vision in, 608–610, 609f

drusen with, 717–718 multifocal ERG in, 334

Sorsby’s fundus dystrophy and, 772 diagnostic flowcharts for, 515–517, 516f electronegative electroretinogram in, 813

fluorescein angiography in, 536, 538, 538f–539f, 540 hyperabnormal ERG responses in, 536, 538, 538f–539f, 540 juvenile. See Stargardt disease

multifocal ERG in, 334, 505, 510–511

pattern ERG in, 342–345, 343f–346f, 505, 510–511, 512f–513f

visual evoked potentials in, 510–511, 513f vitelliform. See also Best vitelliform macular dystrophy

differential diagnosis of, 765, 765t in X-linked retinoschisis, 823, 824f

Macular schisis, fluorescein angiogram of, 423–425, 425f Maculoscope, 727

Magnetic resonance imaging, functional, 214–215, 216f–217f Magneto-encephalogram (MEG), 214–215

Magnitude estimation, 403–404 Magnitude production, 403–404 Mains interference, 615–617, 616f, 618

reduction of, 617–618, 617f theories of, 616–617, 616f

Malattia Leventinese, 717, 718f–719f, 721

Malingering, electrodiagnostic testing in, 637–640, 638f–639f Masking, in therapeutic trials, 544

Matched-subjects design, 433

Maternally inherited diabetes and deafness (MIDD), 668–669, 668t M channels, 38

Mean, 431

standard error of, 432 Median, 431

Media opacities, visual evoked potentials with, 231 Melanoma-associated retinopathy (MAR), 691–697

clinical presentation of, 696

versus congenital stationary night blindness, 696–697, 697f electro-oculogram in, 135

electroretinogram in, 510, 696, 697f, 818 synaptic transmission in, 88

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), 665, 667–669, 668t

MERRF (myoclonic epilepsy with ragged red fibers), 665–669 Mesopic (term), 404

Metarhodopsin, 68–69, 69f Metathetic sensations, 399–400 Methanol toxicity, 659

mfERG. See Multifocal electroretinogram mfVEP. See Multifocal visual evoked potential Mice

electroretinogram in, 899–907, 900f a-wave analyses in, 902–906, 902f basic recording technique for, 900

b-wave analyses in, 900, 901f, 903, 904f, 906f cone-mediated responses in, 899–900, 901f, 906, 906f factors affecting, 900–901

general testing protocol for, 903 Naka-Rushton analysis of, 903, 904f oscillatory potentials in, 903, 905f phototransduction in, 902–903

rod-mediated responses in, 899–900, 901f, 903, 904f–905f, 906 rod- versus cone-mediated comparisons in, 906

specialized recording techniques for, 901 standard strains for, 903

lateral geniculate nucleus of, 937–938

Leber congenital amaurosis in, 747, 749, 900 Purkinje cell degenerative (pcd), 32 retinal-degenerative (rd), 32 retinal-degenerative slow (rds), 32

retina of, 936–937

retinitis pigmentosa in, 783 striate cortex of, 939

visual evoked potentials in, 935–939, 941–944 flash, 941–942, 942f

pattern, 942–943, 942f sweep, 942f, 943

visual pathway anatomy of, 936–939 Microconductive fiber electrode, 248f Microelectrodes. See Electrode(s) Microfilaments, of photoreceptors, 65, 67f Microtubules, of photoreceptors, 65, 67f

MIDD (maternally inherited diabetes and deafness), 668–669, 668t Middle retina diseases, 675–681

Minimization, in therapeutic trials, 544 Minimum-phase rule, 440–442 Mitochondria, 65, 66f, 665 Mitochondrial disorders, 665–669

clinical manifestations of, 665 criteria for, 665 electro-oculogram in, 667 electrophysiology of, 665–669

in patients genetically defined, 667–669, 668t

in patients without genetic diagnosis, 666–667, 666t full-field (flash) ERG in, 666–669, 666t, 668t

pattern ERG in, 667 rod response in, 666–667

visual evoked potentials in, 667 Mitochondrial myopathies, 665

Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), 665, 667–669, 668t

Mixed design, 433

Mizuo phenomenon, 823, 836–837 Mode, 431

Modified binary search (MOBS), 403 Modulation, definition of, 413 Monkey(s)

cortical visual areas of, 109 electroretinogram of, 150, 150f

lateral geniculate nucleus of, 937, 937f retina of, 936–937, 936f

striate cortex of, 109, 938–939, 938f

visual evoked potentials in, 935–941, 943–944 flash, 939–940, 939f

pattern, 940, 940f sweep, 940, 941f

Monochromatism (achromatopsia), 112–113, 795–796, 798t, 799–800 Motion perception, neurophysiology of, 113

Motion visual evoked potentials, 217–218, 224, 226f, 605 Motivation, and visual evoked potentials, 226

Mouse model. See Mice

Movement errors, in multifocal ERG, 317 M-sequence, 319–327, 464f, 465

binary, 320

for control of CRT stimulator, 321–322

in cross-correlation process, 322–324, 322f–324f cycle contents of, 324

decimation of, 321, 322f

generator program for, 325–327, 335–338 period or length of, 324

photodiode test of, 325, 326f

poor selection of, danger of, 324–325 properties of, 324–325

shift and add property of, 324–325, 324f–325f shift register generation of, 320–321, 321f window property of, 324

Mucolipidosis IV, electroretinogram in, 815, 816f Mucopolysaccharidosis IV, 32

Müller cell(s) cytology of, 30

in electroretinogram

in b-wave generation, 156–157, 159f–160f contribution of, 144–146, 145f

in scotopic threshold response generation, 172–173 in spatial buffering, 141, 141f, 146

embryological origins of, 25 function of, 30

Müller cell sheen retinal dystrophy, electroretinogram in, 813–814 Multifocal electroretinogram (mfERG), 197–199, 483–484, 483f

adaptation in, 313

amplifiers and filters for, 311, 327–329, 330f animal testing of, 331–333

artifacts in

averaging and smoothing, 317 recognition of, 316–317 rejection of, 311

reporting and resolution of, 314 averaging in, 311, 313

blind spot in, 317 calibration of, 310–311

in central retinal vein occlusion, 677

in central serous chorioretinopathy, 685, 686f clinical applications of, 333–335

contrast and background in, 311

contributing factors in response, dissection of, 330–331, 331f–332f

cross-correlation process in, 322–324, 322f–324f CRT stimulation for, 321–322, 327

description of, 309, 310f display options in, 311 eccentric fixation in, 315f, 317 electrical noise in, 314f, 316

electrodes for, 197, 198f, 249, 310, 312, 319 erroneous central peak in, 316f, 317

fast sequence of, 197, 200f fixation monitoring in, 313 fixation targets in, 311 flicker sequence in, 311 frame frequency of, 310

versus full-field ERG, 197–198, 199f, 330 hardware for, 319, 320f

ISCEV guidelines for, 287–288, 309–317 on basic technology, 310–312

on clinical protocol, 312–314 kernel analysis in, 483–484 LCD stimulation for, 327, 328f LED stimulation for, 327, 329f luminance for, 310 measurements in, 313–314

monocular versus binocular recording in, 313 movement errors in, 317

m-sequence of, 319–327 binary, 320

for control of CRT stimulator, 321–322 cycle contents of, 324

decimation of, 321, 322f

generator program for, 325–327, 335–338 period or length of, 324

photodiode test of, 325, 326f

poor selection of, danger of, 324–325 properties of, 324–325

shift and add property of, 324–325, 324f–325f shift register generation of, 320–321, 321f window property of, 324

myopia and, 632–633, 633f negative component of

initial (N1), 197, 199f, 313

Multifocal electroretinogram (mfERG) (continued) second (N2), 197, 199f

nomenclature of peaks in, 310 normal values in, 314

orientation/shadowing error in, 315f, 317 origins of, 310, 329–330

outer retina activity in, 198 patient positioning for, 312 patient preparation for, 312

pharmacological studies of, 331–332 positive component of (P1), 197, 199f, 313 postoperative, 334–335

recording of, 197, 198f, 311–312 choices in, 313

duration of, 313 sequence of, 313

refraction in, 313 reporting of, 313–314

in retinal diseases, 198–199, 201f–202f macular, 334, 505, 510–511

toxic, 335 vascular, 333–334

in retinitis pigmentosa, 199, 202f, 334, 508f screen properties of, 310–311

signal analysis in, 311

slow sequence of, 197, 200f software for, 319–320, 325–327 stimulation for, 310–311 stimulus delivery for, 327 stimulus parameters for, 311 stimulus pattern for, 311 stimulus size for, 311

stimulus source for, 310

sum of responses in, 197, 199f

topographic (3-D) response density plots in, 311–313, 314f trace arrays in, 311, 312f, 313, 314f

waveforms of, 199, 310, 310f preservation of shape, 327–329

wide-field, 335 Multifocal stimuli, 483

Multifocal techniques, 319–335, 483–484. See also Multifocal electroretinogram; Multifocal visual evoked potential

Multifocal visual evoked potential (mfVEP), 197, 199–203, 221 ganglion cell or optic nerve damage in, 202–203

in glaucoma, 202, 335 intersubject variability in, 200 intrasubject variability in, 200–202 kernel analysis in, 483–484

mean/averaged responses of, 200, 203f in multiple sclerosis, 202–203, 204f recording of, 199–200, 203f

Multiple evanescent white dot syndrome (MEWDS), 334, 685–687, 687f

Multiple sclerosis, 867–868, 873–878, 881–882 contrast perimetry in, 875–878

contrast sensitivity in, 875–878, 876f–877f cortical pathology in, 874–875

electrophysiology and psychophysics of, 873–878, 881–882 event-related potentials in, 881–882

correlation with imaging results, 881–882 higher visuocognitive abnormalities in, 881–882 high-pass resolution perimetry in, 877

parallel pathways and, 875–878 pattern ERG in, 873, 875

stimulus specificity and diagnosis of, 873–874 visual acuity in, 875

visual evoked potentials in, 202–203, 204f, 513f, 514, 515f, 867, 873–878, 874f

delay/latency in, 874–875, 876f pattern orientation in, 873–875, 876f

relationship with psychophysical measures, 875 visual field defects in, 875, 877f

Multiple system atrophy, versus Parkinson’s disease, 879 Multivariate statistical analysis, 436–437

Muscarinic (M) channels, 38

Muscular dystrophy, electroretinogram in, 816 M-wave

barium effects on, 167, 168f origins of, 166–168, 167f–168f

versus scotopic threshold response, 171–172 Mydriasis, drug-induced, 661

Mylar electrodes, 247

Myoclonic epilepsy with ragged red fibers (MERRF), 665–669 Myopia

and electroretinogram, 631–634, 632f and multifocal ERG, 632–633, 633f stretched retina hypothesis of, 634

Myosin VIIa, 66

N

Na+/Ca2+ exchanger, 39 Na+/HCO3- cotransporter, 39 Na+/H+ exchanger, 39

NAION. See Nonarteritic ischemic optic neuropathy Naka-Rushton analysis, of mouse model, 903, 904f Na+/K+-ATPase transporter, 39

Na+/K+/2 Cl− cotransporter, 40

NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa), 667–669, 669t, 670f–671f

N35 component, of PERG, 297, 298f, 341–342

N95 component, of PERG, 190–192, 192f, 297, 298f, 341–342, 505 in optic nerve dysfunction, 512–513, 514f

Nectins, 98

Negative electroretinogram, 809–819 in acquired diseases of eye, 816–819

autosomal-dominant inheritance of phenotype for, 814 in clinical practice, 819

definition of, 809

disorders associated with, 809–819, 810t in neurodegenerative disorders, 815–819 origins of, 809

Neglect, hemispatial (hemifield), 114 Neonate(s). See Infant(s)

Neovascular inflammatory vitreoretinopathy, autosomal-dominant, electroretinogram in, 814–815

Neovascularization of iris (NVI), 675–681. See also Central retinal vein occlusion

Neural retina

composition of, 24f, 27, 28f development of, 23–25 scleral surface of, 24f, 27, 28f

Neurodegenerative disorders. See also specific types contrast sensitivity in, 867

electroretinogram in, 815–819

Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), 667–669, 669t, 670f–671f

Neuromuscular junction, 98

Neuronal ceroid lipofuscinoses, 889–895 adult-onset (ANCL), 889

atypical forms of, 889–890 classical forms of, 889

clinical presentation of, 889

electroretinogram in, 815, 815f, 890–893, 891f–894f Finnish variant (vLINCL) of, 889–890

incidence of, 889 infantile-onset (INCL), 889 juvenile-onset (JNCL), 889

late infantile-onset (LINCL), 889 night blindness in, 890 submicrovolt recordings in, 891–892 visual acuity in, 890

Neuronal response, reverse correlation of, 461–471 Neurotransmitters, 86–88, 655, 656t

drug toxicities and, 655, 657–658, 657f release from bipolar cells, 85

release from photoreceptors, 79 relevance to clinical states, 88–91

Newton’s color theory, 597–598 Nidogen, 99, 100f

Night blindness

in cone dystrophy, 795, 797–798 congenital stationary (CSNB), 829–837

color vision in, 834

complete, 510, 511f, 809, 811f, 829–834 dark adaptation in, 409, 409f, 829, 831f electro-oculogram in, 832

electroretinogram in, 507–510, 511f, 809–810, 811f, 829–832, 831f–832f

intensity series in, 832, 833f long-flash photopic, 832, 834f

genetics of, 809–810, 834, 835f incomplete, 510, 511f, 809, 811f, 829–834 initial patient complaints in, 829, 830t

versus melanoma-associated retinopathy, 696–697, 697f oscillatory potentials in, 570, 571f, 577, 577f pathogenesis of, 834

refractive error in, 829, 830f Schubert-Bornschein type of, 829 scotopic threshold response in, 832, 833f visual acuity in, 829, 830f

in gyrate atrophy, 707, 710f inherited, synaptic transmission in, 88 in neuronal ceroid lipofuscinoses, 890

suppressive rod-cone interaction in, 418–419 urban, 795

vitamin A deficiency and, 803–804 Nitric oxide, 88

in amacrine cells, 58, 60, 62f–63f Nocturnal vision, rod specialization for, 47 Noise

electrical, in multifocal ERG, 314f, 316 electronic, 255, 256t

Gaussian, 452–453

for kernel analysis, 482 line, 280

luminance, 603 physiological, 255, 256t

white, for kernel analysis, 479, 480f, 482

Nonarteritic ischemic optic neuropathy (NAION), 699–701 clinical presentation of, 699

versus Foster-Kennedy syndrome, 700–701, 701f pattern ERG in, 700

treatment of, 699

visual evoked potentials in, 699–701, 700f Nonessential nonlinearity, 479

Nonlinear distortion, 443 Nonlinearity, 479, 480f

dynamic, 443 essential, 479

kernel analysis of, 479–484

linear approximation of, 479, 481f nonessential, 479

static, 443

Nonorganic visual loss, 637

Non-parametric psychophysical techniques, 402 Non-parametric statistical testing, 435–436

Nonphotic standing potential responses, 553, 554t, 555f Nonspecific cation channels, 38

Nonsteroidal anti-inflammatory drugs, electro-oculogram effects of, 127

Normal distribution, 431 Normal values

in electroretinogram, 294, 533–536, 534t, 535f in multifocal electroretinogram, 314

in visual evoked potentials, 307 Normative data, 431–432

Notch filter, 240, 257–258, 257f Nougaret, Jean, 781

NRL gene, and retinitis pigmentosa, 781 Nutritional deficiencies, 659 Nyctalopia, mild, cone dystrophy with

ERG findings in, 88–90, 89f synaptic transmission in, 88–91

Nyctalopin, 834 Nystagmus

congenital, in albinism, 377–378, 378f–380f latent, and VEPs in amblyopia, 645, 645f

NYX gene, and congenital stationary night blindness, 835

O

OAT. See Ornithine aminotransferase Object agnosia, 116

Object anomia, 116–117 Occipitofugal pathways, 109–110, 110f

dorsal (where), 109–110, 110f

neuroanatomy and neurophysiology of, 113 syndromes of, 113–115

ventral (what), 109–110, 110f lesions of, 116–117

neuroanatomy and neurophysiology of, 116 Ocular motor apraxia, 113–114

Ocular siderosis, early receptor potential in, 550, 550f Ocular standing potential, 553

“Off c-wave,” 561, 562f

OFF pathways. See ON/OFF pathways Oguchi’s disease, 409, 603, 829, 836–837

dark adaptation in, 829, 831f, 836, 837f–838f electro-oculogram in, 836

electroretinogram in, 834f, 836–837, 837f fundus appearance of, 836, 838f

genetics of, 836–837 pathogenesis of, 837

OMPs (oscillatory membrane potentials), 176, 176f ON/OFF pathways, 51–58, 53f

amacrine cell, 58, 60f

bipolar cell, 51–57, 53f–54f, 57f, 80–82, 80f–81f ganglion cell, 51–52, 55–58, 56f–57f, 86, 87f, 95 in inner plexiform layer, 95

parallel processing in, 80, 80f–81f ON pathways, 51–52, 53f

OPL. See Outer plexiform layer OPs. See Oscillatory potentials

Opsin, 47, 599–600, 599f Optic aphasia, 117 Optic ataxia, 113–114 Optic atrophy

color vision in, 609–610, 610f

dominant, pattern ERG in, 346–347, 348f multifocal VEP in, 202

and pattern ERG, 189–192, 190f–192f temporal

in cone dystrophy, 795, 798f, 799 fluorescein angiogram of, 427, 427f

Optic chiasm dysfunction. See Chiasmal dysfunction (lesions)

Optic nerve misrouting, in albinism, 369, 371f–372f, 514–515, 516f Optic nerve stimulation, potentials evoked by, 176

Optic neuropathy

diagnostic flowcharts for, 515–517, 516f drug-induced, 659

hyperabnormal ERG responses in, 536–538, 539f, 540 ischemic, 699–701

arteritic (AAION), 699 clinical presentation of, 699 histology of, 699

treatment of, 699 conditions associated with, 699

nonarteritic (NAION), 699–701 clinical presentation of, 699

versus Foster-Kennedy syndrome, 700–701, 701f pattern ERG in, 700

treatment of, 699

visual evoked potentials in, 699–701, 700f multifocal VEP in, 202–203

in multiple sclerosis, 867–868, 873–878, 881–882. See also Multiple sclerosis

nutritional, 659

in Parkinson’s disease, 867–873, 878–882. See also Parkinson’s disease

pattern ERG in, 345–347, 347f–348f, 512–513, 514f traumatic, electrophysiology of, 515–517, 517f visual evoked potentials in, 231, 505, 512–513, 514f

Optic primordium, 23 Optic stalk, 23

Optic sulcus, 23 Oregon eye disease, 816

Organic light-emitting diodes (O-LEDs), 273 Orientation error, in multifocal ERG, 315f, 317 Orientation selectivity

in multiple sclerosis, 873–875 in Parkinson’s disease, 873

reverse correlation of, 469–470, 469f Ornithine aminotransferase (OAT), 705

deficiency, in gyrate atrophy, 705, 708–713, 712f Orthogonality, 453

Oscillatory membrane potentials (OMPs), 176, 176f Oscillatory potentials (OPs), 565–578, 566f

analysis of response, methods of, 575–576 artificial variable sum amplitude of, 575 bandwidth filtered versus software-filtered, 566, 567f bandwidth restriction of, 565, 566f, 575–576 b-wave relationship with, 569–570

chronological sequence of, 568

in cone dystrophy, 570, 571f, 576f, 577

in congenital stationary night blindness, 570, 571f, 577, 577f depth profile of, 173–174, 174f

in diabetic retinopathy, 569, 569f diagnostic use of, 576–578 discovery of, 8

early versus late, 568

extraction from raw ERG signal, 565–567, 566f–567f fast Fourier transform analysis of, 566, 567f, 575–576 flash stimulus and, 573–574, 573f

flickering light stimulus and, 572–573, 573f frequency of, 173, 565

generation of

cells involved in, 174–175

in intracellular responses from neurons, 175–176, 175f mechanisms of, 175–176

neuronal interaction/feedback circuits in, 175 ISCEV standard for, 293–294

in mouse, 903, 905f

origins of, 173–176, 567–568

pharmacological manipulation of, 173–174, 569–570, 570f photopic, 173, 174f, 570–573, 571f–572f

in rat, 927

retinal distribution of, 568

in retinitis pigmentosa, 576f, 577, 578f scotopic, 573–575, 573f

shorter-latency versus longer-latency, 568 single-sweep versus averaged, 566–567, 567f

Oscilloscopes, 260 Outcome measures, 541

Outer limiting membrane, 24f, 29 Outer nuclear layer, 93

Outer plexiform layer (OPL), 93 development of, 25 drug/toxic effects on, 657–658

synaptic processing and organization in, 96–97 Outer retina disorders, 683–687

Outer segment, of photoreceptors, 24f, 25, 28–29, 28f, 47, 48f, 65, 66f

Output impedance, of amplifier, 257

P

Paired-flash ERG analysis, 791, 791f

concept and methodology of, 519–520, 520f of dark adaptation, 520–521, 521f

of light adaptation, 521–525, 523f–524f, 526f

of recovery following bright illumination, 525–530, 527f–530f of rod phototransduction and adaptation, 519–530

Parallel processing, 80, 80f–81f

Parameter(s). See also specific tests pathology indications in, 432 population, estimation of, 432

Parameter estimation by sequential testing (PEST), 403 Parametric psychophysical techniques, 402

Parametric statistical testing, 435–436 Parastriate cortex, 109

damage to, syndromes caused by, 111 Parkinson’s disease, 867–873, 878–882

color vision deficits in, 872–873 contrast sensitivity in, 867, 872 corticocortical interactions in, 881 differential diagnosis of, 879 dopamine deficiency in, 868–873

electrophysiology and psychophysics of, 868–873, 878–881 electroretinogram in, 873

event-related potentials in, 878–881, 880f higher visuocognitive abnormalities in, 878–881

levodopa therapy for, visual effects of, 870–871, 872f, 879, 881 neuropharmacology of, 867, 879

non-dopaminergic visual effects in, 871–872 parallel pathways in, 870

pattern ERG in, 868–869, 869f, 871, 872f P300 delays in, 878–879

P100 response in, 878–879, 880f

spatial and temporal frequency in, 868–869, 869f spatial processing in, 869–870, 869f–871f

visual categorization impairment in, 879–880 visual cortical deficits in, 873

visual evoked potentials in, 868, 871–873 Parseval theorem, 453

Patching, and VEPs in amblyopia, 645, 645f Patient compliance, and VEP recording, 232 Patient positioning

for data acquisition, 237–238 for multifocal ERG, 312

for pattern ERG, 341–342 Patient preparation

for electroretinogram, 292–293, 299–300, 558 for multifocal ERG, 312

for pattern ERG, 299

for visual evoked potentials, 305 Patient-related artifacts, 279, 619 Patient safety, amplifiers and, 255–256 Pattern dystrophies, 757–761

clinical findings in, 757 description of, 757

electro-oculogram in, 757–760, 760f electroretinogram in, 757–760, 760f fluorescein angiography in, 425, 757, 758f–759f multifocal electroretinogram in, 757 physiological findings in, 757–760

vitelliform variant of, 765, 765t

Pattern electroretinogram (PERG), 185–194, 341–348, 342f. See also specific disorders/findings

amplification for, 299, 341 artifact rejection in, 299

averaging and signal analysis in, 299 background illumination for, 299

check size dependence (tuning) of, 191–193, 193f clinical applications of, 342–347

color responses in, 604

comparison and combination with other tests, 626–627 components of, 341–342

contrast for, 298

contrast transfer function of, 194, 194f correlation with clinical findings, 628–629, 628t data display systems for, 299

diagnostic flowcharts for, 515–517, 516f electrodes for, 298, 341

field and check size for, 298 frame rate of, 299

in ganglion cell dysfunction, 189–192, 190f–192f, 345–347, 511–512, 514f

generator of, pinpointing of, 186

ISCEV standard for, 287–288, 297–300, 341 on basic technology, 298–299

on clinical protocol, 299–300 on recording equipment, 299

on waveform nomenclature and measurement, 297–298 localization of lesions in, 505–517, 624t–625t

luminance for, 298

luminance versus pattern stimulation in, 185–186, 187f

in macular dysfunction, 342–345, 343f–346f, 505, 510–511, 512f–513f

in malingering and hysteria, 638–640, 638f–639f in mitochondrial disorders, 667

monkey versus human, 190–192, 192f

monocular and binocular recording in, 299–300 N35 component of, 297, 298f, 341–342

N95 component of, 190–192, 192f, 297, 298f, 341–342, 505 normal, 341–342

in optic nerve dysfunction, 345–347, 347f–348f, 512–513, 514f origins of, 341–342

patient positioning for, 341–342 patient preparation for, 299

P50 component of, 190–192, 192f, 297, 298f, 341–342, 505 photopic negative response and, 170

physical source localization in, 187–189, 189f recalibration of, 299

recording of, 341–342 reporting results of, 300

in retinitis pigmentosa, 506–507, 508f reversal rate of, 299

second harmonic in, 185–186 steady-state, 298–299

stimulus parameters for, 298–299

stimulus patterns for, proper versus improper, 185, 188f transient

ISCEV guidelines on, 297, 298f, 299 peaks and components of, 190, 192f Pattern-evoked potentials, aging and, 361–367

Pattern onset/offset VEP, 212f, 222, 223f, 302–303, 305–306, 306f Pattern reversal

for evoked potential evaluation, 210, 222–224, 223f, 225f, 302, 305, 305f, 605

for kernel analysis, 483

P50 component, of PERG, 190–192, 192f, 297, 298f, 341–342, 505 in ganglion cell dysfunction, 511–512, 514f

in macular dysfunction, 510–511, 512f–513f PDA (cis-2,3-piperidine dicarboxylic acid)

a-wave effects of, 153–155, 153f, 155f b-wave effects of, 162, 163f

d-wave effects of, 165 and multifocal ERG, 332

PDE6A/PDE6A genes, and retinitis pigmentosa, 781

Peanut agglutinin (PNA)-binding glycoconjugates, in cone matrix sheaths, 27, 28f, 30, 31f

PERG. See Pattern electroretinogram

Periodic functions, in Fourier analysis, 444–447, 446f–447f, 449f Peristriate cortex, 109

damage to, syndromes caused by, 111 pH, intracellular, regulation of, 42

Phagocytosis, by retinal pigment epithelium, 27 Pharmacological dissection, in ERG, 142 Phase characteristic, 440, 441f

Phase distortions, amplifiers and, 260 Phase-free filtering, 449, 450f

Phase shift, 440–442, 442f Phenothiazine toxicity, 656–657 Phenytoin toxicity, 658

PhNR (photopic negative response), 168–170, 169f Phosducin, 72

Phosphodiesterase activation of, 70 inactivation of, 70

in phototransduction, 67, 68f, 70, 519 in retinitis pigmentosa, 783–784

Phosphodiesterase inhibitor toxicity, 657 Phosphors

for cathode-ray tube, 268, 268f for light-emitting diodes, 273

Photic driving, 208, 221 Photochromatic interval, 406

Photocurrent saturation, 519 Photopic (term), 404

Photopic a-wave, 150, 150f, 593

Photopic b-wave, 161–162, 163f

Photopic ERG, 7–8, 8f, 139–140, 140f, 150, 150f, 292–293, 593 fast flicker, 165, 166f, 293–294

Photopic negative response (PhNR), 168–170, 169f in humans and rodents, 170

relationship to pattern ERG, 170 wavelength of stimuli and, 170

Photopic oscillatory potentials, 173, 174f, 570–573, 571f–572f Photoreceptor(s). See also Cone(s); Rod(s)

activity of, clinical assessment of, 497–500, 498f–499f cell cytology of, 28–30, 49, 50f–51f

cilia of, 65–66, 66f–67f

currents of, and a-wave, 151–152, 151f–152f dark adaptation of, 405–409, 406f drug/toxic effects on, 657

duplicity theory of, 404–405 embryological development of, 25–27 function of, 28–30

health of

early receptor potential assessment of, 550–551 electroretinogram of, 505

measuring with a-wave leading edge, 487–500 hyperpolarizing response of, 49, 52f, 79

inner segment of, 24f, 25, 29, 65, 66f

interface with retinal pigmented epithelium, 23–32, 24f metabolic machinery of, 65, 66f

microfilaments of, 65, 67f microtubules of, 65, 67f morphology of, 28–30, 28f neurotransmitter release from, 79

outer segment of, 24f, 25, 28–29, 28f, 47, 48f, 65, 66f parallel processing in, 80, 80f–81f

pathologies affecting, 31–32 physiology of, 65–75

protein migration/translocation, 72–75, 75f retinal position of, 47

synapses of, 49–62, 53f–54f, 59f synaptic transmission in, 79–91

relevance to clinical states, 88–91 types of, 49

Phototransduction, 66–75 activation cascade of, 67, 68f

cGMP-gated channels in, 67, 70, 71f in cones, 72

in mouse, 902–903 phosphodiesterase in, 67, 68f, 70

relationship to electrical activity, 72, 73f–74f in retinitis pigmentosa, 783–784

rhodopsin in, 67–69, 68f–69f

rod, paired-flash analysis of, 519–530 in rods, 66–72

transducin in, 67, 68f, 70 Photovoltaic effect, and artifact, 280

Physiological change, clinical assessment of, 434–435 Pigeons, anesthetics for, 926t

Pigmentary retinopathy, 665 Pigs, anesthetics for, 926t PI process, 4–5, 5f, 142

PII process, 4–5, 5f, 142

PIII process, 4–5, 5f, 142. See also a-wave; b-wave distal versus proximal, 146

slow, 143–146, 144f–145f

Pituitary tumors, 857. See also Chiasmal dysfunction

Plasma displays, 271 Plato’s color theory, 597 PMMA electrode, 252, 558

PNR (proximal negative response), 166, 167f–168f Point estimate, 432

Polymethylmethacrylate (PMMA) electrode, 252, 558 Polyvinyl (PVA) gel electrodes, 249

Population parameters, estimation of, 432 Positron emission tomography, 214–215 Posterior parietal cortex, 113

disorders of, 113–115

Postreceptoral response. See also Oscillatory potentials a-wave, 152–155, 153f–155f

intrusion on leading edge, 491, 492f b-wave, 475–476, 475f

derivation of, 475, 475f

Postsynaptic potentials, in EEG, 210–211, 212f Potassium channel(s)

calcium-dependent, 38, 42 delayed rectifier, 37, 42

in electro-oculogram, 124–126 in electroretinogram

light-evoked changes in, 157–159, 160f–161f, 167, 168f, 172–173, 172f

in scotopic threshold response generation, 172–173, 172f spatial buffering of, 140–141, 141f, 146

inward rectifier, 37–38 M-type, 38

Power

of electrical signal, 453–454 statistical, 434

Power density, 454

Power density spectrum, 454

PPRPE (preserved para-arteriolar retinal pigment epithelial retinitis pigmentosa), 425, 426f

Preamplifiers, 255–256

Preparation, and visual evoked potentials, 226

Preserved para-arteriolar retinal pigment epithelial retinitis pigmentosa (PPRPE), 425, 426f

P100 response, 17, 229, 305 aging and, 361–365, 363f–364f

in Parkinson’s disease, 878–879, 880f

P300 response, in Parkinson’s disease, 878–879, 880f Pressure-induced retinopathy, electrophysiology of, 515–517, 517f Preterm birth, and visual acuity, 355–356, 356f

Primary open angle glaucoma, 851. See also Glaucoma Primary visual cortex

damage to, disorders associated with, 110–111 human, 109, 110f

monkey, 109, 938–939, 938f mouse, 939

Principal component analysis, of VEPs in albinism, 373–374, 374f, 382–385

Processes of ERG (PI, PII, PIII), 4–5, 5f, 142 Progressive external ophthalmoplegia, 665

Progressive retinal atrophy, in dogs, 913–915, 914f–915f, 923, 924t Progressive rod-cone degeneration (prcd), 32

in dogs, 914–915, 915f

Progressive rod-cone dysplasia, in dogs, 914–915, 915f Proline supplementation, for gyrate atrophy, 711–712 Prosopagnosia, 116

Protanopes (protans)

early receptor potential in, 585, 589–591, 589f–590f

genetic carriers, ERG responses in, 587f, 588–589, 588f–589f genetic development of, 600

rapid off-response in, 585–589, 586f–588f

suppressive rod-cone interaction in, 419

visual evoked potentials in, 604–607, 605f–607f Protanopia, 599. See also Protanopes

Protein migration/translocation in photoreceptors, 72–75, 74f Prothetic sensations, 399–400

Proximal negative response (PNR), 166, 167f–168f Proximal PIII, 146

Pseudoisochromatic plates, 599

Pseudorandom sequence, for kernel analysis, 479, 482–483 Psychic paralysis of gaze, 113–114

Psychophysic(s) definition of, 399

fundamental concepts of, 399–400 Psychophysical techniques, 399–409, 542

adaptive, 402–403 classical, 400

clinical applications of, 404

for color vision testing, 607–610

versus electrophysiological approaches, 399 in glaucoma/hypertension, 854–855

in multiple sclerosis, 875 non-parametric, 402 parametric, 402 suprathreshold, 403–404

Ptosis, drug-induced, 661

Pulse density modulation, of LEDs, 274 Pulse width modulation, of LEDs, 274 Pupillary size, aging and, 365

Pure alexia, 116–117, 117f

Purkinje cell degenerative (pcd) mice, 32 PVA gel electrodes, 249

p-value, 433–434 P-wave, 176

Pyridoxine-nonresponsive gyrate atrophy, 705, 706f–707f, 708–711, 709f–710f

Pyridoxine-responsive gyrate atrophy, 705, 706f–710f, 708–712, 708f, 711f

Q

Quality of life, 542–543 Questionnaires, 542–543 QUEST method, 403 Quinine retinopathy, 841–842

clinical course of, 841

electroretinogram in, 819, 820f, 841–842, 842f fluorescein angiography in, 841

pattern ERG in, 842f

visual evoked potentials in, 841–842

R

Rab escort protein-1 (REP-1), in choroideremia, 779 Randomized controlled trial, 541

Range, statistical, 431 Raster, 268, 322 Rat(s)

anesthetics for, 926t oscillatory potentials in, 927 RCS, 32

RDH5 gene, and fundus albipunctatus, 835–836 RDH12 gene, and Leber congenital amaurosis, 751 RDH5 gene mutations, 784

RDS/peripherin gene

and drusen, 717, 720–721, 720f, 722f and retinitis pigmentosa, 783

Rebound, 470

Receiver operating characteristic (ROC) curve, 401, 434–435 Receptive field(s)

in alert animal, 465–466, 466f–467f of cones, 49, 52f

dopamine and, 869–870, 869f–871f first-order, 463, 464f

and Fourier analysis, 451

of ganglion cells, 55, 56f, 57–58 of horizontal cells, 52–54, 55f, 79

mapping spatial structure of, 463–465, 464f reverse correlation of, 461–471

Recovery following bright illumination, 525–530, 527f–530f Rectification, 443, 443f

Red-green color deficiency, 599 classification of, 588

ERG recordings in, 585–591 Red-sensitive cones, 48, 599, 599f

pathways/synapses of, 56–57, 57f Refractive error

in congenital stationary night blindness, 829, 830f and electroretinogram, 631–634, 632f

and multifocal ERG, 632–633, 633f in Oguchi’s disease, 836

Refsum’s disease, infantile, electroretinogram in, 815–816, 817f Regression analyses, 436

Repeated measurements design, 433

Reporting, ISCEV standards for, 294–295, 300, 307–308 Response latency, of visual evoked potentials, 208 Response maps, 465

Retina. See also specific entries cells of, 49, 50f–51f development of, 23–25

embryological origins of, 23–25 functional organization of, 47–62, 48f–51f neural. See Neural retina

Retinal, 47

Retinal artery occlusion branch, 334

central, 681

c-wave in, 561, 561f

electroretinogram in, 507, 681, 816–817 Retinal pigment epithelium (RPE)

black layer of, 47

cell cytology of, 27–28 development of, 25

disorders/dysfunction of, 683–687. See also specific disorders electro-oculogram of, 505–506, 623–624

drug/toxic effects on, 655–657 electrode positioning in, 5–6 embryological origins of, 23–25

fast capacitative compensation by, 40 functions of, 27–28, 37–42

interface with photoreceptors, 23–32, 24f intracellular pH regulation by, 42 intracellular signaling in, 42

light peak/dark trough ratio in, 553 membrane mechanisms of, 37–42, 124–126 morphology of, 27–28

pathologies affecting, 31–32

pattern dystrophies of, 425, 757–761 phagocytosis by, 27

responses related to, 553, 554t, 555f slow responses of, 557

synthesis and secretion by, 27–28 transepithelial potential of, 146

Retinal pigment epithelium (RPE) (continued) transport by, 27, 37–42

ion, 37–42, 41f

lactic acid, 40, 41f, 42

voltage difference across, 11, 123–126, 124f–125f. See also Electro-oculogram

Retinal vein occlusion branch, 681 central, 675–681

electroretinogram in, 675–681, 676f–680f, 816–818, 818f amplitudes in, 675–676, 676f–677f

intensity-response analysis in, 677–678, 680f temporal factors in, 676–677, 678f–679f

ischemic, 817, 818f multifocal ERG in, 677 nonischemic, 817

photoreceptor function in, 679–680, 680f Retinitis pigmentosa, 781–792

autoimmune retinopathy with, 691–697 versus choroideremia, 777

clinical features of, 781

clinical-test result correlation in, 628–629, 628t Coats’ reaction in, 427, 428f

conditions associated with, 781 electro-oculogram in, 624

electroretinogram in, 506–507, 506f, 508f, 623, 784–791, 812–813, 812f–813f

amplitude-retinal illuminance functions in, 787–791, 789f–790f

a-wave analysis in, 506–507, 790f, 791 c-wave in, 560f, 561

extensions of protocol for, 787–791 full-field, sensitivity of, 786–787, 787f paired-flash method in, 791, 791f protocol for, 784–786, 785f–787f

flicker ERG in, 581, 582f–583f

fluorescein angiogram of, 425, 426f, 427, 428f fundus appearance of, 781, 782f

genetic analysis of, 781–784, 782t light adaptation in, 594–595, 595t mouse model of, 783

multifocal electroretinogram in, 199, 202f, 334, 508f oscillatory potentials in, 576f, 577, 578f

pattern ERG in, 506–507, 508f

photoreceptor responses in, 496f–498f, 497, 506–507, 506f, 508f, 783–784

phototransduction cascade in, 783–784

preserved para-arteriolar retinal pigment epithelial, 425, 426f prevalence of, 781

psychophysical approaches in, 399 suppressive rod-cone interaction in, 418–419 visual cycle in, 784

X-linked, 781

alcohol electro-oculogram in, 134–135, 134f oscillatory potentials in, 576f, 577

Retinol, transport of, 27

Retinoschisis, juvenile (X-linked), 823–825 a-wave analysis in, 824–825, 826f b-wave analysis in, 824–825, 825f–826f differential diagnosis of, 823 electro-oculogram in, 823–824

electroretinogram in, 810–812, 811f, 823–825, 825f–826f fluorescein angiogram of, 424, 425f, 823, 825f

fundus appearance of, 823, 824f gene identification in, 823

photoreceptor and inner retinal responses in, 824–825, 826f

scotopic threshold response in, 824 suppressive rod-cone interaction in, 419

Retinovascular disorders. See also specific types electroretinogram in, 816–818

Retrochiasmal dysfunction (lesions), 665, 860–863 bilateral, 861–863

cortical blindness in, 861–863 unilateral, 860–861

visual evoked potentials in, 231, 307, 515, 860–863, 861f–862f Reverse correlation, 461–471

in alert animal, 465–466, 466f–467f basics of, 462–463, 462f

of color selectivity, 469–470, 469f of depth selectivity, 469–470 early technical limitations of, 465

of orientation selectivity, 469–470, 469f potential pitfalls in, 470–471

of second-order kernels, 467f, 468

of simple cell receptive fields, 463–465, 464f space-time maps in, 465, 466f

suppression versus no response in, 470 Rhodopsin, 28–29, 47, 48f, 65

activation of, 67–68, 68f cycle of, 69f

and early receptor potential, 549–551 inactivation of, 68–69, 69f

in retinitis pigmentosa, 783–784 vitamin A deficiency and, 803, 805f

Rhodopsin kinase, in Oguchi’s disease, 836–837 Riddoch phenomenon, 111

“Rim” protein, 29

RLBP1 gene, and retinitis pigmentosa, 781

ROC (receiver operating characteristic) curve, 401, 434–435 Rod(s)

activity of, clinical assessment of, 497–500 biochemistry of, 29–30

cell cytology of, 28–30 cilia of, 65–66, 66f–67f

currents of, and a-wave, 151–152, 151f–152f definition of, 47

disc membranes of, 29

in duplicity theory, 404–405 embryological development of, 25–27 functional organization of, 47–48

health of, measuring with a-wave leading edge, 487–500 image properties of, 49–50

inner segments of, 24f, 25, 29, 65, 66f microfilaments of, 65, 67f microtubules of, 65, 67f

morphology of, 28–30 neurotransmitter release from, 79 in nocturnal vision, 47

outer segments of, 24f, 25, 28–29, 28f, 47, 48f, 65, 66f phototransduction in, 66–72

paired-flash ERG analysis of, 519–530 physiology of, 65–75

protein migration/translocation in, 72–75, 74f

recovery following bright illumination, 525–530, 527f–530f responses of. See Rod response

spatial density of, 405

suppressive interaction with cones, 417–420. See also Suppressive rod-cone interaction

synaptic transmission in, 79–91 Rod-cone break, 406, 406f, 407, 407f

Rod-cone dysplasia, in dogs, 913–915, 914f–915f Rod monochromatism, 795–796, 798t

Rod response, 72, 73f–74f, 405. See also specific disorders/findings a-wave, 154–155, 154f–155f, 157f, 487–500, 488f, 809

age and, 493, 494f

alternative models of, 493–495, 495f high-intensity stimulation of, 487–489, 488f–490f model of, 489–491, 490f–492f

in retinal disease, 495–497, 496f

S and Rmax parameters of, 495–497, 496f b-wave, 473–476, 474f, 632–633, 635f clinical assessment of, 497–500, 498f–499f

dark-adapted, 405–409, 406f, 520–521, 521f, 595–596, 596f in early receptor potential, 549–551

in ERG, ISCEV standard for, 293 e-wave, 166

hyperpolarizing, 49, 79

light-adapted, 521–525, 523f–524f, 526f in mitochondrial disorders, 666–667

in mouse, 899–900, 901f, 903, 904f–905f, 906 paired-flash ERG analysis of, 519–530

RP. See Retinitis pigmentosa

RPE. See Retinal pigment epithelium

RPE65 gene

and Leber congenital amaurosis, 746–748 and retinitis pigmentosa, 784

RPGR gene, and retinitis pigmentosa, 781

RPGRIP-1 gene, and Leber congenital amaurosis, 750–751

S

Sample and hold amplifier, 241, 242f Sampling, of visual evoked potentials, 229 Schopenhauer’s color theory, 597–599

Scleral search coil method, of ocular motor assessment, 377 Scotoma(s)

in Bietti’s crystalline dystrophy, 735 in chiasmal dysfunction, 857

in Sorsby’s fundus dystrophy, 771 Scotopic (term), 404

Scotopic a-wave, 150, 150f Scotopic b-wave, 160–161, 163f

stimulus-response functions for, 473–476, 474f, 476f

Scotopic (dark-adapted) ERG, 7–8, 8f, 139–140, 140f, 150, 150f, 292–293, 595–596, 596f

Scotopic oscillatory potentials, 573–575, 573f Scotopic threshold response (STR), 150–151, 168

in congenital stationary night blindness, 832, 833f depth distribution of, 171–172, 171f

in dogs, 912

K+-Müller cell mechanism for, 172–173, 172f versus M-wave, 171–172

negative, 170–171, 171f neuronal origins of, 173 origins of, 170–173 positive, 170–171, 171f sensitivity of, 172, 172f

as separate response from proximal retina, 171–173 in X-linked retinoschisis, 824

Second c-wave, 149

Second harmonic, in pattern ERG, 185–186 Second messenger(s)

calcium as, 41f, 42

in electro-oculogram, 126 and light peak, 149, 149f

Second-order kernels, 479–482, 480f reverse correlation of, 468

Seebeck, August, 599

Sensory scaling, 403–404 Serotonin, 88

in Parkinson’s disease, 872 SFD. See Sorsby’s fundus dystrophy

Shadowing error, in multifocal ERG, 315f, 317

Shift and add property, of m-sequences, 324–325, 324f–325f Shift register sequence generation, 320–321, 321f Short-wavelength automated perimetry (SWAP), 607 Shutter systems, 266–267

Sidekicks, 98, 99f

Siderosis, ocular, early receptor potential in, 550, 550f Signal analysis, basic concepts of, 439–444

Signal averaging, 242

Signal detection theory, 400–402 Signal extraction, 241–242 Signal-to-noise ratio

improving, with averaging, 455

in stimulus-response functions, 475 Significance level, 433

Sildenafil toxicity, 657

Silent substitution, in color vision testing, 602 Simple cell receptive fields

in alert animal, 465–466, 466f–467f mapping spatial structure of, 463–465, 464f

Simultanagnosia, 113–114

Single-cell recordings, ERG correlation with, 142 Single-flash cone ERG, 293

Single photon emission computed tomography (SPECT), 214 Skewed distribution, 431

Skin electrodes, 248f, 250–251

Slow oscillation ERG, 557, 558f, 561–562, 562f Slow PIII, of ERG, 143–146, 144f–145f Smoothing artifacts, 317

Snellen visual acuity, 541 Sodium/calcium exchanger, 39 Sodium/HCO3- cotransporter, 39 Sodium/hydrogen exchanger, 39 Sodium/potassium-ATPase transporter, 39

Sodium/potassium/chloride cotransporter, 40 Software

control, 242

for multifocal ERG, 319, 325–327 Sorsby’s fundus dystrophy (SFD), 769–772

and age-related macular degeneration, 772 clinical features of, 769

color vision in, 769

dark adaptation defect in, 409, 769–771 drusen in, 717, 719f, 720, 723–724 electro-oculogram in, 769 electroretinogram in, 769, 770f–771f fundus findings in, 769, 770f

genetics of, 720, 771 histopathology of, 769 pattern ERG in, 769, 772f psychophysics of, 769–771 treatment of, 771–772 visual field defects in, 771

Source-sink analysis, 142

Spatial buffer currents, in ERG, 140–141, 141f, 146 Spatial contrast, 414–415, 414f

loss of, 414, 415f testing of, 415–416

Spatial Fourier analysis, 449–451

Spatial frequency, in Fourier analysis, 450–451 Spatial summation, in EEG, 210 Spielmeyer-Sjögren syndrome, 889

Spielmeyer-Vogt disease, 889 S potentials, 49

Spreading depression (SD), 177 Squirrel

anesthetics for, 926t d-wave of, 165, 165f

SRCI. See Suppressive rod-cone interaction SST-1 Scotopic Sensitivity Tester, 408 Staircase method, 402–403, 403f Standard deviation, 431–432

Standard error of mean, 432 Standing potential

definition of, 557

nonphotic stimuli/responses of, 553, 554t, 555f Starburst amacrine cells, 61f, 86

Stargardt disease, 727–732 clinical presentation of, 727 color vision in, 609, 610f

versus cone-rod dystrophy, 727–732 electro-oculogram in, 624 electroretinogram in, 727, 728f

fluorescein angiography in, 426, 427f, 536, 538f genetics of, 727–732, 732f

hyperabnormal ERG responses in, 536, 538f incidence of, 727

multifocal ERG in, 334, 727, 730f–731f pattern ERG in, 343–344, 511, 512f

Stargardt-fundus flavimaculatus, 727. See also Stargardt disease Static, 443

Statistics, 431–437

Steady-state electro-oculogram, 128 Steady-state evoked potential, 15

Steady-state stimulus, for visual evoked potentials, 221 Stereopsis, in infants, 357–358, 357f–359f

Stiles two-color technique, 602 Stimulators, 265–275

Stimulus. See also specific types and tests spatially structured, 265 unstructured, 265

Stimulus-response functions, 465 parameters for, 476, 476f

for scotopic b-wave, 473, 476f signal-to-noise ratio in, 475 stimulus intensity for, 473–474, 474f

STR. See Scotopic threshold response Stretched retina hypothesis, 634 Striate cortex

damage to, disorders associated with, 110–111 human, 109, 110f

monkey, 109, 938–939, 938f mouse, 939

Stroboscope artifacts, 619 Subretinal space, 23

changes in, fast capacitative compensation for, 40 ERG electrodes in, 143, 143f

Substance P, 88 Sulpiride toxicity, 658

Superposition principle, 439

Suppressive rod-cone interaction (SRCI), 417–420 background of, 417–418

clinical perspective on, 418 in color vision disorders, 419 electroretinogram of, 417

flicker stimulus for, 417–418, 418f–419f newer developments in, 420

in night blindness, 418–419

parameters for, 417 pharmacological studies of, 417 in X-linked conditions, 419–420

Supranormal ERG responses. See Hyperabnormal ERG responses Synapse(s), 49–62, 53f–54f, 59f, 93–105

development of, 97–105, 99f flat contact, 96, 97f

in inner plexiform layer, 57–62, 59f, 93–96, 94f–95f invaginating, 96, 97f

molecular organization of, 96–97, 98f in outer plexiform layer, 96–97, 97f

retinal layers of, basic organization of, 93–96 stabilization of, 97–105

Synaptic gain, 82

Synaptic ribbon, 96, 97f–98f Synaptic transmission, 79–91

adhesion in, 97–105, 99f–100f postsynaptic elements of, 96–97, 97f–98f presynaptic elements of, 96, 97f–98f relevance to clinical states, 88–91

Synchronous amplification (detection), 456–457, 457f–458f System analysis, 454–455

T

Tamoxifen toxicity, 659 Tapetum cellulosum, 923 Tapetum lucidum, 923

Teller Acuity Cards, 353, 357–358 Temporal contrast, 413–414, 414f, 415 Temporal optic atrophy

in cone dystrophy, 799

fluorescein angiogram of, 427, 427f Temporal summation, in EEG, 210–211

10/20 system, of electrode placement, 227, 228f TEP (transepithelial potential), 146, 553

Test(s), 623–629, 624t–625t. See also specific tests and disorders comparison and combination of, 626–627, 628t correlation with clinical findings, 628–629, 628t definitive, 628–629, 628t

Test signals, in Fourier analysis, 447 Tetrodotoxin (TTX)

in ERG studies, 142

in multifocal ERG, 332–333 in pattern ERG, 190–192, 192f

Thalamus, as pacemaker for cortical activation, 213–214

Théorie Analytique de la Chaleur (Fourier), 444 Therapeutic trials

case selection for, 544

ceiling and floor effects in, 543 electrophysiology in, 542

endpoints of, continuous versus categorical variables as, 543 ethical issues in, 544

evaluating patients for, technical issues in, 541–544 interventions in, 544

masking in, 544

outcome measures in, 541 psychophysical tests in, 542 questionnaires in, 542–543

small sample sizes in, strategies to overcome, 543–544 statistical considerations in, 543

study design of, 541

visual acuity measures in, 541 visual field measures in, 541–542

Threshold classes of, 400

definition of, 400 detection, 400 difference, 400

psychophysical measurement of, 400

Tissue inhibitor of metalloproteinase 3 gene (TIMP3) and dominant drusen, 717, 719–720

and Sorsby’s fundus dystrophy, 720, 771 Toxicology, 655–661. See also specific drugs Tracking procedure, 400

Transducin, 67, 68f activation of, 70 inactivation of, 70

migration/translocation of, 72–75, 74f Transepithelial potential (TEP), 146, 553 Transfer function, 440

Transport

by ciliary cytoskeleton, 65–66 intraflagellar, 66

of lactic acid, 40, 41f, 42

membrane proteins involved in, 37–39 by retinal pigment epithelium, 37–42, 41f

Transporters, 39–40 Treatment condition, 432–433

Trichromacity. See also Color vision history of, 599–600

Tritan color confusion line, 602 Tritanopia, 599

visual evoked potentials in, 604–607, 606f–607f t-test, 436

TULP1 gene, and retinitis pigmentosa, 781

U

Undersampling, of visual evoked potentials, 229 United Parkinson’s Disease Rating Scale, 872 Unit step function, 447

Univariate statistical analysis, 436–437 Urban night blindness, 795, 797–798 Usherin, 100f, 105

Usher syndrome, 781 versus choroideremia, 779

fluorescein angiogram of, 424–425, 425f light adaptation in, 594–595, 595t

V

Variance, statistical, 431

VECPs. See Visual evoked potentials

Venous occlusions, 675–681. See also Branch retinal vein occlusion (BRVO); Central retinal vein occlusion (CRVO)

Ventral pathway, 109–110, 110f lesions of, 116–117

neuroanatomy and neurophysiology of, 116 VEPs. See Visual evoked potentials

Vernier acuity, and VEPs in amblyopia, 646

Veterinary guidelines, 927–929, 928f, 930f. See also Animal testing; specific animals

Viagra toxicity, 657 Vigabatrin retinopathy, 658

electro-oculogram in, 135 multifocal ERG in, 335

Visual acuity

in congenital stationary night blindness, 829, 830f electronic (EVA), 541

in multiple sclerosis, 875

in neuronal ceroid lipofuscinoses, 890

normal maturation of, 354–355, 355f preterm birth and, 355–356, 356f testing of

in drug toxicities, 660 in infants, 232, 353–359 measures for, 541

potential pitfalls in, 353–354, 354f

visual evoked potentials for, 231–232, 232f, 353–359 Visual allesthesia, 114–115, 115f

Visual amnesia, 117 Visual cortex, 109

dorsal (where) pathway of, 109–110, 110f neuroanatomy and neurophysiology of, 113 syndromes of, 113–115

human, 109, 110f

monkey, 109, 938–939, 938f mouse, 939

primary (V1), 109, 110f

damage to, disorders associated with, 110–111 V2 (parastriate), 109, 110f

damage to, syndromes caused by, 111 V3 (peristriate), 109, 110f

damage to, syndromes caused by, 111

V4 (human color center), 109, 110f, 112f, 600 damage to, syndromes caused by, 112–113

V5 (area MT), 109, 110f

damage to, syndromes caused by, 113 ventral (what) pathway of, 109–110, 110f

lesions of, 116–117

neuroanatomy and neurophysiology of, 116

Visual evoked cortical potential (VECP). See Visual evoked potentials Visual evoked potentials (VEPs), 15–18, 207–232, 867, 868f. See also

specific disorders/findings aging and, 361–367

accommodation changes with, 366, 366f–367f amplitude changes with, 361, 363f

contrast threshold changes with, 362–364, 365f gender differences in, 362, 364f

general changes with, 361–362

luminance threshold changes with, 364, 365f peak latency changes with, 361–362, 364f pupillary size and, 365

temporal frequency changes with, 362, 363f in albinism, 369, 373–395, 373f

age and, 386–396, 390f–394f averaging of, 380–382, 383f checkerboard stimulus for, 378–382 data analysis of, 375, 376f

genetic differences in, 386, 387f–389f

hemispheric asymmetry in, 375–377, 376f, 382–395, 385f, 387f–394f

latency of, 382, 384f methodology for, 375–377

misrouting test of, 369, 375–377, 514–515, 516f pattern onset/offset, 378–380, 381f–384f pattern reversal, 378–380, 381f

principal component analysis of, 373–374, 374f, 382–385 stimulus for, 375

topography of, versus normal controls, 382–395 alternatives to, 214–215

in amblyopia, 644–647 binocular, 646–647

binocular summation and facilitation of, 646 dichoptic stimulation of, 646–647 interocular differences in, 644

latent nystagmus and, 645, 645f

Visual evoked potentials (VEPs) (continued) patching and, 645, 645f

pattern assessment of, 644–645 threshold measurements of, 646 Vernier acuity and, 646

amplifier characteristics for, 229, 304–305 amplitude of, 230, 305, 440, 441f analysis techniques for, 229–231

animal, 935–944 appearance/disappearance, 222, 223f applications of, 231–232

arousal and, 224–226 attention and, 224–226

averaging of, 207–208, 304–305

in chiasmal and retrochiasmal dysfunction, 231, 307, 505, 514–515, 516f, 857–860, 858f–860f

to chromatic stimuli, 224 cognitive set and, 226

color, 218, 604–607, 605f–607f

coma or reduced level of consciousness and, 232 comparison and combination with other tests, 626–627 components (waves) of, 15–16, 16f, 211–213

contrast transfer function of, 194, 194f correlation with clinical findings, 628–629, 628t in cortical blindness, 651–652

works reporting abnormal, 652 works reporting normal, 651–652 works reporting recovery of, 652

cortical sources of, localization of, 211–213, 213f–215f definition of, 207

diagnostic flowcharts for, 515–517, 516f

different stimuli for and different types elicited, 207 electrodes for, 226–229, 252–253, 304

ISCEV guidelines for, 304 number of, 227–229

positioning of, 207, 226–227, 228f, 304, 304f problems with, 227

electroencephalogram of, 207–210 emotion and, 226

expectancy and, 224–226

extrinsic and intrinsic activation of, 207 eye position control for, 229

figure-ground segregation and, 219–220, 219f filtering of, 229, 258, 259f, 260

form of, 222f–223f, 225f–226f, 230, 230f Fourier analysis of, 230

frequency contents of, 230

in “functional disorders,” 231–232

in ganglion cell dysfunction, 511–512, 514f history of, 15–18, 208–210

in infants, 17, 232, 306, 353–359

for fusion and stereopsis testing, 357–358, 357f–359f multiple sweep paradigms for, 358

of normal maturation, 353–354, 354f preterm birth and, 355–356, 356f special considerations for, 358–359

sweep, reliability and validity of, 356–357, 357f waveform development in, 361, 362f

interpretation of, 308

ISCEV standard for, 287–288, 301–308, 303t on basic technology, 302–305, 303t

on clinical protocol, 305–308

on measurement and reporting, 307–308 Laplacian derivation of, 230–231

latency of, 224, 229, 305, 442 lesions affecting, 17–18

during life span, 17

localization of lesions with, 510–517, 624t–625t in macular dysfunction, 510–511, 513f

in malingering and hysteria, 637–640, 638f–639f mirroring of visual system by, 208

in mitochondrial disorders, 667 monkey, 935–941, 943–944

flash, 939–940, 939f pattern, 940, 940f sweep, 940, 941f

motion, 217–218, 224, 226f, 605 motivation and, 226

mouse, 935–939, 941–944 flash, 941–942, 942f pattern, 942–943, 942f sweep, 942f, 943

multifocal, 197, 199–203, 221

ganglion cell or optic nerve damage in, 202–203 in glaucoma, 202, 335

intersubject variability in, 200 intrasubject variability in, 200–202 kernel analysis in, 483–484 mean/averaged responses of, 200, 203f in multiple sclerosis, 202–203, 204f recording of, 199–200, 203f

normal flash, 221, 222f, 232, 304, 306, 307f normal values in, 307

in optic nerve dysfunction, 231, 505, 512–513, 514f patient preparation for, 305

pattern onset/offset, 212f, 222, 223f, 302–303, 305–306, 306f pattern reversal stimulus for, 222–224, 223f, 225f, 302, 305, 305f,

605

pattern stimulation of, 17 pediatric, 306–307

phase characteristic of, 440, 441f poor patient compliance and, 232 preparation and, 226

in pressure-induced retinopathy, 515–517, 517f recording of, 207, 226–229

multi-channel, 307 parameters for, 304 rectification of, 443, 443f response latency of, 208

sampling and undersampling of, 229 signals and noise in, 255, 256t

standard transient responses in, description of, 305–306 stimulation of

check size for, 220 contrast for, 220 field size for, 220 luminance for, 220

modulation in color space, 218 modulation in depth, 218–219 modulation in space, 215–216 modulation in time, 216–217 modulation in time and space, 217–218

modulation of spatial frequency, 219, 231–232 parameters for, 220–221, 302, 303t

physiological targeting of and responses to, 221–226 steady-state, 221

techniques for, 216–221 temporal frequency for, 220–221

synchronization of stimulus monitor for, 229 for visual acuity testing

in infants, 232, 353–359

media opacities and retinal dysfunctions in, 231

objective assessment in, 231–232, 232f potential pitfalls in, 353–354, 354f

Visual evoked subcortical potential (VESP), 16–17 Visual field defects

in chiasmal dysfunction, 857 in drug toxicities, 660

in glaucoma, 851, 852f

in gyrate atrophy, 707, 710f in multiple sclerosis, 875, 877f

in Sorsby’s fundus dystrophy, 771 Visual field measures, 541–542 Visual hypoemotionality, 117 Visual latency, 440–442, 464 Visual-limbic disconnection, 117

Visual-verbal disconnection, 116–117 Visual-visual disconnection, 116 Visuospatial processing

disorders of, 113–115

dorsal pathway in, 109–110, 110f, 113 Vitamin A, 47

and dark adaptation, 409, 803, 805f deficiency of, 803–804

conditions associated with, 803–804 electroretinogram in, 803, 804f–805f fundus appearance of, 803, 804f

metabolism of, 803 supplementation, 409, 803

Vitelliform (term), 763

Vitelliform macular lesions, differential diagnosis of, 765, 765t Vitreous humor, 93

Voltage-activated chloride channels, 39 Voltage-controlled oscillator (VCO), 274 Voltage-dependent calcium channels, 38, 79 von Kries, Johannes, 599

W

Wagner disease, 823

Wavelets, ERG. See Oscillatory potentials

Weak signal artifact, 316f, 317

Werblin-Westheimer procedure, 420 “What” (ventral) pathway, 109–110, 110f

lesions of, 116–117

neuroanatomy and neurophysiology of, 116 “Where” (dorsal) pathway, 109–110, 110f

neuroanatomy and neurophysiology of, 113 syndromes of, 113–115

White light-emitting diode, 272–273, 273f White noise, for kernel analysis, 479, 480f, 482 Wide-field multifocal ERG (WF-mfERG), 335 Window property, of m-sequence, 324

X

Xenon flash lamps, 265–266, 267f X-linked albinism, 373, 386, 387f–389f X-linked cone dystrophy, 795, 796f, 800 X-linked retinitis pigmentosa, 781

alcohol electro-oculogram in, 134–135, 134f oscillatory potentials in, 576f, 577 suppressive rod-cone interaction in, 419

X-linked retinoschisis, 823–825 a-wave analysis in, 824–825, 826f

b-wave analysis in, 824–825, 825f–826f differential diagnosis of, 823 electro-oculogram in, 823–824

electroretinogram in, 810–812, 811f, 823–825, 825f–826f fluorescein angiogram of, 424, 425f, 823, 825f

fundus appearance of, 823, 824f gene identification in, 823

photoreceptor and inner retinal responses in, 824–825, 826f

scotopic threshold response in, 824 suppressive rod-cone interaction in, 419

x-wave, of electroretinogram, in dogs, 7–8, 912

Z

Zero-order kernels, 479

P 1 Immunostained monkey retina close to the fovea. Some neurons of each of the layers are immunolabeled with antibodies against GCAP (photoreceptors), calbindin (horizontal cells and some bipolar cells), calretinin (AII amacrine cells and two other varieties of amacrine cells), and parvalbumin (ganglion cells).

Photo, photoreceptor layer—rods and cones; OPL, outer plexiform layer; bc, bipolar cells; hc, horizontal cells; INL, inner nuclear layer; amac, amacrine cells; IPL, inner plexiform layer; GCL, ganglion cell layer; gc, ganglion cells. (See figure 6.4.)

P 2 A drawing of a slice of the human retina showing all the nerve cells we currently understand on the basis of their shape, function, and neurocircuitry. The photoreceptors lie deep at the back of the retina against the pigment epithelial cells (top of drawing), and the ganglion cells lie at the superficial surface of the

retina (bottom of drawing). Bipolar cells and horizontal and amacrine cells pack the middle of the retina with two plexiform layers dividing them, where synaptic interactions take place. (See figure 6.5.)

P 3 A drawing, based on an original from Polyak (1941), showing the neurocircuitry of the fovea in the primate retina. Midget or P cell pathways consist of a single cone, two midget bipolar cells, and two midget ganglion cells. Because P cells carry information from only one cone, it will also be spectrally tuned. Red and green cones pass either ON center/OFF surround information or OFF center/ON surround information concerning which are both spectrally and spatially opponent (small red and green circles and rings). Blue cones have their own pathway through a dedicated blue ON center bipolar cell feeding to the

lower dendrites of a bistratified blue/yellow ganglion cell type. The yellow message carried to the top tier of the bistratified ganglion cells dendrites comes from a diffuse bipolar cell (yellow) that contacts green and red cones. M ganglion cells of the fovea carry a message from diffuse ON center or OFF center bipolar cells (orange and brown bipolar cells) and form the parallel OFF and ON center, achromatic channels (gray and white circles and rings) concerned with movement and contrast to the brain. (See figure 6.11.)

P 4 A, An immunostained image of rod bipolar cells immunostained with antibodies against protein kinase c (PKC). B, Small-field bistratified AII amacrine cells are immunostained with antibodies to parvalbumin (PV). C, Dopamine-containing cells are immunostained with antibodies to tyrosine hydroxylase (TOH) as seen in a flat mount of the retina. Thousands of dopamine cell processes cross each other and make a dense network of processes in the top part of the inner plexiform layer, to synapse on various cell types, among them the AII amacrine cell. D, Two mirror symmetric amacrine cell populations, known as starburst cells, are immunostained for their acetylcholine neurotransmitter (ChAT) and seen in flat mount of retina. One set of starburst cells sits in

the ganglion cell layer, and the other sits in the amacrine cell layer. Their respective dendritic plexi run and synapse in sublamina b and sublamina a. Starburst amacrine cells are thought to influence ganglion cells to be able to transmit messages concerning direction of movement in the visual field. These cells are particularly well developed in animals with visual streaks in their retinas. E, A17 amacrine cells immunolabeled with antibodies to serotonin (Ser) and also to GABA. A17 cells connect rod bipolar axon terminals in reciprocal GABAc receptor–activated circuits across the entire retina. (E from Vaney DI: Many diverse types of retinal neurons show tracer coupling when injected with biocytin or Neurobiotin. Vision Res 1998; 38:1359–1369.) (See figure 6.14.)

P 5 The cytoskeleton of photoreceptors is composed principally of microtubules and microfilaments. The axoneme in the connecting cilium is composed of nine microtubule doublets, typical of nonmotile sensory cilia, and project to nearly the distal end of

the outer segment. Microfilaments are found in the connecting cilia as well. In the inner segment, microtubules form the molecular train tracks between the Golgi complex and the connecting cilium. (See figure 7.2.)

R hu

PDE

Na+

cGMP

g

GMP

Na+

P 6 The activation cascade of the phototransduction pathway. Light is absorbed by rhodopsin (R). Photoactivated rhodopsin (R*) binds heterotrimeric transducin (T), catalyzing the exchange of GTP for GDP on the a-subunit.

Activated transducin removes an inhibitory subunit from the cGMP phosphodiesterase (PDE), which hydrolyzes cGMP to GMP. Reduction of cGMP causes the cyclic nucleotide-gated channels to close. (See figure 7.3.)

11-cis retinal

R

opsin

P

P

P

PP2A

opsin P

P

P

ARR

RDH

R*

P

OH ARR

all-trans retinol

P 7 The rhodopsin cycle. Light is absorbed by rhodopsin (R), becoming photoactivated (R*). R* is phosphorylated on C-terminal serine and threonine residues by rhodopsin kinase (RK). Phosphorylated, photoactivated rhodopsin is bound by arrestin, blocking the ability of R*P to bind to transducin (T). Arrestin remains bound

hu

T b a g

R*

T* a

b g

ATP(n)

R* RK

P

P

P

ADP(n)

ARR

until the all-trans retinal chromophore is reduced by a retinal dehydrogenase (RDH) to all-trans retinol and released from the phosphoopsin. The phospho-opsin is dephosphorylated by protein phosphatase 2A (PP2A) and opsin regenerated back to rhodopsin by the binding a new 11-cis retinal molecule. (See figure 7.4.)

Na+

Ca++

Na+

Ca++

Na+

Ca++

Na+

Ca++/ K+

Na+

K+

ATP

ADP

glutamate

P 8 Ion circulation across the photoreceptor membrane. In the dark photoreceptor, cGMP-gated channels are open, allowing influx of Na+ and Ca2+ ions. Calcium balance is maintained by the action of a Na+/Ca2+ exchanger, which uses the Na+ gradient to extrude Ca2+. The sodium balance is maintained by a Na+/K+ pump, which

Na+

K+

ATP

ADP

glutamate

uses ATP to return Na+ against its ionic gradient. In response to light, one or more cGMP-gated channels are closed, resulting in a hyperpolarization of the cell membrane, since the Na+/K+ pump continues to operate. Membrane hyperpolarization causes a decrease in glutamate release from the synaptic terminal. (See figure 7.5.)

ARRESTIN

ROS

RIS

nuclei

synaptic terminal

P 9 Translocation of photoreceptor proteins in response to light. In a dark-adapted Xenopus retina, arrestin (upper panels) immunolocalizes to the inner segments, axonemes (arrows), and synaptic terminals. Transducin (lower panels) immunolocalizes to the outer segments. In response to 45 minutes of adapting light,

there is a massive translocation of the proteins, with arrestin moving to the outer segments and transducin moving to the inner segments. In Xenopus, if the frog is maintained in the adapting light for an extended period of time (>2 hours), the proteins translocate back to their respective cellular compartments. (See figure 7.8.)

P 10 Radial section of a dogfish retina viewed in a fluorescence microscope. In the center of the field is a rod bipolar cell injected with the fluorescent dye in situ after recording light responses, as in Figure 8.1. In the upper part of the photomicrograph, the autofluorescent rod outer segments can be seen. The larger bipolar cell dendrites extending through the outer plexiform layer have filled with fluorescent dye. The fine axon

ings to be made. (Source: From Ashmore JF, Falk G: Responses of rod bipolar cells in the dark-adapt retina of the dogfish, Scyliorhinus canicula. J Physiol (Lond) 1980; 300:115–150. Used by permission.) (See figure 8.2.)

P 11 Mammalian retinal signaling pathways. On-pathways are shown in green, off-pathways in blue (and are labelled ON or OFF above). Synapses are shown by arrows with (+) indicating sign conserving and (-) sign indicating reversing. Dark gray cells hyperpolarize in response to light. Gap junctions are indicated in red. Symbols: r, rod; c, cone; rb, rod bipolar cell; AII, amacrine cell; gc,

ganglion cell; PRL photo-receptor layer; OPL, outer plexiform layer; INL, inner nuclear layer; GCL ganglion cell layer. Horizontal cells have been excluded from the diagram. (Source: Reproduced from Demb JB, Pugh EN: Connexin36 forms synapses essential for night vision. Neuron 2002; 336:551–553. Used by permission.) (See figure 8.7.)

P 12 Santiago Ramón y Cajal’s schematic drawing of the parafoveal region of the vertebrate retina. In this illustration, Cajal demonstrates his insight into the connectivity of the retina and the dynamic polarization of retinal neurons and consequently information transfer from photoreceptors to bipolar cells and ganglion cells. In addition to vertical organization, Cajal illustrates the lateral pathways. A, Inner and outer segments. B, Outer nuclear layer. C, Outer plexiform layer. D, Inner nuclear layer. E, Inner plexiform

layer. F, Ganglion cell layer. G, Nerve fiber layer. b, rods; a, cones; c, horizontal cell; d, cone bipolar cells; e, rod bipolar cell; g, ganglion cell; h, centrifugal fiber. (Note: Not all suggestions implicit in this prescient drawing have been found correct. For example, rod bipolars do not make direct contact with ganglion cells—see text.) (Source: The original figure is in the collection of the Cajal Institute, CSIC, Madrid.) (See figure 9.1.)

P 13 Diagrammatic scheme of the molecular organization of the photoreceptor synapse is shown. The ribbon (large, gray, saclike structure) is studded with synaptic vesicles; in association with the ribbon are cytomatrix molecules bassoon and piccolo; Munc13 is seen at the release site. Ribeye, not shown in this figure, labels the ribbon itself. Directly opponent to the release site are the molecules

of the transmitter response cascade; these include both iontropic (IGluR) and metabotropic (mGluR) glutamate receptors and clustering molecules. Outside the release area, other molecules are expressed, including various cell adhesion molecules and, in the photoreceptor, glumate receptors. (Source: This figure was kindly supplied by Dr. J. H. Brandstätter for use in this chapter.) (See figure 9.4.)

P 14 The process of target recognition and synapse formation is idealized in this cartoon. Presynaptic terminals express certain target recognition molecules on their leading processes; here, these are conceived of as homophilic binding molecules (such as CAM, nectins, or sidekicks). Target selection is based on the expression of homophilic partners on the postsynaptic (A to B transition); on binding to the postsynaptic receptor pair, a variety of proteins are recruited to the synapse (B, colored circles and diamonds); these ele-

ments produce a reorganization of the cytoskeleton (actin and microtubule, gray circles and rods, respectively) and assembly of the elements of the release mechanism, including the synaptic vesicle (green circles), and proteins of the release cascade (black ovals). Homophilic molecules and other molecules (arrows) are recruited to stabilize the synapse. (Source: Figure 2 from Ackley BD, Jin Y: Genetic analysis of synaptic target recognition and assembly. Trends Neurosci 2004; 27:540–547. (See figure 9.5.)

P 16 Laminin deletion results in a disruption of the transsynaptic molecular organization of the photoreceptor synapse. Immunohistochemical localization of the bassoon (red) and mGluR6 (blue) in wild-type retina demonstrates the normal arrangement of molecules. Bassoon, associated with the ribbon, is

directly opponent to mGluR6, the transmitter receptor that is expressed in invaginating bipolar cells. In the laminin-mutant (b2 null) mouse, both molecules are expressed by mGluR6 is delocalized and not concentrated at the synapse. (Source: This is taken from the author’s unpublished work.) (See figure 9.9.)

P 17 Variable genotype and phenotype in a representative sample of albinos including autosomal-recessive oculocutaneous, tyrosinase-negative albinism (left column), X-chromosomal ocular albinism, and autosomal-recessive oculocutaneous,

tyrosinase-positive albinism (right column). Foveal hypoplasia, reduced visual acuity, and VEP optic pathway misrouting are common features regardless of inheritance mode or phenotypic expression. (See figure 25.1.)

Outside Foveation Period

(Vm ean = 20 deg/s)

During Foveation Period (Vmean = 3 deg/s)

P 19 Schematic of an eye movement recording of a patient with CN. Vertical yellow bars indicate foveation periods when retinal velocity approaches zero. This can readily be observed from the lower velocity trace. Two sets of VEP averages are depicted:

one obtained from VEP responses following visual stimulation outside foveation periods and another obtained from VEP responses following visual stimulation during foveation periods. The latter are significantly more robust. (See figure 25.14.)

P 20 Depicted are VEP averages (black traces) in an albino during OU, OD, and OS viewing extracted from periods with low mean ocular velocity (less than 5 degrees/second). Also depicted are VEP averages (red traces) extracted from responses to pattern-onset

pattern onset (40/460ms)

stimulation during high mean ocular velocity. Five channels positioned across the occiput and one difference channel (i.e., VEP channel 4 positioned at left occiput subtracted from VEP channel 2 positioned at right occiput) also are presented. (See figure 25.15.)

Electrode Position (left right)

P 21 VEP misrouting test. Left eye (OS), and right eye (OD) pattern onset/offset (40 ms/460 ms) VEP responses (check size = 55¢) from an X-chromosomal ocular albino (left panel) and a patient with nondecussating retinal-fugal fiber syndrome (right panel). Fundi of both patients are shown in figures 25.2A and 25.2B, respectively. VEP amplitude distribution across the electrode array for OD and OS stimulation is depicted below the VEP traces. In the case of contralateral asymmetry (left) in the albino, following left eye stimulation (OS), a major positive peak of the pattern onset response lateralizes to the right occiput, and with right eye stimu-

Electrode Position (left right)

lation, a major positive peak lateralizes to the left occiput. This interocular occipital lateralization yields a highly significant interocular asymmetry index of 1.67 at 90 ms. For comparison, occipital lateralization in an achiasmat is also presented. In the case of ipsilateral asymmetry (right) in an achiasmat, following left eye stimulation (OS), a major positive peak of the pattern onset response lateralizes to the left occiput, and with right eye stimulation, a major positive peak lateralizes to the right occiput. This rare interocular ipsilateral VEP response lateralization results in a highly significant interocular asymmetry index of -1.97 at 90 ms. (See figure 25.18.)

A

P 22 Serial fundus photographs of the same patient dated 1986 (A) and 1994 (B) showing increased retinal pigmentation from salt-and-pepper retinopathy to frank bone spiculing. Note that the

B

magnification in part B is higher, showing more central encroachment of the pigmentary changes. Both images demonstrate substantial arterial attenuation. (See figure 55.2.)

A

B

C

P 23 Central serous chorioretinopathy. A, An eccentric serous detachment superior to the optic disk causes a localized visual field defect inferior to the physiologic blind spot. B,C: Attenuation of the multifocal ERG is seen in the region corresponding to the visual field defect. (Courtesy of Donald Hood, Ph.D.) (See figure 57.2.)

P 24 Birdshot chorioretinitis. Pale fundus lesions are neither raised nor depressed relative to the surrounding retina. (Courtesy of Alan Friedman, M.D.) (See figure 57.3.)

P 25 Multiple evanescent white dot syndrome (MEWDS). Pale white dots are seen early in the course of the disorder. (Courtesy of Wayne Fuchs, M.D.) (See figure 57.4.)

Photopic

Rod isolated

BrFl Scotopi

11 V

91 V

76 V

83 V

115 V

47 V

65 V

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Rod isolated

Bright Flash

Dark-adapted

51 V

25 V

57 V

56 V

96 V

P 29 Fundus appearance of right eye of a 12-year-old girl with early pyridoxine-nonresponsive gyrate atrophy (A) (same patient as in figure 12.1 in Weleber and Kennaway), a 28-year-old woman with pyridoxine-responsive gyrate atrophy (B) (patient 1), a 37-year-old woman with pyridoxine-responsive gyrate atrophy (C)

(patient 3), and a 40-year-old man with pyridoxine-nonresponsive gyrate atrophy (D) (patient 4). (From Weleber RG, Kennaway NG: Gyrate atrophy of the choroid and retina. In Heckenlively JR (ed): Retinitis Pigmentosa. Philadelphia, JB Lippincott, 1988, pp 198–220. Used by permission.) (See figure 60.4.)

P 30 A, Fundus photo from left eye showing lipofuscin accumulation within the posterior pole. B, mfERG from same patient

A

B

showing selective loss of responses from the central 10 degrees. (See figure 62.2)

P 31 Model for the function of RmP (ABCR) protein in disk membranes. A, Wild-type, in which ABCT is a transporter (flippase) for N-ret-PE. B, abcr-/- mouse (and patients with reduced flippase activity). N-ret-PE trapped in the disk combines with a second molecule of all-trans-retinal to produce A2PE-H2. A2PE-H2 is ultimately hydrolyzed to form A2E. Many of these reactions occur in the RPE after disks containing the excessive trapped A2PE-H2 are shed as part of the normal phagocytotic process. The A2E accumulates as lipofuscin in the RPE and may ultimately damage intracellular membranes and destroy the overburdened RPE cells within the macula. A2E: N-retinylidene-N-retinyl-ethanolamine; A2PE-H2: N-retinyli- dene-N-retinyl-PE; atRAL: all-trans-retinal; atRDH: all-trans-retinal dehydrogenase; atROL: all-trans-retinol; ops: opsin; PE: phosphatidylethanolamine; PM: plasma membrane. (From Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH: Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell 1999; 98:13–23.) (See figure 62.3.)

P 32 Same patient as in figure 63.1 at 45 years of age (A and B). Note the further loss of pigment epithelium and choriocapillaris over the nine-year interval. (From Wilson DJ et al: Bietti’s crystalline

P 33 Fundus appearance of a 61-year-old man with the regional form of Bietti’s crystalline dystrophy (patient 3 in Wilson DJ et al: Bietti’s crystalline dystrophy: A clinicopathological correlative study. Arch Ophthalmol 1989; 107:213–221.). The visual fields had

dystrophy: A clinicopathological correlative study. Arch Ophthalmol 1989; 107:213–221. Used by permission.) (See figure 63.2.)

not changed over those determined nine years previously, but the visual acuity had decreased from 20/30 J1 to 20/40 J2. (See figure 63.6A.)

P 34 Fundus photographs representing various stages of macular lesions that can be observed in patients with Best macular dystrophy. Top left, Stage I: mild degree of foveal pigment mottling and nonspecific hypopigmentation. Top right, Stage II: typical vitelliform or egg-yolk-like lesion. Second row left, Stage IIIa: scrambled or “fried egg” phase as the vitelliform lesion becomes diffusely more amorphous and diluted in appearance. Second row right, Stage IIIb: pseudohypopyon phase in which the yellow substance in the vitelliform cyst develops a layered

appearance as a consequence of partial resorption. Third row left, Stage IIIc: only a sparse amount of yellowish substance remains as resorption of the vitelliform lesion is almost complete. Third row right, Stage IIId shows atrophic changes of both the retinal pigment epithelium and choriocapillaris vessels. Bottom, Stage IV: both less and more extensive examples are depicted. Characteristic feature is a fibrotic-gliotic-appearing scar in addition resorption of the vitelliform material. (See figure 66.1.)

P 35 Left fundus of a patient with SFD showing large disciform scar. (See figure 67.1.)

P 36 Left fundus of a patient with SFD showing atrophy of the retinal pigment epithelium and choriocapillaris at the posterior pole. (See figure 67.2.)

A

B

P 37 Fundus photographs of a 17-year-old CHM affected male showing preserved deep choroidal vessels and central macula, normal-appearing retinal vessels and optic nerve, and no pigment dispersion. A, OD. B, OS. Vision: 20/20 OU. (See figure 68.1.)

P 39 Fundus photograph showing the posterior pole of a 42- year-old patient with XlRP. Note the “waxy disk,” the attenuated retinal vessels, and the bone spicule–like pigmentary deposits throughout the midperiphery. (See figure 69.1.)

B

P 40 Symmetric, round atrophy of fovea centralis is typically seen in a number of types of cone dystrophy or degeneration. A, In this case of X-linked cone dystrophy with tapetal sheen, the atrophy of the foveal centralis is highlighted by the surrounding sheen. This 54-year-old man had photosensitivity OU and a history of retinal detachment in his right eye; his visual acuity was 20/200 OU. B, While the sheen is seen as patches in the periphery. These patients exhibit the Mizuo-Nakamura effect on dark adaptation. (See figure 70.1.)

P 41 Cone dystrophy with foveal crystals. Right eye of a 58- year-old woman with urban night blindness with nonrecordable photopic ERG and normal scotopic ERGs. Visual acuity was OD 20/40, OS 20/60, and Goldmann visual fields were full. (See figure 70.2.)

P 43 Temporal optic nerve head atrophy is commonly seen in many cone degenerations; illustrated here by a 9-year-old boy with rod monochromatism with temporal pallor. Sometimes the temporal edge of the nerve is flattened or missing. (See figure 70.5.)

A

P 42 Fundus photographs of patients with inherited cone dystrophies; A, A 60-year-old man with blue-cone monochromatism who recently noted some mild decreases in his central vision from 20/60 to 20/200, presumably from aging. B, A 54-year-old woman with 20/400 vision OU from a large dominant pedigree

B

with cone dystrophy from a GUCY2D gene mutation, with foveal centralis atrophy giving a “cookie cutter” appearance to macula. This pattern is characteristic of many cone dystrophies. (See figure 70.4.)

P 44 Senile cone degeneration in an 80-year-old woman with failing vision over ten years, who was found to have poor photopic ERGs with both eyes. Her right eye had a 45 uV b-wave amplitude while the left eye was barely recordable with count finger vision. Rod responses were abnormal. Visual fields were full with central scotomata. Many patients with senile cone degeneration have regional atrophy with crystallike drusen deposits. (See figure 70.7.)

P 45 Cone dystrophy with apparent foveal structure. This 22-year-old woman presented with a history of color blindness and photosensitivity for at least ten years. The family history was negative. Her vision was 20/200 OU, and her photopic ERG was nonrecordable, while her scotopic waveforms were within normal limits. Her Goldmann visual field was full OU. On fundus examination, she appeared to have some foveal structure; but on close inspection, the fovea centralis showed atrophy and mild granularity. (See figure 70.8.)

P 46 Fundus photograph of a 53-year-old woman with documented vitamin A deficiency from complications secondary to bowel resection in Crohn’s disease. Her barely recordable ERG and night vision became normal after parenteral vitamin A and E therapy. (Courtesy of John Heckenlively, M.D.) (See figure 71.1.)

P 47 Fundus photograph of XLRS-affected male with juvenile retinoschisis showing spoke-wheel pattern of foveal cysts covering an area of approximately one disk diameter. (See figure 73.1.)

P 51 Simplified schema of the D1–D2 interaction of the retina. The D1 DA pathway enhances the surround signal, while the D2 pathway enhances the center signal. Experimental results suggest that these two DA pathways are not independent of each other: D2 is involved in the D1 pathway participating in a negative

feedback loop, providing a greater D1 effect when D2 receptors are blocked. (Adapted from Bodis-Wollner I, Tzelepi A: Push-pull model of dopamine’s action in the retina. In Hung GK, Ciuffreda KC (eds): Models of the visual system. Kluwer Academic Publishers, 2002, pp 191–214; with permission.) (See figure 79.5.)

P 52 Computer-averaged ERGs, using intravenous propofol sedation, to a modified ISCEV protocol in a patient with infantile NCL from the Arg151 stop mutation of the CLN1 gene that encodes PPT1. The tracings from the right and left eyes are shown in black; the red tracings show the average of both eyes from a normal subject age 1.6 years. The scotopic blue and red flash stimuli were matched in normal control subjects to produce equal rod amplitudes. Note

the sizable rod a-wave and profoundly subnormal rod b-wave for the blue flash, the electronegative configuration of the scotopic ERG to the bright white flash, and the subnormal, prolonged photopic cone response. (Reproduced with permission from Weleber RG: The dystrophic retina in multisystem disorders: The electroretinogram in neuronal ceroid lipofuscinosis. Eye 1998; 12:580–590.) (See figure 80.2.)

P 53 Computer-averaged ERGs to modified ISCEV protocol in three patients with late infantile NCL. The tracings from the right and left eyes are shown in black; the red tracings show the average of both eyes from an age-similar normal subject. Note the sizable but delayed rod responses, the prolongation of the scotopic oscilla-

tory potentials, and the subnormal, prolonged cone responses. (Reproduced with permission from Weleber RG: The dystrophic retina in multisystem disorders: The electroretinogram in neuronal ceroid lipofuscinosis. Eye 1998; 12:580–590.) (See figure 80.3.)

P 54 Computer-averaged ERGs to a modified ISCEV protocol in three patients with juvenile NCL from mutation of the CLN3 gene. The tracings from the right and left eyes are shown in black; the red tracings show the average of both eyes from an age-similar normal subject. All responses were elicited using the same Ganzfeld stimulator, but because a different computer system was used for recording the responses for Case 6, a different normal is shown.

Note the profoundly subnormal rod responses, the electronegative configuration of the scotopic ERG to the bright white flash for Cases 5 and 6, and the subnormal photopic responses, which were greater for the b-wave than the a-wave for Case 5. (Reproduced with permission from Weleber RG: The dystrophic retina in multisystem disorders: The electroretinogram in neuronal ceroid lipofuscinosis. Eye 1998; 12:580–590.) (See figure 80.4.)

P 55 Fundus appearance in 4-year-old patient with LCHAD deficiency and early retinal degeneration. Note the characteristic dark brown spot in the fovea, the early thinning and atrophy of the retinal pigment epithelium (RPE), and the early pigment dispersion with fine clumping. The ERG was still normal at this stage. (See figure 80.5.)

P 56 Fundus appearance in a patient with later stage LCHAD deficiency and retinal degeneration. Note the more extensive atrophy of the RPE and choroid in the posterior pole. (See figure 80.6.)