Strabismus patterns after cataract surgery in adults.

New-onset binocular diplopia after cataract surgery in adults is a rare but significant complication. The aim of this study was to analyze causes, risk factors, and treatment outcomes. Forty consecutive patients with new-onset binocular diplopia after uncomplicated cataract surgery were enrolled in this retrospective study at a tertiary medical center. We evaluated risk factors including type of anesthesia, preoperative presence of strabismus, and others regarding their effect on the development of diplopia after cataract surgery. We further analyzed ocular alignment and motility at presentation and during the clinical course. The majority of the patients with new-onset diplopia presented after cataract surgery on the left eye (28 of 40). Vertical strabismus occurred in 37 of 40 patients, and regional (peri- or retrobulbar) anesthesia was the main risk factor for postoperative diplopia (present in 37 of 40). There were four distinct ocular dysmotility patterns in patients with vertical strabismus: deficient elevation with (type 1a) or without over-depression (type 1b), deficient depression (type 2), or normal motility (type 3). After surgery of the right eye, most patients (6 of 9) showed type 2. After cataract surgery on the left eye, type 1a was most common (20 of 24). Three patients had horizontal strabismus due to a decompensated heterophoria or convergence insufficiency. In total, 17 patients required strabismus surgery (mean 1.3 operations, range 1-3). Regional anesthesia was the main risk factor for new-onset diplopia after cataract surgery in adults. Distinct strabismus patterns were observed for left and right eyes.d.

Effect of unilateral vertical transposition of the horizontal rectus muscles on vertical strabismus.

PURPOSE: To study the effect of vertically transposing both horizontal eye muscles of one eye in the same direction on vertical strabismus. METHODS: Retrospective analysis of 33 patients in whom vertical transposition of the medial and lateral rectus muscles was combined with a recession/resection or recession/plication procedure. Preoperative ocular alignment was compared with that 1 day and 3 months postoperatively. RESULTS: Mean preoperative vertical deviation was 7.8 ± 4.3 (median 7.5, range 3-25) prism diopters (PD) at distance and 7.8 ± 4.1 (7, 0-18) PD at near. Vertical transposition of the horizontal rectus muscles averaged 5.6 ± 1.6 mm and reduced the vertical deviation to 3.4 ± 4.2 PD (2, 0-16) at distance and 2.9 ± 3.7 PD (2, 0-14) at near. Mean effect on the vertical deviation was 0.9 ± 0.7 (0.8, -0.8 to 2.13) PD/mm at distance and 0.9 ± 0.9 (0.83, -1 to 3) PD/mm at near, it was similar in patients operated on for esotropia and for exotropia. The surgical effect on the horizontal deviation was 2.1 ± 1.1 PD/mm (distance) and 2.6 ± 1 PD/mm (near). Both the vertical and horizontal surgical dose correlated with the effect in a linear way, but the variability was greater for the vertical transposition. CONCLUSIONS: Vertical transposition of the horizontal rectus muscles in the same direction allows for correction of vertical strabismus. This procedure may be performed during primarily horizontal strabismus surgery, without operating on an additional extraocular muscle. The transposition distance correlates with the surgical effect but predictability of the effect is limited.

Ophthalmologic health status of an aging population-data from the Berlin Aging Study II (BASE-II).

PURPOSE: Vision of the elderly may be affected by typical age-related diseases like cataract and macular degeneration. Little is known about the effect of aging on visual difficulties and vision-related quality of life. This study was conducted to compare the ophthalmological health status of younger and older individuals within a large cohort study of residents of a greater metropolitan area (Berlin Aging Study II [BASE-II]). METHODS: A total of 1655 participants (805 men) aged 60 years and older and 494 participants (232 men) aged between 22 and 48 years from the Berlin Aging Study II were included in the analysis. The subjects were examined during a 2-day clinical examination period. History of ocular diseases, vision-related quality of life using the visual function questionnaire (VFQ- 25), refraction, distance and near visual acuity, tonometry, and color vision were provided. RESULTS: Older subjects performed significantly worse concerning distance and near visual acuity, color vision, and vision-related quality of life compared to young subjects. Intraocular pressure showed no significant difference between groups. Individuals are often unaware of existing eye diseases. CONCLUSION: The prevalence of ocular diseases and the impairment of vision increases with age. Although 98% of elderly subjects have reported to suffer from any ocular disease, subjective quality of life seems to be affected to a lesser extent.

[Multifocal Electroretinography in Patients with Poppers Maculopathy]. / Multifokale Elektroretinografie bei Patienten mit Poppers-Makulopathie.

BACKGROUND: Maculopathy is a potential side effect of amyl nitrite or "poppers" abuse. It is characterized by a sudden, painless decrease in visual acuity. While the funduscopic changes are subtle, optical coherence tomography shows alterations of the outer retinal layers in the fovea. However, the extent of retinal dysfunction remains poorly understood. MATERIALS/METHODS: We compared the multifocal electroretinogram of 6 patients with poppers maculopathy to that of a control group consisting of 6 healthy subjects. Response densities and implicit times of N1 and P1 were analyzed. RESULTS: Response densities and implicit times of both N1 and P1 were lower in the patients with poppers maculopathy than in the control group, particularly in ring 1 and rings 4 and 5. The only statistically significant finding, however, was a reduced N1 response density of one hexagon in the patient group. No significant differences were found considering the sum response or the averaged rings 1 to 5. CONCLUSION: Compared to a healthy control group, the multifocal electroretinogram of patients with poppers maculopathy shows no relevant impairment. This contrasts the marked effect of the disease on visual acuity. In clinical practice, poppers maculopathy cannot be diagnosed by multifocal electroretinography.

Facilitating the analysis of the multifocal electroretinogram using the free software environment R.

PURPOSE: The large amount of data rendered by the multifocal electroretinogram (mfERG) can be analyzed and visualized in various ways. The evaluation and comparison of more than one examination is time-consuming and prone to create errors. Using the free software environment R we developed a solution to average the data of multiple examinations and to allow a comparison of different patient groups. METHODS: Data of single mfERG recordings as exported in .csv format from a RETIport 21 system (version 7/03, Roland Consult) or manually compiled .csv files are the basis for the calculations. The R software extracts response densities and implicit times of N1 and P1 for the sum response, each ring eccentricity, and each single hexagon. Averages can be calculated for as many subjects as needed. The mentioned parameters can then be compared to another group of patients or healthy subjects. Application of the software is illustrated by comparing 11 patients with chloroquine maculopathy to a control group of 7 healthy subjects. RESULTS: The software scripts display response density and implicit time 3D plots of each examination as well as of the group averages. Differences of the group averages are presented as 3D and grayscale 2D plots. Both groups are compared using the t-test with Bonferroni correction. The group comparison is furthermore illustrated by the average waveforms and by boxplots of each eccentricity. CONCLUSIONS: This software solution on the basis of the programming language R facilitates the clinical and scientific use of the mfERG and aids in interpretation and analysis.

FUNDUS AUTOFLUORESCENCE FINDINGS IN EARLY CHLOROQUINE MACULOPATHY.

BACKGROUND/PURPOSE: Toxic maculopathy is a rare but severe complication of chloroquine intake. Although the phenotype of established maculopathy was analyzed in detail, few data exist on the ophthalmologic findings in the early stage. METHODS: The authors present 4 female patients with unequivocal signs of chloroquine maculopathy (bilateral [peri-]central scotoma in the visual fields, structural alterations of the macula in the optical coherence tomography) but normal or atypical findings as to fundus autofluorescence imaging. RESULTS: In all patients, optical coherence tomography showed perifoveal thinning and subtle alterations of the outer retinal layers. In one patient, the latter was limited to the pericentral region, whereas it showed a more diffuse distribution in two other patients. One patient showed a combination of pericentral and diffuse damage. Multifocal electroretinography was recorded in three patients and revealed the typical (peri-)central amplitude reductions. CONCLUSION: A normal fundus autofluorescence does not rule out toxic maculopathy. Optical coherence tomography and multifocal electroretinography seem to be more sensitive in the early stage of the disease. In case of typical complaints and visual fields, the optical coherence tomography has to be evaluated for subtle alterations of the outer retina. Their presence justifies the cessation of the drug. Multifocal electroretinography may be of special value in these problematic cases.

Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions.

A significant portion of patients diagnosed with vitelliform macular dystrophy (VMD) do not carry causative mutations in the classic VMD genes BEST1 or PRPH2. We therefore performed a mutational screen in a cohort of 106 BEST1/PRPH2-negative VMD patients in two genes encoding secreted interphotoreceptor matrix proteoglycans-1 and -2 (IMPG1 and IMPG2). We identified two novel mutations in IMPG1 in two simplex VMD cases with disease onset in their early childhood, a heterozygous p.(Leu238Pro) missense mutation and a homozygous c.807 + 5G > A splice site mutation. The latter induced partial skipping of exon 7 of IMPG1 in an in vitro splicing assay. Furthermore, we found heterozygous mutations including three stop [p.(Glu226*), p.(Ser522*), p.(Gln856*)] and five missense mutations [p.(Ala243Pro), p.(Gly1008Asp), p.(Phe1016Ser), p.(Tyr1042Cys), p.(Cys1077Phe)] in the IMPG2 gene, one of them, p.(Cys1077Phe), previously associated with VMD. Asymptomatic carriers of the p.(Ala243Pro) and p.(Cys1077Phe) mutations show subtle foveal irregularities that could characterize a subclinical stage of disease. Taken together, our results provide further evidence for an involvement of dominant and recessive mutations in IMPG1 and IMPG2 in VMD pathology. There is a remarkable similarity in the clinical appearance of mutation carriers, presenting with bilateral, central, dome-shaped foveal accumulation of yellowish material with preserved integrity of the retinal pigment epithelium (RPE). Clinical symptoms tend to be more severe for IMPG1 mutations.

De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy.

X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. 'LIAVA', 'LVAVA') with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the 'LIAVA' haplotype derived from an ancestral less deleterious 'LIAVS' haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.

RETINAL LESION EVOLUTION IN SUSAC SYNDROME.

PURPOSE: To describe retinal lesion development in Susac syndrome during acute, postacute, and late phases of the disease. METHODS: Cross-sectional study of four patients with Susac syndrome and longitudinal short-interval case study of one additional patient. Retinal changes were analyzed with high-resolution spectral domain optical coherence tomography and retinal fluorescein angiography. RESULTS: Retinal Susac syndrome lesions comprise four different lesion sections, which can be distinguished in acute and postacute phases of the disease: a primary section at the site of branch retinal artery occlusion, which spans more layers than supplied by the affected vessel; hypoxic sections from superficial and deep capillary networks; and an axonal damage section with degenerating axons from perished ganglion cells in the main and hypoxic sections. In the later stages, main and hypoxic lesion sections can no longer be distinguished, and both show degeneration from outer plexiform to retinal nerve fiber layers. CONCLUSION: The dynamics of lesion development and morphologically distinct lesion sections suggest more complex mechanisms of lesion evolution beyond an isolated endothelial immune reaction and subsequent hypoxic tissue damage. The characteristic lesion morphology assists in differentiating the diagnosis of acute visual loss in neuroinflammatory disease. Specificity of the identified changes has to be determined in future studies also including patients with other retinal vascular diseases.

Poppers Maculopathy: Complete Restitution of Macular Changes in OCT after Drug Abstinence.

BACKGROUND: "Poppers" is a slang term for a group of alkyl nitrites that are used as recreational drugs. Their inhalative intoxication leads to muscle relaxation, analgesia, and euphoria. Maculopathy is a rare but serious side-effect. PATIENTS/METHODS: Clinical, imaging, and electrophysiological findings of seven patients with maculopathy after consumption of poppers were presented. RESULTS: All seven patients were male with a median age of 35 years (range 28-45 years), the median duration of periodical poppers use until the onset of symptoms was 9.8 years (one day to 25 years). Five of seven patients were HIV-positive, one patient was negative, and the HIV-status of one patient was unknown. Median average of visual acuity at presentation was 20/30 in each eye. In all patients, optical coherence tomography (OCT) showed pathognomonic alterations of the outer foveal retina. One patient showed an almost complete restitution of the maculopathy six months after cessation of drug use and following the oral intake of Lutein. Imaging alterations returned to normal and visual acuity recovered from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes. Follow up of two other cases showed no relevant functional decline or improvement. DISCUSSION: Toxic maculopathy due to the consumption of poppers is an important differential diagnosis in acute visual loss without clinico-morphological correlate. Optical coherence tomography is the only reliable diagnostic tool in these cases. Complete recovery of visual function and macular morphology is rare, even after cessation of drug abuse. Oral lutein therapy may have a beneficial effect.

Retinal pathology in Susac syndrome detected by spectral-domain optical coherence tomography.

OBJECTIVE: The aim of this non-interventional study was to characterize retinal layer pathology in Susac syndrome (SuS), a disease with presumably autoimmune-mediated microvessel occlusions in the retina, brain, and inner ear, in comparison to the most important differential diagnosis multiple sclerosis (MS). METHODS: Seventeen patients with SuS and 17 age- and sex-matched patients with relapsing-remitting MS (RRMS) and healthy controls (HC) were prospectively investigated by spectral-domain optical coherence tomography (OCT) including intraretinal layer segmentation in a multicenter study. Patients with SuS additionally received retinal fluorescein angiography (FA) and automated perimetry. RESULTS: Patchy thinning of the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer compared to corresponding sectors in RRMS and HC eyes (p < 0.003 for SuS vs RRMS and HC) was observed in 23/34 (68%) SuS eyes, particularly in temporal quadrants. The outer nuclear layer (ONL) and photoreceptor layers (PRL) were not affected. FA performed in 15/17 patients with SuS was negative for disease-specific branch retinal artery occlusions in all but 1 eye at the time of OCT examination and revealed no additional vascular abnormalities, even in severely damaged OCT areas. In a subset of patients with SuS, associations of visual field data with distinct retinal layers were observed. CONCLUSION: Distinct OCT patterns of scattered, scar-like intraretinal pathology in SuS eyes, sparing the ONL and PRL, suggest a retinal, but not choroidal, vascular pathomechanism and clearly differentiate SuS from RRMS. Depending on the disease stage, OCT and FA provide specific complementary diagnostic information in SuS.

Common synonymous variants in ABCA4 are protective for chloroquine induced maculopathy (toxic maculopathy).

BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) are used to treat auto-immune related diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus. Both drugs however can cause retinal toxicity eventually leading to irreversible maculopathy and retinopathy. Established risk factors are duration and dosage of treatment while the involvement of genetic factors contributing to toxic maculopathy is largely unclear. To address the latter issue, this study aimed to expand on earlier efforts by (1) evaluating risk-altering variants known to be associated with age-related macular degeneration (AMD), a frequent maculopathy in individuals over 55 years of age, and (2) determining the contribution of genetic variants in the coding sequence of the ABCA4 gene. METHODS: The ABCA4 gene was analyzed by deep sequencing technology using a personal genome machine (Ion Torrent) with 200 bp read length. Assessment of AMD variants was done by restriction enzyme digestion of PCR products and TaqMan SNP genotyping. Effect sizes, p-values and confidence intervals of common variants were evaluated by logistic regression (Firth's bias corrected). To account for multiple testing, p-values were adjusted according to the false discovery rate. RESULTS: We found no effects of known AMD-associated variants on the risk of toxic maculopathy. In contrast, we report a statistically significant association of common variants in the ABCA4 gene with retinal disease, assessed by a score-based variance-component test (PSKAT = 0.0055). This association remained significant after adjustment for environmental factors like age and duration of medication and was driven by three common variants in ABCA4 (c.5682G > C, c.5814A > G, c.5844A > G), all conferring a reduced risk for toxic maculopathy. CONCLUSIONS: Our findings demonstrate that minor alleles of common genetic variants in ABCA4 significantly reduce susceptibility to develop toxic maculopathy under CQ treatment. A refined risk profile based on genetic and environmental factors may have implications for revised recommendations in CQ as well as HCQ treatment.

Influence of chloroquine intake on the multifocal electroretinogram in patients with and without maculopathy.

PURPOSE: To evaluate the effect of long-term chloroquine intake on the multifocal electroretinogram (mfERG) in female patients with and without maculopathy. METHODS: Retrospective analysis of the mfERGs recorded in three different groups: (1) patients with bilateral maculopathy having taken chloroquine, (2) patients without maculopathy having taken chloroquine, and (3) healthy control subjects (age-matched to group 2) who never took chloroquine. MfERGs of each group were averaged, and the data of each patient group were compared to the control group. The main outcome measures were N1 and P1 characteristics and the ring ratio analysis. RESULTS: In group 1, 11 female subjects (22 eyes) were included, group 2 consisted of nine patients (18 eyes) and group 3 of seven healthy female subjects (14 eyes). Compared with healthy controls, patients in group 1 showed significantly reduced response densities of both N1 and P1 across all ring eccentricities except ring 5. Implicit times were significantly delayed only concerning N1 (ring 4 and the sum response of the left eye of group 1). P1 implicit times showed no significant alterations in either group. Ring ratios of the response densities were significantly higher mainly concerning group 1 (N1: ring 5/ring 2 and ring 5/ring 4 of the right eye; P1: all ring ratios of the right eye and all ratios except ring 5/ring 1 and ring 5/ring 4 of the left eye). The only ring ratio being significantly higher in group 2 was P1 ring 5/ring 1 ratio of the right eye. CONCLUSIONS: In the absence of clinically apparent maculopathy, chloroquine intake was not associated with major alterations of the mfERG.

Clinical results and higher-order aberrations after 1.4-mm biaxial cataract surgery and implantation of a new aspheric intraocular lens.

PURPOSE: The purpose of this study was to analyze the clinical outcome and higher-order aberrations (HOAs) after 1.4-mm biaxial microincision cataract surgery (B-MICS) and implantation of a new aspheric intraocular lens (IOL). MATERIAL AND METHODS: A total of 157 eyes of 106 patients were enrolled in this prospective, single-center study. The B-MICS (1.4 mm, 26 eyes) was followed by an implantation of a microincision aspheric Incise® IOL MJ14T (Bausch & Lomb, Rochester, N.Y., USA). The control groups consisted of patients operated with 1.8-mm (coaxial MICS, Akreos MI60, 41 eyes), 2.2-mm (small incision cataract surgery, Tecnis ZCB00, 44 eyes) and 2.2-mm (small incision cataract surgery, CT Asphina, 46 eyes) coaxial phacoemulsification with implantation of an aspheric IOL. Intraoperative and postoperative complications, best-corrected visual acuity, HOAs for a 5.0-mm pupil using the iTrace aberrometer (Tracey Technologies, Houston, Tex., USA) and endothelial cell loss were evaluated. The difference among the groups was evaluated by analysis of variance. RESULTS: In the Incise group, the mean best-corrected visual acuity improved significantly from 0.4 ± 0.27 logMAR preoperatively to 0.05 ± 0.07 postoperatively. The root mean square of total ocular HOAs was measured at 0.419 ± 0.191 µm, spherical aberration was measured at 0.168 ± 0.072 µm and coma was measured at 0.213 ± 0.200 µm. The best-corrected visual acuity (p = 0.097), total ocular HOA (p = 0.630) and coma (p = 0.193) showed no statistically significant difference between the 4 groups. CONCLUSION: The aspheric microincision IOL was safely implanted through a 1.4-mm incision and showed similarly good postoperative outcome in comparison to 1.8- and 2.2-mm coaxial phacoemulsification.

Phenotyping heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with CLN3 mutations.

PURPOSE: The objective of this study was to establish an ophthalmologic phenotype of heterozygous carriers of juvenile neuronal ceroid lipofuscinosis (CLN3 disease, Batten disease). METHODS: The eyes and vision of nine heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with classical CLN3 mutations were examined using the following methods: clinical examination, visual acuity, ophthalmoscopy, optical coherence tomography (macular thickness and peripapillary retinal nerve fibre layer measurement [RNFL]), fundus autofluorescence measurement, infrared imaging, and full-field and multifocal electroretinogram. Optical coherence tomography and electrophysiological data were statistically compared with age- and sex-matched control groups. RESULTS: The basic clinical examination as well as the fundus autofluorescence and infrared images of the macular region were unremarkable. Neither the electrophysiological examinations nor optical coherence tomography yielded fundamental abnormalities. There were only two significant-albeit most likely clinically irrelevant-differences that occurred in comparison to the control group: a decrease in RNFL of the nasal quadrant in the OCT and a prolongation of the N1 implicit time of the second-ring eccentricity in the multifocal electroretinogram. CONCLUSIONS: The eyes and vision of heterozygous carriers of CLN3 disease showed normal features when compared to a control group, which controverts a previously suggested retinal dysfunction in these subjects.

Aqualase® revisited: endothelial cell loss strongly depends on lens density.

PURPOSE: To analyze the dependence between corneal endothelial cell loss by Aqualase® cataract surgery and the nuclear opalescence grade of the lens. PATIENTS AND METHODS: A total of 100 eyes of 92 patients were enrolled in this prospective, single-center study. Patients were randomly assigned to the Aqualase (50 eyes) or the phacoemulsification group (50 eyes). The nuclear density was classified with the Lens Opacities Classification System III. All procedures were performed by the same surgeon. Preoperatively and 1 week postoperatively, endothelial cell counts were obtained using a noncontact specular microscope (Konan, Japan). RESULTS: (1) Aqualase group: the group of patients with a nuclear density of 1-2 (17 patients) showed no significant endothelial cell loss (4.1%, p = 0.163). The endothelial cell loss in grade 3 cataracts (28 eyes) was 13.9% (p = 0.004) and in grade 4 cataracts (5 eyes) 69.1% (p = 0.043), being statistically significant in both groups. (2) Phacoemulsification group: in nuclear density groups 1 and 2, endothelial cell loss was 6.3% (p = 0.41), in group 3 it was 17.6% (p = 0.001) and in group 4 it was 14.9% (p = 0.08). Only in nuclear opalescence grade 4 there was a significant difference between the Aqualase and the phacoemulsification procedure (p = 0.008). CONCLUSION: Endothelial cell loss by Aqualase technology depends strongly on the nuclear opalescence grade. In low- and medium-density cataracts, Aqualase does not seem to provoke significant endothelial cell loss. Due to very high endothelial loss in hard nuclei, Aqualase is unsuitable for these cataracts.

Effects of the AMPA antagonist ZK 200775 on visual function: a randomized controlled trial.

BACKGROUND: ZK 200775 is an antagonist at the alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor and had earned attention as a possible neuroprotective agent in cerebral ischemia. Probands receiving the agent within phase I trials reported on an alteration of visual perception. In this trial, the effects of ZK 200775 on the visual system were analyzed in detail. METHODOLOGY: In a randomised controlled trial we examined eyes and vision before and after the intravenous administration of two different doses of ZK 200775 and placebo. There were 3 groups of 6 probands each: Group 1 recieved 0.03 mg/kg/h, group 2 0.75 mg/kg/h of ZK 200775, the control group received 0.9% sodium chloride solution. Probands were healthy males aged between 57 and 69 years. The following methods were applied: clinical examination, visual acuity, ophthalmoscopy, colour vision, rod absolute threshold, central visual field, pattern-reversal visual evoked potentials (pVEP), ON-OFF and full-field electroretinogram (ERG). PRINCIPAL FINDINGS: No effect of ZK 200775 was seen on eye position or motility, stereopsis, pupillary function or central visual field testing. Visual acuity and dark vision deteriorated significantly in both treated groups. Color vision was most remarkably impaired. The dark-adapted ERG revealed a reduction of oscillatory potentials (OP) and partly of the a- and b-wave, furthermore an alteration of b-wave morphology and an insignificantly elevated b/a-ratio. Cone-ERG modalities showed decreased amplitudes and delayed implicit times. In the ON-OFF ERG the ON-answer amplitudes increased whereas the peak times of the OFF-answer were reduced. The pattern VEP exhibited lower amplitudes and prolonged peak times. CONCLUSIONS: The AMPA receptor blockade led to a strong impairment of typical OFF-pathway functions like color vision and the cone ERG. On the other hand the ON-pathway as measured by dark vision and the scotopic ERG was affected as well. This further elucidates the interdependence of both pathways. TRIAL REGISTRATION: ClinicalTrials.gov NCT00999284.