Cytomegalovirus-associated chorioretinitis after liver transplantation: case report and review of the literature.

A cytomegalovirus (CMV) donor positive/recipient negative liver transplant recipient developed CMV syndrome with presumed colitis 2 weeks after discontinuing the standard 3 months of valganciclovir prophylaxis. Treatment with intravenous ganciclovir (GCV) reduced, but did not clear, CMV replication. A CMV UL97 mutation (M460V) conferring GCV resistance was identified. Reduction of immunosuppression was followed by rapidly rising lymphocyte counts as well as by clearance of CMV viremia and of clinical symptoms. However, bilateral chorioretinitis was diagnosed 2 weeks later and treated with foscarnet and cidofovir. Then, right eye vitritis occurred necessitating vitrectomy due to a partially rhegmatogeneous retinal detachment. Because chorioretinitis-vitritis after rising lymphocyte counts and clearance of CMV viremia was strongly suggestive of an immune reconstitution syndrome (IRS)-like disease, we investigated CMV-specific T-cells in the peripheral blood available during follow-up. We found strong CD8(+) but only low CD4(+) T-cell responses (4.77% vs.<0.1%) to the CMV immediate early pp72, while responses to CMV-lysate or CMV-pp65 (CD4(+) <0.01%; CD8(+)<0.01%) were low. Over 16 weeks of follow-up, pp72-specific CD8(+) responses declined, while responses to pp65 gradually increased (CD4(+) 0.16%; CD8(+) 0.76%) indicating a slowly adapting CMV-specific cellular T-cell response. Review of 12,653 published liver transplant patients identified only 14 (0.1%) reported cases of CMV-associated chorioretinitis at a median 41.7 weeks post transplant. CMV-associated opthalmologic complications late post transplantation may possibly involve 2 different entities of cytopathic retinitis and IRS-like chorioretinitis-vitritis.

Dissociated hysteresis of static ocular counterroll in humans.

In stationary head roll positions, the eyes are cyclodivergent. We asked whether this phenomenon can be explained by a static hysteresis that differs between the eyes contra- (CE) and ipsilateral (IE) to head roll. Using a motorized turntable, healthy human subjects (n = 8) were continuously rotated about the earth-horizontal naso-occipital axis. Starting from the upright position, a total of three full rotations at a constant velocity (2 degrees/s) were completed (acceleration = 0.05 degrees/s2, velocity plateau reached after 40 s). Subjects directed their gaze on a flashing laser dot straight ahead (switched on 20 ms every 2 s). Binocular three-dimensional eye movements were recorded with dual search coils that were modified (wires exiting inferiorly) to minimize torsional artifacts by the eyelids. A sinusoidal function with a first and second harmonic was fitted to torsional eye position as a function of torsional whole body position at constant turntable velocity. The amplitude and phase of the first harmonic differed significantly between the two eyes (paired t-test: P < 0.05): on average, counterroll amplitude of IE was larger [CE: 6.6 +/- 1.6 degrees (SD); IE: 8.1 +/- 1.7 degrees), whereas CE showed more position lag relative to the turntable (CE: 12.5 +/- 10.7 degrees; IE: 5.1 +/- 8.7 degrees). We conclude that cyclodivergence observed during static ocular counterroll is mainly a result of hysteresis that depends on whether eyes are contra- or ipsilateral to head roll. Static hysteresis also explains the phenomenon of residual torsion, i.e., an incomplete torsional return of the eyes when the first 360 degrees whole body rotation was completed and subjects were back in upright position (extorsion of CE: 2.0 +/- 0.10 degrees; intorsion of IE: 1.4 +/- 0.10 degrees). A computer model that includes asymmetric backlash for each eye can explain dissociated torsional hysteresis during quasi-static binocular counterroll. We hypothesize that ocular torsional hysteresis is introduced at the level of the otolith pathways because the direction-dependent torsional position lag of the eyes is related to the head roll position and not the eye position.

Residual torsion following ocular counterroll.

A recent study on static ocular counterroll suggested the existence of residual torsion (RT): when healthy subjects repositioned their head to the upright position after sustained static tilt, eye position differed from the original ocular torsion measured prior to the static head tilt. Our experiments aimed at further characterizing this phenomenon. Using a three-dimensional motorized turntable, healthy human subjects (n = 8) were rotated quasi-statically (0.05 deg/s2, 2 deg/s velocity plateau reached after 40 s) from the upright position about the naso-occipital axis. Three full whole-body rotations were completed while subjects fixed upon a blinking laser dot straight ahead in otherwise complete darkness. Three-dimensional eye movements were recorded with modified dual search coils (wires exiting inferiorly). Torsional position of the right eye at consecutive upright body positions was analyzed. The torsional eye position before the beginning of the chair rotation was defined as zero torsion. On average, the right eye was intorted by 1.3 degrees or extorted by 2.0 degrees after the first full chair rotation in the clockwise or counterclockwise direction, respectively. These torsional offset values of the right eye did not significantly change after the two subsequent full chair rotations. We conclude that RT observed after static ocular counterroll is the result of static hysteresis, that is, a position lag of the eye, which depends on the direction of head roll. The fact that residual torsion did not further increase after the first rotation cycle emphasizes that RT is a static rather than a dynamic phenomenon.

The value of white blood cell count in patients with swollen discs.

BACKGROUND: A broad differential diagnosis has to be considered in a patient with swollen discs. Myeloproliferative disorders such as leukemia and lymphoma can in rare cases cause infiltrative optic neuropathy. HISTORY AND SIGNS: Two patients initially presented with slowly progressive severe visual loss. History was unremarkable except for previously noted slightly elevated white blood cell count for which - according to their general physicians - no treatment or work-up was required. At presentation, bilateral disc swelling was present. Magnetic resonance imaging showed enhancement of the entire optic nerves sparing the chiasm. No other intracranial lesion was found. Cerebrospinal fluid contained no malignant cells. THERAPY AND OUTCOME: After bone marrow aspiration the diagnosis of non-Hodgkin's lymphoma and granulocytic leukemia, respectively, was made. Treatment resulted in visual recovery. CONCLUSION: Work-up in a patient with swollen discs should always include white blood cell count. If the result is abnormal further exploration should be pursued. Elevated white blood cell count may be the only hint of optic nerve infiltration caused by a myeloproliferative disorder and its treatment can result in remarkable recovery.

Three-dimensional binocular kinematics of torsional vestibular nystagmus during convergence on head-fixed targets in humans.

When a human subject is oscillated about the nasooccipital axis and fixes upon targets along the horizontal head-fixed meridian, angular eye velocity includes a vertical component that increases with the horizontal eccentricity of the line-of-sight. This vertical eye movement component is necessary to prevent retinal slip. We asked whether fixation on a near head-fixed target during the same torsional vestibular stimulation would lead to differences of vertical eye movements between the right and the left eye, as the directions of the two lines-of-sight are not parallel during convergence. Healthy human subjects (n = 6) were oscillated (0.3 Hz, +/-30 degrees) about the nasooccipital axis on a three-dimensional motor-driven turntable. Binocular movements were recorded using the dual search coil technique. A head-fixed laser dot was presented 1.4 m (far head-fixed target) or 0.25 m (near head-fixed target) in front of the right eye. We found highly significant (P < 0.01) correlations (R binocular = 0.8, monocular = 0.59) between the convergence angle and the difference of the vertical eye velocity between the two eyes. The slope of the fitted linear regression between the two parameters (s = 0.45) was close to the theoretical slope necessary to prevent vertical retinal slippage (predicted s = 0.5). Covering the left eye did not significantly change the slope (s = 0.52). In addition, there was a marked gain reduction (approximately 35%) of the torsional vestibuloocular reflex (VOR) between viewing the far and the near targets, confirming earlier results by others. There was no difference in torsional gain reduction between the two eyes. Lenses of +3 dpt positioned in front of both eyes to decrease the amount of accommodation did not further change the gain of the torsional VOR. In conclusion, ocular convergence on a near head-fixed target during torsional vestibular stimulation leads to deviations in vertical angular velocity between the two eyes necessary to prevent vertical double vision. The vertical deviation velocity is mainly linked to the amount of convergence, since it also occurs during monocular viewing of the near head-fixed target. This suggests that convergence during vestibular stimulation automatically leads to an alignment of binocular rotation axes with the visual axes independent of retinal slip.

Three-dimensional Hess screen test with binocular dual search coils in a three-field magnetic system.

PURPOSE: To establish an objective Hess screen test that allows a simultaneous and binocular analysis of all three axes of eye rotation. METHODS: In orthotropic and strabismic human subjects, both eyes were recorded with dual scleral search coils in a three-field magnetic system. Before mounting the search coil annuli on the eyes, the voltage offsets of each channel and the relative magnitudes of the three magnetic fields were determined. For calibration, subjects were only required to fix monocularly on a single reference target. During fixation of targets on the Hess screen by the uncovered eye, the three-dimensional eye position of both the occluded and the viewing eye was simultaneously measured. RESULTS: For clinical interpretation, an easy to understand graphical description of the three-dimensional Hess screen test was developed. Positions of orthotropic and strabismic eyes tended to follow Listing's law, which in both eyes allowed the determination of the primary position, that is, the position of gaze from which pure horizontal and pure vertical movements do not lead to an ocular rotation about the line-of-sight. To a first approximation, the location of primary position is a result of the summation of the individual rotation axes of the six extraocular muscles and thus can be used to infer which muscle is paretic. CONCLUSIONS: The three-dimensional Hess screen test with binocular dual search coils in a three-field magnetic system is an objective method to assess the ocular alignment in three dimensions with high precision. From these recordings, the clinician can relate deviations of primary position to specific eye muscle palsies.

The influence of iris color on the pupillary light reflex.

BACKGROUND: This study was carried out to investigate the effect of iris color on the pupillary light reflex (PLR) in normal healthy volunteers. METHODS: Pupil perimetry was performed on 50 healthy volunteers with the Octopus 1-2-3 automated perimeter. Within the 30-deg visual field, 33 test locations were investigated four times. Stimulus parameters were Goldmann size V (1.72 degrees), intensity 1632 cd/m2, stimulus time 200 ms, background illumination 0 cd/m2, and interstimulus interval 3 s. Pupillometric parameters studied were initial pupil size, amplitude (magnitude of pupillary contraction), latency time, contraction time, pre-PLR movement, contraction velocity, and redilation velocity. Pupillometric parameters were investigated by analysis of variance by the independent variables blue and brown irides. RESULTS: Iris color (blue vs brown) influenced statistically significantly (P < 0.05) amplitude (0.504 mm vs 0.594 mm), contraction time (401 ms vs 407 ms), contraction velocity (13.75 mm2/s vs 16.01 mm2/s), and redilation velocity (4.80 mm2/s vs 5.66 mm2/s). Iris color did not influence initial pupil size (4.78 mm vs 4.83 mm), latency time (520 mm vs 521 ms), and pre-PLR movement (0.328 mm2/s vs 0.325 mm2/s). CONCLUSIONS: Pupillary contraction amplitude and velocity depended on iris color, whereas pupil size and latency time were independent of iris color. Therefore, iris color might be considered when, evaluating pupillary movements in pupil perimetry.

[Measuring nerve fiber thickness with laser scanning polarimetry in aging]. / Nervenfaserschichtdickenmessung mittels Laser-Scanning-Polarimetrie im Altersvergleich.

PURPOSE: In glaucoma, visual field defects are a late sign of retinal nerve fiber layer damage. Scanning laser polarimetry directly quantifies nerve fiber layer thickness (NFLT) and may allow early detection of defects and progression during follow-up. METHODS: The NFLT of 54 healthy eyes of 54 subjects (age range from 14 to 83 years) was measured with a scanning laser polarimeter (Nerve Fiber Analyzer II). Measurements were performed along an ellipse 1.75 disc diameters away from the disc margin. For each subject an average image was calculated from three measurements. The ellipse was divided into four sectors by the internal software. All measurements were performed by the same examiner. All examined eyes had a normal ophthalmological examination, normal eye pressure and a normal computerized perimetry. RESULTS: The mean NFLT was thicker in the superior (91.3 microns +/- 16.7 microns) and inferior sector (90.8 microns +/- 15.6 microns) as compared to the temporal (53.7 microns +/- 15.4 microns) and nasal sector (60.0 microns +/- 14.8 microns). There was an inverse linear correlation between age and NFLT (Pearson's correlation-coefficient r = -0.30, p < 0.025). On the average, the mean NFLT decreased by 2.5 microns for each decade of age. The interindividual variation of the NFLT (mean standard deviation (s) = 16.1 microns) was, even after correction for age, much larger than the intraindividual variation (s = 6.6 microns). CONCLUSIONS: In normal subjects the NFLT decreases with age. The interindividual NFLT variation is, even after correction for age, much larger than the intraindividual. Therefore, scanning laser polarymetry might be especially useful for follow-up of NFLT.

Evaluation of the Brusini glaucoma staging system for typing and staging of perimetric results.

BACKGROUND: Brusini's recently introduced glaucoma staging system (GSS) categorizes visual-field damages into different types (i.e. generalized, mixed and localized) and classifies them into stages similar to those of Aulhorn-Karmeyer. Basically, the Brusini GSS is a scatterplot of mean defect (x-axis) and corrected loss variance (CLV; y-axis). The Brusini GSS charts are claimed to be simple to understand due to their 2-dimensional spatial representation and there is no subjective interpretation necessary, since their numerical presentation provides an objective evaluation. Inter- and intraindividual comparisons are, thus, provided 'at a glance'. METHODS: Retrospectively, 610 visual fields (Octopus 201, Program G1) for each eye of 32 glaucoma patients were inspected on screen with PeriData 7.0. The performance of the Brusini GSS was evaluated in terms of typing of visual-field defect and staging as defined by the Aulhorn-Karmeyer classification. RESULTS: Typing of defects into 'normal' and various degrees of generalized and localized damage agreed with PeriData in 89% of fields; 5% were wrongly classified as normal by the Brusini GSS. The type of visual defect showed in 1.3% fields as marked and in 5% a minor discrepancy. Most of the 11% of nonagreement was due to high short-term fluctuation. Agreement could potentially be enhanced by using loss variance instead of CLV Staging of visual-field defects with Brusini GSS charts was in agreement with the Aulhorn-Karmeyer classification in 73% of fields. CONCLUSION: The authors recommend the Brusini GSS because of its simplicity to concisely describe visual-field damage for clinical use as well as research work and because of the remarkably good agreement with the well-known Aulhorn-Karmeyer classification.

Optimizing distribution and number of test locations in perimetry.

BACKGROUND: Short programs with few test locations have been proposed for glaucoma screening. Program G1x of the Octopus 1-2-3 automated perimeter is divided into four stages and permits the examination to be stopped after 16, 32, 45, or all 59 test locations. We investigated whether such short programs provide information comparable with that supplied by standard programs in glaucoma. MATERIALS AND METHODS: In 99 visual fields of 81 glaucomatous and 18 glaucoma-suspect right eyes, mean defect (MD) and loss variance (LV) of the entire visual field were compared with MD and LV of the 4 stages of Program G1x. RESULTS: MD of the entire visual field averaged 0.40 dB, with averages of -0.17 dB, 0.34 dB, 0.47 dB, and 1.04 dB for stages 1, 2, 3, and 4, respectively. LV of the entire visual field averaged 13.0 dB2 and was similar for all four stages. CONCLUSIONS: The results show that the 16 test locations of stage 1 of Program G1x underestimate the visual-field damage present in the entire field. We recommend examination of at least 32 test locations, i.e., two stages of Program G1x. However, a prospective study is required to evaluate the sensitivity and specificity of short programs for glaucoma screening. The selection of test locations for the stages might be improved.

[Pupil perimetry with the Octopus 1-2-3. Initial experiences]. / Pupillenperimetrie mit dem OCTOPUS 1-2-3. Erste Erfahrungen.

PURPOSE: Development of a clinically useful pupil perimetry on an OCTOPUS 1-2-3. MATERIALS AND METHODS: Various test parameters were investigated on a moderately modified OCTOPUS 1-2-3. We evaluated the pupillary responses of 122 eyes of 122 healthy volunteers qualitatively. RESULTS: Pleasing pupillary responses were obtained with the following parameters: 200 ms stimuli, Goldmann size 5 (1.5 degrees), background illumination 3 apostilb. Acoustic signals 0.5 seconds before stimulus presentation were helpful to minimize blinking artifacts. The pupillary reactions were fare stronger in central areas of the visual field than in mid-peripheral areas (i.e. 26 degrees). CONCLUSIONS: Pupil perimetry can be preformed on a moderately modified OCTOPUS 1-2-3. The results reveal considerable inter- and intra-individual variability. Equal pupillary responses at all eccentricities would improve subsequent mathematical evaluation.