Tos T. J. M. Berendschot

Ocular toxoplasmosis: clinical features and prognosis of 154 patients

PURPOSEnTo ascertain the clinical features, visual outcome, and recurrence rates of ocular toxoplasmosis (OT) in a large series of patients. To determine the efficacy of various treatment strategies and identify the patients at risk of visual loss.nnnDESIGNnRetrospective noncomparative observational case series.nnnPARTICIPANTSnOne hundred fifty-four consecutive patients with active lesions of OT (first attack and/or recurrence) were identified in a cohort of 1300 consecutive patients with uveitis. Mean follow-up was 5.8 years.nnnINTERVENTIONnA review of the medical records of 154 patients with active OT.nnnMAIN OUTCOME MEASURESnPatients were subdivided according to clinical and laboratory criteria. Numerous variables were compared per patient and group, including age and gender distribution, onset and course of infection, clinical ocular features, laboratory data, therapeutic strategies and their outcomes, number of recurrences, complications, final visual acuity, and features associated with poor visual outcome.nnnRESULTSnPrimary retinal lesions were observed in 28% and a combination of active lesions and old retinochoroidal scars in 72% of the patients at first presentation to the ophthalmologist. Mean age at first presentation with an active OT lesion was 29.5 years. Patients with primary OT were older than those with a combination of active lesions and old scars (P < 0.001). Serologic characteristics of the acute phase of systemic infection were found in 11% of the patients. Ocular involvement in these patients was associated with advanced age at onset (P < 0.001) and was characterized by severe intraocular inflammation. Most (82%) of the patients with serologic characteristics of the acute phase of systemic infection had primary lesions (compared with 23% of OT in the chronic phase of systemic infection; P < 0.001). Extensive retinal lesions were more frequently observed during the acute phase of systemic infection (P = 0.02) and in patients with primary OT (P < 0.04). Recurrences, which developed in 79% of all patients followed for more than 5 years, were located predominantly in previously affected eyes (with old scars) in contrast to the sporadic cases of recurrence in the healthy contralateral eye (P < 0.0001). Standard short-term therapeutic modalities had no effect on visual outcome or future recurrence rates. Legal blindness in one or both eyes was confirmed for 24% of the patients. Blindness of both eyes was more frequent in patients with congenital OT (P < 0.001). Risk factors for visual loss included congenital infection, OT manifesting during the acute phase of systemic infection, central location and/or extensive retinal lesions, and the administration of corticosteroids without a shield of antiparasitic drugs.nnnCONCLUSIONSnLegal blindness in at least one eye developed in 24% of the patients with OT. Recurrences, which developed in 79% of the patients with long-term follow-up, were located predominantly in eyes with toxoplasmic scars. Various short-term therapeutic modalities had no effect on visual outcomes or future recurrence rates, with the exception of a poor visual outcome for patients who received corticosteroids without a shield of antiparasitic drugs.

The Pathways of Light Measured in Fundus Reflectometry

We measured the spectral reflectance of the fovea of ten normal subjects in four conditions, i.e. under dark-adapted and bleached conditions and at two retinal angles of incidence. The objective was to study optical pathways through the photoreceptor layer, resulting in a model that simultaneously explains spectral, directional and bleaching properties of the fovea. On theoretical grounds, we propose that small reflections from the stack of discs in the cone outer segments are the origin of the directional component of foveal reflection. Non-directional reflection occurs at the inner limiting membrane and at all layers posterior to the outer segments. With four reflectance spectra as input, the model allows determination of the density of the photostable absorbers, the lens, macular pigment, melanin and blood. Because of the simplified modeling of the layers posterior to the photoreceptor layer, the values for the density of melanin and blood are not necessarily comparable to physiological data. The density of the visual pigment calculated with this model is consistent with psychophysical data, with estimates for the ten subjects ranging from 0.41 to 0.80. The long wavelength sensitive cone fraction is calculated as 0.56.

L/M cone ratios in human trichromats assessed by psychophysics, electroretinography, and retinal densitometry.

Estimates of the relative numbers of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cones vary considerably among normal trichromats and depend significantly on the nature of the experimental method employed. Here we estimate L/M cone ratios in a population of normal observers, using three psychophysical tasks-detection thresholds for cone-isolating stimuli at different temporal frequencies, heterochromatic flicker photometry, and cone contrast ratios at minimal flicker perception--as well as flicker electroretinography and retinal densitometry. The psychophysical tasks involving high temporal frequencies, specifically designed to tap into the luminance channel, provide average L/M cone ratios that significantly differ from unity with large interindividual variation. In contrast, the psychophysical tasks involving low temporal frequencies, chosen to tap into the red-green chromatic channel, provide L/M cone ratios that are always close to unity. L/M cone ratios determined from electroretinographic recordings or from retinal densitometry correlate with those determined from the high-temporal-frequency tasks. These findings suggest that the sensitivity of the luminance channel is directly related to the relative densities of the L and the M cones and that the red-green chromatic channel introduces a gain adjustment to compensate for differences in L and M cone signal strength.

Fundus reflectance: historical and present ideas

In 1851 Helmholtz introduced the ophthalmoscope. The instrument allowed the observation of light reflected at the fundus. The development of this device was one of the major advancements in ophthalmology. Yet ophthalmoscopy allows only qualitative observation of the eye. Since 1950 attempts were made to address the challenging, quantitative assessment of the amount of light reflected by the fundus. At first, only comparative measurements were possible, applied in the study of macular and visual pigments. With improvements in light detecting techniques, and with the advent of microprocessors, the measurement of spectral and spatial distribution of the reflectance became feasible. This led to the development of models that explained the observed wavelength dependence and the directional behavior of light reflected from the fovea. The models allowed a quantitative assessment of many parameters on absorption and reflection by structures in the human eye. This paper provides a review of both the experimental and theoretical progress, and summarizes the results of fundamental and clinical research using fundus reflectometry.

Simultaneous measurement of foveal spectral reflectance and cone-photoreceptor directionality

An instrument for simultaneous measurement of foveal spectral reflectance and cone-photoreceptor directionality is described. The key element is an imaging spectrograph (spectral range of 420-790 nm) with its entrance slit conjugate to the pupil plane of a human eye. A 1.9-deg spot on the retina is sampled in 1 s. Video observation of the retina and the pupil facilitates proper alignment. Measurements were performed on 21 healthy subjects. Model analysis of the spectra provided densities of photostable ocular absorbers. As an example, macular pigment and melanin are discussed in more detail. Spatial profiles exhibited the optical Stiles-Crawford effect, reflecting cone-photoreceptor directionality.

Local photoreceptor alignment measured with a scanning laser ophthalmoscope.

The aim of this study was to develop a fast test for local photoreceptor alignment. Photoreceptor alignment is an important indicator of retinal integrity. Digitized images of fundus reflectance were obtained for 20-30 pupil entry positions with a custom built scanning laser ophthalmoscope (SLO). The data permitted the calculation of curve peakedness of the optical Stiles-Crawford effect (SCE) as a function of retinal location. We found that the peakedness is low in the central 0.5 deg, reaches a maximum at an eccentricity of 1-2 deg and gradually drops with increasing eccentricity. These data are in conformity with the anatomy of foveal cones. Additionally, the psychophysical SCE was measured with red light and an 8 deg stimulus. The mean peak position of the SCE in the pupil plane for both methods was similar, but the optical SCE was clearly steeper. The SLO provides a fast, reliable and objective way to determine local receptor alignment in the central retina.

Fast assessment of the central macular pigment density with natural pupil using the macular pigment reflectometer

We built a new macular pigment reflectometer (MPR) for fast and objective measuring of the optical density of macular pigment in the human eye, using the undilated eye. The design is based on the spectral reflectance from a spot of white light at the fovea. To evaluate its performance, we measured the macular pigment of 20 healthy subjects, ages 18 to 79 years, under four conditions: (1) natural pupil in the dark, (2) natural pupil with dim room light, (3) dilated pupil in the dark, and for comparison with a different technique, (4) heterochromatic flicker photometry (HFP) in dim room light with natural pupil. Condition 1 was repeated in a subset of 10 subjects after an interval of at least 3 days. Data analysis with a model of reflectors and absorbers in the eye provided the density of the macular pigment in conditions 1 to 3. Dim room light and pupil dilatation had no influence on measured density. Mean within subjects variation was typically 7%. Mean difference between test and retest after at least 3 days was 1%. Correlation between MPR and HFP was r=0.56 (p=0.012). Mean within subjects variation with HFP was 19%. The new instrument holds promise for specific applications such as epidemiological research.

Foveal cone mosaic and visual pigment density in dichromats.

1. Optical reflectance spectra of the fovea were measured in ten subjects with normal colour vision, ten protanopes and seven deuteranopes. Four conditions were used: perpendicular and oblique angle of incident and reflected light on the retina, both in a dark‐adapted and a fully bleached state. 2. The spectra were analysed to assess the effects of dichromacy on the cone mosaic. A replacement model, i.e. one where the total number of cones remains unchanged and all cones are filled with a single type of pigment, was found to fit our data best. 3. The analysis of the spectral fundus reflectance also provided estimates for densities of photo‐labile and photo‐stable retinal pigments and fraction of long wavelength‐sensitive (LWS) cones. Visual pigment density was 0.39 for protanopes and 0.42 for deuteranopes, significantly lower than the 0.57 found for colour normals. Macular pigment density was 0.54 for colour normals, 0.46 for protanopes and 0.42 for deuteranopes. 4. For colour normals the LWS cone fraction was 0.56, in agreement with psychophysical literature. The LWS cone fraction for protanopes was ‐0.04, and for deuteranopes 0.96, consistent with their Rayleigh matches.

Photoreceptor function in unilateral amblyopia

We investigated whether photoreceptor function in amblyopic eyes differed from that in non-amblyopic eyes. Photoreceptor function was assessed with the optical Stiles-Crawford effect (SCE), psychophysical SCE, and foveal visual pigment density in both eyes of ten unilateral amblyopic subjects. Optical SCE and density measurements were carried out with a custom-built scanning laser ophthalmoscope (SLO). Amblyopic and normal eyes did not differ in Stiles-Crawford effect, nor in foveal visual pigment density. Contrary to suggestions in the literature, we found no indication of retinal dysfunction at the level of the cone photoreceptors in amblyopic eyes.

Effect of smoking on orbital fat and muscle volume in Graves' orbitopathy.

BACKGROUNDnSmoking adversely affects the course and severity of Graves orbitopathy (GO). Cigarette smoke enhances adipogenesis in cultured human orbital fibroblasts. The present study tested our hypothesis that smoking is associated with increased orbital fat in GO patients.nnnMETHODSnThis was an observational case series study. In 95 consecutive patients with untreated GO, the ratios of fat volume/orbital volume (FV/OV) and muscle volume/OV (MV/OV) were calculated with validated software. The most affected orbit of each patient was chosen for analysis. Patients were divided into two groups based on smoking behavior. One group was current smokers (Sm+) and the other were those who never smoked or those who had not smoked for at least 1 year (Sm-). Patients were grouped in tertiles of FV/OV and MV/OV and contrast in OVs between the Sm+ and Sm- group. The main characteristics of GO were analyzed using Jonckheere-Terpstra trend analysis and Mann-Whitney U-test.nnnRESULTSnThe proportion of current smokers was not different in GO patients when divided in tertiles according to their FV/OV. In contrast, analysis of MV/OV tertiles showed a trend to a higher prevalence of current smokers in patients with larger MVs. Smoking did not influence FV, but the Sm+ group had significantly larger MVs than the Sm- group.nnnCONCLUSIONnSmoking is associated with an increase in extraocular MV in untreated patients with GO and not with an increase in FV.