Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial.

PURPOSE: To compare interferon (IFN) beta with methotrexate (MTX) in the treatment of intermediate uveitis with macular edema. DESIGN: Monocentric, prospective, randomized, controlled clinical trial. SETTING: Specialized uveitis center at the University of Heidelberg. PATIENT OR STUDY POPULATION: Patients with either primary intermediate uveitis or uveitis associated with multiple sclerosis. MAIN INCLUSION CRITERIA: Visual acuity of 20/30 or worse (0.2 logarithm of the minimal angle of resolution) and macular edema of more than 250 µm (central 1-mm in optical coherence tomography; Stratus). Randomization into either IFN beta 44 µg subcutaneously 3 times weekly or 20 mg MTX subcutaneously once weekly. MAIN OUTCOME MEASURES: At 3 months, the primary outcome parameter of mean change in visual acuity was evaluated and efficacy was determined. Secondary parameters were macular edema by optical coherence tomography, inflammatory activity, and retinal sensitivity by microperimetry (MP-1; Nidek). In case of treatment failure, switching to the other treatment arm was possible. RESULTS: Nineteen patients were included. Ten were randomized to MTX, and 9 were randomized to IFN beta. At 3 months, visual acuity improved a mean 0.31 logarithm of the minimal angle of resolution (range, -0.02 to -0.96, 15.6 letters on the Early Treatment Diabetic Retinopathy Study chart) in the IFN beta group versus a mean 0.09 logarithm of the minimal angle of resolution (range, 0.12 to -0.38, 4.7 letters) in the MTX arm (P = .0435, Mann-Whitney U test). Macular thickness decreased by a mean of 206 µm (range, -41 to -416 µm) in the IFN arm, but increased by 47 µm (range, 108 to -28 µm) in the MTX group (P < .0001). CONCLUSIONS: Although the sample size is small, results of the trial support superiority of IFN beta over MTX in the treatment of macular edema in the setting of intermediate uveitis.

Visual functions in phenylketonuria-evaluating the dopamine and long-chain polyunsaturated fatty acids depletion hypotheses.

BACKGROUND: In phenylketonuria presymptomatic treatment following newborn screening prevents severe mental and physical impairment. The reasons for subtle impairments of cerebral functions despite early treatment remain unclear. We assessed a broad spectrum of visual functions in early-treated patients with phenylketonuria and evaluated two hypotheses-the dopamine and the long-chain polyunsaturated fatty acids (LCPUFAs) depletion hypotheses. METHODS: Contrast sensitivity, colour vision, electroretinography, frequency doubling technology campimetry (FDT), and their relation with blood phenylalanine and docosahexaenoic acid levels were assessed in 36 patients with phenylketonuria and 18 age-matched healthy controls. RESULTS: Contrast sensitivity was significantly lower and total error scores in colour vision significantly higher in patients than controls. Electroretinography results differed significantly between patients and controls. We found a trend for the effect of phenylalanine-levels on contrast sensitivity and a significant effect on colour vision/FDT results. Docosahexaenoic acid levels in erythrocytes were not associated with visual functions. CONCLUSION: This is the first evaluation of visual functions in phenylketonuria using a comprehensive ophthalmological test battery. We found no evidence supporting the long-chain polyunsaturated fatty acids depletion hypothesis. However, the effect of phenylalanine-levels on visual functions suggests that imbalance between phenylalanine and tyrosine may affect retinal dopamine levels in phenylketonuria. This is supported by the similar patterns of visual functions in patients with phenylketonuria observed in our study and patients with Parkinson's disease.

Use of fundus perimetry (microperimetry) to quantify macular sensitivity.

The advances in retinal imaging technologies have led to enormous innovation towards diagnostic in current ophthalmology, enabling the practitioner to detect early retinal changes and to document treatment effects. While, in the past, retinoscopy, visual acuity testing and perimetry played the major role in functional diagnostics, today, laser-based systems like laser scanning imaging systems especially for fluorescein-angiography, optical coherence tomography, electrodiagnostic systems and the analysis of retinal vessels may be used as well. However, the challenge to correlate subjective alterations or clinical changes with visual function, still remains. Micro- or fundus perimetry offers the option to test retinal sensitivity while directly observing the fundus. In this paper, we review the literature encompassing the results of more than 25 years of fundus perimetry, i.e. perimetry under simultaneous visualization of the fundus. During this time, results on known diseases and reproducibility of the technique were published, but a lot of work was also performed on the combination of different examination methods, allowing a synopsis of long-term results and new approaches by combining different methods and improving each of them. The first part of this review attends to improvements of the method. The second part addresses the clinical and diagnostic values. The final part is dedicated to diagnostic and long-term observation of fundus perimetric results beginning with common and rare diseases like age-related macular degeneration, macular holes and diabetic retinopathy, various types of macular dystrophies ending with challenges in conventional perimetry like glaucoma and malingering. Due to the experience and progress in the field of fundus perimetry and retinal imaging, the method has long passed its role of observing and has all the potential for prediction, early detection and treatment-monitoring of macular diseases.

Late-onset retinal dystrophy in alpha-mannosidosis.

alpha-Mannosidosis is a rare lysosomal storage disease that is caused by an inherited deficiency of the lysosomal alpha-mannosidase. Clinical symptoms include coarse facial features, skeletal involvement (dysostosis multiplex), hearing disabilities, mental retardation and hepatosplenomegaly. Only few cases with ocular symptoms have been reported, mainly with lenticular opacities. We report on two brothers with complex neurological symptoms who presented with late-onset retinal dystrophy and were followed up for 6 years.

Fundus perimetry with the Micro Perimeter 1 in normal individuals: comparison with conventional threshold perimetry.

PURPOSE: To determine differential light threshold values obtained with the Micro Perimeter 1 (MP1) in healthy volunteers and to correlate them with conventional automated static threshold perimetry using the Octopus 101 Perimeter. DESIGN: Prospective comparative observational study. PARTICIPANTS: Thirty healthy volunteers. METHODS: In 30 eyes of 30 healthy volunteers, static threshold perimetry was performed with the MP1 Micro Perimeter (Nidek Inc., Italy) and the Octopus 101 (Haag-Streit AG, Switzerland) in the same eye in random order. MAIN OUTCOME MEASURES: Differential light threshold values obtained with the MP1 and their difference to differential light threshold values with the Octopus. Differential light sensitivity was compared for 21 matching points in a rectangular test grid using similar examination settings with Goldmann III stimuli, stimulus presentation time of 100 msec, and white background illumination (1.27 cd/m2). RESULTS: For the 21 matching locations, mean differential light thresholds with the MP 1 and the Octopus were 15.5+/-0.8 decibels (dB) (range, 13.0-17.1) and 30.2+/-1.2 dB (range, 27.7-32.0), respectively. On the average, the Octopus showed higher threshold values for all test locations than the MP1. The mean difference between both examinations was 14.6+/-1.8 dB for all locations and 14.8+/-1.7 dB excluding the test locations at the blind spot. With a considerably high grade of variation according to the test point location, the difference between the 2 devices varied from 11.4 to 18.3 dB, showing a vertical asymmetry with a larger difference in the lower part of the visual field. Linear regression of the perimetric results for each test point location, excluding the area of the blind spot and the lower line of the test grid, showed significant correlation (r = 0.56; P = 0.036). CONCLUSIONS: The results show that the MP1 provides reproducible threshold values with a systematic difference compared with standard Octopus perimetry of approximately 15 dB. With a larger difference in the lower part of the visual field, differential light sensitivity values in microperimetry with the MP1 are comparable to the threshold values obtained with the Octopus 101 using a correction factor of 11.4 to 18.3 dB according to stimulus location.

Microperimetry--comparison between the micro perimeter 1 and scanning laser ophthalmoscope--fundus perimetry.

PURPOSE: To compare microperimetry using the scanning laser ophthalmoscope (SLO, Rodenstock, Germany) and the recently introduced Micro Perimeter 1 (Nidek Technologies, Italy). DESIGN: Prospective comparative observational study. METHODS: Fundus perimetry with static threshold perimetry was performed using the SLO and the MP1 in 68 eyes of 40 consecutive patients with different retinal diseases for example, central serous chorioretinopathy, macular dystrophy, and age-related macular degeneration. With both instruments, an automated 4-2-1 staircase strategy with Goldmann III stimuli and a comparable number of stimuli were applied. The depth and size of the detected scotomata as well as the location and stability of fixation were compared between both instruments. RESULTS: There was good concordance of results, with 75% (51 of 68 eyes) showing an equal defect. Whereas the MP1 showed larger defects (depth and size) in 23.5% (16/68) of eyes studied than the SLO, the defects appeared larger with the SLO in 1 eye. Concerning fixation analysis, similar results were found for fixation stability with stable fixation in 47.1% (MP1: 32/68) and 48.5% (SLO: 33/68) and likewise for the location of fixation with foveal fixation in 54.4% (37/68) with the MP1 and the SLO. Whereas the average number of stimuli was similar for both instruments (MP1 56.8 +/-16.1, SLO 62.9 +/- 17.0), examination time was prolonged with the MP1 (MP1: 11m 35s +/- 3m 47s, SLO: 10m 29s +/- 3m 23s). Throughout all examinations, fundus visualization with the SLO was superior to the MP1. CONCLUSIONS: For automated threshold microperimetry the MP1 provides results comparable to our SLO perimetry. Both instruments enable detection of sensitivity loss of the central visual field and an analysis of fixation behavior during microperimetry. Nevertheless, the MP1, with its automated real-time image alignment, facilitates examination. Additionally, the enlarged field allows testing in an area of 44 x 36 degrees instead of the 33 x 21 degree-area of the SLO. However, in comparison to our SLO-software, the current software of the MP1 requires improvements before exact measurements of defined retinal diseases are possible.