A new digitised screen test for strabismus measurement.

PURPOSE: Our study presents a digitised tangent screen test for ocular motility analysis according to the Harms and Hess tests (measurement of the squint angle in all fields of vision). This test uses an image beamer to display the tangent screen, a position sensor to measure the patient's head orientation, and a distance sensor to measure the fixation distance. Digital measurement of head orientation allows for a test procedure that eliminates the conventional requirement for a light pointer in the patient's hand. Thus, the digital screen test is presented, and the uncertainty of the measurement system is evaluated. METHODS: A mathematical relationship was given between the measured squint angles, as well as the angle of diagnostic gaze direction, and the influence quantities on their measurement uncertainty. The individual uncertainties resulted from deviations in the measured values by the position and distance sensors, the calibration of the projection image of the beamer in length units, and the finite image resolution of the beamer. The individual standard uncertainties of the influence quantities were determined. The combined standard measurement uncertainties of the squint and gaze direction angles were given based on the model equation of the error propagation law at the tangent table according to Harms at a test distance of 2.5 m. The patient's uncertainty contribution to the mobility analysis was not considered. RESULTS: The combined standard uncertainty of the measurement system (coverage factor k = 2 for 95% confidence level) for the squint angle is ≤ 0.43° for the angle of diagnostic gaze direction ≤ 3.13° at the test distance of 2.5 m. The individual standard uncertainties of the influence quantities on the angles are (k = 1): 1.55°/1.01° (horizontal/vertical angle of the position sensor), 0.19° (distance sensor), 0.06° (calibration of the projection image of the beamer), and 0.02° (image resolution of the beamer). The maximum valid test distance of the digital screen test is 3.8 m. CONCLUSION: The digital screen test is compact and can be used at different locations. Compared to the traditional test, the time required for examination via the digitised test is less; additionally, its documentation is simplified. The measurement uncertainty of the diagnostic gaze direction angle is dominated by the sensor drift of the position sensor in the horizontal direction (yaw angle) and is due to the sensor technology. However, this drift error does not affect the squint angle measurement result nor its measurement uncertainty because the measurement principle used here is based on the congruence between the position cross and the fixation object and the confusion principle and compensates for the drift error. The measurement uncertainties of the determined measurement system are the lower limits of the uncertainties in the clinical use of the digital screen test if there are no effects due to significant patient deviations.

Safety and Toxicology of Ocular Gene Therapy with Recombinant AAV Vector rAAV.hCNGA3 in Nonhuman Primates.

The purpose of this study was to examine the toxicity and side effects of a recombinant adeno-associated virus 8 (AAV8) vector, aimed to treat cyclic nucleotide gated channel alpha 3 (CNGA3)-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1 × 1011 vector genomes (vg)), or a high dose (1 × 1012 vg) of rAAV.hCNGA3. In the 13-week study, an extra group received single high-dose intravitreal injections. Here we present the group results of the histological examinations carried out after necropsy from the 28-day study, the retinal functional (electroretinography) in the 13-week study, and clinical observations from both studies. Treatment-related adverse effects were not found, and parameter changes were mostly related to the surgical procedure. The treatment of achromatopsia with rAAV.hCNGA3 is therefore deemed safe to apply to humans.