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Transcorneal electrical stimulation (TES) is used as therapy for retinal diseases such as retinitis pigmentosa (RP) and was suggested for assessing retinal sensitivity by determining phosphene thresholds, subjective luminance impressions caused by retinal stimulation. Further applications concerned the accommodation process, revealing an improved accommodative amplitude in presbyopic eyes after TES treatment. The respective changes of the ciliary muscle (CM), the structure most important for near vision, during TES are yet unknown. In a pilot study, we aimed to assess whether monocular TES leads to morphological and functional CM changes and whether central accommodation control is affected. Ten healthy, near-emmetropic adults participated in the trial (4 females, age 26.3 ± 3.6 years). Using a wavefront and a stimulus generator, a biphasic square-wave stimulus (2 s positive and 6 s negative amplitude) of 0 μA average current was produced and transferred to the eye by means of a Dawson-Trick & Litzkow electrode. Prior to the stimulation, an individual determination of phosphene thresholds served to define individual TES current amplitudes, which ranged between 60 and 100 μA. Optical coherence tomography (OCT) imaging of the right eye's temporal ciliary muscle was performed before and during ipsi- as well as contralateral monocular TES in randomized order in the morning and afternoon of the same day. During imaging, subjects fixated a target at 4 m distance and refraction was simultaneously recorded via eccentric infrared photorefraction. OCT images were assessed using previously published custom-developed software, allowing the definition of selective CM thickness (CMT) readings, and plotting of continuous CMT profiles along the muscle border. CMT profiles revealed that both stimulations, on the ipsi- and contralateral eye, induced a thickening of the CM compared to the non-stimulated state. The selective CMT readings confirmed a significant increase with ipsi- (31 ± 30 μm; p = 0.010) and contralateral (25 ± 16 μm; p = 0.001) TES. However, refraction during far vision was not significantly affected by either stimulation (ipsilateral [n = 5]: median Δ w/-w/o  = 0 D; contralateral [n = 7]: Δ w/-w/o  = 0.13 D). Pupil size on average increased during TES, but without reaching significance (ipsilateral [n = 5] median Δ w/-w/o  = 0.23 mm, contralateral [n = 7] Δ w/-w/o  = 0.39 mm). Ipsilateral CM thickening could be explained by local changes within the stimulated ciliary muscle, such as increased blood flow or interstitial fluid rise induced by TES. However, the CMT increase in the right eye when TES was performed contralaterally, on the left eye, indicates an involvement of the central control circuit of accommodation. Further possible explanations for this finding are a synchronization of neuronal activities in the visual pathway, the release of vasoactive neuropeptides, or effects on the central blood pressure regulation. Given a neuromodulation effect on the CM function, TES might have implications for children with accommodation insufficiencies and as additional therapy in myopia control management, e.g. in combination with multifocal contact lens treatment. Our study is important for the clinical application of TES, and the outcome might add crucial knowledge to the current understanding of the accommodation process and inform research and treatment of both myopia and presbyopia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Studies on the electrical excitability of retinal neurons show that photoreceptors and other cell types can be selectively activated by distinct stimulation frequencies in vitro. Yet, this principle still needs to be validated in humans in vivo. As a first step, this study explored the frequency preferences of human rods by means of transcorneal electrostimulation (TES), using the electrically-elicited pupillary responses (EEPRs) as an objective readout. The stimulation paradigm contained a 1.2 Hz sinusoidal envelope, which was superimposed on variable carrier frequencies (4-30 Hz). These currents were delivered to one of the participant's eyes via a corneal electrode and consensual pupillary reactions were recorded from the contralateral eye. The responsiveness of the retina at each frequency was assessed based on the EEPR dynamics. Differences between healthy participants and patients with retinitis pigmentosa were evaluated to identify the preferred frequency range of rods. The responsiveness of healthy individuals revealed a clear peak around 6-8 Hz. In contrast, the pupillary responses of patients were significantly reduced in the lower frequency range. These findings suggest that the responses in this frequency bin were selectively mediated by rods. This work provides evidence that different retinal cell types can be selectively activated via TES in vivo, and that this effect can be captured noninvasively using EEPRs. This knowledge may be exploited for the diagnostics and therapy of retinal diseases, e.g., to design cell-specific functional tests for the degenerating retina, or to optimize stimulation paradigms which are currently used by retinal prostheses., Competing Interests: Declaration of competing interest No conflicting relationship exists for any author., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There is evidence for a possible link between myopia development and near vision. We investigated the effect of prolonged nearwork on ciliary muscle (CM) morphology and accommodation in 18 myopic and 17 emmetropic subjects (age 19 to 25). The CM was imaged during far (0.25 D) and near vision (4 D) using optical coherence tomography (OCT), and accommodation to a step pulse (0.25 D - 4 D - 0.25 D, 15 s each) was assessed by eccentric infrared photorefraction before and after a 30-min reading task at 25 cm. OCT images were analyzed using a custom-developed semi-automatic segmentation algorithm to determine CM thickness (CMT) profiles and selective CMT readings. Accommodation was assessed using a non-linear model. On average, the CM got thinner after nearwork, predominantly at 0.0-1.4 mm posterior to the scleral spur in emmetropes, and at 1.0-1.9 mm in myopes. Selective CMT readings confirmed a significant thinning after nearwork (univariate ANOVA F 1,66  = 26.313, p < 0.001), without any influence of the subjects' refractive state (F 1,66  = 1.887, p = 0.174) or the target distance (F 1,66  = 0.014, p = 0.907). The mean accommodation response for targets at infinity was significantly increased after nearwork (F 1,32  = 7.775, p = 0.009), with a larger myopic shift in myopes (F 1,32  = 11.310, p = 0.002). No change in velocity of accommodation was found. Sharing properties of striated muscles, the CM was expected to increase its thickness, but the opposite was found. Previous studies suggesting sustained nearwork to result in a CM spasm cannot be confirmed by the data presented here. Further research exploring the possible impact of sympathetic innervation is necessary as it is activated during intense nearwork., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The purpose was to evaluate retinal function by measuring pupillary responses to sinusoidal transcorneal electrostimulation in healthy young human subjects. This work also translates data from analogous in vitro experiments and connects it to the pupillary responses obtained in human experiments. 14 healthy human subjects participated (4 males, 10 females); for the in vitro experiments, two male healthy mouse retinas (adult wild-type C57B/6J) were used. Pupillary responses to sinusoidal transcorneal electrostimulation of varying stimulus carrier frequencies (10, 20 Hz; envelope frequency constantly kept at 1.2 Hz) and intensities (10, 20, 50 μA) were recorded and compared with those obtained with light stimulation (1.2 Hz sinusoidal blue, red light). A strong correlation between the sinusoidal stimulation (electrical as well as light) and the pupillary sinusoidal response was found. The difference between the lag of electrical and light stimulation allowed the estimation of an intensity threshold for pupillary responses to transcorneal electrostimulation (mean ± SD: 30 ± 10 μA (10 Hz); 38 ± 10 μA (20 Hz)). A comparison between the results of the two stimulation frequencies showed a not statistically significant smaller lag for 10 Hz (10 Hz: 633 ± 90 ms; 20 Hz: 725 ± 178 ms; 50 μA intensity). Analogous in vitro experiments on murine retinas indicated a selective stimulation of photoreceptors and bipolar cells (lower frequencies) and retinal ganglion cells (higher frequencies) and lower stimulation thresholds for the retinal network with sinusoidal compared to pulsatile stimulation - emphasizing that sinusoidal waveforms are well-suited to our purposes. We demonstrate that pupillary responses to sinusoidal transcorneal electrostimulation are measurable as an objective marker in healthy young subjects, even at very low stimulus intensities. By using this unique approach, we unveil the potential for an estimation of the individual intensity threshold and a selective activation of different retinal cell types in humans by varying the stimulation frequency. This technique may have broad clinical utility as well as specific relevance in the monitoring of patients with hereditary retinal disorders, especially as implemented in study protocols for novel therapies, e.g. retinal prostheses or gene therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Although both epidemiology and community medicine are difficult to define, the relationship between them can be described in practical terms. Examples are given in which cardiovascular epidemiological studies demonstrated the need (a) for improving existing community health care services, (b) for extending them, (c) for transposing them to new settings, (d) for starting preventive measures early in life, and (e) for inducing population-wide changes. However, community medicine has many limitations, calling for a better information base, and also calling for more epidemiological research.

Hypertension control is a complex process with many facets; it is dependent upon many factors, e.g., local culture, economic factors, and organization of health care. Examples from the practice of hypertension control in Europe are quoted to illustrate various levels of such activities, their scope, and the methods used. Different operational approaches are illustrated with a number of locally appropriate solutions. Measures of program effect, such as changes in population blood pressure levels, awareness and treatment status of hypertension, drug consumption, and morbidity and mortality statistics, are also examined. Finally, some special issues are summed up: the community problem of "mild" hypertension, sex differences in achieving hypertension control, and partial "overtreatment" (unwarranted drug therapy) in the community. More data are needed on the quality of hypertension control in the populations of Europe.