The origin of myopia is multifactorial, with nearwork as one possible risk factor. Spectacles with peripheral positive defocus aim to inhibit further ocular elongation. However, myopic eyes of young adults were found to become longer with positive defocus. Additionally, they showed reduced ability to use chromatic cues for detecting the retinal defocus sign. Possible underlying retinal differences to non-myopes are yet to be determined. The ciliary muscle (CM) was imaged in near-emmetropes and myopes (18–30 years of age) using optical coherence tomography after consecutively watching a movie for 30 min (i) in focus and (ii) with +3.00 D lenses, to assess possible interactions of defocus with accommodation. After a 2-h break, long flash electroretinograms (ERG) were measured after clear and defocused viewing. ERG b- and d-waves served as proxies to evaluate retinal ON- and OFF-responses. At a separate visit for a subgroup, the ERG experiment was exploratively repeated under red-light restriction. B-wave amplitudes were reduced (−4.74 µV) and delayed (+0.30 ms, both p < 0.001) in both groups after experiencing defocus. The CM became significantly thinner in myopes only (−19.43 µm, p = 0.007). Exploratory outcomes with red filters revealed smaller b-wave amplitudes with defocus (Δ = −6.44 µV, p = 0.003), as well as delayed b-waves without (Δ = 1.03 ms) and with defocus (Δ = 0.67 ms, both p < 0.001) in both groups. OFF-response proxies of the myopic sub-group showed reduced i-waves after defocus, independent of light conditions. Sustained positive defocus reduced physiological proxies for retinal ON activity irrespective of the refractive error. After defocus exposure, the CM of myopes reacted similarly to after sustained nearwork, as found previously. Altered OFF-response proxies in myopes after blur could point to modified retinal processing. Paediatric trials are required to assess whether these acute physiological responses following fixed-sequence defocus exposure relate to ocular growth signals, myopia progression or optical treatment response.
PURPOSE:To evaluate the feasibility of surgical implantation of electrical components needed for the operation of biomimetic artificial intraocular lenses (IOLs) for presbyopia correction in phakic non-human primates. This included positioning a ring electrode into the posterior chamber sulcus, securing a circuit board-mounted implant under the superior rectus muscle, and placing a battery pack in the orbit. The full implant allows for recording and transmission of electrical signals within the ciliary muscle during accommodation. METHODS:The implant consists of a microcontroller, a biopotential amplifier, and a Bluetooth transmitter on a flexible printed circuit board (PCB), a battery, and the ring electrode. After mobilization and placement of traction sutures under three muscles, the PCB was positioned under the superior rectus muscle. The ring-shaped electrode was pushed into the anterior chamber via a clear cornea tunnel incision in the upper temporal quadrant. The electrode was carefully advanced under the iris with two forceps to prevent tilting and damaging the anterior capsule until its final position under the iris above the ciliary muscle. RESULTS:During the implantation tests, in two eyes the ring electrode broke during the advancement into the posterior chamber underneath the iris. After optimizing the process, the device was successfully implanted in three eyes of three living phakic primates. An inflammatory response was visible during the postoperative follow-up period, but postmortem histopathological analysis revealed no clinically relevant adverse changes. CONCLUSIONS:The primate model demonstrated the feasibility of the surgical implantation of a circular electrode into the posterior chamber. Regarding future developments of biomimetic accommodative IOLs, a concomitant improvement of surgical techniques and the device is crucial to ensure treatment success.
Ageing results in the progressive loss of near vision, known as presbyopia, which impacts individuals and society. Existing corrective methods offer only partial compensation and do not restore dynamic focusing at varying distances. This work presents a closed-loop correction system for presbyopia, employing biopotential signals from the ciliary muscle and an artificial neural network to predict the eye’s accommodative state in real time. Non-invasive contact lens electrodes collect biopotential data, which are preprocessed and classified using a multi-layer perceptron. The classifier output guides a control system that adjusts an external focus-tunable lens, enabling both accommodation and disaccommodation similar to a young eye. The system demonstrated an accuracy of 0.79, with F1-scores of 0.78 for prediction of accommodation and 0.77 for disaccommodation. Using the system in two presbyopic subjects, near visual acuity improved from 0.28 and 0.38 to 0.04 and −0.03 logMAR, while distance acuity remained stable. Despite challenges such as signal quality and individual variability, the findings demonstrate the feasibility of restoring near-natural accommodation in presbyopia using neuromuscular signals and adaptive lens control. Future research will focus on system validation, expanding the dataset, and pre-clinical testing in implantable devices.
Purpose:The link between nearwork and myopia is controversially discussed. Features of the viewing target may stimulate eye growth, for example, black-on-white text was found to stimulate retinal OFF pathways and promote choroidal thinning, whereas inverted text led to ON pathway stimulation and thicker choroids. We used electroretinograms (ERGs) to compare retinal activity for both stimuli in the parafovea in emmetropes and myopes and studied the effects of adaptation. Methods:ERGs were recorded in 42 subjects (18-30 years) during 200 ms-flashes on a CRT monitor, superimposed with an annulus or circles filled with gray or inverted or standard text. Ganzfeld ERGs (500 ms) were taken before and after 30 minutes of reading standard or inverted text at 25 cm to determine adaptation effects. The ON- (b-wave) and OFF-responses (d-wave) were analyzed using linear mixed effects models and pointwise t-testing. Results:(1) Stimulus size affected retinal ON-responses of both groups (p < 0.001), with larger responses to a 6 to 12 degrees annulus than to a 12-degree circle. (2) Myopes displayed larger ON-responses to inverted text contrast than emmetropes within 6 to 12 degrees. (3) After adaptation to text, ON-responses were reduced (p = 0.010) irrespective of refraction and contrast. (4) Emmetropes showed reduced ON- and OFF-responses to inverted text contrast. (5) Only emmetropes had reduced ON- and larger OFF-responses after adapting to standard text. Conclusions:Myopes had largest ON-responses with inverted contrast in the perifovea. Emmetropes displayed larger adaptive changes after ON/OFF stimulation. In both groups, inverted contrast still reduced ON-responses, suggesting that efficient activation of retinal ON channels to inhibit myopia might require additional OFF channel suppression.
Augmented reality display performance depends strongly on features of the human visual system. This is especially true for retinal scan glasses, which use laser beam scanning and transparent holographic optical combiners. Human-centered approaches allow us to go beyond conventional optical metrology and evaluate display performance as it is perceived in actual augmented reality use cases. Here, we first present a theoretical formula for the retinal scan luminance and ambient contrast ratio calculated from optical powers, wavelengths, field of view, and human pupil diameter. As a promising insight, we found that the pupil diameter dependence is beneficial in assimilating the virtual image luminance to the ambient luminance. Second, we designed and performed a psychophysical experiment to assess perceived resolution in augmented reality settings using a fully functional retinal scan glasses prototype. We present the results of the trials and illustrate how this approach can be used in the further development of augmented reality smart glasses.
To see near objects clearly, the ciliary muscle shapes the human eye's crystalline lens to adjust its refractive power, a process known as accommodation. This contraction of the ciliary muscle also results in an electrical potential change. Previous work from the 1950s and 1960s reported electrical voltages in the microvolt range that were attributed to the accommodating ciliary muscle, however without clarifying the interaction between lens and muscle. Here, we present data of 12 emmetropic participants using a custom-developed scleral contact lens electrode which enables to record accommodation-dependent biopotentials of the ciliary muscle with an accuracy up to the millivolt range. Therefore, participants alternately shifted their focus from far to various near targets while the biopotentials of the ciliary muscle and the actual refractive change of the crystalline lens were recorded by a contact lens electrode and an eccentric infrared Photorefractor. In addition, the impact of confounding biopotentials such as squinting and eye movements was investigated. Our research points to a potentially new objective method of measuring accommodative change. Understanding these biopotentials could lead to the development of self-focusing visual aids as an alternative way of vision correction in presbyopes.
This study assessed the diagnostic potential of chromatic pupil campimetry (CPC) using relative maximal constriction amplitude (relMCA), pupillary light response (PLR) latency, and pupillary escape to differentiate optic neuropathies (ON) from healthy individuals and identify specific ON subtypes. CPC testing used red and blue stimuli at central (0°) and peripheral (20°) locations to measure relMCA, latency, and pupillary escape. Patients with various ON etiologies, including glaucoma (n = 20), optic nerve compression by meningioma (n = 18), chiasm compression (n = 4), Leber hereditary optic neuropathy (LHON; n = 4), and autosomal dominant optic atrophy (ADOA; n = 3), were tested. Linear mixed-effects models and post hoc Tukey tests were used to analyze differences across subgroups of ON etiologies and a healthy control group (n = 40), regarding signal eccentricities and locations. Pupillary escape was significantly higher in ON patients during central red stimulation (p = 0.0007). Glaucoma and meningioma groups showed reduced relMCA and prolonged latency for both stimuli compared to controls (p < 0.0001 to p = 0.0058). RelMCA during blue stimulation was lower in glaucoma patients than in ADOA (p = 0.0183). LHON patients exhibited significantly prolonged PLR latency during blue stimulation compared to healthy (p = 0.0284). CPC effectively distinguished glaucoma and meningioma from healthy controls but was less reliable for differentiating ON subtypes. Our results indicate, that central pupillary escape is associated with inner retinal dysfunction.
PURPOSE:Determination of the amplitude of accommodation (AoA) is a clinical technique used in ophthalmology and optometry to assess the eye's ability to focus on near objects. This study compares the reliability of a novel motorized push-up variant with conventional manual push-up and push-down methods for the determination of AoA in 26 emmetropes. METHODS:The motorized push-up method reduces limitations of the manual methods, such as differences due to varying examiner abilities, ruler placement (forehead, zygomatic bone, spectacle plane), and inconsistent target movement speeds. This is achieved by providing a participant-controlled, constant target movement of 2 cm/s, with the medial zone of the zygomatic bone as the reference point for ruler placement. Additionally, digital image-based and traditional ruler-based AoA measurements were compared. The participants' impressions of the three methods were assessed based on ease of use, confidence in measurement reliability, and comfort of experience, using a questionnaire. RESULTS:The comparison of the AoA across the methods revealed no statistically significant differences. However, the concordance correlation coefficient was highest between the motorized and manual push-up method (ρc = 0.72). All methods showed good test-retest reliability with the highest ICC found for the motorized push-up method (0.83), which also had the narrowest limits of agreement interval for accommodative demand (3.22 cm). Beyond digital and ruler-based measurements showed underestimation by both rulers, with a mean bias of 0.3 cm for the motorized ruler compared to about 2.0 cm for the conventional ruler. The questionnaire responses suggest that the motorized version outperforms the manual versions being 5 times more likely to score higher for ease of use and 6 times more likely for confidence in measurement reliability. CONCLUSION:These findings demonstrate that the motorized push-up method effectively measures the AoA, reduces interfering factors, and provides higher reliability without compromising precision, making it a valuable alternative to conventional methods.
The measurement of electrical potentials in the human body is becoming increasingly important in healthcare as a valuable diagnostic parameter. In ophthalmology, while these signals are primarily used to assess retinal function, other applications, such as recording accommodation-related biopotentials from the ciliary muscle, remain poorly understood. Here, we present the development and evaluation of a novel implantable ring electrode for recording biopotentials from the ciliary muscle. Inspired by capsular tension rings, the electrode was fabricated using laser cutting, wiring, and physical vapor deposition coating. The constant impedance and weight over a simulated aging period of 391 days, demonstrated the electrode’s stability. In vivo testing in non-human primates further validated the electrode’s surgical handling and long-term stability, with no delamination or tissue ingrowth after 100 days of implantation. Recorded biopotentials from the ciliary muscle (up to 700 µV) exceeded amplitudes reported in the literature. While the results are promising, further research is needed to investigate the signal quality and origin as well as the correlation between these signals and ciliary muscle activity. Ultimately, this electrode will be used in an implanted device to record ciliary muscle biopotentials to control an artificial lens designed to restore accommodation in individuals with presbyopia.
Purpose: To compare the effects of spatially uniform glare and point light sources on visual acuity (VA) of individuals with normal vision under everyday contrast and illuminance conditions, and to investigate the related subjective perception of glare. Methods: VA was assessed with spatially uniform glare (120 cm x 120 cm) lighting (VA-CAL test) and with four point light sources in either the paracentral (13.3 degree) or the near-peripheral visual field (23.5 degree). For all conditions, the illuminance and the optotype contrast (Landolt rings) were varied in four steps from 25 to 2200 lux and five steps from 20% to 80%, respectively. In addition to visual acuity testing, the subjective glare discomfort score was assessed for each illuminance using the Photoaversion Severity Questionnaire (PSQ). Results: Twelve volunteers with normal vision (22 to 32 years, 6 women, 6 men) were enrolled in the study. Overall, regardless of the type of glare, increasing illuminance improved VA, while decreasing the contrast reduced VA. A statistically significant difference of 0.06 logMAR for the different types of glare was found only between uniform and point light glare in the near-periphery. The discomfort scores increased with illuminance, but did not differ statistically significantly between the different types of glare. Conclusions: Both uniform and point light sources are a good way to measure daily visual performance in glare and show comparable results in influencing VA and subjective discomfort in everyday conditions. Translational Relevance: Uniform light sources are just as suitable for testing visual acuity under glare as point light sources, although we recommend using uniform light for assessing daytime performance and punctual light for testing fitness to drive at night. Key words: Visual acuity, light sources, glare, visual performance ### Competing Interest Statement J.Hilmers, EyeServ GmbH (C); T.Strasser, EyeServ GmbH (C); M.Koschka, None; E.Zrenner, EyeServ GmbH (C), EyeServ GmbH (P) ### Funding Statement This work was financially supported by the Tistou and Charlotte Kerstan Foundation 2000. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of the Faculty of Medicine, University of Tuebingen gave the approval for this work (431/2019BO2). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.
To optimize latency calculation in chromatic pupillography for a more robust evaluation of pupillary light response (PLR) dynamics in a normative collective. The PLR of 150 healthy participants aged 18–79 years (median 46 years, 94 females) measured by L-cone- and rod-favoring stimulation protocols in Chromatic Pupil Campimetry (CPC) was analyzed. Three calculation methods of latency to constriction onset after light stimulus were tested. 1: intersection of mean baseline pupil diameter and linear fit through the descending part of the pupillogram (20 data points) at each stimulus position in the central visual field (30°), 2: intersection of a linear fit through the baseline and linear fit using less (15) data points through the pupillary contraction phase at each stimulus position and 3: mean per eccentricity gained by averaged pupillograms. Equivalence testing (two one-sided t-tests, TOST) was used for comparison of the methods. The longest mean latencies were found with calculation 1 in both photopic and scotopic stimulation, followed by calculation 2. Latency calculation per eccentricity (3) resulted in the shortest mean latencies. The differences in latency results of the three calculation methods increased with increasing eccentricity in both stimulation protocols. Calculation 2 and 3 were equivalent up to 12° eccentricity in photopic and up to 20° eccentricity in scotopic stimulation. The use of the intersection of a linear fit through the baseline with a linear fit containing an adjusted number of data points adapted to the characteristics of the pupillary contraction phase appears to be suitable to provide consistent latency calculation, particularly for small constriction amplitudes and noisy data as they may occur in patients with e.g. hereditary retinal degenerations. The evaluation of mean latency per eccentricity is equivalent and may be advantageous in difficult clinical test results with low amplitudes.
In this work, we present a sclera-attachable eye implant to measure ciliary muscle local field potentials (LFPs) as a demonstrator for a preclinical study. The recorded values can be plotted and filtered in real-time. It records with a single differential channel with sampling rates of up to 250 Hz and offers a programmable gain amplifier. We show the measurement quality with in vivo measurements. The system is powered by a CR1025 coin cell battery and different measures are presented to improve measurement quality and run-time. The impact of battery non-idealities is investigated. The implant measures 18x12 mm with an actual area of 168 mm 2 and consumes up to 375 μA in ACTIVE mode with a total measurement run-time of up to 80 hours. The whole system, including the battery, is implantable into the orbital cavity and a standby time of 6 months is obtained.