Augenklinik

In Vivo Cone Photoreceptor Topography of the Human Foveola

Wed, 06 Aug 2025 00:00:00 GMT

In Vivo Cone Photoreceptor Topography of the Human Foveola Ameln, Julius; Witten, Jenny L.; Gutnikov, Aleksandr; Lukyanova, Veronika; Holz, Frank G.; Harmening, Wolf M. PURPOSE. To study in vivo cone topography of the normal human foveola.
METHODS. The fovea in both eyes of 30 healthy participants was imaged with adaptive optics scanning light ophthalmoscopy. High-resolution image montages spanning two degrees of visual angle were created and cone center locations annotated. Continuous cone density maps were computed by a Voronoi cell area approach to also yield the topographical center, the cone density centroid (CDC). Cone density profiles were extracted and fit with a four-parameter decay function, D = D₀ / (1 + (E/a)^b)^c, with D as cone density (cones/mm²), D₀ as cone density at the CDC, and E as eccentricity (µm).
RESULTS. Across eyes, D₀ was 175,474 ± 20,543 cones/mm², on average (range 136,001–216,209 cones/mm²). Density dropped anisotropically along the meridians, shallower horizontally, with average best fit parameters (a, b, c) of 61.95, 2.469, 0.268 for horizontal, and 59.11, 2.012, 0.357, for vertical profiles, respectively. In radially averaged profiles, cone density reached 50% of D₀ at 151 ± 17 µm eccentricity (range 128–193 µm). Temporal cone density was slightly higher than nasal. Most topographical metrics were highly correlated between fellow eyes.
CONCLUSIONS. Despite a 1.6-fold range in absolute cone density, foveolar density profiles could be well described by a sigmoidal decay function across all eyes. This established a normative cone density profile of the healthy foveola. It allowed cone density estimation in cases of only partially available data, which alleviates resolution demands for future studies and renders possible retrospective analyses of foveolar cone topography in suboptimal imagery.

A new generation of patient-reported outcome measures with large language models

Mon, 24 Mar 2025 00:00:00 GMT

A new generation of patient-reported outcome measures with large language models Terheyden, Jan Henrik; Pielka, Maren; Schneider, Tobias; Holz, Frank G.; Sifa, Rafet Background Patient-reported outcome measures (PROMs) are cornerstones of patient-centered clinical medicine and reflect patients' abilities, difficulties, perceptions and behaviors. The highly structured questionnaire format of PROMs currently limits their real-world validity and acceptability to patients, which becomes increasingly relevant with the high clinical interest in PROM data. In this short commentary, we aim to demonstrate the potential use of large language models (LLMs) in the context of PROM data collection and interpretation.
Main body The popularization of LLMs enables the development of a new generation of PROMs generated and administered through digital technology that interact with patients and score their responses in real time based on artificial intelligence. LLM-PROMs will need to be developed with multi-stakeholder input and careful validation against established PROMs. LLM-PROMs could complement traditional PROMs particularly in real-world clinical applications.
Conclusion LLM-PROMs could allow quantifying patient-relevant dimensions based on less structured contents and foster the use of patient-reported data in digital, clinical applications of PROMs.

The Spectrum of Functional, Structural and Patient-Reported Outcomes in Intermediate Age-Related Macular Degeneration

Mon, 03 Feb 2025 00:00:00 GMT

The Spectrum of Functional, Structural and Patient-Reported Outcomes in Intermediate Age-Related Macular Degeneration Terheyden, Jan Henrik; Holz, Frank G.; Behning, Charlotte; Dunbar, Hannah M.P.; Schmitz-Valckenberg, Steffen; Tufail, Adnan; Schmid, Matthias; Crabb, David P.; Saßmannshausen, Marlene; Binns, Alison; Hoyng, Carel B.; Zakaria, Nadia; Poor, Stephen; Moll, Klaus-Peter; Cosette, Deborah; Martinho, Cecília; Batuca, Joana; Cunha-Vaz, José; Luhmann, Ulrich F.O.; Leal, Sergio; Finger, Robert P. Introduction: There is an unmet medical need for therapies in intermediate age-related macular degeneration (iAMD). The prospective European multi-center cohort study MACUSTAR validates structural, functional and patient-reported iAMD endpoints for use in future trials. The multiplicity of assessments allows characterizing iAMD in more dimensions than previously available. We describe the heterogeneity of assessments in the iAMD baseline cohort of the MACUSTAR study. Methods: A wide range of assessments were administered across 20 European study sites in accordance with established guidelines. These assessments encompassed multiple structural evaluations, such as color fundus photography, fundus autofluorescence, and optical coherence tomography. Additionally, functional tests were conducted, including assessments of best-corrected and low-luminance visual acuity (VA), Moorfields acuity, contrast sensitivity, reading speed, mesopic and scotopic microperimetry, and dark adaptometry. Moreover, patient-reported outcome assessments, specifically the Vision Impairment in Low Luminance questionnaire, were also incorporated into the evaluation process. Associations between variables were investigated using Phi coefficients, Pearson correlation coefficients and age-corrected regression models. Results: Five-hundred eighty-five individuals with iAMD (66% women; mean (standard deviation) age: 72±7 years) were included in the MACUSTAR study. Forty-nine percent had pigmentary abnormalities, 27% had reticular pseudodrusen; 10% and 9% had incomplete and complete retinal pigment epithelium and outer retinal atrophy at baseline, respectively. Mean best-corrected VA, low-luminance VA and mesopic average threshold on microperimetry at baseline were 0.03±0.11 logMAR, 0.24±0.16 logMAR and 23.3±3.7 dB. Mean VILL subscale scores at baseline were 2±2 to 2±3 logits. Phi coefficients between structural assessments ranged between 0.17 and 0.22 (median 0.21); correlation coefficients between function tests ranged between 0.07 and 0.69 (median 0.34) and between VILL scores ranged between 0.21 and 0.68 (median 0.23). Conclusion: The findings from this broad and comprehensive spectrum of assessments of structure, function, and patient-reported outcomes in iAMD suggest that the disease spectrum is diverse and heterogeneous and that further efforts are necessary to fully understand and characterize iAMD in all its complexities. A further in-depth characterization will enable novel enrichment strategies for clinical trials in iAMD.

Spatially Resolved Association of Structural Biomarkers on Retinal Function in Non-Exudative Age-Related Macular Degeneration Over 4 Years

Tue, 30 Apr 2024 00:00:00 GMT

Spatially Resolved Association of Structural Biomarkers on Retinal Function in Non-Exudative Age-Related Macular Degeneration Over 4 Years Saßmannshausen, Marlene; Döngelci, Senem; Vaisband, Marc; Emde, Leon von der; Sloan, Kenneth R.; Hasenauer, Jan; Holz, Frank G.; Schmitz-Valckenberg, Steffen; Ach, Thomas PURPOSE. To longitudinally assess the impact of high-risk structural biomarkers for natural disease progression in non-exudative age-related macular degeneration (AMD) on spatially resolved mesopic and scotopic fundus-controlled perimetry testing.
METHODS. Multimodal retinal imaging data and fundus-controlled perimetry stimuli points were semiautomatically registered according to landmark correspondences at each annual visit over a period of up to 4 years. The presence of sub-RPE drusen, subretinal drusenoid deposits, pigment epithelium detachments (PEDs), hyper-reflective foci (HRF), vitelliform lesions, refractile deposits, and incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) were graded at each stimulus position and visit. Localized retinal layer thicknesses were extracted. Mixed-effect models were used for structure–function correlation.
RESULTS. Fifty-four eyes of 49 patients with non-exudative AMD (mean age, 70.7 ± 9.1 years) and 27 eyes of 27 healthy controls (mean age, 63.4 ± 8.9 years) were included. During study course, presence of PED had the highest functional impact with a mean estimated loss of −1.30 dB (P < 0.001) for mesopic and −1.23 dB (P < 0.001) for scotopic testing, followed by HRF with −0.89 dB (mesopic, P = 0.001) and −0.87 dB (scotopic, P = 0.005). Subretinal drusenoid deposits were associated with a stronger visual impairment (mesopic, −0.38 dB; P = 0.128; scotopic, −0.37 dB; P = 0.172) compared with sub-RPE drusen (−0.22 dB, P = 0.0004; −0.18 dB, P = 0.006). With development of c-RORA, scotopic retinal sensitivity further significantly decreased (−2.15 dB; P = 0.02). Thickening of the RPE–drusen–complex and thinning of the outer nuclear layer negatively impacted spatially resolved retinal sensitivity.
CONCLUSIONS. The presence of PED and HRF had the greatest prognostic impact on progressive point-wise sensitivity losses. Higher predominant rod than cone-mediated localized retinal sensitivity losses with early signs of retinal atrophy development indicate photoreceptor preservation as a potential therapeutic target for future interventional AMD trials.