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PURPOSE: Macular telangiectasia Type 2 (MacTel) is an inherited retinal disease following an autosomal dominant pattern with late onset and reduced penetrance. Fluorescence lifetime imaging ophthalmoscopy (FLIO) enhances diagnosis by showing distinct changes in MacTel. This study investigates FLIO-associated changes in clinically unaffected family members. METHODS: Eighty-one patients with MacTel (61 ± 12 years), 33 clinically healthy children under age 40 years of these MacTel patients (MacTel-C; 31 ± 6 years), 27 other family members (children over age 40 years, siblings, and parents) and 30 controls were investigated with the Heidelberg FLIO. All subjects underwent multimodal conventional imaging, including optical coherence tomography, blue-light reflectance, fluorescein angiography, and macular pigment imaging. RESULTS: All 81 patients with MacTel showed typical FLIO patterns. Of the 33 investigated MacTel-C with completely normal eye examinations and conventional imaging, 12 (36%) show FLIO patterns consistent with early MacTel. CONCLUSION: Prolonged FLIO lifetimes in the parafoveal area within the short spectral channel, especially temporally, are MacTel-specific. Fluorescence lifetime imaging ophthalmoscopy detects these lifetime patterns in over one-third of clinically unaffected MacTel-C. Although further studies will be necessary to determine the specificity of FLIO, it may help diagnose MacTel before conventional imaging modalities show changes or patients experience visual disturbances. Early detection may facilitate future gene discovery studies and interventional trials.

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Autofluorescence-based imaging techniques have become very important in the ophthalmological field. Being noninvasive and very sensitive, they are broadly used in clinical routines. Conventional autofluorescence intensity imaging is largely influenced by the strong fluorescence of lipofuscin, a fluorophore that can be found at the level of the retinal pigment epithelium. However, different endogenous retinal fluorophores can be altered in various diseases. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is an imaging modality to investigate the autofluorescence of the human fundus in vivo. It expands the level of information, as an addition to investigating the fluorescence intensity, and autofluorescence lifetimes are captured. The Heidelberg Engineering Spectralis-based fluorescence lifetime imaging ophthalmoscope is used to investigate a 30-deg retinal field centered at the fovea. It detects FAF decays in short [498 to 560 nm, short spectral channel (SSC) and long (560 to 720 nm, long spectral channel (LSC)] spectral channels, the mean fluorescence lifetimes (τm) are calculated using bi- or triexponential approaches. These are meant to be relatively independent of the fluorophore's intensity; therefore, fluorophores with less intense fluorescence can be detected. As an example, FLIO detects the fluorescence of macular pigment, retinal carotenoids that help protect the human fundus from light damages. Furthermore, FLIO is able to detect changes related to various retinal diseases, such as age-related macular degeneration, albinism, Alzheimer's disease, diabetic retinopathy, macular telangiectasia type 2, retinitis pigmentosa, and Stargardt disease. Some of these changes can already be found in healthy eyes and may indicate a risk to developing such diseases. Other changes in already affected eyes seem to indicate disease progression. This review article focuses on providing detailed information on the clinical findings of FLIO. This technique detects not only structural changes at very early stages but also metabolic and disease-related alterations. Therefore, it is a very promising tool that might soon be used for early diagnostics.

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Purpose: To investigate fundus autofluorescence (FAF) lifetimes in patients with nonexudative AMD. Methods: A total of 150 eyes of 110 patients (mean age: 73.2 ± 10.7 years) with nonexudative AMD, as well as a healthy group of 57 eyes in 38 subjects (mean age: 66.5 ± 8.7 years), were included. Investigations were conducted at the University Eye Clinic in Jena, Germany, as well as the Moran Eye Center in Salt Lake City, Utah, USA, using the Heidelberg Engineering Spectralis-based fluorescence lifetime imaging ophthalmoscope (FLIO). A 30° retinal field centered at the fovea was investigated. FAF decays were detected in short (498-560 nm) and long (560-720 nm, LSC) spectral channels. The mean fluorescence lifetimes (τm) were calculated. Optical coherence tomography scans and fundus photographs were also recorded. Results: In patients with nonexudative AMD, FLIO shows a ring-shaped pattern of prolonged τm in the LSC. This pattern occurs in all patients with AMD (including very early stages) and in one-third of the healthy controls. FAF lifetimes were longer with more advanced stages. The presence of drusen is associated with prolonged τm when compared with the healthy fundus, but drusen identification is difficult with FLIO only. Conclusions: FLIO detects a clear pattern of changes within the fundus, which appears to be AMD-associated. These changes are already visible in early AMD stages and not masked by the presence of other coexisting retinal diseases. These findings may be useful for the early diagnosis of AMD and to distinguish AMD from other retinal diseases.

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Purpose: To describe different patterns of macular pigment (MP) seen in fluorescence lifetime imaging ophthalmoscopy (FLIO) and to analyze ex vivo fluorescence characteristics of carotenoids. Methods: A total of 31 eyes of young healthy subjects, 4 eyes from patients with albinism, 36 eyes with macular telangiectasia type 2 (MacTel), 24 eyes with retinitis pigmentosa, and 1 eye with a macular hole were included in this clinic-based, cross-sectional study. All subjects underwent Heidelberg Engineering FLIO and MP measurements (dual-wavelength autofluorescence). Fundus autofluorescence (FAF) lifetimes of a 30° retinal field were detected in two spectral channels (SSC: 498-560 nm; LSC: 560-720 nm), and amplitude-weighted mean fluorescence lifetimes (τm) were calculated. Additionally, autofluorescence lifetimes of known dilutions of lutein and zeaxanthin were measured in a cuvette in free- and protein-associated states. Results: MP shows a significant inverse correlation to foveal FAF lifetimes measured with FLIO (SSC: r = -0.608; P < 0.001). Different distribution patterns can be assigned to specific disease-related changes. Two patients with albinism, who did not have MP, were found to be missing short FAF lifetimes. In solvent, lutein and zeaxanthin show very short autofluorescence lifetimes (∼50-60 ps; SSC), as do their respective binding proteins (∼40-50 ps; SSC). When combining carotenoids with their specific binding proteins, the decay times shift to longer means (∼70-90 ps; SSC). Conclusions: This study expands upon previous findings of an impact of MP on short FAF lifetimes by describing ex vivo autofluorescence lifetimes of carotenoids and different in vivo autofluorescence patterns that can be associated with certain diseases.

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PURPOSE: We investigated fundus autofluorescence (FAF) lifetimes in patients with retinitis pigmentosa (RP) using fluorescence lifetime imaging ophthalmoscopy (FLIO). METHODS: A total of 33 patients (mean age, 40.0 ± 17.0 years) with RP and an age-matched healthy group were included. The Heidelberg FLIO was used to detect FAF decays in short (SSC; 498-560 nm) and long (LSC; 560-720 nm) spectral channels. We investigated a 30° retinal field and calculated the amplitude-weighted mean fluorescence lifetime (τm). Additionally, macular pigment measurements, macular optical coherence tomography (OCT) scans, fundus photographs, visual fields, and fluorescein angiograms were recorded. Genetic studies were performed on nearly all patients. RESULTS: In RP, FLIO shows a typical pattern of prolonged τm in atrophic regions in the outer macula (SSC, 419 ± 195 ps; LSC, 401 ± 111 ps). Within the relatively preserved retina in the macular region, ring-shaped patterns were found, most distinctive in patients with autosomal dominant RP inheritance. Mean FAF lifetimes were shortened in rings in the LSC. Central areas remained relatively unaffected. CONCLUSIONS: FLIO uniquely presents a distinct and specific signature in eyes affected with RP. The ring patterns show variations that indicate genetically determined pathologic processes. Shortening of FAF lifetimes in the LSC may indicate disease progression, as was previously demonstrated for Stargardt disease. Therefore, FLIO might be able to indicate disease progression in RP as well. TRANSLATIONAL RELEVANCE: Hyperfluorescent FLIO rings with short FAF lifetimes may provide insight into the pathophysiologic disease status of RP-affected retinas potentially providing a more detailed assessment of disease progression.