Fluorescence lifetime imaging ophthalmoscopy and the influence of oral lutein/zeaxanthin supplementation on macular pigment (FLOS) - A pilot study.

BACKGROUND & AIMS: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical MPOD measurements and might contribute to a metabolic mapping of the retina in the future. Our aim was to show that oral supplementation of L and Z affects the FLIO signal in a positive way in patients with AMD. METHODS: This was a prospective, single center, open label cohort study. Patients with early and intermediate AMD received oral L and Z supplementation during three months, and were observed for another three months after therapy termination. All visits included measurements of clinical parameters, serum L and Z concentration, MPOD measurements using heterochromatic flicker photometry, dual wavelength autofluorescence imaging, and FLIO. Correlation analysis between FLIO and MPOD were performed. RESULTS: Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8 ng/ml; 95% CI: 81.26-419.9, and 77.1 ng/ml; 95% CI: 5.3-52.0, respectively). Mean MPOD units significantly increased (mean difference 0.06; 95% CI: 0.02-0.09; at 0.5°, 202; 95% CI: 58-345; at 2°, 1033; 95% CI: 288-1668; at 9° of eccentricity, respectively) after three months of supplementation with macular xanthophylls, which included L and Z. Median FLIO lifetimes in the foveal center significantly decreased from 277.3 ps (interquartile range 230.2-339.1) to 261.0 ps (interquartile range 231.4-334.4, p = 0.027). All parameters returned to near-normal values after termination of the nutritional supplementation. A significant negative correlation was found between FLIO and MPOD (r2 = 0.57, p < 0.0001). CONCLUSIONS: FLIO is able to detect subtle changes in MPOD after L and Z supplementation in patients with early and intermediate AMD. Our findings confirm the previous described negative correlation between FLIO and MPOD. Macular xanthophylls seem to contribute to short foveal lifetimes. This study is registered at ClinicalTrials.gov (identifier number NCT04761341).

FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY AS PREDICTOR OF LONG-TERM FUNCTIONAL OUTCOME IN MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To assess whether macular fluorescence lifetimes may serve as a predictor for long-term outcomes in macula-off rhegmatogenous retinal detachment. METHODS: A single-center observational study was conducted. Patients with pseudophakic macula-off rhegmatogenous retinal detachment were included and evaluated 1 and 6 months after successful reattachment surgery. Fluorescence lifetime imaging ophthalmoscopy lifetimes in the central Early Treatment Diabetic Retinopathy Study grid subfield, in two distinct channels (short spectral channel and long spectral channel) were analyzed. Best-corrected visual acuity optical coherence tomography of the macula and fluorescence lifetimes were measured at month 1 and month 6. RESULTS: Nineteen patients were analyzed. Lifetimes of the previously detached retinas were prolonged compared with the healthy fellow eyes. Short lifetimes at month 1 were associated with better best-corrected visual acuity improvement (short spectral channel: r2 = 0.27, P < 0.05, long spectral channel: r2 = 0.23, P < 0.05) and with good final best-corrected visual acuity (short spectral channel: r2 = 0.43, P < 0.01, long spectral channel: r2 = 0.25, P < 0.05). Lifetimes were prolonged in some cases of outer retinal damage in optical coherence tomography scans. CONCLUSION: Fluorescence lifetime imaging ophthalmoscopy might serve as a prediction tool for functional recovery in pseudophakic macula-off rhegmatogenous retinal detachment. Retinal fluorescence lifetimes could give insight in molecular processes after rhegmatogenous retinal detachment.

LONGITUDINAL FOVEAL FLUORESCENCE LIFETIME CHARACTERISTICS IN GEOGRAPHIC ATROPHY USING FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY.

PURPOSE: Short foveal fluorescence lifetimes (fFLT) in geographic atrophy are typically found in eyes with foveal sparing (FS) but may also occur in eyes without FS. We investigated whether short fFLT could serve as a functional biomarker for disease progression in geographic atrophy. METHODS: Thirty three eyes were followed over the course of 4 to 6 years. Foveal sparing was assessed using fluorescence lifetime imaging ophthalmoscopy, optical coherence tomography, fundus Autofluorescence, and macular pigment optical density. RESULTS: Eyes with FS exhibited shorter fFLT compared with eyes without FS. Short fFLT (<600 ps) were measured in all eyes with FS and half of the eyes without FS. Eyes with FS showed a bigger increase in fFLT per year (+39/+30 ps (short spectral channel/long spectral channel) in FS versus +29/+22 ps (short spectral channel/long spectral channel) in non FS). The best-corrected distance visual acuity correlated significantly with fFLT (P = 0.018 and P = 0.005 for short spectral channel/long spectral channel). Macular pigment optical density measurements correlated significantly with fFLT but not in all spectral channels (P ranging from 0.018 to 0.077). CONCLUSION: In geographic atrophy, shorter fFLT are associated with FS but they can also be observed in eyes without FS. Our longitudinal data suggest that shorter fFLT features in eyes with loss of FS represent an earlier stage of disease and may be more prone to loss of the visual acuity.

FLUORESCENCE LIFETIME PATTERNS IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: Type 2 idiopathic macular telangiectasia (MacTel) is a rare bilateral neurodegenerative disease characterized by alterations in the macular capillary network leading to central vision loss. The purpose of this study was to quantify disease-specific retinal fluorescence lifetime patterns in patients with MacTel using fluorescence lifetime imaging ophthalmoscopy. PARTICIPANTS: Both eyes of 14 patients (mean age ± SEM, 67.8 ± 6.4 years) with a clinical diagnosis of MacTel Type 2 and 14 healthy age-matched controls (age 69.8 ± 6.4 years) were included in this study. METHODS: All participants were imaged with a fluorescence lifetime imaging ophthalmoscope (Heidelberg Engineering, Germany). Mean retinal fluorescence lifetimes (Tm) were obtained in the short spectral channels (498-560 nm) and long spectral channels (560-720 nm). Clinical features, fundus images, fundus autofluorescence intensity images, spectral domain optical coherence tomography, and corresponding macular pigment optical density measurements using a modified confocal scanning laser ophthalmoscope (mpHRA) were further analyzed. Patients were classified into five phenotypic subgroups using the Gass and Blodi classification. RESULTS: Mean fluorescence lifetimes were significantly prolonged temporal to the fovea in patients with MacTel compared with healthy controls (mean ± SEM: short spectral channels 543 ± 61 ps vs. 304 ± 9 ps; P < 0.0001; long spectral channels: 447 ± 26 ps vs. 348 ± 11 ps; P < 0.0001), and appeared as a crescent or ring-shaped pattern. Prolonged lifetime patterns correlated with decreased macular pigment density on macular pigment optical density measurements. Follow-up examinations were performed in four MacTel patients, which revealed an increase of short spectral channel Tm of 22% over 2.1 years in the temporal fovea. CONCLUSION: This study confirms that fundus autofluorescence lifetimes display characteristic patterns in patients with MacTel Type 2 disease and provide information about macular pigment and possibly photoreceptor loss. Fluorescence lifetime prolongation correlates with disease severity and may therefore be a useful addition to other imaging modalities for assessing disease progression in MacTel Type 2.

FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY: Findings After Surgical Reattachment of Macula-Off Rhegmatogenous Retinal Detachment.

PURPOSE: The purpose of this study was to investigate fluorescence lifetime imaging ophthalmoscopy lifetimes after macula-off rhegmatogenous retinal detachment (RRD) repair. METHODS: Fifty-eight patients with successful macula-off RRD reattachment surgery were included. Retinal autofluorescence was excited with 470 nm, and amplitude-weighted mean fluorescence lifetimes (Tm) were measured in a short spectral channel (SSC, 498-560 nm) and a long spectral channel (LSC, 560-720 nm). Tm were obtained within a standardized Early Treatment Diabetic Retinopathy Study grid and correlated with Tm. The unaffected fellow eye served as control. RESULTS: Fifty-eight patients (age: 65 ± 1.6 years, 11 women) were imaged at median 1.5 months postoperatively. Tm were significantly prolongxxxed within areas of previously detached retina in the long spectral channel and particularly in the central subfield in the short spectral channel. Short lifetimes in the center of the Early Treatment Diabetic Retinopathy Study grid correlated with better visual acuity (short spectral channel; r = 0.18, P = 0.001, long spectral channel; r = 0.08, P = 0.03). Areas of residual subretinal fluid pockets in four RRD eyes displayed short fluorescence lifetimes. CONCLUSION: Areas of previously detached retina exhibit significant fluorescence lifetime changes. We found a significant correlation of fluorescence lifetimes within the fovea with visual acuity after successful RRD repair. Our data suggests that the prolongation of fluorescence lifetimes in the fovea is mainly driven by loss of macular pigment. Therefore, fluorescence lifetime imaging ophthalmoscopy may be useful in the prediction of long-term functional outcomes after macula-off RRD surgery.

Fluorescence Lifetime Patterns of Retinal Pigment Epithelium Atrophy in Patients with Stargardt Disease and Age-Related Macular Degeneration.

PURPOSE: To investigate whether autofluorescence lifetime patterns within retinal pigment epithelium (RPE) atrophy differ between age-related macular degeneration (AMD) and Stargardt disease (STGD). METHODS: Mean retinal autofluorescence lifetimes were measured in a short and a long spectral channel (SSC: 498-560 nm; LSC: 560-720 nm). Mean retinal fluorescence lifetimes were analyzed with corresponding clinical features, fundus images, fundus autofluorescence intensity images, and optical coherence tomography. Mean fluorescence lifetime values of atrophic areas were compared between the two cohorts and within the same patient to adjacent nonatrophic regions. RESULTS: Mean fluorescence lifetimes within areas with RPE atrophy of 13 patients with STGD (mean age ± SEM 43.7 ± 5 years) and 30 patients with geographic atrophy (mean age: 78 ± 2 years) were analyzed and compared to age-matched healthy participants. The mean area of RPE atrophy in STGD and AMD was 6.6 ± 2.3 mm2 (range: 0.66-33.17 mm2) and 17.5 ± 3.8 mm2 (range: 0.58-50.02 mm2), respectively. In patients with AMD, atrophic areas revealed significantly longer mean fluorescence lifetime values as compared with patients with STGD (SSC: 997 ± 60 vs. 363 ± 26 ps; LSC: 880 ± 46 vs. 393 ± 23 ps; p < 0.0001). CONCLUSIONS: This study established that RPE atrophy in patients secondary to STGD and AMD display distinctive mean fluorescence lifetime characteristics. As retinal fluorescence lifetimes within areas of RPE atrophy were significantly longer in AMD patients, the analysis of specific lifetime patterns may provide additional insight into the disease processes and the pathogenetic mechanisms in the development of atrophic patches in AMD and STGD.

Fluorescence Lifetimes in Patients With Hydroxychloroquine Retinopathy.

Purpose: To investigate fundus autofluorescence lifetime features in patients with hydroxychloroquine (HCQ) retinopathy, and to identify early markers of retinal alterations in patients due to HCQ. Methods: Patients attending screening for HCQ retinopathy were imaged with a fluorescence lifetime imaging ophthalmoscope. Mean retinal fluorescence lifetimes (Tm) were obtained in a short spectral channel (SSC, 498-560 nm) and a long spectral channel (LSC, 560-720 nm). Screening modalities included fundus images, fundus autofluorescence intensity images (FAF), spectral-domain optical coherence tomography (SD-OCT), visual fields, and multifocal electroretinogram (mfERG). Results: Forty-two eyes of 21 patients on HCQ therapy and 40 eyes of 20 healthy age-matched controls were included. Fourteen eyes of 7 patients with HCQ retinopathy (mean age, 66.1 [SD, 7.7] years) and 28 eyes of 14 patients (mean age, 46.1 [SD, 7.9] years) receiving HCQ without retinopathy were identified. Patients with HCQ retinopathy showed a parafoveal ring-shaped or oval area of prolonged mean fluorescence lifetimes. In these areas, mean (±SEM) lifetimes were 374 ± 7 ps in the SSC, and on average 19.4% longer compared to the control group (P = 0.0001). Patients on HCQ without retinopathy had retinal fluorescence lifetimes that were similar to the control group. Conclusions: This study shows that HCQ retinopathy displays characteristic mean fluorescence lifetimes.

RETINAL FLECKS IN STARGARDT DISEASE REVEAL CHARACTERISTIC FLUORESCENCE LIFETIME TRANSITION OVER TIME.

PURPOSE: Stargardt disease is the most common inherited juvenile macular dystrophy and is characterized by yellowish flecks across the posterior pole. The purpose of this study was to investigate fluorescence lifetime changes of retinal flecks over time using fluorescence lifetime imaging ophthalmoscopy. METHODS: Longitudinal fluorescence lifetime data of 12 patients with Stargardt disease (mean age ± SEM, 42.25 ± 2.1 years; range, 28-58 years) were acquired using a fluorescence lifetime imaging ophthalmoscope based on a Heidelberg Engineering Spectralis system. Retinal autofluorescence was excited with a 470-nm laser. The emitted fluorescence was detected in two wavelength channels: a short spectral channel (498-560 nm) and a long spectral channel (560-720 nm). The mean retinal autofluorescence lifetimes were calculated and further analyzed with corresponding color fundus images, autofluorescence intensity images, and spectral domain optical coherence tomography. Patients were classified into three subtypes. RESULTS: All patients with Stargardt disease displayed characteristic autofluorescence lifetime patterns. Mean fluorescence lifetime values within areas of yellow flecks were significantly prolonged (long spectral channel 484 ps) compared with the surrounding tissue (long spectral channel 297 ps). In 91.6% of the eyes, flecks with short fluorescence lifetimes (long spectral channel 255 ps) were identified. Short lifetime flecks progressed to flecks with characteristic long lifetimes in 75.1% of eyes within a mean interval of 29.2 months (range 3-45 months). Between baseline and follow-up, the rate of newly developed short lifetime flecks (number/per year) based on subtypes was 2.62 in Group 1, 1.43 in Group 2, and 0.81 in Group 3. CONCLUSION: Recent onset flecks in Stargardt disease display short fluorescence lifetimes and convert into longer fluorescence lifetime flecks over time. This transition may represent a change in the composition of retinal deposits with accumulation of lipofuscin and retinoid by-products from the visual cycle. With emerging treatment options, these findings may prove useful to monitor disease progression and therapeutic effects.

Selective non-operative management for penetrating extremity trauma: A paradigm shift in management?

BACKGROUND: Selective non-operative management (SNOM) has been proposed as a safe and adequate strategy for penetrating extremity trauma (PET) management. This may reduce unwarranted surgical exploration and enhance cost-effectiveness. Our experience at a UK major trauma centre advocates SNOM-PET as a viable and safe strategy for selected patients. A PET management algorithm is proposed. METHODS: A retrospective review was undertaken for isolated PET from October 2015 to October 2016. Examination findings were recorded as positive if neurovascular or tendon deficits were elicited. Surgical exploration was recorded as positive if neurovascular or tendon injuries were found. Diagnostic statistics were employed for upper limb (UL) and lower limb (LL) examinations. RESULTS: One hundred sixty patients [112 UL and 48 LL PET injuries] were included. Fifty-six out of 112 (50%) patients with UL PET had no examination findings. Twenty-three out of 56 (41%) patients had negative surgical explorations and 33 of 56 (59%) patients had positive surgical explorations. Thirty-four out of 48 patients with LL PET had no examination findings. All 34 patients had negative surgical explorations. The sensitivity (0.61 vs 1.00, p = 0.005), specificity (0.82 vs 0.97, p = 0.043) and negative predictive value (NPV; 0.41 vs 1.00, p < 0.001) were lower for UL PET than for LL PET examinations. There were no statistically significant differences in sensitivity, specificity as well as NPV and positive predictive value between plastic surgery residents and emergency medicine residents for UL and LL examinations. CONCLUSION: This is the first UK evaluation of SNOM-PET. It may be safely utilised for LL PET. UL PET should be surgically explored. SNOM-PET may avoid unwarranted surgical exploration, associated complications and cost.