PURPOSE:To observe fundus autofluorescence (FAF) lifetimes and peak emission wavelength (PEW) of drusen with respect to the pathology of the overlying RPE in the follow-up of AMD-patients.METHODS:Forty eyes of 38 patients (age: 75.1 ± 7.1 years) with intermediate AMD were included. FAF lifetimes and PEW were recorded by fluorescence lifetime imaging ophthalmoscopy (FLIO). Twenty-six eyes had a follow-up investigation between months 12 and 36, and 10 at months 37-72. AMD progression was retrieved from color fundus photography (CFP) and OCT. Drusen were classified with respect to changes in the overlying RPE into groups no, questionable or faint, and apparent hyperpigmentation based on CFP.RESULTS:Among the 210 hyperautofluorescent drusen found at baseline, those with hyperpigmentation had longer lifetimes and shorter PEW than those without. Drusen without hyperpigmentation had shorter lifetimes and PEW than neighboring RPE (all p < 0.001) at baseline, but drusen lifetimes increased, and PEW shortened further over follow-up. Eyes, showing AMD progression, had significantly longer FAF lifetimes at baseline than non-progressing eyes: 282 ± 102 ps versus 245 ± 98 ps, p < 0.001 and 365 ± 44 ps vs. 336 ± 48 ps, p = 0.025 for short and long wavelength FLIO channel, respectively.CONCLUSIONS:Depending on hyperpigmentation properties, drusen show lifetimes and PEW different from that of adjacent RPE which change over the natural history of AMD. This difference and change, however, might reflect progressive dysmorphia of the RPE rather than representing fluorescence of drusen material itself. Nevertheless, the observed FAF changes could make FLIO a useful tool for the early detection of AMD progression risk.

Purpose To investigate the haemoglobin concentration and oxygenation in the optic disc in glaucoma patients vs. controls. Methods Thirty-one eyes of primary open angle glaucoma patients (mean age: 64.9 ± 2.1 years) and 31 eyes of 31 healthy controls (65.5 ± 2.0 years) were included. Perimetry, optical coherence tomography (OCT), and OCT angiography were performed. Multispectral imaging was used to record the optic disc reflectance at wavelengths 522 nm, 548 nm, 555 nm, 586 nm, and 610 nm, and haemoglobin concentration and oxygenation (SO 2 ) were calculated from these measures. This was done in the rest and under stimulation of neuronal activity by flicker light. Results The haemoglobin concentration was significantly lower ( p < 0.001) in the rim (40.0 ± 6.3) and the excavation (35.7 ± 8.0) of the glaucoma patients’ discs than in controls (45.7 ± 7.5). SO 2 was not different in general, but lower in a subgroup of 18 glaucoma patients with ischaemic disc rims than in non-ischaemic ones (median 26.8%, interquartile range (IQR): 29.5% vs. 51.9%, IQR 32.0%, p = 0.02) as well as in controls (41.0%, IQR 30.6%, p = 0.01). Flicker light stimulation significantly increased the haemoglobin concentration in the controls (+ 1.3 ± 3.6, p = 0.048) as well as in the rim of glaucoma discs (+ 2.6 ± 5.0, p = 0.006) and SO 2 in the controls only (+ 15.4 ± 23.6%, p = 0.001). The haemoglobin concentration was significantly correlated with the perimetric mean defect, retinal nerve fibre layer (RNFL) thickness and para-papillary perfusion density. Conclusions The optic disc haemoglobin concentration and oxygenation are quantifiable from multispectral imaging and reduced in glaucoma. The correlation of haemoglobin concentration with perfusion density, RNFL thickness and visual field loss indicates its implication in glaucoma pathology.

PURPOSE. To measure fundus autofluorescence (FAF) lifetimes and peak emission wavelengths (PEW) of subretinal drusenoid deposits (SDD) in age-related macular degeneration (AMD) and their development over time. METHODS. Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in 30 eyes with optical coherence tomography (OCT)-confirmed early or intermediate AMD and SDD. Contrasts of mean lifetimes in short- (SSC) and long-wavelength channels (LSC), PEW, and relative fluorescence intensity were determined as differences of the respective measures at individual SDD and their environment. Measurements were made at baseline and at follow-up intervals 1 (13-36 months) and 2 (37-72 months), respectively. RESULTS. Of 423 SDD found at baseline, 259, 47, and 117 were hypoautofluorescent, isoautofluorescent, and hyperautofluorescent, respectively. FAF lifetimes of SDD were significantly longer than those of their environment by 14.5 ps (SSC, 95% confidence interval [CI], 13.3-15.7 ps) and 3.9 ps (LSC, 3.1-4.7 ps). PEW was shorter by 1.53 nm (1.071.98 nm, all contrasts P < 0.001) with higher contrasts for hyperfluorescent SDD. Over follow-up, SDD tended to hyperautofluorescence (relative intensities increased by 3.4% [95% CI, 2.9%-4.1%; P < 0.001] in follow-up 2). Hyperautofluorescence was associated with disruption of the ellipsoid zone on OCT. Disease progression to late-stage AMD was associated with higher lifetime contrast in SSC (15.9ps [14.2-17.6 ps] vs. 11.7 ps [9.9-13.5 ps], P < 0.001) at baseline. CONCLUSIONS. SDD show longer FAF lifetimes and shorter PEW than their environments. A high lifetime contrast of SDD in SSC might predict disease progression to late-stage AMD.

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new imaging modality in ophthalmology. For clinical investigations, the amplitude-weighted mean of two or three lifetime components is usually analyzed. In this study, we investigated the effects of fixation of lifetime components. This resulted in slightly higher fit errors but mean lifetimes were highly correlated to those from fits with variable individual lifetimes. Furthermore, this approach resulted in a similarly good discrimination of diabetic retinopathy patients from controls, a reduction of the computational workload, a de-noising of the mean lifetime images and allows higher local resolution. Thus, fixation of lifetimes in the fit of FLIO data could be superior for clinical routine analysis of FLIO data.

Retinal oxygen saturation (SO2) during flicker light stimulation was measured non-invasively in humans with age-related macular degeneration (AMD). Furthermore, the differences between early and late stages of AMD were evaluated. In 60 eyes of 45 AMD patients (74 ± 8.3 years) and 23 eyes of 23 healthy controls (73.4 ± 7.4 years), the SO2 of arterioles and venules was measured with the oximetry module of the Retinal Vessel Analyzer. Arterial SO2, venous SO2 and arteriovenous SO2 difference at baseline and with the flicker were assessed and compared with controls. From the difference between the arteriovenous SO2 under flicker stimulation and at baseline, the parameter delta av. Diff was calculated. Subgroup analyses of non-exudative (dry) AMD, exudative (wet) AMD and their end stages, geographic atrophy (GA) and disciform scar (DS) were performed. In comparison with healthy subjects (mean − 4.90, CI [− 6.32, − 3.43]), the parameter delta av. Diff was significantly reduced in all AMD patients (mean − 2.20, CI − 3.15, −1.23, p = 0.003), dry AMD (mean − 1.97, CI − 3.31, −0.63, p = 0.013) and wet AMD (mean − 2.35, CI − 3.50, − 1.19, p = 0.025). The comparison between wet and dry AMD revealed no significant results (p = 1). The comparison between AMD subgroups and healthy controls (median (IQR) − 4.29 (− 8.32; − 2.42) %) showed significant differences in non-neovascular (early dry AMD) (median (IQR) − 2.43 (− 4.59; − 0.74) %, p = 0.038), GA (median (IQR) 0.10 (− 4.02; 3.15) %, p = 0.019) and DS (median (IQR) − 1.67 (− 3.52; − 0.12) %, p = 0.03). A nearly significant reduction was observed in exudative (early wet) AMD (median (IQR) − 2.71 (− 5.84; − 0.2) %, p = 0.055). Minimal, not statistically significant differences of delta av. Diff were found between AMD subgroups. None of the baseline parameters was significantly different between patients and healthy controls, even after flicker light stimulation. Non-invasive retinal oximetry with flicker light stimulation seems to be a suitable method to study the pathogenetic mechanisms of AMD. The mathematically derived parameter delta av. Diff appears to be more sensitive than arteriovenous SO2 difference. Results suggest that the regulation of retinal oxygen supply, oxygen consumption or both is impaired in AMD.

Background On festive days worldwide eyes are severely injured by fireworks. The data on the number and severity are to date not registered in Germany. Objective How frequent are firework-induced injuries in Germany, who are the affected, how serious are the injuries, which forms of treatment are necessary and how frequent are accompanying injuries? Method A German nationwide online-based survey was carried out in all inpatient eye departments and data over the last 3 consecutive years were descriptively analyzed. Results From New Years Eve 2016/2017, when 41 eye departments sent in data, the participation could be increased to 51 eye departments in 2018/2019. More than one third (33-39%) of all 1356 patients over 3 years were minors, 60% were younger than 25 years old and roughly 60% of patients were injured as bystanders or in an unclear situation. In total 25% of all eye injuries were considered severe and required inpatient treatment. Accompanying injuries of the other eye, the face and hands were more frequent in minors than in adults. Eyeball ruptures were reported in 10 minors and 38 adults over the 3 years. Conclusion Particularly minors and bystanders need better protection.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory chorioretinopathy, which mainly affects young light-skinned, myopic adults between 20 and 30 years of age. The exact aetiology of APMPPE is unknown. Some patients report a viral or flu-like illness preceding the onset of APMPPE symptoms. This condition is usually bilateral and self-limiting with a good overall prognosis. Visual loss is sudden, but usually temporary. Relapses are very rare. Foveal involvement may lead to a worse visual prognosis. There is no current consensus on treatment. A wait-and-see approach with monitoring at short intervals is often sufficient. Based on a case example from our clinic we will demonstrate symptoms, diagnostic work-up and treatment options.

Purpose:To investigate the autofluorescence lifetimes as well as spectral characteristics of soft drusen and retinal hyperpigmentation in age-related macular degeneration (AMD).Methods:Forty-three eyes with nonexudative AMD were included in this study. Fluorescence lifetime imaging ophthalmoscopy (FLIO), which detects autofluorescence decay over time in the short (SSC) and long (LSC) wavelength channel, was performed. The mean autofluorescence lifetime (τm) and the spectral ratio (sr) of autofluorescence emission in the SSC and LSC were recorded and analyzed. In total, 2760 soft drusen and 265 hyperpigmented areas were identified from color fundus photographs and spectral domain optical coherence tomography (SD-OCT) images and superimposed onto their respective AF images. τm and sr of these lesions were compared with fundus areas without drusen. For clearly hyperfluorescent drusen, the local differences compared to fundus areas without drusen were determined for lifetimes and sr.Results:Hyperpigmentation showed significantly longer τm (SSC: 341 ± 81 vs. 289 ± 70 ps, P < 0.001; LSC: 406 ± 42 vs. 343 ± 42 ps, P < 0.001) and higher sr (0.621 ± 0.077 vs. 0.539 ± 0.083, P < 0.001) compared to fundus areas without hyperpigmentation or drusen. No significant difference in τm was found between soft drusen and fundus areas without drusen. However, the sr was significantly higher in soft drusen (0.555 ± 0.077 vs. 0.539 ± 0.081, P < 0.0005). Hyperfluorescent drusen showed longer τm than surrounding fundus areas without drusen (SSC: 18 ± 42 ps, P = 0.074; LSC: 16 ± 29 ps, P = 0.020).Conclusions:FLIO can quantitatively characterize the autofluorescence of the fundus, drusen, and hyperpigmentation in AMD.Translational Relevance:The experimental FLIO technique was applied in a clinical investigation. As FLIO yields information on molecular changes in AMD, it might support future diagnostics.

To discriminate non‐proliferative diabetic retinopathy (NPDR) patients from healthy controls by fluorescence lifetime imaging ophthalmoscopy (FLIO).

Zheng Zhang, Shen Wu, Jost B. Jonas, Jingxue Zhang, Kegao Liu, Qingjun Lu and Ningli Wang Dynein, kinesin and morphological changes in optic nerve axons in a rat model with cerebrospinal fl uid pressure reduction: the Beijing Intracranial and Intraocular Pressure (iCOP) study 266 Lisa Ramm, Susanne Jentsch, Sven Peters, Lydia Sauer, Regine Augsten and Martin Hammer Dependence of diameters and oxygen saturation of retinal vessels on visual fi eld damage and age in primary open-angle glaucoma 276

Martin Hammer, Johanna Schmidt, Sven Peters, Lydia Sauer, Nicole Muller, Matthias Klemm, Regine Augsten, Daniel Meller

To investigate the impact of macular pigment (MP) on fundus autofluorescence (FAF) lifetimes in vivo by characterizing full‐thickness idiopathic macular holes (MH) and macular pseudo‐holes (MPH).

Purpose : The pathophysiology of geographic atrophy (GA) is not yet fully understood and prognostic factors are still under discussion. Little is known about how the macular pigment (MP) changes during the progress of the disease. Monitoring fundus autofluorescence (FAF) lifetimes in GA using Fluorescence-lifetime-Imaging-Ophthalmoscopy (FLIO) may lead to novel insights, especially since FLIO can detect MP. Methods : Using FLIO (Heidelberg-Engineering, Heidelberg, Germany), time-resolved FAF of 20 eyes with GA has been recorded in two spectral channels (ch1: 498-560nm; ch2: 560-720nm) and approximated by a series of three exponentials, resulting in three lifetimes: (τ1-τ3). Their amplitude-weighted mean (τm) per channel and pixel was utilized as the main parameter for statistical analysis. A FAF image was acquired with each measurement; OCT scans and fundus photography were obtained. τm was averaged over the standardized ETDRS grid and the area of the fovea (diameter 0,1mm). Of special interest were differences between the fovea and the Inner Ring (IR) of the grid. These differences (τm (IR) minus τm (fovea)) were correlated to the best corrected visual acuity (BCVA). Results : Mean FAF lifetimes in GA differ according to the individual progression of the disease. Additionally to hypo- and hyperfluorescent regions detectable with FAF, FLIO visualizes differences within these regions: The presence of MP results in shorter FAF lifetimes (250-400 ps) compared to other atrophic regions (>700 ps) (figure 1). These short FAF decays are often related to a spared fovea. The τm differences between the IR and the Fovea (τm (IR) minus τm (fovea)) correlate with the BCVA (r:0.6; p<0.01 for both channels). Conclusions : Whereas conventional FAF images only show differences in the fluorescence intensity, FLIO can additionally distinguish between different atrophic areas, better showing the presence of MP, resulting in different lifetimes and possibly detecting spared regions. FLIO is a new imaging method to monitor GA. If FLIO can provide information on the GA progression needs to be further evaluated. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

259–266. Siaudvytyte L, Januleviciene I, Ragauskas A, Bartusis L, Siesky B & Harris A (2015): Update in intracranial pressure evaluation methods and translaminar pressure gradient role in glaucoma. Acta Ophthalmol 93: 9–15. Wang N, Xie X, Yang D et al. (2012): Orbital cerebrospinal fluid space in glaucoma: the Beijing intracranial and intraocular pressure (iCOP) study. Ophthalmology 119: 2065–2073. Wostyn P, De Groot V, Van Dam D, Audenaert K & De Deyn PP (2013): Senescent changes in cerebrospinal fluid circulatory physiology and their role in the pathogenesis of normal-tension glaucoma. Am J Ophthalmol 156: 5–14.e2.

PURPOSE:To investigate the interrelationship between the oxygen supply of the retina and its regulation with the severity of primary open-angle glaucoma (POAG).METHODS:Central retinal artery (CRAE) and vein (CRVE) diameters and oxygen saturation of peripapillary retinal vessels in 41 patients suffering from POAG (64.1 ± 12.9 years) and 40 healthy volunteers (63.6 ± 14.1 years) were measured using the retinal vessel analyzer. All measures were taken before and during flicker light stimulation. The mean retinal nerve fiber layer thickness (RNFLT) was determined by OCT and the visual field mean defect (MD) was identified using perimetry.RESULTS:In glaucoma patients, CRAE (r = -0.48 p = 0.002) and CRVE (r = -0.394 p = 0.014) at baseline were inversely related to MD, while arterial and venous oxygen saturation showed no significant dependence on the severity of the damage. However, the flicker light-induced change in arterio-venous difference in oxygen saturation was correlated with the MD (r = 0.358 p = 0.027). The diameters of arteries and veins at baseline decreased with reduction of the mean RNFLT (arteries: r = 0.718 p < 0.001; veins: r = 0.685 p < 0.001).CONCLUSION:Vessel diameters showed a strong correlation with RNFLT and MD. This, as well as the reduction of stimulation-induced change in arterio-venous oxygen saturation difference with visual field loss, may be explained by a reduction of the retinal metabolic demand with progressive loss of neuronal tissue in glaucoma.

PURPOSE:To characterize the macular region and to investigate the influence of the macular pigment (MP) on fundus autofluorescence (FAF) lifetimes in vivo.METHODS:Forty-eight healthy subjects with a mean age of 24.1 ± 3.6 years (range, 20-37 years) were included. A 30° retinal field was investigated using the fluorescence lifetime imaging ophthalmoscope (FLIO), based on a Heidelberg Engineering Spectralis system, detecting FAF decays in a short (498-560 nm; ch1)- and a long (560-720 nm; ch2)-wavelength channel. The mean fluorescence lifetime τm was calculated from a 3-exponential approximation of the FAF decays. Macular pigment optical density (MPOD) was measured by one-wavelength reflectometry, and macular optical coherence tomogram (OCT) scans were recorded. Correlations between τm and MPOD were analyzed.RESULTS:The τm showed shortest values at the macular region with a mean of 82 ps (ch1) and 126 ps (ch2). We found a strong correlation of τm to the MPOD (ch1: r = -0.760; ch2: r = -0.663; P < 0.001), as well as a topologic agreement of shortest τm with highest MPOD.CONCLUSIONS:Macular pigment, which is known to have very short fluorescence decays, considerably contributes to the macular autofluorescence (AF). This study gives indirect evidence for a strong impact of MP on macular τm, although no direct measurement of MP autofluorescence lifetimes in vivo is possible at this point. Potentially, imaging the FAF lifetimes could lead to a novel methodology for the detection of macular pigment properties and pathology-induced changes in the living human retina.