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Purpose Central serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy. Material and methods This is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 μs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®). Results Mean CRT at BSL was 387.69 ± 110.4 μm. CRT significantly decreased by 106.31 μm in wk4 (95%-KI: 21.42–191.2; p = 0.01), by 133.63 μm in wk12 (95%-KI: 50.22–217.03; p = 0.001) and by 133.81 μm (95%-KI: 48.88–218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures. Conclusion Single or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.

Purpose To evaluate the relationship between macular pigment optical density (MPOD) and glaucoma. Methods Forty-three patients with an established glaucoma diagnosis (25 females, 18 males, mean age 70 (range 34-84)) and 43 healthy controls (28 females, 15 males, mean age 62 (range 30-87)) were included in this prospective diagnostic case-control study. All subjects underwent detailed eye examination including ophthalmoscopy, best-corrected visual acuity, biomicroscopy, measurement of the axial length of the eye, objective refraction, lens status, central foveal thickness on spectral-domain optical coherence tomography (SD-OCT). In all glaucoma patients, a visual field assessment and a measurement of the retinal nerve fibre layer (RNFL) on SD-OCT were done. MPOD was determined using the macula pigment module of the Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) at 0.51°, 1.02° and 1.99° retinal eccentricity using two-wavelength autofluorescence imaging. Results In the glaucoma group, the median of the visual field mean defect was 5.1 db (quartiles 3.0 and 13.5) and the mean RNFL-thickness global was 65.9 µm (SD ± 16.1). Median MPOD measured at 0.51°, 1.02° and 1.99° retinal eccentricity in the glaucoma group was 0.42 DU, 0.34 DU and 0.13 DU, in the control group 0.40 DU, 0.35 DU and 0.12 DU respectively. There was no statistically significant difference of median MPOD between glaucomatous and control eyes (p=0.510, 0.735, 0.481). No significant relation between MPOD at 1.02 retinal eccentricity and the presence of glare symptoms was found (p=0.948). However, age seems to correlate with median MPOD measured at 1.02 retinal eccentricity (p=0.017). Conclusion There was no evidence for lower MPOD levels in our glaucoma patients; lower MPOD was not related to the presence of glare symptoms. However there seems to be a positive correlation between age and MPOD at 1.02° retinal eccentricity. To further investigate the relation between glare reported by glaucoma patients and glare disability linked to lower MPOD levels, additional studies are necessary that include both detailed inquiry of the quality of glare and a glare quantification and precise analysis of MPOD levels in glaucoma patients.

Background Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. Methods For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. Results TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. Conclusions SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.

Autosomal recessive bestrophinopathy (ARB) has been reported as clinically heterogeneous. Eighteen patients (mean age: 22.5 years, 15 unrelated families) underwent ophthalmological examination, fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Molecular genetic testing of the BEST1 gene was conducted by the chain-terminating dideoxynucleotide Sanger methodology. Onset of symptoms (3 to 50 years of age) and best-corrected visual acuity (0.02&ndash, 1.0) were highly variable. Ophthalmoscopic and retinal imaging defined five phenotypes. Phenotype I presented with single or confluent yellow lesions at the posterior pole and midperiphery, serous retinal detachment, and intraretinal cystoid spaces. In phenotype II fleck-like lesions were smaller and extended to the far periphery. Phenotype III showed a widespread continuous lesion with sharp peripheral demarcation. Single (phenotype IV) or multifocal (phenotype V) vitelliform macular dystrophy-like lesions were observed as well. Phenotypes varied within families and in two eyes of one patient. In addition, OCT detected hyperreflective foci (13/36 eyes) and choroidal excavation (11/36). Biallelic mutations were identified in each patient, six of which have not been reported so far [c.454C&gt, T/p.(Pro152Ser), c.620T&gt, A/p.(Leu207His), c.287_298del/p.(Gln96_Asn99del), c.199_200del/p.(Leu67Valfs*164), c.524del/p.(Ser175Thrfs*19), c.590_615del/p.(Leu197Profs*26)]. BEST1-associated ARB presents with a variable age of onset and clinical findings, that can be categorized in 5 clinical phenotypes. Hyperreflective foci and choroidal excavation frequently develop as secondary manifestations.

Introduction: The evaluation of retinal vessels and the retinal blood flow is important for ocular diseases. We introduce a spectral domain optical coherence tomography (SD-OCT) based method for facilitating a retinal blood vessel analysis using the scattering properties of retinal vessels. The intensity of the distal shadow of vessels caused by the scattered signal is measured, correlated with the pulsatile ocular blood flow (POBF), and its repeatability is analyzed.Methods: About 20 eyes of 20 healthy, young participants (mean age 23.15 years, standard deviation 2.3 years) were included in the analysis. Participants underwent ophthalmic diagnostics including three repeated SD-OCT examinations and measurement of POBF. The vessel shadow intensity analysis is based on peripapillary SD-OCT scans and automatically analyses the intensity of the distal vessel shadow compared to its surroundings.Results: The distal shadow of arteries in SD-OCT scans correlated with the POBF (r = 0.647, p = 0.002). Furth...

We aimed to evaluate the neuroprotective efficacy of rasagiline in pseudophakic patients who had surgery for macula-off rhegmatogenous retinal detachment (RRD). This was a 6-month, prospective, randomized, double-blind, placebo-controlled pilot study. Patients presenting with acute macula-off RRD were recruited and randomized 1:1 to receive rasagiline 1 mg/day or placebo for 7 days. Best-corrected visual acuity (BCVA) and optical coherence tomography were acquired 1 day before as well as 2 days, 3 weeks, 3 months and 6 months after surgery. We screened 26 patients with RRD whereof 23 were eventually included and randomized. The primary outcome was final BCVA. Secondary outcomes included central retinal thickness (CRT) and adverse events (AE). We evaluated photoreceptor cells (prc) recovery through morphological measurements. The baseline characteristics were comparable between groups. BCVA significantly improved in both groups (letters gained: rasagiline 61.5 ± 18.1 vs placebo 55.3 ± 29.2, p = 0.56), but no significant inter-group difference was found at any visit. CRT was stable 3 weeks after surgery onwards, with no inter-group difference. No treatment-emergent AE occurred. Significant prc restoration was observed from 3 weeks to 6 months after surgery, without inter-group difference at either visit. Ellipsoid zone integrity (β = 0.517, p = 0.008) and foveal bulge (β = 0.387, p = 0.038) were significant predictors of good final BCVA. In conclusion, perioperative oral treatment with rasagiline 1 mg/day for 7 days did not show significant benefits on visual or anatomical outcomes in macula-off RRD patients.

Spectral domain optical coherence tomography (SD-OCT) has become a standard diagnostic tool in the surgical management of vitreomacular interface disorders. The high-resolution cross-sectional information obtained from SD-OCT is a perfect complement to vitreoretinal surgery. It provides detailed intraoperative anatomical views that are not possible with a microscope.To investigate the value of intraoperative real-time OCT with respect to improvement of surgical techniques in the management of vitreomacular disorders.A review of the current literature was conducted and an analysis of own systematically evaluated data was included to provide a comprehensive overview of potential applications for the clinical use of intraoperative real-time OCT in macular surgery.Intraoperative real-time OCT can provide detailed visualization of epiretinal membranes and help to identify whether complete membrane removal has been achieved following surgery. In addition, it can provide qualitative and quantitative information that has previously not been available and assist in surgical decision-making. Intraoperative real-time OCT allows membrane peeling to be performed in selected cases without using retinal dyes, whereas it is not ideal for accurately guiding the surgeon while performing maneuvers.Intraoperative real-time OCT provides high-resolution visualization of the effects of surgical maneuvers on the microarchitecture of the retina and surrounding tissues and will fill a gap in the understanding of the pathophysiology and prognostic factors of vitreomacular disorders; however, with currently available systems, accurate intraoperative real-time guidance of surgical maneuvers is hindered by several limiting factors.

Bacterial orbital cellulitis is a life-threatening infection of the postseptal orbital tissue. It can occur in the context of sinusitis, particularly in children and adolescents. Ocular complications include exposure keratopathy, increased intraocular pressure, occlusion of the central retinal artery or vein and optic neuropathy. Rarely, a subperiosteal abscess can occur, and osteomyelitis can lead to spread of the infection to the cerebrum. A rapid diagnosis and targeted therapy are essential for saving the eye as well as the life of the patient.

Background and Objectives To evaluate the changes in the size of choroidal neovascularization (CNV) lesion using spectral domain-optical coherence tomography (SD-OCT) in patients with treatment-resistant neovascular age-related macular degeneration (AMD) who were switched from ranibizumab to aflibercept. Materials and Methods In this prospective case-series, 33 eyes of 30 patients with treatment-resistant neovascular AMD were included. Treatment-resistant neovascular AMD was defined as choriodal neovascularization secondary to AMD determined by subretinal fluid and/or intraretinal fluid/cysts after more than 6 months of monthly ranibizumab therapy. Enrolled eyes were received intravitreal aflibercept injections at weeks 0, 4, and 8. Maximum area of CNV lesion in the cross-sectional area in the B-scan was measured using Heidelberg Eye Explorer software. The same cross-sectional sections containing maximum area of CNV lesion were used during the follow-up. CNV subtypes were determined based on fluorescein angiography images prior to ranibizumab therapy. Main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and area of CNV lesion. Results There were five classic (15%), seven minimally classic (21%), and 21 occult subtypes of CNV (64%). Four weeks after the third injection, BCVA improvement and reduction of the retinal thickness in nine standard ETDRS subfields were significant (both P

Selective retina therapy (SRT) targets the retinal pigment epithelium (RPE) with pulsed laser irradiation by inducing microbubble formation (MBF) at the intracellular melanin granula, which leads to selective cell disruption. The following wound healing process rejuvenates the chorio-retinal junction. Pulse energy thresholds for selective RPE effects vary intra- and interindividually. We present the evaluation of an algorithm that processes backscattered treatment light to detect MBF as an indicator of RPE cell damage since these RPE lesions are invisible during treatment. Eleven patients with central serous chorioretinopathy and four with diabetic macula edema were treated with a SRT system, which uses a wavelength of 527 nm, a repetition rate of 100 Hz, and a pulse duration of 1.7 μs. Fifteen laser pulses with stepwise increasing pulse energy were applied per treatment spot. Overall, 4626 pulses were used for algorithm parameter optimization and testing. Sensitivity and specificity were the metrics maximized through an automatic optimization process. Data were verified by fluorescein angiography. A sensitivity of 1 and a specificity of 0.93 were achieved. The method introduced in this paper can be used for guidance or automatization of microbubble-related treatments like SRT or selective laser trabeculoplasty.

Purpose Selective retina therapy (SRT) has shown great promise compared to conventional retinal laser photocoagulation as it avoids collateral damage and selectively targets the retinal pigment epithelium (RPE). Its use however is challenging in terms of therapy monitoring and dosage because an immediate tissue reaction is not biomicroscopically discernibel. To overcome these limitations real time optical coherence tomography (OCT) might be useful to monitor retinal tissue during laser application. We have thus evaluated a proprietary OCT system for its capability of mapping optical changes introduced by SRT in retinal tissue. Methods Freshly enucleated porcine eyes covered in DMEM upon collection were utilized and a total of 175 scans from ex vivo porcine eyes were analyzed. The porcine eyes were used as an ex vivo model and results compared to two time resolved OCT scans recorded from a patient undergoing SRT treatment (SRT Vario Medical Laser Center Lübeck). In addition to OCT fluorescin angiography and fundus photography were performed on the patient and OCT scans were subsequently investigated for optical tissue changes linked to laser application. Results Biomicroscopically invisible SRT lesions were detectable in OCT by changes in the RPE / Bruch's complex both in vivo and the porcine ex vivo model. Laser application produced clearly visible optical effects such as hyper reflectivity and tissue distortion in the treated retina. Tissue effects were even discernible in time resolved OCT imaging when no hyper reflectivity persisted after treatment. Data from ex vivo porcine eyes showed similar to identical optical changes while effects visible in OCT appeared to correlate with applied pulse energy leading to an additional reflective layer when lesions became visible in indirect ophthalmoscopy. Conclusions Our results support the hypothesis that real time high resolution OCT may be a promising modality to obtain additional information about the extent of tissue damage caused by SRT treatment. Data shows that our ex vivo porcine model adequately reproduces the effects occurring in vivo and thus can be used to further investigate this promising imaging technique.

Bernd Junker,1 Jens F Jordan,2 Carsten Framme,1 Amelie Pielen1 1University Eye Hospital, Medical School Hannover, Hannover, 2Eye Center, Medical Center, University of Freiburg, Freiburg, Germany Importance: This study is the first description of the use of the intraoperative optical coherence tomography (iOCT) for trabecular meshwork surgery with the Trabectome in a regular clinical setting.Background: The aim of this study is to evaluate intraoperatively the immediate success of ab interno trabeculotomy with the Trabectome defined as a removal of the trabecular meshwork.Design: This is a retrospective clinical study performed in the University Eye Hospital, Medical School Hannover.Participants: A total of nine consecutive Caucasian patients suffering from primary open angle glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma took part in the study.Methods: All patients underwent ab interno trabeculotomy surgery with the Trabectome using a commercially available iOCT to visualize the anterior chamber angle (ACA) before and after the procedure. The visualization was done using a modified Swan-Jacobs lens (all nine patients) or without lens (view from above, five patients).Main outcome measures: The main outcome of this study is the success of visualization of the ACA on iOCT, especially the postprocedural visualization of the wound gap after removal of the trabecular meshwork.Results: Using the view from above, the ACA could be visualized before and after the procedure in only two of the five cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before the procedure and the trabecular meshwork opening after the procedure in all nine patients.Conclusion: The iOCT can be used to objectify the immediate success of the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno trabeculotomy with the Trabectome. The procedure itself cannot be captured sufficiently via iOCT. Keywords: glaucoma, imaging, iOCT, trabecular meshwork surgery

PURPOSE Modifications in ocular blood flow may play a significant role in glaucoma development. Optical coherence tomography angiography (OCT-A) is based on the detection and analysis of the reflection behaviour of motion in a static environment and therefore is able to quantify the retinal flow density. We used this new technology to examine the density of the active flow vasculature in the macular area in glaucoma patients compared to healthy patients. METHODS Thirty patients with primary open-angle glaucoma (mean age: 72.6 ± 7.1 years) and 21 healthy patients (mean age: 70.3 ± 8.6 years) were recruited. Patients received perimetry and OCT measurements of the peripapillary retinal nerve fibre layer thickness (RNFLT) and macular retinal thickness and OCT-A of the macular area in the superficial and deep retinal (DR) plexus. Flow density of the OCT-A scan was calculated by binarisation and quantification of the pixel density. RESULTS Macular flow density was globally and nasally reduced in glaucoma patients in the superficial (globally: p = 0.0203; nasally: p = 0.0003) and DR plexus (globally: p = 0.0113, nasally: p

To observe the excursions of short-term intraocular pressure (IOP) after 20-G pars-plana vitrectomy (ppV).In a prospective study, 851 patients (age: mean 63 ± 15 years) underwent unilateral ppV for various vitreoretinal diseases using different endotamponades [Balanced Salt Solution (BSS) 33.1%, Air 7.2%, SF(6) 33.6%, silicon oil 5000 cst 26.1%]. Intraocular pressure was measured in all patients before and at 3, 6, 24 and 48 hr after surgery. Survival analysis was performed to determine the cumulative hazard of IOP changes depending on endotamponade and time point after ppV (Log-Rang - Mantel Cox; p0.0001). At baseline, IOP ranged from 0 to 50 mmHg (mean IOP: 15.3 ± 5.3 mmHg). Mean IOP after surgery revealed a slight elevation (3 hr: 16.5 ± 11.0 mmHg; 6 hr 16.9 ± 9.8 mmHg; 24 hr 19.7 ± 8.0 mmHg; 48 hr 17.3 ± 6.2 mmHg; range: 0-64 mmHg). Silicon oil filling revealed highest mean values at already 3 hr after surgery (21.8 mmHg). Also, BSS filling showed a peak after 3 hr; however, mean values were lower. Equivalent high IOP values as for silicon oil tamponade were found for gas filling; however, maximal peak was reached after 24 hr but not after 3 hr post-treatment. The cumulative hazard in all patients to reach IOP ≥ 30 mmHg after 24 hr was 23.9%; (IOP ≥ 40 mmHg = 8.2%). Herein, oil filling revealed highest risk at all time points after surgery. The risk of suffering from IOP5 mmHg lasting longer than 6 hr was only 1.2% after 20 G vitrectomy.Intraocular pressure measurements after ppV are important to prevent unintentional high IOP, especially within the early phase (3 hr post-treatment) in eyes with silicon oil filling. Gas filling leads to prolonged IOP increase (24 hr post-treatment). Long-lasting hypotony (≥ 6 hr) is very rare after 20G vitrectomy.

To identify differences in extracellular matrix contents between idiopathic epiretinal membranes (IEM) of cellophane macular reflex (CMRM) or preretinal macular fibrosis (PMFM) type.

Purpose: To assess the interobserver variability (IOV) in indicating retreatment for neovascular Age-related macular degeneration 4 weeks after three Ranibizumab loading doses using spectral domain OCT (SD-OCT) as the primary objective diagnostic tool. Material and methods: Four observers decided for or against 4th Ranibizumab injection in 108 patients by six different rating rounds (RR) based on the SD-OCT findings after the loading doses. Postoperative OCT images were supplemented consecutively with information from a chart review as the ‘patients subjective estimation of vision (SE)’, the course of best-corrected visual acuity (BCVA) and the preoperative OCT as well as all information collectively. Agreement rates (AR) and Kappa statistics were calculated. Results: Based on post-treatment OCT findings only (RR1), mean reinjection rate of all observers was 37.5%. Adding supplementary information, mean reinjection rate decreased to 20% when all information was available reflecting the ‘real’ situation (RR 6). Interobserver agreement rates varied from 66.7% to 90.7% depending on rating rounds and interobserver pairs. Mean AR and Kappa values (KV) were as following: AR 81.6%, KV 0.61 (RR1: ‘only post-OP OCT’); AR 76.7%, KV 0.33 (RR2: post-OP OCT + SE); AR 80.3%, KV 0.45 (RR3: post-OP OCT + BCVA); AR 80.7%, KV 0.46 (RR4: pre- and post-OP OCT); AR 82.2%, KV 0.49 (RR5: post-OP OCT + SE + BCVA); and finally AR 83.6%, KV 0.47 (RR6: pre- and post-OP OCT + SE + BCVA). The overall mean agreement rate was 80.9% with a Kappa of 0.47. Conclusion: IOV for indicating retreatment after three Ranibizumab loading doses reveals only moderate agreement in Kappa statistics, which seems to be too low considering the high costs for retreatments. More concise guidelines based on the post-treatment OCT scans as the presumably most sensitive and noninvasive objective tool to follow choroidal neovascularization activity by judging the course of sub- and intraretinal fluid are necessary.

Spectral domain optical coherence tomography (SD-OCT) in patients can deliver retinal cross-sectional images with high resolution. This may allow the evaluation of the extent of damage to the retinal pigment epithelium (RPE) and the neurosensory retina after laser treatment. This article aims to investigate the value of SD-OCT in comparing laser lesions produced by conventional laser photocoagulation and selective retina treatment (SRT).In a retrospective study, conventional retinal laser (CRL) lesions and SRT laser lesions were evaluated with SD-OCT. One hundred seventy-five CRL lesions were investigated in 10 patients with diabetic maculopathy at timepoints between 1 hr and 4 years after treatment. Ninety-one SRT lesions were examined in 9 patients with central serous retinopathy, geographic atrophy, and diabetic maculopathy at timepoints between 1 hr and 2 years. CRL lesions were applied with an ophthalmoscopically slightly grayish-white appearance (Nd:YAG laser at 532-nm wavelength; power 100-200 mW; retinal spot diameter 100 microm; pulse duration 100 ms). SRT lesions were applied with a Nd:YLF (527 nm; pulse duration 200 ns [30 pulses at 100 Hz]; energy 100-200 microJ/pulse; retinal spot diameter 200 microm) and were visible only angiographically.All CRL lesions were characterized by high reflectivity in OCT images throughout the full thickness of the neurosensory tissue 1 hr after irradiation, suggesting complete neurosensory coagulation. Strong contraction through the full thickness of the neurosensory layers was observed within 7 days after treatment. In contrast, the neural retina appeared unaffected after SRT. For both lesion types, the RPE layer appeared to be regular or thinner immediately after treatment, whereas within a period of 4 weeks, a RPE thickening indicating RPE proliferation was observable. One year and later after treatment, CRL lesions were characterized by RPE atrophy combined with significant damage of the neurosensory tissue. SRT lesions aged one year and older revealed unaffected neurosensory structures and an intact RPE layer.Spectral domain OCT can be used clinically to follow the development of laser-induced lesions over time. Postoperative RPE proliferation was observed in both CRL and SRT laser lesions. RPE atrophy appeared subsequently only in CRL lesions, whereas the neurosensory retina appeared unaffected following SRT. These results suggest the selective effect of SRT in humans without causing adverse effects to the neurosensory retina.

The purpose of this study was to characterise an ex-vivo adult porcine retina-retinal pigment epithelium (RPE) perfusion organ culture model. Fresh porcine full-thickness retina-RPE-choroid tissue samples were clamped into tissue carriers and mounted in two-compartment containers. The retinal and choroidal sides were continuously perfused with culture medium. pO(2), [Na(+)], [K(+)], [Cl(-)], [glucose], [lactate], and pH were measured in the medium. Tissue samples were examined after 24h, 4, 7, and 10 days in culture. The morphology of the retina and the RPE was examined by light and electron microscopy (LM, EM). The retinal cellular integrity was further examined by immunohistochemistry (Ki 67, GFAP, rhodopsin, synaptophysin, syntaxin, NF 200, TUNEL-test). Fresh porcine full-thickness retina-RPE-choroid tissue samples and tissue samples in static organ culture served as controls. LM, EM, and immunohistochemistry showed intact retinal and RPE cytoarchitecture kept in perfusion culture. Photoreceptor outer segments showed first signs of degeneration after 24h, significant signs of apoptosis and necrosis appeared in the retina after 4 days in perfusion culture. Control tissue samples kept in static culture showed disintegration of the retinal cytoarchitecture after 4 days in culture. The data show that adult porcine retina-RPE tissue can be maintained morphologically intact in perfusion organ culture for at least 10 days. Although first signs of degeneration set in after 24h the structural preservation of the tissue in perfusion organ culture is superior to that in static culture. The perfusion culture model of the retina refines organotypic in vitro test systems and may help to reduce the number of necessary animal experiments in retina and RPE research. It offers new perspectives for the safety testing of substances designed for intraocular application.

Purpose: Up to date several approaches have been undertaken to achieve an ‘easy-to-handle’ animal model of choroidal neovascularizations (CNVs) in rabbits; however, so far in none of the studies could healthy retinal tissue be maintained, which is mandatory to further investigate the effects of photodynamic therapy (PDT) or anti-vascular-endothelial-growth-factor treatments. It was our aim to reevaluate and verify the method of inducing experimental CNVs in rabbits using subretinally injected linoleic acid hydroperoxide (LHP) as proposed by Tamai et al. and to use it for experimental PDT. Material and Methods: In 33 eyes of Chinchilla breed rabbits LHP of two different concentrations (25 and 100 µg/50 µl) was injected into the subretinal space via a transvitreal approach under guidance of an operation microscope. Ophthalmoscopic and angiographic examinations were performed on days 3, 7, 14 and 28 after surgery. Preliminary PDT with different experimental parameter sets was performed in 3 eyes using the new photosensitizer Tookad. Results: Using LHP in the higher concentration, an angiographically determined CNV induction was observed in 27% of all injection sites (n = 34) on days 14 and 28 revealing early well-demarcated and progressive leakage. No CNV was detected at the lower LHP concentration (60 injection sites). Subretinal CNV was verified histologically revealing vessel formation above the retinal pigment epithelium level. Herein, a significant damage to the outer retinal layers was always observed; however, the general structure of the choriocapillary layer was maintained. Tookad PDT was clinically able to completely stop leakage in 1 case and reduce leakage in 2 cases. Histologically the choriocapillary layer was occluded. Conclusion: Subretinal injection of LHP induces angiographically well-demarcated classic CNVs in rabbits; however, the CNV rate was low, and histology revealed severe damage of the outer retinal layers but not of the choriocapillary layer, which is important for studying PDT interactions. Preliminary experimental PDT could clinically stop or reduce leakage from angiographic CNV. Due to the small CNV rate and the significant collateral retinal tissue damage, this model seems to be only of partial suitability for investigating new treatment modalities in CNV.

Background Post-translational protein modification by lipid peroxidationproducts orglycation is a feature of aging as well as pathologic processes in postmitotic cells at the ocular fundus exposed to an oxidative environment. The accumulationofmodifiedproteinssuchasthose found inlipofuscinand advanced glycation end products (AGEs) contribute greatly to the fundus auto-fluorescence. The distinct fluorescence spectra of lipofuscin and AGE enable their differentiation in multispectral fundus fluorescence imaging. Method A dual-centre consecutive case series of 78 pseudophacic patients is reported. Digital colour fundus photographs as well as auto-fluorescence images were taken from 33 patients with age related macular degeneration (AMD), 13 patients with diabetic retinopathy (RD), or from 32 cases without pathologic findings (controls). Fluorescence was excited at 475–515 nm or 476–604 nm and recorded in the emission bands 530–675 nm or 675–715 nm, respectively. Fluorescence images excited at 475–515 nm were taken by a colour CCD-camera (colour-fluorescence imaging) enabling the separaterecording of green and red fluorescence. The ratio of green versus red fluorescence was calculated within a representative region of each image. Results The 530–675 nm auto-fluorescence in AMD patients was dominated by the red emission (green vs. red ratio, g/r=0.861). In comparison, the fluorescence of the diabetics was green-shifted (g/r=0.946; controls: g/r= 0.869). Atrophic areas (geographic atrophy, laser scars) showed massive hypo-fluorescence in both emission bands. Hyper-fluorescent drusen and exudates, unobtrusive in the colour fundus images as well as in the fluorescence images with emission >667 nm, showed an impressive green-shift in the colour-fluorescence image. Conclusions Lipofuscin is the dominant fluorophore at long wavelengths (>675 nm or red channel of the colour fluorescence image). In the green spectral region, we found an additional emission of collagen and elastin (optic disc, sclera) as well as deposits in drusen and exudates. The green shift of the auto-fluorescence in RD may be a hint of increased AGE concentrations.

To carry out a prospective investigation of the functional and morphological outcome of idiopathic epiretinal membrane (IEM) surgery with or without the assistance of indocyanine green (ICG) in a randomised controlled clinical trial. Sixty patients who underwent vitrectomy with removal of IEM combined with cataract surgery were randomly allocated to two groups: 27 patients were operated on with ICG 0.1% in glucose 5%, 33 patients without ICG. Functional outcome was assessed 3-4 months postoperatively with improvement of best-corrected visual acuity (BCVA), Amsler grid test, and automated and kinetic perimetry. Postoperative residual or recurrent IEM was assessed with bio-microscopy, and macular oedema with optical coherence tomography (OCT). Improvement in BCVA was the main outcome measure. BCVA improved in 49 patients, remained unchanged in five and decreased in five. Improvement in BCVA and reduction of macular oedema were statistically significant within both groups (P

Purpose: Central serous chorioretinopathy (CSC) affects mostly young and middle-aged adults. Typically, a serous retinal detachment occurs with a focal leakage point in fluorescein angiography. Fundus autofluorescence (AF) is related to the lipofuscin within the retinal pigment epithelium (RPE). As CSC is thought to be associated with RPE disorders, AF measurements might be able to detect distinct changes within the RPE level. The purpose of this study was to compare AF patterns in acute and chronic-recurrent CSC and to evaluate the potential value of AF as a non-invasive monitoring tool. Methods: From 85 patients diagnosed with CSC (mean age 43 years), AF images were retrospectively evaluated and compared with angiographic and ophthalmoscopic findings. Fluorescein angiography and AF measurements were performed using a Heidelberg retina angiograph. Autofluorescence was excited at a wavelength of 488 nm and detected above 500 nm. Results: Acute CSC as determined by an acute decrease in visual acuity (VA) within the last 6 weeks, focal point leakage and neurosensory retinal detachment was diagnosed in 39 patients. In 36 of those patients (92%), a significantly decreased AF at the leakage point (72%) and/or decreased AF in the area of neurosensory detachment (77%) were observed. Regarding chronic-recurrent CSC as determined by a decrease in VA for longer than 6 weeks and mottled hyperfluorescent appearance in angiography, abnormalities in AF were observed in 44/46 patients (96%). In those patients, decreased or mottled AF was observed at the leakage point itself (76%), whereas significantly increased AF was seen in the area of residual neurosensory retinal detachment (85%). Conclusions: In acute CSC, decreased AF is presumably due to a blockage caused by oedema, whereas in chronic-recurrent forms, irregular and increased AF is observed, possibly reflecting reactive RPE changes secondary to RPE defects and neurosensory detachment. If these findings could be systematically underlined by prospective clinical studies, AF might be an interesting non-invasive tool for monitoring RPE changes in CSC and for performing differential diagnosis.

Non-invasive imaging of the retinal pigment epithelium (RPE) using autofluorescence became recently available with the introduction of confocal laser scanning ophthalmoscopes. Fundus autofluorescence is usually excited at a wavelength of 488nm and the emitted light is detected above 500nm. This intrinsic autofluorescence was shown to derive from the lipofuscin accumulating within the RPE either with age or also due to different hereditary or degenerative diseases of the macula as e.g. age-related macular degeneration. Since a variety of macular diseases correlate with distinct RPE changes, specific patterns of autofluoresce nce could be evaluated within the recent years for diagnostic and prognostic reasons in those RPE-related diseases. Moreover autofluorescence can also be regarded as a monitoring tool after therapeutic applications as macular surgery or laser treatment. Other new applications try to determine macular pigment density using autofluorescence or use it to evaluate oxygen-dependent cell metabolism. This review summarizes the recent findings of autofluoresce nt patterns in specific diseases and therapeutic approaches and emphasizes on the tremendous potential of this novel imaging method.

* BACKGROUND AND OBJECTIVE: To determine whether fundus autofluorescence imaging is able to show changes in retinal pigment epithelium (RPE) fluorescence after thermal laser photocoagulation. * PATIENTS AND METHODS: In vivo imaging of fundus autofluorescence was performed with a scanning laser ophthalmoscope. A laser with a wavelength of 488 nm was used for excitation of the tissue and autofluorescence was detected above 500 nm using a barrier filter. One hundred eight eyes of 87 patients who had had previous laser treatment were monitored. The appearance and size of the laser lesions were documented and correlated to the time of treatment. Immediate changes were observed prospectively in 13 eyes; long-term follow-up was studied retrospectively in 95 eyes. * RESULTS: In all patients but one, autofluorescence was decreased in the area of laser lesions 1 hour after laser treatment. After 1 month, previously decreased autofluorescence in all lesions changed to significantly increased autofluorescence, which was stable up to 6 months after treatment. Mixed forms were present approximately 6 to 12 months after treatment, showing a central island of increased autofluorescence surrounded by a ring of decreased autofluorescence. After 1 to 2 years, lesions again changed to complete dark spots, enlarging later on. * CONCLUSION: RPE destruction and subsequent proliferation after continuous wave laser photocoagulation can be visualized noninvasively by autofluorescence imaging. Immediate decreased autofluorescence may indicate acute damage of the RPE, subsequent increased autofluorescence seems to indicate proliferative behavior of the RPE, and final dark spots can indicate RPE atrophy secondary to a denaturation of neurosensory retinal tissue. Thus, autofluorescence can be used in the long-term monitoring of RPE changes after laser treatment. The enlargement of the laser atrophy zone demonstrates the potential risk of visual loss after central laser photocoagulation even years after treatment. [Ophthalmic Surg Lasers Imaging 2004;35:131-138.]

Purpose: To study the effects of conventional laser application on the retinal pigment epithelium (RPE) in a perfusion tissue culture model of porcine retinal pigment epithelium without overlying neurosensory retina. Methods: RPE with underlying choroid was prepared from enucleated porcine eyes and fixed in a holding ring (Minusheet®). Specimens were then placed in two-compartment tissue culture containers (MinuCell & Minutissue, Bad Abbach, Germany) and were cultured during continuous perfusion with culture medium at both sides of the entire specimen, the upper RPE and the lower choroid (12 specimens out of 6 eyes). Cultures were kept for 1, 3, 7 and 14 days and were examined histologically. Laser treatment was performed on each tissue ring by application of 3 × 3 laser burns one day after culture began (argon ion laser, wavelength: 514 nm, pulse duration: 100 ms; spot size: 200 µm) using different energy levels (400–1,000 mW); (16 specimens out of 8 eyes). Results: During laser treatment a marked lightening of the RPE with centrifugal spreading was observed. Using higher levels of energy, a contraction of the RPE towards the center of the laser spot was noticed. One day after laser photocoagulation histology revealed destruction of RPE; within 3–7 days of culture, migration and proliferation of neighboring cells was observed in several lesions. After 7 days the initial defect of the irradiated area was covered with dome shaped RPE cells and after 14 days multilayered RPE cells were showing ongoing proliferation. However, there were also cases without proliferation after laser treatment. The non-treated, continuously perfused RPE showed regular appearance in histological sections: during the first 7 days of culture, light microscopy revealed a normal matrix with a well-differentiated RPE monolayer. Subsequently proliferation even without treatment was observed and after 14 days the RPE became multilayered. Conclusion: It was possible to study the early healing response to the effect of laser treatment using the permanently perfused tissue culture system. A marked proliferation and repair of the laser defect could be observed in several but not all lesions. After 14 days even without laser treatment a proliferative multilayered RPE was present. Although this limits the use of the system for longer than 7 days, it seems to be useful for investigation of RPE-related disorders.

PURPOSE Optical coherence tomography (OCT) was used to analyze the thickness of various retinal layers of patients following successful macula-off retinal detachment (RD) repair. METHODS Optical coherence tomography scans of patients after successful macula-off RD repair were reanalyzed with a subsegmentation algorithm to measure various retinal layers. Regression analysis was performed to correlate time after surgery with changes in layer thickness. In addition, patients were divided in two groups. Group 1 had a follow-up period after surgery of up to 7 weeks (range, 21-49 days). In group 2, the follow-up period was >8 weeks (range, 60-438 days). Findings were compared to a group of age-matched healthy controls. RESULTS Correlation analysis showed a significant positive correlation between inner nuclear-outer plexiform layer (INL-OPL) thickness and time after surgery (P=0.0212; r2=0.1551). Similar results were found for the ellipsoid zone-retinal pigment epithelium complex (EZ-RPE) thickness (P=0.005; r2=0.2215). Ganglion cell-inner plexiform layer thickness (GCL-IPL) was negatively correlated with time after surgery (P=0.0064; r2=0.2101). For group comparison, the retinal nerve fiber layer in both groups was thicker compared to controls. The GCL-IPL showed significant thinning in group 2. The outer nuclear layer was significantly thinner in groups 1 and 2 compared to controls. The EZ-RPE complex was significantly thinner in groups 1 and 2 compared to controls. In addition, values in group 1 were significantly thinner than in group 2. CONCLUSIONS Optical coherence tomography retinal layer thickness measurements after successful macular-off RD repair revealed time-dependent thickness changes. Inner nuclear-outer plexiform layer thickness and EZ-RPE thickness was positively correlated with time after surgery. Ganglion cell-inner plexiform layer thickness was negatively correlated with time after surgery.

Background: Anatomic and functional results of macularholes using vitrectomy and platelet-concentrate (PC) or autologous whole blood (WB) were investigated without peeling any epiretinal membrane in order to minimize retinal trauma. Methods: 44 patients with macular holes stage II, III and IV underwent a vitrectomy with removal of posterior cortical vitreous (in stage II and III) and C2F6 gas endotamponade. No peeling of any epiretinal membrane or the ILM was performed. In 14 patients autologous WB was injected and in 30 patients autologous PC. The mean follow-up time was 9.3 months.Results: An anatomic closure was observed in 36.4%of patients in the WB-group and in 93.9% of patients in the PC-group. SLO-microperimetry showed a reduction of absolute scotomas in 80% of the WB- and in 75% of the PC-group. In the WB- group 1 retinal detachment and 1 branch vein occlusion occurred; in the PC-group 3 retinal detachments, 1 central artery occlusion, 1 macular pucker,1 cystoid macular edema, 1 late reopening and 1 secondary glaucoma were observed. Inboth groups no endophthalmitis occurred. Conclusion: If autologous platelet concentrate is available, high anatomic success rates can be achieved without aggressive membrane removal,which may cause retinal damage. Autologous whole blood cannotbe recommended as an alternative adjunct for the treatment of macular holes without membrane removal.

Background Subretinal hemorrhage in age related macular degeneration (AMD) usually causes acute visual loss and is associated with poor visual prognosis. In order to prevent retinal damage and to perform laser treatment of the underlying choroidal neovascularization (CNV) the subretinal hemorrhage has to be removed from the macular region. This could be achieved by intravitreal injection of tissue plasminogen activator (tPA) and gas. Patients and methods In 8 consecutive patients, suffering from a massive macular hemorrhage (duration of visual problems: mean 9 days), tissue plasminogen activator (tPA) (40 micrograms in 400 microliters BSS) and SF6-gas (0.75 ml) was transsclerally injected into the vitreous cavity to achieve liquification and displacement of the hemorrhage. Results In all patients liquification and displacement of the hemorrhage out of the macular region was achieved during follow up. During the first week after operation a significant increase of visual acuity was noticed in all patients, however ophthalmoscopically there was just little reduction of the hemorrhage in the foveolar area. After successful removal of the blood the choroidal neovascularization was treated successfully by laser coagulation in one patient. No laser treatment was performed in the other patients because of the subfoveal location of the neovascularisation or because of disciform scar. Visual acuity increased 4 lines after surgery. In one case the procedure was complicated by a persistent vitreous hemorrhage and vitrectomy had to be performed in another patient due to an endophthalmitis. Conclusion Intravitreal injection of tPA assisted gas displacement of subretinal hemorrhage due to AMD leads to a significant increase of visual acuity during the first week after operation. Although a nearly complete removal of the hemorrhage out of the macular area could be achieved, it was difficult to differentiate this from the spontaneous course. Laser photocoagulation could be performed in only few cases.

Purpose To investigate microrobots as an assistive tool for minimally invasive intraocular surgery and to demonstrate mobility and controllability inside the living rabbit eye. Methods A system for wireless magnetic control of untethered microrobots was developed. Mobility and controllability of a microrobot are examined in different media, specifically vitreous, balanced salt solution (BSS), and silicone oil. This is demonstrated through ex vivo and in vivo animal experiments. Results The developed electromagnetic system enables precise control of magnetic microrobots over a workspace that covers the posterior eye segment. The system allows for rotation and translation of the microrobot in different media (vitreous, BSS, silicone oil) inside the eye. Conclusions Intravitreal introduction of untethered mobile microrobots can enable sutureless and precise ophthalmic procedures. Ex vivo and in vivo experiments demonstrate that microrobots can be manipulated inside the eye. Potential applications are targeted drug delivery for maculopathies such as AMD, intravenous deployment of anticoagulation agents for retinal vein occlusion (RVO), and mechanical applications, such as manipulation of epiretinal membrane peeling (ERM). The technology has the potential to reduce the invasiveness of ophthalmic surgery and assist in the treatment of a variety of ophthalmic diseases.

Background/Aims: To investigate the long-term effects of multiple intravitreal injections (IVTs) of ranibizumab (Lucentis) on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration. Methods: In 320 eyes, IOP measurements were performed at baseline prior to injection and compared with IOP measurements of the last visit. Correlations between mean IOP change and total number of IVTs, visual acuity or patient age were tested. Results: The mean IOP increase was 0.8 ± 3.1 mm Hg (p < 0.0001). Seven eyes showed final IOP values between 22 and 25 mm Hg. The mean follow-up was 22.7 ± 14.1 months. No further correlations between IOP change and number of IVTs, visual acuity or patient age have been found. Conclusions: This study demonstrated a statistically significant IOP increase in patients treated with repeated injections of ranibizumab. However, IOP increase required no glaucoma treatment during the study. Therefore, repeated injections with ranibizumab can be considered safe with regard to long-term IOP changes in patients without ocular hypertension or glaucoma.

Blue-light fundus autofluorescence (FAF) imaging is currently widely used for assessing dry age-related macular degeneration (ARMD). However, at this wavelength, the fovea appears as circular zone of marked hypofluorescence, due to the absorption of macular pigment (MP). This dark spot could be misinterpreted as an atrophic area and could lead to difficulties in identifying small, central changes. The purpose of the study was to analyze differences in image quality, FAF patterns, and lesion size, when using conventional blue-light (Λ(1) = 488 nm) and green-light (Λ(2) = 514 nm) FAF.Patients older than 50 years with central areas of geographic atrophy (GA) secondary to ARMD were enrolled. Images were recorded with a modified confocal scanning laser ophthalmoscope (cSLO). Image quality and patterns were analyzed. The quantification of the GA was performed with customized image-analysis software.In total, 95 eyes were included. The borders of the central atrophic patches and the boundaries of the preserved foveal island were better identified in 514-nm images. In both excitation wavelengths the signal-to-noise ratio was sufficient for the identification of the FAF pattern. Significant differences were observed in the size of the GA areas detected in the 488- and 514-nm wavelength images (4.29 ± 3.76 mm(2) vs. 3.80 ± 3.68 mm(2); P0.001).The green-light FAF images (514 nm) are superior for the accurate analysis of small, central, pathologic changes, and for the determination of the central GA lesion size. Using only blue-light FAF could lead to an overinterpretation of the size of atrophic patches and the center involvement, because it suggests the presence of atrophy in the fovea.

This article gives an overview of the vitreal anatomy and its changes in ageing, which have a significant impact on the two main retinal complications after damage of the vitreolenticular barrier, namely retinal detachment and cystoid macular edema. The possible reasons and pathomechanisms for this entity of retinal diseases in the context of anterior segment interaction are highlighted, and a summary of references is provided showing the epidemiology and consequences of such interventions.

The progress of wet age-related macular degeneration can now be controlled by intravitreal drug injection. This approach requires repeated injections, which could be avoided by delivering the drug to the retina. Intraocular implants are a promising solution for drug delivery near the retina. Currently, their accurate placement is challenging, and they can only be removed after a vitrectomy. In this paper, we introduce an approach for minimally invasive retinal drug delivery using magnetic intraocular inserts. We briefly discuss the electromagnetic-control system for magnetic implants and then focus on evaluating their ability to move in the vitreous humor. The mobility of magnetic intraocular implants is estimated in vitro with synthesized vitreous humors, and ex vivo with experiments on cadaver porcine eyes. Preliminary results show that with such magnetic implants a vitrectomy can be avoided.

For geographic atrophy (GA) due to age-related macular degeneration (AMD) there is so far no approved treatment option. Usually, increased autofluorescence (AF) levels of different patterns adjacent to the atrophic area indicate lipofuscin-laden retinal pigment epithelium (RPE) cells at a high risk for apoptosis. Herein, SRT was used to selectively treat these cells to stimulate RPE proliferation, in order to reduce or ideally stop further growth of the atrophic area.Six eyes of six patients with bilateral equally pronounced GA were treated by SRT, while the fellow eye served as control. Irradiation was performed using a prototype SRT laser (Medical Laser Center Lübeck, Nd:YLF laser; 527 nm; 200 ns/1.7 micros pulse duration; 30 repetitive pulses at 100 Hz). Test lesions with increasing energies were applied at the lower vessel arcade to determine the individual angiographic and ophthalmoscopic threshold radiant exposures. Treatment was then performed in the area of increased AF adjacent to the GA using energies between both thresholds. The GA progression rates of treated and fellow eyes were evaluated.After a 1-year follow-up, a progression of the atrophic area was observed in the treated eyes (0.7-8.0 mm(2)/yr, mean 3.0 mm(2)/yr; 46%/yr) whereas the progression rates of the fellow eyes were insignificantly lower (0.46-4.04 mm(2)/yr, mean 1.9 mm(2)/yr; 30%/yr; p = 0.134). The progression rate in the treated eyes of two patients increased significantly, while in the other four patients, the progression rates were nearly the same between both eyes. Moreover, one of these two eyes showed an unexpected RPE reaction after treatment, since all laser lesions led to RPE atrophy and thus an accelerated enlargement of the GA occurred.SRT in the hyperautofluorescent areas of GA was not able to stop or slow down the progression of GA. However, modified treatment strategies might be more promising, e.g. placing the spots outside the hyperautofluorescent areas where RPE apoptosis is postulated. Moreover, SRT studies on GA might be more successfully performed on specific subgroups of GA, based on autofluorescence and other findings.

To evaluate the significance of multislice CT for the diagnosis of uncertain penetrating globe injuries.Based on a retrospective chart review between 2002 and 2007, we identified 59 patients presenting with severe ocular trauma with uncertain rupture of the globe due to massive subconjunctival and/or anterior chamber hemorrhage. The IOP (intraocular pressure) was within normal range in all patients. High resolution multidetector CT (MD-CT) scans (16 slice scans) with axial and coronar reconstructions were performed in all patients. The affected eye was examined for signs of penetrating injury such as abnormal eye shape, scleral irregularities, lens dislocation or intravitreal hemorrhages. Four experienced radiologists read the CT scans independently. Beside the diagnosis, the relevant morphological criteria and the optimal plane orientation (axial or coronar) were specified. The sensitivity, specificity, and negative and positive predictive value were calculated. Additionally the interobserver variability was determined by applying the Cohen's kappa test. Surgical sclera inspections were performed in all cases as a standard of reference. The evaluations of the CT examination were compared with the surgery reports.59 patients were evaluated (42 men, 17 women). The mean age was 29 years (range 7 - 91). In 17 patients a rupture of the globe was diagnosed during surgery. 12 of these 17 penetrating injuries (70.6 %) were classified correctly by MDCT, 5 of the 17 (29.4 %) were not detectable. 42 patients did not have an open globe injury. 41 of these patients were diagnosed correctly negative by MDCT, and one patient was classified false positive. This results in a sensitivity of 70 % with a specificity of 98 %. There was high inter-rater agreement with kappa values between 0.89 - 0.96. Most discrepancies were caused by wrong negative findings. The most frequent morphologic criteria for open globe injury were the deformation (n = 10) and the volume reduction (n = 7) of the globe. These changes were most certain and visible in the axial orientation.In about one third of all unclear cases with rupture of the globe due to severe trauma, CT evaluation failed to correctly diagnose the open globe injury, which might lead to a delay in necessary surgical intervention. Thus, surgical sclera inspection is always mandatory in such unclear trauma cases regardless of the MD-CT results.

Background: It has been shown that selective retina treatment (SRT) using a train of 1.7 microseconds laser pulses allows selective damage of the retinal pigment epithelium (RPE) while sparing the adjacent photoreceptors and thus avoiding laser scotoma. It was the purpose of this work to investigate SRT laser effects with Q-switched pulses of only 8 nanoseconds in duration by evaluating the angiographic and ophthalmoscopic damage thresholds and the damage range by histology in a rabbit model. Materials and Methods: A flash lamp pumped frequency doubled (532 nm) Nd:YAG laser with 8 nanoseconds pulse duration was used. In total 210 laser lesions, each calculated to be 102 mm in diameter on retina, were applied through a slit lamp onto the fundus of six eyes of Chinchilla Bastard rabbits. The rabbits were irradiated with increasing energies with single pulses and a train of 10 laser pulses at 10 Hz. After treatment fundus photography and angiography were performed to determine the damage thresholds (ED50-probability of RPE cell damage and neurosensory retinal damage) as well as the safety range between both thresholds (ratio of angiographic ED86 vs. ophthalmoscopic ED14). Selected histology was taken for single and repetitive pulse lesions after treatment. Results: Angiographic and ophthalmoscopic ED50-thresholds decreased with increasing number of pulses. For single pulse application ophthalmoscopic and angiographic ED50 were determined to 365 and 144 mJ/cm 2 , respectively. Regarding 10 pulses 266 and 72 mJ/cm 2 were found. No retinal hemorrhages or disruptions were observed for both sets of parameters. The therapeutic window between angiographic and ophthalmoscopic threshold revealed a factor of 3.1 for single pulses and 2.3 for repetitive pulse irradiation. The safety range respectively had a factor of 0.8 (single pulses) and 1.7 (10 pulses). Histologic examination of laser lesions with single and repetitive pulses at radiant exposures within the therapeutic window—292 and 213 mJ/cm 2 respectively—revealed damaged RPE, intact Bruch’s membrane and choriocapillaries. Photoreceptors were partly spared but also damaged to various extents. Conclusions: Short laser pulses of 8 nanoseconds pulse duration can damage the RPE without retinal hemorrhage or disruption. Selective damage of the RPE without affecting the photoreceptors can only rarely be achieved due to the small safety range. Thus, so far microsecond laser pulses for SRT seems favorable compared to nanosecond pulses in order to prevent unintentional photoreceptor damage. Lasers Surg. Med. 40:20–27, 2008. 2008 Wiley-Liss, Inc.

PURPOSE. Selective targeting of the retinal pigment epithelium (RPE) with repetitive laser pulses that minimize thermal damage to the adjacent photoreceptors is a promising new therapeutic modality for RPE-related retinal diseases. The selectivity of an alternative, more versatile scanning approach was examined in vivo by using a broad range of scanning parameters. METHODS. Acousto-optic deflectors repeatedly scanned the focus of a continuous wave (cw)-laser across the retina of Dutch belted rabbits, producing microsecond irradiation at each RPE cell. Two irradiation patterns forming separated lines (SEP) or interlaced lines (INT), different dwell times (2.5‐75 s), and repetition numbers (10 and 100 scans with 100-Hz repetition rate) were tested. Thresholds were evaluated by fundus imaging and angiography. Histology was performed for selected parameters. RESULTS. Selective RPE cell damage was obtained with moderate laser power. The angiographic threshold power decreased with pulse duration, number of exposures, and applying the INT pattern. Ophthalmoscopic thresholds, indicating onset of thermal coagulation, were higher than twice the angiographic threshold for most tested parameters. Histology confirmed selective RPE cell damage for SEP irradiation with 7.5 and 15 s; slower scan speeds or closed lines caused photoreceptor damage. CONCLUSIONS. A cw-laser scanner can be set up as a highly compact and versatile device. Selective RPE damage is feasible with dwell times up to 15 s. Greatest selectivity is achieved with short exposure times and separated scan lines. Interlaced lines and long exposure times facilitate heat conduction into photoreceptors. A scanner is an attractive alternative for pulsed selective targeting, because both selective targeting and thermal photocoagulation can be realized. (Invest Ophthalmol Vis Sci. 2007;48:1782‐1792) DOI:10.1167/iovs.06-0797

Purpose To investigate the complication profile and the long-term functional outcome of combined pars plana vitrectomy and scleral-fixated sutured posterior chamber lens (PC IOL) implantation. Design Retrospective, consecutive, interventional case series. Methods The records of 63 patients (mean age, 67.5 years) were reviewed retrospectively (follow-up, 12 to 132 months; mean, 43.5 months). The underlying ocular pathologic features; the intraoperative, early (within two weeks after surgery), and late complications (more than two weeks after surgery); final best-corrected visual acuity (BCVA); and the refractive outcome were recorded. Results Fifty-nine of 63 procedures (93.7%) were performed without complications. Intraoperative complications included vitreous hemorrhage (n = 2), a retinal tear (n = 1), and a rupture of the iris base (n = 1). Early complications included transient raise of intraocular pressure (IOP; n=19), transient vitreous hemorrhage (n = 2), scleral tunnel insufficiency (n = 5), pupillary capture of intraocular lens [IOL] (n = 6), persistent vitreous (n = 3), and choroidal hemorrhage (n = 1). Late complications occurred in 12 patients: rhegmatogenous retinal detachment (n = 4), proliferative vitreoretinopathy retinal detachment secondary to the underlying ocular pathologic features (n = 2), choroidal hemorrhage (n = 1), macular pucker (n = 1), and IOL dislocation (n = 4), including two cases of suture break. Mean BCVA in logarithm of the minimum angle of resolution units improved significantly from 1.025 (standard deviation [SD], 0.654) to 0.766 (SD, 0.750; P = .03). Mean cylindric equivalent significantly changed from 0.92 diopters (D; SD, 1.075) to 1.76 D (SD, 1.344; P = .005). Conclusions The surgical procedures were performed safely in approximately 94% of patients. Most postoperative complications were minor: significant ones occurred in approximately 20%, whereas suture breaks were observed rarely. The only moderate long-term functional improvement in this case series was mainly determined by the underlying ocular pathologic features.

PURPOSE To assess the correlation between hyperreflective foci (HF) and visual and anatomical outcomes in treatment-resistant neovascular age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). METHODS This was a prospective interventional case series. Thirty-three eyes of 30 consecutive patients with treatment-resistant neovascular AMD were enrolled. Intravitreal aflibercept injections were performed at week 0 (baseline), week 4, and week 8. Spectral-domain OCT images were obtained before each injection and 4 weeks after the third injection. The main focus was on the measurement of choroidal neovascularization (CNV) size in the cross-sectional area in the B-scan through the fovea, and HF number along line segments of 1- and 3-mm length passing through the fovea. RESULTS Mean number of HF in the radius of 500 μm decreased from 8.36 ± 7.58 to 4.15 ± 3.39 (P = 0.02). Mean number of HF in the radius of 1500 μm was reduced from 21.30 ± 12.47 to 10.45 ± 6.34 (P < 0.001). Mean CNV area decreased from 0.35 ± 0.22 to 0.22 ± 0.16 mm2 (P < 0.001). There was a significant positive correlation between HF reduction in the radius of 500 μm and decrease in central subfield thickness (CST) (r = 0.43, P = 0.01), but no statistically significant correlation was found between HF decline in the radius of 1500 μm and other parameters. CONCLUSIONS Switching from ranibizumab to aflibercept caused significant decrease in the number of HF 1 month after aflibercept upload, and HF decrease in the radius of 500 μm was correlated positively with the reduction in CST.

Retinal pigment epithelial (RPE)-rips in age-related macular degeneration (AMD)-associated pigment epithelial detachment (PED) occur in the natural course of the disease but also after therapy (e.g. laser photocoagulation, photodynamic therapy), possibly triggered by the specific therapy. We report here on four patients that received intravitreal bevacizumab (Avastin) for AMD-associated vascularised PED and developed RPE-rips during the follow-up.The case reports of four consecutive patients that developed RPE-rips after intravitreal injection of bevacizumab at 1 mg/0.1 ml were reviewed.The RPE-rips occurred in all patients between 1 week and 1 month following intravitreal injection. Two of the four patients improved in vision despite the rip, but 3 months after the initial intervention, three patients suffered deterioration in visual acuity and had to be re-injected.Improvement in visual acuity may occur following intravitreal bevacizumab despite RPE-rips, but the patients need close follow-up and eventual re-treatment in the case of deterioration.

BACKGROUND AND OBJECTIVE To describe fundus autofluorescence patterns in choroidal neovascularization secondary to age-related macular degeneration before and after photodynamic therapy (PDT). PATIENTS AND METHODS Sixty-eight consecutive eyes were indicated for PDT after standard fluorescein angiography, which showed completely classic choroidal neovascularization (CNV) (n = 52), occult with no classic CNV (n = 7), and predominantly classic CNV (n = 9). Standardized PDT was performed and patients were examined 2 to 3 months later. Angiography and autofluorescence measurements were performed again and compared with preoperative values. RESULTS At baseline, autofluorescence was mainly decreased in areas of completely classic CNV (79%), but showed a regular or mottled pattern in occult CNV. A slightly increased (50%) or normal (50%) autofluorescence was seen at the rim of the classic lesions within the junctional zone. Membrane demarcation was improved (90%) in classic membranes 2 to 3 months after PDT. After PDT for occult membranes, a transformation into classic membranes with residual leakage and need for further PDT was observed (6 of 7 eyes), showing the described autofluorescence patterns. For the mixed type of CNV, both described patterns of autofluorescence distribution were found. CONCLUSION Especially classic CNVs reveal distinct characteristics of significantly decreased autofluorescence, presumably due to their localization above the retinal pigment epithelium level, leading to blockage of autofluorescence. Autofluorescence patterns after PDT included enhanced demarcation of the membrane, suggesting reactive retinal pigment epithelial changes. Autofluorescence might be an interesting tool to distinguish noninvasively between classic and occult CNV in age-related macular degeneration and to monitor changes after PDT. [Ophthalmic Surg Lasers Imaging 2006;37:406-414.] AUTHORS From the University Eye Hospital Regensburg (CF, RS, TT, AW, HGS, V-PG), Regensburg; and the University Eye Hospital Kiel (AB), Kiel, Germany. Accepted for publication March 9, 2005. Address reprint requests to Carsten Framme, MD, University Eye Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany.

PURPOSE: To report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE) evaluated by optical coherence tomography (OCT), fundus autofluorescence (AF) and microperimetry, both in the acute phase and after resolution of symptoms. METHODS: Complete ophthalmological evaluation, including fluorescein angiography, OCT, AF, and microperimetry upon presentation and 1 month later, after lesions have subsided. An attempt to correlate the findings on presentation and changes after resolution is performed using the results of these new investigational techniques. RESULTS: APMPPE showed hyperreflectance in OCT at the level of the outer retinal layers, without increase in retinal thickness. AF revealed early decreased fluorescence due to a masking effect, and later reveals increased fluorescence after resolution of OCT findings. Function is disturbed at the lesion sites, as shown by microperimetry, and later returns to near normal values on microperimetry. CONCLUSION: APMPPE shows outer retinal layers changes on OCT, which resolve totally after subsidence of the acute phase. AF shows areas of increased fluorescence after resolution, with near normal return of function on microperimetry.

BACKGROUND: Current PDT treatment for age-related macular degeneration uses a standard radiant exposure of 50 J/cm(2) at an irradiance of 600 mW/cm(2). However; there is a general problem with the unusually high irradiance; in fact, the rate of photochemical production of singlet oxygen may be limited by insufficiently oxygenized neovascular tissue. It was the aim of this study to evaluate the efficacy of verteporfin (Visudyne) photoactivation to induce thrombosis of choriocapillaries and in experimentally induced corneal neovascularizations in rabbits by varying irradiance and retinal radiant exposure. MATERIALS AND METHODS: The light-dose threshold to induce micro-thrombosis in the choriocapillaries (seven eyes) and in corneal neovascularizations (eight eyes) of Chinchilla-Bastard rabbits using different retinal irradiances (100 and 600 mW/cm(2)) at different radiant exposures (20, 10, 5, 2.5, 1.25, 0.62, and 0.3 J/cm(2)) was evaluated. Induction of neovascularizations was performed 7 days prior to PDT treatment using intracorneal silk sutures. A dose of 2 mg/kg verteporfin was intravenously infused 10 min before standard PDT. The criterion for vascular thrombosis was vessel closure as determined by fluorescein angiography 1 h and 1 day post exposure. RESULTS: Experiments on the choroid revealed vessel closure 1 h after irradiation at ED(50) = 10.8 J/cm(2) (both 600 and 100 mW/cm(2)) and after 24 h at ED(50) = 2.4 J/cm(2) (600 mW/cm(2)) versus 1.8 J/cm(2) (100 mW/cm(2)). Vessel closure was enhanced at irradiation with 100 mW/cm(2). Regarding corneal neovascularizations, vessel thrombosis was observable by dark appearance of irradiated clotted neovascular tissue and angiographically by a lack of leakage at ED(50) thresholds of 0.62 J/cm(2) (1 h) and 0.41 J/cm(2) (1 day) for 100 mW/cm(2) and of 0.99 J/cm(2) (1 h), and 0.67 J/cm(2) (1 day) for 600 mW/cm(2). Thus in both experiments thresholds for vessel closure were reduced by a factor of 1.5 for the lower intensity. Histology revealed more selective vessel occlusion without RPE and photoreceptor damage for 100 mW/cm(2) rather than 600 mW/cm(2) intensity at threshold irradiation. CONCLUSION: Low-intensity PDT with verteporfin for neovascular tissue seems to be more effective than regular high-intensity PDT. Future preclinical trials should address the issue of proper dosimetry for effective PDT in age-related macular degeneration.

Introduction: The selective RPE treatment (SRT) is a new method, which targets retinal diseases associated with disorders in the retinal pigment epithelium (RPE). By applying a train of μs laser pulses, it is possible to selectively damage RPE cells while sparing the adjacent photoreceptors and the neural retina. Due to the ophthalmoscopic invisibility of the RPE effects we investigated an optoacoustic (OA) on-line dosimetry system to monitor RPE damage non-invasively. Material and Methods: For in vitro experiments porcine RPE was irradiated with a Nd:YLF laser pulse train (527nm, 1.7μs, 5-40μJ, 30 pulses, 100 Hz). Pressure waves (optoacoustic transients) generated at the RPE were measured with a piezoelectric transducer. The RPE cell damage was visualised by fluorescence microscopy by means of the vitality stain CalceinAM. During 27 patient treatments (527nm, 1.7μs, 50-150μJ, 30 pulses, 100 Hz) the optoacoustic signals were measured with an ultrasonic transducer embedded in the contact lens. The RPE leakage was visualized by fluorescein and ICG angiography. Results: In vitro: Below the RPE cell damage threshold, the optoacoustic transients from each single pulse are almost similar. With RPE damage, fluctuations of the individual transients are observed during the pulse train. These fluctuations can be explained by statistical irregular microbubble formation around the strong light absorbing melanosomes inside the RPE cells, which occur after the temperature exceeds the vaporization threshold. The transient microbubbles probably lead to RPE cell disruption. An optoacoustic value (OA-value) calculated from the fluctuations was defined in order to assess RPE damage. Patient treatment: If optoacoustic pulse-to-pulse fluctuations were measured, RPE leakage was observed in fluorescein and ICG angiography. In 96% of the irradiated areas, RPE-leakage in fluorescein angiography and OA-value correlated. The stronger the optoacoustic pulse-to-pulse fluctuations, thus the higher the OA-value, the more intense angiographic leakage was observed in ICG-angiography. Conclusion: A non-invasive optoacoustic on-line dosimetry control to monitor RPE damage during SRT was developed. In order to avoid invasive angiography, it is currently evaluated in a multicenter clinical SRT study.

Fundus autofluorescence (AF) is derived from the lipofuscin contained by the retinal pigment epithelial cells. Using a scanning laser ophthalmoscope, two-dimensional AF measurements of the ocular fundus can be achieved. Directly after conventional photocoagulation and also after selective RPE laser treatment (SRT) with ophthalmoscopically non-visible laser lesions, irradiated areas reveal reduced AF, indicating RPE damage. Since the green treatment laser beam could also be used for AF excitation, the aim of this study was to evaluate whether absolute measurements of AF can be performed, and also possible changes in AF detected, online during SRT.SRT was carried out by use of a frequency-doubled Nd:YLF laser (wavelength 527 nm, pulse duration 1.7 micros, repetition rate 500 and 100 Hz, number of pulses 100 and 30, single pulse energy 50-130 microJ) in vitro (porcine RPE; retinal spot size 160 microm) and during patient treatment (retinal spot size 176 microm). During irradiation, fluorescence light from the RPE was decoupled from the laser light inside the slit lamp and detected by a photomultiplier or photodiode at wavelengths above 550 nm. Additionally, temperature-dependent fluorescence intensity measurements of A2-E, the main fluorescent component of lipofuscin, were performed in a different in-vitro setup.The intensity of AF decreased over the number of applied pulses during laser irradiation, and this trend was more pronounced in porcine RPE samples than during human treatment. In vitro, the AF intensity decreased by about 22%; however, only a weak signal was detected. When treating patients, the AF intensity was strong and the rate of decay of fluorescence intensity with number of pulses was greater when irradiating at 500 Hz than at the 100 Hz repetition rate. However, for both repetition rates the AF decay was merely up to 6-8% over the number of pulses per laser spot. Fluorescence intensity of A2-E decreased linearly with increasing temperature at about 1% per 1 degrees C and was completely reversible.Online measurements of AF during selective RPE laser treatment are possible and reveal a decay in AF as a function of the number of laser pulses applied to the RPE. If A2-E results can be transferred to RPE fluorescence, the AF decay could be related to the temperature increase within the tissue during treatment. Further clinical studies-in SRT as well as in conventional laser photocoagulation-might be able to show online AF changes on different areas of the retina and on different pathologies. Due to the temperature dependence of the fluorescence, on-line AF measurements during laser treatments such as photocoagulation or TTT may be able to be used as a real-time method for temperature monitoring.

In all fundus laser treatments of the eye, the temperature increase is not exactly known. In order to optimize treatments, an online temperature determination is preferable. We investigated a noninvasive optoacoustic method to monitor the fundus temperature during pulsed laser irradiation. When laser pulses are applied to the fundus, thermoelastic pressure waves are emitted, due to thermal expansion of the heated tissue. Using a constant pulse energy, the amplitude of the pressure wave increases linearly with an increase in the base temperature of between 30 and 80 degrees C. This method was evaluated in vitro on porcine retinal pigment epithelium (RPE) cell samples and clinically during selective RPE treatment with repetitive microsecond laser pulses. During the irradiation of porcine RPE with a neodymium-doped yttrium (Nd:YLF) laser (527 nm, 1.7 micros, 500 Hz repetition rate, 160 mJ/cm(2)) an increase in the base temperature of 30+/-4 degrees C after 100 pulses was found. During patient treatments, a temperature increase of 60+/-11 degrees C after 100 pulses with a 500-Hz repetition rate and 7+/-1 degrees C after 30 pulses with 100 Hz at 520 mJ/cm(2) was found. All measured data were in good agreement with heat diffusion calculations. Optoacoustic methods can be used to noninvasively determine retinal temperatures during pulsed laser treatment of the eye. This technique can also be adapted to continuous-wave photocoagulation, photodynamic therapy and transpupillary thermotherapy, or other fields of laser-heated tissue.

Aim: Selective retinal pigment epithelium (RPE) laser treatment is a new technique which selectively damages the RPE while sparing the neural retina. One difficulty is the inability to visualise the laser lesions. The aim of the study was to investigate whether fundus autofluorescence (AF) is changed because of the RPE damage, and thus might be used for treatment control. Additionally, the clinical course of patients with various macular diseases was evaluated. Methods: 26 patients with macular diseases (diabetic maculopathy (DMP), soft drusen maculopathy (AMD), and central serous retinopathy (CSR)) were treated and followed up for at least 6 months. Treatment was performed with a train of repetitive short laser pulses (800 ns) of a frequency doubled Nd:YAG laser (parameters: 532 nm, 50 and 500 pulses at 100 and 500 Hz, retinal spot diameter 200 μm, pulse energies 75–175 μJ). AF was excited by 488 nm and detected by a barrier filter at 500 nm (HRA, Heidelberg Engineering, Germany). Patients were examined by ophthalmoscopy, fluorescein angiography, and autofluorescence measurements at various times after treatment (10 minutes, 1 hour, 1 and 6 weeks, 3, 6, and 12 months). Results: Fluorescein angiography showed leakage from the irradiated areas for about 1 week after treatment. None of the laser lesions was ophthalmoscopically visible during treatment. Identification of the lesions was possible by AF imaging showing an intensity decay in the irradiated area in 22 out of 26 patients, predominantly in patients with CSR and AMD. Lesions could be identified 10 minutes after treatment as hypoautofluorescent spots, which were more pronounced 1 hour later. During follow up the laser spots became hyperautofluorescent. In patients with DMP some AF images were less helpful because of diffuse oedema and larger retinal thickness. In these cases ICG angiography was able to confirm therapeutic success very well. Most of the patients have had benefit from the treatment, with best results obtained for CSR patients. Conclusion: Imaging of non-visible selective RPE laser effects can be achieved by AF measurements predominantly in patients without retinal oedema. Therefore, AF may replace invasive fluorescein angiography in many cases to verify therapeutic laser success. Selective laser treatment has the potential to improve the prognosis of macular diseases without the risk of laser scotomas.

Laser photocoagulation is a well-established treatment modality for a variety of retinal disorders, but is difficult to use near the fovea due to thermal retinal destruction. Certain diseases, such as drusen maculopathy, are thought to be caused by a dysfunction of the Retinal Pigment Epithelium. For those diseases selective targeting of the RPE, sparing the adjoining photoreceptors, might be the appropriate treatment to avoid laser scotoma, as it has been shown with application of a train of ms laser pulses by Birngruber and Roider. Our new approach is to use a conventional green cw laser and rapidly scan a small laser spot over the retina so as to produce microsecond(s) -illumination at each RPE cell. Two scanning devices were developed using acousto-optic deflectors. For the in vitro experiments the ED50 value RPE cell damage was 170 mW with 100 exposures, scanning with a speed of 1 spot diameter/3 microsecond(s) . In vivo experiments demonstrated an angiographic ED50 threshold of 66 mW for 100 exposures while scanning with an effective illumination time of 5 microsecond(s) . The ophthalmoscopic threshold was higher than a factor of 2 times the angiographic ED50. Using separated scan lines we show selectivity in the form of surviving cells in between irradiated lines. Selective destruction of RPE cells is possible using laser-scanning devices.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Objective: The selective damage of the retinal pigment epithelium (RPE) with repetitive microsecond(s) laser pulses is a new technique for the treatment of several retinal diseases. RPE can selectively be damaged by simultaneously sparing off the adjacent photoreceptor tissue. Objective of this study is to investigate whether optoacoustic (OA) transients occurring during irradiation might be used to control the invisible treatment effect. Setup: A train of frequency doubled Nd:YLF laser pulses (527 nm, 1.7microsecond(s) pulse length, 500Hz rep. rate) were applied via a laser slit lamp on porcine RPE samples. The acoustic transients were recorded with a broadband transducer. Results: At low radiant exposures ( 150 mJ/cm2), the OA transients differ from pulse to pulse within a pulse train, which can be attributed to microbubble formation around the strong absorbing melanosomes inside the RPE cells. FFT spectra of the OA transients show slight differences in the frequency spectrum with the different radiant exposures.