Search

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.

The therapeutic effect of laser treatment for macular diseases is related to the damage to the retinal pigment epithelium (RPE) and the subsequent restoration of the defect due to RPE proliferation. In contrast to conventional laser treatment, it is possible to damage the RPE selectively and to spare the photoreceptors by using repetitive microsecond laser pulses. It was the aim of the study to investigate the influence of pulse duration and number of pulses on angiographically and ophthalmoscopically visible retinal damage thresholds in order to optimize treatment modalities.In total, 625 laser lesions with various parameters were applied to the retina in 11 eyes of 6 Chinchilla breed rabbits using an experimental laser system (Nd:YLF at 527 nm). Pulse duration (1.7 microseconds and 200 nanoseconds) and number of pulses (100, 10, and 1 pulses) were varied at a constant repetition rate of 100 Hz. Damage thresholds were determined in terms of ophthalmoscopic and fluorescein angiographic visibility, and the therapeutic window (TW; angiographic ED(50) vs. ophthalmoscopic ED(50)) as well as the safety range (SR; angiographic ED(84) vs. ophthalmoscopic ED(16)) between both thresholds were calculated. Selected laser lesions were evaluated by histology.Generally, the ED(50) radiant exposure for angiographic visibility decreases for shorter laser pulses and with an increase in the number of pulses. The TW for both pulse durations (1.7 microseconds and 200 nanoseconds) was wider with 100 pulses than with single pulses. The widest TW was found for 100 pulses at 200 nanoseconds pulse duration (5.9-fold above the angiographic threshold), and the smallest TW with a factor of 1.6 was found for 1.7 microseconds single pulses. In terms of SR, only irradiation with 100 pulses at 200 nanoseconds pulse duration was associated with a ratio2. Independently of pulse duration, histological examination of laser sites 1 hour after irradiation revealed widely intact photoreceptors, while the underlying RPE was damaged.Pulse duration and number of pulses have a significant influence on RPE damage thresholds and consecutively on TW and SR. Because fundus pigmentation in humans may vary intra- and interindividually by a factor of 2, a large TW and ideally also a large SR should be ensured in a clinical treatment context. In rabbits, the safety range with 200 nanoseconds pulses is higher than with the pulse duration of 1.7 microseconds currently in clinical use. These findings suggest the need for clinical pilot studies to prove whether these results can be transposed to the situation in humans.

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.

In absolute dry eyes the use of pharmaceutical lubricants can be insufficient to prevent progressive conjunctival and corneal epitheliopathy and the severe symptoms associated. In this situation a microvascular autologous submandibular gland transplant can be used to continuously provide a natural tear substitute. We studied the effect of this salivary tear film on the ocular surface in a prospective controlled clinical study.We examined 20 eyes with a viable submandibular gland transplant and 20 severely dry eyes without or with a nonviable transplant as a control for the first postoperative year. Visual acuity, baseline-tear secretion, fluorescein break-up time and slit-lamp microscopical grading of ocular surface features, Rose Bengal staining and conjunctival impression cytology were evaluated.Postoperatively baseline-tear secretion and break-up time were significantly better in the group with a viable submandibular gland transplant than in the controls. The biomicroscopical staging of eyes with a salivary tear film was stable or showed a trend to improvement, while controls showed a trend to deteriorate. A successful submandibular gland transplant reduced the conjunctival and corneal neovascular hyperaemia. However, in 6 eyes with an excessive salivary epiphora, a microcystic epithelial oedema was observed. The epiphora and the associated oedema could be successfully controlled by means of a surgical reduction of the transplant.Following successful autologous submandibular gland transplantation lubrication and comfort are significantly improved and the ocular surface is stabilised during the first postoperative year. Severe preoperative morphological alterations and the salivary character of the new tear film prevent a more obvious improvement of the ocular surface.

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.

PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for >= 4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. larger-scale studies are warranted to confirm these observations. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for >= 4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. larger-scale studies are warranted to confirm these observations. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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.

* BACKGROUND: Macular holes usually are diagnosed by biomicroscopy. Fluorescence angiography (FLA) is helpful especially for judging early stages or pseudoforamina. The importance of fundus-autofluorescence in macular hole surgery was studied. * PATIENTS AND METHODS: Twenty-five consecutive patients with macular holes (n = 21) and clinically-similar appearances (n = 4) were examined biomicroscopically. In addition, fundus-autofluorescence and FLA were determined by Heidelberg-Retina-Angiograph (HRA, Heidelberg, Germany). A vitrectomy was performed on 16 patients with macular hole stage II, III, and IV, and membrane peeling was performed if necessary. Platelet-concentrate as an adjuvant agent was used in all surgeries, and all 16 patients were examined afterward. RESULTS: In all patients with macular hole stage III and IV (n = 18), fundus-autofluorescence revealed a marked hyperfluorescent spot in the foveolar region and also a hyperfluorescence in FLA. Patients with macular hole stage II (n = 3) showed a slight punctured hyperautofluorescence and a subtle window-defect in the FLA. Postoperatively, the autofluorescence was normal in all eyes with a closed macular hole (87.5%). In some patients, a variable punctured hyperautofluorescence was noticed (n = 3). In eyes with pseudoforamina, the autofluorescence was normal (n = 4). * CONCLUSION: In macular hole diagnostics, fundus-autofluorescence is able to replace invasive fluorescence angiography. The autofluorescence is helpful for the examination of pseudoforamina and might be useful for estimating therapeutic success. [Ophthalmic Surg Lasers 2001;32:383-390]

The selective damage of the retinal pigment epithelium (RPE) is a new treatment method for several retinal diseases. By applying a train of microsecond(s) laser pulses it is possible to selectively damage these cells and simultaneously spare the adjacent photoreceptor and neural tissue. Due to the ophthalmologic invisibility of the RPE cell damage we investigate an optoacoustic (OA) control system to monitor the RPE cell damage. Setup: The irradiation was performed with a frequency doubled Nd:YLF laser by applying a train of +s laser pulses. In vitro, the OA transients were received by an ultrasonic broadband transducer. During treatment an OA contact lens with embedded transducer was used. In vitro: Freshly enucleated porcine RPE samples with CalceinAM as life/death staining were used. Below RPE cell damage threshold a classic thermoelastic transient was found. Above cell damage threshold the OA transient differs form pulse to pulse. This can be explained by microbubble formation around the strong absorbing melanosomes inside the RPE cells. In vivo: We found the same pulse to pulse deviations of the OA transient above the fluoresceine angiographic detectable RPE damage threshold during treatment. This system give us a new approach to non-invasively monitor the selective RPE treatment.

Objective: The selective damage of the retinal pigment epithelium (RPE) with repetitive µs 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, 1.7µs 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 (< 100 mJ/cm2) we found a bipolar pressure transient due to thermoelastic expansion of the RPE. The pressure waves from the individual pulses of one pulse train show nearly identical transients. The transients differ slightly from different sites on the sample. At higher 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.

Background: This study aimed to characterise the composition of the pre-ocular fluid after transplantation of the autologous submandibular gland (SMG) for patients with severe dry eye. · Methods: Stimulated and unstimulated pre-ocular fluid from 15 patients (17 eyes) with a viable SMG graft (“SMG-salivary tears”), as well as normal tears and SMG saliva (20 normal subjects/ 20 eyes), was sampled. As global tear parameters, fern pattern analysis and SDS gel electrophoresis were performed. As specific quality parameters, total protein content, secretory immunoglobulin A (SIgA), lysozyme, amylase, sodium, potassium and osmolality were measured using routine laboratory methods. The flow rate of SMG-salivary tears was determined in 5 patients by means of sequential scintillography. · Results: The fern pattern of SMG-salivary tears was coarse and thus more similar to normal SMG saliva than tears. SDS gel electrophoresis of the SMG-salivary tears showed albumin and two unidentified proteins in addition to the normal tear pattern. Osmolality and total protein content of SMG-salivary tears were higher than in normal SMG saliva, but still lower than in normal tears. High activities of normal tear antibacterial proteins (SIgA, lysozyme and amylase) were detected in the salivary tears. Stimulation of the secretion did not alter the composition of SMG-salivary tears. The flow rate of SMG-salivary tears was closer to that of normal tears than normal SMG saliva. · Conclusion: Salivary tears resulting from SMG-transplantation represent condensed SMG saliva. Thus their quality is intermediate between normal tears and normal SMG saliva. High levels of secretory proteins demonstrate that the gland maintains an active function. Surgical denervation and residual tear components from the ocular surface are the most likely factors to cause the complex differences between normal SMG saliva and SMG-salivary tears. The effects of this secretion on the ocular surface are currently being evaluated in a clinical and laboratory study.

A poly(methyl methacrylate)(PMMA) intraocular lens (IOL) dislocated into the vitreous cavity in 2 patients after a neodymium:YAG (Nd:YAG) laser posterior capsulotomy. In Case 1, the capsulotomy was performed 19 months after extracapsular cataract extraction (ECCE) and sulcus fixation of an IOL. Six months later the IOL dislocated posteriorly. In Case 2, ECCE with intracapsular IOL implantation was followed 4 years later by an Nd:YAG capsulotomy; 6 months later the IOL dislocated into the vitreous cavity within the intact capsular bag. Different mechanisms were responsible for the dislocation: in case 1, radial tearing of the large capsular defect with IOL loosening and dislocation into the vitreous cavity; in Case 2, zonulysis and IOL dislocation within the intact capsular bag. A neodymium:YAG capsulotomy may cause delayed IOL dislocation into the vitreous cavity.

Hyperreflective foci (HFs) are observable within the neurosensory retina in diabetic macular edema (DME) using spectral domain optical coherence tomography (SD-OCT). HFs have also been seen in wet age-related macular degeneration (AMD), although the origin is still unknown; however, they reduced significantly during anti-VEGF (vascular endothelial growth factor) therapy, and their baseline amount seemed to correlate with treatment success. In this study the behavior of HFs was evaluated during anti-VEGF therapy for DME.Fifty-one patients (mean age: 67 years) underwent SD-OCT before and one month after one anti-VEGF injection (ranibizumab: n = 30; bevacizumab: n = 21). The HFs were semiquantitatively counted, assigned to three groups (group A: HFs n = 1-10; group B: n = 11-20; group C: n20), and correlated to the course of visual acuity and foveal thickness (paired t-test). Additionally the baseline HbA1c was categorized and correlated to baseline HFs (Spearman Rho).In all eyes, HFs of various amounts were detected in the foveal and parafoveal area. The mean number of HFs reduced significantly from 16.02 to 14.32 in all patients (P = 0.000), whereas foveal thickness reduced from 445.5 to 373.9 μm (P = 0.000) and visual acuity increased from 62.0 to 66.0 ETDRS letters (P = 0.003). Regarding the three HF groups, a reduction of the level stages was observed in 43.1% (stable: 54.9%; more: 2.0%). This reflects a HF distribution change from 31.4% to 62.7% (group A), from 45.1% to 31.4% (group B), and from 23.5% to 5.9% (group C). The HbA1c correlated significantly to the overall HF amount at baseline (0.880; P = 0.000); however, no distinct overall correlation was found between the HF reduction and the course of visual acuity or retinal thickness. Only in cases of complete edema resolution (25%) did HFs reduce significantly (P = 0.008).As in wet AMD, HFs are frequently found in DME and behave similarly under anti-VEGF therapy. Thus, a HF reduction was observable mainly in cases of complete edema resolution; however, no distinct correlation with visual acuity was noticed, presumably mainly due to the enhanced inhomogeneity in the disease progress of DME. Interestingly, the baseline HF amount seems to correlate positively with HbA1c values indicating the severity of disease.

The purpose of this study was to analyze predictive factors for best-corrected visual acuity (BCVA) after anti-VEGF treatment in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).This prospective study enrolled treatment-naive patients with ME secondary to CRVO. BCVA, ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (SD-OCT) imaging were performed. SD-OCT was analyzed for integrity of the external limiting membrane (ELM), photoreceptor inner segments (IS), and outer segments (OS). Patients were treated with intravitreal bevacizumab (1.25 mg) or ranibizumab (0.5 mg). BCVA outcome was analyzed 4 weeks after the first injection.Sixty-two eyes of 62 patients (39 men, 23 women; mean age: 67 ±16 years) were included. In 55%, the ELM was intact. These eyes also showed intact photoreceptor IS/OS in horizontal and vertical single scans. Disturbed ELM was seen in 45% and was accompanied by focal disintegration of IS/OS. Four weeks after injection, 58% showed clinically relevant increases of BCVA (≥5 letters). Mean BCVA ranged from 20 to 86 letters. The mean BCVA increase was 18 ± 12 letters in eyes with intact ELM compared with 4 ± 10 letters with disturbed ELM (P0.001).Depending on the integrity of the outer retinal layers, the authors observed rapid and clinically relevant improvement in BCVA after the first anti-VEGF injection. In the development of an optimal treatment regime, the indication for treatment and re-treatment should be based on functional and morphologic findings, such as the deterioration of outer retinal layers. Intact ELM in SD-OCT imaging is associated with better visual outcomes after intravitreal anti-VEGF treatment in patients with ME secondary to CRVO.

To observe detailed changes in neurosensory retinal structure after anti-VEGF upload in age-related macular degeneration (AMD), by using spectral domain optical coherence tomography (SD-OCT).The retinal structure was observed by using SD-OCT in 61 patients, before and 1 month after the third ranibizumab injection (upload phase). The main focus of attention was a subjective determination of the amount and behavior of the numerous small, dense particles (SDPs) frequently observed within the outer and inner neurosensory layers in eyes with neovascular AMD. The Spearman rho correlation was used for statistical analysis.In all eyes, various amounts of SDPs were seen within the neurosensory layer of the foveal and parafoveal area. In 54%, the amount of SDPs became significantly less after ranibizumab therapy (stable, 41%; higher, 5%). SDP reduction correlated positively with the reduction of retinal disease according to OCT (P = 0.000), with central foveal thickness (P = 0.040), and with the improvement in best corrected visual acuity (BCVA; P = 0.006). The baseline amount of SDPs also correlated positively with the increase in BCVA (P = 0.005).The origin of the SDPs observable in SD-OCT is unknown, but they may represent migrating RPE cells or leukocytes, indicating a certain status of retinal inflammation. The amount of SDPs is substantially reduced after ranibizumab upload therapy and correlates positively with BCVA. Moreover, an initial large number of SDPs may indicate a higher grade of inflammation, but the presence of a high number enhances the effect of ranibizumab therapy. Thus, the amount of SDPs before treatment may be a predictive factor for the therapy's outcome.

It is unclear whether anti-VEGF monotherapy in age-related macular degeneration (AMD) achieves morphologic CNV regression or only stops further CNV growth. In this study, spectral domain-optical coherence tomography (SD-OCT) was used to image CNV structure before and after anti-VEGF treatment.Out of 107 consecutive patients, a prospective CNV evaluation was possible in 78 of them. Newly diagnosed CNV (classic CNV: n = 16; occult CNV: n = 54; minimal classic CNV: n = 8) due to AMD was imaged before and 4 weeks after anti-VEGF upload in three intravitreal injections of ranibizumab. Qualitative (structural changes) and quantitative measurements (diameter and thickness) of the CNV were obtained from the OCT images.Classic CNV components were observed above the RPE/photoreceptor complex, whereas occult CNVs stayed below. Of all postoperative OCTs, 59% revealed complete dry retinal structures, 27% showed reduced edema, and 14% showed edema remaining unchanged. Mean macular thickness decreased significantly from 427 to 303 microm (P = 0.000). Qualitatively, overall CNV architecture appeared to be unchanged in 78%, was reduced in thickness in 18%, and became larger in 4%. Quantitatively, in all CNV subtypes, the diameter of the CNV lesions (preoperative, 2813 microm; postoperative, 2804 microm) did not change after treatment (classic CNV: P = 0.390; occult CNV: P = 0.405, minimal classic CNV: P = 0.092) independent of postoperative retinal edema. The overall thickness of the lesion, however, was reduced from 205 to 175 microm (P = 0.000). Thickness reduction was significantly enhanced especially in CNV with classic components (n = 24; 252 to 197 microm; P = 0.000; reduction, 22%), whereas reduction was smaller but also significant in occult CNV (183 to 164 microm; P = 0.003; reduction, 10%).With SD-OCT, CNV size can be two-dimensionally determined and followed up after intravitreal anti-VEGF treatment. In only 4% of CNV was enlargement observed, whereas in 78%, CNV architecture appeared qualitatively unchanged, independent of retinal edema. Quantitative measurements underlined stable CNV diameters for all subtypes but revealed significant reduction of thickness especially for classic CNV components. In this series, ranibizumab monotherapy was able to morphologically stop further CNV growth but, in most patients, did not lead to a major regression of CNV, especially of its occult components.

Background So called 'dense deposits' in the retina of a patient suffering from membranoproliferative glomerulonephritis type II (MPGN II) were first demonstrated in 1989. Appearence of subretinal neovascular membranes associated with MPGN II in three patients was described in 1990. Patient and methods We present a 45-year-old male patient, whose insufficiency of the kidney due to a membranoproliferative glomerulonephritis type II required peritoneal dialysis and later transplantation. In both eyes fundus examination revealed typical disseminated, partly confluencing, drusen-like 'dense deposits' and exsudative degeneration of the macula due to subretinal neovascular membranes. Visual acuity was less than 20/400 and visual fields were reduced to small excentrics islands. There was an atrophy of the optic nerve with nearly extinguished VEP in both eyes. Conclusion Flecked changes of the retina called 'dense deposits' associated with membranoproliferative glomerulonephritis type II have to be differentiated in particular from drusen, as well as metabolic-toxic and degenerative retinopathy. Development of subretinal neovascular membranes is attributed to altered retinal pigment epithelium, similar to age-related macular degeneration. An atrophy of the optic nerve associated with this disease has not been described so far. It is possible that vascular damage because of hypertensive changes due to renal dysfunction is the reason for the optic nerve atrophy. With another hypothesis this could be caused by intraocular pressure due to a risen flow of water into the vitreous cavity following the altered osmotic gradient after peritoneal dialysis.

PURPOSE. To determine the efficacy of Tookad (WST09; NegmaLerads, Magny-Les-Hameaux, France) photodynamic therapy (T-PDT) by evaluating the angiographic and histologic closure of choroidal vessels at different radiance exposures, drug dosages, and intervals between photosensitizer injection and laser application in a rabbit model. METHODS. Chinchilla Bastard rabbits were injected intravenously with three different dye concentrations (2.5, 5, and 10 mg/kg) before application of light. In every group T-PDT was performed at four different times after injection: 5, 15, 30, and 60 minutes with different radiance exposures ranging from 200 to 3 J/cm 2 . Fundus photographs and fluorescein angiograms were obtained 90 minutes after injection. Follow-up angiographies were performed at days 1, 3, 7, and 14 after initial treatment. Histology was performed in selected cases immediately after treatment and on days 1, 3, and 7. RESUITS. Immediately after irradiation, most of the visible lesions were angiographically hyperfluorescent due to damaged vessel endothelium and associated RPE damage. Lesions from high-radiance exposures revealed immediate hypofluorescence, indicating vessel closure. Hypofluorescent lesions appeared mainly during day 1 (all lesions angiographically visible, some hypofluorescent) to day 3 (all lesions hypofluorescent) after treatment. At day 7, ophthalmoscopically visible hyperpigmentation took place in all lesions. ED 50 thresholds for angiographic hypofluorescence determined at day 3 after treatment with 2.5 mg/kg were 18.8 J/cm 2 (5 minutes), 62.0 J/cm 2 (15 minutes), and >100 J/cm 2 (30 minutes); with 5 mg/kg, 8.4 J/cm 2 (5 minutes), 22.8 J/cm 2 (15 minutes), 54.5 J/cm 2 (30 minutes), and >100 J/cm 2 (60 minutes); and with 10 mg/kg, 11.7 J/cm 2 (30 minutes) and 54.1 J/cm 2 (60 minutes). Histology of the angiographically hypofluorescent lesions revealed vessel thrombosis in all groups 1 hour after PDT up to 7 days after treatment. Sparing of photoreceptors indicated selectivity of T-PDT; however, slight damage was partly observable. After 7 days, localized proliferation of the RPE cells was noted and was enhanced 14 days after treatment. CONCLUSIONS. T-PDT has the potential to achieve selective choroidal vessel occlusion with proper parameter selection, such as (1) 2.5 mg/kg, 5 minutes, 100 J/cm 2 ; (2) 5 mg/kg, 5 minutes, 25 J/cm 2 ; or (3) 5 mg/kg, 15 minutes, 50 J/cm 2 ; however, slight damage to the photoreceptors cannot be ruled out. RPE proliferation indicates primary RPE damage due to PDT, also described with the use of all other photosensitizers.

The selective retina treatment SRT targets retinal diseases associated with disorders in the retinal pigment epithelium RPE. Due to the ophthalmoscopic invisibility of the laser-induced RPE effects, we investigate a noninvasive optoacoustic real-time dosimetry system. In vitro porcine RPE is irradiated with a Nd:YLF laser 527 nm, 1.7-s pulse duration, 5t o 40J, 30 pulses, 100-Hz repetition rate. Generated acoustic transients are measured with a piezoelectric trans- ducer. During 27 patient treatments, the acoustic transients are mea- sured with a transducer embedded in an ophthalmic contact lens. After treatment, RPE damage is visualized by fluorescein angiographic leakage. Below the RPE damage threshold, the optoacoustic transients show no pulse-to-pulse fluctuations within a laser pulse train. Above threshold, fluctuations of the individual transients among each other are observed. If optoacoustic pulse-to-pulse fluctuations are present, RPE leakage is observed in fluorescein angiography. In 96% of the irradiated areas, RPE leakage correlated with the optoacoustic defined threshold value. A noninvasive optoacoustic real-time dosimetry for SRT is developed and proved in vitro and during patient treatment. It detects the ophthalmoscopically invisible laser-induced damage of RPE cells and overcomes practical limitations of SRT for use in private practice. © 2005 Society of Photo-Optical Instrumentation Engineers.

Selective targeting of the retinal pigment epithelium (RPE) is a new strategy for treating certain retinal disorders while preserving adjacent photoreceptors. The treatment currently relies on a complex laser system to produce the required microsecond pulse structure. In our new approach, we scan the focus of a continuous-wave (cw) laser beam with acousto-optic deflectors to produce microsecond-long exposures at each RPE cell. Experiments were performed in vitro with a bench-top scanner on samples of young bovine RPE and in vivo on Dutch belted rabbits with a slit-lamp adapted scanner. Effective dose 50% (ED50) for RPE damage was determined in vitro by fluorescence cell viability assay and in vivo by fluorescein angiography. Damage to individual RPE cells was achieved with laser power on the order of 100 mW. Using separated scan lines, we demonstrate selectivity in the form of alternating lines of dead and surviving cells that resemble the scan pattern. Selectivity is also shown by the absence of retinal thermal coagulation in vivo. Selective RPE damage is feasible by rapidly scanning a cw laser beam. The scanning device is an attractive alternative to conventional laser coagulation and pulsed laser targeting of the RPE.

BACKGROUND Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER NCT02164604 ; Date of registration: 13.06.2014.

Background The majority of cases of endophthalmitis are caused by exogenous pathogens; only 5–10 % are of endogenous origin. One cause of these rare cases of endogenous endophthalmitis is Listeria monocytogenes. Twenty-six cases of endophthalmitis due to this pathogen have been published over the last twenty years. The aim of this review is to summarize the main risk factors and common clinical findings of endogenous endophthalmitis due to Listeria monocytogenes. Case presentation We report on a 62-year-old female presenting with a sterile hypopyon iritis with secondary glaucoma and an underlying rheumatoid disease. In microbiological analysis we identified Listeria monocytogenes. Further we searched through all published cases for typical signs, risk factors, details of medical and surgical treatment and outcome of endogenous endophthalmitis due to this rare pathogen. Ocular symptoms in almost all of these published cases included pain, redness of the eye, and decreased vision. Main clinical features included elevated intraocular pressure and fibrinous anterior chamber reaction, as well as a dark hypopyon. While the infection is typically spread endogenously, neither an exogenous nor endogenous source of infection could be identified in most cases. Immunocompromised patients are at higher risk of being infected than immunocompetent patients. The clinical course of endophthalmitis caused by Listeria monocytogenes had different visual outcomes. In some cases, the infection led to enucleation, blindness, or strong visual loss, whereas most patients showed a tendency of visual improvement during therapy. Conclusion Early diagnosis and treatment initiation are crucial factors in the outcome of endogenous endophthalmitis caused by Listeria monocytogenes. This possible differential diagnosis should be kept in mind while treating patients with presumable sterile hypopyon and anterior uveitis having a high intraocular pressure. A bacterial source should be considered with a prompt initiation of systemic antibiotic treatment, mainly in immunocompromised patients, who develop endogenous anterior uveitis. An appropriate microbiological sampling is essential to detect atypical microorganisms and to choose an effective antibiotic treatment.