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Background and Objectives: 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. Study Design/Materials and Methods: 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 ED50 vs. ophthalmoscopic ED50) as well as the safety range (SR; angiographic ED84 vs. ophthalmoscopic ED16) between both thresholds were calculated. Selected laser lesions were evaluated by histology. Results: Generally, the ED50 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 ratio > 2. Independently of pulse duration, histological examination of laser sites 1 hour after irradiation revealed widely intact photoreceptors, while the underlying RPE was damaged. Conclusions: 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. Lasers Surg. Med. 34:206–215, 2004. 2004 Wiley-Liss, Inc.

* 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.]

A2-E is the dominant fluorophore of lipofuscin in the retinal pigment epithelium. In an in-vitro setup, we determined the temperature-dependent changes of the A2-E fluorescence with the aim of also assessing the potential value of such measurements for determining retinal temperature by autofluorescence measurements during laser treatment.A2-E was biosynthesized and diluted in Dimethyl Sulfoxide (DMSO) to 1 microM. Fluorescence measurements were performed with a photospectrometer under various temperatures ranging from 20 degrees C to 75 degrees C. Autofluorescence was excited at 467 nm, and emission was detected around 632 nm.A2-E fluorescence intensity showed a linear decrease concomitant with temperature increment. At 75 degrees C, the fluorescence intensity decreased by 43% compared to at 20 degrees C. Fluorescence intensity was completely reversible dependent on the temperature, which cannot be explained by thermal A2-E alteration.If the A2-E temperature-dependent fluorescence in-vitro is transferable to human fundus auto-fluorescence, then it may be possible to apply an autofluorescence-based online detection device for noninvasive determination of fundus temperature during in vivo laser treatment. This is of clinical relevance, especially for the application of photodynamic therapy (PDT) and transpupillary thermotherpy (TTT).

Purpose: Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. Material and Methods: In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. Results: Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. Conclusion: SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases.

Hintergrund. Die selektive RPE-Laser-Behandlung ist eine neue Technik, mit der selektiv das RPE geschadigt wird und die neurosensorische Netzhaut intakt bleibt. Ein Problem stellt die ophthalmoskopische Nicht-Sichtbarkeit der Laserlasionen dar. Es war daher Ziel dieser Studie zu untersuchen, ob die Fundus-Autofluoreszenz (AF), die ihren Ursprung im Lipofuscin der RPE-Zellen hat, durch den Laserschaden verandert wird, so dass dieses als nichtinvasive Behandlungskontrolle verwendet werden kann. Material und Methode. Es wurden 26 Patienten mit makularen Erkrankungen [Diabetische Makulopathie (DMP), Drusenmakulopathie (AMD) und Retinopathia centralis serosa (RCS)] mit kurzen repetitiven Laserimpulsen (800 ns) eines grunen Nd:YAG Lasers (Parameter: 532 nm, 100 und 50 Pulse bei 500 und 125 Hz; Spotdurchmesser: 200 μm, Pulsenergien: 70–175 μJ) behandelt. Die AF wurde mit 488 nm angeregt und durch einen Sperrfilter uber 500 nm detektiert (HRA, Heidelberg Engineering). Die Patienten wurden postoperativ zu unterschiedlichen Zeitpunkten mittels Ophthalmoskopie, Fluoreszenzangiographie und AF-Messungen untersucht (1 h; 1,6 Wochen; 3, 6, 12 Monate). Ergebnisse. Die Fluoreszenzangiographie zeigte eine Leckage der bestrahlten Areale uber eine Woche. Keine der Laserlasionen war wahrend der Behandlung ophthalmoskopisch sichtbar. Eine Identifikation der Laserherde war durch AF-Messungen moglich, die einen Intensitatsabfall bei 22 von 26 Patienten, insbesondere denen mit RCS und AMD, zeigten. Die Lasionen waren direkt nach der Behandlung als hypoautofluoreszente Laserspots sichtbar. Nach einer Woche wurden die Herde hyperautofluoreszent. Bei Patienten mit DMP waren die Messungen aufgrund von Odem und groserer Netzhautdicke in einigen Fallen nicht erfolgreich. Schlussfolgerung. Durch AF-Messungen konnen ophthalmoskopisch nicht sichtbare Lasionen nach selektiver RPE-Laser-Behandlung, insbesondere bei Patienten ohne Netzhautodem, dargestellt werden. Daher hat die AF das Potenzial, die invasive Fluoreszenzangiographie zur Verifikation des Lasererfolges in vielen Fallen zu ersetzen.

* BACKGROUND AND OBJECTIVE: In both clinical and animal studies, it has been shown that repetitive short laser pulses can cause selective retinal pigment epithelium damage (RPE) with sparing of photoreceptors. Our purpose was to determine the ophthalmoscopic and angiographic damage thresholds as a function of pulse durations by using different pulsed laser systems to optimize treatment modalities. * MATERIALS AND METHODS: Chinchilla breed rabbits were narcotized and placed in a special holding system. Laser lesions were applied using a commercial laser slit lamp, contact lens, and irradiation with a frequency-doubled Nd: YLF laser (wavelength: 527 nm; repetition rate: 500 Hz; number of pulses: 100; pulse duration: 5 µß, 1.7 µß, 200 ns) and an argon-ion laser (514 nm, 500 Hz, 100 pulses, 5 µß and 200 ms). In all eyes, spots with different energies were placed into the regio macularis with a diameter of 102 µp? (tophat profile). After treatment, fundus photography and fluorescein angiography were performed and radiant exposure for ED50 damage determined. Speckle measurements at the fiber tips were performed to determine intensity peaks in the beam profile. * RESULTS: Using the Nd:YLF laser system, the ophthalmoscopic ED50 threshold energies were 25.4 µ] (5 µß), 32 µ] (1.7 µß), and 30 µ] (200 ns). The angiographic ED50 thresholds were 13.4 µ] (5 µ8), 9.2 µ] (1.7 µß), and 6.7 µ] (200 ns). With the argon laser, the angiographic threshold for 5 µß pulses was 5.5 µ). The ophthalmoscopic threshold could not he determined because of a lack of power; however, it was >12 µ}. For 200 ms, the ED50 radiant exposures were 20.4 mW ophthalmoscopically and 19.2 mW angiographically. Speckle factors were found to be 1.225 for the Nd: YLF and 3.180 for the argon laser. Thus, the maximal ED50-threshold radiant exposures for the Nd:YLF were calculated to be 362 mj/cm2 (5 µß), 478 mj/cm2 (1.7 µ-s), and 438 mj/cm2 (200 ns) ophthalmoscopically. Angiographically, the thresholds were 189 mj/cm2 (5 µß), 143 mj/cm2 (1.7 µ-s), and 97 mj/cm2 (200 ns). For the argon laser, the maximal ED50 radiant exposure threshold was 170 mj/cm2 angiographically. * CONCLUSION: The gap between the angiographic and the ophthalmoscopic thresholds for the 200 ns regime (4.5 times above angiographic ED50) was wider than for the 1.7 µ$ regime (3.3 times above the angiographic ED50). This would suggest the appropriate treatment would be 200 ns pulses. However, histologies have yet to prove that nonvisible mechanical effects increase with shorter pulse durations and could reduce the "therapeutic window." When comparing the thresholds with 5 µß pulses from the argon and Nd:YLF laser, it demonstrates that intensity modulations in the beam profile must be considered. [Ophthalmic Surg Lasers 200233:400-409]

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.

Hintergrund. Die konventionelle Behandlung des Zentralarterienverschlusses (ZAV) fuhrt in der Regel zu unbefriedigenden Ergebnissen. Eine invasive Therapiemoglichkeit stellt die selektive intraarterielle Fibrinolyse (IF) der A. ophthalmica dar. Zur Nutzen-Risiko-Abwagung beider Verfahren analysierten wir retrospektiv die Akten von 62 Patienten mit ZAV. Weiterhin wurde das Risikospektrum fur einen ZAV untersucht. Material und Methode. Krankenakten uber einen Zeitraum von 5 Jahren wurden ausgewertet und Patienten nach IF (n=17) und nach konventioneller Therapie (Drucksenkung, rheologische Masnahmen; n=45) hinsichtlich des Visus verglichen. Ausschlusskriterien fur die IF waren: Eintreffen spater als 8 h nach dem Verschlussereignis, medizinische Kontraindikationen wie Blutungsneigung, vorangegangene Operationen und hohes Alter (≥85 Jahre). Die IF wurde mit Urokinase (n=7) oder tPA (n=10) durchgefuhrt. Ergebnisse. Bei 22 von 62 Patienten (35%) wurde eine IF erwogen, wobei in funf Fallen aufgrund einer Gefasstenose darauf verzichtet werden musste, so dass insgesamt 17 Patienten eine IF erhielten. Bei 40 Patienten (65%) wurde primar keine IF aufgrund von Ausschlusskriterien angestrebt. Diese waren wie folgt: 47% (19/40) trafen spater als 8 h nach dem Verschlussereignis ein, 17% (7/40) stimmten der IF nicht zu, 15% (6/40) wiesen medizinische Kontraindikationen auf, 13% (5/40) waren uber 85 Jahre. Bei 8% (3/40) wurde ein IF nicht in Erwagung gezogen, da ein zilioretinales Gefas mit noch gutem Visus vorlag oder sich wahrend der Untersuchung ein spontaner Visusanstieg ergab. Vier von 17 Patienten mit IF zeigten eine Visusverbesserung um mindestens zwei Zeilen, 12/17 hatten keine Veranderung, und 1/17 wies eine Verschlechterung um mindestens zwei Zeilen auf. Von den konservativ behandelten Patienten erreichten 16/45 eine Visusverbesserung um mindestens zwei Zeilen, bei 29/45 ergab sich keine Visusanderung. Bei drei Patienten mit IF musste aufgrund einer akuten Halbseitensymptomatik die Therapie abgebrochen werden. Haufigster Risikofaktor fur den ZAV war der systemische Hypertonus bei 32% aller Patienten gefolgt vom Nikotinabusus (16%). Schlussfolgerung. Insgesamt zeigte sich, dass ein Grosteil der Patienten mit ZAV fur eine eventuelle IF als Therapie der Wahl zu spat die Klinik erreicht. Bezogen auf den Visus ergab sich jedoch statistisch kein Unterschied zwischen IF und konventioneller Behandlung. Aufgrund des Komplikationsrisikos bei der IF sollte eine prospektive Studie den Stellenwert der IF festlegen. Konsequente Blutdruckeinstellung ist als notwendige Prophylaxe gegen einen ZAV anzusehen.

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.

Hintergrund: Eine isolierte Aspergillose des Sinus sphenoidalis ist eine schwierige Diagnose, da die oftmals missgedeuteten Beschwerden und die klinischen Symptome dieser seltenen Erkrankung sich erst spat entwickeln und den Patienten zuerst auch zum Augenarzt fuhren konnen. Da bei den in der Regel immuninkompetenten Patienten auch eine Lebensbedrohung mit haufig letalem Ausgang besteht, ist eine dringende Abklarung und Behandlung indiziert. Kasuistik: Wir berichten uber einen immunkompetenten Patienten, bei dem nach externer Voroperation einer Mukozele eine Aspergillusinfektion der Nasennebenhohlen und Orbita zu einem akuten einseitigen Visus- und Gesichtsfeldverlust fuhrte (Visus 0,1). Eine sofortige antimykotische systemische Therapie wurde eingeleitet und die Orbita und der Canalis opticus operativ von der Mykose saniert. Dabei zeigte sich der N. opticus in der Orbitaspitze zirkular durch den Pilz ummauert. Nach der Operation kam es innerhalb von 2 Wochen langsam zu einer vollstandigen visuellen Rehabilitation (Visus 1,0) und Normalisierung des Gesichtsfeldes seit nun uber einem Jahr. Schlussfolgerung: Der Leitbefund eines in der Anamnese einseitigen Visusverlustes und HNO-arztliche Voroperationen in Zusammenhang mit dem Symptom eines persistierenden Kopfschmerzes kann aus augenarztlicher Sicht den Verdacht auf eine Aspergillusinfektion nahe legen. Die richtige Diagnose bei dieser seltenen Erkrankung – insbesondere bei immunkompetenten Patienten – sollte moglichst schnell gestellt sein, um einen irreversiblen Sehverlust vermeiden zu konnen und bei bereits fortgeschrittenem Stadium der Erkrankung die ernste Lebensbedrohung des Patienten durch Pilzmeningitis zu verhindern.

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.

BACKGROUND After conventional buckling procedures for pseudophakic retinal detachment the primary reattachment rate is 60 to 90% according to literature. Primary vitrectomy may be advantageous in these cases. The purpose of this study was to investigate the spectrum and role of potential side effects like anisometropia and diplopia, to find arguments for or against primary vitrectomy. Also risk factors for pseudophakic retinal detachment were analyzed in our study group, because they may be different from former studies, which were mostly undertake at the time of ec cataract extraction. PATIENTS AND METHODS The data from 115 patients (120 eyes) with pseudophakic retinal detachment, who undergone buckling procedure between 1991 and 1996 were retrospectively reviewed. We analyzed the retinal reattachment rate, choroidal detachment, postoperative visual acuity, refraction, occurrence of diplopia, anisometropia and metamorphopsia. RESULTS The primary retinal reattachment rate was 83.3%. There was a retinal redetachment rate of 16.7%. The primary PVR-rate was 4.2%. After the first reoperation an reattachment rate of 91.6% could be achieved, after the second one an overall rate of 95%. A choroidal detachment occurred in 29.2%. Postoperatively (26.5 months +/- 17.2) we found a cellophane maculopathy in 26.5% with consecutive metamorphopsia in 12.1%. 13 patients (15.9%) complained about diplopia, which had to be corrected by operation in 2 cases and prismatic glasses in 4 cases. Anisometropia could be deserved in 16.4%. The buckling procedures caused refractive changes of -1.80 dpt +/- 1.78 after an encircling band and +0.38 dpt +/- 1.01 after a plombage (average -1.05 +/- 1.86). 20% of patients treated with an encircling band developed anisometropia and only 8.3% of patients with a plombage. Postoperatively the visual acuity raised significantly from 0.3 to 0.6 (median). Best visual recovery could be observed in patients, who underwent only one operation. CONCLUSIONS The primary retinal reattachment rate in pseudophakic retinal redetachment after conventional buckling procedures in our patients are comparable to those in the literature. In spite of phacoemulsification the risk-factors for pseudophakic retinal detachment has not changed. A considerable number of patients complained about postoperative complications like anisometropia and diplopia, which could be avoided by primary vitrectomy. To compare anatomic and functional results of both procedures a randomized prospective study should be undertaken.

BACKGROUND: Severe open globe injuries are frequent emergencies in an ophthalmologic clinic and required immediate operation. The extent of these injuries is various depending on the mechanism of the injury and involvement of ocular tissue. In many cases a full visual rehabilitation can be achieved but in a lot of cases blindness results. To prevent such severe eye injuries it is important to judge the leading injury mechanisms. For this we collected our data about open globe injuries. PATIENTS AND METHODS: Retrospectively we collected the data from 103 consecutive patients in the year 1996 and 1997, presenting with an open globe eye injury followed by operation. The data contained personal patients data, information about mechanism of injury, visual acuity, operation and rehabilitation. Statistical analysis was performed using binomimal-test and t-test for paired and unpaired samples (p < 0.05). RESULTS: 85.4% were male. Most of the injuries happened at home (38%) and at the working place (31%). Assaultive injuries happened in 6.8%. 35% of all patients were craftmen (mechanics, electricians, or the locksmith were preferred). Pensioners were affected in 14.6% of all cases followed by small children (7.8%) and school children (7.8%). In 50% of all cases metal and glass were responsible for the trauma, explosions were noticed in 8.7%. An intraocular foreign body was found in 37.9%. In 62% of all cases no second operation was necessary. An enucleation during the follow-up was performed in 2 cases. CONCLUSION: At least a third of all severe eye injuries would have been preventable. Concerning the non-preventable injuries accidents at home and in children were predominating. The rate of the open globe injuries was 2.32 in 100.000 people, which is about the same like in US-American studies. Most of the injuries happened at home because of carelessness and would have been avoidable. The rate of injuries at the working place is significantly higher than in the USA but there were significantly more gun-shot-injuries or offensive accidents abroad. The rate of accidents at home and in traffic were the same. We think that public campaigns and prevention strategies can help to reduce the potential risk of severe eye injuries.

Background The circumscript cutaneous sclerosis is an inflammato-edematous erythema of the skin, usually leading to a plaque-like sclerosis and cutaneous atrophy. The etiology of this disease remains unknown, but some authors presume a systemic infection with Borrelia burgdorferi as the underlying pathological condition. Patient We present a case of a 66-year-old male patient who suffered from episcleritis of his left eye. Funduscopy showed an unilateral papillary edema. Visual acuity was 1.0. The patient had multiple erythemata of the skin of the body-trunk and the arms. On histological examination the lesions were compatible with circumscript sclerosis. Neurological examination was normal. Brain imaging (MRI), CSF examination and serology showed no pathological findings, although the patient presented with raised antibodies against Borrelia burgdorferi (IgG positive, IGM negative). Intravenous antibiotic treatment and topical steroids for three weeks resulted in a complete recovery of the scleritis, but had no effect on the papillary edema. Conclusion Inflammatory pathological findings of the eye can be associated with circumscript sclerosis, a disease, that is normally limited to the skin. The pathological mechanism remains unclear. The presumption of an underlying borreliosis could not be confirmed in this case.

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.

BACKGROUND The Schimmelpenning-Feuerstein-Mims-syndrome is a phacomatosis of unknown pathogenesis and is presumed to be based on alterations in early embryogenesis. The syndrome is expressed by congenital nevi characterized by hyperplasia of the sebaceous glands and papillary acanthosis. Other manifestations include ophthalmic, neurologic, cardiovascular, skeletal and urogenital involvement. Eye-findings are variable and may affect all parts of the organ. All patients have a nevus sebaceus of the skin and many of them are described to suffer from seizures and/or mental retardation and/or abnormalities of the central nervous system/skull. The atypical constellation of findings in our case makes it of interest to report and give a short review. PATIENT A 17-year-old boy with Schimmelpenning-Feuer-stein-Mims-syndrome has been followed up by us since birth. RESULTS Beside an unilateral combined nevus sebaceus and verrucosus of the face, neck and skull and an aplasia of a rib there were marked ocular symptoms. The affected right eye showed a dermoid, a wide lid-opening, microcornea, stenosis of the lacrimal ducts, a high myopic fundus, the optic disc with an inverse conus and a posterior scleral staphyloma. There were no seizures or mental retardation combined with normal radiologic findings of the central nervous system and the skull. CONCLUSION The presented findings in our patient with Schimmelpenning-Feuerstein-Mims-syndrome emphasized the high variability of the expression of this disease, which may lead to difficulties in establishing correct diagnosis to prevent unnecessary examinations and inadequate therapies.

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.

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.

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.

To identify differences in extracellular matrix contents between idiopathic epiretinal membranes (IEM) of cellophane macular reflex (CMRM) or preretinal macular fibrosis (PMFM) type.Idiopathic epiretinal membranes were analysed by light and quantitative transmission electron microscopy, immunohistochemistry and Western blotting. Substantial differences between CMRM and PMFM were observed regarding the nature of extracellular fibrils. In CMRM the fibrils were thin, with diameters between 6 and 15 nm. Between the fibrils, aggregates of long-spacing collagen were observed. In PMFM the diameters of fibrils measured either 18-26 or 36-56 nm. Using immunogold electron microscopy, 6-15 nm fibrils in CMRM were labelled for collagen type VI, while the fibrils in PMFM remained unstained. Using Western blotting and immunohistochemistry, a strong signal for collagen type VI was observed in all CMRM, while immunoreactivity was weak or absent in PMFM. In contrast, PMFM showed immunoreactivity for collagen types I and II, which was weak or absent in CMRM. Both types of membranes showed immunoreactivity for collagen types III and IV, laminin and fibronectin with similar intensity.The presence of high amounts of collagen type VI in CMRM and the relative absence of collagen types I and II is the major structural difference to PMFM.

An unintentional embolization of retinal arteries is rare and has been documented as a complication after embolization of arteries supplying head and neck tumors. However, occlusion of the central retinal artery with severe loss of vision has never been reported to be a complication from embolization of tumor-supplying ethmoidal branches of the ophthalmic artery. A 40 year-old male patient with a history of right nephrectomy for renal cell carcinoma underwent preoperative radiological embolization of an ethmoidal metastasis after having experienced a life-threatening sinus bleeding. Repeated probing of the ophthalmic artery with an endovascular microcatheter for particle embolization of the tumor-supplying arteries was performed under anticoagulation with heparin. Postoperatively, a standard ophthalmological examination including extended vascular evaluation by angiography was performed. After extended probing of the ophthalmic artery a marked reduction in its blood flow occurred. Despite post-interventional imaging showing persisting perfusion of the central retinal and ciliary arteries, the patient developed complete loss of vision on this side four days later. At this time fundoscopy and fluorescein angiography revealed a recanalized central artery occlusion, while indocyanin angiography showed infarctions of the choroid. Radiological intervention via the ophthalmic artery can result in complete loss of vision, even after limited and transient obstruction of the vessel.

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 compare the efficacy of pars plana vitrectomy (ppV) with intravitreal injection of recombinant tissue plasminogen activator (rtPA) and gas versus ppV with subretinal injection of rtPA and intravitreal injection of gas.Nonrandomized, retrospective, interventional, comparative consecutive series including 47 patients with submacular hemorrhage. Eighteen patients were treated with ppV, intravitreal injection of rtPA and 20% SF6 gas [group A: mean age 78 years, mean duration of symptoms 6.6 days, 15 age-related macular degeneration (AMD), three retinal arterial macroaneurysm (RAMA)]. Twenty-nine patients were treated with ppV, subretinal injection of rtPA and intravitreal injection of SF6 gas (group B: mean age 75 years, mean duration of symptoms 5.9 days, 26 AMD, two RAMA, one blunt ocular trauma). The main outcome measure was complete displacement of submacular hemorrhage from the fovea.Complete displacement of submacular hemorrhage was achieved in less patients in group A (22%) than in group B (55%) (p = 0.025). In group A, mean best-corrected visual acuity (BCVA) change was logMAR -0.14, standard deviation (SD) = 0.64, and in group B logMAR -0.32, SD = 0.68 without statistically significant difference between the two groups (p = 0.2, Mann-Whitney test). Complications (retinal detachment, vitreous hemorrhage, and recurrence of submacular hemorrhage) were more frequent in group B than in group A.ppV with subretinal injection of rtPA and intravitreal injection of gas was more effective than ppV with intravitreal injection of rtPA and gas in terms of complete displacement of submacular hemorrhage; however, it may be associated with a higher rate of postoperative complications. Functional improvement in the majority of patients suggests the absence of direct retinal toxicity of subretinally applied rtPA.

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.

Ascorbic acid is known to influence proliferation and functional properties of several cell types and is therefore widely used in tissue engineering. In this study, the effect of ascorbic acid on the proliferation and functional properties of hyalocytes was evaluated. Hyalocytes were cultured with different amounts of ascorbic acid in classical two-dimensional (2-D) cultures and a three-dimensional (3-D) pellet culture system. Ascorbic acid enhanced hyalocyte proliferation dose-dependently at concentrations between 0.1 and 3 microg/mL; proliferation was constant over a wide concentration range up to 150 microg/mL, concentrations of 500 microg/mL showed toxic effects. In 2-D hyalocyte culture, the accumulation of glycosaminoglycans (GAG) and collagens increased in response to ascorbic acid supplementation of 10 or 200 microg/mL. Normalized to the cell number, GAG production was not influenced, whereas collagen production increased. These results could be verified in a pellet-like 3-D culture system. Ascorbic acid also influenced hyalocytes on the mRNA level; the expression of COL11A1 was clearly enhanced by ascorbic acid. To conclude, ascorbic acid modulates proliferation and collagen accumulation of hyalocytes; it also influences mRNA expression of the cells. Taken together with the fact that ascorbic acid is present in high concentrations in the vitreous body, this vitamin seems to be an important factor for in vitro hyalocyte culture.

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.

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.

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.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.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%).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.

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.