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Calcification of hydrophilic intraocular lenses (IOL) is a rare complication. We report about the uneventful replacement of an opacified hydrophilic IOL. The patient presented 4 years after uneventful cataract surgery with a reduction of visual acuity due to calcification of the IOL. Macroscopically, the optic and the haptics were opacified. Light and scanning electron microscopy revealed granular deposits on the external surface of the IOL and numerous fine granular deposits within the optic of the IOL which were distributed in a line parallel to the surface of the IOL.

For human trials with retinal prostheses it is mandatory to develop procedures to safely explant and possibly reimplant the devices. This prompted us to investigate in a small exploratory study the safety of repeated transchoroidal implantation and explantation procedures of complex subretinal devices in laboratory animals.Repeated transchoroidal surgery was performed in four rabbits. The rabbits were examined by clinical examination and funduscopy. Function was assessed by electroretinography and cortical recordings following light and subretinal electrical stimulation. Sections of the retina and of the implantation channel were examined by light microscopy.Using the same access route, repeated transchoroidal subretinal implantation surgery was successfully performed in all cases. Fixation of implants was stable for up to 13 months; retinas remained attached at all examination dates. Electroretinograms and visual evoked cortical potential proved retinal and visual pathway integrity. Subretinal electrical stimulation elicited retinal and cortical responses. While retinal morphology at earlier stages was found to be essentially unaltered, atrophic disorganization in the region of the subretinal channel was observed after 10 months and after subretinal electrical stimulation.Repeated transchoroidal surgery can be safely performed for implantation, explantation, and reimplantation of subretinal devices in rabbits. With modifications, we believe the technique can be applied in human surgery.

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

To investigate the safety and performance of perfluorohexylethan (O62), a partially fluorinated alkane, as an intraoperative tool and heavy ocular endotamponade in complex vitreoretinal surgery.In a prospective clinical study, O62 was used as a postoperative ocular endotamponade in 11 eyes of 11 patients after pars plana vitrectomy for the following inferior pathologic conditions, proliferative vitreoretinopathy (n = 8), rhegmatogenous retinal redetachment with inferior tears (n = 1), and inferior giant tear (n = 2). The median duration of the O62 tamponade was 43 days (range, 17-55 days), and the median follow-up period after removal of the tamponade was 16 months.The initial postoperative retinal attachment rate was 100%. In 7 of 11 eyes, the retina remained attached during the O62 tamponade and after its removal. During the tamponade period, no epiretinal membrane formation or macular pucker was observed in these seven eyes. Recurrent retinal detachments with proliferative vitreoretinopathy developed in 4 of 11 eyes under the tamponade. The median follow-up after removal of O62 was 16 months. A secondary cataract developed in all five phakic eyes. Severe emulsification was noted in all patients starting in the second week after surgery causing a decrease of visual acuity and a significantly reduced funduscopic view. In the early postoperative period, a marked inflammatory reaction in the anterior segment was seen in all patients. Slightly whitish precipitates were noted in 2 of 11 eyes. A transient increase in intraocular pressure up to 35 mmHg was observed in 2 of 11 eyes.O62 showed good tamponade properties for the inferior retina over 6 weeks. However, its use as a postoperative retinal tamponade is limited by its severe emulsification propensity and unclear inflammatory potential.

Background: To evaluate the ocular toxicity of trypan blue (TB) injected into the vitreous cavity of rabbit eyes. TB is a dye that could be useful for staining epiretinal membranes during vitrectomy surgery. Methods: Ten New Zealand White (NZW) rabbits underwent gas-compression vitrectomy. Rabbits were divided into three groups to receive injections of 0.1 ml basic salt solution, 0.1 ml of a 0.06% TB solution or 0.1 ml of a 0.2% TB solution. Ocular toxicity was assessed by slit-lamp biomicroscopy, ophthalmoscopy, electroretinography and histology. Results: Transient posterior capsule opacification was noted in all animals. No significant reductions in a-wave or b-wave amplitudes were found in any of the animals. Light and electron microscopic examination of the inferior retina in the 0.2% TB-treated eyes showed damaged photoreceptors and marked disorganization. Immunohistochemical staining for rhodopsin was strongly reduced in those sections and staining for proliferation with Ki-67 was positive. No histological abnormalities were found in the upper retina of the 0.2% TB-treated eyes or in any part of the retina of the 0.06% TB-treated or control eyes. No histological abnormalities were found in any of the anterior chamber angle specimens. Conclusions: Although no signs of toxicity were found after the prolonged presence of TB at a concentration of 0.06% in the vitreous cavity of rabbit eyes, marked damage occurred in the lower retina of 0.2% TB-treated eyes. The short-term presence of TB at a concentration of 0.06% in the vitreous cavity is harmless to the rabbit eye but a higher concentration of TB could be unsafe.

Es wird eine Ubersicht uber den Stand der Entwicklungen eines subretinalen, elektronischen Mikrophotodioden-Arrays gegeben, mit dem degenerierte Photorezeptoren ersetzt werden konnen. Verschiedene Prototypen wurden entwickelt, getestet und bei verschiedenen Versuchstieren bis zur Dauer von 18 Monaten implantiert. Die Tatsache, dass mit subretinalen Elektroden elektrische Antworten vom visuellen Kortex von Schweinen abgeleitet werden konnen und Antworten auch in vitro in Netzhauten von Ratten mit Netzhautdegenerationen nachweisbar sind, zeigt die Sinnhaftigkeit dieses Ansatzes. Allerdings sind noch wichtige Fragen der Biokompatibilitat, der Langzeitstabilitat und der Art des vermittelbaren Bildeindrucks zu bearbeiten, bevor an einen Einsatz beim Menschen zu denken ist.

Purpose Development of synthetic eye prosthesis to provide a long term stable keratoprostesis Methods Synthetic hydrophobic and hydrophilic biomaterials were selectively modified by physical and chemical nanotechnological methods. The modified biomaterials were tested in cell culture experiments (fibroblasts L929 and primary epithelial cells, porcine) and implanted into rabbits eyes. The hydrophobic material was implanted finally into eyes of ultima ratio patients. Results After very successful in vitro evaluation, keratoprostheses were implanted to rabbit eyes (New Zealand white rabbit) and showed excellent in vivo performance in the animal experiment.As for the hydrophibic material, no adverse reaction was observed after follow up of 2.5 years in human eyes. Conclusion We could develop a new keratoprosthesis which is well tolerated in human eye.

Laser-assisted in situ keratomileusis (LASIK) requires precise corneal flap cutting. Especially the creation of thin flaps has recently gained importance for thin-flap LASIK. Currently, there is a trend towards faster femtosecond lasers that can produce flaps in a short period of time. We analyzed flaps created with a 200-kHz femtosecond laser concerning their cut precision, morphology, and histology.Femtosecond laser flap cutting was performed on 36 porcine cadaver eyes using the prototype 200-kHz femtosecond laser UltraFlap (WaveLight GmbH, Erlangen, Germany). The eyes were assigned to 3 thickness groups, with a cut depth of 100 µm, 130 µm, or 180 µm, respectively. Additionally, flap diameters were varied, ranging from 8.0 mm to 9.5 mm. Flap thicknesses were determined with a micrometer gauge. Flap diameters were measured with a sliding caliper. Furthermore, flaps were created for histologic examination.There were no complications during flap creation. The mean flap thickness and standard deviation was (in micrometers) 96.33 ± 7.45 (intended thickness: 100), 134.67 ± 4.96 (intended thickness: 130), and 174.59 ± 9.35 (intended thickness: 180), respectively. The flap diameter revealed a mean (in mm) of 8.03 ± 0.15 (intended diameter: 8.0), 8.56 ± 0.10 (intended diameter: 8.5), 9.09 ± 0.10 (intended diameter: 9.0), and 9.54 ± 0.15 (intended diameter: 9.5), respectively. Histologic examination showed very little to almost no changes in the structure of the corneal stroma.Flap creation could be performed easily without any complications. The morphology and accuracy of the cuts were very reliable and precise. Histology showed a smooth cut.

Purpose To evaluate the possible side effects on human and porcine cadaver eyes induced by excimer laser ablation with 3 ablation frequencies. Setting Augenklinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany. Methods Central epithelial abrasion was performed on porcine and human donor eyes. Next, the porcine eyes were photoablated (−9.00 diopters) at 1 of 3 frequencies (200 Hz, 500 Hz, or 1000 Hz) using a prototype 1000 Hz excimer laser. The human eyes were ablated at 1000 Hz. The surface of the stroma as well as the structure and ultrastructure of the corneal cells and stroma were examined using light microscopy, transmission electron microscopy, and scanning electron microscopy (SEM). Special attention was given to the detection of potential thermal damage and the evaluation of corneal smoothness. Results Histopathologic examination showed very low to almost no differences between the 3 repetition rates. In all cases, SEM showed an equally smooth surface. Conclusions The structural and ultrastructural evaluation of corneas treated with ablation frequencies of 200 Hz, 500 Hz, and 1000 Hz showed no specific side effects associated with the high repetition rates. The ablation quality was comparable in the 3 frequency groups. However, the treatment time was significantly less with a high repetition rate, indicating the clinical potential in refractive surgery of excimer lasers with a repetition rate of 1000 Hz. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

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.

Background: Translocation of a free autologous graft consisting of retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in patients with exudative age-related macular degeneration is currently being evaluated in clinical practice. Angiographic studies in these patients suggest that their grafts become revascularised. Aim: To investigate the histological evidence of revascularisation of the graft in a porcine model. Methods: In 11 pigs (11 eyes), an RPE-choroid graft was translocated from the mid-periphery to an intact or an intentionally damaged RPE and Bruch's membrane at the recipient site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections were evaluated using immunohistochemistry. Results: Bridging vessels between recipient layer and graft were identified from 1 week to 3 months after surgery. This reconnection occurred regardless of whether the Bruch's membrane of the recipient site was left intact or intentionally damaged at the time of transplantation. The vasculature of the graft appeared open and perfused. Vessels with transcapillary pillars and conglomerates of small new vessels were present in the graft. Conclusions: This study showed histological evidence for revascularisation by angiogenesis of a free autologous RPE-choroid graft.

Subretinal implants intend to replace photoreceptor function in patients suffering from degenerative retinal disease by topically applying electrical stimuli from the subretinal space. This study intended to prove the feasibility of a newly developed transchoroidal surgery and, furthermore, of a subretinal electrode array, which closely resembles envisioned human implants to electrically stimulate the visual system in rabbits.Five rabbits (ten eyes) were implanted with a 4x2-electrode array via a transchoroidal access to the subretinal space. The electrodes were connected to an arbitrary stimulus generator to apply voltage pulses. Retinae were accessed by light microscopy after stimulation with various intensities.The stimulating foil could be introduced into the subretinal space in all eyes. In seven of ten eyes electrically evoked cortical potentials following subretinal electrical stimulation could be elicited. Threshold voltages ranged from less than 0.1 to 2.38 V with a corresponding threshold charge of approximately 1.0 nC per electrode or 10 micro C/cm(2). Histology revealed localized retinal damage over some of the electrodes succeeding stimulation strengths of 2 V and consistent damage over all electrodes succeeding voltages of 3 V.The study demonstrates the feasibility of the transchoroidal surgical access to place subretinal implants in rabbit eyes and provides proof of successful cortical activation following subretinal electrical stimulation by an electrode array envisioned for human implantations.

Background. Heavy tamponades for pathologies in the lower part of the retina are a new development, and different tamponades have recently come into clinical use: semifluorinated alkanes (F6H6, F6H8) and their oligomers (OL62HV). Method. Nine patients had been operated on using F6H8 (n=5) and by OL62HV (n=4). In all cases the reasons for using the tamponades were complicated retinal detachments in the lower part. In three cases the use was primary and in six cases tamponades were used after reoperations. In all cases the endotamponade was removed within 6 weeks. Fluorescein angiography (FLA) was performed in the F6H8 group. Results. In the F6H8 group dispersion developed in two of the three aphacic patients. In two out of five cases soft epiretinal membranes and cellular material could be found between the substance and the lower periphery. In two membranes examined by light microscopy, cystic cells and amorphous material could be found. In one case (PDRP, aphacic) cyclophotocoagulation had to be performed because of persistent elevated IOP. FLA was unremarkable. In the OL62HV group, severe recurrent PVR reaction occurred in the lower periphery (2/4) and unusual precipitates were observed (4/4). In one case, after a normal postoperative period (VA 0.05 after 5 days) an extensive cellular reaction on the complete surface of the tamponade occurred. After 5 weeks VA was no light perception. During removal of the oligomer unusual adherent cellular components were found on the surface of the retina. The retina appeared necrotic, showed constricted retinal vessels and there was optic atrophy. Histologically, fluffy epiretinal material and a lens capsule obtained from one eye filled with OL62HV resembled the appearance with F6H8. Conclusion. Heavy endotamponades on the basis of semifluorinated alkanes can lead to an unusual biological reaction and need further investigation before clinical use.

This paper presents the virtual fixture control methods for a hybrid parallel-serial micromanipulator, which is designed for assisting ophthalmic surgeons. Virtual fixtures are features of surgical robotic setups to improve quality of the surgery and reduces the operation risk. In the domain of ophthalmic surgery lack of virtual fixtures in manual operations has limited, and sometimes even blocked, the treatment options. The contribution of this paper is concept analysis and implementation of flexible virtual fixture for the novel hybrid parallel-serial mechanism and experimentally evaluation of this concept. The virtual fixture using this mechanism enables the user to adjust them even during the procedure. Pivoting around a Remote Center of Motion (RCM), which in retinal surgery is the incision point, is the most famous virtual fixture of ophthalmic surgery. Autonomous RCM adjustment for Vitreo-Retinal surgery, implying retinal reachability study, is the secondary contribution which is investigated in this paper.