Main Principles of Vitrectomy Using Intraocular Tamponades - A Basic Course in Surgery. / Grundlagen der Vitrektomie unter Verwendung intraokularer Tamponaden ­ ein chirurgischer Basiskurs.

This article is intended to clearly present the basic principles for the use of intraocular tamponades in vitreous/retinal surgery in the event of retinal detachment and other pathologies using additional video footage. It examines the various gases, silicone oils and perfluorocarbon liquids with their indications, administration and in particular intraoperative handling including pitfalls and complications. Characteristic animations show the principles of use in surgery in a comprehensible way. The two lead authors dedicate this article to their teacher Prof. Dr. V.-P. Gabel, who in the early 1990s successfully established the first vitrectomy courses for ophthalmologists at Regensburg University Eye Clinic each year. Many colleagues who still work in retinal surgery today first started learning about this segment on these courses. The other coauthors participated under his supervision in annual vitrectomy wet labs run by the German Academy of Ophthalmology.

[The Conundrum of Relationships in the Multivariate Dataset of nvAMD Treatment]. / Die Frage nach Zusammenhängen in multivariaten Datensätzen zur Behandlung der nvAMD.

Background The evaluation of relationships in clinical case series is complicated by statistical pitfalls, one of which is spurious correlation. In this case, one or more potential factors are actually not related to a target measure, yet it may be wrongly inferred that they are. This may be due to either coincidence or the presence of a one or more confounding unregarded factors. In randomised clinical trials, it is attempted to eliminate such confounding factors or to control them by randomisation. However, this approach is not applicable in retrospective case series, and other statistical methods must be applied, such as multivariate analyses, taking into account all known variables. Patients/Material and Methods Statistical evaluation of the impact of different variables on the change in visual acuity after year 2 in a cohort of 1300 cases of nvAMD. The investigated variables are: visual acuity (VA) at baseline, central retinal thickness at baseline, age at baseline, mean interval between visits, number of injections, initial gain in VA after upload, and a change of the anti-VEGF compound. The target outcome measure was the change in VA as letter score at the end of year 2. Results All investigated variables have a marked impact on VA outcome when only single regression analysis is performed. Initial analysis of a switch in therapy gives a seemingly large effect on VA. However, multivariate analysis to avoid spurious correlations shows that only the following variables influence VA outcome with statistical significance: VA at baseline, initial gain in VA after upload, number of injections, mean interval between visits, and central retinal thickness at baseline. A switch in therapy had no statistically significant effect on VA outcome. Conclusion A switch in anti-VEGF therapy is not causally related to better VA outcome. In the statistical evaluation of non-randomised, retrospective case series, special attention must be given to potential confounding variables. When subgroups under investigation are not well balanced for confounding factors, misleading spurious correlations can result, leading to incorrect inferences.

[Real-life Data on the Treatment of Diabetic Macular Oedema in Germany]. / Daten zur Behandlungsrealität des diabetischen Makulaödems mit Ranibizumab.

Background Controlled prospective clinical trials on the treatment of diabetic macular oedema (DME) using anti-VEGF compounds show very good results in visual acuity gain over several years. To date, only limited data are available from comparable studies under real-life settings in clinical routine. However, real-life data from other indications for anti-VEGF treatment suggest that, in clinical routine, gain in visual acuity is less pronounced and cannot be maintained over a longer period of time, which is related to the significantly lower number of injections administered in clinical routine. Here we report a case series from our clinical routine of patients treated with ranibizumab for visual significant DME. Patients/Material and Methods Retrospective case series of 335 cases with follow-up of up to 3 years. All cases in our clinic treated for visual significant DME with at least one injection of ranibizumab were evaluated for the course of visual acuity gain and number of injections received. Results A mean gain in visual acuity (VA) of + 5.6 and + 3.7 letters was found in years one and two, respectively, with a median VA of logMAR 0.52 (decimal 0.3) at baseline. The steepest increase in VA is found during the first 4 months, with a less pronounced increase up to month 16. The mean number of injections was 5.7, 3.2 and 1.1 for years one, two, and three, respectively. Conclusions Results of real life treatment in clinical routine are found to fall behind controlled, prospective trials, as found to the findings in other anti-VEGF indications: mean gain in VA is lower than in prospective trials, and the initial gain cannot be fully maintained over a prolonged time period. Similarly, the number of injections received is markedly lower than in controlled trials. This can partially be explained by differences in study populations and a negative selection bias in longer term results. However, additional barriers that hamper timely treatment tailored to disease activity requirements must be identified and circumvented where possible.

[Time Course of Changes in Visual Acuity After a Single Injection of Aflibercept or Ranibizumab in Neovascular Age-related Macular Degeneration - Analysis of Aggregated Real Life Data]. / Der zeitliche Verlauf der Visusentwicklung nach einer Injektion von Aflibercept oder Ranibizumab bei der neovaskulären altersbedingten Makuladegeneration.

Background Treatment of neovascular age-related macular degeneration (nvAMD) under real life conditions may differ from controlled prospective trials with respect to the number of injections and long term preservation of visual acuity. In many instances, intervals for controls and re-injection cannot be maintained as frequently as required. This case series examines actual intervals for control and re-injection visits, in order to estimate how prolonged intervals have an impact on momentary visual acuity and how long term visual outcome is affected. Patients/Material and Methods Retrospective case series of 1,324 eyes with nvAMD, treated with a total of 8,150 ranibizumab injections (according to the PRN regimen) or 1,725 aflibercept injections (according to a fixed regimen), during the observation period of up to 3 years. The evaluation covered the time interval between visits, impact of this on the course of visual acuity, as well as the number of injections throughout treatment. Results Planned intervals of 4 or 8 weeks between visits were more often exceeded in the PRN regimen than with the fixed regimen. Visual acuity does not peak after 4 weeks, but only between 6 and 8 weeks. No statistically significant difference between aflibercept and ranibizumab was found. If the mean interval for re-injection was maintained at 4 - 6 weeks, this gave the greatest gains in visual acuity at end of years 1 and 2, respectively. Any prolongation of these intervals was accompanied by worse long term visual acuity. The fixed regimen is associated with consistently briefer re-treatment intervals during years 2 and 3, than with the PRN regimen. Conclusion Our data point to the importance of frequent controls accompanied by timely retreatment, as these have a major impact on visual outcome. It therefore appears to be more important to choose a treatment plan that facilitates frequent re-injections than to select either of the two compounds.

[Real-life Evidence on Treatment Outcomes of Neovascular Age-related Macular Degeneration in Germany]. / Real-Life-Evidenz zur Therapie der neovaskulären altersabhängigen Makuladegeneration in Deutschland.

Treatment of neovascular age-related macular degeneration (AMD) with anti-vascular endothelial growth factor agents has been improved since its introduction in Germany. Several observational studies have demonstrated an increased frequency of injections in parallel with improved visual outcomes during the first year of treatment over the last 7 years. These results are reflected in several case series. However, studies with a longer follow-up reported that visual function regressed to baseline vision following an initial improvement, e.g. during the first three years of treatment. A delay in treatment initiation has been reported mainly for rural areas and management models involving more than one ophthalmologist or institution. Encouragingly, recent data confirm a positive trend towards reducing treatment delay, increasing injection frequency and improving treatment outcomes. Still, further improvements are needed to attain optimal treatment outcomes achievable under routine clinical conditions in Germany.

Management of submacular hemorrhage with intravitreal versus subretinal injection of recombinant tissue plasminogen activator.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical evaluation of experimentally induced choroidal neovascularizations in pigmented rabbits by subretinal injection of lipid hydroperoxide and consecutive preliminary photodynamic treatment with Tookad.

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 microg/50 microl) 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.

Long-term safety and functional outcome of combined pars plana vitrectomy and scleral-fixated sutured posterior chamber lens implantation.

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.

Retreatment of full-thickness macular hole: predictive value of optical coherence tomography.

AIM: To determine whether the efficacy of re-operation for idiopathic full-thickness macular hole (FTMH) remaining open after initial surgery with internal limiting membrane (ILM) peeling is correlated with macular hole configuration as determined by optical coherence tomography (OCT), macular hole size, macular hole duration before the first operation, or type of tamponade (gas or silicone oil). METHODS: A retrospective consecutive interventional case series of 28 patients (28 eyes) with a persisting macular hole after vitrectomy, ILM peel, and gas tamponade. 28 patients underwent repeat surgery involving vitrectomy and gas (n = 15) or silicone oil tamponade (n = 12) or no tamponade (n = 1). Autologous platelet concentrate (n = 22), autologous whole blood (n = 1), or no adjuvant (n = 5) was used. Preoperative OCT was undertaken in all eyes. The main outcome measures were anatomical closure and improvement of best-corrected visual acuity (BCVA). RESULTS: Anatomical closure was achieved in 19 of 28 eyes (68%). BCVA improved in 12 eyes, remained unchanged in nine, and worsened in seven. BCVA improved in 11 of 19 eyes with anatomical closure, and in one of eight eyes without closure. Anatomical closure and improvement of BCVA correlated with preoperative macular hole configuration on OCT, with higher rates of closure (18 of 20 eyes versus one of eight eyes, p = 0.001) and greater improvement of BCVA (p = 0.048) in eyes with a cuff of subretinal fluid at the break margin. Macular hole size, type of tamponade, macular hole duration before the first operation, or preoperative BCVA did not significantly correlate with visual or anatomical outcome. CONCLUSION: Macular hole configuration seems to be a strong prognostic indicator of anatomical closure and may help identify those patients most likely to benefit from re-operation.

Evaluation of the new photosensitizer Tookad (WST09) for photodynamic vessel occlusion of the choroidal tissue in rabbits.

PURPOSE: To determine the efficacy of Tookad (WST09; Negma-Lerads, Magny-Les-Hameaux, France) photodynamic therapy (T-PDT) by evaluating the angiographic and histologic closure of choroidal vessels at different radiance exposures, drug dosages, and intervals between photosensitizer injection and laser application in a rabbit model. METHODS: Chinchilla Bastard rabbits were injected intravenously with three different dye concentrations (2.5, 5, and 10 mg/kg) before application of light. In every group T-PDT was performed at four different times after injection: 5, 15, 30, and 60 minutes with different radiance exposures ranging from 200 to 3 J/cm2. Fundus photographs and fluorescein angiograms were obtained 90 minutes after injection. Follow-up angiographies were performed at days 1, 3, 7, and 14 after initial treatment. Histology was performed in selected cases immediately after treatment and on days 1, 3, and 7. RESULTS: Immediately after irradiation, most of the visible lesions were angiographically hyperfluorescent due to damaged vessel endothelium and associated RPE damage. Lesions from high-radiance exposures revealed immediate hypofluorescence, indicating vessel closure. Hypofluorescent lesions appeared mainly during day 1 (all lesions angiographically visible, some hypofluorescent) to day 3 (all lesions hypofluorescent) after treatment. At day 7, ophthalmoscopically visible hyperpigmentation took place in all lesions. ED50 thresholds for angiographic hypofluorescence determined at day 3 after treatment with 2.5 mg/kg were 18.8 J/cm2 (5 minutes), 62.0 J/cm2 (15 minutes), and >100 J/cm2 (30 minutes); with 5 mg/kg, 8.4 J/cm2 (5 minutes), 22.8 J/cm2 (15 minutes), 54.5 J/cm2 (30 minutes), and >100 J/cm2 (60 minutes); and with 10 mg/kg, 11.7 J/cm2 (30 minutes) and 54.1 J/cm2 (60 minutes). Histology of the angiographically hypofluorescent lesions revealed vessel thrombosis in all groups 1 hour after PDT up to 7 days after treatment. Sparing of photoreceptors indicated selectivity of T-PDT; however, slight damage was partly observable. After 7 days, localized proliferation of the RPE cells was noted and was enhanced 14 days after treatment. CONCLUSIONS: T-PDT has the potential to achieve selective choroidal vessel occlusion with proper parameter selection, such as (1) 2.5 mg/kg, 5 minutes, 100 J/cm2; (2) 5 mg/kg, 5 minutes, 25 J/cm2; or (3) 5 mg/kg, 15 minutes, 50 J/cm2; however, slight damage to the photoreceptors cannot be ruled out. RPE proliferation indicates primary RPE damage due to PDT, also described with the use of all other photosensitizers.

Fundus autofluorescence before and after photodynamic therapy for choroidal neovascularization secondary to age-related macular degeneration.

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.

Transscleral implantation and neurophysiological testing of subretinal polyimide film electrodes in the domestic pig in visual prosthesis development.

Loss of photoreceptor function is responsible for a variety of blinding diseases, including retinitis pigmentosa. Advances in microtechnology have led to the development of electronic visual prostheses which are currently under investigation for the treatment of human blindness. The design of a subretinal prosthesis requires that the stimulation device should be implantable in the subretinal space of the eye. Current limitations in eye surgery have to be overcome to demonstrate the feasibility of this approach and to determine basic stimulation parameters. Therefore, polyimide film-bound electrodes were implanted in the subretinal space in anaesthetized domestic pigs as a prelude to electrical stimulation in acute experiments. Eight eyes underwent surgery to demonstrate the transscleral implantability of the device. Four of the eight eyes were stimulated electrically. In these four animals the cranium was prepared for epidural recording of evoked visual cortex responses, and stimulation was performed with sequences of current impulses. All eight subretinal implantation procedures were carried out successfully with polyimide film electrodes and each electrode was implanted beneath the outer retina of the posterior pole of the operated eyes. Four eyes were used for neurophysiological testing, involving recordings of epidural cortical responses to light and electrical stimulation. A light stimulus response, which occurred 40 ms after stimulation, proved the integrity of the operated eye. The electrical stimuli occurred about 20 ms after the onset of stimulation. The stimulation threshold was approximately 100 microA. Both the threshold and the cortical responses depended on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. The subretinal implantation of complex stimulation devices using the transscleral procedure with consecutive subretinal stimulation is feasible in acute experiments in an animal model approximating to the situation in humans. The domestic pig is an appropriate animal model for basic testing of subretinal implants. Animal experiments with chronically implanted devices and long-term stimulation are advisable to prepare the field for successful human experiments.

Positioning of electronic subretinal implants in blind retinitis pigmentosa patients through multimodal assessment of retinal structures.

PURPOSE: To optimize methods for positioning subretinal visual implants, customizing their cable length, guiding them to the predetermined retinal position, and evaluating their performance. METHODS: Ten eyes of 10 patients (6 male, 4 female, mean age 46.4 years) were investigated before implantation of a subretinal visual implant. The structural characteristics of the retina as well as the ocular dimensions were determined. Topographic images of the prospective implantation site were subdivided into grids of squares. Each square received a weighted score for suitability. The sum of the scores was calculated, and the region with the highest score was chosen for the implant. In each case, the implant's power supply cable length was calculated by means of magnetic resonance imaging. The planned and achieved positions before and after implantation were compared. RESULTS: The mean light sensitivity ratio between the area actually covered by the chip and that of the planned position was 90.8% with an SD of 11.4%. In two cases with almost perfect positioning, the computed ratio was 100%. Measurements showed that to achieve a 95% sensitivity rate the difference between the planned and achieved chip position must be less than 1.7 mm. Preoperative calculations of the intraocular cable length proved accurate in all cases. CONCLUSIONS: Preoperative evaluation of retinal structures and eye morphology is useful for guiding a retinal implant to the designated area. It is a meaningful tool for planning and performing retinal chip implantation, and it optimizes personalized implantation. (ClinicalTrials.gov numbers, NCT00515814, NCT01024803.).

Maintenance of adult porcine retina and retinal pigment epithelium in perfusion culture: characterisation of an organotypic in vitro model.

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

Surgical removal of idiopathic epiretinal membrane with or without the assistance of indocyanine green: a randomised controlled clinical trial.

PURPOSE: To carry out a prospective investigation of the functional and morphological outcome of idiopathic epiretinal membrane (IEM) surgery with or without the assistance of indocyanine green (ICG) in a randomised controlled clinical trial. METHODS: Sixty patients who underwent vitrectomy with removal of IEM combined with cataract surgery were randomly allocated to two groups: 27 patients were operated on with ICG 0.1% in glucose 5%, 33 patients without ICG. Functional outcome was assessed 3-4 months postoperatively with improvement of best-corrected visual acuity (BCVA), Amsler grid test, and automated and kinetic perimetry. Postoperative residual or recurrent IEM was assessed with bio-microscopy, and macular oedema with optical coherence tomography (OCT). Improvement in BCVA was the main outcome measure. RESULTS: BCVA improved in 49 patients, remained unchanged in five and decreased in five. Improvement in BCVA and reduction of macular oedema were statistically significant within both groups (P < 0.01). Improvement in BCVA was not statistically significantly different whether ICG was used or not [0.17 (logarithm of minimum angle of resolution; logMAR) with ICG and 0.24 (logMAR) without ICG] (P = 0.59). There was no statistically significant difference in preoperative or postoperative BCVA, reduction of macular oedema, postoperative Amsler grid test, or incidence of residual or recurrent IEM between the two groups. Visual field defects were detected in two patients operated on with ICG. CONCLUSIONS: Removal of IEM with or without the assistance of ICG equally improved visual function and macular morphology.

Implantation and testing of subretinal film electrodes in domestic pigs.

By definition, an electronic subretinal visual prosthesis requires the implantation of stimulation electrodes in the subretinal space of the eye. Polyimide film electrodes with flat contacts were implanted subretinally and used for electrical stimulation in acute experiments in anaesthetised domestic pigs. In two pigs, the film electrode was inserted through a sclerostomy into the vitreous cavity and, subsequently, via a retinotomy into the subretinal space around the posterior pole (ab interno approach). In three other pigs the sclera and pigment epithelium were opened for combined ab interno and transscleral positioning of the subretinal electrode. In all cases, perfluorocarbon liquid (PFCL) was used to establish a close contact between the film electrode and the outer retina. After cranial preparations of three pigs for epidural recording of visual cortex responses, retinal stimulation was performed in one pig with a film electrode implanted ab interno and in two pigs with film electrodes implanted by the ab interno and transscleral procedure. The five subretinal implantations were carried out successfully and each polyimide film electrode tip was positioned beneath the outer retina of the posterior pole. The retina was attached to the stimulation electrode in all cases. Epidural cortical responses to light and electrical stimulation were recorded in three experiments. Initial cortical responses to Ganzfeld light and to electrical stimuli occurred about 40 and 20 ms, respectively, after stimulation onset. The stimulation threshold was approximately 100 microA and, like the cortical response amplitudes, depended both on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. Our results in a domestic pig model demonstrate that polyimide film electrodes can be implanted subretinally and tested by recording cortical responses to electrical stimulation. These findings suggest that the domestic pig could be an appropriate animal model for basic testing of subretinal implants.

Subretinal implantation and testing of polyimide film electrodes in cats.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. One concept under investigation is an electronic subretinal prosthesis to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: In the subretinal prosthesis design concept, an array of stimulation electrodes is placed in the subretinal space. To test the feasibility of the concept and to determine basic stimulation parameters, wire-bound stimulation devices were used in acute trials for up to 12 h in three eyes in anaesthetised cats. These wire-bound stimulation elements were based on strips of polyimide film. The film strips were introduced through a sclerostomy into the vitreous cavity and via a retinotomy into the subretinal space during a modification of the standard three-port vitrectomy procedure. On entry through the retinotomy, the film was advanced mechanically to the desired position in the area centralis. Perfluorocarbon liquid (PFCL) was used to establish close contact between the electrode array and the outer retina. Stimulation was performed with computer-generated sequences of current waveforms in acute trials immediately after surgical implantation of the stimulation film. Cortical recordings in the primary visual cortex were performed with electrodes placed in locations corresponding to the retinal stimulus site. RESULTS: All three implantations were carried out successfully with the stimulation array implanted beneath the outer retina of the area centralis of the operated eye. The retina was attached over the stimulation array in all cases. No cortical responses were recorded in one of the stimulation sessions. The results from another session revealed clear intracortical responses to subretinal stimulation with polyimide films. Following single-site retina stimulation, the estimates of spatial cortical resolution and temporal resolution were approximately 1 mm and 20-50 ms, respectively. DISCUSSION: Our results indicate that focal subretinal stimulation evokes localised spatio-temporal distribution of cortical responses. These findings offer hope that coarse restoration of vision may be feasible by subretinal electrical stimulation.

Fundus autofluorescence in acute and chronic-recurrent central serous chorioretinopathy.

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

Retinal replacement--the development of microelectronic retinal prostheses--experience with subretinal implants and new aspects.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. Different concepts of retinal replacement are currently under investigation. The aim of the retinal prostheses is to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: Within the field of visual prosthetic developments mainly two retinal based concepts are under investigation. One of the concepts is the epiretinal implant which acquires images of an external camera and after preprocessing by a computer reading this visual information into the human visual system. In the subretinal prosthesis design concept an array of stimulation electrodes is placed in the subretinal space. True to the concept the image falling on the retina and its light impulses are converted into electrical currents by microphotodiodes and the retina is stimulated with these locally. To test the feasibility of the concepts the biocompatibility and to determine basic stimulation parameters a lot of animal experiments and first human experiments were carried out. RESULTS: Currently the research conducted by teams in Germany, the USA and Japan into epiretinal and subretinal implants has reached the stage where clinical trials can now be performed. Individual pilot studies were carried out for both the epiretinal and the subretinal implant by different research groups. DISCUSSION: The results achieved by the researchers indicate that cortical action potentials can be triggered by electric retinal stimulation with both concepts. The experimental work has highlighted a whole range of obstacles, not all of which have yet been fully resolved. These findings offer hope that coarse restoration of vision may be feasible by electrical stimulation.