Klaus Heimann

Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy: results of a multicenter clinical trial

PURPOSE To assess the efficacy and safety of adjunctive daunorubicin during vitrectomy surgery in eyes with idiopathic proliferative vitreoretinopathy (PVR). METHODS Two hundred eighty-six eyes (286 patients) with stage C2 (Retina Society Classification, 1983) or more advanced preoperative PVR in which surgery with silicone oil was planned were enrolled in a multicenter, prospective, randomized, controlled clinical trial. Standardized surgery plus adjunctive daunorubicin perfusion was compared with surgery alone. Outcomes assessed were retinal attachment without additional vitreoretinal surgery 6 months after standardized surgery, number of and time until vitreoretinal reoperations within 1 year of standardized surgery, and change in visual acuity 1 year after standardized surgery, evaluated by photodocumentation, number of reoperations, and measurement of best-corrected visual function. Outcomes were determined 6 months after operation and reevaluated after 1 year of follow-up. RESULTS Six months after standardized surgery, complete retinal reattachment without additional vitreoretinal surgery was achieved in 62.7% (89/142) of eyes in the daunorubicin group vs 54.1% (73/135) in the control group (P = .07, one-sided). However, in the daunorubicin group, significantly fewer vitreoretinal reoperations were performed within 1 year postoperatively (P = .005, one-sided) to achieve the same overall 1-year retinal reattachment rate (80.2% [105/131] vs 81.8% [103/126]). The rate of patients with no vitreoretinal reoperations was 65.5% (95/145) in the daunorubicin group vs 53.9% (76/141) in the control group. There was no difference in the best-corrected visual acuity. No severe adverse effect related to daunorubicin was identified. CONCLUSIONS Although the rate of anatomic success after 6 months failed to show significance, some benefit of the adjunctive treatment exists, especially a tendency toward increased rate of reattachment and a significant reduction in the number of reoperations. This shows that human PVR is amenable to pharmacologic treatment.

Polypoidal choroidal vasculopathy pattern in age-related macular degeneration - A clinicopathologic correlation.

Purpose: To report the histopathologic features of surgically removed submacular tissue from an elderly patient with a pattern of polypoidal choroidal vasculopathy on indocyanine green angiography. Methods: Clinical examination including fluorescein and indocyanine green angiography and light microscopy of surgical specimen. Results: A thick yellow proteinaceous subretinal fluid was seen in the right macula of an 81‐year‐old white man. Fluorescein angiography indicated progressive leakage from undetermined source apart from a few focal hyperfluorescent points. Indocyanine green angiography showed several polyps as well as dilated choroidal vessels in the macula and along the superior temporal arcade. A large plaque was visualized in the late phase. Microscopically, the specimen consisted of a thick fibrovascular membrane located on the choroidal side of the retinal pigment epithelium (RPE). The RPE layer was discontinuous whereas on its choroidal side an almost intact layer of diffuse drusen was observed. A group of dilated thin‐walled vessels were found that appeared to be saccular on serial sections. Some of these were located almost immediately under the diffuse drusen. Conclusion: Histologic examination of submacular tissue removed from an eye with polypoidal choroidal vasculopathy showed several aneurysmal dilatations located directly under diffuse drusen within a sub‐RPE, intra‐Bruchs fibrovascular membrane.

Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits.

BACKGROUND In the ongoing discussion concerning the realization of an epiretinal prosthesis for electric stimulation of retinal ganglion cells, long-term fixation of such a device is a crucial question. We evaluated surgical techniques for implantation and fixation of electrically inactive microelectrode arrays (MA) into the retinas of rabbits and secondary tissue reactions to the implant. METHODS Vitrectomy and laser coagulation of the prospective fixation area were performed in rabbits. Implantation of MAs was performed 3 weeks later in 10 animals. The MA was fixated using retinal tacks. The follow-up included ophthalmoscopy and electrophysiology. At the end of the follow-up, the enucleated eyes were processed for light microscopy using standard procedures and grinding techniques. RESULTS Nine of 10 rabbits were implanted without serious complications. Clinical and electrophysiologic data through 6 months of follow-up did not indicate any adverse effect of the surgery, the implant, or the tack itself. No change in retinal architecture underneath the implant was found by light microscopy. In these cases, the implant was stable at its original fixation area. In three cases, mild cataract formation was observed, and in one case, a total retinal detachment was found. CONCLUSION Tack fixation of electrode arrays for electric stimulation of the inner retinal surface seems to be a useful approach in long-term implantation of an epiretinal prosthesis.

Clinicopathological correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation.

AIMS To analyse the histopathology of classic and occult choroidal neovascular membrane surgical specimens in age related macular degeneration. METHODS 35 membranes, from a consecutive series of surgically removed choroidal neovascular membranes in age related macular degeneration, were classified as classic or occult following the guidelines of the Macular Photocoagulation Study. Membranes with classic as well as occult components were considered as mixed membranes. The membranes were serially sectioned and stained with haematoxylin and eosin, Masson trichrome, periodic acid-Schiff, and phosphotungstic acid haematoxylin stain. The correlation has been made in a masked fashion. RESULTS 31 membranes (19 classic, 10 occult, and two mixed membranes) could be analysed histologically. 18 classic choroidal neovascular membranes had a major subretinal fibrovascular component and 10 of these had an additional, minor fibrovascular component under the retinal pigment epithelium. The 10 occult membranes contained a fibrovascular component under the retinal pigment epithelium and the two mixed membranes contained fibrovascular tissue on both sides of the retinal pigment epithelium. Fibrin and remains of outer segments tended to occur at the lateral edges of classic membranes and to cover the inner surface of occult membranes. CONCLUSION Classic choroidal neovascularisation in age related macular degeneration is predominantly composed of subretinal fibrovascular tissue while occult choroidal neovascularisation is composed of fibrovascular tissue at the choroidal side of the retinal pigment epithelium.

Primary vitrectomy for pseudophakic retinal detachment.

AIM/BACKGROUND: Viewing the peripheral retina is the major problem in the repair of pseudophakic retinal detachments. Conventional buckling procedures in pseudophakic eyes are complicated by persistent retinal (re-) detachment and proliferative vitreoretinopathy (PVR) more often than in phakic eyes. METHODS: Primary vitrectomy was performed in 33 consecutive cases for pseudophakic retinal detachment with the help of liquid perfluorocarbons and a wide angle viewing system, following a standardised procedure. All eyes have passed the 12 month follow up examination. RESULTS: The primary reattachment rate was 94%. PVR was observed in one case (3%). Seventy nine per cent (26 eyes) regained vision of 20/50 or better, with a median visual acuity of 20/30. The most frequent complication was transient glaucoma during the early postoperative period in 48% (16 eyes) requiring carboanhydrase inhibitors. CONCLUSION: The main advantage of primary vitrectomy over conventional buckling seems to be the better intraoperative sight to the most peripheral retinal holes, controlled removal of vitreous traction, and focused endolaser coagulation. This may explain the low rate of PVR after primary vitrectomy. Also, visual results tended to be better compared with conventional surgical techniques possibly because of removed vitreous opacities, and because of a superior retinal reattachment rate as well as the reduced rate of PVR.

Iris pigment epithelium transplantation

Abstract• Background: Iris pigment epithelium (IPE) cells and retinal pigment epithelium (RPE) cells possess the same embryonic origin. It is also known that the pigmented epithelial cells in the eye have a high transdifferentiation potential. In this study we transplanted IPE cells into the subretinal space of albino Royal College of Surgeons (RCS) rats and evaluated their influence on the degeneration of the photoreceptors. • Methods: IPE cells of Long Evans rats were isolated and pure cultures were obtained. The isolated cells were transplanted into the subretinal space of RCS rats. Light microscopic and morphometric analysis were carried out. • Results: The IPE transplants survived in the subretinal space and attached themselves to the Bruchs membrane. The transplanted cells were able to delay the degeneration of the photoreceptors for up to 3 months. • Conclusion: These results suggest that IPE cells could be successfully transplanted and survive in the subretinal space. In the transplanted eyes the photoreceptors were preserved for a period of 3 months. Further studies are needed to explore the capability of IPE cells to assume the main functions of RPE cells in the subretinal space and their potential in the therapy of selective degenerative diseases of the retina.

Proliferative vitreoretinopathy — is it anything more than wound healing at the wrong place?

Proliferative vitreoretinopathy (PVR) is a reactive process of the ocular tissue after perforating trauma, retinal detachment, and surgical manipulations. Although several studies, most of them experimental, have focused on the detection of specific etiologic factors in the development of PVR, there is compelling evidence that PVR is nothing more than a physiologic tissue repair process with undesirable consequences for the retina. Important features of PVR involving the role of platelets, mononuclear phagocytes, and fibroblasts parallel the chain of events observed in tissue repair elsewhere in the body. Numerous experimental models for PVR, originally designed to find specific stimuli for the generation of intraocular traction membrane formation, have shown that the process of PVR is the common pathway of the eyes reaction to vitreoretinal trauma of any kind. Accordingly, vitreoretinal surgeons could learn a lot from the work of other disciplines, e.g. surgery and dermatology, on wound healing, and the factors known to modify wound healing elsewhere in the body should be taken into consideration. The well-established impairment of tissue repair processes caused by medical treatment with corticosteroids and cytotoxic agents suggests a combined medical approach to PVR as an adjunct to surgical treatment, using refined methods of application and dosage. Steroids and cytotoxic drugs will influence the course of PVR by suppressing macrophage recruitment and the initial inflammatory reaction as well as the proliferative phase of wound healing with traction retinal detachment, respectively.

Intraocular Daunorubicin for the Treatment and Prophylaxis of Traumatic Proliferative Vitreoretinopathy

Daunorubicin has been used in the treatment of advanced cases of human posttraumatic proliferative vitreoretinopathy. To reduce the failure rate of trauma surgery from proliferative vitreoretinopathy recent efforts have been directed toward the pharmacologic inhibition of cellular reproliferation. We administered intravitreal daunorubicin to 15 patients after vitrectomy and before silicone oil or gas injection. A solution containing 7.5 micrograms/ml of daunorubicin was infused over a ten-minute period. Anatomic success was obtained in 14 patients, and one patient had a renewed traction retinal detachment. Visual acuity improved in all patients postoperatively. We found no toxic effects to the optic nerve, the retina, the lens, or the cornea.

Macrophages in proliferative vitreoretinopathy and proliferative diabetic retinopathy : differentiation of subpopulations

Macrophages have long been known to play a major role in the pathogenesis of proliferative vitreoretinal disorders. Using the monoclonal antibodies EBM11 (pan macrophage), 27E10 (early inflammatory stage marker), and RM3/1 (healing phase marker), different subpopulations of macrophages were differentiated in surgically removed membranes from patients with macular pucker (n = 6), proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (n = 11), traumatic PVR (n = 19), and proliferative diabetic retinopathy (PDR) (n = 11). Macrophages were predominantly found in traumatic PVR and PDR. Some healing phase (RM3/1) macrophages were detected in all disease entities. Inflammatory stage macrophages (positive staining for 27E10) could not be detected in PVR following rhegmatogenous retinal detachment and idiopathic macular pucker. In traumatic PVR inflammatory stage macrophages were associated with a short history of disease whereas in PDR all types of macrophages could be detected regardless of clinical history and duration of the disease.

Evoked cortical potentials after electrical stimulation of the inner retina in rabbits

Abstract Background: Electrical stimulation of the retina using implantable devices may be one possible approach in the treatment of blindness causing progressive degeneration of the outer retina. Stimulation of ganglion cells or fibers could be achieved by epiretinal positioning of a microelectrode array as one component of a retinal prosthesis. Experiments were performed in rabbits to determine whether it is possible to elicit cortical responses with current pulses delivered via an epiretinal placed microelectrode array. Methods: Polyimide-based microelectrode arrays with platinum electrodes and silicon-based TiN electrode arrays were implanted and placed onto the retinal surface of healthy pigmented rabbits after vitrectomy. The devices were temporarily fixated under PFCL and connected to constant current sources delivering bi- or monophasic current pulses. Cortical evoked potentials were recorded using subcutaneously implanted EEG electrodes over the visual cortex. Results: The surgical procedures for implantation and fixation could be performed without serious complications. The electrode array could be placed in the area of the visual streak. Cortical potentials could be recorded after pulse train stimulation either with biphasic or with monophasic pulses. At threshold, pulses of 10 µA/phase and 100 µs/phase were necessary for detection of an electrically evoked cortical potential (EEP). Charge delivery at threshold varied between 0.1 and 0.3 nC/phase and charge densities varied between 1 and 12 µC/cm2. The EEP amplitude increased with increasing stimulus strength. The cortical response could be completely blocked with a retrobulbar injection of 4 ml lidocaine 2%. Conclusion: Constant current pulses delivered via Retina Stimulator devices equipped either with platinum electrodes or with TiN electrodes placed onto the inner retinal surface were able to elicit cortical potentials in the rabbit visual system. At threshold the charge delivery seems to be in a safe range.