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K Heimann

Publications and source records attributed to K Heimann.

At least 55 records · Page 3Linked to original sources
PubMed1999

Current understanding on the role of retinal pigment epithelium and its pigmentation.

Retinal pigment epithelium (RPE) is a monolayer of cuboidal cells that is strategically placed between the rod and cone photoreceptors and the vascular bed of the choriocapillaris. It has many important functions, such as phagocytic uptake and breakdown of the shedded photoreceptor membranes, uptake, processing, transport and release of vitamin A (retinol), setting up the ion gradients within the interphotoreceptor matrix, building up the blood-retina barrier, and providing all transport from blood to the retina and back. This short review focuses on the role of the pigment granules in RPE. Although the biology of the pigment granules has been neglected in the past, they do seem to be involved in many important functions, such as protection from oxidative stress, detoxification of peroxides, and binding of zinc and drugs, and, therefore, serve as a versatile partner of the RPE cell. Melanin plays a role in the development of the fovea and routing of optic nerves. New findings show that the melanin granules are connected to the lysosomal degradation pathway. Most of these functions are not yet understood. Deficit of melanin pigment is associated with age-related macula degeneration, the leading cause of blindness.

Age Factors↗
PubMed1999

Ultimate fate of rod outer segments in the retinal pigment epithelium.

To investigate the degradation pathway of rod outer segments (ROS) in vivo, we injected gold-labeled ROS into the subretinal space of rabbits using a pars plana approach. Histology and electron microscopy performed on the specimens 72 hr after ROS injection revealed that the retina over the injection site was reattached, the retinal pigment epithelial (RPE) cells were intact, and gold granules were localized inside melanin granules and melanosomes. These results indicate that, in RPE, in vivo degradation of ROS is associated with melanosomes.

Animals↗
PubMed1999

Cellular photoablation to control postoperative fibrosis in a rabbit model of filtration surgery.

AIM: To evaluate the feasibility of cellular photoablation using fluorescence generated photoreaction products as a method to control postoperative fibrosis. METHODS: The fluorescent probe, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF-AM) is a cell membrane permeable compound rendered membrane impermeable and fluorescent upon cleavage by intracellular esterases. Rabbits (ChBB:CH; n=20) received a unilateral subconjunctival injection of BCECF-AM (40, 70, 80, or 100 microg) 30 minutes before surgery followed by intraoperative illumination with diffuse blue light (450-490 nm; 51.9 x 10(3) cd/m(2)) for 10 minutes. Controls received either the probe or illumination. Antifibrotic efficacy was established by clinical response and histological examination. Clinical response was assessed by comparing intraocular pressure (IOP) between the treated experimental eye and the fellow eye, which served as control. Success was defined by >20% difference in IOP. RESULTS: IOP was significantly decreased in all groups within 4 days postoperatively. In control groups IOP rose within 10 days to normal levels. This was similar in the group receiving 40 microg of BCECF-AM. In the other groups (subconjunctival injection of 70-100 microg BCECF-AM) IOP was significantly (p < 0.02) decreased for 2-3 weeks. Clinical and histological examination revealed no toxic damage to adjacent tissues. CONCLUSIONS: Cellular photoablation in contrast with chemotherapeutic agents acts on cells that have incorporated BCECF-AM and have been exposed to light at the appropriate wavelength. Though safety and reliability demand further studies this method might be an useful therapeutic approach to control postoperative fibrosis in humans undergoing filtration surgery.

Animals↗
PubMed1999

GAIP, a Galphai-3-binding protein, is associated with Golgi-derived vesicles and protein trafficking.

Proteins of the regulators of G protein signaling (RGS) family bind to Galpha subunits to downregulate their signaling in a variety of systems. Galpha-interacting protein (GAIP) is a mammalian RGS protein that shows high affinity for the activated state of Galphai-3, a protein known to regulate post-Golgi trafficking of secreted proteins in kidney epithelial cells. This study aimed to localize GAIP in epithelial cells and to investigate its potential role in the regulation of membrane trafficking. LLC-PK1 cells were stably transfected with a c-myc-tagged GAIP cDNA. In the transfected and untransfected cells, GAIP was found in the cytosol and on cell membranes. Immunogold labeling showed that membrane-bound GAIP was localized on budding vesicles around Golgi stacks. When an in vitro assay was used to generate vesicles from isolated rat liver and Madin-Darby canine kidney cell Golgi membranes, GAIP was found to be concentrated in fractions of newly budded Golgi vesicles. Finally, the constitutive trafficking and secretion of sulfated proteoglycans was measured in cell lines overexpressing GAIP. We show evidence for GAIP regulation of secretory trafficking before the level of the trans-Golgi network but not in post-Golgi secretion. The location and functional effects of GAIP overlap only partially with those of Galphai-3 and suggest multiple roles for GAIP in epithelial cells.

Animals↗
PubMed1999

Rescue effects of IPE transplants in RCS rats: short-term results.

PURPOSE: The aim of this study was to investigate the possible rescue effect of subretinal iris pigment epithelial (IPE) cell transplantation in Royal College of Surgeons (RCS) rats by light and electron microscopic histology. METHODS: IPE cells were harvested from 20- to 26-day-old Long-Evans rats and were directly trans planted transsclerally into the subretinal space of 32 16- to 20-day-old RCS rats using a 32-gauge Hamilton syringe. Specimens of transplanted eyes were embedded for electron microscopy after 8 weeks. Specimens from the iris and retinal pigment epithelium (RPE) of Long-Evans rats and RPE from RCS rats without surgical treatment were also embedded. Sham surgery was also performed in 8 eyes. RESULTS: The IPE cells transplanted into the subretinal space were localized between host RPE and retina, had round cell shapes without polar organization, and contained phagosomes resulting from rod outer segment (ROS) uptake. The underlying host RPE cells were heavily pigmented. RPE cells from RCS rats revealed fragmentation of endoplasmic reticulum, which distinguishes them ultrastructurally from pigment epithelial cells of Long-Evans rats. Ultrastructural alterations were observed in the cytoplasm of transplanted cells. Melanin granules in the IPE cells were found in large vacuoles, which also contained phagosomes originating from ROS uptake. In 13 eyes, 1 to 4 rows and 5 to 8 rows of saved photoreceptors were detected facing transplanted IPE cells in 6 (46%) and 4 (31%) eyes, respectively, 2 months after surgery. However, in 10 (53%) and 7 (37%) of 19 eyes, 1 to 4 rows and 5 to 8 rows, respectively, were also found at sites without IPE cells in the plane of section. ROS directed toward transplanted IPE cells were seen in one case, but these rods were shortened and disorganized. At most sites between transplanted cells and inner segments of photoreceptors, outer segments and cellular debris were absent. In eyes without transplanted cells no photoreceptor cells were alive at the age of 2 months. After sham surgery 6 (75%) eyes had 1 to 4 rows and 2 (25%) 5 to 8 rows of photoreceptors. CONCLUSIONS: Transplanted IPE cells can take up and degrade ROS in vivo in RCS rats. Uptake of ROS alters the morphology of pigment granules in transplanted IPE cells. Pigmentation is an uncertain marker for identifying transplanted pigment cells. IPE transplants are not as good as RPE transplants in rescuing photoreceptors. However, there is a significant difference between transplanted eyes and nontreated eyes. The rescue effect of IPE cells was not significantly different from that of sham surgery.

Animals↗
PubMed1999

Ultrastructural localization of light-induced lipid peroxides in the rat retina.

PURPOSE: Localization of light-induced lipid peroxides in the rat retina at an ultrastructural level as benzidine-reactive substances. METHODS: Long-Evans rats with nondilated pupils were exposed to intense light of 6000 lux for 12 or 24 hours. Control animals were kept under physiological light conditions. Rats with dilated pupils were exposed to a light intensity of 50 lux or 150,000 lux for 1 hour. For ultrastructural localization the enucleated eyes were fixed in a 0.1-M cacodylate buffer (pH 7.4) containing 2% glutaraldehyde for 2 hours. Pieces of the superior part of the central eyecup were incubated overnight with tetramethylbenzidine (TMB; pH 3.0) at 4 degrees C, postfixed with 1.5% OSO4, and embedded for electron microscopy. RESULTS: In animals exposed to intense light, electron-dense structures appeared exclusively throughout the rod outer segments after an irradiation of 6000 lux for 24 hours or 150,000 lux for 1 hour and were absent in animals with nondilated pupils kept at physiological light conditions. Dilation of the pupils leads to the appearance of electron-dense structures after just 1 hour of 50 lux, whereas rats with nondilated pupils withstand even a 12-hour irradiation with 6000 lux. No electron-dense structures were found when no TMB was used in incubation. CONCLUSIONS: The appearance of electron-dense structures in the rod outer segments depends on the incubation with TMB and intensive light exposure of the rat. Dilation of the pupils lowers the threshold for the emergence of electron-dense structures significantly. This strongly supports the view that light-induced lipid peroxides in the rat retina are localized at an ultrastructural level as benzidine-reactive substances. This protocol presents a tool for the generation and ultrastructural localization of lipid peroxides in rat retinas.

Animals↗
PubMed1998

Vesicle budding on Golgi membranes: regulation by G proteins and myosin motors.

One of the main functions of the Golgi complex is to generate transport vesicles for the post-Golgi trafficking of proteins in secretory pathways. Many different populations of vesicles are distinguished by unique sets of structural and regulatory proteins which participate in vesicle budding and fusion. Monomeric and heterotrimeric G proteins regulate vesicle budding and secretory traffic into and out of the Golgi complex. An inventory of G protein alpha subunits associated with Golgi membranes highlights their diverse involvement and potential for coupling Golgi trafficking, through various signal transduction pathways, to cell growth or other more specialized cell functions. Cytoskeletal proteins are now also known to associate specifically with the Golgi complex and Golgi-derived vesicles. Amongst these, conventional and unconventional myosins are recruited to vesicle membranes. Several roles in vesicle budding and vesicle trafficking can be proposed for these actin-based motors.

Animals↗
PubMed1998

The mRNA expression of cytokines and their receptors in cultured iris pigment epithelial cells: a comparison with retinal pigment epithelial cells.

It has been suggested that human iris pigment epithelial (IPE) cells isolated from iridectomized tissue could be used as autologous cells for transplantation into the subretinal space in diseases with dysfunctional retinal pigment epithelium (RPE). RPE cells synthesize a number of cytokines and their receptors which are important for its proper function. Nearly nothing is known about the capacity of IPE to synthesize cytokines or responding to them. To compare the mRNA expression of 36 cytokines or their receptors in cultured adult IPE cells and RPE cells we used semi-quantitative reverse transcription polymerase chain reactions (RT-PCR). Included in our assay were cytokines with known expression in RPE to get a broad basis for comparing IPE cells: basic fibroblast growth factor (bFGF or FGF-2), and one of its receptor (FGFR-1), epidermal growth factor (EGF), and its receptor EGF-R, transforming growth factor beta(TGFbeta), and its type III receptor TGFbeta-R3, the platelet-derived growth factors and receptors (PDGF A, PDGF B, PDGF-Ralpha, PDGF-Rbeta), tumor necrosis factor alpha(TNFalpha), and two receptors TNF-R1 and TNF-R2, insulin (INS) with receptor INS-R, insulin-like growth factors (IGF1, IGF2), and receptors (IGF1-R, IGF2-R), vascular endothelial growth factor (VEGF), and two receptors (VEGF-R1 or FLT-1 and VEGF-R2 or FLK-1), the receptor for VEGF-C: VEGF-R3 or FLK-4, interleukin 6 (IL6), and its receptor (IL6-R), nerve growth factor (NGF), interleukin 1alpha(IL1alpha), and a receptor (IL1-R). In addition, cytokines or their receptors not known to be expressed in RPE were included to widen our picture of cytokine gene expression in the eye: stem cell factor (SCF), its receptor (SCF-R), low-affinity nerve growth factor receptor p75 (p75(NGF-R), ciliary neutrothropic factor (CNTF), and its receptor (CNTF-R), glycoprotein 130 interleukin 6 transducer (gp130 (IL6-SD), leukemia inhibitory factor (LIF), and its receptor (LIF-R). Semi-quantitative expression data were obtained using series of fivefold dilutions of each cDNA and a fixed number of PCR cycles. The expression of RPE 65, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and beta2-microglobulin (B2MG) was used as a control for cellular origin, RNA quality and PCR conditions. With the exception of insulin and tumor necrosis factor alphaall other cytokines analysed and their receptors were expressed in both IPE and RPE cells, even though the levels varied. No qualitative or quantitative difference were observed in the mRNA expression level of 34 (94%) of the cytokines or receptors between IPE and RPE. In contrast, the mRNA expression level of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 [VEGF-RS (FLK-1)] was lower in IPE than in RPE cells. As an increased expression of VEGF in the RPE in maculae with age-related macular disease could be involved in its pathogenesis, a decreased expression of angiogenic growth factors in IPE cells could possibly be beneficial for the therapy of age-related maculopathy if indeed other tasks of non-functional RPE cells could be performed by IPE cells. The similarity of the mRNA expression pattern in 94% of the cytokines analyzed supports the assumption that IPE cells potentially can perform functions of RPE cells in the appropriate environment.

Adult↗
PubMed1998

The topoisomerase I inhibitors, camptothecin and beta-lapachone, induce apoptosis of human retinal pigment epithelial cells.

The aim of the study was to determine whether the topoisomerase I inhibitors, camptothecin and beta-lapachone, are suitable agents for the adjuvant pharmacotherapy of proliferative vitreoretinopathy (PVR). The effects of the drugs on cultured human retinal pigment epithelial (RPE) cells were examined using growth assays, cytotoxicity assays, single cell agarose gel electrophoresis, in situ DNA end labeling and immunoblot analysis for apoptosis-regulatory proteins. Both agents killed RPE cells in a concentration-and time-dependent manner. Cell death was apoptotic as assessed by single cell agarose gel electrophoresis and in situ DNA end labeling. Camptothecin, but not beta-lapachone, induced accumulation of p53 and the major growth arrest-associated p53 response protein, p21. Both drugs enhanced expression of the proapoptotic BAX protein. Camptothecin, but not beta-lapachone, synergistically enhanced RPE cell apoptosis induced by the cytotoxic cytokine, CD95 ligand (CD95L). This effect was linked to camptothecin-induced inhibition of RNA synthesis. Atypical topoisomerase I inhibitors may be promising agents for the adjuvant pharmacotherapy of PVR. Experimental studies to assess possible ocular toxicity upon local administration and to confirm its therapeutic efficacy in an animal model of PVR are required.

Apoptosis↗
PubMed1998

The nonradioisotopic representation of differentially expressed mRNA by a combination of RNA fingerprinting and differential display.

In many applications, an understanding of differentially expressed genes in different tissues or owing to an applied stimulus is important. However, the wide use of two rather similar polymerase chain reaction (PCR)-based techniques for the identification of differentially expressed mRNAs (RNA fingerprinting by arbitrarily primed PCR [RAP-PCR] and differential display [DDRT-PCR]) has shown that reproducibility is still a problem. By combining features of both RAP-PCR and DDRT-PCR, a technique has recently been developed that avoids some of the disadvantages, but the use of radioisotopes for band detection still limits its application. We have improved this technique for analyzing differentially expressed mRNA by resolving the amplified products on nondenaturing polyacrylamide gels and subsequently staining the gels with silver nitrate. Our modification allows the identification of differentially expressed bands with a very high accuracy. Therefore these bands can be very easily reamplified and sequenced directly. Subsequently the differential expression can be verified by semiquantitative RT-PCR with specific primers derived from sequence data. These improvements, together with nonradioactive sequencing techniques, make it possible to do DD analysis completely without a health hazardous owing to radioactivity. The nonradioisotopic differentially expressed mRNA-PCR (DEmRNA-PCR) is a reliable and useful modification of available differential expression methods.

Cells, Cultured↗
PubMed1998

[Ultrastructural localization of lipid peroxides in the eye. Presentation of a new method].

UNLABELLED: Lipid peroxidation is considered a prominent feature of age-related retinal degeneration. It is known that lipid peroxides can oxidize benzidine. This property was used to localize lipid peroxides ultrastructurally in the retina. METHODS: (1) Lipid peroxides were formed by incubation of linoleic acid with lipoxygenase from soybean, separated by thin layer chromatography and incubated with tetramethylbenzidine. (2) Lipid peroxides were formed by incubation of porcine retinae with soybean lipoxygenase in an oxygensaturated atmosphere. For ultrastructural localization, isolated retinae with and without enzymatically synthesized lipid peroxides were fixed with 2% glutaraldehyde, incubated with 0.5 mg/ml tetramethylbenzidine and embedded for electron microscopy. (3) Eye cups from Syrian golden hamsters were treated in the same way except for incubation with lipoxygenase. The hamsters were kept under constant illumination (1000 lux) for 12 h to enhance lipid peroxidation. RESULTS: (1) Tetramethylbenzidine was oxidized by linoleic acid peroxides. (2) In the isolated retinae of pigs lipid peroxides became visible as electron-dense structures in the rod outer segments (ROS) after treatment with lipoxygenase and were lacking in the other parts of the retina. Without treatment with lipoxygenase lipid peroxides were only infrequently seen in ROS. (3) In the eyes of light-exposed hamsters, electron-dense reaction products of lipid peroxides were particularly prominent between the basal infoldings of the RPE and within the apical parts of the ROS. CONCLUSION: Light or enzymatically induced lipid peroxides can be localized ultrastructurally due to their ability to react with tetramethylbenzidine and osmium in the absence of H2O2 to an electron-dense reaction product. Lipid peroxides seem to be removed from the RPE via Bruch's membrane and blood vessels. Disturbance of this pathway may enhance lipofuscin or drusen formation.

Animals↗
PubMed1998

Autologous platelet treatment for optic disc pit associated with persistent macular detachment.

PURPOSE: To determine the effectiveness of autologous platelets in repair of optic disc pit associated with persistent macular detachment. PATIENT: We report on a 44-year-old woman with optic disc pit associated with persistent macular detachment. The patient underwent an uneventful pars plana vitrectomy with autologous platelets injected over the optic disc pit. Good anatomical and functional results were obtained. CONCLUSION: This surgical approach may be a valuable adjunct to the surgical management of optic disc pit associated with persistent macular detachment.

Adult↗
PubMed1998

Temporary vitreous gas tamponade by perfluoromethylcyclopentane.

Using perfluoromethylcyclopentane (FMCP; US patent no. 5,441,989, granted 1995) we have developed a new vitreous gas tamponade in a rabbit model that allows complete filling of the vitreous cavity without vitrectomy and without a significant increase in intraocular pressure. In humans this procedure would allow the blockage of inferior and posterior retinal holes without special positioning of the patient. Perfluoromethylcyclopentane (FMCP), a liquid perfluorocarbon with a boiling point slightly above body temperature, is injected in minute volumes into the vitreous cavity, where it vaporizes, thereby filling a gas volume approximately 500 times its liquid volume. FMCP was injected into the midvitreous in six rabbits (six eyes). After 2-3 days a complete gas tamponade was achieved in three eyes. Two eyes showed 75-90% filling, and one eye was filled only 50% with gas. Intraocular pressure was highest in the completely filled eyes, ranging from 26.6 to 38.8 mmHg. In all eyes the maximum expansion of the gas bubble lasted 2 weeks. One eye developed a retinal detachment. All eyes showed transient subcapsular cataracts. The results of this study showed that intravitreal injection of FMCP, a new perfluorocarbon liquid, results in a complete gas tamponade of the vitreous cavity which lasts 2 weeks without severe intraocular pressure rise and without vitrectomy. This procedure will be especially useful for eyes that have retinal detachment from inferior or posterior retinal holes. Injection of a conventional gas such as SF6 or C3F8 usually does not block retinal holes in inferior or posterior locations without tedious positioning and risk of (transient) glaucoma. Since the mechanism of transition of FMCP from liquid to gas in the vitreous is poorly understood, we are currently studying FMCP vaporization in an in vitro eye model.

Animals↗
PubMed1998

Phagocytosis of rod outer segments by human iris pigment epithelial cells in vitro.

BACKGROUND: We set out to evaluate the growth potential of human iris pigment epithelial (hIPE) cells in vitro, to establish whether these cells acquire the ability to phagocytose rod outer segments (ROS) and to compare the phagocytic activity of hIPE to that of human retinal pigment epithelial (hRPE) cells. METHODS: hIPE and hRPE cells were isolated and cultured from human donor eyes and surgical specimens and growth characteristics were analyzed. HIPE and hRPE of an eye of a 46-year-old donor were used for the phagocytosis assay. Phagocytosis was evaluated by adding ROS isolated from porcine retina to cultures of hIPE and hRPE, which had been labeled with the pH-sensitive fluorescent dye, carboxy-SNAFL. After 4 h the number of ingested ROS was counted with a light microscope. For each cell type phagosomes in 500 cells were counted. The epithelial characteristics of the cells used in this study were evidenced by their morphology. RESULTS: Morphologically cultured hIPE are indistinguishable from the hRPE cultured from the same donor eye and show a similar pattern of cytokeratin distribution. Cultured hIPE acquire the ability to phagocytose ROS at a level slightly lower than hRPE; hIPE contained 0.76 phagosomes per cell, hRPE 0.99 phagosomes per cell. CONCLUSION: The morphology of hIPE in culture and the acquisition of the phagocytic phenotype indicate that these cells have the ability to differentiate into cells that have characteristics in common with hRPE. The acquisition of phagocytic activity suggests that it is feasible to culture hIPE from surgical iridectomies and that these cultured cells can be transplanted into the subretinal space in individuals with retinal degenerations.

Cells, Cultured↗
PubMed1998

External beam radiation in patients suffering from exudative age-related macular degeneration. A matched-pairs study and 1-year clinical follow-up.

BACKGROUND: The aim of this prospective study was to ascertain whether external beam irradiation is effective in patients with subretinal neovascularization (SRN) due to age-related macular degeneration (AMD). METHODS: All patients had subfoveal SRN due to AMD as verified by fluoresceinangiography. Two hundred and eighty-seven patient-eyes were treated by external beam irradiation (total dose of 16 Gy in 2-Gy fractions, 5 times a week) from January 1996. The analysis was restricted to those 73 patients with a minimum follow-up of 11 months. Eighteen patients with subfoveal SRN who refused treatment served as control group (CG). 18 patients of the treatment group (TG) were matched for visual acuity, refraction and extent of SRN. The statistical analysis was performed with the unpaired t-test. RESULTS: The mean age of the CG was 73.9 years (range 66.9-81.3 years) and of the TG 75.6 years (range: 65.7-80.6 years). The median follow-up was 13.5 months (range 11.9-18.4 months) in the CG and 12.9 months (range 11-13.9 months) in the TG. The initial visual acuity (VA) was 20/80 in both groups. After 7 months the follow-up revealed median VA of 20/400 in the CG and 20/160 in the TG (P=0.0335). The final median VA was 20/400 in both groups, with a range from 20/40 to 20/1000 in the CG and from 20/63 to 20/500 in the TG (P=0.2433). The SRN doubled in size during this time in both groups. CONCLUSION: These results suggest that external beam irradiation applied in 2-Gy fractions 5 times a week slows down the visual loss in exudative AMD for a short time. Nevertheless, the patients' reading vision could not be saved in the long term.

Aged↗
PubMed1998

Unilateral pigmentary degeneration of the retina associated with heterochromia iridis.

BACKGROUND: For the past 5 years, a 56-year-old patient has been displaying monocular progressive pigmentary changes in the left eye. Heterochromy of the left eye has been known since childhood. The other eye is clinically and functionally normal. The patient was adopted and he has no children. Therefore, we have no family history. METHODS: The patient was examined clinically and by means of electroretinography, electrooculography, perimetry, computer tomography, pulsatile ocular blood flow (POBF) measurement, serology and Doppler sonography. RESULTS: Electrophysiology displayed a considerable reduction of scotopic and photopic ERGs, a reduced dark-through, and a reduced light-rise in the left eye, whereas the fellow eye was normal. The visual field was limited to 5 deg around the fixation point, and a peripheral crescent-shaped arch encircled the temporal-inferior quadrant concomitant to the pigmentary changes. By computer tomography and Doppler sonography a vascular affection was excluded. The left eye displayed lower POBF values. All serological tests were found negative. CONCLUSION: The clinical picture and negative exclusion criteria indicate a unilateral retinitis pigmentosa. However, with regard to the literature an unequivocal diagnosis can only be made upon hereditary evidence.

Blood Flow Velocity↗
PubMed1998

Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy: results of a multicenter clinical trial. Daunomycin Study Group.

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.

Adult↗