The effect of combined daunorubicin and triamcinolone acetonide treatment on a refined experimental model of proliferative vitreoretinopathy.

Prior studies have shown that intravitreal daunorubicin (9-15 nmol) and triamcinolone acetonide (2 mg) are effective individually in preventing retinal detachment in experimental proliferative vitreoretinopathy. This report compares the efficacy of the combination of daunorubicin (15 nmol) and triamcinolone acetonide (2 mg) with that of daunorubicin alone in a refined experimental model of proliferative vitreoretinopathy. The degree of retinal detachment in each treatment group was graded, with the unequivocal absence or presence of retinal detachment used as an indicator of treatment success or failure. Both treatments (daunorubicin alone and in combination with triamcinolone acetonide) effectively prevented retinal detachment. However, there was no significant difference in the rate of retinal detachment between the two treatment groups. These results indicate that combination therapy with daunorubicin/triamcinolone is no more effective at preventing retinal detachment than daunorubicin alone.

Aclacinomycin A in the treatment of experimental proliferative vitreoretinopathy. Efficacy and toxicity in the rabbit eye.

PURPOSE: Aclacinomycin A is an oligosaccharide anthracycline that, by contrast with daunomycin, lacks carcinogenicity. The authors evaluated the efficacy of aclacinomycin A in prevention of experimental proliferative vitreoretinopathy (PVR) and its toxicity on the rabbit retina. METHODS: Dutch-belted rabbit were used to create a model for traction retinal detachment. Seven to 10 days after vitreous gas compression, 25,000 homologous fibroblasts were injected into the vitreous cavity. Subsequently, the eyes received either sham injections or doses of 6, 30, or 60 nmol of aclacinomycin A, respectively. The fundus findings were documented on days 7, 14, and 28 after the fibroblast injection. The toxicity studies were conducted according to the same protocol as was used for the efficacy evaluation but without the fibroblast injection. Simultaneous electroretinograms were recorded on days 0, 3, 7, and 14 from the right eyes that were injected with 30 or 60 nmol of aclacinomycin A and the left eyes that were sham injected. Morphologic studies were conducted on the eyes enucleated on days 3, 7, and 14 after drug exposure. RESULTS: Intraocular administration of 30 nmol of aclacinomycin A on day 2 after fibroblast injection resulted in a detachment rate of 37.5% (controls, 100%; P < 0.01, by Fisher's exact test). Administration of 60 nmol of aclacinomycin A 3 days after fibroblast injection resulted in a detachment rate of 26.7% (controls, 100%; P < 0.0001). Six nanomoles of aclacinomycin A 3 days after fibroblast injection had no effect. No electroretinogram changes were present in eyes treated with 30 nmol of aclacinomycin A. Such recordings from eyes exposed to 60 nmol of aclacinomycin A demonstrated decreased a- and b-waves on day 3; these completely recovered by day 7. Morphologic studies of these eyes revealed no damage to the retina. CONCLUSIONS: These results suggest that aclacinomycin A should be considered an alternative to daunomycin for treatment of human PVR because, in addition to its lack of carcinogenicity, it shows good efficacy and causes less retinal toxicity.

[Temporary keratoprosthesis, vitrectomy and autokeratoplasty in endophthalmitis treatment]. / Temporäre Keratoprothese, Vitrektomie und Autokeratoplastik zur Endophthalmitisbehandlung.

Postsurgical endophthalmitis frequently requires emergency vitrectomy. Loss of corneal transparency can preclude vitreoretinal surgery. Due to the narrow time frame in which surgical treatment needs to be performed, donor corneas are often not available for grafting. In addition, the risk of primary graft failure is higher in eyes with acute endophthalmitis. Later regrafting after primary graft failure carries a higher risk of graft rejection. By a clinical case of endophthalmitis after cataract surgery, we demonstrate the surgical technique of combined pars plana vitrectomy, keratoprosthesis, and autokeratoplasty. Loss of corneal transparency precluded standard pars plana vitrectomy with fundus contact lenses. The cornea was trephined and replaced by a keratoprosthesis. The trephined cornea was stored in tissue culture medium and pars plana vitrectomy was performed. At the end of the procedure, the keratoprosthesis was removed and the patient's own cornea was re-implanted. The transparency of the cornea improved during the postoperative course, permitting slit-lamp biomicroscopy of the anterior segment.

[EOG in adult vitelliform macular degeneration, butterfly-shaped pattern dystrophy and Best disease]. / EOG bei adulter vitelliformer Makuladegeneration (AVMD), schmetterlingsförmiger Patterndystrophie und Morbus Best.

OBJECTIVES: We evaluated the EOG in the various stages of foveomacular dystrophy (also called adult-onset vitelliform macular dystrophy) and compared these findings to those in Best's disease and butterfly-shaped dystrophy. PATIENTS AND METHODS: The records of 49 patients (98 eyes) in whom foveomacular dystrophy had been diagnosed by ophthalmoscopy or by fundus photographs and fluorescein angiography were retrospectively reviewed. Fifty-seven eyes were followed up (range 1.1-20 years, mean 10.4 years). EOG was elicited according to the method of Rohde and Täumer. The results were compared to those in Best's disease and butterfly-shaped dystrophy. RESULTS: In foveomacular dystrophy all mean EOG values were within normal ranges. There was no difference between the various stages of the disease. In Best's disease only the dark-adapted steady-state potential was in the normal range. The amplitude and the implicit time of the light peak were significantly different from those in patients with foveomacular dystrophy (P < 0.05 ANOVA). In butterfly-shaped dystrophy all the EOG parameters were normal. The ratio of the light peak to steady-state potential was significantly lower in foveomacular dystrophy than in butterfly-shaped dystrophy. CONCLUSION: In foveomacular dystrophy the mean values of the EOG were normal. Despite the morphological similarity we found more pronounced electrophysiological differences from Best's disease than from butterfly-shaped dystrophy.

[Ultrasound biomicroscopy for localization of artificial lens haptics after trans-scleral suture fixation]. / Ultraschallbiomikroskopie (UBM) zur Lokalisation der Kunstlinsenhaptik nach transskleraler Nahtfixation.

Correct positioning of transscleral haptics for sulcus fixation of IOL haptics may be difficult due to lack of visual control by the surgeon. We determined the haptic sites in eyes which underwent secondary IOL implantation with transscleral suturing using ultrasound biomicroscopy (UBM) (Humphrey Instruments, Inc., San Leandro, CA, USA). Eighteen eyes of 17 patients were included in the study. The follow-up time ranged from 1 to 36 months (mean: 7 months). The positions of 36 IOL-haptics were documented by UBM examination. Twelve haptics (33%) were found in the sulcus, whereas 18 haptics (50%) were located posteriorly to the sulcus. Six haptics (17%) were identified anteriorly to the sulcus. There were no complications resulting from dislocation. In one of the eyes, suture infection occurred requiring surgical revision and antibiotic therapy.

[A rare manifestation of sarcoidosis]. / Seltene Manifestation einer Sarkoidose.

This article reports the case of a 14-year-old boy who was presented in the case conference with symptoms of decreased visual acuity, scintillating scotomas and photophobia. Physical examination revealed right facial paralysis, parotid gland swelling, high fever and poor general condition. Ophthalmoscopy revealed anterior and posterior uveitis including macular edema and chorioretinal infiltrates. Angiography revealed a dense pattern of hyperfluorescent lesions and these observations resulted in the diagnosis of Heerfordt syndrome. Under systemic prednisolone therapy, symptoms were reduced and visual acuity recovered.

Retinal separation, retinotomy, and macular relocation: I. Experimental studies in the rabbit eye.

An animal model in the rabbit eye was utilized to study mobilization and relocation of the fovea as a potentially beneficial surgical approach to age-related macular disease. After lentectomy and vitrectomy, the retina was completely separated from the pigment epithelium by means of infusion into the subretinal space. A 360 degrees peripheral retinotomy was performed. The retina was rotated up to 60 degrees around the optic nerve as axis and reattached. Scanning and transmission electron microscopy revealed the relative intactness of outer segments and pigment epithelium after this procedure, both acutely and 3 days following reattachment.

Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration?

Three cases of age-related maculopathy with severe and recent massive submacular hemorrhage were treated by performing complete vitrectomy. A total retinal detachment was created by infusion of fluid underneath the retina, followed by a peripheral circumferential retinotomy. This allowed access to the subretinal space for removal of blood and membranes and, more importantly, permitted rotation of the retina with relocation of the fovea. Rotations between 30 degrees and 80 degrees were achieved. One patient with 5 months' follow-up had a visual improvement from 1/200 to 20/80 and excyclorotation of images. The other two patients developed proliferative vitreoretinopathy after initially successful rotation. Their retinas were reattached after surgical removal of the membranes and silicone oil tamponade, but visual function remained low. The rationale for this treatment is that relocating the fovea to an area where pigment epithelium is less diseased than in the central area may allow for recovery of some useful vision.

Subretinal lavage: a technique of continuous subretinal irrigation for removal of traumatic submacular hemorrhage.

A 12-year-old female patient suffered a horse kick to her face, resulting in various orbital fractures and blunt eye trauma. Upon ophthalmoscopy, an extensive subretinal hemorrhage was revealed under the macula, reaching to both vascular arcades. The visual acuity was 20/300. Five days after the accident, the patient was referred for vitreoretinal surgery. After standard vitrectomy, a small retinotomy was made at the temporal raphe. A second infusion was directed under the retina, thereby separating it carefully from the clot. The blot clot was exposed to tissue plasminogen activator (0.012 mg/0.1 ml) for 30 min. The liquefied blood was then washed out by continuous irrigation with buffered saline solution. The procedure was terminated by gas tamponade. Eleven days after surgery, the patient's vision had returned to 20/60. At 10 months after surgery, her vision was 20/30. No new hemorrhage was observed, nor did any fibrovascular proliferation occur from choroidal rupture. Continuous infusion instead of use of syringes for irrigation reduces the frequency of instrument passages through the pars plana and vitreous base, which may help reduce the risk of iatrogenic ora lesions. Surgery should be performed within 7 days to avoid toxic or metabolic retinal damage.

[Subretinal transplantation of confluent pigment epithelium: a novel device for non-traumatic tissue handling]. / Subretinale Transplantation von konfluentem Pigmentepithel: Ein neues Instrument zur atraumatischen Gewebeaufnahme.

BACKGROUND: Subretinal transplantation of pigment epithelium may be a therapeutic option in the treatment of age-related macular degeneration. Suspensions of pigment epithelial cells as well as confluent cell layers are being considered. METHODS: We developed a surgical device which permits to load living tissue, without exerting mechanical stress to the cells themselves, and to deliver it precisely onto the subretinal target site. RESULTS: After having been grown to confluency on extracellular matrix, the tissue can be fixed on a cannulated spoon by creating a vacuum on its undersurface. The spoon is connected to a silicone tube attached to a syringe. The syringe is used to produce a vacuum which is delivered to the tissue through the perforated surface of the spoon. After directing the spoon into the subretinal space, the tissue can be discharged by releasing the vacuum. CONCLUSIONS: In previous studies large cannulas have been used for injecting coherent cell layers underneath the retina. This technique frequently resulted in major distortion of the tissue. Furthermore, correct apico-basal orientation of the tissue often could not be achieved. We present a novel concept of a device which exerts vacuum to the entire underside of the graft allowing to hold it in position without distorting it. By releasing the vacuum, the graft can be positioned in the site of RPE atrophy. (Patent Reg. No. 29819018.4, München, Germany, 1998).

Human and porcine anterior lens capsule as support for growing and grafting retinal pigment epithelium and iris pigment epithelium.

PURPOSE: To establish a method for transplantation of cultured monolayers of RPE and IPE into the subretinal space, anterior lens capsule was evaluated for its suitability to serve as growth support and carrier for transplantation procedures. MATERIALS AND METHODS: Twenty-four anterior lens capsules were obtained from porcine eyes. The same number of human lens capsules was obtained during cataract surgery. Six lens capsules of each species were stored at -80 degrees C. Subsequently, the capsules were transferred onto type-I collagen. A second set of six lens capsules was treated identically except for the cryo treatment. A third set of six capsules was initially exposed to 0.05% trypsin for 30 min. Suspended porcine RPE and IPE cells (5 x 10(4) cells/well) were seeded on the top of each capsule. The remaining six lens capsules served as controls and were incubated in uncoated 12-well dishes without undergoing experimental treatment. The cultures were maintained in a water-saturated atmosphere at 37 degrees C with 5% CO(2). Six days later, viability, morphology, and cell density were determined. The capsules covered by a confluent monolayer of cells were transferred into uncoated wells and cultivated for another 10 days. At the end of the experiment, light and phase-contrast microscopy was performed on all capsules. RESULTS: Storage at -80 degrees C and exposure to trypsin resulted in significant reduction of cellular contamination. The highest cell density was found after 5 days when capsules which had undergone cryopreservation or trypsin exposure served as support for RPE and IPE. The pigment cell layer was firmly attached to the capsules and permitted a transfer to other culture flasks without significant cell loss. The IPE cell layer remained confluent after transfer to uncoated culture flasks, while the RPE cell layer ceased to proliferate 10 days after transfer. CONCLUSIONS: Lens capsules may be suitable for growing and supporting monolayers of pigment epithelial cells. Especially IPE cells formed stable monolayers on anterior lens capsules which could be transferred to secondary culture flasks without inflicting damage on the cells.

Growth inhibition of human Tenon's capsule fibroblasts and rabbit dermal fibroblasts with non-carcinogenic N-alkylated anthracyclines.

Bleb fibrosis after glaucoma filtering surgery and proliferative vitreoretinopathy after retinal detachment surgery are complications caused by proliferation of fibroblasts or fibroblastlike cells. The anthracycline daunomycin (DNM) has been used for treatment of those proliferative processes in humans. However, complications such as conjunctival necrosis and corneal or scleral ulcerations have been reported after administration of DNM to glaucoma patients. Intravitreal administration of DNM in rabbit eyes resulted in morphological and functional retinal damage. DNM also has the undesired general effect of carcinogenicity. N-Alkylation of the aminosugar moiety of DNM results in reduction or loss of carcinogenicity. We evaluated the inhibitory effect of the new non-carcinogenic N-alkylated analogues aclacinomycin A (ACA), N,N-dimethyladriamycin (AD280), and N-trifluoroacetyladriamycin-14-O-hemiadipate (AD143) on the growth of cultured human Tenon's capsule fibroblasts and rabbit dermal fibroblasts. Using DNM as a positive control, we conducted proliferation assays that demonstrated that ACA and AD280 inhibited fibroblast growth as effectively as DNM. AD143 was less efficacious. The magnitude of cellular growth inhibition was concentration dependent for all drugs tested. Extension of exposure times resulted in increased rates of cell death. Our in vitro studies suggest that further evaluation of ACA and AD280 should be carried out in animal models of ocular proliferative disorders.

[The combination of retrobulbar block with general anaesthesia may lead to pre-emptive analgesia in patients undergoing pars plana vitrectomy]. / Die Kombination von retrobulbärer Leitungsanästhesie und Allgemeinanästhesie führt zu präemptiver Analgesie bei Pars-plana-Vitrektomien.

SUBJECT: To determine whether additional regional blocking provides pre-emptive analgesia in patients undergoing elective pars plana vitrectomy. METHODS: In a prospectively randomised, double-blinded trial we investigated the potential benefit of combining regional anaesthesia (RA) with general anaesthesia (GA). In each group 25 patients undergoing pars plana vitrectomy were either done under GA (group A), GA combined with retrobulbar block (group B) or GA combined with peribulbar block (group C). Patients were examined by assessing NAS (numeric analogue scale). RESULTS: At all times, patients of group B experienced significantly less pain than patients in either group A or C (p < 0.001). There were no significant differences in pain scores between patients in groups A and C. Only 4 patients in group B required analgesics, whereas 17 patients in group A and 12 patients in group C. CONCLUSION: Certain ophthalmic operations are likely to cause postoperative pain when performed under GA alone, whereas the combination of retrobulbar block with GA reduces the development of pain as pre-emptive analgesia.

N,N-dimethyladriamycin for treatment of experimental proliferative vitreoretinopathy: efficacy and toxicity on the rabbit retina.

N,N-Dimethyladriamycin (Me-2-ADM) derives from adriamycin (doxorubicin) by N-methylation of its aminosugar moiety. In contrast to the parent agent, Me-2-ADM lacks mutagenicity and carcinogenicity. To evaluate its suitability for treatment of proliferative vitreoretinopathy (PVR), we studied the ability of Me-2-ADM to prevent traction retinal detachment in a model of PVR in rabbits. The model was created by intravitreal injection of 25,000 homologous dermal fibroblasts after vitreous gas compression. Two days after fibroblast injection, 5, 10 or 30 nmol Me-2-ADM was administered into the vitreous cavity. The control group received sham injections. All control eyes developed traction retinal detachments. Administration of 5 nmol Me-2-ADM slightly reduced the rate of retinal detachments to 90%. No retinal detachments occurred in the group treated with 10 nmol Me-2-ADM while 11% of eyes treated with 30 nmol Me-2-ADM developed retinal detachments. At day 28 of the study, light microscopic examination of retinas treated with 30 nmol Me-2-ADM revealed severe retinal damage while no such damage was present in eyes treated with 10 nmol. To exclude early retinal damage, 10 nmol Me-2-ADM were injected into eyes that had undergone vitreous gas compression but no fibroblast injection. On day 3, 7, and 14 after drug administration, ERGs were recorded simultaneously from drug treated and sham treated (contralateral) eyes. Light microscopy and transmission electron microscopy (TEM) were performed. Only transient ERG changes were observed at day 7, which recovered by day 14. All morphological findings in drug exposed eyes were in the range of normal when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[Autologous subretinal transplantation of cultivated porcine iris pigment epithelial cells (IPE)]. / Autologe subretinale Transplantation von kultivierten porzinen Irispigmentepithelzellen (IPE).

BACKGROUND: Subretina transplantation of epithelium may be a therapeutic option for surgical treatment of age-related macular degeration (AMD). Various experimental data have demonstrated that homologous transplantation of retinal pigment epithelium (RPE) can prevent photoreceptor deterioration. However, most investigators experienced immunogenic graft rejection when using homologous pigmented cells for grafting. Autologous cells were soon considered as an alternative for subretinal grafting. Particularly iris pigment epithelium (IPE) appeared suitable to replace homologous RPE for it embryogenetic similarity and its simple availability. Recent studies have shown, that IPE is capable of taking over functions of RPE in maintaining retinal metabolism. the purpose of this study was to evaluate if autologous IPE cells would survive when being transplanted subretinally. In addition, immunogenic reponses to the presence of "foreign" iris pigment cells needed to be excluded. MATERIALS AND METHODS: Iris tissue was obtained by peripheral iridectomy in the anesthetized pig. Sheets of pigment iris epithelium were separated from the specimens and transferred into tissue culture. After the cells had been grown to confluency, cell suspensions were injected into the subretinal space of the donor animal's fellow eye. After 4 weeks, the grafted eye was enucleated and examined histologically.. RESULTS: The histological exam revealed that the graft cells had survived in the subretinal space. No evidence of immunogenic rejection was observed. CONCLUSION: Autologous IPE-cells can survive in the host's sub-retinal space without creating inflammatory reactions. Transplanted IPE appears to interact with photoreceptor outer segments.

Factors independently associated with increased risk of pain development after ophthalmic surgery.

BACKGROUND AND OBJECTIVE: Little has been documented about the development of pain after ophthalmic surgery. This study was designed to assess the incidence and severity of postoperative pain following ophthalmic surgery, and to identify key factors independently associated with development of such pain. METHODS: In a prospective, observational cohort study, 500 patients undergoing elective ophthalmic surgery were examined by assessing numerical analogue scales and analgesic requirements. RESULTS: Depending on anatomical location of surgery, operations could be classified into creating 'more severe' or 'less severe pain'. Patients undergoing posterior segment, corneal and muscle surgery exhibited the highest numerical analogue scale scores (risk ratio 4.5, 95% CI 3.01-6.79, P < 0.0001). Anterior segment surgery, which per se did not create much pain, resulted in significantly more pain when performed under general anaesthesia compared to regional anaesthesia (risk ratio 6.52, 95% CI 2.33-18.2, P < 0.0001). No other factors independently associated with an increased risk of developing serious postoperative pain could be identified. CONCLUSIONS: Patients undergoing certain ophthalmic operations, especially if performed under general anaesthesia, are more likely to experience serious postoperative pain.

Ocular toxicity of daunomycin: effects of subdivided doses on the rabbit retina after vitreous gas compression.

Daunomycin is a potent antiproliferative agent which has been shown to prevent experimental proliferative vitreoretinopathy. However, toxic effects on the rabbit retina have been reported even for the lowest effective doses. In a previous report we demonstrated that subdivided doses rather than single doses of daunomycin improves the efficacy in prevention of experimental proliferative vitreoretinopathy. To evaluate whether dose subdivision would also have an alleviating effect on drug toxicity, we administered 15 nmol daunomycin in doses of 10 nmol and 5 nmol 4 h apart into the vitreous cavity of rabbit eyes which had previously undergone vitreous gas compression. All contralateral eyes received sham treatment. Simultaneous electroretinographic recordings from both eyes on days 0, 3, 7, and 14 demonstrated a significant b-wave decline in drug-exposed eyes. Morphological studies on these eyes revealed no retinal damage. Our findings suggest that dose subdivision does not eliminate the retinal toxicity of daunomycin.