Marc Veckeneer

Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial

PURPOSE To evaluate the safety and preliminary efficacy of 4 doses and several exposure times of intravitreal microplasmin given before pars plana vitrectomy for vitreomacular traction maculopathy. DESIGN A multicenter, prospective, uncontrolled, dose-escalation, phase I/II clinical trial. PARTICIPANTS Sixty patients enrolled into 6 successive cohorts. INTERVENTION A single intravitreal injection of microplasmin at 1 of 4 doses (25, 50, 75, or 125 microg in 100 microl) administered either 1 to 2 hours, 24 hours, or 7 days before planned pars plana vitrectomy. MAIN OUTCOME MEASURES For safety, a complete ophthalmologic examination, fundus photography, fluorescein angiography, Humphrey visual fields, and electrophysiology; for efficacy, posterior vitreous detachment (PVD) induction as assessed by B-scan ultrasound and ease of PVD induction at the time of vitrectomy. RESULTS The use of microplasmin led to a progressively higher incidence of PVD induction on ultrasonography with increasing time exposure. A PVD before surgery was observed with 25 microg microplasmin in 0, 2, and 5 patients with increasing exposures (2 hours, 24 hours, 7 days). With increasing dose, a PVD before surgery was observed by ultrasound as follows: 25 microg, 0; 50 microg, 1; 75 microg, 2; 125 microg, 3. However, at surgery, with a 125-microg dose, these patients had a discontinuous layer of vitreous present on the retinal surface resulting from the induction of an anomalous PVD in the form of vitreoschisis. One retinal detachment developed shortly after administration of microplasmin. Two developed after surgery. There were no other safety concerns. CONCLUSIONS Results from this initial clinical trial evaluating intravitreal microplasmin show the drug to be well tolerated and capable of inducing a pharmacologic PVD in some patients. These results warrant evaluation of microplasmin in larger, controlled trials.

Trypan blue not toxic for retinal pigment epithelium in vitro.

PURPOSE To investigate whether trypan blue has a toxic effect on cultured retinal pigment epithelial (retinal pigment epithelium) cells. DESIGN Experimental study with a direct live/dead cell staining technique using fluorescent dyes. METHODS Cultured human retinal pigment epithelium cells were exposed for 5 minutes to various concentrations of trypan blue (0.06%, 0.15%, 0.30%), and cell viability was confocally measured. RESULTS No increased cell death was found in cultures incubated in any of the trypan blue concentrations used. CONCLUSION These findings indicate that a short exposure of trypan blue does not have a toxic effect on cultured retinal pigment epithelium cells.

Double vital staining using trypan blue and infracyanine green in macular pucker surgery

Aims: To study the clinical properties of double vital staining in premacular fibrosis, facilitating complete removal of all epiretinal tissue. Methods: In a two step surgery, the epiretinal pucker was removed after staining with trypan blue, whereafter the inner limiting membrane was peeled after staining with infracyanine green. Results: In all 30 patients, a separate epiretinal layer and inner limiting membrane were removed from the macular area. Pathological examination showed different histological properties of the removed layers. An increased visual acuity was measured in 26 patients, and a slightly decreased visual acuity in one patient. Conclusion: The described double staining technique could be a novel valuable tool that may help to achieve optimal anatomical and functional recovery after surgery for premacular fibrosis

Randomized clinical trial of cryotherapy versus laser photocoagulation for retinopexy in conventional retinal detachment surgery

PURPOSE To investigate whether the method of retinopexy influences the visual recovery rate and the breakdown of the blood-ocular barrier after conventional retinal detachment surgery. METHODS Forty-eight patients (48 eyes) with primary rhegmatogenous retinal detachment entered into the study. All eyes were phakic, had an attached macula, and were scheduled for conventional scleral buckling surgery. Patients were randomly assigned to have either laser or cryotherapy for retinopexy. All visual acuity and flare measurements were performed by a masked observer. The interventional procedure was cryopexy at the time of scleral buckling surgery or postoperative (4 weeks) laser photocoagulation. Visual acuity testing with ETDRS chart and aqueous flare measurement with laser flare photometry were performed by a masked observer at standard intervals: preoperatively and 1 day, 7 days, 4 weeks, and 10 weeks postoperatively. Analysis of covariance by multiple linear regression was used for statistical evaluation. RESULTS Postoperative flare values from patients receiving cryotherapy were significantly higher at each measurement point in time (P < or =.001). The visual recovery was slower in the patients receiving cryotherapy (1 week, P =.003; 4 weeks, P =.03; 10 weeks, P =.081). CONCLUSION Laser flare photometry proved sufficiently sensitive to quantify an increase in aqueous flare after limited external retinal cryotherapy. Postoperative flare, as a measure of blood-ocular barrier breakdown, was significantly higher and visual recovery slower in the cryotherapy group. Visual acuity after 10 weeks was not significantly different between both groups.

Gelatinase B in proliferative vitreoretinal disorders.

PURPOSE To investigate whether gelatinases A and B are involved in the pathogenesis of proliferative vitreoretinal disorders. METHODS In a prospective study of 101 consecutive patients, vitreous and paired serum samples were obtained from 38 patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy, 25 patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy, and 38 patients with proliferative diabetic retinopathy. Gelatinase activities were determined by quantitative zymography. RESULTS All vitreous samples contained comparable levels of the constitutive gelatinase A. Inducible gelatinase B was detected in eight (32%) of 25 vitreous samples from patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy (mean +/- SD, 319.5 +/- 521.0 scanning units), in 17 (44.7%) of 38 vitreous samples from patients with proliferative vitreoretinopathy (560.6 +/- 718.9 scanning units), and in 34 (89.5%) of 38 vitreous samples from patients with proliferative diabetic retinopathy (1,707.2 +/- 1,220.3 scanning units). The incidence of detection of gelatinase B in proliferative diabetic retinopathy cases was significantly higher than it was in rhegmatogenous retinal detachment with no proliferative vitreoretinopathy and proliferative vitreoretinopathy cases (P < .001). Gelatinase B levels in the vitreous samples of patients with proliferative diabetic retinopathy were higher than the levels found in patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy and in patients with proliferative vitreoretinopathy (P = .0152). Gelatinase A was detected in all the tested sera, whereas none of the tested paired serum samples contained detectable gelatinase B activity. CONCLUSIONS Gelatinase B may play an important role in extracellular matrix degradation associated with neovascularization in proliferative diabetic retinopathy.

An epidemic of sticky silicone oil at the Rotterdam Eye Hospital. Patient review and chemical analyses

PurposeTo report and study the phenomenon of abnormal silicone oil adherent to the retina at the time of removal in a number of patients.Materials and methodsChart review was performed to identify possible patient or procedural factors that could predispose to sticky silicone oil formation. Gas chromatography-mass spectroscopy and nuclear magnetic resonance spectroscopy analyses were performed on sticky silicone oil samples, on perfluorocarbon liquid and on silicone oil samples straight from the vial.ResultsSticky silicone oil remnants were seen on the retina in 28 out of 234 silicone oil removal procedures between January 2001 and November 2002. Forceful removal was complicated in two patients by a choroidal hemorrhage and in one patient by a retinal tear. The use of perfluoro-octane (PFO; C8F18) rather than perfluorodecalin (C10F18) was related to the phenomenon (P < 0.001). Gas chromatography-mass spectroscopy analysis revealed a significant presence of PFO in samples of sticky silicone oil, and traces of partially fluorinated carbon liquid were found in the sticky oil as well as in the PFO samples.ConclusionsThe use of PFO may have been a predisposing factor for the occurrence of sticky silicone oil. While the presence of silicone oil remnants on the retina did not cause lasting side effect, forceful attempts at removal can lead to complications.

Persistent subretinal fluid after surgery for rhegmatogenous retinal detachment: hypothesis and review

BackgroundPersistent subretinal fluid after rhegmatogenous retinal detachment (RRD) surgery is responsible for delayed recovery, and may affect the final visual outcome. Cause, consequences, and treatment remain elusive.DesignLiterature review and case series.MethodsWe reviewed the pathophysiological principles and therapeutic options from the literature, and we report the results from a subretinal fluid cytology study. Nine eyes from nine patients with macula-involving RRD underwent surgical repair. The cellular content of subretinal fluid (SRF) was studied by electron microscopy and anti-rhodopsin immunostaining. All eyes were assessed postoperatively with optical coherence tomography for the detection of persistent submacular fluid (PSF) (Ethics Committee Ghent University Hospital, registration number B6702006169).ResultsCertain patient characteristics as well as surgical methods were implicated. PSF appears to occur more frequently in patients with longstanding detachments treated with buckling surgery. Several therapeutic options have been suggested but safety and efficacy remain unclear. We found PSF in three eyes on postoperative OCT scans, which corresponded to the three cell-rich subretinal samples.ConclusionsPSF after successful RRD repair seems to be related to fluid composition. We hypothesize, in the absence of an effective treatment, that a modified surgical drainage, including a washout of the subretinal space, could evacuate the subretinal fluid more completely, and may prevent this complication.

Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene

PURPOSE To investigate COL9A1 in two families suggestive of autosomal recessive Stickler syndrome and to delineate the associated phenotype. METHODS The probands of two consanguineous autosomal recessive Stickler families were evaluated for homozygosity using SNP microarray in one and haplotype analysis in the other. Subsequently, the entire COL9A1 open reading frame was analyzed by DNA sequencing in all members of the respective families. Several family members were investigated for dysmorphic features as well as ophthalmic, audiologic, and radiologic abnormalities. RESULTS A novel homozygous COL9A1 mutation (p.R507X) was identified in two affected Turkish sisters, and the previously published mutation (p.R295X) was found in a Moroccan boy. Ophthalmic assessment revealed myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Intervertebral disc bulging was observed in one patient and in two heterozygous carriers of the p.R507X mutation. CONCLUSIONS A second, novel mutation was identified in COL9A1, causing autosomal recessive Stickler syndrome together with the previously described nucleotide change in two separate families. Although the overall phenotype was comparable to autosomal dominant Stickler, vitreous changes that may enable recognition of patients who are likely to carry mutations in COL9A1 were identified, and exudative retinal detachment was observed as a new finding in Stickler syndrome.

Postoperative laser coagulation as retinopexy in patients with rhegmatogenous retinal detachment treated with scleral buckling surgery: a prospective clinical study.

Purpose To evaluate postoperative laser photocoagulation as retinopexy mode in patients with rhegmatogenous retinal detachment treated with scleral buckling surgery. Methods The authors conducted a prospective feasibility study of consecutive patients with rhegmatogenous retinal detachment treated with scleral buckling surgery and postoperative laser during an 18-month period with a minimal follow-up of 6 months. Outcome measures were total retinal reattachment and the occurrence of proliferative vitreoretinopathy (PVR). Results A total of 123 patients (124 eyes) were included in this study. Seventy-six percent were phakic and 24% were pseudophakic. Fifty percent presented with one horseshoe tear, 15% with multiple tears, 30% with round breaks, and 5% with no identifiable break. Ten percent presented with a vitreous hemorrhage and 25% with three or four quadrants of detached retina. Six patients had PVR C1. Twelve patients required a postoperative gas injection, five patients received an additional buckle, and five patients underwent a vitrectomy, in four because of PVR. In all patients the retina was fully reattached at the end of follow-up. Planned postoperative laser coagulation took place 1 day to 10 weeks (median 3½ weeks) after buckling surgery. Buckling material was removed in three patients without redetachment. Conclusion Postoperative laser coagulation is a feasible alternative retinopexy mode in scleral buckling surgery, with encouraging anatomical results and a low incidence of PVR.

Novel 'heavy' dyes for retinal membrane staining during macular surgery: multicenter clinical assessment.

Purpose:  To evaluate the feasibility of two novel ‘heavy’ dye solutions for staining the internal limiting membrane (ILM) and epiretinal membranes (ERMs), without the need for a prior fluid‐air exchange, during macular surgery.